tbuckley/cabot-search huggingface dataset:
Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action
Authors: Maureen E Hillenmeyer, Elke Ericson, Ronald W Davis, Corey Nislow, Daphne Koller, Guri Giaever
Journal: Genome biology (2010)

We systematically analyzed the relationships between gene fitness profiles (co-fitness) and drug inhibition profiles (co-inhibition) from several hundred chemogenomic screens in yeast. Co-fitness predicted gene functions distinct from those derived from other assays and identified conditionally dependent protein complexes. Co-inhibitory compounds were weakly correlated by structure and therapeutic class. We developed an algorithm predicting protein targets of chemical compounds and verified its accuracy with experimental testing. Fitness data provide a novel, systems-level perspective on the cell.
Endoscopic Variceal Ligation plus Propranolol vs. Transjugular Intrahepatic Portosystemic Stent Shunt: A Long-Term Randomized Trial
Authors: P. Sauer, J. Hansmann, G. M. Richter, W. Stremmel, A. Stiehl
Journal: Endoscopy (2002)

Background and Study Aims: After a first variceal bleeding episode in patients with cirrhosis of the liver, treatment with transjugular intrahepatic portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus propranolol were compared, with regard to prevention of variceal rebleeding, complications, and mortality. Patients and Methods: 85 patients were randomly allocated to receive TIPS (n = 43) or EVL (n = 42). The groups were comparable regarding age, sex, etiology of liver cirrhosis, and liver function. Results: The mean observation times were 4.1 years in the TIPS group and 3.6 years in the EVL group. Although the probability of rebleeding was higher in the EVL group (29.9 %) than in the TIPS group (19.4 %), the difference was not statistically significant. Three of five patients of the EVL group successfully underwent TIPS placement after treatment failure. The probability of TIPS dysfunction requiring shunt revision was 89 %. Hepatic encephalopathy was observed more often in the TIPS group (40.5 %) than in the EVL group (20.5 %; P < 0.05). The probability of survival was similar in both groups (TIPS group 75.9 %, EVL group 82.2 %; n.s.). Conclusions: In view of its good efficacy and the lower cost of treatment, endoscopic ligation plus propranolol may be recommended as initial procedure for prevention of recurrent variceal hemorrhage, whereas TIPS seems to be the preferable procedure in patients with recurrent bleeding after adequate endoscopic and pharmacological treatment.
Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic stem cell transplantation reverse the disease phenotype in canine leukocyte adhesion deficiency
Authors: Thomas R. Bauer, Kate E. Creevy, Yu-chen Gu, Laura M. Tuschong, Robert E. Donahue, Mark E. Metzger, Lisa J. Embree, Tanya Burkholder, John D. Bacher, Chris Romines, Marvin L. Thomas, Lyn Colenda, Dennis D. Hickstein
Journal: Blood (2004)
c-Cbl Inhibition Improves Cardiac Function and Survival in Response to Myocardial Ischemia
Authors: Khadija Rafiq, Mikhail A. Kolpakov, Rachid Seqqat, Jianfen Guo, Xinji Guo, Zhao Qi, Daohai Yu, Bhopal Mohapatra, Neha Zutshi, Wei An, Hamid Band, Archana Sanjay, Steven R. Houser, Abdelkarim Sabri
Journal: Circulation (2014)

The proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor and nonreceptor tyrosine kinases, resulting in their ubiquitination and downregulation. However, the function of c-Cbl in the control of cardiac function is currently unknown. In this study, we examined the role of c-Cbl in myocyte death and cardiac function after myocardial ischemia.We show increased c-Cbl expression in human ischemic and dilated cardiomyopathy hearts and in response to pathological stress stimuli in mice. c-Cbl-deficient mice demonstrated a more robust functional recovery after myocardial ischemia/reperfusion injury and significantly reduced myocyte apoptosis and improved cardiac function. Ubiquitination and downregulation of key survival c-Cbl targets, epidermal growth factor receptors and focal adhesion kinase, were significantly reduced in c-Cbl knockout mice. Inhibition of c-Cbl expression or its ubiquitin ligase activity in cardiac myocytes offered protection against H2O2 stress. Interestingly, c-Cbl deletion reduced the risk of death and increased cardiac functional recovery after chronic myocardial ischemia. This beneficial effect of c-Cbl deletion was associated with enhanced neoangiogenesis and increased expression of vascular endothelial growth factor-a and vascular endothelial growth factor receptor type 2 in the infarcted region.c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis, and causes adverse cardiac remodeling after myocardial infarction. These findings point to c-Cbl as a potential therapeutic target for the maintenance of cardiac function and remodeling after myocardial ischemia.
Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction
Authors: Ole Fröbert, Bo Lagerqvist, Göran K. Olivecrona, Elmir Omerovic, Thorarinn Gudnason, Michael Maeng, Mikael Aasa, Oskar Angerås, Fredrik Calais, Mikael Danielewicz, David Erlinge, Lars Hellsten, Ulf Jensen, Agneta C. Johansson, Amra Kåregren, Johan Nilsson, Lotta Robertson, Lennart Sandhall, Iwar Sjögren, Ollie Östlund, Jan Harnek, Stefan K. James
Journal: New England Journal of Medicine (2013)

The clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality.We conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days.No patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI.Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.).
Modification of kidney barrier function by the urokinase receptor
Authors: Changli Wei, Clemens C Möller, Mehmet M Altintas, Jing Li, Karin Schwarz, Serena Zacchigna, Liang Xie, Anna Henger, Holger Schmid, Maria P Rastaldi, Peter Cowan, Matthias Kretzler, Roberto Parrilla, Moïse Bendayan, Vineet Gupta, Boris Nikolic, Raghu Kalluri, Peter Carmeliet, Peter Mundel, Jochen Reiser
Journal: Nature Medicine (2007)
Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial
Authors: Amy P Abernethy, Christine F McDonald, Peter A Frith, Katherine Clark, James E Herndon, Jennifer Marcello, Iven H Young, Janet Bull, Andrew Wilcock, Sara Booth, Jane L Wheeler, James A Tulsky, Alan J Crockett, David C Currow
Journal: The Lancet (2010)
Production of a panel of recombinant gliadins for the characterisation of T cell reactivity in coeliac disease
Authors: E H Arentz-Hansen
Journal: Gut (2000)

<h3>BACKGROUND/AIMS</h3> Coeliac disease is a chronic intestinal disorder most probably caused by an abnormal immune reaction to wheat gliadin. The identification of the HLA-DQ2 and HLA-DQ8 as the molecules responsible for the HLA association in coeliac disease strongly implicates a role for CD4 T cells in disease pathogenesis. Indeed, CD4 T cells specific for gliadin have been isolated from the small intestine of patients with coeliac disease. However, identification of T cell epitopes within gliadin has been hampered by the heterogeneous nature of the gliadin antigen. To aid the characterisation of gliadin T cell epitopes, multiple recombinant gliadins have been produced from a commercial Nordic wheat cultivar. <h3>METHODS</h3> The α-gliadin and γ-gliadin genes were amplified by polymerase chain reaction from cDNA and genomic DNA, cloned into a pET expression vector, and sequenced. Genes encoding mature gliadins were expressed in<i>Escherichia coli </i>and tested for recognition by T cells. <h3>RESULTS</h3> In total, 16 α-gliadin genes with complete open reading frames were sequenced. These genes encoded 11 distinct gliadin proteins, only one of which was found in the Swiss-Prot database. Expression of these gliadin genes produced a panel of recombinant α-gliadin proteins of purity suitable for use as an antigen for T cell stimulation. <h3>CONCLUSION</h3> This study provides an insight into the complexity of the gliadin antigen present in a wheat strain and has defined a panel of pure gliadin antigens that should prove invaluable for the future mapping of epitopes recognised by intestinal T cells in coeliac disease.
P20 Fatigue and Poor Lung Function Are Significantly Associated with Impaired Health-Related Quality of Life (HRQoL) in a Large Cohort of Patients with Chronic Pulmonary Aspergillosis
Authors: KA Al-shair, GT Atherton, DK Kennedy, GP Powell, DWD Denning
Journal: Thorax (2012)

