bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke
Authors: Tu Wen-Jun , Qiu Han-Cheng , Liu Ya-Kun , Liu Qiang , Zeng Xianwei , Zhao Jizong 
Published: August 2020

Abstract
Background
Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS).

Methods
This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models.

Results
This study included 4274 patients (median age 68 years [interquartile ranges {IQR}: 61–76]; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P < 0.001 and P < 0.001). In multivariable models adjusted for factors that confirmed in the univariate model, elevated serum levels of adiponectin were associated with a higher risk of MACCE (Quartile[Q]4 vs. Q1, Hazard ratio[HR] = 4.95 [95% confidence interval {CI}: 3.03–7.06]) and mortality (Q4 vs. Q1, HR = 5.63 [95% CI 3.15–7.99]). Adiponectin improved the prognostic value of the National Institutes of Health Stroke Scale (NIHSS) to predict MACCE (combined areas under the curve [AUC], 0.76; 95% CI 0.68–0.88; P = 0.001) and mortality (0.78[0.69–0.91]; P < 0.01). Subgroups analysis indicated that the prognostic role of adiponectin was more pronounced in women and patients with high levels of N-terminal-pro B-type natriuretic peptide(NT-pro BNP) (P < 0.001 and P < 0.001).

Conclusions
Elevated serum levels of adiponectin were associated with a higher risk of MACCE and mortality independent of traditional risk factors in ischemic stroke patients.
Disruption of super-enhancer-driven tumor suppressor gene RCAN1.4 expression promotes the malignancy of breast carcinoma
Authors: Deng Rong , Huang Jun-Hao , Wang Yan , Zhou Li-Huan , Wang Zi-Feng , Hu Bing-Xin , Chen Yu-Hong , Yang Dong , Mai Jia , Li Zhi-Ling , Zhang Hai-Liang , Huang Yun , Peng Xiao-Dan , Feng Gong-Kan , Zhu Xiao-Feng , Tang Jun 
Published: August 2020

AbstractBackgroundSuper-enhancers (SEs) play a crucial role in cancer, which is often associate with activated oncogenes. However, little is known about how SEs facilitate tumour suppression. Individuals with Down syndrome exhibit a remarkably reduced incidence of breast cancer (BC), moving the search for tumor suppressor genes on human chromosome 21 (HSA21). In this study, we aim to identify and explore potential mechanisms by which SEs are established for tumor suppressor RCAN1.4 on HSA21 in BC.MethodsIn silico analysis and immunohistochemical staining were used to assess the expression and clinical relevance of RCAN1.4 and RUNX3 in BC. Function experiments were performed to evaluate the effects of RCAN1.4 on the malignancy of breast carcinoma in vitro and in vivo. ChIP-seq data analysis, ChIP-qPCR, double-CRISPR genome editing, and luciferase reporter assay were utilized to confirm RUNX3 was involved in regulating RCAN1.4-associated SE in BC. The clinical value of co-expression of RCAN1.4 and RUNX3 was evaluated in BC patients.ResultsHere, we characterized RCAN1.4 as a potential tumour suppressor in BC. RCAN1.4 loss promoted tumour metastasis to bone and brain, and its overexpression inhibited tumour growth by blocking the calcineurin-NFATc1 pathway. Unexpectedly, we found RCAN1.4 expression was driven by a ~ 23 kb-long SE. RCAN1.4-SEdistalwas sensitive to BRD4 inhibition, and its deletion decreased RCAN1.4 expression by over 90% and induced the malignant phenotype of BC cells. We also discovered that the binding sites in the SE region of RCAN1.4 were enriched for consensus sequences of transcription factor RUNX3. Knockdown of RUNX3 repressed the luciferase activity and also decreased H3K27ac enrichment binding at the SE region of RCAN1.4. Furthermore, abnormal SE-driven RCAN1.4 expression mediated by RUNX3 loss could be physiologically significant and clinically relevant in BC patients. Notably, we established a prognostic model based on RCAN1.4 and RUNX3 co-expression that effectively predicted the overall survival in BC patients.ConclusionsThese findings reveal an important role of SEs in facilitating tumour suppression in BC. Considering that the combination of low RCAN1.4 and low RUNX3 expression has worse prognosis, RUNX3-RCAN1.4 axis maybe a novel prognostic biomarker and therapeutic target for BC patients.
How should community health workers in fragile contexts be supported: qualitative evidence from Sierra Leone, Liberia and Democratic Republic of Congo
Authors: Raven Joanna , Wurie Haja , Idriss Ayesha , Bah Abdulai Jawo , Baba Amuda , Nallo Gartee , Kollie Karsor K. , Dean Laura , Steege Rosie , Martineau Tim , Theobald Sally 
Published: August 2020

