Sinusoidal obstruction syndrome.

PubMed

Valla, Dominique-Charles; Cazals-Hatem, Dominique

2016-09-01

Sinusoidal obstruction syndrome (SOS) is characterized by damage to small hepatic vessels affecting particularly sinusoidal endothelium. Damaged sinusoids can be associated with a partial or complete occlusion of small hepatic veins, hence the previous denomination of hepatic veno-occlusive disease (VOD). Exposure to certain exogenous toxins appears to be specific to this condition and is frequently included in its definition. Typical histopathological features of SOS in a liver biopsy specimen are presented in the text. The purpose of this article is to provide an overview on the different entities corresponding to this general definition. Such entities include: (i) liver disease related to pyrrolizidine alcaloids; (ii) liver injury related to conditioning for hematopoietic stem cell transplantation; (iii) vascular liver disease occurring in patients treated with chemotherapy for liver metastasis of colorectal cancer; and (iv) other liver diseases related to toxic agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Smoking-related interstitial lung diseases.

PubMed

Caminati, A; Graziano, P; Sverzellati, N; Harari, S

2010-12-01

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

D’Andrea’s disease (angiomegaly): a currently well-defined nosological entitys.

PubMed

Taurone, S; Spoletini, M; Di Matteo, F M; Mele, R; Tromba, L; Grippaudo, F R; Minni, A; Artico, M

2017-01-01

In 1997 D’Andrea et al. described a new nosological entity the characteristics of which consisted of lengthening, dilation and tortuosity of blood vessels, arteries or veins, less prominent, but also less circumscribed than an aneurysm. This condition does not necessarily imply specific aneurysm formation although aneurysms at multiple sites are a frequent observation. The term used by authors for angiomegaly of the venous system was venomegaly and the analogous condition of the arterial system was termed arteriomegaly. Although tortuosity and dilation of arteries and veins have been widely reported, suggesting a systemic disorder which affects the structural integrity of all vessels, most papers dealing with this intriguing condition did not describe any alterations in the components of vessel walls. In the present paper, the authors describe a well-defined condition, D’Andrea’s Disease (or DD, in this article), analyzing its salient morphological and clinical features and clarifying this pathological condition as a distinct and now well-defined nosological entity.

Karl Jaspers on the disease entity: Kantian ideas and Weberian ideal types.

PubMed

Walker, Chris

2014-09-01

Jaspers' nosology is indebted to Immanuel Kant's theory of knowledge. He drew the distinction of form and content from the Transcendental Analytic of Kant's Critique of Pure Reason. The distinction is universal to all knowledge, including psychopathology. Individual experience is constituted by a form or category of the Understanding to give a determinate or knowable object classified into the generic type of a real disease entity. The application of form and content is limited by the boundaries of experience. Beyond this boundary are wholes whose conception requires Ideas of reason drawn from the Transcendental Dialectic. Wholes are regulated by Ideas of reason to give an object or schema of the Idea collected into ideal types of an ideal typical disease entity. Jaspers drew ideal types from Max Weber's social theory. He anticipated that, as knowledge advanced, ideal typical disease entities would become real disease entities. By 1920, this had been the destiny of general paralysis as knowledge of its neuropathology, serology and microbiology emerged. As he presented the final edition of General Psychopathology in 1946, Jaspers was anticipating the transition of schizophrenia from ideal typical to real disease entity. Almost 70 years later, with knowledge of its aetiology still unclear, schizophrenia remains marooned as an ideal typical disease entity - still awaiting that crucial advance! © The Author(s) 2014.

Translation of the Department of Defense Disease and Injury Codes to the Eighth Revision International Classification of Diseases for use by the Military Services.

DTIC Science & Technology

1976-06-01

with, the DDDIC entity. 3. The ICDA-8 contracts groups of diseases or accidents which had been presented in expanded form in the DDDIC. Example: DDDIC...DDDIC. 4. The ICDA-8 expands groups of entities which had been presented in more condensed folin in the DDDIC. Example: DDDIC ICDA-8 Code Ntmuber Code...rapidly find a disease entity and all closely related entities. At the Naval Health Research Center (N11RC) a new code nunber was given to each

Osteoarticular manifestations of celiac disease and non-celiac gluten hypersensitivity.

PubMed

Dos Santos, Stéphanie; Lioté, Frédéric

2017-05-01

Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg. The diagnosis is confirmed by positive specific antibody, anti-transglutaminase or anti-endomysium, specific lesions of the small intestine and a response to strict gluten-free diet. The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia. In the absence of risk factor, osteoporosis, in a premenopausal women or in a man less than 55 years, more is if it is severe and refractory to medications, need to rheumatologists on the track of celiac disease in the absence of digestive symptoms. Osteomalacia is related to secondary hypovitaminosis D malabsorption. Supplementation by calcifediol, water-soluble vitamin D, may be indicated. Celiac disease is associated with an autoimmune disease in almost 1/3 of the cases. Knowing these potential associations allows earlier diagnosis in patients whose only manifestation, a concomitant disease. Anemia, chronic fatigue or unexplained polyarthralgia are symptoms associated with celiac disease to look for specific antibodies. The aim of early diagnosis is to prevent the emergence of other systemic disorders and avoid complications such as bone fractures and cancer, especially intestinal lymphoma. Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out, among patients without specific antibodies and without intestinal lesion of celiac disease. This entity is a cause, at least in part, of increasing interest in gluten-free diet in the general population. Copyright © 2016. Published by Elsevier SAS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, N.R.; Covey, R.P. Jr.; Haglund, W.

The growth of apple seedlings (Malus domestica Brokh.) is negatively correlated with soil arsenic and zero growth occurs at about 450 ppm total arsenic. Soil arsenic concentrations less than 150 ppm, which are frequently found in orchard soils, contribute less to the replant problem than biological factors. Growth of apple trees was increased 50% or more by preplant soil fumigation with methyl bromide or trichloronitromethane (chloropicrin) in 87.5% of the trials in 17 apple orchard soils tested. Non-specific plant pathogens in orchard soils attack cereals as well as apple seedlings, but apple orchard soils also contain an entity that specificallymore » affects apples. This is probably the same unknown entity that is responsible for specific apple replant disease in Europe, Australia, and elsewhere.« less

Retrieval of radiology reports citing critical findings with disease-specific customization.

PubMed

Lacson, Ronilda; Sugarbaker, Nathanael; Prevedello, Luciano M; Ivan, Ip; Mar, Wendy; Andriole, Katherine P; Khorasani, Ramin

2012-01-01

Communication of critical results from diagnostic procedures between caregivers is a Joint Commission national patient safety goal. Evaluating critical result communication often requires manual analysis of voluminous data, especially when reviewing unstructured textual results of radiologic findings. Information retrieval (IR) tools can facilitate this process by enabling automated retrieval of radiology reports that cite critical imaging findings. However, IR tools that have been developed for one disease or imaging modality often need substantial reconfiguration before they can be utilized for another disease entity. THIS PAPER: 1) describes the process of customizing two Natural Language Processing (NLP) and Information Retrieval/Extraction applications - an open-source toolkit, A Nearly New Information Extraction system (ANNIE); and an application developed in-house, Information for Searching Content with an Ontology-Utilizing Toolkit (iSCOUT) - to illustrate the varying levels of customization required for different disease entities and; 2) evaluates each application's performance in identifying and retrieving radiology reports citing critical imaging findings for three distinct diseases, pulmonary nodule, pneumothorax, and pulmonary embolus. Both applications can be utilized for retrieval. iSCOUT and ANNIE had precision values between 0.90-0.98 and recall values between 0.79 and 0.94. ANNIE had consistently higher precision but required more customization. Understanding the customizations involved in utilizing NLP applications for various diseases will enable users to select the most suitable tool for specific tasks.

Retrieval of Radiology Reports Citing Critical Findings with Disease-Specific Customization

PubMed Central

Lacson, Ronilda; Sugarbaker, Nathanael; Prevedello, Luciano M; Ivan, IP; Mar, Wendy; Andriole, Katherine P; Khorasani, Ramin

2012-01-01

Background: Communication of critical results from diagnostic procedures between caregivers is a Joint Commission national patient safety goal. Evaluating critical result communication often requires manual analysis of voluminous data, especially when reviewing unstructured textual results of radiologic findings. Information retrieval (IR) tools can facilitate this process by enabling automated retrieval of radiology reports that cite critical imaging findings. However, IR tools that have been developed for one disease or imaging modality often need substantial reconfiguration before they can be utilized for another disease entity. Purpose: This paper: 1) describes the process of customizing two Natural Language Processing (NLP) and Information Retrieval/Extraction applications – an open-source toolkit, A Nearly New Information Extraction system (ANNIE); and an application developed in-house, Information for Searching Content with an Ontology-Utilizing Toolkit (iSCOUT) – to illustrate the varying levels of customization required for different disease entities and; 2) evaluates each application’s performance in identifying and retrieving radiology reports citing critical imaging findings for three distinct diseases, pulmonary nodule, pneumothorax, and pulmonary embolus. Results: Both applications can be utilized for retrieval. iSCOUT and ANNIE had precision values between 0.90-0.98 and recall values between 0.79 and 0.94. ANNIE had consistently higher precision but required more customization. Conclusion: Understanding the customizations involved in utilizing NLP applications for various diseases will enable users to select the most suitable tool for specific tasks. PMID:22934127

Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

PubMed Central

Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H.

2014-01-01

Background Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research. PMID:24662942

Triple confusion: An interesting case of proteinuria in pregnancy.

PubMed

Guru, Pramod K; Ramaeker, Devon M; Jeybalan, Arundhathi; Shah, Nirav A; Bastacky, Sheldon; Liang, Kelly V

2016-01-01

Pregnancy-related renal diseases are unique and need special attention, both for diagnosis and management. The major confounding factors for diagnosis are the physiological multiorgan changes that occur throughout the gestational period. Proper diagnosis of the renal disease is also important, given the impact of varied management options both on the maternal and fetal health. A young middle-aged female with a long-standing history of diabetes presented to the hospital with worsening proteinuria in her second trimester of pregnancy. Clinical history, examinations, and laboratory analysis did not give any clues for diagnosis of a specific disease entity. This led us to take the risk of renal biopsy for a tissue diagnosis. The odds of renal biopsy favored the management decision in her case, thereby avoiding the confusions prior to biopsy. The pathological diagnosis is a surprise though not a unique entity on its own (minimal change disease in pregnancy). The case illustrates the disparity of clinical presentations and the pathology in patients, and the importance of renal biopsy in pregnant patients in particular.

Is orphan drug status beneficial to tropical disease control? Comparison of the American and future European orphan drug acts.

PubMed

Trouiller, P; Battistella, C; Pinel, J; Pecoul, B

1999-06-01

OBJECTIVES To quantify past outcomes of tropical pharmacology research and development (R & D) and to assess past benefits of the American orphan drug act and potential benefits of the future European orphan drug regulation on tropical diseases. This paper presents two analyses: a 1983-97 retrospective study of the United States Orphan Drug Act concerning rare diseases and a prospective study of the European Proposal for a Regulation Concerning Orphan Drugs and its possible impact on tropical diseases. Different programmes have in the past tried to stimulate R & D in this area, but results remain limited. Of 1450 new chemical entities marketed between 1972 and 1997, 13 were specifically for tropical diseases and considered as essential drugs. Between 1983 & 1997, the US Orphan Drug Act approved 837 drugs and marketing of 152 new molecular entities (NMEs). Three NMEs have been designated for malaria and human African trypanosomiasis. Seven others, already commonly used in tropical diseases, received either orphan designation or an orphan approval for another indication. Pharmaceutical companies benefit from the US framework only when the US market exclusivity clause was applicable. Future European orphan drug regulation appears to be similar to the US Orphan Drug Act. CONCLUSION The orphan drug programmes relating to rare diseases have met with some success. Considering tropical diseases rare diseases seems inadequate to boost pharmaceutical R & D. However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of 'diseases of exception'.

45 CFR 162.610 - Implementation specifications for covered entities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Implementation specifications for covered entities... Implementation specifications for covered entities. (a) The standard unique employer identifier of an employer of... Statement, from the employer. (b) A covered entity must use the standard unique employer identifier (EIN) of...

45 CFR 162.610 - Implementation specifications for covered entities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Implementation specifications for covered entities... Implementation specifications for covered entities. (a) The standard unique employer identifier of an employer of... Statement, from the employer. (b) A covered entity must use the standard unique employer identifier (EIN) of...

Self-assembling software generator

DOEpatents

Bouchard, Ann M [Albuquerque, NM; Osbourn, Gordon C [Albuquerque, NM

2011-11-25

A technique to generate an executable task includes inspecting a task specification data structure to determine what software entities are to be generated to create the executable task, inspecting the task specification data structure to determine how the software entities will be linked after generating the software entities, inspecting the task specification data structure to determine logic to be executed by the software entities, and generating the software entities to create the executable task.

[Angiolymphoid hyperplasia with eosinophilia with bilateral involvement of the lacrimal glands].

PubMed

Baráková, Drahomíra; Sâch, Josef; Kuchynka, Pavel; Rêdinová, Magdalena; Kocur, Ivo

2002-05-01

Angiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura's disease are two rarely occurring disorders very similar to each other; however, they are individual nosological entities. For a long time they were considered as a single disease due to the frequency of similar characteristics. The majority of authors have recently considered these diseases as two individual entities with some reciprocal specifications, both clinical as well as morphological. We report on the case of a 76-year old male white European who had suffered for more than six years from subcutaneous tumour formations in different parts of the body. Eyelid oedema on the right side with palpable resistance under the upper temporal edge of the orbit initially occurred five years after the first symptoms of the disease. A similar finding occurred on the left side after eight months. The tumours on both sides were surgically removed and sent for histological analysis. A unilateral recurrence of the finding appeared after one year, followed by surgical intervention and histological examination. Tumour infiltrate in the first two orbita excisions was topically related to lacrimal gland structures; these structures were not found in the third excision. The case was histologically diagnosed as ALHE despite some similar characteristics with Kimura's disease. The diagnosis of ALHE was histologically supported, especially by the absence of lymphatic follicle formations and fibrotisation in the infiltrate, and the identification of the appearance of epitheloid up to histiocytoid of proliferating endothelium, which forms small lumens. The diagnosis of ALHE was additionally supported by the fact that the incidence of Kimura's disease in white Europeans is very rare. According to our findings, both entities overlap one another, even in some characteristics considered to be distinguishing. The question arises, therefore, whether the strict separation of these nosological entities can indeed be determined with one hundred percent accuracy.

Therapies in inborn errors of oxidative metabolism

PubMed Central

Schiff, Manuel; Bénit, Paule; Jacobs, Howard T.; Vockley, Jerry; Rustin, Pierre

2014-01-01

Mitochondrial diseases encompass a wide range of presentations and mechanisms, dictating a need to consider both broad-based and disease-specific therapies. The manifestations of mitochondrial dysfunction and the response to therapy vary between individuals. This probably reflects the genetic complexity of mitochondrial biology, which requires an excess of 2000 genes for proper function, with numerous interfering epigenetic and environmental factors. Accordingly, we are increasingly aware of the complexity of these diseases which involve far more than merely decreased ATP supply. Indeed, recent therapeutic progress has addressed only specific disease entities. In this review present and prospective therapeutic approaches will be discussed on the basis of targets and mechanism of action, but with a broad outlook on their potential applications. PMID:22633959

Differential CXC and CX3C Chemokine Expression Profiles in Aqueous Humor of Patients With Specific Endogenous Uveitic Entities.

PubMed

El-Asrar, Ahmed M Abu; Berghmans, Nele; Al-Obeidan, Saleh A; Gikandi, Priscilla W; Opdenakker, Ghislain; Van Damme, Jo; Struyf, Sofie

2018-05-01

To determine the levels of the neutrophil chemoattractants CXCL1, CXCL2, CXCL5, CXCL6, and CXCL8, the T helper 1 chemoattractants CXCL9, CXCL10 and CXCL11, the lymphoid chemokines CXCL12 and CXCL13 and the soluble form of the transmembrane chemokines CXCL16 and CX3CL1, in aqueous humor samples from patients with specific uveitic entities. Aqueous humor samples from patients with active uveitis associated with Behçet's disease (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt-Koyanagi-Harada (VKH) disease (n = 12), and healthy controls (n = 9) were assayed with the use of a multiplex assay. All chemoattractant levels were significantly higher in all patients than in the controls. The levels of all neutrophil chemoattractants and CXCL10, CXCL16, and CX3CL1 were significantly higher in nongranulomatous uveitis (Behçet's disease and HLA-B27-associated uveitis) than in granulomatous uveitis (sarcoidosis and VKH disease), whereas the levels of the B cell chemoattractant CXCL13 were significantly higher in granulomatous uveitis than in nongranulomatous uveitis. CXCL13 levels were highest in the patients with VKH disease. CXCL9, CXCL11, and CXCL12 levels did not differ significantly. Inflammation in nongranulomatous uveitis appears to be driven by neutrophils and T helper 1 lymphocytes, whereas B lymphocytes may contribute to the inflammatory process in granulomatous uveitis, particularly in VKH disease.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders

PubMed Central

de Pedro-Cuesta, Jesús; Martínez-Martín, Pablo; Rábano, Alberto; Alcalde-Cabero, Enrique; José García López, Fernando; Almazán-Isla, Javier; Ruiz-Tovar, María; Medrano, Maria-José; Avellanal, Fuencisla; Calero, Olga; Calero, Miguel

2016-01-01

Background: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific “drivers”, i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities. Objectives and Methods: Redefining drivers as “neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms”, we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns. Results: We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson’s disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer’s disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus. Conclusion: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these. PMID:26923014

KSHV-associated multicentric Castleman disease: A tangle of different entities requiring multitarget treatment strategies.

PubMed

Carbone, Antonino; De Paoli, Paolo; Gloghini, Annunziata; Vaccher, Emanuela

2015-07-15

Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder presenting with heterogeneous pathological and clinical features. It comprises disease entities with a complex aetiology and overlapping pathogenesis. MCD can be found in association with HIV infection, plasma-cell dyscrasias, Kaposi sarcoma (KS), B-cell lymphomas including primary effusion lymphoma (PEL) and its solid variant, and Hodgkin lymphoma. In KSHV-associated MCD cases, a common association is KS and a specific variant of lymphoma referred to as "plasmablastic lymphoma," also called "large B-cell lymphoma arising in KSHV-associated MCD" lacking EBV infection. MCD is often referred to as human interleukin-6 (hIL-6) syndrome, since an overproduction of IL-6 occurs in MCD-associated diseases as well as in MCD itself. hIL-6 and a viral IL-6 (vIL-6) homolog encoded by KSHV can independently or together lead to flares of KSHV-associated MCD. Recently, a new clinical entity was proposed to describe a severe systemic infection/reactivation of KSHV: KSHV inflammatory syndrome (KICS). KICS may contribute in inducing the inflammatory symptoms seen in some patients with severe KS or PEL. The precise relationship of KICS to KSHV-associated MCD is unclear and it is possible that KICS may be prodromal symptoms to frank KSHV-associated MCD. Options for treatment of KSHV-associated MCD and related diseases include monoclonal antibodies, chemotherapy, immune modulators, virus-activated cytotoxic therapy and antiviral therapies. A comprehensive understanding of the intricacies of the HIV-KSHV coinfection will probably lead to additional advances in therapy and managements for these disorders. © 2014 UICC.

Conversation Intention Perception based on Knowledge Base

DTIC Science & Technology

2014-05-01

Yi Liu Gastritis Fracture Vomit Pain Bleeding thirst Anti-acid Clarithromycin styptic Aspirin Symptom Medicine Disease 1/117 1/157 1/20...occurrence frequency. Firstly, we compute the distance between two entities. For example, distance between entity Gastritis and entity Vomit is...considered as one as they are connected directly, distance between entity Gastritis and entity Fracture is two since they are con- nected through entity

Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome.

PubMed

Lötvall, Jan; Akdis, Cezmi A; Bacharier, Leonard B; Bjermer, Leif; Casale, Thomas B; Custovic, Adnan; Lemanske, Robert F; Wardlaw, Andrew J; Wenzel, Sally E; Greenberger, Paul A

2011-02-01

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called "asthma endotypes." An "endotype" is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism. Criteria for defining asthma endotypes on the basis of their phenotypes and putative pathophysiology are suggested. Using these criteria, we identify several proposed asthma endotypes and propose how these new definitions can be used in clinical study design and drug development to target existing and novel therapies to patients most likely to benefit. This PRACTALL (PRACtical ALLergy) consensus report was produced by experts from the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Identifying new diseases and their causes: the dilemma of illnesses in Gulf War veterans.

PubMed

Gardner, John W; Gibbons, Robert V; Hooper, Tomoko I; Cunnion, Stephen O; Kroenke, Kurt; Gackstetter, Gary D

2003-03-01

Since the Gulf War, investigation continues of symptoms and illnesses among its veterans. Yet, identifying a specific "Gulf War Syndrome" remains elusive. With new disease entities, causal associations are relatively easily established when the condition is serious, verifiable, and has excess disease rates in specific groups. In common conditions, many excess cases are required to establish association with a specific exposure. Establishing causality in syndromes with variable symptoms is difficult because specific diagnostic algorithms must be established before causal factors can be properly investigated. Searching for an environmental cause is futile in the absence of an operational disease case definition. Common subjective symptoms (without objective physical or laboratory findings) account for over one-half of all medical outpatient visits, yet these symptoms lack an identified physical cause at least one-third of the time. Our medical care system has difficulty dealing with disorders where there is no identified anatomic abnormality or documented metabolic/physiological dysfunction.

On chronic fatigue syndrome and nosological categories.

PubMed

Sharif, Kassem; Watad, Abdulla; Bragazzi, Nicola Luigi; Lichtbroun, Michael; Martini, Mariano; Perricone, Carlo; Amital, Howard; Shoenfeld, Yehuda

2018-05-01

Chronic fatigue syndrome (CFS) is a heterogeneous disease which presents with pronounced disabling fatigue, sleep disturbances, and cognitive impairment that negatively affects patients' functional capability. CFS remains a poorly defined entity and its etiology is still in question. CFS is neither a novel diagnosis nor a new medical condition. From as early as the eighteenth century, a constellation of perplexing symptoms was observed that resembled symptoms of CFS. Commencing with "febricula" and ending with CFS, many names for the disease were proposed including neurocirculatory asthenia, atypical poliomyelitis, Royal Free disease, effort syndrome, Akureyri disease, Tapanui disease, chronic Epstein-Barr virus syndrome, and myalgic encephalitis. To date, it remains unclear whether CFS has an autoimmune component or is a condition that precedes a full-blown autoimmune disease. Research suggests that CFS may overlap with other diseases including postural orthostatic tachycardia syndrome (POTS), autoimmune syndrome induced by adjuvants (ASIA), and Sjögren's syndrome. Additionally, it has been postulated that the earliest manifestations of some autoimmune diseases can present with vague non-specific symptoms similar to CFS. Sometimes only when exposed to a secondary stimulus (e.g., antigen) which could accelerate the natural course of the disease would an individual develop the classic autoimmune disease. Due to the similarity of symptoms, it has been postulated that CFS could simply be an early manifestation of an autoimmune disease. This paper will provide a historical background review of this disease and a discussion of CFS as an entity overlapping with multiple other conditions.

TaggerOne: joint named entity recognition and normalization with semi-Markov Models

PubMed Central

Leaman, Robert; Lu, Zhiyong

2016-01-01

Motivation: Text mining is increasingly used to manage the accelerating pace of the biomedical literature. Many text mining applications depend on accurate named entity recognition (NER) and normalization (grounding). While high performing machine learning methods trainable for many entity types exist for NER, normalization methods are usually specialized to a single entity type. NER and normalization systems are also typically used in a serial pipeline, causing cascading errors and limiting the ability of the NER system to directly exploit the lexical information provided by the normalization. Methods: We propose the first machine learning model for joint NER and normalization during both training and prediction. The model is trainable for arbitrary entity types and consists of a semi-Markov structured linear classifier, with a rich feature approach for NER and supervised semantic indexing for normalization. We also introduce TaggerOne, a Java implementation of our model as a general toolkit for joint NER and normalization. TaggerOne is not specific to any entity type, requiring only annotated training data and a corresponding lexicon, and has been optimized for high throughput. Results: We validated TaggerOne with multiple gold-standard corpora containing both mention- and concept-level annotations. Benchmarking results show that TaggerOne achieves high performance on diseases (NCBI Disease corpus, NER f-score: 0.829, normalization f-score: 0.807) and chemicals (BioCreative 5 CDR corpus, NER f-score: 0.914, normalization f-score 0.895). These results compare favorably to the previous state of the art, notwithstanding the greater flexibility of the model. We conclude that jointly modeling NER and normalization greatly improves performance. Availability and Implementation: The TaggerOne source code and an online demonstration are available at: http://www.ncbi.nlm.nih.gov/bionlp/taggerone Contact: zhiyong.lu@nih.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27283952

TaggerOne: joint named entity recognition and normalization with semi-Markov Models.

PubMed

Leaman, Robert; Lu, Zhiyong

2016-09-15

Text mining is increasingly used to manage the accelerating pace of the biomedical literature. Many text mining applications depend on accurate named entity recognition (NER) and normalization (grounding). While high performing machine learning methods trainable for many entity types exist for NER, normalization methods are usually specialized to a single entity type. NER and normalization systems are also typically used in a serial pipeline, causing cascading errors and limiting the ability of the NER system to directly exploit the lexical information provided by the normalization. We propose the first machine learning model for joint NER and normalization during both training and prediction. The model is trainable for arbitrary entity types and consists of a semi-Markov structured linear classifier, with a rich feature approach for NER and supervised semantic indexing for normalization. We also introduce TaggerOne, a Java implementation of our model as a general toolkit for joint NER and normalization. TaggerOne is not specific to any entity type, requiring only annotated training data and a corresponding lexicon, and has been optimized for high throughput. We validated TaggerOne with multiple gold-standard corpora containing both mention- and concept-level annotations. Benchmarking results show that TaggerOne achieves high performance on diseases (NCBI Disease corpus, NER f-score: 0.829, normalization f-score: 0.807) and chemicals (BioCreative 5 CDR corpus, NER f-score: 0.914, normalization f-score 0.895). These results compare favorably to the previous state of the art, notwithstanding the greater flexibility of the model. We conclude that jointly modeling NER and normalization greatly improves performance. The TaggerOne source code and an online demonstration are available at: http://www.ncbi.nlm.nih.gov/bionlp/taggerone zhiyong.lu@nih.gov Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

A transition-based joint model for disease named entity recognition and normalization.

PubMed

Lou, Yinxia; Zhang, Yue; Qian, Tao; Li, Fei; Xiong, Shufeng; Ji, Donghong

2017-08-01

Disease named entities play a central role in many areas of biomedical research, and automatic recognition and normalization of such entities have received increasing attention in biomedical research communities. Existing methods typically used pipeline models with two independent phases: (i) a disease named entity recognition (DER) system is used to find the boundaries of mentions in text and (ii) a disease named entity normalization (DEN) system is used to connect the mentions recognized to concepts in a controlled vocabulary. The main problems of such models are: (i) there is error propagation from DER to DEN and (ii) DEN is useful for DER, but pipeline models cannot utilize this. We propose a transition-based model to jointly perform disease named entity recognition and normalization, casting the output construction process into an incremental state transition process, learning sequences of transition actions globally, which correspond to joint structural outputs. Beam search and online structured learning are used, with learning being designed to guide search. Compared with the only existing method for joint DEN and DER, our method allows non-local features to be used, which significantly improves the accuracies. We evaluate our model on two corpora: the BioCreative V Chemical Disease Relation (CDR) corpus and the NCBI disease corpus. Experiments show that our joint framework achieves significantly higher performances compared to competitive pipeline baselines. Our method compares favourably to other state-of-the-art approaches. Data and code are available at https://github.com/louyinxia/jointRN. dhji@whu.edu.cn. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Determining similarity of scientific entities in annotation datasets

PubMed Central

Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

2015-01-01

Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug–drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called ‘AnnSim’ that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1–1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ PMID:25725057

Determining similarity of scientific entities in annotation datasets.

PubMed

Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

2015-01-01

Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug-drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called 'AnnSim' that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1-1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ © The Author(s) 2015. Published by Oxford University Press.

A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease

PubMed Central

Wormser, Gary P.; Strle, Franc; Shapiro, Eugene D.; Dattwyler, Raymond J.; Auwaerter, Paul G.

2018-01-01

In older studies, a chronic distal symmetric sensory neuropathy was reported as a relatively common manifestation of late Lyme disease in the United States. However, the original papers describing this entity had notable inconsistencies and certain inexplicable findings, such as reports that this condition developed in patients despite prior antibiotic treatment known to be highly effective for other manifestations of Lyme disease. More recent literature suggests that this entity is seen rarely, if at all. A chronic distal symmetric sensory neuropathy as a manifestation of late Lyme disease in North America should be regarded as controversial and in need of rigorous validation studies before acceptance as a documented clinical entity. PMID:27914746

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies.

PubMed

McAllister, Brian P; Williams, Emmanuelle; Clarke, Kofi

2018-06-02

Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease. Simple algorithms for care based on a comprehensive multidisciplinary approach are proposed. Refractory and non-responsive celiac diseases in the setting of a gluten-free diet are examined as are novel non-dietary therapies. Finally, the association of other disease states including psychiatric illness, infertility, lymphoproliferative malignancy, and mortality is explored with special attention paid to autoimmune and atopic disease.

78 FR 22270 - Special Fraud Alert: Physician-Owned Entities

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

...] Special Fraud Alert: Physician-Owned Entities AGENCY: Office of Inspector General (OIG), HHS. ACTION... Physician-Owned Entities. Specifically, the Special Fraud Alert addressed physician-owned entities that... publication of the Special Fraud Alert on Physician-Owned Entities, an inadvertent error appeared in the DATES...

A study of EMR-based medical knowledge network and its applications.

PubMed

Zhao, Chao; Jiang, Jingchi; Xu, Zhiming; Guan, Yi

2017-05-01

Electronic medical records (EMRs) contain an amount of medical knowledge which can be used for clinical decision support. We attempt to integrate this medical knowledge into a complex network, and then implement a diagnosis model based on this network. The dataset of our study contains 992 records which are uniformly sampled from different departments of the hospital. In order to integrate the knowledge of these records, an EMR-based medical knowledge network (EMKN) is constructed. This network takes medical entities as nodes, and co-occurrence relationships between the two entities as edges. Selected properties of this network are analyzed. To make use of this network, a basic diagnosis model is implemented. Seven hundred records are randomly selected to re-construct the network, and the remaining 292 records are used as test records. The vector space model is applied to illustrate the relationships between diseases and symptoms. Because there may exist more than one actual disease in a record, the recall rate of the first ten results, and the average precision are adopted as evaluation measures. Compared with a random network of the same size, this network has a similar average length but a much higher clustering coefficient. Additionally, it can be observed that there are direct correlations between the community structure and the real department classes in the hospital. For the diagnosis model, the vector space model using disease as a base obtains the best result. At least one accurate disease can be obtained in 73.27% of the records in the first ten results. We constructed an EMR-based medical knowledge network by extracting the medical entities. This network has the small-world and scale-free properties. Moreover, the community structure showed that entities in the same department have a tendency to be self-aggregated. Based on this network, a diagnosis model was proposed. This model uses only the symptoms as inputs and is not restricted to a specific disease. The experiments conducted demonstrated that EMKN is a simple and universal technique to integrate different medical knowledge from EMRs, and can be used for clinical decision support. Copyright © 2017 Elsevier B.V. All rights reserved.

Leiomyosarcoma: One disease or distinct biologic entities based on site of origin?

PubMed

Worhunsky, David J; Gupta, Mihir; Gholami, Sepideh; Tran, Thuy B; Ganjoo, Kristen N; van de Rijn, Matt; Visser, Brendan C; Norton, Jeffrey A; Poultsides, George A

2015-06-01

Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin. Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years. Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS. © 2015 Wiley Periodicals, Inc.

Patterns of uveitis in a tertiary eye care center in Iran.

PubMed

Soheilian, Masood; Heidari, Kumars; Yazdani, Shahin; Shahsavari, Mohsen; Ahmadieh, Hamid; Dehghan, Mohammad

2004-12-01

To identify the distribution and characteristics of new uveitis referrals to a tertiary eye care center in Tehran. A three-year prospective study was carried out to obtain information on 544 new patients referred with uveitis. A complete ophthalmologic examination was performed in all cases; a routine set of tests and an additional battery of directed workup were conducted when indicated. Mean age was 32.3 years. There was no significant sex predominance. The most common forms of uveitis were anterior (38.4%) vs. other anatomical forms, chronic (62.1%) vs. acute (28.3%), nongranulomatous (85.5%) vs. granulomatous (14.5%), and noninfectious (83.5%) vs. infectious (16.5%). With regard to etiology, 45.5% were idiopathic, 19.9% were due to specific ocular disease, and 37.3% were associated with systemic disorders. Behcet's disease was the most common noninfectious disease and toxoplasmosis the most common infectious entity. The most prevalent causes were idiopathic, Fuchs' heterochromic iridocylitis, and seronegative spondyloarthropathies in anterior uveitis; toxoplasmosis, Eales disease, and toxocariasis in posterior uveitis; idiopathic, sarcoidosis, and multiple sclerosis in intermediate uveitis; and, finally, Behcet's disease, idiopathic, and Vogt-Koyanagi-Harada syndrome in panuveitis. The most frequent cause in patients under 16 years of age was pars planitis. Over 80% of the patients belonged to middle-to-upper socioeconomic classes. Uveitis significantly affected patients' lives in 63.1% of the cases. Although the current study was performed at a referral center, it may reflect to some extent the different distribution of uveitis in Iran and probably other Middle Eastern countries. Some entities such as presumed ocular histoplasmosis were not found, cytomegalovirus retinitis and birdshot chorioretinopathy were extremely rare, and HLA-B27-associated iridocyclitis was less commonly observed. In contrast, Behcet's disease, Fuchs' heterochromic iridocyclitis, Eales disease, and toxocariasis were among the more prevalent entities.

77 FR 40951 - Medicare Program; End-Stage Renal Disease Prospective Payment System, Quality Incentive Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-11

...This rule proposes to update and make revisions to the End- Stage Renal Disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2013. This rule also proposes to set forth requirements for the ESRD quality incentive program (QIP), including for payment year (PY) 2015 and beyond. This proposed rule will implement changes to bad debt reimbursement for all Medicare providers, suppliers, and other entities eligible to receive bad debt. (See the Table of Contents for a listing of the specific issues addressed in this proposed rule.)

Thoracic perspective revisited in chronic liver disease.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Kumar, Sachin; Arora, Ankur

2015-08-01

A variety of chest manifestations are seen in patients with chronic liver diseases, namely hepatopulmonary syndrome, portopulmonary hypertension, intrathoracic portosystemic collaterals, hepatic hydrothorax, infections, drug-induced changes, manifestations of hepatocellular carcinoma, gynecomastia, acute respiratory distress syndrome, autoimmune changes, aspiration pneumonitis and changes due to α1-antitrypsin deficiency. Gastroenterologists and radiologists should be aware of these entities; knowledge of the imaging findings specific to each condition is of prime importance for managing such patients. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

[Neuromuscular diseases were always difficult to diagnose].

PubMed

Claus, D

2013-06-01

The Deutsche Zeitschrift fuer Nervenheilkunde (German Journal for Neurology) was founded as a specifically neurological journal at the end of the nineteenth century and soon became a European platform for scientific discussion of neurological topics. Papers also came from the USA, Scandinavia and Russia. The difficulties of the diagnosis and definition of clinical entities are illustrated in cases of botulism, myotonic dystrophy and myasthenia gravis.

National Biocontainment Training Center

DTIC Science & Technology

2016-10-01

and the high containment capabilities of the Galveston National Laboratory. U.S. Food and Drug Administration Training – Marisa Hickey, D.V.M., MPH...in the Netherlands focused specifically on “healthy food and healthy environment.” The CVI is the national reference laboratory that is focused on...the health of both animals and humans. They provide research for government and commercial entities on animal diseases that threaten the food supply

GeneView: a comprehensive semantic search engine for PubMed.

PubMed

Thomas, Philippe; Starlinger, Johannes; Vowinkel, Alexander; Arzt, Sebastian; Leser, Ulf

2012-07-01

Research results are primarily published in scientific literature and curation efforts cannot keep up with the rapid growth of published literature. The plethora of knowledge remains hidden in large text repositories like MEDLINE. Consequently, life scientists have to spend a great amount of time searching for specific information. The enormous ambiguity among most names of biomedical objects such as genes, chemicals and diseases often produces too large and unspecific search results. We present GeneView, a semantic search engine for biomedical knowledge. GeneView is built upon a comprehensively annotated version of PubMed abstracts and openly available PubMed Central full texts. This semi-structured representation of biomedical texts enables a number of features extending classical search engines. For instance, users may search for entities using unique database identifiers or they may rank documents by the number of specific mentions they contain. Annotation is performed by a multitude of state-of-the-art text-mining tools for recognizing mentions from 10 entity classes and for identifying protein-protein interactions. GeneView currently contains annotations for >194 million entities from 10 classes for ∼21 million citations with 271,000 full text bodies. GeneView can be searched at http://bc3.informatik.hu-berlin.de/.

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

Cystic renal tumors: new entities and novel concepts.

PubMed

Moch, Holger

2010-05-01

Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways.

Does targeted, disease-specific public research funding influence pharmaceutical innovation?

PubMed

Blume-Kohout, Margaret E

2012-01-01

Public funding for biomedical research is often justified as a means to encourage development of more (and better) treatments for disease. However, few studies have investigated the relationship between these expenditures and downstream pharmaceutical innovation. In particular, although recent analyses have shown a clear contribution of federally funded research to drug development, there exists little evidence to suggest that increasing targeted public research funding for any specific disease will result in increased development of drugs to treat that disease. This paper evaluates the impact of changes in the allocation of U. S. National Institutes of Health (NIH) extramural research grant funding across diseases on the number of drugs entering clinical testing to treat those diseases, using new longitudinal data on NIH extramural research grants awarded by disease for years 1975 through 2006. Results from a variety of distributed lag models indicate that a sustained 10 percent increase in targeted, disease-specific NIH funding yields approximately a 4. 5 percent increase in the number of related drugs entering clinical testing (phase I trials) after a lag of up to 12 years, reflecting the continuing influence of NIH funding on discovery and testing of new molecular entities. In contrast, we do not see evidence that increases in NIH extramural grant funding for research focused on specific diseases will increase the number of related treatments investigated in the more expensive, late-stage (phase III) trials.

"Disease entity" as the key theoretical concept of medicine.

PubMed

Hucklenbroich, Peter

2014-12-01

Philosophical debates about the concept of disease, particularly of mental disease, might benefit from reconsideration and a closer look at the established terminology and conceptual structure of contemporary medical pathology and clinical nosology. The concepts and principles of medicine differ, to a considerable extent, from the ideas and notions of philosophical theories of disease. In medical theory, the concepts of disease entity and pathologicity are, besides the concept of disease itself, of fundamental importance, and they are essentially connected to the concepts cause of disease or etiological factor, natural course or natural history of disease, and pathological disposition. It is the concept of disease entity that is of key importance for understanding medical pathology and theory of disease. Its central role is shown by a short reconstruction of its main features and its intrinsic connection to the concept of pathologicity. The meaning of pathologicity is elucidated by explicating the underlying criteria. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Lymph nodes fine needle cytology in the diagnosis of infectious diseases: clinical settings.

PubMed

Natella, Valentina; Cozzolino, Immacolata; Sosa Fernandez, Laura Virginia; Vigliar, Elena

2012-01-01

Lymph node reactive hyperplasia, caused by specific infectious etiologic factors, represents the most frequent cause of enlarged peripheral lymph nodes. The main infectious agents are viruses, pyogenic bacteria, mycobacteria, fungi and protozoa that may determine unspecific or specific pathological entities, such as cat-scratch disease, toxoplasmosis or infectious mononucleosis. Lymph node fine needle cytology (FNC) is a safe, simple, cost-effective and efficient technique that quickly provides information about the cell population and the nature of the process. FNC can also provide suitable material for ancillary techniques, such as flow cytometry, immunocytochemistry, molecular biology and microbiological examinations. This study focuses on the cytological features of benign lymphadenopathy of infectious origin and their possible contribution to the clinical setting definition of corresponding patients.

A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and “pan-leukemia” antigens

PubMed Central

Walz, Simon; Schuster, Heiko; Berlin, Claudia; Neidert, Marian Christoph; Schemionek, Mirle; Brümmendorf, Tim H.; Vucinic, Vladan; Niederwieser, Dietger; Kanz, Lothar; Salih, Helmut Rainer; Kohlbacher, Oliver; Weisel, Katja; Rammensee, Hans-Georg; Stevanović, Stefan; Walz, Juliane Sarah

2017-01-01

Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape. We found the cancer HLA peptidome datasets to cluster specifically along entity and lineage lines, suggesting that the immunopeptidome directly reflects the differences in the underlying (tumor-)biology. In line with these findings, we only detected a small set of entity-spanning antigens, which were predominantly characterized by low presentation frequencies within the different patient cohorts. These findings suggest that design of T-cell immunotherapies for the treatment of HM should ideally be conducted in an entity-specific fashion. PMID:28159928

Autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus.

PubMed

Saeb-Lima, Marcela; Charli-Joseph, Yann; Rodríguez-Acosta, Elva Dalia; Domínguez-Cherit, Judith

2013-08-01

Neutrophilic dermatoses have long been known to be associated with autoinmune systemic diseases. Recently, a small number of cases of a disorder distinct from Sweet syndrome or bullous lupus erythematosus (LE) have been described as specifically related to systemic LE under diverse terms, including nonbullous neutrophilic dermatosis, nonbullous neutrophilic LE, and Sweet-like neutrophilic dermatosis. We describe 7 patients that developed urticarial lesions in the context of a known or concurrently diagnosed autoimmune connective tissue disease. Of a total of 7 patients, 6 were afflicted by systemic LE and 1 by rheumatoid arthritis and secondary Sjögren syndrome. Histological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, vacuolar alteration along the dermal-edidermal junction, and no vasculitis. Most patients had active systemic disease at the time of the cutaneous eruption. Skin lesions resolved rapidly after the administration of immunomodulating agents. In conclusion, we provide additional evidence of the existence of a recently defined nonbullous neutrophilic dermatosis in the context of autoimmune connective tissue diseases and propose the term autoimmunity-related neutrophilic dermatosis as an appropriate designation. Furthermore, we believe that this entity should prompt physicians to screen the presence of an active systemic disorder in afflicted patients.

Should DSM-V Designate “Internet Addiction” a Mental Disorder?

PubMed Central

2009-01-01

There is considerable controversy with respect to so-called internet addiction and whether it ought to be reified as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The relationship between “addiction” and various compulsive or impulsive behaviors is also a source of confusion. Some psychiatrists have argued that internet addiction shows the features of excessive use, withdrawal phenomena, tolerance, and negative repercussions that characterize many substance use disorders; however, there are few physiological data bearing on these claims. It is not clear whether internet addiction usually represents a manifestation of an underlying disorder, or is truly a discrete disease entity. The frequent appearance of internet addiction in the context of numerous comorbid conditions raises complex questions of causality. In order to make nosological decisions regarding internet addiction, we require a more general model of what counts as “disease,” and as a specific disease. Based on a model emphasizing intrinsic suffering and incapacity, as well as data regarding course, prognosis, temporal stability, and response to treatment, it appears premature to consider internet addiction as a discrete disease entity. However, growing research suggests that some individuals with internet addiction are at significant risk and merit our professional care and treatment. Carefully controlled studies are required to settle these controversies. PMID:19724746

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature.

PubMed

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-11-05

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.

States' implementation of the Section 510 abstinence education program, FY 1999.

PubMed

Sonfield, A; Gold, R B

2001-01-01

As part of its reworking of the nation's welfare system in 1996, Congress enacted a major new abstinence education initiative (Section 510 of Title V of the Social Security Act), projected to spend $87.5 million in federal, state and local funds per year for five years. The new program is designed to emphasize abstinence from sexual activity outside of marriage, at any age, rather than premarital abstinence for adolescents, which was typical of earlier efforts. The actual message and impact of the program, however, will depend on how it is implemented. Program coordinators in all 50 states, the District of Columbia and Puerto Rico were surveyed concerning implementation of the Section 510 abstinence education program in FY 1999. The questionnaire asked about expenditures and activities performed, about policies established for a variety of specific situations and about how the term "sexual activity" is defined and what specific components of the federal definition of "abstinence education" are emphasized. Forty-five jurisdictions spent a total of $69 million through the Section 510 program in FY 1999. Of this total, $33 million was spent through public entities, $28 million was spent through private entities and $7million (in 22 jurisdictions) was spent through faith-based entities. Almost all jurisdictions reported funding school-related activities, with 38 reporting in-school instruction and presentations. Twenty-eight jurisdictions prohibited organizations from providing information about contraception (aside from failure rates), even at a client's request, while only six jurisdictions prohibited information about sexually transmitted diseases. Few reported having a policy or rendering guidance about providing services addressing sexual abuse, sexual orientation or existing pregnancy and parenthood. Only six respondents said they defined "sexual activity" for purposes of the program, and 16 reported focusing on specific portions of the federal definition of "abstinence education." More than one in 10 Section 510 dollars were spent through faith-based entities. Programs commonly conducted in-school activities, particularly instruction and presentations, not only through public entities, but also through private and faith-based entities. Most jurisdictions prohibited the provision of information about contraception, about providers of contraceptive services or about both topics, even in response to a direct question and when using other sources of funding. Most also left definitions of "abstinence" and "sexual activity" as local decisions, thus not clearly articulating what the program is designed to encourage clients to abstain from.

COMPUTING THERAPY FOR PRECISION MEDICINE: COLLABORATIVE FILTERING INTEGRATES AND PREDICTS MULTI-ENTITY INTERACTIONS.

PubMed

Regenbogen, Sam; Wilkins, Angela D; Lichtarge, Olivier

2016-01-01

Biomedicine produces copious information it cannot fully exploit. Specifically, there is considerable need to integrate knowledge from disparate studies to discover connections across domains. Here, we used a Collaborative Filtering approach, inspired by online recommendation algorithms, in which non-negative matrix factorization (NMF) predicts interactions among chemicals, genes, and diseases only from pairwise information about their interactions. Our approach, applied to matrices derived from the Comparative Toxicogenomics Database, successfully recovered Chemical-Disease, Chemical-Gene, and Disease-Gene networks in 10-fold cross-validation experiments. Additionally, we could predict each of these interaction matrices from the other two. Integrating all three CTD interaction matrices with NMF led to good predictions of STRING, an independent, external network of protein-protein interactions. Finally, this approach could integrate the CTD and STRING interaction data to improve Chemical-Gene cross-validation performance significantly, and, in a time-stamped study, it predicted information added to CTD after a given date, using only data prior to that date. We conclude that collaborative filtering can integrate information across multiple types of biological entities, and that as a first step towards precision medicine it can compute drug repurposing hypotheses.

COMPUTING THERAPY FOR PRECISION MEDICINE: COLLABORATIVE FILTERING INTEGRATES AND PREDICTS MULTI-ENTITY INTERACTIONS

PubMed Central

REGENBOGEN, SAM; WILKINS, ANGELA D.; LICHTARGE, OLIVIER

2015-01-01

Biomedicine produces copious information it cannot fully exploit. Specifically, there is considerable need to integrate knowledge from disparate studies to discover connections across domains. Here, we used a Collaborative Filtering approach, inspired by online recommendation algorithms, in which non-negative matrix factorization (NMF) predicts interactions among chemicals, genes, and diseases only from pairwise information about their interactions. Our approach, applied to matrices derived from the Comparative Toxicogenomics Database, successfully recovered Chemical-Disease, Chemical-Gene, and Disease-Gene networks in 10-fold cross-validation experiments. Additionally, we could predict each of these interaction matrices from the other two. Integrating all three CTD interaction matrices with NMF led to good predictions of STRING, an independent, external network of protein-protein interactions. Finally, this approach could integrate the CTD and STRING interaction data to improve Chemical-Gene cross-validation performance significantly, and, in a time-stamped study, it predicted information added to CTD after a given date, using only data prior to that date. We conclude that collaborative filtering can integrate information across multiple types of biological entities, and that as a first step towards precision medicine it can compute drug repurposing hypotheses. PMID:26776170

[Amyloidosis maculosa: diagnosis in primary care].

PubMed

Toribio da Pena, S R; Olmos, O; Borbujo, J; Bastos Amigo, J A; Jiménez-Sánchez, F; Alonso, A

1990-01-01

Amyloidosis maculosa is a clinical entity with low incidence factor in our medium, which basically affects middle-aged women. The lesion is characterised by the presence of poorly defined, hyperpigmented, brownish or greyish maculae that converge and focus basically on the upper back and shoulders, usually accompanied by pruritus. Three patients were erroneously catalogued for years as having pityriasis versicolor. Two of these patients presented a typical clinical amyloidosis maculosa, and the third presented a less common manifestation of the disease: a single, well-defined lesion in the subscapular region. We believe that the approach to the diagnosis of pityriasis versicolor with hyperpigmented lesions that do not respond to specific treatment should be revised. Although amyloidosis maculosa has a low incidence in our medium, it is an entity which should not be discarded in these cases.

Longitudinal cystic fibrosis care.

PubMed

Antunovic, S S; Lukac, M; Vujovic, D

2013-01-01

Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis.

Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive diagnostic and organ-specific criteria.

PubMed

Umehara, Hisanori; Okazaki, Kazuichi; Nakamura, Takuji; Satoh-Nakamura, Tomomi; Nakajima, Akio; Kawano, Mitsuhiro; Mimori, Tsuneyo; Chiba, Tsutomu

2017-05-01

IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.

MRI appearance of massive renal replacement lipomatosis in the absence of renal calculus disease

PubMed Central

Fitzgerald, E; Melamed, J; Taneja, S S; Rosenkrantz, A B

2011-01-01

Renal replacement lipomatosis is a rare benign entity in which extensive fibrofatty proliferation of the renal sinus is associated with marked renal atrophy. In this report, we present a case of massive renal replacement lipomatosis demonstrated on MRI. The presentation was atypical given an absence of associated renal calculus disease, and an initial CT scan was interpreted as suspicious for a liposarcoma. The differential diagnosis and key MRI findings that served to establish this specific diagnosis are reviewed. Histopathological correlation is also presented, as the patient underwent nephroureterectomy. PMID:21257835

neXtA5: accelerating annotation of articles via automated approaches in neXtProt.

