tbuckley/cabot-search huggingface dataset:
COSCA (Core Outcome Set for Cardiac Arrest) in Adults: An Advisory Statement From the International Liaison Committee on Resuscitation
Authors: Kirstie Haywood, Laura Whitehead, Vinay M. Nadkarni, Felix Achana, Stefanie Beesems, Bernd W. Böttiger, Anne Brooks, Maaret Castrén, Marcus EH Ong, Mary Fran Hazinski, Rudolph W. Koster, Gisela Lilja, John Long, Koenraad G. Monsieurs, Peter T. Morley, Laurie Morrison, Graham Nichol, Valentino Oriolo, Gustavo Saposnik, Michael Smyth, Ken Spearpoint, Barry Williams, Gavin D. Perkins
Journal: Circulation (2018)

Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on Resuscitation, sought to develop a consensus core outcome set for cardiac arrest for effectiveness trials. Core outcome sets are primarily intended for large, randomized clinical effectiveness trials (sometimes referred to as pragmatic trials or phase III/IV trials) rather than for pilot or efficacy studies. A systematic review of the literature combined with qualitative interviews among cardiac arrest survivors was used to generate a list of potential outcome domains. This list was prioritized through a Delphi process, which involved clinicians, patients, and their relatives/partners. An international advisory panel narrowed these down to 3 core domains by debate that led to consensus. The writing group refined recommendations for when these outcomes should be measured and further characterized relevant measurement tools. Consensus emerged that a core outcome set for reporting on effectiveness studies of cardiac arrest (COSCA) in adults should include survival, neurological function, and health-related quality of life. This should be reported as survival status and modified Rankin scale score at hospital discharge, at 30 days, or both. Health-related quality of life should be measured with ≥1 tools from Health Utilities Index version 3, Short-Form 36-Item Health Survey, and EuroQol 5D-5L at 90 days and at periodic intervals up to 1 year after cardiac arrest, if resources allow.
Involvement of angiotensin II/angiotensin-(1–7) fibrinolytic pathway in improvement of liver fibrosis in chronic hepatitis C patients who had sustained virological response by direct-acting antiviral therapy: a prospective trial
Authors: N. Teeratorn, K. Thanapirom, S. Suksawatamnuay, P. Thaimai, S. Sittisomwong, K. Sonsiri, N. Srisoonthorn, S. Sriphoosanaphan, N. Tanpowpong, B. Chaopathomkul, S. Treeprasertsuk, Y. Poovorawan, P. Komolmit
Journal: Journal of Hepatology (2018)
David Oliver: Accountability—individual blame versus a “just culture”
Authors: David Oliver
Journal: BMJ (2018)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following David Oliver: Accountability—individual blame versus a "just culture" Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Systematic detection of portal or splenic vein thrombosis after splenectomy for immune cytopenia
Authors: Caroline Morbieu, Francesco Brunetti, Laurence Baranès, Laetitia Languille, Nicolas Limal, Valentine Loustau, Philippe Bierling, Marc Michel, Bertrand Godeau, Matthieu Mahévas
Journal: American Journal of Hematology (2018)

FIG URE 1 Site of portal or splenic vein thrombosis (PSVT). (A) Schematic drawing with classification of PVST according to Ikeda (1). (B) Localization of PSVT with representative images of enhanced CT-scan in portal phase
Abstract 15212: Npa7, a First in Class Dual Receptor Activator With Renoprotective Properties
Authors: Laura M Meems, Brenda K Huntley, Gail J Harty, Shuchong Pan, John C Burnett
Journal: Circulation (2016)

