tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors
Authors: Alina S. Shomuradova, Murad S. Vagida, Savely A. Sheetikov, Ksenia V. Zornikova, Dmitry Kiryukhin, Aleksei Titov, Iuliia O. Peshkova, Alexandra Khmelevskaya, Dmitry V. Dianov, Maria Malasheva, Anton Shmelev, Yana Serdyuk, Dmitry V. Bagaev, Anastasia Pivnyuk, Dmitrii S. Shcherbinin, Alexandra V. Maleeva, Naina T. Shakirova, Artem Pilunov, Dmitry B. Malko, Ekaterina G. Khamaganova, Bella Biderman, Alexander Ivanov, Mikhail Shugay, Grigory A. Efimov
Journal: Immunity (2020)
Abstract 13740: Validation of Paris Risk Score to Predict Long-term Bleeding Events After Percutaneous Coronary Intervention in Japanese Population
Authors: Takeshi Shimizu, Takuya Ando, Joh Akama, Fumiya Anzai, Yuki Muto, Yusuke KIMISHIMA, Takatoyo Kiko, Akiomi YOSHIHISA, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2020)

Introduction: It has been reported that East Asian people have higher bleeding risks than Western people. The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score was developed to estimate the bleeding risk after percutaneous coronary intervention (PCI). However, the utility of PARIS bleeding score for predicting long-term bleeding risks has not been validated in Japanese population. Methods: Consecutive 1061 patients who underwent PCI and survived to discharge were divided into three groups based on the category of PARIS bleeding risk score: low risk group (0-3 risk points), intermediate risk group (4-7 risk points) and high risk group (8-15 risk points), then we compared patient characteristics and followed bleeding events. Results: The numbers of patients at low, intermediate and high risk groups were 113 (10.7%), 420 (39.6%) and 528 (49.8%), respectively. Clinical characteristics for three groups were as follows: atrial fibrillation (low, intermediate and high risk groups; 8.2%, 8.9% and 21.6%, P &amp;lt 0.001, respectively), peripheral artery disease (3.1%, 9.1% and 22.1%, P &amp;lt 0.001), coronary multi-vessel disease (38.9%, 44.3% and 54.4%, P = 0.001), use of statin (97.3%, 89.6% and 71.7%, P &amp;lt 0.001) and proton-pump inhibitors (69.1%, 72.5%, and 78.9%, P = 0.02). Among 1061 patients, a total of 74 bleeding events were occurred during the follow-up period (mean of 1742 days). In the Kaplan-Meier analysis, the cumulative incidence of bleeding events significantly increased from low risk group to intermediate and high risk group (P &amp;lt 0.001). The risk score showed a significant prognostic value in predicting bleeding events (area under the receiver operating characteristic curve, 0.674; 95% confidence interval, 0.615-0.733). Conclusions: The PARIS bleeding risk score successfully stratified the long-term bleeding risk in patients with coronary artery disease after PCI in Japanese population.
Effect of School-Based Body Mass Index Reporting in California Public Schools
Authors: Kristine A. Madsen, Hannah R. Thompson, Jennifer Linchey, Lorrene D. Ritchie, Shalika Gupta, Dianne Neumark-Sztainer, Patricia B. Crawford, Charles E. McCulloch, Ana Ibarra-Castro
Journal: JAMA Pediatrics (2020)

