bluuebunny/crossref_metadata_2025_split huggingface dataset:
How have predictors, moderators, mediators, treatment response, remission and resistance been defined and measured in randomised controlled trials for adolescent depression? A scoping review protocol
Authors: Courtney Darren , Watson Priya , Chan Benjamin W C , Bennett Kathryn J , Neprily Kirsten , Zentner Tabitha , Rodak Terri , Narrandes Renira , Szatmari Peter 
Published: June 2020

IntroductionAmong randomised controlled trials for depressed adolescents, the extent of variation in how depressive symptom outcomes are defined is unknown. The variability in which potential predictors of these outcomes are tested is also unclear. This paper is a protocol describing the methods of a planned scoping review. The scoping review will examine and summarise how change in depressive symptoms have been described in RCT treatment studies to date. This review will report the measures used to describe change in depressive symptoms and whether the measure was used as a continuous or binary outcome or both. This review will describe how dichotomous outcome terms are defined to describe change in depression severity. This review will also examine predictors, moderators and mediators of change in depressive symptoms within RCTs.Methods and analysisIn this paper, we describe the protocol for our scoping review. Following the format outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, a research librarian will develop an operationalised search strategy, which we will apply to the MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature databases. We will search for papers from inception to 6 February 2020. A hand search for key citations will also be conducted. Investigator-raters will screen articles, first via the titles and abstracts and then through full-text reviews. We will include articles with randomised control design which assess the treatment of adolescents with major depressive disorder. We will systematically extract and synthesise prespecified data which includes: definition of depression used for participant inclusion, measures used to evaluate changes in depression, type of outcome used (continuous, binary or both), definitions of dichotomous terms to denote change in depression (eg, response, remission, recovery, etc) and reported predictors/moderators/mediators of change.Ethics and disseminationEthics approval is not required. Findings will be presented in journal publications and at conferences.
Physiotherapists’ pain attitudes and beliefs towards chronic low back pain and their association with treatment selection: a cross-sectional study
Authors: Alshehri Mansour Abdullah , Alzahrani Hosam , Alotaibi Mazyad , Alhowimel Ahmed , Khoja Omar 
Published: June 2020

ObjectivesThe main aim of this study was to investigate physiotherapists’ pain attitudes and beliefs towardss non-specific chronic low back pain (NSCLBP) and identify whether they are associated with treatment selection.DesignCross-sectional study.SettingSaudi Arabia (SA).ParticipantsAn online survey was distributed to physiotherapists from April 2018 to January 2019.Primary and secondary outcome measures(1) Biomedical and biopsychosocial treatment orientations were assessed using the Pain Attitudes and Beliefs Scale for Physiotherapists. (2) Frequent potential treatments used by physiotherapists for individuals with NSCLBP were identified through a 20-item survey. (3) The association between physiotherapists’ pain attitudes and beliefs and treatment selection was investigated. Descriptive analysis, Pearson’s correlation and multinomial logistic regression were used to analyse the data using SPSS (V.26).ResultsA total of 304 responses were included in the analysis. The biomedical (34.45±7.84) and biopsychosocial (31.74±5.67) treatment orientations were relatively low. The most frequent treatments used by physiotherapists were home exercises (87.1%), patient education (82.0%), specific back exercises (80.6%), electrotherapy (61.9%), soft tissue release (58.8%) and spinal mobilisation or manipulation (57.8%). Physiotherapists with a stronger biomedical treatment orientation were more likely to use treatments (p<0.05) such as specific back exercises, electrotherapy, soft tissue release, hydrotherapy, massage, lumbar supports and acupuncture. However, physiotherapists with a stronger biopsychosocial treatment orientation were more likely to use cognitive functional therapy (p<0.01).ConclusionsBiomedical and biopsychosocial treatment orientations were relatively low among physiotherapists in SA. Although treatments such as home exercises and patient education were frequently used, some passive and traditional treatments not recommended by clinical practice guidelines continue to be commonly used by physiotherapists in SA. This study has confirmed that physiotherapists’ pain attitudes and beliefs are significantly associated with treatment selection when managing individuals with NSCLBP.Trial registration numberResearchregistry3944.
Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants
Authors: Capiau Andreas , Mehuys Els , Van Tongelen Inge , Christiaens Thierry , De Sutter An , Steurbaut Stephane , Moudallel Souad , Rydant Silas , Vrijens Bernard , de Backer Tine L M , Boussery Koen 
Published: June 2020

