tbuckley/cabot-search huggingface dataset:
Abstract 13644: Depict Analysis Suggests Enrichment of Heart Valve Tissue Expression in African Rheumatic Heart Disease Patients From the RHDGen GWAS Study Cohort
Authors: Tafadzwa Machipisa, Michael Chong, Guillaume Pare, Mark E Engel
Journal: Circulation (2021)

Introduction: Rheumatic heart disease (RHD) is a sequela of rheumatic fever that results in permanent heart valve damage. While it remains the primary cause of cardiac surgery in Africa, its pathophysiology is poorly understood.Genome-wide association studies (GWASs) are ‘hypothesis-free’, genetic discovery tools for common complex diseases. Recently, our African GWAS of RHD susceptibility uncovered a novel locus (11q24.1; OR=1.63; 95% CI, 1.38-1.94; P=4.36x10 -8 ) which may explain the disproportionate burden in Africans.Here we further report secondary analyses investigating tissue type expression enrichment among suggestively associated loci, to elucidate the underlying biological processes involved in RHD susceptibility. Aims and Objectives: This study sought to identify tissue types enriched in gene-set analyses associated with RHD GWAS susceptibility data in Africans. Methods: A multicenter, ethnically matched case-control GWAS was performed in 2,548 RHD cases and 2,261 controls, from eight African countries. All 4,809 participants were assessed according to the 2012 World Heart Federation (WHF) criteria for echocardiographic diagnosis of RHD. After cleaning, the GWAS data were stratified by ethnicity and an association test was run via mixed linear models in GCTA that adjusted for gender, chip type and the first ten principal components. Using the resulting GWAS summary statistics suggestive loci (P&lt;1x10 -5 ), we conducted secondary analyses in DEPICT (Data-driven Expression Prioritized Integration for Complex Traits) to test for association with RHD and its related traits and tissues, to validate the GWAS findings. Results: DEPICT indicated promising and biologically relevant results; the most enriched tissues were heart valves (p=2.47x10 -3 ; False Discovery Rate (FDR)=&lt;0.20). Discussion and Conclusion: Our results indicate that genetic susceptibility to RHD may involve perturbed gene expression signatures characteristic of heart valves, known for their pathogenic involvement in RHD development. Future larger studies are warranted to identify the specific genes involved.
Abstract 18797: Casein Kinase II (csnk2a2) is Associated With Leucocyte Telomere Shortening and Increased Cardiovascular Disease Risk in Diabetes
Authors: Praveen Natt, Richa Saxena, Patrick Dib, Sarju Ralhan, Gurpreet S Wander, Donald Stowell, Marvin Peyton, Dharambir Sanghera
Journal: Circulation (2013)

The shorter telomere length has been linked to the pathology of cardiovascular disease (CVD) and type 2 diabetes (T2D), and is widely considered as a marker for biological aging. A genome-wide association scan (GWAS) analysis of shorter leucocyte telomere length (LTL) conducted on 1,616 participants from the Sikh Diabetes Study (SDS) identified 338 top independent signals (p&lt;10-4) to be significantly associated with a shorter LTL independent of T2D. Most promising 48 SNPs were further replicated through genotyping in an additional Punjabi Sikh sample (n=2,397). In combined meta-analysis in the Punjabi Sikh populations (n=4,013/1,946 T2D cases), we identified a novel locus in association with LTL at 16q21 represented by an intronic SNP in the CSNK2A2 (p=4.4x10-8). Our findings also revealed an independent association of shorter LTL with T2D and cardio metabolic risk. The mean LTL showed a gradual decline from healthy subjects to individuals with T2D and CHD with respective mean LTL being 2.10 in healthy, 1.95 in T2D, 1.69 in CHD, and 1.59 in T2D+CHD. Interestingly, the telomeric repeat binding factor 1(TRF1) serves as a substrate for CSNK2A2, which phosphorylates and initiates its binding to telomere. CSNK2A2 also interacts with multiple genes and miRNAs in pathway controlling LTL and CVD. To further understand the functional significance of the genetic variation CSNK2A2 and other genes in association with CHD and telomere replication pathway, we analyzed the expression of 84 miRNA in carotid aortic plaque and muscle tissues obtained from CHD patients who had undergone coronary artery bypass graft (CABG) using miScript miRNA Human CVD arrays (Qiagen, Chatsworth, CA). Our initial analysis revealed a significant difference (p&lt;0.05) in expression of miR208 that regulates CSNK2A2. Additionally, expression of miR155 associated with TERF1 and miR1 associated with TERF2 were down-regulated, and expression of miR185/miR27a/miR183- associated with POT1 was elevated in atherosclerotic plaque compared to muscle. Future functional studies may provide clinically important insights on the interplay between genetic variants in CSNK2A2 and other LTL pathway genes and their interaction with miRNA in atherosclerotic tissues for affecting CVD risk in diabetes.
