bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ‘novel’ model for integrating Sport and Exercise Medicine (SEM) and Musculoskeletal (MSK) management into primary care in the UK
Authors: Heron Neil 
Published: November 2015

BackgroundMusculoskeletal (MSK) symptoms are common within primary care but some general practitioners (GPs)/family physicians do not feel comfortable managing these symptoms, preferring to refer onwards. We aimed to establish a reproducible GP-staffed MSK and sport and exercise medicine (SEM) clinic within primary care, in keeping with recent policy changes within the UK health system.MethodsA monthly MSK and SEM clinic was held within a Belfast GP practice, staffed by 1 GP with a specialist interest in MSK/SEM conditions, and its performance was reviewed over two 3-month periods. Parameters audited included diagnoses, patient satisfaction and secondary care referral rates.Results83 patients, 36 males and 47 females, were reviewed in the clinic and the main presenting joint was the shoulder. Patient self-reported satisfaction with the service was high. Comparing referral rates between August and October 2013 and the same period in 2014, overall referrals from the practice were reduced by 147, orthopaedic and rheumatology referrals were reduced by 2 and 3, while physiotherapy and X-ray referrals were reduced by 47 and 90, respectively. Comparing the referral rates between January and March 2014 and the same period in 2015, overall outpatient referrals were reduced by 152, orthopaedic and rheumatology referrals were reduced by 9 and 4, while physiotherapy and X-ray referrals were reduced by 41 and 3, respectively.DiscussionWe present a novel, reproducible service model for managing MSK/SEM symptoms in primary care which could be commissioned by local groups. This model can make sound economic sense and deliver high patient satisfaction within primary care, reducing waiting times and the secondary care referral burden.
The Child Sport Concussion Assessment Tool (Child SCAT3): normative values and correspondence between child and parent symptom scores in male child athletes
Authors: Porter Shaun , Smith-Forrester Jenna , Alhajri Najah , Kusch Cody , Sun Jonathan , Barrable Bill , Panenka William J , Virji-Babul Naznin 
Published: November 2015

BackgroundChildren and youth are at increased risk of sustaining sport-related concussions. There is a need to develop age-specific tools to evaluate the effects of concussion. The objective of this study was to determine normative values for the Child Sport Concussion Assessment Tool (Child SCAT3) in child athletes and evaluate the symptom scoring agreement between the child and parent.MethodsChild SCAT3 was administered to ice hockey players enrolled in a regional minor hockey association. Statistical analyses were performed to evaluate the differences between child and parent reporting as well as those based on age.Results227 athletes (7–12 years of age) completed the Child SCAT3. 29 players reported a history of concussion. For the objective components, the average total Standard Assessment of Concussion adapted to a child version (SAC-C) score of 24.4 was made up by orientation (3.7), immediate memory (12.9), concentration (3.8) and delayed recall (3.9) sections. Average errors in the modified Balance Error Scoring System (BESS) were 1.6, tandem gait time 14.9 s and coordination score 0.95. For the subjective component, children reported an average of eight symptoms and a severity of 11; parents reported seven symptoms with a severity of 9. Overall, children reported higher symptom severity in comparison with their parents. In addition, parents significantly underestimated both physical and sleep-related symptoms in comparison with the children's scores.ConclusionsResults provide representative scores for the Child SCAT3 in young male ice hockey players. Clinicians should be aware that parents tend to underestimate their child's symptoms and symptom severity, particularly in the domains of physical symptoms and sleep. Encouraging objective symptom documentation with sleep or pain diaries, for example, may be useful for reliable clinical assessment in this age group.
Exercise as medicine—the use of group medical visits to promote physical activity and treat chronic moderate depression: a preliminary 14-week pre–post study
Authors: Adams David J , Remick Ronald A , Davis Jennifer C , Vazirian Sara , Khan Karim M 
Published: November 2015

