tbuckley/cabot-search huggingface dataset:
Abstract 16966: MicroRNA-92a Differentially Regulates Cell Cycle Proliferation and Angiogenesis in Huvec And Hepg2 Cells
Authors: Nikhil C Adi, Jennipher Adi, Keith A Webster
Journal: Circulation (2011)

Introduction: The conserved miR17~92 cluster, is up-regulated in tumors, and its OE promotes tumor angiogenesis and growth. Recent studies indicate that miR92a is anti-angiogenic while the regulation of angiogenesis by miR17/20 is context-dependent. Hypothesis: miR92a action is also context and cell type-dependent and differentially regulates cell growth and angiogenesis in tumor vs endothelial cells. Methods: HepG2 and HUVECs were transfected with pre and anti miR92a molecules. Cell proliferation was assayed in both cell types using BrdU 48hr after transfection. HUVEC-Matrigel tube formation assays were implemented in parallel to assess angiogenic potential. VEGF was measured in spent media from HepG2 cells and the same media was used in HUVEC tube formation. Protein lysates were collected for WB 48hr after transfections of both cell types. Results: Pre-miR92a transfection inhibited proliferation of HUVECs while anti-miR92a, but not pre-miR92a inhibited proliferation of HepG2 cells (all, p&lt;0.05). Pre-miR transfection blocked HUVEC tube formation (p&lt;0.01). Tube formation was supported by spent medium from HepG2 cells ± transfection with pre-miR-92a but the ability of HepG2 spent medium to support tube formation was blocked by transfection with anti miR92a (all, p&lt;0.05). Consistent with the latter result, VEGF levels in spent HepG2 media were decreased by transfection with anti-miR92a. In HepG2 cells transfection of anti-miR92a increased PTEN expression and decreased AKT-P-Thr308 (both p&lt;0.05) PTEN and AKT-P-Thr-308 were not affected by miR92a transfection of HUVECs, however pre-miR-92a significantly decreased eNOS, ITG5α, and CCND1 protein levels (all, p&lt;0.05). These results support our hypothesis that miR92a has opposite effect on the angiogenic properties of HepG2 vs HUVECs. Conclusions: MiR92a augments proliferation of HepG2 cells and promotes angiogenesis by inhibiting PTEN, activating Akt and increasing VEGF expression and secretion. Conversely, miR92a inhibits angiogenesis of HUVECs by targeting angiogenic regulators. The differential contextual functions of miR92a explain why this regulation supports tumor growth and angiogenesis while blocking EC function.
SELF EXPANDABLE VALVES HAVE LOWER PARAVALVULAR LEAK TWO YEARS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT COMPARED WITH BALLOON VALVES: RESULTS FROM THE MARSHFIELD AORTIC VALVE EXPERIENCE PILOT SUBSTUDY
Authors: Peter Umukoro, Paul Yeung-Lai-Wah, Sunil Pathak, Sabri Elkhidir, Brooke Delgoffe, Richard Berg, Kelley Anderson, Romel Garcia-Montilla
Journal: Journal of the American College of Cardiology (2019)
Author Correction: Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation
Authors: Sebastian Zundler, Emily Becker, Marta Spocinska, Monique Slawik, Loreto Parga-Vidal, Regina Stark, Maximilian Wiendl, Raja Atreya, Timo Rath, Moritz Leppkes, Kai Hildner, Rocío López-Posadas, Sören Lukassen, Arif B. Ekici, Clemens Neufert, Imke Atreya, Klaas P. J. M. van Gisbergen, Markus F. Neurath
Journal: Nature Immunology (2019)
COMPARISON OF PARAVALVULAR AORTIC REGURGITATION WITH MONITORED ANESTHESIA CARE VERSUS GENERAL ANESTHESIA FOR NEWER GENERATION TRANSCATHETER HEART VALVES
Authors: Prakash Patel, Jake Rosen, Zehang Chen, Jay Giri, Saif Anwaruddin, Prashanth Vallabhajosyula, Wilson Szeto, Yianni Augoustides, Howard Herrmann, Nimesh Desai
Journal: Journal of the American College of Cardiology (2019)
Abstract 422: Recognition of Pharyngeal Pain as an Angina Equivalent
Authors: Salih N Grevious, Marcelo Fernandes, Manuel Rivera
Journal: Circulation Research (2018)

