tbuckley/cabot-search huggingface dataset:
Temporal dynamics of inflammatory cytokines/chemokines during sofosbuvir and ribavirin therapy for genotype 2 and 3 hepatitis C infection
Authors: Aaron F. Carlin, Paula Aristizabal, Qinghua Song, Huan Wang, Matthew S. Paulson, Luisa M. Stamm, Robert T. Schooley, David L. Wyles
Journal: Hepatology (2015)

The analysis of inflammatory cytokines and chemokines produced during hepatitis C virus (HCV) infection has advanced our understanding of viral‐host interactions and identified predictors of treatment response. Administration of interferons (IFNs) made it difficult to interpret biomarkers of immune activation during treatment. Direct‐acting antiviral (DAA) regimens without IFN are now being used to treat HCV with excellent efficacy. To gain insight into HCV‐host interactions occurring before, during, and after HCV treatment, we performed a case‐control study that measured serial plasma levels of IFN‐γ‐inducible protein 10 (IP‐10), monocyte chemoattractant protein 1 (MCP‐1), macrophage inflammatory protein 1 beta (MIP‐1β), and interleukin‐18 (IL‐18) in 131 patients with chronic HCV treated with sofosbuvir (SOF) plus ribavirin (RBV). A linear regression analysis using baseline factors identified strong positive associations between elevated alanine aminotransferase and pretreatment IP‐10 and between the presence of cirrhosis and elevated pretreatment IL‐18. Mean IP‐10, MCP‐1, MIP‐1β, and IL‐18 levels all decline on therapy, but display different dynamics late in treatment and after cessation of therapy. On treatment, IP‐10 and MIP‐1β levels were significantly higher in individuals who achieved sustained virological response (SVR). Logistic regression analyses examining treatment response in all patients demonstrated significant associations between higher baseline MIP‐1β levels and smaller decreases in MIP‐1β early in treatment and SVR. Higher early MIP‐1β levels were also significantly associated with SVR in subsets of patients with cirrhosis and individuals with genotype 3 (GT3) infection, two factors associated with decreased responsiveness to treatment. Conclusion : Changes in IP‐10 levels mirror HCV RNA, suggesting that IP‐10 is an indicator of innate immune viral recognition. MIP‐1β levels remain elevated in GT2/3 patients who achieved SVR, suggesting differential immune activation in those who respond to SOF/RBV therapy and a potential role in predicting treatment responses. (H epatology 2015;62:1047‐1058)
Thermal, physiological and perceptual strain mediate alterations in match-play tennis under heat stress
Authors: Julien D Périard, Sébastien Racinais, Wade L Knez, Christopher P Herrera, Ryan J Christian, Olivier Girard
Journal: British Journal of Sports Medicine (2014)

This study compared the thermal, physiological and perceptual responses associated with match-play tennis in HOT (∼34°C wet-bulb-globe temperature (WBGT)) and COOL (∼19°C WBGT) conditions, along with the accompanying alterations in match characteristics.12 male tennis players undertook two matches for an effective playing time (ie, ball in play) of 20 min, corresponding to ∼119 and ∼102 min of play in HOT and COOL conditions, respectively. Rectal and skin temperatures, heart rate, subjective ratings of thermal comfort, thermal sensation and perceived exertion were recorded, along with match characteristics.End-match rectal temperature increased to a greater extent in the HOT (∼39.4°C) compared with the COOL (∼38.7°C) condition (p<0.05). Thigh skin temperature was higher throughout the HOT match (p<0.001). Heart rate, thermal comfort, thermal sensation and perceived exertion were also higher during the HOT match (p<0.001). Total playing time was longer in the HOT compared with the COOL match (p<0.05). Point duration (∼7.1 s) was similar between conditions, while the time between points was ∼10 s longer in the HOT relative to the COOL match (p<0.05). This led to a ∼3.4% lower effective playing percentage in the heat (p<0.05). Although several thermal, physiological and perceptual variables were individually correlated to the adjustments in time between points and effective playing percentage, thermal sensation was the only predictor variable associated with both adjustments (p<0.005).These adjustments in match-play tennis characteristics under severe heat stress appear to represent a behavioural strategy adopted to minimise or offset the sensation of environmental conditions being rated as difficult.
Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to Pre-S- and S-encoded viral surface antigens
Authors: Guido Gerken, Patricia Paterlini, Michael Manns, Chantal Housset, Sylvie Terre, Hans-Peter Dienes, Georg Hess, Wolfram H. Gerlich, Pierre Berthelot, Karl-Hermann Meyer Zum Büschenfelde, Christian Brechot
Journal: Hepatology (1991)