Abstract
Background
Community health workers (CHWs) are critical players in fragile settings, where staff shortages are particularly acute, health indicators are poor and progress towards Universal Health Coverage is slow. Like other health workers, CHWs need support to contribute effectively to health programmes and promote health equity. Yet the evidence base of what kind of support works best is weak. We present evidence from three fragile settings—Sierra Leone, Liberia and Democratic Republic of Congo on managing CHWs, and synthesise recommendations for best approaches to support this critical cadre.

Methods
We used a qualitative study design to explore how CHWs are managed, the challenges they face and potential solutions. We conducted interviews with decision makers and managers (n = 37), life history interviews with CHWs (n = 15) and reviewed policy documents.

Results
Fragility disrupts education of community members so that they may not have the literacy levels required for the CHW role. This has implications for the selection, role, training and performance of CHWs. Policy preferences about selection need discussion at the community level, so that they reflect community realities. CHWs’ scope of work is varied and may change over time, requiring ongoing training. The modular, local and mix of practical and classroom training approach worked well, helping to address gender and literacy challenges and developing a supportive cohort of CHWs. A package of supervision, community support, regular provision of supplies, performance rewards and regular remuneration is vital to retention and performance of CHWs. But there are challenges with supervision, scarcity of supplies, inadequate community recognition and unfulfilled promises about allowances. Clear communication about incentives with facility staff and communities is required as is their timely delivery.

Conclusions
This is the first study that has explored the management of CHWs in fragile settings. CHWs’ interface role between communities and health systems is critical because of their embedded positionality and the trusting relationships they (often) have. Their challenges are aligned to those generally faced by CHWs but chronic fragility exacerbates them and requires innovative problem solving to ensure that countries and communities are not left behind in reforming the way that CHWs are supported.
The opioid crisis: need for systems science research
Authors: Jalali Mohammad S. , Botticelli Michael , Hwang Rachael C. , Koh Howard K. , McHugh R. Kathryn 
Published: August 2020

AbstractThe opioid epidemic in the United States has had a devastating impact on millions of people as well as on their families and communities. The increased prevalence of opioid misuse, use disorder and overdose in recent years has highlighted the need for improved public health approaches for reducing the tremendous harms of this illness. In this paper, we explain and call for the need for more systems science approaches, which can uncover the complexities of the opioid crisis, and help evaluate, analyse and forecast the effectiveness of ongoing and new policy interventions. Similar to how a stream of systems science research helped policy development in infectious diseases and obesity, more systems science research is needed in opioids.
Focus on the morphogenesis, fate and the role in tumor progression of multivesicular bodies
Authors: Peng Xueqiang , Yang Liang , Ma Yingbo , Li Yan , Li Hangyu 
Published: August 2020

AbstractMultivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression.
Effect of novel technology-enabled multidimensional physical activity feedback in primary care patients at risk of chronic disease – the MIPACT study: a randomised controlled trial
Authors: Peacock Oliver J. , Western Max J. , Batterham Alan M. , Chowdhury Enhad A. , Stathi Afroditi , Standage Martyn , Tapp Alan , Bennett Paul , Thompson Dylan 
Published: August 2020

