bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and determinants of depressive and anxiety symptoms in adults with type 2 diabetes in China: a cross-sectional study
Authors: Sun Nianquan , Lou Peian , Shang Yan , Zhang Pan , Wang Jian , Chang Guiqiu , Shi Chunlei 
Published: August 2016

ObjectivesTo evaluate the prevalence and determinants of anxiety and depression and to assess their impact on glycaemic control in participants with type 2 diabetes mellitus.DesignA cross-sectional study.SettingCommunity-based investigation in Xuzhou, China.Participants893 Chinese men and women aged 18–84 years who fulfilled the inclusion criteria.MethodsPeople with type 2 diabetes completed the Pittsburgh Sleep Quality Index and the Zung Self-Rating Anxiety and Depression Scales. Demographic and physiological characteristics were recorded. Multiple logistic regression was used to evaluate the combined effect of factors associated with anxiety and depression and to assess the effects of anxiety and depression on glycaemic control.ResultsThe prevalence of depressive symptoms and anxiety symptoms was 56.1% and 43.6%, respectively. Multivariate logistic regression analysis indicated that anxiety symptoms were associated with being woman, low income, chronic disease, depressive symptoms and poor sleep quality. Depressive symptoms were associated with being woman, older age, low education level, being single, diabetes complications, anxiety symptoms and poor sleep quality. Glycaemic control was not related to anxiety symptoms (OR=1.31, 95% CIs 0.94 to 1.67) or depressive symptoms (OR=1.23, 95% CI 0.85 to 1.63). A combination of depressive symptoms and anxiety symptoms was associated with poor glycaemic control (relative excess risk due to interaction: 4.93, 95% CI 2.09 to 7.87; attributable proportion due to interaction: 0.27, 95% CI 0.12 to 0.45).ConclusionsThere was a high prevalence of depressive and anxiety symptoms in this Chinese sample of participants, although depression and anxiety were not singly associated with glycaemic control. However, a combination of depressive and anxiety symptoms was negatively correlated with glycaemic control in participants with type 2 diabetes.
Neighbourhoods for Active Kids: study protocol for a cross-sectional examination of neighbourhood features and children's physical activity, active travel, independent mobility and body size
Authors: Oliver Melody , McPhee Julia , Carroll Penelope , Ikeda Erika , Mavoa Suzanne , Mackay Lisa , Kearns Robin A , Kyttä Marketta , Asiasiga Lanuola , Garrett Nicholas , Lin Judy , Mackett Roger , Zinn Caryn , Moewaka Barnes Helen , Egli Victoria , Prendergast Kate , Witten Karen 
Published: August 2016

IntroductionNew Zealand children's physical activity, including independent mobility and active travel, has declined markedly over recent decades. The Neighbourhoods for Active Kids (NfAK) study examines how neighbourhood built environments are associated with the independent mobility, active travel, physical activity and neighbourhood experiences of children aged 9–12 years in primary and intermediate schools across Auckland, New Zealand's largest city.Methods and analysisChild-specific indices of walkability, destination accessibility and traffic exposure will be constructed to measure the built environment in 8 neighbourhoods in Auckland. Interactive online-mapping software will be used to measure children's independent mobility and transport mode to destinations and to derive measures of neighbourhood use and perceptions. Physical activity will be measured using 7-day accelerometry. Height, weight and waist circumference will be objectively measured. Parent telephone interviews will collect sociodemographic information and parent neighbourhood perceptions. Interviews with school representative will capture supports and barriers for healthy activity and nutrition behaviours at the school level. Multilevel modelling approaches will be used to understand how differing built environment variables are associated with activity, neighbourhood experiences and health outcomes.DiscussionWe anticipate that children who reside in neighbourhoods considered highly walkable will be more physically active, accumulate more independent mobility and active travel, and be more likely to have a healthy body size. This research is timely as cities throughout New Zealand develop and implement plans to improve the liveability of intensifying urban neighbourhoods. Results will be disseminated to participants, local government agencies and through conventional academic avenues.
Cancer and the family: assessment, communication and brief interventions—the development of an educational programme for healthcare professionals when a parent has cancer
Authors: Grant Lucy , Sangha Amrit , Lister Sara , Wiseman Theresa 
Published: August 2016

