bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent and joint effects of sedentary time and cardiorespiratory fitness on all-cause mortality: the Cooper Center Longitudinal Study
Authors: Shuval Kerem , Finley Carrie E , Barlow Carolyn E , Nguyen Binh T , Njike Valentine Y , Pettee Gabriel Kelley 
Published: November 2015

ObjectivesTo examine the independent and joint effects of sedentary time and cardiorespiratory fitness (fitness) on all-cause mortality.Design, setting, participantsA prospective study of 3141 Cooper Center Longitudinal Study participants. Participants provided information on television (TV) viewing and car time in 1982 and completed a maximal exercise test during a 1-year time frame; they were then followed until mortality or through 2010. TV viewing, car time, total sedentary time and fitness were the primary exposures and all-cause mortality was the outcome. The relationship between the exposures and outcome was examined utilising Cox proportional hazard models.ResultsA total of 581 deaths occurred over a median follow-up period of 28.7 years (SD=4.4). At baseline, participants’ mean age was 45.0 years (SD=9.6), 86.5% were men and their mean body mass index was 24.6 (SD=3.0). Multivariable analyses revealed a significant linear relationship between increased fitness and lower mortality risk, even while adjusting for total sedentary time and covariates (p=0.02). The effects of total sedentary time on increased mortality risk did not quite reach statistical significance once fitness and covariates were adjusted for (p=0.05). When examining this relationship categorically, in comparison to the reference category (≤10 h/week), being sedentary for ≥23 h weekly increased mortality risk by 29% without controlling for fitness (HR=1.29, 95% CI 1.03 to 1.63); however, once fitness and covariates were taken into account this relationship did not reach statistical significance (HR=1.20, 95% CI 0.95 to 1.51). Moreover, spending >10 h in the car weekly significantly increased mortality risk by 27% in the fully adjusted model. The association between TV viewing and mortality was not significant.ConclusionsThe relationship between total sedentary time and higher mortality risk is less pronounced when fitness is taken into account. Increased car time, but not TV viewing, is significantly related to higher mortality risk, even when taking fitness into account, in this cohort.
Correlates of sport participation in adults with long-standing illness or disability
Authors: Heron Neil , Kee Frank , Cupples Margaret E , Tully Mark A 
Published: November 2015

BackgroundLittle is known about why people with a long-standing illness/disability are less likely to participate in sport than others. This study aimed to identify for the first time sport participation levels and their correlates among Northern Ireland (NI) adults who report a long-standing illness/disability.MethodUsing data collected in the Continuous Household Survey, an annual survey of a random sample of the NI population, during 2007–2011, we examined responses for the total sample, those with a long-term illness/disability and those with no long-term health issues. We conducted univariate binary regression analysis for the whole sample and for those with a long-standing illness or disability, using sport participation as the dependent variable, and then carried significant variables into a multivariate analysis.ResultsThe sample included 13 683 adults; 3550 (26%) reported a long-term illness or disability. Multivariate analysis showed that, for the total sample and for those with a long-standing illness or disability, sport participation correlated positively with being male, aged <56 years, having a household car/van, health being ‘fairly good’/‘good’ in the previous year, doing work and living in an urban location. Also, for those with a long-standing illness or disability, being single and less socioeconomically deprived correlated positively with sport participation.ConclusionsThe findings suggest that more focused efforts may promote sport participation for people with a long-standing illness or disability who are female, older, not working, living rurally, married/cohabiting, socioeconomically deprived and report having had poor health in the past year. Our findings should inform public health policy and help in developing initiatives to support sport participation and reduce health inequalities.
Cardiac systolic regional function and synchrony in endurance trained and untrained females
Authors: Hedman Kristofer , Tamás Éva , Bjarnegård Niclas , Brudin Lars , Nylander Eva 
Published: November 2015

BackgroundMost studies on cardiac function in athletes describe overall heart function in predominately male participants. We aimed to compare segmental, regional and overall myocardial function and synchrony in female endurance athletes (ATH) and in age-matched sedentary females (CON).MethodsIn 46 ATH and 48 CON, echocardiography was used to measure peak longitudinal systolic strain and myocardial velocities in 12 left ventricular (LV) and 2 right ventricular (RV) segments. Regional and overall systolic function were calculated together with four indices of dyssynchrony.ResultsThere were no differences in regional or overall LV systolic function between groups, or in any of the four dyssynchrony indices. Peak systolic velocity (s′) was higher in the RV of ATH than in CON (9.7±1.5 vs 8.7±1.5 cm/s, p=0.004), but not after indexing by cardiac length (p=0.331). Strain was similar in ATH and CON in 8 of 12 LV myocardial segments. In septum and anteroseptum, basal and mid-ventricular s′ was 6–7% and 17–19% higher in ATH than in CON (p<0.05), respectively, while s′ was 12% higher in CON in the basal LV lateral wall (p=0.013). After indexing by cardiac length, s′ was only higher in ATH in the mid-ventricular septum (p=0.041).ConclusionsWe found differences between trained and untrained females in segmental systolic myocardial function, but not in global measures of systolic function, including cardiac synchrony. These findings give new insights into cardiac adaptation to endurance training and could also be of use for sports cardiologists evaluating female athletes.
Previous injury as a risk factor for reinjury in rock climbing: a secondary analysis of data from a retrospective cross-sectional cohort survey of active rock climbers
Authors: Jones Gareth , Llewellyn David , Johnson Mark I 
Published: November 2015

BackgroundThe aim of this article is to report the findings of a secondary analysis of a previous injury study to consider previous injury as a risk factor for reinjury in rock climbing.MethodsWe completed a secondary analysis of 201 questionnaires that were gathered as part of a retrospective cross-sectional cohort survey that investigated the epidemiology of injuries in a representative sample of British rock climbers. Participants had actively engaged in rock climbing over the previous 12-month period and were recruited from six indoor climbing centres and five outdoor climbing venues (men n=163, mean±SD, age=35.2±11.8 years, participating in rock climbing=13.88+11.77 years; women n=38, mean±SD, age=35.1±10.7 years, participating in rock climbing=11.62+9.19 years).ResultsOf the 101 participants who sustained a previous injury, 36 were found to have sustained at least one reinjury. The total number of reinjuries was 82, with the average probability of sustaining at least one reinjury being 35.6% (95% CI 34.71% to 36.8%; p<0.001, McNemar's χ2test) with the relative risk of reinjury being 1.55 (95% CI 1.34 to 1.80). The fingers were the most common site of reinjury (12 participants, 26%; χ2=43.12, df=5, p<0.001).ConclusionsPrevious injury was found to be a significant risk factor for reinjury, particularly at the site of the fingers. Technical difficulty in bouldering and sport climbing behaviours were significantly associated with repetitive overuse reinjury. As participatory figures increase, so does the likelihood that a high proportion of climbers may sustain a reinjury of the upper extremity.
Reduction in cardiorespiratory fitness after lung resection is not related to the number of lung segments removed
Authors: Edvardsen Elisabeth , Anderssen Sigmund A , Borchsenius Fredrik , Skjønsberg Ole Henning 
Published: November 2015

AimTo evaluate the effect of lung cancer surgery on cardiorespiratory fitness (CRF), and to assess the agreement between the predicted postoperative (ppo) V̇O2peakand actually measured postoperative peak oxygen uptake (V̇O2peak).MethodsBefore and 4–6 weeks after lung cancer surgery, 70 patients (35 women) underwent measurements of pulmonary function and CRF via a cardiopulmonary exercise test. In addition, the 23 non-exercising patients underwent measurements after 6 months. The ppo V̇O2peakcalculated from the number of functional segments removed was compared with the actually measured postoperative values of V̇O2peakfor accuracy and precision.ResultsAfter surgery, the V̇O2peakdecreased from 23.9±5.8 to 19.2±5.5 mL/kg/min (−19.6±15.7%) (p<0.001). The breathing reserve increased by 5% (p=0.001); the oxygen saturation remained unchanged (p=0.30); the oxygen pulse decreased by −1.9 mL/beat (p<0.001); the haemoglobin concentration decreased by 0.7 g/dL (p=0.001). The oxygen pulse was the strongest predictor for change in V̇O2peak; adjusted linear squared: r2=0.77. Six months after surgery, the V̇O2peakremained unchanged (−3±15%, p=0.27). The ppo V̇O2peak(mL/kg/min) was 18.6±5.4, and the actually measured V̇O2peakwas 19.2±5.5 (p=0.24). However, the limits of agreement were large (CI −7.4 to 8.2). The segment method miscalculated the ppo V̇O2peakby more than ±10 and ±20% in 54% and 25% of the patients, respectively.ConclusionsThe reduction in V̇O2peakand lack of improvement 6 months after lung cancer surgery cannot be explained by the loss of functional lung tissue. Predicting postoperative V̇O2peakbased on the amount of lung tissue removed is not recommendable due to poor precision.Trial registration numberNCT01748981.
Health promotion activities of sports clubs and coaches, and health and health behaviours in youth participating in sports clubs: the Health Promoting Sports Club study
Authors: Kokko Sami , Selänne Harri , Alanko Lauri , Heinonen Olli J , Korpelainen Raija , Savonen Kai , Vasankari Tommi , Kannas Lasse , Kujala Urho M , Aira Tuula , Villberg Jari , Parkkari Jari 
Published: November 2015

IntroductionSports clubs form a potential setting for health promotion, but the research is limited. The aim of the Health Promoting Sports Club (HPSC) study was to elucidate the current health promotion activities of youth sports clubs and coaches, and to investigate the health behaviours and health status of youth participating in sports clubs compared to non-participants.Methods and analysisThe study design employs cross-sectional multilevel and multimethod research with aspirations to a prospective cohort study in the next phase. The setting-based variables at sports clubs and coaching levels, and health behaviour variables at the individual level, are investigated using surveys; and total levels of physical activity are assessed using objective accelerometer measurements. Health status variables will be measured by preparticipation screening. The health promotion activity of sports clubs (n=154) is evaluated by club officials (n=313) and coaches (n=281). Coaches and young athletes aged 14–16 (n=759) years evaluate the coaches’ health promotion activity. The survey of the adolescents’ health behaviours consist of two data sets—the first is on their health behaviours and the second is on musculoskeletal complaints and injuries. Data are collected via sports clubs (759 participants) and schools 1650 (665 participants and 983 non-participants). 591 (418 athletes and 173 non-athletes) youth, have already participated in preparticipation screening. Screening consists of detailed personal medical history, electrocardiography, flow-volume spirometry, basic laboratory analyses and health status screening, including posture, muscle balance, and static and dynamic postural control tests, conducted by sports and exercise medicine specialists.Ethics and disseminationThe HPSC study is carried out conforming with the declaration of Helsinki. Ethical approval was received from the Ethics Committee of Health Care District of Central Finland. The HPSC study is close-to-practice, which generates foundations for development work within youth sports clubs.
Validation of a free fall acrobatics intervention protocol to reduce neck loads during parachute opening shock
Authors: Westman Anton , Äng Björn O 
Published: November 2015

BackgroundElevated neck pain prevalence among skydivers is associated with exposure to repeated parachute opening shock (POS). A study is planned to evaluate a preventive free fall acrobatics intervention, but prior assessment of the protocol is necessary given the complex and safety-critical study environment.AimTo validate an intervention protocol to reduce POS neck loads.MethodsA protocol was developed based on observational data and theoretical calculations. Six experts rated each component of the protocol on a four-point Likert scale, regarding relevance, simplicity/feasibility and safety, and responded to open-ended questions. Two iterations were made, each followed by consensus panel protocol revisions. The content validity index (CVI) was used to quantify ratings. A measure of universal agreement (CVI/UA) was computed as the proportion of components that achieved a rating ≥3 by all raters. For safety, a high-sensitivity CVI/UA was computed with a rating of no <4 (highest score) as acceptable.ResultsCVI/UA for relevance increased from 0.80 in the first assessment to 1.00 in the second; for simplicity from 0.50 to 0.63; and for safety from 0.70 to 1.00. High-sensitivity CVI/UA for safety increased from 0.10 to 0.75. Responses to open-ended questions included safety concerns for free fall stability, altitude awareness and concerns over comprehensibility.ConclusionsThe proposed protocol has been improved in assessed relevance, simplicity and safety, and is considered validated for the start of the empirical trial. To what degree complex interventions should be preceded by open prevalidation is discussed.
Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis
Authors: Westerlind Helga , Mellander Marie-Rose , Bresso Francesca , Munch Andreas , Bonfiglio Ferdinando , Assadi Ghazaleh , Rafter Joseph , Hübenthal Matthias , Lieb Wolfgang , Källberg Henrik , Brynedal Boel , Padyukov Leonid , Halfvarson Jonas , Törkvist Leif , Bjork Jan , Andreasson Anna , Agreus Lars , Almer Sven , Miehlke Stephan , Madisch Ahmed , Ohlsson Bodil , Löfberg Robert , Hultcrantz Rolf , Franke Andre , D'Amato Mauro 
Published: November 2015

ObjectiveCollagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role.DesignThree independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin.ResultsForty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10−10for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10−11; OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis).ConclusionsHLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.
Research in progress—LungSEARCH: a randomised controlled trial of surveillance for the early detection of lung cancer in a high-risk group
Authors: Spiro Stephen G , Hackshaw Allan 
Published: November 2015

Low-dose CT screening for lung cancer is effective but expensive. Therefore, cheaper or more focused screening strategies may be required. LungSEARCH is a randomised prospective trial of 1568 high-risk individuals (ie, current or former moderate to heavy smokers with mild/moderate COPD) who undergo either annual sputum cytology/cytometry testing or no screening. Those with abnormal sputum then receive annual CT and fluorescent bronchoscopy for the remainder of 5 years, to identify early stage lung cancer. It is hoped that these simple initial tests could identify those requiring expensive CT scans, and the aim is to demonstrate a stage shift towards early stage cancers.Trial registration numbers ISRCTN: ISRCTN80745975, clinicaltrials.gov: NCT00512746.
Application of Evolutionary Principles to Cancer Therapy
Authors: Enriquez-Navas Pedro M. , Wojtkowiak Jonathan W. , Gatenby Robert A. 
Published: November 2015

Abstract
The dynamic cancer ecosystem, with its rich temporal and spatial diversity in environmental conditions and heritable cell phenotypes, is remarkably robust to therapeutic perturbations. Even when response to therapy is clinically complete, adaptive tumor strategies almost inevitably emerge and the tumor returns. Although evolution of resistance remains the proximate cause of death in most cancer patients, a recent analysis found that evolutionary terms were included in less than 1% of articles on the cancer treatment outcomes, and this has not changed in 30 years. Here, we review treatment methods that attempt to understand and exploit intratumoral evolution to prolong response to therapy. In general, we find that treating metastatic (i.e., noncurable) cancers using the traditional strategy aimed at killing the maximum number of tumor cells is evolutionarily unsound because, by eliminating all treatment-sensitive cells, it enables rapid proliferation of resistant populations—a well-known evolutionary phenomenon termed “competitive release.” Alternative strategies, such as adaptive therapy, “ersatzdroges,” and double-bind treatments, shift focus from eliminating tumor cells to evolution-based methods that suppress growth of resistant populations to maintain long-term control. Cancer Res; 75(22); 4675–80. ©2015 AACR.
A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells
Authors: Gullà Annamaria , Di Martino Maria Teresa , Gallo Cantafio Maria Eugenia , Morelli Eugenio , Amodio Nicola , Botta Cirino , Pitari Maria Rita , Lio Santo Giovanni , Britti Domenico , Stamato Maria Angelica , Hideshima Teru , Munshi Nikhil C. , Anderson Kenneth C. , Tagliaferri Pierosandro , Tassone Pierfrancesco 
Published: November 2015

