bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring country-wide equitable government health care facility access in Uganda
Authors: Dowhaniuk Nicholas 
Published: January 2021

AbstractBackgroundRural access to health care remains a challenge in Sub-Saharan Africa due to urban bias, social determinants of health, and transportation-related barriers. Health systems in Sub-Saharan Africa often lack equity, leaving disproportionately less health center access for the poorest residents with the highest health care needs. Lack of health care equity in Sub-Saharan Africa has become of increasing concern as countries enter a period of simultaneous high infectious and non-communicable disease burdens, the second of which requires a robust primary care network due to a long continuum of care. Bicycle ownership has been proposed and promoted as one tool to reduce travel-related barriers to health-services among the poor.MethodsAn accessibility analysis was conducted to identify the proportion of Ugandans within one-hour travel time to government health centers using walking, bicycling, and driving scenarios. Statistically significant clusters of high and low travel time to health centers were calculated using spatial statistics. Random Forest analysis was used to explore the relationship between poverty, population density, health center access in minutes, and time saved in travel to health centers using a bicycle instead of walking. Linear Mixed-Effects Models were then used to validate the performance of the random forest models.ResultsThe percentage of Ugandans within a one-hour walking distance of the nearest health center II is 71.73%, increasing to 90.57% through bicycles. Bicycles increased one-hour access to the nearest health center III from 53.05 to 80.57%, increasing access to the tiered integrated national laboratory system by 27.52 percentage points. Significant clusters of low health center access were associated with areas of high poverty and urbanicity. A strong direct relationship between travel time to health center and poverty exists at all health center levels. Strong disparities between urban and rural populations exist, with rural poor residents facing disproportionately long travel time to health center compared to wealthier urban residents.ConclusionsThe results of this study highlight how the most vulnerable Ugandans, who are the least likely to afford transportation, experience the highest prohibitive travel distances to health centers. Bicycles appear to be a “pro-poor” tool to increase health access equity.
Adapting the SPOTLIGHT Virtual Audit Tool to assess food and activity environments relevant for adolescents: a validity and reliability study
Authors: Andersen Oddbjørn Klomsten , O’Halloran Siobhan A. , Kolle Elin , Lien Nanna , Lakerveld Jeroen , Arah Onyebuchi A. , Gebremariam Mekdes K. 
Published: January 2021

Abstract
Background
Physical inactivity and unhealthy diet are key behavioral determinants underlying obesity. The neighborhood environment represents an important arena for modifying these behaviors, and hence reliable and valid tools to measure it are needed. Most existing virtual audit tools have been designed to assess either food or activity environments deemed relevant for adults. Thus, there is a need for a tool that combines the assessment of food and activity environments, and which focuses on aspects of the environment relevant for youth.

Objective
The aims of the present study were: (a) to adapt the SPOTLIGHT Virtual Audit Tool (S-VAT) developed to assess characteristics of the built environment deemed relevant for adults for use in an adolescent population, (b) to assess the tool’s inter- and intra-rater reliability, and (c) to assess its criterion validity by comparing the virtual audit to a field audit.

Methods
The tool adaptation was based on literature review and on results of a qualitative survey investigating how adolescents perceived the influence of the environment on dietary and physical activity behaviors. Sixty streets (148 street segments) in six neighborhoods were randomly selected as the study sample. Two raters assessed the inter- and intra-rater reliability and criterion validity, comparing the virtual audit tool to a field audit. The results were presented as percentage agreement and Cohen’s kappa (κ).

Results
Intra-rater agreement was found to be moderate to almost perfect (κ = 0.44–0.96) in all categories, except in the category aesthetics (κ = 0.40). Inter-rater agreement between auditors ranged from fair to substantial for all categories (κ = 0.24–0.80). Criterion validity was found to be moderate to almost perfect (κ = 0.56–0.82) for most categories, except aesthetics and grocery stores (κ = 0.26–0.35).

