tbuckley/cabot-search huggingface dataset:
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Authors: Kristina Behnke, Yuan Zhuang, Haifeng C. Xu, Balamurugan Sundaram, Maria Reich, Prashant V. Shinde, Jun Huang, Nastaran Fazel Modares, Alexei V. Tumanov, Robin Polz, Jürgen Scheller, Carl F. Ware, Klaus Pfeffer, Verena Keitel, Dieter Häussinger, Aleksandra A. Pandyra, Karl S. Lang, Philipp A. Lang
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. It is with great appreciation that we read the comment from Ait Ahmed et al., who raise questions that are equally interesting and important. In our manuscript, we identified an important role of B cells during liver regeneration. We found that the presence of B cells was essential for liver regeneration after partial hepatectomy (PHx). In line with these results, presence of a functional spleen as well as B cell–activating factor of the tumor necrosis factor (TNF) family was needed for liver regeneration. Mechanistically, a lack of B cells was associated with the reduced presence of CD169+ cells, which contributed to interleukin‐6 (IL‐6) production.1 Ait Ahmed et al. point out that tissue‐resident liver macrophages might contribute to the observed findings. Indeed, macrophages are key players during liver regeneration,2 and one could consider that a lack of B cells would directly affect liver macrophages during PHx. We observed raised numbers of CD169+ cells in the liver after PHx. We have not further addressed whether these cells are liver‐resident macrophages differentiating into CD169+ cells or whether they are infiltrations of CD169+ cells. Notably, the increase of CD169+ cells was abolished following splenectomy, suggesting that splenic factors influence this process. Kupffer cells can express CD169 and, accordingly, can be depleted in CD169‐DTR mice.3 In our settings, we observed a rather low yield of hepatic CD169+ cells at the time we treated mice with diphtheria toxin. Therefore, we consider it most likely that CD169+ cells and/or B cells are important pacemakers for other macrophage subsets. Depletion of B cells and/or CD169+ cells might therefore impact the presence and function of Kupffer cells during liver regeneration. Indeed, Kupffer cells are producers of IL‐6,4 and we found that a lack of CD169+ cells limited IL‐6 production during PHx. Application of Hyper‐IL‐6 could compensate for CD169+ cell depletion. Further characterization of the interplay among liver resident macrophages, B cells, CD169 expression, and IL‐6 during liver damage and regeneration is a highly interesting issue that should be addressed in future studies. In conclusion, we agree with the authors that further characterization of macrophage subsets—including tissue‐resident macrophages—during liver regeneration is needed and that there are open questions regarding how these subsets communicate with each other.
Nivolumab for Relapsed or Residual Haematological Malignancies after Allogeneic Haematopoietic Stem Cell Transplantation (NIVALLO)
Authors: Eric Wong, Emily Dawson, Joanne Davis, Rachel Koldej, Mandy Ludford-Menting, Matthew Lansdown, Heather Lambie, Jeffrey Szer, Andrew P. Grigg, David Ritchie
Journal: Blood (2018)
NATIONWIDE IN-HOSPITAL MORTALITY AND COMPLICATIONS IN PATIENTS WITH CARDIOGENIC SHOCK AND ST ELEVATION MYOCARDIAL INFARCTION THAT UNDERWENT PERCUTANEOUS LEFT VENTRICULAR SUPPORT DEVICE PLACEMENT
Authors: Brent Dembo, James Kogut, Sumeet Lall, Tariq Ahmad, Ryan Wilson, Chad Zack
Journal: Journal of the American College of Cardiology (2019)
SOLUBLE NEPRILYSIN IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION
Authors: Melissa Lyle, Seethalakshmi Iyer, Margaret Redfield, Yogesh Reddy, G. Michael Felker, Thomas Cappola, Adrian Hernandez, Steven McNulty, Christopher Scott, John Burnett, Naveen Pereira
Journal: Journal of the American College of Cardiology (2019)
Loss of HDAC11 Promotes Myeloid-Derived Suppressor Cells Inhibition of T Cell Function in a Murine Lymphoma Microenvironment
Authors: Jie Chen, Fengdong Cheng, Michael Wang, Eva Sahakian, John J. Powers, Javier Pinilla Ibarz, Mitchell R. Smith, Eduardo Sotomayor
Journal: Blood (2018)
Abstract 543: Uncovering the Mechanisms by Which Fatty Acid Oxidation Suppresses Cardiomyocyte Hypertrophy
Authors: Julia Ritterhoff, Dan Shao, Stephen C Kolwicz, Zhenglong Liu, Rong Tian
Journal: Circulation Research (2018)

