tbuckley/cabot-search huggingface dataset:
Abstract 17592: SYNTAX Score Predicts Major Adverse Cardiac Events Among Patients who Underwent Coronary Angiography for Investigation of Chronic Coronary Artery Disease
Authors: Felipe C Fuchs, Jorge P Ribeiro, Flavio D Fuchs, Marco V Wainstein, Luiz C Bergoli, Rodrigo V Wainstein, Alessandra C Kerkhoff, Vanessa Zen, Leila B Moreira, Sandra C Fuchs
Journal: Circulation (2012)

Background: The classification of coronary lesions by several scores helps to establish the prognosis of chronic coronary artery disease (CAD), but they are not widely used in clinical practice. Th...
Impact of Omitting Prophylactic Antibiotics, to Preserve Gut Microbiota, on the Incidence of Bacteraemia during the Pre-Engraftment Period of Allogenic Hematopoietic Stem Cell Transplantation
Authors: Claudie Roy, Simon Frédéric Dufresne, Miguel Chagnon, Silvy Lachance
Journal: Blood (2018)
Human LAP<sup>+</sup>GARP<sup>+</sup>FOXP3<sup>+</sup> regulatory T cells attenuate xenogeneic graft versus host disease
Authors: Huihui Wang, Hyo Song, Anha V. Pham, Laurence J. Cooper, Janika J. Schulze, Sven Olek, Dat Q. Tran
Journal: Theranostics (2019)

Adoptive transfer of regulatory T cells (FOXP3 + Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD).A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion.Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP).The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer.The TSDR methylation was determined by epigenetic human FOXP3 qPCR Assay.Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively.Results: LAP + repurification results in >90% LAP + FOXP3 + Tregs, leaving behind FOXP3 -and FOXP3 + nonTregs within the LAP -population.After 4-week expansion, the LAP + Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity.In the xGVHD model, exogenous CD25 -PBMC administered alone results in a median survival of 32 days.The co-transfer of LAP + Tregs increased median survival to 47 days, while the LAP parent (CD25 + ) and LAP -nonTregs had median survival of 39 and 31 days, respectively.Conclusions: These preclinical data together provide evidence that LAP + Tregs are highly purified with fully suppressive function for cell therapy.This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP + Tregs to prevent or treat GVHD and other autoimmune diseases.Key words: regulatory T cells (Tregs)
Climate change and lung health: presidential failure, professional responsibility
Authors: Nicholas S Hopkinson, Nicholas Hart, Gisli Jenkins, Margaret Rosenfeld, Alan Robert Smyth, Alexander J K Wilkinson, Naftali Kaminski
Journal: Thorax (2019)

> Ignorance, allied with power, is the most ferocious enemy justice can have. James Baldwin

On the eve of President Trump’s inauguration in 2017, we published an editorial setting out the threat that climate change poses to lung health. We urged the incoming President to face up to his responsibilities and take steps to address this growing existential threat.1 We drew a parallel with the actions of two conservative leaders in the 1980s, Ronald Reagan and Margaret Thatcher who, faced with unequivocal scientific evidence, led the decisive steps necessary to avert the destruction of the ozone layer.2 3 Rather than being contrary to his stated goals, acting on climate change, we wrote ‘is one way in which President Trump can make good on his promises to improve the wellbeing of Americans, increase America’s energy independence, and act with fiscal prudence. Investing in green infrastructure creates jobs. It reduces healthcare costs, as 1/4 - 1/3 of the costs of decarbonising come straight back as health economic gains’.4

Sadly, 2 years on our worst fears have been realised. The USA is experiencing an unprecedented wave of natural disasters attributable to climate change, including widespread wildfires, destructive storms and temperature swings. However, rather than providing global leadership, the Trump administration has not merely abdicated responsibility but is actively sabotaging efforts to mitigate climate change by announcing plans to withdraw from the Paris Climate accords.5 Clear evidence in the most recent Intergovernmental Panel on Climate Change report sets …
Incorporating Weight Loss Medications Into Hepatology Practice for Nonalcoholic Steatohepatitis
Authors: Albert Do, Eric J. Kuszewski, Karl A. Langberg, Wajahat Z. Mehal
Journal: Hepatology (2019)