AbstractBackgroundTechnological progress has enabled the provision of personalised feedback across multiple dimensions of physical activity that are important for health. Whether this multidimensional approach supports physical activity behaviour change has not yet been examined. Our objective was to examine the effectiveness of a novel digital system and app that provided multidimensional physical activity feedback combined with health trainer support in primary care patients identified as at risk of chronic disease.MethodsMIPACT was a parallel-group, randomised controlled trial that recruited patients at medium (≥10 and < 20%) or high (≥20%) risk of cardiovascular disease and/or type II diabetes from six primary care practices in the United Kingdom. Intervention group participants (n = 120) received personal multidimensional physical activity feedback using a customised digital system and web-app for 3 months plus five health trainer-led sessions. All participants received standardised information regarding physical activity. Control group participants (n = 84) received no further intervention. The primary outcome was device-based assessment of physical activity at 12 months.ResultsMean intervention effects were: moderate-vigorous physical activity: -1.1 (95% CI, − 17.9 to 15.7) min/day; moderate-vigorous physical activity in ≥10-min bouts: 0.2 (− 14.2 to 14.6) min/day; Physical Activity Level (PAL): 0.00 (− 0.036 to 0.054); vigorous physical activity: 1.8 (− 0.8 to 4.2) min/day; and sedentary time: 10 (− 19.3 to 39.3) min/day. For all of these outcomes, the results showed that the groups were practically equivalent and statistically ruled out meaningful positive or negative effects (>minimum clinically important difference, MCID). However, there was profound physical activity multidimensionality, and only a small proportion (5%) of patients had consistently low physical activity across all dimensions.ConclusionIn patients at risk of cardiovascular disease and/or type II diabetes, MIPACT did not increase mean physical activity. Using a sophisticated multidimensional digital approach revealed enormous heterogeneity in baseline physical activity in primary care patients, and practitioners may need to screen for low physical activity across dimensions rather than rely on disease-risk algorithms that are heavily influenced by age.Trial registrationThis trial is registered with the ISRCTN registry (ISRCTN18008011; registration date 31 July 2013).
Scale-up of the Physical Activity 4 Everyone (PA4E1) intervention in secondary schools: 12-month implementation outcomes from a cluster randomized controlled trial
Authors: Sutherland Rachel , Campbell Elizabeth , McLaughlin Matthew , Nathan Nicole , Wolfenden Luke , Lubans David R. , Morgan Philip J. , Gillham Karen , Oldmeadow Chris , Searles Andrew , Reeves Penny , Williams Mandy , Kajons Nicole , Bailey Andrew , Boyer James , Lecathelinais Christophe , Davies Lynda , McKenzie Tom , Hollis Jenna , Wiggers John 
Published: August 2020

Abstract
Background
‘Physical Activity 4 Everyone’ (PA4E1) was an efficacious multi-component school-based physical activity (PA) program targeting adolescents. PA4E1 has seven PA practices. It is essential to scale-up, evaluate effectiveness and assess implementation of such programs. Therefore, the aim is to assess the impact of implementation support on school practice uptake of the PA4E1 program at 12 and 24 months.

Methods
A cluster randomised controlled trial, utilising a type III hybrid implementation-effectiveness design, was conducted in 49 randomly selected disadvantaged Australian Government and Catholic secondary schools. A blinded statistician randomly allocated schools to a usual practice control (n = 25) or the PA4E1 program group (n = 24), with the latter receiving seven implementation support strategies to support school PA practice uptake of the seven practices retained from the efficacy trial. The primary outcome was the proportion of schools adopting at least four of the seven practices, assessed via telephone surveys with Head Physical Education Teachers and analysed using exact logistic regression modelling. This paper reports the 12-month outcomes.

Results
Schools were recruited from May to November 2017. At baseline, no schools implemented four of the seven practices. At 12 months significantly more schools in the program group had implemented four of the seven practices (16/24, 66.7%) than the control group (1/25, 4%) (OR = 33.0[4.15–1556.4], p < 0.001). The program group implemented on average 3.2 (2.5–3.9) more practices than the control group (p < 0.001, mean 3.9 (SD 1.5) vs 0.7 (1.0)). Fidelity and reach of the implementation support intervention were high (both > 80%).

Conclusions
Through the application of multiple implementation support strategies, secondary schools were able to overcome commonly known barriers to implement evidence based school PA practices. As such practices have been shown to result in an increase in adolescent PA and improvements in weight status, policy makers and practitioners responsible for advocating PA in schools should consider this implementation approach more broadly when working with schools. Follow-up is required to determine whether practice implementation is sustained.

Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12617000681358 registered 12th May 2017.
Facilitating community participation in family planning and contraceptive services provision and uptake: community and health provider perspectives
Authors: Silumbwe Adam , Nkole Theresa , Munakampe Margarate N. , Cordero Joanna Paula , Milford Cecilia , Zulu Joseph Mumba , Steyn Petrus S. 
Published: August 2020

Abstract
Background
Although community participation has been identified as being important for improved and sustained health outcomes, designing and successfully implementing it in large scale public health programmes, including family planning and contraceptive (FP/C) service provision, remains challenging. Zambian participants in a multi-country project (the UPTAKE project) took part in the development of an intervention involving community and healthcare provider participation in FP/C services provision and uptake. This study reports key thematic areas identified by the study participants as critical to facilitating community participation in this intervention.

