bluuebunny/crossref_metadata_2025_split huggingface dataset:
A co-production approach guided by the Behaviour Change Wheel to develop an intervention for reducing sedentary behaviour after stroke
Authors: Hall Jennifer , Morton Sarah , Hall Jessica , Clarke David J , Fitzsimons Claire F , English Coralie , Forster Anne , Mead Gillian E , Lawton Rebecca 
Published: July 2020

Abstract
Background: Stroke survivors are highly sedentary; thus, breaking up long uninterrupted bouts of sedentary behaviour could have substantial health benefit. However, there are no intervention strategies specifically aimed at reducing sedentary behaviour tailored for stroke survivors. The purpose of this study was to use co-production approaches to develop an intervention to reduce sedentary behaviour after stroke.Methods: A series of five co-production workshops with stroke survivors, their caregivers, stroke service staff, exercise professionals, and researchers were conducted in parallel in two stroke services (England and Scotland). Workshop format was informed by the Behaviour Change Wheel (BCW) framework for developing interventions and incorporated systematic review and empirical evidence. Taking an iterative approach, data from activities and audio recordings were analysed following each workshop and findings used to inform subsequent workshops, to inform both the activities of the next workshop and ongoing intervention development.Findings: Co-production workshop participants (n = 43) included 17 staff, 14 stroke survivors, six caregivers, and six researchers. The target behaviour for stroke survivors is to increase standing and moving, and the target behaviour for caregivers and staff is to support and encourage stroke survivors to increase standing and moving. The developed intervention is primarily based on co-produced solutions to barriers to achieving the target behaviour. The developed intervention includes 34 behaviour change techniques. The intervention is to be delivered through stroke services, commencing in the inpatient setting and following through discharge into the community. Participants reported that taking part in intervention development was a positive experience. Conclusions: To our knowledge, this is the first study that has combined the use of co-production and the BCW to develop an intervention for use in stroke care. In-depth reporting of how a co-production approach was combined with the BCW framework, including the design of bespoke materials for workshop activities, should prove useful to other researchers and practitioners involved in intervention development in stroke.
Older persons are frailer after an emergency care visit to the out-of-hours General Practitioner Cooperative in the Netherlands: a cross-sectional descriptive TOPICS-MDS study
Authors: Bloemhoff Anneke , Schoon Yvonne , Smulders Kien , Akkermans Reinier , Vloet Lilian , Berg Karen van den , Berben Sivera 
Published: July 2020

Abstract
Background: In the Netherlands, community-dwelling older people with primary care emergency problems contact the General Practitioner Cooperative (GPC) after hours. However, frailty remains an often unobserved hazard with adverse health outcomes. The aim of this study was to provide insight into differences between older persons with or without GPC emergency care visits (reference group) regarding frailty and healthcare use.Methods: A cross-sectional descriptive study design was based on data from the public data repository of The Older Persons and Informal Caregivers Survey Minimum Dataset (TOPICS-MDS). Frailty in older persons (65+ years, n=32,149) was measured by comorbidity, functional and psychosocial aspects, quality of life and a frailty index. Furthermore, home care use and hospital admissions of older persons were identified. We performed multilevel logistic and linear regression analyses. A random intercept model was utilised to test differences between groups, and adjustment factors (confounders) were used in the multilevel analysis.Results: Compared to the reference group, older persons with GPC contact were frailer in the domain of comorbidity (mean difference 0.52; 95% CI 0.47-0.57, p <0.0001) and functional limitations (mean difference 0.53; 95% CI 0.46-0.60, p <0.0001), and they reported less emotional wellbeing (mean difference -4.10; 95% CI -4.59- -3.60, p <0.0001) and experienced a lower quality of life (mean difference -0.057; 95% CI -0.064- -0.050, p <0.0001). Moreover, older persons more often reported limited social function (OR = 1.50; 95% CI 1.39-1.62, p <0.0001) and limited perceived health (OR = 1.50, 95% CI 1.39-1.62, p <0.0001). Finally, older persons with GPC contact more often used home care (OR = 1.37; 95% CI 1.28-1.47, p <0.0001) or were more often admitted to the hospital (OR = 2.88; 95% CI 2.71-3.06, p <0.0001).Conclusions: Older persons with out-of-hours GPC contact for an emergency care visit were significantly frailer in all domains and more likely to use home care or to be admitted to the hospital compared to the reference group. Potentially frail older persons seemed to require adequate identification of frailty and support (e.g., advanced care planning) both before and after a contact with the out-of-hours GPC.
Spatial-temporal analysis of Tuberculosis in Chongqing, China 2011-2018
Authors: Yu Ya , Wu Bo , Wu Chengguo , Wang Qingya , Hu Daiyu , Chen Wei 
Published: July 2020

