tbuckley/cabot-search huggingface dataset:
Dose–response association between moderate to vigorous physical activity and incident morbidity and mortality for individuals with a different cardiovascular health status: A cohort study among 142,493 adults from the Netherlands
Authors: Esmée A. Bakker, Duck-chul Lee, Maria T. E. Hopman, Eline J. Oymans, Paula M. Watson, Paul D. Thompson, Dick H. J. Thijssen, Thijs. M. H. Eijsvogels
Journal: PLoS Medicine (2021)

Moderate to vigorous physical activity (MVPA) is strongly associated with risk reductions of noncommunicable diseases and mortality. Cardiovascular health status may influence the benefits of MVPA. We compare the association between MVPA and incident major adverse cardiovascular events (MACE) and mortality between healthy individuals, individuals with elevated levels of cardiovascular risk factors (CVRF), and cardiovascular disease (CVD).
Abstract 11858: A Metabolomic Study of Thrombosis After Cardiac Surgery in Children With Congenital Heart Disease
Authors: Zainab Adelekan, Alissa Jorgenson, David Watson, Weihong Tang, JENNIFER FROST, Leah Zupancich, Kathleen Garland, David Dassenko, R Erik Edens, David M Overman, Marnie T Huntley, Shengxu Li
Journal: Circulation (2021)

Background: Thrombosis is a major complication after cardiac surgery in children with congenital heart disease (CHD), and it significantly increases the risk of mortality and other complications and prolongs hospital stay. The underlying mechanisms for the development of thrombosis after cardiac surgery in children with CHD remain poorly understood. Aim: To identify novel circulating metabolites before cardiac surgery that are associated with the development of thrombosis in children with CHD after surgery. Methods: Untargeted metabolomic data on 1,006 metabolites were measured in plasma from 100 children (age range: 0 days-18 years) with CHD undergoing cardiac surgery. A total of 740 metabolites met quality control criteria (call rate&gt;70% and Spearman correlation coefficient between blind duplicates&gt;0.5). Kruskal Wallis test was used to examine the difference in concentrations of individual metabolites between those who developed thrombosis and those who did not. Results: In total, 16 children (16%) developed thrombosis. Among the 740 metabolites, 170 showed differences at a false discovery rate (FDR) of less than 0.01. The top three metabolites showing the strongest associations with thrombosis were 5-methylthioadenosine (MTA), cytidine, and eicosapentaenoate (EPA; 20:5n3) with an FDR of 0.003. Pathway analysis showed that pathways of Arginine biosynthesis (P=7.67х10 -4 ), nicotinate and nicotinamide metabolism (P=0.001), and aminoacyl-tRNA biosynthesis (P=0.008) were significantly enriched. Conclusion: We have identified promising novel metabolites associated with thrombosis in children with CHD who have undergone cardiac surgery. Replication studies are ongoing.
Abstract 10771: Avoidance of Lethal Isotherm Formation in Esophageal Tissue with an Active Cooling Device Under High-Power, Short-Duration Ablation
Authors: Marcela Mercado Montoya, Enrique Berjano, Steven R Mickelsen, James D Daniels, Tatiana Gomez-Bustamante, Pablo Hernandez-Arango, Erik Kulstad
Journal: Circulation (2021)