Annually, US schools screen millions of students' body mass index (BMI) and report the results to parents, with little experimental evidence on potential benefits and harms.To determine the impact of school-based BMI reporting on weight status and adverse outcomes (weight stigmatization and weight-related perceptions and behaviors) among a diverse student population.Cluster randomized clinical trial. The Fit Study (2014-2017) randomized 79 California schools to BMI screening and reporting (group 1), BMI screening only (group 2), or control (no BMI screening or reporting [group 3]) in grades 3 to 8. The setting was California elementary and middle schools. Students in grades 3 to 7 at baseline participated for up to 3 years. A modified intent-to-treat protocol was used. Data analysis was conducted from April 13, 2017, to March 26, 2020.School staff assessed BMI each spring among students in groups 1 and 2. Parents of students in group 1 were sent a BMI report each fall for up to 2 years.Changes in BMI z score and in adverse outcomes (based on surveys conducted each fall among students in grades 4 to 8) from baseline to 1 and 2 years of follow-up.A total of 28 641 students (14 645 [51.1%] male) in grades 3 to 7 at baseline participated in the study for up to 3 years. Among 6534 of 16 622 students with a baseline BMI in the 85th percentile or higher (39.3%), BMI reporting had no effect on BMI z score change (-0.003; 95% CI, -0.02 to 0.01 at 1 year and 0.01; 95% CI, -0.02 to 0.03 at 2 years). Weight dissatisfaction increased more among students having BMI screened at school (8694 students in groups 1 and 2) than among control participants (5674 students in group 3). Results of the effect of BMI reporting on other adverse outcomes were mixed: compared with the control (group 3), among students weighed at school (groups 1 and 2), weight satisfaction declined more after 2 years (-0.11; 95% CI, -0.18 to -0.05), and peer weight talk increased more after 1 year (0.05; 95% CI, 0.01-0.09); however, concerning weight control behaviors declined more after 1 year (-0.06; 95% CI, -0.10 to -0.02).Body mass index reports alone do not improve children's weight status and may decrease weight satisfaction. To improve student health, schools should consider investing resources in evidence-based interventions.ClinicalTrials.gov Identifier: NCT02088086.
Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis
Authors: Christian Nitsche, Paul R. Scully, Kush P. Patel, Andreas A. Kammerlander, Matthias Koschutnik, Carolina Dona, Tim Wollenweber, Nida Ahmed, George D. Thornton, Andrew D. Kelion, Nikant Sabharwal, James D. Newton, Muhiddin Ozkor, Simon Kennon, Michael Mullen, Guy Lloyd, Marianna Fontana, Philip N. Hawkins, Francesca Pugliese, Leon J. Menezes, James C. Moon, Julia Mascherbauer, Thomas A. Treibel
Journal: Journal of the American College of Cardiology (2020)

Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR).This study identified clinical characteristics and outcomes of AS-CA compared with lone AS.Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality.A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36).Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.
Abstract 15821: Patients With Amyloid Cardiomyopathy Who Receive Durable Mechanical Circulatory Support Are at Increased Risk for Mortality and Early Adverse Events
Authors: Katherine C Michelis, Lin Zhong, Wai Hong W Tang, James B Young, Mark H Drazner, Lori R Roth, Matthias PELTZ, Ambarish Pandey, Jan Griffin, Mathew S Maurer, Justin L Grodin
Journal: Circulation (2020)

Introduction: Amyloid cardiomyopathy (ACM) is recognized increasingly as a cause of advanced heart failure. There are limited data describing clinical outcomes for ACM patients who receive durable mechanical circulatory support (MCS). Methods: This analysis included adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with a primary diagnosis of dilated cardiomyopathy (DCM, N=19,921), non-amyloid restrictive cardiomyopathy (RCM, N=248), or ACM (N=48) who received durable MCS of any type or strategy from 2005-2017. We compared baseline characteristics and adverse events for the 3 groups. The primary endpoint was death with heart transplantation as a competing risk with follow-up censored at device explantation. Results: Patients with ACM (N=48) were older (61 y [IQR 55-69] versus 58 y [IQR 49-66] for DCM and 55 y [IQR 46-62] for non-amyloid RCM, P&lt;0.001), and more likely to be male (85% versus 79% for DCM and 63% for non-amyloid RCM, P&lt;0.001) and INTERMACS profile 1 (30% versus 18% for DCM and 21% for non-amyloid RCM, P=0.04) at implant. Use of biventricular support (concomitant left and right ventricular assist devices or total artificial heart) was highest in the ACM group (41% versus 7% and 19% for DCM and non-amyloid RCM groups, respectively, P&lt;0.001). ACM patients experienced a higher frequency of major bleeding (48% versus 29% for DCM and 34% for non-amyloid RCM, P=0.005), neurologic dysfunction (22% versus 10% for DCM and 14% for non-amyloid RCM, P=0.006), and renal dysfunction (20% versus 10% for DCM and 17% for non-amyloid RCM, P&lt;0.001) within 3 months. Risk of death at a median follow-up of 1 year was highest for the ACM group compared to DCM and non-amyloid RCM (Log-rank, P=0.014). Conclusion: Compared to DCM or non-amyloid RCM patients, those with durable MCS for ACM have the highest risk of early adverse events and lowest survival. These data highlight concerns with durable MCS for ACM.
Abstract 17264: Predictive Value of Plasma Ceramide C24:0/C16:0 Ratio in Patients With Heart Failure With Preserved Ejection Fraction in the TOPCAT Study
Authors: Linda R Peterson, Xuntian Jiang, Hannah Campbell, Sharon Cresci
Journal: Circulation (2020)

