bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075
Authors: Faivre Emily J. , Wilcox Denise , Lin Xiaoyu , Hessler Paul , Torrent Maricel , He Wei , Uziel Tamar , Albert Daniel H. , McDaniel Keith , Kati Warren , Shen Yu 
Published: October 2016

Abstract
Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and hematologic malignancies. The function of BET family member BRD4 at enhancers/superenhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here, the hypothesis was tested that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the androgen receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075. DHT-stimulated transcription of AR target genes was inhibited by ABBV-075 without significant effect on AR protein expression. Furthermore, ABBV-075 disrupted DHT-stimulated recruitment of BET family member BRD4 to gene-regulatory regions cooccupied by AR, including the well-established PSA and TMPRSS2 enhancers. Persistent BET inhibition disrupted the composition and function of AR-occupied enhancers as measured by a reduction in AR and H3K27Ac ChIP signal and inhibition of enhancer RNA transcription. ABBV-075 displayed potent antiproliferative activity in multiple models of resistance to second-generation antiandrogens and inhibited the activity of the AR splice variant AR-V7 and ligand-binding domain gain-of-function mutations, F877L and L702H. ABBV-075 was also a potent inhibitor of MYC and the TMPRSS2-ETS fusion protein, important parallel transcription factor drivers of CRPC.
Implications: The ability of BET family inhibitor ABBV-075 to inhibit transcription activation downstream of the initiating events of transcription factors like AR and TMPRSS2:ETS fusion proteins provides a promising therapeutic option for CRPC patients who have developed resistance to second-generation antiandrogens. Mol Cancer Res; 15(1); 35–44. ©2016 AACR.
Action observation training of community ambulation for improving walking ability of patients with post-stroke hemiparesis: a randomized controlled pilot trial
Authors: Park Hyun-Ju , Oh Duck-Won , Choi Jong-Duk , Kim Jong-Man , Kim Suhn-Yeop , Cha Yong-Jun , Jeon Su-Jin 
Published: October 2016

Purpose: To investigate the effects of action observation training involving community-based ambulation for improving walking ability after stroke. Design: Randomized, controlled pilot study. Setting: Inpatient rehabilitation hospital. Subjects: A total of 25 inpatients with post-stroke hemiparesis were randomly assigned to either the experimental group ( n = 12) or control group ( n = 13). Intervention: Subjects of the experimental group watched video clips demonstrating four-staged ambulation training with a more complex environment factor for 30 minutes, three times a week for four weeks. Meanwhile, subjects of the control group watched video clips, which showed different landscape pictures. Main measures: Walking function was evaluated before and after the four-week intervention using a 10-m walk test, community walk test, activities-specific balance confidence scale, and spatiotemporal gait measures. Results: Changes in the values for the 10-m walk test (0.17 ±0.19 m/s vs. 0.05 ±0.08 m/s), community walk test (–151.42 ±123.82 seconds vs. 67.08 ±176.77 seconds), and activities-specific balance confidence (6.25 ±5.61 scores vs. 0.72 ±2.24 scores) and the spatiotemporal parameters (i.e. stride length (19.00 ±11.34 cm vs. 3.16 ±11.20 cm), single support (5.87 ±5.13% vs. 0.25 ±5.95%), and velocity (15.66 ±12.34 cm/s vs. 2.96 ±10.54 cm/s)) indicated a significant improvement in the experimental group compared with the control group. In the experimental group, walking function and ambulation confidence was significantly different between the pre- and post-intervention, whereas the control group showed a significant difference only in the 10-m walk test. Conclusions: Action observation training of community ambulation may be favorably used for improving walking function of patients with post-stroke hemiparesis.
Population-Level Measures to Predict Obesity Burden in Public Schools: Looking Upstream for Midstream Actions
Authors: Jayawardene Wasantha P. , Lohrmann David K. , Dickinson Stephanie , Torabi Mohammad R. 
Published: October 2016

