bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis
Authors: Aushev Vasily N. , Lee Eunjee , Zhu Jun , Gopalakrishnan Kalpana , Li Qian , Teitelbaum Susan L. , Wetmur James , Degli Esposti Davide , Hernandez-Vargas Hector , Herceg Zdenko , Parada Humberto , Santella Regina M. , Gammon Marilie D. , Chen Jia 
Published: November 2017

AbstractPurpose: Breast cancer is among the leading causes of cancer-related death; discovery of novel prognostic markers is needed to improve outcomes. Combining systems biology and epidemiology, we investigated miRNA-associated genes and breast cancer survival in a well-characterized population-based study.Experimental Design: A recently developed algorithm, ActMiR, was used to identify key miRNA “activities” corresponding to target gene degradation, which were predictive of breast cancer mortality in published databases. We profiled miRNA-associated genes in tumors from our well-characterized population-based cohort of 606 women with first primary breast cancer. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI), after 15+ years of follow-up with 119 breast cancer–specific deaths.Results: miR-500a activity was identified as a key miRNA for estrogen receptor–positive breast cancer mortality using public databases. From a panel of 161 miR-500a–associated genes profiled, 73 were significantly associated with breast cancer–specific mortality (FDR &lt; 0.05) in our population, among which two clusters were observed to have opposing directions of association. For example, high level of SUSD3 was associated with reduced breast cancer–specific mortality (HR = 0.3; 95% CI, 0.2–0.4), whereas the opposite was observed for TPX2 (HR = 2.7; 95% CI, 1.8–3.9). Most importantly, we identified set of genes for which associations with breast cancer–specific mortality were independent of known prognostic factors, including hormone receptor status and PAM50–derived risk-of-recurrence scores. These results are validated in independent datasets.Conclusions: We identified novel markers that may improve prognostic efficiency while shedding light on molecular mechanisms of breast cancer progression. Clin Cancer Res; 24(3); 581–91. ©2017 AACR.
Clinical Application of Circulating Tumor DNA in the Genetic Analysis of Patients with Advanced GIST
Authors: Xu Hao , Chen Liang , Shao Yang , Zhu Dongqin , Zhi Xiaofei , Zhang Qiang , Li Fengyuan , Xu Jianghao , Liu Xisheng , Xu Zekuan 
Published: November 2017

Abstract
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of digestive tract. In the past, tissue biopsy was the main method for the diagnosis of GISTs. Although, circulating tumor DNA (ctDNA) detection by next-generation sequencing (NGS) may be a feasible and replaceable method for diagnosis of GISTs. We retrospectively analyzed the data for ctDNA and tissue DNA detection from 32 advanced GIST patients. We found that NGS obviously increased the positive rate of ctDNA detection. ctDNA detection identified rare mutations that were not detected in tissue DNA detection. Tumor size and Ki-67 were significant influencing factors of the positive rate of ctDNA detection and concordance between ctDNA and tissue DNA detection. In all patients, the concordance rate between ctDNA and tissue DNA detection was 71.9%, with moderate concordance, but the concordance was strong for patients with tumor size &gt; 10 cm or Ki-67 &gt; 5%. Tumor size, mitotic figure, Ki-67, and ctDNA mutation type were the significant influencing factors of prognosis, but only tumor size and ctDNA mutation type, were the independent prognostic factors for advanced GIST patients. We confirmed that ctDNA detection by NGS is a feasible and promising method for the diagnosis and prognosis of advanced GIST patients. Mol Cancer Ther; 17(1); 290–6. ©2017 AACR.
Competitive Kinase Enrichment Proteomics Reveals that Abemaciclib Inhibits GSK3β and Activates WNT Signaling
Authors: Cousins Emily M. , Goldfarb Dennis , Yan Feng , Roques Jose , Darr David , Johnson Gary L. , Major Michael B. 
Published: November 2017

