tbuckley/cabot-search huggingface dataset:
Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts
Authors: Zhen-Ao Zhao, Xinglong Han, Wei Lei, Jingjing Li, Zhuangzhuang Yang, Jie Wu, Mengchao Yao, Xing-Ai Lu, Lingjuan He, Yihuan Chen, Bin Zhou, Shijun Hu
Journal: Circulation Research (2018)

Aging is one of the most significant risk factors for cardiovascular diseases, and the incidence of myocardial ischemia increases dramatically with age. Some studies have reported that cardiosphere-derived cells (CDCs) could benefit the injured heart. Nevertheless, the convincing evidence on CDC-induced improvement of aging heart is still limited.In this study, we tested whether the CDCs isolated from neonatal mice could benefit cardiac function in aging mice.We evaluated cardiac function of PBS- (n=15) and CDC-injected (n=19) aging mice. Echocardiography indicated that left ventricular (LV) ejection fraction (57.46%±3.57% versus 57.86%±2.44%) and LV fraction shortening (30.67%±2.41% versus 30.51%±1.78%) showed similar values in PBS- and CDC-injected mice. The diastolic wall thickness of LV was significantly increased after CDC injection, resulting in reduced diastolic LV volume. The pulse-wave Doppler and tissue Doppler imaging indicated that aging mice receiving PBS or CDC injection presented similar values of the peak early transmitral flow velocity, the peak late transmitral flow velocity, the ratio of the peak early transmitral flow velocity to the peak late transmitral flow velocity, and the ratio of the peak early transmitral flow velocity to the peak early diastolic mitral annular velocity, respectively. Pressure-volume loop experiment indicated that the LV end-diastolic pressure-volume relationship and end-systolic pressure-volume relationship were comparable in both PBS- and CDC-injected mice. Postmortem analysis of aging mouse hearts showed similar fibrotic degree in the 2 groups. In addition, the aging markers showed comparable expression levels in both PBS- and CDC-injected mice. The systemic aging performance measures, including exercise capacity, hair regrowth capacity, and inflammation, showed no significant improvement in CDC-injected mice. Finally, the telomere length was comparable between PBS- and CDC-injected mice.Together, these results indicate that CDCs do not improve heart function and systemic performances in aging mice.
Publisher Correction: Reduction of liver fibrosis by rationally designed macromolecular telmisartan prodrugs
Authors: Matthew R. Golder, Jenny Liu, Jannik N. Andersen, Michail V. Shipitsin, Farrukh Vohidov, Hung V.-T. Nguyen, Deborah C. Ehrlich, Sung Jin Huh, Bhavatarini Vangamudi, Kyriakos D. Economides, Allison M. Neenan, James C. Ackley, Joelle Baddour, Sattanathan Paramasivan, Samantha W. Brady, Eric J. Held, Lawrence A. Reiter, Jennifer K. Saucier-Sawyer, Paul W. Kopesky, Donald E. Chickering, Peter Blume-Jensen, Jeremiah A. Johnson
Journal: Nature Biomedical Engineering (2018)
A Comparison of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline and the 2017 American Diabetes Association Diabetes and Hypertension Position Statement for U.S. Adults With Diabetes
Authors: Paul Muntner, Paul K. Whelton, Mark Woodward, Robert M. Carey
Journal: Diabetes Care (2018)

OBJECTIVE To determine the concordance in the prevalence of hypertension and pharmacological antihypertensive treatment recommendations for U.S. adults with diabetes using definitions from the 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline and the 2017 American Diabetes Association (ADA) diabetes and hypertension position statement. RESEARCH DESIGN AND METHODS We analyzed data for U.S. adults with diabetes in the U.S. National Health and Nutrition Examination Survey (NHANES), 2011–2016 (n = 2,266). Diabetes was defined by treatment with glucose-lowering medication, glycosylated hemoglobin ≥6.5%, fasting serum glucose ≥126 mg/dL, or nonfasting serum glucose ≥200 mg/dL. BP was measured three times and antihypertensive medication use was self-reported. RESULTS The prevalence (95% CI) of hypertension among U.S. adults with diabetes was 77.1% (73.9, 80.0) and 66.3% (63.4, 69.1) according to the ACC/AHA and ADA definitions, respectively. Also, 22.9% (20.0, 26.1) did not have hypertension according to either definition, and the concordance in hypertension status was 89.2% (87.2, 91.0). Among U.S. adults with diabetes not taking antihypertensive medication, 52.8% (47.7, 57.8) were not recommended to initiate antihypertensive medication by either the ACC/AHA or the ADA document and 22.4% (19.2, 25.9) were recommended to initiate it by both documents (overall concordance 75.2% [70.4, 79.4]). Among those taking antihypertensive medication, 45.3% (41.3, 49.4) and 50.4% (46.5, 54.2) had BP above the goal in neither and both documents, respectively (overall concordance 95.7% [93.4, 97.2]). CONCLUSIONS A high percentage of U.S. adults with diabetes are provided identical antihypertensive treatment recommendations by the ACC/AHA BP guideline and the ADA diabetes and hypertension position statement.
Abstract 17456: Early Repolarization is Associated With Resuscitated Sudden Cardiac Arrest but not Autopsy-Proven Sudden Arrhythmic Death
Authors: Venkata A Narla, Ellen Moffatt, Phillip Ursell, Rana Khan, Annie Bedigian, Jeffrey Olgin, Zian H Tseng
Journal: Circulation (2016)

