tbuckley/cabot-search huggingface dataset:
Abstract 17503: ETV2 Functions as a Pioneer Factor and Regulates the Endothelial Lineage
Authors: Wuming Gong, Satyabrata Das, Javier Sierra-Pagan, Mary G Garry, Daniel J Garry
Journal: Circulation (2020)

Background: Genetic mutations perturb the multipotent progenitors, which results in congenital cardiovascular disease. Therefore, it is essential to decipher the pioneer factors and the regulatory pathways that govern the specification and differentiation of mesodermal progenitors and use this information to develop targeted therapies to promote cardiovascular regeneration. Etv2 as an essential transcription factor for the development of cardiac, endothelial and hematopoietic lineages. In the present study, we used ES/EB differentiation and MEF reprogramming systems, to define Etv2 as a novel pioneer factor that relaxes the closed chromatin and drives endothelial development. Results: Using the iHA-Etv2 ES cell line, we engineered a mouse that inducibly overexpresses ETV2. The bulk RNA-seq, single cell RNA-seq data and ATAC-seq experiments showed that inducing Etv2 in MEFs and ES/EBs activated the downstream endothelial marker genes and promoted the development of endothelial lineages, supporting the notion that Etv2 functioned as a master regulator to drive the endothelial lineage development in different cellular contexts. We found that similar to other known pioneer factors, Etv2 was intrinsically able to target and bind the nucleosomes, and this capability appeared to be independent of the cellular context. To further define the mechanism, we performed Etv2, Brg1 and H3K27ac ChIP-seq analyses during MEF reprogramming and ES/EB differentiation. We found that Brg1 maintains and stabilizes the binding of Etv2 on the nucleosome, and Etv2 requires Brg1 to activate downstream genes during reprograming. Conclusion: In these studies, we defined Etv2 as a novel pioneer factor that relaxed the closed chromatin and promoted the endothelial lineage in both ES/EB differentiation and MEF reprogramming. The definition of these mechanisms will enhance our understanding of cardiovascular development and regeneration and serve as a platform for therapeutic applications for patients with congenital or aging related cardiovascular diseases.
Abstract 15542: Late Pulmonary Hypertension in Surgically Palliated D-transposition of the Great Arteries: A 55-year Review
Authors: Blair Suter, Dylan Hall, Eric S Ebenroth, Larry W Markham, Michael Johansen
Journal: Circulation (2020)

Introduction: Pulmonary hypertension (PH) has been described following surgical palliation for transposition of the great arteries (D-TGA). While early pulmonary vascular disease is associated with late repair, the increasing prevalence of late PH has been observed following the intra-atrial baffle procedure (ABP), Mustard/Senning. A previous study from our institution identified patients with precapillary PH. More recent studies have described predominately postcapillary PH, suggesting multiple, differing mechanisms for this complication. Hypothesis: While heart failure is a common complication following ABP and is associated with postcapillary PH, we hypothesize that precapillary PH can be identified in a subset of patients. Methods: A retrospective descriptive study was performed at a single institution. Using 6 th World Symposium on Pulmonary Hypertension definitions. PH was defined as a mean pulmonary artery pressure &gt;20mmHg. Etiology of PH was defined as precapillary (≥3 Wood units) versus postcapillary (pulmonary artery wedge pressure &gt;15 mmHg). Results: We reviewed 157 D-TGA patients following ABP, finding 33 patients with PH. Mean age at last evaluation was 36.6 (14-54) years. Current condition: 22 alive, 7 dead, and 4 lost to follow-up. Etiology of PH: 10 precapillary, 8 postcapillary, 8 mixed, 2 borderline PH, and 2 did not undergo catherization. Additionally, 2 patients had pulmonary venous baffle obstruction and 1 had left lung hypoplasia. Of patients with recent imaging, 21 of 25 had systemic RV systolic dysfunction on echocardiogram or MRI. Conclusions: Late-onset PH in D-TGA following ABP is a significant long-term complication and warrants vigilant surveillance. This highlights the limitations of imaging and need for catheterization for complete evaluation. In this study, we observed precapillary PH in a majority of patients with PH, which differs from some previous studies. Identifying the etiology of PH could drastically alter treatment strategies and has implications for transplant consideration. Further studies are needed to identify the clinical attributes that contribute to this process.
Re: Paul Abrams, Lynda D. Constable, David Cooper, et al. Outcomes of a Noninferiority Randomised Controlled Trial of Surgery for Men with Urodynamic Stress Incontinence After Prostate Surgery (MASTER). Eur Urol 2021;79:812–23
Authors: Erik B. Cornel, Niek F. Casteleijn
Journal: European Urology (2021)
Trends and Characteristics of Retracted Articles in the Biomedical Literature, 1971 to 2020
Authors: Mario Gaudino, N. Bryce Robinson, Katia Audisio, Mohamed Rahouma, Umberto Benedetto, Paul Kurlansky, Stephen E. Fremes
Journal: JAMA Internal Medicine (2021)

