tbuckley/cabot-search huggingface dataset:
TREATMENT OPTIMIZATION WITH SODIUM/GLUCOSE COTRANSPORTER-2 INHIBITORS, DIPEPTIDYL PEPTIDASE-4 INHIBITORS OR GLYCAGONE LIKE PEPTIDE-1 IMPROVES VASCULAR DYSFUNCTION AND ACHIEVES BETTER GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Gerasimos Siasos, Evanthia Bletsa, Panagiota Stampouloglou, Konstantinos Mourouzis, Vasiliki Tsigkou, Nikolaos Gouliopoulos, Alexis Antonopoulos, Evangelos Oikonomou, Anastasia Thanopoulou, Andromahi Vryonidou, Stavroula A. Paschou, Marianna Politou, Nikolaos Tentolouris, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2019)
THE ABSORB BIORESORBABLE VASCULAR SCAFFOLDS ARE ASSOCIATED WITH LOW WALL SHEAR STRESS COMPARED TO XIENCE V: A BIOMECHANICAL ANALYSIS OF THE ABSORB III IMAGING STUDY
Authors: Arnav Kumar, Bill Gogas, Elizabeth W. Thompson, Hossein Hosseini, David Molony, Adrien Lefieux, Karthic Chandran, Mohamad Raad, David Sternheim, Sonu Gupta, Mostafa Vasigh, Don P. Giddens, Alessandro Veneziani, Patrick W. Serruys, Spencer King, Gregg Stone, Habib Samady
Journal: Journal of the American College of Cardiology (2019)
ASSOCIATION ANALYSIS BETWEEN LEFT ATRIAL FUNCTION AND LEFT ATRIAL APPENDAGE FUNCTION IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION
Authors: Go Hashimoto, Makoto Suzuki, Shiho Ide, Hiromasa Hayama, Kenji Makino, Takenori Otsuka, Raisuke Iijima, Hidehiko Hara, Masao Moroi, Masato Nakamura
Journal: Journal of the American College of Cardiology (2019)
SUBENDOCARDIAL VIABILITY RATIO ASSOCIATES WITH ECHOCARDIOGRAPHIC PARAMETERS OF DIASTOLIC FUNCTION: INSIGHTS FROM THE BOGALUSA HEART STUDY
Authors: Camilo Fernandez-Alonso, Alexander C. Razavi, Alexander Romero, Jose Nativi-Nicolau, Rupert P. Barshop, Lydia Bazzano
Journal: Journal of the American College of Cardiology (2019)
Abstract 499: Identification and Characterization of Lamin-Associated Domains in Cardiac Myocytes Isolated From Human Patients With Dilated Cardiomyopathy Caused by LMNA Pathogenic Variant and Their Effects on Gene Expression and DNA Methylation
Authors: Sirisha C Marreddy, Priyatansh Gurha, Hin Hu, Mary Sweet, Matthew Taylor, Luisa Mestroni, Cristian Coarfa, Ali J Marian
Journal: Circulation Research (2018)

Rationale: Lamin A/C (LMNA) is a nuclear inner membrane protein that interacts with genome through Lamin-Associated Domains (LADs) and regulates gene expression. Mutations in the LMNA gene causes a diverse array of diseases that are collectively referred to as laminopathies. Dilated cardiomyopathy (DCM) is a major component of laminopathies and the leading cause of premature death. Objective: To identify and characterize LADs in cardiac myocytes, cardiac DNA methylation status, and transcriptomes and integrate the findings to find the pathogenic pathways in DCM Methods: We performed ChIP-Seq, reduced representative bisulfite sequencing (RRBS), and RNA-Seq in 5 control and 5 DCM hearts, the later with defined pathogenic variants. ChIP-Seq was performed using an anti-LMNA antibody on protein extracts from FACS-isolated myocyte nuclei, identified by expression of PCM1. RRBS was performed on whole heart DNA extracts to identify methylation state of ~ 500,000 CpG sites. RNA-Seq was performed on whole heart ribosome-depleted RNA extracts. LADs were identified using Enriched Domain Detector (EDD). Results: We identified 370±50 LADs with an average size of ~ 1Mbp (range: 0.5 to 10 Mb), collectively covering about 12,000 genes and 12% of the genomic regions in the control myocytes. The number and size of the LADs were unchanged in DCM. However, genomic locations of LADs had shifted, leading to loss of 3,302 genes from the LADs. Integration of LADs, CpG methylation, and transcript levels showed CpG hypermethylation and suppressed transcript levels in the LADs both in control and in DCM hearts. However, the effects were differential and LADs were associated with increased hypermethylation and further suppression of gene expression in DCM hearts. Pathway analysis of integrated omic datasets identified TGFβ1 and cell cycle pathways as the most activated and MPAK and glycolytic pathways as the most repressed pathways in DCM hearts. Conclusions: LADs, CpG methylation and transcriptomes are dysregulated in cardiac myocytes in patients with DCM caused by LMNA pathogenic variants. The dysregulated biological pathways provide potential targets for interventions in DCM caused by LMNA mutations.
