tbuckley/cabot-search huggingface dataset:
Abstract 9139: Two Decade Trends in Cardiovascular Health Among Adults With Cardiovascular Disease in the United States Using a Revised American Heart Association Life's Simple 7 Framework
Authors: Yumin Gao, Nino Isakadze, Eamon Duffy, Qicong Sheng, Jie Ding, Zane MacFarlane, Scott T McClure, Yingying Sang, Elizabeth Selvin, Kuni Matsushita, Seth S Martin
Journal: Circulation (2021)

Introduction: The American Heart Association Life’s Simple 7 (LS7) framework is used to promote cardiovascular health. Trends in cardiovascular health of US adults with a history of cardiovascular disease (CVD) are not well characterized. Hypothesis: To assess trends in LS7 factors in US adults with CVD. Methods: In 4,233 adults with a self-reported history of CVD (i.e., myocardial infarction, stroke, angina, and heart failure) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, we constructed a revised 14-point LS7 score. The revision included Healthy Eating Index-2015 for scoring diet, non-HDL-cholesterol for cholesterol, hemoglobin A1c and self-reported diabetes for blood glucose, blood pressure cutoffs that reflect current guidelines for adults with CVD, and removal of medication use in scoring cardiovascular health (Figure). We used multivariable linear regression to examine trends in cardiovascular health, accounting for weights and the complex survey design. Results: After adjusting for age, sex, and race/ethnicity, the mean revised LS7 score in US adults with CVD remained low from 5.72 in 1999-2002 to 5.80 in 2015-2018 (p-for-trend=0.084) (Figure). Improvements were noted in cholesterol control (7.0% achieving ideal in 1999-2002 to 28.9% in 2015-2018, p-for-trend &lt;0.001) and smoking cessation (32.8% ideal in 1999-2002 to 37.9% in 2015-2018, p-for-trend=0.037). There were declines in blood glucose and weight control (65.6% and 24.2% ideal in 1999-2002 to 52.6% and 14.7% in 2015-2018, p-for-trends &lt;0.001). Proportions achieving ideal remained low and unchanged for diet and physical activity (1.4% and 2.8% in 1999-2002 to 0.7% and 3.9% in 2015-2018, p-for-trend=0.61 and 0.41). Conclusions: Over the last two decades in US adults with CVD, among LS7 factors, cholesterol and smoking improved, while glucose and weight worsened, with an overall concerning trend of persistently suboptimal cardiovascular health.
Systematic Pan-Cancer Characterization of Nuclear Receptors Identifies Potential Cancer Biomarkers and Therapeutic Targets
Authors: Junjie Jiang, Jiao Yuan, Zhongyi Hu, Mu Xu, Youyou Zhang, Meixiao Long, Yi Fan, Kathleen T. Montone, Janos L. Tanyi, Omid Tavana, Ho Man Chan, Lin Zhang, Xiaowen Hu
Journal: Cancer Research (2021)

The nuclear receptor (NR) superfamily is one of the major druggable gene families, representing targets of approximately 13.5% of approved drugs. Certain NRs, such as estrogen receptor and androgen receptor, have been well demonstrated to be functionally involved in cancer and serve as informative biomarkers and therapeutic targets in oncology. However, the spectrum of NR dysregulation across cancers remains to be comprehensively characterized. Through computational integration of genetic, genomic, and pharmacologic profiles, we characterized the expression, recurrent genomic alterations, and cancer dependency of NRs at a large scale across primary tumor specimens and cancer cell lines. Expression levels of NRs were highly cancer-type specific and globally downregulated in tumors compared with corresponding normal tissue. Although the majority of NRs showed copy-number losses in cancer, both recurrent focal gains and losses were identified in select NRs. Recurrent mutations and transcript fusions of NRs were observed in a small portion of cancers, serving as actionable genomic alterations. Analysis of large-scale CRISPR and RNAi screening datasets identified 10 NRs as strongly selective essential genes for cancer cell growth. In a subpopulation of tumor cells, growth dependencies correlated significantly with expression or genomic alterations. Overall, our comprehensive characterization of NRs across cancers may facilitate the identification and prioritization of potential biomarkers and therapeutic targets, as well as the selection of patients for precision cancer treatment. SIGNIFICANCE: Computational analysis of nuclear receptors across multiple cancer types provides a series of biomarkers and therapeutic targets within this protein family.
