tbuckley/cabot-search huggingface dataset:
Abstract 498: Functional Annotation of <i>TNNT2</i> Variants of Uncertain Significance With Induced Pluripotent Stem Cell-derived Cardiomyocytes
Authors: Wenjian Lv, Lyon Qiao, Nataliya Petrenko, Wenjun Li, Anjali T Owens, Chris McDermott-Roe, Kiran Musunuru
Journal: Circulation Research (2018)

The introduction of clinical sequencing is dramatically increasing the discovery of variants of uncertain significance (VUSs) in genes linked to inherited cardiomyopathies. We have established a platform for rapid and efficient insertion of TNNT2 gene variants into an induced pluripotent stem cell (iPSC) line to generate an allelic series of isogenic clones for differentiation into cardiomyocytes (iPSC-CMs) for functional annotation of the variants. We first used CRISPR-Cas9 to introduce known pathogenic variants into iPSCs from a healthy person or to correct pathogenic variants in iPSCs from patients with severe cardiomyopathy. Whereas normal/corrected iPSC-CMs responded to isoproterenol treatment with a 50%-70% increase in spontaneous beating rate as assessed by patch-clamp studies, iPSC-CMs with pathogenic variants had minimal responses (close to 0%). Due to the inefficiency of CRISPR-Cas9 in introducing/correcting variants in iPSCs, we next used dual integrase cassette exchange (DICE) to allow for the introduction of a large number of variants in parallel into a pool of cells. In a single pilot use of the DICE platform, we isolated heterozygous clones with 14 unique variants, &gt;10% of all TNNT2 coding variants cataloged in ClinVar. We found that iPSC-CMs with any of 7 VUSs or likely pathogenic variants were impaired in their response to isoproterenol, in contrast to control DICE-treated iPSC-CMs. Finally, we sought to apply the DICE platform to a patient case in real time. A 65-year-old woman with severe hypertrophic cardiomyopathy underwent gene panel testing that identified a single VUS, TNNT2 E251D. Between the first and second clinic visits (~10 weeks), we were able to use DICE to rapidly and efficiently generate iPSC-CMs with the E251D variant and determine they had normal responses to isoproterenol, suggesting that the variant is not pathogenic. Guided by this finding, we recommended that the patient’s children and grandchildren not undergo cascade genetic screening for the E251D variant. In conclusion, this work establishes the feasibility of rapid functional annotation of cardiomyopathy gene variants, which after further validation could be incorporated into clinical practice as a line of evidence to support variant classification.
Abstract 343: Lin28 Enhances Cardiac Repair by Reprogramming Metabolism of Cardiac Progenitor Cells
Authors: Ai Wen Tan, Justin Kurian, Daria Harlamova, Tao Wang, Sadia Mohsin, Steven R Houser, Mohsin Khan
Journal: Circulation Research (2018)

Rationale: Cardiac progenitor cells (CPCs) possess incredible repair properties in the neonatal heart but are prone to disease and age diminishing their efficacy. Interestingly, CPCs stemness is linked to a unique metabolic phenotype altered once cells undergo proliferation and commitment. Recent data indicates Lin28 as metabolic regulator of pluripotency, enhancing tissue repair after injury. Nevertheless, there are no studies characterizing the effect of Lin28 on CPC biology or cardiac repair. Objective: Determine the effect of Lin28 on CPC function and cardiac repair after injury. Methods and Results: Lin28a was highly expressed during embryonic mice heart development and disappeared in adult heart, resulting in a concomitant upregulation of Let-7 expression. Next, we engineered CPCs with Lin28a (CPC-Lin) lentivirus along with green fluorescent protein (GFP) while CPCs expressing GFP (CPC-G) were served as controls. Relative to CPC-G, increased proliferation of CPC-Lin associated with concurrent decrease in apoptosis was observed, as measured by CyQuant and annexin-V based FACS analysis, respectively. We found that CPC-Lin enhanced glycolysis together with increased expression of glycolytic enzymes, as measured by seahorse and qRT-PCR, respectively. Interestingly, CPC-Lin also increased oxidative phosphorylation, as evidenced by the increase in oxygen consumption rate and intracellular ATP production. Higher immunostaining expression of stemness markers (Nanog and Sox2) together with decreased senescence-associated-beta-galactosidase (SA-β-gal) activity was observed in CPC-Lin. To determine in vivo efficacy, CPCs were transplanted to the heart after myocardial infarction (MI). Increased proliferation as indicated by co-localized immunostaining expression of p-histone and GFP was observed in CPC-Lin 2 days after transplantation. Echocardiography analysis revealed that CPC-Lin improved cardiac function by increasing ejection shortening percentage and fractional shortening percentage. Conclusions: Metabolic reprogramming of CPCs with Lin28a promotes cardiac repair by modifying metabolism of CPCs, together with enhanced cell proliferation, survival, and in vivo cardiac function after MI.
The Role of Endotoxin in Septic Shock
Authors: James C. Hurley
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Correction: Oncogenic KRAS Confers Chemoresistance by Upregulating NRF2
Authors: Shasha Tao, Shue Wang, Seyed Javad Moghaddam, Aikseng Ooi, Eli Chapman, Pak K. Wong, Donna D. Zhang
Journal: Cancer Research (2019)