Abstract
Background: China is a country with a high burden of pulmonary tuberculosis (PTB). Chongqing is in the southwest of China, where the notification rate of PTB ranks tenth in China. This study analyzed the temporal and spatial distribution characteristics of PTB in Chongqing in order to improve TB control measures.Methods: A spatial-temporal analysis has been performed based on the data of PTB from 2011 to 2018, which was extracted from the National Surveillance System. The effect of TB control was measured by variation trend of pathogenic positive PTB notification rate and total TB notification rate. Time series, spatial autonomic correlation and spatial-temporal scanning methods were used to identify the temporal trends and spatial patterns at county level.Results: A total of 188,528 cases were included in this study. A downward trend was observed in PTB between 2011 and 2018 in Chongqing. The peak of PTB notification occurred in late winter and early spring annually. By calculating the value of Global Moran's I and Local Getis’s Gi*, we found that PTB was spatially clustered and some significant hot spots were detected in the southeast and northeast of Chongqing. One most likely cluster and three secondary clusters were identified by Kulldorff’s scan spatial-temporal Statistic.Conclusions: This study identified seasonal patterns and spatial-temporal clusters of PTB cases in Chongqing. Priorities should be given to southeast and northeast of Chongqing for better TB control.
3-Methylxanthine production through biodegradation of theobromine by Aspergillus sydowii PT-2
Authors: ZHOU bin-xing , Ma Cunqiang , Zheng Chengqin , Xia Tao , Ma Bingsong , Liu Xiaohui 
Published: July 2020

Abstract
Background: Methylxanthines, including caffeine, theobromine and theophylline, are natural and synthetic compounds in tea, which could be metabolized by certain kinds of bacteria and fungi. Previous studies confirmed that several microbial isolates from Pu-erh tea could degrade and convert caffeine and theophylline. We speculated that these candidate isolates also could degrade and convert theobromine through N-demethylation and oxidation. In this study, seven tea-derived fungal strains were inoculated into various theobromine agar medias and theobromine liquid mediums to assess their capacity in theobromine utilization. Related metabolites with theobromine degradation were detected by using HPLC in the liquid culture to investigate their potential application in the production of 3-methylxanthine. Results: Based on theobromine utilization capacity, Aspergillus niger PT-1, Aspergillus sydowii PT-2, Aspergillus ustus PT-6 and Aspergillus tamarii PT-7 have demonstrated the potential for theobromine biodegradation. Particularly, A. sydowii PT-2 and A. tamarii PT-7 could degrade theobromine significantly (p < 0.05) in all given liquid mediums. 3,7-Dimethyluric acid, 3-methylxanthine, 7-methylxanthine, 3-methyluric acid, xanthine, and uric acid were detected in A. sydowii PT-2 and A. tamarii PT-7 culture, respectively, which confirmed the existence of N-demethylation and oxidation in theobromine catabolism. 3-Methylxanthine was common and main demethylated metabolite of theobromine in the liquid culture. 3-Methylxanthine in A. sydowii PT-2 culture showed a linear relation with initial theobromine concentrations that 177.12 ± 14.06 mg/L 3-methylxanthine was accumulated in TLM-S with 300 mg/L theobromine. Additionally, pH at 5 and metal ion of Fe2+ promoted 3-methylxanthine production significantly (p < 0.05). Conclusions: This study is the first to confirm that A. sydowii PT-2 and A. tamarii PT-7 degrade theobromine through N-demethylation and oxidation, respectively. A. sydowii PT-2 showed the potential application in 3-methylxanthine production with theobromine as feedstock through the N-demethylation at N-7 position.
Health-related publications on people living in fragile states in the alert zone: a bibliometric analysis
Authors: Sweileh Waleed 
Published: July 2020