<h3>Introduction</h3> Fatigue is a prominent disabling symptom in several chronic pulmonary diseases; however, its impact on HRQoL in patients with chronic pulmonary aspergillosis (CPA) has not been investigated. <h3>Method</h3> Our 154 patients with CPA completed the Manchester COPD Fatigue Scale (MCFS), <i>Thorax 2009</i>)) and the SGRQ in our specialist referral centre. MCFS measures total fatigue and sub-components comprehensively. Lung function and body mass index were measured. Univariate and multivariate linear and binary analysis, and the principal component analysis (PCA) were used. <h3>Results</h3> The mean (SD) age (61.1 (10.8)) years and 44% were female; FEV1% (63.3 (24.9)), BMI (23.7 (5.2)), SGRQ total score (55.6 (23.5) and MCFS total score (30 (14.9)). PCA showed that 27 items of MCFS loaded clearly on three components: physical and psychosocial and cognitive fatigue. Univariate analysis showed a strong association between total SGRQ score and MCFS score (r=0.81, p&lt;0.001). Using total SGRQ as a dependent variable, linear multi-variate analysis showed that fatigue was the strongest factor (beta = 0.83 p&lt;0.0001) associated with impaired health status followed by FEV<sub>1</sub>% (beta= –0.22, p=0.009), but no statistically significant association with age, BMI and pack/years. This model explained 70% of the variance of SGRQ total score. Using patients’ self-assessment grades of SGRQ (Very poor, poor, fair, good and very good), one-way ANOVA showed that patients with “very poor” health status had the highest fatigue scores (45 (6.4)), following by poor (35 (10.1)), fair (30 (10.4)), good (14 (10.9)) and very good (0) (p&lt;0.001). Splitting the group to (very poor and poor) versus (fair, good and very good), the ROC curve analysis indicated significant ability of MCFS and its components to detect change in HS (AUC=0.82; range 0.75–0.9, p&lt;0.0001) as demonstrated in figure 1. Furthermore, binary regression analysis showed that only fatigue score (OR=0.92, 95% CI 0.87–0.97; p=0.002) and FEV<sub>1</sub>% (OR=1.04, 95% CI 1.01–1.07, p=0.02) are significantly associated with impaired health status after correcting to age, gender and DLCO%. <h3>Conclusion</h3> This is the first study directly implicating fatigue as a major factor affecting health-related-quality of life in patients with CPA.
Long-term outcome of pulmonary function in farmer's lung: a 14 year follow-up with matched controls
Authors: R Erkinjuntti-Pekkanen, JI Kokkarinen, HO Tukiainen, J Pekkanen, K Husman, EO Terho
Journal: European Respiratory Journal (1997)

The long-term outcome of pulmonary function was evaluated in farmer's lung (FL) patients compared to representative control farmers. This is, to our knowledge, the first such study which has included a control group. Clinical examinations were conducted in 89 FL patients and 84 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yrs. The mean transfer factor of the lung for carbon monoxide (TL,CO) was on average 12% lower (p &lt; 0.001) in FL patients compared to control farmers. In spirometry, the mean maximum expiratory flow at 50% of vital capacity (MEF50) was lower (p = 0.08) in FL patients but there were no differences in mean vital capacity (VC) or forced expiratory volume in one second (FEV1) between FL patients and control farmers. However, airway obstruction, defined as an FEV1/VC less than 88% of predicted, was more common in FL patients than in control farmers (33 versus 17%; p = 0.02). Patients who had had recurrent episodes of FL had a significantly lower mean TL,CO compared to those FL patients who had experienced only a single episode. In conclusion, impairment of the pulmonary transfer factor is the most important long-term consequence of farmer's lung. However, farmer's lung may also lead to development of airway obstruction.
Hepatitis C virus: Detection of intracellular virus particles by electron microscop
Authors: Y K Shimizu, S M Feinstone, M Kohara, R H Purcell, H Yoshikura
Journal: Hepatology (1996)

