tbuckley/cabot-search huggingface dataset:
Abstract 14836: Dual Dysfunction of Kir2.1 at the Sarcolemma and the Sarcoplasmic Reticulum Underlies Arrhythmogenesis in a Mouse Model of the Andersen-Tawil Syndrome Type 1
Authors: Alvaro Macias, Andrés González-Guerra, Ana Isabel Moreno Manuel, Francisco Miguel Cruz Uréndez, García Nieves, Lilian Karina Gutierrez-Espinosa de los Monteros, Marta Roche, Francisco José Bermúdez Jimenez, María Linarejos Vera-Pedrosa, Juan A. Bernal, Jose Jalife
Journal: Circulation (2020)

Introduction: Andersen-Tawil syndrome type 1 (ATS1) is associated with fatal cardiac arrhythmias. However, the underlying mechanisms are poorly understood. Hypothesis: Cardiac-specific expression of trafficking deficient Kir2.1 channels in mice in-vivo recapitulates the cardiac electrical phenotype of ATS1 and investigate the underlying mechanisms. Methods: We generated a new mouse model of ATS1 by a single i.v. injection of cardiac specific adeno-associated viral (AAV) transduction with Kir2.1 Δ314-315 , which recapitulated the ATS1 ECG phenotype without modifying ventricular function. The animal and cellular, structural and functional analyses were carried out by ECG, intracardiac stimulation, patch-clamping, membrane fractionation, western blot, immunolocalization and live calcium imaging. Results: AAV-Kir2.1 Δ314-315 mice were significantly more sensitive to flecainide than control, increasing the PR and QRS intervals over time. Kir2.1 Δ314-315 mice had increased vulnerability to cardiac fibrillation. Patch-clamping in ventricular cardiomyocytes from Kir2.1 Δ314-315 mice demonstrated significantly reduced I K1 and I Na , depolarized resting membrane potential and prolonged action potential. Immunolocalization in control mice revealed two bands of Kir2.1 staining, one colocalizing with Na V 1.5 and AP1 near the Z disk, the other near the H zone. Membrane fractionation and western blot experiments demonstrated two distinct levels of Kir2.1 protein expression, one at the sarcolemmal fraction together with Na V 1.5 and the other at the sarcoplasmi creticulum (SR). Kir2.1 Δ314-315 cardiomyocytes showed disruption of the Kir2.1-Nav1.5 channelosome at the sarcolemma, indicating dysfunctional trafficking o fboth channels. In addition, the SR Kir2.1 was disrupted and calcium transient dynamics were altered, resulting in frequent abnormal spontaneous calcium release events, and revealing an excitation-contraction coupling defect. Conclusions: Cardiac-specific AAV transduction with Kir2.1 Δ314-315 in mice recapitulates the ATS1 phenotype by disrupting localization and function of Kir2.1at the SR, and the Kir2.1-Na V 1.5 channelosome at the sarcolemma, revealing anovel dual mechanism of arrhythmogenesis.
Could Flozins Be the Statins for Risk-Based Primary Prevention of Heart Failure?
Authors: Priya M. Freaney, Donald M. Lloyd-Jones, Sadiya S. Khan
Journal: JAMA Cardiology (2021)

This Viewpoint synthesizes available data for the role of sodium-glucose cotransporter-2 inhibitor in heart failure and proposes a theoretical framework to evaluate flozins in primary prevention of heart failure akin to the role of statins in atherosclerotic cardiovascular disease.
Abstract 9702: Should We Wait for the Gradient to Reach 40 mmHg in Paradoxical Low-flow Aortic Stenosis?
Authors: Ezequiel Guzzetti, Mohamed-Salah Annabi, Anthony Poulin, Bin Zhang, Dimitri Kalavrouziotis, Christian Couture, francois dagenais, Philippe Pibarot, Marie Annick Clavel
Journal: Circulation (2019)

Background: There are uncertainties regarding the optimal therapeutic strategy for low-flow and normal flow low-gradient (LF/NF LG) aortic stenosis (AS): both watchful waiting until mean gradient r...
Abstract MP64: Higher Visit-to-Visit Blood Pressure Variability In Early And Middle Childhood Is Associated With Higher Blood Pressure In Adolescence
Authors: Mingyu Zhang, Lawrence J Appel, Xiaobin Wang, Noel T Mueller
Journal: Circulation (2021)

