tbuckley/cabot-search huggingface dataset:
Liver fibrosis in women with chronic hepatitis C: evidence for the negative role of the menopause and steatosis and the potential benefit of hormone replacement therapy
Authors: L. Codes, T. Asselah, D. Cazals-Hatem, F. Tubach, D. Vidaud, R. Parana, P. Bedossa, D. Valla, P. Marcellin
Journal: Gut (2006)

<b>Background and aims:</b> The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). <b>Methods:</b> From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. <b>Results:</b> 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2–F4, Metavir score) had a longer known duration of infection (&gt;15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0–F1). Women with F2–F4 were more often menopausal (67% <i>v</i> 47%). The probability of fibrosis F2–F4 was lower for menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more severe in menopausal women. <b>Conclusions:</b> Severity of fibrosis was associated with a longer duration of infection (&gt;15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.
Mortality in Iraq Associated with the 2003–2011 War and Occupation: Findings from a National Cluster Sample Survey by the University Collaborative Iraq Mortality Study
Authors: Amy Hagopian, Abraham D. Flaxman, Tim K. Takaro, Sahar A. Esa Al Shatari, Julie Rajaratnam, Stan Becker, Alison Levin-Rector, Lindsay Galway, Berq J. Hadi Al-Yasseri, William M. Weiss, Christopher J. Murray, Gilbert Burnham
Journal: PLoS Medicine (2013)

Based on a survey of 2,000 randomly selected households throughout Iraq, Amy Hagopian and colleagues estimate that close to half a million excess deaths are attributable to the recent Iraq war and occupation. Please see later in the article for the Editors' Summary
Determinants of primary medical care quality measured under the new UK contract: cross sectional study
Authors: Matt Sutton, Gary McLean
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To identify factors associated with the quality of primary medical care incentivised under the new UK general medical services contract. <b>Design</b> Cross sectional study. <b>Setting</b> NHS Ayrshire and Arran area, Scotland. <b>Participants</b> 60 general practices. <b>Main outcome measures</b> Quality scores reflecting the total points achieved on the 10 clinical domains and holistic care. Univariate and multivariate regression analyses were used to relate quality scores to measures of population characteristics, urban-rural location, general practitioner characteristics, clinical team size and composition, practice characteristics, and income from other sources. <b>Results</b> Deprivation was associated with higher scores. Quality scores increased with the size of the clinical team. Practices with higher income from other sources had lower quality scores. Practices that were accredited, had training status, or contained younger general practitioners had higher quality scores, but these effects were explained by other associated factors. 53% of the variation in quality scores was explained by a multivariate model, which included measures of deprivation, clinical team size and composition, and financial incentives. <b>Conclusions</b> Population characteristics showed little association with the quality of primary medical care incentivised under the UK general medical services contract. Larger clinical teams delivered higher quality clinical care, but the nurse-doctor composition of the clinical team did not influence quality. Practices that were more likely to respond to financial incentives because of previous behaviour or lower income from other sources recorded higher quality. If generalisable, the results suggest that initiatives to improve primary medical care quality should focus on the structure and resourcing of providers.
Familial liver disease
Authors: Y Reddy, Z Twaij, P D Mullins
Journal: Gut (2007)

A 52-year-old man presented with malaise and abnormal liver function tests: alanine aminotransferase 71 IU/ml (0–50), γ-glutamyltransferase 465 IU/ml (0–60), alkaline phosphatase 167 IU/ml (30–140), bilirubin 19 μmol (3–28). He had never …
Survival of patients with biopsy-proven usual interstitial pneumonia and nonspecific interstitial pneumonia
Authors: R.L. Riha, E.E. Duhig, B.E. Clarke, R.H. Steele, R.E. Slaughter, P.V. Zimmerman
Journal: European Respiratory Journal (2002)

This is the first Australian study to examine survival and clinical characteristics in biopsy-proven idiopathic interstitial pneumonia. A cohort of 70 patients from a single institution between January 1990 and December 1999 was reviewed. All patients were Caucasian, 23 (33%) female. Mean age+/-SD at diagnosis was 60+/-12 yrs for males and 54+/-14 yrs for females. A total 24% of patients had never smoked. The histopathological diagnoses were usual interstitial pneumonia (UIP) (n=59), nonspecific interstitial pneumonia (NSIP) (n=7), desquamative interstitial pneumonia (n=3) and acute interstitial pneumonia (n=11). Clinical and functional characteristics of the two main histological subgroups of UIP and NSIP showed significantly older patients in the UIP group and a significantly lower mean forced expiratory volume in one second (FEV1) in the NSIP group. Median survival for UIP was 78 months compared with 178 months for NSIP. No survival difference between treated and untreated patients with UIP was found. Multivariate analysis revealed smoking alone to be predictive of poorer survival. This study demonstrates the best median survival for usual interstitial pneumonia of available series and confirms a survival difference between usual interstitial pneumonia and nonspecific interstitial pneumonia. Furthermore, the reported results may have implications for treatment timing using conventional protocols currently recommended.
Dysbiosis of the Gut Microbiota Is Associated with HIV Disease Progression and Tryptophan Catabolism
Authors: Ivan Vujkovic-Cvijin, Richard M. Dunham, Shoko Iwai, Michael C. Maher, Rebecca G. Albright, Mara J. Broadhurst, Ryan D. Hernandez, Michael M. Lederman, Yong Huang, Ma Somsouk, Steven G. Deeks, Peter W. Hunt, Susan V. Lynch, Joseph M. McCune
Journal: Science Translational Medicine (2013)