In the original version of [this article][1] ([1][2]), the HMOX1 Western blot band in Fig. 1B was inadvertently duplicated from the HMOX1 Western blot band in Fig. 3B. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.

1.  1.[↵][
ASSESSMENT OF MICROVASCULAR DYSFUNCTION USING QUANTITATIVE FLOW RATIO IN PATIENTS WITH TAKOTSUBO SYNDROME
Authors: Ron Waksman, Yuichi Ozaki, Nieves Gonzalo, Carlos Salazar Trivino, Kayode Kuku, Hernan Mejia Renteria, Alexandre Kajita, Ivan Nunez Gil, Javier Escaned, Hector M. Garcia-Garcia
Journal: Journal of the American College of Cardiology (2019)
FINAL 5-YEAR OUTCOMES OF THE EVOLVE II TRIAL: A PROSPECTIVE RANDOMIZED INVESTIGATION OF A NOVEL BIOABSORBABLE POLYMER-COATED, EVEROLIMUS-ELUTING SYNERGY STENT
Authors: Dean J. Kereiakes, Stephan Windecker, Robert Jobe, Shamir R. Mehta, Ian Joseph Sarembock, Robert Feldman, Bernardo Stein, Christophe Dubois, Timothy Grady, Shigeru Saito, Takeshi Kimura, Paul Underwood, Dominic Allocco, Ian Meredith
Journal: Journal of the American College of Cardiology (2019)
Association of Improvement in Fractional Flow Reserve With Outcomes, Including Symptomatic Relief, After Percutaneous Coronary Intervention
Authors: Stephane Fournier, Giovanni Ciccarelli, Gabor G. Toth, Anastasios Milkas, Panagiotis Xaplanteris, Pim A. L. Tonino, William F. Fearon, Nico H. J. Pijls, Emanuele Barbato, Bernard De Bruyne
Journal: JAMA Cardiology (2019)

Whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) is associated with symptomatic relief or improved outcomes has not been well investigated.To investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (ΔFFR) on patients' symptoms and 2-year outcomes.This study is a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) 1 (NCT00267774; 2009) and FAME 2 (NCT01132495; 2012), with inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018.Measure of post-PCI FFR.Vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization.This analysis included 639 patients from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (ΔFFR≤0.18), 282 into the middle tertile (0.19≤ΔFFR≤0.31), and 278 into the highest tertile (ΔFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n = 25 of 277 [9.1%]) compared with the highest tertile (n = 13 of 278 [4.7%]; hazard ratio, 2.01 [95% CI, 1.03-3.92]; P = .04). In addition, a significant association was observed between ΔFFR and symptomatic relief (odds ratio, 1.33 [95% CI, 1.02-1.74]; P = .02).In this analysis of 2 randomized clinical trials, the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This suggests that measuring FFR before and after PCI provides clinically useful information.
HEMIDIAPHRAGM PARALYSIS IN A PATIENT WITH PATENT FORAMEN OVALE RESULTS IN INTRACARDIAC SHUNT AND HYPOXIC RESPIRATORY FAILURE
Authors: Musab Alqasrawi, Abdullahi Oseni, Abdul Qazi, Chad Ward, Ala Mohsen, Aref Bin Abdulhak, Sidakpal Panaich
Journal: Journal of the American College of Cardiology (2019)
STRUCTURAL AND ELECTROPHYSIOLOGY COLLABORATIVE TEAM APPROACH TO PATIENTS WITH PRE-EXISTING RIGHT BUNDLE BRANCH BLOCK UNDERGOING TRANS CATHETER AORTIC VALVE REPLACEMENT: THE PROTECT ALGORITHM
Authors: Adnan Kassier, Rachel Rogers, Andre Gauri, Stefan Jovinge, William Merhi, Nagib Chalfoun
Journal: Journal of the American College of Cardiology (2019)
Organelle crosstalk in the kidney
Authors: Tsuyoshi Inoue, Hiroshi Maekawa, Reiko Inagi
Journal: Kidney International (2019)

Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases. The UPR pathway in the ER also regulates mitochondrial metabolic status, indicating the pathophysiological significance of organelle crosstalk between the ER and mitochondria via the UPR pathway. In recent years, it has become obvious that communication among organelles also is conducted through direct interactions at membrane contact sites (MCSs). Organelles exchange materials including lipids, ions, and proteins at the MCS. Accordingly, alterations to these networks, such as impaired ER-mitochondria MCSs, have been linked to several diseases such as neurodegeneration and diabetes. In this review, we describe the roles of organelles in kidney diseases and the mechanisms underlying organelle communication at the MCS, and especially at the mitochondria-associated ER membrane. Potential treatment options that are focused on organelle crosstalk are discussed, in addition to the relationship between this phenomenon and various diseases, especially kidney diseases.
USEFULNESS OF COMBINED ANALYSIS OF ABSOLUTE AND RELATIVE PARAMETERS USING 13N-AMMONIA POSITRON EMISSION TOMOGRAPHY FOR DETECTION OF SIGNIFICANT CORONARY ARTERY DISEASE
Authors: Tatsuya Shigematsu, Hideki Okayama, Naoto Kawaguchi, Shinsuke Kido, Yosei Iseki, Kenshou Matsuda, Tetsuya Aono, Yuta Tanaka, Saki Hosokawa, Tetsuya Kosaki, Go Kawamura, Yoshitaka Kawada, Go Hiasa, Tadakatsu Yamada, Hiroshi Matsuoka, Yukio Kazatani
Journal: Journal of the American College of Cardiology (2019)
THIRTY-DAY READMISSION RATES OF CAROTID ENDARTERECTOMY VERSUS CAROTID ARTERY STENTING: A NATIONWIDE ANALYSIS
Authors: Varunsiri Atti, Sushruth Edla, Varun Kumar, Byomesh Tripathi, Nileshkumar Patel, Mark Terence Mujer, Srikanth Yandrapalli, Nikhil Nalluri, Vikramaditya Samala Venkata, Saroj Neupane, Howard Rosman, Rajendra Mehta
Journal: Journal of the American College of Cardiology (2019)
BCR affinity differentially regulates colonization of the subepithelial dome and infiltration into germinal centers within Peyer’s patches
Authors: Adi Biram, Anneli Strömberg, Eitan Winter, Liat Stoler-Barak, Ran Salomon, Yoseph Addadi, Rony Dahan, Gur Yaari, Mats Bemark, Ziv Shulman
Journal: Nature Immunology (2019)
Abstract 12720: Trends of Cardiac Complications in Patients With Rheumatoid Arthritis: An Insight From National Inpatient Sample;2005-2014
Authors: Dhrubajyoti Bandyopadhyay, Upasana Banerjee, Vivek A Modi, Faris Haddadin, Alba M Estrella, Karan Sud, Raktim K Ghosh, Adrija Hajra, Sridevi Rajeeve, Sandipan Chakraborty, Angela M Palazzo
Journal: Circulation (2018)

Introduction: Rheumatoid arthritis(RA) a chronic inflammatory disease is a risk factor for cardiac disease. Treatment of RA with various anti-inflammatory medications can affect the development of ...
Consultants urge BMA to withdraw from negotiations with “spineless” pay review body
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Hospital consultants have demanded a formal withdrawal from pay negotiations with the Review Body on Doctors and Dentists Remuneration (DDRB) in protest at a decade of falling income.

