bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Weight Loss with or without Exercise on Inflammatory Markers and Adipokines in Postmenopausal Women: The SHAPE-2 Trial, A Randomized Controlled Trial
Authors: van Gemert Willemijn A. , May Anne M. , Schuit Albertine J. , Oosterhof Blanche Y.M. , Peeters Petra H. , Monninkhof Evelyn M. 
Published: February 2016

Abstract
Background: We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women.
Methods: Women were randomized to a diet (n = 97), mainly exercise (n = 98), or control group (n = 48). Goal of both interventions was to lose 5 to 6 kg bodyweight by a hypocaloric diet or an exercise program (4 hours/week) combined with a small caloric intake restriction. Outcomes after 16 weeks included serum high-sensitive C–reactive protein (hsCRP), IL6, adiponectin, and leptin.
Results: Both intervention groups achieved the target weight loss. Controls remained weight stable. Compared with control, hsCRP decreased with mainly exercise [treatment effect ratio (TER) = 0.64] and borderline statistically significant with diet (TER = 0.77). There was a suggestively larger effect of exercise, directly compared with diet (TER = 0.83). Leptin decreased with both interventions: mainly exercise (TER = 0.55) and diet (TER = 0.59), versus control. Effects attenuated and lost significance after adjusting for change in body fat percentage, and to a lesser extent when adjusting for fitness. No effects were seen on IL6 and adiponectin.
Conclusions: A 16-week randomized intervention inducing comparable weight loss by a hypocaloric diet or mainly exercise, resulted in favorable effects on serum hsCRP and leptin. We found a possible more beneficial effect on hsCRP with mainly exercise versus diet. These effects of exercise were established by changes in body fat percentage and physical fitness.
Impact: A modest amount of weight loss in postmenopausal women reduces hsCRP and leptin levels which might be associated with a lower breast cancer risk. Cancer Epidemiol Biomarkers Prev; 25(5); 799–806. ©2016 AACR.
MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival
Authors: Radoul Marina , Chaumeil Myriam M. , Eriksson Pia , Wang Alan S. , Phillips Joanna J. , Ronen Sabrina M. 
Published: February 2016

Abstract
The current standard of care for glioblastoma (GBM) is surgical resection, radiotherapy, and treatment with temozolomide (TMZ). However, resistance to current therapies and recurrence are common. To improve survival, agents that target the PI3K signaling pathway, which is activated in approximately 88% of GBM, are currently in clinical trials. A challenge with such therapies is that tumor shrinkage is not always observed. New imaging methods are therefore needed to monitor response to therapy and predict survival. The goal of this study was to determine whether hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) and 1H magnetic resonance spectroscopy (MRS) can be used to monitor response to the second-generation dual PI3K/mTOR inhibitor voxtalisib (XL765, SAR245409), alone or in combination with TMZ. We investigated GS-2 and U87-MG GBM orthotopic tumors in mice, and used MRI, hyperpolarized 13C MRSI, and 1H MRS to monitor the effects of treatment. In our study, 1H MRS could not predict tumor response to therapy. However, in both our models, we observed a significantly lower hyperpolarized lactate-to-pyruvate ratio in animals treated with voxtalisib, TMZ, or combination therapy, when compared with controls. This metabolic alteration was observed prior to MRI-detectable changes in tumor size, was consistent with drug action, and was associated with enhanced animal survival. Our findings confirm the potential translational value of the hyperpolarized lactate-to-pyruvate ratio as a biomarker for noninvasively assessing the effects of emerging therapies for patients with GBM. Mol Cancer Ther; 15(5); 1113–22. ©2016 AACR.
Neighborhood and Acute Myocardial Infarction Mortality as Related to the Driving Time to Percutaneous Coronary Intervention–Capable Hospital
Authors: Balamurugan Appathurai , Delongchamp Robert , Im Lucille , Bates Joseph , Mehta Jawahar L. 
Published: February 2016

Background

Driving time to a percutaneous coronary intervention (
PCI
)–capable hospital is important in timely treatment of acute myocardial infarction (
AMI
). Our objective was to determine whether driving time from one's residence to a
PCI
‐capable hospital contributes to
AMI
deaths. We conducted a cross‐sectional study of age‐ and sex‐adjusted mortality in census block groups to evaluate this question.