Purpose: To estimate school-level obesity burden, as reflected in prevalence of obesity, based on the characteristics of students’ socioeconomic and geographic environments. Design: Secondary analysis of cross-sectional data. Setting: Public schools (N = 504) from 43 of 67 counties in Pennsylvania. Participants: Kindergarten through grade 12 students (N = 255 949). Measures: School-level obesity prevalence for the year 2014 was calculated from state-mandated student body mass index (BMI) measurements. Eighteen aggregate variables, characterizing schools and counties, were retrieved from federal data sources. Analysis: Three classification variables—excess weight (BMI ≥ 85th percentile), obesity (BMI ≥ 95th percentile), and severe obesity (BMI > 35% or 120% of 95th percentile)—each with 3 groups of schools (low-, average-, and high-prevalence) were created for discriminant function analysis, based on state mean and standard deviation of school distribution. Analysis tested each classification model to reveal school- and county-level dimensions on which school groups differed from each other. Results: Discriminant functions for obesity, which contained school enrollment, percentage of students receiving free/reduced-price lunch, percentage of black/Hispanic students, school location (suburban/other), percentage of county adults with postsecondary education, and percentage of county adults with obesity, yielded 67.86% correct classification (highest accuracy), compared to 34.23% schools classified by chance alone. Conclusion: In the absence of mandated student BMI screenings, the model developed in this study can be used to identify schools most likely to have high obesity burden and, thereafter, determine dissemination of enhanced resources for the implementation of proven prevention policies and programs.
Feasibility and Reliability of the System for Observing Play and Leisure Activity in Youth (SOPLAY) for Measuring Moderate to Vigorous Physical Activity in Children Visiting an Interactive Children’s Museum Exhibition
Authors: Agaronov Alen , Leung May May , Garcia Jeanette M. , Kwan Amy , Yeh Ming-Chin , Zarcadoolas Christina , Platkin Charles S. 
Published: October 2016

Purpose: To test the feasibility and reliability of a direct observation method for measuring moderate to vigorous physical activity (MVPA) in children visiting an interactive children’s museum exhibition. Design: Direct observation was used to assess MVPA in children visiting an interactive children’s museum exhibition on 2 weekend days in winter 2013. Setting: The Children’s Museum of Manhattan’s EatSleepPlay™: Building Health Every Day exhibition. Participants: Children (group level) visiting the museum exhibition. Measures: System for Observing Play and Leisure Activity in Youth (SOPLAY). Analyses: Interobserver reliability was analyzed for MVPA and activity type. Two-group analyses were conducted using a series of Wilcoxon rank sum tests. Results: A total of 545 children were observed over 288 observations. No significant differences were found between observers for MVPA ( r = .91, P = .6804) or activity type (κ = .90, P = .6334). Children participated in MVPA during 35.2% of all observations. No significant differences were found for participation in MVPA between boys (37.6%) and girls (32.8%, P = .1589). Conclusion: The SOPLAY may be a useful tool for measuring MVPA in interactive children’s museum exhibitions. Research with multiple museum settings and diverse groups of children over longer periods of time is warranted to further establish the feasibility and reliability of the SOPLAY for measuring MVPA in this novel setting.
The physical health of Indigenous and non-Indigenous patients participating in residential rehabilitation programs: a comparison study
Authors: Meehan Tom , Jones Donna , Stedman Terry , Johnson Dean , Suetani Shuichi , Foreman Emma 
Published: October 2016

