bluuebunny/crossref_metadata_2025_split huggingface dataset:
A framework for distributed health professions training: using participatory action research to build consensus
Authors: Van Schalkwyk Susan C. , Couper Ian D. , Blitz Julia , De Villiers Marietjie R. 
Published: May 2020

Abstract
Background
There is a global trend towards providing training for health professions students outside of tertiary academic complexes. In many countries, this shift places pressure on available sites and the resources at their disposal, specifically within the public health sector. Introducing an educational remit into a complex health system is challenging, requiring commitment from a range of stakeholders, including national authorities. To facilitate the effective implementation of distributed training, we developed a guiding framework through an extensive, national consultative process with a view to informing both practice and policy.

Methods
We adopted a participatory action research approach over a four year period across three phases, which included seven local, provincial and national consultative workshops, reflective work sessions by the research team, and expert reviews. Approximately 240 people participated in these activities. Engagement with the national department of health and health professions council further informed the development of the Framework.

Results
Each successive ‘feedback loop’ contributed to the development of the Framework which comprised a set of guiding principles, as well as the components essential to the effective implementation of distributed training. Analysis further pointed to the centrality of relationships, while emphasising the importance of involving all sectors relevant to the training of health professionals. A tool to facilitate the implementation of the Framework was also developed, incorporating a set of ‘Simple Rules for Effective distributed health professions training’. A national consensus statement was adopted.

Conclusions
In this project, we drew on the thinking and practices of key stakeholders to enable a synthesis between their embodied and inscribed knowledge, and the prevailing literature, this with a view to further enaction as the knowledge generators become knowledge users. The Framework and its subsequent implementation has not only assisted us to apply the evidence to our educational practice, but also to begin to influence policy at a national level.
Identifying and selecting implementation theories, models and frameworks: a qualitative study to inform the development of a decision support tool
Authors: Strifler Lisa , Barnsley Jan M. , Hillmer Michael , Straus Sharon E. 
Published: May 2020

Abstract
Background
Implementation theories, models and frameworks offer guidance when implementing and sustaining healthcare evidence-based interventions. However, selection can be challenging given the myriad of potential options. We propose to inform a decision support tool to facilitate the appropriate selection of an implementation theory, model or framework in practice. To inform tool development, this study aimed to explore barriers and facilitators to identifying and selecting implementation theories, models and frameworks in research and practice, as well as end-user preferences for features and functions of the proposed tool.

Methods
We used an interpretive descriptive approach to conduct semi-structured interviews with implementation researchers and practitioners in Canada, the United States and Australia. Audio recordings were transcribed verbatim. Data were inductively coded by a single investigator with a subset of 20% coded independently by a second investigator and analyzed using thematic analysis.

Results
Twenty-four individuals participated in the study. Categories of barriers/facilitators, to inform tool development, included characteristics of the individual or team conducting implementation and characteristics of the implementation theory, model or framework. Major barriers to selection included inconsistent terminology, poor fit with the implementation context and limited knowledge about and training in existing theories, models and frameworks. Major facilitators to selection included the importance of clear and concise language and evidence that the theory, model or framework was applied in a relevant health setting or context. Participants were enthusiastic about the development of a decision support tool that is user-friendly, accessible and practical. Preferences for tool features included key questions about the implementation intervention or project (e.g., purpose, stage of implementation, intended target for change) and a comprehensive list of relevant theories, models and frameworks to choose from along with a glossary of terms and the contexts in which they were applied.

Conclusions
An easy to use decision support tool that addresses key barriers to selecting an implementation theory, model or framework in practice may be beneficial to individuals who facilitate implementation practice activities. Findings on end-user preferences for tool features and functions will inform tool development and design through a user-centered approach.
Adaptive design: adaptation and adoption of patient safety practices in daily routines, a multi-site study
Authors: Dekker - van Doorn Connie , Wauben Linda , van Wijngaarden Jeroen , Lange Johan , Huijsman Robbert 
Published: May 2020