Gut-resident microbial populations may influence intestinal homeostasis during HIV disease.
A study of total serum alkaline phosphatase activity in men following partial gastrectomy
Authors: J. Ambler, A. G. Green, C. N. Pulvertaft
Journal: Gut (1970)

Total serum alkaline phosphatase (SAP) activity has been measured in 463 men with partial gastrectomy (Polya type), and in a control group of 271 men with vagotomy with pyloroplasty or gastroenterostomy. An analysis of variance of the values in the range of 3.0 to 11.5 KA units/100 ml showed that the enzyme serum activity is influenced by three independent factors: age, ABO blood group, and the type of operation. Marginally raised levels (12.0-17.0 KA units/100 ml) were found to be affected by the same factors, and it was concluded that these levels do not, usually, indicate either bone or liver disease. In 18 men the total serum alkaline phosphatase was over 17.0 KA units: 16 had Paget's disease of bone, and two had liver disease.
Transmission of drug-susceptible and drug-resistant mycobacterium tuberculosis among households contacts
Authors: Nora Morcillo, Belen Imperiale, Beatriz Di Giulio, Martin Zumarraga, Angel Cataldi
Journal: European Respiratory Journal (2013)

The increase of multidrug-resistant Mycobacterium tuberculosis strains and the advent of the extensively drug-resistant tuberculosis (M/XDR-TB) are alarming the health-care providers about their active transmission in the communities.  The aim of this study was to estimate the ability of drug-resistant (DR) M. tuberculosis -mainly M/XDR-TB- to be transmitted among households contacts, comparing this capability with that from drug-susceptible strains (DS).  Methods. Patients’ clinical and epidemiological data were collected as well as the drug-susceptibility and genetic patterns of the isolates. Relative fitness (RF) was also calculated for each one of the isolates. MDR was detected and/or confirmed by molecular methods. The BACTEC MGIT960™ system with the Epicenter™ software was used to perform fitness experiments. A combination of bacterial plus clinical and epidemiological data was used to estimate the probable transmission sense.  A total of 38 households and 169 cases were identified: 96 (56.8%) men; HIV+: 25 (14.8%); 107 (63.3%) never treated cases. A total of 405 contacts (average: 3.1/case, range: 2-12) from M/XDR (162), DR (60) and DS (183) were investigated for TB. M/XDR was found in 78 (46.2%) patients from 23 households; 21 (27.0%) MDR considered as index cases generated 33 (42.3%) secondary cases (rate: 1.6) while 5 DR (no MDR) and 15 fully drug-susceptible index cases produced 15 (rate: 3.0) and 46 (rate: 3.1) secondary cases respectively. From 24 (30.7%) MDR no secondary cases were found.  An average RF drop of 16.7% was found for MDR strains. MDR, DS and DR strains were transmitted to 20.4%, 25.1% and 25.0% of their respectively studied household contacts.
STRESS-PERFUSION CMRI PROVIDES ROBUST PROGNOSTIC INFORMATION FOR DIABETIC PATIENTS AT RISK FOR MAJOR ADVERSE CARDIAC EVENTS
Authors: Jiazuo H. Feng, Ravi Shah, Siddique Abbasi, Otávio Coelho Filho, Bobak Heydari, Ron Blankstein, Michael Steigner, Michael Jerosch-Herold, Raymond Kwong
Journal: Journal of the American College of Cardiology (2013)
The Impact of Insurance on Access to Cancer Clinical Trials at a Comprehensive Cancer Center
Authors: Justin F. Klamerus, Suanna S. Bruinooge, Xiaobu Ye, Mandi L. Klamerus, Dorothy Damron, Dina Lansey, John C. Lowery, Luis A. Diaz, Jean G. Ford, Norma Kanarek, Charles M. Rudin
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Cancer patients at Johns Hopkins undergo insurance clearance to verify coverage for enrollment to interventional clinical trials. We sought to explore the impact of insurance clearance on disparities in access to cancer clinical trials at this urban comprehensive cancer center. Experimental Design: We evaluated the frequency of insurance-based denial of access to cancer clinical trials over a 5-year period after initiation of a formal insurance clearance process. We used a case-control design to compare demographic and clinical parameters of patients denied or approved for clinical trials participation by their insurance company in a 3-year interval. Results: From July 2003 to July 2008, insurance requests for clinical trial participation were submitted on 4,617 consented cancer patients at Johns Hopkins. A total of 628 patients (13.6%) with health insurance were denied therapeutic trial enrollment owing to lack of insurance coverage for participation. A total of 254 patients denied enrollment from 2005 to 2007 were selected for further analysis. Two-hundred sixty randomly selected patients approved for clinical trial participation served as controls. Patients approved were on average older (59.2 versus 54.9 years) than patients denied (P = 0.0001). Residents of Pennsylvania, which lacks a state law mandating cancer clinical trial coverage for residents, were overrepresented among the denied patients (P = 0.0009). No statistically significant variance in the likelihood of insurance denial was found on the basis of sex, race, stage of disease, or presence of comorbidities. Conclusions: Denial of access to therapeutic clinical trials, even among insured patients, is a significant barrier to clinical cancer research. This barrier spans racial, ethnic, and gender categories. Clin Cancer Res; 16(24); 5997–6003. ©2010 AACR.
Naturally occurring lymphocyte-mediated immunity to endogenous type-C virus in the mouse. Blocking of the lymphocyte reactivity with antisera to the virus.
Authors: M Kende, R Hill, M Dinowitz, J R Stephenson, G J Kelloff
Journal: The Journal of Experimental Medicine (1979)