Introduction: Association between early repolarization (ER) on ECG and sudden cardiac arrest (SCA) risk has been suggested by epidemiologic studies with variable prognostic results. This associatio...
Analysis of Cell Type-Specific Effects of MicroRNA-92a Provides Novel Insights Into Target Regulation and Mechanism of Action
Authors: Eva-Maria Rogg, Wesley T. Abplanalp, Corinne Bischof, David John, Marcel H. Schulz, Jaya Krishnan, Ariane Fischer, Chiara Poluzzi, Liliana Schaefer, Angelika Bonauer, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2018)

MicroRNAs (miRs) regulate nearly all biological pathways. Because the dysregulation of miRs can lead to disease progression, they are being explored as novel therapeutic targets. However, the cell type-specific effects of miRs in the heart are poorly understood. Thus, we assessed miR target regulation using miR-92a-3p as an example. Inhibition of miR-92a is known to improve endothelial cell function and recovery after acute myocardial infarction.miR-92a-3p was inhibited by locked nucleic acid (LNA)-based antimiR (LNA-92a) in mice after myocardial infarction. Expression of regulated genes was evaluated 3 days after myocardial infarction by RNA sequencing of isolated endothelial cells, cardiomyocytes, fibroblasts, and CD45+ hematopoietic cells.LNA-92a depleted miR-92a-3p expression in all cell types and derepressed predicted miR-92a-3p targets in a cell type-specific manner. RNAseq showed endothelial cell-specific regulation of autophagy-related genes. Imaging confirmed increased endothelial cell autophagy in LNA-92a treated relative to control animals. In vitro inhibition of miR-92a-3p augmented EC autophagy, derepressed autophagy-related gene 4a, and increased luciferase activity in autophagy-related gene 4a 3'UTR containing reporters, whereas miR-92a-3p overexpression had the opposite effect. In cardiomyocytes, LNA-92a derepressed metabolism-related genes, notably, the high-density lipoprotein transporter Abca8b. LNA-92a further increased fatty acid uptake and mitochondrial function in cardiomyocytes in vitro.Our data show that miRs have cell type-specific effects in vivo. Analysis of miR targets in cell subsets disclosed a novel function of miR-92a-3p in endothelial cell autophagy and cardiomyocyte metabolism. Because autophagy is upregulated during ischemia to supply nutrients and cardiomyocyte metabolic-switching improves available substrate utilization, these prosurvival mechanisms may diminish tissue damage.
Abstract 332: Simulation to Derive the Operating Characteristics of a Bayesian Adaptive Clinical Trial Design to Determine Optimal Duration of Hypothermia Following Out-of-Hosptial Cardiac Arrest
Authors: William J Meurer, Scott Berry, Viswanathan Ramakrishnan, Robert Silbergleit
Journal: Circulation (2013)

