bluuebunny/crossref_metadata_2025_split huggingface dataset:
The roles of health maintenance organizations in the implementation of a social health insurance scheme in Enugu, Southeast Nigeria: a mixed-method investigation
Authors: Obikeze Eric , Onwujekwe Obinna 
Published: March 2020

Abstract
Background
In Nigeria, health maintenance organizations (HMOs) are the purchasers of health insurance with a social National Health Insurance Scheme for civil servants. However the roles of HMOs in implementation of social health insurance are not clear. This study determined the roles of HMOs in implementation of the national social health insurance scheme in Enugu, Southeast Nigeria.

Methods
A partially mixed sequential dominant status design was employed in the study. Quantitative data were collected from 613 Federal Government employees that are registered with the National Health Insurance Scheme (NHIS) as part of the Formal Sector Social Health Insurance Program (FSSHIP) using an interviewer-administered questionnaire. Test for sampling adequacy was ensured (KMO, 0.701) and likewise the sphericity of the data using Bartlett’s test (Chi [1] 796.72, p-value < 0.001). For the qualitative study, there was document review and in-depth interviews. A total of 28 in-depth interviews were conducted with key stakeholders comprising of managers of HMOs, NHIS manager, providers of health care and personnel in the State Ministry of Health among others. Thematic analysis was used for the qualitative data.

Results
One-third (31.5%) of respondents said that roles of HMOs were very important, while 23% said that their roles were not important. More than half (57.70%) ranked HMOs very low in their roles, while 24.10% ranked them highest. Concentration index shows that the poor were satisfied (−.10), while the rich were highly satisfied (0.13) with roles of HMOs. The qualitative data analysis showed that most of the respondents were not satisfied with the roles of HMOs based on the themes that were developed and analyzed.

Conclusion
There is clear understanding of the functions of HMOs among respondents in the study although they generally think that HMOs are not meeting the expectations of the scheme. There is need for the Federal Government through the National Health Insurance Scheme to provide more effective guidelines for HMOs, supervise and monitor the implementation of such guidelines for HMOs to improve on their roles.
Prevalence and associated factors of self-treatment behaviour among different elder subgroups in rural China: a cross-sectional study
Authors: Xu Wanchun , Li Zhong , Pan Zijing , He Ruibo , Zhang Liang 
Published: March 2020

Abstract
Background
Self-treatment is a common and widespread behaviour, of which the risks are multiplied in old age. However, the determinants of self-treatment among elders in rural China remain unclear. This study aims to explore the prevalence and associated factors of self-treatment among elders in rural China, trying to discover the vulnerable groups as well as the service gaps among the rural elders.

Methods
Based on a multi-stage stratified random sampling method, a cross-sectional household survey was conducted among 30 villages in Sinan County, an impoverished county in western China. Data were collected through a household–individual combined questionnaires. The analysis was restricted to elders who reported illness within the last 2 weeks, and the final sample size was 330 (individuals). Bivariate and multiple logistic regression analysis were performed in the whole sample group and four subgroups to obtain the prevalence ratios regarding the associated factors.

Results
In the present study, 35.2% of the elders with illness within the last 2 weeks reported self-treatment. The variables associated with self-treatment in the whole sample group were health status (OR 6.75, 95%CI 1.93–23.60), recent alcohol consumption (OR 0.42, 95%CI 0.21–0.83) and the utilisation of family practice services (OR 0.59, 95%CI 0.36–0.96); the same predictors were found in the subgroup of elders with chronic diseases. No significant predictors were found in the subgroup of elders without chronic diseases. Empty-nest elders with higher affinity to traditional Chinese medicine (OR 0.39, 95%CI 0.18–0.86) or drinking alcohol recently (OR 0.28, 95%CI 0.09–0.82) were less likely to self-treat, while the non-empty-nest elders who were no less than 75 years old (OR 3.10, 95%CI 1.33, 7.22) or at better health status (OR 9.20, 95%CI 1.73–48.75) were more likely to self-treat.

