tbuckley/cabot-search huggingface dataset:
Abstract 251: The Role of Adenosine Derived From Mesenchymal Stromal Cell on Neutrophil Extracellular Trap Formation in Myocardial Ischemia Reperfusion
Authors: Kai Xu, Eric Shin, Lanfang Wang, Juline Deppen, Rebecca Levit
Journal: Circulation Research (2018)

Introduction: In response to tissue damage or infection, neutrophils expel their chromatin into the extracellular space in a thrombotic and inflammatory process called neutrophil extracellular traps(NETs). There is increasing evidence that NETs play a role in myocardial ischemia/reperfusion (MI/R) injury. NETs are found in thrombi aspirated from coronary arteries, atherosclerotic plaques, and deep vein thrombosis. However, nothing is known about the regulation of NETs in vivo. We hypothesized that adenosine, well know for anti-inflammatory effects, reduces NET formation. After MI/R, adenosine is made from conversion of ATP released from damaged cells. Methods: Neutrophils were isolated from human venous blood and stimulated to produce NETs by PMA, a PKC agonist and is well known to induce robust NET formation and serves as a positive control. NETs were quantified by Sytox green fluorescent to quantify extracellular DNA and immunohistochemical staining for citrullinated histone H3, a specific marker of NETs. Results: Neutrophils treated with PMA increased NET production (1.81fold vs unstimulate groups, p&lt;0.001, n=27-28). Neutrophils treated with adenosine (10uM) had a 30.2% decrease NET formation (p&lt;0.001, n=15). There are four adenosine receptors called A1, A2a, A2b, and A3. We used agonists and antagonists’ strategy to check probable receptors involved in suppression NETs signal. We find both A2a receptor agonist-CGS 21680 and A2b agonist-BAY 60-6583 can suppress NETs formation (29.6% and 29.3% respectively p&lt;0.001, n=5-6). But only A2a antagonist-ZM241385 can reverse adenosine’s inhibition (13.8%v.s.24.7%, p&lt;0.05, n=6). Conclusion: Adenosine can downregulate NET formation in vitro likely through A2a receptor activation. Future studies will investigate A2a receptor using genetic knock out, as well as in vivo significance of NET inhibition in MI/R.
Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets
Authors: Liu Zhang, Shailendra Shakya, Li Wu, Jiangtao Wang, Guanghui Jin, Huimin Sun, Xianzhen Yin, Lixin Sun, Jiwen Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2019)

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid (SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional (3D) information of SA particles in tablets was detected by a quantitative and non-invasive 3D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography (SR-µCT). SA particles in glipizide tablets prepared by using unmodified SA (GUT), reprocessed SA (GRT), as well as reference listed drug (RLD) of glipizide tablets were analyzed by SR-µCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-µCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.
Climate Change and Physical Activity: Estimated Impacts of Ambient Temperatures on Bikeshare Usage in New York City
Authors: Alexandra K. Heaney, Daniel Carrión, Katrin Burkart, Corey Lesk, Darby Jack
Journal: Environmental Health Perspectives (2019)

Background: Physical activity is one of the best disease prevention strategies, and it is influenced by environmental factors such as temperature. Objectives: We aimed to illuminate the relation between ambient temperature and bikeshare usage and to project how climate change-induced increasing ambient temperatures may influence active transportation in New York City. Methods: The analysis leverages Citi Bike® bikeshare data to estimate participation in outdoor bicycling in New York City. Exposure–response functions are estimated for the relation between daily temperature and bike usage from 2013 to 2017. The estimated exposure–response relation is combined with temperature outputs from 21 climate models (run with emissions scenarios RCP4.5 and RCP8.5) to explore how climate change may influence future bike utilization. Results: Estimated daily hours and distance ridden significantly increased as temperatures increased, but then declined at temperatures above 26–28°C. Bike usage may increase by up to 3.1% by 2070 due to climate change. Future ridership increases during the winter, spring, and fall may more than offset future declines in summer ridership. Discussion: Evidence suggesting nonlinear impacts of rising temperatures on health-promoting bicycle ridership demonstrates how challenging it is to anticipate the health consequences of climate change. We project increases in bicycling by mid-century in NYC, but this trend may reverse as temperatures continue to rise further into the future. https://doi.org/10.1289/EHP4039
The significant global economic burden of bronchiectasis: a pending matter
Authors: Wei-jie Guan, Xiao-rong Han, David de la Rosa-Carrillo, Miguel Angel Martinez-Garcia
Journal: European Respiratory Journal (2019)