Abstract
Background: Fragile states pose a global challenge. Assessing health research activity on people living in these states can help identify neglected health domains in fragile settings. The objective of the current study was to assess and describe health research activity on people living in fragile states in the alert zone. Method: A bibliometric method was applied using SciVerse Scopus. Research articles published on people in fragile states in the alert zone were retrieved and analyzed. The Fragile State Index (FSI) score was used for selection of states in the alert zone. The analysis was limited to one year; 2018. Results: The search query found 2299 research articles giving an average of 2 research articles per one million population per year in the selected fragile states. The number of research articles per one million population was not significantly correlated (p=0.053; r= - 0.349) with FSI scores. However, it was significantly correlated with the extent of international research collaboration (P<0.01, r=065). Research on communicable diseases was the largest research domain (763 articles; 33.2%) followed by maternal/women’s health (430 articles; 18.7%), non-communicable diseases (291 articles; 12.7%), health system/policy (271 articles; 11.8%) and psychosocial and mental health (89; 3.9%). There were three research themes in the research domain of infectious diseases: HIV/AIDS; water-borne infectious diseases; and miscellaneous infectious diseases such as tuberculosis and malaria. The top ten cited articles were mainly on infectious diseases, particularly on malaria and Lassa fever. Of all the retrieved documents, 727 (31.6%) research articles appeared in national/regional journals while the remaining appeared in international journals. The World Health organization was the most active funding organization for research on fragile states. Top ten active institutions were mainly based in fragile states with the lowest FSI score, specifically Ethiopia, Uganda, Nigeria, and Pakistan. Conclusion: Research on fragile states was relatively low. Research on mental health and health system/policy should be encouraged. Collaboration and funding might help academic institutions in fragile states to make health problems in these countries more visible
Dynamic RMST Curves for Survival Analysis in Clinical Trials
Authors: Liao Jason , Liu G. Frank , Wu Wen-Chi 
Published: July 2020

Abstract
Background: The data from immuno-oncology (IO) therapy trials often show delayed effects, cure rate, crossing hazards, or some mixture of these phenomena. Thus, the proportional hazards (PH) assumption is often violated such that the commonly used log-rank test can be very underpowered. In these trials, the conventional hazard ratio for describing the treatment effect may not be a good estimand due to the lack of an easily understandable interpretation. To overcome this challenge, restricted mean survival time (RMST) has been strongly recommended for survival analysis in clinical literature due to its independence of the PH assumption as well as a more clinically meaningful interpretation. The RMST also aligns well with the estimand associated with the analysis from the recommendation in ICH E-9 (R1), and the test/estimation coherency. Currently, the Kaplan Meier (KM) curve is commonly applied to RMST related analyses. Due to some drawbacks of the KM approach such as the limitation in extrapolating to time points beyond the follow-up time, and the large variance at time points with small numbers of events, the RMST may be hindered. Methods: The dynamic RMST curve using a mixture model is proposed in this paper to fully enhance the RMST method for survival analysis in clinical trials. It is constructed that the RMST difference or ratio is computed over a range of values to the restriction time τ which traces out an evolving treatment effect profile over time.Results: This new dynamic RMST curve overcomes the drawbacks from the KM approach. The good performance of this proposal is illustrated through three real examples. Conclusions: The RMST provides a clinically meaningful and easily interpretable measure for survival clinical trials. The proposed dynamic RMST approach provides a useful tool for assessing treatment effect over different time frames for survival clinical trials. This dynamic RMST curve also allows ones for checking whether the follow-up time for a study is long enough to demonstrate a treatment difference. The prediction feature of the dynamic RMST analysis may be used for determining an appropriate time point for an interim analysis, and an evaluation tool for study recommendation from data monitoring committee (DMC).
Association between pelvic obliquity and scoliosis, hip displacement and asymmetric hip abduction in children with cerebral palsy. A cross-sectional registry study
Authors: Hägglund Gunnar 
Published: July 2020

