bluuebunny/crossref_metadata_2025_split huggingface dataset:
School-based intervention study examining approaches for well-being and mental health literacy of pupils in Year 9 in England: study protocol for a multischool, parallel group cluster randomised controlled trial (AWARE)
Authors: Hayes Daniel , Moore Anna , Stapley Emily , Humphrey Neil , Mansfield Rosie , Santos Joao , Ashworth Emma , Patalay Praveetha , Bonin Eva , Evans-Lacko Sara , Moltrecht Bettina , Nisbet Kirsty , Thornton Emma , Lange Aurelie , Stallard Paul , Thompson Abigail , Boehnke Jan Rasmus , Deighton Jessica 
Published: September 2019

IntroductionThe prevalence of emotional difficulties in young people is increasing. This upward trend is largely accounted for by escalating symptoms of anxiety and depression. As part of a public health response, there is increasing emphasis on universal prevention programmes delivered in school settings. This protocol describes a three-arm, parallel group cluster randomised controlled trial, investigating the effectiveness and cost-effectiveness of two interventions, alongside a process and implementation evaluation, to improve mental health and well-being of Year 9 pupils in English secondary schools.MethodA three-arm, parallel group cluster randomised controlled trial comparing two different interventions, the Youth Aware of Mental Health (YAM) or the Mental Health and High School Curriculum Guide (The Guide), to Usual Provision. Overall, 144 secondary schools in England will be recruited, involving 8600 Year 9 pupils. The primary outcome for YAM is depressive symptoms, and for The Guide it is intended help-seeking. These will be measured at baseline, 3–6 months and 9–12 months after the intervention commenced. Secondary outcomes measured concurrently include changes to: positive well-being, behavioural difficulties, support from school staff, stigma-related knowledge, attitudes and behaviours, and mental health first aid. An economic evaluation will assess the cost-effectiveness of the interventions, and a process and implementation evaluation (including a qualitative research component) will explore several aspects of implementation (fidelity, quality, dosage, reach, participant responsiveness, adaptations), social validity (acceptability, feasibility, utility), and their moderating effects on the outcomes of interest, and perceived impact.Ethics and disseminationThis trial has been approved by the University College London Research Ethics Committee. Findings will be published in a report to the Department for Education, in peer-reviewed journals and at conferences.Trial registration numberISRCTN17631228.ProtocolV1 3 January 2019. Substantial changes to the protocol will be communicated to the trials manager to relevant parties (eg, ISRCTN).
Is microdiffusion imaging able to improve the detection of cervical myelopathy? Study protocol of a prospective observational trial (MIDICAM-Trial)
Authors: Hohenhaus Marc , Egger Karl , Klingler Jan-Helge , Hubbe Ulrich , Reisert Marco , Wolf Katharina 
Published: September 2019

IntroductionThe diagnosis of degenerative cervical myelopathy (DCM) is difficult in numerous patients due to the limited correlation of clinical symptoms, electrophysiology and MRI. This applies especially for early disease stages with mild symptoms or in uncertainty due to comorbidities. Conventional MRI myelopathy signs show a restricted sensitivity to clinical symptoms of at most 60%. It is desirable to select patients for surgical treatment as early as possible before irreversible neurological damage occurs. To improve treatment, a more reliable imaging is necessary. Microdiffusion imaging (MIDI) is an innovative MRI modality to depict tissue alterations within one voxel based on diffusion-weighted imaging (DWI) postprocessing. By separating the affected area into several mesoscopic compartments, pathological changes might be detected more sensitive through this subtle tissue resolution. We hypothesise, that MIDI shows myelopathic alterations more sensitive than conventional MRI and improves the correlation to functional impairment.Methods and analysisIn this prospective, observational trial, 130 patients with a relevant degenerative cervical spinal stenosis receive MRI including MIDI and a standard clinical and electrophysiological assessment. Special subvoxel diffusion parameters are calculated. Clinical follow-ups are conducted after 3, 6 and with additional MRI and electrophysiology after 12 months. The primary endpoint is the sensitivity of MIDI to detect functional myelopathy defined by clinical and electrophysiological features correlated to conventional MRI myelopathy signs. Twenty healthy subjects will be included as negative control. The results will provide new insights into the development of mesoscopic spinal cord alterations in DCM associated to the clinical course. Aim is to improve the diagnostics of incipient myelopathy through this new modality.Ethics and disseminationThe study protocol is approved by the Ethics Committee of the University of Freiburg (reference 261/17). The results will be published in a peer-reviewed journal.Trial registration numberDRKS00012962.
Anticoagulation adherence and its associated factors in patients with atrial fibrillation: a cross-sectional study
Authors: Chen Pei-Ti , Wang Tsae-Jyy , Hsieh Ming-Hsiung , Liu Ju-Chi , Liu Chieh-Yu , Wang Kwua-Yun , Laio Wen-Chun 
Published: September 2019