The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis B virus carriers. Hepatitis B virus DNA was detectable in the serum of HBsAg-positive virus carriers using aliquots as small as 100 al. The detection limit for cloned hepatitis B virus DNA was 100 ag. Primer pairs for different regions of the HBV genome resulted in different sensitivity. Detection of the amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay. Using several primer pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80% of HBe antibody-positive symptomatic HBsAg carriers and 57% of asymptomatic HBe antibody-positive HBsAg carriers were found to have hepatitis B virus DNA in the serum. During antiviral therapy hepatitis B virus DNA disappeared by the polymerase chain reaction assay in patients who became HBeAg negative, but polymerase chain reaction detected a relapse earlier than did the conventional dot blot. Pre-S antigens were assayed in serum and liver samples from most chronic carriers by enzyme-linked immunosorbent assay and/or immunoblot. Although most viremic carriers were strongly positive for pre-S1 and pre-S2 antigens, some hepatitis B virus DNA-positive HBsAg carriers did not have detectable pre-S antigens, and vice versa. Our data show that assay of hepatitis B virus DNA in the serum by polymerase chain reaction is by far more proficient than by dot blot and that it cannot be replaced by serological assays of HBeAg or pre-S antigen.
Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials
Authors: Mark A Hlatky, Derek B Boothroyd, Dena M Bravata, Eric Boersma, Jean Booth, Maria M Brooks, Didier Carrié, Tim C Clayton, Nicolas Danchin, Marcus Flather, Christian W Hamm, Whady A Hueb, Jan Kähler, Sheryl F Kelsey, Spencer B King, Andrzej S Kosinski, Neuza Lopes, Kathryn M McDonald, Alfredo Rodriguez, Patrick Serruys, Ulrich Sigwart, Rodney H Stables, Douglas K Owens, Stuart J Pocock
Journal: The Lancet (2009)
The genome of Rhizobium leguminosarum has recognizable core and accessory components
Authors: J Peter W Young, Lisa C Crossman, Andrew WB Johnston, Nicholas R Thomson, Zara F Ghazoui, Katherine H Hull, Margaret Wexler, Andrew RJ Curson, Jonathan D Todd, Philip S Poole, Tim H Mauchline, Alison K East, Michael A Quail, Carol Churcher, Claire Arrowsmith, Inna Cherevach, Tracey Chillingworth, Kay Clarke, Ann Cronin, Paul Davis, Audrey Fraser, Zahra Hance, Heidi Hauser, Kay Jagels, Sharon Moule, Karen Mungall, Halina Norbertczak, Ester Rabbinowitsch, Mandy Sanders, Mark Simmonds, Sally Whitehead, Julian Parkhill
Journal: Genome biology (2006)

Rhizobium leguminosarum is an alpha-proteobacterial N2-fixing symbiont of legumes that has been the subject of more than a thousand publications. Genes for the symbiotic interaction with plants are well studied, but the adaptations that allow survival and growth in the soil environment are poorly understood. We have sequenced the genome of R. leguminosarum biovar viciae strain 3841.
DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial–Mesenchymal Transition in Human Breast Cancer
Authors: Qi Lv, Wei Wang, Jianfei Xue, Fang Hua, Rong Mu, Heng Lin, Jun Yan, Xiaoxi Lv, Xiaoguang Chen, Zhuo-Wei Hu
Journal: Cancer Research (2012)