Final Results of a Phase 1/2 Study of SYK Inhibitor Entospletinib in Combination with Obinutuzumab in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)
Authors: Alexey V. Danilov, Vi Lam, Bria Thurlow, Stephen E. Spurgeon, Byung Park, Kirsten Orand, Adam S Kittai
Journal: Blood (2021)
Abstract 11483: A 7-Year Arterial Stiffness and Carotid Intima-Media Thickness Progression Predict Obesity, High Lean Mass, and Incident Hypertension from Age 17.7 to 24.5 Years: the ALSPAC Study
Authors: Andrew O Agbaje, Alan R Barker, Tomi-Pekka Tuomainen
Journal: Circulation (2021)

Introduction: An American Heart Association’s statement recommended investigating the natural history of arterial stiffness and blood pressure (BP) vis-à-vis the rate at which arterial stiffness and BP increase with age. Hypothesis: To test whether carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression independently predict increased fat mass and BP. Methods: We studied 3862 participants from the Avon Longitudinal Study of Parents and Children birth cohort. cfPWV and cIMT were measured by ultrasound scan, total and trunk fat mass, and lean mass by dual-energy Xray absorptiometry scan, body mass index (BMI), BP, heart rate, fasting insulin, glucose, high sensitivity C-reactive protein, and lipid profile were measured at ages 17.7 and 24.5 years. Participants at &gt;75th percentile of total and trunk fat mass or having &gt;24.9 kg/m 2 BMI were classified as overweight and obese, &gt;75th percentile as high lean mass, and &gt;120/80 mm Hg as elevated BP and hypertension. Data were analysed with logistic regression and linear mixed models, adjusting for cardiometabolic and lifestyle factors. Results: Among 1719 [44.5%] male and 2143 [55.5%] female participants, cfPWV at 17.7 years independently predicted systolic hypertension [Odds ratio (OR) 1.19 (1.01 - 1.40); p=0.043], diastolic hypertension [OR 1.77 (1.32 - 2.38); p&lt;0.0001], BMI-obesity [OR 1.19 (1.01 - 1.41); p=0.041], and trunk fat mass-obesity [OR 1.24 (1.03 - 1.49); p=0.023] at age 24.5 years. cIMT at 17.7 years predicted high lean mass [OR 54.29 (0.73 - 4053.52); p=0.069] at 24.5 years with borderline significance. A 7-year increase in cfPWV was directly associated with the 7-year increase in lean mass [Effect estimate 0.09 kg (0.05 - 0.13); p&lt;0.0001], systolic BP [21.58 mmHg (14.32 - 28.84); p&lt;0.0001] and diastolic BP [31.74 mmHg (24.90 - 38.57); p&lt;0.0001], but inversely associated with BMI [-0.03 kg/m 2 (-0.06 - -0.01); p=0.039]. cIMT progression from age 17.7 - 24.5 years was directly associated with the 7-year increase in total fat mass, trunk fat mass, lean mass, BMI, and diastolic BP. Conclusions: Arterial stiffness and cIMT progression independently predicted obesity, high lean mass, and incident hypertension among young adults.