Introduction:  Acute decompensated heart failure (ADHF) is a disease with high morbidity and mortality. Available treatment of ADHF oftentimes induces cardiorenal syndrome (CRS), which is a strong predictor of mortality, and warrants innovative drugs with novel modes of action as well as cardio-renoprotective properties. We used an innovative strategy to engineer a novel multivalent peptide (NPA7), which is a fusion of a 22 amino acid sequence of a pGC-A receptor (pGC-A) activator, and the Mas receptor (MasR) agonist ANG1-7 that possess complementary cardio-renoprotective properties. We hypothesized that NPA7 is a dual receptor activator  in vitro  with renoprotective properties in an experimental model of HF  in vivo .   Methods and Results:  First, we successfully synthesized NPA7 by solid phase peptide synthesis. Second, we confirmed  in vitro  binding of NPA7 to pGCA ( green ) and MasR ( red ), selectively overexpressed in HEK293 cells (GCA++ and Mas++, respectively) (figure 1A-B). We then assessed  in vitro  dual receptor activation using second messengers cGMP (pGC-A) and cAMP (MasR) as read-out (figure 1C-D). As proximal tubular injury is a contributing mechanism of CRS we defined presence of both pGC-A and MasR in human primary proximal tubular (PPT) cells (figure 1E-F). Finally, since renal vasoconstriction in CRS may contribute to renal hypoxia and injury, we defined potential renal vasodilating actions of NPA7 in a canine model of HF (renal blood flow NPA7  vs.  baseline: +26.7 ± 13.1 ml/min, p vs.  baseline: +0.098 ± 0.024 ml/min, p   Conclusion:  In conclusion, this study shows that NPA7 is a dual pGC-A/MasR activator  in vitro,  that its molecular receptor targets are present in human PTT cells, and that NPA7 induces renal vasodilation in an experimental model of HF. Altogether, this study lays the groundwork for further studies on NPA7s cardiorenal protective properties  in vivo .
Abstract 12227: Early Stimulation of Fast-Conducting Endocardial Tissue Underlies Improvements in Endocardial Pacing
Authors: Eoin R Hyde, Gernot Plank, Christopher A Rinaldi, Steven A Niederer
Journal: Circulation (2015)

Introduction: Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute haemodynamic response compared to LV epicardial pacing (EPI-CRT). The mechanisms underlying this improved response remain controversial. Hypothesis: We used computational electrophysiological models to test the hypotheses that the following ordered cardiac properties are advantageous to ENDO-CRT: fast endocardial conduction (FEC), inherent geometry, asymmetric transmural conduction, and tissue anisotropy. Methods: Cardiac activation was simulated using the mono-domain tissue excitation model in 2D canine and human, and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) vs epicardial (ep) LV pacing (defined as %dLV=100*(LVLATep- LVLATen)/LVLATep and %dT=100*( TLATep- TLATen)/TLATep respectively). Results: Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodelled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular paced canine model resulted in %dLV and %dT values of -7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding FEC to this model altered %dLV and %dT to 13.1% and 10.1%, respectively. Conclusions: Our results provide a physiological explanation for improved response to ENDO-CRT. We predict that patients with viable fast-conducting endocardial tissue and/or distal Purkinje network, as well as concentric remodelling, are more likely to benefit from reduced ATs and increased synchrony arising from endocardial pacing.
Invasive fungal infections in Acute on chronic liver failure – An Asia Pacific experience from the AARC consortium
Authors: S. Taneja, S. Rathi, R.K. Dhiman, A. Duseja, A. Choudhury, P. Jain, I. Paulson, H. Deverbhavi, S.-S. Tan, C. Eapen, A. Goel, S. Shah, C. Kalal, A. Kadir Dokmeci, A. Shukla, D.J. Kim, J.-D. Jia, D. Amarapurkar, G.H. Lee, S.G. Lim, N.R. Padaki, S.S. Hamid, W. Jafri, Z. Abbas, S.K. Sarin
Journal: Journal of Hepatology (2018)
Self-rated walking pace and all-cause, cardiovascular disease and cancer mortality: individual participant pooled analysis of 50 225 walkers from 11 population British cohorts
Authors: Emmanuel Stamatakis, Paul Kelly, Tessa Strain, Elaine M Murtagh, Ding Ding, Marie H Murphy
Journal: British Journal of Sports Medicine (2018)

