tbuckley/cabot-search huggingface dataset:
Ecosystem perspectives are needed to manage zoonotic risks in a changing climate
Authors: Rory Gibb, Lydia H V Franklinos, David W Redding, Kate E Jones
Journal: BMJ (2020)

Better understanding of how environmental changes affect pathogens, hosts, and disease vectors can help prevent and respond to zoonoses, write Rory Gibb and colleagues Climate change and biodiversity loss are among this century's greatest threats to human health and are exposing people worldwide to increasing food and water insecurity, extreme weather, pollution, and infectious disease threats.12 Zoonotic infectious diseases are situated at this nexus between environmental change, ecosystems, and health. Zoonotic pathogens and parasites are maintained in an animal reservoir and regularly or sporadically spill over to cause disease in humans,3 sometimes leading to sustained human-to-human or vectorborne epidemics (eg, severe acute respiratory syndrome coronaviruses (SARS-CoV), Ebola, plague) but more commonly to endemic or sporadic disease (eg, leptospirosis, helminthiases, Lyme disease, hantavirus diseases). ### Glossary of terms
Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high‐risk acute heart failure patients
Authors: Jan Biegus, Robert Zymliński, Jeffrey Testani, Dominik Marciniak, Agata Zdanowicz, Ewa A. Jankowska, Waldemar Banasiak, Piotr Ponikowski
Journal: European Journal of Heart Failure (2020)
Abstract 16772: Aerobic Capacity (VO <sub>2peak</sub> ) in Congenital Heart Disease: Prognostic Implications
Authors: Andrea Soares, Emily Mansour, Alyssa Puritz, Min Zhao, chao cao, Philip Barger, Randi E Foraker, Susan B RACETTE, Linda R Peterson
Journal: Circulation (2020)

Introduction: Cardiopulmonary exercise testing provides information about functional capacity via direct measurement of respiratory gas exchange. Whether peak oxygen consumption during exercise (VO 2peak ) is predictive of outcomes in patients with congenital heart disease is controversial. Hypothesis: VO 2peak has prognostic implications for death, left ventricular assist device (LVAD) placement, and cardiac transplant in adult patients with congenital cardiac diseases. Methods: Congenital heart disease patients were selected from a registry of cardiac patients who completed a VO 2peak exercise test at Washington University School of Medicine between May 1993 and October 2012. Diagnoses were verified by chart review and classified according to American Heart Association guidelines. Outcome data were verified via medical record, Social Security Death Index, or phone interview. A Cox proportional-hazard regression analysis was used to investigate the association between patient survival time and one or more predictor variables. Survival time was defined as the time elapsed between VO 2peak test and the earliest outcome of death, heart transplant, or LVAD placement. Results: The sample included 149 patients (49% women, mean ± SD age of 33.4 ± 11.5 years and body mass index of 25.7 ± 5.4 kg/m 2 ). Mean follow-up time was 11.8 ± 3.2 years. Mean VO 2peak was 23.0 ± 7.3 mL/kg/min for men and 20.0 ± 6.4 mL/kg/min for women. Age was comparable between men and women in the sample. In the univariate analysis, higher VO 2peak was associated with longer event-free survival time (HR 0.91, 95% CI 0.85-0.98, p= 0.01). In the multivariable analysis, higher VO 2peak was shown to be protective, independent of age and sex (HR 0.90, 95% CI 0.83-0.97, p=0.004). Conclusions: Among patients with congenital cardiac disease, higher VO 2peak independently predicted longer event-free survival. VO 2peak is a valuable clinical prognostic tool for patients with congenital cardiac disease.
Abstract 17293: Hyperglycemia Enhances Pro-Inflammatory Properties of Macrophage-Derived Exosomes to Drive Hematopoiesis in Apolipoprotein E-Deficient Mouse
Authors: Laura Bouchareychas, Phat Duong, Tuan Anh Phu, Eric Alsop, bessie meechoovet, Ryo Yamamoto, Hiromitsu Nakauchi, kendall Van Keuren-Jensen, Robert Raffai
Journal: Circulation (2020)

