tbuckley/cabot-search huggingface dataset:
Effects of school-based before-school physical activity programmes on children’s physical activity levels, health and learning-related outcomes: a systematic review
Authors: James Woodforde, Tahlia Alsop, Jo Salmon, Sjaan Gomersall, Michalis Stylianou
Journal: British Journal of Sports Medicine (2021)

Objective To review and evaluate the impact of school-based, before-school physical activity (PA) programmes on children’s PA levels, health and learning-related outcomes. Design Systematic review. Data sources PubMed, PsycINFO, Scopus, Embase and ERIC were searched in January 2021. Eligibility criteria for selecting studies (1) Original research published in English, (2) sample included typically developing school-age children and/or adolescents, (3) examined school-based PA programmes delivered before school, (4) included a comparator and (5) reported associations with PA, physical health, learning-related and/or psychosocial outcomes. Studies examining before-school active transport or sport were excluded. Results Thirteen articles representing 10 studies were included (published 2012–2020); seven conducted in primary schools. Programmes ranged between 3 weeks and 6 months, primarily operating daily and for 25–40 min. One study examined a programme informed by theory; six incorporated fidelity measures. Data synthesis, considering consistency of findings, showed indeterminate associations for the domains of physical health, learning-related and psychosocial outcomes. Among subdomains, synthesis showed positive associations with before-school and daily PA, cardiorespiratory and muscular fitness, readiness to learn and an inverse association with adiposity. Risk of bias was high/serious or insufficiently detailed across studies and outcome domains, except PA, which included moderate-risk studies. Conclusion There is limited available evidence on school-based, before-school PA programmes, with some positive associations at domain and subdomain levels. Continued research is justified to understand the role of before-school programmes for facilitating PA. Future research should follow recommended practice for intervention design and process evaluation, and address under-represented contexts, including secondary schools. PROSPERO registration number CRD42020181108.
Abstract 9317: Soluble Guanylate Cyclase Activator Treatment Improves Vasomotor Function in an Accelerated-Ageing Mouse Model
Authors: Ehsan Ataei Ataabadi, Keivan Golshiri, René de Vries, Renata M. C. Brandt, Ingrid Van Der Pluijm, Jan H Danser, Peter SANDNER, Anton Roks
Journal: Circulation (2021)

Introduction: Vascular ageing is a key driver of cardiovascular diseases. Mice with partial deletion of the repair enzyme gene Ercc1 ( Ercc1 Δ/- ) display accelerated vascular ageing which is associated with decreased nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling, oxidative stress, inflammation, and cellular senescence. Restoring this pathway could be an effective treatment opportunity for vascular ageing. We therefore, investigated the therapeutic potential of the sGC activator BAY 56-6544, which can activate oxidized and heme-free sGC in Ercc1 Δ/- mice. Design and Method: Ercc1 Δ/- and wild-type (WT) mice received either vehicle or BAY 54-6544 chow for 8 weeks. Blood pressure (BP) and in-vivo vasodilation (reactive hyperemia: RH) were measured at 15 and 16 weeks respectively. Mice were sacrificed at 17 weeks. Thoracic aorta (TA) endothelium-dependent (ED) and -independent (EI) relaxations were assessed (wire-myograph). Afterwards, we investigated the expression level of senescent markers p16 and p21 and inflammatory markers Il-6 and Ccl2 in aorta by qPCR. Results: BP was similar in all groups. RH was decreased in Ercc1 Δ/- vs. WT (P=0.03) and significantly improved after BAY 54-6544 treatment to the same level as in WT. In vehicle-treated Ercc1 Δ/- mice maximal NO-mediated relaxation in TA to acetylcholine (ED) and sodium nitroprusside (EI) were decreased as compared to WT (ED: 46.97±7.04 vs. 72.33±3.03, P=0.0001; EI: 75.47±5.27 vs. 88.30±3.64, P=0.02). Although BAY 54-6544 treatment did not improve ED response significantly, it improved EI relaxation in Ercc1 Δ/- to the same level as in WT (EI 88.54±3.26). EI response in BAY 54-6544-treated WT was the same as in vehicle-treated one (86.98±3.56). mRNA expression of p16, p21 and Ccl2 were significantly higher in vehicle-treated Ercc1 Δ/- , whereas BAY 54-6544 treatment could attenuate this increase. Conclusion: DNA repair deficiency in Ercc1 Δ/- mice causes a disruption of NO-sGC-cGMP signaling and a decrease of vasodilator response. Treatment with the BAY 54-6544 improved NO-mediated vasodilation and attenuated vascular senescence and inflammation markers. Thus, BAY 54-6544 could be a potential therapeutic treatment to attenuate vascular ageing.
HIV-1 Vif suppresses antiviral immunity by targeting STING
Authors: Yu Wang, Gui Qian, Lingyan Zhu, Zhuo Zhao, Yinan Liu, Wendong Han, Xiaokai Zhang, Yihua Zhang, Tingrong Xiong, Hao Zeng, Xianghui Yu, Xiaofang Yu, Xiaoyan Zhang, Jianqing Xu, Quanming Zou, Dapeng Yan
Journal: Cellular and Molecular Immunology (2021)
Abstract 14084: Computationally Identified Shape Differences In The Left Atrium On Pre-ablation Ct Scans Appear To Be Associated With Recurrence Of Atrial Fibrillation
Authors: Golnoush Asaeikheybari, Amogh Hiremath, Rakesh Shiradkar, Majd El-harasis, M. Benjamin Shoemaker, John Barnard, Amit Gupta, Mina K Chung, Anant Madabhushi
Journal: Circulation (2021)