There is an urgent need for practical approaches to patients with nonalcoholic steatohepatitis (NASH). Total body weight loss (TBWL) is an important approach, as its effects are amplified in the liver, with 10% TBWL resulting in a 50% loss of liver triglycerides and improvement in all aspects of NASH histology. Lifestyle changes are the first step in addressing TBWL, but uncommonly result in the range required to improve liver histology in NASH (7%‐10%). Weight loss medications (WLMs) are an effective additional tool because they can provide TBWL in the 7%‐10% range, have a well‐characterized clinical profile, have clear guidelines, and meet approved criteria for their use (body mass index greater than 27 kg/m 2 ) for most NASH patients. Use of WLMs requires shared decision making with the patient, which hepatologists, due to their understanding of the natural history of NASH, are uniquely positioned to provide. WLMs do present the challenge of incorporating new medications into the hepatology clinic, but this will be necessary with all medications to manage NASH. WLMs provide a practical intervention that can be incorporated into hepatology clinics and can be offered to most NASH patients. NASH‐specific medicines in clinical trials offer partial histological responses, and TBWL will likely enhance this. Conclusion: WLMs provide the hepatologist with effective and welcome clinical intervention beyond the diagnosis and staging of NASH and provide patients with a sense of empowerment about the treatment of their liver disease.
FRI-221-Management of drug-drug interactions in chronic hepatitis C patients treated with second generation direct acting antivirals in Belgium
Authors: Stefan Bourgeois, Jean-Pierre Mulkay, Mike Cool, Verhelst Xavier, Geert Robaeys, Luc Lasser, Veronique Lefebvre, Isabelle Colle, Christophe Van Steenkiste, Jochen Decaestecker, Stephanie Coulon, Katrien Venken, Thomas Vanwolleghem
Journal: Journal of Hepatology (2019)
Heart Failure Site-Based Research in the United States
Authors: Mitchell A Psotka, Susan E Ammon, Mona Fiuzat, Biykem Bozkurt, Eugene S Chung, Robert T Cole, Stephen J Greene, David Kraus, Bonnie Ky, Colleen K McIlvennan, Palak Shah, John R Teerlink, Mary Norine Walsh, Mariell Jessup, Christopher M O'Connor
Journal: JACC Heart Failure (2019)
SAT-037-Applying the new nutritional screening and assessment algorithm to estimate malnutrition prevalence in Greek cirrhotic patients as suggested by the 2018 EASL nutritional guidelines for chronic liver disease
Authors: Alexandra Georgiou, George Papatheodoridis, Alexandra Alexopoulou, Melanie Deutsch, Ioannis Vlachogiannakos, Panagiota Ioannidou, Maria Vasiliki Papageorgiou, Nikolaos Papadopoulos, Panagiotis Tsibouris, Maria Papavdi, Mary Yannakoulia, Meropi Kontogianni
Journal: Journal of Hepatology (2019)
FRI-089-Genetic deletion of Keap in hepatocytes improves liver damage, but triggers hepatitis in an Nrf2-dependent manner, in experimental toxic liver injury
Authors: Laura Moran Blanco, Nuria López-Alcántara, Olga Estévez, Pierluigi Ramadori, Christoph J. Wruck, Iris Asensio, Javier Vaquero, Rafael Bañares, Yulia Nevzorova, Francisco Javier Cubero
Journal: Journal of Hepatology (2019)
Abstract 470: Computational Identification of NKX2-5 Binding Sites and Downstream Gene Targets Using Transcription Factor Motif and Human Heart-specific Experimental Data
Authors: Nicholas Tan, Mina K Chung, Jonathan D Smith, David R Van Wagoner, John Barnard
Journal: Circulation Research (2016)