ObjectiveThis study developed and piloted an educational intervention to support healthcare professionals (HCPs) to provide supportive care for families when a parent has cancer.MethodsProgramme development followed the Medical Research Council (MRC) framework, beginning with examination of theory and research, and consultation with experts. The programme content incorporated attachment theory, child development and family systems theory. It was piloted thrice with HCPs from a cancer centre. The evaluation involved a questionnaire, comprising open-ended questions, completed before and after the programme. Data from the questionnaire were analysed using framework analysis.Results31 HCPs from varying disciplines participated. The programme was evaluated positively by participants. Before the programme, participants had significant concerns about their professional competence, which included: managing their own emotions; a perceived sensitivity around raising child and family matters with patients and a lack of specialist experience, skills and knowledge. After completing the programme, participants reported greater understanding and knowledge, increased confidence to approach patients about family matters, greater skill to initiate conversations and explore family concerns and guiding parent–child communication according to the child's level of understanding, and an increased engagement and resilience for caring for parents with cancer.Significance of the resultsSupporting HCPs to provide family-centred care is likely to reduce psychological difficulties in families where a parent has cancer. Further work is planned to disseminate the programme, evaluate the transfer of skills into practice, assess how HCPs manage the emotional demands of providing supportive care over time, and consider on-going professional support for HCPs.
Adolescent mental health and earnings inequalities in adulthood: evidence from the Young-HUNT Study
Authors: Evensen Miriam , Lyngstad Torkild Hovde , Melkevik Ole , Reneflot Anne , Mykletun Arnstein 
Published: August 2016

BackgroundPrevious studies have shown that adolescent mental health problems are associated with lower employment probabilities and risk of unemployment. The evidence on how earnings are affected is much weaker, and few have addressed whether any association reflects unobserved characteristics and whether the consequences of mental health problems vary across the earnings distribution.MethodsA population-based Norwegian health survey linked to administrative registry data (N=7885) was used to estimate how adolescents' mental health problems (separate indicators of internalising, conduct, and attention problems and total sum scores) affect earnings (≥30 years) in young adulthood. We used linear regression with fixed-effects models comparing either students within schools or siblings within families. Unconditional quantile regressions were used to explore differentials across the earnings distribution.ResultsMental health problems in adolescence reduce average earnings in adulthood, and associations are robust to control for observed family background and school fixed effects. For some, but not all mental health problems, associations are also robust in sibling fixed-effects models, where all stable family factors are controlled. Further, we found much larger earnings loss below the 25th centile.ConclusionsAdolescent mental health problems reduce adult earnings, especially among individuals in the lower tail of the earnings distribution. Preventing mental health problems in adolescence may increase future earnings.
Acute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp): the impact of occlusion time on clinical outcome of directly admitted and transferred patients
Authors: Prothmann Sascha , Schwaiger Benedikt J , Gersing Alexandra S , Reith Wolfgang , Niederstadt Thomas , Felber Alexandra , Kurre Wiebke 
Published: August 2016

ObjectivesAcute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp) is a prospective multicenter study assessing the efficacy and safety of the pREset stent retriever for the treatment of intracranial vessel occlusion. Determination of the effect of transfer status on clinical outcome was a secondary objective.MethodsEfficacy was measured by recanalization success (Thrombolysis in Cerebral Infarction score ≥2b) and favorable clinical outcome at 90 days (modified Rankin Scale 0–2). Intracranial hemorrhage (ICH) and death at 90 days were safety measures. The outcome of directly admitted (DAP) and transferred (TP) patients was investigated using multivariable regression models.ResultsFour study centers included 100 patients (mean age 68.3 years, median National Institutes of Health Stroke Scale score 15). Recanalization success was achieved in 84.4% after a mean of 1.7 passes. ICH was detected in 14.0%, with 2.0% being symptomatic. At 90 days, 62.5% of the patients had a favorable outcome and 7.3% died. TP had longer occlusion times (289 vs 180 minutes, p<0.001) and a lower rate of favorable outcome (58.0% vs 78.4%, p=0.046) than DAP. Multivariable regression revealed occlusion time as the critical determinant (OR=0.963, 95% CI 0.931 to 0.997, p=0.032), whereas transfer status itself showed no significant association (OR=0.565, CI 0.133 to 2.393, p=0.438).ConclusionspREset proved to be safe and effective for the treatment of acute intracranial vessel occlusion. Increased occlusion time impaired clinical outcome in TP.Trial registration numberNCT02437409; Results.
Mentoring perception, scientific collaboration and research performance: is there a ‘gender gap’ in academic medicine? An Academic Health Science Centre perspective
Authors: Athanasiou Thanos , Patel Vanash , Garas George , Ashrafian Hutan , Hull Louise , Sevdalis Nick , Harding Sian , Darzi Ara , Paroutis Sotirios 
Published: August 2016

AbstractObjectivesThe ‘gender gap’ in academic medicine remains significant and predominantly favours males. This study investigates gender disparities in research performance in an Academic Health Science Centre, while considering factors such as mentoring and scientific collaboration.Materials and methodsProfessorial registry-based electronic survey (n=215) using bibliometric data, a mentoring perception survey and social network analysis. Survey outcomes were aggregated with measures of research performance (publications, citations and h-index) and measures of scientific collaboration (authorship position, centrality and social capital). Univariate and multivariate regression models were constructed to evaluate inter-relationships and identify gender differences.ResultsOne hundred and four professors responded (48% response rate). Males had a significantly higher number of previous publications than females (mean 131.07 (111.13) vs 79.60 (66.52), p=0.049). The distribution of mentoring survey scores between males and females was similar for the quality and frequency of shared core, mentor-specific and mentee-specific skills. In multivariate analysis including gender as a variable, the quality of managing the relationship, frequency of providing corrective feedback and frequency of building trust had a statistically significant positive influence on number of publications (all p&lt;0.05).ConclusionsThis is the first study in healthcare research to investigate the relationship between mentoring perception, scientific collaboration and research performance in the context of gender. It presents a series of initiatives that proved effective in marginalising the gender gap. These include the Athena Scientific Women's Academic Network charter, new recruitment and advertisement strategies, setting up a ‘Research and Family Life’ forum, establishing mentoring circles for women and projecting female role models.
Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis
Authors: Sweeney Shannon R , Kavanaugh Arthur , Lodi Alessia , Wang Bo , Boyle David , Tiziani Stefano , Guma Monica 
Published: August 2016

ObjectiveTo determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire1H-NMR and ultra high pressure liquid chromatography (UPLC)–MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that1H-NMR and UPLC–MS/MS may be promising tools for predicting response to rituximab.
Competition during enrichment of pathogenicEscherichia colimay result in culture bias
Authors: Conrad Cheyenne C. , Stanford Kim , McAllister Tim A. , Thomas James , Reuter Tim 
Published: August 2016

Deadly outbreaks and illnesses due to Shiga toxin-producing Escherichia coli (STEC) occur worldwide; however, the cultivation methods required for adequate monitoring and traceback investigations are inefficient at best. Detection of STEC relies heavily on enrichment; yet no standard media or protocols exist. Furthermore, whether enrichment may bias detection of multiple STEC serogroups from complex samples is unknown. Thus, 14 STEC strains of serogroups O157 and the top six non-O157s (O26, O45, O103, O111, O121, and O145) were enriched in pairs for 6–78 h in broth and evaluated by quantitative polymerase chain reaction (qPCR). Here we show that a conventional 6-h enrichment protocol did not result in intra-species culture bias for the isolates tested. However, subsequent enrichments often produced biased cultures, with differences in the qPCR gene copy number ≥2 log10apparent in 12%, 38%, and 52% of competitions after 30, 54, and 78 h of consecutive enrichments, respectively. Some strains were able to prevail and (or) out-compete the opponent strain in 100% of competitions. Our results suggest that culture bias should be considered and (or) evaluated further due to the potential implications during routine pathogen screening and outbreak investigations.
NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine
Authors: Valerie Nicholas C.K. , Hagenkort Anna , Page Brent D.G. , Masuyer Geoffrey , Rehling Daniel , Carter Megan , Bevc Luka , Herr Patrick , Homan Evert , Sheppard Nina G. , Stenmark Pål , Jemth Ann-Sofie , Helleday Thomas 
Published: August 2016

Abstract
Thiopurines are a standard treatment for childhood leukemia, but like all chemotherapeutics, their use is limited by inherent or acquired resistance in patients. Recently, the nucleoside diphosphate hydrolase NUDT15 has received attention on the basis of its ability to hydrolyze the thiopurine effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of thiopurines. In particular, increasing evidence suggests an association between the NUDT15 missense variant, R139C, and thiopurine sensitivity. In this study, we elucidated the role of NUDT15 and NUDT15 R139C in thiopurine metabolism. In vitro and cellular results argued that 6-thio-dGTP and 6-thio-GTP are favored substrates for NUDT15, a finding supported by a crystallographic determination of NUDT15 in complex with 6-thio-GMP. We found that NUDT15 R139C mutation did not affect enzymatic activity but instead negatively influenced protein stability, likely due to a loss of supportive intramolecular bonds that caused rapid proteasomal degradation in cells. Mechanistic investigations in cells indicated that NUDT15 ablation potentiated induction of the DNA damage checkpoint and cancer cell death by 6-thioguanine. Taken together, our results defined how NUDT15 limits thiopurine efficacy and how genetic ablation via the R139C missense mutation confers sensitivity to thiopurine treatment in patients. Cancer Res; 76(18); 5501–11. ©2016 AACR.
CRISPR/Cas9-Mediated Trp53 and Brca2 Knockout to Generate Improved Murine Models of Ovarian High-Grade Serous Carcinoma
Authors: Walton Josephine , Blagih Julianna , Ennis Darren , Leung Elaine , Dowson Suzanne , Farquharson Malcolm , Tookman Laura A. , Orange Clare , Athineos Dimitris , Mason Susan , Stevenson David , Blyth Karen , Strathdee Douglas , Balkwill Frances R. , Vousden Karen , Lockley Michelle , McNeish Iain A. 
Published: August 2016

Abstract
There is a need for transplantable murine models of ovarian high-grade serous carcinoma (HGSC) with regard to mutations in the human disease to assist investigations of the relationships between tumor genotype, chemotherapy response, and immune microenvironment. In addressing this need, we performed whole-exome sequencing of ID8, the most widely used transplantable model of ovarian cancer, covering 194,000 exomes at a mean depth of 400× with 90% exons sequenced &gt;50×. We found no functional mutations in genes characteristic of HGSC (Trp53, Brca1, Brca2, Nf1, and Rb1), and p53 remained transcriptionally active. Homologous recombination in ID8 remained intact in functional assays. Further, we found no mutations typical of clear cell carcinoma (Arid1a, Pik3ca), low-grade serous carcinoma (Braf), endometrioid (Ctnnb1), or mucinous (Kras) carcinomas. Using CRISPR/Cas9 gene editing, we modeled HGSC by generating novel ID8 derivatives that harbored single (Trp53–/–) or double (Trp53–/–;Brca2–/–) suppressor gene deletions. In these mutants, loss of p53 alone was sufficient to increase the growth rate of orthotopic tumors with significant effects observed on the immune microenvironment. Specifically, p53 loss increased expression of the myeloid attractant CCL2 and promoted the infiltration of immunosuppressive myeloid cell populations into primary tumors and their ascites. In Trp53–/–;Brca2–/– mutant cells, we documented a relative increase in sensitivity to the PARP inhibitor rucaparib and slower orthotopic tumor growth compared with Trp53–/– cells, with an appearance of intratumoral tertiary lymphoid structures rich in CD3+ T cells. This work validates new CRISPR-generated models of HGSC to investigate its biology and promote mechanism-based therapeutics discovery. Cancer Res; 76(20); 6118–29. ©2016 AACR.
Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization
Authors: Chen Min-Min , Xiao Xiao , Lao Xiang-Ming , Wei Yuan , Liu Rui-Xian , Zeng Qiu-Hui , Wang Jun-Cheng , Ouyang Fang-Zhu , Chen Dong-Ping , Chan Ka-Wo , Shi Dai-Chao , Zheng Limin , Kuang Dong-Ming 
Published: August 2016

Abstract
The existence, regulation, and functions of IL21+ immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21+ TFH-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4+ T-cell population at levels comparable with the TFH cells present in lymph nodes. However, these TFH-like cells displayed a unique CXCR5−PD-1lo/−BTLA−CD69hi tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of TFH cells. Toll-like receptor 4 (TLR4)–elicited innate monocyte inflammation was important for IL21+ TFH-like cell induction in tumors, and activation of STAT1 and STAT3 was critical for TFH-like cell polarization in this process. Importantly, the TFH-like cells operated in IL21–IFNγ-dependent pathways to induce plasma cell differentiation and thereby create conditions for protumorigenic M2b macrophage polarization and cancer progression. Thus, induction of TFH-like cells links innate inflammation to immune privilege in tumors.
Significance: We identified a novel protumorigenic IL21+ TFH-like cell subset with a CXCR5−PD-1− BTLA−CD69hi tissue-resident phenotype in hepatoma. TLR4-mediated monocyte inflammation and subsequent T-cell STAT1 and STAT3 activation are critical for TFH-like cell induction. TFH-like cells operate via IL21–IFNγ pathways to induce plasma cells and create conditions for M2b macrophage polarization. Cancer Discov; 6(10); 1182–95. ©2016 AACR.
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O retorno ao trabalho na perspectiva de terapeutas ocupacionais: facilitadores e barreiras
Authors: Rossi da Silva Talita Naiara , Oliveira Alves Gisele Beatriz , Assis Marcella Guimarães 
Published: August 2016

Este estudo tem como objetivo compreender as percepções dos terapeutas ocupacionais em relação aos fatores facilitadores e as barreiras para o retorno ao trabalho. Fundamentase na abordagem qualitativa. Participaram cinco terapeutas ocupacionais que atuam no Instituto Nacional de Seguro Social da Região Metropolitana de Belo Horizonte. A coleta de dados foi realizada por meio de questionário online. As respostas foram analisadas a partir da análise de conteúdo da qual emergiram três categorias temáticas: Segurados: aspectos pessoais e interrelacionais; Empresas e INSS: fatores organizacionais e recursos humanos; e Políticas Públicas: capacitação e contratação de trabalhadores. Os resultados apontaram entre os facilitadores para o retorno ao trabalho a motivação dos trabalhadores, a qualificação, a integração entre INSS e as empresas, e as políticas que apoiam a capacitação. Como barreiras foram reveladas as experiências profissionais restritas, a desarticulação entre as áreas do INSS, o desinteresse das empresas para adaptar situações de trabalho e a descontinuidade dos recursos para a Reabilitação Profissional. O retorno ao trabalho é um processo multifatorial e requer a atuação de diferentes atores sociais na transformação do trabalho para potencializar os facilitadores e modificar as barreiras.