Introduction: Therapeutic hypothermia (TH) improves outcomes in comatose survivors of cardiac arrest, but optimal duration of cooling is unknown. An innovative adaptive trial may address this question efficiently and with fewer prior assumptions, but its complexity requires simulation to characterize the trial’s power and accuracy. Objective: To evaluate the operating characteristics (OC) of an adaptive clinical trial designed to characterize the TH duration response relationships for patients with shockable and non-shockable rhythms. Methods: The proposed ICECAP trial design uses a flexible, Bayesian normal dynamic linear model to estimate the relationship between duration of TH and 90 day modified Rankin Scale. The trial initially allocates 150 patients equally to 12, 24, or 48 hrs of cooling and models duration-response. The model then iteratively refines itself using response adaptive randomization ratios updated every 100 subsequent enrollments to time windows from 6 to 72 hours as needed to identify transitions in duration-response. Shockable and non-shockable rhythms are fitted separately. Sample sizes from 1600-2300 were simulated. The design was tested under hypothetical scenarios of no treatment effect, small, medium and large effects, and harm (outcomes worsen with duration). Each combination of sample size and scenario was simulated 1000 times. Results: The proportion of trials correctly identifying the target duration (for both rhythm types) ranged from 72% (N=1600), to 81% (N=2300). A sample size of 1800 had 85% power to select the target (the true or larger adjacent) duration. OC remained robust in specific challenging scenarios including a very early plateau with similar efficacy at 18-72 hours, and an inverted U with efficacy upsloping to 18 hours and diminishing from 30-72 hours. In the null scenario, identical outcomes for all durations from 6-72 hours, the design only incorrectly identifies a winning dose in 4-7% of trials. It was also efficient in this scenario, terminating 35% of trials early for futility. In harm scenarios, trials terminate early 86% of the time. Conclusions: The ICECAP trial design performs well under a variety of scenarios. Flexible, adaptive Bayesian trial designs are promising and ready to be implemented.
Clinicopathologic features of breast cancer in the Texas-Mexico border city of El Paso.
Authors: Zeina A. Nahleh, Jenny Zhou, Adolph Ulloa
Journal: Journal of Clinical Oncology (2012)

e11549 Background: Breast cancer is the leading cause of cancer death in Hispanic women in Texas. El Paso, TX is a large border city of 900,000, 85% Hispanic. Very limited research has been published on this population. Methods: After IRB approval, we analyzed the variables at initial diagnosis of 111 consecutive patients with breast cancer treated at a single academic institution in El Paso, in 2011. Descriptive statistics were utilized. Results: Mean age was 54 years; 101 were Hispanics (91%), 4 White non-Hispanic, 4 African-Americans and 2 Middle Eastern. Six patients (5%) had stage 0, 61 (55%) localized (stages I and II), 32 (29%) loco-regional (stage III), and 12 (11%) stage IV disease. Histology was: 104 ductal (94%), 6 lobular (5%) and 1 neuroendocrine. Sixty two patients (59%) had Estrogen Receptor (ER) positive tumors versus 32 (31%) ER negative. 79 patients (75%) had HER2 negative and 25 (24%) HER2 positive tumors, 1 had unknown HER2. Sixty two (59%) invasive tumors were ER / PR positive/HER2 negative; 11 (10%) were ER/ PR positive/HER2 positive; 14 (13%) ER/PR negative/ HER2 positive; and 17 (16%) Triple negative. 36 patients (32%) were diagnosed at younger than 50 years; 13 (12%) between ages 30 and 40. 16 (45%) of these patients present at advanced or metastatic stages. The Median BMI was 35.5 (range 18-50.4). Treatment was as follows: Mastectomy 44 patients (42%) versus lumpectomy 56 (54%); 84 patients (76%) received chemotherapy and 71 patients (64%) received hormonal therapy. 14 patients (13 %) had cancer recurrences at median of 5.5 years. Conclusions: Consistent with other studies, Hispanic breast cancer patients in El Paso are diagnosed at a younger age , more advanced stages and have a higher prevalence of ER negative and HER2 positive tumors, compared to non-Hispanic historical controls. In addition, our patients had a higher prevalence of metastatic stage IV at diagnosis 11% compared to 6% statewide. Breast cancers among Hispanic women may comprise a distinct biologic spectrum of tumors. Also, more focused research looking at the geographical and socioeconomic differences should be conducted. Dietary and lifestyle habits should also be investigated. Increasing awareness particularly among young Hispanic women is needed.
Human AML activates the aryl hydrocarbon receptor pathway to impair NK cell development and function
Authors: Steven D. Scoville, Ansel P. Nalin, Luxi Chen, Li Chen, Michael H. Zhang, Kathleen McConnell, Susana Beceiro Casas, Gabrielle Ernst, Abd Al-Rahman Traboulsi, Naima Hashi, Monica Williams, Xiaoli Zhang, Tiffany Hughes, Anjali Mishra, Don M. Benson, Jennifer N. Saultz, Jianhua Yu, Aharon G. Freud, Michael A. Caligiuri, Bethany L. Mundy-Bosse
Journal: Blood (2018)
Azo-based small molecular hypoxia responsive theranostic for tumor-specific imaging and therapy
Authors: Ying Zhou, Mrinmoy Maiti, Amit Sharma, Miae Won, Le Yu, Lan Xi Miao, Jinwoo Shin, Arup Podder, Kondapa Naidu Bobba, Jiyou Han, Sankarprasad Bhuniya, Jong Seung Kim
Journal: Journal of Controlled Release (2018)
TIP: A Web Server for Resolving Tumor Immunophenotype Profiling
Authors: Liwen Xu, Chunyu Deng, Bo Pang, Xinxin Zhang, Wei Liu, Gaoming Liao, Huating Yuan, Peng Cheng, Feng Li, Zhilin Long, Min Yan, Tingting Zhao, Yun Xiao, Xia Li
Journal: Cancer Research (2018)

