tbuckley/cabot-search huggingface dataset:
Abstract 12623: Vascular Regenerative Capacity: A Window into the Pathobiology of Obesity Paradox
Authors: Anurag Mehta, Qi Meng, Shivang Desai, Melroy D'Souza, Annie Ho, Shabatun Islam, Devinder S Dhindsa, Aditi Nayak, Ayman Alkhoder, Ananya Hooda, Anil Varughese, Syed Ahmad, Ali Mokhtari, Iraj Hesaroieh, Laurence Sperling, Yi-An Ko, Edmund Waller, Arshed A Quyyumi
Journal: Circulation (2020)

Introduction: Obese patients (BMI≥30 kg/m 2 ) with CAD have better outcomes as compared with non-obese patients, but the underlying pathobiology is unclear. Hypothesis: Obesity is directly associated with vascular regenerative capacity, measured as circulating progenitor cell (CPC) count, and this association provides insight into obesity paradox pathobiology. Methods: CPCs were enumerated by flow cytometry as CD45 med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 y, 66% women, 23% Black, 28% obese) and 1,277 patients with CAD (66 y, 39% women, 22% Black, 39% obese). Association of obesity with CPC counts was analyzed using multivariable-adjusted linear regression models. Association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-y follow-up was studied using Kaplan-Meir survival curves and Cox models. Results: Obesity was independently associated with 16-34% higher CPC count (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated after adjusting for measures of systemic inflammation, insulin resistance, or insulin secretion. Cardiorespiratory fitness and android fat only partly attenuated the obesity-CPC relationship. In patients with CAD, obesity was independently associated with 8-12% higher CPC counts, and with 30% lower outcome risk. Lower CPC counts were associated with outcome risk in obese patients. Obese patients with high CD34+ count (≥median) were at a lower risk, while obese participants with low counts (&lt;median) were at a similar risk as compared with non-obese patients with high counts. The highest risk was observed in non-obese patients with low counts. Similar results were observed with CD34+/CD133+ and CD34+/CXCR4+ cells. Conclusions: Obesity is directly associated with vascular regenerative capacity, and the obesity paradox in CAD is observed in obese patients with high, but not low, CPC counts.
대한간학회지 제2차 춘계학술대회 초록집 : 간경변증에 의한 울혈성 위병변에서의 Nitric Oxide Synthase(NOS) 분포 -면역화학검사-
Authors: 문영수 ( Mun Yeong Su ), 강한걸 ( Kang Han Geol ), 홍사준 ( Hong Sa Jun ), 이광재 ( Lee Gwang Jae ), 김영수 ( Kim Yeong Su ), 함기백 ( Ham Gi Baeg ), 김진홍 ( Kim Jin Hong ), 조성원 ( Jo Seong Won ), 임현이 ( Im Hyeon I )
Journal: Clinical and Molecular Hepatology (1996)
Abstract 12990: High Fat Diet Delays Reverse Remodeling of Pulmonary Artery in Hypoxia-induced Pulmonary Hypertension Mice
Authors: Koichi Sugimoto, Tetsuro Yokokawa, Tomofumi Misaka, Sayoko Yokokawa, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2020)

