tbuckley/cabot-search huggingface dataset:
Effects of physical activity interventions on cognitive and academic performance in children and adolescents: a novel combination of a systematic review and recommendations from an expert panel
Authors: Amika S Singh, Emi Saliasi, Vera van den Berg, Léonie Uijtdewilligen, Renate H M de Groot, Jelle Jolles, Lars B Andersen, Richard Bailey, Yu-Kai Chang, Adele Diamond, Ingegerd Ericsson, Jennifer L Etnier, Alicia L Fedewa, Charles H Hillman, Terry McMorris, Caterina Pesce, Uwe Pühse, Phillip D Tomporowski, Mai J M Chinapaw
Journal: British Journal of Sports Medicine (2018)

Objective To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations. Design Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality. Data sources PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus. Eligibility criteria for selecting studies PA-intervention studies in children with at least one cognitive or academic performance assessment. Results Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes. Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the ‘PA–performance’ relationship and miscellaneous topics. Conclusion There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance. The expert panel confirmed that more ‘high-quality’ research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis. PROSPERO registration number CRD42017082505.
Acute Left Ventricular Unloading Reduces Atrial Stretch and Inhibits Atrial Arrhythmias
Authors: Kiyotake Ishikawa, Shin Watanabe, Philyoung Lee, Fadi G. Akar, Ahyoung Lee, Olympia Bikou, Kenneth Fish, Changwon Kho, Roger J. Hajjar
Journal: Journal of the American College of Cardiology (2018)
Body Iron Stores and the Risk of Carotid Atherosclerosis
Authors: StefanKiechl, JohannWilleit, GeorgEgger, WernerPoewe, FriedrichOberhollenzer
Journal: Circulation (1997)

Background Fe2+ released from tissue iron stores may accelerate lipid peroxidation by virtue of its pro-oxidant properties and thus promote early atherogenesis. Methods and Results The present prospective survey addresses the potential association between serum ferritin concentrations and the 5-year progression of carotid atherosclerosis as assessed by ultrasonographic follow-up evaluations. The study population comprises a random sample of 826 men and women 40 to 79 years old. Serum ferritin was one of the strongest risk predictors of overall progression of atherosclerosis. The main part of this association appeared to act through modification of the atherogenic potential of LDL cholesterol (OR [95% CI] for a 1–SD unit increase in ferritin at LDL levels of 2.5, 3.6, and 4.9 mmol/L: 1.55 [1.30 to 1.85], 1.77 [1.40 to 2.24], and 2.05 [1.50 to 2.80]; P=.0012 for effect modification). Changes in iron stores during the follow-up period modified atherosclerosis risk, in that a lowering was beneficial and furth...
Abstract 1000: PD-L1 binding peptide identified by phage peptide display inhibits PD-1/PD-L1 interaction and activates T cells
Authors: Smriti Gurung, Fatima Khan, Soo-Woong Lee, Jaewon Yoon, Byungheon Lee
Journal: Cancer Research (2018)

Abstract Immune suppressive mechanism within the tumor microenvironment inhibits antitumor T cell function, leading to evasion of tumor from immune attack. One of the mechanisms is the up-regulation of programmed death-ligand 1 (PD-L1) expression on tumor cells which binds to programmed cell death protein 1 (PD-1) on activated T cells and inhibits T cell functions. Inhibiting the PD-L1/PD-1 interaction could reverse the tumor microenvironment and enhance the endogenous antitumor immune response. To identify a novel peptide that selectively binds to PD-L1, we screened a phage-displayed peptide library against cells transiently expressing PD-L1 at high levels. After multiple rounds of screening, selected phage clones were sequenced. Of these, two phage clones showed more selective binding to cells expressing PD-L1 compared to a control clone. The peptides displayed on the clones were synthesized for further study and named as PD-L1Pep-1 (9mer) and PD-L1Pep-2 (7mer). Fluorescein-conjugated PD-L1Pep-1 and PD-L1Pep-2 selectively bound to cells highly expressing PD-L1, whereas only negligible binding to cells expressing PD-L1 at low levels. The cell binding of the PD-L1-binding peptides was enhanced after treatment of cells with interferon-γ which is a potent inducer of PD-L1 in many types of cancer cells. FACS analysis showed that the pre-treatment of cells with an anti-PD-L1 antibody competed and reduced the cell binding of the PD-L1-binding peptides, suggesting the antibody and peptides bind to the same epitope on PD-L1. Co-culture experiments of CT26 mouse colon tumor cells with primary T cells isolated from a mouse spleen showed that, similar to the anti-PD-L1 antibody, the PD-L1-binding peptides increased the secretion of Interleukin-2 and interferon-γ by the T cells, indicating that the PD-L1-binding peptides can reactivate the T cells that were suppressed by the co-cultured tumor cells. In-vivo fluorescence imaging of BALB/c mice bearing subcutaneously transplanted CT26 mouse colon tumor cells showed tumor targeting ability of the PD-L1-binding peptides to PD-L1-expressing tumor. These findings suggest that PD-L1Pep-1 and PD-L1Pep-2 can inhibit PD-L1/PD-1 interaction and activate T cells in vivo and hold a potential as a cancer immunotherapeutic. Keywords: Colon tumor, immunotherapy, PD-L1, peptide, phage display Citation Format: Smriti Gurung, Fatima Khan, Soo-Woong Lee, Jaewon Yoon, Byungheon Lee. PD-L1 binding peptide identified by phage peptide display inhibits PD-1/PD-L1 interaction and activates T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1000.
Calreticulin Destabilizes Glucose Transporter-1 mRNA in Vascular Endothelial and Smooth Muscle Cells Under High-Glucose Conditions
Authors: HanaTotary-Jain, TallyNaveh-Many, YaelRiahi, NuritKaiser, JürgenEckel, ShlomoSasson
Journal: Circulation Research (2005)