Conclusion
The adapted version of the S-VAT can be used to provide reliable and valid data on built environment characteristics deemed relevant for physical activity and dietary behavior among adolescents.
Factors associated with health-related quality of life of military policemen in Salvador, Brazil: cross-sectional study
Authors: Barreto Carla Requião , Carvalho Fernando Martins , Lins-Kusterer Liliane 
Published: January 2021

Abstract
Background
Brazil is a violent society and police officers play a fundamental role in this scenario. Police work is a stressful occupation. Dealing with routine violence, police officers must have high standards of physical and mental health. Patrolling the streets involves several risks and stressful situations that may hamper military policemen's quality of life. The identification of factors associated with health-related quality of life may help in planning and providing adequate care to military policemen. This study aimed to identify factors associated with health-related quality of life of military policemen in Salvador, Brazil.

Methods
A cross-sectional design study investigated a random sample of 329 male military police officers, engaged in patrolling the streets of Salvador, Brazil. A structured questionnaire applied to the policemen collected information about age, education, marital status, income, house ownership, car ownership, police rank, working day, alcohol consumption, smoking, frequency of vigorous physical activity, obesity (body mass index ≥ 30.0), and work ability. Health-related quality of life was evaluated through the 36-Item Short Form Health Survey Questionnaire (SF-36). Work ability was assessed through the Work Ability Index questionnaire. Poor work ability was defined by a 7–27 points score. Multiple linear regression models were used to measure the impact of police officers characteristics on the variation in the Physical Component and Mental Component Summary scores.

Results
Normalised scores were below 50.0% for seven out of the eight SF-36 domains and for the two component summaries. The SF-36 Physical Component Summary was significantly (P < 0.05) associated with poor work ability, while the Mental Component Summary was associated with poor work ability, excessive alcohol consumption, and younger age (24–34 years). Multivariate analysis estimated that the Physical Component Summary was 7.386 units (%) lower among policemen with poor work ability compared to those with moderate/good/excellent work ability. The Mental Component Summary was 12.755 units lower among those with poor work ability, 5.354 units lower among those with excessive alcohol consumption, and 5.532 units higher among those with younger age.

Conclusions
The military police officers investigated presented low health-related quality of life, associated with younger age, excessive alcohol consumption, and poor work ability.
Metabotropic glutamate receptor 5 inhibits α-synuclein-induced microglia inflammation to protect from neurotoxicity in Parkinson’s disease
Authors: Zhang Ya-Nan , Fan Jing-Kai , Gu Li , Yang Hui-Min , Zhan Shu-Qin , Zhang Hong 
Published: January 2021

Abstract
Background
Microglia activation induced by α-synuclein (α-syn) is one of the most important factors in Parkinson’s disease (PD) pathogenesis. However, the molecular mechanisms by which α-syn exerts neuroinflammation and neurotoxicity remain largely elusive. Targeting metabotropic glutamate receptor 5 (mGluR5) has been an attractive strategy to mediate microglia activation for neuroprotection, which might be an essential regulator to modulate α-syn-induced neuroinflammation for the treatment of PD. Here, we showed that mGluR5 inhibited α-syn-induced microglia inflammation to protect from neurotoxicity in vitro and in vivo.

Methods
Co-immunoprecipitation assays were utilized to detect the interaction between mGluR5 and α-syn in microglia. Griess, ELISA, real-time PCR, western blotting, and immunofluorescence assays were used to detect the regulation of α-syn-induced inflammatory signaling, cytokine secretion, and lysosome-dependent degradation.

Results
α-syn selectively interacted with mGluR5 but not mGluR3, and α-syn N terminal deletion region was essential for binding to mGluR5 in co-transfected HEK293T cells. The interaction between these two proteins was further detected in BV2 microglia, which was inhibited by the mGluR5 specific agonist CHPG without effect by its selective antagonist MTEP. Moreover, in both BV2 cells and primary microglia, activation of mGluR5 by CHPG partially inhibited α-syn-induced inflammatory signaling and cytokine secretion and also inhibited the microglia activation to protect from neurotoxicity. We further found that α-syn overexpression decreased mGluR5 expression via a lysosomal pathway, as evidenced by the lysosomal inhibitor, NH4Cl, by blocking mGluR5 degradation, which was not evident with the proteasome inhibitor, MG132. Additionally, co-localization of mGluR5 with α-syn was detected in lysosomes as merging with its marker, LAMP-1. Consistently, in vivo experiments with LPS- or AAV-α-syn-induced rat PD model also confirmed that α-syn accelerated lysosome-dependent degradation of mGluR5 involving a complex, to regulate neuroinflammation. Importantly, the binding is strengthened with LPS or α-syn overexpression but alleviated by urate, a potential clinical biomarker for PD.

