bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new integrated approach for adolescent health and well-being: the AVATAR project
Authors: Mastorci Francesca , Bastiani Luca , Trivellini Gabriele , Doveri Cristina , Vassalle Cristina , Pingitore Alessandro 
Published: March 2020

Abstract
Background
Limited number of studies examined the relationship between factors (lifestyle, social, emotional, cognitive) affecting adolescents’ health and well-being. The aims of this study were to identify the more important variables of the different components affecting adolescents’ health [lifestyle habits (LH); emotional status (ES); social context (SC); and cognitive abilities (CA)], and explore the relationship between the aforementioned components.

Methods
Data were collected between 2017 and 2018 from 756 eligible students, recruited from 5 Italian junior high school, by using KIDSCREEN-52 and cognitive processing using the Stroop Test. School engagement was estimated through questions concerning the scholastic achievement.

Results
Of 756 adolescents, 395 were boys with a mean (SD) age of 12.19 (0.81) years. Compared to International T-value of reference group for KIDSCREEN-52, autonomy, bullying, psychological well-being and mood were lower than the reference groups, while self-perception score was higher. For LH, the most important predictor was autonomy (p < .0001). The most important aspects in the SC were the relationship with the parents (p < .0001), and the adolescent’s relationships with peers (p < .0001). For ES, mood variables had the greatest contribution (p < .0001). The School performance related to Language & Literature (p < .0001) was the most important predictor in the CA latent variable. LH was positively associated with SC (p < .0001), ES (p < .0001), and CA (p < .0001). SC was positively associated with ES (p < .0001) and with CA (p < .0001).

Conclusions
This study suggests the importance of an integrated approach to characterize adolescents’ health and well-being. The approach suggested here may highlight additive synergistic effects of the various components in health and well-being assessment that may not be considered with a late approach and focused only on single factors.
Prioritising health research in KwaZulu-Natal: has the research conducted met the research needs?
Authors: Khumalo G. , Desai R. , Xaba X. , Moshabela M. , Essack S. , Lutge E. 
Published: March 2020

Abstract
Background
The KwaZulu-Natal (KZN) Health Act of 2009 mandates the Provincial Health Research and Ethics Committee to develop health research priorities for the province. During 2013, the KZN Department of Health embarked on a research prioritisation process for the province. Priority research questions were generated by an inclusive process, in which a variety of stakeholders in health research in the province were engaged. The aim of this study was to determine whether research conducted at public health facilities in KZN between 01 January 2014 and 31 March 2017 met the research priorities of the province developed through the provincial research prioritisation process of 2013.

Methods
This was a mixed methods study. Qualitative thematic analysis was used to categorise priority research questions generated in the priority-setting process and the titles of research projects conducted after that process into themes. Quantitative analysis was used to determine the correlation between themes of the priority questions, and those of the research projects conducted after the prioritisation exercise. Statistical Package for Social Science version 25 was used to analyse the data.

Results
In 72% of thematic areas, there were disproportionately more priority questions than there were research projects conducted. There is thus a large disjuncture between the priorities developed through the provincial research prioritisation process of 2013 and the research projects conducted after that process in terms of major research areas.

Conclusions
Ensuring that research conducted responds to priority questions raised is important because it ensures that research responds to locally important issues and to the concerns of local actors. Local health managers, communities and researchers should work together to ensure that the research conducted in their areas respond to the research priorities of those areas. Health Research Committees and local ethics committees can play important roles in facilitating the responsiveness to research priorities.
Optimization of small RNA library preparation protocol from human urinary exosomes
Authors: Olivares Dolores , Perez-Hernandez Javier , Perez-Gil Daniel , Chaves Felipe J. , Redon Josep , Cortes Raquel 
Published: March 2020

Abstract
Background
Sequencing of miRNAs isolated from exosomes has great potential to identify novel disease biomarkers, but exosomes have low amount of RNA, hindering adequate analysis and quantification. Here, we have assessed several steps in developing an optimized small RNA (sRNA) library preparation protocol for next-generation sequencing (NGS) miRNA analysis from urinary exosomes.

Methods
A total of 24 urinary exosome samples from donors were included in this study. RNA was extracted by column-based methods. The quality of extracted RNA was assessed by spectrophotometric quantification and Bioanalyzer software analysis. All libraries were prepared using the CleanTag small RNA library preparation protocol and the effect of our additional modifications on adapter-dimer presence, sequencing data and tagged small RNA library population was also analyzed.

Results
Our results show that good quality sequencing libraries can be prepared following our optimized small RNA library preparation protocol from urinary exosomes. When the size selection by gel purification step was included within the workflow, adapter-dimer was totally removed from cDNA libraries. Furthermore, the inclusion of this modification step within small RNA library protocol augmented the small RNA mapped reads, with an especially significant 37% increase in miRNA reads, and the gel purification step made no difference to the tagged miRNA population.