AbstractBackgroundMost interventions to improve patient safety (Patient Safety Practices (PSPs)), are introduced without engaging front-line professionals. Administrative staff, managers and sometimes a few professionals, representing only one or two disciplines, decide what to change and how. Consequently, PSPs are not fully adapted to the professionals’ needs or to the local context and as a result, adoption is low. To support adoption, two theoretical concepts, Participatory Design and Experiential Learning were combined in a new model: Adaptive Design. The aim was to explore whether Adaptive Design supports adaptation and adoption of PSPs by engaging all professionals and creating time to (re) design, reflect and learn as a team. The Time Out Procedure (TOP) and Debriefing (plus) for improving patient safety in the operating theatre (OT) was used as PSP.MethodsQualitative exploratory multi-site study using participatory action research as a research design. The implementation process consisted of four phases: 1) start-up: providing information by presentations and team meetings, 2) pilot: testing the prototype with 100 surgical procedures, 3) small scale implementation: with one or two surgical disciplines, 4) implementation hospital-wide: including all surgical disciplines. In iterations, teams (re) designed, tested, evaluated, and if necessary adapted TOPplus. Gradually all professionals were included. Adaptations in content, process and layout of TOPpluswere measured following each iteration. Adoption was monitored until final implementation in every hospital’s OT.Results10 Dutch hospitals participated.Adaptations varied per hospital, but all hospitals adapted both procedures. Adaptations concerned the content, process and layout of TOPplus. Both procedures were adopted in all OTs, but user participation and time to include all users varied between hospitals. Ultimately all users were actively involved and TOPpluswas implemented in all OTs.ConclusionsEngaging all professionals in a structured bottom-up implementation approach with a focus on learning, improves adaptation and adoption of a PSP. As a result, all 10 participating hospitals implemented TOPpluswith all surgical disciplines in all OTs. Adaptive Design gives professionals the opportunity to adapt the PSP to their own needs and their specific local context. All hospitals adapted TOPplus, but without compromising the essential features for its effectiveness.
ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer
Authors: Lin Chun-Lin , Tan Xi , Chen Meizhen , Kusi Meena , Hung Chia-Nung , Chou Chih-Wei , Hsu Ya-Ting , Wang Chiou-Miin , Kirma Nameer , Chen Chun-Liang , Lin Ching-Hung , Lathrop Kate I. , Elledge Richard , Kaklamani Virginia G. , Mitsuya Kohzoh , Huang Tim H.-M. 
Published: May 2020

Abstract
Background
Chromothripsis is an event of genomic instability leading to complex chromosomal alterations in cancer. Frequent long-range chromatin interactions between transcription factors (TFs) and targets may promote extensive translocations and copy-number alterations in proximal contact regions through inappropriate DNA stitching. Although studies have proposed models to explain the initiation of chromothripsis, few discussed how TFs influence this process for tumor progression.

Methods
This study focused on genomic alterations in amplification associated regions within chromosome 17. Inter−/intra-chromosomal rearrangements were analyzed using whole genome sequencing data of breast tumors in the Cancer Genome Atlas (TCGA) cohort. Common ERα binding sites were defined based on MCF-7, T47D, and MDA-MB-134 breast cancer cell lines using univariate K-means clustering methods. Nanopore sequencing technology was applied to validate frequent rearrangements detected between ATC loci on 17q23 and an ERα hub on 20q13. The efficacy of pharmacological inhibition of a potentially druggable target gene on 17q23 was evaluated using breast cancer cell lines and patient-derived circulating breast tumor cells.

Results
There are five adjoining regions from 17q11.1 to 17q24.1 being hotspots of chromothripsis. Inter−/intra-chromosomal rearrangements of these regions occurred more frequently in ERα-positive tumors than in ERα-negative tumors. In addition, the locations of the rearrangements were often mapped within or close to dense ERα binding sites localized on these five 17q regions or other chromosomes. This chromothriptic event was linked to concordant upregulation of 96 loci that predominantly regulate cell-cycle machineries in advanced luminal tumors. Genome-editing analysis confirmed that an ERα hub localized on 20q13 coordinately regulates a subset of these loci localized on 17q23 through long-range chromosome interactions. One of these loci, Tousled Like Kinase 2 (TLK2) known to participate in DNA damage checkpoint control, is an actionable target using phenothiazine antipsychotics (PTZs). The antiproliferative effect of PTZs was prominent in high TLK2-expressing cells, compared to low expressing cells.