Abstract
Background: Pelvic obliquity (PO) is common in individuals with cerebral palsy (CP). I analysed the prevalence of PO in a population of children with CP and its associations with scoliosis, hip displacement and asymmetric hip abduction. Methods: Over a 5-year period all pelvic radiographs from the Swedish surveillance programme for CP and the recorded data for scoliosis and hip abduction in children from southern Sweden at Gross Motor Function Classification System (GMFCS) levels II–V were analysed. PO and hip displacement calculated as migration percentage (MP) were measured on supine pelvic radiographs and compared with side difference in hip abduction. Statistical analyses comprised chi-squared testing and binominal confidence intervals. Results: In total, 337 children were analysed, of whom 79 had a PO of >5°. The proportion of children with PO increased from 16% in GMFCS level II to 34% in level V. Scoliosis combined with PO was reported in 38 children, of whom 34 (89%, 95% confidence interval [CI] 80–99%) had the convexity opposite the high side of the PO. Asymmetric abduction with PO was reported in 45 children, of whom 40 (89%, CI 79–99%) had reduced abduction on the high side of the PO. Asymmetric MP of >5% with PO was seen in 62 children, of whom 50 had higher MP on the high side of the PO (81%, CI 71–90%). Children in GMFCS levels II–IV more often had isolated infra-pelvic association with PO (47% versus 19% in GMFCS V, P=0.025), while combined supra- and infrapelvic association was more common in GMFCS level V (65% versus 30% in GMFCS II–IV, P=0.004). Isolated infrapelvic or no association was seen in 74% of children < 10 years of age while 76% of children >11 years old had suprapelvic or combined supra- and infrapelvic association with PO ( P=0.0001). Conclusions: There was a strong association between the high side of PO and the side of scoliosis, highest MP and lowest range of abduction when PO was measured in supine position. PO was more often associated with infrapelvic factors. PO was seen in young children indicating the need for early awareness of this complication.
Spatial Estimation of Soil Erosion Using RUSLE Modeling: A case study of Dolakha District, Nepal
Authors: Thapa Pawan 
Published: July 2020

Abstract
Background: Soil erosion causes topsoil loss, which decreases fertility in agricultural land. Spatial estimation of soil erosion essential for an agriculture-dependent country like Nepal for developing its control plans. This study evaluated impacts on Dolakha using the Revised Universal Soil Loss Equation (RUSLE) model; analyses the effect of Land Use and Land Cover (LULC) on soil erosion. Results: The soil erosion rate categorized into six classes based on the erosion severity, and 5.01% of the areas found under extreme severe erosion risk (> 80 Mg ha-1yr-1) addressed by decision-makers for reducing its rate and consequences. Followed by 10 % classified between high and severe range from 10 to 80 Mg ha-1yr-1. While 15% and 70% of areas remained in a moderate and low-risk zone, respectively. Result suggests the area of the north-eastern part suffers from a high soil erosion risk due to steep slope. Conclusions: The result produces a spatial distribution of soil erosion over Dolakha, which applied for conservation and management planning processes, at the policy level, by land-use planners and decision-makers.
Identification and validation of an immune-related prognostic signature for hepatocellular carcinoma
Authors: Xia Xinxin , Liu Hui , Li Yuejun 
Published: July 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. The immune system plays vital roles in HCC initiation and progression. The present study aimed to construct an immune-gene related prognostic signature (IRPS) for predicting the prognosis of HCC patients. Methods: Gene expression data were retrieved from The Cancer Genome Atlas database. Univariate Cox regression analysis was carried out to identify differentially expressed genes that associated with overall survival. The IRPS was established via Lasso and multivariate Cox regression analysis. Both Cox regression analyses were conducted to determine the independent prognostic factors for HCC. Next, the association between the IRPS and clinical-related factors were evaluated. The prognostic values of the IRPS were further validated using the International Cancer Genome Consortium (ICGC) dataset. Gene set enrichment analyses (GSEA) were conducted to understand the biological mechanisms of the IRPS. Results: A total of 62 genes were identified to be candidate immune-related prognostic genes. Transcription factors-immunogenes network was generated to explore the interactions among these candidate genes. According to the results of Lasso and multivariate Cox regression analysis, we established an IRPS and confirmed its stability and reliability in ICGC dataset. The IRPS was significantly associated with advanced clinicopathological characteristics. Both Cox regression analyses revealed that the IRPS could be an independent risk factor influencing the prognosis of HCC patients. The relationships between the IRPS and infiltration immune cells demonstrated that the IRPS was associated with immune cell infiltration. GSEA identified significantly enriched pathways, which might assist in elucidating the biological mechanisms of the IRPS. Furthermore, a nomogram was constructed to estimate the survival probability of HCC patients. Conclusions: The IRPS was effective for predicting prognosis of HCC patients, which might serve as novel prognostic and therapeutic biomarkers for HCC.
Uterine Transcriptome Analysis Reveals Mechanism Underlying the Ultrastructure Differences of Eggshell in Young and Aged Laying Hens
Authors: Feng Jia , Zhang Hai-jun , Wu Shu-geng , Qi Guang-hai , Wang J. 
Published: July 2020