Introduction: Atrioesophageal fistula (AEF) is a severe complication of left atrial ablation for the treatment of atrial fibrillation. Thermal injury is the proposed mechanism, and a potential pathway occurs through exceeding the lethal isotherm of esophageal tissue in contact with the left atrial posterior wall. Active cooling with a novel cooling device has been shown to significantly reduce thermal injury, with no AEFs encountered after more than 4200 treatments worldwide. We aimed to evaluate the effects of active cooling when specifically using newer high-power short-duration (HPSD) ablation settings to further estimate the protective mechanisms of this novel approach to reduce serious injury. Hypothesis: Active cooling may preclude attainment of a lethal isotherm in esophageal tissue under HPSD ablation. Methods: We developed a model of the left atrium and esophagus, and simulated radiofrequency (RF) ablation of the left atrium under HPSD settings. Tissue thickness was set to typical posterior-wall parameters (Figure). Power settings were evaluated at 50 W for 10 seconds, and 90 W for 4 seconds. Active cooling was set to a typical 4 °C coolant temperature. Lethal isotherm temperature was taken as 50 °C. Results: In both scenarios of HPSD ablation, the peak esophageal mucosal temperature reached 39° C in control conditions, using no active cooling. With active cooling in place, peak temperatures remained below 11 °C (Figure). Peak temperatures at the epi-esophageal region of esophageal tissue exceeded the lethal isotherm of 50 °C in control conditions, but remained at or below the lethal isotherm with active cooling in place. Conclusions: Based on our mathematical modeling, esophageal cooling significantly reduced temperature rise and prevented the achievement of temperatures thought to be lethal to esophageal tissue. This finding may offer a mechanistic rationale for the absence of serious esophageal injury encountered to date using this approach.
Finding hope in COP26
Authors: Rita Issa, Jacob Krzanowski
Journal: BMJ (2021)

The conference of parties (COP)-the annual climate conference convened by the United Nations Framework Convention on Climate Change-ended recently with a sense of frustration punctuated by small, but significant wins.This COP was the 26th attempt for nation states, civil society, UN agencies, and industry to negotiate action on an unprecedented global catastrophe driven by unfettered fossil fuel consumption and environmental degradation.Delayed by the pandemic, pushed by growing climate activism, and six years after the Paris Agreement, COP26 held promise that the wealthiest and most powerful actors would understand the gravity of humanity's situation and be moved to accountable, decisive, and just commitments.
Abstract 9125: Prognostic Implications of Coronary Revascularization With Diagnostic Imaging Tests
Authors: Takao Kato
Journal: Circulation (2021)

Introduction: The differences in the prognostic impact of coronary revascularization with non-invasive diagnostic imaging tests (SPECT versus coronary CT) remain to be elucidated. Hypothesis: We aimed to test the hypothesis that the association of the prognostic impact of coronary revascularization with physician-referred non-invasive diagnostic imaging tests (single photon emission computed tomography [SPECT] versus [vs.] coronary computed tomography (CT) angiography) for coronary artery disease was not different. Methods: From the multicenter data of 2780 patients with stable angina, enrolled prospectively between January 2006 and March 2008 in Japan, who had undergone physician-referred imaging tests, 1205 patients in SPECT as an initial strategy and 625 patients in CT as an initial strategy were analyzed. We assessed the effect of revascularization (within 90 days) in each diagnostic imaging stratum and the interaction between the two strata. Results: A total of 210 (17.4%) patients in the SPECT stratum and 149 (23.8%) in the CT stratum underwent revascularization. Although in each stratum, the cumulative 1-year incidence of MACEs was significantly higher in patients who underwent revascularization than in those who did not (SPECT stratum: 9.1 vs. 1.2%, log-rank P&lt;0.0001; CT stratum: 6.1 vs. 0.8%, log-rank P=0.0001), there was no interaction between the risk of revascularization and the imaging strata (SPECT stratum: adjusted hazard ratio [95% confidence interval], 4.25 [1.86-9.72]; CT stratum: 4.13 [1.16-14.73]; interaction: P=0.97). Conclusions: The association of revascularization with the outcomes of patients with suspected coronary artery disease was not different between SPECT-first and CT-first strategies in a physician-referred fashion.
Abstract 10070: All Caregivers Are Not Alike: Stress, Caregiving Effort, and Self-Care in Heart Failure and Dementia Caregivers
Authors: Barbara Riegel, Massimo Lauren, Kathryn H Bowles, Miatta Goba, debbie Gordon, Karen B Hirschman, Quinn J Ryan, JOSEPH M RHODES, Michael A Stawnychy
Journal: Circulation (2021)