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The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti–Vascular Endothelial Growth Factor Injections
Authors: Samir N. Patel, Peter H. Tang, Philip P. Storey, Jeremy D. Wolfe, Jordana Fein, Sumit P. Shah, Eric Chen, Ashkan Abbey, Philip J. Ferrone, Chirag P. Shah, Michelle C. Liang, Maxwell S. Stem, M. Ali Khan, Yoshihiro Yonekawa, Sunir J. Garg
Journal: Ophthalmology (2021)
Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data
Authors: Daniela K Schlüter, Josh S Ostrenga, Siobhán B Carr, Aliza K Fink, Albert Faro, Rhonda D Szczesniak, Ruth H Keogh, Susan C Charman, Bruce C Marshall, Christopher H Goss, David Taylor-Robinson
Journal: Thorax (2021)

Rationale A previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results. Objectives To compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences. Methods We used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections ( Pseudomonas aeruginosa , Staphylococcus aureus ) and treatments (rhDnase, hypertonic saline, inhaled antibiotics). Results We included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK. Conclusions Children with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.
Long Noncoding RNA Cardiac Physiological Hypertrophy–Associated Regulator Induces Cardiac Physiological Hypertrophy and Promotes Functional Recovery After Myocardial Ischemia-Reperfusion Injury
Authors: Rongrong Gao, Lijun Wang, Yihua Bei, Xiaodong Wu, Jiaqi Wang, Qiulian Zhou, Lichan Tao, Saumya Das, Xinli Li, Junjie Xiao
Journal: Circulation (2021)

Background: The benefits of exercise training in the cardiovascular system have been well accepted; however, the underlying mechanism remains to be explored. Here, we report the initial functional characterization of an exercise-induced cardiac physiological hypertrophy–associated novel long noncoding RNA (lncRNA). Methods: Using lncRNA microarray profiling, we identified lncRNAs in contributing the modulation of exercise-induced cardiac growth that we termed cardiac physiological hypertrophy–associated regulator (CPhar). Mice with adeno-associated virus serotype 9 driving CPhar overexpression and knockdown were used in in vivo experiments. Swim training was used to induce physiological cardiac hypertrophy in mice, and ischemia reperfusion injury surgery was conducted to investigate the protective effects of CPhar in mice. To investigate the mechanisms of CPhar’s function, we performed various analyses including quantitative reverse transcription polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), functional rescue experiments, mass spectrometry, in vitro RNA transcription, RNA pulldown, RNA immunoprecipitation, chromatin immunoprecipitation assay, luciferase reporter assay, and coimmunoprecipitation assays. Results: We screened the lncRNAs in contributing the modulation of exercise-induced cardiac growth through lncRNA microarray profiling and found that CPhar was increased with exercise and was necessary for exercise-induced physiological cardiac growth. The gain and loss of function of CPhar regulated the expression of proliferation markers, hypertrophy, and apoptosis in cultured neonatal mouse cardiomyocytes. Overexpression of CPhar prevented myocardial ischemia reperfusion injury and cardiac dysfunction in vivo. We identified DDX17 (DEAD-Box Helicase 17) as a binding partner of CPhar in regulating CPhar downstream factor ATF7 (activating transcription factor 7) by sequestering C/EBPβ (CCAAT/enhancer binding protein beta). Conclusions: Our study of this lncRNA CPhar provides new insights into the regulation of exercise-induced cardiac physiological growth, demonstrating the cardioprotective role of CPhar in the heart, and expanding our mechanistic understanding of lncRNA function, as well.
Evaluation of Racial/Ethnic Differences in Treatment and Mortality Among Women With Triple-Negative Breast Cancer
Authors: Beomyoung Cho, Yunan Han, Min Lian, Graham A. Colditz, Jason D. Weber, Cynthia Ma, Ying Liu
Journal: JAMA Oncology (2021)