Introduction: Catheter-based ablation is an increasingly utilized management strategy for atrial fibrillation (AF); however, a major problem is AF recurrence post-ablation. There is increasing interest in the use of advanced image analysis to better understand differences in left atrial (LA) shape that may be associated with a higher recurrence risk and potential sites of recurrence. Hypothesis: Factors which lead to the post-ablation recurrence prompt LA differential remodeling. The significant shape difference regions among AF recurrence (AF+) and AF non-recurrence (AF-) patients can be identified from pre-ablation CT scans. Those regions could potentially represent future sites of recurrence and hence could be targets for ablation. Methods: This study included pre-ablation CT-scans of 51 AF+ and 51 AF- patients. Two separate atlases were created by registering Left atrial CT volumes of AF+ and AF- patients to their representative templates (T+ and T- respectively). The atlases were co-registered to a common canonical frame of reference (T-) and a non-parametric General Linear Model (GLM) based t-test with 500 permutations was used to identify the regions (Surface of interest (SOI)) that are statistically significant (p-value&lt;0.1) between the two classes. To reduce sensitivity in the template selection, we constructed an ensemble SOI based on SOIs obtained from 10 different templates and made the frequency map of overlap SOIs. Results: The registration accuracy in the final common frame in terms of average Dice similarity coefficient was in the range of 0.85-0.94 over the 10 SOI constructions. The frequency map revealed the maximum overlap of SOIs in an area where left pulmonary veins enter the left atrium. This could potentially represent a new target for ablation. Conclusions: An ensemble atlas-based shape differentiation method revealed SOI regions that are structurally associated with recurrence and might potentially represent targets for ablation.
Abstract MP206: Cortical Bone Derived Stem Cells Modulate The Adaptive Immune Response Post-MI
Authors: Marcus J Wagner, Lindsay Kraus, Tabito Kino, Mohsin Khan, Sadia Mohsin
Journal: Circulation Research (2021)

Background: The inflammatory response mounted following myocardial infarction (MI) is closely coupled to myocardial wound healing processes such as angiogenesis, fibroblast maturation, and cardiomyocyte survival. A consortium of pro-reparative Tregs occupy the myocardium during ischemic injury and are essential in modulating cardiac homeostasis. However, Treg exposure to chronic, ischemic microenvironments compromises Tregs’ pro-reparative signatures and induces pathogenic remodeling of Tregs, compromising cardiac wound healing. Cortical Bone Derived Stem Cells (CBSCs) have superior engraftment capabilities compared to other stem cell types and can modulate the post-MI inflammatory response by establishing anti-inflammatory paracrine signaling dominance and the expansion of CD45+ leukocytes and CD4+ T cells residence in the MI heart. Therefore, we hypothesized CBSC cell therapy can modulate the recruitment and phenotype of Treg residence in the MI heart to permit their enhanced cardiogenic properties. Methods and Results: Animals that received intramyocardial injection of CBSCs along the infarct border zone of the permanently ligated LAD possessed smaller infarct sizes and improved cardiac function, that paralleled pro-reparative, TNFRII+ Treg expansion and repressed pathogenic TNFRI+, Treg residence 1- and 8- weeks post-MI compared to Mesenchymal Stem Cells (MSCs) or vehicle (PBS) treated animals. Similar TNFRI/II Treg dynamics were also observed in the spleen. Diphtheria toxin (DTR) mediated Treg ablation and S1P1 agonist administration, in the presence of CBSC therapy, reverted pro-reparative Treg expansion and solicited infarct size expansion and compromised cardiac function. The exposure of CBSC paracrine secretome to naïve CD4+ T cell cultures induces pro-reparative TNFRII+ Treg expansion. Paracrine profiling of CBSC secretome identifies Osteoprotegerin (OPG) enrichment and OPG depletion, via siRNA and lentivirus, compromises T cell survival signaling and pro-reparative, TNFRII+ Treg establishment both in vitro and in the MI heart. Conclusions: CBSCs can modulate the induction and preservation of pro-reparative TNFRII+ Tregs in the MI heart to solicit cardiac repair during acute and chronic ischemic injury.
Comment on “Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics”
Authors: Hilma Hólm, Patrick Sulem, Vinicius Tragante, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Kari Stefansson
Journal: Science Translational Medicine (2021)

