tbuckley/cabot-search huggingface dataset:
Abstract 13477: Feasibility and Prognostic Value of Vasodilator Stress Perfusion Cardiovascular Magnetic Resonance in Patients With Atrial Fibrillation
Authors: Theo Pezel, Francesca Sanguineti, Marine Kinnel, Valentin Landon, Thomas Hovasse, Solenn Toupin, Philippe Garot, Thierry Unterseeh, Stephane Champagne, Yves Louvard, Marie Claude Morice, Jerome Garot
Journal: Circulation (2020)

Introduction: Because most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with atrial fibrillation (AF) is unknown. Hypothesis: To assess the feasibility and the prognostic value of vasodilator stress perfusion CMR in patients with AF. Methods: Between 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease (CAD) and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiogram before and after CMR. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR. Results: Of 639 patients (72±9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed the follow-up (median 5.1 years); 80 had a MACE. Stress CMR was well tolerated. Using Kaplan-Meier analysis, the presence of ischemia or LGE was associated with the occurrence of MACE (HR 7.56; 95% CI: 4.86-11.80 and HR 2.41; 95% CI: 1.55-3.74 respectively; for both p &lt;0.001). In a multivariable Cox regression including clinical and CMR indexes, the presence of ischemia or LGE was an independent predictor of MACE (HR 5.98; 95% CI: 3.68-9.73 and HR 2.61; 95% CI: 1.89-3.60 respectively; for both p &lt;0.001). Conclusions: In patients with AF, stress perfusion CMR is feasible, safe and has a good discriminative prognostic value to predict the occurrence of MACE.
Deconstructing tradition: Trans reproduction and the need to reform birth registration in England and Wales
Authors: Liam Davis
Journal: International Journal of Transgender Health (2020)

Background: Trans reproduction is often met with reproach when compared with the norm of the cisgender, heterosexual, nuclear family (referred to here as the 'traditional' family). This is notably seen in birth registration where a 'traditional' family is more likely to access, and agree with, the terms provided on the birth certificate (that is, 'mother' and 'father').Aims: This study aimed to explore the differential treatment between 'traditional' and trans families in England and Wales within birth registration in case law, legislation, and primary research.Methods: Case law and legislation were analyzed to identify any differential treatment within birth registration, particularly how parental statuses are ascribed. An online survey (with 310 responses) was conducted, seeking views on constructions of 'mothers', respondents' reactions to trans families, and understandings of sex/gender and parenthood generally.Results: Themes developed from the survey data focused on the significance of the 'traditional' family as the optimal structure, manifesting in the need to ensure 'coherency and certainty' of the birth registration system regarding how parents should be registered. This need for coherency and certainty functioned to undermine trans families (who were presumed to be discreet about their child's conception), and also raised concerns that the child might not be able to locate their (biogenetic) 'origins'.Discussion: The paper concludes by discussing the implications of the research for the acceptance of trans families in law and society, and suggests the need to unmoor the birth registration system from its (cis-hetero)normative underpinnings, allowing trans parents to be registered as they wish on the birth certificate.
Cirrhosis and Severe Acute Respiratory Syndrome Coronavirus 2 Infection in US Veterans: Risk of Infection, Hospitalization, Ventilation, and Mortality
Authors: George N. Ioannou, Peter S. Liang, Emily Locke, Pamela Green, Kristin Berry, Ann M. O’Hare, Javeed A. Shah, Kristina Crothers, McKenna C. Eastment, Vincent S. Fan, Jason A. Dominitz
Journal: Hepatology (2020)