A 64-year-old man presented to his physician with a 5-day history of throat pain and hoarseness. An initial diagnosis of pharyngitis was made, and the patient was sent home with a 7-day course of antibiotic therapy. He returned 6 days after his initial visit with persistent symptoms, which he now described as worsening on exertion such as when lifting weights. He was sent for a neck computed tomography to evaluate cervical soft tissues: No masses, enhancing lesions, lymphadenopathies, or imaging findings suggesting vocal cord paresis were noted. An ECG was ordered by the patient’s primary care physician and demonstrated new lateral T-wave inversions. The patient was also referred to ENT, and via direct laryngoscopy normal true vocal cords and questionable evidence of laryngopharyngeal reflux were visualized. He was then recommended to begin lifestyle modifications and start empiric treatment with omeprazole twice daily. Due to the ECG findings, an exercise stress test was ordered. During the exercise stress test, He developed throat tightness and the study was converted to a Lexiscan nuclear stress test. The stress test revealed inferior wall ischemia of moderate severity. Consequently, a coronary cath demonstrated quadruple vessel disease with 75% occlusion of left main, 70% stenosis of proximal LAD, 60% stenosis of the first diagonal, and total occlusion of the mid RCA. After undergoing quadruple coronary bypass surgery, the patient experienced a total resolution of his throat pain. Discussion: When approaching craniofacial pain elicited with exertion, it is essential for the clinician to consider ischemic heart disease as an etiology. Furthermore, the link of pain with physical activity and, additionally, pain relief with rest should drive the physician to consider cardiac ischemia. Isolated craniofacial pain or sole pharyngeal pain of cardiac origin are infrequent indicators of significant coronary artery disease. In a prospective multicenter study, only 6% of patients with confirmed ischemic cardiomyopathy presented with craniofacial pain as the only complaint. This case illustrates the importance of a thorough history and physical examination as well as a broad differential diagnosis when evaluating patients with throat pain and hoarseness.
Abstract 115: Chromatin Microenvironments With Distinct Functionality During Cardiac Stress
Authors: Manuel Rosa-Garrido, Douglas J. Chapsky, Maximilian Cabaj, Elaheh Karbassi, Thomas Vondriska
Journal: Circulation Research (2018)

Loss of the chromatin structural protein CTCF induces heart failure. Chromatin capture experiments (Hi-C), which detect genomic interactions, revealed global remodeling of chromatin structure after cardiac-specific depletion of CTCF or pressure overload (TAC). In the present study, we investigated epigenomic features (histone marks and DNA methylation) contributing to distinct behaviors of chromatin microenvironments. CTCF-KO or TAC induced gene expression changes mediated by a shift in compartmentalization between active and inactive chromatin (~4% of the genome). At the transcriptome level, genes significantly dysregulated in disease were involved in cardiac function ( e.g. , Mybpc3, Lmna , Hand2 ), chromatin structure ( e.g. , Hmgb2 , Rad21 ), and histone modification ( e.g. , Hdac4 , Mapk14, Foxo1 ). Our Hi-C data allowed us to correlate changes in gene expression with localization within the nucleus, showing efficient segregation of differentially expressed genes into specific neighborhoods with similar expression behavior. Analyses of histone marks in these neighborhoods reveal enrichment of activating and inhibiting marks, H3K9ac and H3K9me3, respectively, in the specialized chromatin environments associated with gene expression or silencing. DNA methylation studies showed that transcriptionally active neighborhoods tended to have unmethylated CpGs, while repressive environments were methylated. Our Hi-C data also showed how active environments positively influence the expression of the genes that physically interact with them. For example, 351 unique genes with interacting partner genes had increased H3K9ac after TAC, and their 3D interacting partners included 200 upregulated genes and 104 downregulated genes, demonstrating similar transcriptional behavior in areas with similar epigenomic features and anatomical distribution in the nucleus. Heart failure involves conserved structural reprogramming of these chromatin microenvironments.
Abstract 584: FTO-Dependent m6A Regulates Cardiomyocyte and Cardiac Function During Remodeling and Repair
Authors: Prabhu Mathiyalagan, Marta Adamiak, Joshua Mayourian, Yaxuan Liang, Yassine Sassi, Neha Agarwal, Divya Jha, Kiyotake Ishikawa, Shihong Zhang, Erik Kohlbrenner, Xiaoke Yin, Elena Chepurko, Jiqiu Chen, Maria G Trivieri, Rajvir Singh, Manuel Mayr, Kenneth Fish, Djamel Lebeche, Roger J Hajjar, Susmita Sahoo
Journal: Circulation Research (2018)