Methods and Results

We studied all (14 027)
AMI
deaths that occurred during 2008–2012 in Arkansas to assess the relationship between driving time from the population center of a block group (neighborhood) to the nearest
PCI
‐capable hospital. We estimated standardized mortality ratios in block groups that were adjusted for education (population over 25 years of age who did not graduate from high school), poverty (population living below federal poverty level), population density (population per square mile), mobility (population residing at the same address as 1 year ago), black (population that is black), rurality (rural households), geodesic distance, and driving time. The median geodesic distance and driving time were 12.8 miles (interquartile range 3.6–30.1) and 28.3 minutes (interquartile range 9.6–58.7), respectively. Risks in neighborhoods with long driving times (90th percentile) were 26% greater than risks in neighborhoods with short driving times (10th percentile), even after adjusting for education, poverty, population density, rurality, and black race (
P
<0.0001).

Conclusions

AMI
mortality increases with increasing driving time to the nearest
PCI
‐capable hospital. Improving the healthcare system by reducing time to arrive at a
PCI
‐capable hospital could reduce
AMI
deaths.
Relationships between Hourly Rainfall Intensity and Atmospheric Variables over the Contiguous United States
Authors: Lepore Chiara , Allen John T. , Tippett Michael K. 
Published: February 2016

Abstract
Rainfall intensity displays relationships with atmospheric conditions such as surface temperature, and these relationships have implications for how the intensity of rainfall varies with climate. Here, hourly gauge measurements of rainfall over the contiguous United States (CONUS) are related to atmospheric variables taken from the North American Regional Reanalysis for the period 1979–2012. This analysis extends previous work relating the rainfall process to the environment by including a wider range of variables in univariate and bivariate quantile regressions. Known covariate relationships are used to quantify the regional contributions of different weather regimes to rainfall occurrence and to identify preferential atmospheric states for rainfall occurrence. The efficiency of different sets of regressors is evaluated, and the results show that both moisture availability and vertical instability should be taken into account, with CAPE in combination with specific humidity or dewpoint temperature being the most powerful regressors. Different regions and seasons behave differently, pointing to the challenges of constructing global or CONUS-wide models for representing the rainfall process. In particular, the relationships between environment and rainfall in the west of the United States are different from other regions, reflecting nonlocal rainfall processes. Most of the coastal and eastern United States display relatively low regional variability in the relationships between rainfall and environment.
Fixation of distal radial epiphyseal fracture: Comparison of K-wire and prebent intramedullary nail
Authors: Cai Haoqi , Wang Zhigang , Cai Haiqing 
Published: February 2016

Objective To compare the use of crossed K-wire and prebent intramedullary nail techniques for the fixation of distal radius metaphyseal fracture in children. Methods Intraoperative and follow-up data for children with distal radius metaphyseal fracture, treated using crossed K-wire or prebent intramedullary nail fixation, were retrospectively analysed. Patient groups were matched for age, sex and clinical parameters (fracture location, affected side, fracture type). Results Patients treated using prebent intramedullary nail fixation ( n = 52) had significantly shorter surgery duration, fewer intraoperative X-radiographs, and lower prevalence of postoperative redisplacement and malalignment deformity than those treated using crossed K-wire fixation ( n = 52). Both techniques resulted in similar postoperative complications and recovery of forearm rotation. Conclusions Prebent intramedullary nail fixation has a better functional outcome than crossed K-wire fixation in the treatment of distal radial epiphyseal fracture in children.
The lived experience of people with mental health and substance misuse problems: Dimensions of belonging
Authors: Blank Alison , Finlay Linda , Prior Sarah 
Published: February 2016