Background and Aims Whether patients with cirrhosis have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and the extent to which infection and cirrhosis increase the risk of adverse patient outcomes remain unclear. Approach and Results We identified 88,747 patients tested for SARS‐CoV‐2 between March 1, 2020, and May 14, 2020, in the Veterans Affairs (VA) national health care system, including 75,315 with no c irrhosis– S ARS‐CoV‐2‐negative (C0‐S0), 9,826 with no cirrhosis–SARS‐CoV‐2‐positive (C0‐S1), 3,301 with cirrhosis–SARS‐CoV‐2‐negative (C1‐S0), and 305 with cirrhosis–SARS‐CoV‐2‐positive (C1‐S1). Patients were followed through June 22, 2020. Hospitalization, mechanical ventilation, and death were modeled in time‐to‐event analyses using Cox proportional hazards regression. Patients with cirrhosis were less likely to test positive than patients without cirrhosis (8.5% vs. 11.5%; adjusted odds ratio, 0.83; 95% CI, 0.69‐0.99). Thirty‐day mortality and ventilation rates increased progressively from C0‐S0 (2.3% and 1.6%) to C1‐S0 (5.2% and 3.6%) to C0‐S1 (10.6% and 6.5%) and to C1‐S1 (17.1% and 13.0%). Among patients with cirrhosis, those who tested positive for SARS‐CoV‐2 were 4.1 times more likely to undergo mechanical ventilation (adjusted hazard ratio [aHR], 4.12; 95% CI, 2.79‐6.10) and 3.5 times more likely to die (aHR, 3.54; 95% CI, 2.55‐4.90) than those who tested negative. Among patients with SARS‐CoV‐2 infection, those with cirrhosis were more likely to be hospitalized (aHR, 1.37; 95% CI, 1.12‐1.66), undergo ventilation (aHR, 1.61; 95% CI, 1.05‐2.46) or die (aHR, 1.65; 95% CI, 1.18‐2.30) than patients without cirrhosis. Among patients with cirrhosis and SARS‐CoV‐2 infection, the most important predictors of mortality were advanced age, cirrhosis decompensation, and high Model for End‐Stage Liver Disease score. Conclusions SARS‐CoV‐2 infection was associated with a 3.5‐fold increase in mortality in patients with cirrhosis. Cirrhosis was associated with a 1.7‐fold increase in mortality in patients with SARS‐CoV‐2 infection.
Eusociality Shapes Convergent Patterns of Molecular Evolution across Mitochondrial Genomes of Snapping Shrimps
Authors: Solomon T C Chak, Juan Antonio Baeza, Phillip Barden
Journal: Molecular Biology and Evolution (2020)

Eusociality is a highly conspicuous and ecologically impactful behavioral syndrome that has evolved independently across multiple animal lineages. So far, comparative genomic analyses of advanced sociality have been mostly limited to insects. Here, we study the only clade of animals known to exhibit eusociality in the marine realm-lineages of socially diverse snapping shrimps in the genus Synalpheus. To investigate the molecular impact of sociality, we assembled the mitochondrial genomes of eight Synalpheus species that represent three independent origins of eusociality and analyzed patterns of molecular evolution in protein-coding genes. Synonymous substitution rates are lower and potential signals of relaxed purifying selection are higher in eusocial relative to noneusocial taxa. Our results suggest that mitochondrial genome evolution was shaped by eusociality-linked traits-extended generation times and reduced effective population sizes that are hallmarks of advanced animal societies. This is the first direct evidence of eusociality impacting genome evolution in marine taxa. Our results also strongly support the idea that eusociality can shape genome evolution through profound changes in life history and demography.
Abstract 17329: Characterizing Disparities Among Frail Cardiovascular Patients
Authors: Gloria Y Kim, Arati A Gangadharan, Chloe Powell, Matthew Corriere
Journal: Circulation (2020)

Introduction: Frailty is associated with increased risk of adverse health events among cardiovascular patients. Phenotype-based approaches to frailty assessment typically rely upon sex and body mass index as co-variables. Hypothesis: We hypothesized that race, ethnicity, disadvantaged community index (DCI), and health insurance coverage are associated with frailty. To test this hypothesis, we prospectively measured grip strength in a cohort of cardiovascular patients and evaluated the relationships of frailty with disparity measures. Methods: Patients treated in outpatient cardiovascular center clinics were evaluated for frailty using dominant hand grip strength. Grip strength, adjusted by gender and BMI, were used to determine frailty. Insurance status was categorized as Private, Medicaid, or Medicare based on primary coverage. Frailty was then evaluated stratified by DCI and health insurance status. Associations were evaluated using multivariable models. Results: Over 10 months, 3,986 patient grips were measured. Of these, 34.9% (n=1,392) were considered frail. Mean age was 63.5±15.6 years and 47.3% (n=1,885) were female. African American/black made up 7.73% (n=308) of the cohort and Asians/Pacific Islander 2.13% (n=85). A third of patients (32.7%) had private insurance, 2,187 (54.9%) had Medicare, and 291 (7.3%) had Medicaid. The average DCI score was 35.3±27.6. Patients with Medicare had the highest prevalence of frailty (47.4% versus 17.0% for Private Insurance and 26.5% for Medicaid; P&lt;0.001). Individuals living in distressed communities were more likely to be frail (39.3% versus 34.4%; P=0.04). Furthermore, patients of Asian backgrounds are most likely to be frail (49.4% versus 34.2% among whites; P=0.01). Conclusions: When assessing insurance status related to frailty, frailty incidence was highest among patients with Medicaid insurance status. Further, age, race, insurance status, and distressed community index are associated with frailty defined by grip strength among cardiovascular patients. There may be a large segment of at-risk individuals who are missed because they do not fit the well characterized variables associated with frailty, including older age, female gender, both high and low BMI, and functional decline.
Abstract 13669: Slow Conduction Zone of Left Atrium is a Precursor to Low Voltage Area in Patients With Atrial Fibrillation
Authors: Hideyuki Kishima, Takanao Mine, Ryo Kitagaki, Eiji Fukuhara, Masaharu Ishihara
Journal: Circulation (2020)