Conclusion
Self-treatment was prevalent among the elders in rural China. Better health status, no recent alcohol consumption and no utilisation of family practice are associated with self-treatment among rural elders. Older elders in the non-empty nest group were more likely to self-treat, while the empty-nest elders with self-care habits in traditional Chinese medicine were less likely to self-treat. Deeper understanding of the self-treatment behaviour among rural elders may provide insights for identifying the potential service gaps and developing improvement strategies in the health care delivery system for the elderly in China.
m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer
Authors: Zhang Bo , Wu Qiong , Li Ben , Wang Defeng , Wang Lei , Zhou You Lang 
Published: March 2020

Abstract
Background
The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles of RNA N6-methyladenosine (m6A) modification in tumor microenvironment (TME) cell infiltration remain unknown.

Methods
We comprehensively evaluated the m6A modification patterns of 1938 gastric cancer samples based on 21 m6A regulators, and systematically correlated these modification patterns with TME cell-infiltrating characteristics. The m6Ascore was constructed to quantify m6A modification patterns of individual tumors using principal component analysis algorithms.

Results
Three distinct m6A modification patterns were determined. The TME cell-infiltrating characteristics under these three patterns were highly consistent with the three immune phenotypes of tumors including immune-excluded, immune-inflamed and immune-desert phenotypes. We demonstrated the evaluation of m6A modification patterns within individual tumors could predict stages of tumor inflammation, subtypes, TME stromal activity, genetic variation, and patient prognosis. Low m6Ascore, characterized by increased mutation burden and activation of immunity, indicated an inflamed TME phenotype, with 69.4% 5-year survival. Activation of stroma and lack of effective immune infiltration were observed in the high m6Ascore subtype, indicating a non-inflamed and immune-exclusion TME phenotype, with poorer survival. Low m6Ascore was also linked to increased neoantigen load and enhanced response to anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients with lower m6Ascore demonstrated significant therapeutic advantages and clinical benefits.

Conclusions
This work revealed the m6A modification played a nonnegligible role in formation of TME diversity and complexity. Evaluating the m6A modification pattern of individual tumor will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies.

Graphical abstract
Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance
Authors: Bhat Ajaz A. , Younes Salma N. , Raza Syed Shadab , Zarif Lubna , Nisar Sabah , Ahmed Ikhlak , Mir Rashid , Kumar Sachin , Sharawat Surender K. , Hashem Sheema , Elfaki Imadeldin , Kulinski Michal , Kuttikrishnan Shilpa , Prabhu Kirti S. , Khan Abdul Q. , Yadav Santosh K. , El-Rifai Wael , Zargar Mohammad A. , Zayed Hatem , Haris Mohammad , Uddin Shahab 
Published: March 2020

AbstractEarly-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.
Commercial 4-dimensional echocardiography for murine heart volumetric evaluation after myocardial infarction
Authors: Rutledge Cody , Cater George , McMahon Brenda , Guo Lanping , Nouraie Seyed Mehdi , Wu Yijen , Villanueva Flordeliza , Kaufman Brett A. 
Published: March 2020

Abstract
Background
Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as the mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these geometric assumptions. New ECHO technology, including 4-dimensional ultrasound (4D-US), improves on these traditional models. This paper aims to compare commercially available 4D-US to M-mode and 2D-US in a mouse model of CAL.

Methods
37 mice underwent CAL surgery, of which 32 survived to a 4 week post-operative time point. ECHO was completed at baseline, 1 week, and 4 weeks after CAL. M-mode, 2D-US, and 4D-US were taken at each time point and evaluated by two separate echocardiographers. At 4 weeks, a subset (n = 12) of mice underwent cardiac magnetic resonance (CMR) imaging to serve as a reference standard. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were compared among imaging modalities. Hearts were also collected for histologic evaluation of scar size (n = 16) and compared to ECHO-derived wall motion severity index (WMSI) and global longitudinal strain as well as gadolinium-enhanced CMR to compare scar assessment modalities.