Background: Despite its functional importance in various fundamental bioprocesses, the studies of N6-methyladenosine (m6A) in the heart are lacking. In this study, we investigated the role of fat mass and obesity-associated (FTO), an m6A demethylase, in cardiac contractile function during homeostasis and remodeling. Methods: We used clinical human samples, preclinical pig and mouse models and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes. We modulated expression of FTO using AAV9 (in vivo), adenovirus (both in vivo and in vitro) and siRNAs (in vitro). We performed methylated (m6A) RNA immunoprecipitation sequencing (MeRIP-seq) to map transcriptome-wide m6A, and MeRIP qPCR assays to map and validate m6A in individual transcripts, in healthy and failing hearts and myocytes. We performed proteomics analysis using stable isotope labeling with amino acids in cell culture to study m6A role in mRNA to protein translation. Results: We discovered that FTO has decreased expression in failing mammalian hearts and hypoxic cardiomyocytes, thereby increasing m6A in RNA and decreasing cardiomyocyte contractile function. Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is carried out by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts, thus preventing their degradation and improving their protein expression under ischemia. Conclusion: Collectively, our study demonstrates the functional importance of FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.
EARLY CARDIAC CATHETERIZATIONS AFTER CONGENITAL HEART OPERATIONS ARE NOT ASSOCIATED WITH INCREASED RISK OF ACUTE ADVERSE EVENTS: A REPORT FROM THE CONGENITAL CARDIAC CATHETERIZATION OUTCOMES PROJECT WORKING GROUP
Authors: Ryan Leahy, Jeffrey Zampi, Fatima Ali, Aimee Armstrong, Shawn Batlivala, Ryan Callahan, Todd Gudausky, Michael Hainstock, George Nicholson, Michael O'Byrne, Brian Quinn, Shabana Shahanavaz, Sara Trucco, Lisa Bergersen
Journal: Journal of the American College of Cardiology (2019)
Planetary health: WONCA urges family doctors to commit to action
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The World Organisation of Family Doctors (WONCA) has issued a new declaration urging family doctors around the world to commit to acting on planetary health.1

It lists several ways in which family doctors can get involved, including advising patients on how they can benefit their own health and that of the environment, such as by their choice of food, using active transport and reducing their air and car travel, and their energy choices.

The declaration …
SIROLIMUS USE ASSOCIATED WITH LATE-ONSET PERICARDIAL EFFUSION AFTER RENAL TRANSPLANTATION
Authors: Stephani Chang Wang, Eugene Pashkovetsky, Muste Justin, Ashar Ata, Mikhail Torosoff, Steven Fein, Nikolas Chandolias, David Conti, Radmila Lyubarova
Journal: Journal of the American College of Cardiology (2019)
TREATMENT WITH BIOLOGIC THERAPY IN PSORIASIS IS ASSOCIATED WITH A REDUCTION IN CORONARY ARTERY INFLAMMATION, ASSESSED BY PERIVASCULAR FAT ATTENUATION INDEX
Authors: Youssef Elnabawi, Evangelos Oikonomou, Amit Dey, Jennifer Mancio, Justin Rodante, Joel Gelfand, Marcus Chen, David Bluemke, Cheerag Shirodaria, Charalambos Antoniades, Nehal Mehta
Journal: Journal of the American College of Cardiology (2019)
Abstract 411: Mitochondrial NAD(H) Signaling in Cardiac Physiology and Pathology
Authors: Qingxun Hu, Pei Wang, Rong Tian, Wang Wang
Journal: Circulation Research (2018)