Introduction: Macrophage-derived exosomes have emerged as important mediators in cell-to-cell communication by influencing inflammatory signaling and the immune function. Hypothesis: We aimed to explore whether hyperglycemia can enhance intercellular communication between mature macrophages and hematopoietic progenitors via exosomes to promote inflammation and diabetic atherosclerosis. Methods: Bone marrow derived macrophages (BMDM) from C57BL/6 mice were cultured with normal (5.5 mM) or high glucose concentrations (25 mM). Exosomes were isolated by cushioned-density gradient ultracentrifugation method followed by nanoparticle tracking and western blot analysis. Inflammatory properties of high glucose exosomes (BMDM-HG-exo) or normoglycemic exosomes (BMDM-NG-exo) were tested in vitro by exposing them to naïve BMDM. The capacity for BMDM-derived exosomes to alter systemic and vascular inflammation were next tested by infusing 25-30 weeks-old ApoE -/- mice fed a chow diet with exosomes three times a week, for four weeks. Results: Our data show that BMDM-HG-exo can stimulate the expression of inflammatory cytokines and generate reactive oxygen species in recipient cultured BMDM. Furthermore, our findings show that intraperitoneally injected exosomes distribute to numerous organs and tissues including the bone marrow and the spleen. HG-exo enhance the expansion of multipotent and lineage committed hematopoietic progenitors in the spleen, leading to an enhanced atherosclerotic progression. Conclusions: We identify that exosomes derived from cultured BMDM exposed to high glucose have the capacity to exert inflammatory signaling in vitro , and in vivo. Our findings suggest that exosomes produced by macrophages exposed to hyperglycemia could represent an unsuspected source of inflammation to accelerate atherosclerosis in diabetes.
Abstract 13912: 17-Beta-Estradiol Directly Regulates Microtubule Dynamics: New Insights Into Sex-Differences in Right Ventricular Function in Pulmonary Hypertension
Authors: Sasha Z Prisco, Ping Y Xiong, Rebecca Goldblum, Francois Potus, Kenneth Martinez Algarin, Lauren Rose, Thenappan Thenappan, Melissa K Gardner, Stephen L Archer, Kurt W Prins
Journal: Circulation (2020)

Introduction: Female sex is associated with better right ventricular (RV) function in pulmonary hypertension (PH). The female sex hormone 17-beta-estradiol is postulated to mediate these differences, but the molecular mechanisms underlying these observations are incompletely defined. Interestingly, 17-beta-estradiol induces microtubule depolymerization in cell culture, which may be relevant to RV dysfunction because microtubule remodeling promotes RV dysfunction via dysregulation of junctophilin-2 (MT-JPH2 pathway). We speculate that 17-beta-estradiol modulates the MT-JPH2 pathway and preserves RV function in PH. Methods: Pressure-volume assessments quantified RV function in monocrotaline (MCT) and pulmonary artery-banded (PAB) rats. Immunoblots quantified the tubulin and junctophilin-2 protein content in RV extracts. Echocardiography quantified RV function by RV fractional area change for 379 human PH patients. Sedimentation experiments, fluorescence-based polymerization assessments, and total internal reflection fluorescence (TIRF) microscopy examined the effects of 17-beta-estradiol on microtubules. Results: Female sex results in better RV function and less dysregulation of the MT-JPH2 pathway in both MCT and PAB rats. Moreover, in human PH, female sex was associated with better RV function, which persisted after adjusting for afterload. 17-beta-estradiol inhibited microtubule polymerization in vitro and TIRF microscopy showed 17-beta-estradiol localized to microtubule tips and prevented further microtubule polymerization. Conclusions: Preclinical and human studies show that females are better able to tolerate RV pressure overload. There are blunted microtubule-mediated t-tubule remodeling and preserved RV function in female MCT and PAB rats. In human PH, females have better RV function. These findings may be due to 17-beta-estradiol directly regulating microtubule dynamics as shown by sedimentation and polymerization assays and TIRF microscopy. These results provide additional insights into sex-differences in RV function in PH.
Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release
Authors: Jillian N. Simon, Besarte Vrellaku, Stefania Monterisi, Sandy M. Chu, Nadiia Rawlings, Oliver Lomas, Gerard A. Marchal, Dominic Waithe, Fahima Syeda, Parag R. Gajendragadkar, Raja Jayaram, Rana Sayeed, Keith M. Channon, Larissa Fabritz, Pawel Swietach, Manuela Zaccolo, Philip Eaton, Barbara Casadei
Journal: Circulation (2020)

Kinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, PKARIα (type-1 protein kinase A) can be reversibly oxidized, forming interprotein disulfide bonds in the holoenzyme complex. However, the effect of PKARIα disulfide formation on downstream signaling in the heart, particularly under states of oxidative stress such as ischemia and reperfusion (I/R), remains unexplored.Atrial tissue obtained from patients before and after cardiopulmonary bypass and reperfusion and left ventricular (LV) tissue from mice subjected to I/R or sham surgery were used to assess PKARIα disulfide formation by immunoblot. To determine the effect of disulfide formation on PKARIα catalytic activity and subcellular localization, live-cell fluorescence imaging and stimulated emission depletion super-resolution microscopy were performed in prkar1 knock-out mouse embryonic fibroblasts, neonatal myocytes, or adult LV myocytes isolated from "redox dead" (Cys17Ser) PKARIα knock-in mice and their wild-type littermates. Comparison of intracellular calcium dynamics between genotypes was assessed in fura2-loaded LV myocytes, whereas I/R-injury was assessed ex vivo.In both humans and mice, myocardial PKARIα disulfide formation was found to be significantly increased (2-fold in humans, P=0.023; 2.4-fold in mice, P<0.001) in response to I/R in vivo. In mouse LV cardiomyocytes, disulfide-containing PKARIα was not found to impact catalytic activity, but instead led to enhanced AKAP (A-kinase anchoring protein) binding with preferential localization of the holoenzyme to the lysosome. Redox-dependent regulation of lysosomal two-pore channels by PKARIα was sufficient to prevent global calcium release from the sarcoplasmic reticulum in LV myocytes, without affecting intrinsic ryanodine receptor leak or phosphorylation. Absence of I/R-induced PKARIα disulfide formation in "redox dead" knock-in mouse hearts resulted in larger infarcts (2-fold, P<0.001) and a concomitant reduction in LV contractile recovery (1.6-fold, P<0.001), which was prevented by administering the lysosomal two-pore channel inhibitor Ned-19 at the time of reperfusion.Disulfide modification targets PKARIα to the lysosome, where it acts as a gatekeeper for two-pore channel-mediated triggering of global calcium release. In the postischemic heart, this regulatory mechanism is critical for protection from extensive injury and offers a novel target for the design of cardioprotective therapeutics.
Abstract 116: Impella Device Success: Walking Home After Cardiogenic Shock From Ventricular Fibrillation
Authors: Christopher Smith, Vivek Menon, Dantwan Smith
Journal: Circulation (2020)