Objective: To examine the differences in the physical health of Indigenous and non-Indigenous patients with severe mental illness (SMI) undergoing psychiatric rehabilitation. Methods: An audit of the physical health of patients ( n = 361) in all publicly funded residential rehabilitation programs in Queensland was carried out in late 2014. Data collection focused on clinical and lifestyle factors associated with physical health. Results: The prevalence of smoking, substance use and type 2 diabetes in Indigenous patients was significantly higher than rates found in non-Indigenous patients. Metabolic syndrome was also significantly higher in indigenous patients, with 66% of Indigenous patients compared to 46% of non-Indigenous patients meeting criteria for metabolic syndrome. Conclusions: Patients with SMI in residential rehabilitation programs have poor physical health. Our findings underscore the need for clinicians to develop and evaluate interventions aimed at improving the metabolic profile of those with SMI in residential rehabilitation programs. Historical factors and cultural traditions need to be considered when designing lifestyle interventions for Indigenous patients.
Are inspectors’ assessments reliable? Ratings of NHS acute hospital trust services in England
Authors: Boyd Alan , Addicott Rachael , Robertson Ruth , Ross Shilpa , Walshe Kieran 
Published: October 2016

The credibility of a regulator could be threatened if stakeholders perceive that assessments of performance made by its inspectors are unreliable. Yet there is little published research on the reliability of inspectors’ assessments of health care organizations’ services. Objectives We investigated the inter-rater reliability of assessments made by inspectors inspecting acute hospitals in England during the piloting of a new regulatory model implemented by the Care Quality Commission (CQC) during 2013 and 2014. Multi-professional teams of inspectors rated service provision on a four-point scale for each of five domains: safety; effectiveness; caring; responsiveness; and leadership. Methods In an online survey, we asked individual inspectors to assign a domain and a rating to each of 10 vignettes of service information extracted from CQC inspection reports. We used these data to simulate the ratings that might be produced by teams of inspectors. We also observed inspection teams in action, and interviewed inspectors and staff from hospitals that had been inspected. Results Levels of agreement varied substantially from vignette to vignette. Characteristics such as professional background explained only a very small part of the variation. Overall, agreement was higher on ratings than on domains, and for groups of inspectors compared with individual inspectors. A number of potential causes of disagreement were identified, such as differences regarding the weight that should be given to contextual factors and general uncertainty about interpreting the rating and domain categories. Conclusion Groups of inspectors produced more reliable assessments than individual inspectors, and there is evidence to support the utility of appropriate discussions between inspectors in improving reliability. The reliability of domain allocations was lower than for ratings. It is important to define categories and rating levels clearly, and to train inspectors in their use. Further research is needed to replicate these results now that the model has been fully implemented, and to understand better the impact that inspector uncertainty and disagreement may have on published CQC ratings.
A Value Analysis of Lean Processes in Target Value Design and Integrated Project Delivery
Authors: Nanda Upali , K. Rybkowski Zofia , Pati Sipra , Nejati Adeleh 
Published: October 2016

Objective: To investigate what key stakeholders consider to be the advantages and the opportunities for improvement in using lean thinking and tools in the integrated project delivery (IPD) process. Method: A detailed literature review was followed by case study of a Lean-IPD project. Interviews with members of the project leadership team, focus groups with the integrated team as well as the design team, and an online survey of all stakeholders were conducted. Analysis: Statistical analysis and thematic content analysis were used to analyze the data, followed by a plus–delta analysis. Results: (1) Learning is a large, implicit benefit of Lean-IPD that is not currently captured by any success metric; (2) the cardboard mock-up was the most successful lean strategy; (3) although a collaborative project, the level of influence of different stakeholder groups was perceived to be different by different stakeholders; (4) overall, Lean-IPD was rated as better than traditional design–bid–build methods; and (5) opportunities for improvement reported were increase in accurate cost estimating, more efficient use of time, perception of imbalance of control/influence, and need for facilitation (which represents different points of view). Conclusion: While lean tools and an IPD method are preferred to traditional design–bid–build methods, the perception of different stakeholders varies and more work needs to be done to allow a truly shared decision-making model. Learning was identified as one of the biggest advantages.
Long-term clinical outcomes in patients with ST-segment elevation acute myocardial infarction complicated by cardiogenic shock due to acute pump failure
Authors: Kawaji Tetsuma , Shiomi Hiroki , Morimoto Takeshi , Furukawa Yutaka , Nakagawa Yoshihisa , Kadota Kazushige , Ando Kenji , Mizoguchi Tetsu , Abe Mitsuru , Takahashi Mamoru , Kimura Takeshi ,   on behalf of the CREDO-Kyoto AMI investigators
Published: October 2016