: Systematically tracking the tumor immunophenotype is required to understand the mechanisms of cancer immunity and improve clinical benefit of cancer immunotherapy. However, progress in current research is hindered by the lack of comprehensive immune activity resources and easy-to-use tools for biologists, clinicians, and researchers to conveniently evaluate immune activity during the "cancer-immunity cycle." We developed a user-friendly one-stop shop web tool called TIP to comprehensively resolve tumor immunophenotype. TIP has the capability to rapidly analyze and intuitively visualize the activity of anticancer immunity and the extent of tumor-infiltrating immune cells across the seven-step cancer-immunity cycle. Also, we precalculated the pan-cancer immunophenotype for 11,373 samples from 33 The Cancer Genome Atlas human cancers that allow users to obtain and compare immunophenotype of pan-cancer samples. We expect TIP to be useful in a large number of emerging cancer immunity studies and development of effective immunotherapy biomarkers. TIP is freely available for use at http://biocc.hrbmu.edu.cn/TIP/. SIGNIFICANCE: TIP is a one-stop shop platform that can help biologists, clinicians, and researchers conveniently evaluate anticancer immune activity with their own gene expression data.See related commentary by Hirano, p. 6536.
Abstract P117: Physical Activity Decreases Cardiovascular Events via an Inflammatory Pathway: The Strong Heart Study
Authors: Parmanand Singh, Zaid Almarzooq, Mary Roman, Richard Devereux
Journal: Circulation (2016)

Background: Prior work has shown that fibrinogen, an accepted pro-inflammatory marker, predicts cardiovascular (CV) events. While it is known that physical activity imparts CV health benefits, its impact on systemic inflammation has not been fully explored. Objectives: To investigate the relationship between activity, inflammation, and CV death, we tested the hypotheses that, (i) activity results in less CV death, and (ii) the CV benefit of activity is partially due to lower systemic inflammation. Methods: We examined the association between activity (leisure-time plus occupational as METS-hours per week) and CV death among 4,038 adults (mean age 56 ± 3) without baseline CV disease in phase I of Strong Heart Study (1989-1991), a longitudinal study among American Indians. Regression models were used to assess associations between activity, fibrinogen and CV death. Kaplan-Meir analysis was used to plot survival based on activity. Results: After 10 years of follow-up (1989-1999), 308 fatal CV events occurred. Compared to subjects with minimal activity, those with higher activity levels had a significantly lower risk of CV death (p=0.002, Fig 1A). Odds ratios were 0.79 (95% CI: 0.59-1.06), 0.65 (0.48-0.88), and 0.46 (0.33-0.65) for increasing activity (in quartiles), after adjustment for age, sex, smoking, diabetes, hypertension, LDL, and renal disease. In addition, increasing activity was associated with lower fibrinogen levels (p&lt;0.001; Fig. 1B). Moreover, increasing activity resulted in lowest CV death in subjects with low fibrinogen levels, a benefit that extended to patients with high fibrinogen levels (Fig 1C). These results persisted independent of traditional CV risk factors and body fat (p&lt;0.001). Conclusion: In a population-based study of American Indians, physical activity was associated with less CV death, in part, mediated via an anti-inflammatory pathway. This study identifies activity as an important modulator of CV outcomes among American Indians, possibly due to lower levels of systemic inflammation.
What is seen and what is not seen in the economy: An effect of our evolved psychology
Authors: Pascal Boyer, Michael Bang Petersen
Journal: Behavioral and Brain Sciences (2018)