The natural immune response in mice to their endogenous type-C viruses involves a complex interaction between cellular and humoral immune mechanisms. The virus-specific immune reactivities are a function of age and appear only subsequent to endogenous virus expression. Cellular immune activity was found to reside in a population of lymphocytes that were characterized as natural killer cells based on their absence of theta surface antigens or immunoglobulin or complement receptors. Cellular and humoral virus-specific immune responses co-occur in the same animal and pretreatment of virus-positive target cells with sera from virus-positive aging mice is capable of partially blocking the cytotoxic activity of reactive lymphocytes. The blocking activity of sera from individual mice increases as a function of age and endogenous virus expression and is highly correlated with the virus-specific complement-dependent cytotoxic activity of these sera. Mouse sera, whether naturally immune or immune as a result of hyperimmunization with type-C virus, exhibit blocking activity that can be removed by absorption with purified type-C virus or purified viral glycoprotein (gp 70) but not by absorption with noninfected syngeneic cells. High-titered and highly specific antisera directed against certain individual R-MuLV structural proteins reveal blocking activity. Monospecific antisera to gp 70 and p 12 exhibited high-titered blocking reactivities which are absorbable by the respective purified proteins. Blocking activity of antisera directed against other viral structural proteins could not be excluded with certainty. These findings raise the possibility that immunity in the mouse to endogenous type-C virus or virus-infected cells involves competition between serum-blocking activity and natural-killer cell activity and further provides a unique model system for studying the mechanism of action of blocking antisera known to have monospecific reactivity against defined and purifiable transplantation antigens.
Gene expression and hepatitis C virus infection
Authors: T Asselah, I Bieche, A Sabbagh, P Bedossa, R Moreau, D Valla, M Vidaud, P Marcellin
Journal: Gut (2008)

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. Up to 70% of patients will have persistent infection after inoculation, making this disease a significant cause of morbidity and mortality. The severity of disease varies widely, from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Since the discovery of HCV, the treatment of hepatitis C has considerably improved. Recently, combination of pegylated interferons with ribavirin gives a response rate of about 55%. Treatment is indicated in patients with moderate or severe fibrosis. The tolerability of combination treatment is relatively poor, with a frequent flu-like syndrome and an impaired quality of life. In addition to viral and environmental behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in HCV infection. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome or predict the response to treatment. This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment.
Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus
Authors: Jason S. Knight, Wenpu Zhao, Wei Luo, Venkataraman Subramanian, Alexander A. O’Dell, Srilakshmi Yalavarthi, Jeffrey B. Hodgin, Daniel T. Eitzman, Paul R. Thompson, Mariana J. Kaplan
Journal: Journal of Clinical Investigation (2013)