Genetic data do not provide evidence for SOST inhibition causing cardiovascular disease.
NIMG-55. AUGMENTED INTELLIGENCE IS SUPERIOR TO ARTIFICIAL INTELLIGENCE! HUMAN-COMPUTER SYNERGY FOR GENERATING HIGH QUALITY GLIOBLASTOMA SUB-REGION SEGMENTATIONS
Authors: Satyam Ghodasara, Ujjwal Baid, Spyridon Bakas, Michel Bilello, Suyash Mohan
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Artificial intelligence (AI) is poised to improve diagnostic methods in neuro-oncologic imaging and contribute to patient management by analyzing pre-operative MRI scans. AI results are better interpreted by compartmentalizing glioblastoma into distinct sub-regions, i.e., necrotic core, enhancing tumor, peritumoral T2/FLAIR signal abnormality (ED). Manual delineation of these sub-regions by expert neuroradiologists is impractical, requiring hours for intricate cases. Computer-aided segmentation (CAS) can mitigate this issue but is limited in the quality of the produced segmentations. We hypothesize that CAS followed by expert refinements is more practical/time-efficient. METHODS CAS was used on a total of 359 glioblastoma patients with four MRI sequences (T1, T1Gd, T2, T2-FLAIR) from each patient. All segmentations were sent to expert neuroradiologist annotators for manual refinements. Once refined, our team including two senior attending neuroradiologists with ≥13 years of experience each, reviewed and either approved or returned the segmentations to individual annotators for further refinements. Total time required to refine and review the finalized segmentations was measured. RESULTS Following one round of refinements by expert annotators, 244/359 (68%) segmentations were approved by our team while 115/359 (32%) segmentations contained a variety of errors that required a second round of refinements. The most common observed errors were 1) missed ED in the anterior/inferior temporal lobes and corpus callosum (37/115 cases, 32%) and 2) erroneous segmentation of normal choroid plexus and blood vessels (14/115 cases, 12%). The expert annotators required 120 hours to refine all 359 segmentations, and our team required 26 additional hours to review them, resulting in 24 minutes/segmentation following CAS. CONCLUSION Our findings support the value of a well-communicated annotation protocol to coordinate CAS and expert annotators. With CAS, our team and expert annotators rapidly finalized segmentations for 359 glioblastoma patients, demonstrating the value of a synergistic approach to creating high quality tumor sub-region segmentations.
Abstract 13194: Regional Disparities in Clinical and Socioeconomic Characteristics of African-American Patients With Cardiac Amyloidosis Served by Two Inner City Hospitals
Authors: Mukunthan Murthi, Talal Asif, Aman Gupta, Karen Vega, Anna P Pinelo Coll Cardenas, Stanley F Fernandez, Saurabh Malhotra
Journal: Circulation (2021)