Abstract P440: Cardiac Tissue Chip Model Provides A Platform For Studying Age-related Cardiovascular Complications By Recapitulating Important Hallmarks Of Senescence And Myocardial Ischemia
Authors: Sachin Budhathoki, Caleb Graham, Palaniappan Sethu, Ramaswamy Kannappan
Journal: Circulation Research (2021)

Introduction: With the rise in the elderly population, there has been an exponential growth in cardiovascular diseases and age-related complications. This necessitates a platform for studying cardiovascular disease in the context of aging. Hypothesis: An engineered cardiac tissue model that can recapitulate critical aspects of aging can be used to study age-related diseases of the cardiovascular system. Methods: Senescence was induced in rat cardiomyoblasts using an acute low-dose doxorubicin treatment. The presence of important senescent markers in the cells like enlarged and flattened nuclei, increased ROS activity, elevated p53 production, DNA damage response foci, and increased expression of cell cycle inhibitor p16 INK4a was evaluated. These senescent cells were then used to engineer cardiac tissue, which was subjected to hemodynamic stresses associated with the pressure-volume changes in the heart. Myocardial ischemia was imposed in the aging cardiac tissue model using hypoxic treatment. Results: Under normal hemodynamic loading, the engineered cardiac tissue retained its cardiac cell characteristics and showed cell alignment along with age-related changes in structure and gene expression. The myocardial ischemic model of the tissue revealed major pathological hallmarks of the disease like increased cell death and natriuretic peptide expression. Conclusion: Our model and methodology provide an effective platform for studying the cardiovascular disease pathologies associated with aging and screening drugs against age-related complications.
Deep neural network for video colonoscopy of ulcerative colitis: a cross-sectional study
Authors: Kento Takenaka, Toshimitsu Fujii, Ami Kawamoto, Kohei Suzuki, Hiromichi Shimizu, Chiaki Maeyashiki, Osamu Yamaji, Maiko Motobayashi, Akira Igarashi, Ryoichi Hanazawa, Shuji Hibiya, Masakazu Nagahori, Eiko Saito, Ryuichi Okamoto, Kazuo Ohtsuka, Mamoru Watanabe
Journal: The Lancet. Gastroenterology & hepatology (2021)
Association of Seafood Consumption and Mercury Exposure With Cardiovascular and All-Cause Mortality Among US Adults
Authors: Yangbo Sun, Buyun Liu, Shuang Rong, Jing Zhang, Yang Du, Guifeng Xu, Linda G. Snetselaar, Robert B. Wallace, Hans-Joachim Lehmler, Wei Bao
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although seafood is known to contain heart-healthy omega-3 fatty acids, many people choose to limit their seafood consumption because of fear of mercury exposure from seafood. It is imperative to clarify the potential health effects of current mercury exposure in contemporary populations. <h3>Objective</h3> To examine the association of seafood consumption and mercury exposure with all-cause and cardiovascular disease (CVD)–related mortality in the US general population. <h3>Design, Setting, and Participants</h3> This prospective cohort study included adults 20 years or older who participated in the 2003 to 2012 cycles of the National Health and Nutrition Examination Survey; data were linked to mortality records through December 31, 2015. Data analysis was performed from January to March 10, 2021. <h3>Exposures</h3> Seafood consumption was assessed through two 24-hour dietary recalls, and mercury exposure was assessed by blood mercury levels. <h3>Main Outcomes and Measures</h3> All-cause and CVD-related mortality. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs of mortality associated with usual seafood consumption and blood mercury concentration quartiles. <h3>Results</h3> This study included 17 294 participants (mean [SD] age, 45.9 [17.1] years; 9217 [53.3%] female) with a mean (SD) blood mercury concentration of 1.62 (2.46) μg/L. During 131 276 person-years of follow-up, 1076 deaths occurred, including 181 deaths from CVD. The multivariable-adjusted HR for an increase in seafood consumption of 1 oz equivalent per day and all-cause mortality was 0.84 (95% CI, 0.66-1.07) and for CVD-related mortality was 0.89 (95% CI, 0.54-1.47). Blood mercury level was not associated with all-cause or CVD-related mortality. Comparing the highest with the lowest quartile of blood mercury concentration, the multivariable-adjusted HRs were 0.82 (95% CI, 0.66-1.05) for all-cause mortality and 0.90 (95% CI, 0.53-1.52) for CVD-related mortality. <h3>Conclusions and Relevance</h3> In this cohort study of US adults, seafood consumption and mercury exposure with the current seafood consumption level were not significantly associated with the risk of all-cause or CVD-related mortality. These findings may inform future public health guidelines regarding mercury exposure, seafood consumption, and cardiovascular health promotion.
