tbuckley/cabot-search huggingface dataset:
8 24 Week treatment regimen with peginterferon alpha-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in HCV genotype 1 or 4 ‘super-responders’
Authors: P. Ferenci, U. Bergholz, H. Laferl, T.M. Scherzer, A. Maieron, M. Gschwantler, H. Brunner, R.R. Hubmann, C. Datz, M. Bischof, R. Stauber, P. Steindl-Munda
Journal: Journal of Hepatology (2006)
Rational belief and social interaction
Authors: Daniel M. Hausman
Journal: Behavioral and Brain Sciences (2003)

Game theory poses problems for modeling rational belief, but it does not need a new theory of rationality. Experimental results that suggest otherwise often reveal difficulties in testing game theory, rather than mistakes or paradoxes. Even though the puzzles Colman discusses show no inadequacy in the standard theory of rationality, they show that improved models of belief are needed.
Systematic identification and quantification of phase variation in commensal and pathogenic Escherichia coli
Authors: Amir Goldberg, Ofer Fridman, Irine Ronin, Nathalie Q Balaban
Journal: Genome Medicine (2014)

Bacteria have been shown to generate constant genetic variation in a process termed phase variation. We present a tool based on whole genome sequencing that allows detection and quantification of coexisting genotypes mediated by genomic inversions in bacterial cultures. We tested our method on widely used strains of Escherichia coli, and detected stable and reproducible phase variation in several invertible loci. These are shown here to be responsible for maintaining constant variation in populations grown from a single colony. Applying this tool on other bacterial strains can shed light on how pathogens adjust to hostile environments by diversifying their genomes.
Efficacy of community-based physiotherapy networks for patients with Parkinson's disease: a cluster-randomised trial
Authors: Marten Munneke, Maarten J Nijkrake, Samyra HJ Keus, Gert Kwakkel, Henk W Berendse, Raymund AC Roos, George F Borm, Eddy M Adang, Sebastiaan Overeem, Bastiaan R Bloem
Journal: The Lancet Neurology (2009)
Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial
Authors: David A. Morrow, James A. de Lemos, Marc S. Sabatine, Stephen D. Wiviott, Michael A. Blazing, Amy Shui, Nader Rifai, Robert M. Califf, Eugene Braunwald
Journal: Circulation (2006)

Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain.We measured the serum concentration of hsCRP at 30 days (n=3813) and 4 months in patients with non-ST-elevation or ST-elevation acute coronary syndrome randomly assigned to an early intensive versus delayed conservative simvastatin strategy in the Aggrastat-to-Zocor Trial. Patients with hsCRP >3 mg/L at 30 days had significantly higher 2-year mortality rates than those with hsCRP 1 to 3 mg/L or hsCRP <1 mg/L (6.1% versus 3.7% versus 1.6%, P<0.0001). Results were similar with hsCRP measured at 4 months. After adjusting for age, gender, diabetes, smoking, cardiovascular history, index event, lipid levels, and randomly assigned treatment, patients with hsCRP >3 mg/L were at more than 3-fold higher risk of death (HR, 3.7; 95% CI, 1.9 to 7.2) compared with those with hsCRP <1 mg/L. "Average" levels of hsCRP (1 to 3 mg/L) were also associated with increased risk compared with those with hsCRP <1 mg/L (HR, 2.3; 95% CI, 1.2 to 4.6). Patients allocated to early intensive statin therapy were more likely to achieve hsCRP levels <1 mg/L at 30 days (P=0.028) and 4 months (P<0.0001).Achieved levels of hsCRP at 30 days and 4 months after acute coronary syndrome are independently associated with long-term survival. Patients treated with more aggressive statin therapy are more likely to achieve lower levels of hsCRP.
High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems
Authors: J H Henriksen
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> Static and dynamic functions of the wall of large arteries are largely unknown in cirrhosis in vivo. The present study was undertaken to determine arterial compliance (COMP<sub>art</sub>) in relation to vasodilator and vasoconstrictor systems in patients with cirrhosis. In addition, vasoactivity was manipulated by inhalation of oxygen. <h3>STUDY POPULATION AND METHODS</h3> In 20 patients with alcoholic cirrhosis and 12 controls we determined COMP<sub>art</sub> (stroke volume relative to pulse pressure), cardiac output, plasma volume, systemic vascular resistance, central circulation time, plasma catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. <h3>RESULTS</h3> COMP<sub>art</sub>was significantly increased in cirrhotic patients compared with controls (1.32 <i>v</i> 1.06 ml/mm Hg; p&lt; 0.05) and inversely related to plasma adrenaline levels (<i>r</i>=−0.53; p&lt;0.02) but positively related to circulating levels of CGRP (<i>r</i>=0.58; p&lt;0.01). No significant relation was found for plasma noradrenaline, renin activity, or endothelin-1. COMP<sub>art</sub> was positively related to plasma volume (<i>r</i>=0.50; p&lt;0.02) and inversely to systemic vascular resistance (<i>r</i>=−0.69; p&lt;0.001) and central circulation time (<i>r</i>=−0.49; p&lt;0.02). During oxygen inhalation, COMP<sub>art</sub> decreased (−13%; p&lt;0.005) and systemic vascular resistance increased (+10%; p&lt;0.001) towards normal values without significant changes in mean arterial pressure. Plasma adrenaline (−16%; p&lt;0.01) decreased and the relation to COMP<sub>art</sub> disappeared. The relation of COMP<sub>art</sub> to CGRP and circulatory variables remained unchanged. <h3>CONCLUSION</h3> Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline, renin, endothelin-1). Thus the altered static and dynamic characteristics of the wall of large arteries are intimately associated with circulatory and vasodilatory derangement in cirrhosis but biomanipulation indicates that the changes are, at least in part, reversible during isobaric conditions.
Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia
Authors: Michael J. Koren, Robert P. Giugliano, Frederick J. Raal, David Sullivan, Michael Bolognese, Gisle Langslet, Fernando Civeira, Ransi Somaratne, Patric Nelson, Thomas Liu, Rob Scott, Scott M. Wasserman, Marc S. Sabatine
Journal: Circulation (2013)