Methods
This was an exploratory qualitative research study, conducted in Kabwe District, Central Province, in 2017. Twelve focus group discussions were conducted with community members (n = 114), two with healthcare providers (n = 19), and ten in-depth interviews with key community and health sector stakeholders. Data were analyzed using a thematic analysis approach.

Results
Four thematic categories were identified by the participants as critical to facilitating community participation in FP/C services. Firstly, accountability in the recruitment of community participants and incorporation of community feedback in FP/C.
programming. Secondly, engagement of existing community resources and structures in FP/C services provision. Thirdly, building trust in FP/C methods/services through credible community-based distributors and promotion of appropriate FP/C methods/services. Fourthly, promoting strategies that address structural failures, such as the feminisation of FP/C services and the lack FP/C services that are responsive to adolescent needs.

Conclusions
Understanding and considering community members’ and healthcare providers’ views regarding contextualized and locally relevant participatory approaches, facilitators and challenges to participation, could improve the design, implementation and success of participatory public health programmes, including FP/C.
Can kinematic parameters of 3D reach-to-target movements be used as a proxy for clinical outcome measures in chronic stroke rehabilitation? An exploratory study
Authors: Adans-Dester Catherine , Fasoli Susan E. , Fabara Eric , Menard Nicolas , Fox Annie B. , Severini Giacomo , Bonato Paolo 
Published: August 2020

AbstractBackgroundDespite numerous trials investigating robot-assisted therapy (RT) effects on upper-extremity (UE) function after stroke, few have explored the relationship between three-dimensional (3D) reach-to-target kinematics and clinical outcomes. The objectives of this study were to 1) investigate the correlation between kinematic parameters of 3D reach-to-target movements and UE clinical outcome measures, and 2) examine the degree to which differences in kinematic parameters across individuals can account for differences in clinical outcomes in response to RT.MethodsTen chronic stroke survivors participated in a pilot RT intervention (eighteen 1-h sessions) integrating cognitive skills training and a home-action program. Clinical outcome measures and kinematic parameters of 3D reach-to-target movements were collected pre- and post-intervention. The correlation between clinical outcomes and kinematic parameters was investigated both cross-sectionally and longitudinally (i.e., changes in response to the intervention). Changes in clinical outcomes and kinematic parameters were tested for significance in both group and subject-by-subject analyses.Potential associations between individual differences in kinematic parameters and differences in clinical outcomes were examined.ResultsModerate-to-strong correlation was found between clinical measures and specific kinematic parameters when examined cross-sectionally. Weaker correlation coefficients were found longitudinally. Group analyses revealed significant changes in clinical outcome measures in response to the intervention; no significant group changes were observed in kinematic parameters. Subject-by-subject analyses revealed changes with moderate-to-large effect size in the kinematics of 3D reach-to-target movements pre- vs. post-intervention. Changes in clinical outcomes and kinematic parameters varied widely across participants.ConclusionsLarge variability was observed across subjects in response to the intervention. The correlation between changes in kinematic parameters and clinical outcomes in response to the intervention was variable and not strong across parameters, suggesting no consistent change in UE motor strategies across participants. These results highlight the need to investigate the response to interventions at the individual level. This would enable the identification of clusters of individuals with common patterns of change in response to an intervention, providing an opportunity to use cluster-specific kinematic parameters as a proxy of clinical outcomes.Trial registrationClinicalTrials.gov,NCT02747433. Registered on April 21st, 2016
Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties
Authors: Bendtsen Katja Maria , Gren Louise , Malmborg Vilhelm Berg , Shukla Pravesh Chandra , Tunér Martin , Essig Yona J. , Krais Annette M. , Clausen Per Axel , Berthing Trine , Loeschner Katrin , Jacobsen Nicklas Raun , Wolff Henrik , Pagels Joakim , Vogel Ulla Birgitte 
Published: August 2020

Abstract
Background
Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black.

Results
Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15–22 nm, specific surface area: 152–222 m2/g, and count median mobility diameter: 55–103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12–0.60), polycyclic aromatic hydrocarbon content (1–27 μg/mg) and acid-extractable metal content (0.9–16 μg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS.

Conclusions
We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.