Abstract
The cellular and organismal phenotypic response to a small-molecule kinase inhibitor is defined collectively by the inhibitor's targets and their functions. The selectivity of small-molecule kinase inhibitors is commonly determined in vitro, using purified kinases and substrates. Recently, competitive chemical proteomics has emerged as a complementary, unbiased, cell-based methodology to define the target landscape of kinase inhibitors. Here, we evaluated and optimized a competitive multiplexed inhibitor bead mass spectrometry (MIB/MS) platform using cell lysates, live cells, and treated mice. Several clinically active kinase inhibitors were profiled, including trametinib, BMS-777607, dasatinib, abemaciclib, and palbociclib. MIB/MS competition analyses of the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors abemaciclib and palbociclib revealed overlapping and unique kinase targets. Competitive MIB/MS analysis of abemaciclib revealed 83 target kinases, and dose–response MIB/MS profiling revealed glycogen synthase kinase 3 alpha and beta (GSK3α and β) and Ca2+/calmodulin-dependent protein kinase II delta and gamma (CAMKIIδ and γ) as the most potently inhibited. Cell-based and in vitro kinase assays show that in contrast to palbociclib, abemaciclib directly inhibits GSK3α/β and CAMKIIγ/δ kinase activity at low nanomolar concentrations. GSK3β phosphorylates β-catenin to suppress WNT signaling, while abemaciclib (but not palbociclib or ribociclib) potently activates β-catenin-dependent WNT signaling. These data illustrate the power of competitive chemical proteomics to define kinase target specificities for kinase inhibitors, thus informing clinical efficacy, dose-limiting toxicities, and drug-repurposing efforts.
Implications: This study uses a rapid and quantitative proteomics approach to define inhibitor-target data for commonly administered therapeutics and provides a cell-based alternative to in vitro kinome profiling. Mol Cancer Res; 16(2); 333–44. ©2017 AACR.
Treatment and Outcomes of Working Aged Adults with Stroke: Results from a National Prospective Registry
Authors: Lannin Natasha A. , Anderson Craig S. , Kim Joosup , Kilkenny Monique , Bernhardt Julie , Levi Christopher , Dewey Helen M. , Bladin Christopher , Hand Peter , Castley Helen , Hill Kelvin , Faux Steven , Grimley Rohan , Grabsch Brenda , Middleton Sandy , Donnan Geoffrey , Cadilhac Dominique A. 
Published: November 2017

<b><i>Background:</i></b> Given the potential differences in etiology and impact, the treatment and outcome of younger patients (aged 18–64 years) require examination separately to older adults (aged ≥65 years) who experience acute stroke. <b><i>Methods:</i></b><i></i> Data from the Australian Stroke Clinical Registry (2010–2015) including demographic and clinical characteristics, provision of evidence-based therapies and health-related quality of life (HRQoL) post-stroke was used. Descriptive statistics and multilevel regression models were used for group comparisons. <b><i>Results:</i></b> Compared to older patients (age ≥65 years) among 26,220 registrants, 6,526 (25%) younger patients (age 18–64 years) were more often male (63 vs. 51%; <i>p</i> &#x3c; 0.001), born in Australia (70 vs. 63%; <i>p</i> &#x3c; 0.001), more often discharged home from acute care (56 vs. 38%; <i>p</i> &#x3c; 0.001), and less likely to receive antihypertensive medication (61 vs. 73%; <i>p</i> &#x3c; 0.001). Younger patients had a 74% greater odds of having lower HRQoL compared to an equivalent aged-matched general population (adjusted OR 1.74, 95% CI 1.56–1.93, <i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b><i></i> Younger stroke patients exhibited distinct differences from their older counterparts with respect to demographic and clinical characteristics, prescription of antihypertensive medications and residual health status.
The Festival of Dionysus in 2 Macc 6:7b
Authors: Scolnic Benjamin Edidin 
Published: November 2017

AbstractRecent scholarship has maintained that the Dionysian rites of 2 Macc 6:7b are not historical because evidence of this cult in Seleukid official policy is seen as meager at best. A review of AntiochusIV’s coinage, his procession at Daphne, his designation of Geron the Athenian as enforcer of the imposed cult, and other allusions to promiscuity in the Temple may indicate that this reference to Dionysian practices is at least plausible.
Seeing Christ, Reading Nature
Authors: Ribouillault Denis 
Published: November 2017