Introduction: The highest prevalence of cardiac amyloidosis (CA) in the United States (US) is reported among African American (AA) individuals, with a significant regional variation in this prevalence. We aimed to study the clinical, demographic and socioeconomic differences among AA patients diagnosed with CA from inner city hospital located in different regions of the US. Methods: Demographic, clinical and socioeconomic data on patients diagnosed with CA was collected from Buffalo General Medical Center, Buffalo, NY (Northeast region; Erie County) and Cook County Health, Chicago, NY (Midwest region; Cook County). CA was diagnosed based on a combination of pyrophosphate scintigraphy and assessment of paraproteinemia. Socio-economic data from zip code of patient’s residence was obtained from publicly available 2010 census summary data. Results: Overall, 80 patients were tested for CA in Erie County and 150 patients in Cook County, of which 58 (72.5%) and 128 (85.3%) were AA, respectively. Among AA patients, 16 (28%) from Erie County and 29 (23%) from Cook County were diagnosed with CA (Table). Despite younger age, and a lower prevalence of male gender, CAD, hypertension and aortic stenosis, Cook County patients had more severe cardiomyopathy, given a significantly lower ejection fraction at presentation. Additionally, patients from Cook County had lower socioeconomic status as evident by a lower average income, fewer social security beneficiaries, greater unemployment and a greater prevalence of uninsured population. Conclusions: Despite similar racial background, there are significant demographic, clinical and socioeconomic differences among AA patients with CA from two different regions in the US. Within race disparities, that could be influenced by regional socioeconomic differences, may drive clinical outcomes of AA patients with CA.
Abstract 9998: Association of Hospital Procedural Volume with Outcomes in Heart Transplantation
Authors: Abdul Minhas, Robert Ariss, SALIK NAZIR, Keerat Ahuja, Muhammmad Khan, Tariq Jamal Siddiqi, Richard Krasuski, Stephen J Greene, Marat Fudim
Journal: Circulation (2021)

Background: Studies have shown an inverse relationship between procedural volume and outcomes for numerous procedures. The aim of this study was to evaluate the association of heart transplant (HT) procedural volume and in-hospital clinical outcomes. Methods: We conducted a retrospective analysis of adult hospitalizations from the Nationwide Readmissions Database (NRD) 2018. International Classification Diseases (ICD) codes were used to identify patients who underwent HT. Hospitals were categorized into 3 groups on the basis of tertiles of annual procedural volume: low (1-14 procedures/year), medium (14 to 27 procedures /year), and high (28 to 115 procedures /year). Hierarchical mixed effect logistic regression modeling with hospital as a random effect was used to examine the association between hospital procedural volume and outcomes. These models were adjusted for patient-level and hospital-level characteristics. Low volume hospitals were used as the reference category. Results: This study included 1689 procedures performed across 69 hospitals ( Table ). On multivariate analysis, there was no statistically significant difference in inpatient mortality, discharge to nursing home/long term care facility, stroke, acute kidney injury, bleeding requiring transfusion, pericardial complications, vascular complications or length of stay among low, medium and high-volume centers ( Table ). Interestingly there was a trend toward lower length of stay and lower inpatient mortality in high volume centers that did not reach statistical significance. Conclusion: Our study did not find any association between hospital HT procedural volume and clinical outcomes. Further studies are needed to confirm this.
Abstract 13819: Circulating PON Lactonase Activity Predicts Major Adverse Cardiac Events in Subjects With Atherosclerotic Renal Artery Disease
Authors: David J Kennedy, Jacob Connolly, Zhen Sun, Pamela S Brewster, Tyler Reid, Prabhatchandra Dube, Christopher J Cooper, Lance D Dworkin, Deepak Malhotra, Steven Haller, David J Kennedy
Journal: Circulation (2021)

