bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Sildenafil Citrate on Exercise Capacity in Athletes With Spinal Cord Injury
Authors: Perret Claudio , Van Biesen Debbie , Strupler Matthias , Pit-Grosheide Pia , Vanlandewijck Yves 
Published: March 2020

Purpose: Ingestion of sildenafil citrate has performance-enhancing effects at high altitudes above 3800 m in able-bodied individuals. It is unknown whether it can improve the performance of athletes with spinal cord injury (SCI) at moderate altitudes (<2200 m), relevant to Paralympic competitions. As most men with SCI suffer from erectile dysfunction of neurologic origin and use sildenafil on a regular basis, it seems important to study the impact of sildenafil on exercise capacity. The outcome of this study is also relevant to the antidoping community. Methods: Twenty-seven healthy male wheelchair athletes with a motor-complete SCI participated in this prospective double-blind, randomized, placebo-controlled study. The participants performed arm cranking exercise to exhaustion at sea level and moderate altitude (2200 m) after ingestion of 50 mg sildenafil citrate or a placebo. Peak power output, peak oxygen uptake, peak heart rate, rating of perceived exertion, oxygen saturation, and lactate concentrations at exhaustion were measured. Results: Friedman analysis showed that peak power output at sea level was significantly higher (P = .004) under placebo treatment (median [minimum; maximum]: 120 W [35; 170]) compared with sildenafil (115 W [40; 165]). Blood oxygen saturation under sildenafil treatment at sea level (98% [81; 100]) was significantly higher (P = .006) compared with sildenafil treatment at moderate altitude (94% [85; 100]). All other parameters revealed no impact of sildenafil or altitude. Conclusions: In this study, the ingestion of sildenafil citrate in athletes with SCI demonstrated no positive effects on peak arm-cranking-exercise capacity compared with placebo either at sea level or at moderate altitude.
Determination of Submaximal and Maximal Training Zones From a 3-Stage, Variable-Duration, Perceptually Regulated Track Test
Authors: Molinari Claire A. , Palacin Florent , Poinsard Luc , Billat Véronique L. 
Published: March 2020

Purpose: To validate a new perceptually regulated, self-paced maximal oxygen consumption field test (the Running Advisor Billat Training [RABIT] test) that can be used by recreational runners to define personalized training zones. Design: In a cross-sectional study, male and female recreational runners (N = 12; mean [SD] age = 43 [8] y) completed 3 maximal exercise tests (2 RABIT tests and a University of Montreal Track Test), with a 48-hour interval between tests. Methods: The University of Montreal Track Test was a continuous, incremental track test with a 0.5-km·h−1 increment every minute until exhaustion. The RABIT tests were conducted at intensities of 11, 14, and 17 on the rating of perceived exertion (RPE) scale for 10, 5, and 3 minutes, respectively, with a 1-minute rest between efforts. Results: The 2 RABIT tests and the University of Montreal Track Test gave similar mean (SD) maximal oxygen consumption values (53.9 [6.4], 56.4 [9.1], and 55.4 [7.6] mL·kg−1·min−1, respectively, P = .722). The cardiorespiratory and speed responses were reliable as a function of the running intensity (RPE: 11, 14, and 17) and the relative time point for each RPE stage. Indeed, the oxygen consumption, heart rate, ventilation, and speed values did not differ significantly when the running time was expressed as a relative duration of 30%, 60%, or 90% (ie, at 3, 6, and 9 min of a 10-min effort at RPE 11; P = .997). Conclusions: The results demonstrate that the RABIT test is a valid method for defining submaximal and maximal training zones in recreational runners.
Has working-age morbidity been declining? Changes over time in survey measures of general health, chronic diseases, symptoms and biomarkers in England 1994–2014
Authors: Geiger Ben Baumberg 
Published: March 2020