The heart is a high energy-consuming organ and mitochondrial dysfunction is widely observed in heart failure. Previously, we reported that imbalanced NADH/NAD+ homeostasis in cardiomyocyte is responsible for stress-induced mitochondrial protein hyper-acetylation and accelerated progression to heart failure, which can be rescued by supplementing NAD+ precursor. The goals of this study are to develop novel fluorescent biomarkers and directly monitor mitochondrial NAD(H) redox regulation under pathophysiological conditions in adult cardiomyocytes. We constructed adenoviruses containing mitochondria-targeted NAD+ biosensor and NADH/NAD+ ratio biosensor (SoNar). We validated their mitochondrial targeting and ability to monitor acute changes in NAD+ and NADH/NAD+ ratio in adult cardiomyocytes. Pyruvate (1 mM) acutely increased mitochondrial NAD+ level and NADH/NAD+ ratio consistent with the notion that stimulating mitochondrial metabolism expanded NAD+ pool and promoted the reduction of NAD+ to NADH, which exceeded NADH consumption. In contrast, glucose (10 mM) slightly increased NADH/NAD+ ratio and palmitate had no acute effect suggesting that metabolism is only mildly stimulated and the NAD+ pool remains stable. However, palmitate treatment for 24 hr did decrease NAD+ and increase NADH/NAD+ ratio in mitochondria suggesting that the effects of physiological substrates on mitochondrial NAD(H) redox status are slow, accumulative or indirect through modulating other mitochondrial functions. Elevating cytosolic calcium with caffeine increased mitochondrial NAD+ level and decreased NADH/NAD+ ratio suggesting accelerated NADH to NAD+ turnover. Calcium has been shown to boost both energy production and utilization, but its overall impact on energy homeostasis is not clear. Our results indicate that acute increase in cytosolic calcium may have a more profound effect on energy utilization. Finally, ischemia reperfusion induced acute fluctuations in NADH and NADH/NAD+ ratio. Taken together, these results provide the first glimpse into the real-time modulation of compartmentalized NAD(H) redox state and new clues as to how mitochondrial redox is tightly controlled by mitochondrial metabolism in adult cardiomyocytes.
IMPACT OF ANEMIA ON IN-HOSPITAL MORTALITY OF HEART FAILURE PATIENTS: A NATIONAL DATABASE ANALYSIS
Authors: Aravdeep Jhand, Raviteja Guddeti, Aiza Ahmad, Abhishek Thandra, Ryan Walters, Venkata Andukuri, Venkata Alla, Aiman Smer
Journal: Journal of the American College of Cardiology (2019)
NOVEL PREDICTORS OF PERSISTENT LEFT BUNDLE BRANCH BLOCK AND PERMANENT PACEMAKER IMPLANTATION AFTER EDWARDS SAPIEN 3 TAVR
Authors: Syed Zaid, Miriam Brinkert, Hasan Ahmad, Ryan Kaple, Cenap Undemir, Martin Cohen, Steven Lansman, Asaad Khan, Jason Kovacic, George Dangas, Samin Sharma, Annapoorna Kini, Stefan Toggweiler, Gilbert Tang
Journal: Journal of the American College of Cardiology (2019)
MENTAL STRESS-INDUCED CHANGE IN PLASMA STROMAL DERIVED FACTOR-1 PREDICTS ADVERSE CARDIOVASCULAR OUTCOMES IN HEART FAILURE
Authors: Jeong Hwan Kim, Muhammad Hammadah, Ibhar Al Mheid, Kobina Wilmot, Ronnie Ramadan, Chang Liu, Yi-An Ko, Samaah Sullivan, Bruno Lima, Pratik Pimple, Ayman Alkhoder, Malik Obideen, Naser Abdelhadi, Afif Martini, Mohamad M. Gafeer, Rami Abdulbaki, Tiffany Dong, Amit Shah, Laura Ward, Doug Bremner, Brad D. Pearce, David Sheps, Paolo Raggi, Viola Vaccarino, Arshed A. Quyyumi
Journal: Journal of the American College of Cardiology (2019)
DOES MORPHOLOGY OF THE THROMBUS FORMED IN THE LEFT ATRIAL APPENDAGE INDICATE PERI-DEVICE LEAK IN PATIENTS WITH WATCHMAN DEVICE: RESULTS FROM A SINGLE-CENTER STUDY
Authors: Omer Gedikli, Sanghamitra Mohanty, Chintan Trivedi, Domenico Della Rocca, Qiong Chen, Alfredo Tapia, Sharan Sharma, John Burkhardt, Javier Sanchez, Joe Gallinghouse, Amin Al-Ahmad, Rodney Horton, Dhanunjaya Lakkireddy, Andrea Natale
Journal: Journal of the American College of Cardiology (2019)
Abstract 309: Small-molecule PDE4 Activators Limit Isoproterenol-induced Hypertrophy in Rat Neonatal Cardiomyocytes
Authors: Ganga Baskar, Abigail Boyd, Lina Abou Saleh, Thomas Boudreaux, Davis Diamond, Puay-Wah Phuan, Alan Verkman, Wito Richter
Journal: Circulation Research (2018)

