bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)-Based proteomic analysis of mRNA splicing relevant proteins in aging HSPCs
Authors: Lian Xiaolan , Zhang Lina 
Published: December 2019

Abstract
Background: HSPC aging was closely associated with the organism aging, senile diseases and hematopoietic related diseases. Therefore, study on HSPC aging born great significance to further elucidate the mechanisms of aging and to treat hematopoietic disease resulted from HSPC aging. Little attention had been paid to mRNA splicing as a mechanism underlying HSPC senescence. Results: We used our lab’s patented aging model of HSPCs in vitro to analyze mRNA splicing relevant proteins alterations with iTRAQ based proteomic analysis. We found that not only the notable mRNA splicing genes such as SR, hnRNP, WBP11, Sf3b1, Ptbp1 and U2AF1 but also the scarcely reported mRNA splicing relavant genes such as Rbmxl1, Dhx16, Pcbp2, Pabpc1 were significantly down-regulated. We further verified their genes expressions by qRT-PCR. In addition, we reported the effect of Spliceostatin A (SSA), which inhibits mRNA splicing in vivo and in vitro, on HSPC aging. Conclusions: It was concluded that mRNA splicing emerged as an important vulnerability of HSPC aging. This study improved our understanding of the role of mRNA splicing in the HSPC aging process.
Determinants of self-paid rotavirus vaccination status in Kanazawa city, Japan, including socioeconomic factors, parents’ perception, and children’s characteristics
Authors: Hara Megumi , Koshida Rie , Araki Kaoru , Kondo Masahide , Hirota Yoshio 
Published: December 2019

Abstract
Background: Japan’s National Immunization Program does not cover rotavirus vaccine and no government subsidies are available. This study aimed to measure the uptake of and determinants that influenced self-paid rotavirus vaccination, including socioeconomic status and relative poverty. Methods: We conducted a cross-sectional study at health check-ups for all children aged 18 months in Kanazawa city, Japan, between December 2017 and July 2018. Community nurses collected information on self-paid vaccination history, parents’ perceptions of and recommendations for rotavirus vaccine, and socioeconomic status, in interviews using a standardized questionnaire. We used multivariable logistic regression to assess vaccine uptake and possible determinants. Results: In total, 1,282 participants were enrolled. The estimated rotavirus vaccine coverage was 69.9%. Rotavirus vaccine uptake was positively correlated with the following: parents’ perceptions that rotavirus gastroenteritis is serious and that the rotavirus vaccine is effective; pediatrician’s recommendations; information from the city office, articles in magazines and on the Internet; and parents’ education level. Lower household income was negatively correlated with rotavirus vaccination. The high price of vaccine, fear about adverse reactions to the vaccine, number of household members and siblings, and children’s characteristics were not correlated with rotavirus vaccination. Poverty was negatively correlated with rotavirus vaccination, even after adjustment for other determinants (adjusted odds ratio 0.49, 95% confidence interval: 0.26–0.90). Conclusion: Parents’ perceptions, socioeconomic status, and relative poverty are determinants of vaccination. This study suggests that appropriate information about rotavirus vaccine, subsidies for those of lower socioeconomic status, and national recommendations are necessary to achieve higher coverage.
Lipidome analysis of breast milk composition in humans, monkeys, bovids, and pigs.
Authors: Mitina Aleksandra , Mazin Pavel , Vanyushkina Anna , Anikanov Nikolay , Mair Waltraud , Guo Song , khaitovich philipp 
Published: December 2019

Abstract
Background Lipids contained in breast milk are an essential source of energy and structural materials for a growing infant. Furthermore, lipids’ long-chain unsaturated fatty acid residues can directly participate in infant tissue formation. Here, we used untargeted mass spectrometric measurements to assess breast milk lipid composition in seven mammalian species: humans, two macaque species, cows, goats, yaks, and pigs.Results Analysis of the main milk lipid class, triacylglycerides, revealed species-specific differences in the composition of fatty acid residues for each of seven species. While human milk showed more medium and long-chain unsaturated fatty acids, pig milk composition was the most distinct, featuring the highest proportion of long-chain polyunsaturated fatty acids. Conclusions We show that breast milk lipidome composition is dynamic across mammalian species, changed extensively in pigs, and contains features particular to humans.
GIS-modelled built-environment exposures reflecting daily mobility for applications in child health research
Authors: Mizen Amy , Fry Richard , Rodgers Sarah E 
Published: December 2019