Abstract Epithelial-to-mesenchymal transition (EMT), a crucial developmental program, contributes to cancer invasion and metastasis. In this study, we show that death-effector domain-containing DNA-binding protein (DEDD) attenuates EMT and acts as an endogenous suppressor of tumor growth and metastasis. We found that expression levels of DEDD were conversely correlated with poor prognosis in patients with breast and colon cancer. Both in vitro and in vivo, overexpression of DEDD attenuated the invasive phenotype of highly metastatic cells, whereas silencing of DEDD promoted the invasion of nonmetastatic cells. Via direct interaction with the class III PI-3-kinase (PI3KC3)/Beclin1, DEDD activated autophagy and induced the degradation of Snail and Twist, two master regulators of EMT. The DEDD–PI3KC3 interaction led to stabilization of PI3KC3, which further contributed to autophagy and the degradation of Snail and Twist. Together, our findings highlight a novel mechanism in which the intracellular signaling protein DEDD functions as an endogenous tumor suppressor. DEDD expression therefore may represent a prognostic marker and potential therapeutic target for the prevention and treatment of cancer metastasis. Cancer Res; 72(13); 3238–50. ©2012 AACR.
Silence Is Golden: Gene Hypermethylation and Survival in Large-Cell Lymphoma
Authors: M. E. Dolan
Journal: JNCI Journal of the National Cancer Institute (2002)

Much effort has been directed at identifying molecular markers in human tumors that predict response and/or survival after treatment with chemotherapeutic agents. Molecular predictors help to identify patients most likely to benefit from a particular therapy, with the ultimate goal of selecting optimal treatment for each patient. Gene microarray analysis has already identified genes that may be useful for predicting the clinical behavior of certain tumors (1,2). In malignant lymphoma, microarray analysis has clearly identified subgroups of tumors within the category of diffuse large B-cell lymphoma (B-DLCL) that are histologically indistinguishable but differ considerably in outcome after treatment with standard therapies (3). The specific genes responsible for the different outcomes have not yet been identified. In this issue of the Journal, Esteller et al. (4) describe a new predictive marker of survival in patients with B-cell lym
DNA Methylation and Structural and Functional Bimodality of Vertebrate Promoters
Authors: N. Elango, S. V. Yi
Journal: Molecular Biology and Evolution (2008)

Human promoters divide into 2 classes, the low CpG (LCG) and the high CpG (HCG), based on their CpG dinucleotide content. The LCG class of promoters is hypermethylated and is associated with tissue-specific genes, whereas the HCG class is hypomethylated and associated with broadly expressed genes. By analyzing several chordate genomes separated for hundreds of millions of years, here we show that the divide between low CpG and high CpG promoters is conserved in several distantly related vertebrate taxa (including human, chicken, frog, lizard, and fish) but not in close invertebrate outgroups (sea squirts). Furthermore, LCG and HCG promoters are distinctively associated with tissue-specific and broadly expressed genes in these distantly related vertebrate taxa. Our results indicate that the function of DNA methylation on gene expression is conserved across these vertebrate taxa and suggest that the 2 classes of promoters have evolved early in vertebrate evolution, as a consequence of the advent of global DNA methylation.
Mobile phone use and risk of glioma in adults: case-control study
Authors: Sarah J Hepworth, Minouk J Schoemaker, Kenneth R Muir, Anthony J Swerdlow, Martie J A van Tongeren, Patricia A McKinney
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To investigate the risk of glioma in adults in relation to mobile phone use. <b>Design</b> Population based case-control study with collection of personal interview data. <b>Setting</b> Five areas of the United Kingdom. <b>Participants</b> 966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29 February 2004 and 1716 controls randomly selected from general practitioner lists. <b>Main outcome measures</b> Odds ratios for risk of glioma in relation to mobile phone use. <b>Results</b> The overall odds ratio for regular phone use was 0.94 (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk for reported phone use ipsilateral to the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk (0.75, 0.61 to 0.93) for contralateral use. <b>Conclusions</b> Use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma. This is consistent with most but not all published studies. The complementary positive and negative risks associated with ipsilateral and contralateral use of the phone in relation to the side of the tumour might be due to recall bias.
Paediatric hepatocellular carcinoma due to somatic CTNNB1 and NFE2L2 mutations in the setting of inherited bi-allelic ABCB11 mutations
Authors: Sílvia Vilarinho, E. Zeynep Erson-Omay, Akdes Serin Harmanci, Raffaella Morotti, Geneive Carrion-Grant, Jacob Baranoski, A.S. Knisely, Udeme Ekong, Sukru Emre, Katsuhito Yasuno, Kaya Bilguvar, Murat Günel
Journal: Journal of Hepatology (2014)
Urinary Free Cortisol in Chronic Fatigue Syndrome
Authors: A J Cleare, D Blair, S Chambers, S Wessely
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors measured 24-hour urinary free cortisol in a group of well-characterized patients with chronic fatigue syndrome. METHOD: They obtained 24-hour urine collections from 121 consecutive clinic patients with chronic fatigue syndrome and 64 comparison subjects without the syndrome. RESULTS: Urinary free cortisol was significantly lower in the subjects with chronic fatigue syndrome regardless of the presence or absence of current or past comorbid psychiatric illness. Lower levels of urinary free cortisol were not related to medication use, sleep disturbance, or disability levels. CONCLUSIONS: There is mild hypocortisolism in chronic fatigue syndrome. Whether a primary feature or secondary to other factors, hypocortisolism may be one factor contributing to the symptoms of chronic fatigue syndrome.
Single measures of performance do not reflect overall institutional quality in colorectal cancer surgery
Authors: Alex M Almoudaris, Elaine M Burns, Alex Bottle, Paul Aylin, Ara Darzi, Charles Vincent, Omar Faiz
Journal: Gut (2012)