Background: While NKX2-5 plays pivotal roles in human cardiac development and disease, no ChIP-Seq studies of NKX2-5 in human cardiac tissues currently exist, resulting in an incomplete understanding of its direct gene targets. Modern computational methods which identify binding sites using transcription factor motif and tissue-specific experimental data can help to fill this knowledge gap. Objective: To use computational methods to identify likely NKX2-5 binding sites and downstream gene targets using human heart-specific experimental data. Methods: Human cardiomyocyte DNAse hypersensitivity data (2 replicates) were downloaded from the Encyclopedia of DNA Elements (ENCODE) database. The position weight matrix (PWM) representing the transcription factor motif of NKX2-5 was obtained from JASPAR. We applied the Protein Interaction Quantification (PIQ) algorithm to detect NKX2-5 binding sites using the PWM and DNAse hypersensitivity data as inputs. RNA-Seq data from 108 human heart-specific samples (atrial appendages and left ventricles) were downloaded from the Genotype-Tissue Expression (GTEx) database. Protein-coding genes significantly expressed in the heart (RPKM &lt;= 1 based on the GTEx RNA-Seq data) that were within 100kb of the predicted binding sites were then identified. Pathway analysis of these genes was performed using Ingenuity Pathway Analysis (IPA). Results: 1283 binding sites for NKX2-5 were discovered by PIQ. Of 12698 protein-coding, heart-expressed genes, 625 were within 100kb of these binding sites. The identified genes were highly enriched in physiologic categories like “Vasculogenesis” and “Development of Cardiovascular Tissue” (p = 2.36x10-9 and 2.31x10-8 respectively). Notable genes included: cardiac transcription factors (MEF2A, TBX20); growth factors (TGFB2, BMP2); muscle and ion channel function (ACTA2, BIN1), and; calcium signaling (CALM2, CAMK2D). Conclusion: By using computational analyses of transcription factor motif and human heart-specific experimental data, we have identified candidate downstream targets of NKX2-5. Future work will include validation studies in an external cohort and analysis of associations between these candidate genes and cardiac disease.
SAT-222-Improvement in liver fibrosis among patients with hepatitis C who achieved sustained viral response after direct acting antivirals treatment, in country of Georgia
Authors: Maia Butsashvili, George Kamkamidze, David Metreveli, Lia Gvinjilia, Tatia Kuchuloria, Amiran Gamkrelidze, Mamuka Zakalashvili, Ekaterine Dolmazashvili, Vakhtang Kerashvili, Muazzam Nasrullah, Francisco Averhoff
Journal: Journal of Hepatology (2019)
FRI-140-Chemokine (C-X-C motif) ligand 13-mediated recruitment of intrahepatic chemokine (C-X-C motif) receptor 5+CD8+1 cells contribute to viral control in chronic hepatitis B patients and hepatitis B virus mouse model
Authors: Yongyin Li, Libo Tang, Chengcong Chen, Shuqin Gu, Yang Zhou, Ling Guo, Weibin Wang, Jian Sun, Jie Peng, Jinlin Hou
Journal: Journal of Hepatology (2019)
FRI-274-Exercise modulates gut microbiota and intestinal barrier functionality counteracting early obesity and NAFLD in an in vivo model
Authors: David Porras, Sara Carbajo-Pescador, María Juarez-Fernández, Susana Martínez-Flórez, María-Victoria García-Mediavilla, María José Cuevas, José Luís Mauriz, Francisco Jorquera, Javier González-Gállego, Esther Nistal, Sonia Sínchez-Campos
Journal: Journal of Hepatology (2019)
THU-175-Eligibility and feasibility of hepatitis C treatment in the era of direct-acting antiviral agents: Our experience in real-world practice
Authors: Monica Schiavini, Simona Landonio, Carlo Magni, Simone Passerini, Fosca Niero, Alessandro Luciano Croci, Matteo Passerini, Matteo Bolis, Guido Gubertini, Elena Angeli, Annalisa Mainini, Riccardo Giorgi, Stefania Vimercati, Giuliano Rizzardini
Journal: Journal of Hepatology (2019)
LBP-20-VK2809, a Novel Liver-Directed Thyroid Receptor Beta Agonist, Significantly Reduces Liver Fat with Both Low and High Doses in Patients with Non-Alcoholic Fatty Liver Disease: A Phase 2 Randomized, Placebo-Controlled Trial
Authors: Rohit Loomba, Joel Neutel, Rizwana Mohseni, David Bernard, Randall Severance, Michael Dao, Satinder Saini, Carmen Margaritescu, Ken Homer, Brian Tran, Marianne Mancini, Hiroko Masamune, Brian Lian
Journal: Journal of Hepatology (2019)
DUBbing Ferroptosis in Cancer Cells
Authors: Boyi Gan
Journal: Cancer Research (2019)