Chidamide Maintenance Therapy after Induction or Salvage Treatment in Patients with Peripheral T-Cell Lymphoma Ineligible for Autologous Stem Cell Transplantation
Authors: Wei Guo, Yangzhi Zhao, Xingtong Wang, Jia Li, Qiang Guo, Junna Li, Ken H. Young, Ou Bai
Journal: Blood (2021)
A GLP‐1/GLP‐2 receptor dual agonist to treat NASH: Targeting the gut‐liver axis and microbiome
Authors: Eun Ran Kim, Jeong Su Park, Jin Hee Kim, Ji Young Oh, In Jeong Oh, Da Hyun Choi, Yu seol Lee, I. Seul Park, SeungWon Kim, Da Hyun Lee, Jae Hee Cheon, Jin‐Woo Bae, Minyoung Lee, Jin Won Cho, In Bok An, Eun Joo Nam, Sang‐In Yang, Myung‐Shik Lee, Soo Han Bae, Yong‐ho Lee
Journal: Hepatology (2021)

Abstract Background and Aims Currently there is no Food and Drug Administration–approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut‐liver axis in their pathogenesis, we investigated the therapeutic effect of a long‐acting dual agonist of glucagon‐like peptide (GLP)‐1 and GLP‐2 receptors in mice with NAFLD/NASH. Approach and Results C57BL/6J mice were fed a choline‐deficient high‐fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1‐Fc, GLP2‐Fc, or GLP1/2‐Fc fusion (GLP1/2‐Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well‐developed NASH phenotypes. GLP1/2‐Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2‐Fc were found in in vitro cell systems. GLP1/2‐Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2‐Fc–mediated protection. We confirmed that FMT exerted an additive effect on GLP1‐Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis. Conclusions A long‐acting dual agonist of GLP‐1 and GLP‐2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.
Ivosidenib (IVO) in Combination with Azacitidine (AZA) in Newly Diagnosed (ND) Older Patients with IDH1 R132-Mutated Acute Myeloid Leukemia (AML) Induces High Response Rates: A Phase 2 Sub-Study of the Beat AML Master Trial
Authors: Prapti Patel, Amy S. Ruppert, Uma Borate, Eytan M. Stein, Maria R. Baer, Wendy Stock, Tibor Kovacsovics, William Blum, Martha L. Arellano, Gary J. Schiller, Rebecca L. Olin, James M. Foran, Mark R. Litzow, Tara L. Lin, Matthew C. Foster, Robert L. Redner, Zeina Al-Mansour, Christopher R. Cogle, Michael M. Boyiadzis, Ronan Swords, Robert H. Collins, Jo-Anne Vergilio, Nyla A. Heerema, Leonard Rosenberg, Ashley Owen Yocum, Sonja Marcus, Timothy Chen, Franchesca Druggan, Mona Stefanos, Theophilus J Gana, Abigail B. Shoben, Brian J. Druker, Amy Burd, John C. Byrd, Ross L. Levine, Alice S. Mims
Journal: Blood (2021)
Abstract 9476: Global Representation of Leaders, Collaborators, and Enrolled Participants in Heart Failure Clinical Trials: A Systematic Bibliometric Review
Authors: Jie Wei Zhu, NhatChinh Le, Sunny Wei, Liesl Zuhlke, Renato D Lopes, Faiez Zannad, Harriette G Van Spall
Journal: Circulation (2021)

Introduction: The geographic representation of investigators and participants in heart failure (HF) randomized clinical trials (RCTs) may not reflect the global burden of disease. Objectives: We assessed the geographic diversity of RCT leaders and explored associations with the geographic representation of enrolled participants among impactful HF RCTs. Methods: We searched MEDLINE, EMBASE, and CINAHL for HF RCTs published in journals with impact factor ≥ 10 between January 2000 and June 2020. We used the Jonckheere-Terpstra test to assess temporal trends and multivariable logistic regression models to explore associations between predictors and outcomes. Results: There were 414 eligible RCTs. Only 80 of 828 trial leaders (9.7%; 95% CI: 7.8% to 11.8%), and 453 of 4656 collaborators (9.7%; 95% CI: 8.8% to 10.6%) were from outside Europe and North America, with no change in temporal trends. The adjusted odds of trial leadership outside Europe and North America were lower with industry funding (aOR: 0.33; 95% CI: 0.15 to 0.75; P = 0.008). Among 157,416 participants in whom geography was reported, only 14.5% (95% CI: 14.3% to 14.7%) were enrolled outside Europe and North America, but odds of enrolment were ten-fold greater with trial leadership outside Europe and North America (aOR: 10.0; 95% CI 5.6-19.0; P &lt; 0.001). Conclusions: Regions disproportionately burdened with HF are under-represented in HF trial leadership, collaboration, and enrolment. RCT leadership outside Europe and North America is independently associated with participant enrolment in under-represented regions. Increasing research capacity outside Europe and North America could enhance trial diversity and generalizability.
