tbuckley/cabot-search huggingface dataset:
The Inferelator: an algorithm for learning parsimonious regulatory networks from systems-biology data sets de novo
Authors: Richard Bonneau, David J Reiss, Paul Shannon, Marc Facciotti, Leroy Hood, Nitin S Baliga, Vesteinn Thorsson
Journal: Genome biology (2006)

We present a method (the Inferelator) for deriving genome-wide transcriptional regulatory interactions, and apply the method to predict a large portion of the regulatory network of the archaeon Halobacterium NRC-1. The Inferelator uses regression and variable selection to identify transcriptional influences on genes based on the integration of genome annotation and expression data. The learned network successfully predicted Halobacterium's global expression under novel perturbations with predictive power similar to that seen over training data. Several specific regulatory predictions were experimentally tested and verified.
OC-026 Diagnostic Yields Of Sehcat Scanning And Glucose Hydrogen Breath Testing In Pelvic Radiation Disease
Authors: R Stacey, J Turner, J Green
Journal: Gut (2014)

<h3>Introduction</h3> Late Gastrointestinal side effects following radiotherapy are common but under reported by patients and poorly recognised by clinicians<sup>.1</sup> Pelvic radiation disease (PRD) can present up to 30 years after radiotherapy treatment with a range of symptoms, including rectal bleeding, abdominal pain and diarrhoea. Many of these patients experience troublesome symptoms of diarrhoea secondary to Bile acid Malabsorption (BAM) and small intestinal bacterial overgrowth (SIBO). In our centre we have access to 23-seleno-25-homo-tauro-cholic acid (SeHCAT) nuclear medicine scanning and glucose hydrogen breath testing for the investigation of BAM and SIBO associated with PRD. The majority of data on patients with pelvic radiation disease has been published by one specialist centre (The Royal Marsden Hospital). We audited the diagnostic yields for investigation of small intestinal manifestations of PRD. <h3>Methods</h3> We identified 77 patients referred to gastroenterology clinic at University Hospital Llandough, Cardiff with suspected pelvic radiation disease via a departmental database. All patients were investigated via the Royal Marsden algorithm and BSG guidance. We then identified all patients with diarrhoeal symptoms and audited the results of any SeHCAT and glucose hydrogen breath tests and their diagnostic yields. <h3>Results</h3> 26 patients (36%) had diarrhoeal symptoms. Within this group, 24 patients underwent SeHCAT scanning, with 45% having positive results. 19 were referred for glucose hydrogen breath tests of which 53% had positive results. 17% had both positive SeHCAT and Glucose hydrogen breath tests. Not all patients received both tests due to various reasons (clinical decision, patient choice and non attendance). <h3>Conclusion</h3> PRD is common but under investigated. BSG guidance on its management exists<sup> [1] </sup>and an algorithmic approach has been shown to be beneficial<sup>.2</sup> Diarrhoea occurs frequently in PRD, and we have found that SeHCAT scanning and Glucose Hydrogen breath tests in these patients have a high diagnostic yield for BAM and SIBO respectively. SIBO and BAM can exist concurrently in this group, and our data supports a thorough and systematic algorithmic approach. Clinicians should have a low threshold for requesting these tests in patients with suspected PRD. <h3>References</h3> 1 Andreyev HJN, Davidson SE, Gillespie C, Allum WH, Swarbrick E. British Society of Gastroenterology, <i>et al</i>. Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer. <i>Gut</i> 2012:179–92 2 Andreyev HJN, Benton BE, Lalji A, Norton PC, Kabir M, Gage PH, <i>et al</i>. ArticlesAlgorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial. <i>Lancet</i>. Elsevier Ltd; 2013 Sep 20:1–9 <h3>Disclosure of Interest</h3> None Declared.
Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart.
Authors: R W Alexander, K M Kent, J J Pisano, H R Keiser, T Cooper
Journal: Journal of Clinical Investigation (1975)