Abstract
Purpose: The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma.
Experimental Design: Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan.
Results: miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of human bone marrow (BM) stromal cells. Decreased multiple myeloma cell growth induced by inhibition of miR-221/222 plus melphalan was associated with a marked upregulation of pro-apoptotic BBC3/PUMA protein, a miR-221/222 target, as well as with modulation of drug influx–efflux transporters SLC7A5/LAT1 and the ABC transporter ABCC1/MRP1. Finally, in vivo treatment of SCID/NOD mice bearing human melphalan-refractory multiple myeloma xenografts with systemic locked nucleic acid (LNA) inhibitors of miR-221 (LNA-i-miR-221) plus melphalan overcame drug resistance, evidenced by growth inhibition with significant antitumor effects together with modulation of PUMA and ABCC1 in tumors retrieved from treated mice.
Conclusions: Taken together, our findings provide the proof of concept that LNA-i-miR-221 can reverse melphalan resistance in preclinical models of multiple myeloma, providing the framework for clinical trials to overcome drug resistance, and improve patient outcome in multiple myeloma. Clin Cancer Res; 22(5); 1222–33. ©2015 AACR.
Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling
Authors: Wang Tao , Song Wen , Chen Yuan , Chen Ruibao , Liu Zhuo , Wu Licheng , Li Mingchao , Yang Jun , Wang Liang , Liu Jihong , Ye Zhangqun , Wang Chenguang , Chen Ke 
Published: November 2015

Abstract
Purpose: Flightless I (FLII), member of the gelsolin superfamily of actin-remodeling proteins, functions as a transcriptional coregulator. We aim to evaluate a tumor-suppressive function of FLII in regulating androgen receptor (AR) in prostate cancer progression.
Experimental Design: We examined FLII protein and mRNA expression in clinical prostate cancer specimens by immunohistochemistry. Kaplan–Meier analysis was conducted to evaluate the difference in disease-overall survival associated with the expression levels of FLII and AR. Prostate cancer cells stably expressing FLII or shRNA knockdown were used for functional analyses. Immunoprecipitation, Luciferase reporter, and immunofluorescence staining assays were performed to examine the functional interaction between FLII and AR.
Results: Our analysis of the expression levels of FLII in a clinical gene expression array dataset showed that the expression of FLII was positively correlated with the overall survival of prostate cancer patients exhibiting high levels of AR expression. Examination of protein and mRNA levels of FLII showed a significant decrease of FLII expression in human prostate cancers. AR and FLII formed a complex in a ligand-dependent manner through the ligand-binding domain (LBD) of AR. Subsequently, we observed a competitive binding to AR between FLII and the ligand. FLII inhibited AR transactivation and decreased AR nuclear localization. Furthermore, FLII contributed to castration-sensitive and castration-resistant prostate cancer cell growth through AR-dependent signaling, and reintroduction of FLII in prostate cancer cells sensitized the cells to bicalutamide and enzalutamide treatment.
Conclusions: FLII plays a tumor-suppressive role and serves as a crucial determinant of resistance of prostate cancer to endocrine therapies. Clin Cancer Res; 22(6); 1531–44. ©2015 AACR.
Orolaelaps (Acari: Mesostigmata: Melicharidae): description of two new species, redescription of Orolaelaps quisqualis and new characterisation of the genus
Authors: SOURASSOU NAZER FAMAH , MORAES GILBERTO JOSE , SANTOS JANDIR CRUZ 
Published: November 2015

Until now, the genus Orolaelaps De Leon was known only from the USA. Two new species of this genus, namely Orolaelaps piracicabensis n. sp. and Orolaelaps tupiniquim n. sp., are described from specimens collected in the State of São Paulo, Brazil. Orolaelaps quisqualis De Leon, the type species of the genus, is redescribed and an updated diagnosis of Orolaelaps is provided.