Bronchiectasis should no longer be considered an "orphan lung disease" in view of its prevalence globally [1]. For instance, the prevalence of bronchiectasis has been found to range from 67 to 566.1 per 100 000 inhabitants in Europe and North America ( i.e. Germany [2], Spain [3], the UK [4] and the USA [5]), and has reached 1200 per 100 000 inhabitants among those aged 40 years or older in China [6]. Bronchiectasis confers a considerable economic burden on healthcare services worldwide <http://ow.ly/mTkF30nbEu7>
CHARACTERISTICS AND LONGER-TERM OUTCOMES OF PEDIATRIC PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY: A TERTIARY CARE CENTER EXPERIENCE
Authors: Alaa Alashi, Laurence Svensson, Jared Klein, Kenneth Zahka, Nicholas Smedira, Hani Najm, Robert Stewart, Harry Lever, Peter Aziz, Elizabeth Saarel, Milind Desai
Journal: Journal of the American College of Cardiology (2019)
THE SAFETY OF ANTICOAGULATION FOR ATRIAL FIBRILLATION WITH DOAC VERSUS WARFARIN IN PATIENTS WITH VARIOUS STAGES OF RENAL FUNCTION
Authors: Amber Makani, Samir Saba, Sandeep Jain, Aditya Bhonsale, Oscar Marroquin, Suresh Mulukutla
Journal: Journal of the American College of Cardiology (2019)
Two roads for oncolytic immunotherapy development
Authors: Howard L. Kaufman, Praveen K. Bommareddy
Journal: Journal for ImmunoTherapy of Cancer (2019)

Oncolytic viruses are an emerging class of immunotherapy agents for cancer treatment. In this issue of JITC, Machiels et al. reports early phase data from an oncolytic adenovirus given by intravenous (IV) administration. While this may allow easy access to metastatic lesions, there is limited data supporting the therapeutic effectiveness of this approach. Further studies should include assessment of viral replication in tumor tissue and consider comparative trials using IV and intratumoral delivery to fully optimize oncolytic immunotherapy.
CONTEMPORARY ETIOLOGIES, TREATMENT STRATEGIES, AND OUTCOMES OF LEFT VENTRICULAR THROMBUS
Authors: Cian McCarthy, Sean Murphy, Ramkumar V. Venkateswaran, Avinainder Singh, Leslie L. Chang, Melvin G. Joice, Arman Qamar, Muthiah Vaduganathan, James Januzzi, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2019)
Abstract 348: Epigenetic Regulation in Heart Regeneration
Authors: Shuo Tian, Ienglam Lei, Peter X Ma, Zhong Wang
Journal: Circulation Research (2018)

Existing treatments for myocardial infarction (MI) include Medication, intervention, and surgical bypass. These strategies are mainly used to prevent disease progression, but do not address the fundamental problem of cardiomyocyte loss. Therefore, developing new effective therapeutic strategies to preserve the pumping function after MI is highly desired. Acute injuries, such as MI, are companied with quick and massive loss of histone acetylation in injured cells, which lead to severe organ damage. Therefore, maintaining proper histone acetylation in a swift manner will likely protect the affected cell and organ function. In this study, we showed that valproic acid (VPA), a pan HDAC inhibitor and a FDA approved drug for epilepsy and bipolar disorders, reduced ~50% of the infarct size and preserves the pumping function of heart after MI in rats. Moreover, 60 min after infarction, VPA administration still significantly decreased infarct size in MI rats. Mechanistically, we identified that that VPA treatment triggered a Foxm1 pathway, which in turn activated genes essential for cell survival and proliferation and inflammation suppression. Importantly, overexpression of Foxm1 provided similar heart protective effect after MI as VPA treatment. In contrast, inhibition of Foxm1 activity abolished the cardiac protective effect of VPA. In parallel, we have applied novel biodegradable nanofibrous microspheres as cell carriers for cell transplantation. These microspheres dramatically improve engraftment of exogenously delivered cells and functional recovery of the infarcted hearts. Intriguingly, the efficacy of cell engraftment appears to correlate with the cell carrier’s ability to maintain the acetylation status of the cells. We expect that the combined HDAC inhibitor treatment with cell carrier-mediated CM transplantation will work synergistically to regenerate infarcted heart functioning and lead to effective clinical applications in heart regeneration therapy.
FIVE-YEAR OUTCOMES FOLLOWING PERCUTANEOUS CORONARY INTERVENTION BY AGE AND SEX: AN INDIVIDUAL PATIENT DATA POOLED ANALYSIS FROM 21 RANDOMIZED TRIALS
Authors: Heidi S. Lumish, Mahesh Madhavan, Bjorn Redfors, Yiran Zhang, Patrick Serruys, Pieter Smits, Clemens von Birgelen, Ioanna Kosmidou, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
A Case for n-of-1 Trials—Reply
Authors: Richard L. Kravitz, Ida Sim, Naihua Duan
Journal: JAMA Internal Medicine (2019)