Conclusion
This study demonstrates a new approach for identifying tumorigenic drivers from genomic regions highly susceptible to ERα-related chromothripsis. We found a group of luminal breast tumors displaying 17q-related chromothripsis for which antipsychotics can be repurposed as treatment adjuncts.
Long-term exposure to particulate air pollution and brachial artery flow-mediated dilation in the Old Order Amish
Authors: Salimi Shabnam , Yanosky Jeff D. , Huang Dina , Montressor-Lopez Jessica , Vogel Robert , Reed Robert M. , Mitchell Braxton D. , Puett Robin C. 
Published: May 2020

Abstract
Background
Atmospheric particulate matter (PM) has been associated with endothelial dysfunction, an early marker of cardiovascular risk. Our aim was to extend this research to a genetically homogenous, geographically stable rural population using location-specific moving-average air pollution exposure estimates indexed to the date of endothelial function measurement.

Methods
We measured endothelial function using brachial artery flow-mediated dilation (FMD) in 615 community-dwelling healthy Amish participants. Exposures to PM < 2.5 μm (PM2.5) and PM < 10 μm (PM10) were estimated at participants’ residential addresses using previously developed geographic information system-based spatio-temporal models and normalized. Associations between PM exposures and FMD were evaluated using linear mixed-effects regression models, and polynomial distributed lag (PDL) models followed by Bayesian model averaging (BMA) were used to assess response to delayed effects occurring across multiple months.

Results
Exposure to PM10 was consistently inversely associated with FMD, with the strongest (most negative) association for a 12-month moving average (− 0.09; 95% CI: − 0.15, − 0.03). Associations with PM2.5 were also strongest for a 12-month moving average but were weaker than for PM10 (− 0.07; 95% CI: − 0.13, − 0.09). Associations of PM2.5 and PM10 with FMD were somewhat stronger in men than in women, particularly for PM10.

Conclusions
Using location-specific moving-average air pollution exposure estimates, we have shown that 12-month moving-average estimates of PM2.5 and PM10 exposure are associated with impaired endothelial function in a rural population.
Associations of ambient air pollutants with regional pulmonary tuberculosis incidence in the central Chinese province of Hubei: a Bayesian spatial-temporal analysis
Authors: Liu Fuqiang , Zhang Zhixia , Chen Hongying , Nie Shaofa 
Published: May 2020

AbstractBackgroundAir pollution and pulmonary tuberculosis (PTB) are still serious worldwide problems, especially in areas of developing countries. Whether there is an association between high ambient air pollutant concentrations and PTB has not been fully explored.MethodsBayesian spatial-temporal models were constructed to analyse the association between ambient air pollutants (particulate matter with aerodynamic diameters of ≤10 μm (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2)) and PTB incidence, adjusting for socioeconomic covariates. We collected data on pulmonary TB, ambient air pollution (PM10, SO2and NO2) concentrations and socioeconomic covariates from 17 prefectures in the central Chinese province of Hubei between Jan 1, 2006, and Dec 31, 2015.ResultsFor every annual 10 μg/m3increase in SO2, the relative risk (RR) of PTB incidence was 1.046 (95% credible interval [CI], 1.038–1.054) in the study area. Moreover, we found positive associations with each annual 10 μg/m3increase in ambient air pollutants (PM10, SO2and NO2) in females but only with SO2in males. A significant association for each 10 μg/m3increase in SO2was observed in all the age groups, with a significant association for PM10only in children under 14 years of age. A significant response relationship was also observed at a 0–1 month moving average lag for each 10 μg/m3increase in SO2.ConclusionsHigh ambient air pollution concentrations in areas of developing countries might increase the risk of regional PTB incidence, especially for women and young people. Precautions and protective measures and efforts to reduce ambient air pollutant concentrations should be strengthened in developing countries.
Graphene oxide suppresses the growth and malignancy of glioblastoma stem cell-like spheroids via epigenetic mechanisms
Authors: Wang Xu , Zhou Wenjuan , Li Xian , Ren Jun , Ji Guangyu , Du Jingyi , Tian Wenyu , Liu Qian , Hao Aijun 
Published: May 2020