Background/objectives Walking pace is associated with risk of premature mortality. However, whether this relationship is independent of total volume of physical activity and highest physical activity intensity remains unclear. We examined the associations between walking pace and cause-specific mortality, investigating the potential modifying effect of factors such as total physical activity volume, highest physical activity intensity, age, sex and body mass index (BMI). Methods Prospective pooled analysis of 11 population-based baseline surveys in England and Scotland between 1994 and2008 that were linked with mortality records. Multivariate-adjusted Cox proportional hazards models examined associations between walking pace (slow, average, brisk/fast) and all-cause, cancer and cardiovascular disease (CVD) mortality. Results 50 225 walkers were entered in the core analyses. Among participants who did not experience an event in the first 2 years of follow-up (n=49 731), walking at an average or brisk/fast pace was associated with a reduced risk of all-cause (20% (95% CI 12% to 28%) and 24% (95% CI 13% to 33%), respectively) and CVD mortality (24% (95% CI 9% to 36%) and 21% (95% CI 1% to 38%), respectively), compared with reporting walking at a slow pace. In stratified analyses, such associations were evident among those over 50 years, those not meeting the physical activity recommendations and those who did not undertake vigorous-intensity activity. There were no interactions by sex or BMI. No associations were seen between pace and cancer mortality. Conclusion Walking benefits health. Assuming causality, these analyses suggest that increasing walking pace could reduce risk for all-cause and CVD mortality. Walking pace could be emphasised in public health messages, especially in situations when increase in walking volume or frequency is less feasible.
DGAT2 Inhibition Alters Aspects of Triglyceride Metabolism in Rodents but Not in Non-human Primates
Authors: David G. McLaren, Seongah Han, Beth Ann Murphy, Larissa Wilsie, Steven J. Stout, Haihong Zhou, Thomas P. Roddy, Judith N. Gorski, Daniel E. Metzger, Myung K. Shin, Dermot F. Reilly, Heather H. Zhou, Marija Tadin-Strapps, Steven R. Bartz, Anne-Marie Cumiskey, Thomas H. Graham, Dong-Ming Shen, Karen O. Akinsanya, Stephen F. Previs, Jason E. Imbriglio, Shirly Pinto
Journal: Cell Metabolism (2018)
Ex vivo characterization of co-inhibitory molecules on MHC class II tetramer positive HCV-specific CD4+ T cells in HCV infection
Authors: C. Ackermann, S. Kummer, M. Smits, V. Matzat, F. Piecha, J. Eberhard, T. Böttler, J.S.Z. Wiesch
Journal: Journal of Hepatology (2018)
Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa
Authors: Jeremy D. Keenan, Robin L. Bailey, Sheila K. West, Ahmed M. Arzika, John Hart, Jerusha Weaver, Khumbo Kalua, Zakayo Mrango, Kathryn J. Ray, Catherine Cook, Elodie Lebas, Kieran S. O’Brien, Paul M. Emerson, Travis C. Porco, Thomas M. Lietman
Journal: New England Journal of Medicine (2018)

We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations.
Computed tomography-guided endoscopic sinusotomy for an ileal pouch presacral sinus
Authors: Sara El Ouali, Joseph Veniero, Bo Shen
Journal: Endoscopy (2018)

Endoscopic sinusotomy for ileal pouch sinus, a detrimental complication caused by chronic anastomotic leak, is an effective and safe treatment option [1]. Endoscopic sinusotomy requires access to the sinus from the pouch lumen and has been considered infeasible in patients with a sealed sinus. We describe herein the first endoscopic sinusotomy for a sealed sinus using computed tomography (CT)-guided wire placement.
15HYAL2 and CD44v6: towards new molecular signatures of plaque instability
Authors: R Vinci, D Pedicino, E Pisano, I Porto, R Vergallo, A Ruggio, D Flego, A Severino, G Liuzzo, F Crea
Journal: Cardiovascular Research (2018)