Background: Previous studies suggest the association of metabolic disorder with pulmonary hypertension. Elevated pulmonary artery pressure induced by hypoxia in mice returns to normal when they are placed back in normoxia. In this study, we investigated the effect of high-fat diet (HFD) on pulmonary artery pressure and reverse remodeling of pulmonary artery in mouse model of hypoxia-induced pulmonary hypertension. Methods: We used the female C57/Bl6 mice at the age of 8 weeks. After exposed to hypoxia (10% oxygen for 4 weeks) for induction of pulmonary hypertension, mice were returned to normoxic condition and fed HFD or low-fat diet (LFD) for 12 weeks. Results: The body weight (BW), glucose, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C), but not triglyceride (TG) were significantly increased in HFD group (36.9±5.1 vs. 24.0±1.4 g [BW], P&lt;0.05; 404.2±55.1 vs. 326.5±8.7 mg/dl [glucose], P&lt;0.05; 10.2±3.6 vs. 7.5±0.9 mg/dl [LDL-C], P&lt;0.05; 47.2±10.0 vs. 30.9±8.7 mg/dl [HDL-C], P&lt;0.05 and 40.0±21.1 vs. 53.4±12.9 mg/dl [TG], P=0.09). The right ventricular systolic pressure (RVSP) measured by a micro-manometer catheter and the Fulton index in HFD group were significantly higher than those in LFD group (23.8±2.3 vs. 19.3±2.9 mmHg [RVSP], P&lt;0.05; 0.30±0.06 vs. 0.25±0.04 [Fulton index], P&lt;0.05, respectively). The medial smooth muscle area (expressed as a percentage of the external area of the vessel) was larger in HFD group (40.1±5.3 vs. 34.5±3.1%, P&lt;0.05). In addition, the levels of active caspase-3 detected by Western blotting was lower in HFD group than in LFD group. TUNEL staining revealed that the apoptosis of pulmonary artery smooth muscle cells was suppressed in HFD group. Conclusion: Our results suggest that metabolic disorder attenuates pulmonary artery reverse remodeling, at least in part, by suppressing apoptosis of pulmonary artery smooth muscle cells when hypoxia-induced pulmonary hypertension mice were returned to normoxia.
Abstract P001: Retirement Age And 20-year Cognitive Decline: The Atherosclerosis Risk In Communities Neurocognitive Study
Authors: Albert Liu, Mehul D Patel, Alden L Gross, Thomas Mosley, Andreea Rawlings, Andrea L Schneider, Anna Kucharska-newton, A Richey Sharrett, Rebecca F Gottesman, Silvia Koton
Journal: Circulation (2021)

Background: The effect of retirement on cognitive functioning is not clear. We examined the association between age at retirement, midlife occupation, and cognitive decline in the large Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. Methods: Retirement status after ARIC visit 4 (1996-98) was reported in annual follow-up questionnaires administered in 1999-2007 (n= 8,426), and classified as occurring before or after age 70. Current or most recent occupation at visit 1 (1987-89) was categorized based on 1980 US census major occupation groups and tertiles of Nam-Powers-Boyd occupational status score (a measure of socioeconomic status of occupations, hereby used as a proxy for occupational complexity). Generalized estimating equation models were used to examine the associations of retirement with trajectories of a global cognitive factor score, assessed in 1990-92 (visit 2), 1996-98 (visit 4) and 2011-2013 (visit 5). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. To account for attrition, we also performed multiple imputation by chained equations. Results: Retirement before age 70 is associated with higher educational level and higher occupational status score in white men and women, and in black men. We observed associations between retirement before age 70 and lower baseline cognitive scores, as well as slower cognitive decline in white men and women, and in black men (Figure). The results did not change substantially after adjusting for the occupational status score or accounting for attrition. Conclusion: Retirement before age 70 was significantly associated with lower baseline cognitive scores and slower cognitive decline in whites and in black men. The lack of similar associations in black women and the investigation of reasons for the observed associations warrant further research.
Abstract P101: Premenopausal Life’s Simple 7 Score Is Associated With High-density Lipoprotein Metrics Later In Life: The SWAN HDL Study
Authors: Alexis Nasr, Karen A Matthews, Maria M Brooks, Trevor Orchard, Dan McConnell, Jeffrey T Billheimer, Daniel J Rader, Emma Barinas-Mitchell, Norman Wang, Samar R El Khoudary
Journal: Circulation (2021)