Abstract Ferroptosis, a form of iron-dependent, nonapoptotic cell death that is induced by excessive lipid peroxidation, has been recently identified as a new tumor suppression mechanism. In this issue of Cancer Research, Liu and colleagues demonstrate that the deubiquitinase (DUB) OTUB1 is frequently overexpressed in human cancers, and functions to “dub” (trim) the ferroptosis process in cancer cells and promotes tumor development by stabilizing the cystine transporter, SLC7A11. This study not only reveals a hitherto unappreciated regulatory mechanism of ferroptosis but also identifies potential therapeutic targets for cancer treatment. See related article by Liu et al., p. 1913
THU-143-High effectiveness of elbasvir/grazoprevir treatment in patients with HCV genotype 1a infection in German real-world: Results from the German hepatitis C registry (DHC-R)
Authors: Holger Hinrichsen, Albrecht Stoehr, Markus Cornberg, Hartwig Klinker, Renate Heyne, Christine John, Karl-Georg Simon, Manfred Bilzer, Veronika Guenther, Vanessa Witte, Stefan Zeuzem
Journal: Journal of Hepatology (2019)
SAT-151-What are the predictors of impairment of patient-reported outcome in non-alcoholic steatohepatitis?
Authors: Zobair Younossi, Maria Stepanova, Quentin Anstee, Vincent Wai-Sun Wong, Stephen Harrison, Takeshi Okanoue, Manuel Romero Gomez, Stephen Djedjos, Robert Myers, Issah Younossi, Andrei Racilla, Fatema Nader
Journal: Journal of Hepatology (2019)
Cardiomyocyte PKA Ablation Enhances Basal Contractility While Eliminates Cardiac β-Adrenergic Response Without Adverse Effects on the Heart
Authors: Ying Zhang, Wei Eric Wang, Xiaoying Zhang, Ying Li, Biyi Chen, Chong Liu, Xiaojie Ai, Xiaoxiao Zhang, Ying Tian, Chen Zhang, Mingxin Tang, Christopher Szeto, Xiang Hua, Mingxin Xie, Chunyu Zeng, Yingjie Wu, Lin Zhou, Weizhong Zhu, Daohai Yu, Steven R. Houser, Xiongwen Chen
Journal: Circulation Research (2019)