PubMed

Mottin, Luc; Gobeill, Julien; Pasche, Emilie; Michel, Pierre-André; Cusin, Isabelle; Gaudet, Pascale; Ruch, Patrick

2016-01-01

The rapid increase in the number of published articles poses a challenge for curated databases to remain up-to-date. To help the scientific community and database curators deal with this issue, we have developed an application, neXtA5, which prioritizes the literature for specific curation requirements. Our system, neXtA5, is a curation service composed of three main elements. The first component is a named-entity recognition module, which annotates MEDLINE over some predefined axes. This report focuses on three axes: Diseases, the Molecular Function and Biological Process sub-ontologies of the Gene Ontology (GO). The automatic annotations are then stored in a local database, BioMed, for each annotation axis. Additional entities such as species and chemical compounds are also identified. The second component is an existing search engine, which retrieves the most relevant MEDLINE records for any given query. The third component uses the content of BioMed to generate an axis-specific ranking, which takes into account the density of named-entities as stored in the Biomed database. The two ranked lists are ultimately merged using a linear combination, which has been specifically tuned to support the annotation of each axis. The fine-tuning of the coefficients is formally reported for each axis-driven search. Compared with PubMed, which is the system used by most curators, the improvement is the following: +231% for Diseases, +236% for Molecular Functions and +3153% for Biological Process when measuring the precision of the top-returned PMID (P0 or mean reciprocal rank). The current search methods significantly improve the search effectiveness of curators for three important curation axes. Further experiments are being performed to extend the curation types, in particular protein-protein interactions, which require specific relationship extraction capabilities. In parallel, user-friendly interfaces powered with a set of JSON web services are currently being implemented into the neXtProt annotation pipeline.Available on: http://babar.unige.ch:8082/neXtA5Database URL: http://babar.unige.ch:8082/neXtA5/fetcher.jsp. © The Author(s) 2016. Published by Oxford University Press.

neXtA5: accelerating annotation of articles via automated approaches in neXtProt

PubMed Central

Mottin, Luc; Gobeill, Julien; Pasche, Emilie; Michel, Pierre-André; Cusin, Isabelle; Gaudet, Pascale; Ruch, Patrick

2016-01-01

The rapid increase in the number of published articles poses a challenge for curated databases to remain up-to-date. To help the scientific community and database curators deal with this issue, we have developed an application, neXtA5, which prioritizes the literature for specific curation requirements. Our system, neXtA5, is a curation service composed of three main elements. The first component is a named-entity recognition module, which annotates MEDLINE over some predefined axes. This report focuses on three axes: Diseases, the Molecular Function and Biological Process sub-ontologies of the Gene Ontology (GO). The automatic annotations are then stored in a local database, BioMed, for each annotation axis. Additional entities such as species and chemical compounds are also identified. The second component is an existing search engine, which retrieves the most relevant MEDLINE records for any given query. The third component uses the content of BioMed to generate an axis-specific ranking, which takes into account the density of named-entities as stored in the Biomed database. The two ranked lists are ultimately merged using a linear combination, which has been specifically tuned to support the annotation of each axis. The fine-tuning of the coefficients is formally reported for each axis-driven search. Compared with PubMed, which is the system used by most curators, the improvement is the following: +231% for Diseases, +236% for Molecular Functions and +3153% for Biological Process when measuring the precision of the top-returned PMID (P0 or mean reciprocal rank). The current search methods significantly improve the search effectiveness of curators for three important curation axes. Further experiments are being performed to extend the curation types, in particular protein–protein interactions, which require specific relationship extraction capabilities. In parallel, user-friendly interfaces powered with a set of JSON web services are currently being implemented into the neXtProt annotation pipeline. Available on: http://babar.unige.ch:8082/neXtA5 Database URL: http://babar.unige.ch:8082/neXtA5/fetcher.jsp PMID:27374119

The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia

PubMed Central

DeBaun, Michael R; Strunk, Robert C

2016-01-01

Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management. PMID:27353685

[CLINICAL ENTITIES AND CHARACTERISTICS OF PAIN IN PATIENTS WITH RHEUMATIC DISEASES].

PubMed

Prus, Višnja; Kardum, Željka

Musculoskeletal pain is the most common symptom present in almost all rheumatic diseases. Rheumatic diseases include more than 150 clinical entities. There is no uniform classification of rheumatic diseases. In general, we distinguish inflammatory rheumatic diseases, non-inflammatory degenerative articular diseases, systemic connective tissue diseases, metabolic disorders with articular manifestations, and regional and extended pain syndromes. According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensation associated with tissue damage or reported simultaneously with such damage. Pain has a physical, mental, and social component. In rheumatic diseases the pain is mostly chronic and may severely impair the patient’s general condition. The defining criteria involve a period of more than 3 or 6 months, and according to some definitions more than 6 weeks. In most cases the pain is nociceptive rather than neuropathic. Musculoskeletal pain, especially chronic pain, is a global public health problem because of its prevalence, as well as the frequently associated muslculoskeletal function impairment and development of chronic pain syndrome, which can be considered as a separate clinical entity and requires a biopsychosocial treatment approach.

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies

PubMed Central

Abu-Shakra, M; Buskila, D; Ehrenfeld, M; Conrad, K; Shoenfeld, Y

2001-01-01

OBJECTIVES—To review the autoimmune and rheumatic manifestations of patients with malignancy.
METHODS—A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes.
RESULTS—Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy.
CONCLUSION—Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

 PMID:11302861

A dramatic, objective antiandrogen withdrawal response: case report and review of the literature

PubMed Central

Lau, Yiu-Keung; Chadha, Manpreet K; Litwin, Alan; Trump, Donald L

2008-01-01

Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation. PMID:18986533

Acquired bilateral telangiectatic macules: a distinct clinical entity.

PubMed

Park, Ji-Hye; Lee, Dong Jun; Lee, Yoo-Jung; Jang, Yong Hyun; Kang, Hee Young; Kim, You Chan

2014-09-01

We evaluated 13 distinct patients with multiple telangiectatic pigmented macules confined mostly to the upper arms to determine if the clinical and histopathological features of these cases might represent a specific clinical entity. We retrospectively investigated the clinical, histopathologic, and immunohistochemical features of 13 patients with multiple telangiectatic pigmented macules on the upper arms who presented between January 2003 and December 2012. Epidermal pigmentation, melanogenic activity, melanocyte number, vascularity, epidermal thickness, and perivascular mast cell number of the specimens were evaluated. Clinically, the condition favored middle-aged men. On histopathologic examination, the lesional skin showed capillary proliferation and telangiectasia in the upper dermis. Histochemical and immunohistochemical analysis revealed basal hyperpigmentation and increased melanogenic activity in the lesional skin (P < .05). No significant difference in epidermal thickness or mast cell number was observed between the normal perilesional skin and the lesional skin. The clinical and histopathologic features of these lesions were relatively consistent in all patients. In addition, the features are quite distinct from other diseases. Based on clinical and histologic features, we suggest the name acquired bilateral telangiectatic macules for this new entity.

Dissecting disease entities out of the broad spectrum of bipolar-disorders.

PubMed

Levine, Joseph; Toker, Lilach; Agam, Galila

2018-01-01

The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.

CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease.

PubMed

Anders, Hans-Joachim; Huber, Tobias B; Isermann, Berend; Schiffer, Mario

2018-06-01

The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has prompted research efforts to tackle the growing epidemic of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited success of much of this research might in part be due to the fact that not all patients diagnosed with DKD have renal dysfunction as a consequence of their diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or a combination of both DKD and NDKD. Preclinical studies using models that more accurately mimic these three entities might improve the ability of animal models to predict clinical trial outcomes. Moreover, improved insights into the pathomechanisms that are shared by these entities - including sodium-glucose cotransporter 2 (SGLT2) and renin-angiotensin system-driven glomerular hyperfiltration and tubular hyper-reabsorption - as well as those that are unique to individual entities might lead to the identification of new treatment targets. Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses NDKD as well as DKD could help solve some of the urgent unmet medical needs of patients affected by these conditions.

[Allogeneic hematopoietic cell transplantation for Hodgkin's disease, mantle cell lymphoma and other rare entities: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

PubMed

Gauthier, Jordan; Chantepie, Sylvain; Bouabdallah, Krimo; Jost, Edgar; Nguyen, Stéphanie; Gac, Anne-Claire; Damaj, Gandhi; Duléry, Rémy; Michallet, Mauricette; Delage, Jérémy; Lewalle, Philippe; Morschhauser, Franck; Salles, Gilles; Yakoub-Agha, Ibrahim; Cornillon, Jérôme

2017-12-01

Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic haematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript specifically reports on our conclusions regarding Hodgkin's lymphoma as well as rarer entities, such as T cell lymphomas. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

[Cystic renal neoplasms. New entities and molecular findings].

PubMed

Moch, H

2010-10-01

Renal neoplasms with dominant cysts represent a broad spectrum of known as well as novel renal tumor entities. Established renal tumors with dominant cysts include cystic nephroma, mixed epithelial and stromal tumor, synovial sarcoma and multilocular cystic renal cancer (WHO classification 2004). Novel tumor types have recently been reported, which are also characterized by marked cyst formation. Examples are tubulocystic renal cancer and renal cancer in end-stage renal disease. These tumors are very likely to be included in a future WHO classification due to their characteristic phenotype and molecular features. Cysts and clear cell renal cell carcinoma frequently coexist in the kidneys of patients with von Hippel-Lindau disease. Cysts are also a component of many sporadic clear cell renal cell carcinomas. Multilocular cystic renal cell carcinoma is composed almost exclusively of cysts and is regarded as a specific subtype of clear cell renal cancer. Recent molecular findings suggest that clear cell renal cancer may develop via a cyst-dependent mechanism in von Hippel-Lindau syndrome as well as via cyst-independent molecular pathways in sporadic clear cell renal cancer.

Regulatory T Cell Therapy for Uveitis: A New Promising Challenge.

PubMed

Foussat, Arnaud; Gregoire, Sylvie; Clerget-Chossat, Nathalie; Terrada, Celine; Asnagli, Hélène; Lemoine, François M; Klatzmann, David; LeHoang, Phuc; Forte, Miguel; Bodaghi, Bahram

2017-05-01

Uveitis is a sight-threatening primary intraocular inflammation of various origins in mainly young and active patients. Due to the absence of biomarkers in most of the cases, the current treatment of noninfectious entities remains nonspecific, using corticosteroids, conventional immunosuppressors, and more recently biological agents. Identification of regulatory T cells in different models of autoimmune uveitis together with the evaluation of this important subpopulation in different entities paved the way for new therapeutic strategies, in addition to exclusive pharmaceutical approaches. Upregulation of regulatory T cells induced by biological agents has been recently highlighted. Development of cell therapy in autoimmune diseases is at its stammering needing more experimental data and robust clinical trials to demonstrate safety and efficacy before larger developments. Specific or polyclonal Tregs may be used, but it is of utmost importance to determine the method of selection, the level of activation, and the route of administration. Mastering immune cell therapy remains a challenging goal in patients with autoimmune diseases, but it may significantly enlarge our therapeutic possibilities in severe and refractory situations.

Data Base Design Using Entity-Relationship Models.

ERIC Educational Resources Information Center

Davis, Kathi Hogshead

1983-01-01

The entity-relationship (ER) approach to database design is defined, and a specific example of an ER model (personnel-payroll) is examined. The requirements for converting ER models into specific database management systems are discussed. (Author/MSE)

Differential diagnosis in inflammatory bowel disease colitis: State of the art and future perspectives

PubMed Central

Tontini, Gian Eugenio; Vecchi, Maurizio; Pastorelli, Luca; Neurath, Markus F; Neumann, Helmut

2015-01-01

Distinction between Crohn’s disease of the colon-rectum and ulcerative colitis or inflammatory bowel disease (IBD) type unclassified can be of pivotal importance for a tailored clinical management, as each entity often involves specific therapeutic strategies and prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, we have performed a literature search to address the problem of differential diagnosis in IBD colitis, revised current and emerging diagnostic tools and refined disease classification strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD, better reflecting diverse disease behaviors based on specific pathogenic pathways. PMID:25574078

Balancing Overscreening and Underdiagnosis in Secondary Hypertension: The Case of Fibromuscular Dysplasia.

PubMed

Ruzicka, Marcel; Kucharski, Sarah E; Hiremath, Swapnil

2017-05-01

Knowledge about fibromuscular dysplasia (FMD) has broadened over the last several decades. It is no longer considered a rare and benign entity limited to renal arteries and causing just hypertension. It affects other parts of the arterial tree nearly as frequently as the renal arteries. Complications of undiagnosed and untreated extrarenal FMD can be debilitating and life threatening. However, this disease, specifically extrarenal FMD, is not well known to many physicians and patients. Combined with the nonspecific symptoms and signs of the disease, this leads to delayed diagnosis and missed opportunity to prevent serious vascular complications. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasmacytoid dendritic cell leukaemia/lymphoma: towards a well defined entity?

PubMed

Garnache-Ottou, Francine; Feuillard, Jean; Saas, Philippe

2007-02-01

CD4(+)/CD56(+) haematodermic neoplasm or 'early' plasmacytoid dendritic cell leukaemia/lymphoma (pDCL) was described as a disease entity in the last World Health Organisation/European Organisation for Research and Treatment of Cancer classification for cutaneous lymphomas. These leukaemia/lymphomas co-express CD4 and CD56 without any other lineage-specific markers and have been identified as arising from plasmacytoid dendritic cells. Despite a fairly homogeneous pattern of markers expressed by most pDCL, numerous distinctive features (e.g. cytological aspects and aberrant marker expression) have been reported. This may be related to the 'lineage-independent developmental' programme of dendritic cells, which may be able to develop from either immature or already committed haematopoietic progenitors. This highlights the need for specific validated markers to diagnose such aggressive leukaemia. Here, we propose--among others (e.g. T-cell leukaemia 1)--blood dendritic cell antigen-2 and high levels of CD123 expression as potential markers. In addition, we propose a multidisciplinary approach including several fields of haematology to improve pDCL diagnosis.

75SeHCAT scan in bile acid malabsorption in chronic diarrhoea.

PubMed

Mena Bares, L M; Carmona Asenjo, E; García Sánchez, M V; Moreno Ortega, E; Maza Muret, F R; Guiote Moreno, M V; Santos Bueno, A M; Iglesias Flores, E; Benítez Cantero, J M; Vallejo Casas, J A

Chronic diarrhoea is a common entity in daily clinical practice and it leads to a loss in these patients quality of life. It may be the main symptom of multiple ethiologies including bile acid malabsorption (BAM) which has a comparable prevalence to celiac disease. The BAM results from imbalances in the homeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease or ileal dysfunction (BAM type i), it can be considered idiopathic or primary (BAM type ii) or associated with other gastrointestinal entities (BAM type iii). Among the different diagnostic methods available, 75 SeHCAT study is the primary current method due to its sensitivity, specificity, safety and low cost. The main disadvantage is that it's not available in all countries, so other diagnostic methods have appeared, such as serum measurement of FGF19 and C4, however they are significantly more complex and costly. The first-line treatment of bile acid diarrhoea is bile acid sequestrant, such as cholestyramine, which can be difficult to administer due to its poor tolerability and gastrointestinal side effects. These are less prominent with newer agents such as colesevelam. In summary, the BAM is a common entity underdiagnosed and undertreated, so it is essential to establish a diagnosis algorithm of chronic diarrhoea in which the 75 SeHCAT study would be first or second line in the differential diagnosis of these patients. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Evaluation and Cross-Comparison of Lexical Entities of Biological Interest (LexEBI)

PubMed Central

Rebholz-Schuhmann, Dietrich; Kim, Jee-Hyub; Yan, Ying; Dixit, Abhishek; Friteyre, Caroline; Hoehndorf, Robert; Backofen, Rolf; Lewin, Ian

2013-01-01

Motivation Biomedical entities, their identifiers and names, are essential in the representation of biomedical facts and knowledge. In the same way, the complete set of biomedical and chemical terms, i.e. the biomedical “term space” (the “Lexeome”), forms a key resource to achieve the full integration of the scientific literature with biomedical data resources: any identified named entity can immediately be normalized to the correct database entry. This goal does not only require that we are aware of all existing terms, but would also profit from knowing all their senses and their semantic interpretation (ambiguities, nestedness). Result This study compiles a resource for lexical terms of biomedical interest in a standard format (called “LexEBI”), determines the overall number of terms, their reuse in different resources and the nestedness of terms. LexEBI comprises references for protein and gene entries and their term variants and chemical entities amongst other terms. In addition, disease terms have been identified from Medline and PubmedCentral and added to LexEBI. Our analysis demonstrates that the baseforms of terms from the different semantic types show only little polysemous use. Nonetheless, the term variants of protein and gene names (PGNs) frequently contain species mentions, which should have been avoided according to protein annotation guidelines. Furthermore, the protein and gene entities as well as the chemical entities, both do comprise enzymes leading to hierarchical polysemy, and a large portion of PGNs make reference to a chemical entity. Altogether, according to our analysis based on the Medline distribution, 401,869 unique PGNs in the documents contain a reference to 25,022 chemical entities, 3,125 disease terms or 1,576 species mentions. Conclusion LexEBI delivers the complete biomedical and chemical Lexeome in a standardized representation (http://www.ebi.ac.uk/Rebholz-srv/LexEBI/). The resource provides the disease terms as open source content, and fully interlinks terms across resources. PMID:24124474

Noun and knowledge retrieval for biological and non-biological entities following right occipitotemporal lesions.

PubMed

Bruffaerts, Rose; De Weer, An-Sofie; De Grauwe, Sophie; Thys, Miek; Dries, Eva; Thijs, Vincent; Sunaert, Stefan; Vandenbulcke, Mathieu; De Deyne, Simon; Storms, Gerrit; Vandenberghe, Rik

2014-09-01

We investigated the critical contribution of right ventral occipitotemporal cortex to knowledge of visual and functional-associative attributes of biological and non-biological entities and how this relates to category-specificity during confrontation naming. In a consecutive series of 7 patients with lesions confined to right ventral occipitotemporal cortex, we conducted an extensive assessment of oral generation of visual-sensory and functional-associative features in response to the names of biological and nonbiological entities. Subjects also performed a confrontation naming task for these categories. Our main novel finding related to a unique case with a small lesion confined to right medial fusiform gyrus who showed disproportionate naming impairment for nonbiological versus biological entities, specifically for tools. Generation of visual and functional-associative features was preserved for biological and non-biological entities. In two other cases, who had a relatively small posterior lesion restricted to primary visual and posterior fusiform cortex, retrieval of visual attributes was disproportionately impaired compared to functional-associative attributes, in particular for biological entities. However, these cases did not show a category-specific naming deficit. Two final cases with the largest lesions showed a classical dissociation between biological versus nonbiological entities during naming, with normal feature generation performance. This is the first lesion-based evidence of a critical contribution of the right medial fusiform cortex to tool naming. Second, dissociations along the dimension of attribute type during feature generation do not co-occur with category-specificity during naming in the current patient sample. Copyright © 2014 Elsevier Ltd. All rights reserved.

A systematic review of the literature of the three related disease entities cheilitis granulomatosa, orofacial granulomatosis and Melkersson - Rosenthal syndrome.

PubMed

Wehl, Goetz; Rauchenzauner, Markus

2018-05-14

Melkersson Rosenthal syndrome (MRS) is a rare disorder of unknown etiology and comprises the triad: orofacial edema, recurrent facial paralysis and lingua plicata. In the current literature confusing heterogeneity exists, mixing together the historically grown terms cheilitis granulomatosa or granulomatous cheilitis, Melkersson Rosenthal syndrome and the umbrella term orofacial granulomatosis (OFG). We provide a systematic review comprising all three disease entities of orofacial granulomatosis using the computerized database "Pubmed Medline" entering the key words "orofacial granulomatosis" (141 references), "Melkersson-Rosenthal syndrome" (207 references), "granulomatous cheilitis" or "cheilitis granulomatosa" (102 references) back to 1956. Full text journals and case studies were included, and data synthesis was performed individually. Etiology remains unclear for all three disease entities. Etiological relatedness to chronic inflammatory bowel disease is under discussion and effectiveness was found for different treatments, e.g. local triamcinolone injections, antibiotics, surgical interventions, TNF alpha blockers or exclusive enteral nutrition. No randomized controlled trial concerning the therapy of orofacial granulomatosis was found. As a consequence, therapeutic conclusions are drawn mainly from small case series, thus limiting the evidence of therapeutic interventions. OFG with the sub-entities MRS and cheilitis granulomatosa is an etiological obscure disease process with various possible therapeutic interventions potentially alleviating the disease course but to broaden treatment knowledge further study in randomized controlled trials are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

Cytogenetics in the management of lymphomas and lymphoproliferative disorders in adults and children: an update by the Groupe francophone de cytogénétique hématologique (GFCH).

PubMed

Lefebvre, Christine; Callet-Bauchu, Evelyne; Chapiro, Elise; Nadal, Nathalie; Penther, Dominique; Poirel, Hélène-Antoine

2016-10-01

Non-Hodgkin's lymphomas and lymphoproliferative disorders include a high number of heterogeneous entities, described in the 2008 WHO classification. This classification reflects the crucial role of a multidisciplinary approach which integrates cytogenetic results both for the notion of clonality and for differential diagnosis between these entities. The prognostic impact of some cytogenetic abnormalities or genome complexity is also confirmed for many of these entities. Novel provisional entities have been described, such as BCLU (B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) for which karyotype is critical to distinguish BCLU from Burkitt's lymphoma. The karyotype can be established from any tumour or liquid infiltrated by lymphoma cells. Recent adaptations of technics for cellular cultures according to the subtype of known (or suspected) lymphoma have significantly improved the percentage of informative karyotypes. Conventional karyotypes remain the best technical approach recommended for most of these subtypes. Interphase and/or metaphase FISH also represents a solid and rapid approach, because of the significant number of recurrent (sometimes specific) rearrangements of these entities. Next generation sequencing technologies contribute to enrich genomic data and substantially improve the understanding of oncogenic mechanisms underlying these lymphoid malignancies. Some molecular biomarkers are already part of the diagnostic process (for example, somatic mutation of MYD88 in Waldenström disease) thus reinforcing the essential principle of a multidisciplinary approach for the diagnosis of all the mature lymphoid malignancies.

Segregation of anterior temporal regions critical for retrieving names of unique and nonunique entities reflects underlying long-range connectivity

PubMed Central

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2015-01-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. PMID:26707082

16 CFR 803.5 - Affidavits required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... entity whose voting securities or non-corporate interests are to be acquired has received notice in... acquire voting securities or non-corporate interests of the issuer or unincorporated entity; (iii) The specific classes of voting securities or non-corporate interests of the issuer or unincorporated entity...

Assessment of disease named entity recognition on a corpus of annotated sentences.

PubMed

Jimeno, Antonio; Jimenez-Ruiz, Ernesto; Lee, Vivian; Gaudan, Sylvain; Berlanga, Rafael; Rebholz-Schuhmann, Dietrich

2008-04-11

In recent years, the recognition of semantic types from the biomedical scientific literature has been focused on named entities like protein and gene names (PGNs) and gene ontology terms (GO terms). Other semantic types like diseases have not received the same level of attention. Different solutions have been proposed to identify disease named entities in the scientific literature. While matching the terminology with language patterns suffers from low recall (e.g., Whatizit) other solutions make use of morpho-syntactic features to better cover the full scope of terminological variability (e.g., MetaMap). Currently, MetaMap that is provided from the National Library of Medicine (NLM) is the state of the art solution for the annotation of concepts from UMLS (Unified Medical Language System) in the literature. Nonetheless, its performance has not yet been assessed on an annotated corpus. In addition, little effort has been invested so far to generate an annotated dataset that links disease entities in text to disease entries in a database, thesaurus or ontology and that could serve as a gold standard to benchmark text mining solutions. As part of our research work, we have taken a corpus that has been delivered in the past for the identification of associations of genes to diseases based on the UMLS Metathesaurus and we have reprocessed and re-annotated the corpus. We have gathered annotations for disease entities from two curators, analyzed their disagreement (0.51 in the kappa-statistic) and composed a single annotated corpus for public use. Thereafter, three solutions for disease named entity recognition including MetaMap have been applied to the corpus to automatically annotate it with UMLS Metathesaurus concepts. The resulting annotations have been benchmarked to compare their performance. The annotated corpus is publicly available at ftp://ftp.ebi.ac.uk/pub/software/textmining/corpora/diseases and can serve as a benchmark to other systems. In addition, we found that dictionary look-up already provides competitive results indicating that the use of disease terminology is highly standardized throughout the terminologies and the literature. MetaMap generates precise results at the expense of insufficient recall while our statistical method obtains better recall at a lower precision rate. Even better results in terms of precision are achieved by combining at least two of the three methods leading, but this approach again lowers recall. Altogether, our analysis gives a better understanding of the complexity of disease annotations in the literature. MetaMap and the dictionary based approach are available through the Whatizit web service infrastructure (Rebholz-Schuhmann D, Arregui M, Gaudan S, Kirsch H, Jimeno A: Text processing through Web services: Calling Whatizit. Bioinformatics 2008, 24:296-298).

BioCreative V CDR task corpus: a resource for chemical disease relation extraction.

PubMed

Li, Jiao; Sun, Yueping; Johnson, Robin J; Sciaky, Daniela; Wei, Chih-Hsuan; Leaman, Robert; Davis, Allan Peter; Mattingly, Carolyn J; Wiegers, Thomas C; Lu, Zhiyong

2016-01-01

Community-run, formal evaluations and manually annotated text corpora are critically important for advancing biomedical text-mining research. Recently in BioCreative V, a new challenge was organized for the tasks of disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction. Given the nature of both tasks, a test collection is required to contain both disease/chemical annotations and relation annotations in the same set of articles. Despite previous efforts in biomedical corpus construction, none was found to be sufficient for the task. Thus, we developed our own corpus called BC5CDR during the challenge by inviting a team of Medical Subject Headings (MeSH) indexers for disease/chemical entity annotation and Comparative Toxicogenomics Database (CTD) curators for CID relation annotation. To ensure high annotation quality and productivity, detailed annotation guidelines and automatic annotation tools were provided. The resulting BC5CDR corpus consists of 1500 PubMed articles with 4409 annotated chemicals, 5818 diseases and 3116 chemical-disease interactions. Each entity annotation includes both the mention text spans and normalized concept identifiers, using MeSH as the controlled vocabulary. To ensure accuracy, the entities were first captured independently by two annotators followed by a consensus annotation: The average inter-annotator agreement (IAA) scores were 87.49% and 96.05% for the disease and chemicals, respectively, in the test set according to the Jaccard similarity coefficient. Our corpus was successfully used for the BioCreative V challenge tasks and should serve as a valuable resource for the text-mining research community.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-3-cdr/. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

Diabetes as a model for the disparate public response to acute versus chronic diseases.

PubMed

Bergman, Michael; Lonier, Jacqueline; Fink, Dorothy

2016-03-01

The public health outcry toward infectious entities appears to dwarf chronic diseases such as diabetes. This disparity is particularly astonishing given the considerable prevalence of diabetes and prediabetes. Diseases associated with short-term morbidity and mortality therefore seem to garner attention and demand an immediate public health response, whereas chronic illnesses, which can be considerably more devastating in the longer term, receive relatively less notoriety. It should not, however, be misconstrued that one disease entity is more important than the other--it is critical that both acute and chronic entities are given balanced attention in the public health, governmental, and scientific realms. The current perspective reflects on the disparate public health purviews toward acute and chronic illnesses, describes why prevention is so difficult and challenging, and addresses what can be done to reverse this trend. If there is any hope of conquering the spiraling prediabetes and diabetes epidemics, the medical community must grapple with the complex issues herein raised.

Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

PubMed

Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

1999-04-01

Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

Rare cancers in The Netherlands: a population-based study.

PubMed

van der Zwan, Jan M; van Dijk, Boukje A C; Visser, Otto; van Krieken, Han J H J M; Capocaccia, Riccardo; Siesling, Sabine

2018-07-01

The conventional definition for rare disease is based on prevalence. Because of differences in prognosis, a definition on the basis of incidence was deemed to be more appropriate for rare cancers. Within the European RARECARE project, a definition was introduced that defines cancers as rare when the crude incidence rate is less than six per 100 000 per year. In this study, we applied the RARECARE definition for rare cancer to the Netherlands; this to identify the usefulness of the definition in a single country and to provide more insight into the burden of rare cancers in the Netherlands. Data for 2004 through 2008 were extracted from the Netherlands Cancer Registry and classified according to the RARECARE entities (tumour groupings). Crude and European standardized incidence rates were calculated. Out of the 260 entities, 223 (86%) were rare according to the definition, accounting for 14 000 cancers (17% of all). Considerable fluctuations in crude rates over years were observed for the major group of cancers. Rare tumours in the Netherlands constituted 17% of all newly diagnosed tumours, but were divided over 223 different entities, indicating the challenge that faces clinicians. To make the definition of rare cancers better applicable, it should be refined by taking into consideration the sex-specific incidence for sex-specific cancer sites. Moreover, a mean incidence over 5 years will provide more solid insight into the burden, eliminating large fluctuations in time of most of the cancers.

Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome

PubMed Central

Milacic, Marija; Haw, Robin; Rothfels, Karen; Wu, Guanming; Croft, David; Hermjakob, Henning; D’Eustachio, Peter; Stein, Lincoln

2012-01-01

Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of “cancer” pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics. PMID:24213504

What's all the fuss about? facts and figures about bone marrow failure and conditions.

PubMed

Mukherjee, Sudipto; Sekeres, Mikkael A

2012-12-01

The epidemiology of bone marrow failure conditions is not well understood. Although several population-based studies conducted in the last two decades have generated a wealth of information, it is still very challenging to interpret disease incidence and prevalence, particularly due to changes in disease classification, misdiagnosis of patients, frequent underreporting and use of different referent populations to calculate rates. Despite these limitations, the available epidemiologic data have revealed significant ethnic, geographic and clinical differences in disease biology that have implications for prevention and treatment strategies. With advances made in targeted therapies facilitated by identification of molecular biomarkers and increased use of curative bone marrow transplantation approach, the natural history of these disease entities is already changing. The epidemiology of these diseases seems to be the next frontier as knowledge gained about the risk factors and pathobiologic correlates could significantly help in designing patient-specific therapies with improved outcomes.

Morbus Behçet - a rare disease in Central Europe.

PubMed

Woźniacka, Anna; Sysa-Jędrzejowska, Anna; Jurowski, Piotr; Jabłkowski, Maciej; Kot, Marek

2015-12-10

Behçet's disease (BD) is a multiorgan inflammatory disease of complex and not entirely elucidated etiology, which was originally diagnosed in patients with aphthous stomatitis, genital ulcerations and ocular manifestations. The entity is endemic in countries of Eastern and Central Asia, especially Turkey and Iran, but rarely seen in Central Europe. As there are no specific diagnostic laboratory tests or histopathologic findings which confirm the preliminary diagnosis, the final diagnosis should be based on clinical criteria. Frequently a definitive diagnosis is established within several years or months after the first manifestations appear. The increased number of cases, recently described worldwide also in the Polish population, indicates that the disease could spread out of endemic areas. The aim of this manuscript is to present the clinical picture, diagnosis criteria and therapeutic approaches of this "international disease" which currently is observed not only in emigrants from Asia but also in native Polish citizens.

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

PubMed

Knobler, R; Moinzadeh, P; Hunzelmann, N; Kreuter, A; Cozzio, A; Mouthon, L; Cutolo, M; Rongioletti, F; Denton, C P; Rudnicka, L; Frasin, L A; Smith, V; Gabrielli, A; Aberer, E; Bagot, M; Bali, G; Bouaziz, J; Braae Olesen, A; Foeldvari, I; Frances, C; Jalili, A; Just, U; Kähäri, V; Kárpáti, S; Kofoed, K; Krasowska, D; Olszewska, M; Orteu, C; Panelius, J; Parodi, A; Petit, A; Quaglino, P; Ranki, A; Sanchez Schmidt, J M; Seneschal, J; Skrok, A; Sticherling, M; Sunderkötter, C; Taieb, A; Tanew, A; Wolf, P; Worm, M; Wutte, N J; Krieg, T

2017-09-01

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum. © 2017 European Academy of Dermatology and Venereology.

[Constitutional syndrome: clinical entity or a mixed bag].

PubMed

Suárez-Ortega, Saturnino; Puente-Fernández, Alicia; Santana-Baez, Sergio; Godoy-Díaz, Davinia; Serrano-Fuentes, Miriam; Sanz-Peláez, Oscar

2013-01-01

Fatigue, anorexia and involuntary weight loss have been included under the term constitutional syndrome. These manifestations accompany many diseases in which the diagnosis is made by specific symptoms and signs. However, these events are generally the main reason for consultation and the patient does not report other specific data. This forces us to rigorously investigate the possible causes of the disorder. Usually, three manifestations coexist: asthenia, anorexia and weight loss, but sometimes the patient has only one or two of them. The causes of constitutional symptoms are varied and can be divided into three groups: psychiatric diseases, neoplasms and non-neoplastic diseases. The etiological identification is usually done with a simple protocol, which rules out malignancy; the rest of the cases of uncertain etiology are subject to evolution. The constitutional syndrome correlates well with good prognosis or medical functional processes. Although no clinical guidelines have been developed, score scales may help for the etiological assessment. Given the myriad of different causes of the constitutional syndrome, the treatment of this illness depends primarily on the etiology.

Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer.

PubMed

Brägelmann, Johannes; Klümper, Niklas; Offermann, Anne; von Mässenhausen, Anne; Böhm, Diana; Deng, Mario; Queisser, Angela; Sanders, Christine; Syring, Isabella; Merseburger, Axel S; Vogel, Wenzel; Sievers, Elisabeth; Vlasic, Ignacija; Carlsson, Jessica; Andrén, Ove; Brossart, Peter; Duensing, Stefan; Svensson, Maria A; Shaikhibrahim, Zaki; Kirfel, Jutta; Perner, Sven

2017-04-01

Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities ( n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer ( n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq. Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19 In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro , inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion. Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. Clin Cancer Res; 23(7); 1829-40. ©2016 AACR . ©2016 American Association for Cancer Research.

Politics, culture, and the legitimacy of disease: the case of Buerger's disease.

PubMed

Lockwood, Stephen J; Bresler, Scott C; Granter, Scott R

2016-09-01

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

42 CFR 401.719 - Monitoring and sanctioning of qualified entities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Data for Performance Measurement § 401.719 Monitoring and sanctioning of qualified entities. (a) CMS... methods: (1) Audits. (2) Submission of documentation of data sources and quantities of data upon the request of CMS and/or site visits. (3) Analysis of specific data reported to CMS by qualified entities...

The fourth disease, 1900-2000.

PubMed

Weisse, M E

2001-01-27

Measles and scarlet fever were differentiated from one another in the 17th century. Rubella was accepted as the third distinct paediatric exanthem in 1881. Nil Filatow in 1885 and Clement Dukes in 1894 described two distinct forms of rubella, and in 1900 Dukes proposed that one of these forms of rubella was a separate entity which he called the fourth disease. For the past five decades, fourth disease has been considered a non-entity, perhaps a mild form of scarlet fever, but certainly not a distinct disease. In 1979 Keith Powell resurrected the idea of the fourth disease and argued that it was caused by exotoxin-producing Staphylococcus aureus. We present additional arguments for the existence of fourth disease, as well as information to link the disease to S. aureus.

DARPA DICE Manufacturing Optimization

DTIC Science & Technology

1993-01-01

Entity ................................................... 13 3.3.4 Labor Entity ....................................................... 14 3.3.5 Equipment...51 4.2.13.4 Labor Specification .................................... 52 4.2.13.5 Facility Specification .................................. 543...resources. A I resource is any facility, labor , equipment, or consumable material used in the manufacturing U UNCLASSIFIED CDRL No.0002AB-5 process. A

Translating Guidelines Into Practice: Interpreting the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk.

PubMed

Waite, Laura H; Phan, Yvonne L; Spinler, Sarah A

2017-10-01

In 2016, the American College of Cardiology released a decision pathway, based on expert consensus, to guide use of non-statin agents in the management of atherosclerotic cardiovascular disease risk. The purpose of this article is to assist practitioners, health systems and managed care entities with interpreting this consensus statement in order to simplify implementation of the recommendations into patient care. Major themes from the consensus statement are briefly summarized and explained. Drug therapy recommendations are condensed into a single algorithm, while tables correlate each recommended regimen with the appropriate patient population from both a patient-level and systems-level perspective. Finally, a patient case with evidence-based decision support is explored. These tools allow practitioners to make appropriate patient-specific decisions about the use of non-statin pharmacotherapy and enable health systems and managed care entities to more readily identify guideline-appropriate use of these agents upon review of patient profiles or prescribing patterns. This article provides resources for healthcare providers that facilitate uptake of these recommendations into clinical practice.

[Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

PubMed

Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

2014-03-01

Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Delayed immediate-type hypersensitivity to red meat and innards: current insights into a novel disease entity.

PubMed

Fischer, Jörg; Biedermann, Tilo

2016-01-01

The development of component-resolved diagnostics instead of whole extracts has brought about major advances in recent years. Particularly remarkable has been the identification of new disease entities based on the detection of IgE antibodies against specific individual components. In this context, delayed immediate-type hypersensitivity to red meat and innards plays a key role. This disorder is more common in German-speaking countries and likely still underdiagnosed. Affected individuals exhibit delayed type I reactions following the consumption of red meat or innards (responses to the latter are more rapid). All patients have IgE antibodies against the oligosaccharide galactose-α-1,3-galactose - alpha-gal. Those affected also have to avoid alpha-gal-containing drugs such as cetuximab or gelatin-containing colloidal solutions. Also referred to as alpha-gal syndrome, this condition is unique in that it is characterized by type I hypersensitivity to a sugar instead of a protein. Given that many patients have a history of recurrent episodes of acute urticaria or angioedema, dermatologists should be familiar with the alpha-gal syndrome. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Early- and late-onset Alzheimer disease: Are they the same entity?

PubMed

Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

2018-05-01

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Relatedness-based Multi-Entity Summarization

PubMed Central

Gunaratna, Kalpa; Yazdavar, Amir Hossein; Thirunarayan, Krishnaprasad; Sheth, Amit; Cheng, Gong

2017-01-01

Representing world knowledge in a machine processable format is important as entities and their descriptions have fueled tremendous growth in knowledge-rich information processing platforms, services, and systems. Prominent applications of knowledge graphs include search engines (e.g., Google Search and Microsoft Bing), email clients (e.g., Gmail), and intelligent personal assistants (e.g., Google Now, Amazon Echo, and Apple’s Siri). In this paper, we present an approach that can summarize facts about a collection of entities by analyzing their relatedness in preference to summarizing each entity in isolation. Specifically, we generate informative entity summaries by selecting: (i) inter-entity facts that are similar and (ii) intra-entity facts that are important and diverse. We employ a constrained knapsack problem solving approach to efficiently compute entity summaries. We perform both qualitative and quantitative experiments and demonstrate that our approach yields promising results compared to two other stand-alone state-of-the-art entity summarization approaches. PMID:29051696

Frontal Tasks and Behavior in Rigid or Tremor-Dominant Parkinson Disease.

PubMed

Moretti, Rita; Milner, Vera; Caruso, Paola; Gazzin, Silvia; Rumiati, Raffaella

2017-08-01

Parkinson disease (PD) is not an unambiguous entity, and there is a general consensus for the statement that an akinetic-rigid dominant type of presentation has a worse prognosis, in the follow-up. The aim of our study was to examine the differences in frontal tasks and behavior, in 2 PD naive groups: the rigid and the tremor-dominant types of presentation, according to motor scores. Our study has showed some important differences in frontal tasks and in behavior, performing more apathy, aggressiveness, and irritability in the rigid type, and more depression and anxiety in the tremor-dominant type. The former group causes the caregiver more distress and has a very rapid disease progression. It can be argued that rigid type PD presentation needs specific dedicated cares and more strong clinical attention.

Nailfold capillaroscopy microscopy - an interdisciplinary appraisal.

PubMed

Klein-Weigel, Peter Franz; Sunderkötter, Cord; Sander, Oliver

2016-09-01

Nailfold capillaroscopy is a method of great diagnostic value in the differential diagnosis of primary versus secondary Raynaud´s phenomenon, of systemic sclerosis versus other so called connective tissue diseases and of additional diagnostic value in other entities. Rheumatologists, dermatologists, and angiologists in Germany have convened in an interdisciplinary working group in which they synergistically combined their expertise to develop a common nomenclature and standards for the technical performance of nailfold capillary microscopy. The article gives an overview of historical and technical aspects of capillaroscopy, morphologic findings, and disease-specific patterns. It also provides a critical appraisal of its significance in the diagnosis and sequelae of these interdisciplinarily-managed diseases including its performance in children and gives an excursion in the potential perspectives of capillaroscopy in less common indications.

Department of Defense Data Model, Version 1, Fy 1998, Volume 6.

DTIC Science & Technology

1998-05-31

Definition: A REQUIREMENT TO WITHHOLD PAYMENT ON A SPECIFIC CONTRACT. (5104) (1) (A) 138 Entity Report DOD Data Model VI FY98 Attribute Names...424 Entity Report DOD Data Model VI FY98 Entity Name: PAYMENT -MEANS-FINANCIAL-INSTITUTION-ACCOUNT Definition: THE ASSOCIATION OF A FINANCIAL...A) 453 Entity Report DOD Data Model VI FY98 Definition: PETITION FOR PAYMENT PRIOR TO PERFORMANCE BY A PERSONNEL-RESOURCE. Attribute Names

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

From Genetics to Genomics: A Short Introduction for Pediatric Neurologists.

PubMed

Neubauer, Bernd A; Lemke, Johannes R

2016-01-01

It is estimated that in humans approximately 50% of all 22500 genes are needed for the development and maintenance of the nervous system. The introduction of high-throughput technology in genetic analysis has therefore major implications, not only for the investigation of specific disease entities but also for the diagnostic workup of single individuals with neurologic disorders of genetic origin. A short primer for clinicians is presented, addressing aspects of current developments in medical genomics. Significant findings of the last years are exemplified in an educational manner to provide a basic understanding of disease mechanisms that were unraveled by recent genomic analysis. Georg Thieme Verlag KG Stuttgart · New York.

Discovering New Diseases to Accelerate Precision Medicine.

PubMed

Macrae, Calum A

2017-01-01

A rate-limiting step in multiple areas of medicine is the limited number of discrete disorders that current technologies are able to identify. Most clinical disease entities are aggregates of large numbers of discrete biological processes that simply happen to share one or two common features. We have begun to translate a wide range of new technologies to the clinic in an effort to improve the resolution and the efficiency of bedside diagnostics with a view to improving drug trials, genetic studies, and the effectiveness of the clinician in a digital environment. The general trajectory for change that new technologies will bring is outlined with some specific examples of areas where such change has already begun to occur.

Viral Heart Disease and Acute Coronary Syndromes - Often or Rare Coexistence?

PubMed

Pawlak, Agnieszka; Wiligorska, Natalia; Wiligorska, Diana; Frontczak-Baniewicz, Malgorzata; Przybylski, Maciej; Krzyzewski, Rafal; Ziemba, Andrzej; Gil, Robert J

2018-01-01

Clinical presentation of viral myocarditis can mimic acute coronary syndrome and making diagnosis of viral heart disease (VHD) may be challenging. The presence of coronary artery disease (CAD) does not always exclude VHD and these entities can coexist. However, the incidence of co-occurrence of CAD and VHD is not precisely known. Moreover, inflammatory process caused by viruses may result in atherosclerotic plaque destabilization. The goal of this work is to summarize the current knowledge about co-occurrence of VHD and CAD. This article presents the importance of inflammatory process in both diseases and helps to understand pathophysiological mechanisms underlying their coexistence. It provides information about making differential diagnosis between these entities, including clinical presentation, noninvasive imaging features and findings in endomyocardial biopsy. Although currently there are no standard therapy strategies in coexistence of VHD and CAD, we present some remarkable aspects of treatment of patients, in whom VHD co-occurs with CAD. Viral heart disease may occur both in patients without and with atherosclerotic plaques in coronary arteries. Destabilization of atherosclerotic plaques in coronary arteries can be facilitated by inflammatory process. Increased inflammatory infiltrates in the coronary lesions of patients with VHD can lead to plaques' instability and consequently trigger acute coronary syndrome. In this article we attempted to present that co-occurrence of VHD and CAD may have therapeutic implications and as specific antiviral treatment is currently available, proper diagnosis and treatment can improve patient's condition and prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

ADO: a disease ontology representing the domain knowledge specific to Alzheimer's disease.

PubMed

Malhotra, Ashutosh; Younesi, Erfan; Gündel, Michaela; Müller, Bernd; Heneka, Michael T; Hofmann-Apitius, Martin

2014-03-01

Biomedical ontologies offer the capability to structure and represent domain-specific knowledge semantically. Disease-specific ontologies can facilitate knowledge exchange across multiple disciplines, and ontology-driven mining approaches can generate great value for modeling disease mechanisms. However, in the case of neurodegenerative diseases such as Alzheimer's disease, there is a lack of formal representation of the relevant knowledge domain. Alzheimer's disease ontology (ADO) is constructed in accordance to the ontology building life cycle. The Protégé OWL editor was used as a tool for building ADO in Ontology Web Language format. ADO was developed with the purpose of containing information relevant to four main biological views-preclinical, clinical, etiological, and molecular/cellular mechanisms-and was enriched by adding synonyms and references. Validation of the lexicalized ontology by means of named entity recognition-based methods showed a satisfactory performance (F score = 72%). In addition to structural and functional evaluation, a clinical expert in the field performed a manual evaluation and curation of ADO. Through integration of ADO into an information retrieval environment, we show that the ontology supports semantic search in scientific text. The usefulness of ADO is authenticated by dedicated use case scenarios. Development of ADO as an open ADO is a first attempt to organize information related to Alzheimer's disease in a formalized, structured manner. We demonstrate that ADO is able to capture both established and scattered knowledge existing in scientific text. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Quantum theory and human perception of the macro-world.

PubMed

Aerts, Diederik

2014-01-01

We investigate the question of 'why customary macroscopic entities appear to us humans as they do, i.e., as bounded entities occupying space and persisting through time', starting from our knowledge of quantum theory, how it affects the behavior of such customary macroscopic entities, and how it influences our perception of them. For this purpose, we approach the question from three perspectives. Firstly, we look at the situation from the standard quantum angle, more specifically the de Broglie wavelength analysis of the behavior of macroscopic entities, indicate how a problem with spin and identity arises, and illustrate how both play a fundamental role in well-established experimental quantum-macroscopical phenomena, such as Bose-Einstein condensates. Secondly, we analyze how the question is influenced by our result in axiomatic quantum theory, which proves that standard quantum theory is structurally incapable of describing separated entities. Thirdly, we put forward our new 'conceptual quantum interpretation', including a highly detailed reformulation of the question to confront the new insights and views that arise with the foregoing analysis. At the end of the final section, a nuanced answer is given that can be summarized as follows. The specific and very classical perception of human seeing-light as a geometric theory-and human touching-only ruled by Pauli's exclusion principle-plays a role in our perception of macroscopic entities as ontologically stable entities in space. To ascertain quantum behavior in such macroscopic entities, we will need measuring apparatuses capable of its detection. Future experimental research will have to show if sharp quantum effects-as they occur in smaller entities-appear to be ontological aspects of customary macroscopic entities. It remains a possibility that standard quantum theory is an incomplete theory, and hence incapable of coping ultimately with separated entities, meaning that a more general theory will be needed.

Transfer learning for biomedical named entity recognition with neural networks.

PubMed

Giorgi, John M; Bader, Gary D

2018-06-01

The explosive increase of biomedical literature has made information extraction an increasingly important tool for biomedical research. A fundamental task is the recognition of biomedical named entities in text (BNER) such as genes/proteins, diseases, and species. Recently, a domain-independent method based on deep learning and statistical word embeddings, called long short-term memory network-conditional random field (LSTM-CRF), has been shown to outperform state-of-the-art entity-specific BNER tools. However, this method is dependent on gold-standard corpora (GSCs) consisting of hand-labeled entities, which tend to be small but highly reliable. An alternative to GSCs are silver-standard corpora (SSCs), which are generated by harmonizing the annotations made by several automatic annotation systems. SSCs typically contain more noise than GSCs but have the advantage of containing many more training examples. Ideally, these corpora could be combined to achieve the benefits of both, which is an opportunity for transfer learning. In this work, we analyze to what extent transfer learning improves upon state-of-the-art results for BNER. We demonstrate that transferring a deep neural network (DNN) trained on a large, noisy SSC to a smaller, but more reliable GSC significantly improves upon state-of-the-art results for BNER. Compared to a state-of-the-art baseline evaluated on 23 GSCs covering four different entity classes, transfer learning results in an average reduction in error of approximately 11%. We found transfer learning to be especially beneficial for target data sets with a small number of labels (approximately 6000 or less). Source code for the LSTM-CRF is available athttps://github.com/Franck-Dernoncourt/NeuroNER/ and links to the corpora are available athttps://github.com/BaderLab/Transfer-Learning-BNER-Bioinformatics-2018/. john.giorgi@utoronto.ca. Supplementary data are available at Bioinformatics online.

42 CFR 401.707 - Operating and governance requirements for qualified entities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... a list of all measures it intends to calculate and report, the geographic areas it intends to serve... the geographic area(s) the entity would serve, including the following: (i) A specific description of the geographic area or areas it intends to serve. (ii) A specific description of how each measure...

42 CFR 401.707 - Operating and governance requirements for qualified entities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... a list of all measures it intends to calculate and report, the geographic areas it intends to serve... the geographic area(s) the entity would serve, including the following: (i) A specific description of the geographic area or areas it intends to serve. (ii) A specific description of how each measure...

42 CFR 401.707 - Operating and governance requirements for qualified entities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... a list of all measures it intends to calculate and report, the geographic areas it intends to serve... the geographic area(s) the entity would serve, including the following: (i) A specific description of the geographic area or areas it intends to serve. (ii) A specific description of how each measure...

Segregation of anterior temporal regions critical for retrieving names of unique and non-unique entities reflects underlying long-range connectivity.

PubMed

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2016-02-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category-specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus (UNC) was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus (ILF) was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Person- and place-selective neural substrates for entity-specific semantic access.

PubMed

Fairhall, Scott L; Anzellotti, Stefano; Ubaldi, Silvia; Caramazza, Alfonso

2014-07-01

Object-category has a pronounced effect on the representation of objects in higher level visual cortex. However, the influence of category on semantic/conceptual processes is less well characterized. In the present study, we conduct 2 fMRI experiments to investigate the semantic processing of information specific to individual people and places (entities). First, during picture presentation, we determined which brain regions show category-selective increases during access to entity-specific semantic information (i.e., nationality) in comparison to general-category discrimination (person vs. place). In the second experiment, we presented either words or pictures to assess the independence of entity-specific category-selective semantic representations from the processes used to access those representations. Convergent results from these 2 experiments show that brain regions exhibiting a category-selective increase during entity-specific semantic access are the same as those that show a supramodal (word/picture) category-selective response during the same task. These responses were different from classical "perceptual" category-selective responses and were evident in the medial precuneus for people and in the retrosplenial complex as well as anterior/superior sections of the transverse occipital sulcus and parahippocampal gyrus for places. These results reveal the pervasive influence of object-category in cortical organization, which extends to aspects of semantic knowledge arbitrarily related to physical/perceptual properties. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Paraneoplastic syndromes in rheumatology].

PubMed

Schmalzing, Marc

2018-05-01

Rheumatic paraneoplastic syndromes are paraneoplastic arthritis, palmar fasciitis and polyarthritis syndrome, remitting seronegative symmetrical synovitis with pitting edema, pancreatic panniculitis with polyarthritis, paraneoplastic vasculitis, cancer-associated myositis, hypertrophic osteoarthropathy (Marie-Bamberger disease) and tumor-induced osteomalacia. Typical clinical manifestations, pathogenesis, prognosis, and treatment of this entity are presented. Knowledge of these disease entities can lead to timely diagnosis of the underlying malignant disease and to a higher probability of a cure. Response of the paraneoplastic inflammatory manifestations to corticosteroids, non-steroidal anti-inflammatory drugs or immunosuppressants is often insufficient. Curative removal of the malignant disease is crucial for the course of the paraneoplastic syndrome. When a paraneoplastic etiology of rheumatic symptoms is suspected, a step-wise diagnostic strategy is advisable.