Introduction: The slow conduction zone (SCZ) in the left atrium (LA) has attracted attention as an arrhythmia substrate of atrial fibrillation (AF). However, the occurrence mechanism of SCZ remains unclear. Hypothesis: The SCZ is related to the low voltage area (LVA) or the LA anatomical contact areas (CoAs) with other organs in patients with AF. Methods: We studied 100 patients (49 non-paroxysmal AF, 66 males, 67.9 ± 9.9 years) who received catheter ablation for AF. High-density LA mapping during right atrial appendage pacing at a rate of 100 bpm after pulmonary vein isolation were constructed. Isochronal activation maps were created at 5-ms interval setting, and the SCZ was identified on the activation map by finding a site with isochronal crowding of ≥3 isochrones, which are calculated as ≤27 cm/s (Figure). The LVA was defined as the following; mild (&lt;1.3 mV), moderate (&lt;1.0 mV), and severe LVA (&lt;0.5 mV). The CoAs (ascending aorta-anterior LA, descending aorta-posterior LA, and vertebrae-posterior LA) were assessed using computed tomography. Results: The SCZ was distributed linearly (Figure), and observed in 95 of 100 patients (95%). The SCZ was most frequently observed in the anterior wall region (77%). A longer SCZ was significantly associated with a larger LA size and a prevalence of non-PAF. The 51.2±36.2% of SCZ overlapped with mild LVA, 32.9±32.8% of SCZ with moderate LVA, and 14.6±22.0% of SCZ with severe LVA. In contrast, only 25.6±28.0 % of SCZ matched with the CoAs. Conclusion: The slow conduction zone reflects LA electrical remodeling and may be a precursor finding of the low voltage zone, not LA contact areas in patients with atrial fibrillation.
Abstract 17195: Raas Modulation Through ARNI Therapy but Not ACE-Inhibitor Therapy Improves Cardiac Systolic Function and Cardiac Aerobic Functional Capacity in Patients With HFrEF
Authors: Avinash K Pandey, Jennifer Reinhart, A. Shekhar Pandey, Subodh Verma
Journal: Circulation (2019)

Introduction: Heart Failure with reduced ejection fraction (HFrEF) carries a high risk of mortality and hospitalization. Exercise capacity/aerobic fitness & ejection fraction have both been shown t...
Abstract 14736: Aquaporin 1 Modulates H <sub>2</sub> o <sub>2</sub> -mediated Endothelial Inflammaging
Authors: Seyed Soheil Saeedi Saravi
Journal: Circulation (2020)