Ventricular fibrillation is a fatal arrhythmia due to its detrimental impact on cardiac output. Managing patients in V-Fib arrest is often challenging, but newer mechanical support devices such as Impella CP 5.0 (Abiomed, Danvers, MD) are proving to be an excellent adjunct to inotrope and vasopressor therapy. We present a 75-year-old female with a medical history of atrial fibrillation and obstructive sleep apnea that presented to the ER unresponsive. On arrival, the patient was pulseless and initial rhythm on telemetry revealed ventricular fibrillation. The patient demonstrated minimally reactive pupils to light, negative corneal reflex, and lower extremity clonus. ROSC was achieved with electric defibrillation and two rounds of CPR. Chest radiograph revealed mild bilateral pulmonary congestion. Head CT revealed no acute intracranial pathology. The patient was placed on targeted temperature management protocol for the next 48 hours. Emergent left heart catheterization revealed no signs of occlusive coronary disease. TTE revealed left ventricular ejection fraction 5-10%, likely from stunned myocardium. The patient continued to clinically decline and decision was made to place an Impella device for further hemodynamic support. Unlike ECMO, the Impella fully unloaded the LV and allowed diastolic coronary filling. The patient ultimately demonstrated significant improvement and repeat TTE revealed an improved EF of 45-50%. Prior to hospital discharge, an AICD was placed for primary SCD prevention. The patient maintained close outpatient follow-up with her cardiologist and PCP. This case illustrates the importance life-saving mechanical support devices such as Impella in the setting of cardiogenic shock, even from non-ischemic ventricular fibrillation.
New Statin Use and Mortality in Older Veterans
Authors: Ali Ahmed, Wen-Chih Wu, Charles Faselis
Journal: JAMA (2020)

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Abstract 15588: Prediction of Mortality Using Standard 12-lead Electrocardiogram With Deep Neural Network
Authors: Yu Chang Huang, Chang-Fu Kuo, Yu Chun Hsu, Yueh Peng Chen, Jung-Sheng Chen, Ming Shien Wen
Journal: Circulation (2020)

Background: Electrocardiogram (ECG) is a low-cost, inexpensive, non-invasive, and ubiquitous test to detect structural or electrical cardiac abnormalities. The ECG interpretation is a visual task to correlate specific patterns with diseases. Subtle ECG patterns that are invisible to the human eyes may be useful for patient risk stratification. We aimed to develop a deep neural network to predict mortality using standard 12-lead ECG. Methods: We obtained the entire clinical MUSE database of Chang Gung Memorial Hospital for standard resting 12-lead 10-sec ECG voltage-time traces, which were linked to the National Death Registry for all-cause and cause-specific mortality. Ten thousand patients remained alive at one year from the ECG examination date, and 10000 patients died within one year were randomly selected to train a one-dimensional deep neural network to predict mortality risk. Data was split into 16,000 patients for the training and 4,000 patients for the validation sets. We prepared a separate held-out dataset of 19,737 randomly selected patients whose ECG traces were fed to the model to predict their mortality risk. Results: The mean age of the held-out dataset was 60.0±16.7 years, and 50.0% were female. Among them, 3,807 died during a mean follow-up period of 6.0 years (maximum period, 14 years). The model achieved an area under the receiver operator curve of 0.85 on the held-out dataset. The age- and sex-weighted Kaplan-Meier curve for the mortality was shown in figure 1, which stratified by the model prediction for survival status (log-rank test, p &lt; 0.001). Using a Cox proportional hazards model, the ECG algorithm predicted death is associated with an age- and sex-adjusted hazard ratio of 3.2 (95% confidence interval, 3.0-3.4) for all-cause mortality and 2.9 (95% CI, 2.4-3.5) for cardiovascular mortality. Conclusion: The deep learning model could extract prognostic information from standard 12-lead ECG and predict mortality with reasonable precision.
Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations
Authors: Ju-Sheng Zheng, Jian’an Luan, Eleni Sofianopoulou, Fumiaki Imamura, Isobel D. Stewart, Felix R. Day, Maik Pietzner, Eleanor Wheeler, Luca A. Lotta, Thomas E. Gundersen, Pilar Amiano, Eva Ardanaz, María-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Rudolf Kaaks, Nasser Laouali, Francesca Romana Mancini, Peter M. Nilsson, N. Charlotte Onland-Moret, Anja Olsen, Kim Overvad, Salvatore Panico, Domenico Palli, Fulvio Ricceri, Olov Rolandsson, Annemieke M.W. Spijkerman, María-José Sánchez, Matthias B. Schulze, Núria Sala, Sabina Sieri, Anne Tjønneland, Rosario Tumino, Yvonne T. van der Schouw, Elisabete Weiderpass, Elio Riboli, John Danesh, Adam S. Butterworth, Stephen J. Sharp, Claudia Langenberg, Nita G. Forouhi, Nicholas J. Wareham
Journal: Diabetes Care (2020)