IMPACT OF HEMODIALYSIS ON EARLY DEGENERATION OF BIOPROSTHESIS AND CLINICAL OUTCOME AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Norihiko Kamioka, Hope Caughron, John Lisko, Jose Binongo, Zakaria Almuwaqqat, Patricia Keegan, Patrick Gleason, Isida Byku, Lucia Alvarez, Shawn Reginauld, Aneesha Maini, Kendra Grubb, Chandan Devireddy, Kreton Mavromatis, Bradley Leshnower, James Stewart, Robert Guyton, Peter Block, Adam B. Greenbaum, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2019)
PROGNOSTIC VALUE OF CONTRAST-FLOW QUANTITATIVE FLOW RATIO IN PATIENTS WITH REVASCULARIZATION DEFERRAL BASED ON PRESERVED FRACTIONAL FLOW RESERVE
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)
Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas
Authors: Scott Newman, Liying Fan, Allison Pribnow, Antonina Silkov, Stephen V. Rice, Seungjae Lee, Ying Shao, Bridget Shaner, Heather Mulder, Joy Nakitandwe, Sheila Shurtleff, Elizabeth M. Azzato, Gang Wu, Xin Zhou, Raymond Barnhill, John Easton, Kim E. Nichols, David W. Ellison, James R. Downing, Alberto Pappo, Philip M. Potter, Jinghui Zhang, Armita Bahrami
Journal: Nature Medicine (2019)
A CASE REPORT: NEAR-INFRARED SPECTROSCOPY ULTRASONOGRAPHY CAN DETECT THE PLAQUE STABILIZATION OF NON-CULPRIT LESION IN ACS PATIENTS BY THE COMBINATION THERAPY OF PCSK9 INHIBITOR AND STATIN
Authors: Noriyuki Wakana, Hideo Tsubata, Kan Zen
Journal: Journal of the American College of Cardiology (2019)
Abstract 238: Ube2v1 Promotes Mutant αB-crystallin-induced Protein Aggregation
Authors: Na Xu, Patrick McLendon, James Gulick, Hanna Osinska, Jeffrey Robbins
Journal: Circulation Research (2018)

Background: Compromised protein quality control causes the accumulation of misfolded proteins and intracellular aggregates, contributing to cardiac disease and heart failure. An unbiased genome-wide short hairpin RNA screen was performed to seek novel genes that could prevent or clear proteotoxic aggregates in a model of desmin-related cardiomyopathy, caused by the R120G mutation of αB-crystallin (CryAB R120G ). Among a total of 236 hits, we validated a candidate gene named ubiquitin-conjugating E2 enzyme variant 1 (ube2v1). Ube2v1 expression is detectable in the heart and the literature states that it must bind to ube2n to form a heterodimer. The heterodimer then catalyzes the synthesis of Lys63-linked poly-ubiquitin chains, participating in DNA repair and the damage response. Ube2v1 protein levels were increased in CryAB R120G transgenic hearts. However, the function of ube2v1 in cardiac proteotoxicity is completely unknown. To assess whether and how ube2v1 impacts cardiac protein aggregation catalyzed by cardiomyocyte-specific expression of mutated CryAB. Methods and Results: Neonatal rat ventricular cardiomyocytes (NRVMs) were infected with adenoviruses expressing either wild-type CryAB or CryAB R120G . Subsequently, loss- and gain-of-function experiments were performed using ube2v1 siRNA or recombinant adenovirus mediated ube2v1 overexpression. Knockdown of ube2v1 decreased aggregate accumulation and attenuated cytotoxicity caused by CryAB R120G expression, while overexpressing ube2v1 enhanced aggregate formation. Ubiquitin proteasome system (UPS) function was analyzed using a UPS reporter protein consisting of a short degron, CL1, fused to the COOH-terminus of green fluorescent protein (GFPu). Knockdown of ube2v1 improved proteasomal function and promoted the degradation of insoluble ubiquitinated proteins in CryAB R120G cardiomyocytes, but did not alter autophagic flux. Conclusions: Inhibition of ube2v1 improves CryAB R120G -induced aggregate formation through enhancing proteasome activity. It provides a novel therapeutic target to treat cardiac proteinopathies.