Background: Aquaporin 1 (AQP1), a key regulator of endothelial cell function, transports hydrogen peroxide (H 2 O 2 ) into the cells. H 2 O 2 -mediated inflammation has been implicated in endothelial dysfunction, yet specific roles of AQP1-mediated signaling pathways underlying age-dependent endothelial dysfunction remains incompletely understood. Methods: In these studies, we dissected AQP1-regulated inflammation modulation of eNOS signaling pathways in human aortic endothelial cells (HAEC) from passages 5 to 15 by exploiting siRNA approaches, live cell fluorescence imaging with genetically-encoded H 2 O 2 biosensor HyPer, biochemical and in vitro endothelial function assays. Results: We discovered that AQP1 expression remarkably increases in senescent HAEC (P.15) in association with significant increased SA-βgal activity compared to young cells (P.5). H 2 O 2 levels were increased in senescent cell cytosol revealed by fluorescence HyPer imaging. We found that senescence-associated increase in AQP1-mediated H 2 O 2 led to enhanced TNF-α, unlike HO-1, transcription (p&lt;0.01). Moreover, immunofluorescence assay documented that AQP1 gene knock-down significantly ameliorated senescence-associated elevation of adhesion molecule ICAM-1. Immunoblot analyses demonstrated that increased AQP1 protein levels in senescent HAEC leads to significant increase in caveolin-1 phosphorylation (2-fold) and decreases in phosphorylation of AMPK (Thr172; 4-fold) and eNOS (Ser1177; 2-fold) compared to young ECs (for each, p&lt;0.05, n&gt;6). We discovered that AQP1 knock-down improved the reduced angiogenesis and wound healing capacity in association with eNOS down-regulation in senescent endothelial cells. Conclusion: These results establish that AQP1 plays a crucial role in the regulation of H 2 O 2 -mediated inflammation-associated endothelial senescence, and AQP1 deletion improves endothelial dysfunction by ameliorating ROS-modulated inflammaging.
Abstract 13666: The Association of White Blood Cell Count and Bleeding in Acute Coronary Syndrome: An Insight Into the Atlas ACS-TIMI 51 Trial
Authors: Fahad Alkhalfan, Tarek Nafee, Megan Yee, Gerald C Chi, Arzu Kalayci, Alexei Plotnikov, Eugene Braunwald, C. Michael Gibson
Journal: Circulation (2019)

Introduction: An elevated white blood cell (WBC) count is associated with an increased risk of ischemic events among acute coronary syndrome (ACS) patients, but the association between WBC count an...
Abstract 15838: Atrial Natriuretic Peptide Compensatory Response is Impaired in Human Acute Decompensated Heart Failure
Authors: Shawn H Reginauld, Jeson Sangaralingham, Seethalakshmi R Iyer, John C BURNETT
Journal: Circulation (2020)

Atrial and B-type natriuretic peptides (ANP and BNP) are cardiac hormones secreted as compensatory measures to preserve cardiorenal homeostasis. Treating heart failure (HF) with sacubitril/valsartan increased ANP and not BNP, suggesting the ANP system may confer therapeutic benefit. Thus, the presence of an ANP deficient subgroup of HF patients possibly posing higher risk for HF severity, underscores a need to characterize both, the biologically active and inactive (NT-proANP and NT-proBNP) natriuretic peptides (NPs)(latter resistant to degradation), to highlight the extent of NP production in HF. Characterizing neprilysin (NEP) activity may also provide insights into the degree of NP degradation in HF. This study aims to both highlight the cardiac NP response in acute decompensated HF(ADHF) by measuring molecular forms of ANP and BNP together with defining circulating soluble NEP activity as to assess mechanisms impairing the NP response in HF. We recruited 47 healthy individuals with neither cardiovascular nor metabolic disease and compared ANP, BNP, NT-proANP, NT-proBNP, and NEP activity levels with 107 recruited ADHF patients. In ADHF, compared to a healthy setting, median ANP, BNP, NT-proANP, and NT-proBNP were all elevated (15.7 vs. 118.1 pg/mL , p&lt;0.0001; 23 vs. 515 pg/ml, p&lt;0.0001; 60.1 vs. 651.6 pg/mL, p&lt;0.0001; 46 vs. 3330 pg/mL, p&lt;0.0001, respectively). However, circulating NEP activity was significantly lower in ADHF than in healthy circulation (32 vs. 12.3 nM/mL/min, p&lt;0.0001). NPs did not correlate with NEP activity in healthy circulation. However, only ANP (r = 0.4788, p&lt;0.0001) and NT-proANP (r = 0.6819, p&lt;0.0001) correlated with NEP activity in ADHF. The presence of an impaired ANP response in ADHF, underscored by insufficient increases in NT-proANP than NT-proBNP, suggests decreased ANP production may induce not only an ANP deficient ADHF state, but be characteristic of ADHF. The presence of NEP activity in ADHF circulation, despite lower NEP activity compared to healthy individuals, suggests ANP degradation may second impaired production, further lowering ADHF ANP levels. Our studies support augmenting the ANP system in ADHF through either endogenous stimulation or exogenous supplementation as optimal therapeutic strategies.
Abstract 14975: Increased Morbidity and Mortality in Patients With Hypoplastic Left Heart Syndrome and Genetic Abnormalities
Authors: Alyson R Pierick, Trudy A Pierick, Benjamin E Reinking
Journal: Circulation (2020)