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is an “emerging epidemic” as nearly half of all patients with HF have HFpEF. However, most HF biomarkers, including plasma brain natriuretic peptide, have less robust utility in HFpEF than in those with HF with reduced ejection fraction. In order to better understand HFpEF and its associated morbidity and mortality, it is vital to identify robust biomarkers that predict outcomes in patients who suffer from HFpEF. Ceramides are bioactive lipids involved in signaling, cell death programs, mitochondrial function, and cell structure. Our group showed that the ratio of specific plasma ceramides (C24:0/C16:0) is inversely related to primary incident HF and to death in large community-based cohorts. Whether plasma C24:0/C16:0 has utility in prediction of secondary events/outcomes in patients with HFpEF is unclear. Hypothesis: We hypothesized that there is an association between plasma C24:0/16:0 ratio and outcomes in HFpEF. Methods: Data and plasma was obtained from 477 subjects in the TOPCAT study via the BioLINCC biobank. Plasma ceramides C24:0 and C16:0 were measured using targeted liquid chromatograph/tandem mass spectrometry. Results: Inclusion criteria for TOPCAT was age &gt;50 years, ejection fraction of 45% or higher and diagnosis of HF. Subjects were randomized to treatment with spironolactone or placebo. In the 477 subjects who provided samples to BioLINCC, the mean age was 69.3 years; 47% were women; 43.9% were from the United States; 94.4% had hypertension; 31 were African American. Mean follow-up was 3.3 years. Univariate analysis showed that time to hospitalization for heart failure was inversely related to plasma C24:0/C16:0 concentration (Hazard ratio 0.901 [Confidence bounds 0.82,0.99], P = 0.026. Conclusions: Plasma ceramide (C24:0/C16:0) is inversely related to time to hospitalization in patients with HFpEF. Plasma C24:0/C16:0 may be a useful new biomarker in HFpEF and may point to novel, targetable pathophysiologic pathways .
Abstract 14359: Single Nucleotide Polymorphisms in Genes Involved in L-arginine / Dimethylarginine Metabolism Predispose for Pulmonary Hypertension and Acute Mountain Sickness at High Altitude
Authors: Juliane Hannemann, Julia Zummack, PATRICIA SIQUES, JULIO BRITO, Rainer Boeger
Journal: Circulation (2020)

Introduction: Chronic (CH) and chronic-intermittent (CIH) exposure to hypoxia at high altitude causes acute or chronic mountain sickness and elevation of mean pulmonary arterial pressure (mPAP). This is paralleled by increased plasma levels of ADMA, an endogenous inhibitor of NO synthesis. ADMA is cleaved by dimethylarginine dimethylaminohydrolase (DDAH1 and DDAH2), whilst symmetric dimethylarginine (SDMA) is cleaved by AGXT2. Arginase (ARG1 and ARG2) competes with endothelial NO synthase (NOS3) for L-arginine as substrate. We have shown previously that baseline ADMA (at sea level) determines mPAP after six months of CIH; cut-off values of 25 mm Hg and 30 mm Hg are being used to diagnose high altitude pulmonary hypertension. Hypothesis: We hypothesized that genetic variability in genes coding for core enzymes of ADMA, SDMA, and L-arginine metabolism may predispose individuals for high altitude disease and pulmonary hypertension. Methods: We genotyped 16 common single nucleotide polymorphisms in the NOS3, DDAH1, DDAH2, AGXT2, ARG1 and ARG2 genes of 69 healthy male Chilean subjects. Study participants adhered to a CIH regimen (5d at 3,550m, 2d at sea level) for six months. Metabolites were measured by LC-MS/MS; mPAP was estimated by echocardiography at six months, and altitude acclimatization was assessed by Lake Louise Score and arterial oxygen saturation. Results: Carriers of the minor allele of DDAH1 rs233112 had a higher mean baseline ADMA level (0.76±0.03 vs. 0.67±0.02 μmol/l; p&lt;0.05), whilst the major allele of DDAH2 rs805304 was linked to an exacerbated increase of ADMA in hypoxia (0.10±0.03 vs. 0.04±0.04 μmol/l; p&lt;0.02). Study participants carrying the minor allele of ARG1 rs2781667 had a relative risk of elevated mPAP (&gt;25 mm Hg) of 1.70 (1.56-1.85; p&lt;0.0001), and carriers of the minor allele of NOS3 rs2070744 had a relative risk of elevated mPAP (&gt;30 mm Hg) of 1.58 (1.47-1.69; p&lt;0.0001). The NOS3 and DDAH2 genes were associated with the incidence of acute mountain sickness. Conclusions: We conclude that genetic variability in the L-arginine / ADMA / NO pathway is an important determinant of high altitude pulmonary hypertension and acute mountain sickness. DDAH1 is linked to baseline ADMA, whilst DDAH2 determines the response of ADMA to hypoxia.
The other face of advanced paternal age: a scoping review of its terminological, social, public health, psychological, ethical and regulatory aspects
Authors: Vincent Couture, Stéphane Delisle, Alexis Mercier, Guido Pennings
Journal: Human Reproduction Update (2020)