Background: Enhanced proliferation of vascular smooth muscle cells (SMC) is associated with various vascular diseases like atherosclerosis and in-stent restenosis.SMC phenotype switching from a quiescent to a proliferative state is among others triggered by various signaling cascades which downregulate essential structural and cytoskeletal proteins.Here, we propose that vasorin, a smooth muscle cell specific protein, is a novel regulator of SMC proliferation and differentiation in vitro and in vivo.Methods/Results: Vasorin was found to be expressed specifically in smooth muscle cells in vitro and in vivo as determined by qPCR, immunofluorescence-and western blot analysis.Upon wireinduced injury of murine femoral arteries, vasorin expression was down regulated in vivo as assessed by qRT-PCR and immunofluorescence (0.12 fold, p<0.001).Mimicking this down regulation in vitro significantly enhanced the proliferation of SMC (100% vs 128.74%, p<0.001).Moreover, SMC lacking vasorin exhibited a reduced expression of various marker molecules of differentiated SMC like smoothelin and calponin as shown by western blot analysis.In contrast, overexpression of vasorin in SMC in vitro significantly reduced the serum-induced proliferation of SMC (100% vs 51.53 %, p<0.001).Mechanistically, we revealed that vasorin directly binds the EGFR and thereby inhibits EGFR phosphorylation and subsequent signaling as assessed by coimmunoprecipitation and western blot analysis.Vasorin was furthermore identified to be a direct target of miRNA-146a as determined by western blot, qRT-PCR and a luciferase assay.miRNA-146a expression was upregulated following wire-induced injury in vivo.Inhibition of miRNA-146a using specific antisense nucleotides (LNAs) restored vasorin expression in SMC in vivo.Following the specific inhibition of miRNA-146a by local application of LNA-miRNA-146a after wire-induced injury of the mouse femoral artery, SMC proliferation was reduced significantly, as assessed by Ki67 immunofluorescence (22.72 % vs 10.26% p<0.05).Consistently, local application of LNA-146a significantly reduced neointima formation (neointima/media ratio 2.84 in control vs 1.72 in treated animals p<0.01).Conclusion: Vasorin is a cell specific regulator of SMC differentiation and proliferation.The expression and function of vasorin is tightly regulated by miR-146a.Restoring vasorin expression via the inhibition of miR-146a prevents de-differentiation and proliferation of SMC following vascular injury and thus prevents neointima formation.Targeting vasorin represents a novel, effective and cell specific approach to prevent neointima formation.
Characterization of BK Polyomaviruses from Kidney Transplant Recipients Suggests a Role for APOBEC3 in Driving In-Host Virus Evolution
Authors: Alberto Peretti, Eileen M. Geoghegan, Diana V. Pastrana, Sigrun Smola, Pascal Feld, Marlies Sauter, Stefan Lohse, Mayur Ramesh, Efrem S. Lim, David Wang, Cinzia Borgogna, Peter C. FitzGerald, Valery Bliskovsky, Gabriel J. Starrett, Emily K. Law, Reuben S. Harris, J. Keith Killian, Jack Zhu, Marbin Pineda, Paul S. Meltzer, Renzo Boldorini, Marisa Gariglio, Christopher B. Buck
Journal: Cell Host & Microbe (2018)
A dose-response relationship in the association between ursodeoxycholic acid treatment and prolonged transplant-free survival in primary biliary cholangitis
Authors: A. Van der Meer, M. Harms, W.J. Lammers, C. Corpechot, D. Thorburn, P. Invernizzi, H. Janssen, P.M. Battezzati, F. Nevens, K. Lindor, A. Floreani, C. Ponsioen, M.J. Mayo, A. Pares, A.L. Mason, K.V. Kowdley, G. Hirschfield, H. Van Buuren, B. Hansen
Journal: Journal of Hepatology (2018)
Locum is struck off over “relentless” sexual harassment
Authors: Clare Dyer
Journal: BMJ (2018)

A former locum specialist registrar has been struck off the UK medical register for a “relentless” campaign of sexual harassment against a foundation year 1 doctor and for “grossly negligent” treatment of a patient.