Introduction: Hypoplastic left heart syndrome (HLHS) is a genetically heterogenous, severe form of congenital heart disease. Hypothesis: Patients with reported genetic abnormalities will have worse outcomes than those without reported genetic abnormalities. Methods: This was a retrospective review of patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) phase I registry. Registry enrollment occurred at discharge following stage 1 palliation. Patients were placed into one of three groups: major syndromes (Turner, Down, CHARGE, DiGeorge, Jacobsen, VATER, heterotaxy), other genetic abnormality, or no reported genetic abnormality. Demographic and clinical variables were compared using Pearson Chi-square, one-way ANOVA, or Kruskal-Wallis test. Tukey post-hoc test was applied to adjust p-values for pairwise group comparisons. Outcomes of length of stay, death, and combined outcomes of death, not a candidate for stage 2 palliation and transplant were compared among the groups. Results: Of the 2182 patients, major syndromes were reported in 110 (5%), other genetic abnormalities in 126 (5.8%) and no abnormalities in 1946 (89.2%). Those with major syndromes weighed less at birth and the time of stage I palliation, were more likely to be female and have a primary cardiac diagnosis of unbalanced AVC. Those with major syndromes or other genetic abnormalities were more likely to have moderate to severe AV valve regurgitation, moderate to severe ventricular dysfunction, arrhythmia requiring therapy, and major anomalies of other organ systems compared to those with no abnormalities. Patients with no reported genetic abnormalities reached full oral feeds sooner after the Norwood (19 vs 24 days), were more likely to be discharged on all oral feeds (75% vs 59% and 62%) and were discharged earlier (35 vs 45 and 43 days). For the outcome of death, there was no significant difference among the groups. The combined outcome of death, not a candidate for stage 2 palliation, and heart transplant was more likely in those with a major syndrome after adjusting for covariates. Conclusions: Patients with HLHS and major syndromes or other genetic abnormalities experience greater morbidity and mortality during the interstage period.
Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation
Authors: Jason G. Andrade, George A. Wells, Marc W. Deyell, Matthew Bennett, Vidal Essebag, Jean Champagne, Jean-Francois Roux, Derek Yung, Allan Skanes, Yaariv Khaykin, Carlos Morillo, Umjeet Jolly, Paul Novak, Evan Lockwood, Guy Amit, Paul Angaran, John Sapp, Stephan Wardell, Sandra Lauck, Laurent Macle, Atul Verma
Journal: New England Journal of Medicine (2020)

Guidelines recommend a trial of one or more antiarrhythmic drugs before catheter ablation is considered in patients with atrial fibrillation. However, first-line ablation may be more effective in maintaining sinus rhythm. We randomly assigned 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation to undergo catheter ablation with a cryothermy balloon or to receive antiarrhythmic drug therapy for initial rhythm control. All the patients received an implantable cardiac monitoring device to detect atrial tachyarrhythmia. The follow-up period was 12 months. The primary end point was the first documented recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. The secondary end points included freedom from symptomatic arrhythmia, the atrial fibrillation burden, and quality of life. At 1 year, a recurrence of atrial tachyarrhythmia had occurred in 66 of 154 patients (42.9%) assigned to undergo ablation and in 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66; P<0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received antiarrhythmic drugs (hazard ratio, 0.39; 95% CI, 0.22 to 0.68). The median percentage of time in atrial fibrillation was 0% (interquartile range, 0 to 0.08) with ablation and 0.13% (interquartile range, 0 to 1.60) with antiarrhythmic drugs. Serious adverse events occurred in 5 patients (3.2%) who underwent ablation and in 6 patients (4.0%) who received antiarrhythmic drugs. Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).
Inhibition of CpG methylation improves the barrier integrity of bronchial epithelial cells in asthma
Authors: Paulina Wawrzyniak, Krzysztof Krawczyk, Swati Acharya, Ge Tan, Marcin Wawrzyniak, Emmanuel Karouzakis, Anita Dreher, Bogdan Jakiela, Can Altunbulakli, Marek Sanak, Liam O‘Mahony, Kari Nadeau, Cezmi A. Akdis
Journal: Allergy (2020)

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