A motion passed by the annual BMA consultants conference on 27 February called on hospital consultants “to formally pull out of the [DDRB] mechanism.”

The BMA has already given evidence to the review body for 2019-20 and has called for a review of the DDRB process1 after some consultants received a “derisory” below inflation pay rise last year,2 despite scrapping of …
Abstract 551: p22phox Protects the Heart Against Pressure Overload
Authors: Wataru Mizushima, Yanfei Yang, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2018)

Reactive oxygen species (ROS), including superoxide and hydrogen peroxide, play an important role in the stress response in the heart. p22phox is associated with Nox isoforms, thereby forming NADPH oxidase (NOX) complexes and generating ROS in various tissues, including the heart. However, the exact role of p22phox in cardiomyocytes remains to be elucidated. The level of p22phox protein in adult cardiomyocytes (ACM) isolated from mouse hearts subjected to transverse aortic constriction (TAC) for 1 and 4 weeks was significantly higher (150% and 250%, respectively) than in those from sham operated mouse hearts. In order to test the role of endogenous p22phox during TAC, we generated cardiac-specific p22phox knockout (p22phox cKO) mice. These mice did not have any significant cardiac phenotype at baseline. One week after TAC, p22phox cKO mice exhibited a lower left ventricular (LV) ejection fraction (LVEF) and higher lung weight (LW) and LV weight to tibia length (TL) ratios than control mice (LVEF: 64.3±4.3 vs. 46.4±4.8 %, LW/TL: 8.2±0.3 vs. 13.4±4.8, LV/TL: 6.0±0.5 vs. 7.5±0.4 p&lt;0.05), indicating that endogenous p22phox plays a protective role against heart failure during the early phase of pressure overload (PO). Four weeks after TAC, p22phox cKO mice exhibited further deceases in LVEF and increases in LW/TL, and increased cardiac fibrosis compared to control mice (LVEF: 60.2±18.1 vs. 33.7±10.7 %, LW/TL: 13.1±7.2 vs. 26.2±4.3, relative fibrosis: 1±0.75 vs. 4.4±1.0 p&lt;0.02). However, there was no significant difference in LV/TL or cardiomyocyte cell size between p22phox cKO mice and control mice, suggesting that cardiac hypertrophy is suppressed at the later stage of PO. These results indicate that endogenous p22phox is protective against PO and mediates compensatory cardiac hypertrophy during the late phase of PO.
IMPACT OF HEMODYNAMIC SUPPORT WITH IMPELLA ON SUBSEQUENT ACUTE KIDNEY INJURY RELATIVE TO PREDICTED RISK IN PATIENTS UNDERGOING HIGH-RISK PERCUTANEOUS CORONARY INTERVENTION: AN ANALYSIS FROM THE PROSPECTIVE CVAD STUDY
Authors: Michael P. Flaherty, Jeffrey Moses, Ralf Westenfeld, Igor Palacios, Roxana Mehran
Journal: Journal of the American College of Cardiology (2019)
THE IMPACT OF DIABETES AND HBA1C ON ELDER-PATIENTS AFTER PERCUTANEOUS CORONARY INTERVENTION: FROM SHINANO REGISTRY
Authors: Ayumu Nagae, Ken Nishikawa, Takashi Miura, Minami Taki, Masanori Kobayashi, Masafumi Kanai, Takashi Yanagisawa, Naoto Hashizume, Kyuhachi Otagiri, Kyoko Shoin, Yusuke Miyashita, Koki Fujimori, Daisuke Sunohara, Hisanori Yui, Shusaku Maruyama, Chie Nakamura, Daisuke Kashiwagi, Keisuke Senda, Takahiro Sakai, Tamon Katou, Tatsuya Saigusa, Soichiro Ebisawa, Ayako Okada, Hirohiko Motoki, Koichiro Kuwahara
Journal: Journal of the American College of Cardiology (2019)
Abstract 13827: Vector Velocity Imaging Differentiates Right Ventricular Dysfunction in RV Myocardial Infarction and Submassive Pulmonary Embolism
Authors: Umar Khan, Ram Padmanabhan, Gerard Aurigemma, Dennis Tighe
Journal: Circulation (2012)