Experiments were performed to evaluate the role of prostaglandin synthesis in the regulation of coronary blood flow in dog hearts. The left main coronary artery was cannulated and flow measured both in otherwise intact animals and in canine heart-lung preparations. Prostaglandin E was measured by radioimmunoassay. Reactive hyperemia (flow after occlusion release) was induced by coronary occlusion for 10, 15, and 20 s and was 39 plus or minus 13 (mean plus or minus SEM), 66 plus or minus 21, and 82 plus or minus 24 ml, respectively. Indomethacin, an inhibitor of prostaglandin synthetase, reduced reactive hyperemia at 10, 15, and 20 s to 15 plus or minus 5, 33 plus or minus 11, and 47 plus or minus 17 ml, respectively (P smaller than 0.05). Meclofenamate, a different prostaglandin synthetase inhibitor, gave similar results. In a second group of five dogs, prostaglandin production of the heart was examined in response to 20-s occlusions. There was a significant increase in prostaglandin production from a basal level of 18.6 plus or minus 4.9 mg/min to 35.3 plus or minus 5.8 ng/min after occlusion of the coronary artery for 20 s (P smaller than 0.05). After indomethacin, this increase in prostaglandin production was not observed and reactive hyperemia was significantly reduced. Thus, prostaglandin synthesis appears to be important to modulating canine coronary blood flow in response to brief periods of coronary occlusion.
Early sport specialisation, does it lead to long-term problems?
Authors: A Mehran Mostafavifar, Thomas M Best, Greg D Myer
Journal: British Journal of Sports Medicine (2012)

Sports participation is increasing in the USA (US population 313 million inhabitants) and in Icelandic (population 320 thousand inhabitants) adolescents, it is estimated that 35–45 million youth 6–18 years of age participate in some form of organised or recreational athletics.1 ,2 However, sports specialisation including year-round sport-specific training, participation on multiple teams of the same sport and focused participation in a single sport is purported to be increasing in frequency in preadolescent children across the world. There are several factors that contribute to the desire of young athletes to specialise in a single sport including the pursuit of scholarships or professional contracts, being labelled as talented by parents or coaches, retailing industry and media reports.3 A 2006 New York Times article notes “A growing number of coaches, parents, and children believe that the best way to produce superior young athletes is to have them play only one sport from an early age, and to play it virtually year-round.”4 Despite this increase in global sports participation, physical fitness levels of children and adults are declining and more people around the globe are becoming obese and physically inactive.1 The efforts to specialise youth sports underlie the effects of reduced general opportunity for all children to participate …
P1305 VARIATION IN INHIBITOR SUSCEPTIBILITY BETWEEN HCV GENOTYPES MAY EXPLAIN DIFFERENTIAL TREATMENT RESPONSES TO SOFOSBUVIR AND/OR RIBAVIRIN CONTAINING REGIMENS
Authors: E.D. Anton, K. Strommen, A. Rivera, C.J. Petropoulos, W. Huang, J.D. Reeves
Journal: Journal of Hepatology (2014)
Neutrophils from human immunodeficiency virus (HIV)-seronegative donors induce HIV replication from HIV-infected patients' mononuclear cells and cell lines: an in vitro model of HIV transmission facilitated by Chlamydia trachomatis.
Authors: J L Ho, S He, A Hu, J Geng, F G Basile, M G Almeida, A Y Saito, J Laurence, W D Johnson
Journal: The Journal of Experimental Medicine (1995)