Is gluten a cause of gastrointestinal symptoms in people without celiac disease?

PubMed

Biesiekierski, Jessica R; Muir, Jane G; Gibson, Peter R

2013-12-01

The avoidance of wheat- and gluten-containing products is a worldwide phenomenon. While celiac disease is a well-established entity, the evidence base for gluten as a trigger of symptoms in patients without celiac disease (so-called 'non-celiac gluten sensitivity' or NCGS) is limited. The problems lie in the complexity of wheat and the ability of its carbohydrate as well as protein components to trigger gastrointestinal symptoms, the potentially false assumption that response to a gluten-free diet equates to an effect of gluten withdrawal, and diagnostic criteria for coeliac disease. Recent randomized controlled re-challenge trials have suggested that gluten may worsen gastrointestinal symptoms, but failed to confirm patients with self-perceived NCGS have specific gluten sensitivity. Furthermore, mechanisms by which gluten triggers symptoms have yet to be identified. This review discusses the most recent scientific evidence and our current understanding of NCGS.

Call for Standardized Definitions of Osteoarthritis and Risk Stratification for Clinical Trials and Clinical Use

PubMed Central

Kraus, Virginia Byers; Blanco, Francisco J.; Englund, Martin; Karsdal, Morten A.; Lohmander, L. Stefan

2015-01-01

Osteoarthritis is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for osteoarthritis (OA) that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of Osteoarthritis Development) and ROAP (Risk of Osteoarthritis Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages -- REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools. PMID:25865392

Is It Real or Is It Fiction? Children's Bias toward Reality

ERIC Educational Resources Information Center

Martarelli, Corinna S.; Mast, Fred W.

2013-01-01

Children aged 3 to 8 years old and adults were tested on a reality–fantasy distinction task. They had to judge whether particular entities were real or fantastical, and response times were collected. We further manipulated whether the entity is a specific character or a generic fantastical entity. The results indicate that children, unlike adults,…

Integrated Bio-Entity Network: A System for Biological Knowledge Discovery

PubMed Central

Bell, Lindsey; Chowdhary, Rajesh; Liu, Jun S.; Niu, Xufeng; Zhang, Jinfeng

2011-01-01

A significant part of our biological knowledge is centered on relationships between biological entities (bio-entities) such as proteins, genes, small molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an increasing speed, the information on bio-entity relationships is archived in different forms at scattered places. Most of such information is buried in scientific literature as unstructured text. Organizing heterogeneous information in a structured form not only facilitates study of biological systems using integrative approaches, but also allows discovery of new knowledge in an automatic and systematic way. In this study, we performed a large scale integration of bio-entity relationship information from both databases containing manually annotated, structured information and automatic information extraction of unstructured text in scientific literature. The relationship information we integrated in this study includes protein–protein interactions, protein/gene regulations, protein–small molecule interactions, protein–GO relationships, protein–pathway relationships, and pathway–disease relationships. The relationship information is organized in a graph data structure, named integrated bio-entity network (IBN), where the vertices are the bio-entities and edges represent their relationships. Under this framework, graph theoretic algorithms can be designed to perform various knowledge discovery tasks. We designed breadth-first search with pruning (BFSP) and most probable path (MPP) algorithms to automatically generate hypotheses—the indirect relationships with high probabilities in the network. We show that IBN can be used to generate plausible hypotheses, which not only help to better understand the complex interactions in biological systems, but also provide guidance for experimental designs. PMID:21738677

Management Options in Triple-Negative Breast Cancer

PubMed Central

Minami, Christina A.; Chung, Debra U.; Chang, Helena R.

2011-01-01

Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date. PMID:21863131

Hypertriglyceridemia Thalassemia Syndrome: Common Disease, Uncommon Association.

PubMed

Das, Lipsa; Samprathi, Madhusudan; Shukla, Umesh; Bandyopadhyay, Debapriya; Das, Rashmi Ranjan

2016-07-01

Hypertriglyceridemia has been rarely described with thalassemia, an entity called hypertriglyceridemia-thalassemia syndrome. The authors describe a young infant diagnosed with thalassemia major with severe hypertriglyceridemia. The presence of severe hypertriglyceridemia in this child which rapidly resolved after transfusion, probably suggests a self limited mechanism which may not require therapy. Though hypertriglyceridemia has been reported with hemolytic anemias, the mechanism is unclear. This case illustrates that thalassemia may be associated with hypertriglyceridemia; once familial and secondary causes are ruled out, clinicians may wait for spontaneous resolution before considering specific therapy.

75 FR 48274 - Radiation Exposure Compensation Act: Allowance for Costs and Expenses

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... survivors) who have contracted certain cancers and other serious diseases following exposure to radiation... economic impact on a substantial number of small entities for the following reasons: The rule affects claimants or beneficiaries in their individual capacity only. It does not affect small entities as that term...

Syringotropic mycosis fungoides: clinical and histologic features, response to treatment, and outcome in 19 patients.

PubMed

de Masson, Adèle; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Cavelier-Balloy, Bénédicte; Mouly, Frédéric; Rybojad, Michel; Bouaziz, Jean-David; Petit, Antoine; Saussine, Anne; Ronceray, Sophie; Le Gall, François; Ram-Wolff, Caroline; Assouly, Philippe; Dereure, Olivier; Joly, Pascal; Dallot, Alexiane; Dupuy, Alain; Lebbé, Céleste; Moulonguet, Isabelle; Rivet, Jacqueline; Janin, Anne; Bagot, Martine

2014-11-01

A rare variant of mycosis fungoides (MF), syringotropic MF (STMF) is characterized by a particular tropism of the lymphocytic infiltrate for the eccrine structures, and included in the follicular subtype of MF in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. We sought to determine the clinicopathologic features and disease course of patients with STMF. A retrospective study was conducted to identify patients with STMF from 1998 to 2013. Nineteen patients were included: 15 men and 4 women, mean age 55 years (range, 24-86). Most had multiple lesions (n=16, 84%) with associated alopecia (n=12, 63%) and/or punctuated aspect (n=12, 63%). Palms or soles were involved in 10 cases (53%). Folliculotropism was found in 13 cases (68%). After a median follow-up of 70 months (range, 2-140), 3 patients died, 1 from disease-related death. The 5-year overall and disease-specific survival were 100%. The disease-specific survival was significantly higher than in 54 patients with folliculotropic MF without syringotropism (5-year disease-specific survival, 74%; 95% confidence interval, 58%-94%, P=.02). Retrospective setting is a limitation. In the spectrum of adnexotropic MF, STMF appears as a distinct entity from follicular MF, with peculiar clinical characteristics and natural history. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Economic modeling of surgical disease: a measure of public health interventions.

PubMed

Corlew, D Scott

2013-07-01

The measurement of the burden of disease and the interventions that address that burden can be done in various units. Reducing these measures to the common denominator of economic units (i.e., currency) enables comparison with other health entities, interventions, and even other fields. Economic assessment is complex, however, because of the multifactorial components of what constitutes health and what constitutes health interventions, as well as the coupling of those data to economic means. To perform economic modeling in a meaningful manner, it is necessary to: (1) define the health problem to be addressed; (2) define the intervention to be assessed; (3) define a measure of the effect of the health entity with and without the intervention (which includes defining the counterfactual); and (4) determine the appropriate method of converting the health effect to economics. This paper discusses technical aspects of how economic modeling can be done both of disease entities and of interventions. Two examples of economic modeling applied to surgical problems are then given.

Mondor's disease of the breast. A retrospective review.

PubMed

Salemis, Nikolaos S; Merkouris, Stamatios; Kimpouri, Konstantina

2011-01-01

Mondor's disease is a rare benign clinical entity characterized by thrombophlebitis of the superficial veins of the anterolateral thoraco-abdominal wall. Although several predisposing factors have been reported, the exact pathogenesis remains unclear. We retrospectively reviewed the medical records of all patients older than 14 years who were diagnosed with Mondor's disease of the breast at the Breast Cancer Surgery Unit of Army General Hospital over a 3-year period. Five cases of Mondor's disease were identified among 5717 breast examinations performed during the study period. In 4 patients the disease was considered to be idiopathic. Ultrasonography established the diagnosis in all patients but mammography was inconclusive in two cases due to the presence of dense breast tissue. Four patients received symptomatic treatment. All patients had complete clinical resolution within 2-8 weeks of presentation, and they are well without any evidence of recurrence for 3 to 32 months later. No cases were associated with breast cancer. Mondor's disease of the breast is a rare benign self-limiting clinical entity. Ultrasonography is the diagnostic modality of choice but mammography may be inconclusive in the presence of dense breast tissue. Awareness of this rare entity is mandatory to prevent an unnecessary biopsy whereas the patients should be reassured of the benign nature of this disorder. Thorough evaluation is however necessary to rule out an underlying breast cancer or another systemic disease.

[Once again: theoretical pathology].

PubMed

Bleyl, U

2010-07-01

Theoretical pathology refers to the attempt to reintroduce methodical approaches from the humanities, philosophical logic and "gestalt philosophy" into medical research and pathology. Diseases, in particular disease entities and more complex polypathogenetic mechanisms of disease, have a "gestalt quality" due to the significance of their pathophysiologic coherence: they have a "gestalt". The Research group Theoretical Pathology at the Academy of Science in Heidelberg are credited with having revitalized the philosophical notion of "gestalt" for morphological and pathological diagnostics. Gestalt means interrelated schemes of pathophysiological significance in the mind of the diagnostician. In pathology, additive and associative diagnostic are simply not possible without considering the notion of synthetic entities in Kant's logic.

Cutaneous Manifestations of Non-Celiac Gluten Sensitivity: Clinical Histological and Immunopathological Features.

PubMed

Bonciolini, Veronica; Bianchi, Beatrice; Del Bianco, Elena; Verdelli, Alice; Caproni, Marzia

2015-09-15

The dermatological manifestations associated with intestinal diseases are becoming more frequent, especially now when new clinical entities, such as Non-Celiac Gluten Sensitivity (NCGS), are identified. The existence of this new entity is still debated. However, many patients with diagnosed NCGS that present intestinal manifestations have skin lesions that need appropriate characterization. We involved 17 patients affected by NCGS with non-specific cutaneous manifestations who got much better after a gluten free diet. For a histopathological and immunopathological evaluation, two skin samples from each patient and their clinical data were collected. The median age of the 17 enrolled patients affected by NCGS was 36 years and 76% of them were females. On the extensor surfaces of upper and lower limbs in particular, they all presented very itchy dermatological manifestations morphologically similar to eczema, psoriasis or dermatitis herpetiformis. This similarity was also confirmed histologically, but the immunopathological analysis showed the prevalence of deposits of C3 along the dermo-epidermal junction with a microgranular/granular pattern (82%). The exact characterization of new clinical entities such as Cutaneous Gluten Sensitivity and NCGS is an important objective both for diagnostic and therapeutic purposes, since these are patients who actually benefit from a GFD (Gluten Free Diet) and who do not adopt it only for fashion.

Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.

PubMed

Syring, Isabella; Klümper, Niklas; Offermann, Anne; Braun, Martin; Deng, Mario; Boehm, Diana; Queisser, Angela; von Mässenhausen, Anne; Brägelmann, Johannes; Vogel, Wenzel; Schmidt, Doris; Majores, Michael; Schindler, Anne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg; Shaikhibrahim, Zaki; Perner, Sven

2016-04-26

The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles.

Sorting the Alphabet Soup of Renal Pathology: A Review.

PubMed

Curran-Melendez, Sheilah M; Hartman, Matthew S; Heller, Matthew T; Okechukwu, Nancy

2016-01-28

Diseases of the kidney often have their names shortened, creating an arcane set of acronyms which can be confusing to both radiologists and clinicians. This review of renal pathology aims to explain some of the most commonly used acronyms within the field. For each entity, a summary of the clinical features, pathophysiology, and radiological findings is included to aid in the understanding and differentiation of these entities. Discussed topics include acute cortical necrosis, autosomal dominant polycystic kidney disease, angiomyolipoma, autosomal recessive polycystic kidney disease, acute tubular necrosis, localized cystic renal disease, multicystic dysplastic kidney, multilocular cystic nephroma, multilocular cystic renal cell carcinoma, medullary sponge kidney, paroxysmal nocturnal hemoglobinuria, renal papillary necrosis, transitional cell carcinoma, and xanthogranulomatous pyelonephritis. Copyright © 2016 Mosby, Inc. All rights reserved.

From loose body to osteochondritis dissecans: a historical account of disease definition

PubMed Central

TARABELLA, VITTORIO; FILARDO, GIUSEPPE; DI MATTEO, BERARDO; ANDRIOLO, LUCA; TOMBA, PATRIZIA; VIGANÒ, ANNA; MARCACCI, MAURILIO

2016-01-01

Osteochondritis dissecans (OCD) is a rare yet fascinating disease affecting young, active patients. It remains a ‘mysterious disease’ whose etiopathology, still unclear, is the subject of ongoing studies aiming improving the knowledge of this condition and, therefore, treatment options, too. Even though the first descriptions of intra-articular loose bodies date back to very ancient times, it is only relatively recently that, thanks to the contribution of some very eminent physicians, it became recognized as a specific orthopaedic condition. The aim of the present manuscript is to trace the main steps in the journey that led to the acknowledgement of OCD as an autonomous clinical entity, and to recall the prominent figures involved. PMID:27900309

Autoantibodies against TIF-1-γ and CADM-140 in Spanish patients with clinically amyopathic dermatomyositis (CADM): clinical significance and diagnostic utility.

PubMed

Cuesta-Mateos, C; Colom-Fernández, B; Portero-Sainz, I; Tejedor, R; García-García, C; Concha-Garzón, M J; De las Heras-Alonso, M E; Martínez, M A; Juarez, C; Muñoz-Calleja, C

2015-03-01

Patients with clinically amyopathic dermatomyositis (CADM) appear to be at risk for developing cancer and interstitial lung diseases, but population data to confirm this hypothesis are limited. Moreover, CADM presents cutaneous and histological findings that may overlap with subacute cutaneous lupus erythematosus (SCLE). To determine the association between myositis-specific autoantibodies, myositis-associated autoantibodies and CADM in Spanish patients. In addition, to study the usefulness of these autoantibodies in the differential diagnosis between CADM and SCLE. Serum samples were tested for myositis-specific autoantibodies and myositis-associated autoantibodies through immunoprecipitation and other standardized methods. Anti-CADM-p140 and anti-p155 antibodies were the only myositis-specific autoantibodies found and were associated with interstitial lung diseases and cancer respectively. No myositis-associated autoantibodies were found in CADM. Moreover, clinical subsets and proportions seemed to differ from Asian cohorts, where anti-CADM-p140 is considered a CADM hallmark antibody and a risk factor for the development of interstitial lung disease. Interestingly, anti-SSA was highly associated with SCLE, whereas no myositis-specific autoantibodies were found in this entity. Association between CADM and myositis-specific autoantibodies and differences between CADM and SCLE were tested on a relatively small cohort of patients. There is an association between cancer-associated myositis and interstitial lung diseases and their hallmark autoantibodies in our cohort. In addition, the combined determination of myositis-specific autoantibodies and SSA autoantibodies may help to accurately discriminate SCLE from CADM. © 2014 European Academy of Dermatology and Venereology.

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

PubMed

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

PubMed Central

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations. PMID:28721389

A systems biology approach to the global analysis of transcription factors in colorectal cancer.

PubMed

Pradhan, Meeta P; Prasad, Nagendra K A; Palakal, Mathew J

2012-08-01

Biological entities do not perform in isolation, and often, it is the nature and degree of interactions among numerous biological entities which ultimately determines any final outcome. Hence, experimental data on any single biological entity can be of limited value when considered only in isolation. To address this, we propose that augmenting individual entity data with the literature will not only better define the entity's own significance but also uncover relationships with novel biological entities.To test this notion, we developed a comprehensive text mining and computational methodology that focused on discovering new targets of one class of molecular entities, transcription factors (TF), within one particular disease, colorectal cancer (CRC). We used 39 molecular entities known to be associated with CRC along with six colorectal cancer terms as the bait list, or list of search terms, for mining the biomedical literature to identify CRC-specific genes and proteins. Using the literature-mined data, we constructed a global TF interaction network for CRC. We then developed a multi-level, multi-parametric methodology to identify TFs to CRC. The small bait list, when augmented with literature-mined data, identified a large number of biological entities associated with CRC. The relative importance of these TF and their associated modules was identified using functional and topological features. Additional validation of these highly-ranked TF using the literature strengthened our findings. Some of the novel TF that we identified were: SLUG, RUNX1, IRF1, HIF1A, ATF-2, ABL1, ELK-1 and GATA-1. Some of these TFs are associated with functional modules in known pathways of CRC, including the Beta-catenin/development, immune response, transcription, and DNA damage pathways. Our methodology of using text mining data and a multi-level, multi-parameter scoring technique was able to identify both known and novel TF that have roles in CRC. Starting with just one TF (SMAD3) in the bait list, the literature mining process identified an additional 116 CRC-associated TFs. Our network-based analysis showed that these TFs all belonged to any of 13 major functional groups that are known to play important roles in CRC. Among these identified TFs, we obtained a novel six-node module consisting of ATF2-P53-JNK1-ELK1-EPHB2-HIF1A, from which the novel JNK1-ELK1 association could potentially be a significant marker for CRC.

Towards improving phenotype representation in OWL

PubMed Central

2012-01-01

Background Phenotype ontologies are used in species-specific databases for the annotation of mutagenesis experiments and to characterize human diseases. The Entity-Quality (EQ) formalism is a means to describe complex phenotypes based on one or more affected entities and a quality. EQ-based definitions have been developed for many phenotype ontologies, including the Human and Mammalian Phenotype ontologies. Methods We analyze formalizations of complex phenotype descriptions in the Web Ontology Language (OWL) that are based on the EQ model, identify several representational challenges and analyze potential solutions to address these challenges. Results In particular, we suggest a novel, role-based approach to represent relational qualities such as concentration of iron in spleen, discuss its ontological foundation in the General Formal Ontology (GFO) and evaluate its representation in OWL and the benefits it can bring to the representation of phenotype annotations. Conclusion Our analysis of OWL-based representations of phenotypes can contribute to improving consistency and expressiveness of formal phenotype descriptions. PMID:23046625

Biobanking for Personalized Medicine.

PubMed

Liu, Angen; Pollard, Kai

2015-01-01

A biobank is an entity that collects, processes, stores, and distributes biospecimens and relevant data for use in basic, translational, and clinical research. Biobanking of high-quality human biospecimens such as tissue, blood and other bodily fluids along with associated patient clinical information provides a fundamental scientific infrastructure for personalized medicine. Identification of biomarkers that are specifically associated with particular medical conditions such as cancer, cardiovascular disease and neurological disorders are useful for early detection, prevention, and treatment of the diseases. The ability to determine individual tumor biomarkers and to use those biomarkers for disease diagnosis, prognosis and prediction of response to therapy is having a very significant impact on personalized medicine and is rapidly changing the way clinical care is conducted. As a critical requirement for personalized medicine is the availability of a large collection of patient samples with well annotated patient clinical and pathological data, biobanks thus play an important role in personalized medicine advancement. The goal of this chapter is to explore the role of biobanks in personalized medicine and discuss specific needs regarding biobank development for translational and clinical research, especially for personalized medicine advancement.

Lifelong-RL: Lifelong Relaxation Labeling for Separating Entities and Aspects in Opinion Targets.

PubMed

Shu, Lei; Liu, Bing; Xu, Hu; Kim, Annice

2016-11-01

It is well-known that opinions have targets. Extracting such targets is an important problem of opinion mining because without knowing the target of an opinion, the opinion is of limited use. So far many algorithms have been proposed to extract opinion targets. However, an opinion target can be an entity or an aspect (part or attribute) of an entity. An opinion about an entity is an opinion about the entity as a whole, while an opinion about an aspect is just an opinion about that specific attribute or aspect of an entity. Thus, opinion targets should be separated into entities and aspects before use because they represent very different things about opinions. This paper proposes a novel algorithm, called Lifelong-RL , to solve the problem based on lifelong machine learning and relaxation labeling . Extensive experiments show that the proposed algorithm Lifelong-RL outperforms baseline methods markedly.

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

PubMed

Bisceglia, M; Spagnolo, D; Galliani, C; Fisher, C; Suster, S; Kazakov, D V; Cooper, K; Michal, M

2006-08-01

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Unsupervised Medical Entity Recognition and Linking in Chinese Online Medical Text

PubMed Central

Gan, Liang; Cheng, Mian; Wu, Quanyuan

2018-01-01

Online medical text is full of references to medical entities (MEs), which are valuable in many applications, including medical knowledge-based (KB) construction, decision support systems, and the treatment of diseases. However, the diverse and ambiguous nature of the surface forms gives rise to a great difficulty for ME identification. Many existing solutions have focused on supervised approaches, which are often task-dependent. In other words, applying them to different kinds of corpora or identifying new entity categories requires major effort in data annotation and feature definition. In this paper, we propose unMERL, an unsupervised framework for recognizing and linking medical entities mentioned in Chinese online medical text. For ME recognition, unMERL first exploits a knowledge-driven approach to extract candidate entities from free text. Then, the categories of the candidate entities are determined using a distributed semantic-based approach. For ME linking, we propose a collaborative inference approach which takes full advantage of heterogenous entity knowledge and unstructured information in KB. Experimental results on real corpora demonstrate significant benefits compared to recent approaches with respect to both ME recognition and linking. PMID:29849994

Visual impairment caused by periorbital edema in an infant with acute hemorrhagic edema of infancy.

PubMed

Freitas, Priscila; Bygum, Anette

2013-01-01

Acute hemorrhagic edema of infancy (AHEI) is a cutaneous vasculitis seen in children. Many consider it to be a clinical variant of Schönlein-Henoch purpura, but others regard it as a separate entity because of its benign nature, age of onset, lack of visceral involvement, and frequent absence of vascular immunoglobulin A deposition. It is clinically characterized by large "cockade" or rosette-shaped, annular, purpuric lesions involving the face and extremities; erythematous edema; and mild fever. It seems to appear secondary to a history of viral or bacterial infection, course of antibiotics, or vaccination. Because of the unknown etiology and benign character, which leads to spontaneous complete recovery, there is no specific treatment necessary for AHEI, and according to the literature, systemic corticosteroids do not seem to alter the course of the disease. We report the case of an 11-month-old boy who manifested massive periorbital edema along with all of the clinical characteristics of this entity and showed clear improvement of the symptoms after a 24-hour administration of systemic corticosteroid therapy. Given the positive effect of this therapy, we propose that systemic corticosteroids should be used to ameliorate the acute manifestations and avoid the rapid progression of the disease. © 2012 Wiley Periodicals, Inc.

Pleuroparenchymal fibroelastosis: is it also an idiopathic entity?

PubMed

Portillo, Karina; Guasch Arriaga, Ignasi; Ruiz-Manzano, Juan

2015-10-01

Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that has been recently included in the updated consensus on idiopathic interstitial pneumonias. It shares some clinical features with other chronic interstitial pneumonias (dyspnea, dry cough), and is radiologically characterized by pleural and subpleural parenchymal fibrosis and elastosis, mainly in the upper lobes. The main histological findings include pleural fibrosis and prominent subpleural and parenchymal fibroelastosis. Its characterization is based on the increasing number of cases reported in the literature, so several aspects of the etiology, pathogenesis and natural history are still unknown. Although some cases have been described as idiopathic, PPFE has been reported as a complication after bone marrow transplantation, lung transplantation and chemotherapy, especially with alkylating agents.Spontaneous or iatrogenic pneumothorax is a frequently reported complication of invasive diagnostic tests for identifying PPFE. The disease course is variable, ranging from slow progression to rapid clinical deterioration. No treatment has shown evidence of efficacy, and lung transplantation remains the only option for patients who fulfill the diagnostic criteria for this option. Recognizing and disseminating the specific features of PPFE is essential to raise the level of clinical suspicion for this entity, and to implement appropriate multidisciplinary diagnostic management. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium.

PubMed

Musselwhite, Laura W; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C; Wellems, Thomas E; Tavera, Gloria; Goulding, Rebecca E; Guillen, Ethan

2012-01-01

Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases.

Chemical-induced disease relation extraction with various linguistic features.

PubMed

Gu, Jinghang; Qian, Longhua; Zhou, Guodong

2016-01-01

Understanding the relations between chemicals and diseases is crucial in various biomedical tasks such as new drug discoveries and new therapy developments. While manually mining these relations from the biomedical literature is costly and time-consuming, such a procedure is often difficult to keep up-to-date. To address these issues, the BioCreative-V community proposed a challenging task of automatic extraction of chemical-induced disease (CID) relations in order to benefit biocuration. This article describes our work on the CID relation extraction task on the BioCreative-V tasks. We built a machine learning based system that utilized simple yet effective linguistic features to extract relations with maximum entropy models. In addition to leveraging various features, the hypernym relations between entity concepts derived from the Medical Subject Headings (MeSH)-controlled vocabulary were also employed during both training and testing stages to obtain more accurate classification models and better extraction performance, respectively. We demoted relation extraction between entities in documents to relation extraction between entity mentions. In our system, pairs of chemical and disease mentions at both intra- and inter-sentence levels were first constructed as relation instances for training and testing, then two classification models at both levels were trained from the training examples and applied to the testing examples. Finally, we merged the classification results from mention level to document level to acquire final relations between chemicals and diseases. Our system achieved promisingF-scores of 60.4% on the development dataset and 58.3% on the test dataset using gold-standard entity annotations, respectively. Database URL:https://github.com/JHnlp/BC5CIDTask. © The Author(s) 2016. Published by Oxford University Press.

Sieve-based coreference resolution enhances semi-supervised learning model for chemical-induced disease relation extraction.

PubMed

Le, Hoang-Quynh; Tran, Mai-Vu; Dang, Thanh Hai; Ha, Quang-Thuy; Collier, Nigel

2016-07-01

The BioCreative V chemical-disease relation (CDR) track was proposed to accelerate the progress of text mining in facilitating integrative understanding of chemicals, diseases and their relations. In this article, we describe an extension of our system (namely UET-CAM) that participated in the BioCreative V CDR. The original UET-CAM system's performance was ranked fourth among 18 participating systems by the BioCreative CDR track committee. In the Disease Named Entity Recognition and Normalization (DNER) phase, our system employed joint inference (decoding) with a perceptron-based named entity recognizer (NER) and a back-off model with Semantic Supervised Indexing and Skip-gram for named entity normalization. In the chemical-induced disease (CID) relation extraction phase, we proposed a pipeline that includes a coreference resolution module and a Support Vector Machine relation extraction model. The former module utilized a multi-pass sieve to extend entity recall. In this article, the UET-CAM system was improved by adding a 'silver' CID corpus to train the prediction model. This silver standard corpus of more than 50 thousand sentences was automatically built based on the Comparative Toxicogenomics Database (CTD) database. We evaluated our method on the CDR test set. Results showed that our system could reach the state of the art performance with F1 of 82.44 for the DNER task and 58.90 for the CID task. Analysis demonstrated substantial benefits of both the multi-pass sieve coreference resolution method (F1 + 4.13%) and the silver CID corpus (F1 +7.3%).Database URL: SilverCID-The silver-standard corpus for CID relation extraction is freely online available at: https://zenodo.org/record/34530 (doi:10.5281/zenodo.34530). © The Author(s) 2016. Published by Oxford University Press.

Medical Named Entity Recognition for Indonesian Language Using Word Representations

NASA Astrophysics Data System (ADS)

Rahman, Arief

2018-03-01

Nowadays, Named Entity Recognition (NER) system is used in medical texts to obtain important medical information, like diseases, symptoms, and drugs. While most NER systems are applied to formal medical texts, informal ones like those from social media (also called semi-formal texts) are starting to get recognition as a gold mine for medical information. We propose a theoretical Named Entity Recognition (NER) model for semi-formal medical texts in our medical knowledge management system by comparing two kinds of word representations: cluster-based word representation and distributed representation.

Annual Report to The President and The Congress of the Advisory Panel to Assess Domestic Response Capabilities for Terrorism Involving Weapons of Mass Destruction (2nd). II. Toward a National Strategy for Combating Terrorism

DTIC Science & Technology

2000-12-15

over many years, for responses to natural disasters, disease outbreaks, and accidents. Those capabilities can and should be used as a base for...terminated. 57 Many response entities had used those services and had included that capability in their response plans. This is one more example of... Many Federal entities 58 conduct or facilitate various exercises and offer State and local response entities opportunities to participate. Most agencies

Text mining facilitates database curation - extraction of mutation-disease associations from Bio-medical literature.

PubMed

Ravikumar, Komandur Elayavilli; Wagholikar, Kavishwar B; Li, Dingcheng; Kocher, Jean-Pierre; Liu, Hongfang

2015-06-06

Advances in the next generation sequencing technology has accelerated the pace of individualized medicine (IM), which aims to incorporate genetic/genomic information into medicine. One immediate need in interpreting sequencing data is the assembly of information about genetic variants and their corresponding associations with other entities (e.g., diseases or medications). Even with dedicated effort to capture such information in biological databases, much of this information remains 'locked' in the unstructured text of biomedical publications. There is a substantial lag between the publication and the subsequent abstraction of such information into databases. Multiple text mining systems have been developed, but most of them focus on the sentence level association extraction with performance evaluation based on gold standard text annotations specifically prepared for text mining systems. We developed and evaluated a text mining system, MutD, which extracts protein mutation-disease associations from MEDLINE abstracts by incorporating discourse level analysis, using a benchmark data set extracted from curated database records. MutD achieves an F-measure of 64.3% for reconstructing protein mutation disease associations in curated database records. Discourse level analysis component of MutD contributed to a gain of more than 10% in F-measure when compared against the sentence level association extraction. Our error analysis indicates that 23 of the 64 precision errors are true associations that were not captured by database curators and 68 of the 113 recall errors are caused by the absence of associated disease entities in the abstract. After adjusting for the defects in the curated database, the revised F-measure of MutD in association detection reaches 81.5%. Our quantitative analysis reveals that MutD can effectively extract protein mutation disease associations when benchmarking based on curated database records. The analysis also demonstrates that incorporating discourse level analysis significantly improved the performance of extracting the protein-mutation-disease association. Future work includes the extension of MutD for full text articles.

Clinical implications of omics and systems medicine: focus on predictive and individualized treatment.

PubMed

Benson, M

2016-03-01

Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples. © 2015 The Association for the Publication of the Journal of Internal Medicine.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

PubMed Central

Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.

2017-01-01

The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947

Quantum theory and human perception of the macro-world

PubMed Central

Aerts, Diederik

2014-01-01

We investigate the question of ‘why customary macroscopic entities appear to us humans as they do, i.e., as bounded entities occupying space and persisting through time’, starting from our knowledge of quantum theory, how it affects the behavior of such customary macroscopic entities, and how it influences our perception of them. For this purpose, we approach the question from three perspectives. Firstly, we look at the situation from the standard quantum angle, more specifically the de Broglie wavelength analysis of the behavior of macroscopic entities, indicate how a problem with spin and identity arises, and illustrate how both play a fundamental role in well-established experimental quantum-macroscopical phenomena, such as Bose-Einstein condensates. Secondly, we analyze how the question is influenced by our result in axiomatic quantum theory, which proves that standard quantum theory is structurally incapable of describing separated entities. Thirdly, we put forward our new ‘conceptual quantum interpretation’, including a highly detailed reformulation of the question to confront the new insights and views that arise with the foregoing analysis. At the end of the final section, a nuanced answer is given that can be summarized as follows. The specific and very classical perception of human seeing—light as a geometric theory—and human touching—only ruled by Pauli's exclusion principle—plays a role in our perception of macroscopic entities as ontologically stable entities in space. To ascertain quantum behavior in such macroscopic entities, we will need measuring apparatuses capable of its detection. Future experimental research will have to show if sharp quantum effects—as they occur in smaller entities—appear to be ontological aspects of customary macroscopic entities. It remains a possibility that standard quantum theory is an incomplete theory, and hence incapable of coping ultimately with separated entities, meaning that a more general theory will be needed. PMID:25009510

Special Appropriation Act Projects

EPA Pesticide Factsheets

EPA is sometimes directed to provide funding to a specific entity for study, purpose, or activity.This information will be of interest to a community or other entity that has been identified in one of EPA's appropriations acts to receive such funding.

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

Dyssomnias, parasomnias, and sleep disorders associated with medical and psychiatric diseases.

PubMed

Barthlen, G M; Stacy, C

1994-03-01

Sleep disorders can be intrinsic, as are insomnia or narcolepsy, or can be accounted for by external factors, such as noise, altitude, drug or alcohol abuse, or shift work. The arousal disorders, common in children, are usually benign and disappear by puberty. Sleep-wake transition disorders such as sleep starts are benign as well, and may occur at any age. The parasomnias comprise different entities such as nightmares, REM-sleep behavior disorder, sleep enuresis, and bruxism. Diagnosis and treatment often require a multidisciplinary approach. Virtually every psychiatric, neurologic, or medical disease, when of sufficient severity, leaves its specific fingerprint on sleep; some disorders, such as peptic ulcer disease, gastroesophageal reflux, or epilepsy, tend to be exacerbated during sleep. Fortunately, most sleep disorders are amenable to therapy, which can include counseling, sleep hygiene, withholding of an offending agent, behavioral therapy, light therapy, or cautious drug therapy.

Duodenal perforation: an unusual complication of sickle cell anemia.

PubMed

Acıpayam, Can; Aldıç, Güliz; Akçora, Bülent; Çelikkaya, Mehmet Emin; Aşkar, Hasan; Dorum, Bayram Ali

2014-01-01

Duodenal perforation in childhood is a rare condition with a high mortality rate if not treated surgically. Primary gastroduodenal perforation is frequently associated with peptic ulcer and exhibits a positive family history. Helicobacter pylorus is the most significant agent. Secondary gastroduodenal perforation may be a finding of specific diseases, such as Crohn disease, or more rarely may be associated with diseases such as cystic fibrosis or sickle cell anemia. A 14-year-old boy presented with abdominal and back pain. The patient was operated on for acute abdomen and diagnosed with duodenal perforation. Helicobacter pylorus was negative. There was no risk factor to account for duodenal perforation other than sickle cell anemia. Surgical intervention was successful and without significant sequelae. Duodenal perforation is a rare entity described in patients with sickle cell anemia. To our knowledge, this is the first report of duodenal perforation in a patient sickle cell anemia.

Duodenal perforation: an unusual complication of sickle cell anemia

PubMed Central

Acıpayam, Can; Aldıç, Güliz; Akçora, Bülent; Çelikkaya, Mehmet Emin; Aşkar, Hasan; Dorum, Bayram Ali

2014-01-01

Duodenal perforation in childhood is a rare condition with a high mortality rate if not treated surgically. Primary gastroduodenal perforation is frequently associated with peptic ulcer and exhibits a positive family history. Helicobacter pylorus is the most significant agent. Secondary gastroduodenal perforation may be a finding of specific diseases, such as Crohn disease, or more rarely may be associated with diseases such as cystic fibrosis or sickle cell anemia. A 14-year-old boy presented with abdominal and back pain. The patient was operated on for acute abdomen and diagnosed with duodenal perforation. Helicobacter pylorus was negative. There was no risk factor to account for duodenal perforation other than sickle cell anemia. Surgical intervention was successful and without significant sequelae. Duodenal perforation is a rare entity described in patients with sickle cell anemia. To our knowledge, this is the first report of duodenal perforation in a patient sickle cell anemia. PMID:25422692

Cardiovascular Disease in Women: Clinical Perspectives

PubMed Central

Garcia, Mariana; Mulvagh, Sharon L.; Merz, C. Noel Bairey; Buring, Julie E.; Manson, JoAnn E.

2016-01-01

Cardiovascular disease (CVD) continues to be the leading cause of death among women in the United States, accounting for approximately one of every three female deaths. Sex-specific data focused on CVD has been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focuses on novel and unique aspects of cardiovascular health in women and sex-differences as they relate to clinical practice in the prevention, diagnosis, and treatment of CVD. This review also provides current approaches to the evaluation and treatment of acute coronary syndromes that are more prevalent in women, including: myocardial infarction associated with non-obstructive coronary arteries, spontaneous coronary artery dissection, and stress-induced cardiomyopathy (Takotsubo Syndrome). Other CVD entities with higher prevalence or unique considerations in women, such as heart failure with preserved ejection fraction, peripheral arterial disease and abdominal aortic aneurysms, are also briefly reviewed. Lastly, recommendations for cardiac rehabilitation are addressed. PMID:27081110

Activity of selected aromatic amino acids in biological systems.

PubMed

Krzyściak, Wirginia

2011-01-01

Besides the structural function in proteins, aromatic amino acids are precursors of many important biological compounds essential for normal functioning of the human organism. Many of these compounds may be used as markers for identification of specific pathological states. Comprehensive knowledge about the metabolism of aromatic amino acids and mechanisms of action of their metabolites made it possible to develop effective treatments for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds could not only be involved in the pathogenesis of many disease entities but could also be used as an important tool in prediction of many diseases. This paper contains a review of published literature on aromatic amino acids in the context of physiological processes of the human body and chosen social disorders, such as cancers; psychiatric disorders: depression, anxiety states, schizophrenia, bipolar affective disorders; neurodegenerative, and cardiovascular diseases; chronic kidney insufficiency or diabetes.

A Quantitative Systems Pharmacology Approach to Infer Pathways Involved in Complex Disease Phenotypes.

PubMed

Schurdak, Mark E; Pei, Fen; Lezon, Timothy R; Carlisle, Diane; Friedlander, Robert; Taylor, D Lansing; Stern, Andrew M

2018-01-01

Designing effective therapeutic strategies for complex diseases such as cancer and neurodegeneration that involve tissue context-specific interactions among multiple gene products presents a major challenge for precision medicine. Safe and selective pharmacological modulation of individual molecular entities associated with a disease often fails to provide efficacy in the clinic. Thus, development of optimized therapeutic strategies for individual patients with complex diseases requires a more comprehensive, systems-level understanding of disease progression. Quantitative systems pharmacology (QSP) is an approach to drug discovery that integrates computational and experimental methods to understand the molecular pathogenesis of a disease at the systems level more completely. Described here is the chemogenomic component of QSP for the inference of biological pathways involved in the modulation of the disease phenotype. The approach involves testing sets of compounds of diverse mechanisms of action in a disease-relevant phenotypic assay, and using the mechanistic information known for the active compounds, to infer pathways and networks associated with the phenotype. The example used here is for monogenic Huntington's disease (HD), which due to the pleiotropic nature of the mutant phenotype has a complex pathogenesis. The overall approach, however, is applicable to any complex disease.

SMARCB1/INI1 inactivation in renal medullary carcinoma.

PubMed

Calderaro, Julien; Moroch, Julien; Pierron, Gaelle; Pedeutour, Florence; Grison, Camille; Maillé, Pascale; Soyeux, Pascale; de la Taille, Alexandre; Couturier, Jérome; Vieillefond, Annick; Rousselet, Marie Christine; Delattre, Olivier; Allory, Yves

2012-09-01

Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied. Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription. The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities. © 2012 Blackwell Publishing Ltd.

MONTRA: An agile architecture for data publishing and discovery.

PubMed

Bastião Silva, Luís; Trifan, Alina; Luís Oliveira, José

2018-07-01

Data catalogues are a common form of capturing and presenting information about a specific kind of entity (e.g. products, services, professionals, datasets, etc.). However, the construction of a web-based catalogue for a particular scenario normally implies the development of a specific and dedicated solution. In this paper, we present MONTRA, a rapid-application development framework designed to facilitate the integration and discovery of heterogeneous objects, which may be characterized by distinct data structures. MONTRA was developed following a plugin-based architecture to allow dynamic composition of services over represented datasets. The core of MONTRA's functionalities resides in a flexible data skeleton used to characterize data entities, and from which a fully-fledged web data catalogue is automatically generated, ensuring access control and data privacy. MONTRA is being successfully used by several European projects to collect and manage biomedical databases. In this paper, we describe three of these applications scenarios. This work was motivated by the plethora of geographically scattered biomedical repositories, and by the role they can play altogether for the understanding of diseases and of the real-world effectiveness of treatments. Using metadata to expose datasets' characteristics, MONTRA greatly simplifies the task of building data catalogues. The source code is publicly available at https://github.com/bioinformatics-ua/montra. Copyright © 2018 Elsevier B.V. All rights reserved.

Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis

PubMed Central

Sung, Jaeyun; Kim, Seunghyeon; Cabatbat, Josephine Jill T.; Jang, Sungho; Jin, Yong-Su; Jung, Gyoo Yeol; Chia, Nicholas; Kim, Pan-Jun

2017-01-01

A system-level framework of complex microbe–microbe and host–microbe chemical cross-talk would help elucidate the role of our gut microbiota in health and disease. Here we report a literature-curated interspecies network of the human gut microbiota, called NJS16. This is an extensive data resource composed of ∼570 microbial species and 3 human cell types metabolically interacting through >4,400 small-molecule transport and macromolecule degradation events. Based on the contents of our network, we develop a mathematical approach to elucidate representative microbial and metabolic features of the gut microbial community in a given population, such as a disease cohort. Applying this strategy to microbiome data from type 2 diabetes patients reveals a context-specific infrastructure of the gut microbial ecosystem, core microbial entities with large metabolic influence, and frequently produced metabolic compounds that might indicate relevant community metabolic processes. Our network presents a foundation towards integrative investigations of community-scale microbial activities within the human gut. PMID:28585563

Paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of prostate-specific antigen after TURP.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-01-21

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Paroxysmal atrial fibrillation is a frequent complication of acute myocardial infarction. It has been reported that subclinical hyperthyroidism is not associated with CHD or mortality from cardiovascular causes but it is sufficient to induce an increase in atrial fibrillation rate and increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. It has also been reported that serum prostate-specific antigen (PSA) decreases drastically in patients who undergo transurethral resection of the prostate(TURP). We present a case of paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of PSA after TURP in a 78-year-old Italian man. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.

[On classification of changes in necrotizing lesions of the midface].

PubMed

Szyfter, W; Wierzbicka, M

1996-01-01

Lethal midline granuloma syndrome (LMG) describes lesions of the midface and is characterized by a progressive and often fatal ulceration and destruction of the upper air way involving the nose, the paranasal sinuses, the palate and the soft tissues of the face. Under the term LMG we distinguish four entities: idiopathic midline destructive disease (IMDD), polymorphic reticulosis (PR), non Hodkin's lymphoma and Wegener's granulomatosis (WG). Review of the literature allows to present the differential diagnosis making use of latest technological achievements in clinical immunology and immunohistochemistry. First of all the LMG must be discriminated from localized WG occurring in the midface. The clinical, serological and histopathological findings in WG are described. Literature review is carried out and recent concepts of it's etiology and pathogenesis are presented. Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA) with specificity for proteinase 3 (PR 3) are valuable marker for differential diagnosis and specificity are discussed. We make a comparison between the "limited" or "non renal" WG and "classical" or "renal" form of the disease.

Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis.

PubMed

Sung, Jaeyun; Kim, Seunghyeon; Cabatbat, Josephine Jill T; Jang, Sungho; Jin, Yong-Su; Jung, Gyoo Yeol; Chia, Nicholas; Kim, Pan-Jun

2017-06-06

A system-level framework of complex microbe-microbe and host-microbe chemical cross-talk would help elucidate the role of our gut microbiota in health and disease. Here we report a literature-curated interspecies network of the human gut microbiota, called NJS16. This is an extensive data resource composed of ∼570 microbial species and 3 human cell types metabolically interacting through >4,400 small-molecule transport and macromolecule degradation events. Based on the contents of our network, we develop a mathematical approach to elucidate representative microbial and metabolic features of the gut microbial community in a given population, such as a disease cohort. Applying this strategy to microbiome data from type 2 diabetes patients reveals a context-specific infrastructure of the gut microbial ecosystem, core microbial entities with large metabolic influence, and frequently produced metabolic compounds that might indicate relevant community metabolic processes. Our network presents a foundation towards integrative investigations of community-scale microbial activities within the human gut.

Temporary Mechanical Circulatory Support: A Review of the Options, Indications, and Outcomes

PubMed Central

Gilotra, Nisha A; Stevens, Gerin R

2014-01-01

Cardiogenic shock remains a challenging disease entity and is associated with significant morbidity and mortality. Temporary mechanical circulatory support (MCS) can be implemented in an acute setting to stabilize acutely ill patients with cardiomyopathy in a variety of clinical situations. Currently, several options exist for temporary MCS. We review the indications, contraindications, clinical applications, and evidences for a variety of temporary circulatory support options, including the intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), CentriMag blood pump, and percutaneous ventricular assist devices (pVADs), specifically the TandemHeart and Impella. PMID:25674024

68Ga-Labeled PSMA Uptake in Nonprostatic Malignancies: Has the Time Come to Remove "PS" From PSMA?

PubMed

Malik, Dharmender; Kumar, Rajender; Mittal, Bhagwant Rai; Singh, Harmandeep; Bhattacharya, Anish; Singh, Shrawan Kumar

2018-04-23

PET/CT with Ga-labeled prostate-specific membrane antigen (PSMA) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in a number of nonprostatic benign and malignant pathologies. Apparently, angioneogenesis is the mechanism attributed to increased Ga-PSMA uptake at these sites. Here we illustrate the utility of Ga-PSMA in 5 nonprostatic malignancies that could open up new possibilities for diagnostics and theranostic concepts with PSMA labeled radioligands in nonprostate tumor entities.

[MCTD--mixed connective tissue disease].

PubMed

Haustein, Uwe-Frithjof

2005-02-01

Mixed connective tissue disease is a disease entity characterized by overlapping symptoms of lupus erythematosus (LE), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA). Diagnostic criteria include high titers of antibodies against U1RNP as well as the presence of at least 3 of 5 of the following clinical features: edema of hands, synovitis, myositis, Raynaud phenomenon and acroscierosis. In terms of the pathogenesis, genetic as well as infectious (viral) factors appear to play a role. The acceptance of MCTD as a distinct disease entity is controversial. Terms such as "undifferentiated connective tissue disease" or "overlapping syndromes" are not helpful. One-quarter of MCTD patients transform into LE, while one-third progress to SSc. Therapeutic recommendations are glucocorticoids in combination with immunosuppressive agents and endothelin receptor antagonists. Double blind studies are not available. The prognosis is relatively good. Causes of death include pulmonary hypertension, infections and both pulmonary and cardiac failure.

Normocalcemic primary hyperparathyroidism

PubMed Central

Bilezikian, John P.; Silverberg, Shonni J.

2011-01-01

SUMMARY Primary hyperparathyroidism is a common disorder of mineral metabolism characterized by incompletely regulated, excessive secretion of parathyroid hormone from one or more of the parathyroid glands. The historical view of this disease describes two distinct entities marked by two eras. When primary hyperparathyroidism was first discovered about 80 years ago, it was always symptomatic with kidney stones, bone disease and marked hypercalcemia. With the advent of the multichannel autoanalyzer about 40 years ago, the clinical phenotype changed to a disorder characterized by mild hypercalcemia and the absence of classical other features of the disease. We may now be entering a 3rd era in the history of this disease in which patients are being discovered with normal total and ionized serum calcium concentrations but with parathyroid hormone levels that are consistently elevated. In this article, we describe this new entity, normocalcemic primary hyperparathyroidism, a forme fruste of the disease. PMID:20485897

Clinical features of hidradenitis suppurativa and Crohn disease: what do these two entities have in common?

PubMed

Vilarrasa Rull, E; González Lama, Y

2016-09-01

Hidradenitis suppurativa (HS) and Crohn disease (CD) are chronic, recurrent inflammatory diseases. They share certain clinical characteristics and flares are common in both. Both entities are usually diagnosed between the second and third decades of life and share risk factors such as smoking and overweight. In CD, as in HS, acute untreated episodes of inflammation can lead to sequels such as abscesses, fistulas and stenosis. Consequently, early management is of the utmost importance. Some patients have both diseases. The estimated prevalence of SH in CD patients is 12.4%-17.9%, while the prevalence of CD in HS patients is around 3%. The presence of HS in patients with inflammatory bowel disease (IBD) is associated with an earlier onset of IBD and with more frequent need for anti-TNF-alpha therapy and surgical resection. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

PCOS remains a diagnosis of exclusion: a concise review of key endocrinopathies to exclude.

PubMed

Kyritsi, Eleni Magdalini; Dimitriadis, George K; Kyrou, Ioannis; Kaltsas, Gregory; Randeva, Harpal S

2017-01-01

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS. © 2016 John Wiley & Sons Ltd.

Urokinase-receptor (u-PAR): an essential player in multiple games of cancer: a review on its role in tumor progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease.

PubMed

Laufs, Stephanie; Schumacher, Jens; Allgayer, Heike

2006-08-01

The relevance of the u-PA system in mediating tumor-associated proteolysis, invasion and metastasis, amongst other phenomena associated with tumor progression, has been clearly demonstrated in diverse cancer entities. This review will update on the biological and clinical relevance of the urokinase-receptor (u-PAR). Specifically, the article focuses on the potential importance of u-PAR for the development of minimal residual disease in solid cancer, and in this context reviews the biological relevance of the u-PAR for tumor cell dormancy. Furthermore, transcriptional mechanisms regulating u-PAR in vitro and in vivo, and their potential clinical and therapeutic relevance in gastrointestinal cancers, are elucidated.

Patients' Illness Perception as a Tool to Improve Individual Disease Management in Primary Cutaneous Lymphomas.

PubMed

Porkert, Stefanie; Lehner-Baumgartner, Eva; Valencak, Julia; Knobler, Robert; Riedl, Elisabeth; Jonak, Constanze

2018-02-07

The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL). Illness perception reflects patients' individual concepts of understanding and interpretation of the disease, influencing illness behaviour and health-related quality of life (HRQOL). This study investigated the clinical relevance of the relationships between illness perception, illness behaviour, and HRQOL in CTCL and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ-R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to illness perception, whereas illness perception was significantly associated with HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and socio-demographics. Only IPQ-R results provided practical information on patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and CBCL might be a useful instrument to improve individual disease management.

Review article: Probiotics in gastrointestinal and liver diseases.

PubMed

Jonkers, D; Stockbrügger, R

2007-12-01

Probiotics, defined as live micro-organisms with beneficial effects for the host, are widely applied in gastrointestinal and liver diseases. To review the available evidence of clinical trials on probiotics in gastrointestinal and liver diseases, with a major focus on irritable bowel syndrome, inflammatory bowel disease, pancreatitis and chronic liver diseases. Evidence for the therapeutic or preventive application of particular probiotic strains is available for antibiotic-associated diarrhoea, rota-virus-associated diarrhoea and pouchitis. Results are encouraging for irritable bowel syndrome, ulcerative colitis and for reducing side effects by Helicobacter pylori eradication therapies, but are less clear for Crohn's disease, lactose intolerance and constipation. In general, for most of these patient groups, more placebo-controlled methodologically well-designed studies that pay attention to both clinical outcome and mechanistic aspects are required. The application in liver disease and pancreatitis is promising, but more human trials have to be awaited. Possible mechanisms of probiotics include modulation of the intestinal microbiota and the immune system, but different bacterial may have different effects. Further insight into disease entities and the functioning of probiotic strains is required to be able to select disease-specific strains, which have to be tested in well-designed placebo-controlled studies.