P70.20 Impact of KRAS and Co-occurring Mutations on NSCLC Master Regulator Network as Determined by Computational Omics Biology Model.
Authors: M. Castro, A.K. Ganti, A. Kumar, S. Khandelwal, S. Mohapatra, D. Lala, A. Alam, P. Nair, A. Tyagi, S. Prasad, A. Agrawal, N. Mundkur, S. Patel, D. Singh, V. Joseph, A.R. Amara, S. Choudhury, S. Kulkarni, N. Prasad, S. Basu, A. Balla, A. Choudhary, S. Kapoor, V. Velcheti
Journal: Journal of Thoracic Oncology (2021)
Multidisciplinary approaches for elucidating genetics and molecular pathogenesis of urinary tract malformations
Authors: Kamal Khan, Dina F. Ahram, Yangfan P. Liu, Rik Westland, Rosemary V. Sampogna, Nicholas Katsanis, Erica E. Davis, Simone Sanna-Cherchi
Journal: Kidney International (2021)
Abstract 13182: Dapagliflozin and Changes in Metabolic Syndrome in Patients With Type 2 Diabetes: A DECLARE TIMI 58 Sub-Analysis
Authors: Filipe A Moura, Itamar RAZ, Avivit Cahn, Erica Goodrich, Deepak L Bhatt, Lawrence A Leiter, JOHN WILDING, Ingrid A Gause-nilsson, Ofri Mosenzon, Marc S Sabatine, Stephen D Wiviott
Journal: Circulation (2021)

Introduction: SGLT2 inhibitors reduce cardiovascular (CV) risk in a broad range of patients including those with and without type 2 diabetes mellitus (DM). In addition, non-glycemic effects modify parameters that define metabolic syndrome (MetS) such as weight, BP, and lipid profile. In this context, we investigated the effects of dapagliflozin on key components of MetS and the association with outcomes. Methods: 17,160 patients with DM were randomized to dapagliflozin or placebo in DECLARE-TIMI 58. Since all had DM, MetS was classified using a modification of IDF criteria requiring BMI ≥30 kg/m 2 and ≥1 of the following: triglycerides ≥150 mg/dL, HDL-C &lt;40 in men or &lt;50 mg/dL in women, SBP ≥130 or DBP ≥85 mmHg. Classification of MetS and its subcomponents were tracked at baseline and follow-up visits (6-48 months). An analysis adjusted for baseline characteristics and treatment was performed to assess the association of MetS with key outcomes. Results: At baseline, 53% had MetS. On adjusted analysis, MetS was predictive of CV death or hospitalization for heart failure (CVD/HHF) (HR 1.28, 95%CI 1.11-1.47, p&lt;0.001), HHF (HR 1.62, 95%CI 1.33-1.97, p&lt;0.001), and MI (HR 1.22, 95%CI 1.05-1.4, p=0.008). From 6 to 48 months, there was a lower prevalence of MetS in the dapagliflozin arm (47.9% vs. 52.5%, p&lt;0.001, Figure 1), as well as lower prevalence of BMI ≥30 kg/m 2 (54.9% vs. 58.0%), low HDL-C (38.7% vs. 42.6%), and elevated BP (58.2% vs. 65.7%) with p&lt;0.001 for each. In the dapagliflozin arm, there were lower odds of progression to MetS (10.5% vs. 13.5%; OR 0.76, 95%CI 0.64-0.89, p&lt;0.001) and, in those with MetS at baseline, higher odds of regression (24.6% vs. 18.3%; OR 1.45, 95%CI 1.29-1.64, p&lt;0.001) at 48 months. Conclusions: The presence of MetS is prognostically important in patients with DM. Dapagliflozin led to significant early and sustained changes in the likelihood of MetS.