To our knowledge, there is no consensus regarding differences in treatment and mortality between non-Hispanic African American and non-Hispanic White women with triple-negative breast cancer (TNBC). Little is known about whether racial disparities vary by sociodemographic, clinical, and neighborhood factors.To examine the differences in clinical treatment and outcomes between African American and White women in a nationally representative cohort of patients with TNBC and further examine the contributions of sociodemographic, clinical, and neighborhood factors to TNBC outcome disparities.This population-based, retrospective cohort study included 23 123 women who received a diagnosis of nonmetastatic TNBC between January 1, 2010, and December 31, 2015, followed up through December 31, 2016, and identified from the Surveillance, Epidemiology, and End Results data set. The study was conducted from July 2019 to November 2020. The analyses were performed from July 2019 to June 2020.Race and ethnicity, including non-Hispanic African American and non-Hispanic White race.Using logistic regression analysis and competing risk regression analysis, we estimated odds ratios (ORs) of receipt of treatment and hazard ratios (HRs) of breast cancer mortality in African American patients compared with White patients.Of 23 213 participants, 5881 (25.3%) were African American women and 17 332 (74.7%) were White women. Compared with White patients, African American patients had lower odds of receiving surgery (OR, 0.69; 95% CI, 0.60-0.79) and chemotherapy (OR, 0.89; 95% CI, 0.81-0.99) after adjustment for sociodemographic, clinicopathologic, and county-level factors. During a 43-month follow-up, 3276 patients (14.2%) died of breast cancer. The HR of breast cancer mortality was 1.28 (95% CI, 1.18-1.38) for African American individuals after adjustment for sociodemographic and county-level factors. Further adjustment for clinicopathological and treatment factors reduced the HR to 1.16 (95% CI, 1.06-1.25). This association was observed in patients living in socioeconomically less deprived counties (HR, 1.26; 95% CI, 1.14-1.39), urban patients (HR, 1.21; 95% CI, 1.11-1.32), patients having stage II (HR, 1.19; 95% CI, 1.02-1.39) or III (HR, 1.15; 95% CI, 1.01-1.31) tumors that were treated with chemotherapy, and patients younger than 65 years (HR, 1.24; 95% CI, 1.12-1.37).In this retrospective cohort study, African American women with nonmetastatic TNBC had a significantly higher risk of breast cancer mortality compared with their White counterparts, which was partially explained by their disparities in receipt of surgery and chemotherapy.
Advancing health equity: The Association of Black Gastroenterologists and Hepatologists
Authors: Pascale M. White, Ugonna Iroku, Rotonya M. Carr, Folasade P. May, Sophie Balzora, Valerie Antoine-Gustave, Adjoa Anyane-Yeboa, Darrell M. Gray, Alexandra Guillaume, Rachel B. Issaka, Renee L. Williams
Journal: Nature Reviews Gastroenterology & Hepatology (2021)
Abstract 16631: Frailty Phenotype is Associated With 1-Year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry
Authors: Anuradha Lala, Palak Shah, Lauren Cooper, Maria Mountis, Shawn W Robinson, David Lanfear, Jerry D Estep, Urlich Jorde, Neal Jeffries, Lynne W Stevenson, Shokoufeh Khalatbari, Catherine A Spino, Blair Richards, Douglas Mann, Garrick C Stewart, Keith D Aaronson
Journal: Circulation (2018)

