bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of arc migration in the development of the Lesser Antilles: A new tectonic model for the Cenozoic evolution of the eastern Caribbean
Authors: Allen R.W. , Collier J.S. , Stewart A.G. , Henstock T. , Goes S. , Rietbrock A. ,   the VoiLA Team
Published: August 2019

Abstract
Continental arc systems often show evidence of large-scale migration both toward and away from the incoming plate. In oceanic arc systems, however, while slab roll-back and the associated processes of backarc spreading and arc migration toward the incoming plate are commonplace, arc migration away from the incoming plate is rarely observed. We present a new compilation of marine magnetic anomaly and seismic data in order to propose a new tectonic model for the eastern Caribbean region that includes arc migration in both directions. We synthesized new evidence to show two phases of backarc spreading and eastward arc migration toward the incoming Atlantic. A third and final phase of arc migration to the west subdivided the earlier backarc basin on either side of the present-day Lesser Antilles arc. This is the first example of regional multidirectional arc migration in an intra-oceanic setting, and it has implications for along-arc structural and geochemical variations. The back and forth arc migrations were probably due to the constraints imposed by the neighboring American plates on this isolated subduction system, rather than variations in subducting slab buoyancy.
Pubertal boy presenting with mild disproportionate short stature
Authors: Pellegrin Maria Chiara , Tornese Gianluca , Barbi Egidio 
Published: August 2019

­A boy aged 12 years was referred with short stature. He was born at term, of adequate weight (10–25th centile) and length (10–25th centile), which settled to just below the third centile from 18 months of age, with a growth deceleration in the last 6 months (growth velocity −2.1 standard deviation score, according to Tanner charts). He was otherwise asymptomatic. His mother’s height was 155 cm, and father’s height 158 cm, and he was growing near his target height centile (−2.26 SDS, <3rd centile).On examination, his height was −2.22 SDS, with normal weight and body mass index (BMI). Pubertal stage corresponded to Tanner 2, with a testicular volume of 4 mL. His legs and forearms appeared shorter, with arm span/height ratio 0.93 (normal value >0.965) and sitting height/height ratio 0.56 (slightly above the normal upper value of 0.55). He resembled his father, whose wrists were abnormally curved (figure 1). The patient’s hand X-ray showed that bone age was similar to chronological age.Figure 1Disproportionate mesomelic short stature in the patient and in his father.QuestionsWhat is the most likely diagnosis?Constitutional growth delayGrowth hormone deficiencySHOX gene deficiencyIdiopathic short statureWhich diagnostic test should be considered?How should this patient be managed?Answers can be found on page 2.
Efficacy of adaptive e-learning for health professionals and students: a systematic review and meta-analysis
Authors: Fontaine Guillaume , Cossette Sylvie , Maheu-Cadotte Marc-André , Mailhot Tanya , Deschênes Marie-France , Mathieu-Dupuis Gabrielle , Côté José , Gagnon Marie-Pierre , Dubé Veronique 
Published: August 2019

ObjectiveAlthough adaptive e-learning environments (AEEs) can provide personalised instruction to health professional and students, their efficacy remains unclear. Therefore, this review aimed to identify, appraise and synthesise the evidence regarding the efficacy of AEEs in improving knowledge, skills and clinical behaviour in health professionals and students.DesignSystematic review and meta-analysis.Data sourcesCINAHL, EMBASE, ERIC, PsycINFO, PubMed and Web of Science from the first year of records to February 2019.Eligibility criteriaControlled studies that evaluated the effect of an AEE on knowledge, skills or clinical behaviour in health professionals or students.Screening, data extraction and synthesisTwo authors screened studies, extracted data, assessed risk of bias and coded quality of evidence independently. AEEs were reviewed with regard to their topic, theoretical framework and adaptivity process. Studies were included in the meta-analysis if they had a non-adaptive e-learning environment control group and had no missing data. Effect sizes (ES) were pooled using a random effects model.ResultsFrom a pool of 10 569 articles, we included 21 eligible studies enrolling 3684 health professionals and students. Clinical topics were mostly related to diagnostic testing, theoretical frameworks were varied and the adaptivity process was characterised by five subdomains: method, goals, timing, factors and types. The pooled ES was 0.70 for knowledge (95% CI −0.08 to 1.49; p.08) and 1.19 for skills (95% CI 0.59 to 1.79; p<0.00001). Risk of bias was generally high. Heterogeneity was large in all analyses.ConclusionsAEEs appear particularly effective in improving skills in health professionals and students. The adaptivity process within AEEs may be more beneficial for learning skills rather than factual knowledge, which generates less cognitive load. Future research should report more clearly on the design and adaptivity process of AEEs, and target higher-level outcomes, such as clinical behaviour.PROSPERO registration numberCRD42017065585
Factors associated with maternity waiting home use among women in Jimma Zone, Ethiopia: a multilevel cross-sectional analysis
Authors: Kurji Jaameeta , Gebretsadik Lakew Abebe , Wordofa Muluemebet Abera , Sudhakar Morankar , Asefa Yisalemush , Kiros Getachew , Mamo Abebe , Bergen Nicole , Asfaw Shifera , Bedru Kunuz Haji , Bulcha Gebeyehu , Labonte Ronald , Taljaard Monica , Kulkarni Manisha 
Published: August 2019