ObjectiveThe evidence that regular physical activity can treat depressive disorders is increasingly robust. However, motivating patients with depression to engage in physical activity can be challenging. Interdisciplinary group medical visits (GMVs) with an integrated physical activity component may be a novel means to support patients in becoming more active.MethodsWe conducted a ‘pre–post’ pilot study within a primary care setting. Participants were adults (≥18 years) with a chronic major depressive disorder or a bipolar 2 disorder (depression; chronic). A psychiatrist and exercise therapist co-led a series of 14 weekly 2 h GMVs. Each group visit combined specific medical advice, physical activity, patient discussions and a targeted educational component. Participants also attended 11 weekly hatha yoga classes. Primary outcome was ‘steps’ as measured by accelerometer (SenseWear) as well as depression (Patient Health Questionnaire, PHQ-9) and anxiety (Generalised Anxiety Disorder, GAD-7) ratings.Results14 of 15 participants (93.3%) completed the 14-week programme. After 3 months postintervention, median depression scales (PHQ-9) decreased 38% from 16 to 10 (p<0.01; IQR pre/post 8/12); and median anxiety scales (GAD-7) decreased 50% from 13 to 6.5 (p<0.05; IQR 8.5/9). Median daily ‘steps’ increased 71% from 3366 to 5746 (IQR 2610/6237), though this was not significant (p>0.10).ConclusionsWhile other studies have examined the efficacy of GMVs in addressing chronic illnesses and the promotion of lifestyle changes, none to our knowledge have embedded physical activity within the actual patient visits. Interdisciplinary GMVs (eg, psychiatrist/exercise professional) may be a means to decrease depression and anxiety ratings within clinical care while improving physical activity.
Rethinking the role of fat oxidation: substrate utilisation during high-intensity interval training in well-trained and recreationally trained runners
Authors: Hetlelid Ken J , Plews Daniel J , Herold Eva , Laursen Paul B , Seiler Stephen 
Published: November 2015

BackgroundAlthough carbohydrate is the predominant fuel source supporting high-intensity exercise workloads, the role of fat oxidation, and the degree to which it may be altered by training status, is less certain.MethodsWe compared substrate oxidation rates, using indirect calorimetry, during a high-intensity interval training (HIT) session in well-trained (WT) and recreationally trained (RT) runners. Following preliminary testing, 9 WT (VO2max71±5 mL/min/kg) and 9 RT (VO2max55±5 mL/min/kg) male runners performed a self-paced HIT sequence consisting of six, 4 min work bouts separated by 2 min recovery periods on a motorised treadmill set at a 5% gradient.ResultsWT and RT runners performed the HIT session with the same perceived effort (rating of perceived exertion (RPE) =18.3±0.7 vs 18.2±1.1, respectively), blood lactate (6.4±2.1 vs 6.2±2.5 mmol/L) and estimated carbohydrate oxidation rates (4.2±0.29 vs 4.4±0.45 g/min; effect size (ES) 90% confidence limits (CL)=−0.19±0.85). Fat oxidation (0.64±0.13 vs 0.22±0.16 g/min for WT and RT, respectively) accounted for 33±6% of the total energy expenditure in WT vs 16±6% in RT most likely very large difference in fat oxidation (ES 90% CL=1.74±0.83) runners. Higher rates of fat oxidation had a very large correlation with VO2max(r=0.86; 90% CI (0.7 to 0.94).ConclusionsDespite similar RPE, blood lactate and carbohydrate oxidation rates, the better performance by the WT group was explained by their nearly threefold higher rates of fat oxidation at high intensity.
The impact of 12 weeks walking football on health and fitness in males over 50 years of age
Authors: Arnold Josh Timothy , Bruce-Low Stewart , Sammut Luke 
Published: November 2015