Abstract
Background: Lower eggshell quality in the late laying period leads to economic loss. It is a major threat to the quality and safety of egg products. Age-related variations in ultrastructure were thought to induce this deterioration. Eggshell mineralization is a highly complex process under precise regulation of genes and biological pathways in uterus of laying hens. Herein, we evaluated the physical, mechanical and ultrastructure properties of eggshell and conducted RNA sequencing to learn the transcriptomic differences in uterus between laying hens in the peak (young hens) and late phase (aged hens) of production.Results: The declined breaking strength and fracture toughness of eggshell were observed in aged hen group compared to those in young hen group, accompanied with ultrastructure variations including the increased thickness of mammillary layer and the decreased incidence of early fusion. During the initial stage of eggshell formation, a total of 183 differentially expressed genes (DEGs; 125 upregulated and 58 downregulated) were identified in uterus of laying hens in the late phase in relative to those at peak production. The DEGs annotated to Gene Ontology terms related to antigen processing and presentation were downregulated in aged hens compared to young hens. The contents of proinflammatory cytokine IL-1β in uterus were higher in aged hens relative to those in young hens. Besides, the genes of some matrix proteins potentially involved in eggshell mineralization, such as ovalbumin, versican and glypican 3, were also differentially expressed between two groups.Conclusions: Altered gene expression of matrix proteins along with the compromised immune function in uterus of laying hens in the late phase of production may conduce to age-related impairments of eggshell ultrastructure and mechanical properties. The current study enhances our understanding of the age-related deteriorations in eggshell ultrastructure and provides potential targets for improvement of eggshell quality in the late laying period.
Correction of immunosuppression in aged septic rats by human ghrelin and growth hormone through the vagus nerve-dependent inhibition of TGF-β production
Authors: Zhou Mian , Aziz Monowar , Ochani Mahander , Wang Ping 
Published: July 2020

Abstract
Background: Co-administration of human ghrelin and growth hormone (GH) reverse immunosuppression in septic aged animals, but the mechanism remains elusive. Here we hypothesize that ghrelin and GH co-treatment restores the immune response in aged septic rats by inhibiting the production of transforming growth factor-β (TGF-β), an immunoregulatory cytokine, through the vagus nerve. Methods: Male aged Fischer rats (22-23-month-old) were made septic by cecal ligation and puncture (CLP) with or without dissecting the vagus nerve (vagotomy). Human ghrelin and GH or vehicle (PBS) were administrated subcutaneously at 5 h post CLP. After 20 h of CLP, serum and spleens were harvested. Results: Serum TGF-β levels were increased in septic aged rats, while ghrelin and GH treatment significantly reduced its levels. Expression of TGF-β in the spleen was upregulated after sepsis, while ghrelin and GH treatment significantly inhibited its expression. TNF-α and IL-6 levels were significantly reduced after ex vivo LPS stimulation of splenocytes from rats that underwent CLP compared to sham rats; while these levels were significantly higher in splenocytes from ghrelin and GH-treated CLP rats compared to vehicle-treated CLP rats. Ghrelin and GH treatment reduced program death receptor-1 (PD-1) expression, increased human leukocyte antigen (HLA) expression, attenuated lymphopenia, and cleaved caspase-3 levels in splenocytes in septic aged rats. Vagotomy diminished the beneficial effects of ghrelin and GH treatment in septic rats. In vitro, the addition of ghrelin, GH, or ghrelin and GH together had no effect on restoring immune response in splenocytes from CLP rats following LPS stimulation, indicating the requirement of the vagus nerve for ghrelin and GH’s effect. Conclusions: Ghrelin and GH attenuate immunosuppression in aged septic rats through the vagus nerve-dependent inhibition of TGF-β production.