Introduction People with co-occurring mental health and substance misuse problems are among the most excluded in society. A need to feel connected to others has been articulated in the occupational science literature although the concept of belonging itself has not been extensively explored within this paradigm. This paper reports findings from research that explored the meaning and experience of belonging for four people living with dual diagnosis in the United Kingdom. Method Researchers employed an interpretative phenomenological approach to the study. Four semistructured interviews were carried out. The interviews were guided by questions around the meaning of belonging, barriers to belonging and how belonging and not belonging impacted on participants’ lives. Data analysis facilitated the identification of themes across individual accounts and enabled comparisons. Findings Data analysis identified four themes – belonging in family, belonging in place, embodied understandings of belonging and barriers to belonging. Conclusion The findings add further insights into the mutable nature of belonging. A link between sense of belonging and attachment theory has been proposed, along with a way to understand the changeable and dependent nature of belonging through ‘dimensions of belonging’.
Characterization of Disability in Canadians with Mental Disorders Using an Abbreviated Version of a DSM-5 Emerging Measure: The 12-Item WHO Disability Assessment Schedule (WHODAS) 2.0
Authors: Sjonnesen Kirsten , Bulloch Andrew G. M. , Williams Jeanne , Lavorato Dina , B. Patten Scott 
Published: February 2016

Objective: The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a disability scale included in Section 3 of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ( DSM-5) as a possible replacement for the Global Assessment of Functioning Scale (GAF). To assist Canadian psychiatrists with interpretation of the scale, we have conducted a descriptive analysis using data from the 2012 Canadian Community Health Survey–Mental Health component (CCHS-MH). Methods: The 2012 CCHS-MH was a cross-sectional survey of the Canadian community ( n = 23,757). The survey included an abbreviated 12-item version of the WHODAS 2.0. Mental disorder diagnoses were assessed for schizophrenia, other psychosis, major depressive episode (MDE), generalized anxiety disorder (GAD), bipolar I disorder, substance abuse/dependence, and alcohol abuse/dependence. Results: Mean scores ranged from 14.2 (95% CI, 14.1 to 14.3) for the overall community population to 23.1 (95% CI, 19.5 to 26.7) for those with schizophrenia, with higher scores indicating greater disability. Furthermore, the difference in scores between those with lifetime and past-month episodes suggests that the scale is sensitive to changes occurring during the course of these disorders; for example, scores varied from 23.6 (95% CI, 22.2 to 25.1) for past-month MDE to 14.4 (95% CI, 14.2 to 14.7) in the lifetime MDE group without a past-year episode. Conclusion: This analysis suggests that the WHODAS 2.0 may be a suitable replacement for the GAF. As a disability measure, even though it is not a mental health–specific instrument, the 12-item WHODAS 2.0 appears to be sensitive to the impact of mental disorders and to changes over the time course of a mental disorder. However, the clinical utility of this measure requires additional assessment.
A pilot study on the benefit of cognitive rehabilitation in Parkinson’s disease
Authors: Adamski Natalia , Adler Matthias , Opwis Klaus , Penner Iris-Katharina 
Published: February 2016

