tbuckley/cabot-search huggingface dataset:
Genome-wide association study of survival in patients with pancreatic adenocarcinoma
Authors: Chen Wu, Peter Kraft, Rachael Stolzenberg-Solomon, Emily Steplowski, Michelle Brotzman, Mousheng Xu, Poorva Mudgal, Laufey Amundadottir, Alan A Arslan, H Bas Bueno-de-Mesquita, Myron Gross, Kathy Helzlsouer, Eric J Jacobs, Charles Kooperberg, Gloria M Petersen, Wei Zheng, Demetrius Albanes, Marie-Christine Boutron-Ruault, Julie E Buring, Federico Canzian, Guangwen Cao, Eric J Duell, Joanne W Elena, J Michael Gaziano, Edward L Giovannucci, Goran Hallmans, Amy Hutchinson, David J Hunter, Mazda Jenab, Guoliang Jiang, Kay-Tee Khaw, Andrea LaCroix, Zhaoshen Li, Julie B Mendelsohn, Salvatore Panico, Alpa V Patel, Zhi Rong Qian, Elio Riboli, Howard Sesso, Hongbing Shen, Xiao-Ou Shu, Anne Tjonneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Jarmo Virtamo, Kala Visvanathan, Jean Wactawski-Wende, Chengfeng Wang, Kai Yu, Anne Zeleniuch-Jacquotte, Stephen Chanock, Robert Hoover, Patricia Hartge, Charles S Fuchs, Dongxin Lin, Brian M Wolpin
Journal: Gut (2012)

<h3>Background and objective</h3> Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. <h3>Methods</h3> We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10<sup>−5</sup>) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). <h3>Results</h3> In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10<sup>−7</sup>), rs981621 (p=1.65×10<sup>−7</sup>) and rs16861827 (p=3.75×10<sup>−7</sup>), respectively. 131 SNPs with p≤10<sup>−5</sup> were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10<sup>−7</sup>) on chromosome 11p15.4, which is intronic to the <i>SET binding factor 2 (SBF2)</i> gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. <h3>Conclusions</h3> Germline genetic variation in the <i>SBF2</i> locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.
Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial
Authors: Dominique Baeten, Xenofon Baraliakos, Jürgen Braun, Joachim Sieper, Paul Emery, Désirée van der Heijde, Iain McInnes, Jacob M van Laar, Robert Landewé, Paul Wordsworth, Jürgen Wollenhaupt, Herbert Kellner, Jacqueline Paramarta, Jiawei Wei, Arndt Brachat, Stephan Bek, Didier Laurent, Yali Li, Ying A Wang, Arthur P Bertolino, Sandro Gsteiger, Andrew M Wright, Wolfgang Hueber
Journal: The Lancet (2013)
Circulating immune complexes in sarcoidosis.
Authors: N M Johnson, M W NcNicol, J E Burton-Kee, J F Mowbray
Journal: Thorax (1980)

The sera of 50 patients with sarcoidosis were tested for the presence of circulating immune complexes using polyethylene glycol precipitation, followed by single radial immuno diffusion for the amounts of Clg, IgG, IgM, and double diffusion for the presence of IgA. Complexes were detected in 29 (58%) patients. No correlation could be found between the presence of these complexes and the length of history stage, or activity of disease, nor to steroid therapy. Rheumatoid factor was detected in 14 patients (28%), 13 of whom had circulating immune complexes, and 12 of whom had active disease. Total serum C3, CH50, and Clq were normal, as were immunoglobulin levels. In patients with extrathoracic sarcoidosis, especially skin or joint involvement, complexes were commonly found. The aetiological significance of these complexes remains uncertain.
Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study
Authors: Michael Eddleston, Peter Eyer, Franz Worek, Fahim Mohamed, Lalith Senarathna, Ludwig von Meyer, Edmund Juszczak, Ariyasena Hittarage, Shifa Azhar, Wasantha Dissanayake, MH Rezvi Sheriff, Ladislaus Szinicz, Andrew H Dawson, Nick A Buckley
Journal: The Lancet (2005)
Chronic toxicity of chloroform to Japanese medaka fish.
Authors: M W Toussaint, A B Rosencrance, L M Brennan, J R Beaman, M J Wolfe, F J Hoffmann, H S Gardner
Journal: Environmental Health Perspectives (2001)

Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured chloroform concentrations of 0.017, 0.151, or 1.463 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic chloroform concentration. Histopathology was evaluated at 6 and 9 months. Chloroform was not hepatocarcinogenic to the medaka at the concentrations tested. Chronic toxicity was evidenced at these time points by statistically significant ([alpha] = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.463 mg/L chloroform. We assessed hepatocellular proliferation by exposing test fish to 5-bromo-2'-deoxyuridine in the aquarium water for 72 hr after 4 and 20 days of chloroform exposure; we then quantified area-labeling indices of the livers using computer-assisted image analysis. We observed no treatment-related increases in cellular proliferation. We analyzed cells in circulating blood in medaka after 6 months of chloroform exposure. Hematocrit, leukocrit, cell viability, and cell counts of treated fish were not significantly different from those of control fish. Using gas chromatography (GC), we evaluated intrahepatic concentrations of chloroform in fish after 9 months of exposure. Livers from the 0.151 and 1.463 mg/L chloroform-treated fish had detectable amounts of chloroform, but these levels were always lower than the aquaria concentrations of chloroform. Thus, it appeared that chloroform did not bioaccumulate in the liver. Unidentified presumptive metabolite peaks were found in the GC tracings of these fish livers.
The Anatomy and Applied Anatomy of the Mediastinal Fascia
Authors: P. Marchand
Journal: Thorax (1951)

<h3>Abstract</h3> <h3>Introduction</h3> Visiting the hospital is important as a part of check-up in avoiding the major risks of unknown and serious diseases irrespective of any pandemic. Our study aims to understand the attitude and behaviour of common people towards visiting the hospital during COVID-19 pandemic in two major hotspot states of India namely Maharashtra and Karnataka. <h3>Methodology</h3> A cross-sectional study was conducted between July-august 2021 among the population of two states. A total of 636 respondents completed the survey and returned electronically. Data were analysed using suitable statistical tools to achieve the objective of the study. <h3>Results</h3> 74.8% of the respondents were not ready to visit the hospitals during the COVID-19 pandemic unless the symptoms were serious. On the other hand, 25.2% of the of respondents were willing to go to the hospitals. The top three reasons for the reduction in visits are fear of getting infected in the hospitals by COVID-19 patients (72.6%), fear of stepping out of home (31.1%) and fear of COVID-19 infection by the lab equipment (24.5%). <h3>Conclusion</h3> Overall the study revealed that there was a reduction in number of visits to the hospitals for common diseases in people after the pandemic started. But the people were still willing to go to the hospitals if they noticed any major symptoms or symptoms related to COVID-19. Our findings may be useful to develop strategies to address concerns in order to ensure that people don’t get any serious illness because of the fear of COVID-19.
Preconditioning of arteriogenesis
Authors: D SCHOLZ, W SCHAPER
Journal: Cardiovascular Research (2004)