Conclusions
These findings provided evidence for a novel mechanism by which the association of α-syn with mGluR5 was attributed to α-syn-induced microglia activation via modulation of mGluR5 degradation and its intracellular signaling. This may be a new molecular target for an effective therapeutic strategy for PD pathology.
Knowledge of and adherence to radiographic guidelines for low back pain: a survey of chiropractors in Newfoundland and Labrador, Canada
Authors: De Carvalho Diana , Bussières André , French Simon D. , Wade Darrell , Brake-Patten Debbie , O’Keefe Lino , Elliott Barbara , Budgell Ken , O’Reilly Sara , To Daphne , Hall Amanda 
Published: January 2021

Abstract
Background
Low back pain (LBP) rarely requires routine imaging of the lumbar spine in the primary care setting, as serious spinal pathology is rare. Despite evidence-based clinical practice guidelines recommending delaying imaging in the absence of red flags, chiropractors commonly order imaging outside of these guidelines. The purpose of this study was to survey chiropractors to determine the level of knowledge, adherence to, and beliefs about, clinical practice guidelines related to the use of lumbar radiography for LBP in Newfoundland and Labrador (NL), Canada.

Methods
A cross-sectional survey of chiropractors in NL (n = 69) was conducted between May and June 2018, including questions on demographics, awareness of radiographic guidelines, and beliefs about radiographs for LBP. We assessed behavioural simulation using clinical vignettes to determine levels of adherence to LBP guideline recommendations.

Results
The response rate was 77% (n = 53). Half of the participants stated they were aware of current radiographic guideline recommendations, and one quarter of participants indicated they did not use guidelines to inform clinical decisions. The majority of participants agreed that x-rays of the lumbar spine are useful for patients with suspected pathology, are indicated when a patient is non-responsive to 4 weeks of conservative treatment for LBP, and when there are neurological signs associated with LBP. However, a small proportion indicated that there is a role for full spine x-rays (~ 21%), x-rays to evaluate patients with acute LBP (~ 13%), and that patient expectations play a role in decision making (4%). Adherence rate to radiographic guidelines measured using clinical vignettes was 75%.

Conclusions
While many chiropractors in this sample reported being unsure of specific radiographic guidelines, the majority of respondents adhered to guideline recommendations measured using clinical vignettes. Nonetheless, a small proportion still hold beliefs about radiographs for LBP that are discordant with current radiographic guidelines. Future research should aim to determine barriers to guideline uptake in this population in order to design and evaluate tailored knowledge translation strategies to reduce unnecessary LBP imaging.
Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway
Authors: Zhang Yong , Zha Zhengxia , Shen Wenhua , Li Dan , Kang Naixin , Chen Zhong , Liu Yanli , Xu Guoqiang , Xu Qiongming 
Published: January 2021

Abstract
Background
Despite the increased morbidity of ulcerative colitis (UC) in the developing countries, available treatments remain unsatisfactory. Therefore, it is urgent to discover more effective therapeutic strategies. Pulsatilla chinensis was widely used for the treatment of inflamed intestinal diseases including UC for thousands of years in China. Anemoside B4, the most abundant triterpenoid saponin isolated from P. chinensis, exerts anti-inflammatory and antioxidant effects and may be the most active compounds, which is responsible for the therapeutic effects. However, the mechanism how anemoside B4 executes its biological functions is still elusive.