Objective: In midlife women, higher high-density lipoprotein cholesterol (HDL-C) is not always associated with cardio-protection, suggesting a potential dysfunction of HDL. Novel metrics of HDL may provide further information on its cardio-protective features. The AHA developed the Life’s Simple 7 (LS7) score based on 7 lifestyle factors (cholesterol, BMI, diet, physical activity, smoking, glucose and blood pressure). A higher LS7 indicates a healthier lifestyle and is to cardiovascular health. We aimed to assess if higher premenopausal LS7 score is associated with a protective future HDL metrics profile as measured by greater HDL function (cholesterol efflux capacity), lower HDL-triglycerides (HDL-Tg) and higher HDL-phospholipids (HDL-PL) contents, higher large HDL-particles (HDL-P) and lower small HDL-P levels and larger overall HDL size by nuclear magnetic resonance spectroscopy. Methods: We included 529 women [baseline age 46.4 (2.6) years, 57% (299 of 529) White] from the Study of Women’s Health Across the Nation (SWAN) HDL ancillary study who had premenopausal LS7 score followed by repeated HDL metrics at later visits [time between LS7 score and first HDL measure: 3.9 (1.4) years]. Multivariable linear mixed models were used to analyze the independent association between premenopausal LS7 score and each HDL metric. Results: After adjusting for race, education, and baseline age, menopausal status, economic hardship and high-sensitivity C-reactive protein (Table), higher premenopausal LS7 score was associated with lower HDL-Tg (p&lt;0.0001) and higher HDL-PL (p=0.02), greater total HDL-P (p=0.03), large HDL-P (p=0.0001) and HDL-C (p&lt;0.0001), and larger HDL size (p&lt;0.0001) later in life. Premenopausal LS7 score was not related to HDL function. Conclusion: Higher premenopausal LS7 score was not related to HDL function but related to favorable future HDL contents and subclasses. This indicates that a better premenopausal lifestyle and metabolic health may contribute to a better HDL profile later in life.
Abstract MP22: Social Isolation, Social Support, And Cognitive Decline: The Atherosclerosis Risk In Communities Study
Authors: Albert Liu, Silvia Koton, Pamela L Lutsey, Keenan Walker, Priya Palta, A Richey Sharrett, Rebecca F Gottesman, Alden L Gross
Journal: Circulation (2021)

Introduction: Recent evidence supports relationships between social engagement and cognitive function, but the importance of social engagement decades before the onset of cognitive impairment is less well described. We examined associations of midlife social isolation and social support with mid-to-late life cognitive decline. Methods: In 14,083 participants in the Atherosclerosis Risk in Communities (ARIC) Study, social isolation was evaluated in 1990-92 by the Lubben Social Network Scale, discretized into: Isolated, and high, moderate, and low “risk” for isolation. Perceived social support, using the Interpersonal Support Evaluation List-Short Form, was discretized into tertiles. Linear mixed effects models with random intercepts and slopes were used to estimate the cross-sectional and longitudinal (1990-92 to 2011-13) associations of social isolation/social support with general cognitive performance. Models were adjusted for demographic factors and comorbidities, with effect modification explored by race and sex. We used multiple imputation by chained equations (MICE) to account for attrition. Results: Participants were on average 57.0 years old, 56% female, and 24% Black; 3% were “isolated” and 38% reported low social support. On average, men had a higher level of social isolation and lower level of social support. White participants had lower scored risk of social isolation. Socially isolated participants had on average a 0.253 standard deviation (SD) (95% CI 0.181, 0.324) lower baseline cognitive score, but a similar rate of cognitive decline in both the first 6 (difference: 0.002 SD/year, 95% CI -0.008, 0.012) and subsequent 15 years (difference: 0.001 SD/year, 95% CI: -0.006, 0.008), compared to those with lower social isolation level. Compared to participants with the highest level of social support, participants with the lowest level of social support had on average a 0.183 SD (95% CI 0.154, 0.212) lower baseline cognitive score, with a similar rate of cognitive decline in the first 6 years (difference: -0.001 SD/year, 95% CI -0.005, 0.003), but a 0.005 SD/year (95% CI 0.002, 0.007) slower rate of cognitive decline after 6 years, mainly driven by white and male participants. MICE-imputed results did not change. Conclusions: Although higher levels of social isolation and lower levels of social support in midlife were associated with worse cognitive function at baseline, these exposures had only a minimal impact on 20-year cognitive change. Some relationships differed by race and sex. Further studies are needed to better elucidate whether interventions addressing social isolation and support would be effective in the prevention of cognitive decline and dementia.
Fiber Networks: The Plasticity of Nanofibrous Matrix Regulates Fibroblast Activation in Fibrosis (Adv. Healthcare Mater. 8/2021)
Authors: Yuanbo Jia, Yanzhong Wang, Lele Niu, Hang Zhang, Jin Tian, Dengfeng Gao, Xiaohui Zhang, Tian Jian Lu, Jin Qian, Guoyou Huang, Feng Xu
Journal: Advanced Healthcare Materials (2021)