This paper provides a detailed interpretation of a little-known yet extraordinary painting from the Montreal Museum of Fine Arts, Christ in a Landscape by Jan Swart van Groningen (ca. 1530–1540). This work is a perfect illustration of the importance of the popular Christian metaphor of the “Book of Nature” in early modern art, especially in the Reformed circles to which Swart likely belonged. Beyond offering an explanation for the presence of some strange aspects of the landscape (a snail, shells and colored pearls, unicorns, rocks with anthropomorphic features, etc.), the article explores the ways in which the elements of the landscape engaged the viewer in a hermeneutic process, a process of interpretation and reflection on the mysteries of nature and faith. The painting is a meditation on kenosis – the dual nature of Christ as both divine and human, and thus belonging to Nature just like the most insignificant of its creatures.
Modulation of Tropical Cyclogenesis Location and Frequency over the Indo–Western North Pacific by the Intraseasonal Indo–Western Pacific Convection Oscillation during the Boreal Extended Summer
Authors: Wang Qiuyun , Li Jianping , Li Yanjie , Zhang Jingwen , Zheng Jiayu 
Published: November 2017

AbstractThe influence of the intraseasonal Indo–western Pacific convection oscillation (IPCO) on tropical cyclone (TC) genesis location and frequency over the Indo–western North Pacific (WNP) during the boreal extended summer (May–October) is explored. Observational analysis shows that the impacts of the intraseasonal IPCO on TCs over the Indo–WNP include an evident “phase lock of TC genesis location” and distinct differences in TC frequency. In the WNP, in the positive intraseasonal IPCO phase, the atmosphere gains heat through the release of latent heat in cumulus convective condensation, and the anomalous cyclonic circulation weakens the western Pacific subtropical high (WPSH) and enhances TC genesis, thereby tending to produce many more TCs. Moreover, the diminished WPSH and the westward shift of the centers of anomalous cyclonic circulations lock TC genesis locations to the west WNP and lower latitudes (around 5°–20°N), especially in the South China Sea. The almost opposite situation occurs in a negative phase. In the north Indian Ocean, the total TC genesis frequencies in the two intraseasonal IPCO phases are approximate. However, in the positive intraseasonal IPCO phase, the environmental conditions to the north of 13°N are similar to those in the WNP except without the WPSH control, whereas south of 13°N the situation is reversed, leading to a northward shift of the TC genesis location (around 13°–20°N). The negative phase reflects an opposite situation.
The Lifecycle of Semidiurnal Internal Tides over the Northern Mid-Atlantic Ridge
Authors: Vic Clément , Naveira Garabato Alberto C. , Green J. A. Mattias , Spingys Carl , Forryan Alexander , Zhao Zhongxiang , Sharples Jonathan 
Published: November 2017

AbstractThe life cycle of semidiurnal internal tides over the Mid-Atlantic Ridge (MAR) sector south of the Azores is investigated using in situ, a high-resolution mooring and microstructure profiler, and satellite data, in combination with a theoretical model of barotropic-to-baroclinic tidal energy conversion. The mooring analysis reveals that the internal tide horizontal energy flux is dominated by mode 1 and that energy density is more distributed among modes 1–10. Most modes are compatible with an interpretation in terms of standing internal tides, suggesting that they result from interactions between waves generated over the MAR. Internal tide energy is thus concentrated above the ridge and is eventually available for local diapycnal mixing, as endorsed by the elevated rates of turbulent energy dissipation ε estimated from microstructure measurements. A spring–neap modulation of energy density on the MAR is found to originate from the remote generation and radiation of strong mode-1 internal tides from the Atlantis-Meteor Seamount Complex. Similar fortnightly variability of a factor of 2 is observed in ε, but this signal’s origin cannot be determined unambiguously. A regional tidal energy budget highlights the significance of high-mode generation, with 81% of the energy lost by the barotropic tide being converted into modes >1 and only 9% into mode 1. This has important implications for the fraction (q) of local dissipation to the total energy conversion, which is regionally estimated to be ~0.5. This result is in stark contrast with the Hawaiian Ridge system, where the radiation of mode-1 internal tides accounts for 30% of the regional energy conversion, and q < 0.25.
Impact of an Elementary School-Based Intervention on Physical Activity Time and Aerobic Capacity, Georgia, 2013-2014
Authors: Braun Hayley A. , Kay Christi M. , Cheung Patricia , Weiss Paul S. , Gazmararian Julie A. 
Published: November 2017

