tbuckley/cabot-search huggingface dataset:
Abstract 16641: The SGLT2 Inhibitor Ertugliflozin Induces Oxidative Phosphorylation Gene Expression and Improves Systolic Function Independent of Diabetes in Mice
Authors: Dominique Croteau, Ivan Luptak, Fuzhong Qin, Jordan M Chambers, Ion A Hobai, Jena Goodman, Marcello Panagia, David R Pimentel, Deborah A Siwik, Wilson S Colucci
Journal: Circulation (2020)

Background: Inhibitors of sodium glucose linked transporter 2 (SGLT2i) improve heart failure (HF) outcomes in patients independent of diabetes. While animal studies suggest SGLT2i improve cardiac metabolism, the effect of SGLT2i on mitochondrial function in the heart is not known. Our goal was to assess the effects of SGLT2i on mitochondrial function, high energy phosphates and genes encoding mitochondrial proteins in hearts of mice with and without diet-induced diabetes. Methods &amp; Results: Ertugliflozin (Ertu; 0.5 mg/g) was given for 4 months to mice fed a high fat, high sucrose (HFHS) diet that causes diabetic cardiomyopathy or control diet (CD). Mitochondrial function was measured in isolated cardiac mitochondria. Myocardial energetics were assessed by NMR spectroscopy simultaneously with systolic function in isolated beating hearts. Myocardial gene expression was assessed by RNA seq using gene set analysis. HFHS diet caused myocardial hypertrophy and diastolic dysfunction, mitochondrial dysfunction (decreased ATP production, increased reactive oxygen species release) and an impaired energetic response to increased work demand - all of which were prevented by Ertu. Systolic function, as reflected by the rate x pressure product (RPP), was super-normalized to a value 124% of CD hearts at high work demand. In control mice, Ertu had no effect on isolated mitochondria function or high energy phosphates, but similar to HFHS hearts, caused super-normalization of RPP to 125% of CD hearts. Myocardial gene expression analysis revealed oxidative phosphorylation (OXPHOS) as the top scoring gene set that was both down-regulated by HFHS with a normalized enrichment score (NES) of -2.08, and up-regulated by Ertu in HFHS (NES, +3.32 vs HFHS). OXPHOS was the top scoring gene set up-regulated by Ertu a) across all groups while controlling for diet (NES, +3.71) and b) in CD-fed mice only (NES, +3.34). Conclusion: The super-normalization of systolic function and induction of the OXPHOS gene set by Ertu is independent of diabetic status. Pro-metabolic remodeling of the myocardium by Ertu may support increased systolic function and contribute to the beneficial actions of Ertu in states such as HF that are associated with impaired cardiac mitochondrial function.
Iartogenic Postatrial Fibrillation Ablation Left Atrial Tachicardia/Fulutter
Authors: Hashimoto Kenichi, Watanabe Ichiro, Asino Sonoko, Kofune Masayoshi, Kawauchi Kazunori, Yamada Takeshi, Kofune Tatsuya, Ohkubo Kimie, Shindo Atsushi, Sugimura Hidezo, Nakai Toshiko, Kunimoto Satoshi, Saitoh Satoshi
Journal: Circulation (2006)
COVID-19 and global mental health
Authors: Melanie Amna Abas, Benedict Weobong, Rochelle Ann Burgess, Hanna Kienzler, Helen E Jack, Khameer Kidia, Rosemary Musesengwa, Inge Petersen, Pamela Y Collins, Etheldreda Nakimuli-Mpungu
Journal: The Lancet Psychiatry (2021)
Abstract 15630: Gender-related Differences in the Management of Chronic Coronary Syndrome: Registry Data of a Tertiary Center in Brazil
Authors: Carlos V Serrano, Eduardo M Moreira, Cibele L Garzillo, Luiz M Montenegro, Cindy L Tabuse, Mylena C Kormann-Moreira, alexandre W segre, Paula M Bolta, Desiderio Favarato, Fabio G Pitta, Eduardo G Lima, Paulo H Rezende, Whady A Hueb
Journal: Circulation (2020)