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RELATIONSHIP OF BODY COMPOSITION TO INCIDENT HEART FAILURE IN TWO POPULATION-BASED COHORTS OF OLDER ADULTS
Authors: Lili Zhang, Traci M. Bartz, Venkatesh Murthy, Adam Santanasto, Ravi Shah, Luc Djousse, Kenneth Mukamal, Daniel Forman, Calvin Hirsch, Anne Newman, Tamara B. Harris, John S. Gottdiener, Jorge R. Kizer
Journal: Journal of the American College of Cardiology (2019)
Abstract 042: Accelerometer-measured Light Physical Activity is Heart Healthy in Older Women: The OPACH Study
Authors: Andrea Z LaCroix, John Bellettiere, Eileen Rillamas-Sun, Kelly R Evenson, Chongzhi Di, David M Buchner, Marcia L Stefanick, I-Min Lee, Cora E Lewis, Michael J LaMonte
Journal: Circulation (2018)

Background: The longstanding, prevailing paradigm in physical activity (PA) research and US PA guidelines is that moderate to vigorous physical activity (MVPA) for at least 150 minutes/week, preferably in increments of at least 10 minutes, is needed to prevent cardiovascular disease (CVD) in adults. Because light physical activity (LPA; 1.1-&lt;3 metabolic equivalents (METs)) is poorly measured by self-report, we know little about its association with CVD. Methods: Women’s Health Initiative participants in the OPACH Study (n=5861, mean age=78.5±6.7, 33.5% Black, 17.6% Hispanic) without a history of myocardial infarction or stroke wore accelerometers for up to 7 days and were followed for incident CVD for up to 4 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for CVD and coronary heart disease (CHD) across awake wear time adjusted quartiles of MVPA and LPA. Fully adjusted models accounted for age, race-ethnicity, smoking, education, body mass index, systolic blood pressure, co-morbidity score, physical function, and self-rated health. We then examined the LPA association with CVD/CHD after adjustment for MVPA. Results: Higher levels of both LPA and MVPA were associated with reduced risks of CVD and CHD after adjusting for covariates (Table; p-trend &lt;0.05, all). Women with the highest vs. lowest levels of MVPA had markedly reduced risks of CVD (31%) and CHD (50%). Women in the highest vs. lowest quartiles of LPA had 22% reduced risks of CVD and 39% reduced risks of CHD even after adjustment for many indicators of health status and CVD risk factors. The LPA association with CVD persisted after adjustment for MVPA (highest vs. lowest LPA quartile HR: 0.81 for CVD, p-trend=0.01; 0.74 for CHD, p-trend=0.04). Conclusions: LPA is associated with reduced risks of incident CVD and CHD in older women independent of health status indicators, CVD risk factors, and MVPA. Increasing levels of LPA is an achievable behavioral intervention for improving heart health in older women.
SCREENING FOR CORONARY ARTERY CALCIUM IN ASYMPTOMATIC ADULTS BASED ON THE 10-YEAR FRAMINGHAM RISK SCORE IN THE SOCIETY FOR HEART ATTACK PREVENTION AND ERADICATION (SHAPE) COHORT
Authors: Amish Patel, Jeffrey Fine, Ramdas Pai, Morteza Naghavi, Matthew Budoff
Journal: Journal of the American College of Cardiology (2019)
CHRONIC TOTAL OCCLUSION IS ASSOCIATED WITH ADVERSE OUTCOMES IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION: A NATIONWIDE STUDY USING THE NATIONAL INPATIENT SAMPLE (NIS) 1999-2014
Authors: Rishi Shrivastav, Kamala Ramya Kallur, Dipesh Ludhwani, Stuthi Perimbeti, Dhrubajyoti Bandyopadhyay, Bharat Narasimhan, Ramesh Gowda
Journal: Journal of the American College of Cardiology (2019)
Factors Influencing Incidence of Supraventricular Arrhythmias during and after Autologous Stem Cell Transplant in Multiple Myeloma
Authors: Megan Sturdy, Rebecca Ye, Trevor L Jenkins, James Driscoll, Paolo Caimi, Leland Metheny, Rachel Zebrowski, Nicole Ferrari, Merle Kolk, Marcos de Lima, Ehsan Malek
Journal: Blood (2018)
AMIODARONE PROPHYLAXIS PREVENTS ATRIAL FIBRILLATION AFTER SEPTAL MYECTOMY FOR HYPERTROPHIC CARDIOMYOPATHY
Authors: Evan Shalen, Reyhaneh Akhavein, Miriam Elman, Katherine L. Fischer, Meghan Mannello, Howard Song, Stephen Heitner
Journal: Journal of the American College of Cardiology (2019)
Abstract 266: Sex Differences in Survival and Pathological Responses of Hearts, Cardiac Myocytes and Fibroblasts
Authors: Angela K Peter, Tova L Christensen, Cierra J Walker, Christa L Trexler, Christopher D Ozeroff, Kimberly R Lugo, Amy R Perry, Kristi S Anseth, Leslie A Leinwand
Journal: Circulation Research (2018)