Abstract
Background Inaccurately modelled environmental exposures may have important implications for evidence-based policy targeting health promoting or hazardous facilities. Travel routes modelled using GIS generally use shortest network distances or Euclidean buffers to represent journeys with corresponding built-environment exposures calculated along these routes. These methods, however, are an unreliable proxy for calculating child built-environment exposures as child route choice is more complex than shortest network routes.Methods We hypothesised that a GIS model informed by characteristics of the build environment known to influence child route choice could be developed to more accurately model exposures. Using 884 GPS-derived walking commutes to and from school we used logistic regression models to highlight built-environment features important in child route choice (e.g. road type, traffic light count). We then recalculated walking commute routes using a weighted network to incorporate built-environment features. Multilevel regression analyses were used to validate exposure predictions to the retail food environment along the different routing methods.Results Children chose routes with more traffic lights and residential roads compared to the modelled shortest network routes. Compared to standard shortest network routes, the GPS-informed weighted network enabled GIS-based walking commutes to be derived with more than three times greater accuracy (38%) for the route to school and more than 12 times greater accuracy (92%) for the route home.Conclusions This research advocates using weighted GIS networks to accurately reflect child walking journeys to school. The improved accuracy in route modelling has in turn improved estimates of children’s exposures to potentially hazardous features in the environment. Further research is needed to explore if the built-environment features are important internationally. Route and corresponding exposure estimates can be scaled to the population level which will contribute to a better understanding of built-environment exposures on child health and contribute to mobility-based child health policy.
Purified IgG from aquaporin-4 neuromyelitis optica spectrum disorder patients alters blood-brain barrier permeability
Authors: Calvo Alvaro Cobo , Cobo-Calvo Alvaro , Ruiz Anne , Richard Chloé , Blondel Sandrine , Cavagna Sylvie , Strazielle Nathalie , Ghersi-Egea Jean-François , Giraudon Pascal , Marignier Romain 
Published: December 2019

Abstract
Background: Blood-brain barrier (BBB) breakdown is considered one of the key steps for the development and lesion formation of neuromyelitis optica spectrum disorder (NMOSD). However, little is known about the molecular mechanisms involved. The aim of the study was to evaluate the effect of human immunoglobulins from NMOSD patients (NMO-IgG) on BBB properties.Methods: Freshly isolated brain microvessels (IBM) from rat brains that mirror the blood-CNS barrier were used as a study model. At first, analysis of the secretome profile (cytokine protein array) from IBM exposed to purified NMO-IgG, to healthy donor IgG (Control-IgG), or non-treated, was performed. Second, structural BBB properties were analysed by Western blotting (Wb) to measure the expression of tight junction (TJ) proteins (Claudin-5, occludin, and ZO-1) in fresh IBM and primary cultures of brain microvascular endothelial cells (BMEC) after exposition to NMO-IgG and Control-IgG. Finally, functional BBB properties were investigated using two approaches; 1) in the NMO-rat model, the presence of rat-IgG in tissue lysate from brain periventricular regions was analysed using Wb, and 2) in a bicameral model simulating the blood and brain compartments of the BBB, the passage of NMO-IgG and sucrose was assessed by using ELISA.Results: We found that NMO-IgG induces several functional and morphological changes of the BBB in our different study models, including: 1) increase of pro-inflammatory cytokines production (CXCL-10 [IP-10], IL-6, IL1-ra, IL1-β and CXCL-3) by at least three-fold in IBM when exposed to NMO-IgG in comparison to Control-IgG or non-treated IBM; 2) decrease of Claudin-5 levels by 25.6% after treatment of fresh IBM by NMO-IgG compared to Control-IgG (p=0.002), and similarly, decrease of Claudin-5 by at least 20% when BMEC were cultured with NMO-IgG from five different patients; 3) a higher level of rat-IgG accumulated in periventricular regions of NMO-rats compared to Control-rats and an increase the permeability of BBB after NMO-IgG treatment in the bicameral model.Conclusion: Human NMO-IgG induces both structural and functional alterations of BBB properties, suggesting a direct role of NMO-IgG on modulation of BBB permeability in NMOSD.
Bibliometrics indicators in the Caribbean islands: French West Indies authorship analyzed from 1989 to 2018
Authors: CONTARET CEDRIC , CESAIRE Raymond , DELOUMEAUX Jacqueline , NEVIERE Rémi , RESIERE Dabor , CABIE André , SYLVESTRE Emmanuelle , JOACHIM Clarisse , DRAME Moustapha 
Published: December 2019