Abstract 12450: Inflammatory Gene Expression Changes and Immune System Depression in Rats Exposed to a Single 4-hr Exposure to Electronic Cigarette Vapor
Authors: Jessica E Monterrosa Mena, Heng-Wei Hsu, Rebecca J Arechavala, Irene Hasen, Amanda Ting, Bishop Bliss, Jianru Shi, Wangde Dai, Jesus N Chavez, Juan Carreno, Lifu Zhao, Robert A Kloner, Michael T Kleinman
Journal: Circulation (2021)

Introduction: lectronic cigarette (eC) or Vaping induced Lung Injury (EVALI) was first described in the summer of 2019 in patients presenting with acute respiratory distress. Several factors contributing to EVALI are suspected, including use of oil carriers, and heating and power elements. This study examined whether a single acute exposure to eC smoke using two popular heating elements on high or low power levels would induce inflammatory gene expression and proteins, and changes in alveolar macrophage function. Hypothesis: We hypothesize that nichrome, but not stainless-steel atomizers and high power wattage used in the eC device contribute to the extent of changes in pulmonary inflammatory response and alveolar macrophage activity. Methods: Adult Sprague Dawley rats were exposed to clean air (n=8) or eC vapor (50% propylene glycol, 50% vegetable glycerin, tobacco flavoring, no nicotine, n=8) for a single four hour period using devices equipped with stainless steel (SS) or nichrome (NC) heating elements at 45 or 70 wattage power (5 exposure conditions per sex group). Rats were euthanized and bronchoalveolar lavage was performed to collect alveolar macrophages for ex-vivo cell studies. The remaining lung tissue was homogenized for inflammatory protein and gene expression analyses. Results: Significant changes were observed in animals assigned to 70 watts. Increases ranging from 1.5-fold to 2-fold change in expression of the inflammation related genes IL-6, TNF-α and CRP occurred in rats assigned to NC atomizers (p ≤ 0.05), predominantly in males. While the concentration of CRP protein was significantly increased in females, CRP gene expression was decreased at the time point examined. Other proteins were not significantly elevated. Significant (p ≤ 0.05) changes in phagocytic activity were only observed in males exposed to 70 watts NC vapor, which generated exaggerated superoxide production by 4-fold during ex-vivo incubation. Evidence of depressed phagocytic activity was observed in other exposure groups, although not statistically significant. Conclusions: These results demonstrate that a single 4-hr exposure to e-cigarettes can initiate increased gene expression of inflammatory markers IL-6, TNF-α and CRP and oxidative changes in the lung.