Substrate autoregulation of glucose transporter-1 (GLUT-1) mRNA and protein expression provides vascular endothelial and smooth muscle cells a sensitive mechanism to adapt their rate of glucose transport in response to changing glycemic conditions. Hyperglycemia-induced downregulation of glucose transport is particularly important in protecting these cells against an excessive influx of glucose and consequently increased intracellular protein glycation and generation of free radicals; both are detrimental in the development of vascular disease in diabetes. We aimed to investigate the molecular mechanism of high glucose–induced downregulation of GLUT-1 mRNA expression in primary bovine aortic vascular endothelial (VEC) and smooth muscle (VSMC) cell cultures. Using RNA mobility shift, UV cross-linking, and in vitro degradation assays, followed by mass-spectrometric analysis, we identified calreticulin as a specific destabilizing trans-acting factor that binds to a 10-nucleotide cis-acting element (CAE2181-2...
Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E–Knockout Mice
Authors: PetruLiuba, PäiviKarnani, ErkkiPesonen, IlariPaakkari, AndersForslid, LeifJohansson, KennethPersson, TorkelWadström, RicardoLaurini
Journal: Circulation (2000)

Background—Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E–knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation. Methods and Results—Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of NG-nitro-l-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P<0.05...
Abstract 4557: Dual targeting of innate and adaptive checkpoints on tumor cells limits immune evasion
Authors: Yang-Xin Fu, Xiaojuan Liu
Journal: Cancer Research (2018)

Abstract CD47 on tumors inhibits phagocytosis, while PD-L1 limits T cell-mediated tumor killing. However, whether and how these two pathways coordinately evade immune responses are poorly understood. We reveal that both CD47 and PD-L1 on tumors coordinately evade innate and adaptive sensing. Targeted blockade of CD47 and PD-L1 on tumor cells with bispecific anti-PDL1-SIRPα showed better therapeutic efficacy than single blockades with reduced off-tumor targeting. Mechanistically, the dual-targeting approach significantly enhanced DNA sensing in dendritic cells (DC), DC cross-presentation and anti-tumor T cell response. Our data indicate that tumor cells evolve to utilize two-levels of checkpoints to evade anti-tumor immune responses, and tumor cell-specific dual-targeting of both innate and adaptive checkpoints represents a new strategy for increasing efficacy and reducing toxicity. Citation Format: Yang-Xin Fu, Xiaojuan Liu. Dual targeting of innate and adaptive checkpoints on tumor cells limits immune evasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4557.
Intracoronary Injection of Bone Marrow–Derived Mononuclear Cells Early or Late After Acute Myocardial Infarction
Authors: Daniel Sürder, Robert Manka, Viviana Lo Cicero, Tiziano Moccetti, Kaspar Rufibach, Sabrina Soncin, Lucia Turchetto, Marina Radrizzani, Giuseppe Astori, Juerg Schwitter, Paul Erne, Michel Zuber, Christoph Auf der Maur, Peiman Jamshidi, Oliver Gaemperli, Stephan Windecker, Aris Moschovitis, Andreas Wahl, Ines Bühler, Christophe Wyss, Sebastian Kozerke, Ulf Landmesser, Thomas F. Lüscher, Roberto Corti
Journal: Circulation (2013)