Little attention has been paid to the effect of matrix fiber-network plasticity at the microscale. In article number 2001856, Jin Qian, Guoyou Huang, Feng Xu, and co-workers find a significant decrease in plasticity of native fibrotic tissues, which is associated with increased matrix crosslinking. They demonstrate that the decrease of matrix plasticity promotes fibroblast activation and spreading using a plasticity-controlled 3D culture system, which is mediated through cytoskeletal tension and nuclear translocation of Yes-associated protein.
Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy
Authors: Pablo Garcia‐Pavia, Frank Bengel, Dulce Brito, Thibaud Damy, Franz Duca, Sharmila Dorbala, Jose Nativi‐Nicolau, Laura Obici, Claudio Rapezzi, Yoshiki Sekijima, Perry M. Elliott
Journal: European Journal of Heart Failure (2021)
Abstract 13362: Socio-ecological Variables Influenced Moderate-to-vigorous Intensity Physical Activity Levels Amongst Hospital-based Nurses: A Multi-site Study
Authors: Daniel Law, daniele chirico, Tasuku Terada, Stephanie Prince Ware, jordan bernick, Robert D Reid, Andrew Pipe, Heather Tulloch, Jennifer L. Reed
Journal: Circulation (2020)

Introduction: Previous research has shown that nurses are not meeting recommended moderate-to-vigorous intensity PA (MVPA) guidelines (≥150 minutes/week) for optimal cardiovascular disease risk reduction. Socio-ecological approaches have been used to explore the determinants of PA levels. We examined personal, social and environmental factors associated with the MVPA levels of Canadian nurses. Methods: Secondary analysis of data from a multi-site cross-sectional study was undertaken. Nurses were recruited from 14 hospitals in Ontario, Canada. An accelerometer (ActiGraph GT3X) was used to measure MVPA levels (minutes/day). Socio-ecological variables were derived from sociodemographic, anthropometric and cardiometabolic data, and questionnaires assessing determinants of PA (Table 1). Multivariate generalized estimating equations (GEE) were used to explore associations between socio-ecological variables and MVPA levels while accounting for hospital sites. Variables were selected for multivariate analyses if they were significant ( p &lt;0.05) in univariate analyses. Results: A total of 257 nurses (42±12 years) had complete accelerometer (≥10 hours of wear time for ≥4 days) and questionnaire data. Of these nurses, 54% were overweight/obese and 6% were smokers. Multivariate analyses showed positive associations between MVPA levels and high perceived capability to exercise despite common barriers (e.g. poor weather; β=0.13, p =0.02) and feeling connected to their exercise peers (β=1.34, p =0.01). Greater shiftwork associated daytime sleepiness and/or insomnia were inversely associated with MVPA levels (β=-4.87, p &lt;0.01). Conclusion: Future endeavors to accentuate nurses’ PA levels should address modifiable socio-ecological variables such as encouraging exercise despite common barriers, and with peers to whom they feel connected. Nurses should consider increasing time spent engaging in MVPA to minimize the negative effects of shiftwork.
Conjunctival melanoma: New insights in tumour genetics and immunology, leading to new therapeutic options
Authors: Niels J. Brouwer, Robert M. Verdijk, Steffen Heegaard, Marina Marinkovic, Bita Esmaeli, Martine J. Jager
Journal: Progress in Retinal and Eye Research (2021)