Objectives: The objectives of this study were to (1) determine the impact of a 1-year elementary school physical activity intervention on changes in teacher-reported school-based physical activity time and (2) assess the relationship between these changes and changes in student aerobic capacity. Methods: HealthMPowers, a nonprofit organization, provided a multicomponent physical activity intervention to 3479 students in 39 schools in Georgia during 2013-2014. HealthMPowers administered a survey to faculty members before (August 2013) and after (May 2014) the intervention to measure student physical activity times. The organization collected pre- and post-intervention Progressive Aerobic Cardiovascular Endurance Run (PACER) laps (a measure of aerobic capacity that awards 1 lap for each completed 20-meter lap) for 2342 fourth-grade students. We performed linear regression to determine the relationship between school-level changes in teacher-reported school-based physical activity time and student aerobic capacity. Results: The weekly estimated teacher-reported time in physical activity increased by 39 minutes from pre- to post-intervention: 21 minutes for recess, 17 minutes for classroom, and 1 minute for physical education. The mean number of student PACER laps increased by 3 laps from pre- to post-intervention, and 1515 of 2342 (65%) students increased the number of PACER laps completed. We observed a positive association between school-level changes in school-based physical activity time and school-level changes in PACER laps ( r = 0.38; 95% confidence interval, 0.29-0.46). Conclusions: These findings highlight the need for more prospective research into multicomponent physical activity interventions. Rigorous testing, including randomized controlled trials of large-scale implementations, is needed to examine how these school-based interventions might be used to improve the physical activity and fitness of larger populations of children.
Like Peas and Carrots: Combining Wellness Policy Implementation With Classroom Education for Obesity Prevention in the Childcare Setting
Authors: Cotwright Caree J. , Bales Diane W. , Lee Jung Sun , Parrott Kathryn , Celestin Nathalie , Olubajo Babatunde 
Published: November 2017

Objectives: We evaluated an intervention combining policy training and technical assistance for childcare teachers with a nutrition education curriculum to improve (1) the knowledge and self-efficacy of childcare teachers in implementing obesity prevention policies and practices, (2) the quantity and quality of nutrition and physical activity education, and (3) the childcare wellness environment. Methods: Thirteen teachers and 8 administrators (2 of whom were also teachers) from 8 childcare programs in Clarke County, Georgia, participated in the Healthy Child Care Georgia intervention during June-October 2015. The intervention included (1) training and technical assistance on obesity prevention policies, systems, and practices and (2) direct education by teachers using the Eat Healthy, Be Active curriculum. We assessed changes in program wellness policy adoption and teacher knowledge and self-efficacy from pre- to post-intervention through self-report questionnaires, interviews, and focus groups. Results: Teachers’ knowledge scores (maximum score = 100) rose significantly from a mean (SD) pre-intervention of 67.1 (14.6) to post-intervention of 83.2 (14.3) ( P < .001). The mean score for “teaching nutrition and activity to children” (maximum score = 105) rose significantly from 86.9 (8.2) to 93.5 (5.2) ( P = .011) and for “modeling and supporting children” (maximum score = 63) from 55.8 (5.1) to 59.5 (4.5) ( P = .015). The mean (SD) scores for breastfeeding and infant feeding policy/practice adoption (maximum score = 6) increased significantly from 2.5 (1.8) to 3.7 (1.9) ( P = .043) and for nutrition education policy/practice adoption (maximum score = 4) from 2.0 (1.3) to 3.3 (1.4) ( P = .019). The combined approach enhanced classroom nutrition education and improved the adoption of best practices. Conclusion: Future studies should examine the effects of using a combined approach to promote nutrition and physical activity policies and practices in the early care and education setting.
Systems Thinking and Simulation Modeling to Inform Childhood Obesity Policy and Practice
Authors: Powell Kenneth E. , Kibbe Debra L. , Ferencik Rachel , Soderquist Chris , Phillips Mary Ann , Vall Emily Anne , Minyard Karen J. 
Published: November 2017