Infection with a sexually transmitted disease (STD) increases the risk for human immunodeficiency virus (HIV) infection. Polymorphonuclear leukocytes (PMNs) are recruited into the genital tract by STD pathogens, such as Chlamydia trachomatis. Semen of HIV-infected men contains HIV associated with mononuclear cells. This study investigated the interaction among PMNs from HIV-uninfected persons, C. trachomatis, and HIV-infected cells and examined the mechanisms for enhanced HIV replication. We demonstrated that PMNs from HIV-seronegative donors induced HIV replication in mononuclear cells from 17 HIV-infected patients in medium without exogenous IL-2. HIV in the cell-free supernatants from cocultures of PMNs and patients' peripheral blood mononuclear cells (PBMCs) was replication competent, as indicated by their capacity to propagate HIV in a second round of culture using PBMCs from HIV-seronegative individuals and by the fact that proviral DNA was found in these cells. PMNs from HIV-seronegative donors increased HIV replication over 100-fold in chronically HIV-infected cell lines of the monocytic, T, and B cell lineages. Moreover, PMNs increased U1 cells' production of p24 antigen by as much as ninefold when compared with U1 cells cocultured with PBMCs. The addition of C. trachomatis to PMN and U1 coculture increased HIV replication by an additional ninefold at 24 h, whereas C. trachomatis alone had no effect on p24 antigen production by U1 cells. Thus, C. trachomatis serves not only to recruit PMNs, but also to interact with PMNs to increase HIV replication. HIV replication is triggered by contact of HIV-infected cells with PMNs, by the generation of reactive oxygen intermediates (ROIs), and by soluble factors such as TNF-alpha and IL-6. This is based on the findings that production of p24 antigen, IL-6, and TNF-alpha induced by PMNs is abrogated by disrupting or partitioning PMNs from HIV-infected cells; is inhibited by superoxide dismutase and catalase, enzymes that destroy ROIs; is enhanced by differentiated HL60 cells capable of producing ROIs; and is induced by PMNs tested negative for CMV. Furthermore, the production of ROIs is independent of HIV infection of mononuclear cells, since PMNs cocultured with HIV-uninfected parental monocytic and T cell lines generated ROIs. Therefore, the increased risk for acquiring HIV infection associated with chlamydia cervicitis may be related to the local recruitment of PMNs by C. trachomatis and the induction of infectious virus from mononuclear cells present in semen. These observations provide a rationale for strategies to reduce HIV transmission by control of STD.
Inhibitory effect of Y-27632, a ROCK inhibitor, on progression of rat liver fibrosis in association with inactivation of hepatic stellate cells
Authors: Toru Murata, Shigeki Arii, Toshio Nakamura, Akira Mori, Toshimi Kaido, Hiroaki Furuyama, Katsuyoshi Furumoto, Teizo Nakao, Naoki Isobe, Masayuki Imamura
Journal: Journal of Hepatology (2001)
P232 Once-daily co-administration of glycopyrronium and indacaterol via Breezhaler<sup>®</sup>device improves lung function and symptoms in patients with COPD versus indacaterol alone: the GLOW6 study
Authors: W Vincken, J Aumann, D Jack, H Chen, M Henley, P Goyal
Journal: Thorax (2013)

<h3>Introduction</h3> To benefit symptomatic patients with moderate-to-severe COPD not managed by single bronchodilator, COPD management strategies recommend combining bronchodilators with different mechanisms. We compared, once-daily dual bronchodilation by co-administration of the long-acting muscarinic antagonist (LAMA) glycopyrronium 50µg (GLY) and the long-acting β<sub>2-</sub>agonist (LABA) indacaterol 150µg (IND), with IND 150 µg monotherapy. <h3>Methods</h3> In this randomised, multicentre, placebo-controlled, double-blind, parallel-group study, patients with moderate-to-severe COPD were administered with GLY + IND or IND + placebo (1:1; all delivered via Breezhaler<sup>®</sup> device) for 12 weeks. We assessed lung function, dyspnoea (via the transition dyspnoea index [TDI]), patient-reported symptoms, and safety and tolerability over 12 weeks. <h3>Results</h3> Of the 449 patients randomised (GLY + IND [n = 226]; IND [n = 223]), 94.0% completed the study. At Week12, GLY + IND demonstrated a statistically significant improvement in mean trough forced expiratory volume in one second (FEV<sub>1</sub>)over IND (least squares mean treatment difference [Td]: 64 mL; p &lt; 0.001). Significantly greater improvements in FEV<sub>1</sub> area under curve from 30 min to 4h (FEV<sub>1</sub>AUC<sub>30min-4h</sub>) and trough forced vital capacity were observed with GLY + IND vs IND on Day1 (Td: 105 mL, 112 mL, respectively) and at Week12 (Td: 111 mL, 93 mL, respectively), all p &lt; 0.01. GLY + IND demonstrated significant improvements in inspiratory capacity versus IND at most timepoints on Day1 and Week12 (Td: 59 to 159 mL). GLY + IND significantly improved TDI total score versus IND (Td: 0.49, p = 0.037) and a higher proportion of patients on GLY + IND achieved a clinically meaningful improvement (≥1 point) versus IND at Week12 (odds ratio 1.97 favouring GLY + IND; p = 0.004). GLY + IND was also associated with significantly greater improvements in mean daytime respiratory symptom score and the percentage of days being able to perform usual daily activities vs IND over 12 weeks of treatment (Td: -0.1 and 6.2, respectively; both p &lt; 0.05). The overall incidence of adverse events (AEs) and serious AEs (SAEs) was comparable for the GLY + IND and IND groups (AEs: 37.6% vs 34.1%; SAEs: 2.2% vs 2.3%, respectively). <h3>Conclusion</h3> In patients with moderate-to-severe COPD, compared with indacaterol monotherapy, once-daily co-administration of glycopyrronium and indacaterol delivered via Breezhaler<sup>®</sup> device provided superior improvements lung function and early post-dose bronchodilation (from Day1), dyspnoea, symptoms and activities, without adversely affecting safety and tolerability.
A simple index on the day of admission which predicts outcome in acute pancreatitis
Authors: P. Layer
Journal: Gut (2008)