Recent developments in oncology have led to a better molecular and cellular understanding of cancer, and the introduction of novel therapies. Conjunctival melanoma (CoM) is a rare but potentially devastating disease. A better understanding of CoM, leading to the development of novel therapies, is urgently needed. CoM is characterized by mutations that have also been identified in cutaneous melanoma, e.g. in BRAF, NRAS and TERT. These mutations are distinct from the mutations found in uveal melanoma (UM), affecting genes such as GNAQ, GNA11, and BAP1. Targeted therapies that are successful in cutaneous melanoma may therefore be useful in CoM. A recent breakthrough in the treatment of patients with metastatic cutaneous melanoma was the development of immunotherapy. While immunotherapy is currently sparsely effective in intraocular tumours such as UM, the similarities between CoM and cutaneous melanoma (including in their immunological tumour micro environment) provide hope for the application of immunotherapy in CoM, and preliminary clinical data are indeed emerging to support this use. This review aims to provide a comprehensive overview of the current knowledge regarding CoM, with a focus on the genetic and immunologic understanding. We elaborate on the distinct position of CoM in contrast to other types of melanoma, and explain how new insights in the pathophysiology of this disease guide the development of new, personalized, treatments.
Screening for ovarian cancer is ruled out after trial found it did not reduce deaths
Authors: Nikki Nabavi
Journal: BMJ (2021)

A large trial of annual screening tests for ovarian cancer showed they did not reduce deaths despite picking up cancers earlier,1 ruling out the possibility of a national population screening programme.

The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), led by UCL researchers, looked at data from more than 200 000 women who were aged 50-74, and followed them up for an average of 16 years. The women were randomly allocated to one of three groups: no screening, …
Superior Usability of Flow-mediated Dilatation for Predicting Coronary Plaque Vulnerability in Patients with Coronary Artery Disease Compared with C-reactive Protein
Authors: Terashita Daisuke, Sawada Takahiro, Emoto Takuo, Mizoguchi Taiji, Mizuguchi Takao, Okamoto Hiroshi, Matsuo Yosuke, Kim Su-Sik, Takarada Akira
Journal: Circulation (2012)
Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation
Authors: Ta-Chiang Liu, Justin T. Kern, Umang Jain, Naomi M. Sonnek, Shanshan Xiong, Katherine F. Simpson, Kelli L. VanDussen, Emma S. Winkler, Talin Haritunians, Atika Malique, Qiuhe Lu, Yo Sasaki, Chad Storer, Michael S. Diamond, Richard D. Head, Dermot P.B. McGovern, Thaddeus S. Stappenbeck
Journal: Cell Host & Microbe (2021)
Laboratory testing for <scp>ADAMTS13</scp>: Utility for <scp>TTP</scp> diagnosis/exclusion and beyond
Authors: Emmanuel J. Favaloro, Leonardo Pasalic, Brandon Henry, Giuseppe Lippi
Journal: American Journal of Hematology (2021)

The metalloproteinase ADAMTS13 (a disintegrin with a thrombospondin type 1 motif, member 13), also known as VWF (von Willebrand factor) protease, may be assessed in a vast array of clinical conditions. Notably, a severe deficiency of ADAMTS13 characterizes TTP (thrombotic thrombocytopenic purpura), a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. Although prompt identification/exclusion of TTP can be facilitated by rapid ADAMTS13 testing, the most commonly utilized assays are based on ELISA (enzyme linked immunosorbent assay) and require long turnaround time and have relatively limited throughput. Nevertheless, several rapid ADAMTS13 assays are now available, at least in select geographies. The current mini-review discusses these issues, as well as the potential utility of ADAMTS13 testing in a range of other conditions, including coronavirus disease 2019 (COVID-19).
Abstract 17477: Delay in ST Elevation Myocardial Infarction Presentation During the COVID-19 Pandemic in New York
Authors: Eitezaz Mahmood, Arvind Devanabanda, Avneet Singh, rajiv jauhar
Journal: Circulation (2020)