Introduction: The Fried Frailty Phenotype (FFP), defined by weakness, slowness, inactivity, exhaustion and weight loss, predicts adverse outcomes in geriatric populations but has not been studied in advanced heart failure (AHF). The REVIVAL study prospectively collected frailty measures in ambulatory patients with advanced HF to determine relevant components of frailty in this population and the impact on clinical outcomes. Hypothesis: We hypothesize that measures of frailty will be strongly associated with the 1 yr composite outcome of LVAD, UNOS 1A/ B cardiac transplant or death. Methods: The REVIVAL registry enrolled ambulatory patients with AHF on oral Rx (INTERMACS Profiles 4-7). A modified FFP was defined by 5 components:1) weakness: hand grip strength &lt;25% of body weight; 2) slowness: 5-m gait time &lt;6 seconds; 3) weight loss &gt; 10lbs in the past yr; 4) inactivity from 5 Kansas City Cardiomyopathy Questionnaire (KCCQ) activity questions and 5) exhaustion from 2 KCCQ exhaustion questions. A score of 0-1 was deemed not frail, 2 was pre-frail, and ≥3 was considered frail. Event-free survival for each group was determined by the Kaplan-Meier method and the increased hazards of pre-frailty and frailty compared to non-frailty were determined with proportional hazards modeling. Results: Frailty was present in 18% of the 335 patients with complete 5-component FFP data, pre-frailty in 41%, and non-frailty in 41%. During the first year, 89 outcome events occurred, with HR 2.5 (p=0.003, 95% CI 1.4, 4.7) in frail, and HR 1.8 (p=0.029, 95% CI 1.1, 3.2) in the pre-frail, compared to non-frail patients. (Figure) Conclusions: Using the Fried Frailty criteria to classify patients as frail, pre-frail and not-frail helped to identify patients with ambulatory HF at high risk for death, LVAD or transplant at 1 year. Assessment of frailty can improve triage for advanced HF therapies, inform our understanding of comparative outcomes with transplant, LVAD or continued medical therapy.
Robotic distal pancreatectomy reduces pancreatic fistula in patients without visceral obesity as compared to open distal pancreatectomy: A propensity score matching retrospective cohort study
Authors: Haoda Chen, Ziyun Shen, Xiayang Ying, Yuanchi Weng, Yu Jiang, Hao Chen, Zhiwei Xu, Xiaxing Deng, Junjie Xie, Baiyong Shen
Journal: International Journal of Surgery (2021)
Peter Bryan Bailey
Authors: Jana Bailey
Journal: BMJ (2021)

Peter Bryan Bailey spent most of his life in Bristol. He was educated at Colston’s School and attended Bristol University Medical School. He completed his medical training after three years in the Royal Air Force as a physical training instructor. He retained his interest in sport and was an active participant—rugby, fencing, squash in earlier days and later skiing, water sports, and finally golf (although he regretted his poor achievement in golf). He remained an advocate of physical fitness throughout his life and retained …
Identification of Somatic Mutations in Expanded T Cell Clones of Patients with Chronic Graft-Versus-Host Disease (GVHD)
Authors: Giljun Park, Daehong Kim, Sofie Lundgren, Rajiv K Khajuria, Ana M Hurtado, Cecilia Muñoz-Calleja, Laura Cardeñoso, Samuli Eldfors, Pekka Ellonen, Sari Hannula, Oscar Brück, Anna Kreutzman, Andres Jerez, Maija Itälä-Remes, Mikko A Keränen, Satu Mustjoki
Journal: Blood (2017)
CLINICAL RELEVANCE OF CIRCULATING CK-19 MRNA-POSITIVE CELLS DETECTED BEFORE AND DURING FRONT LINE CHEMOTHERAPY IN PATIENTS WITH METASTATIC BREAST CANCER
Authors: N Androulakis, V Bozionelou, M Perraki, S Apostolaki, A Kalykaki, K Kalbakis, A Kotsakis, D Mavroudis, V Georgoulias
Journal: Annals of Oncology (2009)
Helen Salisbury: GPs deserve better than this micromanagement
Authors: Helen Salisbury
Journal: BMJ (2021)

