bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of enrollment decision in the community-based health insurance, North West Ethiopia: a case-control study
Authors: Taddesse Getasew , Atnafu Desta Debalkie , Ketemaw Asmamaw , Alemu Yibeltal 
Published: January 2020

Abstract
Objective
To identify the determinants for enrollment decision in the community-based health insurance program among informal economic sector-engaged societies, North West Ethiopia.

Method
Unmatched case-control study was conducted on 148 cases (member-to-insurance) and 148 controls (not-member-to-insurance program) from September 1 to October 30,2016. To select the villages and households, stratified then simple random sampling method was employed respectively. The data were entered in to Epi-info version 7 and exported to SPSS version 20 for analysis. Descriptive statistics, bi-variable, and multi-variable logistic regression analyses were computed to describe the study objectives and identify the determinants of enrolment decision for the insurance program. Odds ratio at 95% CI was used to describe the association between the independent and outcome variables.

Results
A total of 296 respondents (148 cases and 148 controls) were employed. The mean age for both cases and controls were 42 ± 11.73 and 40 ± 11.37 years respectively. Majority of respondents were males (87.2% for cases and 79% for controls). Family size between 4 and 6 (AOR = 2.26; 95% CI: 1.04, 4.89), history of illness by household (AOR = 3.24; 95% CI: 1.68, 6.24), perceived amount of membership contribution was medium (AOR = 2.3; 95% CI: 1.23, 4.26), being married (AOR = 6; 95% CI:1.43, 10.18) and trust on program (AOR = 4.79; 95% CI: 2.40, 9.55) were independent determinants for increased enrollment decision in the community-based health insurance. While, being merchant (AOR = 0.07; 95% CI: 0.09, 0.6) decreased the enrollment decision.

Conclusion
Societies’ enrollment decision to community-based health insurance program was determined by demographic, social, economic and political factors. Households with large family sizes and farmers in the informal sector should be given maximal attention for intensifying enrollment decision in the insurance program.
RETRACTED ARTICLE: LncRNA miR503HG interacts with miR-31-5p through multiple ways to regulate cancer cell invasion and migration in ovarian cancer
Authors: Zhu Ding , Huang Xueshuang , Liang Fang , Zhao Lijing 
Published: January 2020

AbstractThe role of lncRNA miR503HG has been investigated in several types of cancer, but its functions in ovarian cancer (OC) is unclear. Analysis of TCGA dataset revealed a 50-fold lower expression level of miR503HG in OC tissues than that in non-tumor tissues, indicating the involvement of miR503HG in OC. Results in this study showed that miR503HG was downregulated in OC and predicted poor survival. Expression of miR503HG negatively correlated with the expression of miR-31-5p across OC and non-tumor tissues. RNA-RNA interaction analysis revealed that miR503HG can interact with miR-31-5p. Dual-luciferase assay showed that miR-31-5p and miR503HG may directly interact with each other. Methylation specific PCR (MSP) showed that overexpression of miR503HG led to increased methylation level of miR-31-5p gene. Transwell assay showed that overexpression of miR-31-5p resulted in increased invasion and migration rates of OC cells. Overexpression of MiR503HG played an opposite role and attenuated the effects of overexpressing miR-31-5p. Therefore, miR503HG may promote the methylation of miR-31-5p and serve as its sponge to inhibit OC cell invasion and migration.
A cluster randomized clinical trial to evaluate the effectiveness of the Implementation of Infant Pain Practice Change (ImPaC) Resource to improve pain practices in hospitalized infants: a study protocol
Authors: Bueno Mariana , Stevens Bonnie , Barwick Melanie A. , Riahi Shirine , Li Shelly-Anne , Lanese Alexa , Willan Andrew R. , Synnes Anne , Estabrooks Carole A. , Chambers Christine T. , Harrison Denise , Yamada Janet , Stinson Jennifer , Campbell-Yeo Marsha , Noel Melanie , Gibbins Sharyn , LeMay Sylvie , Isaranuwatchai Wanrudee 
Published: January 2020