We previously demonstrated that a human T-cell line, HPBMa10-2 derived from HPBALL, was capable of supporting a productive infection of hepatitis C virus (HCV). We subsequently found Daudi cells, a human B-cell line, to be susceptible to HCV infection. Employing these cell lines infected with HCV as well as liver obtained during the acute phase of hepatitis C from a chimpanzee, we observed intracellular HCV particles by electron microscopy (EM). We detected viruslike particles with a diameter of approximately 50 nm in the cytoplasmic vesicles. In Daudi cells harvested 15 days after virus inoculation, the appearance of cytoplasmic tubular structures which we originally described for chimpanzee hepatocytes in association with HCV infection was noted. Immunoperoxidase EM using antibodies against HCV core and envelope demonstrated that the particles contained the viral antigens.
Fibrotic Idiopathic Interstitial Pneumonia
Authors: Panagiota I. Latsi, Roland M. du Bois, Andrew G. Nicholson, Thomas V. Colby, Danai Bisirtzoglou, Ageliki Nikolakopoulou, Srihari Veeraraghavan, David M. Hansell, Athol U. Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Survival is linked to the histopathologic distinction between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), the most commonly encountered fibrotic idiopathic interstitial pneumonia. We retrospectively compared the prognostic significance of histopathologic diagnoses, baseline pulmonary function indices, and serial trends in pulmonary function indices (diffusing capacity, FVC, FEV1, the recently defined composite physiologic index) at 6 and 12 months in 104 patients (UIP, n = 63; fibrotic NSIP, n = 41). Survival was lower in UIP than in fibrotic NSIP (p = 0.001) but not in patients with severe functional impairment; mortality during the first 2 years was linked solely to the severity of functional impairment at presentation. The composite physiologic index was the strongest determinant of outcome (p < 0.001). At 6 months, serial diffusing capacity levels (p = 0.003) and histopathologic diagnosis (p = 0.002) were prognostically equivalent. At 12 months, serial pulmonary function trends were the only major prognostic determinant (p < 0.0005 for all variables), with no independent significance associated with the distinction between UIP and fibrotic NSIP. We conclude that at 12 months, serial pulmonary function trends have considerable prognostic value in UIP and NSIP. Their histologic distinction provides no additional prognostic information when pulmonary function trends are clear cut or when functional impairment is severe.
ALLPATHS 2: small genomes assembled accurately and with high continuity from short paired reads
Authors: Iain MacCallum, Dariusz Przybylski, Sante Gnerre, Joshua Burton, Ilya Shlyakhter, Andreas Gnirke, Joel Malek, Kevin McKernan, Swati Ranade, Terrance P Shea, Louise Williams, Sarah Young, Chad Nusbaum, David B Jaffe
Journal: Genome biology (2009)

Abstract We demonstrate that genome sequences approaching finished quality can be generated from short paired reads. Using 36 base (fragment) and 26 base (jumping) reads from five microbial genomes of varied GC composition and sizes up to 40 Mb, ALLPATHS2 generated assemblies with long, accurate contigs and scaffolds. Velvet and EULER-SR were less accurate. For example, for Escherichia coli , the fraction of 10-kb stretches that were perfect was 99.8% (ALLPATHS2), 68.7% (Velvet), and 42.1% (EULER-SR).
A CASE OF INTESTINAL STASIS
Authors: C. D. Maitland
Journal: BMJ (1923)