Introduction: There is scarce data on sex-related differences in chronic coronary syndrome (CCS) management in low-and-middle-income countries. We aimed to describe those in CCS patients in a tertiary center in Brazil. Hypothesis: Multiple gender-related differences may affect management of CCS and, subsequently, influence outcome in developing countries - improvement in tertiary care is justified. Methods: Patients from an outpatient clinic with known history of myocardial infarction (MI), coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), or stable angina with documented coronary artery lesions &gt; 50% were evaluated for differences regarding prescription, laboratory data, symptoms and other clinical variables. Patients were deemed to have optimal goal-directed therapy if blood pressure (BP) was &lt; 140/90 mmHg, LDL-cholesterol &lt; 70 mg/dL and were in use of antithrombotics. We also assessed incidence of MI, stroke or death. Results: 625 patients, 208 (33.3%) women and 417 men, were included. We found no sex-related differences in mean age (65 years, SD 9.6 for the cohort) or in prevalence of previous MI, CABG or PCI. Women had higher systolic BP (134 vs 128 mmHg, p &lt; 0.001), higher left ventricular ejection fraction (56 vs 51%, p &lt; 0.001), lower creatinine clearance (69 vs 73 mL/min, p= 0.04), and higher LDL (103 vs 87 mg/dL, p &lt; 0.001). We found no differences regarding glucose levels, BMI or symptoms. Women were less likely to be prescribed calcium-channel blockers (p = 0.04), but equally likely to be prescribed statins. Gender-related differences in LDL and BP were present even after adjustments. Women were less likely to have optimized goal-directed therapy (14.9% vs 28.3%, p &lt; 0.001), even after adjustments. Gender was not associated with event-free survival on one-year follow-up (97% vs 98%). Conclusions: In this setting, women had higher LDL-cholesterol, higher SBP, and lower proportion of optimized goal-directed therapy than men, but gender was not related to worse one-year prognosis.
Abstract 16686: Improved Diet Quality is Associated With Lower Prevalence of Clonal Hematopoiesis of Indeterminate Potential
Authors: Romit Bhattacharya, Seyedeh M Zekavat, James Pirruccello, Gabriel K Griffin, Alexander G Bick, Pradeep Natarajan
Journal: Circulation (2020)

Introduction: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is a pre-cancerous age-associated condition characterized by somatic mutations (typically in DNMT3A , TET2 , ASXL1 , JAK2 ) in hematopoietic stem cells and is a novel cardiovascular risk factor. Besides tobacco smoking, lifestyle factors that lead to the development of CHIP are currently poorly understood. Hypothesis: We hypothesize that healthy dietary habits are associated with reduced CHIP prevalence. Methods: We analyzed whole exome sequencing data from blood DNA in the UK Biobank to identify CHIP mutations with a variant allele fraction (VAF) &gt;2% in DNMT3A or TET2 . We scored diet quality (unhealthy, intermediate, healthy, and healthy vegetarian) based on American Heart Association guidelines. We associated diet quality with CHIP using multivariate logistic regression adjusting for age, age 2 , sex, smoking, coronary artery disease, type 2 diabetes, Townsend Deprivation Index score, and genetic ancestry. We used the Cochran-Armitage trend test assessed to associate large CHIP (VAF&gt;10%) with diet quality. Results: Among 48,389 individuals in the UK Biobank, CHIP prevalence was 1168 (3.14%). Of these, 543 (1.1%) had unhealthy, 44314 (91.6%) had intermediate, 3111 (6.4%) had healthy, and 421 (0.9%) had healthy vegetarian diets. Poor diet quality was significantly associated with increased prevalence of CHIP. Individuals with an unhealthy diet had higher rates of CHIP (5.0%), compared to intermediate (3.2%, OR 0.63, p=0.05), healthy (2.8%, OR 0.58, p=0.04), and vegetarian diets (1.1%, OR 0.25, p=0.03). Large CHIP clones demonstrated a significant trend with improved diet quality associated with lower CHIP prevalence (p=0.009) among those with unhealthy (1.9%), intermediate (1.3%), healthy (1.0%), and vegetarian (0.0%) diets. Conclusions: Diet quality is associated with CHIP prevalence among 48,389 individuals in the UK Biobank.
Prospects of microbial-engineering for the production of graphene and its derivatives: Application to design nanosystms for cancer theranostics
Authors: Rajeev Singh, Khalid Alshaghdali, Amir Saeed, Mohd Adnan Kausar, Fahad M. Aldakheel, Sadaf Anwar, Debabrata Mishra, Manish Srivastava
Journal: Seminars in Cancer Biology (2021)
Reply to: “Acute-on-chronic liver failure in East-Asia: an underestimated issue with limited data”
Authors: Adrià Juanola, Gabriel Mezzano, James P Hamilton, Pere Ginès, Elsa Solà, Ruben Hernaez
Journal: Gut (2021)