Increasing the cellular levels of the second messenger cAMP, such as via activation of β-adrenergic receptors (βARs), is the most powerful mechanism to acutely increase cardiac output. However, chronic βAR stimulation predisposes to the development of heart failure (HF) by promoting arrhythmias and pathologic cardiac hypertrophy. Cardiac myocyte cAMP levels are tightly regulated by cyclic nucleotide phosphodiesterases (PDEs), a family of isoenzymes that hydrolyze and inactivate cAMP. Prior studies have shown that development of HF is associated with a downregulation of the expression and activity of Type 4 PDEs (PDE4s) in humans and animals. We propose that this reduction in PDE4 is maladaptive and may contribute to the development of HF, because genetic or pharmacologic inactivation of PDE4s is associated with an increased propensity to arrhythmias and development of pathologic cardiac hypertrophy. We propose that, conversely, an increase in PDE4 protein and/or activity would be cardioprotective. To test this hypothesis, we have utilized rat neonatal cardiomyocytes (RNCM) in culture as a model system. Long term treatment with Isoproterenol (Iso) induces hypertrophy in these cells as reflected by increased cell surface/size. To stimulate PDE4 activity, which contributes about 50% of the total cAMP-PDE activity in RNCMs, cells were treated with small-molecule PDE4 activators, which we recently identified in a high throughout screen. We find that small-molecule PDE4 activators reduce Iso-induced cellular cAMP levels as measured by enzyme immuno assay and suppress Iso-induced PKA signaling, such as the PKA-mediated phosphorylation of phospholamban. Moreover, treatment with PDE4 activators alleviates the Iso-dependent increase in cell size in RNCM indicating that pharmacologic PDE4 activation can serve to limit cardiomyocyte hypertrophy.
Changing attitudes, improving lives
Authors: Elizabeth Loder
Journal: BMJ (2019)

Palliative care has an image problem: patients and families have negative views about receiving it, and those who need it commonly enter care reluctantly or too late.Boyd and colleagues (doi:10.1136/bmj.l881)discuss whether these unfavourable ideas might improve if palliative care were rebranded, perhaps as "enhanced" or "best supportive care."The term "end of life care" is not optimal, because palliative interventions are helpful, and should be introduced, well before the end of life.Ultimately the authors conclude that attitudes, not names, should change.But they acknowledge that positive language matters.Rather than describing palliative care as an end of life intervention, doctors and families should instead consider it "an opportunity for specialist advice on managing pain and other symptoms, for help with complex decision making, and in preparing for the future."
Abstract 525: Recapitulating <i>in vivo</i> Fibroblast Differentiation Using a Hydrogel Cell Culture System
Authors: Demetria Fischesser
Journal: Circulation Research (2018)