FTxB3 7r7Unless a loop of intestine has been very severely damaged it is not necessary to resect.It is far safer to pare the edges of the laieration and to close it with two continuous sutures of fine linen thread.Linen thread closes wounds in these damaged tissues more effectively and permanently than fine catgut and does no harm.While the surgeon is closing the perforation gauze rolls are passed into the pelvis and Rlanks to absorb the effusion in these areas.This is a quicker and better method than washing out, And the peritoneum is left dry and less damaged.In late cases a stab wound is made about two inches above the pubis and a tube is inserted to drain the pelvis, but.n early oases the peritoneum is completely closedc2MORTALITY.The mortality of this condition is appalling, and is chiefly due to delay and errors of diagnosis.James Berry and Giuseppi1 have done good service by collecting and analysing 132 cases of rupture of the intestine from cotitusion, from the records of ten London hospitals, previous to 1908.Of Berry's collection, 84 patients were operated upon, with 67-deaths- a mortality of 80 per cent.; but in 15 the ruptures were not found at the operation; 7 of these were in the duodenum.The surgical registrars of twelve London hospitals collected 44 cases occurring between 1908 and 1912.2.In 12 of these tlhere was no operation.Of 32 operated upon, 23 died (72 per cent.).-Taking these two series together, there were 176 cases, with 116 operations, and a mortality of 77 per cent.It is interesting to note that 60 (or over one-third) of the patients' ,weie not submitted to operation.iThis was chiefly dane to thieir 'grave condition on admission, owing to delay or the 'presence of complications.It iscertain that the best results are obtained by quick decision, early operation, and accurate-and rapid work at the operation, followed by careful after-treatment.CASE I.
Diagnostic Criteria for the Classification of Cancer-Associated Weight Loss
Authors: Lisa Martin, Pierre Senesse, Ioannis Gioulbasanis, Sami Antoun, Federico Bozzetti, Chris Deans, Florian Strasser, Lene Thoresen, R. Thomas Jagoe, Martin Chasen, Kent Lundholm, Ingvar Bosaeus, Kenneth H. Fearon, Vickie E. Baracos
Journal: Journal of Clinical Oncology (2014)

Purpose Existing definitions of clinically important weight loss (WL) in patients with cancer are unclear and heterogeneous and do not consider current trends toward obesity. Methods Canadian and European patients with cancer (n = 8,160) formed a population-based data set. Body mass index (BMI) and percent WL (%WL) were recorded, and patients were observed prospectively until death. Data were entered into a multivariable analysis controlling for age, sex, cancer site, stage, and performance status. Relationships for BMI and %WL to overall survival were examined to develop a grading system. Results Mean overall %WL was −9.7% ± 8.4% and BMI was 24.4 ± 5.1 kg/m 2 , and both %WL and BMI independently predicted survival (P &lt; .01). Differences in survival were observed across five categories of BMI (&lt; 20.0, 20.0 to 21.9, 22.0 to 24.9, 25.0 to 27.9, and ≥ 28.0 kg/m 2 ; P &lt; .001) and five categories of %WL (−2.5% to −5.9%, −6.0% to −10.9%, −11.0% to −14.9%, ≥ −15.0%, and weight stable (± 2.4%); P &lt; .001). A 5 × 5 matrix representing the five %WL categories within each of the five BMI categories was graded based on median survival and prognostic significance. Weight-stable patients with BMI ≥ 25.0 kg/m 2 (grade 0) had the longest survival (20.9 months; 95% CI, 17.9 to 23.9 months), and %WL values associated with lowered categories of BMI were related to shorter survival (P &lt; .001), as follows: grade 1, 14.6 months (95% CI, 12.9 to 16.2 months); grade 2, 10.8 months (95% CI, 9.7 to 11.9 months); grade 3, 7.6 months (95% CI, 7.0 to 8.2 months); and grade 4, 4.3 months (95% CI, 4.1 to 4.6 months). Survival discrimination by grade was observed within specific cancers, stages, ages, and performance status and in an independent validation sample (n = 2,963). Conclusion A robust grading system incorporating the independent prognostic significance of both BMI and %WL was developed.
Systems Biology Characterization of Engineered Tissues
Authors: Padmavathy Rajagopalan, Simon Kasif, T.M. Murali
Journal: Annual Review of Biomedical Engineering (2013)

Tissue engineering and molecular systems biology are inherently interdisciplinary fields that have been developed independently so far. In this review, we first provide a brief introduction to tissue engineering and to molecular systems biology. Next, we highlight some prominent applications of systems biology techniques in tissue engineering. Finally, we outline research directions that can successfully blend these two fields. Through these examples, we propose that experimental and computational advances in molecular systems biology can lead to predictive models of bioengineered tissues that enhance our understanding of bioengineered systems. In turn, the unique challenges posed by tissue engineering will usher in new experimental techniques and computational advances in systems biology.