Background: In young adults, higher blood pressure (BP) and visit-to-visit BP variability are independent risk factors for incident cardiovascular disease. No studies have examined if BP and visit-to-visit BP variability during early and middle childhood are independently associated with elevated BP during adolescence. Addressing this question can provide targets for primordial prevention of high BP. Hypotheses: Higher BP and BP variability in early and middle childhood are independently associated with higher BP in adolescence. Methods: We studied 476 children in the Boston Birth Cohort (enrolled 1998-2016) who had BP measured in early (1 to &lt;6 y) or middle childhood (6 to &lt;13y) and in adolescence (13 to &lt;18 y). We modelled visit-to-visit BP variability using variability independent of the mean (VIM). We used linear regression models to examine the associations of mean BP and BP VIM in early and middle childhood (exposures) with mean BP in adolescence (outcome) and adjusted for potential confounders (see Table footnote). Results: After multivariable adjustment, a 1-SD higher level of systolic BP (SBP) in early and middle childhood was associated with a 1.89 (95% CI: 1.03, 2.75) and a 4.31 (95% CI: 3.58, 5.03) mmHg higher SBP in adolescence, respectively. A 1-SD higher level of SBP VIM in early and middle childhood was associated with a 1.46 (95% CI: 0.54, 2.38) and a 0.89 (95% CI: 0.05, 1.73) mmHg higher SBP in adolescence, respectively. Higher diastolic BP (DBP) in early and middle childhood was also associated with higher adolescence DBP, but the magnitude was smaller in comparison with SBP results ( Table ). Childhood DBP VIM was not associated with DBP in adolescence. Conclusion: In this prospective US predominantly minority birth cohort, both BP levels and variability during early and middle childhood are associated with higher BP in adolescence. Our findings underscore the need for health professionals to collect early-life BP data to facilitate opportunities for the primordial prevention of high BP in adolescence and beyond.
Optical Evaluation for Predicting Cancer in Large Nonpedunculated Colorectal Polyps Is Accurate for Flat Lesions
Authors: Sergei Vosko, Neal Shahidi, Mayenaaz Sidhu, W. Arnout van Hattem, Iddo Bar-Yishay, Scott Schoeman, David J. Tate, Luke F. Hourigan, Rajvinder Singh, Alan Moss, Karen Byth, Eric Y.T. Lee, Nicholas G. Burgess, Michael J. Bourke
Journal: Clinical Gastroenterology and Hepatology (2021)
제 7 차 춘계학술대회 초록집 : 포스터 발표 ; 1b 형 만성 HCV 감염자에서 관찰된 Interferon Sensitivity Determining Region ( ISDR ) 의 서열
Authors: 천갑진, 김연수, 김영석, 정준성, 문종호, 조영덕, 심찬섭, 김부성
Journal: Clinical and Molecular Hepatology (2001)
Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India
Authors: Steven J. Clipman, Shruti H. Mehta, Mary A. Rodgers, Priya Duggal, Aylur K. Srikrishnan, Shanmugam Saravanan, Pachamuthu Balakrishnan, Canjeevaran K. Vasudevan, Stuart C. Ray, Muniratnam S. Kumar, Thomas C. Quinn, Gavin A. Cloherty, Gregory M. Lucas, Sunil S. Solomon
Journal: Hepatology (2021)

Background and Aims Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high‐burden populations, such as people who inject drugs (PWID). Approach and Results We used 483 HCV sequences and detailed individual‐level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes. Conclusions This study characterizes HCV phylodynamics among PWID in a low and middle‐income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes.
Abstract 16557: Hemodynamic Stress Activates a Comprehensive Adaptive Program in Murine Aortic Cells That Protects the Aortic Wall and Maintains Aortic Homeostasis
Authors: Chen Zhang, Yanming Li, Pingping Ren, Wei Luo, Lin Zhang, Hong S Lu, Lisa A Cassis, Joseph S Coselli, Alan Daugherty, Scott A Lemaire, Ying H Shen
Journal: Circulation (2020)