Abstract Specific features of our evolved cognitive architecture explain why some aspects of the economy are “seen” and others are “not seen.” Drawing from the commentaries of economists, psychologists, and other social scientists on our original proposal, we propose a more precise model of the acquisition and spread of folk-beliefs about the economy. In particular, we try to provide a clearer delimitation of the field of folk-economic beliefs (sect. R2) and to dispel possible misunderstandings of the role of variation in evolutionary psychology (sect. R3). We also comment on the difficulty of explaining folk-economic beliefs in terms of domain-general processes or biases (sect. R4), as developmental studies show how encounters with specific environments calibrate domain-specific systems (sect. R5). We offer a more detailed description of the connections between economic beliefs and political psychology (sect. R6) and of the probable causes of individual variation in that domain (sect. R7). Taken together, these arguments point to a better integration or consilience between economics and human evolution (sect. R8).
Abstract 18043: Identifying Predictors for All-Cause Mortality in Diabetic Patients in the ACCORD Trial Using Random Survival Forests
Authors: Shamsuzzaman, Tejas Patel, Eileen Navarro Almario, Colin Wu, Bereket Tesfaldet, Jerome Fleg, Gyorgy Csako, Charu Gandotra, George Sopko, Helena Sviglin, Lawton Cooper, Sean Coady, Neha Amin, Avantika Banerjee, Nashwan Farooque, Austin Taylor, Andrew Dodge, Shivani Gupta, Gauri Dandi, Laboni Hoque, Michelle Fennessy, Subha Raman, Carlos Cure, Ruth Kirby, Lijuan Liu, Jue Chen, Ye Yan, Keith Burkhart, Karim Calis, Eric Leifer, Henry Chang, Ana Szarfman, Michael Domanski, Frank Pucino, Yves Rosenberg, Ahmed Hasan
Journal: Circulation (2017)

Background: The ACCORD trial (NC0620) was terminated early due to an unexpected increase in mortality with intensive vs. standard glucose-lowering treatment (targeted HbA1c <6% vs. 7.0-7.9%) i...
Allergen content in German cockroach extracts and sensitization profiles to a new expanded set of cockroach allergens determine in vitro extract potency for IgE reactivity
Authors: Jill Glesner, Stephanie Filep, Lisa D. Vailes, Sabina Wünschmann, Martin D. Chapman, Giovanni Birrueta, April Frazier, Kyoung Yong Jeong, Coby Schal, Leonard Bacharier, Avraham Beigelman, Paula Busse, Véronique Schulten, Alessandro Sette, Anna Pomés
Journal: Journal of Allergy and Clinical Immunology (2018)
Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy
Authors: Yuzhu Hou, Hua Liang, Enyu Rao, Wenxin Zheng, Xiaona Huang, Liufu Deng, Yuan Zhang, Xinshuang Yu, Meng Xu, Helena Mauceri, Ainhoa Arina, Ralph R. Weichselbaum, Yang-Xin Fu
Journal: Immunity (2018)
Electrocardiographic Abnormalities in a Woman in Her 70s With Syncope
Authors: Muazzum M. Shah, Arvind Nishtala, Nora Goldschlager
Journal: JAMA Internal Medicine (2018)

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Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade
Authors: Simone A. Minnie, Rachel D. Kuns, Kate H. Gartlan, Ping Zhang, Andrew N. Wilkinson, Luke Samson, Camille Guillerey, Christian Engwerda, Kelli P. A. MacDonald, Mark J. Smyth, Kate A. Markey, Slavica Vuckovic, Geoffrey R. Hill
Journal: Blood (2018)
Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Incident Diabetic Retinopathy
Authors: Antonios Douros, Kristian B. Filion, Hui Yin, Oriana Hoi Yu, Mahyar Etminan, Jacob A. Udell, Laurent Azoulay
Journal: Diabetes Care (2018)

OBJECTIVE Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis, new users of GLP-1 RAs were compared with new users of insulin. RESULTS During 245,825 person-years of follow-up, 10,763 patients were newly diagnosed with diabetic retinopathy. Compared with current use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy overall (HR 1.00, 95% CI 0.85–1.17). Compared with insulin, GLP-1 RAs were associated with a decreased risk of diabetic retinopathy (HR 0.67, 95% CI 0.51–0.90). CONCLUSIONS The associations with diabetic retinopathy varied according to the type of comparator. When compared with use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy. The apparent lower risk of diabetic retinopathy associated with GLP-1 RAs compared with insulin may be due to residual confounding.