Methods
Here, we used the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model to evaluate the therapeutic effect of anemoside B4. Blood samples of colitis rats were collected for hematology analysis. The inflammation-associated factors were investigated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis was determined with EdU cell proliferation assay and TUNEL assay. The proteins regulated by anemoside B4 were identified by label-free quantitative proteomics. The significantly down-regulated proteins were verified by Western blotting analysis. mRNA expression was analyzed by quantitative real-time RT-PCR.

Results
The results showed that anemoside B4 ameliorated TNBS-induced colitis symptoms, including tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine production, apoptosis and slowed proliferation in colon. Quantitative proteomic analyses discovered that 56 proteins were significantly altered by anemoside B4 in the TNBS-induced rats. These proteins mainly clustered in tricarboxylic acid (TCA) cycle and respiratory electron transport chain. Among the altered proteins, S100A9 is one of the most significantly down-regulated proteins and associated with NF-κB and MAPK signaling pathways in the pathogenesis of UC. Further experiments revealed that anemoside B4 suppressed the expression of S100A9 and its downstream genes including TLR4 and NF-κB in colon. In vitro, anemoside B4 could inhibit the NF-κB signaling pathway induced by recombinant S100A9 protein in human intestinal epithelial Caco-2 cells. Moreover, anemoside B4 inhibits neutrophils recruitment and activation in colon induced by TNBS.

Conclusions
Our results demonstrate that anemoside B4 prevents TNBS-induced colitis by inhibiting the NF-κB signaling pathway through deactivating S100A9, suggesting that anemoside B4 is a promising therapeutic candidate for colitis.
The psychosocial barriers to medication adherence of patients with type 2 diabetes: a qualitative study
Authors: Mostafavi Firoozeh , Alavijeh Fereshteh Zamani , Salahshouri Arash , Mahaki Behzad 
Published: January 2021

AbstractBackgroundThe adherence of diabetic patients to their medication regimen is associated with many psychosocial factors that are still unknown. Therefore, the present study aims to identify the psychosocial barriers to medication adherence of patients with type2 diabetes (T2D).MethodologyThis descriptive qualitative study was done in Isfahan, Iran by conducting in-depth unstructured interviews with 23 purposively selected patients with T2D and 10 healthcare providers (HCPs). The participants were interviewed face-to-face between November 2017 and June 2018 at the patient’s home, a Health Care Center, or at the diabetes clinic. Data analysis was performed using MAXQDA-10 software and the conventional content analysis.ResultsThe analysis of the data led to six categories of perceived psychosocial barriers: 1) fear, concern and distress, 2) exhaustion and burnout, 3) the children’s issues being the priority, 4) poor financial support, 5) communication challenges, and 6) poor work conditions.ConclusionsThis study identified some of the psychosocial barriers to medication adherence of patients with T2D, which will be of great help to researchers and HCPs in designing and implementing effective interventions to overcome these barriers and change patient self-care behaviors and increase their medication adherence.
Neuropilin 1 and Neuropilin 2 gene invalidation or pharmacological inhibition reveals their relevance for the treatment of metastatic renal cell carcinoma
Authors: Dumond Aurore , Brachet Etienne , Durivault Jérôme , Vial Valérie , Puszko Anna K. , Lepelletier Yves , Montemagno Christopher , Pagnuzzi-Boncompagni Marina , Hermine Olivier , Garbay Christiane , Lagarde Nathalie , Montes Matthieu , Demange Luc , Grépin Renaud , Pagès Gilles 
Published: January 2021

AbstractBackgroundDespite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.MethodsWe correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for theNRP1andNRP2genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs.ResultsKnock-out of theNRP1andNRP2genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients.ConclusionsOur study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.
Effects of exogenous adiponectin supplementation in early pregnant PCOS mice on the metabolic syndrome of adult female offspring
Authors: Zuo Meng , Liao Guotao , Zhang Wenqian , Xu Dan , Lu Juan , Tang Manhong , Yan Yue , Hong Chenghao , Wang Yuxia 
Published: January 2021

Abstract
Objective
PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring.

Methods
After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice.

Results
The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05).

Conclusions
APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.