Background: The aorta adapts to changes in its biomechanical environment and insufficient adaptation results in aortic failure. However, the molecular and cellular processes underlying this adaptive response are poorly understood. In this study, we performed single-cell transcriptomic and single-cell epigenomic analyses to investigate gene expression and epigenetic regulation responses in aortas subjected to hemodynamic stress. Methods and Results: Angiotensin II infusion in wild-type mice (C57BL/6J) increased ascending aorta wall thickness that was associated with smooth muscle cell (SMC) proliferation and extracellular matrix (ECM) production. ScRNA-seq revealed an adaptive response in several SMC clusters that was characterized by upregulation of genes in processes such as proliferation, cell junction organization, ECM production and organization, wound healing, as well as DNA repair and anti-oxidation. ScATAC-seq showed increased chromatin accessibility at the locus of these adaptive genes. Motif analysis of the accessible regions showed that several transcription factors and chromatin architecture proteins may be involved in regulating these adaptive response genes. Among these, Yap1 was significantly activated in response to the aortic challenge. YAP1-based ChIP-seq in aortic SMCs indicated that YAP1 and its transcription partners can directly bind to genes involved in the adaptive response to biomechanical stretch. Finally, SMC-specific knockout of Yap1 resulted in a compromised adaptive response and increased expression of genes involved in protein disassembly or degradation, and cell death in all SMC clusters, leading to contractile dysfunction, aortic aneurysm, dissection, and rupture. Conclusion: In mice, hemodynamic stress induces a comprehensive and coordinated adaptive response in SMCs that is critical for maintaining aortic homeostasis. YAP1 in SMCs play an important role in promoting this adaptive response in aortic wall.
Abstract 15273: Estimating Coronary Heart Disease Risk and Treatment Benefit in Patients With Familial Hypercholesterolemia to Enable Shared Decision Making
Authors: Hana Bangash, Seyedmohammad Saadatagah, Ian Hargraves, Justin Gundelach, Ozan Dikilitas, Victor M Montori, Iftikhar J Kullo
Journal: Circulation (2020)

Introduction: Current risk equations for coronary heart disease (CHD) do not take into account family history or cumulative exposure to LDL-C. We modified CHD risk equations for use in familial hypercholesterolemia (FH) patients and developed a decision aid (DA) for FH to facilitate shared decision making (SDM). Methods: Literature review, evidence synthesis and expert input were used to adapt the 30-year Framingham Risk Score (FRS) and 10-year ACC/AHA pooled cohort equations to calculate the CHD risk in individuals with FH aged 20-39 years and ≥40 years, respectively. Based on published data, estimated risk was multiplied by 2 for family history of early CHD or 3 in the presence of a pathogenic variant. Treatment benefit of lipid lowering was estimated based on the ‘cumulative exposure to LDL-C’ model ( JACC 2012; 60 ) using the following equations: Post-treatment 30-yr risk in those aged 20-39 years = Baseline Risk (FRS) x 0.54 delta LDL-C (mmol/L) Post-treatment 10-yr risk in those aged ≥40 years = Baseline Risk (ACC/AHA Pooled Cohort) x 0.72 delta LDL-C (mmol/L) To convey CHD risk and treatment benefit, we developed a DA using an iterative, patient-centered design process for use in FH encounters. Results: Using the DA, providers can discuss baseline CHD risk estimates, lipid lowering drug (LLD) options and the expected post-treatment risk reduction with FH patients. The estimated % LDL-C reduction for each LLD and the predicted risk reduction per mmol/L of LDL-C lowered were obtained from literature review. Lowering LDL-C by 1 mmol/L (39 mg/dL) was associated with a 28% CHD risk reduction over 10 years and a 46% reduction over 30 years ( Eur Heart J 2017; 38 ). We describe 2 examples of estimating CHD risk and treatment benefit in FH cases in Table 1 . Conclusion: We adapted CHD risk prediction equations to account for family history of CHD and presence of a pathogenic FH variant and designed a DA to convey personalized CHD risk estimates and treatment benefit to facilitate SDM with FH patients.
Visualization of Intratumor Pharmacokinetics of [fam-] Trastuzumab Deruxtecan (DS-8201a) in HER2 Heterogeneous Model Using Phosphor-integrated Dots Imaging Analysis
Authors: Mikiko Suzuki, Shigehiro Yagishita, Kiyoshi Sugihara, Yusuke Ogitani, Tadaaki Nishikawa, Mayu Ohuchi, Takashi Teishikata, Takahiro Jikoh, Yasushi Yatabe, Kan Yonemori, Kenji Tamura, Kosei Hasegawa, Akinobu Hamada
Journal: Clinical Cancer Research (2021)