In cardiac hypertrophy, the adult heart switches from mainly using fatty acids to an increased reliance on glucose to maintain its energetic demands. We have previously shown that preserving fatty acid oxidation (FAO) by cardiac-specific deletion of Acetyl-CoA Carboxylase 2 (ACC2) prevents the shift of substrate preference towards glucose, preserves cardiac function and reduces cardiomyocyte hypertrophy during chronic pressure overload. To determine whether maintaining FAO specifically prevented cardiomyocyte hypertrophy, we treated adult rat cardiomyocytes (CMs) with and without adenoviral-mediated ACC2 knock-down (KD) with phenylephrine (PE, 10 μM). ACC2 KD effectively prevented CM hypertrophy after PE stimulation compared to control CMs (+9±6% vs. 42±6%) in medium supplemented with fatty acids (FA) (5.5 mM glucose, 0.4 mM mixed long-chain FAs and 0.1 mU/ml insulin). Whereas PE stimulation in control CMs increased glucose uptake (+28±8%), accumulation of glycolytic intermediates and lactate (+52±15%), this was normalized after ACC2 KD. Inhibiting FAO by etomoxir or increasing glucose utilization by dichloroacetate abolished the antihypertrophic effects of ACC2 KD after PE stimulation. However, replacing glucose with pyruvate or propionate restored the anti-hypertrophic effect of ACC2 KD. The expansion of TCA cycle pool caused by PE stimulation was also suppressed by ACC KD. Furthermore, ACC2 KD resulted in decreased intracellular amino acid levels, consistent to what has been seen in ACC2 knock-out hearts in vivo. This was accompanied by reduced glutamine consumption from the media (-60±25%) in ACC2 KD CMs, indicating reduced glutamine reliance. Taken together, our data suggest that ACC2 KD reduces the utilization of glucose and glutamine; both substrates known to be required for cell growth in vitro and in vivo. This further supports the hypothesis that maintaining FAO prevents the metabolic switch and CM hypertrophy.
Robert Darragh Montgomery
Authors: Charles Montgomery
Journal: BMJ (2019)

From Campbell College, Belfast, Robert Darragh Montgomery won a scholarship to study Medicine at Gonville and Caius College, Cambridge, and later at the Middlesex Hospital, London. He developed an interest in tropical medicine during his short service commission with the Royal Air Force (1951-54,) when he was stationed with the Rhodesian Air Training Group in Bulawayo. This he developed in Kingston, Jamaica, where in 1956 he was appointed to the scientific staff at the Medical Research Council in the tropical …
IMPACT OF CORONARY ARTERY CALCIFICATION IN PATIENTS UNDERGOING REVASCULARIZATION FOR LEFT MAIN CORONARY ARTERY DISEASE: INSIGHTS FROM THE EXCEL TRIAL
Authors: Sabato Sorrentino, Roxana Mehran, Gennaro Giustino, Mengdan Liu, David Kandzari, Marie C. Morice, Anthony Gershlick, Ovidiu Dressler, Joseph Sabik, A. Kappetein, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
ENDOTHELIUM-DEPENDENT CORONARY MICROVASCULAR DYSFUNCTION IS ASSOCIATED WITH ADVANCED CORONARY PLAQUE CHARACTERISTICS IN PATIENTS WITH NONOBSTRUCTIVE CORONARY ATHEROSCLEROSIS
Authors: Shigeo Godo, Michel Corban, Takumi Toya, Rajiv Gulati, Lilach Lerman, Amir Lerman
Journal: Journal of the American College of Cardiology (2019)
Abstract 467: p53 Stabilized iPS Derived Cardiomyocytes Promote Myocardial Repair
Authors: Ramaswamy Kannappan, James F Turner, Vasanthi Rajasekaran, Jianyi Zhang
Journal: Circulation Research (2018)

Rapid and continuous culturing of cells leads to accumulation of oxidative stress and DNA damage. These heterogeneous mixtures of healthy and damaged functionally incompetent cells (FIC) are not suitable for transplantation. We hypothesized that selecting only the healthy cells and use for cell would improve engraftment rate and cardiac function. Utilizing the discriminating nature of p53, inducing apoptosis in damaged cells while retaining cell cycle in healthy cells, we tested whether stabilizing p53 can retain only the healthy cells in the culture. p53 in iPS cultures were stabilized using small-molecule nutlin-3a. Cells that didn’t die due to p53 stabilization were collected and differentiated into cardiomyocytes. The markers for cell stress such as the ROS, superoxide and DNA damage were significantly reduced in p53S cells. Following differentiation p53S-CMs were characterized by high expression of CM markers Nkx2.5, Gata4, TnI, MYL2, MLYK, KCNH2 and CAMK2B. Efficiency of p53S-CM to engraft and remuscularize the injured myocardium were tested in small animal MI model. After one week of cell transplantion cardiac function, infarct size and engraftment rate of cells were comparable between p53S-CM and control-CM recieved groups. At week four significant improvement in cardiac function and reduction in infarct size were observed in both groups. However, improvement in these parameters were more prominent in p53S-CM groups. Macrophage analysis revealed enhanced recruitment of anti-infalmatory M2 macrophages in p53S-CM groups and inflammatory M1 macropaheges in control-CM groups at the injection site. Moreover, p53S-CM exosomes induced predominant M2 polarization while control-CM exosomes favored M1 polarization of RAW264.7 macrophages. Our data clearly shows functionally competent cells can be isolated from a population of heterogeneous cells by stabilizing p53. The p53S-CMs showed superior performance in in vitro and in vivo. Therefore, selecting healthy cells by stabilizing p53 would better repopulate the deteriorating myocardium and improve cardiac performance.