Evolocumab (AMG 145), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks' duration. The longer-term efficacy and safety of PCSK9 inhibition remain undefined.Of 1359 randomized and dosed patients in the 4 evolocumab phase 2 parent studies, 1104 (81%) elected to enroll into the Open-Label Study of Long-term Evaluation Against LDL-C (OSLER) study. Regardless of their treatment assignment in the parent study, patients were randomized 2:1 to receive either open-label subcutaneous evolocumab 420 mg every 4 weeks with standard of care (SOC) (evolocumab+SOC, n=736) or SOC alone (n=368). Ninety-two percent of patients in the evolocumab+SOC group and 89% of patients in the SOC group completed 52 weeks of follow-up. Patients who first received evolocumab in OSLER experienced a mean 52.3% [SE, 1.8%] reduction in LDL-C at week 52 (P<0.0001). Patients who received 1 of 6 dosing regimens of evolocumab in the parent studies and received evolocumab+SOC in OSLER had persistent LDL-C reductions (mean reduction, 50.4% [SE, 0.8%] at the end of the parent study versus 52.1% [SE, 1.0%] at 52 weeks; P=0.31). In patients who discontinued evolocumab on entry into OSLER, LDL-C levels returned to near baseline levels. Adverse events and serious adverse events occurred in 81.4% and 7.1% of the evolocumab+SOC group patients and 73.1% and 6.3% of the SOC group patients, respectively.Evolocumab dosed every 4 weeks demonstrated continued efficacy and encouraging safety and tolerability over 1 year of treatment in the largest and longest evaluation of a PCSK9 inhibitor in hypercholesterolemic patients to date.http://clinicaltrials.gov. Unique identifier: NCT01439880.
Randomized Comparison of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Diabetic Patients
Authors: Akhil Kapur, Roger J. Hall, Iqbal S. Malik, Ayesha C. Qureshi, Jeremy Butts, Mark de Belder, Andreas Baumbach, Gianni Angelini, Adam de Belder, Keith G. Oldroyd, Marcus Flather, Michael Roughton, Petros Nihoyannopoulos, Jens Peder Bagger, Kenneth Morgan, Kevin J. Beatt
Journal: Journal of the American College of Cardiology (2010)
K-ras mutations in the bile of patients with primary sclerosing cholangitis
Authors: S Kubicka
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> The development of cholangiocarcinoma (CCC) is a complication of primary sclerosing cholangitis (PSC). To date, no reliable factors have been described which can define those PSC patients at high risk for the development of CCC and the clinical diagnosis of CCC in PSC patients is difficult. Therefore, molecular markers of cholangiocarcinogenesis, such as K-ras mutations, may improve the early diagnosis of CCC or the timing of liver transplantation. <h3>METHODS</h3> K-ras mutations were analysed by enriched polymerase chain reaction/restriction fragment length polymorphism in the bile fluid of 56 PSC patients and 20 patients with other cholestatic diseases. To assess the value of K-ras mutations as a risk factor for cholangiocarcinogenesis, patients were prospectively investigated over a mean period of 31.5 months. <h3>RESULTS</h3> In contrast with the control group, 17 (30%) patients with PSC revealed K-ras mutations in bile fluid. The mean Mayo score was not significantly different between PSC patients with (mean score 0.70) and without (mean score 0.13; p=0.2) K-ras mutations. In contrast with the group of PSC patients without K-ras mutations, four CCCs and two dysplasia were diagnosed in the group of patients with K-ras mutations during the follow up investigation (p&lt;0.001). <h3>CONCLUSIONS</h3> Our results indicate that K-ras mutations in bile fluid of PSC patients represent frequent early events during cholangiocarcinogenesis. However, most of the PSC patients with K-ras mutations remained tumour free after a long follow up investigation which is in agreement with the fact that these mutations are not specific for malignancy but may also occur in normal bile duct mucosa or in dysplasias. Therefore, analysis of K-ras mutations in bile should not be used for diagnosis of CCC in PSC patients. However, the results of our prospective follow up investigation indicate that K-ras mutations in bile fluid of PSC patients have to be considered as risk factors for the development of CCC which may have implications for the timing of liver transplantation.
Water consumption in free-living adults
Authors: E Al-Jalali, S M Shirreffs
Journal: British Journal of Sports Medicine (2010)

Water is the largest single component of the human body. It is obtained from food and beverage consumption and by metabolic production in the body. This study investigated water consumption in adults living in the UK. 40 males and 40 females (mean±SD age 34±13 years, body mass 72±19 kg, height 169±10 cm, body mass index 25±6 kg/m 2 , mean arterial blood pressure 97±13 mm Hg) completed a three consecutive day dietary record for 1 weekend and 2 week days. Every item consumed (food and drinks), the eating occasion (meal or snack), time, food preparation method, brand of product, location of consumption and details of any people with them were recorded. Females tended to consume more water than males (2402±827 ml/day, 2056±911 ml/day respectively p=0.079). More water was consumed via nonwater beverages than food and plain water (p=0.000): for females this was 1013±552 ml, 556±220 ml and 833±683 ml and for males were 924±637 ml, 567±248 ml and 565±574 ml, respectively. This is equivalent to 27±11% of total daily water intake from food, 45±20% from nonwater beverages and 28±21% from plain water. There was no difference in total water intake on weekend days compared to week days for females 2488±1041 ml, 2446±831 ml and 2272±921 ml (p=0.892) or for males 2132±1353 ml, 2101±1295 ml and 1934±876 ml (p=0.869). There was no difference in total water intake among females and males relative to weekend days and week day 1 and week day 2 (p=0.191), (p=0.160) and (p=0.097). The mean amount of water consumed per person per day in UK population was 2229±882 ml with 1668±766 ml being obtained from beverages. This is similar to previous research1 which found that the total beverage consumption in Britain in 2000/2001 was 1988 ml/day for males and 1585 ml/day for females.
Anti-inflammatory cytokines in cystic fibrosis lung disease
Authors: V. Starosta, F. Ratjen, E. Rietschel, K. Paul, M. Griese
Journal: European Respiratory Journal (2006)