Julian Proctor pursued the junior colleague, named only as Dr B, with unwanted hugging and touching, explicit texts, and requests for a “secret love affair” for nine days from the day he first worked with her at Pilgrim Hospital in Boston, Lincolnshire. When she reported him she was in a state of such distress that …
TCTAP C-218 Trans-graft Transcatheter Aortic Valve Implantation in a Patient with Aorto-bifemoral Bypass
Authors: Simon Chi Ying Chow, Randolph Hung-Leung Wong, Gary Shing-Him Cheung, Eugene Brian Wu, Ka Lung Chui, Chak Yu So
Journal: Journal of the American College of Cardiology (2018)
P312The selective late sodium current inhibitor eleclazine attenuates ventricular fibrillation spectral characteristics modifications produced by acute myocardial stretch
Authors: S Cunyat, I Del Canto Serrano, F J Chorro, P Genoves, L Santamaria, L Such-Miquel, O Arias-Mutis, M Zarzoso, C Soler, L Such
Journal: Cardiovascular Research (2018)
Usage of antiplatelet agents is inversely associated with liver fibrosis in patients with cardiovascular disease
Authors: K. Schwarzkopf, J. Bojunga, S. Rueschenbaum, Y. Martinez, M.M. Muecke, F. Seeger, F. Schoelzel, S. Zeuzem, M. Friedrich-Rust, C. Lange
Journal: Journal of Hepatology (2018)
Targeting protein biotinylation enhances tuberculosis chemotherapy
Authors: Divya Tiwari, Sae Woong Park, Maram M. Essawy, Surendra Dawadi, Alan Mason, Madhumitha Nandakumar, Matthew Zimmerman, Marizel Mina, Hsin Pin Ho, Curtis A. Engelhart, Thomas Ioerger, James C. Sacchettini, Kyu Rhee, Sabine Ehrt, Courtney C. Aldrich, Véronique Dartois, Dirk Schnappinger
Journal: Science Translational Medicine (2018)

Successful drug treatment for tuberculosis (TB) depends on the unique contributions of its component drugs. Drug resistance poses a threat to the efficacy of individual drugs and the regimens to which they contribute. Biologically and chemically validated targets capable of replacing individual components of current TB chemotherapy are a major unmet need in TB drug development. We demonstrate that chemical inhibition of the bacterial biotin protein ligase (BPL) with the inhibitor Bio-AMS (5'-[N-(d-biotinoyl)sulfamoyl]amino-5'-deoxyadenosine) killed Mycobacterium tuberculosis (Mtb), the bacterial pathogen causing TB. We also show that genetic silencing of BPL eliminated the pathogen efficiently from mice during acute and chronic infection with Mtb Partial chemical inactivation of BPL increased the potency of two first-line drugs, rifampicin and ethambutol, and genetic interference with protein biotinylation accelerated clearance of Mtb from mouse lungs and spleens by rifampicin. These studies validate BPL as a potential drug target that could serve as an alternate frontline target in the development of new drugs against Mtb.
Drug-induced encephalopathy in cirrhotic patients with neurological symptoms: A metabolomic study
Authors: N. Weiss, P.B.S. Hilaire, A. Schaefer, M. Rudler, S. Mouri, F. Sedel, F. Fenaille, B. Colsch, C. Junot, D. Thabut
Journal: Journal of Hepatology (2018)
PPARγ agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation
Authors: Ekaterina Legchenko, Philippe Chouvarine, Paul Borchert, Angeles Fernandez-Gonzalez, Erin Snay, Martin Meier, Lavinia Maegel, S. Alex Mitsialis, Eva A. Rog-Zielinska, Stella Kourembanas, Danny Jonigk, Georg Hansmann
Journal: Science Translational Medicine (2018)