Severe pancreatitis is typically associated with (multi-) organ failure originating from local and systemic complications, and requires intensive, often specialised, interdisciplinary management including complex interventions. Severity originates from a “double hit” mechanism, involving an initial phase dominated by the systemic inflammatory response syndrome (SIRS); and, often after transient improvement, subsequent deterioration due to secondary septic complications driven by infected necrosis or pseudocysts. Hence, a prolonged course with consumption of considerable resources is common, and mortality is still substantial. As prevention or early and effective treatment of complications and organ failure count among the most important management aims, it is therefore pivotal to anticipate severe disease with reasonable accuracy. On the other hand, most patients with acute pancreatitis have a mild, uneventful and uncomplicated course, characterised by absence of organ failure or deaths; they can be treated on a peripheral ward and discharged home within a few days. In these patients, unnecessary (over-) treatment should be avoided in the interest of the patient and healthcare resources.

In consequence, intensive research has been devoted for decades to the development and validation of prognostic tools that may allow early and reliably discrimination between mild and severe disease. Numerous single markers (such as C-reactive protein (CRP), trypsin activation peptide (TAP), procalcitonin (PCT) and others) and complex scores (including the traditional Ranson, Glasgow and Acute Physiology …
Autocrine Factors That Sustain Glioma Invasion and Paracrine Biology in the Brain Microenvironment
Authors: D. B. Hoelzinger, T. Demuth, M. E. Berens
Journal: JNCI Journal of the National Cancer Institute (2007)

Invasion is a defining hallmark of glioblastoma multiforme, just as metastasis characterizes other high-grade tumors. Glial tumors invariably recur due to the regrowth of invasive cells, which are unaffected by standard treatment modalities. Drivers of glioma invasion include autocrine signals propagated by secreted factors that signal through receptors on the tumor. These secreted factors are able to diffuse through the peritumoral stroma, thereby influencing parenchymal cells that surround the tumor mass. Here we describe various autocrine motility factors that are expressed by invasive glioma cells and explore the effects that they may have on normal cells present in the path of invasion. Conversely, normal brain parenchymal cells secrete ligands that can stimulate receptors on invasive glioma cells and potentially facilitate glioma invasion or create a permissive microenvironment for malignant progression. Parallel observations have been made for solid tumors of epithelial origin, in which parenchymal and stromal cells either support or suppress tumor invasion. Most autocrine and paracrine interactions involved in glioma invasion constitute known signaling systems in stages of central nervous system development that involve the migration of precursor cells that populate the developing brain. Key paracrine interactions between glioma cells and the brain microenvironment can influence glioma pathobiology and therefore contribute to its poor prognosis. Current therapies for glioma that could have an impact on paracrine communication between tumors and normal cells are discussed. We suggest that cells in the normal brain parenchyma be considered as potential targets for adjuvant therapies to control glioma growth because such cells are less likely to develop resistance than glioma cells.
Sagittal Abdominal Diameter Is a Strong Anthropometric Measure of Visceral Adipose Tissue in the Asian General Population
Authors: Jeong Yoon Yim, Donghee Kim, Seon Hee Lim, Min Jeong Park, Seung Ho Choi, Chang Hyun Lee, Sun Sin Kim, Sang-Heon Cho
Journal: Diabetes Care (2010)