The emergence of overweight as a disease entity: measuring up normality.

PubMed

Jutel, Annemarie

2006-11-01

As Charles Rosenberg [(2002). The tyranny of diagnosis. The Milbank Quarterly, 80, 237-260] has recently written, clinical diagnosis contributes to imposing structure on cultural reality in a manner which is not unproblematic. A social power resides in the process of naming diseases-one, which legitimises concerns, explains reality, naturalises deviance and imposes status. But clinical entities are not static, as both the concerns of society, and the technological ability of practitioners change (what Rosenberg refers to as the "iatrogenesis of nosology"), so too do the range of labels available for identifying disease. In this paper, I argue that being "overweight," once predominantly an adjectival descriptor of corpulence, a physical sign or a symptom, and even, in some cultures, a sign of wealth and status, is undergoing the transformation to disease entity. I suggest that evidence of this is present in both the frequency and the way in which the term is being used by the media, the medical establishment and the laity. I argue that this change stems from the convergence of two particular phenomena. The first is the belief in the neutrality of quantification, and the objectivity that measurement brings to qualitative description. The second is the importance attributed to normative appearance in health. I discuss some of the implications of this evolution and its impact on health practices, including the exploitation of this purported disease state for commercial benefit.

Automatic recognition of topic-classified relations between prostate cancer and genes using MEDLINE abstracts

PubMed Central

Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

2006-01-01

Background Automatic recognition of relations between a specific disease term and its relevant genes or protein terms is an important practice of bioinformatics. Considering the utility of the results of this approach, we identified prostate cancer and gene terms with the ID tags of public biomedical databases. Moreover, considering that genetics experts will use our results, we classified them based on six topics that can be used to analyze the type of prostate cancers, genes, and their relations. Methods We developed a maximum entropy-based named entity recognizer and a relation recognizer and applied them to a corpus-based approach. We collected prostate cancer-related abstracts from MEDLINE, and constructed an annotated corpus of gene and prostate cancer relations based on six topics by biologists. We used it to train the maximum entropy-based named entity recognizer and relation recognizer. Results Topic-classified relation recognition achieved 92.1% precision for the relation (an increase of 11.0% from that obtained in a baseline experiment). For all topics, the precision was between 67.6 and 88.1%. Conclusion A series of experimental results revealed two important findings: a carefully designed relation recognition system using named entity recognition can improve the performance of relation recognition, and topic-classified relation recognition can be effectively addressed through a corpus-based approach using manual annotation and machine learning techniques. PMID:17134477

Automatic recognition of topic-classified relations between prostate cancer and genes using MEDLINE abstracts.

PubMed

Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

2006-11-24

Automatic recognition of relations between a specific disease term and its relevant genes or protein terms is an important practice of bioinformatics. Considering the utility of the results of this approach, we identified prostate cancer and gene terms with the ID tags of public biomedical databases. Moreover, considering that genetics experts will use our results, we classified them based on six topics that can be used to analyze the type of prostate cancers, genes, and their relations. We developed a maximum entropy-based named entity recognizer and a relation recognizer and applied them to a corpus-based approach. We collected prostate cancer-related abstracts from MEDLINE, and constructed an annotated corpus of gene and prostate cancer relations based on six topics by biologists. We used it to train the maximum entropy-based named entity recognizer and relation recognizer. Topic-classified relation recognition achieved 92.1% precision for the relation (an increase of 11.0% from that obtained in a baseline experiment). For all topics, the precision was between 67.6 and 88.1%. A series of experimental results revealed two important findings: a carefully designed relation recognition system using named entity recognition can improve the performance of relation recognition, and topic-classified relation recognition can be effectively addressed through a corpus-based approach using manual annotation and machine learning techniques.

Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease☆

PubMed Central

Bunzeck, Nico; Singh-Curry, Victoria; Eckart, Cindy; Weiskopf, Nikolaus; Perry, Richard J.; Bain, Peter G.; Düzel, Emrah; Husain, Masud

2013-01-01

Background In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Methods Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. Results We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Conclusions Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease. PMID:24025315

Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus.

PubMed

Maslow, Joel N

2017-12-02

The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed.

Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus

PubMed Central

Maslow, Joel N.

2017-01-01

ABSTRACT The past decade and a half has been characterized by numerous emerging infectious diseases. With each new threat, there has been a call for rapid vaccine development. Pathogens such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and the Zika virus represent either new viral entities or viruses emergent in new geographic locales and characterized by novel complications. Both serve as paradigms for the global spread that can accompany new pathogens. In this paper, we review the epidemiology and pathogenesis of MERS-CoV and Zika virus with respect to vaccine development. The challenges in vaccine development and the approach to clinical trial design to test vaccine candidates for disease entities with a changing epidemiology are discussed. PMID:28846484

Rare inflammatory diseases of the white matter and mimics of multiple sclerosis and related disorders.

PubMed

Tardieu, Marc; Deiva, Kumaran

2013-12-01

The spectra of white matter neuroinflammatory diseases and pathological processes inducing inflammatory lesions in the white matter of the central nervous system are wider in children than in adults. The definitions of multiple sclerosis (MS) and of the related clinically isolated syndromes (CIS) and acute disseminated encephalomyelitis (ADEM) have been recently revised leading to a new consensus definition. However, other entities with similarities to these diseases may also develop with monophasic or relapsing white matter inflammation. These conditions include congenital immunogenetic diseases (such as hemophagocytic lymphohistiocytosis), vasculitis, and autoantibody-mediated encephalopathies (Hashimoto encephalopathy, encephalitis with anti-N-methyl-D-aspartate receptor antibodies and neuromyelitis optica). Moreover, infectious diseases, such as Lyme disease, tumors (oligodendroglioma and lymphoma), and even genetic or metabolic diseases should also be considered if the clinical course of the disease does not follow the typical pattern for ADEM or MS. This short review describes these different entities and provides information for the differential diagnosis of inflammatory diseases of the white matter. Georg Thieme Verlag KG Stuttgart · New York.

Diverticular Disease-associated Colitis: What Do We Know? A Review of Literature.

PubMed

Haddad, Fady G; El Bitar, Sandy; Al Moussawi, Hassan; Chang, Qing; Deeb, Liliane

2018-02-24

Diverticular disease (DD) is a leading cause of hospitalizations in developed countries affecting 30-50% of individuals older than 60 years. Identified as a distinct entity since 1980, diverticular disease-associated colitis (DAC) describes the occurrence of mucosal inflammation in a colon segment affected with DD with relative sparing of the rectum and proximal colon. Its prevalence is suggested around 1.3-3.8%. Pathogenesis is multifactorial with multiple reports noting clinicopathological overlap between DAC and inflammatory bowel disease (IBD) especially in patients with granulomatous colitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of IBD. Recurrence rates and long-term outcomes of DAC are not well defined and could range from a benign course to an overt IBD. More studies are needed in order to further characterize this entity.

Immunotactoid Glomerulopathy and Cryoglobulinemic Nephropathy: Two Entities with Many Similarities. A Unified Conceptual Approach.

PubMed

Herrera, Guillermo A; Ojemakinde, Kunle O; Turbat-Herrera, Elba A; Gu, Xin; Zeng, Xu; Iskandar, Samy S

2015-01-01

Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease.

Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

PubMed Central

Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.

2013-01-01

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results. PMID:24324827

42 CFR 410.48 - Kidney disease education services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... either of the following healthcare entities that meets the qualifications and requirements specified in this section to provide kidney disease patient education services— (i) One of the following healthcare... to make informed decisions about their healthcare options related to chronic kidney disease. (ii) The...

42 CFR 410.48 - Kidney disease education services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... either of the following healthcare entities that meets the qualifications and requirements specified in this section to provide kidney disease patient education services— (i) One of the following healthcare... to make informed decisions about their healthcare options related to chronic kidney disease. (ii) The...

Discovery of Predicate-Oriented Relations among Named Entities Extracted from Thai Texts

NASA Astrophysics Data System (ADS)

Tongtep, Nattapong; Theeramunkong, Thanaruk

Extracting named entities (NEs) and their relations is more difficult in Thai than in other languages due to several Thai specific characteristics, including no explicit boundaries for words, phrases and sentences; few case markers and modifier clues; high ambiguity in compound words and serial verbs; and flexible word orders. Unlike most previous works which focused on NE relations of specific actions, such as work_for, live_in, located_in, and kill, this paper proposes more general types of NE relations, called predicate-oriented relation (PoR), where an extracted action part (verb) is used as a core component to associate related named entities extracted from Thai Texts. Lacking a practical parser for the Thai language, we present three types of surface features, i.e. punctuation marks (such as token spaces), entity types and the number of entities and then apply five alternative commonly used learning schemes to investigate their performance on predicate-oriented relation extraction. The experimental results show that our approach achieves the F-measure of 97.76%, 99.19%, 95.00% and 93.50% on four different types of predicate-oriented relation (action-location, location-action, action-person and person-action) in crime-related news documents using a data set of 1,736 entity pairs. The effects of NE extraction techniques, feature sets and class unbalance on the performance of relation extraction are explored.

First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium

PubMed Central

Musselwhite, Laura W.; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C.; Wellems, Thomas E.; Tavera, Gloria; Goulding, Rebecca E.; Guillen, Ethan

2012-01-01

Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases. PMID:22232453

Discourse Model Representation of Referential and Attributive Descriptions.

ERIC Educational Resources Information Center

Onishi, Kristine H.; Murphy, Gregory L.

2002-01-01

Manipulated shared knowledge and focus on specific entities, the verb in the sentence, and whether the description was definite or indefinite. Each factor influenced interpretation of the description. Confirmed that changing verbs alone affected reference choice. Indicated that both referentially and attributively introduced entities are…

The 28-entity IGES test file results using ComputerVision CADDS 4X

NASA Technical Reports Server (NTRS)

Kuan, Anchyi; Shah, Saurin; Smith, Kevin

1987-01-01

The investigation was based on the following steps: (1) Read the 28 Entity IGES (Initial Graphics Exchange Specification) Test File into the CAD data base with the IGES post-processor; (2) Make the modifications to the displayed geometries, which should produce the normalized front view and the drawing entity defined display; (3) Produce the drawing entity defined display of the file as it appears in the CAD system after modification to the geometry; (4) Translate the file back to IGES format using IGES pre-processor; (5) Read the IGES file produced by the pre-processor back into the CAD data base; (6) Produce another drawing entity defined display of the CAD display; and (7) Compare the plots resulting from steps 3 and 6 - they should be identical to each other.

Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

PubMed

Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul

2015-01-01

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.

Small bowel intussusception due to a primary non-Hodgkin's lymphoma. An unusual presentation and clinical course.

PubMed

Salemis, Nikolaos S; Tsiambas, Evangelos; Liatsos, Christos; Karameris, Andreas; Tsohataridis, Efstathios

2010-12-01

Adult intussusception is a rare clinical entity accounting for 5% of all intussusceptions. Symptoms and signs are often vague and non-specific making a preoperative diagnosis difficult. The purpose of this study is to present a rare case of a jejuno-jejunal intussusception due to primary intestinal non-Hodgkin's lymphoma in a patient with an unusual clinical course. A 78-year-old man presented with a 1-month history of abdominal pain, nausea, epigastric fullness, and weight loss. Computed tomography scan and ultrasonography findings were suggestive of small bowel intussusception. Laparotomy revealed a jejuno-jejunal intussusception caused by a primary B cell non-Hodgkin's lymphoma 20 cm distal to the ligament of Treitz. Resection without prior reduction was performed. The patient refused postoperative adjuvant chemotherapy. Seven months later, he presented with upper gastrointestinal bleeding, and the diagnostic evaluation revealed gastric infiltration of large B cell non-Hodgkin's lymphoma. Despite chemotherapy, he died of disseminated progressive disease 7 months later. Adult jejuno-jejunal intussusception due to primary non-Hodgkin's lymphoma is a rare clinical entity. A high index of suspicion is needed as symptoms and signs are not pathognomonic. Appropriate investigations can lead to a prompt preoperative diagnosis. Resection without prior reduction is the treatment of choice. Our patient's refusal of postoperative adjuvant chemotherapy likely resulted in relapse of the disease in another part of the gastrointestinal tract.

[Work-related rhinitis - Is it always an occupational disease?

PubMed

Salski, Witold; Wiszniewska, Marta; Salska, Agata; Tymoszuk, Diana; Walusiak-Skorupa, Jolanta

2016-12-22

Rhinitis is a chronic inflammatory disease of the upper respiratory tract, characterized by a high prevalence and a complex pathogenesis. Work-related rhinitis (WRR) can be divided into occupational rhinitis (OR) and work-exacerbated rhinitis (WER). It is not only considered as a disease entity but also in the context of medical certification as the allergic disease associated with occupational exposure. Epidemiology of work-related rhinitis has been found to vary depending on the occupation and specific exposure, on the other hand the prevalence data may be underestimated due to the lack of uniform diagnostic criteria. This paper reviews the issues comprising the pathogenesis, epidemiology, diagnosis and treatment of patients with work-related rhinitis. It also discusses the significance of the disease in occupational medicine, particularly in terms of preventive worker care, general principles of good practice in primary and secondary WRR prevention and the necessary directions of changes in medical certification in the cases of occupational rhinitis. Med Pr 2016;67(6):801-815. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Ambulatory cardiology network in Greece: Clinical and therapeutic implications in the outpatient setting. The TEVE-SSF study.

PubMed

Panagiotopoulos, Konstantinos E; Panagiotopoulou, Eleni E; Katsaros, Konstantinos; Noikokirakis, Georgios; Mpouziou, Maria; Stamelou, Angeliki; Toumanidis, Savvas

2016-11-15

Community based registries are particularly valuable tools to Preventive Cardiology as they summarize epidemiological data of ischemic heart disease risk factors, medications and lifestyle characteristics. We enrolled 1191 patients, from an outpatient community based cardiology network, dedicated to cover medically, office based professionals. We recorded demographic and lifestyle characteristics, risk factors for ischemic heart disease, all clinical entities diagnosed and therapies which were prescribed for hypertension and lipid disorders specifically. Our population consisted of 659 males (55%) and 532 females (45%), (mean age 46±14). A sedentary lifestyle was almost universal (92%), followed by smoking (44%) and overweight body composition (38%). Unhealthy lifestyle increased significantly during the third decade of life, while multimorbidity ascended during the fifth. Cardiovascular morbidity was present in 611 patients (51%), while 289 patients (24%) were found negative for cardiovascular disease and positive for a different system diagnosis. Lipid disorders (32%) and hypertension (31%) were the most frequent cardiovascular entities. β-Blockers and statins were the most frequently prescribed medications for hypertension and lipid disorders respectively. Cardiovascular morbidity was frequent in this ambulatory middle aged population, whereas multimorbidity (mainly from gastrointestinal and endocrine system) was a significant coexisting problem, even for a cardiology oriented outpatient population. Unhealthy lifestyle is of major importance because it was present in the majority of our patients early in their life and because it was statistically related to hyperlipidemia and hypertension. Preventive Cardiology must introduce special interventions to deescalate the presence of unhealthy lifestyle in young populations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

T-cell lymphomas in South america and europe.

PubMed

Bellei, Monica; Chiattone, Carlos Sergio; Luminari, Stefano; Pesce, Emanuela Anna; Cabrera, Maria Elena; de Souza, Carmino Antonio; Gabús, Raul; Zoppegno, Lucia; Zoppegno, Lucia; Milone, Jorge; Pavlovsky, Astrid; Connors, Joseph Michael; Foss, Francine Mary; Horwitz, Steven Michael; Liang, Raymond; Montoto, Silvia; Pileri, Stefano Aldo; Polliack, Aaron; Vose, Julie Marie; Zinzani, Pier Luigi; Zucca, Emanuele; Federico, Massimo

2012-01-01

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.

T-Cell Lymphomas in South America and Europe

PubMed Central

Bellei, Monica; Chiattone, Carlos Sergio; Luminari, Stefano; Pesce, Emanuela Anna; Cabrera, Maria Elena; de Souza, Carmino Antonio; Gabús, Raul; Zoppegno, Lucia; Zoppegno, Lucia; Milone, Jorge; Pavlovsky, Astrid; Connors, Joseph Michael; Foss, Francine Mary; Horwitz, Steven Michael; Liang, Raymond; Montoto, Silvia; Pileri, Stefano Aldo; Polliack, Aaron; Vose, Julie Marie; Zinzani, Pier Luigi; Zucca, Emanuele; Federico, Massimo

2012-01-01

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies. PMID:23049383

43 CFR 414.3 - Storage and Interstate Release Agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

...; potential environmental impacts and potential effects on threatened and endangered species; comments from... date certain, the consuming entity will: (i) Notify the storing entity to develop a specific quantity... be consistent with its State's laws. (9) The agreement must include a description of: (i) The actions...

43 CFR 414.3 - Storage and Interstate Release Agreements.

Code of Federal Regulations, 2012 CFR

2012-10-01

...; potential environmental impacts and potential effects on threatened and endangered species; comments from... date certain, the consuming entity will: (i) Notify the storing entity to develop a specific quantity... be consistent with its State's laws. (9) The agreement must include a description of: (i) The actions...

43 CFR 414.3 - Storage and Interstate Release Agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

...; potential environmental impacts and potential effects on threatened and endangered species; comments from... date certain, the consuming entity will: (i) Notify the storing entity to develop a specific quantity... be consistent with its State's laws. (9) The agreement must include a description of: (i) The actions...

43 CFR 414.3 - Storage and Interstate Release Agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

...; potential environmental impacts and potential effects on threatened and endangered species; comments from... date certain, the consuming entity will: (i) Notify the storing entity to develop a specific quantity... be consistent with its State's laws. (9) The agreement must include a description of: (i) The actions...

Massive ovarian oedema: a misleading clinical entity.

PubMed

Machairiotis, Nikolaos; Stylianaki, Aikaterini; Kouroutou, Paraskevi; Sarli, Polixeni; Alexiou, Nikolaos Konstantinos; Efthymiou, Elias; Maras, Athanasios; Alexiou, Nikolaos Georgios; Nikolaou, Spyridon Evaggelos; Courcoutsakis, Nikolaos; Papakonstantinou, Eleni; Zarogoulidis, Paul; Barbetakis, Nikolaos; Paliouras, Dimitrios; Gogakos, Apostolos; Machairiotis, Christodoulos

2016-02-03

Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility.

Combining Open-domain and Biomedical Knowledge for Topic Recognition in Consumer Health Questions.

PubMed

Mrabet, Yassine; Kilicoglu, Halil; Roberts, Kirk; Demner-Fushman, Dina

2016-01-01

Determining the main topics in consumer health questions is a crucial step in their processing as it allows narrowing the search space to a specific semantic context. In this paper we propose a topic recognition approach based on biomedical and open-domain knowledge bases. In the first step of our method, we recognize named entities in consumer health questions using an unsupervised method that relies on a biomedical knowledge base, UMLS, and an open-domain knowledge base, DBpedia. In the next step, we cast topic recognition as a binary classification problem of deciding whether a named entity is the question topic or not. We evaluated our approach on a dataset from the National Library of Medicine (NLM), introduced in this paper, and another from the Genetic and Rare Disease Information Center (GARD). The combination of knowledge bases outperformed the results obtained by individual knowledge bases by up to 16.5% F1 and achieved state-of-the-art performance. Our results demonstrate that combining open-domain knowledge bases with biomedical knowledge bases can lead to a substantial improvement in understanding user-generated health content.

Recent advances in malaria drug discovery.

PubMed

Lanteri, Charlotte A; Johnson, Jacob D; Waters, Norman C

2007-06-01

Malaria is responsible for over 300 million clinical cases annually and claims the lives of approximately 1-2 million. With a disease that has plagued humanity throughout history, one would think that better control measures would be in place to decrease the mortality and morbidity associated with malaria. Due to malaria drug resistance, an increase in the number of clinical infections and deaths is soon likely to be observed. Therefore, there is a push to identify and introduce new drug entities for malaria treatment and prophylaxis. In an effort to develop new malaria drugs, several different approaches have been implemented. These include the use of drug combinations of either new or existing antimalarials, exploitation of natural products, identification of resistance reversal or sensitizing agents and the targeting of specific malarial enzymes. Past experience has shown that introduction of the same chemical entities, such as quinolines and antifolates, results in only limited efficacy with resistance developing rapidly within one year of introduction. New approaches to drug discovery should identify novel chemotypes which circumvent the parasite's disposition to drug resistance. This review summarizes current efforts in malaria drug discovery as uncovered in recent patent literature.

Small endogenous molecules as moiety to improve targeting of CNS drugs.

PubMed

Sutera, Flavia Maria; De Caro, Viviana; Giannola, Libero Italo

2017-01-01

A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purinergic, ureic and acidic fragments derivatives, most of which can take advantage from BBB carrier-mediated transporters, where passive diffusion is not permitted. Expert opinion: In the authors' perspective, further progress in this field could expedite successful translation of new chemical entities into clinical trials. Careful rationalization of the linkage between endogenous molecular structures and putative transporters binding sites could allow to useful work-flows and libraries for synthesizing new BBB-crossing therapeutic substances and/or multifunctional drugs for treatments of central disorders.

Chemical-induced disease relation extraction via convolutional neural network.

PubMed

Gu, Jinghang; Sun, Fuqing; Qian, Longhua; Zhou, Guodong

2017-01-01

This article describes our work on the BioCreative-V chemical-disease relation (CDR) extraction task, which employed a maximum entropy (ME) model and a convolutional neural network model for relation extraction at inter- and intra-sentence level, respectively. In our work, relation extraction between entity concepts in documents was simplified to relation extraction between entity mentions. We first constructed pairs of chemical and disease mentions as relation instances for training and testing stages, then we trained and applied the ME model and the convolutional neural network model for inter- and intra-sentence level, respectively. Finally, we merged the classification results from mention level to document level to acquire the final relations between chemical and disease concepts. The evaluation on the BioCreative-V CDR corpus shows the effectiveness of our proposed approach. http://www.biocreative.org/resources/corpora/biocreative-v-cdr-corpus/. © The Author(s) 2017. Published by Oxford University Press.

A Complex Network Perspective on Clinical Science

PubMed Central

Hofmann, Stefan G.; Curtiss, Joshua; McNally, Richard J.

2016-01-01

Contemporary classification systems for mental disorders assume that abnormal behaviors are expressions of latent disease entities. An alternative to the latent disease model is the complex network approach. Instead of assuming that symptoms arise from an underlying disease entity, the complex network approach holds that disorders exist as systems of interrelated elements of a network. This approach also provides a framework for the understanding of therapeutic change. Depending on the structure of the network, change can occur abruptly once the network reaches a critical threshold (the tipping point). Homogeneous and highly connected networks often recover more slowly from local perturbations when the network approaches the tipping point, allowing for the possibility to predict treatment change, relapse, and recovery. In this article we discuss the complex network approach as an alternative to the latent disease model, and we discuss its implications for classification, therapy, relapse, and recovery. PMID:27694457

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Gene therapy in liver diseases: state-of-the-art and future perspectives.

PubMed

Domvri, Kalliopi; Zarogoulidis, Paul; Porpodis, Konstantinos; Koffa, Maria; Lambropoulou, Maria; Kakolyris, Stylianos; Kolios, George; Zarogoulidis, Konstantinos; Chatzaki, Ekaterini

2012-12-01

Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite. In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant amount of experimental data along with the available information from clinical trials are systematically reviewed here and presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.

Liberal Entity Extraction: Rapid Construction of Fine-Grained Entity Typing Systems.

PubMed

Huang, Lifu; May, Jonathan; Pan, Xiaoman; Ji, Heng; Ren, Xiang; Han, Jiawei; Zhao, Lin; Hendler, James A

2017-03-01

The ability of automatically recognizing and typing entities in natural language without prior knowledge (e.g., predefined entity types) is a major challenge in processing such data. Most existing entity typing systems are limited to certain domains, genres, and languages. In this article, we propose a novel unsupervised entity-typing framework by combining symbolic and distributional semantics. We start from learning three types of representations for each entity mention: general semantic representation, specific context representation, and knowledge representation based on knowledge bases. Then we develop a novel joint hierarchical clustering and linking algorithm to type all mentions using these representations. This framework does not rely on any annotated data, predefined typing schema, or handcrafted features; therefore, it can be quickly adapted to a new domain, genre, and/or language. Experiments on genres (news and discussion forum) show comparable performance with state-of-the-art supervised typing systems trained from a large amount of labeled data. Results on various languages (English, Chinese, Japanese, Hausa, and Yoruba) and domains (general and biomedical) demonstrate the portability of our framework.

Liberal Entity Extraction: Rapid Construction of Fine-Grained Entity Typing Systems

PubMed Central

Huang, Lifu; May, Jonathan; Pan, Xiaoman; Ji, Heng; Ren, Xiang; Han, Jiawei; Zhao, Lin; Hendler, James A.

2017-01-01

Abstract The ability of automatically recognizing and typing entities in natural language without prior knowledge (e.g., predefined entity types) is a major challenge in processing such data. Most existing entity typing systems are limited to certain domains, genres, and languages. In this article, we propose a novel unsupervised entity-typing framework by combining symbolic and distributional semantics. We start from learning three types of representations for each entity mention: general semantic representation, specific context representation, and knowledge representation based on knowledge bases. Then we develop a novel joint hierarchical clustering and linking algorithm to type all mentions using these representations. This framework does not rely on any annotated data, predefined typing schema, or handcrafted features; therefore, it can be quickly adapted to a new domain, genre, and/or language. Experiments on genres (news and discussion forum) show comparable performance with state-of-the-art supervised typing systems trained from a large amount of labeled data. Results on various languages (English, Chinese, Japanese, Hausa, and Yoruba) and domains (general and biomedical) demonstrate the portability of our framework. PMID:28328252

A neural joint model for entity and relation extraction from biomedical text.

PubMed

Li, Fei; Zhang, Meishan; Fu, Guohong; Ji, Donghong

2017-03-31

Extracting biomedical entities and their relations from text has important applications on biomedical research. Previous work primarily utilized feature-based pipeline models to process this task. Many efforts need to be made on feature engineering when feature-based models are employed. Moreover, pipeline models may suffer error propagation and are not able to utilize the interactions between subtasks. Therefore, we propose a neural joint model to extract biomedical entities as well as their relations simultaneously, and it can alleviate the problems above. Our model was evaluated on two tasks, i.e., the task of extracting adverse drug events between drug and disease entities, and the task of extracting resident relations between bacteria and location entities. Compared with the state-of-the-art systems in these tasks, our model improved the F1 scores of the first task by 5.1% in entity recognition and 8.0% in relation extraction, and that of the second task by 9.2% in relation extraction. The proposed model achieves competitive performances with less work on feature engineering. We demonstrate that the model based on neural networks is effective for biomedical entity and relation extraction. In addition, parameter sharing is an alternative method for neural models to jointly process this task. Our work can facilitate the research on biomedical text mining.

An automated framework for hypotheses generation using literature.

PubMed

Abedi, Vida; Zand, Ramin; Yeasin, Mohammed; Faisal, Fazle Elahi

2012-08-29

In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF) finds "crisp semantic associations" among entities of interest - that is a step towards bridging such gaps. The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect "crisp" associations, and making assertions about entities (such as disease X is associated with a set of factors Z). Pilot studies were performed using two diseases. A comparative analysis of the computed "associations" and "assertions" with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture "crisp" direct and indirect associations, and provide knowledge discovery on demand. The proposed framework is fast, efficient, and robust in generating new hypotheses to identify factors associated with a disease. A full integrated Web service application is being developed for wide dissemination of the HGF. A large-scale study by the domain experts and associated researchers is underway to validate the associations and assertions computed by the HGF.

Using the Gravity Model to Estimate the Spatial Spread of Vector-Borne Diseases

PubMed Central

Barrios, José Miguel; Verstraeten, Willem W.; Maes, Piet; Aerts, Jean-Marie; Farifteh, Jamshid; Coppin, Pol

2012-01-01

The gravity models are commonly used spatial interaction models. They have been widely applied in a large set of domains dealing with interactions amongst spatial entities. The spread of vector-borne diseases is also related to the intensity of interaction between spatial entities, namely, the physical habitat of pathogens’ vectors and/or hosts, and urban areas, thus humans. This study implements the concept behind gravity models in the spatial spread of two vector-borne diseases, nephropathia epidemica and Lyme borreliosis, based on current knowledge on the transmission mechanism of these diseases. Two sources of information on vegetated systems were tested: the CORINE land cover map and MODIS NDVI. The size of vegetated areas near urban centers and a local indicator of occupation-related exposure were found significant predictors of disease risk. Both the land cover map and the space-borne dataset were suited yet not equivalent input sources to locate and measure vegetated areas of importance for disease spread. The overall results point at the compatibility of the gravity model concept and the spatial spread of vector-borne diseases. PMID:23202882

Using the gravity model to estimate the spatial spread of vector-borne diseases.

PubMed

Barrios, José Miguel; Verstraeten, Willem W; Maes, Piet; Aerts, Jean-Marie; Farifteh, Jamshid; Coppin, Pol

2012-11-30

The gravity models are commonly used spatial interaction models. They have been widely applied in a large set of domains dealing with interactions amongst spatial entities. The spread of vector-borne diseases is also related to the intensity of interaction between spatial entities, namely, the physical habitat of pathogens’ vectors and/or hosts, and urban areas, thus humans. This study implements the concept behind gravity models in the spatial spread of two vector-borne diseases, nephropathia epidemica and Lyme borreliosis, based on current knowledge on the transmission mechanism of these diseases. Two sources of information on vegetated systems were tested: the CORINE land cover map and MODIS NDVI. The size of vegetated areas near urban centers and a local indicator of occupation-related exposure were found significant predictors of disease risk. Both the land cover map and the space-borne dataset were suited yet not equivalent input sources to locate and measure vegetated areas of importance for disease spread. The overall results point at the compatibility of the gravity model concept and the spatial spread of vector-borne diseases.

Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion

PubMed Central

Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

2016-01-01

The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13. Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract PMID:27504009

47 CFR 27.1170 - Payment Issues.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Microwave Relocation from the 2110-2150 Mhz and 2160-2200 Mhz Bands § 27.1170 Payment Issues. Prior to initiating operations for a newly constructed site or modified existing site, an AWS entity or MSS/ATC entity is required to file a notice containing site-specific data with the clearinghouse. The notice...

Abstracts versus Full Texts and Patents: A Quantitative Analysis of Biomedical Entities

NASA Astrophysics Data System (ADS)

Müller, Bernd; Klinger, Roman; Gurulingappa, Harsha; Mevissen, Heinz-Theodor; Hofmann-Apitius, Martin; Fluck, Juliane; Friedrich, Christoph M.

In information retrieval, named entity recognition gives the opportunity to apply semantic search in domain specific corpora. Recently, more full text patents and journal articles became freely available. As the information distribution amongst the different sections is unknown, an analysis of the diversity is of interest.

42 CFR 73.14 - Incident response.

Code of Federal Regulations, 2013 CFR

2013-10-01

... under this part must develop and implement a written incident response plan based upon a site specific risk assessment.2 The incident response plan must be coordinated with any entity-wide plans, kept in... response plan must fully describe the entity's response procedures for the theft, loss, or release of a...

42 CFR 73.14 - Incident response.

Code of Federal Regulations, 2014 CFR

2014-10-01

... under this part must develop and implement a written incident response plan based upon a site specific risk assessment.2 The incident response plan must be coordinated with any entity-wide plans, kept in... response plan must fully describe the entity's response procedures for the theft, loss, or release of a...

Atypical hydroa vacciniforme-like epstein-barr virus associated T/NK-cell lymphoproliferative disorder.

PubMed

Lee, Hye Young; Baek, Jin Ok; Lee, Jong Rok; Park, Sang Hui; Jeon, In Sang; Roh, Joo Young

2012-12-01

Epstein-Barr virus (EBV)-associated T-cell/natural killer (NK)-cell lymphoproliferative disorders (EBV-T/NK-LPDs) accompany severe chronic active EBV infection (CAEBV) or comprise the CAEBV disease entity. The CAEBV disease entity has the common feature of lymphoproliferation of T or NK cells (primarily), and B cells (rarely), with chronic activation of EBV infection. The disease is rare and seems to be more prevalent in East Asian countries. The CAEBV disease entity encompasses heterogenous disorders, including hydroa vacciniforme (HV), hypersensitivity to mosquito bites, EBV-associated hemophagocytic syndrome, NK/T-cell lymphoma, and NK-cell leukemia. Atypical HV-like eruptions are present on sun-exposed and nonexposed areas with facial edema, fever, and hepatosplenomegaly, unlike classic HV. Recently, it has been suggested that classic HV and atypical HV-like eruptions are variants within the same disease spectrum of EBV-T/NK-LPD. We report a Korean boy with an atypical HV-like eruption and various systemic manifestations, including fever, sore throat, abdominal pain, headaches, seizures, and hematologic abnormalities for 2 years. After the initial mild eruption, which resembled a viral exanthem, ulceronecrotic skin lesions gradually developed and were associated with a high-grade fever and constitutional symptoms. He had a CAEBV infection, which showed a predominant proliferation of NK cells with high EBV DNA levels in the peripheral blood. However, in the skin lesions, there were nonneoplastic CD4 T-cell infiltrations predominantly showing a monoclonal T-cell receptor-γ gene rearrangement and positive EBV in situ hybridization.

JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms

PubMed Central

Jones, Amy V; Chase, Andrew; Silver, Richard T; Oscier, David; Zoi, Katerina; Wang, Y Lynn; Cario, Holger; Pahl, Heike L; Collins, Andrew; Reiter, Andreas; Grand, Francis; Cross, Nicholas C P

2014-01-01

Chronic myeloproliferative neoplasms (MPNs) are a group of related conditions characterized by the overproduction of cells from one or more myeloid lineages. More than 95% of cases of polycythemia vera, and roughly half of essential thrombocythemia and primary myelofibrosis acquire a unique somatic 1849G>T JAK2 mutation (encoding V617F) that is believed to be a critical driver of excess proliferation1–4. We report here that JAK2V617F-associated disease is strongly associated with a specific constitutional JAK2 haplotype, designated 46/1, in all three disease entities compared to healthy controls (polycythemia vera, n = 192, P = 2.9 × 10−16; essential thrombocythemia, n = 78, P = 8.2 × 10−9 and myelofibrosis, n = 41, P = 8.0 × 10−5). Furthermore, JAK2V617F specifically arises on the 46/1 allele in most cases. The 46/1 JAK2 haplotype thus predisposes to the development of JAK2V617F-associated MPNs (OR = 3.7; 95% CI = 3.1–4.3) and provides a model whereby a constitutional genetic factor is associated with an increased risk of acquiring a specific somatic mutation. PMID:19287382

Definition of ALI/ARDS.

PubMed

Raghavendran, Krishnan; Napolitano, Lena M

2011-07-01

Although acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are caused by different injuries and conditions, their similar clinical picture makes a compelling case for them to be studied as a single entity. An array of potential specific targets for pharmacologic intervention can be applied to ALI/ARDS as one disease. Although a working definition of ALI/ARDS that includes pulmonary and extrapulmonary causes can have benefit in standardizing supportive care, it can also complicate assessments of the efficacy of therapeutic interventions. In this article, definitions that have been recently used for ALI/ARDS in various clinical studies are discussed individually. Copyright © 2011 Elsevier Inc. All rights reserved.

Network pharmacology: reigning in drug attrition?

PubMed

Alian, Osama M; Shah, Minjel; Mohammad, Momin; Mohammad, Ramzi M

2013-06-01

In the process of drug development, there has been an exceptionally high attrition rate in oncological compounds entering late phases of testing. This has seen a concurrent reduction in approved NCEs (new chemical entities) reaching patients. Network pharmacology has become a valuable tool in understanding the fine details of drug-target interactions as well as painting a more practical picture of phenotype relationships to patients and drugs. By utilizing all the tools achieved through molecular medicine and combining it with high throughput data analysis, interactions and mechanisms can be elucidated and treatments reasonably tailored to patients expressing specific phenotypes (or genotypes) of disease, essentially reigning in the phenomenon of drug attrition.

The Basics of Renal Allograft Pathology.

PubMed

Troxell, Megan L; Houghton, Donald C

2014-09-01

Renal allograft biopsy provides critical information in the management of renal transplant patients, and must be analyzed in close collaboration with the clinical team. The histologic correlates of acute T-cell mediated rejection are interstitial inflammation, tubulitis, and endothelialitis; polyomavirus nephropathy is a potential mimic. Evidence of antibody-mediated rejection includes C4d deposition; morphologic acute tissue injury; and donor specific antibodies. Acute tubular injury/necrosis is a reversible cause of impaired graft function, especially in the immediate post-transplant period. Drug toxicity, recurrent disease, chronic injury, and other entities affecting both native and transplant kidneys must also be evaluated. Copyright © 2014 Elsevier Inc. All rights reserved.

A New Classification System for IgG4 Autoantibodies

PubMed Central

Koneczny, Inga

2018-01-01

IgG4 autoimmune diseases are characterized by the presence of antigen-specific autoantibodies of the IgG4 subclass and contain well-characterized diseases such as muscle-specific kinase myasthenia gravis, pemphigus, and thrombotic thrombocytopenic purpura. In recent years, several new diseases were identified, and by now 14 antigens targeted by IgG4 autoantibodies have been described. The IgG4 subclass is considered immunologically inert and functionally monovalent due to structural differences compared to other IgG subclasses. IgG4 usually arises after chronic exposure to antigen and competes with other antibody species, thus “blocking” their pathogenic effector mechanisms. Accordingly, in the context of IgG4 autoimmunity, the pathogenicity of IgG4 is associated with blocking of enzymatic activity or protein–protein interactions of the target antigen. Pathogenicity of IgG4 autoantibodies has not yet been systematically analyzed in IgG4 autoimmune diseases. Here, we establish a modified classification system based on Witebsky’s postulates to determine IgG4 pathogenicity in IgG4 autoimmune diseases, review characteristics and pathogenic mechanisms of IgG4 in these disorders, and also investigate the contribution of other antibody entities to pathophysiology by additional mechanisms. As a result, three classes of IgG4 autoimmune diseases emerge: class I where IgG4 pathogenicity is validated by the use of subclass-specific autoantibodies in animal models and/or in vitro models of pathogenicity; class II where IgG4 pathogenicity is highly suspected but lack validation by the use of subclass specific antibodies in in vitro models of pathogenicity or animal models; and class III with insufficient data or a pathogenic mechanism associated with multivalent antigen binding. Five out of the 14 IgG4 antigens were validated as class I, five as class II, and four as class III. Antibodies of other IgG subclasses or immunoglobulin classes were present in several diseases and could contribute additional pathogenic mechanisms. PMID:29483905

Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward

PubMed Central

Twisk, Frank N.M.

2016-01-01

Myalgic encephalomyelitis (ME), described in the medical literature since 1938, is characterized by distinctive muscular symptoms, neurological symptoms, and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, is chronic fatigue, which should be accompanied by at least four or more out of eight “additional” symptoms. The use of the abstract, polythetic criteria of CFS, which define a heterogeneous patient population, and self-report has hampered both scientific progress and accurate diagnosis. To resolve the “diagnostic impasse” the Institute of Medicine proposes that a new clinical entity, systemic exercise intolerance disease (SEID), should replace the clinical entities ME and CFS. However, adopting SEID and its defining symptoms, does not resolve methodological and diagnostic issues. Firstly, a new diagnostic entity cannot replace two distinct, partially overlapping, clinical entities such as ME and CFS. Secondly, due to the nature of the diagnostic criteria, the employment of self-report, and the lack of criteria to exclude patients with other conditions, the SEID criteria seem to select an even more heterogeneous patient population, causing additional diagnostic confusion. This article discusses methodological and diagnostic issues related to SEID and proposes a methodological solution for the current “diagnostic impasse”. PMID:26861399

Perceived Animacy Influences the Processing of Human-Like Surface Features in the Fusiform Gyrus

PubMed Central

Shultz, Sarah; McCarthya, Gregory

2014-01-01

While decades of research have demonstrated that a region of the right fusiform gyrus (FG) responds selectively to faces, a second line of research suggests that the FG responds to a range of animacy cues, including biological motion and goal-directed actions, even in the absence of faces or other human-like surface features. These findings raise the question of whether the FG is indeed sensitive to faces or to the more abstract category of animate agents. The current study uses fMRI to examine whether the FG responds to all faces in a category-specific way or whether the FG is especially sensitive to the faces of animate agents. Animate agents are defined here as intentional agents with the capacity for rational goal-directed actions. Specifically, we examine how the FG responds to an entity that looks like an animate agent but that lacks the capacity for goal-directed, rational action. Region-of-interest analyses reveal that the FG activates more strongly to the animate compared with the inanimate entity, even though the surface features of both animate and inanimate entities were identical. These results suggest that the FG does not respond to all faces in a category-specific way, and is instead especially sensitive to whether an entity is animate. PMID:24905285

Induced lexico-syntactic patterns improve information extraction from online medical forums.

PubMed

Gupta, Sonal; MacLean, Diana L; Heer, Jeffrey; Manning, Christopher D

2014-01-01

To reliably extract two entity types, symptoms and conditions (SCs), and drugs and treatments (DTs), from patient-authored text (PAT) by learning lexico-syntactic patterns from data annotated with seed dictionaries. Despite the increasing quantity of PAT (eg, online discussion threads), tools for identifying medical entities in PAT are limited. When applied to PAT, existing tools either fail to identify specific entity types or perform poorly. Identification of SC and DT terms in PAT would enable exploration of efficacy and side effects for not only pharmaceutical drugs, but also for home remedies and components of daily care. We use SC and DT term dictionaries compiled from online sources to label several discussion forums from MedHelp (http://www.medhelp.org). We then iteratively induce lexico-syntactic patterns corresponding strongly to each entity type to extract new SC and DT terms. Our system is able to extract symptom descriptions and treatments absent from our original dictionaries, such as 'LADA', 'stabbing pain', and 'cinnamon pills'. Our system extracts DT terms with 58-70% F1 score and SC terms with 66-76% F1 score on two forums from MedHelp. We show improvements over MetaMap, OBA, a conditional random field-based classifier, and a previous pattern learning approach. Our entity extractor based on lexico-syntactic patterns is a successful and preferable technique for identifying specific entity types in PAT. To the best of our knowledge, this is the first paper to extract SC and DT entities from PAT. We exhibit learning of informal terms often used in PAT but missing from typical dictionaries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The CHEMDNER corpus of chemicals and drugs and its annotation principles.

PubMed

Krallinger, Martin; Rabal, Obdulia; Leitner, Florian; Vazquez, Miguel; Salgado, David; Lu, Zhiyong; Leaman, Robert; Lu, Yanan; Ji, Donghong; Lowe, Daniel M; Sayle, Roger A; Batista-Navarro, Riza Theresa; Rak, Rafal; Huber, Torsten; Rocktäschel, Tim; Matos, Sérgio; Campos, David; Tang, Buzhou; Xu, Hua; Munkhdalai, Tsendsuren; Ryu, Keun Ho; Ramanan, S V; Nathan, Senthil; Žitnik, Slavko; Bajec, Marko; Weber, Lutz; Irmer, Matthias; Akhondi, Saber A; Kors, Jan A; Xu, Shuo; An, Xin; Sikdar, Utpal Kumar; Ekbal, Asif; Yoshioka, Masaharu; Dieb, Thaer M; Choi, Miji; Verspoor, Karin; Khabsa, Madian; Giles, C Lee; Liu, Hongfang; Ravikumar, Komandur Elayavilli; Lamurias, Andre; Couto, Francisco M; Dai, Hong-Jie; Tsai, Richard Tzong-Han; Ata, Caglar; Can, Tolga; Usié, Anabel; Alves, Rui; Segura-Bedmar, Isabel; Martínez, Paloma; Oyarzabal, Julen; Valencia, Alfonso

2015-01-01

The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/.

The CHEMDNER corpus of chemicals and drugs and its annotation principles

PubMed Central

2015-01-01

The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/ PMID:25810773

Mining heart disease risk factors in clinical text with named entity recognition and distributional semantic models.

PubMed

Urbain, Jay

2015-12-01

We present the design, and analyze the performance of a multi-stage natural language processing system employing named entity recognition, Bayesian statistics, and rule logic to identify and characterize heart disease risk factor events in diabetic patients over time. The system was originally developed for the 2014 i2b2 Challenges in Natural Language in Clinical Data. The system's strengths included a high level of accuracy for identifying named entities associated with heart disease risk factor events. The system's primary weakness was due to inaccuracies when characterizing the attributes of some events. For example, determining the relative time of an event with respect to the record date, whether an event is attributable to the patient's history or the patient's family history, and differentiating between current and prior smoking status. We believe these inaccuracies were due in large part to the lack of an effective approach for integrating context into our event detection model. To address these inaccuracies, we explore the addition of a distributional semantic model for characterizing contextual evidence of heart disease risk factor events. Using this semantic model, we raise our initial 2014 i2b2 Challenges in Natural Language of Clinical data F1 score of 0.838 to 0.890 and increased precision by 10.3% without use of any lexicons that might bias our results. Copyright © 2015 Elsevier Inc. All rights reserved.

Course and prognosis in seropositive and seronegative rheumatoid arthritis.

PubMed

Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Kukeli, Anton; Manxhuka-Kërliu, Suzana; Pallaskas, Kelmend; Murtezani, Ardiana; Rexhepi, Mjellma; Rexhepi, Blerta

2013-01-01

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis (RA), diagnosed with negative rheumatoid factor (RF) tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis. The aim of the study was to establish a scientific comparative analysis between RA seronegative and seropositive, regarding course and prognoses of the disease. Two hundred fifty patients with rheumatoid arthritis according to the (American College of Rheumatology) criteria were retrospectively studied by analysis the course and prognoses of disease. All examinees were between 25-60 years of age (Xb=49.9, SD=10.3) with disease duration between 1-27 years (Xbox=6.41, SD=6.47). Course of the disease with "remissions and exacerbations", progressive continual course and bad prognoses, were more presented in seropositive group ofpatients. Partial remission was more common in seronegative patients but according to serostatus and gender has not shown statistically significant difference. Duration of the disease was a specific prognostic sign for both subsets [(r=0.32, p<0.01) seronegative, (r=0.22, p<0.05) seropositive], while age was only a specific prognostic sign for the seropositive subset [(r=0.01, p>0.05) seronegative, (r=0.18, p<0.05) seropositive]. Seropositive and seronegative RA distinguish in course and prognostic feature, but not enough to differentiate them in two different forms of the disease. Regarding the sero-status, differences within sex, with some exceptions, are not relevant.

Overgrowth syndromes with vascular anomalies.

PubMed

Blei, Francine

2015-04-01

Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. Copyright © 2015 Mosby, Inc. All rights reserved.

77 FR 19991 - Fisheries Off West Coast States; Coastal Pelagic Species Fisheries; Annual Specifications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... business entities under the proposed action. The profitability of these vessels as a result of this... sardine ex-vessel price per mt to conduct a profitability analysis because cost data for the harvesting... small entities' profitability compared to last season, due to the much higher HG this fishing season...

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012.

PubMed

Skufca, J; Ollgren, J; Ruokokoski, E; Lyytikäinen, O; Nohynek, H

2017-06-01

In Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11-12 years with a catchup for girls 13-15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations. First diagnosis of CFS/SEID, GBS and POTS in girls aged 11-15 years were obtained from the National Hospital Discharge Register during 2002-2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI). In total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27-1.01) for CFS/SEID, 1.11 (95% CI; 0.71-1.74) for GBS and 4.21 (95%CI; 3.34-5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0-70.3: p=0.029) and POTS (16.5% (95% CI; 7.8-25.9: p<0.05), but not in GBS (5.4% (95% CI; -8.4-21.3: p=0.460). Our findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Territorial energy assessment. Phase I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1981-07-31

The goal of the project is to provide a current perspective on territorial energy problems, to identify existing energy supply and demand data, and to identify energy resources that might be developed and appropriate technology options. The cost of the technical assessment and economic analysis activities required to support the development of specific energy plans is defined and estimated. Information is summarized for the US Territories, the Pacific Trust Territories, and Puerto Rico. An overview and analysis of the the Pacific Island Entities; profiles of the Pacifc Island Entities; and the Caribbean Island Entities are presented. (MCW)

Analysis of a Decision Support System for CASE Tool Selection and the Specification of an Ada to SQL Abstract Interface

DTIC Science & Technology

1991-12-01

34 foreign keys" ,which are keys inherited from conlected entities, the keys would already be defined in the connected entity’s domain primiti le definition...defined for the rootnode re!ationship because all attributes are foreign keys and they are already defined in the connected entities domain primitive...can exchange data with other tools including other tools in the tool vendor’s tool 99 Upper CASE Tool Charactcrizcs set. The important attributes are

Exploiting semantic patterns over biomedical knowledge graphs for predicting treatment and causative relations.

PubMed

Bakal, Gokhan; Talari, Preetham; Kakani, Elijah V; Kavuluru, Ramakanth

2018-06-01

Identifying new potential treatment options for medical conditions that cause human disease burden is a central task of biomedical research. Since all candidate drugs cannot be tested with animal and clinical trials, in vitro approaches are first attempted to identify promising candidates. Likewise, identifying different causal relations between biomedical entities is also critical to understand biomedical processes. Generally, natural language processing (NLP) and machine learning are used to predict specific relations between any given pair of entities using the distant supervision approach. To build high accuracy supervised predictive models to predict previously unknown treatment and causative relations between biomedical entities based only on semantic graph pattern features extracted from biomedical knowledge graphs. We used 7000 treats and 2918 causes hand-curated relations from the UMLS Metathesaurus to train and test our models. Our graph pattern features are extracted from simple paths connecting biomedical entities in the SemMedDB graph (based on the well-known SemMedDB database made available by the U.S. National Library of Medicine). Using these graph patterns connecting biomedical entities as features of logistic regression and decision tree models, we computed mean performance measures (precision, recall, F-score) over 100 distinct 80-20% train-test splits of the datasets. For all experiments, we used a positive:negative class imbalance of 1:10 in the test set to model relatively more realistic scenarios. Our models predict treats and causes relations with high F-scores of 99% and 90% respectively. Logistic regression model coefficients also help us identify highly discriminative patterns that have an intuitive interpretation. We are also able to predict some new plausible relations based on false positives that our models scored highly based on our collaborations with two physician co-authors. Finally, our decision tree models are able to retrieve over 50% of treatment relations from a recently created external dataset. We employed semantic graph patterns connecting pairs of candidate biomedical entities in a knowledge graph as features to predict treatment/causative relations between them. We provide what we believe is the first evidence in direct prediction of biomedical relations based on graph features. Our work complements lexical pattern based approaches in that the graph patterns can be used as additional features for weakly supervised relation prediction. Copyright © 2018 Elsevier Inc. All rights reserved.

New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull base.

PubMed

Thompson, Lester D R; Franchi, Alessandro

2018-03-01

The World Health Organization recently published the 4th edition of the Classification of Head and Neck Tumors, including several new entities, emerging entities, and significant updates to the classification and characterization of tumor and tumor-like lesions, specifically as it relates to nasal cavity, paranasal sinuses, and skull base in this overview. Of note, three new entities (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were added to this section, while emerging entities (SMARCB1-deficient carcinoma and HPV-related carcinoma with adenoid cystic-like features) and several tumor-like entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal hamartoma) were included as provisional diagnoses or discussed in the setting of the differential diagnosis. The sinonasal tract houses a significant diversity of entities, but interestingly, the total number of entities has been significantly reduced by excluding tumor types if they did not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. Refinements to nomenclature and criteria were provided to sinonasal papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall, the new WHO classification reflects the state of current understanding for many relatively rare neoplasms, with this article highlighting the most significant changes.