Abstract BACKGROUND There is a global tendency for parents to conceive children later in life. The maternal dimension of the postponement transition has been thoroughly studied, but interest in the paternal side is more recent. For the moment, most literature reviews on the topic have focused on the consequences of advanced paternal age (APA) on fertility, pregnancy and the health of the child. OBJECTIVE AND RATIONALE The present review seeks to move the focus away from the biological and medical dimensions of APA and synthesise the knowledge of the other face of APA. SEARCH METHODS We used the scoping review methodology. Searches of interdisciplinary articles databases were performed with keywords pertaining to APA and its dimensions outside of biology and medicine. We included scientific articles, original research, essays, commentaries and editorials in the sample. The final sample of 177 documents was analysed with qualitative thematic analysis. OUTCOMES We identified six themes highlighting the interdisciplinary nature of APA research. The ‘terminological aspects’ highlight the lack of consensus on the definition of APA and the strategies developed to offer alternatives. The ‘social aspects’ focus on the postponement transition towards reproducing later in life and its cultural dimensions. The ‘public health aspects’ refer to attempts to analyse APA as a problem with wider health and economic implications. The ‘psychological aspects’ focus on the consequences of APA and older fatherhood on psychological characteristics of the child. The ‘ethical aspects’ reflect on issues of APA emerging at the intersection of parental autonomy, children’s welfare and social responsibility. The ‘regulatory aspects’ group different suggestions to collectively approach the implications of APA. Our results show that the field of APA is still in the making and that evidence is lacking to fully address the issues of APA. The review suggests promising avenues of research such as introducing the voice of fathers of advanced age into the research agenda. WIDER IMPLICATIONS The results of this review will be useful for developing policies and preconception health interventions that consider and include prospective fathers of advanced age.
Impact of Gastric Electrical Stimulation on Economic Burden of Refractory Vomiting: A French Nationwide Multicentre Study
Authors: Guillaume Gourcerol, Benoit Coffin, Bruno Bonaz, Hélène Hanaire, Stanislas Bruley Des Varannes, Frank Zerbib, Robert Caiazzo, Jean Charles Grimaud, François Mion, Samy Hadjadj, Paul Valensi, Lucine Vuitton, Guillaume Charpentier, Alain Ropert, Romain Altwegg, Philippe Pouderoux, Etienne Dorval, Michel Dapoigny, Henri Duboc, Pierre Yves Benhamou, Aurélie Schmidt, Nathalie Donnadieu, Philippe Ducrotte, Bruno Guerci, Guillaume Gourcerol, Benoit Coffin, Bruno Bonaz, Helene Hanaire, Stanislas Bruley des Varannes, Frank Zerbib, Robert Caiazzo, Jean Charles Grimaud, Francois Mion, Samy Hadjadj, Paul Valensi, Lucine Vuitton, Guillaume Charpentier, Alain Ropert, Romain Altwegg, Philippe Pouderoux, Etienne Dorval, Michel Dapoigny, Henri Duboc, Pierre Yves Benhamou, Aurelie Schmidt, Nathalie Donadieu, Philippe Ducrotté, Bruno Guerci
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract 15441: Determining the Optimal Thresholds for Classifying Functional Mitral Regurgitation Severity by Cardiac Magnetic Resonance Imaging in Patients With Non-ischemic Cardiomyopathy
Authors: Tom Kai Ming Wang, Harry Choi, Duygu Kocyigit, Alex Milinovich, Jian Jin, Zoran B Popovic, Wai Hong W Tang, Samir R Kapadia, Brian P Griffin, Scott D Flamm, Deborah H Kwon
Journal: Circulation (2020)