Introduction: Decreased plasma lactonase activity, catalyzed by high-density lipoprotein (HDL)-associated paraoxonase (PON), is associated with increased oxidant stress and cardiovascular risk in settings such as coronary artery disease as well as some etiologies of chronic kidney disease (CKD). However, whether circulating PON lactonase activity predicts outcomes in atherosclerotic renal artery stenosis (ARAS) is unknown. We sought to determine the prognostic value of circulating PON lactonase activity in subjects with ARAS, particularly in relation to established risk factors. Methods/Results: PON lactonase activity was measured in plasma of subjects with ARAS and either systolic hypertension while taking ≥2 antihypertensive drugs or CKD (n=718) enrolled in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study as well as a cohort of apparently healthy, normotensive non-ARAS subjects (n=33). Participants with ARAS were prospectively followed for incident major adverse cardiac events (MACE, composite of cardiovascular death, nonfatal myocardial infarction, and stroke) over a median follow-up period of 43 months (interquartile range, 31 to 55). PON lactonase activity in ARAS subjects was significantly lower compared with that in non-ARAS control subjects [mean±SD, 2466±839 vs 3514±745 pmol/min/mL, P&lt;0.001]. Next, participants were dichotomized based on the baseline plasma levels of PON lactonase activity, into high (&gt; median) or low (≤ median) groups and were used to predict incident MACE at 3 years. Participants with lower PON lactonase activity had increased MACE at 3 years [67/359 (17%) vs 44/359 (12%), p&lt;0.05]. Lower circulating PON lactonase activity (hazard ratio 1.26, 95% CI 1.0 to 1.53, p=0.016) was a predictor of MACE. After adjusting for traditional risk factors and medication use, lower PON lactonase activity (hazard ratio 1.22, 95% CI 1.01 to 1.50, p=0.04) still conferred an increased risk of MACE. Conclusions: In patients with ARAS, decreased circulating PON lactonase activity, a measure of diminished antioxidant properties of HDL, predicts higher risk of incident long-term adverse cardiovascular events in multivariate models adjusting for established clinical and biochemical risk factors.
Associations between public health team engagement in local alcohol licensing and public health and crime outcomes in England and Scotland: a timeseries analysis
Authors: Frank de Vocht, Cheryl McQuire, Claire Ferraro, Philippa Williams, Madeleine Henney, Colin Angus, Matt Egan, Andrea Mohan, Richard Purves, Nason Maani, Niamh Shortt, Laura Mahon, Gemma Crompton, Linda Bauld, Niamh Fitzgerald
Journal: The Lancet (2021)
Abstract 13879: Relationship of Serum Lipid Metabolites and Clonal Hematopoiesis of Indeterminate Potential Among 12,186 Participants of the UK Biobank
Authors: Sumeet A Khetarpal, Md Mesbah Uddin, Satoshi Koyama, Zhi Yu, Akhil Pampana, Abhishek Niroula, Christopher Gibson, Gabriel Griffin, Peter Libby, Benjamin Ebert, Pradeep Natarajan
Journal: Circulation (2021)

Background: Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of leukemogenic mutations in hematopoietic stem cells in asymptomatic individuals, is an emerging age-related risk factor for blood cancers and myriad cardio-metabolic diseases. The spectrum of metabolites that may protect from or predispose to development of CHIP remains unknown. Methods: We obtained CHIP genotypes and measured serum metabolites among UK Biobank, a population-based study of United Kingdom residents aged 40-70 years. CHIP was also categorized by driver genes DNMT3A and TET2 and presence of large CHIP clones (variant allele fraction or VAF &gt; 10%). 152 lipid and lipoprotein metabolites were performed using NMR from blood samples. The relationship of CHIP to metabolites was assessed by multivariate linear regression adjusting for covariates of age, sex, smoking and principal components 1-10. Results: Among the 12,186 included UK Biobank participants with mean (SD) age 57.1 (8.0), we identified CHIP in 701 (5.75%). 313 participants with CHIP had large clones (VAF&gt;10%), and of these, 169 had DNMT3A mutations and 75 had TET2 mutations. Presence of CHIP was nominally associated with multiple measures of HDL and apolipoprotein B-containing lipoprotein metabolites. Among HDL metabolites, CHIP was associated with reductions in the percentage of HDL total cholesterol (ß = -0.09, P = 0.01), free cholesterol (ß = -0.072, P = 0.01) and cholesteryl ester (ß = -0.087, P = 0.01) and increased HDL triglyceride percentage (ß = 0.09, P = 0.01). Similar findings were observed for small, medium and large HDL particles. CHIP was also associated with decreased percentage of small LDL free cholesterol (ß = -0.089, P = 0.016) and phospholipid (ß = -0.106, P = 0.0057) and increased cholesterol ester (ß = 0.105, P = 0.0061). For VLDL, CHIP was associated with increased VLDL particle number (ß = 0.077, P = 0.035) and VLDL phospholipid percentage (ß = 0.085, P = 0.025) in the largest VLDL particles. Similar findings among HDL and VLDL metabolites were seen in those with large CHIP clones due to TET2 mutations but not with large clones due to DNMT3A mutations. Conclusions: These results reveal novel relationships of CHIP with lipid and lipoprotein metabolites in a population-based cohort.
Relapse Analysis and Resistance Mutations of <i> <i>PML-Rara</i> </i> Fusion Gene in Acute Promyelocytic Leukemia Patients Treated with All-Trans Retinoic Acid and Arsenic
Authors: Jiaqi Chen, Hongxing Liu, Fang Wang, Xue Chen, Yang Zhang, Panxiang Cao, Xiaoli Ma, Yu Li
Journal: Blood (2021)