ObjectiveTo investigate anticoagulant adherence and its associated factors, including demographics, clinical variables, atrial fibrillation (AF) severity, knowledge, satisfaction with services, perceived barriers, perceived benefits, symptom severity and self-efficacy in patients with AF.DesignThis is a cross-sectional study.Participants and settingA convenient sample of patients with AF were recruited from cardiology clinics of two teaching hospitals in Taiwan.MeasuresData were collected using the study questionnaires, including the AF-related symptom subscale of the AF Severity Scale, the Knowledge of Warfarin Anticoagulation Treatment Scale, the Satisfaction Scale about Service and Warfarin Treatment, the perceived benefits subscale of the Beliefs about Anticoagulation Survey, the Concerns about Anticoagulation Therapy Scale, The Self-efficacy for Appropriate Medication Use Scale and the short-form Adherence to Reﬁlls and Medications Scale.ResultsA total of 151 patients with AF participated in the study; 53 treated with warfarin and 98 treated with novel oral anticoagulants (NOACs). The difference in adherence to warfarin (mean=8.6; SD=1.6) and NOACs (mean=8.9; SD=2.0) was statistically insignificant. Multiple linear regression analysis showed that perceived barriers (β=0.18, p=0.017) and self-efficacy (β=−0.48, p<0.001) were significant predictors of anticoagulation adherence. For every 1-unit increase in the perceived barriers, there will be a 0.18-unit increase in the adherence to anticoagulation therapy. For every 1-unit increase in the self-efficacy, there will be a 0.48-unit decrease in the adherence to anticoagulation therapy. Perceived barriers and self-efficacy collectively explained 34.0% of the variance in adherence to anticoagulation therapy (F(2,149)=38.11, p<0.001).ConclusionWe found no better adherence to NOACs compared with warfarin. Patients with greater self-efficacy and perceived fewer barriers showed better adherence to anticoagulation therapy.
Cohort profile: role of lipoproteins in cardiovascular disease—the LipidCardio study
Authors: König Maximilian , Joshi Samita , Leistner David M , Landmesser Ulf , Sinning David , Steinhagen-Thiessen Elisabeth , Demuth Ilja 
Published: September 2019

PurposeThe LipidCardio Study was established for in-depth analyses of cardiovascular risk factors, providing well-defined cardiovascular and metabolic phenotypes. In particular, the role of lipoproteins in the pathobiological process and treatment of cardiovascular disease (CVD) will be a main focus.Participants1005 individuals aged 21 years and older undergoing cardiac catheterisation during 17 months at a tertiary academic cardiology centre were enrolled (troponin-positive acute coronary syndrome was exclusion criterion). The baseline data not only contain detailed phenotyping, broad biochemical parameters, genetic data, but also standardised personal and family history, a screening test for cognitive impairment, pulse wave analysis and measurements of hand grip strength, among others. Blood samples were stored in a biobank for future analyses.Findings to dateThe mean age of the participants at enrolment was 70.9±11.1 years (70% male). Coronary angiography provided evidence of obstructive coronary artery disease (CAD) in 69.9% of participants. Those with evidence of CAD were significantly more likely to be male, inactive, diabetic and with a family history of CVD than participants without CAD.About 20% of patients had lipoprotein(a) (Lp(a)) concentrations above 106.9 nmol/L (fifth quintile). These patients had significantly increased odds of obstructive CAD compared with participants in quintiles 1–4 (crude OR 1.70, 95% CI 1.17 to 2.48, p=0.005). There was reasonable evidence that with increasing severity of CAD the odds of having elevated Lp(a) increased. We were able to replicate the established strong association between specified single nucleotide polymorphisms (SNPs) in theLPAgene (rs10455872, rs3798220 and rs186696265) and theAPOEgene (rs7412), and the concentration of Lp(a), validating our phenotype database and biobank.Future plansMortality information will be obtained in 2 year intervals. Follow-up phone interviews will be conducted at 3 and 6 years after enrolment. We seek to cooperate with other researchers, for example, by sharing data and biobank samples.
One-year rehospitalisations for congestive heart failure in Portuguese NHS hospitals: a multilevel approach on patterns of use and contributing factors
Authors: Moita Bruno , Marques Ana Patricia , Camacho Ana Maria , Leão Neves Pedro , Santana Rui 
Published: September 2019

ObjectivesIdentification of rehospitalisations for heart failure and contributing factors flags health policy intervention opportunities designed to deliver care at a most effective and efficient level. Recognising that heart failure is a condition for which timely and appropriate outpatient care can potentially prevent the use of inpatient services, we aimed to determine to what extent comorbidities and material deprivation were predictive of 1 year heart failure specific rehospitalisation.SettingAll Portuguese mainland National Health Service (NHS) hospitals.ParticipantsA total of 68 565 hospitalisations for heart failure principal cause of admission, from 2011 to 2015, associated to 45 882 distinct patients aged 18 years old or over.Outcome measuresWe defined 1 year specific heart failure rehospitalisation and time to rehospitalisation as outcome measures.ResultsHeart failure principal diagnosis admissions accounted for 1.6% of total hospital NHS budget, and over 40% of this burden is associated to patients rehospitalised at least once in the 365-day follow-up period. 22.1% of the patients hospitalised for a principal diagnosis of heart failure were rehospitalised for the same cause at least once within 365 days after previous discharge. Nearly 55% of rehospitalised patients were readmitted within 3 months. Results suggest a mediation effect between material deprivation and the chance of 1 year rehospitalisation through the effect that material deprivation has on the prevalence of comorbidities. Heart failure combined with chronic kidney disease or chronic obstructive pulmonary disease increases by 2.8 and 2.2 times, respectively, the chance of the patient becoming a frequent user of inpatient services for heart failure principal cause of admission.ConclusionsOne-fifth of patients admitted for heart failure are rehospitalised due to heart failure exacerbation. While the role of material deprivation remained unclear, comorbidities considered increased the chance of 1 year heart failure specific rehospitalisation, in particular, chronic kidney disease and chronic obstructive pulmonary disease.
Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer
Authors: Ponnusamy Suriyan , He Yali , Hwang Dong-Jin , Thiyagarajan Thirumagal , Houtman Rene , Bocharova Vera , Sumpter Bobby G. , Fernandez Elias , Johnson Daniel , Du Ziyun , Pfeffer Lawrence M. , Getzenberg Robert H. , McEwan Iain J. , Miller Duane D. , Narayanan Ramesh 
Published: September 2019

Abstract

Purpose:
Androgen receptor (AR)-targeting prostate cancer drugs, which are predominantly competitive ligand-binding domain (LBD)-binding antagonists, are inactivated by common resistance mechanisms. It is important to develop next-generation mechanistically distinct drugs to treat castration- and drug-resistant prostate cancers.

Experimental Design:
Second-generation AR pan antagonist UT-34 was selected from a library of compounds and tested in competitive AR binding and transactivation assays. UT-34 was tested using biophysical methods for binding to the AR activation function-1 (AF-1) domain. Western blot, gene expression, and proliferation assays were performed in various AR-positive enzalutamide-sensitive and -resistant prostate cancer cell lines. Pharmacokinetic and xenograft studies were performed in immunocompromised rats and mice.

Results:
UT-34 inhibits the wild-type and LBD-mutant ARs comparably and inhibits the in vitro proliferation and in vivo growth of enzalutamide-sensitive and -resistant prostate cancer xenografts. In preclinical models, UT-34 induced the regression of enzalutamide-resistant tumors at doses when the AR is degraded; but, at lower doses, when the AR is just antagonized, it inhibits, without shrinking, the tumors. This indicates that degradation might be a prerequisite for tumor regression. Mechanistically, UT-34 promotes a conformation that is distinct from the LBD-binding competitive antagonist enzalutamide and degrades the AR through the ubiquitin proteasome mechanism. UT-34 has a broad safety margin and exhibits no cross-reactivity with G-protein–coupled receptor kinase and nuclear receptor family members.

Conclusions:
Collectively, UT-34 exhibits the properties necessary for a next-generation prostate cancer drug.
Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer
Authors: Yeyeodu Susan T. , Kidd LaCreis R. , Kimbro K. Sean 
Published: September 2019

Abstract
Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health behaviors, etc.) have a strong influence on racial disparities. However, even after controlling for these factors, overall phenotypic differences in breast cancer pathology remain among groups of individuals who vary by geographic ancestry. There is a growing appreciation that chronic/reoccurring inflammation, primarily driven by mechanisms of innate immunity, contributes to core functions associated with cancer progression. Germline mutations in innate immune genes that have been retained in the human genome offer enhanced protection against environmental pathogens, and protective innate immune variants against specific pathogens are enriched among populations whose ancestors were heavily exposed to those pathogens. Consequently, it is predicted that racial/ethnic differences in innate immune programs will translate into ethnic differences in both pro- and antitumor immunity, tumor progression, and prognosis, leading to the current phenomenon of racial/ethnic disparities in cancer. This review explores examples of protective innate immune genetic variants that are (i) distributed disproportionately among racial populations and (ii) associated with racial/ethnic disparities of breast and prostate cancer.
Efficacy of Vinorelbine Monotherapy as Third- or Further-Line Therapy in Patients with Advanced Non-Small-Cell Lung Cancer
Authors: Kang Da Hyun , Kim Ju Ock , Jung Sung Soo , Park Hee Sun , Chung Chaeuk , Park Dongil , Lee Jeong Eun 
Published: September 2019

<b><i>Background:</i></b> The survival rate of patients with lung cancer has increased significantly over the years, but there has been no further progress in third- or fourth-line therapy. We investigated the efficacy and tolerability of monotherapy with weekly vinorelbine, a semi-synthetic vinca alkaloid, in advanced non-small-cell lung cancer (NSCLC) patients who had previously been treated several times. <b><i>Methods:</i></b> In all, 159 NSCLC patients who received vinorelbine monotherapy as third- or further-line therapy between January 2008 and July 2017 were included in this study. Patients received vinorelbine intravenously at a dose of 25–30 mg/m<sup>2</sup>/week. <b><i>Results:</i></b> Their mean age was 62.4 years. The histologic types of tumor were adenocarcinoma (50.9%), squamous cell carcinoma (42.8%), and others (6.2%). The overall response rate was 19.5% (31/159). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI] 2.5–3.5 months), and the median overall survival (OS) after vinorelbine use was 7.6 months (95% CI 6.2–9.0 months). Vinorelbine therapy showed significantly higher efficacy in patients with adenocarcinoma, and these patients had a longer PFS than patients with other types of cancer. Patients who received vinorelbine as fifth- or further-line treatment had a higher response rate and longer PFS and OS than those who received vinorelbine as third- or fourth-line treatment. <b><i>Conclusions:</i></b> Weekly vinorelbine monotherapy may be a feasible therapeutic option for patients with heavily treated, advanced NSCLC, particularly lung adenocarcinoma.
Enhanced Climate Change Response of Wintertime North Atlantic Circulation, Cyclonic Activity, and Precipitation in a 25-km-Resolution Global Atmospheric Model
Authors: Baker Alexander J. , Schiemann Reinhard , Hodges Kevin I. , Demory Marie-Estelle , Mizielinski Matthew S. , Roberts Malcolm J. , Shaffrey Len C. , Strachan Jane , Vidale Pier Luigi 
Published: September 2019

Abstract
Wintertime midlatitude cyclone activity and precipitation are projected to increase across northern Europe and decrease over southern Europe, particularly over the western Mediterranean. Greater confidence in these regional projections may be established by their replication in state-of-the-art, high-resolution global climate models that resolve synoptic-scale dynamics. We evaluated the representation of the wintertime eddy-driven and subtropical jet streams, extratropical cyclone activity, and precipitation across the North Atlantic and Europe under historical (1985–2011) and RCP8.5 sea surface temperature forcing in an ensemble of atmosphere-only HadGEM3-GA3.0 simulations, where horizontal atmospheric resolution is increased from 135 to 25 km. Under RCP8.5, increased (decreased) frequency of northern (southern) eddy-driven jet occurrences and a basinwide poleward shift in the upper-level westerly flow are simulated. Increasing atmospheric resolution significantly enhances these climate change responses. At 25-km resolution, these enhanced changes in large-scale circulation amplify increases (decreases) in extratropical cyclone track density and mean intensity across the northern (southern) Euro-Atlantic region under RCP8.5. These synoptic changes with resolution impact the overall climate change response of mean and heavy winter precipitation: wetter (drier) conditions in northern (southern) Europe are also amplified at 25-km resolution. For example, the reduction in heavy precipitation simulated over the Iberian Peninsula under RCP8.5 is ~15% at 135 km but ~30% at 25-km resolution. Conversely, a shift to more frequent high extratropical cyclone (ETC)-associated precipitation rates is simulated over Scandinavia under RCP8.5, which is enhanced at 25 km. This study provides evidence that global atmospheric resolution may be a crucial consideration in European winter climate change projections.
Priestly Aesthetics: Disability and Bodily Difference in Leviticus 21
Authors: Belser Julia Watts 
Published: September 2019

Leviticus 21:16–23 forbids priests with a wide range of disabilities from offering sacrifice at the altar, a ritual act that Leviticus considers the most sacred responsibility of the priesthood. This essay raises critical questions about the biblical writer’s assumption that God desires the service of those with “perfect” bodies. The essay probes traditional Jewish interpretation of Leviticus 21 and argues that rabbinic texts leach the prohibition of much practical force. Despite offering a path toward more inclusive practice, conventional readings of these texts have left in place power dynamics that presume the inferiority of the disabled body. Yet they also contain the seeds for a conceptual shift that could transform the way contemporary communities engage with disability. Biblical Priests; Disability; Ethics; Jewish Theology; Leviticus 21; Rabbinic Literature; Talmud
Postoperative Analgesic Requirement and Pain Perceptions after Nonaerodigestive Head and Neck Surgery
Authors: Stephenson Elizabeth D. , Farzal Zainab , Jowza Maryam , Hackman Trevor , Zanation Adam , Du Eugenie 
Published: September 2019

ObjectivesLittle data exist on associations between patient factors and postoperative analgesic requirement after head and neck (H&N) surgeries. Such information is important for optimizing postoperative care considering concerns regarding opioid misuse. We analyzed factors associated with narcotic use and pain perception following H&N surgery sparing the upper aerodigestive tract.Study DesignProspective cohort.SettingTertiary referral center.Subjects and MethodsFrom May to October 2017, data were collected for patients undergoing nonaerodigestive H&N procedures requiring hospitalization. Patients completed a preoperative survey querying chronic pain history, narcotic usage, and postoperative pain expectation. Demographics, surgical data, postoperative narcotic use defined by morphine milligram equivalents (MME), pain scores, and Overall Benefit of Analgesia Score (OBAS) were analyzed.ResultsSeventy‐six patients, 44 (57.9%) females and 32 (42.1%) males with a mean age of 54.0 years, met inclusion criteria. The most common procedures were parotidectomy (27.6%) and total thyroidectomy (19.7%). Average cumulative 24‐hour postoperative MME and calculated MME per hospital day (MME/HD, cumulative MME for hospitalization divided by length of stay) were 40.5 ± 30.6 and 60.8 ± 60.1, respectively. Average pain score throughout the initial 24 hours after surgery was 3.7/10 ± 2.0. Female sex and prior chronic pain diagnosis were associated with higher OBAS after multivariate linear adjustments.ConclusionPostoperative narcotic requirement in nonaerodigestive H&N surgery is overall low. Female sex and prior chronic pain diagnosis may be associated with higher postoperative OBAS, a validated assessment of pain and opioid‐related side effects. This study may serve as a comparison for future studies evaluating narcotic‐sparing analgesia and pain perception in nonaerodigestive H&N surgery.