INCIDENCE OF ATRIAL FIBRILLATION DURING PREGNANCY AND ITS IMPACTS ON MATERNAL AND FETAL OUTCOMES: A META-ANALYSIS
Authors: Pavida Pachariyanon, Wisit Cheungpasitporn, Tarun Bathini, Oisin A. O'Corragain, Charat Thongprayoon, Ronpichai Chokesuwattanaskul
Journal: Journal of the American College of Cardiology (2019)
Differential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells
Authors: Shivani K. Thaker, Travis Chapa, Gustavo Garcia, Danyang Gong, Ernst W. Schmid, Vaithilingaraja Arumugaswami, Ren Sun, Heather R. Christofk
Journal: Cell Metabolism (2019)
Abstract 20945: Improved Risk Prediction Using a Comprehensive Cta Risk Score That Incorporates All Aspects of Coronary Atherosclerosis Compared With Standard Cta Classification
Authors: Alexander R van Rosendael, Leslee Shaw, Joe Xie, Aukelien Dimitriu-Leen, Jeff Smit, Arthur Scholte, James Min, Jeroen Bax
Journal: Circulation (2017)

Background: Risk assessment with coronary CTA is traditionally done with maximal stenosis, but this approach does not use the prognostic value of plaque extent, location and composition. This study assessed whether a comprehensive CTA risk model incorporating all aspects of coronary atherosclerosis provides better risk stratification than the commonly used CTA classification of no CAD, non-obstructive and obstructive CAD. Methods: Among 2255 patients with suspected or known CAD the predictive value of the CTA risk score (range from 0-42) was compared with the standard CTA classification. Three risk groups were created based on their best discriminatory performance: 0-5; 6-20; &gt;20. Results: During a mean follow up of 3.6 ± 2.8 years 156 events (death or MI) occurred. Compared with the standard CTA classification, a stronger association with events was observed for the CTA risk score: adjusted HR for 6-20 was: 2.69 (95% CI: 1.55-4.68, P&lt;0.001) and 5.53 (95% CI: 2.82-10.82, P&lt;0.001) for a score &gt; 20 By comparison, adjusted HR for non-obstructive CAD were 1.19 (95% CI: 0.61-2.29, P=0.613) and for obstructive CAD 2.52 (95% CI: 1.33-4.78, P=0.005), Figure 1. Adding the score to a model with clinical variables and the standard CTA classification increased the c-statistic from 0.756 to 0.781 (P&lt;0.001). Furthermore net reclassification analysis confirmed that the novel CTA risk score was able to correctly reclassify a significant proportion of patients compared with the standard CTA classification: categorical NRI 12% (7.4% for events, 4.6% for non-events) using three predicted risk categories 0-5%, 5-15% and &gt;15% Conclusion: A CTA risk model incorporating all aspects of CAD provides better discrimination and reclassification of events compared with the standard CTA scoring model including normal, non-obstructive and obstructive CAD. The proposed model allows more precise risk estimation which may further guide patient treatment.