Acute activation of cardiac fibroblasts as a result of heart failure characterized by cardiomyocyte loss is essential to maintaining proper cardiac structure and function. Chronic fibroblast activation, however, causes excessive fibrotic response leading to fibrosis and organ failure. The role of fibroblasts in this disease process has yet to be fully understood. Many previous in vitro studies have cultured fibroblasts on plastic, which can create an artificial tensile environment causing fibroblasts to behave differently than they do in vivo. To better understand fibroblast behavior, we used a hydrogel cell culture system wherein soft hydrogels mimic healthy heart tissue and stiff hydrogels mimic injured heart tissue. Another critical aspect of this system is an ability to change hydrogel stiffness for existing cultured fibroblasts. The activation of the smooth muscle α-actin (αSMA)-encoding gene (Acta2) and subsequent upregulation of its protein product correlate with fibroblast activation. Therefore, we looked at the induction of the αSMA promoter as well as the expression of αSMA protein. Here we show that stiffer hydrogels cause fibroblast activation more quickly when compared to fibroblasts plated on softer hydrogels. We also observed that on soft hydrogels, fibroblasts have smaller area with fewer branches that are longer compared to fibroblasts on stiff hydrogels. The increase in branch length along with a proclivity to migrate correlates with an increase in contact between fibroblasts on soft hydrogels not seen on stiff hydrogels. Additionally, RNA expression at various stages of differentiation will be compared to the RNA expression profile of injured and uninjured hearts previously collected in our lab. Collectively, these data will be used to classify fibroblasts into specific stages of activation and differentiation, as well as to generate a reliable in vitro model system to study fibroblast dynamics that more closely reflects their properties in vivo .
Assessing an acutely disturbed person in the community
Authors: Aileen O’Brien, Stephen Kaar, Judith Ibison, Julie Chalmers
Journal: BMJ (2019)

### What you need to know

You are urgently called to reception where a 25 year old man is shouting about the building having been taken over by demons. He appears distressed and is not responding to attempts by reception staff to communicate with him. He shouts about his neighbours, that he needs to “sort them out.” You see from his notes he has a history of psychotic episodes. 

It can be difficult to know what to do when a person in severe psychological distress presents to a general practice or community clinic, particularly if they are behaving aggressively, or if they are refusing help. The person may be experiencing a deterioration in their mental health, such as a psychotic episode, or it may be related to substance use or acute social stressors. Most patients who are acutely disturbed present no danger …
PROGNOSTIC VALUE OF THERMODILUTION CORONARY FLOW CAPACITY IN PATIENTS WITH DEFERRAL OF REVASCULARIZATION
Authors: Masahiro Hoshino, Yoshihisa Kanaji, Akinori Sugano, Masao Yamaguchi, Masahiro Hada, Yohei Sumino, Hiroaki Ohya, Yoshinori Kanno, Hidenori Hirano, Haruhito Yuki, Tomoki Horie, Taishi Yonetsu, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2019)
HIGHER MORTALITY AMONG PATIENTS WHO REQUIRED ONE OR MORE DRUGS TO ACHIEVE THE SAME SYSTOLIC BLOOD PRESSURE REGARDLESS OF THE RANDOMIZATION GROUP IN THE SYSTOLIC BLOOD PRESSURE INTERVENTION TRIAL
Authors: John B. Kostis, Chun Pang Lin, Javier Cabrera, Daniel Blickstein, William J. Kostis
Journal: Journal of the American College of Cardiology (2019)
NATURAL HISTORY OF MYOCARDIAL INJURY AND CHAMBER REMODELLING IN ACUTE MYOCARDITIS: A 12-MONTH PROSPECTIVE COHORT STUDY USING CARDIOVASCULAR MAGNETIC RESONANCE IMAGING
Authors: Ahmed Abdelhaleem, Reis Hansen, Yoko Mikami, Sandra Rivest, Alessandro Satriano, Steven Dykstra, Jacqueline Flewitt, Bobby Heydari, Carmen Lydell, Matthias Friedrich, Andrew Howarth, James White
Journal: Journal of the American College of Cardiology (2019)