Co-circulation of influenza A(H1N1)pdm09 and influenza A(H3N2) viruses, World Health Organization (WHO) European Region, October 2018 to February 2019
Authors: Hannah Segaloff, Angeliki Melidou, Cornelia Adlhoch, Dmitriy Pereyaslov, Emmanuel Robesyn, Pasi Penttinen, Sonja J Olsen, WHO European Region
Journal: Eurosurveillance (2019)

In the World Health Organization European Region, the 2018/19 influenza season started in week 49 2018, crossing 10% virus-positivity in sentinel surveillance specimens. At week 5 2019, activity remained elevated with positivity rates at 55%. Both A(H1N1)pdm09 and A(H3N2) viruses circulated widely and detection levels in primary care and hospital settings were similar to past seasons. Hospitalisation data may suggest an increased susceptibility to A(H1N1)pdm09 virus in older age groups.
Ambox: A Randomised Controlled, Crossover Trial Evaluating The Effects Of Ambulatory Oxygen On Health Status In Patients With Fibrotic Interstitial Lung Disease
Authors: D. Visca, L. Mori, V. Tsipouri, S. Canu, M. Bonini, M. Pavitt, S. Fleming, A. Firouzi, M. Farquhar, E. Leung, C. Hogben, A. De Lauretis, M. Kokosi, J. Lee, R. Lyne, N. Rippon, A. Chetta, A. M. Russell, P. Saunders, V. Kouranos, G. Margaritopoulos, T. M. Maher, A. Stockford, P. Cullinan, N. Hopkins, S. Birring, A. U. Wells, J. Whitty, W. Banya, H. Adamali, L. Spencer, P. Sestini, E. A. Renzoni
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
先天性鱼鳞病 : 欧洲护理指南, 第二部分
Authors: J. Mazereeuw‐Hautier, A. Hernandez‐Martin, E.A. O'Toole, A. Bygum, C. Amaro, M. Aldwin, A. Audouze, C. Bodemer, E. Bourrat, A. Diociaiuti, M. Dolenc‐Voljc, I. Dreyfus, M. El Hachem, J. Fischer, A. Ganemo, C. Gouveia, R. Gruber, S. Hadj‐Rabia, D. Hohl, N. Jonca, K. Ezzedine, D. Maier, R. Malhotra, M. Rodriguez, H. Ott, D.G. Paige, A. Pietrzak, F. Poot, M. Schmuth, J.C. Sitek, P. Steijlen, G. Wehr, M. Moreen, A. Vahlquist, H. Traupe, V. Oji
Journal: British Journal of Dermatology (2019)

鱼鳞病是一个用于描述皮肤不停广泛脱屑的术语。有若干种从出生一直持续终生的遗传类型 ‐ “先天性鱼鳞病”。治疗尚未达成一致‐不同的医生使用不同的方法,因此来自欧洲的这组专家合作制定了指南。他们回顾了医学文献,通过会议讨论了证据并给出了建议。一篇单独的论文(第 1 部分)涵盖此皮肤病本身的治疗。这篇论文,即第 2 部分,为先天性鱼鳞病的并发症管理提供了指南。瘙痒、疼痛和感染常见,尤其是真菌感染,有时会发生癌症。紧张的皮肤常妨碍眼睑正常闭合,因此必须使用润肤剂保护他们的眼睛表面;眼睑按摩可能有帮助,维 A 酸类药物可能软化紧张的皮肤,但可能使眼睛干燥加重。手术选择包括注射填塞物或向眼睑移植额外的皮肤:如果使用患者本身的鱼鳞病皮肤,此问题最终还是会再发,来自口腔内的粘膜是一个有希望的选择。听力也常被影响:定期使用油性滴耳液可能防止皮肤积聚导致耳道阻塞,但可能需要冲洗或抽吸。在儿童中,生长可能受到影响,通常推荐补充维生素 D。对于新生儿和复杂性鱼鳞病(如 Netherton 综合征、表皮松解性鱼鳞病和鱼鳞病‐性早熟综合征)的患者,有特殊的考虑。这些治疗指南应有助于改善先天性鱼鳞病患者的结局和生活质量。
CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016
Authors: Deborah Dowell, Tamara M. Haegerich, Roger Chou
Journal: MMWR Recommendations and Reports (2016)

cognitive impairment, and those with cancer and at the end of life, can be at risk for inadequate pain treatment (4).Patients can experience persistent pain that is not well controlled.There are clinical, psychological, and social consequences associated with chronic pain including limitations in complex activities, lost work productivity, reduced quality of life, and stigma, emphasizing the importance of appropriate and compassionate patient care (4).Patients should receive appropriate pain treatment based on a careful consideration of the benefits and risks of treatment options.Chronic pain has been variably defined but is defined within this guideline as pain that