tbuckley/cabot-search huggingface dataset:
ACUTE MYOCARDIAL INFARCTION IN A PATIENT WITH MULTIVESSEL CORONARY ARTERY ANEURYSMS, PECTUS EXCAVATUM, AND THORACIC HEMANGIOMAS
Authors: Felipe Gomes Soares, Carolina C. Athayde, Sebastião C. Castilho, Fábio Akio Nishijuka, Andrea Costa, Carlos J. Cardoso, Leonardo da Cruz Nunes, Heitor Vieira, Nadia Mathias Albuquerque, Jaime Figueiredo, Mônica Medeiros Luna, Marcia Campos, Renata R.T. Castro
Journal: Journal of the American College of Cardiology (2019)
Abstract 275: Quantification of the Mitochondrial Protein Interactome in Failing Hearts
Authors: Arianne Caudal, Juan D Chavez, Chi Fung Lee, Outi Villet, James E Bruce, Rong Tian
Journal: Circulation Research (2018)

Mitochondrial dysfunction is a maladaptive mechanism in the progression of heart failure. However, the cause of mitochondrial dysfunction during cardiac stress remains elusive. To understand the pathogenic role of mitochondria in heart failure, a systems biology approach was used to quantify the protein interaction network by comparing mitochondria isolated from healthy and failing mouse heart. This is achieved by Protein Interaction Reporter (PIR) technology consisting of a cleavable, MS-identifiable, isotope labelled cross-linker, which allows identification and quantification of interacting peptide pairs. Heart failure was induced in three month old, wild-type C57Bl6/NCrl mice using chronic pressure overload by transverse aortic constriction (TAC, n=8) surgery. Age-matched Sham-operated (Sham, n=8) mice were used as controls. Four weeks post-surgery, cardiac function was measured by echocardiography. TAC hearts showed significantly lower contractile function than Sham (fractional shortening 49±2.1% vs 13±4.0%), and were dilated (LVID 2.7±0.34mm vs 3.4±0.46mm). Cardiac hypertrophy of TAC hearts (HW/TL 5.0±0.35 vs 9.1±0.58) was associated with greater lung edema (LW wet/dry 3.9±0.49 vs 4.9±0.24). Freshly isolated mitochondria from TAC and Sham hearts were cross-linked with heavy- or light-isotope labelled crosslinkers, digested, enriched, and analyzed by LC/MS 3 . Released peptide spectra were identified and categorized by known molecular functions using a MitoCarta 2.0 constructed database. We identified 3502 non-redundant cross-linked peptide pairs from 297 proteins, involving 1758 lysine residues linked in 2571 lysine-lysine interactions. From 3502 total links, we detected 2304 intra- and 1016 inter-protein links. Inter-protein changes between TAC/Sham were most prevalent in the electron transport chain and ATP synthasome networks. Intra-protein changes were evident in TCA cycle, fatty acid oxidation, and nucleotide transport, suggesting conformational remodeling. Interactome changes in amino acid metabolism, mitochondrial transcription and translation pathways were undetected. A complete picture of mitochondrial protein landscape in the failing heart will lead us to novel mechanisms and therapy.
DO EXTRA-CARDIAC MANIFESTATIONS PREDICT SEVERITY OF CARDIAC PHENOTYPE IN MARFAN SYNDROME?
Authors: Luciana Teresa Young, Arvind Hoskoppal, Joyce Johnson, Lauren Andrade, L. LuAnn Minich, Zhining Ou, Angela Presson, Ronald Lacro, Shaji Menon
Journal: Journal of the American College of Cardiology (2019)
DKK1 PREDICTS VASCULAR CALCIFICATION AND CLINICAL OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION
Authors: Jagdesh Kandala, Kanramon Watthanasuntorn, Benjamin Dao, Charat Thongprayoon, Jennifer Victory, Melissa Scribani, Paul Jenkins, Deborah Hyink, Paul Klotman, Randolph Hutter
Journal: Journal of the American College of Cardiology (2019)
FRAILTY AS AN EFFECT MEASURE MODIFIER IN OLDER ADULTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Abdulla Damluji, Karen Bandeen-Roche, Daniel Forman, Gary Gerstenblith, Jin Huang, Mauro Moscucci, Jon Resar, Ravi Varadhan, Jeremy Walston, Jodi Segal
Journal: Journal of the American College of Cardiology (2019)
Drug-Eluting Stent Implantation and Long-Term Survival Following Peripheral Artery Revascularization
Authors: Eric A. Secemsky, Harun Kundi, Ido Weinberg, Marc Schermerhorn, Joshua A. Beckman, Sahil A. Parikh, Michael R. Jaff, Jihad Mustapha, Kenneth Rosenfield, Robert W. Yeh
Journal: Journal of the American College of Cardiology (2019)
Abstract 372: Master Transcriptional Regulators of Cardiac Gene Expression in Heart Failure
Authors: Christoph D Rau, Jessica Wang, James Ohearn, Rozeta Avetisyan, Aldons J Lusis, Yibin Wang
Journal: Circulation Research (2018)

Background: Heart failure (HF) is characterized by complex transcriptional networks that direct the heart from a healthy to diseased state. Although some contributing genes have been identified through molecular biology and GWAS, heritability studies suggest that many genes have resisted discovery through these approaches. Identifying connective regulatory loci, especially master transcriptional regulators that affect the expression of many genes, offers a promising means of discovering novel relevant genes that have not been detected with other methods. Methods and Results: Transcriptional regulators of HF were identified using nine-week-old female mice from 93 lines of the Hybrid Mouse Diversity Panel. Mice received 30 ug/g/day of isoproterenol (ISO) for 3 weeks to induce cardiac dysfunction. Transcriptomes were generated from left ventricles of these mice along with age-matched controls. Expression Quantitative Trait Loci (eQTLs) for 13,156 transcripts were identified using a mixed model in three conditions (control, treated, delta). Suggestive (P&lt;1E-4) eQTLs were sorted into 500kb bins tiled across the genome to identify loci that regulate a significant number of transcripts. Ten hotspot loci that regulate over 5% (658 of 13156) of expressed genes were identified, several of which contain genes with known roles in HF, including Drosha , Akap5 and Dicer1 . Several novel regulators were also identified, including the Serine Proteinase Inhibitor, Serpina3n , which resides in a locus that regulates the change in expression of 9.7% (1276 of 13156) of all genes and is strongly correlated with changes in heart weight after ISO treatment. In subsequent in vitro work, Serpina3n knockdown resulted in reduced cellular hypertrophy, changes to hypertrophy-related gene expression, and modulation of the expression of several genes linked to its locus. Conclusion: GWAS performed on over 20,000 transcripts in control and ISO-treated hearts identified 10 genomic loci that regulate over 5% of the expressed genes in the heart. Serpina3n is a novel master regulator of HF. Further analysis of other master regulatory loci will reveal additional genes and improve our understanding of the transcriptional networks that direct the progression towards heart failure.
PRECISION AND STABILITY OF PARAMETERS FOR ASSESSMENT OF LEFT VENTRICULAR SYSTOLIC FUNCTION IN CLINICAL TRIALS: LESSONS FROM THE SUCCOUR TRIAL
Authors: Tomoko Negishi, Paaladinesh Thavendiranathan, Martin Penicka, Jonathan Deblois, Svend Aakhus, Sakiko Miyazaki, Mitra Shirazi, Maurizio Galderisi, Dragos Vinereanu, Goo-Yeong Cho, Krasimira Hristova, Bogdan Popescu, Thomas Marwick, Kazuaki Negishi
Journal: Journal of the American College of Cardiology (2019)
Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors
Authors: Fangjun Chen, Zhengyun Zou, Juan Du, Shu Su, Jie Shao, Fanyan Meng, Ju Yang, Qiuping Xu, Naiqing Ding, Yang Yang, Qin Liu, Qin Wang, Zhichen Sun, Shujuan Zhou, Shiyao Du, Jia Wei, Baorui Liu
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Recent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations. However, timely and efficient identification of neoantigens is still a major obstacle to personalized neoantigen-based cancer immunotherapy.
PERFORMANCE OF AORTIC ANNULAR ASSESSMENT BY 3D TRANSESOPHAGEAL ECHOCARDIOGRAPHY OR MAGNETIC RESONANCE ANGIOGRAPHY WITH FERUMOXYTOL IN PATIENTS WITH CKD UNDERGOING TAVR
Authors: Jordan Weber, Brian West, Olcay Aksoy, William Suh, Jeanne Huchting, Murray Kwon, Richard J. Shemin, Gabriel Vorobiof
Journal: Journal of the American College of Cardiology (2019)
Building digital innovation capacity at a large academic medical center
Authors: Devin M. Mann, Sara Kuppin Chokshi, Rachel Lebwohl, Michael Mainiero, Catherine Dinh-Le, Katherine Driscoll, Steven Robinson, Helen Egger
Journal: npj Digital Medicine (2019)

Academic medical centers (AMCs) today prioritize digital innovation. In efforts to develop and disseminate the best technology for their institutions, challenges arise in organizational structure, cross-disciplinary collaboration, and creative and agile problem solving that are essential for successful implementation. To address these challenges, the Digital DesignLab was created at NYU Langone Health to provide structured processes for assessing and supporting the capacity for innovative digital development in our research and clinical community. Digital DesignLab is an enterprise level, multidisciplinary, digital development team that guides faculty and student innovators through a digital development "pipeline", which consists of intake, discovery, bootcamp, development. It also provides a framework for digital health innovation and dissemination at the institution. This paper describes the Digital DesignLab's creation and processes, and highlights key lessons learned to support digital health innovation at AMCs.
A computer vision system for deep learning-based detection of patient mobilization activities in the ICU
Authors: Serena Yeung, Francesca Rinaldo, Jeffrey Jopling, Bingbin Liu, Rishab Mehra, N. Lance Downing, Michelle Guo, Gabriel M. Bianconi, Alexandre Alahi, Julia Lee, Brandi Campbell, Kayla Deru, William Beninati, Li Fei-Fei, Arnold Milstein
Journal: npj Digital Medicine (2019)

Abstract Early and frequent patient mobilization substantially mitigates risk for post-intensive care syndrome and long-term functional impairment. We developed and tested computer vision algorithms to detect patient mobilization activities occurring in an adult ICU. Mobility activities were defined as moving the patient into and out of bed, and moving the patient into and out of a chair. A data set of privacy-safe-depth-video images was collected in the Intermountain LDS Hospital ICU, comprising 563 instances of mobility activities and 98,801 total frames of video data from seven wall-mounted depth sensors. In all, 67% of the mobility activity instances were used to train algorithms to detect mobility activity occurrence and duration, and the number of healthcare personnel involved in each activity. The remaining 33% of the mobility instances were used for algorithm evaluation. The algorithm for detecting mobility activities attained a mean specificity of 89.2% and sensitivity of 87.2% over the four activities; the algorithm for quantifying the number of personnel involved attained a mean accuracy of 68.8%.
Abstract 15526: Optical Imaging With Polarization-sensitive and Angiographic Optical Coherence Tomography Characterizes Acute and Chronic Myocardial Injuries in the Beating Mouse Heart
Authors: Sun-Joo Jang, Taejin Park, Inho Shin, Hyun-Sang Park, Paul Shin, Wang-Yuhl Oh
Journal: Circulation (2017)

Introduction: Optical coherence tomography (OCT) is a useful imaging method for in vivo tissue imaging with deep penetration and high spatial resolution. However, imaging of the beating heart is st...
Abstract 386: Sex Differences in Vitamin D Alter Inflammation During Heart Disease
Authors: Katelyn A Bruno, Jessica Mathews, Erika Douglass, Anneliese Hill, Leslie Cooper, Jonathan Hoyne, DeLisa Fairweather
Journal: Circulation Research (2018)

An estimated 1 billion people worldwide have deficient or insufficient levels of vitamin D (VitD). Considerable evidence indicates that VitD deficiency is associated with an increased risk of autoimmune and cardiovascular disease (CVD), yet it remains unclear whether low VitD is simply a biomarker or has a true pathologic role. In this study we examined how sex differences in VitD influences various CVDs. We found that patients with CVD had significantly lower VitD than healthy controls (no ICD9/10 codes). In myocarditis patients low VitD correlated to poor ejection fraction (EF) in women with myocarditis (p=0.02), but high VitD correlated with low EF in men (p=0.04). In VDR knockout mice we found that VDR decreased myocarditis in females (p=2E-8) but increased inflammation in males (p=0.03) with an increase in total immune cells (p=0.02), CD3, CD4 and CD8 T cells (p=0.04), and the inflammasome in females. VDR altered Treg (p=0.04), mast cells (p=0.04) and cytokine profiles in males. Additionally, sera VitD levels were significantly higher in WT male mice with myocarditis compared to females. Our findings in VDR mice indicate that VitD/VDR reduces myocarditis in females, but increases disease in males. These data suggest that VitD sufficiency may increase inflammation in men, while VitD deficiency may make disease worse in women. These findings suggest that Vitamin D may have a role in the pathogenesis of inflammatory and cardiovascular disease.
Abstract 24070: Cardiac-Specific Overexpression Of Caveolin-3 Expedites Cardiac Relaxation After Adrenergic Stimulation
Authors: Alice E Zemljic-Harpf, Anna R Busija, Mugdha A Joshi, Basheer F Alas, Jan M Schilling, David M Roth, Paul A Insel, Hemal H Patel
Journal: Circulation (2017)

Introduction: Caveolae are membrane localized signaling platforms that compartmentalize signal transduction proteins such as GPCRs. Previous studies from our laboratory have demonstrated that overexpression of caveolin-3 in cardiac myocytes (Cav3 OE) protects against pressure-overload induced heart failure. Additionally, Cav3 OE mice present increased heart rate variability with lower nocturnal heart rates, but the mechanisms behind these phenotypes remain unclear. Hypothesis: Since Cav3 OE mice are protected from stressful cardiac stimuli, we tested the rationale that Cav3 OE hearts may show altered parasympathetic control of cardiac responses to adrenergic stimulation. Methods: Cav3 OE mice and transgene negative littermate controls (Ctrl) (12-16-week-old, n=10-11 each) were anesthetized with isoflurane and cardiac contractility was assessed by echocardiography at baseline. Isoprenaline (Isuprel USP [Iso], 300 nM i.p.) was administered ~10 min after baseline recordings and cardiac function recorded at 2 min, 5 min, and 10-15 min after Iso. The same animal cohort received a single atropine injection (2 mg/kg i.p) 20 min before isoflurane anesthesia and Iso challenge echocardiography was performed as described above. Results: At baseline, no differences in cardiac contractility (% ejection fraction, %EF±SD) were detected between the two groups ~68±8 %EF. After Iso injection cardiac contractility was increased to ~91±3 %EF in both genotypes at 2 min; however, in Cav3 OE mice cardiac contractility recovered to 83±3 %EF by 5 min post Iso challenge whereas Ctrl animals maintained increased contractility of 92±3 %EF (p &lt; 0.001). Importantly, Cav3 OE mice pre-treated with atropine no longer showed increased recovery at 5 min or 10-15 post Iso (p = 0.007). A three-way ANOVA of the time-course after Iso injection found a significant effect of atropine on the responses of Cav3 OE versus Ctrl hearts to Iso (p = 0.007). Conclusion: We show for the first time that Cav3 OE mice show a faster recovery from hypercontractility after isoproterenol stimulation. Since atropine abrogated this recovery, these data suggest that Cav3 OE mice exhibit increased parasympathetic tone that may be responsible for improved stress adaptation and heart rate variability.
Abstract 547: Pharmacologic ATF6 Activation Confers Global Protection in Widespread Disease Models by Reprogramming Cellular Proteostasis
Authors: Erik A Blackwood, Khalid Azizi, Donna J Thuerauf, Ryan J Paxman, Lars Plate, Jeffery W Kelly, Rockland L Wiseman, Christopher C Glembotski
Journal: Circulation Research (2018)

Pharmacologic activation of stress-responsive signaling pathways provides a promising approach for ameliorating imbalances in proteostasis associated with diverse diseases. However, this approach has not been employed in vivo . Here, using a mouse model of myocardial ischemia/reperfusion, we showed that selective pharmacologic activation of the ATF6 arm of the unfolded protein response (UPR) during reperfusion, a typical clinical intervention point after myocardial infarction, transcriptionally reprograms proteostasis, ameliorates damage and preserves heart function. These effects were lost upon cardiac myocyte-specific Atf6 deletion in the heart, demonstrating the critical role played by ATF6 in mediating pharmacologically activated proteostasis-based protection of the heart. Pharmacological activation of ATF6 was also protective in renal and cerebral ischemia/reperfusion models, demonstrating its widespread utility. Thus, pharmacologic activation of ATF6 represents a first-in-class proteostasis-based therapeutic strategy for ameliorating ischemia/reperfusion damage, underscoring its unique translational potential for treating a wide range of pathologies caused by imbalanced proteostasis.
INITIAL CHANGES IN PEAK AORTIC JET VELOCITY AND MEAN GRADIENT PREDICT PROGRESSION TO SEVERE AORTIC STENOSIS
Authors: Arash Nayeri, Samuel Jackson, Meng Xu, Eric Farber-Eger, Marcia Blair, Inderpreet Saini, Gregg C. Fonarow, Kamran Shamsa, John A. McPherson, Quinn Wells
Journal: Journal of the American College of Cardiology (2019)
The Role of Endotoxin in Septic Shock—Reply
Authors: John C. Marshall, Paul M. Walker, R. Phillip Dellinger
Journal: JAMA (2019)