ObjectivesAs life expectancy has increased in high-income countries, there has been a global debate about whether additional years of life are free from ill-health/disability. However, little attention has been given to changes over time in morbidity in theworking-agepopulation, particularly outside the USA, despite its importance for health monitoring and social policy. This study therefore asks: what are the changes over time in working-age morbidity in England over two decades?Design, setting and participantsWe use a high-quality annual cross-sectional survey, the Health Survey for England (HSE) 1994–2014. HSE uses a random sample of the English household population, with a combined sample size of over 140 000 people. We produce a newly harmonised version of HSE that maximises comparability over time, including new non-response weights. While HSE is used for monitoring population health, it has hitherto not used for investigating morbidity as a whole.Outcome measuresWe analyse all 39 measures that are fully comparable over time—including chronic disease diagnoses, symptomatology and a number of biomarkers—adjusting for gender and age.ResultsWe find a mixed picture: we see improving cardiovascular and respiratory health, but deteriorations in obesity, diabetes, some biomarkers and feelings of extreme anxiety/depression, alongside stability in moderate mental ill-health and musculoskeletal-related health. In several domains we also see stable or rising chronic diseasediagnoseseven wheresymptomatologyhas declined. While data limitations make it challenging to combine these measures into a single morbidity index, there is little systematic trend for declining morbidity to be seen in the measures that predict self-reported health most strongly.ConclusionsDespite considerable falls in working-age mortality—and the assumptions of many policy-makers that morbidity will follow mortality – there is no systematic improvement in overall working-age morbidity in England from 1994 to 2014.
Pediatric Adenotonsillectomy Trial for Snoring (PATS): protocol for a randomised controlled trial to evaluate the effect of adenotonsillectomy in treating mild obstructive sleep-disordered breathing
Authors: Wang Rui , Bakker Jessie P. , Chervin Ronald D. , Garetz Susan L. , Hassan Fauziya , Ishman Stacey L. , Mitchell Ron B. , Morrical Michael G. , Naqvi Syed K. , Radcliffe Jerilynn , Riggan Emily I. , Rosen Carol L. , Ross Kristie , Rueschman Michael , Tapia Ignacio E. , Taylor H. Gerry , Zopf David A. , Redline Susan 
Published: March 2020

IntroductionMild obstructive sleep-disordered breathing (oSDB), characterised by habitual snoring without frequent apnoeas and hypopnoeas on polysomnography, is prevalent in children and commonly treated with adenotonsillectomy (AT). However, the absence of high-level evidence addressing the role of AT in improving health and behavioural outcomes has contributed to significant geographical variations in care and potential for surgery to be both overused and underused.Methods and analysisThe Pediatric Adenotonsillectomy Trial for Snoring (PATS) is a single-blinded, multicentre randomised controlled trial designed to evaluate the effect of AT in treating mild oSDB. Four hundred sixty eligible children, aged 3.0–12.9 years old, will be randomised to either early adenotonsillectomy or to watchful waiting with supportive care (WWSC) with a 1:1 ratio. The study’s coprimary endpoints are (1) change from baseline in executive behaviour relating to self-regulation and organisation skills as measured by the Behavioural Rating Inventory of Executive Function (BRIEF) Global Composite Score (GEC); and (2) change from baseline in vigilance as measured on the Go-No-Go (GNG) signal detection parameter (d-prime). A mixed effects model will be used to compare changes in the BRIEF GEC score and GNG score at 6 and 12 months from baseline between the AT arm and the WWSC arm.Ethics and disseminationThe study protocol was approved by the institutional review board (IRB) at Children’s Hospital of Philadelphia (CHOP) on 3 October 2014 (14–0 11 214). The approval of CHOP as the central IRB of record was granted on 29 February 2016. The results will be published in peer-reviewed journals and presented at academic conferences. The data collected from the PATS study will be deposited in a repository (National Sleep Research Resource, sleepdata.org) after completion of the study to maximise use by the scientific community.Trial registration numberNCT02562040; Pre-results.
Predicting the development of psychological morbidity in inflammatory bowel disease: a systematic review
Authors: Hoogkamer Anna B , Brooks Alenka J , Rowse Georgina , Lobo Alan J 
Published: March 2020