We read with interest the letter from Cao et al 1, and thank them for the interest in our study.2 The authors are concerned about our prevalence estimates of acute-on-chronic liver failure (ACLF) in East Asia. They attributed the difference due to our inclusion of overlapping cohorts,3–6 or failing to include two additional studies.7 8

Cao et al propose to exclude one of the two included studies published in China.3 4 While both cohorts indeed come from the same hospital around the same dates, they provide a different number of participants raising the possibility of …
Abstract P032: Specialized Care Is Associated With Higher Cardiovascular Disease Awareness In Young Women
Authors: Sierra Patterson, Hannah Palfrey, Sarah D De Ferranti, Holly C Gooding
Journal: Circulation (2021)

Introduction: Awareness of CVD and its risk factors is low among young women. This study compared CVD knowledge and preventive behaviors among women ages 15-24 years seen in primary care versus a preventive cardiology clinic. Hypothesis: Young women seen in a preventive cardiology clinic would demonstrate more knowledge about CVD and its causes, and be more likely to engage in preventive behaviors. Methods: We recruited 403 females ages 15-24 years from two clinics in Boston, MA: a primary care clinic (n=331) and a preventive cardiology clinic (n=72). We modified the AHA Women’s Health Survey to assess CVD knowledge and lifestyle behaviors. Using logistic regression, we examined the relationship between clinic type and 1) knowledge about CVD and 2) engagement in preventive behaviors, controlling for age group, primary caregiver education level, and race/ethnicity. Results: Young women in preventive cardiology clinic were more likely to identify CVD as the leading cause of death for women (PR: 1.65, 95% CI: 0.96-2.85) and identify major causes of CVD, such as high cholesterol and family history of CVD (Figure). Preventive cardiology patients were more likely to report maintaining a healthy cholesterol level (PR: 1.33, 95% CI: 1.03-1.71) and were over twice as likely to discuss CVD risk with their provider within the past two years (PR: 2.34, 95% CI: 1.84-2.97), including topics such as nutrition and exercise. Notably, 41 (70%) preventive cardiology patients did not identify CVD as the major cause of mortality in women despite being able to identify CVD risk factors. Additionally, engagement in behaviors targeted in the specialized clinic remained suboptimal (Figure). Conclusion: Young women in a preventive cardiology clinic were more aware of CVD and its risk factors than those seen in primary care. However, gaps remained in knowledge and behavior despite specialized care. Opportunities remain in primary care and preventive cardiology clinics to increase knowledge and promote healthy behavior to reduce CVD risk in women.
Physical Rehabilitation for Older Patients Hospitalized for Heart Failure
Authors: Dalane W. Kitzman, David J. Whellan, Pamela Duncan, Amy M. Pastva, Robert J. Mentz, Gordon R. Reeves, M. Benjamin Nelson, Haiying Chen, Bharathi Upadhya, Shelby D. Reed, Mark A. Espeland, LeighAnn Hewston, Christopher M. O’Connor
Journal: New England Journal of Medicine (2021)