DIFFUSE CORONARY ATHEROSCLEROSIS AND LESS STABLE PLAQUE MORPHOLOGIES ARE MORE PREVALENT IN ASYMPTOMATIC BIOPSY-PROVEN NAFLD PATIENTS: RESULTS FROM THE PROSPECTIVE PREVALENCE STUDY
Authors: Anthony Vande Hei, Kelvin Bush, Emilio Fentanes, James Aden, Angelo Paredes, Stephen Harrison, Dustin Thomas
Journal: Journal of the American College of Cardiology (2019)
TRIMETHYLAMINE-N-OXIDE AND RELATED METABOLITES ARE ASSOCIATED WITH CARDIOVASCULAR EVENTS: RESULTS FROM THE DALLAS HEART STUDY
Authors: Yeela Barkan-Talmor, Colby Ayers, Wai Hong, Wilson Tang, Guy Witberg, Alon Eisen, Ashraf Hamdan, Stanley L. Hazen, James A. de Lemos, Ran Kornowski, Ian Neeland
Journal: Journal of the American College of Cardiology (2019)
Abstract 518: Hemodynamic Instability in Atrial Flutter With Slow Ventricular Response
Authors: Nnamdi A Nwafo
Journal: Circulation Research (2018)

Background: The commonest atrioventricular (AV) conduction ratio in atrial flutter is 2:1, with corresponding ventricular response of about 150 beats/min. Higher degree of AV block with resulting lower ventricular conduction may indicate use of AV nodal blocking drugs, intrinsic conducting system disease, electrolyte abnormalities or hypothermia. Case: An 86-year-old with history of hypertension, hyperlipidemia, hypothyroidism, coronary and carotid artery disease was admitted after a syncopal episode while on a cross country trip. He was hypotensive and profoundly bradycardic(heart rate initially in the 30s). Examination revealed irregular rhythm and right carotid bruit. EKG showed atrial flutter with variable ventricular response ranging from 3:1 to 5:1 (or more) block, with ventricular rate in the 50s and 60s. Echocardiogram showed low normal left ventricular systolic function without regional wall abnormalities, right ventricle enlargement with global systolic dysfunction, and severe left atrial enlargement. Thyroid function was normal. Decision-making: With hemodynamic instability in the setting of atrial flutter, he was started on anticoagulation and intravenous hydration, and after left atrial thrombus was ruled out with a transesophageal echocardiogram, he underwent successful urgent cardioversion. He was then noted to have intermittent Mobitz type II second degree and third degree AV block, prompting urgent temporary transvenous pacemaker (PM) placement, followed by permanent dual chamber PM implantation. He had bleeding from the PM placement site but this was controlled with pressure. Therapy with beta blocker was re-initiated, and electrolytes were supplemented as needed. Vitals signs improved and he was discharged in stable health to follow up with his cardiologist. Conclusion: Urgent or emergent cardioversion is indicated for hemodynamic instability in atrial flutter, even with slow ventricular response. In the absence of use of AV nodal blocking agents, lower rate of ventricular response may indicate intrinsic conducting system disease, and as in the case above, may require PM placement.
STRESS ECHOCARDIOGRAPHY AND SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY HAVE POOR SENSITIVITY FOR DETECTION OF CARDIAC ALLOGRAFT VASCULOPATHY IN HEART TRANSPLANT RECIPIENTS
Authors: Andrew Noll, Serge Harb, Amanda Artis, Ghina Alaaeddine, Paul Cremer, Miriam Jacob, Wael Jaber
Journal: Journal of the American College of Cardiology (2019)
Abstract 428: Cytoglobin: A Novel Regulator of the DNA Damage Response Within Cardiomyocytes
Authors: Sarvjeet Singh, Dylan Rivas, Diana Canseco, Melanie Weiler, Terry Gemelli, Jian Huang, Tara Tassin, John Shelton, James A Richardson, Hesham Sadek, Pradeep P Mammen
Journal: Circulation Research (2018)

Rationale: Oxidative stress is a major determinant of DNA damage within cardiomyocytes both at baseline and following cardiac injury. Cytoglobin (Cygb), a stress responsive hemoprotein, serves as a redox modulator and imparts cytoprotection in a variety of cell types. In addition, Cygb is involved in regulation of myocyte proliferation and differentiation due to its ability to scavenge free radicals and maintain redox equilibrium within the myocytes. Objective: The goal of this study was to investigate the role of Cygb in cardiomyocytes and identify the molecular pathways underlying its cytoprotective function. Method and Results: Utilizing transgenic mice with cardiac specific overexpression of Cygb (TgCygb), we demonstrated that Cygb overexpression