Oral pioglitazone reverses pulmonary hypertensive vascular disease and prevents right heart failure via epigenetic, transcriptional, and metabolic mechanisms.
Two new blood tests for identifying patients with chronic liver diseases, at high risk of primary liver cancer
Authors: T. Poynard, V. Peta, M. Munteanu, J. Moussalli, M. Rudler, P. Lebray, J. Massard, R. Pais, L. Bonyhay, F. Charlotte, V. Thibault, O. Lucidarme, D. Eyraud, E. Savier, O. Scatton, M.A. Valantin, Y. Ngo, A. Ngo, F. Drane, F. Bismut, L. Fartoux, O. Deckmyn, P. Cacoub, O. Rosmorduc, C. Housset, D. Thabut, V. Ratziu
Journal: Journal of Hepatology (2018)
ΔNp63γ/SRC/Slug Signaling Axis Promotes Epithelial-to-Mesenchymal Transition in Squamous Cancers
Authors: Kirtiman Srivastava, Adam Pickard, Stephanie G. Craig, Gerard P. Quinn, Shauna M. Lambe, Jacqueline A. James, Simon S. McDade, Dennis J. McCance
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To investigate the regulation of epithelial-to-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and its importance in tumor invasion. Experimental Design: We use a three-dimensional invasive organotypic raft culture model of human foreskin keratinocytes expressing the E6/E7 genes of the human papilloma virus-16, coupled with bioinformatic and IHC analysis of patient samples to investigate the role played by EMT in invasion and identify effectors and upstream regulatory pathways. Results: We identify SNAI2 (Slug) as a critical effector of EMT-activated downstream of TP63 overexpression in HNSCC. Splice-form–specific depletion and rescue experiments further identify the ΔNp63γ isoform as both necessary and sufficient to activate the SRC signaling axis and SNAI2-mediated EMT and invasion. Moreover, elevated SRC levels are associated with poor outcome in patients with HNSCC in The Cancer Genome Atlas dataset. Importantly, the effects on EMT and invasions and SNAI2 expression can be reversed by genetic or pharmacologic inhibition of SRC. Conclusions: Overexpression of ΔNp63γ modulates cell invasion by inducing targetable SRC-Slug–evoked EMT in HNSCC, which can be reversed by inhibitors of the SRC signaling. Clin Cancer Res; 24(16); 3917–27. ©2018 AACR.
Sub-cutaneously delivered mesenchymal stromal cells and down-regulation of activated vascular endothelium – a novel, clinically ready, therapeutic approach to treating cholestatic liver disease
Authors: V. Vigneswara, N.-T. Luu, M. Alfaifi, L. O’flynn, C. Baan, M. Hoogduijn, M. Gargesha, D. Roy, S. Elliman, G. Hirschfield, P. Newsome
Journal: Journal of Hepatology (2018)
P90Features of the BNP and beta-endorphin expression in hypertension in different models
Authors: S Tischchenko, S V Tishchenko
Journal: Cardiovascular Research (2018)

The multifactorial linear regression model (aR 2 ¼0.559, p<0.001) indicated Ns (B¼6.9460.92,b¼0.72; h<0.001) and mBP (B¼0.41760.057,b¼0.696; h¼0.001) as independent predictors of the NT plasma level in rats.Conclusions: 1) The blood pressure elevation in rats is accompanied by increased expression both of nNOS and iNOS, whereas the eNOS level remained unchanged.2) The changes stated above are accompanied by increased expression of mRNA of all NOS isoforms, including eNOS, which may be an evidence of the eNOS high demand in myocardium.3) Considering the progressive decrease of the nitrates concentration in myocardium homogenates and the simultaneous plasma nitrotyrosine level increase, which are correspond to the mean blood pressure elevation, all the stated above may be considered as development of changes in myocardium, which are identical to endothelial dysfunction, including eNOS uncoupling with the shift of its activity to peroxynitrite production despite of NO.