Introduction: Caregiving for someone with a chronic condition is stressful. Deferring self-care is common among caregivers but little is known about differences among various caregiver groups. The aim of this study was to compare stress, self-care, and self-care confidence in two groups of caregivers. Methods: We compared baseline data from two groups of caregivers (HF and frontotemporal dementia [FTD]) enrolled in an on-going study of an intervention designed to decrease stress and improve self-care. Eligible participants had to report caregiving ≥8 hours/week and neglect of ≥2 self-care behaviors (e.g., adequate sleep). Stress was measured with the Perceived Stress Scale (14 items, 5-point scale, higher score means higher stress). Self-care was measured with the Self-Care Inventory with embedded scales measuring self-care maintenance, monitoring, management, and confidence (30 items, 5-point scale, higher scores mean better self-care). Each self-care scale is standardized 0-100; ≥70 reflects adequate self-care. Baseline data prior to the intervention were compared. Results: Compared to HF caregivers, the FTD caregivers were significantly more likely to be Caucasian (87.1% vs. 60.9%), male (25.8% vs. 14.3%), married to the patient (98.8% vs. 72.5%), and older (64.8±10.1 vs. 54.4±15.1) years. The FTD caregivers had been caregiving for fewer years (5.1±3.7 vs. 7.3±8.6) but their daily caregiving effort was higher (Table). Stress levels did not differ significantly and self-care was poor in both groups. Self-care confidence was higher in HF than FTD caregivers. Conclusions: Although caregiving effort was higher in FTD caregivers, stress levels were comparable and self-care was poor in both HF and FTD groups. Understanding the source of the stress, barriers to self-care, and the factors that promote self-care confidence are important for developing and testing tailored interventions to promote self-care of caregivers.
Normalization of the Immune Microenvironment during Lenalidomide Maintenance Is Associated with Sustained MRD Negativity in Patients with Multiple Myeloma
Authors: David G. Coffey, Francesco Maura, Edgar Gonzalez-Kozlova, Javier Diaz-Mejia3, Ping Luo, Yong Zhang, Yuexin Xu, Edus H. Warren, Eric L Smith, Hearn Jay Cho, Alexander Lesokhin, Benjamin Diamond, Dickran Kazandjian, Trevor J. Pugh, Damian J. Green, Sacha Gnjatic, Ola Landgren
Journal: Blood (2021)
ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice
Authors: Takahiro Nakajima, Toshio Kanno, Satoru Yokoyama, Shigemi Sasamoto, Hikari K. Asou, Damon J. Tumes, Osamu Ohara, Toshinori Nakayama, Yusuke Endo
Journal: The Journal of Experimental Medicine (2021)

T cells possess distinguishing effector functions and drive inflammatory disorders. We have previously identified IL-5–producing Th2 cells as the pathogenic population predominantly involved in the pathology of allergic inflammation. However, the cell-intrinsic signaling pathways that control the pathogenic Th2 cell function are still unclear. We herein report the high expression of acetyl-CoA carboxylase 1 (ACC1) in the pathogenic CD4+ T cell population in the lung and skin. The genetic deletion of CD4+ T cell–intrinsic ACC1 dampened eosinophilic and basophilic inflammation in the lung and skin by constraining IL-5 or IL-3 production. Mechanistically, ACC1-dependent fatty acid biosynthesis induces the pathogenic cytokine production of CD4+ T cells via metabolic reprogramming and the availability of acetyl-CoA for epigenetic regulation. We thus identified a distinct phenotype of the pathogenic T cell population in the lung and skin, and ACC1 was shown to be an essential regulator controlling the pathogenic function of these populations to promote type 2 inflammation.
Abstract 13941: RNA-Sequencing Reveals a Distinct Transcriptomic Signature for Giant Cell Myocarditis and Identifies Novel Druggable Targets
Authors: Juan Qin, Kaushik Amancherla, Javid Moslehi
Journal: Circulation (2021)