Results
4D-US provides close agreement of ESV (Bias: -2.55%, LOA: − 61.55 to 66.66) and EF (US Bias: 11.23%, LOA − 43.10 to 102.8) 4 weeks after CAL when compared to CMR, outperforming 2D-US and M-mode estimations. 4D-US has lower inter-user variability as measured by intraclass correlation (ICC) in the evaluation of EDV (0.91) and ESV (0.93) when compared to other modalities. 4D-US also allows for rapid assessment of WMSI, which correlates strongly with infarct size by histology (r = 0.77).

Conclusion
4D-US outperforms M-Mode and 2D-US for volumetric analysis 4 weeks after CAL and has higher inter-user reliability. 4D-US allows for rapid calculation of WMSI, which correlates well with histologic scar size.
Association of vascular endothelial growth factor polymorphisms with polycystic ovarian syndrome risk: a meta-analysis
Authors: Zhao Jiahui , Li Da , Tang Huaiyun , Tang Lisha 
Published: March 2020

Abstract
Background
Polycystic ovarian syndrome (PCOS) is a multi-gene hereditary disorder caused by the interaction of certain gene variation with environmental factors. Previous studies have shown that vascular endothelial growth factor (VEGF) gene polymorphisms are associated with the risk of polycystic ovarian syndrome. However, the results of these studies remain controversial. We performed the present meta-analysis aiming to further investigate the potential relationship between VEGF polymorphisms and susceptibility to PCOS.

Methods
The following databases were systematically searched: PubMed, EMBASE, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), and Wanfang Databases. The correlation between VEGF polymorphisms and PCOS risk was assessed by calculating pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity and source of control were also conducted. Besides, trial sequential analysis (TSA) was done to verify the reliability of the pooled results.

Results
10 relevant case-control studies were incorporated in this meta-analysis, involving 1347 PCOS cases and 1378 controls. The VEGF rs2010963 polymorphism was associated with decreased PCOS risk in the whole population and the Asian populations. The VEGF rs3025039 polymorphism was associated with decreased PCOS susceptibility and the Asian populations, but increased risk of PCOS was observed among the Caucasian populations. In addition, the results of trial sequential analysis (TSA) showed the negative correlation between rs2010963 and PCOS risk, obtained by our meta-analysis, was stable and reliable.

Conclusion
Overall, different VEGF gene polymorphisms may exert different effects on PCOS susceptibility. The VEGF rs2010963 polymorphism decreases PCOS susceptibility in both the whole population and the Asian populations, and VEGF rs3025039 polymorphism causes lower PCOS susceptibility in the whole population and the Asian populations but higher in the Caucasian populations.
Assessment of dual practice among physicians in Cambodia
Authors: Khim Keovathanak , Goldman Laura N. , Shaw Kristin , Markuns Jeffrey F. , Saphonn Vonthanak 
Published: March 2020

Abstract
Background
Dual practice and multiple job holding are widespread among health workers throughout the world. Although dual practice can help the financially strained public sector retain skilled workers, there are also potential negative consequences if it is not regulated. In Cambodia, there is substantial anecdotal evidence of dual practice among physicians but there is very little data on the extent and prevalence of the practice. This study was conducted by the University of Health Sciences (UHS) to gain insight in to the employment practices of UHS alumni. Results from this survey may help to inform policymakers in rational planning for future health system development related to capacity building and regulation of human resources for health.

Methods
Data were collected from a self-administered survey of UHS graduates who graduated between 1999 and 2012. A total of 162 medical graduates were randomly sampled from a total of 1867 medical graduates between 1999 and 2012. Contacted individuals were asked to complete a written structured questionnaire regarding demographic characteristics, current employment and types of employment, compensation, and job satisfaction. The response rate of graduates sampled was 49% (79 completed questionnaires). The low response rate was primarily due to the difficulty in locating individuals.