Older patients who are hospitalized for acute decompensated heart failure have high rates of physical frailty, poor quality of life, delayed recovery, and frequent rehospitalizations. Interventions to address physical frailty in this population are not well established.We conducted a multicenter, randomized, controlled trial to evaluate a transitional, tailored, progressive rehabilitation intervention that included four physical-function domains (strength, balance, mobility, and endurance). The intervention was initiated during, or early after, hospitalization for heart failure and was continued after discharge for 36 outpatient sessions. The primary outcome was the score on the Short Physical Performance Battery (total scores range from 0 to 12, with lower scores indicating more severe physical dysfunction) at 3 months. The secondary outcome was the 6-month rate of rehospitalization for any cause.A total of 349 patients underwent randomization; 175 were assigned to the rehabilitation intervention and 174 to usual care (control). At baseline, patients in each group had markedly impaired physical function, and 97% were frail or prefrail; the mean number of coexisting conditions was five in each group. Patient retention in the intervention group was 82%, and adherence to the intervention sessions was 67%. After adjustment for baseline Short Physical Performance Battery score and other baseline characteristics, the least-squares mean (±SE) score on the Short Physical Performance Battery at 3 months was 8.3±0.2 in the intervention group and 6.9±0.2 in the control group (mean between-group difference, 1.5; 95% confidence interval [CI], 0.9 to 2.0; P<0.001). At 6 months, the rates of rehospitalization for any cause were 1.18 in the intervention group and 1.28 in the control group (rate ratio, 0.93; 95% CI, 0.66 to 1.19). There were 21 deaths (15 from cardiovascular causes) in the intervention group and 16 deaths (8 from cardiovascular causes) in the control group. The rates of death from any cause were 0.13 and 0.10, respectively (rate ratio, 1.17; 95% CI, 0.61 to 2.27).In a diverse population of older patients who were hospitalized for acute decompensated heart failure, an early, transitional, tailored, progressive rehabilitation intervention that included multiple physical-function domains resulted in greater improvement in physical function than usual care. (Funded by the National Institutes of Health and others; REHAB-HF ClinicalTrials.gov number, NCT02196038.).
How Many Disparate Measurements of Kidney Function Unfairly Allow Selected Candidates to Accumulate Time on the Deceased Donor Kidney Transplant Waiting List?
Authors: Robert W. Steiner
Journal: Journal of the American Society of Nephrology (2021)

A recent editorial in JASN addresses an ongoing ethical controversy in kidney transplantation.[1][1] In some borderline cases, only non-Black candidates may have Modification of Diet in Renal Disease (MDRD)/Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRs at or below the threshold
Th2型免疫欠乏を呈するがTh1機能を保持するTNF/LT-アルファのダブルノックアウトマウス
Authors: Yamamoto M, Mcghee, Kweon M, Bluethmann H, Shimpuku Y, Vancott Jl, Kiyono H
Journal: Journal of Allergy and Clinical Immunology (1997)
ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control
Authors: Joanna DeSalvo, Yuguang Ban, Luyuan Li, Xiaodian Sun, Zhijie Jiang, Darcy A. Kerr, Mahsa Khanlari, Maria Boulina, Mario R. Capecchi, Juha M. Partanen, Lin Chen, Tadashi Kondo, David M. Ornitz, Jonathan C. Trent, Josiane E. Eid
Journal: Journal of Clinical Investigation (2021)

Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that ETV4 and ETV5 acted as drivers of synovial sarcoma growth, most likely through control of the cell cycle. Upon ETV4 and ETV5 knockdown, we observed a striking upregulation of DUX4 and its transcriptional targets that activate the zygotic genome and drive the atrophy program in facioscapulohumeral dystrophy patients. In addition to demonstrating the importance of inhibiting all three FGFRs, the current findings reveal potential nodes of attack for the cancer with the discovery of ETV4 and ETV5 as appropriate biomarkers and molecular targets, and activation of the embryonic DUX4 pathway as a promising approach to block synovial sarcoma tumors.
Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021
Authors: M. Hasib Sidiqi, Morie A. Gertz
Journal: Blood Cancer Journal (2021)

Abstract Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Overlooking the diagnosis of light chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Herein we provide a review of established and investigational treatments for patients with AL amyloidosis and provide algorithms for workup and management of these patients.
Abstract 14696: Limiting the Number of Open Charts in the Electronic Medical Record Does Not Decrease Order Entry Errors in Cardiovascular Inpatient and Intensive Care Units
Authors: Heather Blonksy, Rachel Shirley, Alex Milinovich, Kay Tucker, Allison Weathers, Baruch Fertel, Chiedozie Udeh, Aaron Hamilton, Antonio L Perez
Journal: Circulation (2019)

Introduction: On inpatient and intensive care units, clinicians maintain multiple patient charts open simultaneously to facilitate rapid access to information and order entry as they multi-task. Li...
A Novel Mutation Causing GATA2 Haploinsufficiency Activates a Cryptic Splice Site in Exon 3
Authors: Claudia Wehr, Katja Grotius, Dorothee Bleckmann, Emilia J Kozyra, Sebastian Bode, Björn C Frye, Marcin W. Wlodarski, Maximilian Seidl, Ulrich Salzer
Journal: Blood (2017)
Pragmatic Trials — Need for ADAPTABLE Design
Authors: Colin Baigent
Journal: New England Journal of Medicine (2021)