<h3>Objective</h3> To evaluate overall performance of English colorectal cancer surgical units identified as outliers for a single quality measure—30 day inhospital mortality. <h3>Design</h3> 144 542 patients that underwent primary major colorectal cancer resection between 2000/2001 and 2007/2008 in 149 English National Health Service units were included from hospital episodes statistics. Casemix adjusted funnel plots were constructed for 30 day inhospital mortality, length of stay, unplanned readmission within 28 days, reoperation, failure to rescue-surgical (FTR-S) and abdominoperineal excision (APE) rates. Institutional performance was evaluated across all other domains for institutions deemed outliers for 30 day mortality. Outliers were those that lay on or breached 3 SD control limits. 'Acceptable' performance was defined if units appeared under the upper 2 SD limit. <h3>Results</h3> 5 high mortality outlier (HMO) units and 15 low mortality outlier (LMO) units were identified. Of the five HMO units, two were substandard performance outliers (ie, above 3 SD) on another metric (both on high reoperation rates). A further two HMO institutions exceeded the second but not the third SD limits for substandard performance on other outcome metrics. One of the 15 LMO units exceeded 3 SD for substandard performance (APE rate). One LMO institution exceeded the second but not the third SD control limits for high reoperation rates. Institutional mortality correlated with FTR-S and reoperations (R=0.445, p&lt;0.001 and R=0.191, p&lt;0.020 respectively). <h3>Conclusions</h3> Performance appraisal in colorectal surgery is complex and dependent on stakeholder perspective. Benchmarking units solely on a single performance measure is over simplistic and potentially hazardous. A global appraisal of institutional outcome is required to contextualise performance.
Relapse of respiratory insufficiency one year after organising pneumonia
Authors: J-M. Naccache, M. Kambouchner, F. Girard, M. Antoine, A. Parrot, J. Piquet, M. Brauner, D. Valeyre
Journal: European Respiratory Journal (2004)

A 66-yr-old nonsmoker female presented in June 1998 with a 3-week history of progressive dyspnoea. Her past medical history was noteworthy for idiopathic bilateral uveitis without sequelae between 1978 and 1993, hypercholesterolaemia and angina pectoris. Her medication included fluvastatin, which started in June 1997 (60 mg·day−1), trinitrin patch and acetylsalicylic acid. She had no particular work-related or environmental dust exposure. Examination of the chest revealed bilateral basal crackles. There was no digital clubbing or extrapulmonary signs. At admission, chest radiograph and thoracic computed tomography (CT) scan (fig. 1a⇓) revealed patchy consolidations, predominantly involving the bilateral lower lobes.



Fig. 1.— 
Computed tomography (CT) scans of 1-mm thickness at lung window. a) CT scan revealed irregularly marginated patchy alveolar consolidations with an air bronchogram. The lesions were bilateral and predominantly involved the lower lobes. b) After 1 yr, the consolidations disappeared almost completely. CT scan revealed some linear opacities of irregular thickness. c) CT scan from September 1999. d) CT scan revealed the same lesions with some improvement in May 2003.