Recent evidence suggests that enhanced neutrophil extracellular trap (NET) formation activates plasmacytoid dendritic cells and serves as a source of autoantigens in SLE. We propose that aberrant NET formation is also linked to organ damage and to the premature vascular disease characteristic of human SLE. Here, we demonstrate enhanced NET formation in the New Zealand mixed 2328 (NZM) model of murine lupus. NZM mice also developed autoantibodies to NETs as well as the ortholog of human cathelicidin/LL37 (CRAMP), a molecule externalized in the NETs. NZM mice were treated with Cl-amidine, an inhibitor of peptidylarginine deiminases (PAD), to block NET formation and were evaluated for lupus-like disease activity, endothelial function, and prothrombotic phenotype. Cl-amidine treatment inhibited NZM NET formation in vivo and significantly altered circulating autoantibody profiles and complement levels while reducing glomerular IgG deposition. Further, Cl-amidine increased the differentiation capacity of bone marrow endothelial progenitor cells, improved endothelium-dependent vasorelaxation, and markedly delayed time to arterial thrombosis induced by photochemical injury. Overall, these findings suggest that PAD inhibition can modulate phenotypes crucial for lupus pathogenesis and disease activity and may represent an important strategy for mitigating cardiovascular risk in lupus patients.
Bactericidal Activity of Pyrazinamide and Clofazimine Alone and in Combinations with Pretomanid and Bedaquiline
Authors: Andreas H. Diacon, Rodney Dawson, Florian von Groote-Bidlingmaier, Gregory Symons, Amour Venter, Peter R. Donald, Christo van Niekerk, Daniel Everitt, Jane Hutchings, Divan A. Burger, Robert Schall, Carl M. Mendel
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<MethodsResultsPharmacokineticsMycobacteriologySafety and TolerabilityDiscussionReferencesCITING ARTICLES
Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells
Authors: Anna Mattout, Yair Aaronson, Badi Sri Sailaja, Edupuganti V. Raghu Ram, Arigela Harikumar, Jan-Philipp Mallm, Kae Hwan Sim, Malka Nissim-Rafinia, Emmanuelle Supper, Prim B. Singh, Siu Kwan Sze, Susan M. Gasser, Karsten Rippe, Eran Meshorer
Journal: Genome biology (2015)

Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1α, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state.
Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease
Authors: Bonnie C.H. Kwan, Florian Kronenberg, Srinivasan Beddhu, Alfred K. Cheung
Journal: Journal of the American Society of Nephrology (2007)

Dyslipidemia is an established cardiovascular (CV) risk factor in the general population. In chronic kidney disease (CKD), however, epidemiologic studies ([1][1]–[3][2]) and clinical trials ([4][3]–[12][4]) have raised uncertainties regarding the impact of dyslipidemia on clinical outcomes and,
Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals
Authors: JV Chamary, Laurence D Hurst
Journal: Genome biology (2005)

Abstract Background In mammals, contrary to what is usually assumed, recent evidence suggests that synonymous mutations may not be selectively neutral. This position has proven contentious, not least because of the absence of a viable mechanism. Here we test whether synonymous mutations might be under selection owing to their effects on the thermodynamic stability of mRNA, mediated by changes in secondary structure. Results We provide numerous lines of evidence that are all consistent with the above hypothesis. Most notably, by simulating evolution and reallocating the substitutions observed in the mouse lineage, we show that the location of synonymous mutations is non-random with respect to stability. Importantly, the preference for cytosine at 4-fold degenerate sites, diagnostic of selection, can be explained by its effect on mRNA stability. Likewise, by interchanging synonymous codons, we find naturally occurring mRNAs to be more stable than simulant transcripts. Housekeeping genes, whose proteins are under strong purifying selection, are also under the greatest pressure to maintain stability. Conclusion Taken together, our results provide evidence that, in mammals, synonymous sites do not evolve neutrally, at least in part owing to selection on mRNA stability. This has implications for the application of synonymous divergence in estimating the mutation rate.
Adaptation and possible ancient interspecies introgression in pigs identified by whole-genome sequencing
Authors: Huashui Ai, Xiaodong Fang, Bin Yang, Zhiyong Huang, Hao Chen, Likai Mao, Feng Zhang, Lu Zhang, Leilei Cui, Weiming He, Jie Yang, Xiaoming Yao, Lisheng Zhou, Lijuan Han, Jing Li, Silong Sun, Xianhua Xie, Boxian Lai, Ying Su, Yao Lu, Hui Yang, Tao Huang, Wenjiang Deng, Rasmus Nielsen, Jun Ren, Lusheng Huang
Journal: Nature Genetics (2015)
Noncanonical Mode of ERK Action Controls Alternative αβ and γδ T Cell Lineage Fates
Authors: Sang-Yun Lee, Francis Coffey, Shawn P. Fahl, Suraj Peri, Michele Rhodes, Kathy Q. Cai, Michael Carleton, Stephen M. Hedrick, Hans Joerg Fehling, Juan Carlos Zúñiga-Pflücker, Dietmar J. Kappes, David L. Wiest
Journal: Immunity (2014)