AbstractBackgroundHospitalized infants undergo multiple painful procedures daily. Despite the significant evidence, procedural pain assessment and management continues to be suboptimal. Repetitive and untreated pain at this vital developmental juncture is associated with negative behavioral and neurodevelopmental consequences. To address this knowledge to practice gap, we developed the web-based Implementation of Infant Pain Practice Change (ImPaC) Resource to guide change in healthcare professionals’ pain practice behaviors. This protocol describes the evaluation of the intervention effectiveness and implementation of the Resource and how organizational context influences outcomes.MethodsAn effectiveness-implementation hybrid type 1 design, blending a cluster randomized clinical trial and a mixed-methods implementation study will be used. Eighteen Neonatal Intensive Care Units (NICUs) across Canada will be randomized to intervention (INT) or standard practice (SP) groups. NICUs in the INT group will receive the Resource for six months; those in the SP group will continue with practice as usual and will be offered the Resource after a six-month waiting period. Data analysts will be blinded to group allocation. To address the intervention effectiveness, the INT and SP groups will be compared on clinical outcomes including the proportion of infants who have procedural pain assessed and managed, and the frequency and nature of painful procedures. Data will be collected at baseline (before randomization) and at completion of the intervention (six months). Implementation outcomes (feasibility, fidelity, implementation cost, and reach) will be measured at completion of the intervention. Sustainability will be assessed at six and 12 months following the intervention. Organizational context will be assessed to examine its influence on intervention and implementation outcomes.DiscussionThis mixed-methods study aims to determine the effectiveness and the implementation of a multifaceted online strategy for changing healthcare professionals’ pain practices for hospitalized infants. Implementation strategies that are easily and effectively implemented are important for sustained change. The results will inform healthcare professionals and decision-makers on how to address the challenges of implementing the Resource within various organizational contexts.Trial registrationClinicalTrials.gov,NCT03825822. Registered 31 January 2019.
Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial
Authors: Li Shen , Li Jin-pu 
Published: January 2020

Abstract
Background
IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial.

Methods/design
The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study.

Discussion
The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients.

Trial registration
ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.
TSC patient-derived isogenic neural progenitor cells reveal altered early neurodevelopmental phenotypes and rapamycin-induced MNK-eIF4E signaling
Authors: Martin Pauline , Wagh Vilas , Reis Surya A. , Erdin Serkan , Beauchamp Roberta L. , Shaikh Ghalib , Talkowski Michael , Thiele Elizabeth , Sheridan Steven D. , Haggarty Stephen J. , Ramesh Vijaya 
Published: January 2020

Abstract
Background
Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder with frequent occurrence of epilepsy, autism spectrum disorder (ASD), intellectual disability (ID), and tumors in multiple organs. The aberrant activation of mTORC1 in TSC has led to treatment with mTORC1 inhibitor rapamycin as a lifelong therapy for tumors, but TSC-associated neurocognitive manifestations remain unaffected by rapamycin.

Methods
Here, we generated patient-specific, induced pluripotent stem cells (iPSCs) from a TSC patient with a heterozygous, germline, nonsense mutation in exon 15 of TSC1 and established an isogenic set of heterozygous (Het), null and corrected wildtype (Corr-WT) iPSCs using CRISPR/Cas9-mediated gene editing. We differentiated these iPSCs into neural progenitor cells (NPCs) and examined neurodevelopmental phenotypes, signaling and changes in gene expression by RNA-seq.

Results
Differentiated NPCs revealed enlarged cell size in TSC1-Het and Null NPCs, consistent with mTORC1 activation. TSC1-Het and Null NPCs also revealed enhanced proliferation and altered neurite outgrowth in a genotype-dependent manner, which was not reversed by rapamycin. Transcriptome analyses of TSC1-NPCs revealed differentially expressed genes that display a genotype-dependent linear response, i.e., genes upregulated/downregulated in Het were further increased/decreased in Null. In particular, genes linked to ASD, epilepsy, and ID were significantly upregulated or downregulated warranting further investigation. In TSC1-Het and Null NPCs, we also observed basal activation of ERK1/2, which was further activated upon rapamycin treatment. Rapamycin also increased MNK1/2-eIF4E signaling in TSC1-deficient NPCs.