Regulatory considerations on endpoints in ovarian cancer drug development.

PubMed

Balasubramaniam, Sanjeeve; Kim, Geoffrey S; McKee, Amy E; Pazdur, Richard

2017-07-15

Ovarian cancer remains a disease entity that is responsible for considerable morbidity and mortality among women worldwide. Modern drug research pipelines and accelerated drug development timelines applied to other disease entities have begun to make an impact on treatment options for patients with advanced ovarian cancer, as exemplified by the recent accelerated approval of 2 agents for this disease as the forerunners of a growing number of registrational trials. Regulatory flexibility for this serious and life-threatening condition spurs the consideration of intermediate endpoints for regulatory trial design, including potential applications in the development of newer therapeutic classes such as targeted therapies and immunotherapies for patients with advanced ovarian cancer. Cancer 2017;123:2604-8. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Biopharmaceuticals: From peptide to drug

NASA Astrophysics Data System (ADS)

Hannappel, Margarete

2017-08-01

Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

Biology of acute lymphoblastic leukemia (ALL): clinical and therapeutic relevance.

PubMed

Graux, Carlos

2011-04-01

Acute lymphoblastic leukemia is a heterogeneous disease comprising several clinico-biological entities. Karyotyping of leukemic cells identifies recurrent chromosome rearrangements. These are usually translocations that activate genes encoding transcription factor regulating B- or T-cell differentiation. Gene expression-array confirms the prognostic relevance of ALL subgroups identified by specific chromosomal rearrangements and isolates new subgroups. Analysis of genomic copy number changes and high throughput sequencing reveal new cryptic deletions. The challenge is now to understand how these cooperative genetic lesions interact in order to have the molecular rationales needed to select new therapeutic targets and to develop and combine inhibitors with high levels of anti-leukemic specificity. The aim of this paper is to provide some data on the biology of acute lymphoblastic leukemia which are relevant in clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reactive Granulomatous Dermatitis: A Review of Palisaded Neutrophilic and Granulomatous Dermatitis, Interstitial Granulomatous Dermatitis, Interstitial Granulomatous Drug Reaction, and a Proposed Reclassification.

PubMed

Rosenbach, Misha; English, Joseph C

2015-07-01

The terms "palisaded neutrophilic and granulomatous dermatitis," "interstitial granulomatous dermatitis," and the subset "interstitial granulomatous drug reaction" are a source of confusion. There exists substantial overlap among the entities with few strict distinguishing features. We review the literature and highlight areas of distinction and overlap, and propose a streamlined diagnostic workup for patients presenting with this cutaneous reaction pattern. Because the systemic disease associations and requisite workup are similar, and the etiopathogenesis is poorly understood but likely similar among these entities, we propose the simplified unifying term "reactive granulomatous dermatitis" to encompass these entities. Copyright © 2015 Elsevier Inc. All rights reserved.

Health effects of toxic organic compounds from coal; the case Balkan endemic nephropathy (BEN)

USGS Publications Warehouse

Orem, W.H.; Tatu, C.A.

2001-01-01

Balkan endemic nephropathy (BEN) is a serious kidney disease that occurs only in clusters of rural villages located in tributary valleys of the Danube River in the Balkan Peninsula. It is believed that at least 25,000 persons are suffering from BEN or are suspected of having the disease and that the total number of people at risk may exceed 100,000. BEN was first described as a distinct medical entity in 1956, but it may have existed undescribed for many centuries. The geographic distribution of the disease has not changed significantly since the 1950's. Villages afflicted in the past continue to have cases of BEN, while villages with no history of BEN (some of which are only a few miles from affected villages) have remained free of this disease. Work by the U.S. Geological Survey and others in the early 1990's noted the close correspondence between the location of the affected villages and the occurrence of coal deposits, specifically lignites deposited in the Pliocene Epoch 5.3 million to 1.6 million years ago.

Graph theory enables drug repurposing--how a mathematical model can drive the discovery of hidden mechanisms of action.

PubMed

Gramatica, Ruggero; Di Matteo, T; Giorgetti, Stefano; Barbiani, Massimo; Bevec, Dorian; Aste, Tomaso

2014-01-01

We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases.

Tracheobronchial Manifestations of Aspergillus Infections

PubMed Central

Krenke, Rafal; Grabczak, Elzbieta M.

2011-01-01

Human lungs are constantly exposed to a large number of Aspergillus spores which are present in ambient air. These spores are usually harmless to immunocompetent subjects but can produce a symptomatic disease in patients with impaired antifungal defense. In a small percentage of patients, the trachea and bronchi may be the main or even the sole site of Aspergillus infection. The clinical entities that may develop in tracheobronchial location include saprophytic, allergic and invasive diseases. Although this review is focused on invasive Aspergillus tracheobronchial infections, some aspects of allergic and saprophytic tracheobronchial diseases are also discussed in order to present the whole spectrum of tracheobronchial aspergillosis. To be consistent with clinical practice, an approach basing on specific conditions predisposing to invasive Aspergillus tracheobronchial infections is used to present the differences in the clinical course and prognosis of these infections. Thus, invasive or potentially invasive Aspergillus airway diseases are discussed separately in three groups of patients: (1) lung transplant recipients, (2) highly immunocompromised patients with hematologic malignancies and/or patients undergoing hematopoietic stem cell transplantation, and (3) the remaining, less severely immunocompromised patients or even immunocompetent subjects. PMID:22194666

Recommendations for kidney disease guideline updating: a report by the KDIGO Methods Committee

PubMed Central

Uhlig, Katrin; Berns, Jeffrey S.; Carville, Serena; Chan, Wiley; Cheung, Michael; Guyatt, Gordon H.; Hart, Allyson; Lewis, Sandra Zelman; Tonelli, Marcello; Webster, Angela C.; Wilt, Timothy J.; Kasiske, Bertram L.

2017-01-01

Updating rather than de novo guideline development now accounts for the majority of guideline activities for many guideline development organizations, including Kidney Disease: Improving Global Outcomes (KDIGO), an international kidney disease guideline development entity that has produced guidelines on kidney diseases since 2008. Increasingly, guideline developers are moving away from updating at fixed intervals in favor of more flexible approaches that use periodic expert assessment of guideline currency (with or without an updated systematic review) to determine the need for updating. Determining the need for guideline updating in an efficient, transparent, and timely manner is challenging, and updating of systematic reviews and guidelines is labor intensive. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. This dynamic updating (sometimes referred to as a living guideline model) can be facilitated with the use of integrated electronic platforms that allow updating of specific recommendations. This report summarizes consensus-based recommendations from a panel of guideline methodology professionals on how to keep KDIGO guidelines up to date. PMID:26994574

A Deep Similarity Metric Learning Model for Matching Text Chunks to Spatial Entities

NASA Astrophysics Data System (ADS)

Ma, K.; Wu, L.; Tao, L.; Li, W.; Xie, Z.

2017-12-01

The matching of spatial entities with related text is a long-standing research topic that has received considerable attention over the years. This task aims at enrich the contents of spatial entity, and attach the spatial location information to the text chunk. In the data fusion field, matching spatial entities with the corresponding describing text chunks has a big range of significance. However, the most traditional matching methods often rely fully on manually designed, task-specific linguistic features. This work proposes a Deep Similarity Metric Learning Model (DSMLM) based on Siamese Neural Network to learn similarity metric directly from the textural attributes of spatial entity and text chunk. The low-dimensional feature representation of the space entity and the text chunk can be learned separately. By employing the Cosine distance to measure the matching degree between the vectors, the model can make the matching pair vectors as close as possible. Mearnwhile, it makes the mismatching as far apart as possible through supervised learning. In addition, extensive experiments and analysis on geological survey data sets show that our DSMLM model can effectively capture the matching characteristics between the text chunk and the spatial entity, and achieve state-of-the-art performance.

Extraction of relations between genes and diseases from text and large-scale data analysis: implications for translational research.

PubMed

Bravo, Àlex; Piñero, Janet; Queralt-Rosinach, Núria; Rautschka, Michael; Furlong, Laura I

2015-02-21

Current biomedical research needs to leverage and exploit the large amount of information reported in scientific publications. Automated text mining approaches, in particular those aimed at finding relationships between entities, are key for identification of actionable knowledge from free text repositories. We present the BeFree system aimed at identifying relationships between biomedical entities with a special focus on genes and their associated diseases. By exploiting morpho-syntactic information of the text, BeFree is able to identify gene-disease, drug-disease and drug-target associations with state-of-the-art performance. The application of BeFree to real-case scenarios shows its effectiveness in extracting information relevant for translational research. We show the value of the gene-disease associations extracted by BeFree through a number of analyses and integration with other data sources. BeFree succeeds in identifying genes associated to a major cause of morbidity worldwide, depression, which are not present in other public resources. Moreover, large-scale extraction and analysis of gene-disease associations, and integration with current biomedical knowledge, provided interesting insights on the kind of information that can be found in the literature, and raised challenges regarding data prioritization and curation. We found that only a small proportion of the gene-disease associations discovered by using BeFree is collected in expert-curated databases. Thus, there is a pressing need to find alternative strategies to manual curation, in order to review, prioritize and curate text-mining data and incorporate it into domain-specific databases. We present our strategy for data prioritization and discuss its implications for supporting biomedical research and applications. BeFree is a novel text mining system that performs competitively for the identification of gene-disease, drug-disease and drug-target associations. Our analyses show that mining only a small fraction of MEDLINE results in a large dataset of gene-disease associations, and only a small proportion of this dataset is actually recorded in curated resources (2%), raising several issues on data prioritization and curation. We propose that joint analysis of text mined data with data curated by experts appears as a suitable approach to both assess data quality and highlight novel and interesting information.

Hereditary and non-hereditary microangiopathies in the young. An up-date.

PubMed

Ringelstein, E Bernd; Kleffner, Ilka; Dittrich, Ralf; Kuhlenbäumer, Gregor; Ritter, Martin A

2010-12-15

In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total. Copyright © 2010 Elsevier B.V. All rights reserved.

DES-ncRNA: A knowledgebase for exploring information about human micro and long noncoding RNAs based on literature-mining.

PubMed

Salhi, Adil; Essack, Magbubah; Alam, Tanvir; Bajic, Vladan P; Ma, Lina; Radovanovic, Aleksandar; Marchand, Benoit; Schmeier, Sebastian; Zhang, Zhang; Bajic, Vladimir B

2017-07-03

Noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long ncRNAs (lncRNAs), are important players in diseases and emerge as novel drug targets. Thus, unraveling the relationships between ncRNAs and other biomedical entities in cells are critical for better understanding ncRNA roles that may eventually help develop their use in medicine. To support ncRNA research and facilitate retrieval of relevant information regarding miRNAs and lncRNAs from the plethora of published ncRNA-related research, we developed DES-ncRNA ( www.cbrc.kaust.edu.sa/des_ncrna ). DES-ncRNA is a knowledgebase containing text- and data-mined information from public scientific literature and other public resources. Exploration of mined information is enabled through terms and pairs of terms from 19 topic-specific dictionaries including, for example, antibiotics, toxins, drugs, enzymes, mutations, pathways, human genes and proteins, drug indications and side effects, mutations, diseases, etc. DES-ncRNA contains approximately 878,000 associations of terms from these dictionaries of which 36,222 (5,373) are with regards to miRNAs (lncRNAs). We provide several ways to explore information regarding ncRNAs to users including controlled generation of association networks as well as hypotheses generation. We show an example how DES-ncRNA can aid research on Alzheimer disease and suggest potential therapeutic role for Fasudil. DES-ncRNA is a powerful tool that can be used on its own or as a complement to the existing resources, to support research in human ncRNA. To our knowledge, this is the only knowledgebase dedicated to human miRNAs and lncRNAs derived primarily through literature-mining enabling exploration of a broad spectrum of associated biomedical entities, not paralleled by any other resource.

DES-ncRNA: A knowledgebase for exploring information about human micro and long noncoding RNAs based on literature-mining

PubMed Central

Salhi, Adil; Essack, Magbubah; Alam, Tanvir; Bajic, Vladan P.; Ma, Lina; Radovanovic, Aleksandar; Marchand, Benoit; Zhang, Zhang; Bajic, Vladimir B.

2017-01-01

ABSTRACT Noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long ncRNAs (lncRNAs), are important players in diseases and emerge as novel drug targets. Thus, unraveling the relationships between ncRNAs and other biomedical entities in cells are critical for better understanding ncRNA roles that may eventually help develop their use in medicine. To support ncRNA research and facilitate retrieval of relevant information regarding miRNAs and lncRNAs from the plethora of published ncRNA-related research, we developed DES-ncRNA (www.cbrc.kaust.edu.sa/des_ncrna). DES-ncRNA is a knowledgebase containing text- and data-mined information from public scientific literature and other public resources. Exploration of mined information is enabled through terms and pairs of terms from 19 topic-specific dictionaries including, for example, antibiotics, toxins, drugs, enzymes, mutations, pathways, human genes and proteins, drug indications and side effects, mutations, diseases, etc. DES-ncRNA contains approximately 878,000 associations of terms from these dictionaries of which 36,222 (5,373) are with regards to miRNAs (lncRNAs). We provide several ways to explore information regarding ncRNAs to users including controlled generation of association networks as well as hypotheses generation. We show an example how DES-ncRNA can aid research on Alzheimer disease and suggest potential therapeutic role for Fasudil. DES-ncRNA is a powerful tool that can be used on its own or as a complement to the existing resources, to support research in human ncRNA. To our knowledge, this is the only knowledgebase dedicated to human miRNAs and lncRNAs derived primarily through literature-mining enabling exploration of a broad spectrum of associated biomedical entities, not paralleled by any other resource. PMID:28387604

Going beyond the Evidence: Abstract Laws and Preschoolers' Responses to Anomalous Data

ERIC Educational Resources Information Center

Schulz, Laura E.; Goodman, Noah D.; Tenenbaum, Joshua B.; Jenkins, Adrianna C.

2008-01-01

Given minimal evidence about novel objects, children might learn only relationships among the specific entities, or they might make a more abstract inference, positing classes of entities and the relations that hold among those classes. Here we show that preschoolers (mean: 57 months) can use sparse data about perceptually unique objects to infer…

42 CFR 495.370 - Appeals process for a Medicaid provider receiving electronic health record incentive payments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the... in § 447.253(e) of this chapter for a provider or entity to appeal the following issues related to... entity) has an opportunity to challenge the State's determination under this Part by submitting documents...

78 FR 6794 - Fisheries Off West Coast States; Coastal Pelagic Species Fisheries; Annual Specifications

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... will impact these small entities in the same manner. The profitability of these vessels as a result of... Pacific sardine ex-vessel price per mt to conduct a profitability analysis because cost data for the... rule will decrease the effected small entities' potential profitability compared to last season, due to...

10 CFR 770.6 - May interested persons and entities request that real property at defense nuclear facilities be...

Code of Federal Regulations, 2010 CFR

2010-01-01

... property at defense nuclear facilities be transferred for economic development? 770.6 Section 770.6 Energy DEPARTMENT OF ENERGY TRANSFER OF REAL PROPERTY AT DEFENSE NUCLEAR FACILITIES FOR ECONOMIC DEVELOPMENT § 770.6... transferred for economic development? Any person or entity may request that specific real property be made...

Building Scalable Knowledge Graphs for Earth Science

NASA Technical Reports Server (NTRS)

Ramachandran, Rahul; Maskey, Manil; Gatlin, Patrick; Zhang, Jia; Duan, Xiaoyi; Miller, J. J.; Bugbee, Kaylin; Christopher, Sundar; Freitag, Brian

2017-01-01

Knowledge Graphs link key entities in a specific domain with other entities via relationships. From these relationships, researchers can query knowledge graphs for probabilistic recommendations to infer new knowledge. Scientific papers are an untapped resource which knowledge graphs could leverage to accelerate research discovery. Goal: Develop an end-to-end (semi) automated methodology for constructing Knowledge Graphs for Earth Science.

Risk Factors for Diverticulosis, Diverticulitis, Diverticular Perforation, and Bleeding: A Plea for More Subtle History Taking

PubMed Central

Böhm, Stephan K.

2015-01-01

Background Diverticulosis is a very common condition. Around 20% of diverticula carriers are believed to suffer from diverticular disease during their lifetime. This makes diverticular disease one of the clinically and economically most significant conditions in gastroenterology. The etiopathogenesis of diverticulosis and diverticular disease is not well understood. Epidemiological studies allowed to define risk factors for the development of diverticulosis and the different disease entities associated with it, in particular diverticulitis, perforation, and diverticular bleeding. Methods A comprehensive literature search was performed, and the current knowledge about risk factors for diverticulosis and associated conditions reviewed. Results Non-controllable risk factors like age, sex, and genetics, and controllable risk factors like foods, drinks, and physical activity were identified, as well as comorbidities and drugs which increase or decrease the risk of developing diverticula or of suffering from complications. In naming risk factors, it is of utmost importance to differentiate between diverticulosis and the different disease entities. Conclusion Risk factors for diverticulosis and diverticular disease may give a clue towards the possible etiopathogenesis of the conditions. More importantly, knowledge of comorbidities and particularly drugs conferring a risk for development of complicated disease is crucial for patient management. PMID:26989377

Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion.

PubMed

Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

2016-01-01

The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13.Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract. © The Author(s) 2016. Published by Oxford University Press.

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion*

PubMed Central

Wurm, Philipp; Spindelboeck, Walter; Krause, Robert; Plank, Johannes; Fuchs, Gottfried; Bashir, Mina; Petritsch, Wolfgang; Halwachs, Bettina; Langner, Cord; Högenauer, Christoph

2017-01-01

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition. PMID:28333760

Designing a training tool for imaging mental models

NASA Technical Reports Server (NTRS)

Dede, Christopher J.; Jayaram, Geetha

1990-01-01

The training process can be conceptualized as the student acquiring an evolutionary sequence of classification-problem solving mental models. For example a physician learns (1) classification systems for patient symptoms, diagnostic procedures, diseases, and therapeutic interventions and (2) interrelationships among these classifications (e.g., how to use diagnostic procedures to collect data about a patient's symptoms in order to identify the disease so that therapeutic measures can be taken. This project developed functional specifications for a computer-based tool, Mental Link, that allows the evaluative imaging of such mental models. The fundamental design approach underlying this representational medium is traversal of virtual cognition space. Typically intangible cognitive entities and links among them are visible as a three-dimensional web that represents a knowledge structure. The tool has a high degree of flexibility and customizability to allow extension to other types of uses, such a front-end to an intelligent tutoring system, knowledge base, hypermedia system, or semantic network.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tabatowski, K.; Roggli, V.L.; Fulkerson, W.J.

A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removalmore » of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material.« less

Chemical Entity Semantic Specification: Knowledge representation for efficient semantic cheminformatics and facile data integration

PubMed Central

2011-01-01

Background Over the past several centuries, chemistry has permeated virtually every facet of human lifestyle, enriching fields as diverse as medicine, agriculture, manufacturing, warfare, and electronics, among numerous others. Unfortunately, application-specific, incompatible chemical information formats and representation strategies have emerged as a result of such diverse adoption of chemistry. Although a number of efforts have been dedicated to unifying the computational representation of chemical information, disparities between the various chemical databases still persist and stand in the way of cross-domain, interdisciplinary investigations. Through a common syntax and formal semantics, Semantic Web technology offers the ability to accurately represent, integrate, reason about and query across diverse chemical information. Results Here we specify and implement the Chemical Entity Semantic Specification (CHESS) for the representation of polyatomic chemical entities, their substructures, bonds, atoms, and reactions using Semantic Web technologies. CHESS provides means to capture aspects of their corresponding chemical descriptors, connectivity, functional composition, and geometric structure while specifying mechanisms for data provenance. We demonstrate that using our readily extensible specification, it is possible to efficiently integrate multiple disparate chemical data sources, while retaining appropriate correspondence of chemical descriptors, with very little additional effort. We demonstrate the impact of some of our representational decisions on the performance of chemically-aware knowledgebase searching and rudimentary reaction candidate selection. Finally, we provide access to the tools necessary to carry out chemical entity encoding in CHESS, along with a sample knowledgebase. Conclusions By harnessing the power of Semantic Web technologies with CHESS, it is possible to provide a means of facile cross-domain chemical knowledge integration with full preservation of data correspondence and provenance. Our representation builds on existing cheminformatics technologies and, by the virtue of RDF specification, remains flexible and amenable to application- and domain-specific annotations without compromising chemical data integration. We conclude that the adoption of a consistent and semantically-enabled chemical specification is imperative for surviving the coming chemical data deluge and supporting systems science research. PMID:21595881

Chemical Entity Semantic Specification: Knowledge representation for efficient semantic cheminformatics and facile data integration.

PubMed

Chepelev, Leonid L; Dumontier, Michel

2011-05-19

Over the past several centuries, chemistry has permeated virtually every facet of human lifestyle, enriching fields as diverse as medicine, agriculture, manufacturing, warfare, and electronics, among numerous others. Unfortunately, application-specific, incompatible chemical information formats and representation strategies have emerged as a result of such diverse adoption of chemistry. Although a number of efforts have been dedicated to unifying the computational representation of chemical information, disparities between the various chemical databases still persist and stand in the way of cross-domain, interdisciplinary investigations. Through a common syntax and formal semantics, Semantic Web technology offers the ability to accurately represent, integrate, reason about and query across diverse chemical information. Here we specify and implement the Chemical Entity Semantic Specification (CHESS) for the representation of polyatomic chemical entities, their substructures, bonds, atoms, and reactions using Semantic Web technologies. CHESS provides means to capture aspects of their corresponding chemical descriptors, connectivity, functional composition, and geometric structure while specifying mechanisms for data provenance. We demonstrate that using our readily extensible specification, it is possible to efficiently integrate multiple disparate chemical data sources, while retaining appropriate correspondence of chemical descriptors, with very little additional effort. We demonstrate the impact of some of our representational decisions on the performance of chemically-aware knowledgebase searching and rudimentary reaction candidate selection. Finally, we provide access to the tools necessary to carry out chemical entity encoding in CHESS, along with a sample knowledgebase. By harnessing the power of Semantic Web technologies with CHESS, it is possible to provide a means of facile cross-domain chemical knowledge integration with full preservation of data correspondence and provenance. Our representation builds on existing cheminformatics technologies and, by the virtue of RDF specification, remains flexible and amenable to application- and domain-specific annotations without compromising chemical data integration. We conclude that the adoption of a consistent and semantically-enabled chemical specification is imperative for surviving the coming chemical data deluge and supporting systems science research.

Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review.

PubMed

Koniari, Katerina; Mahera, Helen; Nikolaou, Marinos; Chatzis, Odysseas; Glezakou, Ourania; Magiasis, Vasilios; Kiratzis, Georgios

2011-01-01

Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.

Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

PubMed

Raess, Philipp W; Habashi, Arlette; El Rassi, Edward; Milas, Mira; Sauer, David A; Troxell, Megan L

2015-05-01

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Acute mesenteric ischemia: guidelines of the World Society of Emergency Surgery.

PubMed

Bala, Miklosh; Kashuk, Jeffry; Moore, Ernest E; Kluger, Yoram; Biffl, Walter; Gomes, Carlos Augusto; Ben-Ishay, Offir; Rubinstein, Chen; Balogh, Zsolt J; Civil, Ian; Coccolini, Federico; Leppaniemi, Ari; Peitzman, Andrew; Ansaloni, Luca; Sugrue, Michael; Sartelli, Massimo; Di Saverio, Salomone; Fraga, Gustavo P; Catena, Fausto

2017-01-01

Acute mesenteric ischemia (AMI) is typically defined as a group of diseases characterized by an interruption of the blood supply to varying portions of the small intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process will eventuate in life threatening intestinal necrosis. The incidence is low, estimated at 0.09-0.2% of all acute surgical admissions. Therefore, although the entity is an uncommon cause of abdominal pain, diligence is always required because if untreated, mortality has consistently been reported in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment and are essential to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques may provide new options. Thus, we believe that a current position paper from World Society of Emergency Surgery (WSES) is warranted, in order to put forth the most recent and practical recommendations for diagnosis and treatment of AMI. This review will address the concepts of AMI with the aim of focusing on specific areas where early diagnosis and management hold the strongest potential for improving outcomes in this disease process. Some of the key points include the prompt use of CT angiography to establish the diagnosis, evaluation of the potential for revascularization to re-establish blood flow to ischemic bowel, resection of necrotic intestine, and use of damage control techniques when appropriate to allow for re-assessment of bowel viability prior to definitive anastomosis and abdominal closure.

Selected aspects of polycystic ovarian disease.

PubMed

Goldzieher, J W; Young, R L

1992-03-01

Although there is general agreement about the polycystic ovary as an anatomic entity, a classic description of an associated syndrome remains elusive. This lack of definition, however, has not impeded clinical investigation. This article focuses on the diagnosis, pathogenesis, hypotheses, and treatment of polycystic ovarian disease.

CHEMICAL PRIORITIZATION FOR DEVELOPMENTAL ...

EPA Pesticide Factsheets

Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals, and has been used as an anchor for predictive modeling of ToxCast™ data. Scaling to thousands of untested chemicals requires another approach. ToxPlorer™ was developed as a tool to query and extract specific facts about defined biological entities from the open scientific literature and to coherently synthesize relevant knowledge about relationships, pathways and processes in toxicity. Here, we investigated the specific application of ToxPlorer to weighting HTS assay targets for relevance to developmental defects as defined in the literature. First, we systemically analyzed 88,193 Pubmed abstracts selected by bulk query using harmonized terminology for 862 developmental endpoints (www.devtox.net) and 364,334 dictionary term entities in our VT-KB (virtual tissues knowledgebase). We specifically focused on entities corresponding to genes/proteins mapped across of >500 ToxCast HTS assays. The 88,193 devtox abstracts mentioned 244 gene/protein entities in an aggregated total of ~8,000 occurrences. Each of the 244 assays was scored and weighted by the number of devtox articles and relevance to developmental processes. This score was used as a feature for chemical prioritization by Toxic

Preserving Patient Privacy When Sharing Same-Disease Data.

PubMed

Liu, Xiaoping; Li, Xiao-Bai; Motiwalla, Luvai; Li, Wenjun; Zheng, Hua; Franklin, Patricia D

2016-10-01

Medical and health data are often collected for studying a specific disease. For such same-disease microdata, a privacy disclosure occurs as long as an individual is known to be in the microdata. Individuals in same-disease microdata are thus subject to higher disclosure risk than those in microdata with different diseases. This important problem has been overlooked in data-privacy research and practice, and no prior study has addressed this problem. In this study, we analyze the disclosure risk for the individuals in same-disease microdata and propose a new metric that is appropriate for measuring disclosure risk in this situation. An efficient algorithm is designed and implemented for anonymizing same-disease data to minimize the disclosure risk while keeping data utility as good as possible. An experimental study was conducted on real patient and population data. Experimental results show that traditional reidentification risk measures underestimate the actual disclosure risk for the individuals in same-disease microdata and demonstrate that the proposed approach is very effective in reducing the actual risk for same-disease data. This study suggests that privacy protection policy and practice for sharing medical and health data should consider not only the individuals' identifying attributes but also the health and disease information contained in the data. It is recommended that data-sharing entities employ a statistical approach, instead of the HIPAA's Safe Harbor policy, when sharing same-disease microdata.

Preserving Patient Privacy When Sharing Same-Disease Data

PubMed Central

LIU, XIAOPING; LI, XIAO-BAI; MOTIWALLA, LUVAI; LI, WENJUN; ZHENG, HUA; FRANKLIN, PATRICIA D.

2016-01-01

Medical and health data are often collected for studying a specific disease. For such same-disease microdata, a privacy disclosure occurs as long as an individual is known to be in the microdata. Individuals in same-disease microdata are thus subject to higher disclosure risk than those in microdata with different diseases. This important problem has been overlooked in data-privacy research and practice, and no prior study has addressed this problem. In this study, we analyze the disclosure risk for the individuals in same-disease microdata and propose a new metric that is appropriate for measuring disclosure risk in this situation. An efficient algorithm is designed and implemented for anonymizing same-disease data to minimize the disclosure risk while keeping data utility as good as possible. An experimental study was conducted on real patient and population data. Experimental results show that traditional reidentification risk measures underestimate the actual disclosure risk for the individuals in same-disease microdata and demonstrate that the proposed approach is very effective in reducing the actual risk for same-disease data. This study suggests that privacy protection policy and practice for sharing medical and health data should consider not only the individuals’ identifying attributes but also the health and disease information contained in the data. It is recommended that data-sharing entities employ a statistical approach, instead of the HIPAA's Safe Harbor policy, when sharing same-disease microdata. PMID:27867450

A database of natural products and chemical entities from marine habitat

PubMed Central

Babu, Padavala Ajay; Puppala, Suma Sree; Aswini, Satyavarapu Lakshmi; Vani, Metta Ramya; Kumar, Chinta Narasimha; Prasanna, Tallapragada

2008-01-01

Marine compound database consists of marine natural products and chemical entities, collected from various literature sources, which are known to possess bioactivity against human diseases. The database is constructed using html code. The 12 categories of 182 compounds are provided with the source, compound name, 2-dimensional structure, bioactivity and clinical trial information. The database is freely available online and can be accessed at http://www.progenebio.in/mcdb/index.htm PMID:19238254

Imaging of non-neoplastic duodenal diseases. A pictorial review with emphasis on MDCT.

PubMed

Juanpere, Sergi; Valls, Laia; Serra, Isabel; Osorio, Margarita; Gelabert, Arantxa; Maroto, Albert; Pedraza, Salvador

2018-04-01

A wide spectrum of abnormalities can affect the duodenum, ranging from congenital anomalies to traumatic and inflammatory entities. The location of the duodenum and its close relationship with other organs make it easy to miss or misinterpret duodenal abnormalities on cross-sectional imaging. Endoscopy has largely supplanted fluoroscopy for the assessment of the duodenal lumen. Cross-sectional imaging modalities, especially multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI), enable comprehensive assessment of the duodenum and surrounding viscera. Although overlapping imaging findings can make it difficult to differentiate between some lesions, characteristic features may suggest a specific diagnosis in some cases. Familiarity with pathologic conditions that can affect the duodenum and with the optimal MDCT and MRI techniques for studying them can help ensure diagnostic accuracy in duodenal diseases. The goal of this pictorial review is to illustrate the most common non-malignant duodenal processes. Special emphasis is placed on MDCT features and their endoscopic correlation as well as on avoiding the most common pitfalls in the evaluation of the duodenum. • Cross-sectional imaging modalities enable comprehensive assessment of duodenum diseases. • Causes of duodenal obstruction include intraluminal masses, inflammation and hematomas. • Distinguishing between tumour and groove pancreatitis can be challenging by cross-sectional imaging. • Infectious diseases of the duodenum are difficult to diagnose, as the findings are not specific. • The most common cause of nonvariceal upper gastrointestinal bleeding is peptic ulcer disease.

A corpus for plant-chemical relationships in the biomedical domain.

PubMed

Choi, Wonjun; Kim, Baeksoo; Cho, Hyejin; Lee, Doheon; Lee, Hyunju

2016-09-20

Plants are natural products that humans consume in various ways including food and medicine. They have a long empirical history of treating diseases with relatively few side effects. Based on these strengths, many studies have been performed to verify the effectiveness of plants in treating diseases. It is crucial to understand the chemicals contained in plants because these chemicals can regulate activities of proteins that are key factors in causing diseases. With the accumulation of a large volume of biomedical literature in various databases such as PubMed, it is possible to automatically extract relationships between plants and chemicals in a large-scale way if we apply a text mining approach. A cornerstone of achieving this task is a corpus of relationships between plants and chemicals. In this study, we first constructed a corpus for plant and chemical entities and for the relationships between them. The corpus contains 267 plant entities, 475 chemical entities, and 1,007 plant-chemical relationships (550 and 457 positive and negative relationships, respectively), which are drawn from 377 sentences in 245 PubMed abstracts. Inter-annotator agreement scores for the corpus among three annotators were measured. The simple percent agreement scores for entities and trigger words for the relationships were 99.6 and 94.8 %, respectively, and the overall kappa score for the classification of positive and negative relationships was 79.8 %. We also developed a rule-based model to automatically extract such plant-chemical relationships. When we evaluated the rule-based model using the corpus and randomly selected biomedical articles, overall F-scores of 68.0 and 61.8 % were achieved, respectively. We expect that the corpus for plant-chemical relationships will be a useful resource for enhancing plant research. The corpus is available at http://combio.gist.ac.kr/plantchemicalcorpus .

"Dualities of interest": the inter-organizational relationships between disease-specific nonprofits and the pharmaceutical industry.

PubMed

Paluzzi, Joan E

2012-01-01

Health care and biomedical research environments in the United States are largely characterized by strategic relational practices conducted beyond the public gaze. The very nature of health care has been widely reconceptualized from a response to physical/biological imperatives regulated by health promotion and the epidemiological distribution of diseases to profit/market imperatives regulated by "product/brand" promotion and market dynamics. At critical decision points throughout the system, we find the multinational pharmaceutical industry wielding the influence that its wealth and power have bought. This study contributes to the growing body of work that seeks to illuminate the relationships between the pharmaceutical industry and the various entities that constitute the U.S. health and research systems. Through the use of case studies, it examines the relationships between the multinational pharmaceutical industry and the large disease-specific public and professional nonprofit organizations. It explores several questions, including: Is the concept of what constitutes a conflict of interest being purposefully manipulated? Is the public benevolence afforded to nonprofits extended to their corporate partners in ways that preclude critical oversight of relational dynamics? And are public donations, solicited by and given in good faith to these organizations, inevitably serving the economic interests and profits of donor pharmaceutical companies?

Eosinophilic Mucin Otomastoiditis and Otopolyposis: A Progressive Form of Eosinophilic Otitis Media.

PubMed

Azadarmaki, Roya; Westra, William; Prasad, Sanjay

2015-09-01

The purpose of this study is to introduce and define a disease entity on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis and otopolyposis. A case of a 66-year-old woman with complicated chronic otitis media is reported. A literature review of the National Library of Medicine's online database, with a focus on eosinophilic otitis media and eosinophilic mucin rhinosinusitis, was performed. The authors report the case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis, nasal polyposis, and chronic otitis media who presented with allergic middle ear mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of otic polyps and steroid therapy. Eosinophilic mucin otomastoiditis with otopolyposis is a disease entity on a continuum of eosinophilic otitis media. This disease process shares similarities with eosinophilic mucin rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures. © The Author(s) 2015.

[National health fund and morbidity-based risk structure equalization with focus on haemophilia].

PubMed

König, T

2010-11-01

The Gesundheitsfonds (national health fund) was established in Germany on January 1st, 2009, in combination with the morbidity-based risk structure equalization (RSA) in order to manage the cash flow between the statutory health insurances. The RSA equalizes income differences due to the varying levels of contributory income of the members of a health insurance (basic wage totals) and expenditure differences due to varying distribution of morbidity risks across different health insurances, as well as the varying numbers of non-contributing insured family members. Additionally, insured persons are allocated to morbidity groups according to a classification model based upon diagnoses and prescriptions anticipating medical expenses in the subsequent year. Haemophilia falls, among 80 disease entities, in the morbidity group which generates the highest risk supplement. Matching of prescribed drugs with disease entities facilitates disease grading and improves the accuracy of risk supplements.

Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity

PubMed Central

Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

2015-01-01

Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature. PMID:26980976

Circulating exosomes as new biomarkers for brain disease and injury

NASA Astrophysics Data System (ADS)

Graner, Michael W.; Epple, Laura M.; Dusto, Nathaniel L.; Lencioni, Alex M.; Nega, Meheret; Herring, Matthew; Winston, Ben; Madsen, Helen; Bemis, Lynne T.; Anchordoquy, Thomas J.

2013-05-01

Brain diseases such as cancers, neurodegenerative disorders, or trauma are frequently diagnosed with imaging modalities and sometimes with intracranial biopsies. Treatment response is similarly monitored, along with clinical indications. While these technologies provide important windows into the disease state, they fail to provide us a detailed molecular portrait of the disease and of the changes taking place during therapy. Exosomes are virus-sized nanovesicles derived from the endosomal system and are released extracellularly from essentially all cell types. Exosomes contain intracellular entities (proteins, nucleic acids, metabolites), membrane proteins and lipids, and even extracellular proteins bound to them. Exosomes may be considered as mini-surrogates of their cells of origin, with some content common to all cells/exosomes, but some of the content would be cell-specific. These vesicles are found in all biofluids in humans, and are thus accessible to "liquid biopsy" with harvest of vesicles from such fluids. Current challenges are to identify disease-related markers or panels of markers to distinguish the disease state. Here we will show examples of brain tumor markers found in/on exosomes from cell culture and patient sera, and we will suggest that aspects of the biology of disease may have a relevant place in the search for biomarkers.

Field emission chemical sensor

DOEpatents

Panitz, J.A.

1983-11-22

A field emission chemical sensor for specific detection of a chemical entity in a sample includes a closed chamber enclosing two field emission electrode sets, each field emission electrode set comprising (a) an electron emitter electrode from which field emission electrons can be emitted when an effective voltage is connected to the electrode set; and (b) a collector electrode which will capture said electrons emitted from said emitter electrode. One of the electrode sets is passive to the chemical entity and the other is active thereto and has an active emitter electrode which will bind the chemical entity when contacted therewith.

Challenges in pulmonary fibrosis · 3: Cystic lung disease

PubMed Central

Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

2007-01-01

Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

Developing microRNA therapeutics.

PubMed

van Rooij, Eva; Purcell, Angela L; Levin, Arthur A

2012-02-03

Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.

Virus diseases of farmed shrimp in the Western Hemisphere (the Americas): a review.

PubMed

Lightner, D V

2011-01-01

Penaeid shrimp aquaculture is an important industry in the Americas, and the industry is based almost entirely on the culture of the Pacific White Shrimp, Litopenaeus vannamei. Western Hemisphere shrimp farmers in 14 countries in 2004 produced more than 200,000 metric tons of shrimp, generated more than $2 billion in revenue, and employed more than 500,000 people. Disease has had a major impact on shrimp aquaculture in the Americas since it became a significant commercial entity in the 1970s. Diseases due to viruses, rickettsial-like bacteria, true bacteria, protozoa, and fungi have emerged as major diseases of farmed shrimp in the region. Many of the bacterial, fungal and protozoan caused diseases are managed using improved culture practices, routine sanitation, and the use of chemotherapeutics. However, the virus diseases have been far more problematic to manage and they have been responsible for the most costly epizootics. Examples include the Taura syndrome pandemic that began in 1991-1992 when the disease emerged in Ecuador, and the subsequent White Spot Disease pandemic that followed its introduction to Central America from Asia in 1999. Because of their socioeconomic significance to shrimp farming, seven of the nine crustacean diseases listed by the World Animal Organization (OIE) are virus diseases of shrimp. Of the seven virus diseases of penaeid shrimp, five are native to the Americas or have become enzootic following their introduction. The shrimp virus diseases in the Americas are increasingly being managed by exclusion using a combination of biosecurity and the practice of culturing domesticated specific pathogen-free (SPF) stocks or specific pathogen-resistant (SPR) stocks. Despite the significant challenges posed by disease, the shrimp farming industry of the Americas has responded to the challenges posed by disease and it has developed methods to manage its diseases and mature into a sustainable industry. Copyright © 2010 Elsevier Inc. All rights reserved.

Scalable Entity-Based Modeling of Population-Based Systems, Final LDRD Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cleary, A J; Smith, S G; Vassilevska, T K

2005-01-27

The goal of this project has been to develop tools, capabilities and expertise in the modeling of complex population-based systems via scalable entity-based modeling (EBM). Our initial focal application domain has been the dynamics of large populations exposed to disease-causing agents, a topic of interest to the Department of Homeland Security in the context of bioterrorism. In the academic community, discrete simulation technology based on individual entities has shown initial success, but the technology has not been scaled to the problem sizes or computational resources of LLNL. Our developmental emphasis has been on the extension of this technology to parallelmore » computers and maturation of the technology from an academic to a lab setting.« less

Fungal diseases of amphibians: an overview.

PubMed

Paré, Jean A

2003-05-01

Clinicians should be familiar with the most common fungal diseases of amphibians. Because lesions in mycotic diseases are nonspecific, a diagnosis cannot be established solely on the basis of clinical presentation. Bacterial, mycobacterial, chlamydial, and parasitic infections, and toxic or environmental conditions may mimic mycotic disease to various extents. Furthermore, mycoses may be masked by overwhelming secondary bacterial infection and therefore remain undiagnosed. Skin scrapings, impression smears, biopsies, and fungal culture are all useful tools in confirming or dismissing a diagnosis of mycosis. Whenever possible, an effort should be made to forward samples and biopsies for culture to appropriate laboratories. Providing the laboratory with a tentative etiologic diagnosis may allow for specific selection of more specific agars and culture conditions and maximize the chances of recovering the fungus from lesions. Identification to species level should also be encouraged, if progress is to be made in the understanding of mycoses in amphibians. The morphology of an isolate should be consistent with the microscopic features of the fungus in histological sections of affected tissues, if it is to be firmly incriminated as the cause of disease. A complete necropsy should be conducted on animals that die or are found dead, and, ideally, isolates from confirmed cases of fungal infection should be deposited in scientific collections, so that they are available for later studies. In addendum, readers should be aware that there is recent evidence to suggest that at least some published cases of amphibian basidiobolomycosis were in fact cases of chytridiomycosis [38], and therefore the validity of basidiobolomycosis as a disease entity in amphibians may be revisited in the years to come.

Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

PubMed Central

Ramaiah, Santhosh Kumar Vankayala; Günthner, Roman; Lech, Maciej; Anders, Hans-Joachim

2013-01-01

The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs) are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling. PMID:23803655

Communication about absent entities in great apes and human infants.

PubMed

Bohn, Manuel; Call, Josep; Tomasello, Michael

2015-12-01

There is currently debate about the extent to which non-linguistic beings such as human infants and great apes are capable of absent reference. In a series of experiments we investigated the flexibility and specificity of great apes' (N=36) and 12 month-old infants' (N=40) requests for absent entities. Subjects had the choice between requesting visible objects directly and using the former location of a depleted option to request more of these now-absent entities. Importantly, we systematically varied the quality of the present and absent options. We found that great apes as well as human infants flexibly adjusted their requests for absent entities to these contextual variations and only requested absent entities when the visible option was of lower quality than the absent option. These results suggest that the most basic cognitive capacities for absent reference do not depend on language and are shared by humans and their closest living relatives. Copyright © 2015 Elsevier B.V. All rights reserved.

Mesh Oriented datABase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tautges, Timothy J.

MOAB is a component for representing and evaluating mesh data. MOAB can store stuctured and unstructured mesh, consisting of elements in the finite element "zoo". The functional interface to MOAB is simple yet powerful, allowing the representation of many types of metadata commonly found on the mesh. MOAB is optimized for efficiency in space and time, based on access to mesh in chunks rather than through individual entities, while also versatile enough to support individual entity access. The MOAB data model consists of a mesh interface instance, mesh entities (vertices and elements), sets, and tags. Entities are addressed through handlesmore » rather than pointers, to allow the underlying representation of an entity to change without changing the handle to that entity. Sets are arbitrary groupings of mesh entities and other sets. Sets also support parent/child relationships as a relation distinct from sets containing other sets. The directed-graph provided by set parent/child relationships is useful for modeling topological relations from a geometric model or other metadata. Tags are named data which can be assigned to the mesh as a whole, individual entities, or sets. Tags are a mechanism for attaching data to individual entities and sets are a mechanism for describing relations between entities; the combination of these two mechanisms isa powerful yet simple interface for representing metadata or application-specific data. For example, sets and tags can be used together to describe geometric topology, boundary condition, and inter-processor interface groupings in a mesh. MOAB is used in several ways in various applications. MOAB serves as the underlying mesh data representation in the VERDE mesh verification code. MOAB can also be used as a mesh input mechanism, using mesh readers induded with MOAB, or as a t’anslator between mesh formats, using readers and writers included with MOAB.« less

Genetic Analysis of Pathways to Parkinson Disease

PubMed Central

Hardy, John

2010-01-01

In this review I outline the arguments as to whether we should consider Parkinson disease one or more than one entity and discuss genetic findings from Mendelian and whole-genome association analysis in that context. I discuss what the demonstration of disease spread implies for our analysis of the genetic and epidemiologic risk factors for disease and outline the surprising fact that we now have genetically identified on the order of half our risk for developing the disease. PMID:20955928

Efficient chemical-disease identification and relationship extraction using Wikipedia to improve recall

PubMed Central

Lowe, Daniel M.; O’Boyle, Noel M.; Sayle, Roger A.

2016-01-01

Awareness of the adverse effects of chemicals is important in biomedical research and healthcare. Text mining can allow timely and low-cost extraction of this knowledge from the biomedical literature. We extended our text mining solution, LeadMine, to identify diseases and chemical-induced disease relationships (CIDs). LeadMine is a dictionary/grammar-based entity recognizer and was used to recognize and normalize both chemicals and diseases to Medical Subject Headings (MeSH) IDs. The disease lexicon was obtained from three sources: MeSH, the Disease Ontology and Wikipedia. The Wikipedia dictionary was derived from pages with a disease/symptom box, or those where the page title appeared in the lexicon. Composite entities (e.g. heart and lung disease) were detected and mapped to their composite MeSH IDs. For CIDs, we developed a simple pattern-based system to find relationships within the same sentence. Our system was evaluated in the BioCreative V Chemical–Disease Relation task and achieved very good results for both disease concept ID recognition (F1-score: 86.12%) and CIDs (F1-score: 52.20%) on the test set. As our system was over an order of magnitude faster than other solutions evaluated on the task, we were able to apply the same system to the entirety of MEDLINE allowing us to extract a collection of over 250 000 distinct CIDs. PMID:27060160

Idiopathic Noncirrhotic Portal Hypertension: An Appraisal

PubMed Central

Lee, Hwajeong; Rehman, Aseeb Ur; Fiel, M. Isabel

2016-01-01

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity. PMID:26563701

Towards an Obesity-Cancer Knowledge Base: Biomedical Entity Identification and Relation Detection

PubMed Central

Lossio-Ventura, Juan Antonio; Hogan, William; Modave, François; Hicks, Amanda; Hanna, Josh; Guo, Yi; He, Zhe; Bian, Jiang

2017-01-01

Obesity is associated with increased risks of various types of cancer, as well as a wide range of other chronic diseases. On the other hand, access to health information activates patient participation, and improve their health outcomes. However, existing online information on obesity and its relationship to cancer is heterogeneous ranging from pre-clinical models and case studies to mere hypothesis-based scientific arguments. A formal knowledge representation (i.e., a semantic knowledge base) would help better organizing and delivering quality health information related to obesity and cancer that consumers need. Nevertheless, current ontologies describing obesity, cancer and related entities are not designed to guide automatic knowledge base construction from heterogeneous information sources. Thus, in this paper, we present methods for named-entity recognition (NER) to extract biomedical entities from scholarly articles and for detecting if two biomedical entities are related, with the long term goal of building a obesity-cancer knowledge base. We leverage both linguistic and statistical approaches in the NER task, which supersedes the state-of-the-art results. Further, based on statistical features extracted from the sentences, our method for relation detection obtains an accuracy of 99.3% and a f-measure of 0.993. PMID:28503356

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

PubMed

Hannemann, A; Rees, D C; Tewari, S; Gibson, J S

2015-11-01

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

Proximal tubulopathies associated with monoclonal light chains: the spectrum of clinicopathologic manifestations and molecular pathogenesis.

PubMed

Herrera, Guillermo A

2014-10-01

Lesions associated with monoclonal light and heavy chains display a variety of glomerular, tubular interstitial, and vascular manifestations. While some of the entities are well recognized, including light and heavy chain deposition diseases, AL (light chain) and AH (heavy chain) amyloidosis, and light chain ("myeloma") cast nephropathy, other lesions centered on proximal tubules are much less accurately identified, properly diagnosed, and adequately understood in terms of pathogenesis and molecular mechanisms involved. These proximal tubule-centered lesions are typically associated with monoclonal light chains and have not been reported in patients with circulating monoclonal heavy chains. To determine the incidence of proximal tubulopathies in a series of patients with monoclonal light chain-related renal lesions and characterize them with an emphasis on clinical correlations and elucidation of molecular mechanisms involved in their pathogenesis. A study of 5410 renal biopsies with careful evaluation of light microscopic, immunofluorescence, and electron microscopic findings was conducted to identify these monoclonal light/heavy chain-related lesions. In selected cases, ultrastructural immunolabeling was performed to better illustrate and understand molecular mechanisms involved or to resolve specific diagnostic difficulties. In all, 2.5% of the biopsies were diagnosed as demonstrating renal pathology associated with monoclonal light or heavy chains. Of these, approximately 46% were classified as proximal tubule-centered lesions, also referred to as monoclonal light chain-associated proximal tubulopathies. These proximal tubulopathies were divided into 4 groups defined by characteristic immunomorphologic manifestations associated with specific clinical settings. These are important lesions whose recognition in the different clinical settings is extremely important for patients' clinical management, therapeutic purposes, and prognosis. These entities have been segregated into 4 distinct variants, conceptualized morphologically and clinically. Specific mechanisms involved in their pathogenesis are proposed.

43 CFR 429.26 - When may Reclamation reduce or waive costs or fees?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false When may Reclamation reduce or waive costs... the value of the use ✓ ✓ ✓ (3) The use will benefit the general public with no specific entity or... ✓ ✓ ✓ (5) Applicant is a non-profit or educational entity and the use provides a general public benefit...

Field emission chemical sensor for receptor/binder, such as antigen/antibody

DOEpatents

Panitz, John A.

1986-01-01

A field emission chemical sensor for specific detection of a chemical entity in a sample includes a closed chamber enclosing two field emission electrode sets, each field emission electrode set comprising (a) an electron emitter electrode from which field emission electrons can be emitted when an effective voltage is connected to the electrode set; and (b) a collector electrode which will capture said electrons emitted from said emitter electrode. One of the electrode sets is passive to the chemical entity and the other is active thereto and has an active emitter electrode which will bind the chemical entity when contacted therewith.

[A relational database to store Poison Centers calls].

PubMed

Barelli, Alessandro; Biondi, Immacolata; Tafani, Chiara; Pellegrini, Aristide; Soave, Maurizio; Gaspari, Rita; Annetta, Maria Giuseppina

2006-01-01

Italian Poison Centers answer to approximately 100,000 calls per year. Potentially, this activity is a huge source of data for toxicovigilance and for syndromic surveillance. During the last decade, surveillance systems for early detection of outbreaks have drawn the attention of public health institutions due to the threat of terrorism and high-profile disease outbreaks. Poisoning surveillance needs the ongoing, systematic collection, analysis, interpretation, and dissemination of harmonised data about poisonings from all Poison Centers for use in public health action to reduce morbidity and mortality and to improve health. The entity-relationship model for a Poison Center relational database is extremely complex and not studied in detail. For this reason, not harmonised data collection happens among Italian Poison Centers. Entities are recognizable concepts, either concrete or abstract, such as patients and poisons, or events which have relevance to the database, such as calls. Connectivity and cardinality of relationships are complex as well. A one-to-many relationship exist between calls and patients: for one instance of entity calls, there are zero, one, or many instances of entity patients. At the same time, a one-to-many relationship exist between patients and poisons: for one instance of entity patients, there are zero, one, or many instances of entity poisons. This paper shows a relational model for a poison center database which allows the harmonised data collection of poison centers calls.