ObjectiveTo identify individual-, household- and community-level factors associated with maternity waiting home (MWH) use in Ethiopia.DesignCross-sectional analysis of baseline household survey data from an ongoing cluster-randomised controlled trial using multilevel analyses.SettingTwenty-four rural primary care facility catchment areas in Jimma Zone, Ethiopia.Participants3784 women who had a pregnancy outcome (live birth, stillbirth, spontaneous/induced abortion) 12 months prior to September 2016.Outcome measureThe primary outcome was self-reported MWH use for any pregnancy; hypothesised factors associated with MWH use included woman’s education, woman’s occupation, household wealth, involvement in health-related decision-making, companion support, travel time to health facility and community-levels of institutional births.ResultsOverall, 7% of women reported past MWH use. Housewives (OR: 1.74, 95% CI 1.20 to 2.52), women with companions for facility visits (OR: 2.15, 95% CI 1.44 to 3.23), wealthier households (fourth vs first quintile OR: 3.20, 95% CI 1.93 to 5.33) and those with no health facility nearby or living >30 min from a health facility (OR: 2.37, 95% CI 1.80 to 3.13) had significantly higher odds of MWH use. Education, decision-making autonomy and community-level institutional births were not significantly associated with MWH use.ConclusionsUtilisation inequities exist; women with less wealth and companion support experienced more difficulties in accessing MWHs. Short duration of stay and failure to consider MWH as part of birth preparedness planning suggests local referral and promotion practices need investigation to ensure that women who would benefit the most are linked to MWH services.
Association between maternal education and breast feeding practices in China: a population-based cross-sectional study
Authors: Tang Kun , Wang Hanyu , Tan Shi Hui , Xin Tong , Qu Xueqi , Tang Tianyu , Wang Yuqi , Liu Yuning , Gaoshan Junjian 
Published: August 2019

ObjectiveTo investigate the association between maternal education and breast feeding in the Chinese population, with a consideration of household income and health-seeking behaviours.DesignA nationally representative population-based cross-sectional study.Setting77 counties from 12 geographically distinct regions in China.Participants10 408 mothers with children from 0 to 12 months of age, aged 15–53 years old (mean: 29.15, SD: 5.11) were classified into primary school or below group (n=781), middle school group (n=3842), high school/vocational school group (n=1990), college or above group (n=3795), according to their highest completed education.OutcomesFive breastfeeding outcomes, including early initiation of breast feeding (EIB), exclusive breast feeding (EBF) under 6 months, predominant breast feeding under 6 months, current breast feeding and children ever breast fed, were calculated based on the standardised questionnaire from the WHO and Wellstart International’s toolkit for monitoring and evaluating breastfeeding activities.ResultsThe absolute risk of EIB and EBF in the lowest maternal education level was 64.85% and 26.53%, respectively, whereas the absolute risk of EIB and EBF in the highest maternal education level was 77.21% and 14.06%, respectively. A higher level of maternal education was positively associated with EIB (risk ratio (RR): 1.22; 95% CI: 1.12 to 1.30) and was inversely associated with EBF (RR: 0.59; 95% CI: 0.38 to 0.88). Stratified by household income, a positive association with EIB was observed only in the group with the highest household income and an inverse association with EBF was found in both low household and high household income groups.ConclusionsMothers with a higher education were more likely to initiate early breast feeding when they were also from a high-income household while also being less likely to exclusively breast feed their babies. Routine and successful nursing is crucial for the health of infants and is influenced by maternal education. Future public health interventions to promote breast feeding should consider the issues related to the educational level of mothers.
Efficacy of Xuebijing Injection for Sepsis (EXIT-SEP): protocol for a randomised controlled trial
Authors: Liu Songqiao , Yao Chen , Zhang Junhua , Yang Yi , Qiu Haibo 
Published: August 2019