ObjectiveThis study aimed to assess implementation adherence (how well the patient’s actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users.MethodsA cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ).ResultsA total of 766 patients (mean age 76.2±8.8 years, median CHA2DS2-VASc score 4 (IQR=3–4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8–99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score <25), with unintentional non-adherence (forgetfulness) most frequently reported (15.4%). Although two-thirds of NOAC users indicated to experience adverse drug reactions, the BMQ demonstrated a positive attitude towards NOAC therapy, where necessity beliefs outweigh the concerns.ConclusionsOur data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients’ thromboembolic risk and NOACs’ short half-lives, further optimisation of NOAC use seems warranted in this population.
Clinicopathological significance of CD47 expression in hepatocellular carcinoma
Authors: Kim Hyunsung , Bang Seongsik , Jee Seungyun , Paik Seung Sam , Jang Kiseok 
Published: June 2020

AimsCD47 is upregulated on the surface of various tumour cells, and it is known to inhibit the phagocytosis of tumour cells by macrophages. Immunotherapy that targets CD47 has demonstrated success in preclinical trials and is now under clinical investigation for both solid and haematological malignancies. However, data regarding CD47 expression in hepatocellular carcinoma (HCC) tissue and its correlation with clinical outcomes in patients with HCC remain limited. Here, we investigated the clinicopathological features associated with CD47 expression in HCC.MethodsCD47 expression was evaluated by immunohistochemistry in tissue microarray sections containing 166 HCC tissues. CD47 expression was considered positive if 10% or more tumour cells were stained.ResultsCD47 expression was observed in 36 (21.7%) of 166 HCC tissues and was significantly associated with frequent large vessel invasion, advanced American Joint Committee on Cancer stage and higher Ki-67 proliferation index. In the survival analyses, CD47 expression was not associated with recurrence-free survival or overall survival in total patients with HCC. However, in patients who received surgical resection without any adjuvant treatment, CD47 expression was associated with shorter recurrence-free survival.ConclusionsCD47 expression was significantly associated with adverse pathological features and poor clinical outcomes in patients with HCC who did not receive adjuvant treatment.
Loss of imprinting of the human-specific imprinted gene ZNF597 causes prenatal growth retardation and dysmorphic features: implications for phenotypic overlap with Silver-Russell syndrome
Authors: Yamazawa Kazuki , Inoue Takanobu , Sakemi Yoshihiro , Nakashima Toshinori , Yamashita Hironori , Khono Kaduki , Fujita Hideki , Enomoto Keisuke , Nakabayashi Kazuhiko , Hata Kenichiro , Nakashima Moeko , Matsunaga Tatsuo , Nakamura Akie , Matsubara Keiko , Ogata Tsutomu , Kagami Masayo 
Published: June 2020

BackgroundZNF597, encoding a zinc-finger protein, is the human-specific maternally expressed imprinted gene located on 16p13.3. The parent-of-origin expression of ZNF597 is regulated by the ZNF597:TSS-DMR, of which only the paternal allele acquires methylation during postimplantation period. Overexpression of ZNF597 may contribute to some of the phenotypes associated with maternal uniparental disomy of chromosome 16 (UPD(16)mat), and some patients with UPD(16)mat presenting with Silver-Russell syndrome (SRS) phenotype have recently been reported.MethodsA 6-year-old boy presented with prenatal growth restriction, macrocephaly at birth, forehead protrusion in infancy and clinodactyly of the fifth finger. Methylation, expression, microsatellite marker, single nucleotide polymorphism array and trio whole-exome sequencing analyses were conducted.ResultsIsolated hypomethylation of the ZNF597:TSS-DMR and subsequent loss of imprinting and overexpression of ZNF597 were confirmed in the patient. Epigenetic alterations, such as UPD including UPD(16)mat and other methylation defects, were excluded. Pathogenic sequence or copy number variants affecting his phenotypes were not identified, indicating that primary epimutation occurred postzygotically.ConclusionWe report the first case of isolated ZNF597 imprinting defect, showing phenotypic overlap with SRS despite not satisfying the clinical SRS criteria. A novel imprinting disorder entity involving the ZNF597 imprinted domain can be speculated.
Late functional improvement and 5-year poststroke outcomes: a population-based cohort study
Authors: Ganesh Aravind , Luengo-Fernandez Ramon , Rothwell Peter Malcolm 
Published: June 2020