Conclusion
MEK-ERK and MNK-eIF4E pathways regulate protein translation, and our results suggest that aberrant translation distinct in TSC1/2-deficient NPCs could play a role in neurodevelopmental defects. Our data showing upregulation of these signaling pathways by rapamycin support a strategy to combine a MEK or a MNK inhibitor with rapamycin that may be superior for TSC-associated CNS defects. Importantly, our generation of isogenic sets of NPCs from TSC patients provides a valuable platform for translatome and large-scale drug screening studies. Overall, our studies further support the notion that early developmental events such as NPC proliferation and initial process formation, such as neurite number and length that occur prior to neuronal differentiation, represent primary events in neurogenesis critical to disease pathogenesis of neurodevelopmental disorders such as ASD.
Enhanced efficiency in isolation and expansion of hAMSCs via dual enzyme digestion and micro-carrier
Authors: Gohi Bi Foua Claude Alain , Liu Xue-Ying , Zeng Hong-Yan , Xu Sheng , Ake Kouassi Marius Honore , Cao Xiao-Ju , Zou Kai-Min , Namulondo Sheila 
Published: January 2020

AbstractA two-stage method of obtaining viable human amniotic stem cells (hAMSCs) in large-scale is described. First, human amniotic stem cells are isolated via dual enzyme (collagenase II and DNAase I) digestion. Next, relying on a culture of the cells from porous chitosan-based microspheres in vitro, high purity hAMSCs are obtained in large-scale. Dual enzymatic (collagenase II and DNase I) digestion provides a primary cell culture and first subculture with a lower contamination rate, higher purity and a larger number of isolated cells. The obtained hAMSCs were seeded onto chitosan microspheres (CM), gelatin–chitosan microspheres (GCM) and collagen–chitosan microspheres (CCM) to produce large numbers of hAMSCs for clinical trials. Growth activity measurement and differentiation essays of hAMSCs were realized. Within 2 weeks of culturing, GCMs achieved over 1.28 ± 0.06 × 107hAMSCs whereas CCMs and CMs achieved 7.86 ± 0.11 × 106and 1.98 ± 0.86 × 106respectively within this time. In conclusion, hAMSCs showed excellent attachment and viability on GCM-chitosan microspheres, matching the hAMSCs’ normal culture medium. Therefore, dual enzyme (collagenase II and DNAase I) digestion may be a more useful isolation process and culture of hAMSCs on porous GCM in vitro as an ideal environment for the large-scale expansion of highly functional hAMSCs for eventual use in stem cell-based therapy.
Effects of light availability on leaf attributes and seedling growth of four tree species in tropical dry forest
Authors: Tripathi Sachchidanand , Bhadouria Rahul , Srivastava Pratap , Devi Rajkumari S. , Chaturvedi Ravikant , Raghubanshi A. S. 
Published: January 2020

Abstract
Background
In tropical dry forests, variation in understory light availability due to season and canopy tree density could be a governing factor in establishment and growth of tree seedlings. Species with varying life history traits are expected to respond differentially to such heterogeneity. We investigated the response of seedlings of four tree species in a tropical day forest in relation to spatiotemporal variability of light. We attempt to explore the role of leaf attributes in explaining intra- and inter-specific variations in relative growth rate. Four study sites, each with three contrasting canopy conditions, were selected along a soil moisture gradient. Seedlings of four tree species (viz., Acacia catechu, Bridelia retusa, Lagerstroemia parviflora, and Shorea robusta), varying in life history traits, were monitored for seasonal variations in growth traits across canopy condition and sites for 2 years.

Results
We observed a larger variation in leaf attributes for pioneer species. A. catechu showed highest mean values for leaf dry matter content, leaf nitrogen concentration, leaf phosphorus concentration, net stomatal conductance, net photosynthetic rate, and relative growth rate in high light conditions. S. robusta and B. retusa demonstrated highest mean values for all the leaf attributes (except leaf dry matter content) in low light conditions. However, intermediate values for leaf attributes were observed in L. parviflora which preferred moderate light conditions.