DDx: diagnostic assistance for the radiologist using PACS

NASA Astrophysics Data System (ADS)

Haynor, David R.

1993-09-01

A potentially valuable tool in medical imaging is the development, and integration with PACS, of systems which enhance the interpretive accuracy of the user -- his ability, given a set of findings (in the broad sense, including clinical information about the patient as well as characteristics of the lesion being analyzed), to assign the proper disease label, or diagnosis, to them. Such systems, which we call here interpretive tools (IT), contain a variety of types of information about diseases and their radiologic diagnosis. They can contain information about large numbers of diseases, including statistical information (incidence, characteristic anatomical locations, association with age and gender or with other diseases, probabilities of various findings given a disease), textual information (description of diseases, treatment, literature references, lists of other entities that might be confused with the disease of interest, additional diagnostic points that may not be represented, or even representable, within IT), and image-based information (typical and atypical examples for each entity and radiographic finding, examples of normal anatomy). These databases can be used both for teaching purposes and as a tool for improving interpretive accuracy [Swett, 1987]. This paper describes some of the requirements for these databases and then discusses early work on the implementation of DDx, an IT whose domain is neuroradiology.

Commercial technologies from the SP-100 program

NASA Astrophysics Data System (ADS)

Truscello, Vincent C.; Fujita, Toshio; Mondt, Jack F.

1995-01-01

For more than a decade, the Jet Propulsion Labortory (JPL) and Los Alamos National Laboratory (LANL) have managed a multi-agency funded effort to develop a space reactor power system. This SP-100 Program has developed technologies required for space power systems that can be implemented in the industrial and commercial sectors to improve our competitiveness in the global economy. Initial steps taken to transfer this technology from the laboratories to industrial and commercial entities within the United States include: (1) identifying specific technologies having commercial potential; (2) distributing information describing the identified technologies and interacting with interested commercial and industrial entities to develop application-specific details and requirements; and (3) providing a technological data base that leads to transfer of technology or the forming of teaming arrangements to accomplish the transfer by tailoring the technology to meet application-specific requirements. SP-100 technologies having commercial potential encompass fabrication processes, devices, and components. Examples are a process for bonding refractory metals to graphite, a device to sense the position of an actuator and a component to enable rotating machines to operate without supplying lubrication ( a self-lubricating ball bearing). Shortly after the National Aeronautics and Space Administration (NASA) Regional Technology Transfer Centers widely disseminated information covering SP-100 technologies, over one hundred expressions of interest were received. These early responses indicate that there is a large potential benefit in transferring SP-100 technology. Interactions with industrial and commercial entities have identified a substantial need for creating teaming arrangements involving the interested entity and personnel from laboratories and their contractors, who have the knowledge and ability to tailor the technology to meet application-specific requirements.

Difficulties in differentiating thin basement membrane disease from Alport syndrome.

PubMed

Żurawski, Jakub; Burchardt, Paweł; Seget, Monika; Moczko, Jerzy; Woźniak, Aldona; Grochowalski, Marcin; Salwa-Żurawska, Wiesława

We examined a group of 83 patients (57 children and 26 adults) with thin basement membrane disease and 17 patients with Alport syndrome. We compared the clinical data and, above all, the morphological patterns of both disease entities, with particular focus on not very advanced changes which might lead to a misdiagnosis due to the non-detection of the early stages of Alport syndrome.

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

PubMed

Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

2017-08-31

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

Selective impairment of hippocampus and posterior hub areas in Alzheimer's disease: an MEG-based multiplex network study.

PubMed

Yu, Meichen; Engels, Marjolein M A; Hillebrand, Arjan; van Straaten, Elisabeth C W; Gouw, Alida A; Teunissen, Charlotte; van der Flier, Wiesje M; Scheltens, Philip; Stam, Cornelis J

2017-05-01

Although frequency-specific network analyses have shown that functional brain networks are altered in patients with Alzheimer's disease, the relationships between these frequency-specific network alterations remain largely unknown. Multiplex network analysis is a novel network approach to study complex systems consisting of subsystems with different types of connectivity patterns. In this study, we used magnetoencephalography to integrate five frequency-band specific brain networks in a multiplex framework. Previous structural and functional brain network studies have consistently shown that hub brain areas are selectively disrupted in Alzheimer's disease. Accordingly, we hypothesized that hub regions in the multiplex brain networks are selectively targeted in patients with Alzheimer's disease in comparison to healthy control subjects. Eyes-closed resting-state magnetoencephalography recordings from 27 patients with Alzheimer's disease (60.6 ± 5.4 years, 12 females) and 26 controls (61.8 ± 5.5 years, 14 females) were projected onto atlas-based regions of interest using beamforming. Subsequently, source-space time series for both 78 cortical and 12 subcortical regions were reconstructed in five frequency bands (delta, theta, alpha 1, alpha 2 and beta band). Multiplex brain networks were constructed by integrating frequency-specific magnetoencephalography networks. Functional connections between all pairs of regions of interests were quantified using a phase-based coupling metric, the phase lag index. Several multiplex hub and heterogeneity metrics were computed to capture both overall importance of each brain area and heterogeneity of the connectivity patterns across frequency-specific layers. Different nodal centrality metrics showed consistently that several hub regions, particularly left hippocampus, posterior parts of the default mode network and occipital regions, were vulnerable in patients with Alzheimer's disease compared to control subjects. Of note, these detected vulnerable hubs in Alzheimer's disease were absent in each individual frequency-specific network, thus showing the value of integrating the networks. The connectivity patterns of these vulnerable hub regions in the patients were heterogeneously distributed across layers. Perturbed cognitive function and abnormal cerebrospinal fluid amyloid-β42 levels correlated positively with the vulnerability of the hub regions in patients with Alzheimer's disease. Our analysis therefore demonstrates that the magnetoencephalography-based multiplex brain networks contain important information that cannot be revealed by frequency-specific brain networks. Furthermore, this indicates that functional networks obtained in different frequency bands do not act as independent entities. Overall, our multiplex network study provides an effective framework to integrate the frequency-specific networks with different frequency patterns and reveal neuropathological mechanism of hub disruption in Alzheimer's disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Non compaction cardiomyopathy: Review of a controversial entity.

PubMed

Lorca, Rebeca; Rozado, José; Martín, María

2018-05-11

Non-compaction cardiomyopathy is a heterogeneous and complex entity concerning which there are still many doubts to be resolved. While the American Heart Association includes it among genetic cardiomyopathies, the European Society of Cardiology treats it as an unclassified cardiomyopathy. It may present in a sporadic or familial form, isolated or associated with other heart diseases, affecting only the left ventricle or both and can sometimes appear as a mixed phenotype in patients with other cardiomyopathies. Different forms of clinical presentation are also associated with its different morphological manifestations, and even non-compaction of the left ventricle may be triggered by other physiological or pathological processes. The purpose of this review is an update of this entity and its controversies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Mantle-cell lymphoma.

PubMed

Barista, I; Romaguera, J E; Cabanillas, F

2001-03-01

During the past decade, mantle-cell lymphoma has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small to medium-sized nuclei, are commonly indented or cleaved, and stain positively with CD5, CD20, cyclin D1, and FMC7 antibodies. Because of its morphological appearance and a resemblance to other low-grade lymphomas, many of which grow slowly, this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the BCL1 oncogene was identified as a marker for this disease. Mantle-cell lymphoma is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas.

Primary rhabdomyosarcoma of the pineal gland.

PubMed

Lau, Steven K M; Cykowski, Matthew D; Desai, Shiv; Cao, Ying; Fuller, Gregory N; Bruner, Janet; Okazaki, Ian

2015-05-01

To report a case of primary rhabdomyosarcoma (RMS) of the pineal gland in an adult, as well as review the literature on this rare entity. The case is compared with previous reports of similar entities, with emphasis on this patient's characteristics and clinical presentation, investigations, and management. Diagnosis of primary RMS of the pineal gland was based on the presence of strap cells and multinucleated myotube-like structures, as well as tumor cell expression of skeletal muscle markers consistent with myogenic differentiation. Multimodality treatment was initiated based on pediatric protocols. Unfortunately, the disease progressed on treatment, and the patient survived only 5 months from diagnosis. Pineal RMS is a rare disease with poor prognosis. Optimal management is unknown but likely to involve aggressive multimodality therapy. Copyright© by the American Society for Clinical Pathology.

Pseudotumoral hemicerebellitis as a mimicker of Lhermitte-Duclos disease in children: does neuroimaging help to differentiate them?

PubMed

Bosemani, Thangamadhan; Steinlin, Maja; Toelle, Sandra P; Beck, Jürgen; Boltshauser, Eugen; Huisman, Thierry A G M; Poretti, Andrea

2016-05-01

The clinical presentation and neuroimaging findings of children with pseudotumoral hemicerebellitis (PTHC) and Lhermitte-Duclos disease (LDD) may be very similar. The differentiation between these entities, however, is important because their management and prognosis are different. We report on three children with PTHC. For all three children, in the acute situation, the differentiation between PTHC and LDD was challenging. A review of the literature shows that a detailed evaluation of conventional and neuroimaging data may help to differentiate between these two entities. A striated folial pattern, brainstem involvement, and prominent veins surrounding the thickened cerebellar foliae on susceptibility weighted imaging favor LDD, while post-contrast enhancement and an increased choline peak on (1)H-Magnetic resonance spectroscopy suggest PTHC.

Are herpes virus associated to aggressive periodontitis? A review of literature

PubMed Central

Rodrigues, Patrícia Maria de Sousa; Teixeira, Ana Luísa; Kustner, Eduardo Chimenos; Medeiros, Rui

2015-01-01

Periodontal Disease includes a wide variety of infectious entities with various clinical manifestations in the oral cavity and responses to treatment. The determinants of clinical manifestations of periodontal disease include the type of infectious agent, the host immune response and environmental factors. Aggressive periodontitis (AP) is defined as a type of inflammation with specific clinical and laboratory features, which distinguish it from other types of periodontitis, with high incidence rates in a sub-group of individuals. Bacteria have been frequently mentioned as the agent inciting gingival inflammation and tissue destruction that underlies the pathogenesis of periodontitis. However, recent studies, with some controversial results, have suggested that the herpes family of viruses, including CMV and EBV-1 as well as papillomaviruses, HIV, Human T-lymphotropic virus type 1, Torquetenovirus and hepatitis B and C occur with high frequency in active periodontal lesions. There is a lack of information about this disease and the role of herpesviruses in its pathophysiology. This review provides a critical analysis of the scientific evidence linking bacteria and viruses with AP and their potential impact on clinical characteristics, prognosis and therapy. PMID:26980964

Does chaos theory have major implications for philosophy of medicine?

PubMed

Holm, S

2002-12-01

In the literature it is sometimes claimed that chaos theory, non-linear dynamics, and the theory of fractals have major implications for philosophy of medicine, especially for our analysis of the concept of disease and the concept of causation. This paper gives a brief introduction to the concepts underlying chaos theory and non-linear dynamics. It is then shown that chaos theory has only very minimal implications for the analysis of the concept of disease and the concept of causation, mainly because the mathematics of chaotic processes entail that these processes are fully deterministic. The practical unpredictability of chaotic processes, caused by their extreme sensitivity to initial conditions, may raise practical problems in diagnosis, prognosis, and treatment, but it raises no major theoretical problems. The relation between chaos theory and the problem of free will is discussed, and it is shown that chaos theory may remove the problem of predictability of decisions, but does not solve the problem of free will. Chaos theory may thus be very important for our understanding of physiological processes, and specific disease entities, without having any major implications for philosophy of medicine.

Lymphonodular form of toxoplasmosis.

PubMed

Cicholska, A; Lysakowska, J

1976-01-01

On the basis of 3 cases of lymphoglandular toxoplasmosis recognized after biopsy of lymph nodes the authors established the clinical and morphological syndrome of this disease entity. Attention is called to the possibility of erroneous histological evaluation of the examined lymph nodes owing to the similarity of glandular toxoplasmosis to other diseases of the lymphatic system.

Reemerging Sudan Ebola Virus Disease in Uganda, 2011

PubMed Central

Shoemaker, Trevor; Balinandi, Stephen; Campbell, Shelley; Wamala, Joseph Francis; McMullan, Laura K.; Downing, Robert; Lutwama, Julius; Mbidde, Edward; Ströher, Ute; Rollin, Pierre E.; Nichol, Stuart T.

2012-01-01

Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities. PMID:22931687

Global foot-and-mouth disease research update and gap analysis: 2 - epidemiology, wildlife and economics

USDA-ARS?s Scientific Manuscript database

In 2014, the Global Foot-and-mouth disease Research ings in the fields of (i) epidemiology, (ii) wildlife and (iii) Alliance (GFRA) conducted a gap analysis of foot-and- economics. Although the three sections, epidemiology, wildlife and economics are presented as separate entities, the fields are ...

Hepatitis E indigenous to economically developed countries: to what extent a zoonosis?

PubMed

Teo, Chong Gee

2006-10-01

Hepatitis E, a disease transmitted by hepatitis E virus, is increasingly recognized as being indigenous to affluent, temperate-zone countries. Issues pertaining to disease acquisition and hepatitis E virus infection, particularly in Western countries, are reviewed and highlighted. Clinical hepatitis E in the West, as in Japan, manifests more commonly in older people (>60 years) and in men, but fulminant hepatitis appears less frequent than in Japan. There, specific gastronomic and culinary risk factors associated with disease are being identified, but in the West, data implicating hepatitis E as being foodborne have yet to emerge. While hepatitis E virus subgenomic sequences in Western case patients are found to be closely related to swine hepatitis E virus, a porcine linkage to their infection remains to be established. Weak associations between occupational contact with pigs and risk of infection have been noted. Findings from earlier studies implicating animals that cohabitate with humans as reservoirs, and sewage as vehicles of infection await confirmation. Hepatitis E indigenous to developed countries is a distinct clinico-epidemiological entity. Humans, animals, food and the environment contribute and interact to cause human disease, and to sustain hepatitis E virus endemicity and enzooticity.

Art and rheumatology: the artist and the rheumatologist's perspective.

PubMed

Hinojosa-Azaola, Andrea; Alcocer-Varela, Jorge

2014-10-01

The reflection of medicine in the universal arts has motivated several rheumatologists to discover features of rheumatic diseases depicted by the artist's eyes long before they were defined as specific pathologic entities. The result has been the identification of several pieces of art dating from the Middle Ages, the Renaissance, the Baroque and Post-Impressionist periods that depict clear features of several rheumatic diseases such as RA, OA, camptodactyly and temporal arteritis, among others. On the other hand, great artists such as Pierre-Auguste Renoir, Antoni Gaudí, Raoul Dufy, Paul Klee, Frida Kahlo and Niki de Saint Phalle are good examples of how rheumatic diseases such as RA, scleroderma and chronic pain can influence the artist's perspective, the technique used and the content of their work. Art can serve as a powerful resource to understand the natural course of diseases. By learning through the artist's eyes the way illnesses behave and evolve in time, rheumatologists can trace the history of several conditions. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adenomyosis and 'endometrial-subendometrial myometrium unit disruption disease' are two different entities.

PubMed

Tocci, Angelo; Greco, Ermanno; Ubaldi, Filippo Maria

2008-08-01

The diagnosis of adenomyosis is feasible on pathological specimen examination, while it is unreliable on clinical findings, biopsy, hysteroscopy, sonohysterography, and routine ultrasound or magnetic resonance imaging. Several patterns of 'abnormality' described on imaging have been linked to adenomyosis, but the correlation is weak and the diagnostic accuracy is low outside of a research context. Nevertheless, thickening or abnormality of the subendometrial myometrium, the outer part of the 'endometrial-subendometrial myometrium unit' (thought to be important in human fertility) has been repeatedly documented on imaging, called 'adenomyosis' and linked to infertility. This paper discusses the value of the physiological endometrial-subendometrial myometrium unit in human fertility, reviews the current criteria for its imaging, and reports on its relationship to fertility. It is proposed that endometrial-subendometrial myometrium unit disruption disease is considered as a new entity (distinguished from adenomyosis), the diagnosis of which is feasible and straightforward on imaging and expressed mainly by pathological thickening or abnormality of the subendometrial myometrium (myometrial halo or junctional zone). The study also reports on the influence of abnormal thickening or disruption on human fertility and outcome of assisted reproduction techniques, and demonstrates that this new entity is epidemiologically different from adenomyosis.

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

PubMed

Günther, A; Mosavi, P; Ruppert, C; Heinemann, S; Temmesfeld, B; Velcovsky, H G; Morr, H; Grimminger, F; Walmrath, D; Seeger, W

2000-06-01

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

PubMedPortable: A Framework for Supporting the Development of Text Mining Applications.

PubMed

Döring, Kersten; Grüning, Björn A; Telukunta, Kiran K; Thomas, Philippe; Günther, Stefan

2016-01-01

Information extraction from biomedical literature is continuously growing in scope and importance. Many tools exist that perform named entity recognition, e.g. of proteins, chemical compounds, and diseases. Furthermore, several approaches deal with the extraction of relations between identified entities. The BioCreative community supports these developments with yearly open challenges, which led to a standardised XML text annotation format called BioC. PubMed provides access to the largest open biomedical literature repository, but there is no unified way of connecting its data to natural language processing tools. Therefore, an appropriate data environment is needed as a basis to combine different software solutions and to develop customised text mining applications. PubMedPortable builds a relational database and a full text index on PubMed citations. It can be applied either to the complete PubMed data set or an arbitrary subset of downloaded PubMed XML files. The software provides the infrastructure to combine stand-alone applications by exporting different data formats, e.g. BioC. The presented workflows show how to use PubMedPortable to retrieve, store, and analyse a disease-specific data set. The provided use cases are well documented in the PubMedPortable wiki. The open-source software library is small, easy to use, and scalable to the user's system requirements. It is freely available for Linux on the web at https://github.com/KerstenDoering/PubMedPortable and for other operating systems as a virtual container. The approach was tested extensively and applied successfully in several projects.

PubMedPortable: A Framework for Supporting the Development of Text Mining Applications

PubMed Central

Döring, Kersten; Grüning, Björn A.; Telukunta, Kiran K.; Thomas, Philippe; Günther, Stefan

2016-01-01

Information extraction from biomedical literature is continuously growing in scope and importance. Many tools exist that perform named entity recognition, e.g. of proteins, chemical compounds, and diseases. Furthermore, several approaches deal with the extraction of relations between identified entities. The BioCreative community supports these developments with yearly open challenges, which led to a standardised XML text annotation format called BioC. PubMed provides access to the largest open biomedical literature repository, but there is no unified way of connecting its data to natural language processing tools. Therefore, an appropriate data environment is needed as a basis to combine different software solutions and to develop customised text mining applications. PubMedPortable builds a relational database and a full text index on PubMed citations. It can be applied either to the complete PubMed data set or an arbitrary subset of downloaded PubMed XML files. The software provides the infrastructure to combine stand-alone applications by exporting different data formats, e.g. BioC. The presented workflows show how to use PubMedPortable to retrieve, store, and analyse a disease-specific data set. The provided use cases are well documented in the PubMedPortable wiki. The open-source software library is small, easy to use, and scalable to the user’s system requirements. It is freely available for Linux on the web at https://github.com/KerstenDoering/PubMedPortable and for other operating systems as a virtual container. The approach was tested extensively and applied successfully in several projects. PMID:27706202

Nosological status and definition of schizophrenia: Some considerations for DSM-V and ICD-11.

PubMed

Tandon, Rajiv; Maj, Mario

2008-12-01

Although dementia praecox or schizophrenia has been considered a unique disease entity for the past century, its definitions and boundaries have varied over this period. In this article, we examine the changing conceptualization of schizophrenia over the past 100 years and make some recommendations with regards to its definition in DSM-V and ICD-11. We summarize clinical features of schizophrenia in terms of symptomatology, course, and outcome. We examine factors that lead to changing definitions of a disorder such as schizophrenia, with specific reference to the evolution of its definition from DSM-1 (American Psychiatric Association, Washington, DC, 1952) to the current DSM-IV-TR. Efforts to elucidate the etiology and pathophysiology of schizophrenia have been hampered by its imprecise definition and continuing transformations in its conceptualization. The definition of schizophrenia, at any given time, has been influenced by available diagnostic tools and treatments, other clinical considerations, extant knowledge and scientific paradigms. It is now clear that schizophrenia does not represent a single disease with a unitary etiology or pathogenetic process. Despite limitations in the concept, however, alternative approaches thus far have been unsuccessful in better defining the syndrome of schizophrenia or its component entities. Whereas changing definitions of schizophrenia might impede research into its nature and development of more effective treatments, only a better understanding of schizophrenia can lead to its more precise definition. We consider the implications of our observations for DSM-V and ICD-11 definitions of schizophrenia and summarize some emerging preliminary recommendations. Copyright © 2008 Elsevier B.V. All rights reserved.

Efficient authentication scheme based on near-ring root extraction problem

NASA Astrophysics Data System (ADS)

Muthukumaran, V.; Ezhilmaran, D.

2017-11-01

An authentication protocolis the type of computer communication protocol or cryptography protocol specifically designed for transfer of authentication data between two entities. We have planned a two new entity authentication scheme on the basis of root extraction problem near-ring in this article. We suggest that this problem is suitably difficult to serve as a cryptographic assumption over the platform of near-ring N. The security issues also discussed.

A decision tree for differentiating multiple system atrophy from Parkinson's disease using 3-T MR imaging.

PubMed

Nair, Shalini Rajandran; Tan, Li Kuo; Mohd Ramli, Norlisah; Lim, Shen Yang; Rahmat, Kartini; Mohd Nor, Hazman

2013-06-01

To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P < 0.05) differences between MSA and PD with mean MCP width, anteroposterior diameter of pons and mean FA MCP chosen for the decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.

Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.

PubMed

Iatropoulos, Paraskevas; Daina, Erica; Curreri, Manuela; Piras, Rossella; Valoti, Elisabetta; Mele, Caterina; Bresin, Elena; Gamba, Sara; Alberti, Marta; Breno, Matteo; Perna, Annalisa; Bettoni, Serena; Sabadini, Ettore; Murer, Luisa; Vivarelli, Marina; Noris, Marina; Remuzzi, Giuseppe

2018-01-01

Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment. Copyright © 2018 by the American Society of Nephrology.

ENCOMPASS: A SAGA based environment for the compositon of programs and specifications, appendix A

NASA Technical Reports Server (NTRS)

Terwilliger, Robert B.; Campbell, Roy H.

1985-01-01

ENCOMPASS is an example integrated software engineering environment being constructed by the SAGA project. ENCOMPASS supports the specification, design, construction and maintenance of efficient, validated, and verified programs in a modular programming language. The life cycle paradigm, schema of software configurations, and hierarchical library structure used by ENCOMPASS is presented. In ENCOMPASS, the software life cycle is viewed as a sequence of developments, each of which reuses components from the previous ones. Each development proceeds through the phases planning, requirements definition, validation, design, implementation, and system integration. The components in a software system are modeled as entities which have relationships between them. An entity may have different versions and different views of the same project are allowed. The simple entities supported by ENCOMPASS may be combined into modules which may be collected into projects. ENCOMPASS supports multiple programmers and projects using a hierarchical library system containing a workspace for each programmer; a project library for each project, and a global library common to all projects.

Open Mobile Alliance Secure Content Exchange: Introducing Key Management Constructs and Protocols for Compromise-Resilient Easing of DRM Restrictions

NASA Astrophysics Data System (ADS)

Kravitz, David William

This paper presents an insider's view of the rationale and the cryptographic mechanics of some principal elements of the Open Mobile Alliance (OMA) Secure Content Exchange (SCE) Technical Specifications. A primary goal is to enable implementation of a configurable methodology that quarantines the effects that unknown-compromised entities have on still-compliant entities in the system, while allowing import from upstream protection systems and multi-client reuse of Rights Objects that grant access to plaintext content. This has to be done without breaking compatibility with the underlying legacy OMA DRM v2.0/v2.1 Technical Specifications. It is also required that legacy devices can take at least partial advantage of the new import functionality, and can request the creation of SCE-compatible Rights Objects and utilize Rights Objects created upon request of SCE-conformant devices. This must be done in a way that the roles played by newly defined entities unrecognizable by legacy devices remain hidden.

Prurigo, pruritic folliculitis, and atopic eruption of pregnancy: Facts and controversies.

PubMed

Roth, Maria Magdalena; Cristodor, Patricia; Kroumpouzos, George

2016-01-01

Prurigo (PP) and pruritic folliculitis of pregnancy (PFP) are poorly characterized entities. Traditionally classified under specific dermatoses of pregnancy, they were reclassified under a new umbrella entity, atopic eruption of pregnancy (AEP), which also includes atopic dermatitis (AD) that can worsen or present for the first time in pregnancy. Still, several aspects of AEP have not been adequately elucidated. It needs to be clarified whether it is the intrinsic ("nonallergic" or "atopiform dermatitis") or extrinsic (immunoglobulin E-associated) AD that is affected by pregnancy. Future studies need to examine the postpartum prognosis of AD that develops for the first time during gestation. A revision of diagnostic criteria of AEP will allow a more accurate estimate of its prevalence, as well as clarification of the relationship between AD and specific dermatoses, such as PP and PFP. In this context, this review discusses the history, epidemiologic data, clinicopathologic features, and management of these entities. Copyright © 2016 Elsevier Inc. All rights reserved.

Knee arthrodesis – ultima ratio for the treatment of the infected knee

PubMed Central

Tiemann, Andreas H. H.

2013-01-01

The irretrievable destruction of the knee due to trauma, tumor or infection is the indication for knee arthrodesis. The main reason for knee arthrodesis in terms of infection ist the infected total knee arthroplasty. Central problem is the definition of the term “irretrievable”. It is based on the subjective opinion of the attending physician and depends on his expert knowledge of this specific entity. The preservation of a functioning extremity is the main goal. This article shows the typical indications and contraindications for knee arthrodesis following septic knee diseases. In addition it gives insight into the biomechanical and technical considerations to be kept in mind. Finally the postoperative care and outcome of different techniques are analysed. PMID:26504699

[Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

PubMed

García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

2009-02-01

Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

Psychobiologic correlates of treatment response in schizophrenia.

PubMed

Lieberman, J A; Alvir, J M; Koreen, A; Geisler, S; Chakos, M; Sheitman, B; Woerner, M

1996-03-01

In studies conducted on largely treatment naive patients in their first episode of psychosis, we have found that treatment outcome is quite good and that most patients recover or at least achieve a substantial degree of symptom remission. However, over the course of their illness and in the context of subsequent psychotic episodes, they may experience some decrease in their treatment response from illness progression. In addition, the heterogeneity of treatment outcome is associated with specific clinical (gender, primary negative symptoms of the deficit state, duration of psychosis) and biological variables (pHVA, ventricular volume). It is unclear whether these variables represent aspects of discrete subtypes of schizophrenia or dimensional measures of pathology within the broad context of a unitary disease entity.

[Nailfold capillaroscopy].

PubMed

Geyer, M; Vasile, M; Hermann, W

2014-03-01

Capillaroscopy is performed to evaluate the morphology, frequency and blood flow of nailfold capillaries as well as relevant extracapillary changes in rheumatic conditions. The main indication is the differentiation between primary and secondary Raynaud's phenomenon. Various rheumatic conditions show different and partially typical pathognomonic alterations of the microcirculation or capillary patterns. This simple, noninvasive, inexpensive and effective technique is well suited for early diagnosis, especially of connective tissue diseases. The specific significance is highest for systemic sclerosis which is the most frequently evaluated entity. The corresponding microscopic alterations allow stage-adapted conclusions concerning the acuity of inflammation to be formed. That is not the only reason why capillaroscopy represents an important tool in follow-up controls and together with other techniques, such as flow measurement by laser Doppler, further conclusions can be drawn.

Consensus document. Management of non-alcoholic fatty liver disease (NAFLD). Clinical practice guideline.

PubMed

Aller, Rocío; Fernández-Rodríguez, Conrado; Lo Iacono, Oreste; Bañares, Rafael; Abad, Javier; Carrión, José Antonio; García-Monzón, Carmelo; Caballería, Joan; Berenguer, Marina; Rodríguez-Perálvarez, Manuel; Miranda, José López; Vilar-Gómez, Eduardo; Crespo, Javier; García-Cortés, Miren; Reig, María; Navarro, José María; Gallego, Rocío; Genescà, Joan; Arias-Loste, María Teresa; Pareja, María Jesús; Albillos, Agustín; Muntané, Jordi; Jorquera, Francisco; Solà, Elsa; Hernández-Guerra, Manuel; Rojo, Miguel Ángel; Salmerón, Javier; Caballería, Llorenc; Diago, Moisés; Molina, Esther; Bataller, Ramón; Romero-Gómez, Manuel

2018-05-01

Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

The Role of Femoroacetabular Impingement in Core Muscle Injury/Athletic Pubalgia: Diagnosis and Management.

PubMed

Strosberg, David S; Ellis, Thomas J; Renton, David B

2016-01-01

Chronic groin pain in athletes represents a major diagnostic and therapeutic challenge in sports medicine. Two recognized causes of inguinal pain in the young adult athlete are core muscle injury/athletic pubalgia (CMI/AP) and femoroacetabular impingement (FAI). CMI/AP and FAI were previously considered to be two distinct entities; however, recent studies have suggested both entities to frequently coincide in the athlete with groin pain. This article briefly discusses the role of FAI in CMI/AP and the diagnosis and management of this complex disease.

The Role of Femoroacetabular Impingement in Core Muscle Injury/Athletic Pubalgia: Diagnosis and Management

PubMed Central

Strosberg, David S.; Ellis, Thomas J.; Renton, David B.

2016-01-01

Chronic groin pain in athletes represents a major diagnostic and therapeutic challenge in sports medicine. Two recognized causes of inguinal pain in the young adult athlete are core muscle injury/athletic pubalgia (CMI/AP) and femoroacetabular impingement (FAI). CMI/AP and FAI were previously considered to be two distinct entities; however, recent studies have suggested both entities to frequently coincide in the athlete with groin pain. This article briefly discusses the role of FAI in CMI/AP and the diagnosis and management of this complex disease. PMID:26904546

Philadelphia chromosome-positive lymphoblastic lymphoma-Is it rare or underdiagnosed?

PubMed

Alshomar, Ahmad; El Fakih, Riad

2018-06-15

Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organization classification classifies both LBL and ALL as one disease entity. While chromosome abnormalities are well defined with all of their therapeutic and prognostic implications in ALL, these are not well studied in LBL. Here, we describe a case of Philadelphia chromosome-positive LBL and review the available literature regarding this entity. Copyright © 2018. Published by Elsevier Ltd.

Semi-automated literature mining to identify putative biomarkers of disease from multiple biofluids

PubMed Central

2014-01-01

Background Computational methods for mining of biomedical literature can be useful in augmenting manual searches of the literature using keywords for disease-specific biomarker discovery from biofluids. In this work, we develop and apply a semi-automated literature mining method to mine abstracts obtained from PubMed to discover putative biomarkers of breast and lung cancers in specific biofluids. Methodology A positive set of abstracts was defined by the terms ‘breast cancer’ and ‘lung cancer’ in conjunction with 14 separate ‘biofluids’ (bile, blood, breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial fluid, stool, sweat, tears, and urine), while a negative set of abstracts was defined by the terms ‘(biofluid) NOT breast cancer’ or ‘(biofluid) NOT lung cancer.’ More than 5.3 million total abstracts were obtained from PubMed and examined for biomarker-disease-biofluid associations (34,296 positive and 2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for lung cancer). Biological entities such as genes and proteins were tagged using ABNER, and processed using Python scripts to produce a list of putative biomarkers. Z-scores were calculated, ranked, and used to determine significance of putative biomarkers found. Manual verification of relevant abstracts was performed to assess our method’s performance. Results Biofluid-specific markers were identified from the literature, assigned relevance scores based on frequency of occurrence, and validated using known biomarker lists and/or databases for lung and breast cancer [NCBI’s On-line Mendelian Inheritance in Man (OMIM), Cancer Gene annotation server for cancer genomics (CAGE), NCBI’s Genes & Disease, NCI’s Early Detection Research Network (EDRN), and others]. The specificity of each marker for a given biofluid was calculated, and the performance of our semi-automated literature mining method assessed for breast and lung cancer. Conclusions We developed a semi-automated process for determining a list of putative biomarkers for breast and lung cancer. New knowledge is presented in the form of biomarker lists; ranked, newly discovered biomarker-disease-biofluid relationships; and biomarker specificity across biofluids. PMID:25379168

The Role of the Nurse Practitioner in Military Deployment

DTIC Science & Technology

1996-04-04

diarrheal and other infectious diseases. These disease entities were also described by Withers et al.(1994). 8. A Comparison of MEDREJE Practice...systems, and parasitic and infectious diseases (Defense Intelligence Agency, Medical Capabilities Study, Republic of Bolivia, 1988, DST-18 IOS-355-88...diarrhea, 44 vomiting, mononucleosis , colds and flu, and many small lacerations. If we could have used 2 or 3 more of anything, I think it would have

Dermatology and skin disease in the American Civil War.

PubMed

Cropley, Thomas G

2008-02-01

The Civil War happened at the end of the medical dark ages or, conversely, at the beginning of the modern medical era. The story of how physicians and nurses of the time approached a number of cutaneous diseases of importance in the military context is related. Entities discussed include the army itch/camp itch phenomenon, sexually transmitted diseases, scurvy and nutritional disorders, smallpox and spurious vaccination, and hospital gangrene.

In vivo molecular and genomic imaging: new challenges for imaging physics.

PubMed

Cherry, Simon R

2004-02-07

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

TOPICAL REVIEW: In vivo molecular and genomic imaging: new challenges for imaging physics

NASA Astrophysics Data System (ADS)

Cherry, Simon R.

2004-02-01

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

Efficient chemical-disease identification and relationship extraction using Wikipedia to improve recall.

PubMed

Lowe, Daniel M; O'Boyle, Noel M; Sayle, Roger A

2016-01-01

Awareness of the adverse effects of chemicals is important in biomedical research and healthcare. Text mining can allow timely and low-cost extraction of this knowledge from the biomedical literature. We extended our text mining solution, LeadMine, to identify diseases and chemical-induced disease relationships (CIDs). LeadMine is a dictionary/grammar-based entity recognizer and was used to recognize and normalize both chemicals and diseases to Medical Subject Headings (MeSH) IDs. The disease lexicon was obtained from three sources: MeSH, the Disease Ontology and Wikipedia. The Wikipedia dictionary was derived from pages with a disease/symptom box, or those where the page title appeared in the lexicon. Composite entities (e.g. heart and lung disease) were detected and mapped to their composite MeSH IDs. For CIDs, we developed a simple pattern-based system to find relationships within the same sentence. Our system was evaluated in the BioCreative V Chemical-Disease Relation task and achieved very good results for both disease concept ID recognition (F1-score: 86.12%) and CIDs (F1-score: 52.20%) on the test set. As our system was over an order of magnitude faster than other solutions evaluated on the task, we were able to apply the same system to the entirety of MEDLINE allowing us to extract a collection of over 250 000 distinct CIDs. © The Author(s) 2016. Published by Oxford University Press.

CD-REST: a system for extracting chemical-induced disease relation in literature.

PubMed

Xu, Jun; Wu, Yonghui; Zhang, Yaoyun; Wang, Jingqi; Lee, Hee-Jin; Xu, Hua

2016-01-01

Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug-disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed fromhttp://clinicalnlptool.com/cdr The online CD-REST demonstration system is available athttp://clinicalnlptool.com/cdr/cdr.html. Database URL:http://clinicalnlptool.com/cdr;http://clinicalnlptool.com/cdr/cdr.html. © The Author(s) 2016. Published by Oxford University Press.

Predictive Biomarkers for Linking Disease Pathology and Drug Effect.

PubMed

Mayer, Bernd; Heinzel, Andreas; Lukas, Arno; Perco, Paul

2017-01-01

Productivity in drug R&D continues seeing significant attrition in clinical stage testing. Approval of new molecular entities proceeds with slow pace specifically when it comes to chronic, age-related diseases, calling for new conceptual approaches, methodological implementation and organizational adoption in drug development. Detailed phenotyping of disease presentation together with comprehensive representation of drug mechanism of action is considered as a path forward, and a big data spectrum has become available covering behavioral, clinical and molecular characteristics, the latter combining reductionist and explorative strategies. On this basis integrative analytics in the realm of Systems Biology has emerged, essentially aiming at traversing associations into causal relationships for bridging molecular disease specifics and clinical phenotype surrogates and finally explaining drug response and outcome. From a conceptual perspective bottom-up modeling approaches are available, with dynamical hierarchies as formalism capable of describing clinical findings as emergent properties of an underlying molecular process network comprehensively resembling disease pathology. In such representation biomarker candidates serve as proxy of a molecular process set, at the interface of a corresponding representation of drug mechanism of action allowing patient stratification and prediction of drug response. In practical implementation network analytics on a protein coding gene level has provided a number of example cases for matching disease presentation and drug molecular effect, and workflows combining computational hypothesis generation and experimental evaluation have become available for systematically optimizing biomarker candidate selection. With biomarker-based enrichment strategies in adaptive clinical trials, implementation routes for tackling development attrition are provided. Predictive biomarkers add precision in drug development and as companion diagnostics in clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and Genome Engineering.

PubMed

Jung, Moonjung; Dunbar, Cynthia E; Winkler, Thomas

2015-12-01

The combination of epigenetic reprogramming with advanced genome editing technologies opened a new avenue to study disease mechanisms, particularly of disorders with depleted target tissue. Bone marrow failure syndromes (BMFS) typically present with a marked reduction of peripheral blood cells due to a destroyed or dysfunctional bone marrow compartment. Somatic and germline mutations have been etiologically linked to many cases of BMFS. However, without the ability to study primary patient material, the exact pathogenesis for many entities remained fragmentary. Capturing the pathological genotype in induced pluripotent stem cells (iPSCs) allows studying potential developmental defects leading to a particular phenotype. The lack of hematopoietic stem and progenitor cells in these patients can also be overcome by differentiating patient-derived iPSCs into hematopoietic lineages. With fast growing genome editing techniques, such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or introduction of mutations in cells from healthy individuals enable comparative studies that may identify other genetic or epigenetic events contributing to a specific disease phenotype. In this review, we present recent progresses in disease modeling of inherited and acquired BMFS using reprogramming and genome editing techniques. We also discuss the challenges and potential shortcomings of iPSC-based models for hematological diseases.

Gene therapy for Parkinson's disease: Disease modification by GDNF family of ligands.

PubMed

Kirik, Deniz; Cederfjäll, Erik; Halliday, Glenda; Petersén, Åsa

2017-01-01

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so far have been shown to be safe, none met their primary endpoints in phase II clinical trials designed and powered to test the efficacy of the intervention. Within the scope of this review we aim to describe the state-of-the-art in the field, how different technical parameters were translated from pre-clinical studies in non-human primates to clinical trials, and what these trials taught us regarding important factors that may pave the way to the success of gene therapy for the treatment of Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial cytopathies and the kidney.

PubMed

Emma, Francesco; Salviati, Leonardo

2017-04-01

Mitochondrial cytopathies include a heterogeneous group of diseases that are characterized by impaired oxidative phosphorylation. Current evidence suggests that renal involvement is probably more frequent than originally suspected but remains subclinical in a significant number of patients or is underestimated due to the severity of other clinical manifestations. Until recently, these diseases were thought to develop primarily in pediatric patients but patients that become symptomatic only in adulthood are now well recognized. From a renal standpoint, many patients with severe systemic disease and several patients with oligo-symptomatic clinical pictures have tubular defects, ranging from isolated tubular wasting of electrolytes to complete forms of renal Fanconi syndrome. Aside from rare cases of tubulo-interstitial and cystic diseases, other patients present with glomerular diseases that correspond in the majority of cases to focal segmental glomerulosclerosis lesions. Two specific entities should be singled out, namely the 3243 A>G mutation in the gene encoding for the mitochondrial leucine tRNA because it represents the most frequent form of mitochondrial glomerulopathy, and defects in the biosynthesis of coenzyme Q10 because they represent one of the few treatable forms of mitochondrial cytopathies. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

The contribution of the left anterior ventrolateral temporal lobe to the retrieval of personal semantics.

PubMed

Grilli, Matthew D; Bercel, John J; Wank, Aubrey A; Rapcsak, Steven Z

2018-06-04

Autobiographical facts and personal trait knowledge are conceptualized as distinct types of personal semantics, but the cognitive and neural mechanisms that separate them remain underspecified. One distinction may be their level of specificity, with autobiographical facts reflecting idiosyncratic conceptual knowledge and personal traits representing basic level category knowledge about the self. Given the critical role of the left anterior ventrolateral temporal lobe (AVTL) in the storage and retrieval of semantic information about unique entities, we hypothesized that knowledge of autobiographical facts may depend on the integrity of this region to a greater extent than personal traits. To provide neuropsychological evidence relevant to this issue, we investigated personal semantics, semantic knowledge of non-personal unique entities, and episodic memory in two individuals with well-defined left (MK) versus right (DW) AVTL lesions. Relative to controls, MK demonstrated preserved personal trait knowledge but impaired "experience-far" (i.e., spatiotemporal independent) autobiographical fact knowledge, semantic memory for non-personal unique entities, and episodic memory. In contrast, both experience-far autobiographical facts and personal traits were spared in DW, whereas episodic memory and aspects of semantic memory for non-personal unique entities were impaired. These findings support the notion that autobiographical facts and personal traits have distinct cognitive features and neural mechanisms. They also suggest a common organizing principle for personal and non-personal semantics, namely the specificity of such knowledge to an entity, which is reflected in the contribution of the left AVTL to retrieval. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exercise Related Leg Pain (ERLP): a Review of The Literature

PubMed Central

2007-01-01

Exercise related leg pain (ERLP) is a regional pain syndrome described as pain between the knee and ankle which occurs with exercise. Indiscriminant use of terminology such as “shin splints” has resulted in ongoing confusion regarding the pathoanatomic entities associated with this pain syndrome. Each of the pathoanatomic entities – medial tibial stress syndrome, chronic exertional compartment syndrome, tibial and fibular stress fractures, tendinopathy, nerve entrapment, and vascular pathology – which manifest as ERLP are each described in terms of relevant anatomy, epidemiology, clinical presentation, associated pathomechanics, and intervention strategies. Evidence regarding risk factors for ERLP general and specific pathoanatomic entities are presented in the context of models of sports injury prevention. PMID:21522213

The drug and vaccine landscape for neglected diseases (2000-11): a systematic assessment.

PubMed

Pedrique, Belen; Strub-Wourgaft, Nathalie; Some, Claudette; Olliaro, Piero; Trouiller, Patrice; Ford, Nathan; Pécoul, Bernard; Bradol, Jean-Hervé

2013-12-01

In 1975-99, only 1·1% of new therapeutic products had been developed for neglected diseases. Since then, several public and private initiatives have attempted to mitigate this imbalance. We analysed the research and development pipeline of drugs and vaccines for neglected diseases from 2000 to 2011. We searched databases of drug regulatory authorities, WHO, and clinical trial registries for entries made between Jan 1, 2000, and Dec 31, 2011. We defined neglected diseases as malaria, tuberculosis, diarrhoeal diseases, neglected tropical diseases (NTDs; WHO definition), and other diseases of poverty according to common definitions. Of the 850 new therapeutic products registered in 2000-11, 37 (4%) were indicated for neglected diseases, comprising 25 products with a new indication or formulation and eight vaccines or biological products. Only four new chemical entities were approved for neglected diseases (three for malaria, one for diarrhoeal disease), accounting for 1% of the 336 new chemical entities approved during the study period. Of 148,445 clinical trials registered in Dec 31, 2011, only 2016 (1%) were for neglected diseases. Our findings show a persistent insufficiency in drug and vaccine development for neglected diseases. Nevertheless, these and other data show a slight improvement during the past 12 years in new therapeutics development and registration. However, for many neglected diseases, new therapeutic products urgently need to be developed and delivered to improve control and potentially achieve elimination. None. Copyright © 2013 Pedrique et al. Open Access article distributed under the terms of CC BY-NC-SA. Published by .. All rights reserved.

Using nanoinformatics methods for automatically identifying relevant nanotoxicology entities from the literature.

PubMed

García-Remesal, Miguel; García-Ruiz, Alejandro; Pérez-Rey, David; de la Iglesia, Diana; Maojo, Víctor

2013-01-01

Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature. The desired entities belong to four different categories: nanoparticles, routes of exposure, toxic effects, and targets. The entity recognizer was trained using a corpus that we specifically created for this purpose and was validated by two nanomedicine/nanotoxicology experts. We evaluated the performance of our entity recognizer using 10-fold cross-validation. The precisions range from 87.6% (targets) to 93.0% (routes of exposure), while recall values range from 82.6% (routes of exposure) to 87.4% (toxic effects). These results prove the feasibility of using computational approaches to reliably perform different named entity recognition (NER)-dependent tasks, such as for instance augmented reading or semantic searches. This research is a "proof of concept" that can be expanded to stimulate further developments that could assist researchers in managing data, information, and knowledge at the nanolevel, thus accelerating research in nanomedicine.

Complying with the Health Insurance Portability and Accountability Act. Privacy standards.

PubMed

Shuren, A W; Livsey, K

2001-11-01

The Privacy Rule: Limits the use and disclosure of PHI to purposes of treatment, payment, or routine health care operations. Requires covered entities to provide advance notice to the public of its policy governing disclosure of PHI. Requires entities covered by the Standard to secure general client consent to use and to disclose PHI for treatment, payment, or routine health care operations and to obtain specific client authorization to use or to disclose PHI for all other purposes unless the disclosure is specifically permitted without consent or authorization (e.g., a covered entity may disclose PHI to a health care oversight agency such as the Office of the Inspector General without first obtaining client authorization). In certain situations, a covered entity need only obtain client agreement to disclose PHI which may be oral or inferred from the circumstances surrounding the disclosure. For example, a covered entity could disclose PHI to a relative caring for the individual who is the subject of the health information. Expects covered entities to take measures to protect PHI from both inadvertent and deliberate misuse and disclosure. Requires, except in certain circumstances, the amount of PHI disclosed on any occasion to be limited to the minimum necessary to achieve the purpose of the disclosure. Gives individuals more control of their health information by permitting them to review and amend health information pertaining to themselves and to demand an accounting of persons to whom their health information has been disclosed. Establishes terms under which a covered entity may disclose PHI to a business associate. Permits states to maintain state laws that are more stringent than the Privacy Rule. The statute provides for significant civil and criminal penalties for failure to comply with the Standards. Violations are punishable by fines as much as $250,000 and 10 years imprisonment. The HHS, Office of Civil Rights is charged with enforcing the Standards. The HHS is expected to issue a single Enforcement Rule applicable to all three of the HIPAA Administrative Simplification Standards. Many worksite records will not be protected under the HIPAA Privacy Rule because employers are not covered entities and few occupational health professionals meet the criteria of being considered a covered entity. Nevertheless, occupational health professionals need to be knowledgeable about the application of HIPAA in the occupational health care setting. Furthermore, given that the Rule does not preempt state privacy laws that are more stringent than the Standards, occupational health professionals should monitor legislative activity related to privacy in the states in which they practice. To date, Oregon, Texas, and New Jersey have broadened HIPAA's definitions to create more covered entities and services.

[Pneumonia associated with health care versus community acquired pneumonia: different entities, distinct approaches].

PubMed

Guimarães, C; Lares Santos, C; Costa, F; Barata, F

2011-01-01

Healthcare-associated pneumonia (HCAP) is now identified as a unique entity that differs from community-acquired pneumonia (CAP), and in many ways is similar to nosocomial pneumonia (NP). Patients with the diagnosis of CAP and HCAP admitted to our Pneumology Unit during one year were retrospectively analysed. The objective was to compare the characteristics and the approach of these two entities. 197 patients were included, 144 with CAP and 53 with HCAP. Sex, age, comorbilities, Pneumonia Severity Index (PSI) score, radiological involvement, bacteriology, treatment and outcomes were analysed in the 2 groups. Compared to CAP, HCAP was associated with more severe disease, a higher mortality rate and greater length of hospitalization. HCAP differed from CAP mainly in bacteriology and outcomes. Copyright © 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma.

PubMed

Green, Michael R; Aya-Bonilla, Carlos; Gandhi, Maher K; Lea, Rod A; Wellwood, Jeremy; Wood, Peter; Marlton, Paula; Griffiths, Lyn R

2011-05-01

Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy. 2011 Wiley-Liss, Inc.

Forgetting of Prose as a Function of Interpolated Passage Content and Organization.

ERIC Educational Resources Information Center

Andre, Thomas; And Others

In three studies subjects read two successive passages and then were tested for retention of the first. Each passage described the characteristics of a series of entities (diseases or countries) along a series of dimensions (symptoms, cause, etc., or climate, soil type, etc.). The first passage described five diseases and was organized by name;…

Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment.

PubMed

Komamura, Kazuo; Fukui, Miho; Iwasaku, Toshihiro; Hirotani, Shinichi; Masuyama, Tohru

2014-07-26

In 1990, takotsubo cardiomyopathy (TCM) was first discovered and reported by a Japanese cardiovascular specialist. Since then, this heart disease has gained worldwide acceptance as an independent disease entity. TCM is an important entity that differs from acute myocardial infarction. It occurs more often in postmenopausal elderly women, is characterized by a transient hypokinesis of the left ventricular (LV) apex, and is associated with emotional or physical stress. Wall motion abnormality of the LV apex is generally transient and resolves within a few days to several weeks. Its prognosis is generally good. However, there are some reports of serious TCM complications, including hypotension, heart failure, ventricular rupture, thrombosis involving the LV apex, and torsade de pointes. It has been suggested that coronary spasm, coronary microvascular dysfunction, catecholamine toxicity and myocarditis might contribute to the pathogenesis of TCM. However, its pathophysiology is not clearly understood.

Male Zuska's disease

PubMed Central

Johnson, Shepard P; Kaoutzanis, Christodoulos; Schaub, George A

2014-01-01

Subareolar abscess of the male breast is a rare condition, which can be complicated by a fistula from the areolar skin into a lactiferous duct. In 1951, Zuska et al first characterised this entity in women. Literature on mammillary fistulas in men is scarce and therefore standardisation of treatment does not exist. We present two cases of recurrent subareolar abscesses with draining fistulas. Both patients were successfully treated by complete excision of the lactiferous duct fistula, and continue to do well with no evidence of disease recurrence. When male patients present with a draining subareolar abscess, one should have a high index of suspicion for a mammillary fistula. Failure to identify and surgically excise the fistula may lead to recurrence of the abscess and prolonged morbidity. The most effective management of this uncommon entity includes complete excision of the lactiferous duct fistula. PMID:24706699

Male Zuska's disease.

PubMed

Johnson, Shepard P; Kaoutzanis, Christodoulos; Schaub, George A

2014-04-04

Subareolar abscess of the male breast is a rare condition, which can be complicated by a fistula from the areolar skin into a lactiferous duct. In 1951, Zuska et al first characterised this entity in women. Literature on mammillary fistulas in men is scarce and therefore standardisation of treatment does not exist. We present two cases of recurrent subareolar abscesses with draining fistulas. Both patients were successfully treated by complete excision of the lactiferous duct fistula, and continue to do well with no evidence of disease recurrence. When male patients present with a draining subareolar abscess, one should have a high index of suspicion for a mammillary fistula. Failure to identify and surgically excise the fistula may lead to recurrence of the abscess and prolonged morbidity. The most effective management of this uncommon entity includes complete excision of the lactiferous duct fistula.

Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

PubMed Central

Völzke, Henry

2012-01-01

Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term “non-alcoholic” fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and “non-alcoholic” fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and “non-alcoholic” fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and “non-alcoholic” fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level. PMID:22826613

Is diverticular disease associated with colonic malignancy?

PubMed

Ekbom, Anders

2012-01-01

Colon cancer and diverticular disease have common characteristics; there are increases in the incidences in both disease entities and these diseases are more common in the westernized world. There is also an increase in the age-specific incidence with advancing age. Similar dietary features have been implicated for both diseases and already during the 1960s it was postulated by Burkitt that there is an association. Observational studies initially were able to demonstrate that patients with a history of diverticular disease of the colon had an increased risk of colon cancer, especially in the left side. However, the results from these studies have not been consistent, and problems like selection bias and confounding by indication have been major drawbacks in order to interpret the results and infer causality. Recent studies, which have had a better assessment of diverticular disease by new diagnostic methods, do not support such an association to the same extent as previously. Moreover, surveillance bias has become an increasing problem as patients with diverticular disease of the colon are subjected to a higher diagnostic intensity than other individuals in a population-based setting. A critical evaluation of the studies published so far therefore clearly indicates that the proposed association between diverticular disease and colonic malignancy is not evidence based, which should have an impact on clinical practice as well as on how to deal with these patient groups within the realms of a screening program. Copyright © 2012 S. Karger AG, Basel.

[Reasons for banishing the concept of race from Brazilian medicine].

PubMed

Pena, Sérgio D J

2005-01-01

As part of medicine's canonical framework, the concept of race has been associated with the idea that color and/or biological ancestry are relevant indicators of a predisposition to a certain disease or reaction to drugs. This stance derives from a typological view of human races. The low level of genetic variability and of structuring of the human species is incompatible with the existence of races as biological entities and tells us that color and/or geographical ancestry have little or nothing useful to contribute to medical practice, particularly when it comes to caring for an individual patient. We show that even so-called racial diseases like sickle cell anemia are really the product of evolutionary strategies used by populations exposed to specific infectious agents, whose territories have no unequivocal relation with either color or continental origin. Furthermore, in the words of sociologist Paul Gilroy, the social concept of race is "toxic," contaminating society as a whole, and it has been used to oppress and to foster injustice, even within a medical context.

Primary tuberculous gingival enlargement - A rare clinical entity: Case report and brief review of the literature.

PubMed

Jan, Suhail Majid; Khan, Fayiza Youqoob; Bhat, Muzafar Ahmad; Behal, Roobal

2014-09-01

Tuberculosis (TB) is a chronic specific granulomatous disease and a major cause of death in developing countries. The clinical presentation of TB lesions of the oral cavity varies widely and can manifest as ulcerations, diffuse inflammatory lesions, granulomas and fissures. Oral lesions generally appear secondary to primary TB infection elsewhere, although primary infection of the oral mucosa by Mycobacterium tuberculosis has also been described. We hereby report a case of primary TB of the gingiva manifesting as gingival enlargement. Diagnosis was based on histopathological examination, complete blood count, X-ray chest and immunological investigations with detection of antibodies against M. tuberculosis. Anti-tuberculous therapy was carried out for over 6 months and was followed by surgical excision of the residual enlargement under local anesthesia. After 1-year follow-up, there was no recurrence of the disease. This case report emphasizes the need for dentists to include TB in the differential diagnosis of various types of gingival enlargements.

Emerging approaches for histone deacetylase inhibitor drug discovery.

PubMed

Zwergel, Clemens; Valente, Sergio; Jacob, Claus; Mai, Antonello

2015-06-01

Histone deacetylases (HDACs) are key players in the mediation of gene expression for both cancerous and noncancerous malignancies. Overexpression of these enzymes has been demonstrated in numerous types of cancer with some enzyme isoforms also involved in neurological, inflammatory and viral pathologies. Hence, the development of HDAC inhibitors (HDACis) represents a promising approach for their treatment. Numerous chemical entities have been studied in the recent years and some of them have reached clinical trials. This review summarizes the recent efforts in the drug development of HDACis and their potential application as therapeutic agents in cancerous, neurological, inflammatory and viral diseases. The development of novel potent and selective HDACis is ongoing. However, increased scientific effort is needed to aid the fight of specific types of cancerous or noncancerous disease with more selective agents required to avoid side effects during therapy. An interesting therapeutic approach is the use of HDACis in combination with other epigenetic target modulators to combine their therapeutic potential for a synergistic effect.

Clinical characteristics indicating adenomyosis at the time of hysterectomy: a retrospective study in 291 patients.

PubMed

Taran, F Andrei; Wallwiener, Markus; Kabashi, Drita; Rothmund, Ralf; Rall, Katharina; Kraemer, Bernhard; Brucker, Sara Y

2012-06-01

To better characterize adenomyosis as a disease entity. We retrospectively reviewed the medical records of women undergoing hysterectomy with a histologic diagnosis of adenomyosis, adenomyosis and leiomyomas, and leiomyomas alone. The study included 291 women: 38 with adenomyosis alone, 56 with adenomyosis and leiomyomas, and 197 with leiomyomas alone. In univariate analysis, women with adenomyosis were younger (p = 0.018) and had lower uterine weights (p < 0.001) and more disease-specific symptoms (p = 0.008). In multinomial logistic regression analysis, a lower uterine weight (OR 0.99, CI 95% 0.99-1.0), pelvic pain (OR 4.8, CI 95% 1.5-15.2), a history of smoking (OR 2.6, CI 95% 1.1-6.5) and at least one delivery (OR 4.3, CI 95% 1.5-12.3) were associated with a greater likelihood of having adenomyosis but not leiomyomas alone. Women undergoing hysterectomy with adenomyosis alone have different clinical characteristics from women with adenomyosis and leiomyomas and from those with only leiomyomas.

Discovering Peripheral Arterial Disease Cases from Radiology Notes Using Natural Language Processing

PubMed Central

Savova, Guergana K.; Fan, Jin; Ye, Zi; Murphy, Sean P.; Zheng, Jiaping; Chute, Christopher G.; Kullo, Iftikhar J.

2010-01-01

As part of the Electronic Medical Records and Genomics Network, we applied, extended and evaluated an open source clinical Natural Language Processing system, Mayo’s Clinical Text Analysis and Knowledge Extraction System, for the discovery of peripheral arterial disease cases from radiology reports. The manually created gold standard consisted of 223 positive, 19 negative, 63 probable and 150 unknown cases. Overall accuracy agreement between the system and the gold standard was 0.93 as compared to a named entity recognition baseline of 0.46. Sensitivity for the positive, probable and unknown cases was 0.93–0.96, and for the negative cases was 0.72. Specificity and negative predictive value for all categories were in the 90’s. The positive predictive value for the positive and unknown categories was in the high 90’s, for the negative category was 0.84, and for the probable category was 0.63. We outline the main sources of errors and suggest improvements. PMID:21347073

Multiple myeloma: Diagnosis and management issues in patients with pre-existing chronic kidney disease.

PubMed

Vadlamudi, Srilatha; Annapareddy, Siva Nagendra Reddy

2016-01-01

Multiple myeloma is one of the most common malignancies encountered in clinical practice. Renal involvement in myeloma is a well-recognized entity. Although rare, another special situation that a nephrologist can encounter is myeloma occurring in a patient with preexisting chronic kidney disease (CKD) due to other etiologies. Anemia, bone pains and hypercalcemia, which commonly indicate the diagnosis of myeloma in the general population, are not useful in the presence of CKD. The sensitivity and specificity of serum free light chain assay is decreased in the presence of renal failure. Chemotherapy-related adverse effects are high compared with that in patients without CKD; this is attributed to the decreased clearance of drugs and the additive effect of chemotherapy-related adverse effects to the complications of CKD. Autologous and allogenic bone marrow transplantation can be attempted in this group of patients with non-myeloablative-conditioning regimens. Combined bone marrow and renal transplantation remains a viable option in this group of patients to increase life expectancy and quality of life.

Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency

PubMed Central

Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Fischer, Alain; Franco, Jose Luis; Geha, Raif S.; Hammarström, Lennart; Nonoyama, Shigeaki; Notarangelo, Luigi Daniele; Ochs, Hans Dieter; Puck, Jennifer M.; Roifman, Chaim M.; Seger, Reinhard; Tang, Mimi L. K.

2011-01-01

We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases. PMID:22566844

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

PubMed Central

Divatia, Mukul; Kim, Sun A

2012-01-01

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

PubMed

Domínguez, R O; Pagano, M A; Marschoff, E R; González, S E; Repetto, M G; Serra, J A

2014-01-01

Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA

PubMed Central

Gale, Aaron; Wu, Peiwen; Ma, Rong; Davis, Mark E.

2015-01-01

There is an urgent need for new therapies that can halt or reverse the course of chronic kidney disease with minimal side-effect burden on the patient. Small interfering RNA (siRNA) nanoparticles are new therapeutic entities in clinical development that could be useful for chronic kidney disease treatment because they combine the tissue-specific targeting properties of nanoparticles with the gene-specific silencing effects of siRNA. Recent reports have emerged demonstrating that the kidney, specifically the glomerulus, is a readily accessible site for nanoparticle targeting. Here, we explore the hypothesis that intravenously administered polycationic cyclodextrin nanoparticles containing siRNA (siRNA/CDP-NPs) can be used for delivery of siRNA to the glomerular mesangium. We demonstrate that siRNA/CDP-NPs localize to the glomerular mesangium with limited deposition in other areas of the kidney after intravenous injection. Additionally, we report that both mouse and human mesangial cells rapidly internalize siRNA/CDP-NPs in vitro and that nanoparticle uptake can be enhanced by attaching the targeting ligands mannose or transferrin to the nanoparticle surface. Lastly, we show knockdown of mesangial enhanced green fluorescent protein expression in a reporter mouse strain following iv treatment with siRNA/CDP-NPs. Altogether, these data demonstrate the feasibility of mesangial targeting using intravenously administered siRNA/CDP-NPs. PMID:25734248

Dermatology facing autoinflammatory syndrome.

PubMed

Alecu, Mihail; Coman, Gabriela; Muşetescu, Alina; Cojoacă, Marian Emanuel; Coman, Oana Andreia

2015-01-01

Cutaneous symptoms are characteristic for the autoinflammatory disorders (AIDs), both in the classical autoinflammatory phenotype and in most disorders included in this syndrome, but they are not specific and inconstant. Several skin disorders (pyoderma gangrenosum and pustular acne) may be encountered either isolate or associated with autoinflammatory symptoms, forming well-defined clinical entities within the autoinflammatory syndrome. The high prevalence of cutaneous manifestations is an important characteristic of AIDs. The presence of cutaneous symptoms in AIDs opens the perspective of understanding the contribution of innate immunity mechanisms involved in skin pathology. It is possible that many diseases present the alteration, in various degrees, of the innate immune mechanisms. Recently, dermatology faced two challenges connected to AIDs. The first involves the diagnosis of skin symptoms in a clinical autoinflammatory setting and the investigative approach to identify a disorder classified as AID. The second is to identify the altered mechanisms of inborn immunity among the pathogenetic mechanisms of known dermatological diseases (e.g., neutrophilic dermatoses). On the other hand, cutaneous symptoms are in certain cases regarded as a criterion to asses the efficacy of specific or non-specific therapies with monoclonal antibodies in disorders included in AIDs. Dermatology mostly benefits from the identification and knowledge of AIDs due to the role of innate immunity in skin pathogeny and also due to the large extent of clinical forms resulting from the association of skin symptoms with other disorders included in this group.

Text Mining for Drugs and Chemical Compounds: Methods, Tools and Applications.

PubMed

Vazquez, Miguel; Krallinger, Martin; Leitner, Florian; Valencia, Alfonso

2011-06-01

Providing prior knowledge about biological properties of chemicals, such as kinetic values, protein targets, or toxic effects, can facilitate many aspects of drug development. Chemical information is rapidly accumulating in all sorts of free text documents like patents, industry reports, or scientific articles, which has motivated the development of specifically tailored text mining applications. Despite the potential gains, chemical text mining still faces significant challenges. One of the most salient is the recognition of chemical entities mentioned in text. To help practitioners contribute to this area, a good portion of this review is devoted to this issue, and presents the basic concepts and principles underlying the main strategies. The technical details are introduced and accompanied by relevant bibliographic references. Other tasks discussed are retrieving relevant articles, identifying relationships between chemicals and other entities, or determining the chemical structures of chemicals mentioned in text. This review also introduces a number of published applications that can be used to build pipelines in topics like drug side effects, toxicity, and protein-disease-compound network analysis. We conclude the review with an outlook on how we expect the field to evolve, discussing its possibilities and its current limitations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Phenotypic presentation of chronic cough in children

PubMed Central

2017-01-01

Chronic cough in children is increasingly defined as a cough that lasts more than four weeks. It is recognized as a different entity than cough in adults. As a result, the diagnostic approach and management of chronic cough in children are no longer extrapolated from adult guidelines. These differences are attributed to the various characteristics of the respiratory tract, immunological system and nervous system in children. Specific paediatric guidelines and algorithms for chronic cough are now widely applied. Post-infectious cough, asthma, bronchiectasis, malacia and protracted bacterial bronchitis (PBB) appear to be the major causes of cough in young children. By adolescence, the causes of cough are more likely to be similar to those in adults, namely, gastroesophageal reflux, asthma, and upper airway syndrome. In a primary setting, it is essential to investigate the underlying disease entity that initiates and sustains chronic cough. The use of cough management protocols or algorithms improves clinical outcomes and should differ depending on the associated characteristics of the cough and the child’s clinical history. Performing a thorough history and physical examination is crucial to starting an individualised approach. A correct interpretation of the phenotypic presentation can be translated into guidance for workup. This approach will be helpful for adequate management without the risk of inappropriate investigations or inadequate treatment. PMID:28523136

Enormous knowledge base of disease diagnosis criteria.

PubMed

Xiao, Z H; Xiao, Y H; Pei, J H

1995-01-01

One of the problems in the development of the medical knowledge systems is the limitations of the system's knowledge. It is a common expectation to increase the number of diseases contained in a system. Using a high density knowledge representation method designed by us, we have developed the Enormous Knowledge Base of Disease Diagnosis Criteria (EKBDDC). It contains diagnostic criteria of 1,001 diagnostic entities and describes nearly 4,000 items of diagnostic indicators. It is the core of a huge medical project--the Electronic-Brain Medical Erudite (EBME). This enormous knowledge base was implemented initially on a low-cost popular microcomputer, which can aid in the prompting of typical disease and in teaching of diagnosis. The knowledge base is easy to expand. One of the main goals of EKBDDC is to increase the number of diseases included in it as far as possible using a low-cost computer with a comparatively small storage capacity. For this, we have designed a high density knowledge representation method. Criteria of various diagnostic entities are respectively stored in different records of the knowledge base. Each diagnostic entity corresponds to a diagnostic criterion data set; each data set consists of some diagnostic criterion data values (Table 1); each data is composed of two parts: integer and decimal; the integral part is the coding number of the given diagnostic information, and the decimal part is the diagnostic value of this information to the disease indicated by corresponding record number. For example, 75.02: the integer 75 is the coding number of "hemorrhagic skin rash"; the decimal 0.02 is the diagnostic value of this manifestation for diagnosing allergic purpura. TABULAR DATA, SEE PUBLISHED ABSTRACT. The algebraic sum method, a special form of the weighted summation, is adopted as mathematical model. In EKBDDC, the diagnostic values, which represent the significance of the disease manifestations for diagnosing corresponding diseases, were determined empirically. It is of a great economical, practical, and technical significance to realize enormous knowledge bases of disease diagnosis criteria on a low-cost popular microcomputer. This is beneficial for the developing countries to popularize medical informatics. To create the enormous international computer-aided diagnosis system, one may jointly develop the unified modules of disease diagnosis criteria used to "inlay" relevant computer-aided diagnosis systems. It is just like assembling a house using prefabricated panels.

Cost of specific emergency general surgery diseases and factors associated with high-cost patients.

PubMed

Ogola, Gerald O; Shafi, Shahid

2016-02-01

We have previously shown that overall cost of hospitalization for emergency general surgery (EGS) diseases is more than $28 billion annually and rising. The purposes of this study were to estimate the costs associated with specific EGS diseases and to identify factors associated with high-cost hospitalizations. The American Association for the Surgery of Trauma definition was used to identify hospitalizations of adult EGS patients in the 2010 National Inpatient Sample data. Cost of each hospitalization was obtained using cost-to-charge ratio in National Inpatient Sample. Regression analysis was used to estimate the cost for each EGS disease adjusted for patient and hospital characteristics. Hospitalizations with cost exceeding 75th percentile for each EGS disease were compared with lower-cost hospitalizations to identify factors associated with high cost. Thirty-one EGS diseases resulted in 2,602,074 hospitalizations nationwide in 2010 at an average adjusted cost of $10,110 (95% confidence interval, $10,086-$10,134) per hospitalization. Of these, only nine diseases constituted 80% of the total volume and 74% of the total cost. Empyema chest, colorectal cancer, and small intestine cancer were the most expensive EGS diseases with adjusted mean cost per hospitalization exceeding $20,000, while breast infection, abdominal pain, and soft tissue infection were the least expensive, with mean adjusted costs of less than $7,000 per hospitalization. The most important factors associated with high-cost hospitalizations were the number and type of procedures performed (76.2% of variance), but a region in Western United States (11.3%), Medicare and Medicaid payors (2.6%), and hospital ownership by public or not-for-profit entities (5.6%) were also associated with high-cost hospitalizations. A small number of diseases constitute a vast majority of EGS hospitalizations and their cost. Attempts at reducing the cost of EGS hospitalization will require controlling the cost of procedures. Economic analysis, level IV.

A New Replicator: A theoretical framework for analysing replication

PubMed Central

2010-01-01

Background Replicators are the crucial entities in evolution. The notion of a replicator, however, is far less exact than the weight of its importance. Without identifying and classifying multiplying entities exactly, their dynamics cannot be determined appropriately. Therefore, it is importance to decide the nature and characteristics of any multiplying entity, in a detailed and formal way. Results Replication is basically an autocatalytic process which enables us to rest on the notions of formal chemistry. This statement has major implications. Simple autocatalytic cycle intermediates are considered as non-informational replicators. A consequence of which is that any autocatalytically multiplying entity is a replicator, be it simple or overly complex (even nests). A stricter definition refers to entities which can inherit acquired changes (informational replicators). Simple autocatalytic molecules (and nests) are excluded from this group. However, in turn, any entity possessing copiable information is to be named a replicator, even multicellular organisms. In order to deal with the situation, an abstract, formal framework is presented, which allows the proper identification of various types of replicators. This sheds light on the old problem of the units and levels of selection and evolution. A hierarchical classification for the partition of the replicator-continuum is provided where specific replicators are nested within more general ones. The classification should be able to be successfully applied to known replicators and also to future candidates. Conclusion This paper redefines the concept of the replicator from a bottom-up theoretical approach. The formal definition and the abstract models presented can distinguish between among all possible replicator types, based on their quantity of variable and heritable information. This allows for the exact identification of various replicator types and their underlying dynamics. The most important claim is that replication, in general, is basically autocatalysis, with a specific defined environment and selective force. A replicator is not valid unless its working environment, and the selective force to which it is subject, is specified. PMID:20219099

33 CFR 149.615 - What construction drawings and specifications are required?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What construction drawings and... and Equipment General § 149.615 What construction drawings and specifications are required? (a) To... accepted Certifying Entity (CE) at least three copies of: (1) Each construction drawing and specification...

A Virus-like disease of chinook salmon

USGS Publications Warehouse

Ross, A.J.; Pelnar, J.; Rucker, R.R.

1960-01-01

Consideration is given to a recurring disease of early feeding chinook salmon fingerlings at the Coleman, California, Federal Fish Cultural Station. The infection becomes manifest in the early spring months at low water temperatures and abates as the water temperature rises. Bacteriological studies have failed to yield the presence of a disease agent, either by cultural or staining procedures. The disease has been successfully transmitted from infected fish to healthy fish by the injection of bacteria-free filtrates prepared from diseased fish tissue. The causative agent is therefore believed to be a virus-like entity.

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications.

PubMed

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

: Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype-phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, 'real-world' experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype)

PubMed Central

Hannemann, A.; Rees, D.C.; Tewari, S.; Gibson, J.S.

2015-01-01

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease. PMID:26870793

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications

PubMed Central

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype–phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, ‘real-world’ experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines. PMID:29176389

The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD.

PubMed

Fox, J Craig; Fitzgerald, Mary F

2009-06-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that has been relatively under researched compared to other inflammatory diseases. Indeed, thus far there have been no anti-inflammatory therapies specifically approved for COPD and the available anti-inflammatory therapies were originally developed for asthma. The challenges facing research in COPD are multi-faceted; the mechanisms underlying the complex and heterogeneous pathology of this disease require unravelling; the role of inflammation in disease progression needs to be confirmed and new drugs with potential to successfully treat COPD need to be identified. Many of the compounds in the clinic today have been identified through the work performed in a range of animal models of COPD. These models have provided us with an understanding of disease pathology and potential mechanistic pathways and have given us the means to prioritise new chemical entities before entry into the clinic. This review will summarise currently available models of COPD and highlight how they have been used to take a first generation of anti-inflammatory therapies for COPD into clinical development. The predictive nature of these animal models will become clear as these therapies are clinically evaluated. The recurring challenge will be to take emerging pre-clinical and clinical data and use it to continually improve animal models so that they remain a valuable tool in the drug discovery process.

42 CFR 7.1 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... BIOLOGICAL STANDARDS AND BIOLOGICAL PREPARATIONS § 7.1 Applicability. The provisions of this part are applicable to private entities requesting from the Centers for Disease Control (CDC) reference biological standards and biological preparations for use in their laboratories. ...

42 CFR 7.1 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... BIOLOGICAL STANDARDS AND BIOLOGICAL PREPARATIONS § 7.1 Applicability. The provisions of this part are applicable to private entities requesting from the Centers for Disease Control (CDC) reference biological standards and biological preparations for use in their laboratories. ...

42 CFR 7.1 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... BIOLOGICAL STANDARDS AND BIOLOGICAL PREPARATIONS § 7.1 Applicability. The provisions of this part are applicable to private entities requesting from the Centers for Disease Control (CDC) reference biological standards and biological preparations for use in their laboratories. ...

42 CFR 411.8 - Services paid for by a Government entity.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., as a means of controlling infectious diseases or because the individual is medically indigent. (5... the reasonable costs that the facility incurs in providing the covered services; (B) Twenty percent of...

Identification of proteomic signatures associated with lung cancer and COPD.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Meléndez, R; Salinas, A; González De la Peña, M; Martín-Juan, J; Corral, J; García-Carbonero, R; Carnero, A; Paz-Ares, L

2013-08-26

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway. In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC. Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence. Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35 10(-08)-1.42 10(-02)), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93 10(-11)-1.27 10(-02)), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39 10(-09)-1.58 10(-02)). Copyright © 2013 Elsevier B.V. All rights reserved.

USGS Colorado Water Science Center bookmark

USGS Publications Warehouse

,

2016-12-05

The U.S. Geological Survey Colorado Water Science Center conducts its water-resources activities primarily in Colorado in cooperation with more than 125 different entities. These activities include extensive data-collection efforts and studies of streamflow, water quality, and groundwater to address many specific issues of concern to Colorado water-management entities and citizens. The collected data are provided in the National Water Information System, and study results are documented in reports and information served on the Internet.

Cutaneous Manifestations of Crohn Disease.

PubMed

Hagen, Joshua W; Swoger, Jason M; Grandinetti, Lisa M

2015-07-01

Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

[Parasitic diseases in the Kyrgyz Republic: epidemiological aspects].

PubMed

Usubalieva, Zh M; Toĭgombaeva, V C; Nogoĭbaeva, K A; Mergenov, A E

2009-01-01

The paper analyzes the epidemiological situation associated with intestinal helminthic and protozoan diseases in the Kyrgyz Republic in the past 17 years (1991-2007). The analysis suggests that parasitic diseases are of wide spread in the republic. In the structure of infectious diseases, parasitic diseases account for 45%. Children less than 14 years of age are a risk group, whose proportion is 80%. Enteric nosological entities are prevalent in the structure of parasitic diseases. There has been a long-term trend for a rise in the incidence of echinococcosis and ascariasis and for a decrease in that of enterobiasis and hymenolepiasis.

Accuracy control in Monte Carlo radiative calculations

NASA Technical Reports Server (NTRS)

Almazan, P. Planas

1993-01-01

The general accuracy law that rules the Monte Carlo, ray-tracing algorithms used commonly for the calculation of the radiative entities in the thermal analysis of spacecraft are presented. These entities involve transfer of radiative energy either from a single source to a target (e.g., the configuration factors). or from several sources to a target (e.g., the absorbed heat fluxes). In fact, the former is just a particular case of the latter. The accuracy model is later applied to the calculation of some specific radiative entities. Furthermore, some issues related to the implementation of such a model in a software tool are discussed. Although only the relative error is considered through the discussion, similar results can be derived for the absolute error.

Coloseminal fistula complicating sigmoid diverticulitis.

PubMed

Barret, Maximilien; Cuenod, Charles-André; Jian, Raymond; Cellier, Christophe; Berger, Anne

2014-01-01

We report on a 32-year-old man with a history of chronic lower abdominal pain and urogenital symptoms, leading to the diagnosis of coloseminal fistula complicating diverticular disease. We reviewed the literature on this rare clinical entity and would like to stress the role of pelvic imaging with rectal contrast to investigate complicated forms of diverticular disease. 2014 S. Karger AG, Basel.

Weight loss in individuals with metabolic syndrome given DASH diet counseling when provided a low sodium vegetable juice: A randomized controlled trial

USDA-ARS?s Scientific Manuscript database

Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from ...

Osteochondrosis of the inferior pole of the scapula (Roca disease).

PubMed

Skaf, Abdalla; Taneja, Atul K

2014-03-01

We report a rare case of osteochondrosis of the inferior pole of the scapula in a 14-year-old boy, an amateur swimmer, that was diagnosed by a combination of clinical and imaging findings. Also known as Roca disease, this is the first article to report this entity in the English literature and demonstrates its computerized tomography and MRI features.

Evolution, epidemiology, and population genetics of black flies (Diptera: Simuliidae).

PubMed

Adler, Peter H; Cheke, Robert A; Post, Rory J

2010-10-01

More than 2000 species of black flies feed on vertebrate blood; 1.5% of all species are vectors of pathogens that cause human diseases. Of nine simuliid-borne animal diseases, only two, mansonellosis and onchocerciasis, afflict humans. Onchocerciasis is a debilitating disease infecting an estimated 40 million people in Africa, Latin America, and Yemen, whereas mansonellosis is a mild disease in the Neotropics. Cytogenetic studies of natural populations of more than 500 species of black flies have revealed that the classic morphospecies of taxonomists is typically a complex of two or more reproductively isolated entities, or sibling (cryptic) species. Most vectors of human pathogens are sibling species, each ecologically unique in traits such as breeding habitats, dispersal capabilities, and degree of vector competence. We review the evolution of black flies, the cytogenetics that have revealed about 260 cytologically distinct entities, the molecular studies that continue to expose additional hidden biodiversity, and a case study of the epidemiology of the Simulium damnosum complex, the largest species complex of blood-feeding arthropods on Earth and the premier group of black flies responsible for human onchocerciasis. Copyright 2010 Elsevier B.V. All rights reserved.

From juvenile hyperuricaemia to dysfunctional uromodulin: an ongoing metamorphosis.

PubMed

Venkat-Raman, Gopalakrishnan; Gast, Christine; Marinaki, Anthony; Fairbanks, Lynnette

2016-11-01

Familial juvenile hyperuricaemic nephropathy (FJHN) is a diagnosis that is easily missed. It has taken a long time to clarify the pathophysiology and prevalence of this disease entity which has been shown to be genetically identical to medullary cystic kidney disease (MCKD) type II. The initial suspicion that uric acid was the noxious agent has been replaced by the recognition that a mutant uromodulin (UMOD) is the real culprit-although the exact mechanisms of pathogenicity remain uncertain. The mutation has been traced to the UMOD gene in chromosome 16. The disease is characterised by the classic triad of autosomal dominant inheritance, progressive renal failure beginning in the third to fifth decade of life and gout. Phenotypically similar but genotypically distinct entities have been described over the last 10 years, making a clinical diagnosis difficult. These include mutations in the renin, hepatocyte nuclear factor 1-β and mucin 1 genes. UMOD-associated kidney disease has been proposed as a logical diagnostic label to replace FJHN, but given all these other mutations, an over-arching diagnostic term of 'autosomal dominant tubulointerstitial kidney disease' (ADTKD) has been recently adopted. Allopurinol has been suggested as a therapeutic agent, but unfortunately this was based on non-randomised uncontrolled trials with small patient numbers.

[Childhood scabies: a different entity].

PubMed

Níguez Carbonell, J C; García-Marcos Alvarez, L; Sebastián Raz, J M; García Marcos, V; Guillén Pérez, J J

1988-01-01

Epidemiological, clinical, diagnostic and therapeutic aspects that make scabies a clinical entity with a special personality in the pediatric field, are reviewed. On the epidemiological aspects, a special mention of its unsuspected frequency in this age is made. Scabies is an endemic disease in our country among the more deprived people. On the clinical aspects, the great importance of clinical history and distribution of skin lesions for the early diagnosis is pointed out. Some "alert pointers" are described for this early diagnosis. On the therapeutic field, the importance of the primary care prevention is discussed, and the drug approach for its relieve is commented.

Myofibroblastoma of the male breast: a rare entity with radiologic-pathologic correlation

PubMed Central

Comer, John D.; Cui, Xiaoyan; Eisen, Carolyn Sharyn; Abbey, Genevieve; Arleo, Elizabeth Kagan

2016-01-01

A 73-year old man with a history of multiple genitourinary malignancies was found to have a left retroareolar soft tissue mass on CT assessment of disease, and dedicated breast imaging was recommended. Diagnostic mammography and ultrasonography confirmed a solid mass, for which biopsy was recommended. Pathologic analysis demonstrated a spindle cell neoplasm with an immunoreactivity pattern consistent with myofibroblastoma. While this entity is benign, nonspecific imaging features necessitate tissue sampling for pathologic diagnosis, and, given pathologic rarity, open communication between the radiologist and pathologist is important to establish the correct diagnosis and to recommend appropriate management. PMID:27936420

Paroxysmal myoclonic dystonia with vocalisations: new entity or variant of preexisting syndromes?

PubMed Central

Feinberg, T E; Shapiro, A K; Shapiro, E

1986-01-01

From among 1377 patients with movement disorders, four patients had an unusual movement disorder characterised by paroxysmal bursts of involuntary, regular, repetitive, rhythmic, bilateral, coordinated, simultaneous, stereotypic myoclonus and vocalisations, often associated with tonic symptoms, interference with voluntary functioning, presence of hyperactivity, attention and learning disabilities, and resistance to treatment with haloperidol and other drugs. This symptom complex may represent a new disease entity, referred to here as paroxysmal myoclonic dystonia with vocalisations or a variant or combination of other movement disorders such as Gilles de la Tourette, myoclonic, or dystonic syndromes. PMID:3457101

Semantic Differential Scale Method Can Reveal Multi-Dimensional Aspects of Mind Perception.

PubMed

Takahashi, Hideyuki; Ban, Midori; Asada, Minoru

2016-01-01

As humans, we tend to perceive minds in both living and non-living entities, such as robots. From a questionnaire developed in a previous mind perception study, authors found that perceived minds could be located on two dimensions "experience" and "agency." This questionnaire allowed the assessment of how we perceive minds of various entities from a multi-dimensional point of view. In this questionnaire, subjects had to evaluate explicit mental capacities of target characters (e.g., capacity to feel hunger). However, we sometimes perceive minds in non-living entities, even though we cannot attribute these evidently biological capacities to the entity. In this study, we performed a large-scale web survey to assess mind perception by using the semantic differential scale method. We revealed that two mind dimensions "emotion" and "intelligence," respectively, corresponded to the two mind dimensions (experience and agency) proposed in a previous mind perception study. We did this without having to ask about specific mental capacities. We believe that the semantic differential scale is a useful method to assess the dimensions of mind perception especially for non-living entities that are hard to be attributed to biological capacities.

Seasonal Changes in Color Preferences Are Linked to Variations in Environmental Colors: A Longitudinal Study of Fall.

PubMed

Schloss, Karen B; Heck, Isobel A

2017-01-01

People form associations between colors and entities, which influence their evaluations of the world. These evaluations are dynamic, as specific associations become more or less active in people's minds over time. We investigated how evaluations of colors (color preferences) changed over the course of fall, as color-associated fall entities became more prevalent in the environment. Participants judged their preferences for the same set of colors during nine testing sessions over 11 weeks during fall. We categorized the colors as Leaf and Non-Leaf Colors by matching them to leaves collected during the same period. Changes in preferences for Leaf Colors followed a quadratic pattern, peaking around when the leaves were most colorful and declining as winter approached. Preferences for Non-Leaf Colors did not significantly change. Individual differences in these changes could be explained by preferences for seasonal entities, as predicted by the differential activation hypothesis within the Ecological Valence Theory. The more a given individual liked fall-associated entities, the more their preference for Leaf Colors increased during fall. No analogous relations existed with winter-associated entities or Non-Leaf Colors. These results demonstrate the importance of studying temporal and individual differences for understanding preferences.

Isolation, Analysis and Antimicrobial Activity of the Acidic Fractions of Mastic, Kurdica, Mutica and Cabolica Gums from Genus Pistacia

PubMed Central

Sharifi, Mohammad Sharif; Hazell, Stuart Loyd

2012-01-01

The chemical entities of Mastic, Kurdica, Mutica and Cabolica gums from genus Pistacia have been isolated and characterised by GC-Mass Spectrometry, High Performance Liquid Chromatography and Column Chromatography. These chemical entities were screened for anti-microbial activities against nine strains of Helicobacter pylori and some other Gram-negative and Gram-positive bacteria. The most bioactive components were structurally analysed. These components mimic steroid compounds, in particular, the known antibiotic Fusidic acid. Some of these chemical entities have produced promising data that could lead to the development of a novel class of antimicrobial agents that may have application in the treatment of infectious disease. Kill kinetics have been also performed, and the produced data were evaluated by Generalized Multiplicative Analysis Of Variance (GEMANOVA) for the bactericidal and bacteriostatic activities which can be clinically significant. The isolated components were all bactericidal. PMID:22980113

Primary disorders of the lymphatic vessels--a unified concept.

PubMed

Levine, C

1989-03-01

Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.

Development of an ELISA for sensitive and specific detection of IgA autoantibodies against BP180 in pemphigoid diseases

PubMed Central

2011-01-01

Background Pemphigoids are rare diseases associated with IgG, IgE and IgA autoantibodies against collagen XVII/BP180. An entity of the pemphigoid group is the lamina lucida-type of linear IgA disease (IgA pemphigoid) characterized by IgA autoantibodies against BP180. While for the detection of IgG and IgE autoantibodies specific to collagen XVII several ELISA systems have been established, no quantitative immunoassay has been yet developed for IgA autoantibodies. Therefore, the aim of the present study was to develop an ELISA to detect IgA autoantibodies against collagen XVII in the sera of patients with pemphigoids. Methods We expressed a soluble recombinant form of the collagen XVII ectodomain in mammalian cells. Reactivity of IgA autoantibodies from patients with IgA pemphigoid was assessed by immunofluorescence microscopy and immunoblot analysis. ELISA test conditions were determined by chessboard titration experiments. The sensitivity, specificity and the cut-off were determined by receiver-operating characteristics analysis. Results The optimized assay was carried out using sera from patients with IgA pemphigoid (n = 30) and healthy donors (n = 105). By receiver operating characteristics (ROC) analysis, an area under the curve of 0.993 was calculated, indicating an excellent discriminatory capacity. Thus, a sensitivity and specificity of 83.3% and 100%, respectively, was determined for a cut-off point of 0.48. As additional control groups, sera from patients with bullous pemphigoid (n = 31) and dermatitis herpetiformis (n = 50), a disease associated with IgA autoantibodies against epidermal transglutaminase, were tested. In 26% of bullous pemphigoid patients, IgA autoantibodies recognized the ectodomain of collagen XVII. One of 50 (2%) of dermatitis herpetiformis patients sera slightly topped the cut-off value. Conclusions We developed the first ELISA for the specific and sensitive detection of serum IgA autoantibodies specific to collagen XVII in patients with pemphigoids. This immunoassay should prove a useful tool for clinical and translational research and should essentially improve the diagnosis and disease monitoring of patients with IgA pemphigoid. Moreover, our findings strongly suggest that IgA pemphigoid and IgG bullous pemphigoid represent two ends of the clinical spectrum of an immunological loss of tolerance against components of hemidesmosomes, which is mediated by both IgG and IgA autoantibodies. PMID:21619684

Depressive symptoms in neurodegenerative diseases

PubMed Central

Baquero, Miquel; Martín, Nuria

2015-01-01

Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment. PMID:26301229

Iron deposits in post-mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study.

PubMed

De Reuck, J L; Deramecourt, V; Auger, F; Durieux, N; Cordonnier, C; Devos, D; Defebvre, L; Moreau, C; Caparros-Lefebvre, D; Leys, D; Maurage, C A; Pasquier, F; Bordet, R

2014-07-01

Accumulation of iron (Fe) is often detected in brains of people suffering from neurodegenerative diseases. However, no studies have compared the Fe load between these disease entities. The present study investigates by T2*-weighted gradient-echo 7.0 T magnetic resonance imaging (MRI) the Fe content in post-mortem brains with different neurodegenerative and cerebrovascular diseases. One hundred and fifty-two post-mortem brains, composed of 46 with Alzheimer's disease (AD), 37 with frontotemporal lobar degeneration (FTLD), 11 with amyotrophic lateral sclerosis, 13 with Lewy body disease, 14 with progressive supranuclear palsy, 16 with vascular dementia (VaD) and 15 controls without a brain disease, were examined. The Fe load was determined semi-quantitatively on T2*-weighted MRI serial brain sections in the claustrum, caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, hippocampus, mamillary body, lateral geniculate body, red nucleus, substantia nigra and dentate nucleus. The disease diagnosis was made on subsequent neuropathological examination. The Fe load was significantly increased in the claustrum, caudate nucleus and putamen of FTLD brains and to a lesser degree in the globus pallidus, thalamus and subthalamic nucleus. In the other neurodegenerative diseases no Fe accumulation was observed, except for a mild increase in the caudate nucleus of AD brains. In VaD brains no Fe increase was detected. Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

PubMed

Seethala, Raja R; Stenman, Göran

2017-03-01

The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

Potential of agricultural fungicides for antifungal drug discovery.

PubMed

Jampilek, Josef

2016-01-01

While it is true that only a small fraction of fungal species are responsible for human mycoses, the increasing prevalence of fungal diseases has highlighted an urgent need to develop new antifungal drugs, especially for systemic administration. This contribution focuses on the similarities between agricultural fungicides and drugs. Inorganic, organometallic and organic compounds can be found amongst agricultural fungicides. Furthermore, fungicides are designed and developed in a similar fashion to drugs based on similar rules and guidelines, with fungicides also having to meet similar criteria of lead-likeness and/or drug-likeness. Modern approved specific-target fungicides are well-characterized entities with a proposed structure-activity relationships hypothesis and a defined mode of action. Extensive toxicological evaluation, including mammalian toxicology assays, is performed during the whole discovery and development process. Thus modern agrochemical research (design of modern agrochemicals) comes close to drug design, discovery and development. Therefore, modern specific-target fungicides represent excellent lead-like structures/models for novel drug design and development.

Character-level neural network for biomedical named entity recognition.

PubMed

Gridach, Mourad

2017-06-01

Biomedical named entity recognition (BNER), which extracts important named entities such as genes and proteins, is a challenging task in automated systems that mine knowledge in biomedical texts. The previous state-of-the-art systems required large amounts of task-specific knowledge in the form of feature engineering, lexicons and data pre-processing to achieve high performance. In this paper, we introduce a novel neural network architecture that benefits from both word- and character-level representations automatically, by using a combination of bidirectional long short-term memory (LSTM) and conditional random field (CRF) eliminating the need for most feature engineering tasks. We evaluate our system on two datasets: JNLPBA corpus and the BioCreAtIvE II Gene Mention (GM) corpus. We obtained state-of-the-art performance by outperforming the previous systems. To the best of our knowledge, we are the first to investigate the combination of deep neural networks, CRF, word embeddings and character-level representation in recognizing biomedical named entities. Copyright © 2017 Elsevier Inc. All rights reserved.

Informatics in radiology: an information model of the DICOM standard.

PubMed

Kahn, Charles E; Langlotz, Curtis P; Channin, David S; Rubin, Daniel L

2011-01-01

The Digital Imaging and Communications in Medicine (DICOM) Standard is a key foundational technology for radiology. However, its complexity creates challenges for information system developers because the current DICOM specification requires human interpretation and is subject to nonstandard implementation. To address this problem, a formally sound and computationally accessible information model of the DICOM Standard was created. The DICOM Standard was modeled as an ontology, a machine-accessible and human-interpretable representation that may be viewed and manipulated by information-modeling tools. The DICOM Ontology includes a real-world model and a DICOM entity model. The real-world model describes patients, studies, images, and other features of medical imaging. The DICOM entity model describes connections between real-world entities and the classes that model the corresponding DICOM information entities. The DICOM Ontology was created to support the Cancer Biomedical Informatics Grid (caBIG) initiative, and it may be extended to encompass the entire DICOM Standard and serve as a foundation of medical imaging systems for research and patient care. RSNA, 2010

Discovering latent commercial networks from online financial news articles

NASA Astrophysics Data System (ADS)

Xia, Yunqing; Su, Weifeng; Lau, Raymond Y. K.; Liu, Yi

2013-08-01

Unlike most online social networks where explicit links among individual users are defined, the relations among commercial entities (e.g. firms) may not be explicitly declared in commercial Web sites. One main contribution of this article is the development of a novel computational model for the discovery of the latent relations among commercial entities from online financial news. More specifically, a CRF model which can exploit both structural and contextual features is applied to commercial entity recognition. In addition, a point-wise mutual information (PMI)-based unsupervised learning method is developed for commercial relation identification. To evaluate the effectiveness of the proposed computational methods, a prototype system called CoNet has been developed. Based on the financial news articles crawled from Google finance, the CoNet system achieves average F-scores of 0.681 and 0.754 in commercial entity recognition and commercial relation identification, respectively. Our experimental results confirm that the proposed shallow natural language processing methods are effective for the discovery of latent commercial networks from online financial news.

SKIMMR: facilitating knowledge discovery in life sciences by machine-aided skim reading

PubMed Central

Burns, Gully A.P.C.

2014-01-01

Background. Unlike full reading, ‘skim-reading’ involves the process of looking quickly over information in an attempt to cover more material whilst still being able to retain a superficial view of the underlying content. Within this work, we specifically emulate this natural human activity by providing a dynamic graph-based view of entities automatically extracted from text. For the extraction, we use shallow parsing, co-occurrence analysis and semantic similarity computation techniques. Our main motivation is to assist biomedical researchers and clinicians in coping with increasingly large amounts of potentially relevant articles that are being published ongoingly in life sciences. Methods. To construct the high-level network overview of articles, we extract weighted binary statements from the text. We consider two types of these statements, co-occurrence and similarity, both organised in the same distributional representation (i.e., in a vector-space model). For the co-occurrence weights, we use point-wise mutual information that indicates the degree of non-random association between two co-occurring entities. For computing the similarity statement weights, we use cosine distance based on the relevant co-occurrence vectors. These statements are used to build fuzzy indices of terms, statements and provenance article identifiers, which support fuzzy querying and subsequent result ranking. These indexing and querying processes are then used to construct a graph-based interface for searching and browsing entity networks extracted from articles, as well as articles relevant to the networks being browsed. Last but not least, we describe a methodology for automated experimental evaluation of the presented approach. The method uses formal comparison of the graphs generated by our tool to relevant gold standards based on manually curated PubMed, TREC challenge and MeSH data. Results. We provide a web-based prototype (called ‘SKIMMR’) that generates a network of inter-related entities from a set of documents which a user may explore through our interface. When a particular area of the entity network looks interesting to a user, the tool displays the documents that are the most relevant to those entities of interest currently shown in the network. We present this as a methodology for browsing a collection of research articles. To illustrate the practical applicability of SKIMMR, we present examples of its use in the domains of Spinal Muscular Atrophy and Parkinson’s Disease. Finally, we report on the results of experimental evaluation using the two domains and one additional dataset based on the TREC challenge. The results show how the presented method for machine-aided skim reading outperforms tools like PubMed regarding focused browsing and informativeness of the browsing context. PMID:25097821

Is the common cold a clinical entity or a cultural concept?

PubMed

Eccles, R

2013-03-01

Common cold is the most common infectious disease of mankind and the term is widely used in the clinical literature as though it were a defined clinical syndrome. Clinical studies on this syndrome often use elaborate symptom scoring systems to diagnose a common cold. The symptom scores are based on a study conducted over 50 years ago to retrospectively diagnose experimental cold and this method cannot be applied to diagnosis of common cold in the community. Diagnosis of the common cold by virology is not feasible because of the number of viruses and the variability in the disease states caused by the viruses. Because of the familiarity of subjects with common cold and the variability in symptomatology it seems a more reasonable approach to use self-diagnosis of common cold for clinical research studies and accept that the common cold is a cultural concept and not a clinical entity.

Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract. Management and literature review.

PubMed

Salemis, Nikolaos S; Seretis, Charalambos; Seretis, Fotios; Christofyllakis, Charalambos; Karalis, Georgios

2014-01-01

Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of patients with extremity soft tissue sarcoma and in 4.5% of patients with liposarcoma. Multifocal disease may arise either synchronously or metachronously and has been associated with poor prognosis. Herein, we have described a rare case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract that developed 14 months after the resection of a myxoid buttock liposarcoma. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that multifocal myxoid liposarcoma is a rare clinical entity that usually represents metastatic disease with poor prognosis. A thorough imaging and careful physical examination are essential in the preoperative evaluation and postoperative follow-up of patients with myxoid extremity liposarcomas, as these tumors are known to have a tendency to spread toward extrapulmonary sites, frequently without pulmonary metastases.

Scalp Metastasis as the First Sign of Small-Cell Lung Cancer: Management and Literature Review

PubMed Central

Salemis, Nikolaos S.; Veloudis, Georgios; Spiliopoulos, Kyriakos; Nakos, Georgios; Vrizidis, Nikolaos; Gourgiotis, Stavros

2014-01-01

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor. PMID:25058760

Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract. Management and literature review

PubMed Central

Salemis, Nikolaos S.; Seretis, Charalambos; Seretis, Fotios; Christofyllakis, Charalambos; Karalis, Georgios

2014-01-01

Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of patients with extremity soft tissue sarcoma and in 4.5% of patients with liposarcoma. Multifocal disease may arise either synchronously or metachronously and has been associated with poor prognosis. Herein, we have described a rare case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract that developed 14 months after the resection of a myxoid buttock liposarcoma. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that multifocal myxoid liposarcoma is a rare clinical entity that usually represents metastatic disease with poor prognosis. A thorough imaging and careful physical examination are essential in the preoperative evaluation and postoperative follow-up of patients with myxoid extremity liposarcomas, as these tumors are known to have a tendency to spread toward extrapulmonary sites, frequently without pulmonary metastases. PMID:24678225

Scalp metastasis as the first sign of small-cell lung cancer: management and literature review.

PubMed

Salemis, Nikolaos S; Veloudis, Georgios; Spiliopoulos, Kyriakos; Nakos, Georgios; Vrizidis, Nikolaos; Gourgiotis, Stavros

2014-01-01

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor.

Use of controlled vocabularies to improve biomedical information retrieval tasks.

PubMed

Pasche, Emilie; Gobeill, Julien; Vishnyakova, Dina; Ruch, Patrick; Lovis, Christian

2013-01-01

The high heterogeneity of biomedical vocabulary is a major obstacle for information retrieval in large biomedical collections. Therefore, using biomedical controlled vocabularies is crucial for managing these contents. We investigate the impact of query expansion based on controlled vocabularies to improve the effectiveness of two search engines. Our strategy relies on the enrichment of users' queries with additional terms, directly derived from such vocabularies applied to infectious diseases and chemical patents. We observed that query expansion based on pathogen names resulted in improvements of the top-precision of our first search engine, while the normalization of diseases degraded the top-precision. The expansion of chemical entities, which was performed on the second search engine, positively affected the mean average precision. We have shown that query expansion of some types of biomedical entities has a great potential to improve search effectiveness; therefore a fine-tuning of query expansion strategies could help improving the performances of search engines.

[Thrombotic Microangiopathies].

PubMed

Schubert, Jörg; Dechant, Michael

2018-06-01

Thrombotic microangiopathies are almost devastating diseases leading to death at high frequency if untreated. They consist of at least five distinct entities, TTP, HUS, aHUS, TMA due to drug interference, systemic disease or post therapy TMA. Around 10 years ago there was only one established therapeutic approach as plasmapheresis. Meanwhile, there are new drugs been licensed or within licensing process. Patients with atypical HUS can be treated successfully by the Complement inhibitor Eculizumab. In addition, there is a new inhibitor of von-Willebrand-Polymerisation available. Caplacizumab provides a significantly better remission and decrease in TMA-related death. For therapy associated TMA as VOD/SOS Defibrotide could be established within a phase III study to significantly improve outcomes. In order to select these new medical approaches individual diagnostic parameters need to be established in order to rapidly distinguish between the TMA entities and start targeted therapy. © Georg Thieme Verlag KG Stuttgart · New York.

The periapical space--a dynamic interface.

PubMed

Abbott, P V

2000-10-01

The ultimate aim of endodontic treatment is to encourage the healing of apical periodontitis, or to prevent it from occurring if it was not present prior to treatment. Apical periodontitis is a general term used to describe an inflammatory response to irritation caused by the contents of a root canal system and it has several distinct forms. The most common is a granuloma but this can develop into other disease entities such as an abscess, a periapical pocket cyst or a true cyst, all of which present as radiolucencies. However, periapical radiolucencies may also be caused by extra-radicular infections, foreign body reactions and periapical scars, or they may be due to other tumours and cysts that have not originated from pulp disease. Practitioners must recognize and understand the different pathological entities and the dynamic interactions that occur in the periapical tissues in order to correctly diagnose and treat these conditions.

The periapical space--a dynamic interface.

PubMed

Abbott, Paul V

2002-12-01

The ultimate aim of endodontic treatment is to encourage the healing of apical periodontitis, or to prevent it from occurring if it was not present prior to treatment. Apical periodontitis is a general term used to describe an inflammatory response to irritation caused by the contents of a root canal system and it has several distinct forms. The most common is a granuloma but this can develop into other disease entities such as an abscess, a periapical pocket cyst or a true cyst, all of which present as radiolucencies. However, periapical radiolucencies may also be caused by extra-radicular infections, foreign body reactions and periapical scars, or they may be due to other tumours and cysts that have not originated from pulp disease. Practitioners must recognise and understand the different pathological entities and the dynamic interactions that occur in the periapical tissues in order to correctly diagnose and treat these conditions.

Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment

PubMed Central

Komamura, Kazuo; Fukui, Miho; Iwasaku, Toshihiro; Hirotani, Shinichi; Masuyama, Tohru

2014-01-01

In 1990, takotsubo cardiomyopathy (TCM) was first discovered and reported by a Japanese cardiovascular specialist. Since then, this heart disease has gained worldwide acceptance as an independent disease entity. TCM is an important entity that differs from acute myocardial infarction. It occurs more often in postmenopausal elderly women, is characterized by a transient hypokinesis of the left ventricular (LV) apex, and is associated with emotional or physical stress. Wall motion abnormality of the LV apex is generally transient and resolves within a few days to several weeks. Its prognosis is generally good. However, there are some reports of serious TCM complications, including hypotension, heart failure, ventricular rupture, thrombosis involving the LV apex, and torsade de pointes. It has been suggested that coronary spasm, coronary microvascular dysfunction, catecholamine toxicity and myocarditis might contribute to the pathogenesis of TCM. However, its pathophysiology is not clearly understood. PMID:25068020

Palisaded Neutrophilic and Granulomatous Dermatitis/Interstitial Granulomatous Dermatitis Overlap: A Striking Clinical and Histologic Presentation With "Burning Rope Sign" and Subsequent Mirror-Image Contralateral Recurrence.

PubMed

Kern, Malan; Shiver, Mallory B; Addis, Kristen M; Gardner, Jerad M

2017-09-01

Palisaded neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis are uncommon granulomatous dermatoses that often arise in association with rheumatoid arthritis. These 2 entities have overlapping features and may exist on a spectrum. We report an intriguing case of a 53-year-old man with advanced rheumatoid arthritis who presented with a large indurated painful truncal plaque with a palpable cord in addition to a papulonodular eruption on his dorsal hands. Furthermore, our patient had a recurrence in a near-identical mirror-image pattern on the contralateral trunk. The constellation of clinical and histopathological findings in our patient further suggests that palisaded neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis exist as overlapping disease entities on a continuum. In addition, we propose that recurrence of skin findings may be indicative of the severity of the underlying systemic disease process.

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The intersection of nonalcoholic fatty liver disease and obesity.

PubMed

Woo Baidal, Jennifer A; Lavine, Joel E

2016-01-27

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. Copyright © 2016, American Association for the Advancement of Science.

Roth spots seen on ophthalmoscopy: diseases with which they may be associated.

PubMed

Falcone, P M; Larrison, W I

1995-05-01

Roth spots seen on fundoscopic examination (white-centered hemorrhages) were classically described as septic emboli in patients with subacute bacterial endocarditis (SBE). Many physicians have considered them pathognomonic for this entity. More recent evidence suggests, however, that they are nonspecific and may be found in other disease states. A review of the pathogenesis of these white-centered hemorrhages will be provided, along with some diseases other than SBE in which they may occur.

Passive transfer in domestic and bighorn lambs Total IgG in ewe sera and colostrum and serum IgG kinetics in lambs following colostrum ingestion are similar in domestic sheep and bighorn sheep (ovis aries and ovis canadensis)

USDA-ARS?s Scientific Manuscript database

Pneumonia is a population-limiting disease of bighorn sheep (BHS; Ovis canadensis) and a recognized disease entity in domestic sheep (DS; Ovis aries) worldwide. Respiratory disease in BHS lambs can persist for years after all-age outbreaks, resulting in suppressed lamb recruitment. It has been sugge...

A 7-Gene Signature Depicts the Biochemical Profile of Early Prefibrotic Myelofibrosis

PubMed Central

Skov, Vibe; Burton, Mark; Thomassen, Mads; Stauffer Larsen, Thomas; Riley, Caroline H.; Brinch Madelung, Ann; Kjær, Lasse; Bondo, Henrik; Stamp, Inger; Ehinger, Mats; Dahl-Sørensen, Rasmus; Brochmann, Nana; Nielsen, Karsten; Thiele, Jürgen; Jensen, Morten K.; Weis Bjerrum, Ole; Kruse, Torben A.; Hasselbalch, Hans Carl

2016-01-01

Recent studies have shown that a large proportion of patients classified as essential thrombocythemia (ET) actually have early primary prefibrotic myelofibrosis (prePMF), which implies an inferior prognosis as compared to patients being diagnosed with so-called genuine or true ET. According to the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may be challenging and several studies have not been able to distinguish between them. Most lately, it has been argued that simple blood tests, including the leukocyte count and plasma lactate dehydrogenase (LDH) may be useful tools to separate genuine ET from prePMF, the latter disease entity more often being featured by anemia, leukocytosis and elevated LDH. Whole blood gene expression profiling was performed in 17 and 9 patients diagnosed with ET and PMF, respectively. Using elevated LDH obtained at the time of diagnosis as a marker of prePMF, a 7-gene signature was identified which correctly predicted the prePMF group with a sensitivity of 100% and a specificity of 89%. The 7 genes included MPO, CEACAM8, CRISP3, MS4A3, CEACAM6, HEMGN, and MMP8, which are genes known to be involved in inflammation, cell adhesion, differentiation and proliferation. Evaluation of bone marrow biopsies and the 7-gene signature showed a concordance rate of 71%, 79%, 62%, and 38%. Our 7-gene signature may be a useful tool to differentiate between genuine ET and prePMF but needs to be validated in a larger cohort of “ET” patients. PMID:27579896

Myocardial Infarction in Neonates: A Review of an Entity with Significant Morbidity and Mortality.

PubMed

Papneja, Koyelle; Chan, Anthony K; Mondal, Tapas K; Paes, Bosco

2017-03-01

Coronary artery disease is a global problem with high mortality rates and significant residual sequelae that affect long-term quality of life. Myocardial infarction (MI) in neonates is a recognized, uncommon entity, but the incidence and broad spectrum of the disease is unknown and likely underestimated due to limited reporting which in the majority is confined to acute ischemic events. The challenges involve clinical diagnosis which masquerades in the early phase as non-specific symptoms and signs that are commonly found in a host of neonatal disorders. Precise diagnostic criteria for neonatal MI are lacking, and management is driven by clinical presentation and hemodynamic stabilization rather than an attempt to rapidly establish the root cause of the condition. We conducted a review of the published reports of neonatal MI from 2000 to 2014, to establish an approach to the diagnosis and management based on the existing evidence. The overall evidence from 32 scientific articles stemmed from case reports and case series which were graded as low-to-very low quality. Neonatal MI resembles childhood and adult MI with features that involve characteristic ECG changes, raised biomarkers, and diagnostic imaging, but with lack of robust, standardized criteria to facilitate prompt diagnosis and timely intervention. The mortality rate of neonatal MI ranges from 40 to 50% based on inclusion criteria, but the short-term data reflect normal quality of life in survivors. An algorithm for the diagnosis and management of neonatal MI may optimize outcomes, but at the present time is based on limited evidence. Well-designed clinical studies focusing on the definition, diagnosis, and management of neonatal MI, backed by international consensus guidelines, are needed to alter the prognosis of this serious condition.

Knowledge management for systems biology a general and visually driven framework applied to translational medicine.

PubMed

Maier, Dieter; Kalus, Wenzel; Wolff, Martin; Kalko, Susana G; Roca, Josep; Marin de Mas, Igor; Turan, Nil; Cascante, Marta; Falciani, Francesco; Hernandez, Miguel; Villà-Freixa, Jordi; Losko, Sascha

2011-03-05

To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature. Existing knowledge such as genotype-phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data. Different approaches to this challenge exist but so far none has proven entirely satisfactory. To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies. Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases. From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data. We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects. The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene--disease and gene--compound data which are used for subsequent data analysis, modelling and simulation. Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development.

Knowledge management for systems biology a general and visually driven framework applied to translational medicine

PubMed Central

2011-01-01

Background To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature. Existing knowledge such as genotype - phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data. Different approaches to this challenge exist but so far none has proven entirely satisfactory. Results To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies. Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases. From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data. Conclusions We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects. The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene - disease and gene - compound data which are used for subsequent data analysis, modelling and simulation. Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development. PMID:21375767

Prioritizing PubMed articles for the Comparative Toxicogenomic Database utilizing semantic information

PubMed Central

Wilbur, W. John

2012-01-01

The Comparative Toxicogenomics Database (CTD) contains manually curated literature that describes chemical–gene interactions, chemical–disease relationships and gene–disease relationships. Finding articles containing this information is the first and an important step to assist manual curation efficiency. However, the complex nature of named entities and their relationships make it challenging to choose relevant articles. In this article, we introduce a machine learning framework for prioritizing CTD-relevant articles based on our prior system for the protein–protein interaction article classification task in BioCreative III. To address new challenges in the CTD task, we explore a new entity identification method for genes, chemicals and diseases. In addition, latent topics are analyzed and used as a feature type to overcome the small size of the training set. Applied to the BioCreative 2012 Triage dataset, our method achieved 0.8030 mean average precision (MAP) in the official runs, resulting in the top MAP system among participants. Integrated with PubTator, a Web interface for annotating biomedical literature, the proposed system also received a positive review from the CTD curation team. PMID:23160415

Prioritizing PubMed articles for the Comparative Toxicogenomic Database utilizing semantic information.

PubMed

Kim, Sun; Kim, Won; Wei, Chih-Hsuan; Lu, Zhiyong; Wilbur, W John

2012-01-01

The Comparative Toxicogenomics Database (CTD) contains manually curated literature that describes chemical-gene interactions, chemical-disease relationships and gene-disease relationships. Finding articles containing this information is the first and an important step to assist manual curation efficiency. However, the complex nature of named entities and their relationships make it challenging to choose relevant articles. In this article, we introduce a machine learning framework for prioritizing CTD-relevant articles based on our prior system for the protein-protein interaction article classification task in BioCreative III. To address new challenges in the CTD task, we explore a new entity identification method for genes, chemicals and diseases. In addition, latent topics are analyzed and used as a feature type to overcome the small size of the training set. Applied to the BioCreative 2012 Triage dataset, our method achieved 0.8030 mean average precision (MAP) in the official runs, resulting in the top MAP system among participants. Integrated with PubTator, a Web interface for annotating biomedical literature, the proposed system also received a positive review from the CTD curation team.

Semi-Automated Annotation of Biobank Data Using Standard Medical Terminologies in a Graph Database.

PubMed

Hofer, Philipp; Neururer, Sabrina; Goebel, Georg

2016-01-01

Data describing biobank resources frequently contains unstructured free-text information or insufficient coding standards. (Bio-) medical ontologies like Orphanet Rare Diseases Ontology (ORDO) or the Human Disease Ontology (DOID) provide a high number of concepts, synonyms and entity relationship properties. Such standard terminologies increase quality and granularity of input data by adding comprehensive semantic background knowledge from validated entity relationships. Moreover, cross-references between terminology concepts facilitate data integration across databases using different coding standards. In order to encourage the use of standard terminologies, our aim is to identify and link relevant concepts with free-text diagnosis inputs within a biobank registry. Relevant concepts are selected automatically by lexical matching and SPARQL queries against a RDF triplestore. To ensure correctness of annotations, proposed concepts have to be confirmed by medical data administration experts before they are entered into the registry database. Relevant (bio-) medical terminologies describing diseases and phenotypes were identified and stored in a graph database which was tied to a local biobank registry. Concept recommendations during data input trigger a structured description of medical data and facilitate data linkage between heterogeneous systems.

[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].

PubMed

Villalón-López, José Sebastián; Souto-del Bosque, Rosalía; Alonso-Briones, Marco Vinicio; Trujillo-de Anda, Ana Patricia

2013-01-01

breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67. we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease. metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.

[Tumor and tumor-like benign mesenchymal lesions of the breast].

PubMed

Bisceglia, M; Nirchio, V; Carosi, I; Cappucci, U; Decata, A; Paragone, T; Di Mattia, A L

1995-02-01

All the spectrum is encompassed of those miscellaneous pathologic entities occurring in the mammary stroma which are on record up to date other than "mixed fibroepithelial" tumors (fibroadenomas and phyllodes tumors) and tumors both "pure" and "mixed" originating from myoepithelium (adenomyoepitheliomas and pleomorphic adenomas). Also they were excluded those dysreactive-autoimmune diseases (sarcoidosis, sclerosing lymphocytic lobulitis, lobular granulomatous mastitis) and those inflammatory-infectious conditions (tuberculosis, actinomycosis, foreign body reactions, Mondor's disease) which can mimick breast tumors clinically or on image analysis, but on the contrary not evoking the idea of a tumor on histology. Specifically, inflammatory pseudotumor, myofibroblastoma, leiomyoma, neurinoma/neurofibroma, benign fibrous histiocytoma, hemangiopericytoma, fibromatosis, nodular fascitis, variants of lipoma, mesenchymoma, amartoma and its variants, hemangiomas, pseudoangiomatous hyperplasia of stroma, amyloid tumor, granular cell tumor, are consecutively described and discussed, with a large list of references enclosed to each rubric. Most of the pictures are taken from personally observed lesions of the breast. Only few pictures referred to are from their analogue lesions which occurred in soft parts of other locations, with specific mention of that when it was the case. Of note after reviewing the literature the fact that no glomus tumor, nor Kaposi's sarcoma either sporadic or in the context of any immunodeficiency, nor myelolipoma has been recorded yet.

Finding Related Entities by Retrieving Relations: UIUC at TREC 2009 Entity Track

DTIC Science & Technology

2009-11-01

classes, depending on the categories they belong to. A music album could have any generic name, whereas a laptop model has a more generalizable name. A...names of music albums are simply plain text often capitalized, and so on. Thus, we feel that a better ap- proach would be to first identify the...origin domain of the text to be tagged (e.g., pharmaceutical, music , journal, etc.), and then apply tagging rules that are specific to that domain

Small bowel perforation secondary to metastatic non-small cell lung cancer. A rare entity with a dismal prognosis.

PubMed

Salemis, Nikolaos S; Nikou, Efstathios; Liatsos, Christos; Gakis, Christos; Karagkiouzis, Grigorios; Gourgiotis, Stavros

2012-09-01

The incidence of gastrointestinal metastases from lung cancer is higher than previously thought as they have been reported in 2-14% of the cases in autopsy studies. However, clinically significant metastases are rare. Small bowel perforation secondary to metastatic non-small cell lung cancer is a very rare clinical entity. The aim of this study is to describe a case of ileal perforation in a patient with intestinal metastases of a non-small cell lung cancer, along with a review of the literature. A 57-year-old male with a history of non-small cell lung cancer was referred to our emergency department with signs and symptoms of acute surgical abdomen. A computed tomography scan demonstrated dilated small bowel loops, liver deposits, and signs of perforation of an intra-abdominal hollow viscus. Emergency exploratory laparotomy revealed diffuse purulent peritonitis and a perforated ileal tumor. A segmental small bowel resection and primary anastomosis were performed. Histological and immunohistochemical findings were consistent with a metastatic non-small cell lung carcinoma. Additional evaluation revealed widespread metastatic disease. Unfortunately, despite adjuvant treatment, the patient died of progressive disease 2 months after surgery. Small bowel perforation due to metastatic non-small cell lung cancer is a very rare clinical entity. The possibility of small bowel metastases should be kept in mind in patients with lung cancer presenting with an acute abdomen. Intestinal perforation occurs in advanced stages and is usually a sign of widespread disease. Aggressive surgery can provide effective palliation and may improve short-term survival. The prognosis is however dismal.

The alterations of the sigmoid-rectal junction in diverticular disease of the colon revealed by MR-defecography.

PubMed

Romagnoli, Francesco; Colaiacomo, Maria Chiara; De Milito, Ritanna; Modini, Claudio; Gualdi, Gianfranco; Catani, Marco

2014-01-01

The sigmoidorectal junction (SRJ) has been defined as an anatomical sphincter with particular physiological behavior that regulates sigmoid and rectum evacuation. Its function in clinical conditions, such as diverticular disease has been advocated. The aim of our study is to identify the SRJ and to compare the morphometric and dynamic features of the SRJ between patients with diverticular disease and healthy subjects using MR-defecography. Sixteen individuals, eight with uncomplicated diverticular disease and eight healthy subjects, were studied using MR-defecography to identify the SRJ and to compare the morphometric and dynamic features observed. In each subject studied, MR-defecography was able to identify the SRJ. This resulted in the identification of a discrete anatomical entity with a mean length of 31.23 mm, located in front of the first sacral vertebra (S1) and at a mean distance of 15.55 cm from the anal verge, with a mean wall thickness of 4.45 mm, significantly different from the sigmoid and rectal parietal thickness. The SRJ wall was significantly thicker in patients with diverticular disease than the controls (P = 0.005), showing a unique shape and behavior in dynamic sequences. Our findings support the hypothesis that SRJ plays a critical role in patients with symptomatic diverticular disease; further investigation may clarify whether specific SRJ analysis, such as MR-defecography, would predict inflammatory complications of this diffuse and heterogenic disease.

Functional dyspepsia and nonerosive reflux disease: clinical interactions and their implications.

PubMed

Keohane, John; Quigley, Eamonn M M

2007-08-08

Functional dyspepsia or nonulcer dyspepsia, and nonerosive reflux disease (NERD) or endoscopy-negative reflux disease, are common reasons for referral to a gastroenterologist. Although there is much confusion with regard to definition, recent research would suggest that these 2 conditions are linked and may represent components in the spectrum of the same disease entity, in terms of both symptoms and pathophysiology. Several theories have been proposed regarding the etiology of these disorders, including acid exposure, visceral hypersensitivity, impaired fundal accommodation, delayed gastric emptying, and Helicobacter pylori infection.

[IgG4-related disease].

PubMed

González-Moreno, Juan; Losada López, Inés; Ortego Centeno, Norberto

2015-12-21

IgG4-related disease is a recently described clinicopathological entity showing a wide spectrum of clinical manifestations that share a common pathology. Its most characteristic feature is the formation of inflammatory tumors in different organs, which makes differentiation mainly with neoplastic diseases fundamental. The inflammatory process is typically comprised of IgG4 lymphoplasmacytic cells. The pathophysiological role of the immunoglobulin is not clear. The treatment of choice is corticosteroids. This article aims to summarize the main features of the disease. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

G protein-coupled receptor 91 signaling in diabetic retinopathy and hypoxic retinal diseases.

PubMed

Hu, Jianyan; Li, Tingting; Du, Xinhua; Wu, Qiang; Le, Yun-Zheng

2017-10-01

G protein-coupled receptor 91 (GPR91) is a succinate-specific receptor and activation of GPR91 could initiate a complex signal transduction cascade and upregulate inflammatory and pro-angiogenic cytokines. In the retina, GPR91 is predominately expressed in ganglion cells, a major cellular entity involved in the pathogenesis of diabetic retinopathy (DR) and other hypoxic retinal diseases. During the development of DR and retinopathy of prematurity (ROP), chronic hypoxia causes an increase in the levels of local succinate. Succinate-mediated GPR91 activation upregulates vascular endothelial growth factor (VEGF) through ERK1/2-C/EBP β (c-Fos) and/or ERK1/2-COX-2/PGE2 signaling pathways, which in turn, leads to the breakdown of blood-retina barriers in these disorders. In this review, we will have a brief introduction of GPR91 and its biological functions and a more detailed discussion about the role and mechanisms of GPR91 in DR and ROP. A better understanding of GPR91 regulation may be of great significance in identifying new biomarkers and drug targets for the prediction and treatment of DR, ROP, and hypoxic retinal diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aspergillus serology: Have we arrived yet?

PubMed

Richardson, Malcolm D; Page, Iain D

2017-01-01

Aspergillosis presents in various clinical forms, among them chronic pulmonary aspergillosis, which is a spectrum of disease entities including aspergilloma, chronic cavitary pulmonary aspergillosis, and chronic fibrosing pulmonary aspergillosis. Aspergillus also contributes to fungal allergy and sensitization. Analysis of the immune response to Aspergillus and its antigens is an integral part of the diagnosis of these diseases. Over the past half century, the techniques used to determine antibody titers have evolved from testing for precipitating and agglutinating antibodies by agar gel double diffusion and immunolectrophoresis to enzyme-linked immunosorbent assays using recombinant proteins as capture antigens. A resurgence of interest in the detection of immunoglobulins, primarily Aspergillus-specific IgG, has hinted at the possibility of distinguishing between colonization and invasion in immunocompromised patients with invasive aspergillosis. Even though there appears to be a greater degree of discrimination between the clinical forms of aspergillosis there is still a long way to travel. This review presents illustrative examples of where new diagnostic platforms and technologies have been applied to this intriguing spectrum of diseases. © The Authors 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool?

PubMed

Florez, Jose C

2017-05-01

In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment. In diabetes, precedent for the successful application of pharmacogenetic concepts exists in its monogenic subtypes, such as MODY or neonatal diabetes. Whether similar insights will emerge for the much more common entity of type 2 diabetes remains to be seen. As genetic approaches advance, the progressive deployment of candidate gene, large-scale genotyping and genome-wide association studies has begun to produce suggestive results that may transform clinical practice. However, many barriers to the translation of diabetes pharmacogenetic discoveries to the clinic still remain. This perspective offers a contemporary overview of the field with a focus on sulfonylureas and metformin, identifies the major uses of pharmacogenetics, and highlights potential limitations and future directions.

The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease

PubMed Central

Alt, Yvonne; Grimm, Anna; Schlegel, Liesa; Grambihler, Annette; Kittner, Jens M.; Wiltink, Jörg; Galle, Peter R.; Wörns, Marcus A.; Schattenberg, Jörn M.

2016-01-01

Background Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL). Furthermore we examined factors, which influence patient's physical and mental well-being. Methods A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D), a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA). Results Female gender (5.24 vs. 5.54, p = 0.04), diabetes mellitus type II (4.75 vs. 5.46, p<0.001) and daily drug intake (5.24 vs. 6.01, p = 0.003) were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001). Interestingly, CK18 exhibited significant correlations with obesity (p<0.001) and hyperlipidemia (p<0.001). In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03) and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047). Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003) and inflammation (p<0.001) in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048). Conclusion Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in chronic non-viral liver diseases. These findings support the role of liver-protective therapies for the improvement of the quality of life in chronic liver disease. PMID:26990427

TwiMed: Twitter and PubMed Comparable Corpus of Drugs, Diseases, Symptoms, and Their Relations

PubMed Central

Miyao, Yusuke; Collier, Nigel

2017-01-01

Background Work on pharmacovigilance systems using texts from PubMed and Twitter typically target at different elements and use different annotation guidelines resulting in a scenario where there is no comparable set of documents from both Twitter and PubMed annotated in the same manner. Objective This study aimed to provide a comparable corpus of texts from PubMed and Twitter that can be used to study drug reports from these two sources of information, allowing researchers in the area of pharmacovigilance using natural language processing (NLP) to perform experiments to better understand the similarities and differences between drug reports in Twitter and PubMed. Methods We produced a corpus comprising 1000 tweets and 1000 PubMed sentences selected using the same strategy and annotated at entity level by the same experts (pharmacists) using the same set of guidelines. Results The resulting corpus, annotated by two pharmacists, comprises semantically correct annotations for a set of drugs, diseases, and symptoms. This corpus contains the annotations for 3144 entities, 2749 relations, and 5003 attributes. Conclusions We present a corpus that is unique in its characteristics as this is the first corpus for pharmacovigilance curated from Twitter messages and PubMed sentences using the same data selection and annotation strategies. We believe this corpus will be of particular interest for researchers willing to compare results from pharmacovigilance systems (eg, classifiers and named entity recognition systems) when using data from Twitter and from PubMed. We hope that given the comprehensive set of drug names and the annotated entities and relations, this corpus becomes a standard resource to compare results from different pharmacovigilance studies in the area of NLP. PMID:28468748

TwiMed: Twitter and PubMed Comparable Corpus of Drugs, Diseases, Symptoms, and Their Relations.

PubMed

Alvaro, Nestor; Miyao, Yusuke; Collier, Nigel

2017-05-03

Work on pharmacovigilance systems using texts from PubMed and Twitter typically target at different elements and use different annotation guidelines resulting in a scenario where there is no comparable set of documents from both Twitter and PubMed annotated in the same manner. This study aimed to provide a comparable corpus of texts from PubMed and Twitter that can be used to study drug reports from these two sources of information, allowing researchers in the area of pharmacovigilance using natural language processing (NLP) to perform experiments to better understand the similarities and differences between drug reports in Twitter and PubMed. We produced a corpus comprising 1000 tweets and 1000 PubMed sentences selected using the same strategy and annotated at entity level by the same experts (pharmacists) using the same set of guidelines. The resulting corpus, annotated by two pharmacists, comprises semantically correct annotations for a set of drugs, diseases, and symptoms. This corpus contains the annotations for 3144 entities, 2749 relations, and 5003 attributes. We present a corpus that is unique in its characteristics as this is the first corpus for pharmacovigilance curated from Twitter messages and PubMed sentences using the same data selection and annotation strategies. We believe this corpus will be of particular interest for researchers willing to compare results from pharmacovigilance systems (eg, classifiers and named entity recognition systems) when using data from Twitter and from PubMed. We hope that given the comprehensive set of drug names and the annotated entities and relations, this corpus becomes a standard resource to compare results from different pharmacovigilance studies in the area of NLP. ©Nestor Alvaro, Yusuke Miyao, Nigel Collier. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 03.05.2017.

Implicit Theories of Intelligence and Academic Achievement: A Meta-Analytic Review

PubMed Central

Costa, Ana; Faria, Luísa

2018-01-01

The current study intended to model the link between implicit theories of intelligence (ITI) and students' academic achievement, within a meta-analytic review procedure. To assess studies' effect size, the Pearson's correlation coefficient (r) was used. The review of 46 studies (94 effect sizes) with 412,022 students presented a low-to-moderate association between the ITI and students' academic achievement. The results indicated that incremental theorists are more likely to have higher grades in specific subjects (verbal and quantitative) and in overall achievement. The entity beliefs were positively associated with students' specific verbal and quantitative domains but at a lower magnitude than incremental beliefs. Moreover, the moderator effect analyses results indicated that the link between ITI and students' achievement was not moderated by gender, but there was a moderate association in student's middle school grade. Additionally, the ITI assessment based on the most recent versions of Dweck's scales, the use of specific academic scales instead of general ITI scales, and the use of the original measures rather than adapted versions strongly moderated the link between ITI and achievement. Moreover, students from Eastern continents (Asia and Oceania) reported a positive association between incremental beliefs and achievement, Europe displayed a positive link between entity beliefs and achievement, whereas North America presented negative correlations between entity perspectives and academic achievement. This meta-analysis updates the current evidence supporting the direct link of ITI and students' academic achievement and acknowledges specific effects that ITI could have in different academic outcomes. PMID:29922195

Food Protein-Induced Enterocolitis Instead of Necrotizing Enterocolitis? A Neonatal Intensive Care Unit Case Series.

PubMed

Lenfestey, Mary W; de la Cruz, Diomel; Neu, Josef

2018-05-23

Necrotizing enterocolitis is an important disease in infants born premature. However, other disease entities present with similar signs and symptoms. This series reviews 5 atypical cases initially diagnosed as necrotizing enterocolitis that may be more consistent with food protein-induced enterocolitis. Food protein-induced enterocolitis may be underdiagnosed in this population. Copyright © 2018 Elsevier Inc. All rights reserved.

A rule-based named-entity recognition method for knowledge extraction of evidence-based dietary recommendations

PubMed Central

2017-01-01

Evidence-based dietary information represented as unstructured text is a crucial information that needs to be accessed in order to help dietitians follow the new knowledge arrives daily with newly published scientific reports. Different named-entity recognition (NER) methods have been introduced previously to extract useful information from the biomedical literature. They are focused on, for example extracting gene mentions, proteins mentions, relationships between genes and proteins, chemical concepts and relationships between drugs and diseases. In this paper, we present a novel NER method, called drNER, for knowledge extraction of evidence-based dietary information. To the best of our knowledge this is the first attempt at extracting dietary concepts. DrNER is a rule-based NER that consists of two phases. The first one involves the detection and determination of the entities mention, and the second one involves the selection and extraction of the entities. We evaluate the method by using text corpora from heterogeneous sources, including text from several scientifically validated web sites and text from scientific publications. Evaluation of the method showed that drNER gives good results and can be used for knowledge extraction of evidence-based dietary recommendations. PMID:28644863

Lyme disease: a rigorous review of diagnostic criteria and treatment.

PubMed

Borchers, Andrea T; Keen, Carl L; Huntley, Arthur C; Gershwin, M Eric

2015-02-01

Lyme disease was originally identified in Lyme, Connecticut, based upon an unusual cluster of what appeared to be patients with juvenile rheumatoid arthritis. It was subsequently identified as a new clinical entity originally called Lyme arthritis based on the observation that arthritis was a major clinical feature. However, Lyme arthritis is now called Lyme disease based upon the understanding that the clinical features include not only arthritis, but also potential cardiac, dermatologic and neurologic findings. Lyme disease typically begins with an erythematous rash called erythema migrans (EM). Approximately 4-8% of patients develop cardiac, 11% develop neurologic and 45-60% of patients manifest arthritis. The disease is transmitted following exposure to a tick bite containing a spirochete in a genetically susceptible host. There is considerable data on spirochetes, including Borrelia burgdorferi (Bb), the original bacteria identified in this disease. Lyme disease, if an organism had not been identified, would be considered as a classic autoimmune disease and indeed the effector mechanisms are similar to many human diseases manifest as loss of tolerance. The clinical diagnosis is highly likely based upon appropriate serology and clinical manifestations. However, the serologic features are often misinterpreted and may have false positives if confirmatory laboratory testing is not performed. Antibiotics are routinely and typically used to treat patients with Lyme disease, but there is no evidence that prolonged or recurrent treatment with antibiotics change the natural history of Lyme disease. Although there are animal models of Lyme disease, there is no system that faithfully recapitulates the human disease. Further research on the effector mechanisms that lead to pathology in some individuals should be further explored to develop more specific therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

The specific scintigraphic pattern of "shin splints in the lower leg": concise communication.

PubMed

Holder, L E; Michael, R H

1984-08-01

The clinical entity, "shin splints," is now being recognized, and more specifically characterized by the findings of exercise-induced pain and tenderness to palpation along the posterior medial border of the tibia. In this prospective study, ten patients with this syndrome were evaluated using three-phase bone scintigrams, and a specific scintigraphic pattern was determined. Radionuclide angiograms and blood-pool images were all normal. On delayed images, tibial lesions involved the posterior cortex, were longitudinally oriented, were long, involving one third of the length of the bone, and often showed varying tracer uptake along that length. Obtaining both lateral and medial views was crucial. The location of activity suggested that this entity is related to the soleus muscle. These scintigraphic findings can be used to differentiate shin splints from stress fractures or other conditions causing pain in the lower leg in athletes.

Genetic tests in major psychiatric disorders-integrating molecular medicine with clinical psychiatry-why is it so difficult?

PubMed

Demkow, U; Wolańczyk, T

2017-06-13

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays' medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease.

Genetic tests in major psychiatric disorders—integrating molecular medicine with clinical psychiatry—why is it so difficult?

PubMed Central

Demkow, U; Wolańczyk, T

2017-01-01

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays’ medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease. PMID:28608853

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

PubMed Central

Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa

2015-01-01

Cereal crops and cereal consumption have had a vital role in Mankind’s history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient’s clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis. PMID:26109797

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity.

PubMed

Elli, Luca; Branchi, Federica; Tomba, Carolina; Villalta, Danilo; Norsa, Lorenzo; Ferretti, Francesca; Roncoroni, Leda; Bardella, Maria Teresa

2015-06-21

Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.

Neuroprotective effects of leptin in the context of obesity and metabolic disorders.

PubMed

Davis, Cecilia; Mudd, Jeremy; Hawkins, Meredith

2014-12-01

As the population of the world ages, the prevalence of neurodegenerative disease continues to rise, accompanied by increases in disease burden related to obesity and metabolic disorders. Thus, it will be essential to develop tools for preventing and slowing the progression of these major disease entities. Epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. Experimentally, the fat-derived hormone leptin has been shown to act as a neuroprotective agent in various animal models of dementia, toxic insults, ischemia/reperfusion, and other neurodegenerative processes. Specifically, leptin minimizes neuronal damage induced by neurotoxins and pro-apoptotic conditions. Leptin has also demonstrated considerable promise in animal models of obesity and metabolic disorders via modulation of glucose homeostasis and energy intake. However, since obesity is known to induce leptin resistance, we hypothesize that resistance to the neuroprotective effects of leptin contributes to the pathogenesis of obesity-associated neurodegenerative diseases. This review aims to explore the literature pertinent to the role of leptin in the protection of neurons from the toxic effects of aging, obesity and metabolic disorders, to investigate the physiological state of leptin resistance and its causes, and to consider how leptin might be employed therapeutically in the prevention and treatment of neurodegenerative disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Frontal Assessment Battery as a Useful Tool to Differentiate Mild Cognitive Impairment due to Subcortical Ischemic Vascular Disease from Alzheimer Disease.

PubMed

Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Yang, Chi-Cheng; Tu, Min-Chien

2016-01-01

Prominent executive dysfunction can differentiate vascular dementia from Alzheimer disease (AD). However, it is unclear whether the Frontal Assessment Battery (FAB) screening tool can differentiate subcortical ischemic vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the neural correlates of FAB performance have yet to be clarified. Patients with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A), and demographically matched controls completed the Mini-Mental State Examination, Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal Learning Test, and underwent magnetic resonance imaging. White matter hyperintensities were rated according to the Scheltens scale. TFAB total scale and its Orthographical Fluency subtest were the only measures that could differentiate MCI-V from MCI-A. Discriminative analysis showed that Orthographical Fluency scores successfully identified 73.2% of the cases with MCI-V, with 85.0% sensitivity. Orthographical Fluency scores were specifically associated with lesion load within frontal periventricular, frontal deep white matter, and basal ganglia regions. The TFAB, and especially its 1-min Orthographical Fluency subtest, is a useful screening procedure to differentiate MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to frontosubcortical white matter pathologies disproportionately involved in the two disease entities. © 2016 S. Karger AG, Basel.

Adult dementia: history, biopsy, pathology.

PubMed

Torack, R M

1979-05-01

The historical events in the evolution of Alzheimer's disease are reviewed, including the initial description by Alois Alzheimer and the subsequent controversy regarding the nosological specificity of this entity. The similarity of senile dementia and Alzheimer's disease is emphasized. The basis for the modern concept of Alzheimer's disease as premature or accelerated aging is included in the review. The pathological correlates of the major categories of adult dementia have been described. The traditional criteria of neurofibrillary tangles and senile plaques have been re-evaluated using the current insight into these changes afforded by electron microscopy and biochemistry. The significance of amyloid has been described because it occurs within the senile plaque and also as the essential component of congophilic angiopathy. The new information regarding neuronal cell counts and the loss of choline acetyltransferase has been evaluated in terms of an indication of a pathogenic mechanism of Alzheimer's disease. The current understanding of normal pressure hydrocephalus, Creutzfeldt-Jakob disease, and multi-infarct dementia has been described. Brain biopsy in dementia has been described as having diagnostic, research, pathogenic, and prognostic value. The precautions involving the performance and handling of the biopsy have been stressed, particularly because these procedures involve conditions of possible slow virus etiology. The polemic for Alzheimer's disease as aging or slow virus infection has been summarized. At this time a consideration seems justified that Alzheimer's disease is an age-related, slow virus disease due to a hitherto unknown immune defect. Aging as an etiological agent must be clarified before Alzheimer's disease, in any form, can be considered to be an inevitable consequence of longevity.

Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

PubMed

Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

2016-10-01

Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. © 2016 UICC.

Increased recognition of Powassan encephalitis in the United States, 1999-2005.

PubMed

Hinten, Steven R; Beckett, Geoffrey A; Gensheimer, Kathleen F; Pritchard, Elizabeth; Courtney, Thomas M; Sears, Stephen D; Woytowicz, John M; Preston, David G; Smith, Robert P; Rand, Peter W; Lacombe, Eleanor H; Holman, Mary S; Lubelczyk, Charles B; Kelso, Patsy Tassler; Beelen, Andrew P; Stobierski, Mary Grace; Sotir, Mark J; Wong, Susan; Ebel, Gregory; Kosoy, Olga; Piesman, Joseph; Campbell, Grant L; Marfin, Anthony A

2008-12-01

Powassan virus (POWV) disease is a rare human disease caused by a tick-borne encephalitis group flavivirus maintained in a transmission cycle between Ixodes cookei and other ixodid ticks and small and medium-sized mammals. During 1958-1998, only 27 POWV disease cases (mostly Powassan encephalitis) were reported from eastern Canada and the northeastern United States (average, 0.7 cases per year). During 1999-2005, nine cases (described herein) of serologically confirmed POWV disease were reported in the United States (average, 1.3 cases per year): four from Maine, two from New York, and one each from Michigan, Vermont, and Wisconsin. The Michigan and Wisconsin cases are the first ever reported from the north-central United States. Of these nine patients, 5 (56%) were men, the median age was 69 years (range: 25-91 years), and 6 (67%) had onset during May-July. All but one patient developed encephalitis with acute onset of profound muscle weakness, confusion, and other severe neurologic signs. In one case, no neurologic symptoms were present but the presence of pleocytosis, an elevated cerebrospinal fluid (CSF) protein concentration, and POWV-specific immunoglobulin M in CSF suggested neuroinvasion. All patients recovered from their acute disease, but most had long-term neurologic sequelae. Periresidential ecologic investigations were performed in three cases, including tests of local mammals and ticks for evidence of POWV infection. Woodchucks (Marmota monax), striped skunks (Mephitis mephitis), and a raccoon (Procyon lotor) collected at two of the Maine case-patients' residences had neutralizing antibody titers to POWV. I. cookei were found on woodchucks and skunks and questing in grassy areas of one of these residences; all were negative for POWV. Although POWV disease is rare, it is probably under-recognized, and it causes significant morbidity, and thus is an additional tick-borne emerging infectious disease entity. Because no vaccine or specific therapy is available, the basis of prevention is personal protection from ticks (or "tick hygiene") and reduced exposure to peridomestic wild mammals.

[Bronchopulmonary diseases features in miners of Kolsky Transpolar area].

PubMed

Siurin, S A; Nikanov, A N

2009-01-01

Miners engaged into open-cast and underground extraction of copper-nickel ores in Kolsky Transpolar area have chronic bronchitis as a main nosologic entity among chronic bronchopulmonary diseases (19.1% of the workers). Considerably lower (4.0% of the workers) occurrence concerns chronic obstructive lung disease and bronchial asthma, both developed before the occupational involvement (1.3% of the workers). Complex of occupational and nonoccupational risk factors is connected mostly with smoking that increases COLD/CB risk 10.7-15.8-fold.

History of Morgellons disease: the same name for different psychodermatologic diseases?

PubMed

Ferreira, Bárbara Roque; Roccia, Maria Grazia; Cardoso, José Carlos; França, Katlein; Wollina, Uwe; Lotti, Torello; Fioranelli, Massimo

2017-10-01

"Morgellons disease" has been a controversial topic in the history of psychodermatology. The most consensual scientific opinion is that it is a primary psychiatric disorder, particularly, a delusional disorder, although others were also pointed out. Some authors have suggested that it may correspond to a common dermatosis with secondary psychopathology. The Morgellons Research Foundation has advocated that it is "an emerging infectious" entity. This paper intends to critically review the main ideas and controversies, since its first description.

Chronic parotitis: a challenging disease entity.

PubMed

Harbison, John M; Liess, Benjamin D; Templer, Jerry W; Zitsch, Robert P; Wieberg, Jessica A

2011-03-01

Chronic parotitis is a troubling clinical condition characterized by repeated infection and inflammation of the parotid gland caused by decreased salivary flow or obstruction. Unilateral swelling, pain, and other associated symptoms occur during acute exacerbations of the disease. A variety of laboratory and radiographic tools are available to aid in the diagnosis. Multiple treatment options have been proposed, ranging from conservative medical management to surgical interventions. We present 2 patients with bilateral chronic parotitis who attempted prolonged medical management and ultimately required surgical parotidectomy for control of their disease.

Idiopathic inflammatory myopathies overlapping with systemic diseases

PubMed Central

Lepreux, Sébastien; Hainfellner, Johannes A.; Vital, Anne

2018-01-01

A muscle biopsy is currently requested to assess the diagnosis of an idiopathic inflammatory myopathy overlapping with a systemic disease. During the past few years, the classification of inflammatory myopathy subtypes has been revisited progressively on the basis of correlations between clinical phenotypes, autoantibodies and histological data. Several syndromic entities are now more clearly defined, and the aim of the present review is to clarify the contribution of muscle biopsy in a setting of idiopathic inflammatory myopathies overlapping with systemic diseases. PMID:29154752

[Pyoderma gangrenosum and breast cancer: a new case].

PubMed

Labat, J P; Simon, H; Metges, J P; Lucas, B; Malhaire, J P

2000-06-01

We report here a new case of pyoderma gangrenosum (PG) associated with a breast cancer in a 39-year-old woman. We only found in literature three other reports of this rare entity which seems usually to be associated with monoclonal gammopathy, gastro-intestinal diseases such as Crohn's disease, chronic ulcerative colitis, leukemias or rheumatologic diseases. A commun hapten between of tumor and skin may explain the origin of this inflammatory lesion. In our case, PG could be a paraneoplastic syndrome.

Metal fume fever and polymer fume fever.

PubMed

Greenberg, Michael I; Vearrier, David

2015-05-01

Inhalational exposure to metal-containing fumes generated by welding and related processes may result in the development of the clinical syndrome known as "metal fume fever." Polymer fume fever is a separate and distinct but related disorder that has been associated with inhalational exposure to specific fluorinated polymer products, such as polytetrafluoroethylene or Teflon(®). We undertook a review of the peer-reviewed medical literature as it relates to these two disease entities in order to describe their epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, prevention, and prognosis. We performed a search of the PubMed ( www.pubmed.com ) and Ovid MEDLINE (ovidsp.tx.ovid.com) databases for keywords "metal fume fever," "polymer fume fever," and "fume fever," covering the period 1946 to September 2014, which resulted in a total of 141 citations. Limiting the search to articles published in the English language yielded 115 citations. These 115 articles were manually reviewed for relevance. In addition, the reference lists in each article retrieved were reviewed for additional relevant references. This left 48 relevant citations. Metal fume fever occurs most commonly as an occupational disease in individuals who perform welding and other metal-joining activities for a living. It is estimated that 1,500-2,500 cases of metal fume fever occur annually in the United States. Polymer fume fever was initially identified as an occupational disease but increased regulations have resulted in decreased incidence in the occupational setting. Overheating of Teflon(®)-coated cookware is one of the more common mechanisms for exposure. While the precise pathophysiology associated with the development of metal fume fever is yet to be elucidated, suggested pathophysiologic mechanisms include pro-inflammatory cytokine release, neutrophil activation, and oxygen radical formation. The pathophysiologic mechanism for polymer fume fever has not been definitively elucidated but may involve similar mechanisms to those proposed for metal fume fever. Metal fume fever typically presents with generally non-specific complaints including influenza-like symptoms, fever, shaking chills, arthalgias, myalgias, headache, and malaise. Onset of symptoms typically occurs 4-10 h following the exposure to metal-containing fumes. While metal fume fever is typically benign and self-limited, severe cases of the disease have been reported. In patients with ongoing metal fume exposure over the course of a workweek, tachyphylaxis occurs resulting in improvement in symptoms over the course of the workweek and maximal symptoms occurring after an exposure-free period such as a weekend. The clinical presentation of polymer fume fever is indistinguishable from metal fume fever, with an exposure history being necessary to distinguish the two entities. Chest radiographs are typically normal in cases of metal fume fever and polymer fume fever; however, mild vascular congestion may be demonstrated and severe cases may feature diffuse patchy infiltrates. Laboratory studies are typically not necessary but may demonstrate leukocytosis with leftward shift or an elevated erythrocyte sedimentation rate. The primary treatment for both metal fume fever and polymer fume fever is supportive and directed at symptom relief. Oral hydration, rest, and the use of antipyretics and anti-inflammatory medications (e.g., non-steroidal anti-inflammatory drugs and aspirin) are recommended. A careful workplace exposure assessment analysis conducted by an occupational medicine specialist or clinical toxicologist in concert with a qualified industrial hygienist should be performed. A careful workplace exposure assessment including measurement of ambient zinc and other metal (e.g., chrome, nickel, copper and manganese) fume concentrations or concentrations of fluorocarbon polymer decomposition products at different locations within the workplace should be performed. Metal fume fever is typically a benign and self-limited disease entity that resolves over 12-48 h following cessation of exposure. Metal and polymer fume fevers generally follow a benign course with spontaneous resolution of symptoms, though both have the potential to be serious, especially in those with significant preexisting cardiorespiratory disease.

Mask face: bilateral simultaneous facial palsy in an 11-year-old boy.

PubMed

Güngör, Serdal; Güngör Raif, Sabiha; Arslan, Müjgan

2013-04-01

Bilateral facial paralysis is an uncommon clinical entity especially in the pediatric age group and occurs frequently as a manifestation of systemic disease. The most important causes are trauma, infectious diseases, neurological diseases, metabolic, neoplastic, autoimmune diseases and idiopathic disease (Bell's palsy). We report a case of an 11-year-old boy presenting with bilateral simultaneous peripheral facial paralysis. All possible infectious causes were excluded and the patient was diagnosed as having Bell's palsy (idiopathic). The most important approach in these cases is to rule out a life-threatening disease. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

On certain development aspects of an ipsas-based system-target approach to evaluation of net asset sustainability level projects in high-rise construction

NASA Astrophysics Data System (ADS)

Kazaryan, Ruben

2018-03-01

Problems of accounting and reporting of net assets and the procedure of their formation taking into account the specifics of the economic and legal status of property of a non-commercial autonomous institution are some of the most controversial in the accounting for entities of the public sector. The study focuses on justification of accounting rules for net assets of public sector entities. The methods used in the study are as follows: comparison, synthesis, analysis, logical approach, and system approach. The article examines legal aspects and specifics of recognition of assets of public sector entities in accordance with IPSAS standards (International Public Sector Accounting Standards are a set of accounting standards issued by IPSASB (Council for International Financial Reporting Standards for Public Sector Organizations) used by state-owned enterprises worldwide in preparation of financial statements as of the 31st of August, 2015. The most crucial factor in the modeling of key performance indicators of the system-target approach to estimation of the sustainability level of net assets on the basis of IPSAS is a multicriterial evaluation of the basic management strategy for quality system elements used in operational and strategic planning projects operations in high-rise construction. We offer an alternative evaluation of assets due to be returned to the right holder (the state controller) in the event of liquidation of a public sector entity.

The nature of thinking, shallow and deep

PubMed Central

Brase, Gary L.

2014-01-01

Because the criteria for success differ across various domains of life, no single normative standard will ever work for all types of thinking. One method for dealing with this apparent dilemma is to propose that the mind is made up of a large number of specialized modules. This review describes how this multi-modular framework for the mind overcomes several critical conceptual and theoretical challenges to our understanding of human thinking, and hopefully clarifies what are (and are not) some of the implications based on this framework. In particular, an evolutionarily informed “deep rationality” conception of human thinking can guide psychological research out of clusters of ad hoc models which currently occupy some fields. First, the idea of deep rationality helps theoretical frameworks in terms of orienting themselves with regard to time scale references, which can alter the nature of rationality assessments. Second, the functional domains of deep rationality can be hypothesized (non-exhaustively) to include the areas of self-protection, status, affiliation, mate acquisition, mate retention, kin care, and disease avoidance. Thus, although there is no single normative standard of rationality across all of human cognition, there are sensible and objective standards by which we can evaluate multiple, fundamental, domain-specific motives underlying human cognition and behavior. This review concludes with two examples to illustrate the implications of this framework. The first example, decisions about having a child, illustrates how competing models can be understood by realizing that different fundamental motives guiding people’s thinking can sometimes be in conflict. The second example is that of personifications within modern financial markets (e.g., in the form of corporations), which are entities specifically constructed to have just one fundamental motive. This single focus is the source of both the strengths and flaws in how such entities behave. PMID:24860542

The nature of thinking, shallow and deep.

PubMed

Brase, Gary L

2014-01-01

Because the criteria for success differ across various domains of life, no single normative standard will ever work for all types of thinking. One method for dealing with this apparent dilemma is to propose that the mind is made up of a large number of specialized modules. This review describes how this multi-modular framework for the mind overcomes several critical conceptual and theoretical challenges to our understanding of human thinking, and hopefully clarifies what are (and are not) some of the implications based on this framework. In particular, an evolutionarily informed "deep rationality" conception of human thinking can guide psychological research out of clusters of ad hoc models which currently occupy some fields. First, the idea of deep rationality helps theoretical frameworks in terms of orienting themselves with regard to time scale references, which can alter the nature of rationality assessments. Second, the functional domains of deep rationality can be hypothesized (non-exhaustively) to include the areas of self-protection, status, affiliation, mate acquisition, mate retention, kin care, and disease avoidance. Thus, although there is no single normative standard of rationality across all of human cognition, there are sensible and objective standards by which we can evaluate multiple, fundamental, domain-specific motives underlying human cognition and behavior. This review concludes with two examples to illustrate the implications of this framework. The first example, decisions about having a child, illustrates how competing models can be understood by realizing that different fundamental motives guiding people's thinking can sometimes be in conflict. The second example is that of personifications within modern financial markets (e.g., in the form of corporations), which are entities specifically constructed to have just one fundamental motive. This single focus is the source of both the strengths and flaws in how such entities behave.

Narcolepsy with Long Sleep Time: A Specific Entity?

PubMed Central

Vernet, Cyrille; Arnulf, Isabelle

2009-01-01

Background: The classical narcolepsy patient reports intense feelings of sleepiness (with/out cataplexy), normal or disrupted nighttime sleep, and takes short and restorative naps. However, with long-term monitoring, we identified some narcoleptics resembling patients with idiopathic hypersomnia. Objective: To isolate and describe a new subtype of narcolepsy with long sleep time). Setting: University Hospital Design: Controlled, prospective cohort Participants: Out of 160 narcoleptics newly diagnosed within the past 3 years, 29 (18%) had a long sleep time (more than 11 h/24 h). We compared narcoleptics with (n = 23) and without (n = 29) long sleep time to 25 hypersomniacs with long sleep time and 20 healthy subjects. Intervention: Patients and controls underwent face-to face interviews, questionnaires, human leukocyte antigen (HLA) genotype, an overnight polysomnography, multiple sleep latency tests, and 24-h ad libitum sleep monitoring. Results: Narcoleptics with long sleep time had a similar disease course and similar frequencies of cataplexy, sleep paralysis, hallucinations, multiple sleep onset in REM periods, short mean sleep latencies, and HLA DQB1*0602 positivity as narcoleptics with normal sleep time did. However, they had longer sleep time during 24 h, and higher sleep efficiency, lower Epworth Sleepiness Scale scores, and reported their naps were more often unrefreshing. Only 3/23 had core narcolepsy (HLA and cataplexy positive). Conclusions: The subgroup of narcoleptics with a long sleep time comprises 18% of narcoleptics. Their symptoms combine the disabilities of both narcolepsy (severe sleepiness) and idiopathic hypersomnia (long sleep time and unrefreshing naps). Thus, they may constitute a group with multiple arousal system dysfunctions. Citation: Vernet C; Arnulf I. Narcolepsy with long sleep time: a specific entity? SLEEP 2009;32(9):1229-1235. PMID:19750928