Background: Cardiogenic shock remained the leading cause of death in ST-segment elevation acute myocardial infarction (STEMI) patients even in the primary percutaneous coronary intervention era. Methods: Among 3942 STEMI patients with primary percutaneous coronary intervention within 24 h after symptom-onset in the Coronary Revascularization Demonstrating Outcome Study in Kyoto acute myocardial infarction registry, the study population of the current analysis consisted of 466 STEMI patients who were complicated by cardiogenic shock due to acute pump failure. Results: The cumulative incidence of all-cause death of cardiogenic shock due to acute pump failure was 25.4% at 30 days, 38.7% at one year, and 51.4% at five years. Cumulative five-year incidence of all-cause death in patients with left main coronary artery culprit lesion was extremely high (left main coronary artery: 70.4%, left anterior descending artery: 52.5%, left circumflex artery: 50.6%, and right coronary artery; 44.3%, respectively, log-rank p<0.001). The cumulative five-year incidence of all-cause death in patients with onset-to-balloon time ⩽3 h as well as those with door-to-balloon time ⩽90 min were significantly lower than those without (43.3% versus 55.5%, log-rank p=0.008, and 44.9% versus 55.8%, log-rank p=0.003, respectively). After adjusting for confounders, onset-to-balloon time ⩽3 h and door-to-balloon time ⩽90 min were independently associated with lower long-term risk for all-cause death (hazard ratio: 0.69, 95% confidence interval: 0.49–0.96, p=0.03, and hazard ratio: 0.73, 95% confidence interval: 0.53–0.98, p=0.04, respectively). Conclusions: The long-term mortality of STEMI patients complicated by cardiogenic shock due to acute pump failure remains high even in the current clinical practice. In this high-risk category of patients, shorter onset-to-balloon and door-to-balloon time were associated with significantly lower long-term risk for mortality.
CHA2DS2-VASc risk factors as predictors of stroke after acute coronary syndrome: A systematic review and meta-analysis
Authors: Guerra Federico , Scappini Lorena , Maolo Alessandro , Campo Gianluca , Pavasini Rita , Shkoza Matilda , Capucci Alessandro 
Published: October 2016

Background: Stroke is a rare but serious complication of acute coronary syndrome. At present, no specific score exists to identify patients at higher risk. The aim of the present study is to test whether each clinical variable included in the CHA2DS2-VASc score retains its predictive value in patients with recent acute coronary syndrome, irrespective of atrial fibrillation. Methods: The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. All clinical trials and observational studies presenting data on the association between stroke/transient ischemic attack incidence and at least one CHA2DS2-VASc item in patients with a recent acute coronary syndrome were considered in the analysis. Atrial fibrillation diagnosis was also considered. Results: The whole cohort included 558,193 patients of which 7108 (1.3%) had an acute stroke and/or transient ischemic attack during follow-up (median nine months; 1st–3rd quartile 1–12 months). Age and previous stroke had the highest odds ratios (odds ratio 2.60; 95% confidence interval 2.21–3.06 and odds ratio 2.74; 95% confidence interval 2.19–3.42 respectively), in accordance with the two-point value given in the CHA2DS2-VASc score. All other factors were positively associated with stroke, although with lower odds ratios. Atrial fibrillation, while present in only 11.2% of the population, confirmed its association with an increased risk of stroke and/or transient ischemic attack (odds ratio 2.04; 95% confidence interval 1.71–2.44). Conclusions: All risk factors included in the CHA2DS2-VASc score are associated with stroke/ transient ischemic attack in patients with recent acute coronary syndrome, and retain similar odds ratios to what already seen in atrial fibrillation. The utility of CHA2DS2-VASc score for risk stratification of stroke in patients with acute coronary syndrome remains to be determined.
Generalized Joint Laxity and Ligament Injuries in High School–Aged Female Volleyball Players in Japan
Authors: Sueyoshi Ted , Emoto Gen , Yuasa Tomoki 
Published: October 2016