BackgroundPsychological morbidity in inflammatory bowel disease is common with significant impact on quality of life and health outcomes, but factors which predict the development of psychological morbidity are unclear.AimTo undertake a systematic literature review of the predictors of psychological morbidity in patients with inflammatory bowel disease.MethodsElectronic searches for English-language articles were performed with keywords relating to psychological morbidity according to the Diagnostic and Statistical Manual of Mental Disorders IV and subsequent criteria, and inflammatory bowel disease; in MEDLINE, PsychInfo, Web of Science and EMBASE for studies published from January 1997 to 25 January 2019.ResultsOf 660 studies identified, seven met the inclusion criteria. All measured depression, with three also measuring anxiety. Follow-up duration was variable (median of 18 months range 6–96 months). Risk factors identified for development of psychological morbidity included physical factors: aggressive disease (HR 5.77, 95% CI 1.89 to 17.7) and greater comorbidity burden (OR 4.31, 95% CI 2.83 to 6.57) and psychological risk factors: degree of gratitude (r=−0.43, p<0.01) and parenting stress (R-change=0.03, F(1,58)=35.6, p<0.05). Age-specific risk was identified with young people (13–17 years) at increased risk.ConclusionsIdentifiable risks for the development of psychological morbidity in inflammatory bowel disease include physical and psychological factors. Further research is required from large prospective studies to enable early interventions in those at risk and reduce the impact of psychological morbidity.
Lifestyle modification in older versus younger patients with coronary artery disease
Authors: Jepma Patricia , Jorstad Harald T , Snaterse Marjolein , ter Riet Gerben , Kragten Hans , Lachman Sangeeta , Minneboo Madelon , Boekholdt S Matthijs , Peters Ron J , Scholte op Reimer Wilma 
Published: March 2020

ObjectiveTo compare the treatment effect on lifestyle-related risk factors (LRFs) in older (≥65 years) versus younger (<65 years) patients with coronary artery disease (CAD) in The Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists 2 (RESPONSE-2) trial.MethodsThe RESPONSE-2 trial was a community-based lifestyle intervention trial (n=824) comparing nurse-coordinated referral with a comprehensive set of three lifestyle interventions (physical activity, weight reduction and/or smoking cessation) to usual care. In the current analysis, our primary outcome was the proportion of patients with improvement at 12 months follow-up (n=711) in ≥1 LRF stratified by age.ResultsAt baseline, older patients (n=245, mean age 69.2±3.9 years) had more adverse cardiovascular risk profiles and comorbidities than younger patients (n=579, mean age 53.7±6.6 years). There was no significant variation on the treatment effect according to age (p value treatment by age=0.45, OR 1.67, 95% CI 1.22 to 2.31). However, older patients were more likely to achieve ≥5% weight loss (OR old 5.58, 95% CI 2.77 to 11.26 vs OR young 1.57, 95% CI 0.98 to 2.49, p=0.003) and younger patients were more likely to show non-improved LRFs (OR old 0.38, 95% CI 0.22 to 0.67 vs OR young 0.88, 95% CI 0.61 to 1.26, p=0.01).ConclusionDespite more adverse cardiovascular risk profiles and comorbidities among older patients, nurse-coordinated referral to a community-based lifestyle intervention was at least as successful in improving LRFs in older as in younger patients. Higher age alone should not be a reason to withhold lifestyle interventions in patients with CAD.
Cardiovascular magnetic resonance T2* mapping for the assessment of cardiovascular events in hypertrophic cardiomyopathy
Authors: Gastl Mareike , Gruner Christiane , Labucay Karin , Gotschy Alexander , Von Spiczak Jochen , Polacin Malgorzata , Boenner Florian , Kelm Malte , Ruschitzka Frank , Alkadhi Hatem , Kozerke Sebastian , Manka Robert 
Published: March 2020

BackgroundHypertrophic cardiomyopathy (HCM) is associated with an increased risk of adverse cardiac events. Beyond classic risk factors, relative myocardial ischaemia and succeeding myocardial alterations, which can be detected using either contrast agents or parametric mapping in cardiovascular magnetic resonance (CMR) imaging, have shown an impact on outcome in HCM. CMR may help to risk stratify using parametric T2* mapping. Therefore, the aim of the present study was to evaluate the association of T2* values or fibrosis with cardiovascular events in HCM.MethodsThe relationship between T2* with supraventricular, ventricular arrhythmia or heart failure was retrospectively assessed in 91 patients with HCM referred for CMR on a 1.5T MR imaging system. Fibrosis as a reference was added to the model. Patients were subdivided into groups according to T2* value quartiles.Results47 patients experienced an event of ventricular arrhythmia, 25 of atrial fibrillation/flutter and 17 of heart failure. T2*≤28.7 ms yielded no association with ventricular events in the whole HCM cohort. T2* of non-obstructive HCM showed a significant association with ventricular events in univariate analysis, but not in multivariate analysis. For the combined endpoint of arrhythmic events, there was already an association for the whole HCM cohort, but again only in univariate analyses. Fibrosis stayed the strongest predictor in all analyses. There was no association for T2* and fibrosis with heart failure.ConclusionsDecreased T2* values by CMR only provide a small association with arrhythmic events in HCM, especially in non-obstructive HCM. No information is added for heart failure.
Effect of different size of PbWO4particles on EPDM composite for gamma-ray shielding
Authors: Fan Jinghui , Wu Juying , Ma Yan 
Published: March 2020

Ethylene Propylene Diene Monomer (EPDM) composites filled with 0–400 phr [Formula: see text] (PWO) were prepared by conventional process using a two-roll mill. Surface treatment of the fillers coated with KH570 was conducted to enhance the wettability and lubrication of fillers in the polymer matrix. According to SEM images and mechanical test, both micro- and submicro-fillers disperse homogeneously in the matrix, and adhesion of submicro-fillers to the matrix is stronger than that of micro-fillers. The submicro-PWO composites had better tensile strength and elongation at break than those composites containing micro-PWO powder, but a relatively higher hardness. The photon shielding test was performed to determine the radiation shielding properties of these composites, which showed that attenuation of gamma-rays for the submicro-PWO composites was substantially enhanced compared to micro-PWO reinforced composites.
miR-524-5p inhibits angiogenesis through targeting WNK1 in colon cancer cells
Authors: Li Xiang , Li Zitao , Zhu Ye , Li Zhu , Yao Lihong , Zhang Lamei , Yuan Lin , Shang Yang , Liu Jianting , Li Caijuan 
Published: March 2020

There is increasing evidence that microRNA (miRNA) abnormity is involved in the occurrence and the development of various malignancies, including colon cancer. MiRNA-524–5p has been reported to possess anticancer activity in various tumors, which function is seldom investigated in colon cancer cells. The aim of this study was to explore the effect of the miRNA-524–5p/with-no-lysine kinase 1 (WNK1) system on angiogenesis in a colon cancer cell line (HT-29 and COLO205 cells) and further investigate the potential mechanisms. We found miRNA-524–5p expression was relatively high in COLO205 cells and relatively low in HT-29 cells. Elevating miRNA-524–5p expression inhibited proliferation, induced cycle arrest, diminished vascular endothelial growth factor production, and thereby suppressed angiogenesis in HT-29 cells. WNK1 silencing exerted the ability of antiangiogenesis in HT-29 cells. Besides, miRNA-524–5p deficiency-induced angiogenesis was impeded by WNK1 silence in COLO205 cells. In a murine tumor model, miRNA-524–5p agomir treatment significantly suppressed colon cancer tumorigenicity with the downregulation of WNK1 expression. In summary, our results indicated that miRNA-524–5p inhibited angiogenesis in colon cancer cells via targeting WNK1. NEW & NOTEWORTHY MiRNA-524–5p inhibited angiogenesis in colon cancer cells via targeting with-no-lysine kinase 1.
GPD1 Enhances the Anticancer Effects of Metformin by Synergistically Increasing Total Cellular Glycerol-3-Phosphate
Authors: Xie Jianjiang , Ye Jianheng , Cai Zhiduan , Luo Yong , Zhu Xuejin , Deng Yulin , Feng Yuanfa , Liang Yingke , Liu Ren , Han Zhaodong , Liang Yuxiang , Zheng Yu , Mo Rujun , Zhuo Yangjia , Wu Yongding , Jiang Funeng , Zhu Jianguo , Wu Chin-Lee , Zhong Weide 
Published: March 2020

Abstract

Metformin is an oral drug widely used for the treatment of type 2 diabetes mellitus. Numerous studies have demonstrated the value of metformin in cancer treatment. However, for metformin to elicit effects on cancer often requires a high dosage, and any underlying mechanism for how to improve its inhibitory effects remains unknown. Here, we found that low mRNA expression of glycerol-3-phosphate dehydrogenase 1 (GPD1) may predict a poor response to metformin treatment in 15 cancer cell lines. In vitro and in vivo, metformin treatment alone significantly suppressed cancer cell proliferation, a phenotype enhanced by GPD1 overexpression. Total cellular glycerol-3-phosphate concentration was significantly increased by the combination of GPD1 overexpression and metformin treatment, which suppressed cancer growth via inhibition of mitochondrial function. Eventually, increased reactive oxygen species and mitochondrial structural damage was observed in GPD1-overexpressing cell lines treated with metformin, which may contribute to cell death. In summary, this study demonstrates that GPD1 overexpression enhances the anticancer activity of metformin and that patients with increased GPD1 expression in tumor cells may respond better to metformin therapy.