Results
Of 79 respondents, 96% were currently employed at the time of the survey. However, only 63 of the respondents (80%) were working in the healthcare sector. The 16 respondents (20%) not working in healthcare were excluded from further analyses since they are not relevant to dual practice analysis. The vast majority (87%) of respondents are public sector employees (61.9% in public sector only and 25.4% in both public and private sector). 12.7% of respondents only work in the private sector. Almost half (47.6%) of respondents hold more than one job. For income satisfaction, physicians employed in both sectors have higher satisfaction than physicians employed in the public sector only.

Conclusions
As policymakers in Cambodia consider new approaches to regulation of the practice, it is important to know the context of the practice, the benefits to the healthcare system, and the costs. Recognizing the high prevalence of multiple job holding in Cambodia, as evidenced in our survey of UHS medical graduates, contributes to the discussion as important information that can be used toward meaningful reform.
Rapamycin promotes endothelial–mesenchymal transition during stress-induced premature senescence through the activation of autophagy
Authors: Sasaki Norihiko , Itakura Yoko , Toyoda Masashi 
Published: March 2020

Abstract
Background
Rapamycin is known to be effective in suppressing senescence and the senescence-associated secretory phenotype (SASP). Therefore, it is highly expected to represent an anti-aging drug. Its anti-aging effect has been demonstrated at the mouse individual level. However, there are not many clinical findings with respect to its activity in humans. Here, we aimed to clarify the effect of rapamycin on human endothelial cells (ECs) as an in vitro model of human blood vessels.

Methods
Over the course of oxidative stress-induced senescence using hydrogen peroxide, we examined the effect of rapamycin on human coronary artery ECs (HCAECs). Senescence was evaluated by detecting senescence-associated β-galactosidase (SA-β-Gal) activity and the real-time PCR analysis of p16INK4a. Furthermore, expression levels of SASP factors were examined by real-time PCR and the expression of senescence-related antigens, such as intercellular adhesion molecule-1 (ICAM-1) and ganglioside GM1, were examined by fluorescence-activated cell sorting analysis and immunostaining. The inhibitory effect of rapamycin on mTOR signaling was examined by immunoblotting. The adhesion of leukocytes to HCAECs was evaluated by adhesion assays. Endothelial–mesenchymal transition (EndMT) induced by rapamycin treatment was evaluated by real-time PCR analysis and immunostaining for EndMT markers. Finally, we checked the activation of autophagy by immunoblotting and examined its contribution to EndMT by using a specific inhibitor. Furthermore, we examined how the activation of autophagy influences TGF-β signaling by immunoblotting for Smad2/3 and Smad7.

Results
A decrease in SA-β-Gal activity and the suppression of SASP factors were observed in HCAECs undergoing stress-induced premature senescence (SIPS) after rapamycin treatment. In contrast, ICAM-1 and ganglioside GM1 were upregulated by rapamycin treatment. In addition, leukocyte adhesion to HCAECs was promoted by this treatment. In rapamycin-treated HCAECs, morphological changes and the promotion of EndMT were also observed. Furthermore, we found that autophagy activation induced by rapamycin treatment, which led to activation of the TGF-β pathway, contributed to EndMT induction.

Conclusions
We revealed that although rapamycin functions to inhibit senescence and suppress SASP in HCAECs undergoing SIPS, EndMT is induced due to the activation of autophagy.
TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features
Authors: Torres-Ruiz Jiram , Carrillo-Vazquez Daniel Alberto , Padilla-Ortiz Diana Marcela , Vazquez-Rodriguez Ricardo , Nuñez-Alvarez Carlos , Juarez-Vega Guillermo , Gomez-Martin Diana 
Published: March 2020

Abstract
Background
Monocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed.

Methods
We recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min–max). Differences between groups were assessed with Mann–Whitney U and the Kruskal–Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho.

Results
Twenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM.

Conclusion
Patients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.