OBJECTIVE Finding the anthropometric measure of visceral obesity is essential to clinical practice, because it predicts cardiovascular and metabolic risks. Sagittal abdominal diameter (SAD) has been proposed as an estimate of visceral adipose tissue (VAT). The aim of the present study was to evaluate the usefulness of SAD in predicting visceral obesity by comparing SAD to other anthropometric measures. RESEARCH DESIGN AND METHODS Estimation of subcutaneous and visceral adipose tissue and measurement of SAD and transverse abdominal diameter using computed tomography at the umbilical level were obtained in 5,257 men and women who were enrolled in a health checkup program in Korea. To compare SAD to other anthropometric measures, linear regression analyses were used to determine correlations between anthropometrics and visceral obesity. RESULTS SAD showed a stronger correlation to VAT than waist circumference, BMI, and transverse abdominal diameter in the both sexes (men: r = 0.804, women: r = 0.724). Waist circumference showed generally stronger associations to subcutaneous adipose tissue (SAT) than to VAT (men: r = 0.789 vs. 0.705, women: r = 0.820 vs. 0.636). Even after subdividing according to age or BMI in both sexes and analyzing multiple regressions, SAD showed the strongest correlation to VAT. CONCLUSIONS SAD showed the strongest correlation to VAT irrespective of age, sex, and the degree of obesity compared with other anthropometric measures, whereas waist circumference may have a stronger correlation to SAT than to VAT. The clinical use of SAD has advantages over other anthropometric measures in predicting VAT.
Thymosin-induced suppression of proliferative response of human lymphocytes to mitogens.
Authors: R E Wolf
Journal: Journal of Clinical Investigation (1979)

The proliferative response of human peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and pokeweed mitogen were suppressed by thymosin. Greatest decreases were observed when cells were preincubated with thymosin for 18 h before a 3-d culture with mitogen in the presence of thymosin. However, significant suppression also occurred when lymphocytes were preincubated for 2 h and cultured with thymosin or preincubated for either 2 or 18 h and washed free of thymosin before culture. These effects were related to the concentration of thymosin and time of exposure to thymosin but not merely to a delay in the response to mitogen or to toxicity. The suppression of mitogen-induced proliferation by thymosin appeared to result from effects of thymosin on a suppressor cell because lymphocytes incubated with thymosin did not acquire increased responsiveness to mitogens as did cells incubated for 18 h in its absence and because mixing thymosin-pretreated lymphocytes with cells not preincubated with thymosin resulted in decreased responsiveness to photohemagglutinin.
Non-invasive ventilation during sleep: time to define new tools in the systematic evaluation of the technique
Authors: M. W. Elliott
Journal: Thorax (2010)

Non-invasive ventilation (NIV) has been remarkably effective in the management of chronic respiratory failure, despite initially rudimentary equipment and limited understanding of what was actually happening, minute by minute when ventilation was applied. Modern ventilators, controlled by complex algorithms, and with integrated monitoring allow for sophisticated customisation of ventilatory support to an individual. However, if problems with ventilation are not recognised, and their significance understood, they cannot be fixed. Experience of monitoring during sleep from patients predominantly with sleep apnoea can be transferred and extended to patients receiving NIV. This article, the first in a series, explores the rationale for NIV and how its application to an individual patient can be monitored using simple tools and, when problems are identified, the causes can be identified using sophisticated interpretation of more detailed monitoring. This requires a detailed understanding of how different modes of ventilation work and some knowledge of the algorithms that control each machine. These themes are explored in this article and developed in subsequent articles in the series.
Claudin-3 and Claudin-4 Expression in Ovarian Epithelial Cells Enhances Invasion and Is Associated with Increased Matrix Metalloproteinase-2 Activity
Authors: Rachana Agarwal, Theresa D'Souza, Patrice J. Morin
Journal: Cancer Research (2005)

Claudin proteins form a large family of integral membrane proteins crucial for tight junction formation and function. Our previous studies have revealed that claudin-3 and claudin-4 proteins are highly overexpressed in ovarian cancer. To clarify the roles of claudins in ovarian tumorigenesis, we have generated human ovarian surface epithelial (HOSE) cells constitutively expressing wild-type claudin-3 and claudin-4. Expression of these claudins in HOSE cells increased cell invasion and motility as measured by Boyden chamber assays and wound-healing experiments. Conversely, small interfering RNA (siRNA)-mediated knockdown of claudin-3 and claudin-4 expression in ovarian cancer cell lines reduced invasion. Claudin expression also increased cell survival in HOSE cells but did not significantly affect cell proliferation. Moreover, the claudin-expressing ovarian epithelial cells were found to have increased matrix metalloproteinase-2 (MMP-2) activity indicating that claudin-mediated increased invasion might be mediated through the activation of MMP proteins. However, siRNA inactivation of claudins in ovarian cancer cell lines did not have a significant effect on the high endogenous MMP-2 activity present in these cells, showing that malignant cells have alternative or additional pathways to fully activate MMP-2. Taken together, our results suggest that claudin overexpression may promote ovarian tumorigenesis and metastasis through increased invasion and survival of tumor cells.