Abstract Purpose: We assessed the intratumor pharmacokinetics of [fam-] trastuzumab deruxtecan, T-DXd (known as DS-8201a), a novel HER2-targeted antibody–drug conjugate, using phosphor-integrated dots (PID)-imaging analysis to elucidate its pharmacologic mechanism. Experimental Design: We used two mouse xenograft models administered T-DXd at the concentration of 4 mg/kg: (i) a heterogeneous model in which HER2-positive and HER2-negative cell lines were mixed, and (ii) a homogeneous model in which both cell types were transplanted separately into the same mouse. PID imaging involved immunostaining using novel high-intensity fluorescent nanoparticles. The distribution of T-DXd was assessed by PID imaging targeting the parent antibody, trastuzumab, and the payload, DXd, in serial frozen sections, respectively. Results: After T-DXd administration in the heterogeneous model, HER2 expression tended to decrease in a time-dependent manner. The distribution of trastuzumab and DXd was observed by PID imaging along the HER2-positive area throughout the observation period. A detailed comparison of the PID distribution between trastuzumab and DXd showed that trastuzumab matched almost perfectly with the HER2-positive area. In contrast, DXd exhibited widespread distribution in the surrounding HER2-negative area as well. In the HER2-negative tumor of the homogeneous model, the PID distribution of trastuzumab and DXd remained extremely low throughout the observation period. Conclusions: Our results suggest that T-DXd is distributed to tumor tissues via trastuzumab in a HER2-dependent manner and then to adjacent HER2-negative areas. We successfully visualized the intratumor distribution of T-DXd and its mechanism of action, the so-called “bystander effect.”
心停止と推定された犠牲者に対する心肺蘇生法(t-CPR)の電話補助下による指示の3年間にわたる調査
Authors: Inaba Hideo, Maeda Tetsuo, Nishi Taiki, Wato Yukihira, Goto Yoshikazu, Hashimoto Masaaki
Journal: Circulation (2012)
평론 / 라미부딘데 대한 치료 반응 - 어떤 방법으로 정의되어야 하는가?
Authors: 이한주(Han Chu Lee), 서동진(Dong Jin Suh)
Journal: Clinical and Molecular Hepatology (2001)

ALT, alanine aminotransferase; anti-HBe, antibody to hepatitis B virus e antigen; cccDNA, covalently closed circular DNA; HBcAg, hepatitis B virus core antigen; HBeAg, hepatitis B virus e antigen; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus; HBx, hepatitis B virus x protein; LHBs, large hepatitis B virus surface antigen; MHBs, middle-sized hepatitis B virus surface antigen; PCR, polymerase chain reaction; SHBs, small hepatitis B virus surface antigen.
The Peaks of Medical History. An Outline of the Evolution of Medicine for the Use of Medical Students and Practitioners.
Journal: JAMA (1928)

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Abstract P145: Demographic And Clinical Predictors Of Incident Clinically-recognized Varicose Veins In Older Adults
Authors: Yejin Mok, Shoshana Ballew, Anna Kucharska-newton, Kenneth R Butler, Peter Henke, Pamela L Lutsey, Maya Salameh, Ron C Hoogeveen, Christie M Ballantyne, Elizabeth Selvin, Kunihiro Matsushita
Journal: Circulation (2021)