Background: Functional mitral regurgitation (MR) grading by echocardiography is often challenging, and cardiac magnetic resonance (CMR) may provide more accurate and reproducible assessment, however optimal CMR thresholds have not been established. We aimed to determine clinically significant thresholds of MR-volume and MR-fraction by CMR in patients with non-ischemic cardiomyopathy (NICM). Methods: All patients having CMR with confirmed NICM between 2001/4/1-2019/3/31 were retrospectively studied. Time to death, heart transplant and/or left ventricular assist device is the primary endpoint, and receiver-operative (ROC) characteristics analyses were used to identify significant cut-points for MR-volume and MR-fraction. Results: Mean MR-volume was 11±12% and MR-fraction 14±13% in 840 NICM patients. C-statistics for the primary endpoint (141 events) were MR-volume 0.629 (95%CI: 0.577-0.691) and MR-fraction 0.594 (95%CI 0.542-0.647). Thresholds of MR-volume≥10mL and MR-fraction≥15% had the highest products of sensitivities and specificities (57.4%, 56.8%; and 54.6%, 63.4% respectively) reflecting elevated risk. MR-volume≥35mL and MR-fraction≥40% were associated the best combination of positive and negative predictive values (40.1%, 84.2%; and 38.4%, 84.6% respectively) representing severe risk. The figure illustrates Kaplan-Meier curves of the primary endpoint, categorized into three subgroups based on aforementioned MR-volume and MR-fraction thresholds. Conclusion: Adverse prognosis are observed when MR-volume≥10mL or MR-fraction≥15%, with increasing risk of adverse outcomes as functional MR severity increased in NICM. The proposed MR thresholds from this study for elevated and severe risk are lower than current valvular regurgitation guidelines, suggesting the need for separate classification schema for functional MR.
Abstract 14497: Mri Effects on Pacemaker/ICD Within the Magnetic Field; An Intra-observer Variability Study
Authors: Robert W Biederman, Loretta Gevenosky, Geetha Rayarao, RONALD WILLIAMS, Richard Lombardi, Moneal Shah, Victor Farah, Garima Dahiya, Adam Wetzel, Mark Doyle
Journal: Circulation (2020)

Introduction: The evolution of pacemaker/ICD safety in the magnetic field has triggered considerable interest in more clinical routine use. However, many limitations to widespread adoption of this seemingly implausible idea just a few years ago remain: unresolved impact of the high magnetic field, RF amplitude and oscillatory forces on electronics with possible high field damage to capacitor, solenoid and microcircuitry. However, given recent vender refinements over the last 10 years, we hypothesized that the impact on such circuitry may be far less than expected. Method: Consecutive interrogation of 940 pts who underwent clinically indicated MRI were evaluated over 5 years. This cohort was comprised of neuro/neurosurgical (72%), orthopedic (11%) and cardiac (17%) cases. Routine interrogation was performed within 10 min of entry into the bore of a dedicated Cardiac MRI (GE, 1.5T, WI). As well, reinterrogation was performed within 10 min of departure MRI (average 21±12min). At the time of interrogation pre and post MRI, a separate, repeat interrogation was performed within 5 min of each other such that 2 sets of PM/ICD parameters were obtained pre and post MRI. Result: No complications to either pt or device occurred during the MRI comprising 564 PMs and 376 ICDs. A cardiologist was present guiding the interrogation, configuration, and reconfiguration of the PM/ICD as well was present for entire MRI. There were no significant differences in common clinical parameters. More importantly, there was no difference in any parameter when compared in any order pre to post MRI scan. See Table. Conclusion: Intrinsic variability and inherent changes triggered by MRI environments are clinically insignificant and statistically negligible thereby removing yet another of the last remaining fears and apprehensions for primary PM/ICD failure and destruction as we move towards a more uniform acceptance of this technology for clinically meaningful use, dissemination and acceptance.