Arterial blood gas analysis under supplemental oxygen (6 L·min−1) revealed a partial pressure of oxygen of 8.3 kPa (62 mmHg), a partial pressure of carbon dioxide of 4.3 kPa (32 mmHg) and a pH of 7.46. As a result of rapidly progressive respiratory failure, she was admitted to the intensive care unit. Bronchoalveolar lavage (BAL) analysis showed a 140×106 cells·L−1 increased lymphocyte rate (38%), low CD4/CD8 ratio (0.18), increased neutrophil rate (17%), 44% of macrophages and 1% of eosinophils. Transbronchial lung biopsy, including 20 alveoli, revealed typical lesions of organising pneumonia (fig. 2a⇓). Minor salivary gland biopsy specimens found no sign of Sjogren's syndrome. Antinuclear antibodies were positive at a titre of 1:50 of speckled pattern; anti-JO1 antibodies were positive. Neither clinical nor biological signs of muscular involvement were found. Fluvastatin was stopped.



Fig. 2.— 
a) Transbronchial biopsy …
Pancreas Transplantation as Therapy for Diabetes Mellitus
Authors: R P Robertson, D E R Sutherland
Journal: Annual Review of Medicine (1992)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Interaction between Smoking and Genetic Factors in the Development of Chronic Bronchitis
Authors: Jenny Hallberg, Annica Dominicus, Ulrika K. Eriksson, Maria Gerhardsson de Verdier, Nancy L. Pedersen, Magnus Dahlbäck, Ulf Nihlén, Tim Higenbottam, Magnus Svartengren
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Smoking is a primary risk factor for chronic bronchitis, emphysema, and chronic obstructive pulmonary disease, but since not all smokers develop disease, it has been suggested that some individuals may be more susceptible to exogenous factors, such as smoking, and that this susceptibility could be genetically determined.Objectives: The aim of the present study was to assess, in a population-based sample of twins, the following: (1) to what extent genetic factors contribute to the development of chronic bronchitis, including emphysema, taking sex into consideration, and (2) whether the genetic influences on chronic bronchitis, including emphysema, are separate from those for smoking behavior.Methods: Disease cases and smoking habits were identified in 44,919 twins older than 40 years from the Swedish Twin Registry. Disease was defined as self-reported chronic bronchitis or emphysema, or recurrent cough with phlegm. Individuals who had smoked 10 pack-years or more were defined as smokers. Univariate and bivariate structural equation models were used to estimate the heritability specific for chronic bronchitis and that in common with smoking.Measurements and Main Results: The heritability estimate for chronic bronchitis was a moderate 40% and only 14% of the genetic influences were shared with smoking.Conclusions: Genetic factors independent of those related to smoking habits play a role in the development of chronic bronchitis.
Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis
Authors: Carmel Toomes, Jacqueline James, A. Joseph Wood, Chu Lee Wu, Derek McCormick, Nicholas Lench, Chelsee Hewitt, Leanne Moynihan, Emma Roberts, C. Geoffrey Woods, Alexander Markham, Melanie Wong, Richard Widmer, Khaled Abdul Ghaffar, Michael Pemberton, Ibtessam Ramzy Hussein, Samia A. Temtamy, Robin Davies, Andrew P. Read, Philip Sloan, Michael J. Dixon, Nalin S. Thakker
Journal: Nature Genetics (1999)
Response to Comment on: Satoh-Asahara et al. Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia. Diabetes Care 2012;35:2631–2639
Authors: Noriko Satoh-Asahara, Akira Shimatsu, Hiromichi Wada, Takayoshi Suganami, Koji Hasegawa, Yoshihiro Ogawa
Journal: Diabetes Care (2013)

We appreciate the comments made by Professor Nonogaki regarding our article entitled “Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia,” and we sincerely respond to his comments here (1).

First, Professor Nonogaki described a recent systemic review and meta-analysis demonstrating that supplementation with omega-3 polyunsaturated fatty acids is not associated with a lower risk of all-cause mortality or major coronary events (MCE). However, the median dose of omega-3 including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in 20 trials referenced by this meta-analysis was 1.0 g/day, and the median dose of EPA in these 20 trials was only 0.46 g/day. However, …