Objectives: In 2007, 31.7% of Georgia adolescents in grades 9-12 were overweight or obese. Understanding the impact of policies and interventions on obesity prevalence among young people can help determine statewide public health and policy strategies. This article describes a systems model, originally launched in 2008 and updated in 2014, that simulates the impact of policy interventions on the prevalence of childhood obesity in Georgia through 2034. Methods: In 2008, using information from peer-reviewed reports and quantitative estimates by experts in childhood obesity, physical activity, nutrition, and health economics and policy, a group of legislators, legislative staff members, and experts trained in systems thinking and system dynamics modeling constructed a model simulating the impact of policy interventions on the prevalence of childhood obesity in Georgia through 2034. Use of the 2008 model contributed to passage of a bill requiring annual fitness testing of schoolchildren and stricter enforcement of physical education requirements. We updated the model in 2014. Results: With no policy change, the updated model projects that the prevalence of obesity among children and adolescents aged ≤18 in Georgia would hold at 18% from 2014 through 2034. Mandating daily school physical education (which would reduce prevalence to 12%) and integrating moderate to vigorous physical activity into elementary classrooms (which would reduce prevalence to 10%) would have the largest projected impact. Enacting all policies simultaneously would lower the prevalence of childhood obesity from 18% to 3%. Conclusions: Systems thinking, especially with simulation models, facilitates understanding of complex health policy problems. Using a simulation model to educate legislators, educators, and health experts about the policies that have the greatest short- and long-term impact should encourage strategic investment in low-cost, high-return policies.
Evaluating the Impact of Training in Obesity Prevention Methods on the Counseling, Knowledge, and Skills of WIC Nutritionists in Georgia, 2014-2015
Authors: Palmer Wendy , Henderson Danielle , Stahnke Barbara , Shary Katherine , Hardy Trisha , Welsh Jean A. 
Published: November 2017

Objectives: Motivational interviewing, a client-centered intervention method focused on enhancing intrinsic motivation for behavior change, shows a positive impact on children’s weight status (ie, stabilizing or slowing down weight gain as a child grows). We evaluated the impact of a training program on knowledge and adoption of evidence-based obesity prevention counseling strategies among counselors from Georgia’s Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Methods: Between July 2014 and September 2015, Children’s Healthcare of Atlanta’s Strong4Life program provided 388 WIC counselors in Georgia with a 2-hour training session on motivational interviewing, patient-centered counseling, and goal setting for obesity prevention. We evaluated the training using (1) self-administered pre- and post-training surveys that assessed knowledge of counseling strategies, (2) post-training observation of counseling interactions, and (3) a review of behavior change goal quality pre- and post-training in a random sample of 200 WIC client charts. Results: In a comparison of pre-training knowledge with immediate post-training knowledge among 388 counselors, 81% vs 91% ( P < .001) knew that, to be effective, goals must be important to clients, and 66% vs 94% ( P < .001) knew the 5 A’s (assess, advise, agree, assist, arrange) of counseling. Knowledge improvements were sustained at 3 months post-training. We observed no improvements in the quality of chart-documented behavior goals. Conclusions: WIC nutrition counselors in Georgia were aware of evidence-based counseling strategies but did not consistently apply them. The training program was helpful, but time and additional support are needed to adopt new practices.
Factors influencing two-way referral between hospitals and the community in China: A system dynamics simulation model
Authors: Li Meina , Zhang Yi , Lu Yang , Yu Wenya , Nong Xin , Zhang Lulu 
Published: November 2017

Background: Two-way referrals between hospitals and community healthcare systems (CHSs) are important for optimizing the distribution of medical resources and enabling resource sharing, but referrals are always from CHSs to hospitals. A referral from the hospital to the community is rare in China; this has a highly negative impact on the long-term development of the Chinese health services. The aim of this study was to address influence factors in hospital–community referrals. Methods: We constructed a system dynamics model to address the problem of the two-way referral between hospitals and CHSs and identified potential countermeasures and possible solutions. The Vensim DSS program was used to construct a system dynamics model to represent the problem through model description, causal loop diagrams, and stock and flow diagrams. Results: The model was used to perform intervention experiments, in which the influence on all the sectors of referrals could be observed by changing the system parameters. The experimental results showed a greater difference in medical costs between hospitals and CHSs, more investments to CHSs, higher levels of medical insurance of CHSs, and more referrals from hospitals to CHSs. Conclusions: The system can widen the price gap between hospitals and CHSs, increase information flow, improve medical insurance level of CHSs, and elevate the current level of CHSs through enabling two-way referral between hospitals and CHSs.