Last decade, the shear stress caused by increased blood flow in collateral circulation after occlusion of main artery was recognized as a trigger of vascular remodeling and collateral growth. The goal of this study was to differentiate whether the on-going increased blood flow is necessary for the vascular remodeling or the remodeling, once in progress, develops independently of flow.Femoral artery occlusion was performed in C57B1/6 mice. After 1-3 days, the ligature was removed and normal limb perfusion was re-established, monitored by laser Doppler Imaging (LDI). Two weeks after the first occlusion, both femoral arteries were re-occluded to compare collateral growth on the "naive" and "preconditioned" sides. After perfusion fixation, ultrastructural studies and morphometry of the collateral vessels were performed.Blood flow fell after occlusion to about 15% of control levels and recovered to about 40% by day 3. The reperfusion normalized sustainable blood flow. After the second occlusion, blood flow on both sides fell again to about 15% but recovered to 70% in the "preconditioned" compared to 40% in the "naive" side during the following 3 days. 5-Bromo-2'-desoxy-uridine (BrdU) administered during reperfusion was detected mainly in the neointima that, in many cases, had markedly narrowed the lumen. Two to three days after re-occlusion, a statistically significant lumen enlargement on the "preconditioned" side was observed, while neointima disappeared.Cellular proliferation and remodeling of collateral arteries were induced by short period of increased blood flow (occlusion of the femoral artery) but realized mostly during the low blood flow (reperfusion of the femoral artery). The neointima developing as a result of this remodeling can be recruited as a functional part of the arterial wall if the collateral perfusion increases as a result of repetitive occlusion of the femoral artery. The "medialization" of the neointima might cause the observed quicker gain of collateral lumen diameter and conductance, saving distal muscle tissue from the ischemia.
Relationships Between Circulating Metabolic Intermediates and Insulin Action in Overweight to Obese, Inactive Men and Women
Authors: Kim M. Huffman, Svati H. Shah, Robert D. Stevens, James R. Bain, Michael Muehlbauer, Cris A. Slentz, Charles J. Tanner, Maragatha Kuchibhatla, Joseph A. Houmard, Christopher B. Newgard, William E. Kraus
Journal: Diabetes Care (2009)

OBJECTIVE To determine whether circulating metabolic intermediates are related to insulin resistance and β-cell dysfunction in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In 73 sedentary, overweight to obese, dyslipidemic individuals, insulin action was derived from a frequently sampled intravenous glucose tolerance test. Plasma concentrations of 75 amino acids, acylcarnitines, free fatty acids, and conventional metabolites were measured with a targeted, mass spectrometry–based platform. Principal components analysis followed by backward stepwise linear regression was used to explore relationships between measures of insulin action and metabolic intermediates. RESULTS The 75 metabolic intermediates clustered into 19 factors comprising biologically related intermediates. A factor containing large neutral amino acids was inversely related to insulin sensitivity (SI) (R2 = 0.26). A factor containing fatty acids was inversely related to the acute insulin response to glucose (R2 = 0.12). Both of these factors, age, and a factor containing medium-chain acylcarnitines and glucose were inversely and independently related to the disposition index (DI) (R2 = 0.39). Sex differences were found for metabolic predictors of SI and DI. CONCLUSIONS In addition to the well-recognized risks for insulin resistance, elevated concentrations of large, neutral amino acids were independently associated with insulin resistance. Fatty acids were inversely related to the pancreatic response to glucose. Both large neutral amino acids and fatty acids were related to an appropriate pancreatic response, suggesting that these metabolic intermediates might play a role in the progression to type 2 diabetes, one by contributing to insulin resistance and the other to pancreatic failure. These intermediates might exert sex-specific effects on insulin action.
Diagnostic, Staging, and Grading of Urothelial Carcinomas from Urine: Performance of BCA-1, a Mini-Array Comparative Genomic Hybridisation–Based Test
Authors: Stéphane Larré, Philippe Camparo, Eva Comperat, Sixtina Gil Diez De Medina, Olivier Traxer, Morgan Roupret, Philippe Sebe, Géraldine Cancel-Tassin, Karim Sighar, François Lozach, Olivier Cussenot
Journal: European Urology (2010)
More Evidence That Aspirin Lowers Cancer Risk
Authors: G. Sinha
Journal: JNCI Journal of the National Cancer Institute (2015)

Two studies at September’s American Association for Cancer Research meeting build on evidence suggesting that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of developing several cancers and the risk that cancer will spread. But the evidence isn’t yet strong enough to persuade clinicians to recommend NSAIDs as a preventive. In the first study, Adriana C. Vidal, Ph.D., assistant professor of surgery at Duke University School of Medicine in Durham, N.C., and colleagues studied data from a clinical trial that tested whether taking dutasteride could reduce risk of prostate cancer. The researchers wondered whether men taking NSAIDs concurrently for other conditions were less likely to develop prostate cancer, independent of dutasteride. The trial included 6,390 men, half of whom did not take NSAIDs. Among the other half, 21% took aspirin, 18% took other NSAIDs, and 11% took both. All men had prostate cancer–negative biopsy samples before the trial and received biopsies at 2and 4-year intervals, regardless of prostatespecific antigen level. Compared with participants not taking NSAIDs, men taking aspirin, other NSAIDs, or both cut their risk of prostate cancer by 13%. They also had a 17% reduced risk of high-grade prostate cancer. But researchers found no association between taking NSAIDs and risk of lowgrade prostate cancer. Risk reductions held up regardless of whether patients were in the dutasteride or placebo arm or whether participants were from Europe or North America. People commonly take aspirin to prevent heart attacks. At low doses, it inhibits the enzyme cyclooxygenase 1 (COX-1) in platelets, which then inhibits thromboxane A2. That keeps platelets from aggregating, so blood can’t clot. At high doses, NSAIDs inhibit COX-1 and COX-2 in other cell types. COX-2 regulates expression of prostaglandin E2 (PGE2). How inhibiting COX-2 affects cancer isn’t clear, but researchers think that it interrupts PGE2 in addition to other pathways that promote tumor growth. Many observational and retrospective studies suggest that NSAIDs reduce risk of several cancers. A meta-analysis of eight randomized clinical trials, for example, found that taking daily aspirin for 4 or more years reduced risk of death from cancer by about 20% (Lancet 2011;377:31– 4). But the risk of gastrointestinal bleeding and ulcers makes most clinicians reluctant to add NSAIDs to their box of prevention tools.
Lesson of the month: rowing-induced laryngeal obstruction: a novel cause of exertional dyspnoea: characterised by direct laryngoscopy
Authors: B Panchasara, C Nelson, R Niven, S Ward, J H Hull
Journal: Thorax (2014)

Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for unexplained dyspnoea in athletes. The gold standard means for diagnosis of EILO is direct laryngoscopy, performed continuously, while an athlete undertakes the specific sport that precipitates their symptoms. This report provides the first descriptions of rowing-associated EILO in two competitive rowers presenting with unexplained dyspnoea and cough. The report describes the methodology and safety of the use of continuous laryngoscopy in the context of maximal rowing ergometry and the use of this technique as a therapeutic tool to provide biofeedback.
Short-term effect of changes in smoking behaviour on emphysema quantification by CT
Authors: H. Ashraf, P. Lo, S. B. Shaker, M. de Bruijne, A. Dirksen, P. Tonnesen, M. Dahlback, J. H. Pedersen
Journal: Thorax (2010)

<h3>Background</h3> The effect of smoking cessation and smoking relapse on lung density was studied using low-dose CT. <h3>Methods</h3> Spiral, multidetector, low-dose CT was performed on 726 current and former smokers (&gt;20 pack-years) recruited from a cancer screening trial. Lung density was quantified by calculating the 15th percentile density (PD15), which was adjusted to predicted total lung capacity. Data were analysed by linear regression models. <h3>Results</h3> At baseline mean PD15 was 45 g/l in former smokers (n=178) and 55 g/l in current smokers (n=548), representing a difference of 10 g/l (p&lt;0.001). After smoking cessation (n=77) PD15 decreased by 6.2 g/l (p&lt;0.001) in the first year, and by a further 3.6 g/l (p&lt;0.001) in the second year, after which no further change could be detected. Moreover, the first year after relapse to smoking (n=18) PD15 increased by 3.7 g/l (p=0.02). <h3>Conclusions</h3> Current smoking status has a major influence on lung density assessed by CT, and the difference in lung density between current and former smokers observed in cross-sectional studies corresponds closely to the change in lung density seen in the years after smoking cessation. Current smoking status, and time since cessation or relapse, should be taken into account when assessing the severity of diseases such as emphysema by CT lung density.
Impact of Managed Care on Cancer Trial Enrollment
Authors: C.P. Gross, H.M. Krumholz
Journal: Journal of Clinical Oncology (2005)

Purpose To determine the relationship between managed care market activity and cancer trial enrollment. Methods Trial participant data were obtained from the National Cancer Institute. Participants in cooperative group trials of breast, colorectal, lung, or prostate cancer during the years 1996 through 2001 were assigned to counties based on their zip code of residence. Linear regression was used to determine the relationship between county enrollment rate and two measures of county managed care activity (penetration and index of competition [IOC]), adjusting for other county characteristics. Results In bivariate analysis, there was a strong inverse correlation between trial enrollment rate and IOC (r = −0.23; P &lt; .001) as well as the proportion of the population uninsured (−0.31; P &lt; .001) and the percentage below poverty (−0.16; P &lt; .001). In the multivariate model, greater county managed care competition (IOC) was inversely related to trial enrollment rate (P &lt; .008 for comparison of each quartile v lowest quartile) after accounting for managed care penetration, proportion uninsured, and other county characteristics. Counties in the lowest quartile of managed care penetration tended to have lower enrollment rates than the remaining counties (r = −0.05; P = .048), while counties in the second, third, and fourth quartiles of penetration all had similar enrollment rates to one another. Conclusion Cancer trial enrollment rates were suboptimal across all counties, and counties with higher levels of managed care competition had significantly lower enrollment rates. The relationship between managed care penetration and trial enrollment was less consistent. Future efforts to enhance trial participation should address the potential negative influence of market factors.
Automated Heparin-Delivery System to Control Activated Partial Thromboplastin Time
Authors: Christopher P. Cannon, Jasper Dingemanse, Cornelis H. Kleinbloesem, Thomas Jannett, Kenneth M. Curry, Christian P. Valcke
Journal: Circulation (1999)

Background —Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials. Methods and Results —We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer-based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within ±10 seconds of the target (prespecified primary end point), and 89% were within a ±15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range ±15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples. Conclusions —These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice.
NO metabolite flux across the human coronary circulation
Authors: S ROGERS, A KHALATBARI, B DATTA, S ELLERY, V PAUL, M FRENNEAUX, P JAMES
Journal: Cardiovascular Research (2007)

The theory of a red blood cell derived nitric oxide (NO) reserve conserving NO bioactivity and delivering NO as a function of oxygen demand has been the subject of much interest. We identified the human coronary circulation as an ideal model system in which to analyse NO metabolites because of its large physiological oxygen gradient. Our objective was to identify whether oxygen drove apportion between various NO metabolite species across a single vascular bed.Plasma and red blood cell NO metabolites were assessed from the left main coronary artery, coronary sinus and pulmonary artery (providing cross heart and cross pulmonary analysis) of healthy subjects under resting conditions and following administration of an inhibitor of NO biosynthesis. Physiological parameters and angiographic data were monitored throughout the study.Under baseline conditions we observed significant metabolite flux upon the transit of blood across the coronary and pulmonary vascular beds. Whilst there was no net loss of NO through the coronary circulation (p=0.0759), plasma nitrite/protein NO (excluding nitrate) (p=0.0279) and red blood cell sulphanilamide labile signal (p=0.0143) decreased whereas haemoglobin-bound NO increased three-fold (p=0.005). These changes across the coronary circulation were reversed through the pulmonary circuit with red blood cell sulphanilamide labile signal (p=0.0143) and plasma nitrite/protein NO (p=0.0279) increasing and haemoglobin-bound NO decreasing. Blockade of NO synthesis increased mean arterial blood pressure (p<0.01) and reduced coronary artery diameter (p<0.05), however we observed similar apportion of NO metabolites across the heart and lung with no net loss or gain in total NO metabolites.For the first time in human subjects across the resting coronary circulation we reveal significant re-apportionment of NO between metabolite species which correlate with haemoglobin oxygen saturation. These changes occur even within the transit time of blood across this single vascular bed. We demonstrate no net loss/gain of NO from the total metabolite pool across the coronary circulation even where NO biosynthesis is inhibited.
Risk of colorectal neoplasia associated with the adenomatous polyposis coli E1317Q variant
Authors: M.J. Hall, E. Liberman, O. Dulkart, L. Galazan, E. Sagiv, E. Shmueli, D. Kazanov, A. Hallak, M. Moshkowitz, A. Figer, S. Kraus, M. Inbar, A.I. Neugut, N. Arber
Journal: Annals of Oncology (2009)