typically lasts >3 months or past the time of normal tissue healing (5).Chronic pain can be the result of an underlying medical disease or condition, injury, medical treatment, inflammation, or an unknown cause (4).Estimates of the prevalence of chronic pain vary, but it is clear that the number of persons experiencing chronic pain in the United States is substantial.The 1999-2002 National Health and Nutrition Examination Survey estimated that 14.6% of adults have current widespread or localized pain lasting at least 3 months (6).Based on a survey conducted during 2001-2003 (7), the overall prevalence of common, predominantly musculoskeletal pain conditions (e.g., arthritis, rheumatism, chronic back or neck problems, and frequent severe headaches) was estimated at 43% among adults in the
RELATIONSHIP BETWEEN 3D MITRAL LEAFLET TENTING AND LEFT VENTRICULAR REMODELING IN PATIENTS WITH PRIMARY MITRAL REGURGITATION UNDERGOING TRANSCATHETER EDGE-TO-EDGE MITRAL VALVE REPAIR
Authors: Didem Oguz, Mackram Eleid, Vuyisile Nkomo, Sorin Pislaru, Youssef Maalouf, Jae Oh, Guy Reeder, Charanjit Rihal, Jeremy Thaden
Journal: Journal of the American College of Cardiology (2019)
CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY FOLLOWING HEART SCORE IN PATIENTS SUSPECTED OF ACUTE CORONARY SYNDROME IN THE EMERGENCY DEPARTMENT
Authors: Murat Arslan, Pleunie P.M. Rood, Jeroen Schaap, Eric Boersma, Koen Nieman, Ricardo P.J. Budde, Eric A. Dubois, Admir Dedic
Journal: Journal of the American College of Cardiology (2019)
Downregulation of Morrbid in Tet2-Deficient Preleukemic Cells Overcomes Resistance to Inflammatory Stress and Mitigates Clonal Hematopoiesis
Authors: Zhigang Cai, Jonathan Kotzin, Baskar Ramdas, Sisi Chen, Sai Nelanuthala, Lakshmi Reddy Palam, Ruchi Pandey, Raghuveer Mali, Yan Liu, Mark R. Kelley, George Sandusky, Morvarid Mohseni, Adam Williams, Jorge Henao-Mejia, Reuben Kapur
Journal: Blood (2018)
AN EXPLAINABLE MACHINE LEARNING-BASED RISK PREDICTION MODEL FOR IN-HOSPITAL MORTALITY FOR CHINESE STEMI PATIENTS: FINDINGS FROM CHINA MYOCARDIAL INFARCTION REGISTRY
Authors: Jingang Yang, Yingxue Li, Xiang Li, Tiange Chen, Guotong Xie, Yuejin Yang
Journal: Journal of the American College of Cardiology (2019)
Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets
Authors: Eloi R Verrier, Amélie Weiss, Charlotte Bach, Laura Heydmann, Vincent Turon-Lagot, Arnaud Kopp, Houssein El Saghire, Emilie Crouchet, Patrick Pessaux, Thomas Garcia, Patrick Pale, Mirjam B Zeisel, Camille Sureau, Catherine Schuster, Laurent Brino, Thomas F Baumert
Journal: Gut (2019)

Objective Hepatitis D virus (HDV) is a circular RNA virus coinfecting hepatocytes with hepatitis B virus. Chronic hepatitis D results in severe liver disease and an increased risk of liver cancer. Efficient therapeutic approaches against HDV are absent. Design Here, we combined an RNAi loss-of-function and small molecule screen to uncover host-dependency factors for HDV infection. Results Functional screening unravelled the hypoxia-inducible factor (HIF)-signalling and insulin-resistance pathways, RNA polymerase II, glycosaminoglycan biosynthesis and the pyrimidine metabolism as virus-hepatocyte dependency networks. Validation studies in primary human hepatocytes identified the carbamoyl-phosphatesynthetase 