Rationale: PKA (Protein Kinase A) is a major mediator of β-AR (β-adrenergic) regulation of cardiac function, but other mediators have also been suggested. Reduced PKA basal activity and activation are linked to cardiac diseases. However, how complete loss of PKA activity impacts on cardiac physiology and if it causes cardiac dysfunction have never been determined. Objectives: We set to determine how the heart adapts to the loss of cardiomyocyte PKA activity and if it elicits cardiac abnormalities. Methods and Results: (1) Cardiac PKA activity was almost completely inhibited by expressing a PKA inhibitor peptide in cardiomyocytes (cPKAi) in mice; (2) cPKAi reduced basal phosphorylation of 2 myofilament proteins (TnI [troponin I] and cardiac myosin binding protein C), and one longitudinal SR (sarcoplasmic reticulum) protein (PLB [phospholamban]) but not of the sarcolemmal proteins (Cav1.2 α1c and PLM [phospholemman]), dyadic protein RyR2, and nuclear protein CREB (cAMP response element binding protein) at their PKA phosphorylation sites; (3) cPKAi increased the expression of CaMKII (Ca 2+ /calmodulin-dependent kinase II), the Cav1.2 β subunits and current, but decreased CaMKII phosphorylation and CaMKII-mediated phosphorylation of PLB and RyR2; (4) These changes resulted in significantly enhanced myofilament Ca 2+ sensitivity, prolonged contraction, slowed relaxation but increased myocyte Ca 2+ transient and contraction amplitudes; (5) Isoproterenol-induced PKA and CaMKII activation and their phosphorylation of proteins were prevented by cPKAi; (6) cPKAi abolished the increases of heart rate, and cardiac and myocyte contractility by a β-AR agonist (isoproterenol), showing an important role of PKA and a minimal role of PKA-independent β-AR signaling in acute cardiac regulation; (7) cPKAi mice have partial exercise capability probably by enhancing vascular constriction and ventricular filling during β-AR stimulation; and (8) cPKAi mice did not show any cardiac functional or structural abnormalities during the 1-year study period. Conclusions: PKA activity suppression induces a unique Ca 2+ handling phenotype, eliminates β-AR regulation of heart rates and cardiac contractility but does not cause cardiac abnormalities.
Role of radiotherapy in management of brain metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC): A single-center retrospective study
Authors: Y. Zhao, B. Zhang, Y. Zhang, S. Wang, J. Qian, B.-H. Han
Journal: Annals of Oncology (2019)

Background: Targeted therapies provide benefits in ALK-rearranged patients with brain metastases (BM). However, role of radiotherapy in these patients hasn't been established. This study sought to determine if upfront radiotherapy in combination with targeted therapies can impact patient outcomes. Methods: A total of 60 ALK-rearranged patients with BM were included for analysis. 34 patients developed BM prior to TKIs: 20 patients received radiotherapy followed by crizotinib and 14 received upfront crizotinib. 26 patients developed BM while receiving crizotinib: 13 patients were treated with crizotinib beyond progression after brain radiotherapy and 13 received next-generation TKIs with or without radiotherapy. Overall survival (OS) and intracranial time to progression (IC-TTP) were calculated from the date of BM. Results: Among patients with BM prior to TKIs, upfront radiotherapy cohort had longer IC-TTP (22.9 vs 8.9 months; p = 0.022) and longer OS (28.6 vs 23.3; p = 0.024) compared to upfront crizotinib cohort. Of patients who developed BM while receiving crizotinib, continuation of crizotinib plus radiotherapy for those without extracranial progression can give another intracranial progression-free time. However, next-generation TKIs cohort showed superior median IC-TTP compared to crizotinib beyond progression (11.4 vs 7.2 months; p = 0.006). Patients treated with radiotherapy followed by second TKIs even had much longer IC-TTP (21.8 vs 7.2 months; p = 0.009), though median IC-TTP of second TKIs without radiotherapy failed to reach statistical significance compared with crizotinib beyond progression (10.4 vs 7.2 months; p = 0.1). Conclusions: Upfront radiotherapy provided better outcomes for ALK-positive patients who developed BM before TKIs and during treatment of crizotinib, and should be considered. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Association of Adenoma and Proximal Sessile Serrated Polyp Detection Rates With Endoscopist Characteristics
Authors: Shashank Sarvepalli, Ari Garber, Michael B. Rothberg, Gautam Mankaney, John McMichael, Gareth Morris-Stiff, John J. Vargo, Maged K. Rizk, Carol A. Burke
Journal: JAMA Surgery (2019)

Research demonstrates adenoma detection rate (ADR) and proximal sessile serrated polyp detection rate (pSSPDR) are associated with endoscopist characteristics including sex, specialty, and years in practice. However, many studies have not adjusted for other risk factors associated with colonic neoplasia.To assess the association between endoscopist characteristics and polyp detection after adjusting the factors included in previous studies as well as other factors.This cohort study was conducted in the Cleveland Clinic health system with data from individuals undergoing screening colonoscopies between January 2015 and June 2017. The study analyzed data using methods from previous studies that have demonstrated significant associations between endoscopist characteristics and ADR or pSSPDR. Multilevel mixed-effects logistic regression was performed to examine 7 endoscopist characteristics associated with ADRs and pSSPDRs after controlling for patient demographic, clinical, and colonoscopy-associated factors.Seven characteristics of endoscopists performing colonoscopy.The ADR and pSSPDR, with a hypothesis created after data collection began.A total of 16 089 colonoscopies were performed in 16 089 patients by 56 clinicians. Of these, 8339 patients were male (51.8%), and the median (range) age of the cohort was 59 (52-66) years. Analyzing the data by the methods used in 4 previous studies yielded an association between endoscopist and polyp detection; surgeons (OR, 0.49 [95% CI, 0.28-0.83]) and nongastroenterologists (OR, 0.50 [95% CI 0.29-0.85]) had reduced odds of pSSPDR, which was similar to results in previous studies. In a multilevel mixed-effects logistic regression analysis, ADR was not significantly associated with any endoscopist characteristic, and pSSPDR was only associated with years in practice (odds ratio, 0.86 [95% CI, 0.83-0.89] per increment of 10 years; P < .001) and number of annual colonoscopies performed (odds ratio, 1.05 [95% CI, 1.01-1.09] per 50 colonoscopies/year; P = .02).The differences in ADRs that were associated with 7 of 7 endoscopist characteristics and differences in pSSPDRs that were associated with 5 of 7 endoscopist characteristics in previous studies may have been associated with residual confounding, because they were not replicated in this analysis. Therefore, these characteristics should not influence the choice of endoscopist for colorectal cancer screening. However, clinicians further from their training and those with lower colonoscopy volumes have lower adjusted pSSPDRs and may need additional training to help increase pSSPDRs.
FRI-217-Safety, antiviral activity, and pharmacokinetics of a novel hepatitis B virus capsid assembly modulator, JNJ-, in Asian and non-Asian patients with chronic hepatitis B
Authors: Jeysen Yogaratnam, Fabien Zoulim, Joris Vandenbossche, Oliver Lenz, Willem Talloen, lurie Moscalu, Rosmawati Mohamed, Adrian Streinu-Cercel, Wan-Long Chuang, Stefan Bourgeois, Sheng-Shun Yang, Maria Buti, Javier Crespo, Yi-Cheng Chen, Juan Manuel Pascasio, Christoph Sarrazin, Thomas Vanwolleghem, Umesh Shukla, John Fry
Journal: Journal of Hepatology (2019)
FRI-272-Identification of novel glycans that target gut microbiota-associated ammonia production
Authors: Kelsey Miller, Jonathan W. Leff, Nicholas Beauchemin, Christopher Liu, Mitchell Antalek, David Belanger, Ruth Thieroff-Ekerdt, Michael A. Mahowald, Margaret J. Koziel, Madeline Hartman, Maxwell Hecht, Anastasia Murphy, Brian Meehan
Journal: Journal of Hepatology (2019)
Oral Anticoagulation Therapy and Progression of Calcific Aortic Valve Stenosis
Authors: Lionel Tastet, Philippe Pibarot, Mylène Shen, Marine Clisson, Nancy Côté, Erwan Salaun, Marie Arsenault, Élisabeth Bédard, Romain Capoulade, Rishi Puri, Paul Poirier, Marie-Annick Clavel
Journal: Journal of the American College of Cardiology (2019)