tbuckley/cabot-search huggingface dataset:
P106/O25 DNA methylation in lymphocyte subsets as a mediator of genetic risk in early rheumatoid arthritis
Authors: AD Clark, N Nair, AJ Skelton, AE Anderson, N Thalayasingam, N Naamane, J Diboll, J Massey, S Eyre, A Barton, JD Isaacs, LN Reynard, AG Pratt
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Genome-wide association studies (GWAS) have identified over 100 RA-associated risk loci, whose enrichment for lymphocyte-specific enhancer elements is consistent with a regulatory function of many causal variants in these cells. Epigenetic modifications have also been strongly implicated in RA pathogenesis. <h3>Objectives</h3> To investigate the role of DNA methylation as a mediator of RA genetic risk. <h3>Methods</h3> CD4+ T lymphocyte-specific DNA and RNA were extracted from freshly isolated blood of 43 RA and 60 disease control patients, along with equivalent material from B-lymphocytes of 46 RA and 73 controls. Comparator groups were drug-naïve and matched for age, sex, and acute phase response. Genotyping, gene expression and methylation profiling was carried out using Illumina chip array technology. After mapping genome-wide methylation quantitative trait loci (mQTLs) in <i>cis</i> (&lt;1 Mb), we focused on known RA risk loci, integrating paired normalised gene expression measurements for transcripts within 500 kb of index CpGs. We also sought <i>trans</i> mQTLs, highlighting RA-specific effects. <h3>Results</h3> CD4+ T lymphocyte <i>cis</i>-mQTLs co-localised with 30 independent (r2&lt;0.8) RA-associated SNPs, whilst in B lymphocytes such mQTL effects were present at 31 RA SNPs. 80% of these variants functioned as <i>cis</i>-mQTLs in both cell types. CpG sites subject to <i>cis</i> effects at risk loci were depleted in regions associated with cell type-specific repressed chromatin marks, with enrichment at enhancer regions and those flanking transcription start sites, suggesting active roles in transcriptional regulation. Linear regression identified regulatory effects of these CpG sites on gene expression, and causal inference testing highlighted genes for which risk SNPs most likely modulate gene expression via CpG methylation. Such effects, robust to false discovery rate, were particularly prevalent in CD4+ T lymphocytes, for example implicating <i>ANKRD55</i>, <i>ORMDL3</i>, and <i>FCRL3</i> as causal genes in this cell type. Our analysis of mQTLs acting in <i>trans</i> identified inter-chromosomal SNP-CpG associations, also revealing instances of differential effect size in RA patients and controls. <h3>Conclusions</h3> Here we highlight an important mechanism by which genetic variants may contribute to altered lymphocyte phenotype, and demonstrate the utility of DNA methylation profiling as a tool for the prioritization of candidate genes following GWAS studies in RA. The functional roles of highlighted genes in CD4+ T cells during RA pathogenesis await clarification. <h3>Disclosure of Interest</h3> None declared.
HIS BUNDLE, BIVENTRICULAR, OR RIGHT VENTRICULAR PACING AS A PRIMARY STRATEGY FOR ADVANCED ATRIOVENTRICULAR CONDUCTION DISEASE IN PATIENTS WITH NORMAL OR MILDLY REDUCED EJECTION FRACTION: A NETWORK META-ANALYSIS
Authors: Gilson Fernandes, Leonardo Knijnik, Juan Lopez, Manuel Rivera, Amanda Fernandes, Litsa Lambrakos, Robert Myerburg, Raul Mitrani, Jeffrey Goldberger
Journal: Journal of the American College of Cardiology (2019)
A 22-Year-Old Man With Painful Vesicles on His Flank
Authors: Christopher T. Haley, Stephen K. Tyring
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CORE LABORATORY ASSESSMENT OF NON-FATAL Q-WAVE MYOCARDIAL INFARCTION IN THE GLOBAL LEADERS TRIAL: METHODS AND FINDINGS
Authors: Ernest Spitzer Cano, Ply Chichareon, Eugene McFadden, Rodrigo Modolo, Kuniaki Takahashi, Chun Chin Chang, Norihiro Kogame, Yuki Katagiri, Stephen Hoole, Tommaso Gori, Azfar Zaman, Bernhard Frey, Rui Cruz Ferreira, Olivier F. Bertrand, Sing-Chien Yap, Philippe Steg, Christian Hamm, Peter Jüni, Pascal Vranckx, Marco Valgimigli, Stephan Windecker, Patrick Serruys, Yoshinobu Onuma, Osama Soliman
Journal: Journal of the American College of Cardiology (2019)
The NCCN Older Adult Oncology Panel Remembers Arti Hurria
Authors: Efrat Dotan, Louise C. Walter
Journal: Journal of the National Comprehensive Cancer Network (2019)

2018, the NCCN Older Adult Oncology Panel and the geri- atric oncology community as a whole lost a tremendous leader, mentor, and scientist with the passing of Arti Hurria, MD, in a tragic accident.As the NCCN Older Adult Panel mourns the loss of Dr. Hurria, we felt compelled to write about her outstanding contributions to our field and to each of us personally.