Abstract 9915: Impact of Arteriovenous Fistula and Non-Physiological Flow States in the Evaluation of Aortic Stenosis Among End-Stage Kidney Disease Patients on Dialysis
Authors: Fredrick Ogugua, Julien Ternacle, Holly Rodin, Philippe Pibarot, Gautam R Shroff
Journal: Circulation (2021)

Introduction: Aortic stenosis (AS) progresses rapidly and unpredictably in ESKD and is an independent risk factor for mortality. Making an accurate diagnosis and assessing severity of AS on TTE is critical to inform management decisions. TTE parameters of AS severity could be adversely impacted by presence of an arteriovenous fistula (AVF) and resultant non-physiological flow states in ESKD. We aim to evaluate prevalence of non-physiological flow states in patients with ESKD and AS with AVF vs. other dialysis access types. We hypothesized that TTE parameters vital to accurate determination of severity of AS will defer in ESKD patients with AVF compared to other types of dialysis access. Methods: In this retrospective observational study, we identified unique ESKD patients on dialysis and concomitant AS from a single center between 1/1/2000 to 1/1/2021. Severity of AS was defined per 2014 AHA/ACC guidelines. We analyzed the TTE parameters of AS severity according to dialysis access modality. Aortic valve area (AVA) was determined by the continuity equation. Results: We included 94 patients; mean age 66 yrs, 71% male; 43% black, 40% white. Severe AS was present in 18%, moderate in 41% and mild in 41%. Fifty-three percent of patients had AVF, 17% arteriovenous graft, 15% peritoneal dialysis catheter, and 15% central venous access catheter. TTE parameters of flow state and AS severity did not demonstrate any significant differences across different dialysis access modalities. (Table 1) The results were similar after adjusting for AS severity grades. Conclusions: Among ESKD patients with AS, flow states and TTE parameters of AS severity were not different in the presence of an AVF compared to other dialysis access modalities. This study provides reassurance that conventional TTE parameters, including peak velocity, mean gradient, and AVA used to estimate AS severity can be utilized reliably in dialysis patients with AVF since non-physiological flow states were not prevalent.
Abstract 13535: Predictors of Hemodynamic Changes Between Supine and Upright Measurements in Patients With Heart Failure With Preserved Ejection Fraction versus Controls
Authors: Anastasia M Christ, Rohan Bhat, Mark Schoenike, Liana Brooks, Robyn Farrell, Gregory Lewis
Journal: Circulation (2021)

Introduction: A resting supine pulmonary capillary wedge pressure (rsPCWP) of ≥ 15 mmHg measured by right heart catheterization is considered the hemodynamic “gold standard” diagnostic criteria for heart failure with preserved ejection fraction (HFpEF). However, right heart catheterization is typically performed as a one-time measurement in patients in the supine position. In this study we sought to define the degree to which PCWP changes upon assuming upright posture in HFpEF vs. controls and determinants of postural changes in PCWP. Hypothesis: Patients with elevated rsPCWP will experience a greater fall in PCWP upon assuming upright posture compared to controls and the degree of reduction will be proportionate to BMI. Methods: We performed supine right heart catheterization as well as seated upright hemodynamic measurements in consecutive patients referred to a single center for evaluation of exertional dyspnea. Patients with HFpEF as defined by symptoms and rsPCWP≥15mmHg were compared to controls with normal resting hemodynamics and normal exercise capacity. αPCWP was defined as rsPCWP - upright PCWP. Multivariate linear regression was performed with log transformation of non-normal data. Results: In 209 patients with HFpEF (age 61 + 14, 52% female, BMI 32 + 7) the mean αPCWP was 11.0+4.5 mmHg compared to 3.7mmHg in the control cohort (n=46, age 56 + 18, 57% female, BMI 26.9 + 4, p&lt;0.001). BMI, but not age or sex were associated with αPCWP in HFpEF. After further adjustment for resting PCWP and blood pressure, BMI remained directly related to αPCWP in the HFpEF cohort (p&lt;0.001). NTproBNP levels were significantly related to upright but not supine PCWP in HFpEF. Conclusion: In individuals who meet resting hemodynamic criteria for HFpEF, changes in PCWP with upright positioning are highly variable and change proportionate to BMI.