BackgroundLate functional improvement between 3 and 12 months poststroke occurs in about one in four patients with ischaemic stroke, more commonly in lacunar strokes. It is unknown whether this late improvement is associated with better long-term clinical or health economic outcomes.MethodsIn a prospective, population-based cohort of 1-year ischaemic stroke survivors (Oxford Vascular Study; 2002–2014), we examined changes in functional status (modified Rankin Scale (mRS), Rivermead Mobility Index (RMI), Barthel Index (BI)) from 3 to 12 months poststroke. We used Cox regressions adjusted for age, sex, 3-month disability and stroke subtype (lacunar vs non-lacunar) to examine the association of late improvement (by ≥1 mRS grades, ≥1 RMI points and/or ≥2 BI points between 3 and 12 months) with 5-year mortality and institutionalisation. We used similarly adjusted generalised linear models to examine association with 5-year healthcare/social-care costs.ResultsAmong 1288 one-year survivors, 1135 (88.1%) had 3-month mRS >0, of whom 319 (28.1%) demonstrated late functional improvement between 3 and 12 months poststroke. Late improvers had lower 5-year mortality (aHR per mRS=0.68, 95% CI 0.51 to 0.91, p=0.009), institutionalisation (aHR 0.48, 0.33 to 0.72, p<0.001) and healthcare/social care costs (margin US$17 524, –24 763 to −10 284, p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (eg, 5-year mortality/institutionalisation: aHR 0.59, 0.44 to 0.79, p<0.001) and on examining late improvement per RMI and/or BI (eg, 5-year mortality/institutionalisation with RMI/BI: aHR 0.73, 0.58 to 0.92, p=0.008).ConclusionLate functional improvement poststroke is associated with lower 5-year mortality, institutionalisation rates and healthcare/social care costs. These findings should motivate patients and clinicians to maximise late recovery in routine practice, and to consider extending access to proven rehabilitative therapies during the first year poststroke.
Effects ofTPH2gene variation and childhood trauma on the clinical and circuit-level phenotype of functional movement disorders
Authors: Spagnolo Primavera A , Norato Gina , Maurer Carine W , Goldman David , Hodgkinson Colin , Horovitz Silvina , Hallett Mark 
Published: June 2020

BackgroundFunctional movement disorders (FMDs), part of the wide spectrum of functional neurological disorders (conversion disorders), are common and often associated with a poor prognosis. Nevertheless, little is known about their neurobiological underpinnings, particularly with regard to the contribution of genetic factors. Because FMD and stress-related disorders share a common core of biobehavioural manifestations, we investigated whether variants in stress-related genes also contributed, directly and interactively with childhood trauma, to the clinical and circuit-level phenotypes of FMD.MethodsSixty-nine patients with a ‘clinically defined’ diagnosis of FMD were genotyped for 18 single-nucleotide polymorphisms (SNPs) from 14 candidate genes. FMD clinical characteristics, psychiatric comorbidity and symptomatology, and childhood trauma exposure were assessed. Resting-state functional connectivity data were obtained in a subgroup of 38 patients with FMD and 38 age-matched and sex-matched healthy controls. Amygdala–frontal connectivity was analysed using a whole-brain seed-based approach.ResultsAmong the SNPs analysed, a tryptophan hydroxylase 2 (TPH2) gene polymorphism—G703T—significantly predicted clinical and neurocircuitry manifestations of FMD. Relative to GG homozygotes, T carriers were characterised by earlier FMD age of onset and decreased connectivity between the right amygdala and the middle frontal gyrus. Furthermore, theTPH2genotype showed a significant interaction with childhood trauma in predicting worse symptom severity.ConclusionsThis is, to our knowledge, the first study showing that theTPH2genotype may modulate FMD both directly and interactively with childhood trauma. Because both this polymorphism and early-life stress alter serotonin levels, our findings support a potential molecular mechanism modulating FMD phenotype.
Inclusion body myositis in patients with spinocerebellar ataxia types 3 and 6
Authors: Rietveld Anke , van Gaalen Judith , Saris Christiaan , Okkersen Kees , Küsters Benno , van de Warrenburg Bart , van Engelen Baziel , Sacconi Sabrina , Raaphorst Joost 
Published: June 2020

ObjectivesTo describe the combination of spinocerebellar ataxia (SCA) types 3 and 6 and sporadic inclusion body myositis (IBM).MethodsA description of five patients with SCA type 3 and 6 who were diagnosed with IBM. We explore possible mechanisms explaining the coexistence of both diseases.ResultsThe patients with SCA-3 (n=4) and SCA-6 (n=1) developed asymmetric muscle weakness in a pattern suggestive of IBM in the course of their disease. Based on findings of neurological examination and additional investigations (muscle ultrasound, muscle biopsy), the diagnosis of IBM was made in all patients.ConclusionWe report on five patients with concomitant SCA and IBM. Our cases may merely illustrate coincidental co-occurrence of IBM and SCA-3/SCA-6. However, the presence of SCA mutations could predispose to the development of IBM in some SCA patients, or, the presence of toxic aggregates and malfunctioning of cellular quality control processes in both diseases could indicate a convergence of disease mechanisms.
Prospective study of job stress and risk of infections in Swedish adults
Authors: Ghilotti Francesca , Åkerstedt Torbjörn , Bellocco Rino , Adami Hans-Olov , Trolle Lagerros Ylva 
Published: June 2020

ObjectivesPsychological stress may influence both susceptibility and severity of infections. Although work-related stress is a widespread concern among many employees, few studies have been conducted with the focus on work stressors and infections. We therefore aimed to investigate this association in a prospective cohort study.MethodsOur study included 25 029 employed individuals who filled-out a questionnaire in September 1997 and were followed through record linkages until retirement or December 2016. Work stress was assessed at baseline using a Swedish version of the Demand-Control Questionnaire, whereas hospital contacts related to infections were identified from the National Patient Register. We fitted extensions of the standard Cox model to account for recurrent infections.ResultsIn total, we observed 8257 infections. Individuals in the third tertile of job demand had a 13% higher hazard of infections (HR=1.13; 95% CI=1.03 to 1.24) compared with individuals in the first tertile, specifically an increased incidence of upper respiratory tract infections (HR=1.15; 95% CI=1.00 to 1.33) and urinary tract infections (HR=1.31; 95% CI=1.09 to 1.57) was found. Employees with the highest job control (third tertile) had no lower risk of infections than individuals in the lowest tertile (HR=1.02; 95% CI=0.92 to 1.13). When combining the demand and control dimensions into job strain scale, no association between high job strain and infections was observed (HR=1.08; 95% CI=0.97 to 1.21).ConclusionHigh job demand, but not low job control, is associated with an increased occurrence of infections. No difference was observed in workers with high strain jobs compared with those with low strain jobs.
Management characteristics and prognosis after stroke in China: findings from a large nationwide stroke registry
Authors: Qin Haiqiang , Chen Yiping , Liu Gaifen , Turnbull Iain , Zhang Runhua , Li Zixiao , Wang Yilong , Liu Liping , Zhao Xingquan , Chen Zhengming , Wang Yongjun 
Published: June 2020

Background and purposeThere is limited nationwide evidence about the standard management characteristics of stroke types and prognosis in China. This study aimed to assess clinical characteristics, in-hospital and after-discharge management characteristics and prognosis for stroke types in China.MethodsA nationwide registry recruited 14 244 imaging-confirmed first-ever incident strokes from 132 hospitals across 31 provinces of China during 2007–2008, recording presenting characteristics, diagnostic procedures and in-hospital treatment. After hospital discharge, patients were followed up for 6 months. Conventional statistical methods were used to examine the patterns of management and prognosis.ResultsOverall, 68.7%, 26.9% and 4.4% were ischaemic stroke (IS), intracerebral haemorrhage (ICH), and subarachnoid haemorrhage (SAH), respectively. Only 20% were managed in a dedicated stroke unit. Among IS, 1.3% received thrombolysis within 3 hours after symptom onset, whereas the proportions of receiving in-hospital antiplatelet therapy, neuroprotective agents and traditional Chinese medicines (TCM) were 88.4%, 69.7% and 70.6%, respectively. For ICH, 63.3% and 36.3% received neuroprotective agents and TCM in hospital, respectively. At discharge, 70.7% and 38.0% of the patients with IS were given antiplatelet and statin therapies, respectively, decreasing to 64.8% and 23.9%, respectively, at 6 months. In-hospital mortality was 3.2%, 9.3% and 10.1% for IS, ICH and SAH, respectively, with a further 8.6%, 18.2% and 22.0%, respectively, died by 6 month. Meanwhile, in-hospital recurrence rate was 2.6%, 1.9% and 7.2% for IS, ICH and SAH, respectively, with a further 8.0%, 5.1% and 7.5%, respectively, recurred by 6 month.ConclusionsIn China, the mortality rate of stroke is lower than that reported from west populations, though most strokes are not managed in specialised stroke unit. There is widespread use of some unproven therapies but limited proven treatments, especially after discharge, leading to unnecessary recurrent risks.
Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications
Authors: Bergholz Johann S. , Wang Qiwei , Kabraji Sheheryar , Zhao Jean J. 
Published: June 2020

Abstract
Small-molecule targeted therapies have demonstrated outstanding potential in the clinic. These drugs are designed to minimize adverse effects by selectively attacking cancer cells while exerting minimal damage to normal cells. Although initial response to targeted therapies may be high, yielding positive response rates and often improving survival for an important percentage of patients, resistance often limits long-term effectiveness. On the other hand, immunotherapy has demonstrated durable results, yet for a limited number of patients. Growing evidence indicates that some targeted agents can modulate different components of the antitumor immune response. These include immune sensitization by inhibiting tumor cell–intrinsic immune evasion programs or enhancing antigenicity, as well as direct effects on immune effector and immunosuppressive cells. The combination of these two approaches, therefore, has the potential to result in synergistic and durable outcomes for patients. In this review, we focus on the latest advances on integrating immunotherapy with small-molecule targeted inhibitors. In particular, we discuss how specific oncogenic events differentially affect immune response, and the implications of these findings on the rational design of effective combinations of immunotherapy and targeted therapies.
FORMATION OF FOREIGN LANGUAGE COMMUNICATION COMPETENCE OF FUTURE MEDICAL SPECIALISTS THROUGH INFORMATION AND COMMUNICATION TECHNOLOGIES (FOREIGN EXPERIENCE)
Authors: Kotsyuba R. B. , Prokop I. A. 
Published: June 2020

The paper considers the ways of forming foreign language communication competence of future medical specialists through ICT on the basis of foreign experience. It focuses on five most popular medical universities that, in particular, show high results in terms of medical research, carried out by the students directly: Medical School at Harvard University, School of Medicine at Johns Hopkins University, School of Medicine at New York University, Langone, School of Medicine at Stanford University, School of Medicine at University of California – San Francisco. The paper analyses training programs aimed at the formation of foreign language communication competence of future medical specialists at the above-mentioned Universities: program on the general communication language, “Medical English” distance online courses, professional language for medical students, a particular attention being paid to Michael Mitchel’s online distance course in the framework of the Swedish project. Besides, the paper considers the use of ICT means: Moodle, SpeakApps, PowerPoint, and other programs for presentations; online simulators, programs for making tests, questionnaires and games; cloud based services for the organization of foreign language online clubs, etc.