The publication in the Journal of the results of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness)1 comparing two doses of aspirin for the secondary prevention of cardiovascular disease represents a major step forward in establishing the pragmatic trial as an investigatory tool in the United States. The authors used a range of innovative and low-cost methods to simplify the identification, recruitment, and follow-up of patients: for example, algorithms were used to interrogate electronic health record data to identify eligible patients within the National Patient-Centered Clinical Research Network (PCORnet); patients could access a Web portal to give . . .
Association of RAD51 with homologous recombination deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): analysis of the GeparSixto randomized clinical trial
Authors: A Llop-Guevara, S Loibl, G Villacampa, V Vladimirova, A Schneeweiss, T Karn, D-M Zahm, A Herencia-Ropero, P Jank, M van Mackelenbergh, P A Fasching, F Marmé, E Stickeler, C Schem, R Dienstmann, S Florian, V Nekljudova, J Balmaña, E Hahnen, C Denkert, V Serra
Journal: Annals of Oncology (2021)
132P The psychological impact of the COVID-19 pandemic on patients with early breast cancer
Authors: S. Almeida, D. Frasquilho, G. Cotovio, F. Viana, B. Sousa, J. Oliveira, J. Mattson, C. Marzorati, I. Roziner, E. Karademas, E. Kolokotroni, G.S. Stamatakos, K. Mazzocco, R. Pat-Horenczyk, P. Poikonen-Saksela, F. Cardoso, A. Oliveira-Maia
Journal: Annals of Oncology (2021)
Prostate-Specific Antigen Screening and Active Surveillance for High-Risk Individuals
Authors: Yaw A. Nyame, Michael P. Porter
Journal: JAMA Network Open (2021)

Tyler J. Nelson, BS; Juan Javier-DesLoges, MD, MS; Rishi Deka, PhD; P. Travis Courtney, MAS; Vinit Nalawade, MS; Loren Mell, MD; James Murphy, MD; J. Kellogg Parsons, MD, MHS; Brent S. Rose, MD
Abstract 16154: Baseline Left Ventricular Diameter Predicts Recovery in New Systolic Heart Failure Syndromes
Authors: Daniel Gold, Nathan Kong, Matthew Gold, Tess Allan, Anand Shah, John Blair
Journal: Circulation (2020)

Introduction: It is unknown how often patients with very advanced left ventricular (LV) dilation at initial presentation demonstrate meaningful recovery with medical therapy. Understanding short term treatment outcomes may impact medical decision making and counseling. Hypothesis: Patients with left ventricular end diastolic internal diameter (LVEDD) &gt; 6.5cm will be less likely to recover left ventricular ejection fraction (LVEF) as compared to patients with LVEDD &lt; 6.5cm. Methods: Patients were retrospectively identified by a database search of echocardiogram studies obtained at the University of Chicago between 2008-2018. Manual review was performed to ensure new diagnosis of systolic dysfunction with LVEF ≤ 35% and follow up echocardiogram study within 3 to 9 months of index study. LVEDD was determined from parasternal long axis views per routine. LVEF recovery was specified as LVEF &gt; 35%. Chart review was done to assess for composite death, hospice, transplant, left ventricular assist device, and sustained ventricular tachycardia. Chi-square, multivariable logistic regression, and Kaplan-Meier survival were used for analysis. Results: Out of 100 patients included for analysis, mean age was 59.7 years, 41 were female and 82 were African American. 17.7% of patients’ with LVEDD &gt; 6.5 cm had LVEF recovery compared to 53.0% of patients’ with LVEDD ≤ 6.5 cm (p = 0.008). LVEDD &gt; 6.5 cm was associated with less LVEF recovery even when adjusted for age, gender, hypertension, and diabetes (adjusted odds ratio 0.18, 95% CI 0.04 to 0.65). LVEDD &gt; 6.5cm was associated with worse event free survival (p = 0.004) with a median follow-up time of 2.4 years. Conclusions: An LVEDD of &gt; 6.5cm is associated with diminished LVEF recovery and event free survival when compared to those patients with an LVEDD ≤ 6.5cm. Delaying consideration for advanced therapies and device based therapies in hopes of recovery may be inappropriate for many such patients.