Abstract 9425: Coronary Artery Calcium Measurement and Prediction of Cardiovascular Disease by Different Ct Scanner Types: The Multi-Ethnic Study of Atherosclerosis
Authors: Harpreet S Bhatia, Isac C Thomas, Julie Denenberg, Matthew A Allison, Robyn McClelland, Matthew J Budoff, Elliot McVeigh, Michael H Criqui
Journal: Circulation (2021)

Introduction: Coronary artery calcium (CAC) scoring is a powerful tool for cardiovascular disease (CVD) risk prediction. The Agatston score weighs lesion area upward for density, and is consistent across computed tomography (CT) scanner type. Considering volume and density separately improves risk prediction, but has not been evaluated by CT scanner type. Hypothesis: Our hypothesis was that the predictive value of volume and density scoring would be superior to the Agatston score across CT scanner types. Methods: We used data from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline clinical cardiovascular disease. CAC was measured using either EBCT (electron beam CT) or MDCT (multi-detector CT). We compared risk prediction for coronary heart disease (CHD) and CVD events using the Agatston method and the volume and density scores by scanner type using Cox proportional hazards models with multivariable adjustment among those with baseline CAC &gt; 0. HRs are presented as per standard deviation. Results: The 3,362 MESA participants with CAC &gt;0 were studied. Using the Agatston method, the HR [95% CI] for CHD was 1.28 [1.16-1.42] for EBCT and 1.22 [1.12-1.34] for MDCT. Using the volume score adjusted for density, the HR for CHD was 2.11 [1.70-2.63] for EBCT and 1.71 [1.41-2.07] for MDCT. Density was strongly and inversely associated with CHD. Similar results were seen for CVD risk and in analyses stratified by sex, BMI, age, and baseline statin use. The volume score demonstrated higher areas under the curve (AUC) than the Agatston score with EBCT (0.702, 95% CI 0.665-0.738 vs 0.677, 95% CI 0.638-0.715, p=0.013) and MDCT (0.669, 95% CI 0.632-0.705 vs 0.653, 95% CI 0.616-0.690, p=0.107). Conclusions: Compared with the Agatston score, the CAC volume score, adjusted for density, provides better risk prediction for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CVD risk.
Abstract P388: Extra-cardiac BCAA Catabolism Lowers Blood Pressure And Protects From Heart Failure
Authors: Danielle Murashige, Cholsoon Jang, Michael Neinast, Michael Levin, Jae Woo Jung, Jonathan P Lambert, Joanne Garbincius, Boa Kim, Ingrid Marti-Pamies, Emily Flam, Atsushi Hoshino, Steven Yang, Emilia Roberts, Li Li, Richard K Assoian, John W Elrod, Joshua Rabinowitz, Zoltan Arany
Journal: Circulation Research (2021)

Pharmacologic activation of branched chain amino acid (BCAA) catabolism is protective in numerous models of heart failure (HF). How this protection occurs has remained unclear, although a causative block in cardiac BCAA oxidation has been proposed. We use here in vivo heavy isotope infusion studies to show that cardiac preference for BCAA oxidation increases, rather than decreases, in multiple models of HF. We use various genetic models to show that cardiac-specific activation of BCAA oxidation does not protect from HF, even though systemic activation of BCAA oxidation does. Lowering plasma and cardiac BCAAs by genetic means is also not sufficient to confer protection comparable to that conferred by pharmacologic activation of BCAA oxidation, suggesting alternative mechanisms of protection. Surprisingly, telemetry and invasive hemodynamic studies showed that pharmacological activation of BCAA catabolism lowers blood pressure, a well-established cardioprotective mechanism. The effects on blood pressure occurred independently of nitric oxide (NO), and reflected a vascular resistance to adrenergic constriction. Finally, mendelian randomization studies revealed that elevations in plasma BCAAs portend higher blood pressure in large human cohorts. Together, these data indicate that activation of BCAA oxidation lowers blood pressure and protects from heart failure independently of any direct effects on the heart itself.