Conclusions
This study provides researchers with an optimized small RNA library preparation workflow for next generation sequencing based exosome-associated miRNA analysis that yields a high amount of miRNA mapped reads without skewing the tagged miRNA population significantly.
Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice
Authors: Arai Chikako , Suyama Aki , Arai Shigeyuki , Arai Norie , Yoshizane Chiyo , Koya-Miyata Satomi , Mizote Akiko , Endo Shin , Ariyasu Toshio , Mitsuzumi Hitoshi , Ushio Shimpei 
Published: March 2020

Abstract
Background
Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase.

Methods
Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis.

Results
Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cells in vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce suppression of adipocyte hypertrophy.

Conclusions
The suppression of adipocyte hypertrophy in the presence and absence of trehalase indicates that trehalose mediates effects prior to being hydrolyzed into glucose. In both trehalase KO and WT mice, trehalose treatment increased the rate of CLDs in jejunal epithelium, reduced chylomicron migration from the intestinal epithelium to the periphery, and suppressed adipocyte hypertrophy. Thus, trehalose ingestion could prevent metabolic syndrome by trapping fat droplets in the intestinal epithelium and suppressing rapid increases in chylomicrons.
Changes in quality of life and its associated factors among illicit drug users in Vietnamese mountainous provinces: a 12-month follow-up study
Authors: Tran Bach Xuan , Moir Mackenzie , Nguyen Tam Minh Thi , Do Ha Ngoc , Vu Giang Thu , Dang Anh Kim , Ha Giang Hai , Nguyen Trang Huyen Thi , Vuong Hoang Quan , Ho Tung Manh , Van Dam Nhue , Vuong Trang Thu , Latkin Carl A. , Ho Cyrus S. H. , Ho Roger C. M. 
Published: March 2020

Abstract
Background
Sustainability of methadone maintenance treatment (MMT) program involves regularly assessing its impact on health and social outcomes of drug users in different settings, particularly in disadvantaged areas. In this study, we evaluated the change in quality of life (QoL), and identified associated factors amongst drug users over the course of 12-month MMT in Vietnamese mountainous provinces.

Methods
We conducted a longitudinal study among patients from 6 MMT clinics in three mountainous provinces of Vietnam. At baseline, we screened 300 participants and after a 12-month treatment, 244 participants remained to involve in the study. World Health Organization Quality of Life short form instrument (WHOQOL-BREF) was used to measure the QoL of patients. The magnitude of the changes was extrapolated.

Results
There were significant changes in all four dimensions of quality of life measured by WHOQoL-BREF between baseline and 12 months with the effect size ranged from 0.21 to 0.24. Increased age, being workers compared to unemployment and having health problems or comorbidities were positively related to reduced scores of QoL.

Conclusions
To conclude, we observed a significant increase in the QoL level regarding physical, psychological, social relationships and environmental aspects among people who used drug after 12 months of MMT. Findings from this study emphasize the role of continuously receiving MMT treatment among people using drugs to enhance their QoL.
Effectiveness of naltrexone treatment for alcohol use disorders in HIV: a systematic review
Authors: Farhadian Negin , Moradi Sajad , Zamanian Mohammad Hossein , Farnia Vahid , Rezaeian Shahab , Farhadian Maryam , Shahlaei Mohsen 
Published: March 2020

Abstract
Background
Because alcohol use disorders (AUDs) in patients living with HIV/AIDS are associated with a reduction in therapeutic outcomes and increases the risk of morbidity/mortality, finding an appropriate pharmacotherapy treatment for this disorder is necessary.

Objectives
This systematic review contains studies that examine the effects of pharmacological intervention (oral naltrexone (NTX) or injectable extended-release naltrexone (XR-NTX)) on the persons living with HIV and AUDs.

Methods
A systematic literature search using three electronic databases including Pubmed Medline, Scopus and the Cochrane Library and Google Scholar was conducted and includes articles published from 1995 to 2019. Records were collected by searching relevant keywords and those that meet the inclusion/exclusion criteria are included.

Results
Overall, in this systematic review, the results of 7 relevant studies including pilot and randomized controlled/clinical trials were summarized and reviewed. Among selected records 2 of these assessed the efficacy of NTX and 5 tested the XR-NTX effectiveness in treating AUDs among persons living with HIV (PLH). In summary, with some expectations, NTX and XR-NTX administration in persons living with HIV and AUDs led to reduced alcohol use, improved viral suppression, unchanged ART adherence and has no significant adverse events.