Background— Intracoronary administration of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. Methods and Results— In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD; P =0.74 versus baseline) in the control group, 1.8±8.4% ( P =0.12 versus baseline) in the early group, and 0.8±7.6% ( P =0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, −1.83 to 4.32; P =0.42) for the early therapy group and 0.55 (95% confidence interval, −2.61 to 3.71; P =0.73) for the late therapy group. Conclusions— Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00355186.
Abstract 3427: Gatekeeper inactivation drives glioma progression into secondary glioblastoma
Authors: Kirsi Johanna Granberg, Matti Annala, Serafiina Jaatinen, Joonas Haapasalo, Olli Yli-Harja, Hannu Haapasalo, Wei Zhang, Matti Nykter
Journal: Cancer Research (2018)

Abstract &amp;lt;Glioblastoma (GBM) is the most common and lethal form of brain cancer in humans. Median survival is 15 months with best available treatment. Most GBMs arise de novo (primary GBM), but 5 - 10% progress from lower grade gliomas (secondary GBM). As progression of low grade glioma into secondary GBM significantly impacts prognosis, a better understanding of this process is paramount for treatment and monitoring of affected patients. In this study, we applied whole genome and transcriptome sequencing to primary glioma and relapsed secondary GBM tissue from seven patients with progression. All primary gliomas carried IDH1 mutations, and in all cases the mutation was inherited by the secondary GBM. ATRX alterations in all five astrocytomas and TERT promoter mutations in both 1p19q-codeleted oligoastrocytomas were also inherited in progressed tumors. In five patients, progression was associated with increased genomic instability, whereas mutation load was significantly increased in two other patients. One of them exhibited a hypermutation signature caused by a mutation in the proofreading domain of DNA polymerase epsilon, while the second had lost both copies of the DNA mismatch protein MSH2. In addition, both 1p19q-codeleted tumors had acquired focal inactivating deletions of the protein tyrosine phosphatase PTPRD at progression, suggesting a novel driver mechanism for GBM progression. The most common progression-related genomic alterations were CDKN2A deletions, TP53 mutations, RB1 deletions, PTEN deletions, and deletions of genes crucial to the double strand break repair pathway. Taken together, progression into secondary GBM was significantly related to deletions in tumor suppressor genes as well as TP53 mutations. Disruption of these gatekeepers appears to be a significant mechanism for glioma progression.&amp;gt; Citation Format: Kirsi Johanna Granberg, Matti Annala, Serafiina Jaatinen, Joonas Haapasalo, Olli Yli-Harja, Hannu Haapasalo, Wei Zhang, Matti Nykter. Gatekeeper inactivation drives glioma progression into secondary glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3427.
Abstract 039: Adherence to a Healthy Lifestyle in Relation to Cardiovascular Disease Incidence and Mortality Among Adults With Type 2 Diabetes
Authors: Gang Liu, Yanping Li, Yang Hu, Geng Zong, Shanshan Li, Eric B Rimm, Frank B Hu, JoAnn E Manson, Kathryn M Rexrode, Hyun Joon Shin, Qi Sun
Journal: Circulation (2018)

Objective: To examine the associations of individual and combined low-risk lifestyle practices, including non-smoking, engaging in moderate to vigorous intensity physical activity (≥150 min/week), drinking alcohol in moderation (5-15 g/day for women and 5-30 g/day for men), and eating a high quality diet (top two fifths of Alternative Healthy Eating Index), with the risk of subsequent cardiovascular events among adults with incident diabetes. Methods: The prospective study included 11,527 participants with diabetes diagnosed during follow-up (8,970 women from the Nurses’ Health Study and 2,557 men from the Health Professionals Follow-Up Study), who were free of cardiovascular disease (CVD) and cancer at the time of diabetes diagnosis. Diet and lifestyle factors after diabetes diagnosis were repeatedly assessed every 2-4 years. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of total CVD, coronary heart disease (CHD), and stroke incidence, and CVD mortality. Results: There were 2,311 incident CVD cases (including 498 stroke cases) and 858 CVD deaths during an average of 13.3 years of follow-up. After multivariate adjustment including medication use, the individual low-risk lifestyle factors after diabetes diagnosis were each significantly associated with a lower risk of CVD incidence and mortality. The multivariate-adjusted HR (95% CI) for participants with three or more low-risk lifestyle factors compared with zero was 0.48 (0.40-0.59) for total CVD incidence, 0.53 (0.42-0.66) for CHD incidence, 0.33 (0.21-0.51) for stroke incidence, and 0.32 (0.22-0.47) for CVD mortality (all P trend&lt;0.001). The population-attributable-risk for poor adherence to low-risk lifestyle was 42.6% (26.7%-55.1%) for CVD mortality. In addition, greater improvements in lifestyle factors from pre- to post-diabetes diagnosis were also significantly associated with a lower risk of CVD incidence and mortality. For per one number increment in low-risk lifestyle factors, there was a 16% reduced risk of incident total CVD, a 12% reduced risk of CHD, a 21% reduced risk of stroke, and a 30% reduced risk of CVD mortality (all P &lt;0.001). Similar results were observed when analyses were stratified by diabetes duration, sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle factors before diabetes diagnosis. Conclusions: Greater adherence to an overall healthy lifestyle is associated with a substantially lower risk of CVD incidence and mortality among adults with type 2 diabetes. These findings further support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in diabetic patients.
α-Adrenergic Control of Volume-Regulated Cl− Currents in Rabbit Atrial Myocytes
Authors: DayueDuan, BernardFermini, StanleyNattel
Journal: Circulation Research (1995)