Introduction: Biological sex is an important modifier of cardiovascular disease (CVD). However, women and female animals have traditionally been excluded from clinical trials and most preclinical research studies, resulting in therapeutics that are not as effective, or with different side effects, in women relative to men. Methods and Results: We show here that expression of α- and β-adrenergic receptors, cardiac stiffness, myofibroblast proliferation, and expression of fibrotic markers are sexually dimorphic at baseline. To determine whether pathogenesis was different between the sexes, the β-adrenergic agonist, isoproterenol (ISO), was administered to rats. In response to 7-days of ISO treatment, female animals were more likely to survive than their male counterparts (percent survival: 44% in males versus 77% in females). Both sexes developed significant cardiac hypertrophy, activation of cardiac fetal genes (ANF and β-MHC) compared to vehicle controls. Cardiac myocytes from ISO treated animals took less time to reach peak shortening and displayed increased departure velocity; however, only male ISO treated cells exhibited reduced relaxation times and increased return velocities. Importantly, ISO treated animals developed significant fibrosis prompting us to analyze isolated cardiac fibroblasts at baseline and in response to ISO. We observed significantly increased expression of α-SMA and Col1a, two indicators of myofibroblast activation, only in fibroblasts isolated from ISO treated males. Both ISO treated male and female fibroblasts showed significant increases in periostin and decreases in TCF21, indicative of increases in myofibroblasts and decreases in quiescent fibroblasts, respectively. In addition, both sexes revealed increased fibroblast proliferation in vivo , as measured by EdU incorporation, in response to ISO. Conclusions: Chronic in vivo β-adrenergic receptor stimulation revealed dramatic sex differences in mortality, cardiac hypertrophy, myocyte contractility, and cardiac fetal gene expression. Increases in myofibroblast differentiation and fibroblast proliferation should lead to a robust fibrotic response in both male and female ISO treated animals.
IMPACT OF CONTRACTILE RESERVE BY DOBUTAMINE STRESS ECHOCARDIOGRAPHY IN LOW-GRADIENT AORTIC STENOSIS WHO UNDERWENT AORTIC VALVE PROCEDURE
Authors: Kimi Sato, Samir Kapadia, Amar Krishnaswamy, Stephanie Mick, Milind Desai, Brian Griffin, Lars Svensson, Zoran Popovic
Journal: Journal of the American College of Cardiology (2019)
Abstract 109: G Protein-coupled Receptor Kinase 2 Impairs Fatty Acid Metabolism in the Failing Heart Through Novel Mechanisms
Authors: Jessica M Pfleger, Polina Gross, Jaslyn Johnson, Erhe Gao, Steven R Houser, Walter J Koch
Journal: Circulation Research (2018)