Abstract
Background
Glioblastoma stem-like cells (GSCs) are hypothesized to contribute to self-renewal and therapeutic resistance in glioblastoma multiforme (GBM) tumors. Constituting only a small percentage of cancer cells, GSCs possess “stem-like”, tumor-initiating properties and display resistance to irradiation and chemotherapy. Thus, novel approaches that can be used to suppress GSCs are urgently needed. A new carbon material—graphene oxide (GO), has been reported to show potential for use in tumor therapy. However, the exact effect of GO on GSCs and the inherent mechanism underlying its action are not clear. In this study, we aimed to investigate the usefulness of GO to inhibit the growth and promote the differentiation of GSCs, so as to suppress the malignancy of GBM.

Methods
In vitro effects of GO on sphere-forming ability, cell proliferation and differentiation were evaluated in U87, U251 GSCs and primary GSCs. The changes in cell cycle and the level of epigenetic modification H3K27me3 were examined. GO was also tested in vivo against U87 GSCs in mouse subcutaneous xenograft models by evaluating tumor growth and histological features.

Results
We cultured GSCs to explore the effect of GO and the underlying mechanism of its action. We found, for the first time, that GO triggers the inhibition of cell proliferation and induces apoptotic cell death in GSCs. Moreover, GO could promote the differentiation of GSCs by decreasing the expression of stem cell markers (SOX2 and CD133) and increasing the expression of differentiation-related markers (GFAP and β-III tubulin). Mechanistically, we found that GO had a striking effect on GSCs by inducing cell cycle arrest and epigenetic regulation. GO decreased H3K27me3 levels, which are regulated by EZH2 and associated with transcriptional silencing, in the promoters of the differentiation-related genes GFAP and β-III tubulin, thereby enhancing GSC differentiation. In addition, compared with untreated GSCs, GO-treated GSCs that were injected into nude mice exhibited decreased tumor growth in vivo.

Conclusion
These results suggested that GO could promote differentiation and reduce malignancy in GSCs via an unanticipated epigenetic mechanism, which further demonstrated that GO is a potent anti-GBM agent that could be useful for future clinical applications.
Anti-IL-20 antibody improved motor function and reduced glial scar formation after traumatic spinal cord injury in rats
Authors: Lee Jung-Shun , Hsu Yu-Hsiang , Chiu Yi-Shu , Jou I-Ming , Chang Ming-Shi 
Published: May 2020

Abstract
Background
Spinal cord injury (SCI) causes devastating neurological consequences, which can result in partial or total paralysis. Irreversible neurological deficits and glial scar formation are characteristic of SCI. Inflammatory responses are a major component of secondary injury and play a central role in regulating the pathogenesis of SCI. IL-20 is a proinflammatory cytokine involved in renal fibrosis and liver cirrhosis through its role in upregulating TGF-β1 production. However, the role of IL-20 in SCI remains unclear. We hypothesize that IL-20 is upregulated after SCI and is involved in regulating the neuroinflammatory response.

Methods
The expression of IL-20 and its receptors was examined in SCI rats. The regulatory roles of IL-20 in astrocytes and neuron cells were examined. The therapeutic effects of anti-IL-20 monoclonal antibody (mAb) 7E in SCI rats were evaluated.

Results
Immunofluorescence staining showed that IL-20 and its receptors were expressed in astrocytes, oligodendrocytes, and microglia in the spinal cord after SCI in rats. In vitro, IL-20 enhanced astrocyte reactivation and cell migration in human astrocyte (HA) cells by upregulating glial fibrillary acidic protein (GFAP), TGF-β1, TNF-α, MCP-1, and IL-6 expression. IL-20 inhibited cell proliferation and nerve growth factor (NGF)-derived neurite outgrowth in PC-12 cells through Sema3A/NRP-1 upregulation. In vivo, treating SCI rats with anti-IL-20 mAb 7E remarkably inhibited the inflammatory responses. 7E treatment not only improved motor and sensory functions but also improved spinal cord tissue preservation and reduced glial scar formation in SCI rats.