Background: Submassive pulmonary embolism (SMPE) and right ventricular myocardial infarction (RVMI) may have similar clinical presentation. Recent studies suggest right ventricular dysfunction (RVD...
COMPLETE ATRIOVENTRICULAR BLOCK IS A POOR PROGNOSTIC COMPLICATION IN PATIENTS WITH ANTERIOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN THE ERA OF PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Yosuke Kawamura, Takumi Higuma, Tomohide Endo, Fumie Nishizaki, Shuji Shibutani, Kenji Hanada, Hiroaki Yokoyama, Takashi Yokota, Masahiro Yamada, Hirofumi Tomita
Journal: Journal of the American College of Cardiology (2019)
CARDIAC HAMARTOMA MASQUERADING AS HYPERTROPHIC CARDIOMYOPATHY
Authors: Nikoloz Shekiladze, Appesh Mohandas, Beka Bakhtadze, Nikoloz Koshkelashvili, Xiong Meng-Jun, Varuna Gadiyaram, Mikhael El-Chami
Journal: Journal of the American College of Cardiology (2019)
Generic Seizure Drug Wins Approval
Authors: Rebecca Voelker
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
REDUCTION OF TYPE 1 AND TYPE 2 MYOCARDIAL INFARCTIONS IN PATIENTS TREATED WITH ALIROCUMAB: INSIGHTS FROM THE ODYSSEY TRIAL
Authors: Harvey D. White, Philippe Steg, Michael Szarek, Deepak L. Bhatt, Vera Bittner, Rafael Diaz, Jay Edelberg, Andrejs Erglis, Shaun Goodman, Corinne Hanotin, Robert Harrington, Johan Jukema, Renato Lopes, Kenneth Mahaffey, Angele Moryusef, Robert Pordy, Matthew Roe, Piyamitr Sritara, Pierluigi Tricoci, Andreas Zeiher, Gregory Schwartz
Journal: Journal of the American College of Cardiology (2019)
LONG-TERM ALL-CAUSE AND CAUSE-SPECIFIC MORTALITY IN ASYMPTOMATIC PATIENTS WITH CORONARY ARTERY CALCIUM ≥ 1,000
Authors: Allison Peng, Mohammadhassan Mirbolouk, Zeina Dardari, Olusola Orimoloye, Albert Osei, Michael Blaha
Journal: Journal of the American College of Cardiology (2019)
THE LONG-TERM IMPACT OF PERSISTENT PULMONARY HYPERTENSION IN WOMEN UNDERGOING TAVR WITH NEWER GENERATION VALVE
Authors: Konstantinos Stathogiannis, Konstantinos Toutouzas, Maria Drakopoulou, George Latsios, Andreas Synetos, Maria Xanthopoulou, George Oikonomou, Stergios Soulaidopoulos, Vasiliki Penesopoulou, Eleftherios Tsiamis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2019)
Sociodemographic Profile and Outcomes of Patients with Non-Diffuse Large B-Cell Lymphoma (non-DLBCL) Treated at Minority-Predominant Facilities in the United States
Authors: Vivek Kumar, Taimur Sher, Vivek Roy, Prakash Vishnu, Anne M Hazen, Victoria R. Alegria, Meghna Ailawadhi, Sri Lekha Bodepudi, Zan Tahir Shareef, Fabiola Coromoto Cardozo, Salman Ahmed, Prachi Jani, Aneel Paulus, Asher A. Chanan-Khan, Sikander Ailawadhi
Journal: Blood (2018)