Background: Varicose veins are common in older adults, and associated with major clinical adverse outcomes such as deep venous thrombosis. Although there are a few established risk factors of varicose veins such as female sex, height, and obesity, some other risk factors demonstrated inconsistent results. Aim: To identify demographic and clinical risk factors of incident varicose veins Methods: Using data from the Atherosclerosis Risk in Communities (ARIC) Study over five clinic visits, we constructed a cohort of 6612 adults aged 65-70 years to be able to capture outpatient visits using Medicare data. For each participant, the first visit when meeting age range (65-70 years) was used as baseline. Varicose veins were defined as two outpatient encounters (at least a week apart) or inpatient diagnoses through 2015 (ICD9 codes:454.xx). Participants with clinically-recognized varicose veins prior to baseline were excluded. We explored demographic and clinical predictors routinely evaluated in ARIC visits using Cox regression. Results: During a median follow-up of 15 years, 348 (5%) of participants developed incident clinically-recognized varicose veins. We confirmed female sex, greater height, and higher body mass index were associated with varicose veins ( Table ). In addition, white race, loop diuretic use, prevalent heart failure were independently associated with incident varicosities. In subsample with relevant data, higher cardiac troponin T and natriuretic peptide were also independently associated with varicose veins. When we censored participants who left Medicare fee-for-service, results were largely consistent. Conclusions: In this community-based cohort study of older adults, in addition to established predictors, we found that white race and clinical and treatment factors related to cardiac function were associated with clinically-recognized varicose veins that may help identify those at high-risk of varicose veins.
Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer
Authors: Rebecca G. Philipson, Tahmineh Romero, Jessica K. Wong, Bradley J. Stish, Robert T. Dess, Daniel E. Spratt, Avinash Pilar, Chandana Reddy, Trude B. Wedde, Wolfgang A. Lilleby, Ryan Fiano, Gregory S. Merrick, Richard G. Stock, D. Jeffrey Demanes, Brian J. Moran, Michelle Braccioforte, Phuoc T. Tran, Santiago Martin, Rafael Martinez-Monge, Daniel J. Krauss, Eyad I. Abu-Isa, Luca Valle, Natalie Chong, Thomas M. Pisansky, C. Richard Choo, Daniel Y. Song, Stephen Greco, Curtiland Deville, Todd McNutt, Theodore L. DeWeese, Ashley E. Ross, Jay P. Ciezki, Derya Tilki, R. Jeffrey Karnes, Eric A. Klein, Jeffrey J. Tosoian, Paul C. Boutros, Nicholas G. Nickols, Prashant Bhat, David Shabsovich, Jesus E. Juarez, Patrick A. Kupelian, Matthew B. Rettig, Alejandro Berlin, Jonathan D. Tward, Brian J. Davis, Robert E. Reiter, Michael L. Steinberg, David Elashoff, Eric M. Horwitz, Rahul D. Tendulkar, Amar U. Kishan
Journal: European Urology (2021)
Abstract P039: No Beneficial Associations Between Dairy Products And Kidney Function After Myocardial Infarction
Authors: Anniek C van Westing, Esther Cruijsen, Johanna M Geleijnse
Journal: Circulation (2021)

Introduction: Population-based studies showed beneficial associations between (low-fat) dairy products and kidney function. Kidney function declines with age, which is accelerated after myocardial infarction (MI). Little is known about dairy consumption and kidney function in MI patients. Hypothesis: Dairy intake may slow down kidney function decline after MI. Methods: We analysed 2,247 Dutch post-MI patients (60-80 years, 81% men) from the Alpha Omega Cohort. Dietary intakes, including types of dairy, were assessed at baseline (2002-2006) using a validated 203-item food frequency questionnaire. Glomerular filtration rate was estimated at baseline and after ~40 months, using the Chronic Kidney Disease (CKD) Epidemiology Collaboration equations for serum cystatin C alone (eGFR cysC , in ml/min per 1.73m 2 ). Associations between dairy intake and annual eGFR cysC change were obtained using multivariable linear regression models, adjusting for age, sex, lifestyle and dietary factors. Betas (β), with 95% confidence intervals (95% CI), represent additional eGFR cysC changes on top of annual decline, per increment in dairy intake. Results: At baseline, 22% was obese, 18% had diabetes and 15% had CKD (eGFR cysC &lt;60). Median dairy intakes were 70 g/day for milk (62% consumed low-fat milk), 41 g/day for yogurt and 17 g/day for hard cheeses. The mean ± SD eGFR cysC at baseline was 82 ± 19, which on average declined by 3.42 ± 11.04, corresponding to an annual decline of 0.99 ± 3.21. Total milk consumption was not associated with annual eGFR cysC change in the multivariable model (β: 0.01 per 100 g/day, 95% CI: -0.08;0.10; Figure 1). Associations for hard cheeses (per 10 g/day) and yogurt (per 25 g/day) with eGFR cysC decline were also weak and non-significant. Sensitivity analyses in non-diabetic (n=1,843) or non-CKD patients (n=1,910) yielded similar results (Figure 1). Conclusions: Milk, hard cheeses and yogurt consumption were not associated with eGFR cysC decline in Dutch post-MI patients.