Purpose: Patients with Parkinson’s disease (PD) show inefficiencies in cognitive performance including working memory functions. Since these problems impact on quality of life and overall well-being, the current study was aimed at improving patients’ situations by evaluating the computerized cognitive training tool, BrainStim. Method: A total of 19 healthy controls (HCs) and six patients with PD were included in the study. While all PD patients received cognitive training, the HC sample was subdivided into 12 subjects with training (HC-T) and 10 subjects without (HC-NT). Participants underwent a double baseline assessment, a post-training assessment, and a 3-month follow up on neuropsychological tests and self-report measures on fatigue and depression. Training was administered between the second baseline and postassessment. It comprised 16 supervised sessions according to a standardized training protocol over 4 weeks. Results: Significant improvements in verbal and visuospatial short-term and long-term memory were found in both training groups. In addition, the HC-T improved on mental speed, and verbal and visuospatial working memory. Both training groups showed stable results for all short-term visuospatial measures after 3 months. Further, the HC-T showed stable results for working memory, verbal, and visuospatial short-term and long-term memory. Conclusions: The efficacy of the applied computerized cognitive training tool BrainStim could be verified in patients with PD and healthy age-matched controls. The preliminary findings highlighted the suitability of a specific cognitive intervention to improve cognitive inefficiencies in patients with PD as well as in healthy older people. Further research on cognitive training in combination with PD drug therapy is needed to better understand the mutual interaction and to offer optimal therapeutic approaches to patients.
Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study
Authors: Corre Romain , Greillier Laurent , Le Caër Hervé , Audigier-Valette Clarisse , Baize Nathalie , Bérard Henri , Falchero Lionel , Monnet Isabelle , Dansin Eric , Vergnenègre Alain , Marcq Marie , Decroisette Chantal , Auliac Jean-Bernard , Bota Suzanna , Lamy Régine , Massuti Bartomeu , Dujon Cécile , Pérol Maurice , Daurès Jean-Pierre , Descourt Renaud , Léna Hervé , Plassot Carine , Chouaïd Christos 
Published: February 2016

Purpose Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non–small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. Patients and Methods In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. Results Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007). Conclusion In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.
Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial
Authors: DuBois Steven G. , Marachelian Araz , Fox Elizabeth , Kudgus Rachel A. , Reid Joel M. , Groshen Susan , Malvar Jemily , Bagatell Rochelle , Wagner Lars , Maris John M. , Hawkins Randall , Courtier Jesse , Lai Hollie , Goodarzian Fariba , Shimada Hiroyuki , Czarnecki Scarlett , Tsao-Wei Denice , Matthay Katherine K. , Mosse Yael P. 
Published: February 2016

PurposeAlisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population.Patients and MethodsPatients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m2per day on days 1 to 7 along with irinotecan 50 mg/m2intravenously and temozolomide 100 mg/m2orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained.ResultsTwenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m2, with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib.ConclusionAlisertib 60 mg/m2per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing.
Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Chen Ronald C. , Rumble R. Bryan , Loblaw D. Andrew , Finelli Antonio , Ehdaie Behfar , Cooperberg Matthew R. , Morgan Scott C. , Tyldesley Scott , Haluschak John J. , Tan Winston , Justman Stewart , Jain Suneil 
Published: February 2016

Purpose To endorse Cancer Care Ontario’s guideline on Active Surveillance for the Management of Localized Prostate Cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations. Methods The Active Surveillance for the Management of Localized Prostate Cancer guideline was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and the recommendations. Results The ASCO Endorsement Panel determined that the recommendations from the Active Surveillance for the Management of Localized Prostate Cancer guideline, published in May 2015, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the Active Surveillance for the Management of Localized Prostate Cancer guideline with added qualifying statements. The Cancer Care Ontario recommendation regarding 5-alpha reductase inhibitors was not endorsed by the ASCO panel. Recommendations For most patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the recommended disease management strategy. Factors including younger age, prostate cancer volume, patient preference, and ethnicity should be taken into account when making management decisions. Select patients with low-volume, intermediate-risk (Gleason 3 + 4 = 7) prostate cancer may be offered active surveillance. Active surveillance protocols should include prostate-specific antigen testing, digital rectal examinations, and serial prostate biopsies. Ancillary radiologic and genomic tests are investigational but may have a role in patients with discordant clinical and/or pathologic findings. Patients who are reclassified to a higher-risk category (Gleason score ≥ 7) or who have significant increases in tumor volume on subsequent biopsies should be offered active therapy.
A Mechanism to Enhance Cellular Responsivity to Hormone Action: Krüppel-Like Factor 9 Promotes Thyroid Hormone Receptor-β Autoinduction During Postembryonic Brain Development
Authors: Hu Fang , Knoedler Joseph R. , Denver Robert J. 
Published: February 2016

AbstractThyroid hormone (TH) receptor (TR)-β (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Krüppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation-mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRβ in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs.