bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing recognition of obstetric anal sphincter injuries in six maternity units in Palestine: an interventional quality improvement study
Authors: Ali-Masri Hadil , Hassan Sahar , Ismail Khaled , Zimmo Kaled , Zimmo Mohammed , Fosse Erik , Vikanes Åse , Laine Katariina 
Published: June 2018

ObjectiveTo explore the impact of a training intervention on obstetric anal sphincter injuries’ (OASIS) detection rate.DesignProspective quality improvement interventional study.SettingSix secondary and tertiary maternity units in Palestine.PopulationWomen having singleton vaginal births ≥23 weeks’ gestation or babies weighing ≥500 g (n=22 922). Caesarean births (n=5431), multiple gestations (n=443) and vaginal births of unregistered perineum status (n=800) were excluded.InterventionsTraining programme for enhancing OASIS detection was conducted between 31 January and 31 December 2015. International experts delivered 2-day standardisation workshop teaching OASIS diagnosis and repair to each maternity unit. They also provided additional training to three research fellows employed in three of the maternity units. This was followed by 13-week period of data collection (phase 1). Research fellows then delivered training intervention over 15-week interval (phase 2), including theoretical teaching and ‘onsite’ training in perineal trauma assessment within the six maternity units. Finally, 13-week postintervention observation (phase 3) followed.Primary outcome measureOASIS rates were used as surrogate for OASIS recognition. OASIS rates were compared between different phases and between the two maternity unit groups (research fellow and non-research fellow based) using Pearson’s χ² test.ResultsA total 22 922 women were included. Among primiparous women, OASIS rate was higher in phase 2 (2.8%, p<0.001) and phase 3 (3.1%, p<0.001) than phase 1 (0.5%). However, no significant differences were detected in the rates of severe OASIS (third-degree 3c and fourth-degree tears) between phase 1 and 2 (0.5% vs 0.3%), because this would have required at least 103 women with severe OASIS to be included in each phase. Among parous women, OASIS rate was significantly higher in phase 2 (0.6%, p=0.002) but not in phase 3 (0.4%, p=0.071) compared with phase 1 (0.2%). Research fellows’ maternity units showed higher OASIS rates among primiparous women in phase 2 (3.6% vs 1.4%, p=0.001) and phase 3 (4.3% vs 0.8%, p<0.001) than non-research fellows’ maternity units.ConclusionsThis work is basically an epidemiological study which has identified the prevalence of perineal lacerations and their severity on a large sample of women representative of an entire geographical ethnic region. The quality improvement intervention improved OASIS detection mainly in the research fellows’ maternity units. Regular mandatory national programmes in obstetric perineal trauma assessment and management by local champions are essential to mitigate the risk of missing significant degrees of trauma.
Interventions for mental health problems in children and adults with severe intellectual disabilities: a systematic review
Authors: Vereenooghe Leen , Flynn Samantha , Hastings Richard P , Adams Dawn , Chauhan Umesh , Cooper Sally-Ann , Gore Nick , Hatton Chris , Hood Kerry , Jahoda Andrew , Langdon Peter E , McNamara Rachel , Oliver Chris , Roy Ashok , Totsika Vasiliki , Waite Jane 
Published: June 2018

ObjectiveMental health problems are more prevalent in people with than without intellectual disabilities, yet treatment options have received little attention. The aim of this study was to identify and evaluate the effectiveness of pharmacological and psychological interventions in the treatment of mental health problems in children and adults with severe and profound intellectual disabilities, given their difficulties in accessing standard mental health interventions, particularly talking therapies, and difficulties reporting drug side effects.DesignA systematic review using electronic searches of PsycINFO, PsycTESTS, EMBASE, MEDLINE, CINAHL, ERIC, ASSIA, Science Citation Index, Social Science Citation Index and CENTRAL was conducted to identify eligible intervention studies. Study selection, data extraction and quality appraisal were performed by two independent reviewers.ParticipantsStudy samples included at least 70% children and/or adults with severe or profound intellectual disabilities or reported the outcomes of this subpopulation separate from participants with other levels of intellectual disabilities.InterventionsEligible intervention studies evaluated a psychological or pharmacological intervention using a control condition or pre-post design.OutcomesSymptom severity, frequency or other quantitative dimension (e.g., impact), as assessed with standardised measures of mental health problems.ResultsWe retrieved 41 232 records, reviewed 573 full-text articles and identified five studies eligible for inclusion: three studies evaluating pharmacological interventions, and two studies evaluating psychological interventions. Study designs ranged from double-blind placebo controlled crossover trials to single-case experimental reversal designs. Quality appraisals of this very limited literature base revealed good experimental control, poor reporting standards and a lack of follow-up data.ConclusionsMental ill health requires vigorous treatment, yet the current evidence base is too limited to identify with precision effective treatments specifically for children or adults with severe and profound intellectual disabilities. Clinicians therefore must work on the basis of general population evidence, while researchers work to generate more precise evidence for people with severe and profound intellectual disabilities.PROSPERO registration numberCRD 42015024469.
Does perceived organisational support influence career intentions? The qualitative stories shared by UK early career doctors
Authors: Scanlan Gillian Marion , Cleland Jennifer , Walker Kim , Johnston Peter 
Published: June 2018

IntroductionThe wish to quit or take time out of medical training appears to be related, at least in part, to a strong desire for supportive working and learning environments. However, we do not have a good understanding of what a supportive culture means to early career doctors, and how perceptions of support may influence career decision making. Our aim was to explore this in UK Foundation doctors.MethodsThis was a qualitative study using semistructured interviews incorporating a narrative inquiry approach for data collection. Interview questions were informed by the literature as well as data from two focus groups. Interviews were carried out in two UK locations. Initial data coding and analysis were inductive, using thematic analysis. We then used the lens of Perceived Organizational Support (POS) to group themes and aid conceptual generalisability.ResultsTwenty-one interviews were carried out. Eleven interviewees had applied for specialty training, while ten had not. Support from senior staff and colleagues influenced participants’ job satisfaction and engagement. Positive relationships with senior staff and colleagues seemed to act as a buffer, helping participants cope with challenging situations. Feeling valued (acknowledgement of efforts, and respect) was important. Conversely, perceiving a poor level of support from the organisation and its representatives (supervisors and colleagues) had a detrimental impact on participants’ intentions to stay working within the National Health Service (NHS).ConclusionOverall, this is the first study to explore directly how experiences in early postgraduate training have a critical impact on the career intentions of trainee/resident doctors. We found perceived support in the early stages of postgraduate training was critical to whether doctors applied for higher training and/or intended to stay working in the NHS. These findings have transferable messages to other contexts struggling to recruit and retain junior doctors.
Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations
Authors: Sowalsky Adam G. , Ye Huihui , Bhasin Manoj , Van Allen Eliezer M. , Loda Massimo , Lis Rosina T. , Montaser-Kouhsari Laleh , Calagua Carla , Ma Fen , Russo Joshua W. , Schaefer Rachel J. , Voznesensky Olga S. , Zhang Zhenwei , Bubley Glenn J. , Montgomery Bruce , Mostaghel Elahe A. , Nelson Peter S. , Taplin Mary-Ellen , Balk Steven P. 
Published: June 2018

Abstract
Primary prostate cancer can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant prostate cancer (mCRPC) remains unclear. In this study, we microdissected residual prostate cancer foci in radical prostatectomies from 18 men treated with neoadjuvant-intensive androgen deprivation therapy (leuprolide, abiraterone acetate, and prednisone) and analyzed them for resistance mechanisms. Transcriptome profiling showed reduced but persistent androgen receptor (AR) activity in residual tumors, with no increase in neuroendocrine differentiation. Proliferation correlated negatively with AR activity but positively with decreased RB1 expression, and whole-exome sequencing (WES) further showed enrichment for RB1 genomic loss. In 15 cases where 2 or 3 tumor foci were microdissected, WES confirmed a common clonal origin but identified multiple oncogenic alterations unique to each focus. These findings show that subclones with oncogenic alterations found in mCRPC are present in primary prostate cancer and are selected for by neoadjuvant-intense androgen deprivation therapy. In particular, this study indicates that subclonal RB1 loss may be more common than previously appreciated in intermediate- to high-risk primary prostate cancer and may be an early event, independent of neuroendocrine differentiation, in the development of mCRPC. Comprehensive molecular analyses of primary prostate cancer may detect aggressive subclones and possibly inform adjuvant strategies to prevent recurrence.
Significance: Neoadjuvant androgen deprivation therapy for prostate cancer selects for tumor foci with subclonal genomic alterations, which may comprise the origin of metastatic castration-resistant prostate cancer. Cancer Res; 78(16); 4716–30. ©2018 AACR.
Chemotherapy Sensitizes Therapy-Resistant Cells to Mild Hyperthermia by Suppressing Heat Shock Protein 27 Expression in Triple-Negative Breast Cancer
Authors: Mu Chaofeng , Wu Xiaoyan , Zhou Xinyu , Wolfram Joy , Shen Jianliang , Zhang Dechen , Mai Junhua , Xia Xiaojun , Holder Ashley M. , Ferrari Mauro , Liu Xuewu , Shen Haifa 
Published: June 2018