Lung inflammation plays a pivotal role in the pathogenesis of airway disease in cystic fibrosis (CF). An imbalance between pro- and anti-inflammatory mediators has been observed and a deficiency in the anti-inflammatory response has been proposed, but this concept remains controversial. In the present study, the concentrations of two anti-inflammatory mediators, lipoxin A (LxA4) and Clara cell protein 10 (CC-10), were assessed in bronchoalveolar lavage fluid (BALF) of CF patients with a wide range of endobronchial inflammation and disease controls with neutrophilic inflammation unrelated to CF. No differences were observed in LxA4 BALF concentrations between CF patients and controls with a similar degree of neutrophilic airway inflammation. Concentrations were also similar in CF patients with mild versus more severe airway inflammation. In contrast, CC-10 concentrations were lower in CF patients, but this decrease was limited to patients with more intense airway inflammation. The present data do not support the concept of a primary defect in anti-inflammatory mediators in cystic fibrosis lung disease. Although Clara cell protein concentrations were found to be reduced, these alterations appear to be secondary to neutrophilic airway inflammation rather than due to a primary deficiency.
Cutaneous manifestations of the eosinophilia–myalgia syndrome
Authors: JUDITH R. OURSLER, E.R. FARMER, R. ROUBENOFF, H.S. MOGAVERO, ROSEMARIE M. WATSON
Journal: British Journal of Dermatology (1992)

We report the cutaneous manifestations of the eosinophilia–myalgia syndrome in 10 patients, with specific reference to their clinical course, histopathological features, and immunogenetic studies. Cutaneous manifestations could be classified into three groups: morphoea‐like sclerosis, urticarial and papular lesions, and generalized sclerosis. Despite this polymorphic clinical presentation, the histopathological abnormalities in all cases were strikingly similar, and consisted of superficial and deep perivascular lymphocytic dermal infiltrates, mucin deposition, and fascial inflammation (often in the absence of sclerosis). Immunoperoxidase studies revealed increased numbers of factor XIIIa‐ and MAC 387‐positive cells in the inflammatory infiltrate. Immunogenetic studies demonstrated that 77% (7/9) of patients possessed the HLA‐DR3 or HLA‐DR4 phenotypes. Mean follow‐up of 24 months after discontinuation of l‐tryptophan revealed the presence of persistent severe disabling disease in 30% of patients.
<i>STAT3</i> Polymorphism Predicts Interferon-Alfa Response in Patients With Metastatic Renal Cell Carcinoma
Authors: Noriyuki Ito, Masatoshi Eto, Eijiro Nakamura, Atsushi Takahashi, Taiji Tsukamoto, Hiroshi Toma, Hayakazu Nakazawa, Yoshihiko Hirao, Hirotsugu Uemura, Susumu Kagawa, Hiroomi Kanayama, Yoshiaki Nose, Naoko Kinukawa, Tsuyoshi Nakamura, Nobuyoshi Jinnai, Toyokazu Seki, Masanobu Takamatsu, Yoshihiro Masui, Seiji Naito, Osamu Ogawa
Journal: Journal of Clinical Oncology (2007)

To clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-alpha) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-alpha immunotherapy.We carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-alpha for MRCC.After adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-alpha. Linkage disequilibrium mapping revealed that the SNP in the 5' region of STAT3, rs4796793, was the most significant predictor of IFN-alpha response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN- by STAT3 suppression in an RCC cell line supported the results of the present association study.The present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-alpha therapy in patients with MRCC. An efficient response marker for IFN-alpha needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.
STAG2 is a clinically relevant tumor suppressor in pancreatic ductal adenocarcinoma
Authors: Lisa Evers, Pedro A Perez-Mancera, Elizabeth Lenkiewicz, Nanyun Tang, Daniela Aust, Thomas Knösel, Petra Rümmele, Tara Holley, Michelle Kassner, Meraj Aziz, Ramesh K Ramanathan, Daniel D Von Hoff, Holly Yin, Christian Pilarsky, Michael T Barrett
Journal: Genome Medicine (2014)