Background: Generalized joint laxity has been linked to ligamentous injuries such as anterior cruciate ligament tear and ankle sprain. Purpose/Hypothesis: The purpose of this study was to investigate generalized joint laxity and incidence of ligament injuries in high school–aged female volleyball players. It was hypothesized that volleyball players with a past history of sprains would have increased generalized joint laxity compared with those without any history and that athletes with multiple sprains would demonstrate with a higher generalized joint laxity score than those who had only 1 sprain. Study Design: Case-control study; Level of evidence, 3. Methods: Forty-seven subjects were tested for generalized joint laxity using the Beighton and Horan Joint Mobility Index (BHJMI). They were categorized into 2 groups based on the presence of past ligament injury: injury group (IG) and noninjury group (NG). The IG group was further divided into 2 groups based on whether they had a single ligamentous injury (IGS) or multiple injuries (IGM) in the past to study whether there was any difference in scores between the subgroups. The collected data were analyzed statistically with 1-way analysis of variance. Results: Subjects in the IG group scored significantly higher on the BHJMI than those in the NG group. The mean score for the IG group was 2.40 ± 1.42, as opposed to 1.24 ± 1.09 for the NG group ( P = .006). Eleven subjects in the IG group had suffered multiple injuries or recurrent injuries (IGM) and scored significantly higher than the remaining 19 individuals in the IG group, who had only sustained a single injury (IGS). The mean BHJMI scores were 3.18 ± 1.47 and 1.95 ± 1.22 for IGM and IGS, respectively ( P = .02). Conclusion: Female athletes with a high generalized joint laxity score may be more prone to ligament injury and potentially to recurrent ligament injuries.
Boolean regulatory network reconstruction using literature based knowledge with a genetic algorithm optimization method
Authors: Dorier Julien , Crespo Isaac , Niknejad Anne , Liechti Robin , Ebeling Martin , Xenarios Ioannis 
Published: October 2016

Abstract
Background
Prior knowledge networks (PKNs) provide a framework for the development of computational biological models, including Boolean models of regulatory networks which are the focus of this work. PKNs are created by a painstaking process of literature curation, and generally describe all relevant regulatory interactions identified using a variety of experimental conditions and systems, such as specific cell types or tissues. Certain of these regulatory interactions may not occur in all biological contexts of interest, and their presence may dramatically change the dynamical behaviour of the resulting computational model, hindering the elucidation of the underlying mechanisms and reducing the usefulness of model predictions. Methods are therefore required to generate optimized contextual network models from generic PKNs.

Results
We developed a new approach to generate and optimize Boolean networks, based on a given PKN. Using a genetic algorithm, a model network is built as a sub-network of the PKN and trained against experimental data to reproduce the experimentally observed behaviour in terms of attractors and the transitions that occur between them under specific perturbations. The resulting model network is therefore contextualized to the experimental conditions and constitutes a dynamical Boolean model closer to the observed biological process used to train the model than the original PKN. Such a model can then be interrogated to simulate response under perturbation, to detect stable states and their properties, to get insights into the underlying mechanisms and to generate new testable hypotheses.

Conclusions
Generic PKNs attempt to synthesize knowledge of all interactions occurring in a biological process of interest, irrespective of the specific biological context. This limits their usefulness as a basis for the development of context-specific, predictive dynamical Boolean models. The optimization method presented in this article produces specific, contextualized models from generic PKNs. These contextualized models have improved utility for hypothesis generation and experimental design. The general applicability of this methodological approach makes it suitable for a variety of biological systems and of general interest for biological and medical research. Our method was implemented in the software optimusqual, available online at http://www.vital-it.ch/software/optimusqual/.