AimTo describe and characterise anthropometrical and fitness changes following a 12-week walking football programme in individuals over the age of 50 years.MethodsFollowing ethical approval, 10 male participants (mean (SD): age 66 (7) years) with a range of comorbidities completed a 12-week walking football programme, consisting of a single 2 h training session each week. Body mass, fat mass, fat free mass, maximal oxygen consumption, maximal heart rate, exercise time to exhaustion and isometric hand-grip strength, were assessed at baseline and immediately following the intervention. Week-0–12 intervention differences were determined using means (95% CIs) and t tests; effect sizes were calculated using Cohen's d (0.2 small, 0.5 medium, 0.8 large).Results12 weeks walking football significantly reduced body fat mass (week 0, 27.4 (9.0) kg versus week 12, 24.4 (8.9) kg, p=<0.05, d=1.0) and reduced percentage body fat (week 0, 30.3 (8.2) % versus week 12, 27.5 (8.5) %, p=<0.05, d=1.0). A significant increase in time to volitional exhaustion during increamental exercise (week 0, 545 (102) s versus week 12, 603 (102) s, p=<0.05, d=0.7) was observed without any change in peak blood lactate. Non-significant differences with medium effect sizes were seen for a reduction whole body mass, increase in lean body mass and a reduction in body mass index.ConclusionsThis investigation suggests the potential efficacy of walking football as a public health intervention, even in populations presenting a range of comorbidities, with future research investigating its move to scale.
Understanding the Unique Attributes of MUC16 (CA125): Potential Implications in Targeted Therapy
Authors: Das Srustidhar , Batra Surinder K. 
Published: November 2015

Abstract
CA125, the most widely used ovarian cancer biomarker, was first identified approximately 35 years ago in an antibody screen against ovarian cancer antigen. Two decades later, it was cloned and characterized to be a transmembrane mucin, MUC16. Since then, several studies have investigated its expression, functional, and mechanistic involvement in multiple cancer types. Antibody-based therapeutic approaches primarily using antibodies against the tandem repeat domains of MUC16 (e.g., oregovomab and abagovomab) have been the modus operandi for MUC16-targeted therapy, but have met with very limited success. In addition, efforts have been also made to disrupt the functional cooperation of MUC16 and its interacting partners; for example, use of a novel immunoadhesin HN125 to interfere MUC16 binding to mesothelin. Since the identification of CA125 to be MUC16, it is hypothesized to undergo proteolytic cleavage, a process that is considered to be critical in determining the kinetics of MUC16 shedding as well as generation of a cell-associated carboxyl-terminal fragment with potential oncogenic functions. In addition to our experimental demonstration of MUC16 cleavage, recent studies have demonstrated the functional importance of carboxyl terminal fragments of MUC16 in multiple tumor types. Here, we provide how our understanding of the basic biologic processes involving MUC16 influences our approach toward MUC16-targeted therapy. Cancer Res; 75(22); 4669–74. ©2015 AACR.
A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution
Authors: Walsh Kyle M. , de Smith Adam J. , Hansen Helen M. , Smirnov Ivan V. , Gonseth Semira , Endicott Alyson A. , Xiao Jianqiao , Rice Terri , Fu Cecilia H. , McCoy Lucie S. , Lachance Daniel H. , Eckel-Passow Jeanette E. , Wiencke John K. , Jenkins Robert B. , Wrensch Margaret R. , Ma Xiaomei , Metayer Catherine , Wiemels Joseph L. 
Published: November 2015

Abstract
Genome-wide association studies (GWAS) have identified SNPs in six genes that are associated with childhood acute lymphoblastic leukemia (ALL). A lead SNP was found to occur on chromosome 9p21.3, a region that is deleted in 30% of childhood ALLs, suggesting the presence of causal polymorphisms linked to ALL risk. We used SNP genotyping and imputation-based fine-mapping of a multiethnic ALL case–control population (Ncases = 1,464, Ncontrols = 3,279) to identify variants of large effect within 9p21.3. We identified a CDKN2A missense variant (rs3731249) with 2% allele frequency in controls that confers three-fold increased risk of ALL in children of European ancestry (OR, 2.99; P = 1.51 × 10−9) and Hispanic children (OR, 2.77; P = 3.78 × 10−4). Moreover, of 17 patients whose tumors displayed allelic imbalance at CDKN2A, 14 preferentially retained the risk allele and lost the protective allele (PBinomial = 0.006), suggesting that the risk allele provides a selective advantage during tumor growth. Notably, the CDKN2A variant was not significantly associated with melanoma, glioblastoma, or pancreatic cancer risk, implying that this polymorphism specifically confers ALL risk but not general cancer risk. Taken together, our findings demonstrate that coding polymorphisms of large effect can underlie GWAS “hits” and that inherited polymorphisms may undergo directional selection during clonal expansion of tumors. Cancer Res; 75(22); 4884–94. ©2015 AACR.
p53 Activity Dominates That of p73 upon Mdm4 Loss in Development and Tumorigenesis
Authors: Tashakori Mehrnoosh , Zhang Yun , Xiong Shunbin , You M. James , Lozano Guillermina 
Published: November 2015