Significance:
GPD1 overexpression enhances the anticancer effect of metformin through synergistic inhibition of mitochondrial function, thereby providing new insight into metformin-mediated cancer therapy.
A Feed-Forward Mechanosignaling Loop Confers Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutant Melanoma
Authors: Girard Christophe A. , Lecacheur Margaux , Ben Jouira Rania , Berestjuk Ilona , Diazzi Serena , Prod'homme Virginie , Mallavialle Aude , Larbret Frédéric , Gesson Maéva , Schaub Sébastien , Pisano Sabrina , Audebert Stéphane , Mari Bernard , Gaggioli Cédric , Leucci Eleonora , Marine Jean-Christophe , Deckert Marcel , Tartare-Deckert Sophie 
Published: March 2020

Abstract

Aberrant extracellular matrix (ECM) deposition and stiffening is a physical hallmark of several solid cancers and is associated with therapy failure. BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that is frequently associated with transcriptional reprogramming and a de-differentiated cell state. Melanoma cells secrete their own ECM proteins, an event that is promoted by oncogenic BRAF inhibition. Yet, the contribution of cancer cell–derived ECM and tumor mechanics to drug adaptation and therapy resistance remains poorly understood. Here, we show that melanoma cells can adapt to targeted therapies through a mechanosignaling loop involving the autocrine remodeling of a drug-protective ECM. Analyses revealed that therapy-resistant cells associated with a mesenchymal dedifferentiated state displayed elevated responsiveness to collagen stiffening and force-mediated ECM remodeling through activation of actin-dependent mechanosensors Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF). Short-term inhibition of MAPK pathway also induced mechanosignaling associated with deposition and remodeling of an aligned fibrillar matrix. This provided a favored ECM reorganization that promoted tolerance to BRAF inhibition in a YAP- and MRTF-dependent manner. Matrix remodeling and tumor stiffening were also observed in vivo upon exposure of BRAF-mutant melanoma cell lines or patient-derived xenograft models to MAPK pathway inhibition. Importantly, pharmacologic targeting of YAP reversed treatment-induced excessive collagen deposition, leading to enhancement of BRAF inhibitor efficacy. We conclude that MAPK pathway targeting therapies mechanically reprogram melanoma cells to confer a drug-protective matrix environment. Preventing melanoma cell mechanical reprogramming might be a promising therapeutic strategy for patients on targeted therapies.

Significance:
These findings reveal a biomechanical adaptation of melanoma cells to oncogenic BRAF pathway inhibition, which fuels a YAP/MRTF-dependent feed-forward loop associated with tumor stiffening, mechanosensing, and therapy resistance.
Associations Between Long‐Term Fine Particulate Matter Exposure and Mortality in Heart Failure Patients
Authors: Ward‐Caviness Cavin K. , Weaver Anne M. , Buranosky Matthew , Pfaff Emily R. , Neas Lucas M. , Devlin Robert B. , Schwartz Joel , Di Qian , Cascio Wayne E. , Diaz‐Sanchez David 
Published: March 2020

Background

Environmental health risks for individuals with heart failure (
HF
) have been inadequately studied, as these individuals are not well represented in traditional cohort studies. To address this we studied associations between long‐term air pollution exposure and mortality in
HF
patients.

Methods and Results

The study population was a hospital‐based cohort of individuals diagnosed with
HF
between July 1, 2004 and December 31, 2016 compiled using electronic health records. Individuals were followed from 1 year after initial diagnosis until death or the end of the observation period (December 31, 2016). We used Cox proportional hazards models to evaluate the association of annual average fine particulate matter (
PM
2.5
) exposure at the time of initial
HF
diagnosis with all‐cause mortality, adjusted for age, race, sex, distance to the nearest air pollution monitor, and socioeconomic status indicators. Among 23 302
HF
patients, a 1 μg/m
3
increase in annual average
PM
2.5
was associated with an elevated risk of all‐cause mortality (hazard ratio 1.13; 95% CI, 1.10–1.15). As compared with people with exposures below the current national
PM
2.5
exposure standard (12 μg/m
3
), those with elevated exposures experienced 0.84 (95% CI, 0.73–0.95) years of life lost over a 5‐year period, an observation that persisted even for those residing in areas with
PM
2.5
concentrations below current standards.

Conclusions

Residential exposure to elevated concentrations of
PM
2.5
is a significant mortality risk factor for
HF
patients. Elevated
PM
2.5
exposures result in substantial years of life lost even at concentrations below current national standards.