ADVANCED GLYCATION END PRODUCTS IMPAIR KV-MEDIATED VASODILATION BY ACTIVATING NF-KB PATHWAY OF CORONARY ARTERIES IN ZUCKER DIABETIC FATTY RATS
Authors: Qingbo Liu, Bing Hua, Side Gao, Hehe Cui, Hui Chen, Weiping Li, Hongwei Li
Journal: Journal of the American College of Cardiology (2019)
Abstract 316: Salusin-α Improved Atherosclerosis in High Cholesterol Diet Fed Rabbits by Inhibiting Smooth Muscle Cells Proliferation and Migration
Authors: Gao Shoucui, Wang Xiaojing, Zhao Sihai, Fan Jianglin, Liu Enqi
Journal: Circulation Research (2018)

Aims: To investigate the role of salusin-α in vascular smooth muscle cells (VSMCs) migration and proliferation during atherosclerosis development and its potential molecular mechanism. Methods and results: Salusin-α or saline (vehicle) was continuously infused through osmotic mini-pumps into high cholesterol diet fed male rabbits for 16 weeks. Salusin-α infusion significantly resulted in the reduction of aortic atherosclerosis by 59% (17% and 42%), including 39% (45% and 75%) in the aortic arch ,70% (13% and 44%) in the thoracic aorta, and 72%(7% and 25%) in the abdominal aorta without affecting plasma lipids level. Immunohistochemical staining showed that salusin-α decreased both the VSMCs and macrophage positive area in the atherosclerotic lesions by 69% (0.11 and 0.35) and 54% (0.31 and 0.68 ). In vitro, platelet-derived growth factor-BB induced proliferation and migration of VSMCs were also reduced by salusin-α. In these VSMCs, the phosphorylation of Akt and mTOR were also down-regulated, but not in ERK1/2 and p38MAPK. Conclusions: Our data indicated that Salusin-α might improve atherosclerosis by inhibiting smooth muscle cells proliferation and migration through the Akt/ mTOR pathway.