Conclusions
IL-20 might regulate astrocyte reactivation and axonal regeneration and result in the secondary injury in SCI. These findings demonstrated that IL-20 may be a promising target for SCI treatment.
Transient changes in paretic and non-paretic isometric force control during bimanual submaximal and maximal contractions
Authors: Kim Hyun Joon , Kang Nyeonju , Cauraugh James H. 
Published: May 2020

Abstract
Purpose
The purpose of this study was to investigate transient bimanual effects on the force control capabilities of the paretic and non-paretic arms in individuals post stroke across submaximal and maximal force control tasks.

Methods
Fourteen chronic stroke patients (mean age = 63.8 ± 15.9; stroke duration = 38.7 ± 45.2 months) completed two isometric force control tasks: (a) submaximal control and (b) maximal sustained force production. Participants executed both tasks with their wrist and fingers extending across unimanual (paretic and non-paretic arms) and bimanual conditions. Mean force, force variability using coefficient of variation, force regularity using sample entropy were calculated for each condition.

Results
During the submaximal force control tasks (i.e., 5, 25, and 50% of maximum voluntary contraction), the asymmetrical mean force between the paretic and non-paretic arms decreased from unimanual to bimanual conditions. The asymmetry of force variability and regularity between the two arms while executing unimanual force control tended to decrease in the bimanual condition because of greater increases in the force variability and regularity for the non-paretic arm than those for the paretic arm. During the maximal sustained force production tasks (i.e., 100% of maximum voluntary contraction), the paretic arm increased maximal forces and decreased force variability in the bimanual condition, whereas the non-paretic arm reduced maximal forces and elevated force variability from unimanual to bimanual conditions.

Conclusions
The current findings support a proposition that repetitive bimanual isometric training with higher execution intensity may facilitate progress toward stroke motor recovery.
Establishing exclusive breastfeeding among in-patient malnourished infants in a rural Kenyan hospital: mothers’ experiences of a peer supporter intervention
Authors: Kahindi Jane , Jones Caroline , Berkley James A. , Mwangome Martha 
Published: May 2020

Abstract
Background
The 2013 WHO guidelines for nutritional rehabilitation of hospitalized and non-hospitalized malnourished infants under six months (u6m) recommend the re-establishment of exclusive breastfeeding. However, in most low-income settings these recommendations are not consistently applied. A recently concluded pilot study on the effects of implementing these guidelines among hospitalized malnourished infants u6m of age in Kilifi, Kenya introduced breastfeeding peer supporters (BFPS) to the inpatient setting to support guideline implementation. Here we report a sub-study investigating mothers’ experiences and perceptions of the process of re-establishing exclusive breastfeeding during their infant’s admission to hospital.

Methods
Interviews were conducted with mothers just prior to their infant’s discharge to explore their experiences and perceptions of the breastfeeding support process. A trained social science researcher conducted the interviews in Kiswahili language using a structured interview guide with open questions. Interviews were tape recorded, transcribed and translated into English for analysis. Data were managed and organized using NVIVO version 10 and analyzed using a framework approach.

Results
Twenty mothers were interviewed. While some mothers found re-establishing breastfeeding challenging, they all reported improved knowledge on the relationships between maternal nutrition, stress management, hygiene practices and breastmilk production. They also reported gaining skills in breast care, breastfeeding techniques, hand expression and handling of expressed breastmilk. The breastfeeding peer supporters were said to have provided technical, social and emotional support which facilitated the process of re-establishing exclusive breastfeeding. The mothers identified the key characteristics of an effective and trustworthy BFPS as well as gaps in support.

Conclusion
BFPS are able share knowledge and skills in a way that is understood and appreciated by the mothers of inpatient malnourished infants u6m of age, enhancing the reestablishment of exclusive breastfeeding. Central to the success of BFPS is their ability to develop close and supportive relationships with the mothers based on shared social and cultural backgrounds. Future studies should focus on evaluating the long-term impact of inpatient breastfeeding support strategies on the quality of breastfeeding and growth, as well as on understanding where, when and how BFPS might be incorporated into routine hospital settings.