Introduction: The Covid-19 pandemic has been associated with a reduction in STEMI volume in cardiac catheterization centers around the United States; yet a paradoxical increase in cardiovascular death within the same time period. Hypothesis: We hypothesized that reduction in STEMI volume during the COVID-19 pandemic may have been secondary to patient reluctance to present to the hospital. Methods: We performed a retrospective review of patients who presented to the emergency department from March 1st-April 19th, 2020 and March 1st-April 19th, 2019 across Northwell Health. Data on clinical comorbidities, time from symptoms onset, and patient outcomes was abstracted through manual chart review. The primary outcome of our study was time from onset of chest pain to presentation to the emergency room. Patients with COVID-19 were excluded from analysis. Variables were compared using the Chi-square test for categorical variables and the student-t for continuous variables. Results: In total 197 patients met our inclusion criteria, with 135 (69%) admitted in 2019 as compared to 62 (31%) presenting during the same time period in during the COVID-19 pandemic. There were no significant differences in the age of our patients and in comorbidities such as hypertension, hyperlipidemia, coronary artery disease, diabetes, chronic kidney disease, or chronic obstructive pulmonary disease. Patients who presented for STEMI during the COVID-19 waited significantly longer from time of onset of symptoms as compared to patients in 2019, (13.5 hours vs. 6.5 hours, p = .05). Patients who presented for STEMI in 2020 were more likely to die during hospitalization, but this did not reach statistical significance (9.7% vs 6.7%, p = .45). Conclusions: Reduction in STEMI volume during the COVID-19 pandemic may be related to patient reluctance to present to the hospital. Efforts to reduce the stigma of hospitalizations during the pandemic is important.
9P BRCA1 promoter methylation confers a more favorable prognosis to systemically untreated young triple-negative breast cancer patients than tumour BRCA1 mutation
Authors: Y. Wang, E.H. Rosenberg, G.M.H.E. Dackus, A. Broeks, S. Cornelissen, P.J. van Diest, M. Hauptmann, N. Ter Hoeve, V. De Jong, K. Jozwiak, E. Koop, P.M. Nederlof, M. Opdam, S. Siesling, N. Stathonikos, A. Voogd, W. Vreuls, M. Kok, S.C. Linn, M.K. Schmidt
Journal: Annals of Oncology (2021)
Epigenetic regulation of epithelial dectin‐1 through an IL‐33‐STAT3 axis in allergic disease
Authors: Hwan Mee Yong, Naina Gour, Deepika Sharma, Syed Muaz Khalil, Andrew P. Lane, Stephane Lajoie
Journal: Allergy (2021)

Abstract Allergic diseases arise in susceptible individuals in part because of decrements in protective pathways. The mechanism by which these anti‐inflammatory molecules become repressed remains unclear. We have previously reported that epithelial dectin‐1 prevents aberrant type 2 responses and is downregulated in the epithelium of allergic patients. Here, we report that dectin‐1 is constitutively expressed by the respiratory epithelium in humans and that IL‐33 specifically acts as a repressor of dectin‐1. Mechanistically, this occurs via IL‐33‐dependent STAT3 activation and the subsequent repression of the dectin‐1 gene, CLEC7A. We have identified a novel enhancer region upstream of the proximal promoter of CLEC7A that is only accessible in epithelial cells, but not in hematopoietic cells. Epigenetic repression of CLEC7A through this newly identified locus, downstream of an aberrant IL‐33‐STAT3 axis, occurs in the epithelium of allergic individuals. Collectively, our data identify a mechanism of epigenetic fine‐tuning of dectin‐1 expression in epithelial cells that may participate in allergenicity.