MYOCARDIAL INJURY ASSESSED BY T1 MAPPING AFTER ON-PUMP AND OFF-PUMP CORONARY ARTERY BYPASS GRAFTING: A PRE-SPECIFIED ANALYSIS OF MASS V TRIAL
Authors: Anderson Roberto Dallazen, Gustavo André Boeing Boros, Fernado Faglioni Ribas, Cesar Nomura, Carlos Rochitte, Thamara Morais, Eduardo Lima, Eduardo Martins, Paulo Rezende, Whady Hueb, Jose Ramires, Roberto Kalil Filho
Journal: Journal of the American College of Cardiology (2019)
INCREASED RISK OF PERIOPERATIVE ISCHEMIC STROKE IN PATIENTS WHO UNDERGO NON-CARDIAC SURGERY WITH PREEXISTING PATENT FORAMEN OVALE
Authors: Pedro Arturo Villablanca, Alejandro Lemor, Tanush Gupta, Divyanshu Mohananey, Pablo Michel, Tiberio Frisoli, Dee Dee Wang, Marvin Eng, Harish Ramakrishna, William O'Neill
Journal: Journal of the American College of Cardiology (2019)
Proteomic analysis of neutrophils in ANCA-associated vasculitis reveals a dysregulation in proteinase 3-associated proteins such as annexin-A1 involved in apoptotic cell clearance
Authors: Judith Everts-Graber, Katherine R. Martin, Nathalie Thieblemont, Julie Mocek, Arnaud Roccabianca, Philippe Chafey, Morgane Le Gall, Pascale Tacnet-Delorme, Chris P. Reutelingsperger, Jean-Marc Naccache, Bernard Bonnotte, Alexandre Karras, Xavier Puéchal, Loïc Guillevin, Benjamin Terrier, Philippe Frachet, Mauro Perretti, Luc Mouthon, Véronique Witko-Sarsat
Journal: Kidney International (2019)

Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis associated with anti-neutrophil-cytoplasmic antibodies (ANCA) against proteinase 3 leading to kidney damage. Neutrophils from those patients have increased expression of membrane proteinase 3 during apoptosis. Here we examined whether neutrophils from patients with GPA have dysregulated protein expressions associated with apoptosis. A global proteomic analysis was performed comparing neutrophils from patients with GPA, with healthy individuals under basal conditions and during apoptosis. At disease onset, the cytosolic proteome of neutrophils of patients with GPA before treatment was significantly different from healthy controls, and this dysregulation was more pronounced following ex vivo apoptosis. Proteins involved in cell death/survival were altered in neutrophils of patients with GPA. Several proteins identified were PR3-binding partners involved in the clearance of apoptotic cells, namely calreticulin, annexin-A1 and phospholipid scramblase 1. These proteins form a platform at the membrane of apoptotic neutrophils in patients with GPA but not healthy individuals and this was associated with the clinical presentation of GPA. Thus, our study shows that neutrophils from patients with GPA have an intrinsic dysregulation in proteins involved in apoptotic cell clearance, which could contribute to the unabated inflammation and autoimmunity in GPA. Hence, harnessing these dysregulated pathways could lead to novel biomarkers and targeted therapeutic opportunities to treat kidney disease.Graphical abstract
Abstract 232: NFkB1 Pathway is a Major Dysregulated Biological Pathway in Cardiac Myocytes in Myocyte-Specific Lamin A/C Deficient Mice
Authors: Gaelle Auguste, Priyatansh Gurha, Raffaella Lombardi, Ali J Marian
Journal: Circulation Research (2018)

Lamin A/C (LMNA) is a major component of the nuclear membrane, involved in regulation of gene expression. Mutations in the LMNA gene cause a heterogeneous group of diseases, collectively referred to as laminopathies. Cardiac involvement is one of the most prominent feature of the laminopathies, presenting with dilated cardiomyopathy (DCM), conduction defects, and sudden death. Molecular mechanisms involved in the pathogenesis of cardiac phenotypes in laminopathies are not well known. To gain insights into molecular pathogenesis of DCM caused by LMNA deficiency, Lmna gene was deleted in cardiac myocytes ( Myh6-Cre:Lmna Flox ). Homozygous ( Myh6-Cre:Lmna F/F ) had a normal cardiac function and histology at 2 weeks of age. However, the mice showed progressive cardiac dilatation and dysfunction, interstitial fibrosis, increased apoptosis, and died by 4 weeks of age. To identify transcriptomic changes that precede cardiac dysfunction, cardiomyocytes were isolated from 2-week old wild type (WT) and Myh6-Cre:Lmna F/F mice and analyzed by RNA-Seq. A total of 1,420 genes were differentially expressed between WT and Myh6-Cre:Lmna F/F . Pathways analysis of differentially expressed genes (DEGs) showed enrichment of inflammatory, epithelial to mesenchymal transition, and cell death pathways, whereas mitochondrial oxidative function, adipogenesis, and fatty acid metabolism pathways were depressed in Myh6-Cre:Lmna F/F . Consistently, DEGs were enriched for the binding motif of RELA, the main transcription factor of the NFκB1 pathway. Activation of the NFκB1 pathway was validated by western blot showing increased nuclear localization of RELA. To determine therapeutic benefits of targeting the NFκB1 pathway, mice are being treated a specific inhibitor of NFκB (IKK-16). Effects on survival, cardiac function, apoptosis, and fibrosis are being analyzed. In conclusion, LMNA deficiency results in dysregulation of a large number genes, including NFκB1 pathway target genes that precede the onset of cardiac dysfunction and fibrosis. The findings point to the prominent role of inflammation in the development of cardiac dysfunction in myocyte-specific LMNA deficiency and identify the NFκB1 pathway as a therapeutic target in DCM caused by LMNA deficiency.