The Impact of Degree of Anticoagulation on Thrombotic and Other Complications in Hospitalized COVID-19 Patients
Authors: Rena Zheng, Alexandra Solomon, Madeline DiLorenzo, Iniya Rajendran, Joseph Park, Vrushali Dhongade, Michael Garcia, Allan Walkey, Robert Eberhardt, John Mark Sloan, Janice Weinberg, Elizabeth S Klings
Journal: Blood (2021)
Prognostic Value of Early PET in Patients with Aggressive Non-Hodgkin Lymphoma Treated with Anti-CD19 CAR T-Cell Therapy
Authors: Jennifer L. Crombie, Robert A. Redd, Victor A. Chow, Jordan Gauthier, Erin Mullane, Geoffrey Shouse, Alex F. Herrera, Jason Romancik, Jonathon B. Cohen, Anna Saucier, Roch Houot, Caron Jacobson, Philippe Armand, Brian T. Hess
Journal: Blood (2021)
Racial, Ethnic, and Socioeconomic Disparities in Access to Transcatheter Aortic Valve Replacement Within Major Metropolitan Areas
Authors: Ashwin S. Nathan, Lin Yang, Nancy Yang, Lauren A. Eberly, Sameed Ahmed M. Khatana, Elias J. Dayoub, Sreekanth Vemulapalli, Howard Julien, David J. Cohen, Brahmajee K. Nallamothu, Suzanne J. Baron, Nimesh D. Desai, Wilson Y. Szeto, Howard C. Herrmann, Peter W. Groeneveld, Jay Giri, Alexander C. Fanaroff
Journal: JAMA Cardiology (2021)

Despite the benefits of high-technology therapeutics, inequitable access to these technologies may generate disparities in care.To examine the association between zip code-level racial, ethnic, and socioeconomic composition and rates of transcatheter aortic valve replacement (TAVR) among Medicare patients living within large metropolitan areas with TAVR programs.This multicenter, nationwide cross-sectional analysis of Medicare claims data between January 1, 2012, and December 31, 2018, included beneficiaries of fee-for-service Medicare who were 66 years or older living in the 25 largest metropolitan core-based statistical areas.Receipt of TAVR.The association between zip code-level racial, ethnic, and socioeconomic composition and rates of TAVR per 100 000 Medicare beneficiaries.Within the studied metropolitan areas, there were 7590 individual zip codes. The mean (SD) age of Medicare beneficiaries within these areas was 71.4 (2.0) years, a mean (SD) of 47.6% (5.8%) of beneficiaries were men, and a mean (SD) of 4.0% (7.0%) were Asian, 11.1% (18.9%) were Black, 8.0% (12.9%) were Hispanic, and 73.8% (24.9%) were White. The mean number of TAVRs per 100 000 Medicare beneficiaries by zip code was 249 (IQR, 0-429). For each $1000 decrease in median household income, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.2% (95% CI, 0.1%-0.4%) lower (P = .002). For each 1% increase in the proportion of patients who were dually eligible for Medicaid services, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 2.1% (95% CI, 1.3%-2.9%) lower (P < .001). For each 1-unit increase in the Distressed Communities Index score, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.4% (95% CI, 0.2%-0.5%) lower (P < .001). Rates of TAVR were lower in zip codes with higher proportions of patients of Black race and Hispanic ethnicity, despite adjusting for socioeconomic markers, age, and clinical comorbidities.Within major metropolitan areas in the US with TAVR programs, zip codes with higher proportions of Black and Hispanic patients and those with greater socioeconomic disadvantages had lower rates of TAVR, adjusting for age and clinical comorbidities. Whether this reflects a different burden of symptomatic aortic stenosis by race and socioeconomic status or disparities in use of TAVR requires further study.
<i>Onset of Blast Crises in CML Patients in Treatment-Free Remission: Descriptive Analysis of 4 Cases</i>
Authors: Stephanie Dulucq, Frédéric Bauduer, Jean-Michel Cayuela, Patrice Chevallier, Pascale Cony-Makhoul, Yannick Le Bris, Laurence Legros, Herve Maisonneuve, Lydia Roy, Francois-Xavier Mahon, Sandrine Hayette, Delphine Rea, Franck E. Nicolini
Journal: Blood (2021)
Role of Balloon Pulmonary Valvuloplasty in the Management of Pulmonary Stenosis
Authors: P. Syamasundar Rao
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Although there is definitive evidence for pressure gradient relief both immediately after and at follow-up after balloon pulmonary valvuloplasty (BPV) for pulmonary stenosis (PS), the progression of pulmonary insufficiency (PI) at late follow up emerged as a concern. To address the concern for development of PI during late follow-up, balloon/annuls ratio used for BPV was reduced to 1.2 to 1.25. Recurrence of stenosis was seen in nearly 10% of patients. The causes of recurrence were identified to be balloon/annulus ratio less than 1.2 and immediate post-BPV gradients in excess of 30 mmHg. Recurrent obstructions can be effectively relieved by repeat BPV. The BPV procedure is safe and effective in fetal, neonatal and adult subjects as well. The BPV is also effective in palliating cyanotic congenital heart disease patients with valvar PS. Despite the limitations, BPV is currently considered as therapeutic procedure of choice in the management of congenital PS in both the pediatric and adult populations. BPV provides an excellent alternative to surgical intervention and has become the preferred intervention for initial treatment for PS in neonates, infants, children, adolescents, and adults. Careful follow-up to detect development of significant PI and investigate methods to prevent PI are recommended.