Introduction: Giant cell myocarditis (GCM) is a rare inflammatory heart muscle disease that is often rapidly progressive and carries a poor prognosis. The pathogenesis of GCM is incompletely understood, but is thought to be autoimmune in nature. An improved mechanistic understanding of GCM is critical for identifying novel therapeutic targets and improving survival. Hypothesis: We hypothesized that GCM exhibits a distinct transcriptomic profile. By querying database of drug-gene interactions, novel drug targets could be identified. Methods: We performed RNA-seq utilizing FFPE tissues. Results: Demographics and clinical characteristics of the groups are highlighted in Panel A. Principal component analysis (B) based on complete expression profiles and unsupervised hierarchical cluster analysis of significant differentially expressed genes identified a distinct transcriptomic profile for GCM (C). Consistent with shared histological features, overlap is noted between rejection and lymphocytic myocarditis. Pathway enrichment analysis (D) in GCM showed that upregulated pathways were enriched for neutrophil degranulation, multiple cytokine signaling pathways, and phagocytosis, while downregulated pathways included those involved in muscle contraction and cardiac conduction. The most significantly upregulated genes play roles in innate and adaptive immune responses (E). Querying the Drug Gene Interaction Database (DGIdb) identified several novel biologically-plausible therapeutic targets (F). Conclusions: To our knowledge, this is the first study using RNA-seq to interrogate the transcriptomic profile of GCM. Our results demonstrate that GCM has a gene expression profile that mirrors clinical and histopathological features of GCM, and is distinct from the transcriptomic profiles seen in other healthy and inflammatory cardiac diseases. By querying a drug-gene interaction database, several novel drug targets were identified.
Abstract 13425: Relationship Between Social Vulnerability and Case Fatality Rate at the Level of Counties and County-Equivalents in the Contiguous United States During the COVID-19 Pandemic
Authors: Sohini Mukherjee, Deblina Mukherjee
Journal: Circulation (2021)

Introduction: Pandemics prior to the COVID-19 pandemic have been known to disproportionately affect counties and county-equivalents with high social vulnerability. Social vulnerability refers to the potential negative effects on communities caused by external stresses on human health. Such stresses include natural or human-caused disasters, or disease outbreaks. On the other hand, case fatality rate estimates the proportion of deaths among identified confirmed cases. Hypothesis: A higher social vulnerability is associated with a higher case fatality rate at the levels of counties and county-equivalents in the contiguous United States during the COVID-19 pandemic. Methods: Data from 2990 counties and county-equivalents such as independent cities, districts, and parishes that are considered county-equivalents for census purposes was analyzed. Counties and county-equivalents from the non-contiguous states of Alaska and Hawaii were excluded as well as 59 counties and county-equivalents without available SVI data and/or available CFR data. Available SVI public source data was collected from the Centers for Disease Control and Prevention, while available CFR public source data was collected from the Emory Clinical Cardiovascular Research Institute. Results: Median SVI was 0.5185 [Range: 0.0006-1] and median CFR was 1.56% [Range: 0%-8.77%]. A vaccination rate ratio (RR) and 95% CI for SVI was calculated using Wald’s unconditional maximum likelihood estimation to compare CFRs of counties and county-equivalents with low social vulnerability (SVI: 0%-33%), moderate social vulnerability (33%-66%), and high social vulnerability (66%-100%). A higher SVI was associated with a higher CFR such that the RR for relative differences in CFR between counties and county-equivalents with a low social vulnerability and counties and county-equivalents with a high social vulnerability was 0.83, while the RR for relative differences in CFR between counties and county-equivalents with a moderate social vulnerability and counties and county-equivalents with a high social vulnerability was 0.89. Conclusions: Public policy interventions need to target counties and county-equivalents with a higher social vulnerability to help the most vulnerable of people.
Comparison of Salvage Autologous Hematopoietic Cell Transplantation with Outcomes Following Selinexor Combinations Among Double/Triple Refractory Myeloma Patients
Authors: Guldane Cengiz, Bulent Karakaya, Hulya Yilmaz, Derya Koyun, Ekin Kircali, Sevgi Basboga, Selami Kocak Toprak, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Pervin Topcuoglu, Gunhan Gurman, Trinayan Kashyap, James Niblock, Meral Beksac
Journal: Blood (2021)
Abstract 11002: Assessing Widening Disparities in Hba1c and Systolic Blood Pressure Re-Testing During the Covid-19 Pandemic in LGBTQ+ Focused Federally Qualified Health Centers in Chicago
Authors: Adovich Rivera, Megan Plank, Matthew J Feinstein, Laura Rusie, Lauren B Beach
Journal: Circulation (2021)