IntroductionSepsis is a major challenge with high incidence and is associated with high mortality worldwide. Current management of sepsis remains mainly supportive except for treatment with antibiotics. Both basic research and clinical investigation have shown that the Chinese herbal-derived therapeutic Xuebijing (XBJ) injection is beneficial for patients with sepsis. However, the quality of evidence supporting the therapeutic use of XBJ in sepsis is limited. The aim of this trial is to evaluate the Efficacy of Xuebijing Injection for Sepsis, compared with a placebo, on the outcome of patients with sepsis in the intensive care unit (ICU).Methods and analysisIn this multicentre, blinded randomised controlled trial, we are recruiting a total of 1800 subjects who met Sepsis 3.0 criteria. Subjects will be randomised (1:1) to receive XBJ, every 12 hours for 5 days or a matching placebo and usual care. The primary outcome is 28 days all-cause mortality. Secondary outcomes will be the improvement of Sequential Organ Failure Assessment scores, the improvement of the Acute Physiology and Chronic Health Evaluation II score, duration of mechanical ventilation, mortality in ICU and duration of stay in the ICU. Investigators, participants and statisticians will be blinded to the allocated treatment.Ethics and disseminationThis trial has been approved by all ethics committees of the centres that will participate in this trial. The findings of the study will be disseminated in peer-reviewed journals and present at conferences. Once this study is complete, the results of this trial may help provide evidence-based recommendations for complementary therapeutic options for patients with sepsis.Trial registration numberNCT03238742and ChiCTR-IPR-17012713.
The Uppsala–Stockholm Assisted Reproductive Techniques (UppStART) study
Authors: Iliadou Anastasia N , Öberg Anna Sara , Pege Jessica , Rodriguez-Wallberg Kenny A , Olofsson Jan I , Holte Jan , Wramsby Håkan , Wramsby Margaretha , Cnattingius Sven , Cesta Carolyn E 
Published: August 2019

PurposeThe Uppsala–Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome.ParticipantsRecruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study.Findings to dateSelf-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis.Future plansThrough the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found atwww.ki.se/meb/uppstart
Alcohol outlets and firearm violence: a place-based case–control study using satellite imagery and machine learning
Authors: Jay Jonathan 
Published: August 2019

IntroductionThis article proposes a novel method for matching places based on visual similarity, using high-resolution satellite imagery and machine learning. This approach strengthens comparisons when the built environment is a potential confounder, as in many injury research studies.MethodsAs an example, I apply this method to study the spatial influence of alcohol outlets (AOs) on firearm violence in Philadelphia, Pennsylvania, specifically beer stores and bar/restaurants. Using a case–control framework, city blocks with shootings in 2017–2018 were matched with similar-looking blocks with no shootings, based on analysis with a pretrained convolutional neural network andt-distributed stochastic neighbour embedding. Logistic regression was used to estimate the OR of a shooting on the same block as an AO and within one-block and two-block distances, conditional on additional factors such as land use, demographic composition and illegal drug activity.ResultsThe case–control matches were similar in visual appearance, on human inspection, and were well balanced on covariate measures. The fully adjusted model estimated an increased shootings risk for locations with beer stores within one block,OR=1.5, 95% CI 1.1 to 2.1, p=0.02, and locations with bar/restaurants on the same block,OR=1.6, 95% CI 1.1 to 2.4, p=0.02.ConclusionThese findings align with previous study findings while addressing the concern that AOs might systematically be located in certain kinds of environments, providing stronger evidence of a causal effect on nearby firearm violence. Matching on visual similarity can improve observational injury studies involving place-based risks.
Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS
Authors: Deiva Kumaran , Huppke Peter , Banwell Brenda , Chitnis Tanuja , Gärtner Jutta , Krupp Lauren , Waubant Emmanuelle , Stites Tracy , Pearce Gregory Lewis , Merschhemke Martin 
Published: August 2019

BackgroundIn PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a.ObjectivesTo investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression.MethodsARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc.ResultsIn the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%–94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively.ConclusionsFingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years.Trial registration numberNCT01892722.
Alterations to the Esophageal Microbiome Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma
Authors: Snider Erik J. , Compres Griselda , Freedberg Daniel E. , Khiabanian Hossein , Nobel Yael R. , Stump Stephania , Uhlemann Anne-Catrin , Lightdale Charles J. , Abrams Julian A. 
Published: August 2019

Abstract

Background:
The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma.

Methods:
A case–control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome.

Results:
A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non–Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella. In the study population, patients taking proton pump inhibitors had increased Streptococcus and decreased Gram-negative bacteria overall.

Conclusions:
Shifts in the Barrett's esophagus–associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria.

Impact:
The microbiome may play a role in esophageal carcinogenesis.
COMMD3:BMI1 Fusion and COMMD3 Protein Regulate C-MYC Transcription: Novel Therapeutic Target for Metastatic Prostate Cancer
Authors: Umbreen Syed , Banday Mudassir Meraj , Jamroze Anmbreen , Mansini Adrian P. , Ganaie Arsheed A. , Ferrari Marina G. , Maqbool Raihana , Beigh Firdous H. , Murugan Paari , Morrissey Colm , Corey Eva , Konety Badrinath R. , Saleem Mohammad 
Published: August 2019

Abstract
Gene rearrangement is reported to be associated to the aggressive phenotype and poor prognosis in prostate cancer. We identified a gene fusion between a transcription repressor (BMI1) and transcriptional factor (COMMD3) in human prostate cancer. We show that COMMD3:BMI1 fusion expression is significantly increased in prostate cancer disease in an order: normal tissue &lt; primary &lt; metastatic tumors (Mets). Although elevated TMPRSS-ERG/ETV fusion is reported in prostate cancer, we identified a subtype of Mets exhibiting low TMPRSS:ETV and high COMMD3:BMI1. We delineated the mechanism and function of COMMD3 and COMMD3:BMI1 in prostate cancer. We show that COMMD3 level is elevated in prostate cancer cell models, PDX models (adenocarcinoma, NECaP), and Mets. The analysis of TCGA/NIH/GEO clinical data showed a positive correlation between increased COMMD3 expression to the disease recurrence and poor survival in prostate cancer. We show that COMMD3 drives proliferation of normal cells and promotes migration/invasiveness of neoplastic cells. We show that COMMD3:BMI1 and COMMD3 regulate C-MYC transcription and C-MYC downstream pathway. The ChIP analysis showed that COMMD3 protein is recruited at the promoter of C-MYC gene. On the basis of these data, we investigated the relevance of COMMD3:BMI1 and COMMD3 as therapeutic targets using in vitro and xenograft mouse models. We show that siRNA-mediated targeting of COMMD3:BMI1 and COMMD3 significantly decreases (i) C-MYC expression in BRD/BET inhibitor–resistant cells, (ii) proliferation/invasion in vitro, and (iii) growth of prostate cancer cell tumors in mice. The IHC analysis of tumors confirmed the targeting of COMMD3-regulated molecular pathway under in vivo conditions. We conclude that COMMD3:BMI1 and COMMD3 are potential progression biomarkers and therapeutic targets of metastatic prostate cancer.
Breast Cancer Risk–Associated SNPs in the mTOR Promoter Form De Novo KLF5- and ZEB1-Binding Sites that Influence the Cellular Response to Paclitaxel
Authors: Chen Qiuchen , Deng Xiaolan , Hu Xiaoyun , Guan Shu , He Miao , Wang Yilin , Wei Binbin , Zhang Jing , Zhao Haishan , Yao Weifan , Jin Feng , Liu Yong , Chen Jianjun , Olapade Olufunmilayo I. , Wu Huizhe , Wei Minjie 
Published: August 2019

Abstract

ZEB1 (a positive enhancer) and KLF5 (a negative silencer) affect transcription factors and play inherently conserved roles in tumorigenesis and multidrug resistance. In humans, the rs2295080T-allele at the mTOR promoter locus has been associated with human cancer risk; however, the 63 bp spacing of another SNP rs2295079 has not been identified. Here, we discovered, for the first time, that rs2295079 (-78C/G) and rs2295080 (-141G/T) formed linkage haplotypes, with Ht1 (-78C/-141G) and Ht2 (-78G/-141T) being dominant, which were associated with distinct susceptibility to breast cancer, response to paclitaxel, and clinical outcomes in breast cancer. At the cellular level, compared with Ht1, Ht2 exhibits a much stronger effect on promoting mTOR expression, leading to enhanced tumor cell growth and strengthened resistance to PTX treatment. Mechanistically, the -141T allele of Ht2 creates a novel ZEB1-binding site; meanwhile, the -78C allele of Ht1 exists as an emerging KLF5-binding site, which synergistically induces promote/inhibit mTOR expression, cell proliferation, and excretion of cytotoxic drugs through the ZEB1/KLF5–mTOR–CCND1/ABCB1 cascade, thereby affecting the response to paclitaxel treatment in vivo and in vitro. Our results suggest the existence of a ZEB1/KLF5–mTOR–CCND1/ABCB1 axis in human cells that could be involved in paclitaxel response pathways and functionally regulate interindividualized breast cancer susceptibility and prognosis.

Implications:
This study highlights the function of haplotypes of mTOR -78C/-141G and -78G/-141T, in affecting breast cancer susceptibility and paclitaxel response regulated by ZEB1/KLF5–mTOR–CCND1/ABCB1 axis.