Patients with Acute Myeloid Leukemia on Non-Intensive Therapy: Applicability of the European Leukemia Net Risk Classification
Authors: Pablo Silva, Jon Badiola, Reyes María Martín-Rojas, Ignacio Gómez-Centurión, Gabriela Rodríguez-Macias, Marina Gómez-Llobell, Carolina Martínez-Laperche, Diego Carbonell, Mónica Ballesteros, Ana Pérez-Corral, María Chicano, Patricia Font Lopez, Isabel Pérez-Sánchez, Ismael Buño, Javier Anguita, Mi Kwon, José Luis Díez-Martín
Journal: Blood (2021)
Combination of Decitabine and ATRA in Newly Diagnosed Myelodysplastic Syndromes Subtype EB-Interim Analysis of a Multicenter, Randomized, Open-Label Trial
Authors: Xinping Zhou, Fanjun Meng, Yanjuan Lin, Zheng Ge, Yuemin Kuang, Lu Wang, Jin Zhang, Hai Cheng, Yan Gao, Yulu Tian, Li Huang, Jie Jin, Hongyan Tong
Journal: Blood (2021)
Molecular Characterization Using Oncoscan Chromosome Microarray in an International Cohort of 51 Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Eli Williams, Stefano A Pileri, Maria Rosaria Sapienza, Carlos Barrionuevo, Carlos Bacchi, Maxime Battistella, Tony Petrella, Emmanuella Guenova, Daniela Dueñas, Sandro Casavilca, Joseph D. Khoury, Jose Plaza, Pierluigi Porcu, Alejandro Ariel Gru
Journal: Blood (2021)
Abstract 9219: More Extensive Ablation in Addition to Pulmonary Vein Isolation Can Improve Quality of Life in Elderly Patients With Persistent Atrial Fibrillation: Insights from the Earnest-pvi Trial
Authors: Takashi Kanda, Masaharu Masuda, Koichi Inoue, Yasuyuki Egami, Tetsuya Watanabe, Hitoshi Minamiguchi, Miwa Miyoshi, Akihiro Sunaga, Yohei Sotomi, Tomoharu Dohi, Shugo Hikoso, Yasushi Sakata
Journal: Circulation (2021)

Introduction: Improving the quality of life (QoL) is one of the main purposes of catheter ablation of persistent atrial fibrillation (AF). QoL improvement in persistent AF patients has not been fully clarified. The EARNEST-PVI trial was a multi-center randomized trial comparing clinical outcomes of pulmonary vein isolation (PVI) alone and more intensive ablation in addition to PVI including complex fractionated atrial electrogram (CFAE) and linear ablation (PVI plus). Objective: To investigate the QoL changes after persistent AF ablation and the differences between the PVI-alone strategy and the PVI plus strategy in elderly and non-elderly patients. Methods: In the EARNEST-PVI trial, patients with persistent AF who underwent an initial catheter ablation (n = 512) were randomly assigned in a 1:1 ratio to either PVI alone or PVI plus. Quality of life was assessed at baseline and at 12 months after ablation for AF using the 36-Item Short Form Health Survey. Scores were also converted to a physical health component summary (PCS), a mental health component summary (MCS) and a role/social component summary (RCS). Results: After excluding 68 patients for whom preoperative or postoperative QoL assessment was not available, 444 patients were divided into two groups: those 65 years old and over and those under 65 years old, and assessed whether there was a difference in QoL improvement between the ablation strategies. In non-elderly patients, although there was improvement in all aspects of QoL after ablation, there was no difference between strategies. In contrast, the improvement in PCS was significantly greater in elderly patients who underwent PVI-plus. (PVI group 0.8 ± 10.3 vs. PVI-Plus group 3.8 ± 11.2, P=0.021) Conclusions: While ablation for persistent AF improved QoL regardless of strategy, more extensive ablation in addition to PVI could improve QoL in the elderly patients.