2, aspartate transcarbamylase and dihydroorotase (CAD) enzyme and estrogen receptor alpha (encoded by ESR1 ) as key host factors for HDV life cycle. Mechanistic studies revealed that the two host factors are required for viral replication. Inhibition studies using N-(phosphonoacetyl)-L-aspartic acid and fulvestrant, specific CAD and ESR1 inhibitors, respectively, uncovered their impact as antiviral targets. Conclusion The discovery of HDV host-dependency factors elucidates the pathogenesis of viral disease biology and opens therapeutic strategies for HDV cure.
ASSOCIATION OF RIGHT ATRIAL VOLUME AND FUNCTION WITH INCIDENT ATRIAL FIBRILLATION: RESULTS FROM THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Eric Xie, Ricky Yu, Bharath Ambale Venkatesh, Susan Heckbert, Hooman Bakhshi, Elsayed Soliman, David Bluemke, Steven Kawut, Colin Wu, Saman Nazarian, Joao Lima
Journal: Journal of the American College of Cardiology (2019)
ULTRASOUND TARGETED DELIVERY OF EXOSOMES SECRETED FROM CXCR4 OVEREXPRESSING ADIPOSE MESENCHYMAL STEM CELL PROMOTE ENDOGENOUS REPAIR AFTER MYOCARDIAL INFARCTION
Authors: Qing Deng, Yi-Jia Wang, Dan Jia, Sikai Chen, Yuan-Ting Yang, Qing Zhou
Journal: Journal of the American College of Cardiology (2019)
A-Fib: An Irregular Sonnet
Authors: Daryl Jones
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
PREDICTORS OF ALL-CAUSE MORTALITY IN THE AIM-HIGH TRIAL IDENTIFIED BY MACHINE LEARNING
Authors: Laboni H. Hoque, Amit Dey, Yuan Gu, Victoria Xin, Ruba Shalhoub, Runqiu Wang, Colin Wu, Tian Xin, Eileen Navarro Almario, Tejas Patel, Jerome Fleg, Anna Kettermann, Gyorgy Csako, George Sopko, Helena Sviglin, Gauri Dandi, Nuha Gani, Iffat Chowdhury, Keith Burkhart, Ana Szarfman, Sean Coady, Nehal Mehta, Frank Pucino, Yves Rosenberg, Ahmed Hasan
Journal: Journal of the American College of Cardiology (2019)
Annals Graphic Medicine - Dr. Mom: Aging
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 March 2019Annals Graphic Medicine - Dr. Mom: AgingFREEGrace E. Farris, MDGrace E. Farris, MDMount Sinai School of Medicine, New York, New York (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0043 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0043.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York. You can view her work at her Web site: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 March 2019Volume 170, Issue 5Page: W80-W81KeywordsAgingConflicts of interestDisclosureHospital medicineHospitalists ePublished: 5 March 2019 Issue Published: 5 March 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
MicroRNA-214 promotes chronic kidney disease by disrupting mitochondrial oxidative phosphorylation
Authors: Mi Bai, Huimei Chen, Dan Ding, Ruihua Song, Jiajuan Lin, Yuanyuan Zhang, Yan Guo, Shuang Chen, Guixia Ding, Yue Zhang, Zhanjun Jia, Songming Huang, John Cijiang He, Li Yang, Aihua Zhang
Journal: Kidney International (2019)
Abstract MP35: Association of Genetic Variants with Incident Coronary Heart Disease in African Americans
Authors: Nora Franceschini, Steve Buyske, Lucia A Hindorff, Charles Kooperberg, Eric Boerwinkle
Journal: Circulation (2013)

Introduction: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in the U.S., and disproportionally affects African Americans. Given the evidence for genetic susceptibility ...
Abstract 472: Large-Scale Single-Cell RNA-Seq Identifies Heterogeneous Populations of Human Primary and Induced Pluripotent Stem Cell-Derived Endothelial Cells
Authors: David T Paik, Lei Tian, Jaecheol Lee, Nazish Sayed, Ridhima Mishra, Joseph C Wu
Journal: Circulation Research (2018)

Rationale: Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have risen as a useful tool in cardiovascular research, offering a wide gamut of translational and clinical applications. However, inefficiency of the currently available iPSC-EC differentiation protocol and underlying heterogeneity of derived iPSC-ECs remain as major limitations of iPSC-EC technology. Objective: Here we performed droplet-based single-cell RNA-sequencing (scRNA-seq) of the human iPSCs following iPSC-EC differentiation and of primary endothelial cells isolated from human coronary arteries. Droplet-based scRNA-seq enables analysis of thousands of cells in parallel, allowing comprehensive analysis of transcriptional heterogeneity. Methods and Results: Bona fide iPSC-EC cluster was identified by scRNA-seq, which expressed high levels of endothelial-specific genes. iPSC-ECs sorted by CD144 antibody-conjugated magnetic sorting exhibited standard endothelial morphology and function including tube formation, response to inflammatory signals, and production of nitric oxide. Non-endothelial cell populations resulting from the differentiation protocol were identified, which included immature and atrial-like cardiomyocytes, hepatic-like cells, and vascular smooth muscle cells. Furthermore, scRNA-seq analysis of purified iPSC-ECs revealed transcriptional heterogeneity with four major subpopulations, marked by robust enrichment of CLDN5, APLNR, GJA5, and ESM1 genes respectively. These findings were then cross-analyzed with the primary EC data. Conclusions: Massively parallel scRNA-seq allowed analysis of thousands of human iPSCs subjected to EC differentiation. Results showed inefficiency of the differentiation technique, which can be improved with further studies based on identification of molecular signatures that inhibit expansion of non-endothelial cell types. Subtypes of bona fide human iPSC-ECs were also identified, allowing us to sort for iPSC-ECs with specific biological function and identity. Cross-analysis with scRNA-seq data of human coronary artery ECs reveals transcriptional similarities and dissimilarities of iPSC-ECs to the primary ECs that will be addressed in subsequent studies.
PATTERNS AND PREDICTORS OF REFERRAL FOR INVASIVE MANAGEMENT OF PERIPHERAL ARTERIAL DISEASE IN THE UNITED STATES: INSIGHTS FROM THE PORTRAIT REGISTRY
Authors: Qurat-ul-Ain Jelani, Samit Shah, Tang Yuanyuan, John A. Spertus, Kim Smolderen, Herbert Aronow, Maria Paredes, Robert Attaran, Christopher Regan, Carlos Mena-Hurtado
Journal: Journal of the American College of Cardiology (2019)
PROGNOSTIC IMPLICATION OF GLOBAL MYOCARDIAL BLOOD FLOW AND FLOW RESERVE IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Rikuta Hamaya, Yoshihisa Kanaji, Akinori Sugano, Masahiro Hada, Yoshinori Kanno, Eisuke Usui, Masahiro Hoshino, Masao Yamaguchi, Yohei Sumino, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2019)