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GENDER DIFFERENCES IN CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY DERIVED FRACTIONAL FLOW RESERVE: LESSONS FROM ADVANCE
Authors: Tim Andrew Fairbairn, Lynne Koweek, Jeroen J. Bax, Hitoshi Matsuo, Bjarne Norgaard, Koen Nieman, Neils P.R. Sand, Kristian A. Ovrehus, Gianluca Pontone, Gilbert Raff, Mark Rabbat, Tetsuya Amano, Tomohiro Kawasaki, Takashi Akasaka, Hironori Kitabata, Kavitha Chinnaiyan, Jeroen Sonck, Michael Poon, Bernard De Bruyne, Campbell Rogers, Manesh Patel, Daniel Berman, Jonathon Leipsic
Journal: Journal of the American College of Cardiology (2019)
Mononuclear phagocytes orchestrate prolyl hydroxylase inhibition-mediated renoprotection in chronic tubulointerstitial nephritis
Authors: Gunnar Schley, Bernd Klanke, Joanna Kalucka, Valentin Schatz, Christoph Daniel, Marleen Mayer, Margarete Goppelt-Struebe, Martin Herrmann, Margret Thorsteinsdottir, Runolfur Palsson, Angelika Beneke, Dörthe M. Katschinski, Nicolai Burzlaff, Kai-Uwe Eckardt, Alexander Weidemann, Jonathan Jantsch, Carsten Willam
Journal: Kidney International (2019)
Abstract 250: Pulmonary Hypertension Induced by 15-HETE is Reverse by Apoai Mimetic Peptide 6f Administration
Authors: Gregoire Ruffenach, Ellen I O’Connor, Mylene Vaillancourt, Shervin Sarji, Nancy Cao, Laila Aryan, Christine Cunningham, Victor Grijalva, Soban Umar, Srininivasa T Reddy, Mansoureh Eghbali
Journal: Circulation Research (2018)

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial occlusion leading to increased pulmonary arterial pressure. Recently, a growing body of evidence demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). Recently, our group demonstrated that 15HETE induce PH. Nonetheless, the precise mechanism by which 15HETE participates in PH development remains elusive. In order to investigate this mechanism, we fed wild type mice with a diet rich in 15HETE and examine whether ApoA-I mimetic peptide can rescue PH induced by 15HETE. Methods: Wild type male mice (C57BL/6) were fed for 3 weeks for 3 weeks with regular chow (n=16-21 mice/group), 15HETE (5μg/day), 15HETE diet supplemented with either empty vector or 6F for the last week of 15HETE diet. PH development was assessed every week via serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&amp;E and Oil red O staining. Results: Echocardiography revealed the first sign of PH as early as one week after starting 15HETE diet and a significant decrease in the pulmonary arterial acceleration time (PAAT) after 2 weeks of treatment (16.6±1.9 vs. 20.6±1.4 msec, p&lt;0.05). At the end of three weeks, mice on 15HETE diet had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p&lt;0.05) and RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p&lt;0.05). This increased pressure was concomitant with a significant increase in pulmonary arteriolar thickness in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p&lt;0.05). Furthermore, these WT mice did not develop atherosclerosis as there was no detectable plaque in aorta of the mice on 15HETE diet. At the end of three weeks mice treated with 6F showed a PAAT similar to control value(19±0.5 msec) concomitant with a significantly lower RVSP than mice fed with 15HETE +empty vector (33.6 ±5.7 vs 40.3±4.6, p&lt;0.05). Conclusion: Our data demonstrates that APOA-I mimetic peptide 6F is able to rescue pre-exisiting PH induced by 15-HETE diet in wild type mice.
CORONARY ARTERY DISEASE RISK AND LIPIDOMIC PROFILES IN FAMILIAL HYPERLIPIDEMIAS
Authors: Joel Rämö, Pietari Ripatti, Rubina Tabassum, Sanni Söderlund, Niina Matikainen, Mathias J. Gerl, Christian Klose, Michal Surma, Nathan O. Stitziel, Aki S. Havulinna, Veikko Salomaa, Nelson B. Freimer, Matti Jauhiainen, Aarno Palotie, Marja-Riitta Taskinen, Kai Simons, Samuli Ripatti
Journal: Journal of the American College of Cardiology (2019)
Abstract 19556: Drug-Eluting Balloon versus Standard Balloon Angioplasty for Infrapopliteal Arterial Disease: Meta-Analysis of Randomized Control Trials
Authors: Viswajit Reddy Anugu, Bhavi Pandya, Sainath Gaddam, Nikhil Nalluri, Deepak Asti, Ruben Kandov, Thomas Vazzana, James Lafferty
Journal: Circulation (2016)

Introduction: Drug-eluting balloon (DEB) angioplasty has emerged as a valuable treatment option for peripheral artery disease. The role of DEBs in infrapopliteal arterial (IPA) disease is still con...