Conclusions
Seasonal variations in light availability at the forest floor appear to play an important role in the establishment and growth of tree seedlings in seasonal dry forests. Leaf attributes can be used to explain intra- and inter-specific variation in response to light availability. Leaf attributes in combinations can be used to predict relative growth rate of tree species in tropical dry environment, which apart from soil moisture is also determined by light availability due to seasonal changes and canopy tree density.
The prognostic value of integration of pretreatment serum amyloid A (SAA)–EBV DNA (S‐D) grade in patients with nasopharyngeal carcinoma
Authors: Li Jianpei , Lai Changchun , Peng Songguo , Chen Hao , Zhou Lei , Chen Yufeng , Chen Shulin 
Published: January 2020

AbstractBackgroundSerum amyloid A (SAA) has been associated with the development and prognosis of cancer. The purpose of this study was to evaluate the predictive value of integration of pretreatment SAA–EBV DNA (S‐D) grade and comparison with the TNM staging system in patients with nasopharyngeal carcinoma (NPC). The S‐D grade was calculated based on the cut‐off values of serum SAA and EBV DNA copy numbers which were determined by receiver operating characteristic (ROC) curves. We evaluated the prognostic value of pretreatment SAA, EBV DNA and S‐D grade on overall survival (OS) of NPC patients. We also evaluated the predictive power of S‐D grade with TNM staging system using 4 indices: concordance statistics (C‐index), time‐dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI).ResultsA total of 304 NPC patients were enrolled in this study. Multivariate analysis showed that TNM stage (P = 0.007), SAA (P = 0.013), and EBV DNA (P = 0.033) were independent prognostic factors in NPC. The S‐D grade was divided into S‐D grade 1, S‐D grade 2, and S‐D grade 3, which had more predictive accuracy for OS than TNM staging according to all 4 indices.ConclusionsWe found that the S‐D grade could be used as a new tool to predict the OS in NPC patients.
Systems biology approaches toward autosomal dominant polycystic kidney disease (ADPKD)
Authors: Rahimmanesh Ilnaz , Fatehi Razieh 
Published: January 2020

AbstractBackgroundAutosomal dominant polycystic kidney disease (ADPKD), a common of monogenetic disorder caused by the polycystic kidney disease‐1 (PKD1) or PKD2 genes deficiency. In this study, we have re‐analyzed a microarray dataset to generate a holistic view of this disease.MethodologyGSE7869, an expression profiling dataset was downloaded from the Gene Expression Omnibus (GEO) database. After quality control assessment, using GEO2R tool of GEO, genes with adjusted p‐value ≤ 0.05 were determined as differentially expressed (DE). The expression profiles from ADPKD samples in different sizes were compared. Using CluePedia plugin of Cytoscape software, the protein–protein interaction (PPI) networks were constructed and analyzed by Cytoscape NetworkAnalyzer tool and MCODE application. Pathway enrichment analysis of clustered genes by MCODE with the high centrality parameters in PPI networks was performed using Cytoscape ClueGO plugin. Moreover, by Enrichr database, microRNAs (miRNAs) and transcription factors (TFs) targeted DE genes were identified.ResultsIn this study to explore the molecular pathogenesis of kidney in ADPKD, mRNA expression profiles of cysts from patients in different sizes were re‐analyzed. The comparisons were performed between normal with minimally cystic tissue (MCT) samples, MCTs with small cysts, and small cysts with large cysts. 512, 7024, and 655 DE genes were determined, respectively. The top central genes, e.g. END1, EGFR, and FOXO1 were identified with topology and clustering analysis. DE genes that were significantly enriched in PPI networks are critical genes and their roles in ADPKD remain to be assessed in future experimental studies beside miRNAs and TFs predicted. Furthermore, the functional analysis resulted in which most of them are expected to be associated with ADPKD pathogenesis, such as signal pathways that involved in cell growth, inflammation, and cell polarity.ConclusionWe have here explored systematic approaches for molecular mechanisms assay of ADPKD as a monogenic disease, which may also be used for other monogenetic diseases beside complex diseases to provide suitable therapeutic targets.
Safety, tolerability, and pharmacokinetics of repeated oral doses of 2-hydroxybenzylamine acetate in healthy volunteers: a double-blind, randomized, placebo-controlled clinical trial
Authors: Pitchford Lisa M. , Driver Patricia M. , Fuller John C. , Akers Wendell S. , Abumrad Naji N. , Amarnath Venkataraman , Milne Ginger L. , Chen Sheau-Chiann , Ye Fei , Roberts L. Jackson , Shoemaker M. Benjamin , Oates John A. , Rathmacher John A. , Boutaud Olivier 
Published: January 2020

Abstract
Background
2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer’s disease.

Methods
This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated.

Results
Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10–3.27 h, and an accumulation ratio of 1.38–1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing.

Conclusions
Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement.

Trial registration
Studies are registered at ClinicalTrials.gov (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18).