Abstract α-Adrenergic stimulation is known to play a role in cardiac arrhythmogenesis and to modulate a variety of cardiac K+ currents. The effects of α-adrenergic stimulation on Cl− currents are largely unknown. Many cardiac cell types show a volume-sensitive Cl− current induced by cell swelling (ICl.swell). The present experiments were designed to assess the potential α-adrenergic modulation of ICl.swell in rabbit atrial myocytes. ICl.swell was induced with the use of a hypotonic superfusate, under conditions designed to prevent currents carried by K+, Na+, and Ca2+ ions. A basal Cl− current (ICl.b) was observed under isotonic conditions in 128 of 150 cells (85%), had the same dependency on [Cl−]o as ICl.swell, and was reduced by cell shrinkage induced by hypertonic superfusion, suggesting that ICl.b is carried by the same volume-sensitive Cl− conductance as ICl.swell. Phenylephrine produced a concentration-dependent and near-complete inhibition of ICl.b and ICl.swell, with EC50 values of 86±5 and 72±7 ...
Abstract B27: Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy
Authors: Emily Z. Keung, Jen-Wei Tsai, Ali M. Ali, Janice N. Cormier, Andrew J. Bishop, B. Ashleigh Guadagnolo, Kelly K. Hunt, Keila E. Torres, Neeta Somaiah, Jennifer A. Wargo, Alexander Lazar, Wei-Lien Wang, Cristina L. Roland
Journal: Clinical Cancer Research (2018)

Abstract Introduction: Undifferentiated pleomorphic sarcoma of the extremity and trunk (ET UPS) presents a unique diagnostic and therapeutic challenge. Recently, immunotherapy has been employed in the treatment of patients with advanced UPS with preliminary evidence of benefit in 40% of a small initial cohort (SARC028). However, there is currently a paucity of data characterizing the immune infiltrate population in ET UPS. Radiotherapy (RT) is associated with improved locoregional control in combination with surgery. Localized RT has been shown in other tumor types to promote tumor antigen release and enhance tumor-specific targeting by the adaptive immune system. The aim of this study was two-fold: 1) to characterize the immune infiltrate in ET UPS and 2) to evaluate the effect of preoperative RT on immune cell infiltrates in ET UPS. Methods: We identified 17 matched ET UPS tumor samples before and after RT. Immunohistochemistry for CD8, CD4, PD-L1, PD1, CD3, CD163, and FOXP3 was performed on the matched pairs. Changes in immune infiltrate over time between the pairs were compared with a paired t-test. Results: CD8, CD4, PD-L1, PD1, CD3, CD163, and FoxP3 positive cells were identified in all samples. The effects were variable, but there was an overall trend towards an increase in the density of tumor-infiltrating immune cells of all assayed types in ET UPS following completion of RT, with increases in the median number of CD8 (55 vs. 111 cells/mm2, p=0.17), CD4 (3 vs. 13 cells/mm2, p=0.01), CD3 (158 vs. 219 cells/mm2, p=0.06), CD163 (1363 vs. 2001 cells/mm2, p=0.76), and FOXP3 (14 vs. 25 cells/mm2, p=0.23) positive cells in RT-treated tumor sections. Interestingly, although PD-L1 was not expressed in any pre-RT ET UPS tumors, positive PD-L1 expression was observed in 21% (3/14) of tumors after RT treatment (p=0.07). Conclusion: An immune infiltrate is present in ET UPS at the time of diagnosis, with a trend towards increased density of immune infiltrate and PD-L1 expression after completion of RT. These data support evaluating immune checkpoint inhibitors with standard of care RT in the treatment of ET UPS. Citation Format: Emily Z. Keung, Jen-Wei Tsai, Ali M. Ali, Janice N. Cormier, Andrew J. Bishop, B. Ashleigh Guadagnolo, Kelly K. Hunt, Keila E. Torres, Neeta Somaiah, Jennifer A. Wargo, Alexander Lazar, Wei-Lien Wang, Cristina L. Roland. Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B27.