promoted cardiomyocyte proliferation as compared to the control hearts (NTg) (phospho-Histone 3 IHC: 17 ± 0.7 vs 7 ± 0.5 positive cells/mm 2 TgCygb vs NTg; p&lt;0.05, n=3) . The enhanced cellular proliferation in TgCygb hearts was associated with larger hearts at baseline. However, with exposure to acute cardiac stress (subcutaneous Angiotensin II infusion), TgCygb hearts showed significantly reduced cell death, oxidative stress and an overall lower induction of the DNA damage response pathway as compared to the NTg hearts [TUNEL: 7 ± 0.8 vs 10 ± 1.2 TUNEL positive nuclei/mm 2 , p&lt;0.05, n=3; phospho-ATM IHC: 11 ± 2 vs 22 ± 1.5 phospho-ATM positive cells/mm 2 , p&lt;0.05, n=5, dihydroethidium (DHE) staining: 78 ± 0.6% vs 98 ± 0.7% DHE positive nuclei/mm 2 , p&lt;0.05, n=5]. Using single cell electrophoresis (Comet assay), we demonstrated that Cygb overexpressing cardiomyocytes underwent significantly lower DNA damage due to single and double stranded DNA breaks following exposure to oxidative stress as compared to controls cardiomyocytes (36 ± 2.1 vs 48 ± 3.1; p&lt;0.05, n=6). Finally, chromatin immunoprecipitation, quantitative PCR and immunoblotting indicated that Cygb activates the expression of apurinic/apyrimidinic endonuclease 1 ( Ape1 ) and thus promotes DNA base excision repair following acute cardiac injury. Conclusions: Our data demonstrate that Cygb promotes cellular proliferation and protects cardiomyocytes against oxidative stress-mediated DNA damage by directly activating Ape1 expression.
Residential exposure to petrochemicals and risk of leukemia: Using GIS tools to estimate individual residential exposure levels
Authors: Chu-Ling Yu, Su-Fen Wang, Ming-Tsang Wu, Bi-Jen Pan, Chi-Kung Ho, Thomas J. Smith, Yi Li, Lucille Pothier, David C. Christiani
Journal: Cancer Research (2005)

2200  Occupational studies have reported increased leukemia mortality and risk among petrochemical workers. However, the association between residential exposure to petrochemicals and leukemia remains controversial. We conducted a population-based case-control study in Kaohsiung, southern Taiwan, to investigate the association between residential petrochemical exposure and leukemia risk, with a focus on individuals 29 years of age and younger. A total of 171 cases and 410 controls matched for age (±1 year) and sex were recruited between November 1997 and June 2003. Since assessment of petrochemical impacts depends on accurate exposure estimates, we developed a procedure using geographic information system (GIS) tools to assign exposure estimates for each individual. The resulting individual-level exposure estimates - which we called the exposure opportunity score (EOS) - is an integrated exposure measure that accounts for subject mobility, length of stay at each residence, distance to relevant petrochemical plant(s), monthly prevailing wind direction, and multiple petrochemical plant pollution sources. For modeling purposes, EOS was log-transformed for normality. Conditional logistic regression analyses were performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Different models were fitted for individuals aged 0-19 and 20-29 to evaluate separately childhood vs. adulthood leukemia. There was no significant association between petrochemical exposure and leukemia in the younger age group. For one unit increase in the log-transformed EOS, the adjusted OR was 1.04 (95% CI = 0.79-1.38). On the contrary, a positive association between residential petrochemical exposure and leukemia risk was observed for subjects aged 20-29 years. In this latter age group, the adjusted OR was 1.54 (95% CI = 1.14-2.09) for one unit increase in the log-transformed EOS. In conclusion, we found that residential exposure to petrochemicals was a significant risk factor for leukemia for subjects aged 20-29 years. Also, the study illustrates the utility of GIS tools for providing a more refined exposure estimate for residential exposure to petrochemical pollution. Supported by NIH grants ES09723 and E2, and the Brain Tumor Society.
DIPOLE DENSITY MAPPING OF ATRIAL FIBRILLATION AND SINUS RHYTHM IN THE HUMAN LEFT ATRIUM: A CLINICAL VALIDATION STUDY
Authors: Rui Shi, Paras Parikh, Zhong Chen, Nathan Angel, Mark Norman, Wajid Hussain, Charlie Butcher, Shouvik Haldar, David G. Jones, Omar Riad, Vias Markides, Tom Wong
Journal: Journal of the American College of Cardiology (2019)