Conclusion
The findings of this systematic review suggest the beneficial effects and safety of the NTX and XR-NTX for treating AUDs in PLH. Further studies are needed in the future to focus on the treatment of AUDs in people living with HIV.
The potential drug for treatment in pancreatic adenocarcinoma: a bioinformatical study based on distinct drug databases
Authors: Liu Han , Zhou Qi , Wei Wenjuan , Qi Bing , Zeng Fen , Bao Nabuqi , Li Qian , Guo Fangyue , Xia Shilin 
Published: March 2020

AbstractBackgroundThe prediction of drug-target interaction from chemical and biological data can advance our search for potential drug, contributing to a therapeutic strategy for pancreatic adenocarcinoma (PAAD). We aim to identify hub genes of PAAD and search for potential drugs from distinct databases. The docking simulation is adopted to validate our findings from computable perspective.MethodsDifferently expressed genes (DEGs) of PAAD were performed based on TCGA. With two Cytoscape plugins of CentiScaPe and MCODE, hub genes were analyzed and visualized by STRING analysis of Protein–protein Interaction (PPI). The hub genes were further selected with significant prognostic values. In addition, we examined the correlation between hub genes and immune infiltration in PAAD. Subsequently, we searched for the hub gene-targeted drugs in Connectivity map (Cmap) and cBioportal, which provided a large body of candidate drugs. The hub gene, which was covered in the above two databases, was estimated in Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Herbal Ingredients’ Targets (HIT) database, which collected natural herbs and related ingredients. After obtaining molecular structures, the potential ingredient from TCMSP was applied for a docking simulation. We finalized a network connectivity of ingredient and its targets.ResultsA total of 2616 DEGs of PAAD were identified, then we further determined and visualized 24 hub genes by a connectivity analysis of PPI. Based on prognostic value, we identified 5 hub genes including AURKA (p = 0.0059), CCNA2 (p = 0.0047), CXCL10 (p = 0.0044), ADAM10 (p = 0.00043), and BUB1 (p = 0.0033). We then estimated tumor immune correlation of these 5 hub genes, because the immune effector process was one major result of GO analysis. Subsequently, we continued to search for candidate drugs from Cmap and cBioportal database. BUB1, not covered in the above two databases, was estimated in TCMSP and HIT databases. Our results revealed that genistein was a potential drug of BUB1. Next, we generated two docking modes to validate drug-target interaction based on their 3D structures. We eventually constructed a network connectivity of BUB1 and its targets.ConclusionsAll 5 hub genes that predicted poor prognosis had their potential drugs, especially our findings showed that genistein was predicted to target BUB1 based on TCMSP and docking simulation. This study provided a reasonable approach to extensively retrieve and initially validate putative therapeutic agents for PAAD. In future, these drug-target results should be investigated with solid data from practical experiments.
A recurrent ABCC2 p.G693R mutation resulting in loss of function of MRP2 and hyperbilirubinemia in Dubin-Johnson syndrome in China
Authors: Wu Lina , Li Yanmeng , Song Yi , Zhou Donghu , Jia Siyu , Xu Anjian , Zhang Wei , You Hong , Jia Jidong , Huang Jian , Ou Xiaojuan 
Published: March 2020

Abstract
Background
Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia that is caused by pathogenic mutations in the adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2) gene, which encodes multidrug resistance-associated protein 2 (MRP2). However, little is known about the causative mutation of DJS in China. Recently, we have reported ABCC2 p.G693R mutation in two unrelated cases. In the present study, we investigated the pathogenicity of the ABCC2 p.G693R mutation in DJS in China.

Methods
Clinical and genetic analysis was conducted for the two patients with the ABCC2 p.G693R mutation. Whole exome sequencing for mutations in other known hyperbilirubinemia-related genes was conducted for the cases with ABCC2 p.G693R. Expression and cellular localization of the mutant MRP2 p.G693R were analyzed by Western blotting and immunofluorescence assay, respectively. Organic anion transport activity was evaluated by the analysis of glutathione-conjugated-monochlorobimane.

Results
The two DJS patients with ABCC2 p.G693R mutation, which was conserved among different species, showed typical hyperbilirubinemia phenotype. No pathogenic mutation was identified in the other known hyperbilirubinemia related genes. Functional studies in three cell lines showed that the expression, localization and the organic anion transport activity were significantly compromised by MRP2 p.G693R mutation compared with wild-type MRP2.

Conclusions
The recurrent ABCC2 p.G693R mutation is associated with loss of function of the MRP2 protein and may result in hyperbilirubinemia in DJS in China.
Dynamic LTR retrotransposon transcriptome landscape in septic shock patients
Authors:   MIPrea Study Group, Mommert Marine ,   REALISM Study Group, Tabone Olivier , Guichard Audrey , Oriol Guy , Cerrato Elisabeth , Denizot Mélanie , Cheynet Valérie , Pachot Alexandre , Lepape Alain , Monneret Guillaume , Venet Fabienne , Brengel-Pesce Karen , Textoris Julien , Mallet François 
Published: March 2020

Abstract
Background
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management.

Methods
We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results.

Results
We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features.

Conclusion
We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.
High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer
Authors: Qiu Si-Qi , van Rooijen Johan , Nienhuis Hilde H. , van der Vegt Bert , Timmer-Bosscha Hetty , van Leeuwen-Stok Elise , Walenkamp Annemiek M. E. , van Deurzen Carolien H. M. , de Bock Geertruida H. , de Vries Elisabeth G. E. , Schröder Carolien P. 
Published: March 2020

Abstract
Background
Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival.

Methods
From 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results
Of 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49–0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45–0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47–0.88, P = 0.001).

Conclusions
HGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future.