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer characterized by complex aberrant genomes. A fundamental goal of current studies is to identify those somatic events arising in the variable landscape of PDA genomes that can be exploited for improved clinical outcomes. We used DNA content flow sorting to identify and purify tumor nuclei of PDA samples from 50 patients. The genome of each sorted sample was profiled by oligonucleotide comparative genomic hybridization and targeted resequencing of STAG2. Transposon insertions within STAG2 in a KRASG12D-driven genetically engineered mouse model of PDA were screened by RT-PCR. We then used a tissue microarray to survey STAG2 protein expression levels in 344 human PDA tumor samples and adjacent tissues. Univariate Kaplan Meier analysis and multivariate Cox Regression analysis were used to assess the association of STAG2 expression relative to overall survival and response to adjuvant therapy. Finally, RNAi-based assays with PDA cell lines were used to assess the potential therapeutic consequence of STAG2 expression in response to 18 therapeutic agents. STAG2 is targeted by somatic aberrations in a subset (4%) of human PDAs. Transposon-mediated disruption of STAG2 in a KRASG12D genetically engineered mouse model promotes the development of PDA and its progression to metastatic disease. There was a statistically significant loss of STAG2 protein expression in human tumor tissue (Wilcoxon-Rank test) with complete absence of STAG2 staining observed in 15 (4.3%) patients. In univariate Kaplan Meier analysis nearly complete STAG2 positive staining (>95% of nuclei positive) was associated with a median survival benefit of 6.41 months (P = 0.031). The survival benefit of adjuvant chemotherapy was only seen in patients with a STAG2 staining of less than 95% (median survival benefit 7.65 months; P = 0.028). Multivariate Cox Regression analysis showed that STAG2 is an independent prognostic factor for survival in pancreatic cancer patients. Finally, we show that RNAi-mediated knockdown of STAG2 selectively sensitizes human PDA cell lines to platinum-based therapy. Based on these iterative findings we propose that STAG2 is a clinically significant tumor suppressor in PDA.
The search for genes contributing to endometriosis risk
Authors: Grant W. Montgomery, Dale R. Nyholt, Zhen Zhen Zhao, Susan A. Treloar, Jodie N. Painter, Stacey A. Missmer, Stephen H. Kennedy, Krina T. Zondervan
Journal: Human Reproduction Update (2008)

Genetic variation contributes to the risk of developing endometriosis. This review summarizes gene mapping studies in endometriosis and the prospects of finding gene pathways contributing to disease using the latest genome-wide strategies. To identify candidate-gene association studies of endometriosis, a systematic literature search was conducted in PubMed of publications up to 1 April 2008, using the search terms 'endometriosis' plus 'allele' or 'polymorphism' or 'gene'. Papers included were those with information on both case and control selection, showed allelic and/or genotypic results for named germ-line polymorphisms and were published in the English language. Genetic variants in 76 genes have been examined for association, but none shows convincing evidence of replication in multiple studies. There is evidence for genetic linkage to chromosomes 7 and 10, but the genes (or variants) in these regions contributing to disease risk have yet to be identified. Genome-wide association is a powerful method that has been successful in locating genetic variants contributing to a range of common diseases. Several groups are planning these studies in endometriosis. For this to be successful, the endometriosis research community must work together to genotype sufficient cases, using clearly defined disease classifications, and conduct the necessary replication studies in several thousands of cases and controls. Genes with convincing evidence for association with endometriosis are likely to be identified in large genome-wide studies. This will provide a starting point for functional and biological studies to develop better diagnosis and treatment for this debilitating disease.