OBJECTIVE Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS We identified 11 genomic regions associated with plasma vitamin C (P &amp;lt; 5 × 10−8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
Cannabis Induced Vasospasm Complicated By Iatrogenic Coronary Artery Dissection
Authors: Marina Santos
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Cannabis is the most abused psychoactive drug in the world. Delta 9-tetrahydrocannibol, the main psychoactive compound in marijuana, acts via the endocannabinoid system to elicit various cardiovascular physiological effects, and has been associated with many adverse cardiovascular effects such as acute coronary syndrome, arrhythmias, and sudden cardiac death. It is important to consider cannabis use as a significant risk factor of myocardial infarction, particularly in individuals with no cardiac risk factors, as delay in management can result in fatal outcomes. Coronary angiography as the main exam to definitively diagnose or rule out coronary artery disease is usually safe, but complications also occur. Coronary dissection, despite rare, can be extremely difficult to manage and even be fatal. Iatrogenic causes of coronary dissection include catheter tip or guidewire trauma, vigorous contrast injection and angioplasty balloon overinflation. We present the case of a 41 years old Caucasian woman admitted to cardiology department after an episode of myocardial infarction due to cannabis induced vasospasm. However, the angiography was complicated by iatrogenic coronary artery dissection.
Dupilumab reduces inflammation and restores the skin barrier in patients with atopic dermatitis
Authors: Maria Helena Rohner, Kathrin Thormann, Simone Cazzaniga, Shida Yousefi, Hans‐Uwe Simon, Christoph Schlapbach, Dagmar Simon
Journal: Allergy (2020)

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Abstract 16232: Early Morbidity Affects Survival Beyond the Perioperative Period in On-Pump vs. Off-Pump Coronary Artery Bypass Graft Surgery - A Quantitative Morbidity Analysis of the CORONARY Trial
Authors: Melanie Hebert, Andre Lamy, Nicolas Noiseux, Louis-Mathieu Stevens
Journal: Circulation (2020)

Introduction: Previous large trials found similar outcomes between on- and off-pump CABG. We assessed the hypothesis that quantified early morbidity affects survival after 30 postoperative days by applying the Clavien-Dindo Complications Classification (CDCC) and the Comprehensive Complication Index (CCI) to the CORONARY trial. Methods: All postoperative hospitalization and 30-days follow-up complications were assigned a CDCC grade. CCI were calculated for all patients (n=4752) ( Table 1 ). Kaplan-Meier analysis was used to examine 1-year mortality by CDCC grade in patients alive after 30 postoperative days. Wilcoxon and log-rank were used for comparisons. Results: Median CDCC was 1 [interquartile range: 0, 2] for off-pump and 2 [1, 2] for on-pump CABG (p&lt;0.001). Median CCI was 8.7 [0, 22.6] for off-pump and 20.9 [8.7, 29.6] for on-pump CABG (p&lt;0.001). In on-pump CABG, there were more grade I complications (off: n=1093, 46.0% vs. on: n=1280, 53.8%; p&lt;0.001) and grade II complication (off: n=903, 38.0% vs. on: n=1012, 42.6%; p&lt;0.001) ( Figure 1a ). In on-pump CABG, 17.5% (n=417) had grade IIIa or greater morbidity versus 15.9% (n=378) in off-pump (p=0.133). Survival curves differed significantly based on CDCC grade ( Figure 1b , p&lt;0.001). The CCI was 8.7 [0, 22.6] in patients who survived (n=4514) and 22.6 [8.7, 44.3] in patients who died (n=94) at one year (p&lt;0.001). Conclusions: On-pump CABG is associated with greater early morbidity graded by CDCC and CCI. This affects survival beyond the immediate postoperative period. Similar quantitative analyses have not been used to compare the two techniques and could prove useful to better quantify procedural morbidity in clinical trials.