Introduction: The COVID-19 pandemic caused disruptions in the health services delivery, especially among vulnerable populations. We assessed if the pandemic widened disparities in care for cardiometabolic conditions in a LGBTQ+-focused federally qualified health system in Chicago. Hypothesis: Disparities in monitoring cardiometabolic conditions present in 2019 worsened in 2020. Methods: We analyzed electronic health records from Howard Brown Health. We assessed HbA1c re-testing and control (≤9%) in 2019 and 2020 among people with diabetes (DM) and ≥1 HbA1c test in the prior year (2018 for 2019, 2019 for 2020) (n2019=818, n2020=1033). A similar assessment was done for hypertension (HTN) with systolic blood pressure (SBP) (n2019=2813, n2020=3660). Comparisons per demographic group per year were done using logistic regression adjusting for socio-demographic variables. Results: Re-testing rates declined from 2019 to 2020 for both HbA1c and SBP overall and across all groups. Adjusted analysis showed gay people with DM had higher rates of HbA1c re-testing than people of other sexual orientations in 2019 and experienced a significantly lower re-testing rate decline in 2020. Adjusted analysis for SBP showed that white (vs Hispanic) and straight (vs gay) people with HTN had lower SBP re-testing rates in 2019 and 2020. Rates of controlled SBP (&lt;140mmHg), but not HbA1c (≤9%), declined from 2019 to 2020. Adjusted analyses showed that straight (vs gay) patients had lower controlled HbA1c and SBP rates. Cis males (vs trans males) had lower controlled SBP and white (vs Asian/other) had lower controlled HbA1c. These disparities did not worsen in 2020. Conclusion: The pandemic had mixed impacts on cardiometabolic service disparities in a large LGBTQ+-focused health system. Disparities by sexual orientation for HbA1c widened during the pandemic. Similar worsening was not found for systolic blood pressure, nor for other demographic groups.
Abstract 12482: Exposure to Greenspace Reduces Blood Pressure and Attenuates the Association With Air Pollution in Tamil Nadu, India
Authors: Kevin J Lane, Flannery Black-Ingersoll, sadagopan thanikachalam, Mohan Thanikachalam
Journal: Circulation (2021)

Background: Globally, high systolic blood pressure (SBP) is a major cause for cardiovascular mortality. Air pollution affects SBP and diastolic blood pressure (DBP), but has not been studied in relation to greenness in rapidly urbanizing and polluted areas. Here we assess the association between long-term concentrations of ambient PM 2.5, greenness and blood pressure in the Population study of Urban, Rural, Semi-urban Endovascular disease and Holistic Intervention Study (PURSE-HIS) in Tamil Nadu, India. Methods: The study included 8080 randomly selected participants (mean age 42 years; 58% women). We measured greenness using MODIS satellite derived normalized difference vegetation index (NDVI) at 250 m 2 resolutions. We used modeled estimates of annual average PM 2.5 at 1 km 2 developed for Global Burden of Disease to assign to residences. Brachial SBP and DBP were assessed in the dominant arm and an average of three measurements was used in the analysis. The associations were examined using generalized linear regression models controlling for age, gender, waist circumference, physical activity, sodium intake, smoking, stress, and anxiety. Results: The PM 2.5 exposure estimates ranged from 18μg/m 3 to 35μg/m 3 in the study area. In independent multivariate models IQR increase in PM 2.5 (3.0 μg/m 3 ) was associated with a 5.5 mmHg (95%CI: 4.9, 6.2) change in SBP. Stratification of participants into greenness exposures of high, medium and low, showed markedly higher association of PM 2.5 with SBP when comparing those residing in low greenness areas (5.0 mmHg [95%CI: 3, 6.9]) to those in medium (3.7 mmHg [95%CI: 2.8, 4.6]) and high NDVI areas (1.1 mmHg [95%CI: -0.6, 2.8]). Conclusions: Greenness and PM 2.5 were associated with SBP and DBP independently, with significant modification of this association by greenness. Further studies are required to assess interaction between PM 2.5 and greenness on SBP.