Last week I was working on a new timetable for our surgery, thinking about how and when we might switch back to letting patients book directly into face-to-face appointments.We'd like to be able to offer a choice of telephone, video, or in-person consultations, with the option of written questions too.Despite a recent NHS England document suggesting that GPs should aim to embed total triage we're concerned about its effect on our more vulnerable patients, so it didn't feature in our planning.This turned out to be just as well, as the next bit of guidance we received was a letter informing us of a new "standard operating procedure," whereby all patients requesting a face-to-face appointment should be offered one, with reception areas thrown open to all.
Cell-type-specific effects of genetic variation on chromatin accessibility during human neuronal differentiation
Authors: Dan Liang, Angela L. Elwell, Nil Aygün, Oleh Krupa, Justin M. Wolter, Felix A. Kyere, Michael J. Lafferty, Kerry E. Cheek, Kenan P. Courtney, Marianna Yusupova, Melanie E. Garrett, Allison Ashley-Koch, Gregory E. Crawford, Michael I. Love, Luis de la Torre-Ubieta, Daniel H. Geschwind, Jason L. Stein
Journal: Nature Neuroscience (2021)
Abstract 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model
Authors: Anett Jannasch, Antje Schauer, Virginia Kirchhoff, Runa Draskowsi, Claudia Dittfeld, Ephraim Winzer, Siegfried Labeit, Axel Linke, Sems-Malte Tugtekin, Volker Adams
Journal: Circulation (2020)

Background: The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats. Methods: 20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections. Results: Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1). Conclusions: Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.
Abstract 16811: In-Utero Coxsackievirus Type B Infection is Associated With Congenital Pulmonary Atresia
Authors: Vipul Sharma, Lisa S Goessling, Horacio G Carvajal, Anoop K Brar, Pirooz Eghtesady
Journal: Circulation (2020)

Introduction: Maternal exposure to various pathogens during pregnancy has been well established as a cause of congenital heart defects (CHD). Suggestive, although inconclusive, data exists of an association between Coxsackievirus B (CVB) infection during pregnancy and CHD. Therefore, this study was undertaken to examine association between perinatal infection with CVB and CHD. Hypothesis: CVB infection during pregnancy may play a role in the pathogenesis of CHD. Methods: In a prospective study of 122 pregnant women with pregnancies affected with CHD, circulating CVB IgG and IgM antibodies in the maternal serum were quantified. To determine specific CVB serotypes involved, Neutralizing antibodies (NA) were measured against three CVB serotypes: CVB1-Chi07, CVB3, Nancy, and CVB4, J.V.B. Results: A significant number of the women were positive for CVB antibodies; 31.1% for IgG and 6.6% for IgM. Elevated levels of IgG were seen in 50% of women carrying babies with Pulmonary Atresia (PA) (p=0.04). In addition, 55.6% (p=0.100) of moms carrying babies with Hypoplastic Left Heart Syndrome (HLHS), aortic atresia/mitral stenosis (AA/MS) variant and 47.1% (p=0.127) of HLHS AA/mitral atresia (MA) had positive IgG levels. Among babies of women with positive IgM titers, 75% (p=0.001) had isolated Ventricular Septal Defect (VSD), comprising 26.1% (6/23) of all babies with isolated VSD in the cohort.We also show a possible association between CVB4 and CHD in the cohort. All mothers with positive IgM titers whose babies were born with a VSD had elevated CVB4 NA (p=0.001). Among women with elevated IgG having babies with PA, 40.0% (p=0.061) had elevated CVB1 NA, 70.0% (p=0.014) had elevated CVB3 NA, and 40.0% (p=0.876) had elevated CVB4 NA. Conclusion: We present data from a clinical study suggesting that CVB infection during pregnancy may contribute to the burden of CHD in affected babies. Our data demonstrates not only an association of CVB with CHD in pregnant women but this is the first report showing significant association between in-utero CVB infection and PA. Our study has broad implications for the future understanding and potential management of CHD as well as introduces a new avenue of research for cardiac defects.
Covid-19: Second vaccine doses expedited in areas of England where new variant is high
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: Second vaccine doses expedited in areas of England where new variant is high Jacqui WiseThe government has said it was implementing a "belt and braces" approach to tackle rising cases of the B.1.617.2 variant of SARS-CoV-2, though some experts fear that the measures will not be sufficient as lockdown is eased.