Abstract
Purpose: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with poor prognosis. Conventional chemotherapeutics are generally able to shrink the tumor mass, but often fail to completely eradicate cancer stem–like cells (CSCs) that are responsible for high risk of relapse and frequent metastases. In this study, we examined thermal sensibility of CSCs, developed an approach that enabled concurrent elimination of both the bulk of cancer cells and CSCs, and investigated the underlying mechanism.
Experimental Design: We designed a platform consisting of gold nanoparticle-coated porous silicon microparticle (AuPSM) that was also loaded with docetaxel micelles (mDTXs) to enable concurrent killing of the bulk of cancer cells by released mDTX and CSCs by mild hyperthermia upon stimulation of AuPSM with near infrared. In addition, we examined the role of heat shock proteins in sensitizing CSC killing. Finally, we applied mDTX-loaded AuPSM to treat mice with SUM159 and 4T1 orthotopic tumors and evaluated tumor growth and tumor metastasis.
Results: MDA-MB-231 and SUM159 TNBC cells treated with mDTX-loaded AuPSM and mild hyperthermia displayed significantly reduced efficiencies in mammosphere formation than those treated with mDTX alone or mild hyperthermia alone. Combination treatment also completely inhibited SUM159 orthotopic tumor growth and 4T1 tumor metastasis. Mechanistically, DTX treatment suppressed expression of heat shock protein 27 in cancer cells including the CSCs, rendering cells sensitive to mild hyperthermia.
Conclusions: Our results indicate that chemotherapy sensitizes CSC to mild hyperthermia. We have developed an effective therapeutic approach to eliminate therapy-resistant cells in TNBC. Clin Cancer Res; 24(19); 4900–12. ©2018 AACR.
Integrating Radiosensitivity and Immune Gene Signatures for Predicting Benefit of Radiotherapy in Breast Cancer
Authors: Cui Yi , Li Bailiang , Pollom Erqi L. , Horst Kathleen C. , Li Ruijiang 
Published: June 2018

Abstract
Purpose: Breast cancer is a heterogeneous disease and not all patients respond equally to adjuvant radiotherapy. Predictive biomarkers are needed to select patients who will benefit from the treatment and spare others the toxicity and burden of radiation.
Experimental Design: We first trained and tested an intrinsic radiosensitivity gene signature to predict local recurrence after radiotherapy in three cohorts of 948 patients. Next, we developed an antigen processing and presentation-based immune signature by maximizing the treatment interaction effect in 129 patients. To test their predictive value, we matched patients treated with or without radiotherapy in an independent validation cohort for clinicopathologic factors including age, ER status, HER2 status, stage, hormone-therapy, chemotherapy, and surgery. Disease-specific survival (DSS) was the primary endpoint.
Results: Our validation cohort consisted of 1,439 patients. After matching and stratification by the radiosensitivity signature, patients who received radiotherapy had better DSS than patients who did not in the radiation-sensitive group [hazard ratio (HR), 0.68; P = 0.059; n = 322], whereas a reverse trend was observed in the radiation-resistant group (HR, 1.53; P = 0.059; n = 202). Similarly, patients treated with radiotherapy had significantly better DSS in the immune-effective group (HR, 0.46; P = 0.0076; n = 180), with no difference in DSS in the immune-defective group (HR, 1.27; P = 0.16; n = 348). Both signatures were predictive of radiotherapy benefit (Pinteraction = 0.007 and 0.005). Integration of radiosensitivity and immune signatures further stratified patients into three groups with differential outcomes for those treated with or without radiotherapy (Pinteraction = 0.003).
Conclusions: The proposed signatures have the potential to select patients who are most likely to benefit from radiotherapy. Clin Cancer Res; 24(19); 4754–62. ©2018 AACR.
KDM6B Counteracts EZH2-Mediated Suppression of IGFBP5 to Confer Resistance to PI3K/AKT Inhibitor Treatment in Breast Cancer
Authors: Wang Wenyu , Lim Keng Gat , Feng Min , Bao Yi , Lee Puay Leng , Cai Yu , Chen Yufeng , Zhang Hao , Marzese Diego , Hoon Dave S.B. , Yu Qiang 
Published: June 2018

Abstract
Despite showing promise against PIK3CA-mutant breast cancers in preclinical studies, PI3K/AKT pathway inhibitors demonstrate limited clinical efficacy as monotherapy. Here, we found that histone H3K27me3 demethylase KDM6B-targeted IGFBP5 expression provides a protective mechanism for PI3K/AKT inhibitor-induced apoptosis in breast cancer cells. We found that overexpression of KDM6B and IGFBP5 in luminal breast cancer are positively associated with poorer disease outcomes. Mechanistically, KDM6B promotes IGFBP5 expression by antagonizing EZH2-mediated repression, and pharmacologic inhibition of KDM6B augments apoptotic response to PI3K/AKT inhibitor treatment. Moreover, the IGFBP5 expression is upregulated upon acquired resistance to the PI3K inhibitor GDC-0941, which is associated with an epigenetic switch from H3K27me3 to H3K27Ac at the IGFBP5 gene promoter. Intriguingly, GDC-0941–resistant breast cancer cells remained sensitive to KDM6B or IGFBP5 inhibition, indicating the dependency on the KDM6B–IGFBP5 axis to confer the survival advantage in GDC-0941–resistant cells. Our study reveals an epigenetic mechanism associated with resistance to targeted therapy and demonstrates that therapeutic targeting of KDM6B-mediated IGFBP5 expression may provide a useful approach to mitigate both intrinsic and acquired resistance to the PI3K inhibitor in breast cancer. Mol Cancer Ther; 17(9); 1973–83. ©2018 AACR.
Association of Thromboembolic Risk Score with Left Atrial Thrombus and Spontaneous Echocardiographic Contrast in Non-Anticoagulated Nonvalvular Atrial Fibrillation Patients
Authors: Huang Jun , Liao Hong-tao , Fei Hong-wen , Xue Yu-mei , Zhang Li , Lin Qiong-wen , Ren Si-qi , Zhan Xian-zhang , Fang Xian-hong , Zheng Mu-rui , Wu Shu-lin , Xu Lin 
Published: June 2018

<b><i>Objectives:</i></b> The aim of the study was to examine the association of CHADS2/CHA2DS2-VASc scores with left atrial thrombus (LAT) and spontaneous echocardiographic contrast (SEC) in non-anticoagulated nonvalvular atrial fibrillation (NVAF) spontaneous patients, and to develop a new scoring system for LAT/SEC prediction. <b><i>Methods:</i></b> Consecutive non-anticoagulated NVAF patients with or without LAT/SEC by transesophageal echocardiography were identified in the Guangdong General Hospital. <b><i>Results:</i></b> Among 2,173 patients, the prevalence of LAT/SEC was 4.9%. Both predictive values of CHADS2 and CHA2DS2-VASc scores for the presence of LAT/SEC were low-to-moderate (receiver operating characteristic [ROC] = 0.591 and 0.608, respectively, <i>p</i> = 0.90). By multivariate analysis, non-paroxysmal AF, decreased left ventricular ejection fraction, and left atrial enlargement were positively associated with LAT/SEC, while CHADS2/CHA2DS2VASc scores were not. A new scoring system based on these 3 factors above significantly improved the discrimination for LAT/SEC (ROC = 0.792). <b><i>Conclusions:</i></b> CHADS2/CHA2DS2-VASc scores had limited value in predicting LAT/SEC; a new scoring system that combines AF type and echocardiographic parameters may better predict LAT/SEC as a surrogate for cardioembolic risk in NVAF patients.
Overlapping Boundaries in the City: Mahalle and Kahal in the Early Modern Ottoman Urban Context
Authors: Karagedikli Gürer 
Published: June 2018

AbstractIn the present article, I examine the construction and articulation of urban and communal identities in the early modern Ottoman Empire with special reference to the complex and dynamic local Jewish identities in Edirne. I analyse the terminology used for identifying Jewish litigants at the Islamic court in Edirne based on 12 cases selected from the Islamic court registers. In other words, I scrutinize in which cases the court identified Jews by their membership of a particular congregation (Heb.kahal; pl.kehalim), in which cases by their residential affiliations (Ott.mahalle; pl.mahallat, “urban quarter”), and in which by a combination of these aforementioned ascriptions. In so doing, I attempt to enhance our understanding about pre-modern people who were simultaneously members of multiple religious, spatial, ethnic or occupational sub-communities. More specifically, I examine which of the Jews’ multiple identities (i.e.,kahalas religious/ethnic;mahalleas spatial) were emphasized by the judges of the Muslim courts. I suggest that various identification markers were employed by court personnel to define the Edirne Jews. While in some matters the fiscally, administratively, as well as socially defined spatial identity based on the termmahallewas employed, in other cases the ethnic/communal identity based on the Jewishkahal—that was also a taxable unit—was the prevalent concept.
Legitimacy and Civic Culture: Trust in Democracy in the Czech Republic after EU Accession (2004-2014)
Authors: Sedláčková Markéta , Šafr Jiří 
Published: June 2018

AbstractThis paper investigates the role of civic culture and other political factors in support for democracy in the Czech Republic during the decade followingEUaccession. The goal is to assess the validity of civic virtue theory and to compare the impact of these factors on affective legitimacy using theISSPCitizenship modules 2004 and 2014. The authors’ findings show rather weak but stable effects of the horizontal dimension of civic culture – social trust (but not membership in civic organizations), while the influence of the vertical dimension (trust in institutions, political interest, voting) is more variable, influenced by political turbulences. The time comparison also provides evidence of influence of right-wing political ideology and strong and stable effects of evaluations of political and economic performance.
The Emergence of Trust: Social Figuration in Supply Networks
Authors: Akkermans Henk 
Published: June 2018

AbstractTrust is an essential governance mechanism in present-day supply networks, where many independent parties have to coordinate their activities. It is often assumed that trustful behavior at least partly depends on the inner dispositions of actors. Other theories suggest that this behavior is an emergent property of the supply network, generated by the interactions between the actors in the network. Half a century ago, the social figuration theory of Norbert Elias was the first formulation of such a theory. This research tests this emergent property theory in a series of simulation-based thought experiments. A generic agent-based model of buyer-supplier interactions in a build-to-forecast supply chain is used as a dynamic hypothesis to test this theory. The inner dispositions of the actors towards trust and opportunistic behavior can be changed here. Current trust levels are influenced by these inner dispositions, but are also changed by the perceived behavior of the other party. Trust levels of the actors also determine their behavior. In the simulation this creates vicious or virtuous cycles of mutual trust and performance, so called relationship spirals. Model analysis shows that beyond a certain level of external volatility, the development of trust on both sides no longer bears any direct relation to the inner dispositions of the network parties. This confirms the dynamic hypothesis. It also again establishes the strength of Elias’s original social figuration theory.
Observation of Quasi-2-Day Convective Disturbances in the Equatorial Indian Ocean during DYNAMO
Authors: Yu Hungjui , Johnson Richard H. , Ciesielski Paul E. , Kuo Hung-Chi 
Published: June 2018

Abstract
This study examines the westward-propagating convective disturbances with quasi-2-day intervals of occurrence identified over Gan Island in the central Indian Ocean from mid- to late October 2011 during the Dynamics of the Madden–Julian Oscillation (DYNAMO) field campaign. Atmospheric sounding, satellite, and radar data are used to develop a composite of seven such disturbances. Composites and spectral analyses reveal that 1) the quasi-2-day convective events comprise westward-propagating diurnal convective disturbances with phase speeds of 10–12 m s−1 whose amplitudes are modulated on a quasi-2-day time scale on a zonal scale of ~1000 km near the longitudes of Gan; 2) the cloud life cycle of quasi-2-day convective disturbances shows a distinct pattern of tropical cloud population evolution—from shallow to deep to stratiform convection; 3) the time scales of mesoscale convective system development and boundary layer modulation play essential roles in determining the periodicity of the quasi-2-day convective events; and 4) in some of the quasi-2-day events there is evidence of counterpropagating (westward and eastward) cloud systems along the lines proposed by Yamada et al. Based on these findings, an interpretation is proposed for the mechanisms for the quasi-2-day disturbances observed during DYNAMO that combines concepts from prior studies of this phenomenon over the western Pacific and Indian Oceans.