ASSOCIATION BETWEEN ASSIGNMENT TO AN ACCOUNTABLE CARE ORGANIZATION AND QUALITY OF CARE AND OUTCOMES AMONG MEDICARE BENEFICIARIES HOSPITALIZED FOR HEART FAILURE
Authors: Nancy Luo, Bradley Hammill, Adam DeVore, Haolin Xu, Gregg Fonarow, Adrian Hernandez, Roland Matsouaka, Nancy Albert, Clyde Yancy, Robert Mentz
Journal: Journal of the American College of Cardiology (2019)
Abstract 448: P27 <sup>Kip1</sup> Contributes to Eya4-mediated Development of Acquired Cardiac Hypertrophy
Authors: Tatjana D Williams, Paula-Anahi Arias-Loza, Peter Nordbeck, Oliver Ritter
Journal: Circulation Research (2018)

Introduction: We previously reported that E193, a heterozygous truncating mutation in the transcription cofactor “Eyes absent” (Eya4) leads to late-onset familial DCM and heart failure. Yet a precise role for Eya4 in the myocardium has not been identified. It appears to regulate normal cardiac function via p27 kip1 , a protein shown to be involved in regulating hypertrophic responses in the adult cardiomyocyte. This study was aimed to explore the role of Eya4 in angiotensin II (ATII)-induced cardiac hypertrophy. Methods and results: We used our transgenic mouse model with a constitutive myocardial overexpression of HA-tagged Eya4. Wildtype and Eya4 overexpressing mice were challenged with ATII via osmotic minipumps for four weeks to induce cardiac hypertrophy. Analysis of these animals using magnetic resonance imaging to visualize cardiac structures in detail showed that in response to the sustained ATII stimulation, the Eya4 overexpressing mice exhibited a phenotype with significantly increased parameters of hypertrophy. LV free wall diameter as measured in 7T MRI was 1,7±0,2 in Eya4 mice with ATII compared to 1,3±0,2 mm in WT mice with ATII. This was also confirmed by HW/BW ratio, hemodynamic measurements and cell size measurements. Histology also affirmed the results of the MR imaging. Moreover, Eya4 overexpression induced a significant suppression of p27 protein expression which is in agreement with our in vitro data. This confirmed our hypothesis that Eya4 negatively acts upon p27 expression which facilitates development of myocardial hypertrophy. Conclusion: In summary, we previously described a mutation in Eya4 to disturb cardiac physiology. We now provide evidence that Eya4 is also involved in forms of acquired heart disease. It seems to suppress p27 kip1 , thereby augmenting ATII induced cardiac hypertrophy.
AN UNCANNY CASE OF RIGHT TO LEFT SHUNT
Authors: Mohammad Sadegh Asadi, Olabisi Akanbi, Sandhya Dandluri, Hilda Mariana Gonzalez Bonilla, Urooj Fatima, Nitheesha Ganta, Prafulla Mehrotra, Andre Duerinckx
Journal: Journal of the American College of Cardiology (2019)
Sensing of physiological regulators by innate lymphoid cells
Authors: Cyril Seillet, Nicolas Jacquelot
Journal: Cellular and Molecular Immunology (2019)

Maintenance of homeostasis and immune protection rely on the coordinated action of different physiological systems. Bidirectional communication between the immune system and physiological systems is required to sense and restore any disruption of equilibrium. Recent transcriptomic analyses of innate lymphoid cells (ILCs) from different tissues have revealed that ILCs express a large array of receptors involved in the recognition of neuropeptides, hormones and metabolic signals. ILCs rapidly secrete effector cytokines that are central in the development and activation of early immune responses, but they also constitutively secrete mediators that are important for tissue homeostasis. To achieve these functions effectively, ILCs integrate intrinsic and extrinsic signals that modulate their constitutive and induced activity. Disruption of the regulation of ILCs by physiological regulators leads to altered immune responses with harmful consequences for the organism. An understanding of these complex interactions between the immune system and physiological mediators is crucial to decipher the events leading to the protective versus pathological effects of these cells.
Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation after Double Cord Blood Transplantation
Authors: May Daher, Kai Cao, Rafet Basar, David Marin, Takuye Sekine, Gabriela Rondon, Weicheng Zhao, Nathaniel T Smith, Qing Wang, Li Li, Rima M. Saliba, Sai Ravi Kiran Pingali, Uday Popat, Chitra Hosing, Amanda L. Olson, Betul Oran, Rohtesh S. Mehta, Richard E Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Blood (2018)
FUNCTIONAL CLASSIFICATION DISCORDANCE IN INTERMEDIATE CORONARY STENOSES BETWEEN FRACTIONAL FLOW RESERVE AND ANGIOGRAPHY-BASED QUANTITATIVE FLOW RATIO
Authors: Yoshinori Kanno, Masahiro Hoshino, Akinori Sugano, Yoshihisa Kanaji, Masao Yamaguchi, Yohei Sumino, Hiroaki Ohya, Masahiro Hada, Hidenori Hirano, Haruhito Yuki, Tomoki Horie, Taishi Yonetsu, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2019)
SYNERGISTIC IMPACT OF CORONARY CALCIFICATION AND BIFURCATION TARGET LESIONS ON ADVERSE CARDIOVASCULAR EVENTS FOLLOWING PCI: INSIGHTS FROM A LARGE SINGLE-CENTER PCI REGISTRY
Authors: Jonathan Murphy, Usman Baber, Melissa Aquino, Nitin Barman, Joseph Sweeny, Roxana Mehran, Asaad Khan, Choudhury Hasan, Vishal Kapur, George Dangas, Nileshkumar Patel, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2019)
Abstract 14339: Nonalcoholic Fatty Liver Disease and the Risk of Clinical Cardiovascular Events: A Meta-Analysis
Authors: Toufik Mahfood Haddad, Shadi Hamdeh, Mahesh Anantha Narayanan, Arun Kanmanthareddy, Venkata M Alla
Journal: Circulation (2015)

Background: Numerous studies have assessed the association of Nonalcoholic fatty liver disease (NAFLD) withcardiovascular disease (CVD). However, results have been conflicting due to variability in definitionsof NAFLD and ascertainment of CVD, often combining clinical and surrogate endpoints. We therefore systematically reviewed published literature to assess the association between NAFLD and clinical cardiovascular events. Methods: We searched Medline, Cochrane, google scholar, CINAHL, and Web of Sciencedatabasesusing terms “nonalcoholic fatty liver disease”, “cardiovascular disease”, and their combinations to identify studies published through March 2015. Data from selected studies was extracted and meta-analysis was then performed using Random effects model following the PRISMA guidelines. Publication bias and heterogeneity wereassessed. The main outcome measure was Odds ratio (OR) with 95% CI. Clinical CVD was defined as symptomatic coronary artery disease, myocardial infarction, coronary or peripheral intervention, ischemic stroke, and symptomatic peripheral vascular disease. Results: A total of 7 studies with 14634 patients (NAFLD: 4204; controls: 10430) were included in the final analysis. 3 studies were cross- sectional reporting prevalence, while 4 studies were prospective cohort studies reporting incidence. Patients with NAFLD had a significantly higher risk of clinical CVD compared to controls [OR: 3.17; 95% CI: 1.89-5.30, P&lt;0.01) (figure 1A). There was significant heterogeneity (I2=93%). Funnel plot and Begg’s test did not reveal significant publication bias. Separate analyses of the cohort and cross sectional studies and exclusion sensitivity analysis did not alter the findings (figure 1B). Conclusion: NAFLD is associated with a three fold increase in the risk of clinical CVD compared to controls without NAFLD. These results need to be conformed in large prospective studies.
Do We Really Need Scholarly Quality Improvement?
Authors: Shawn L. Ralston, Patrick W. Brady, Alex R. Kemper
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal