bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neighbourhood Team Development to promote resident centred approaches in nursing homes: a protocol for a multi component intervention
Authors: Boscart Veronique M. , Sidani Souraya , Ploeg Jenny , Dupuis Sherry L. , Heckman George , Kim Jessica Luh , d’Avernas Josie , Brown Paul 
Published: December 2019

Abstract
Background
As the demand for nursing home (NH) services increases, older adults and their families expect exceptional services. Neighbourhood Team Development (NTD) is a multi-component intervention designed to train team members (staff) in the implementation of resident-centered care in NH settings. A neighbourhood is a 32-resident home area within a NH. This paper presents the protocol used to implement and evaluate NTD. The evaluation aimed to 1) examine fidelity with which the NTD was implemented across NHs; 2) explore contextual factors associated with implementation and outcomes of the NTD; and 3) examine effects of NTD on residents, team members, family, and organizational outcomes, and the association between level of implementation fidelity and outcomes.

Methods
The study employed a repeated measure, mixed method design. NTD consisted of a 30-month standardised training and implementation plan to modify the physical environment, organize delivery and services and align staff members to promote inter-professional team collaboration and enhanced resident centeredness. Training was centred in each 32-resident neighbourhood or home area. Quantitative and qualitative data were collected with reliable and valid measures over the course of 3 years from residents (clinical outcomes, quality of life, satisfaction with care, perception of person centeredness, opportunities for social engagement), families (satisfaction with care for relative, person centeredness, relationship opportunities), team members (satisfaction with job, ability to provide person centered care, team relationships) and organizations (retention, turnover, staffing, events) in 6 NHs. Mixed models were used for the analysis.

Discussion
The advantages and limitations of the NTD intervention are described. The challenges in implementing and evaluating this multi-component intervention are discussed as related to the complexity of the NH environment.

Trial registration
ClinicalTrials.gov ID: NCT03415217 (January 30, 2018 – Retrospectively registered).
The functional roles of IGF-1 variants in the susceptibility and clinical outcomes of mild traumatic brain injury
Authors: Wang Yu-Jia , Wong Henry Sung-Ching , Wu Chung-Che , Chiang Yung-Hsiao , Chiu Wen-Ta , Chen Kai-Yun , Chang Wei-Chiao 
Published: December 2019

Abstract
Background
Insulin-like growth factor 1 (IGF-1) is an important pleiotropic hormone that exerts neuroprotective and neuroreparative effects after a brain injury. However, the roles of IGF-1 variants in mild traumatic brain injury (mTBI) are not yet fully understood. This study attempted to elucidate the effects of IGF-1 variants on the risk and neuropsychiatric outcomes of mTBI.

Methods
Based on 176 recruited mTBI patients and 1517 control subjects from the Taiwan Biobank project, we first compared the genotypic distributions of IGF-1 variants between the two groups. Then, we analyzed associations of IGF-1 variants with neuropsychiatric symptoms after mTBI, including anxiety, depression, dizziness, and sleep disturbances. Functional annotation of IGF-1 variants was also performed through bioinformatics databases.

Results
The minor allele of rs7136446 was over-represented in mTBI patients compared to community-based control subjects. Patients carrying minor alleles of rs7136446 and rs972936 showed more dizziness and multiple neuropsychiatric symptoms after brain injury.

Conclusions
IGF-1 variants were associated with the risk and neuropsychiatric symptoms of mTBI. The findings highlight the important role of IGF-1 in the susceptibility and clinical outcomes of mTBI.
HSV-1 triggers paracrine fibroblast growth factor response from cortical brain cells via immediate-early protein ICP0
Authors: Hensel Niko , Raker Verena , Förthmann Benjamin , Detering Nora Tula , Kubinski Sabrina , Buch Anna , Katzilieris-Petras Georgios , Spanier Julia , Gudi Viktoria , Wagenknecht Sylvia , Kopfnagel Verena , Werfel Thomas Andreas , Stangel Martin , Beineke Andreas , Kalinke Ulrich , Paludan Søren Riis , Sodeik Beate , Claus Peter 
Published: December 2019

Abstract
Background
Herpes simplex virus-1 (HSV-1) infections of the central nervous system (CNS) can result in HSV-1 encephalitis (HSE) which is characterized by severe brain damage and long-term disabilities. Different cell types including neurons and astrocytes become infected in the course of an HSE which leads to an activation of glial cells. Activated glial cells change their neurotrophic factor profile and modulate inflammation and repair. The superfamily of fibroblast growth factors (FGFs) is one of the largest family of neurotrophic factors comprising 22 ligands. FGFs induce pro-survival signaling in neurons and an anti-inflammatory answer in glial cells thereby providing a coordinated tissue response which favors repair over inflammation. Here, we hypothesize that FGF expression is altered in HSV-1-infected CNS cells.

Method
We employed primary murine cortical cultures comprising a mixed cell population of astrocytes, neurons, microglia, and oligodendrocytes. Astrocyte reactivity was morphometrically monitored by an automated image analysis algorithm as well as by analyses of A1/A2 marker expression. Altered FGF expression was detected by quantitative real-time PCR and its paracrine FGF activity. In addition, HSV-1 mutants were employed to characterize viral factors important for FGF responses of infected host cells.

Results
Astrocytes in HSV-1-infected cortical cultures were transiently activated and became hypertrophic and expressed both A1- and A2-markers. Consistently, a number of FGFs were transiently upregulated inducing paracrine neurotrophic signaling in neighboring cells. Most prominently, FGF-4, FGF-8, FGF-9, and FGF-15 became upregulated in a switch-on like mechanism. This effect was specific for CNS cells and for a fully functional HSV-1. Moreover, the viral protein ICP0 critically mediated the FGF switch-on mechanism.

Conclusions
HSV-1 uses the viral protein ICP0 for the induction of FGF-expression in CNS cells. Thus, we propose that HSV-1 triggers FGF activity in the CNS for a modulation of tissue response upon infection.
Evaluation of a new software prototype for frameless radiosurgery of arteriovenous malformations
Authors: Schmidhalter Daniel , Henzen Dominik , Herrmann Evelyn , Volken Werner , Mackeprang Paul-Henry , Ermis Ekin , Hemmatazad Hossein , Honegger Jonas , Haas Benjamin , Fix Michael K. , Manser Peter 
Published: December 2019

Abstract
Background
In order to locate an arteriovenous malformation, typically, a digital subtraction angiography (DSA) is carried out. To use the DSA for target definition an accurate image registration between CT and DSA is required. Carrying out a non-invasive, frameless procedure, registration of the 2D-DSA images with the CT is critical. A new software prototype is enabling this frameless procedure. The aim of this work was to evaluate the prototype in terms of targeting accuracy and reliability based on phantom measurements as well as with the aid of patient data. In addition, the user’s ability to recognize registration mismatches and quality was assessed.

Methods
Targeting accuracy was measured with a simple cubic, as well as with an anthropomorphic head phantom. Clearly defined academic targets within the phantoms were contoured on the CT. These reference structures were compared with the structures generated within the prototype. A similar approach was used with patient data, where the clinically contoured target served as the reference structure.
An important error source decreasing the target accuracy comes from registration errors between CT and 2D-DSA. For that reason, the tools in BC provided to the user to check these registrations are very important. In order to check if the user is able to recognize registration errors, a set of different registration errors was introduced to the correctly registered CT and 2D-DSA image data sets of three different patients. Each of six different users rated the whole set of registrations within the prototype.

Results
The target accuracy of the prototype was found to be below 0.04 cm for the cubic phantom and below 0.05 cm for the anthropomorphic head phantom. The mean target accuracy for the 15 patient cases was found to be below 0.3 cm.
In the registration verification part, almost all introduced registration errors above 1° or 0.1 cm were detected by the six users. Nevertheless, in order to quantify and categorize the possibility to detect mismatches in the registration process more data needs to be evaluated.

Conclusion
Our study shows, that the prototype is a useful tool that has the potential to fill the gap towards a frameless procedure when treating AVMs with the aid of 2D-DSA images in radiosurgery. The target accuracy of the prototype is similar to other systems already established in clinical routine.
Organotypic brain slice cultures to model neurodegenerative proteinopathies
Authors: Croft C. L. , Futch H. S. , Moore B. D. , Golde T. E. 
Published: December 2019

AbstractOrganotypic slice cultures of brain or spinal cord have been a longstanding tool in neuroscience research but their utility for understanding Alzheimer’s disease (AD) and other neurodegenerative proteinopathies has only recently begun to be evaluated. Organotypic brain slice cultures (BSCs) represent a physiologically relevant three-dimensional model of the brain. BSCs support all the central nervous system (CNS) cell types and can be produced from brain areas involved in neurodegenerative disease. BSCs can be used to better understand the induction and significance of proteinopathies underlying the development and progression of AD and other neurodegenerative disorders, and in the future may serve as bridging technologies between cell culture and in vivo experiments for the development and evaluation of novel therapeutic targets and strategies. We review the initial development and general use of BSCs in neuroscience research and highlight the advantages of these cultures as an ex vivo model. Subsequently we focus on i) BSC-based modeling of AD and other neurodegenerative proteinopathies ii) use of BSCs to understand mechanisms underlying these diseases and iii) how BSCs can serve as tools to screen for suitable therapeutics prior to in vivo investigations. Finally, we will examine i) open questions regarding the use of such cultures and ii) how emerging technologies such as recombinant adeno-associated viruses (rAAV) may be combined with these models to advance translational research relevant to neurodegenerative disorders.
Changes in circulating microRNA after recumbent isometric yoga practice by patients with myalgic encephalomyelitis/chronic fatigue syndrome: an explorative pilot study
Authors: Takakura Shu , Oka Takakazu , Sudo Nobuyuki 
Published: December 2019

Abstract
Background
Yoga is a representative mind-body therapy. Our previous studies have demonstrated that isometric yoga (i.e. yoga programs that we developed so individuals can practice yoga poses with a self-adjustable isometric load) reduces the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the underlying mechanisms remain unclear. Several studies have suggested that the micro-ribonucleic acid (miRNA) expression of ME/CFS patients is different from that of healthy subjects. However, it has not to date been determined if the practice of isometric yoga can affect miRNA expression. Therefore, we sought to investigate if isometric yoga is associated with changes in the expression levels of serum miRNA of patients with ME/CFS.

Methods
The study included nine patients with ME/CFS who failed to show satisfactory improvement after at least 6 months of treatment administered at our hospital. Patients practiced recumbent isometric yoga for 3 months; they met with a yoga instructor every 2 to 4 weeks and participated in daily in-home sessions. The effect of recumbent isometric yoga on fatigue was assessed by comparing pre- and post-intervention scores on the Japanese version of the 11-item Chalder fatigue scale (CFQ 11). Patient blood samples were drawn pre- and post-intervention, just prior to practicing recumbent isometric yoga with an instructor. The serum was used for miRNA array analysis with known human miRNAs.

Results
The average CFQ 11 score decreased significantly (from 25.3 ± 5.5 to 17.0 ± 5.8, p <  0.0001) after practicing recumbent isometric yoga for 3 months. The miRNA microarray analysis revealed that four miRNAs were significantly upregulated, and 42 were downregulated after the intervention period.

Conclusions
This explorative pilot study is the first to demonstrate changes in the serum levels of several miRNAs after regular practice of recumbent isometric yoga. These miRNAs might represent biomarkers for the fatigue-relieving effects of isometric yoga of patients with ME/CFS.

Trial registration
University Hospital Medical Information Network (UMIN CTR) 000023472. Registered Aug 4, 2016.
An evaluation of the teen and Youth Mental Health First Aid training with a CALD focus: an uncontrolled pilot study with adolescents and adults in Australia
Authors: Uribe Guajardo Maria Gabriela , Kelly Claire , Bond Kathy , Thomson Russell , Slewa-Younan Shameran 
Published: December 2019

Abstract
Background
Australia is an ethnically diverse nation with one of the largest refugee resettlement programs worldwide. Evidence suggests that although the risk of developing mental disorders in culturally linguistically diverse (CALD) adolescents may be elevated, professional help-seeking in CALD youth is low. This study sought to evaluate the face-to-face teen (tMHFA) and Youth Mental Health First Aid (YMHFA) training with a CALD focus, which aimed at improving mental health literacy (MHL) and skills in youth and adults assisting adolescents with mental health problems.

Methods
An uncontrolled pre-, post-, and follow-up design was used to measure improvement in MHL measures in year 10 students and adults.

Results
A total of 372 year 10 students from 2 high schools were trained. 308 responded to the pre-training questionnaire, 220 responded to the post-training questionnaire, and 256 completed the 3-month follow-up questionnaire. A total of 34 adults were trained, 32 responded to the pre-questionnaire and 31 responded to the post-training questionnaire and 20 completed the 3-month follow-up questionnaire. Following training, students were more likely to endorse ‘helpful’ adults as valid sources of help (p < 0.001) and these gains were maintained at follow-up (p < 0.01). Significantly higher levels of concordant (helpful) helping intentions were found after training (p < 0.01), and this was maintained at follow-up (p < 0.05). Significant lower levels of discordant (harmful) helping intentions were found after training (p < 0.001), and this was maintained at follow-up (p < 0.01). A significant improvement in adults’ knowledge of youth mental health problems and Youth Mental Health First Aid was noted from pre- to post-training (p < 0.01) and was maintained at follow-up (p < 0.01). Confidence when helping a young person with mental health problems increased significantly after training (p < 0.001) and this was maintained at follow-up (p < 0.05).

Conclusion
Our findings indicated the training led to an improvement in a number of measures of MHL and helpful intentions of both the adolescents and adults evaluated. These results indicate that CALD tMHFA and YMHFA are a recommended way of upskilling those trained and thereby leading to the improvement youth mental health in areas with high proportion of ethnically diverse groups.
Sample size re-estimation in crossover trials: application to the AIM HY-INFORM study
Authors: Wych Julie , Grayling Michael J. , Mander Adrian P. 
Published: December 2019

Abstract
Background
Crossover designs are commonly utilised in randomised controlled trials investigating treatments for long-term chronic illnesses. One problem with this design is its inherent repeated measures necessitate the availability of an estimate of the within-person standard deviation (SD) to perform a sample size calculation, which may be rarely available at the design stage of a trial. Interim sample size re-estimation designs can be used to help alleviate this issue by adapting the sample size mid-way through the trial, using accrued information in a statistically robust way.

Methods
The AIM HY-INFORM study is part of the Informative Markers in Hypertension (AIM HY) Programme and comprises two crossover trials, each with a planned recruitment of 600 participants. The objective of the study is to test whether blood pressure response to first line antihypertensive treatment depends on ethnicity. An interim analysis is planned to reassess the assumptions of the planned sample size for the study. The aims of this paper are: (1) to provide a formula for sample size re-estimation in both crossover trials; and (2) to present a simulation study of the planned interim analysis to investigate alternative within-person SDs to that assumed.

Results
The AIM HY-INFORM protocol sample size calculation fixes the within-person SD to be 8 mmHg, giving > 90% power for a primary treatment effect of 4 mmHg. Using the method developed here and simulating the interim sample size reassessment, if we were to see a larger within-person SD of 9 mmHg at interim, 640 participants for 90% power 90% of the time in the three-period three-treatment design would be required. Similarly, in the four-period four-treatment crossover design, 602 participants would be required.

Conclusions
The formulas presented here provide a method for re-estimating the sample size in crossover trials. In the context of the AIM HY-INFORM study, simulating the interim analysis allows us to explore the results of a possible increase in the within-person SD from that assumed. Simulations show that without increasing the planned sample size of 600 participants, we can reasonably still expect to achieve 80% power with a small increase in the within-person SD from that assumed.

Trial registration
ClinicalTrials.gov, NCT02847338. Registered on 28 July 2016.
eHealth-supported case management for patients with panic disorder or depression in primary care: Study protocol for a cRCT (PREMA)
Authors:   for the PREMA-study group, Lukaschek Karoline , Mergenthal Karola , Heider Dirk , Hanke Alexander , Munski Kathrein , Moschner Anne , Emig Michelle , van den Akker Marjan , Zapf Antonia , Wegscheider Karl , König Hans-Helmut , Gensichen Jochen 
Published: December 2019

Abstract
Background
Panic disorder (PD), frequently occurring with agoraphobia (AG), and depression are common mental disorders in primary care and associated with considerable individual and societal costs. Early detection and effective treatment of depression and PD/AG are of major importance. Cognitive behavioural exposure exercises have been shown to be effective in reducing anxiety and depressive symptoms. Practice team-based case management can improve clinical outcomes for patients with chronic diseases in primary care. The present study aims at evaluating the effects and cost-effectiveness of a primary care team-based intervention using behavioural therapy elements and case management supported by eHealth components in patients with PD/AG or depression compared to treatment as usual.

Methods/design
This is a two-arm cluster-randomized, controlled trial (cRCT). General practices represent the units of randomisation. General practitioners recruit adult patients with depression and PD ± AG according to the International Classification of Diseases, version 10 (ICD-10). In the intervention group, patients receive cognitive behaviour therapy-oriented psychoeducation and instructions to self-managed exposure exercises in four manual-based appointments with the general practitioner. A trained health care assistant from the practice team delivers case management and is continuously monitoring symptoms and treatment progress in ten protocol-based telephone contacts with patients. Practice teams and patients are supported by eHealth components. In the control group, patients receive usual care from general practitioners. Outcomes are measured at baseline (T0), at follow-up after 6 months (T1), and at follow-up after 12 months (T2). The primary outcome is the mental health status of patients as measured by the Mental Health Index (MHI-5). Effect sizes of 0.2 standard deviation (SD) are regarded as relevant. Assuming a drop-out rate of 20% of practices and patients each, we aim at recruiting 1844 patients in 148 primary care practices. This corresponds to 12.5 patients on average per primary care practice. Secondary outcomes include depression and anxiety-related clinical parameters and health-economic costs.

Discussion
If the intervention is more effective than treatment as usual, the three-component (cognitive behaviour therapy, case-management, eHealth) primary care-based intervention for patients suffering from PD/AG or depression could be a valuable low-threshold option that benefits patients and primary care practice teams.

Trial registration
German clinical trials register, DRKS00016622. Registered on February 22nd, 2019.
Individualised behaviour change strategies for physical activity in multiple sclerosis (IPAC-MS): protocol for a randomised controlled trial
Authors: Goulding Farren L. , Evans Charity D. , Knox Katherine B. , Lim Hyun J. , Levin Michael C. , Donkers Sarah J. 
Published: December 2019

Abstract
Background
Multiple sclerosis (MS) is a chronic, degenerative disease of the central nervous system. Because of the long-term and unpredictable nature of the disease, the burden of MS is significant from both a patient and societal perspective. Despite a recent influx of disease-modifying therapies to treat MS, many individuals continue to experience disability that negatively affects productivity and quality of life. Previous research indicates that physical activity has a positive impact on walking function in individuals with MS, in addition to the usual beneficial effects on overall health. However, most people with MS are not active enough to gain these benefits, and a lack of support to initiate and maintain physical activity has been identified as a major barrier. This study will evaluate the impact of a novel intervention involving individualised behaviour change strategies delivered by neurophysiotherapists on increasing physical activity levels in individuals with MS who are currently inactive.

Methods/design
This single-blind, parallel-group, randomised controlled trial will be conducted in Saskatchewan, Canada. Eligible participants include individuals with MS who are ambulatory but identified as currently inactive by the self-reported Godin Leisure-Time Exercise Questionnaire (GLTEQ). The intervention will be delivered by neurophysiotherapists and includes individualised behaviour change strategies aimed at increasing physical activity over a 12-month period. The control group will receive usual care during the 12-month study period. The primary outcome is the change in physical activity level, as measured by the change in the GLTEQ score from baseline to 12 months. Secondary outcomes include the change in patient-reported outcome measures assessing MS-specific symptoms, confidence and quality of life.

Discussion
Physical activity has been identified as a top research priority by the MS community. Findings from this novel study may result in new knowledge that could significantly impact the management and overall health of individuals with MS.

Trial registration
ClinicalTrials.gov, NCT04027114. Registered on 10 July 2019.