Abstract
Mdm4 negatively regulates the p53 tumor suppressor. Mdm4 loss in mice leads to an embryonic lethal phenotype that is p53-dependent. Biochemical studies indicate that Mdm4 also binds p73, a member of the p53 family, with higher affinity than p53. In this study, the significance of the Mdm4 and p73 interaction in vivo during embryogenesis and tumorigenesis was examined. The data revealed that p73 loss did not rescue either the early Mdm4-deficient embryonic lethality or the runted phenotype of Mdm4Δ2/Δ2 p53+/− embryos. Furthermore, studies in the developing central nervous system wherein both genes have prominent roles indicated that loss of p73 also did not rescue the Mdm4-null brain phenotype as did p53 loss. This p53 dependency occurred despite evidence for p73-specific transcriptional activity. In tumor studies, the combination of Mdm4 overexpression and p73 loss did not alter survival of mice or the tumor spectrum as compared with Mdm4 overexpression alone. In summary, these data demonstrate that the Mdm4–p73 axis cannot override the dominant role of p53 in development and tumorigenesis.
Implications: Genetic characterization of the Mdm4 and p73 interaction during development and tumorigenesis suggests new insight into the role of p53 family members, which may influence treatment options for patients. Mol Cancer Res; 14(1); 56–65. ©2015 AACR.
Uninterrupted Sedentary Behavior Downregulates BRCA1 Gene Expression
Authors: Pettapiece-Phillips Rachael , Kotlyar Max , Chehade Rania , Salmena Leonardo , Narod Steven A. , Akbari Mohammad , Jurisica Igor , Kotsopoulos Joanne 
Published: November 2015

Abstract
BRCA1 mutation carriers face a high lifetime risk of developing breast cancer. Physical activity induces broad transcriptional changes, and multiple studies have documented its beneficial effects across cancers. Because haploinsufficiency predisposes to breast cancer in these women, factors that increase BRCA1 levels may mitigate the effect of the mutation. Whether physical activity modulates BRCA1 expression and whether lifestyle factors could benefit women with a mutation remain unclear. The objective of this study was to systematically evaluate whether physical activity or sedentary behavior affects BRCA1 mRNA expression. Activity levels were assessed in 50 female participants (14 BRCA1 mutation carriers and 36 noncarriers) using the GT3X Actigraph accelerometer, and BRCA1 mRNA expression was quantified from peripheral blood lymphocytes using the Nanostring nCounter Analysis System. There was a significant negative correlation between the longest sedentary bout and BRCA1 mRNA expression (ρ = –0.32; P = 0.02). Women below the median for the longest sedentary bout had significantly higher BRCA1 mRNA levels compared with women above the median (161 vs. 132 counts; P = 0.04; one-sided Mann–Whitney U test). There was no significant relationship between mean metabolic equivalents of task rate or mean sedentary time and BRCA1 mRNA expression (Spearman correlation P ≥ 0.75; P ≥ 0.14; Mann–Whitney U test). These findings suggest that prolonged periods of sedentary behavior are associated with significantly lower BRCA1 mRNA expression. Whether this translates into a potentially more harmful effect in BRCA1 mutation carriers warrants further investigation. Cancer Prev Res; 9(1); 83–88. ©2015 AACR.
Epicardial Radiofrequency Ablation Failure During Ablation Procedures for Ventricular Arrhythmias
Authors: Baldinger Samuel H. , Kumar Saurabh , Barbhaiya Chirag R. , Mahida Saagar , Epstein Laurence M. , Michaud Gregory F. , John Roy , Tedrow Usha B. , Stevenson William G. 
Published: November 2015

Background—
Radiofrequency ablation (RFA) from the epicardial space for ventricular arrhythmias is limited or impossible in some cases. Reasons for epicardial ablation failure and the effect on outcome have not been systematically analyzed.

Methods and Results—

We assessed reasons for epicardial RFA failure relative to the anatomic target area and the type of heart disease and assessed the effect of failed epicardial RFA on outcome after ablation procedures for ventricular arrhythmias in a large single-center cohort. Epicardial access was attempted during 309 ablation procedures in 277 patients and was achieved in 291 procedures (94%). Unlimited ablation in an identified target region could be performed in 181 cases (59%), limited ablation was possible in 22 cases (7%), and epicardial ablation was deemed not feasible in 88 cases (28%). Reasons for failed or limited ablation were unsuccessful epicardial access (6%), failure to identify an epicardial target (15%), proximity to a coronary artery (13%), proximity to the phrenic nerve (6%), and complications (<1%). Epicardial RFA was impeded in the majority of cases targeting the left ventricular summit region. Acute complications occurred in 9%. The risk for acute ablation failure was 8.3× higher (4.5–15.0;
P
<0.001) after no or limited epicardial RFA compared with unlimited RFA, and patients with unlimited epicardial RFA had better recurrence-free survival rates (
P
<0.001).

Conclusions—
Epicardial RFA for ventricular arrhythmias is often limited even when pericardial access is successful. Variability of success is dependent on the target area, and the presence of factors limiting ablation is associated with worse outcomes.
Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age
Authors: Gidding Samuel S. , Rana Jamal S. , Prendergast Christopher , McGill Henry , Carr J. Jeffery , Liu Kiang , Colangelo Laura A. , Loria Catherine M. , Lima Joao , Terry James G. , Reis Jared P. , McMahan C. Alex 
Published: November 2015

Background—
We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later.

Methods and Results—
In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher score and c-statistics for predicting CAC/AAC were calculated. The prevalence of CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence interval [CI], 1.25–1.33 versus OR, 1.12; 95% CI, 1.11–1.14). For AAC, ORs at years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24–1.34 versus OR, 1.22; 95% CI, 1.19–1.26). C-statistic for CAC prediction was higher at year 0 than year 25 (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670). ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10. Including change in PDAY scores with baseline scores improved prediction.

Conclusions—
Atherosclerosis risk and change in risk assessed in young adulthood years before subclinical atherosclerosis imaging provide strong prediction of future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in addition to risk measured at the time of study.
Increasing Daily Precipitation Intensity Associated with Warmer Air Temperatures over Northern Eurasia
Authors: Ye Hengchun , Fetzer Eric J. , Behrangi Ali , Wong Sun , Lambrigtsen Bjorn H. , Wang Crysti Y. , Cohen Judah , Gamelin Brandi L. 
Published: November 2015

Abstract
This study uses 45 years of observational records from 517 historical surface weather stations over northern Eurasia to examine changing precipitation characteristics associated with increasing air temperatures. Results suggest that warming air temperatures over northern Eurasia have been accompanied by higher precipitation intensity but lower frequency and little change in annual precipitation total. An increase in daily precipitation intensity of around 1%–3% per each degree of air temperature increase is found for all seasons as long as a station’s seasonal mean air temperature is below about 15°–16°C. This threshold temperature may be location dependent. At temperatures above this threshold, precipitation intensity switches to decreasing with increasing air temperature, possibly related to decreasing water vapor associated with extreme high temperatures. Furthermore, the major atmospheric circulation of the Arctic Oscillation, Scandinavian pattern, east Atlantic–western Eurasian pattern, and polar–Eurasian pattern also have significant influences on precipitation intensity in winter, spring, and summer over certain areas of northern Eurasia.