Compromised contractility and energetics are hallmarks of the failing heart. Increased G protein-coupled receptor kinase (GRK)2 is central to the pathogenesis of heart failure (HF), via desensitization of beta-adrenergic receptors and, therefore, loss of contractile reserve. Additionally, we, and others, have reported that GRK2 has non-canonical activity that contributes to its pathological functionality in HF. For example, GRK2 can compromise fatty acid (FA) metabolism in cardiomyocytes, the mechanism of which remains unknown. Thus, our aim is to investigate the role of GRK2 in FA metabolism and bioenergetics in the heart. To do this, we measured FA uptake, cluster of differentiation (CD)36 expression, phosphorylation, and ubiquitination, and FA-driven bioenergetics in mice with cardiac-specific overexpression of GRK2, to levels observed in the human failing myocardium, or a GRK2 inhibitory peptide (TgGRK2 and TgβARKct, respectively) or in global heterozygous GRK2 knockout (GRK2 +/- ) mice. Additionally, we determined CD36 expression and phosphorylation following cardiac dysfunction induced by transverse aortic constriction (TAC). The results show a significant reduction in FA uptake rates (0.3-fold) and CD36 protein (0.8-fold), which was associated with an increase in its phospho-serine/threonine (0.7-fold increase) and ubiquitin-lysine (0.7-fold) content in the TgGRK2 mice. In contrast, these parameters were unchanged in the TgβARKct or GRK2 +/- mice. A reduction in CD36 mRNA (0.7-fold) and protein levels (0.2-fold) were detected in post-TAC, failing hearts, which was associated with an increase is its phosphorylation (0.5-fold). Notably, normalization of CD36 protein levels is observed in GRK2 +/- mice post-TAC. Maximal respiratory capacity was also enhanced in TgβARKct and GRK2 +/- cardiomyocytes (0.6- and 0.8-fold, respectively). Together, our results show that up-regulation of GRK2 induces CD36 phosphorylation, ubiquitination, and downregulation, which is associated with reduced FA uptake. Thus, we propose that the increase in GRK2 observed during HF is, at least partly, responsible for reduced FA uptake and oxidation and may be an important nodal switch in substrate utilization during HF pathogenesis.
Stephen I. Katz, MD, PhD, Professional and Personal Remembrances
Authors: John R. Stanley
Journal: JAMA Dermatology (2019)

Stephen I. Katz, MD, PhD (Figure 1), died suddenly on December 20, 2018. It is a testament to his humble nature that such a giant in our field was universally known simply as Steve or Steve Katz. His influence as a physician-scientist in dermatology and beyond cannot be overstated.
Substrate‐Independent Coating with Persistent and Stable Antifouling and Antibacterial Activities to Reduce Bacterial Infection for Various Implants
Authors: Pingyun Yuan, Xinyu Qiu, Xinran Wang, Ran Tian, Lin Wang, Yongkang Bai, Shiyu Liu, Xin Chen
Journal: Advanced Healthcare Materials (2019)

Abstract Implantation of biomedical devices accompanying infections has caused severe problems to public health that require feasible solutions. In this study, a simple approach is reported to fabricate a antimicrobial and antifouling dual‐functional coating. This coating consists of a substrate‐independent layer‐by‐layer (LBL) film formed by poly (diallyldimethylammonium) (PDDA) and poly (styrenesulfonate) (PSS), where parts of PSS and PDDA are physically substituted by hetero‐bifunctional polyethylene glycol (PEG) ending with a carboxyl group and antimicrobial peptide (ε‐Poly‐l‐lysine, ε‐PL). This design (ε‐PL‐PEG‐(PDDA/PSS)9 coating) exhibits not only potent antimicrobial activity against Gram‐positive/negative bacteria but also superior antifouling activity on various substrates, including glass and plastic. Moreover, the antifouling and antibacterial performance can be maintained for a longer period of time under physiological environments even after physical damage of the surface due to the homogeneous interspersion and free migration of ε‐PL‐PEG‐COOH in the LBL film. This allows the supplement of these molecules to the surface against molecule loss during usage. Both in vitro and in vivo (rodent subcutaneous infection model) studies show obvious reduction of the bacteria on the coated substrate and in the surrounding tissues with up to 3.2‐log reduction, even after repeated usage. The inflammation around the implantation area is also significantly inhibited.