Abstract
BackgroundBibliometrics are mathematical methods used in various scientific domains to measure scientific output based on the number of publications, the prestige of the journal, and the number of citations of the research after its publication. To the best of our knowledge, only a few bibliometric studies have been performed in the Caribbean or the French West Indies. The aim of this study was to quantify the collaborations and scientific output between the two university teaching hospitals of Martinique and Guadeloupe, at the regional, national and international level.MethodA bibliometrics analysis was performed from the international databases Web of Science and PubMed, for the period from 1989 to 2018 inclusive (30 years). Three types of bibliometric indicators were used, namely quantitative indicators, performance indicators, and organisation-specific indicators. Affiliations of the first and last authors were identified from PubMed. Between 2014 and 2018, we recorded the affiliations of all authors (from the first to the last author) who collaborated on an article with the University Hospital of either Martinique of GuadeloupeResultsBetween 1989 and 2018, a total of 1,522 indexed articles were published with at least one author affiliated to either the University Hospital of Martinique (N=827) or the University Hospital of Guadeloupe (N=685). The majority of articles for both hospitals were in category Q1 (35.8% for Martinique, and 35.2% for Guadeloupe). In Martinique, over the last 30 years, the 3 main research areas have been clinical neurology, ophthalmology and surgery, together representing 28.7% of all research areas, with the highest number of articles published in the field of clinical neurology (n=81). In the University Hospital of Guadeloupe, the area of hematology was largely represented, with 79 articles published. For both hospitals, the first and last authors of the articles published were mainly from mainland France, and from either Martinique or Guadeloupe university hospitalConclusionThis quantitative and qualitative analysis shows the development of medical and scientific research in Martinique and Guadeloupe over the last three decades, as well as the extent of their collaborative partnerships at national and international level.
Metabolite Secretions of Lactobacillus plantarum YYC-3 May Inhibit Colon Cancer Cell Metastasis by Suppressing the VEGF-MMP2/9 Signaling Pathway
Authors: Yue Yuanchun , Yang Bao-Yu , Lu Jing , Zhang Shu-Wen , Liu Liu , Nassar Khaled , Xu Xiao-Xi , Pang Xiao-Yang , Lv Jia-Ping 
Published: December 2019

Abstract
The authors have requested that this preprint be removed from Research Square.
Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistan families
Authors: Zhou Yingjie , Tariq Muhammad , He Sijie , Abdullah Uzma , Zhang Jianguo , Baig Shahid Mahmood 
Published: December 2019

Abstract
Background: Hearing loss is the most common sensory defect that affects over 6% of the population worldwide. About 50%-60% of hearing loss patients are attributed to genetic causes. Currently more than 100 genes have been reported to cause non-syndromic hearing loss. It’s possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES).Methods: We collected 5 consanguineous pedigrees with hearing loss from Pakistan and applied WES on selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causing genes for them.Results: Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate for 3 pedigrees, which were GIPC3 (c.937T>C), LOXHD1 (c.2935G>A) and TMPRSS3 (c.941T>C). And the remaining 2 pedigrees each contained two candidates, which were TECTA (c.4045G>A) and MYO15A (c.3310G>T and c.1705G>C) for one pedigree and DFNB59 (c.494G>A) and TRIOBP (c.1952C>T) for the other pedigree. The candidates were validated in all available samples by Sanger sequencing.Conclusion: The candidate variants in hearing loss genes were validated to be co-segregated in the pedigrees, which may indicate the reasons for such patients. We also suggested that WES may be suitable strategy for hearing loss gene screening in clinical detection.
Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials
Authors: Patson Noel , Mukaka Mavuto , Otwombe Kennedy N , Kazembe Lawrence , Mathanga Don P , Mwapasa Victor , Kabaghe Alinune N , Eijkemans Marinus JC , Laufer Miriam K , Chirwa Tobias 
Published: December 2019

Abstract
Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of antimalarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. We have therefore conducted a systematic review to establish the current practice in statistical analysis for antimalarial drug safety in pregnancy.Methods We searched PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials for original English articles reporting Phase III (randomized controlled trials) RCTs on antimalarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019.Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n=18, 100%) and mean/median (n=2, 11.1%). Results presentation included tabular (n=16, 88.9%) and text description (n=2, 11.1%). Univariate inferential methods were reported in most trials (n=16, 88.9%); including Chi-square/Fisher`s exact test (n=12, 66.7%), t-test (n=2, 11.1%) and Mann-Whitney/Wilcoxon test (n=1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n=4, 22.2%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n=7, 38.9%).Conclusion The review demonstrated that statistical analysis of safety data in antimalarial drugs for malarial chemoprevention in pregnancy RCTs are inadequate. The analysis insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise antimalarial drug safety evidence development, based on the available data.
The complexity and robustness of gene network inside the story between miRNAs and splicing isoforms in sacred lotus
Authors: Zhang Yue , Rahmani Razgar Seyed , Yang Xingyu , Chen Jinming , Shi Tao 
Published: December 2019

Abstract
BACKGROUND. Gene expression is complex and regulated by multiple molecular mechanisms, such as miRNA-mediated gene inhibition and alternative-splicing of pre-mRNAs. However, coordination of interaction between miRNAs with different splicing isoforms, and the role of splicing isoform in response to different cellular environments are largely unexplored in plants. In this study, we analyzed the miRNA and mRNA transcriptome from lotus ( Nelumbo nucifera ), an economically important flowering plant. RESULTS. Through RNA-seq expression analyses among six lotus tissues, the negative regulatory roles of most miRNAs are reflected by their tissue-biased expression and the negative correlation with their targets in expression. Further, the central roles of miRNAs in the gene network was unveiled as there are more frequent interactions between miRNAs and hub isoforms than between miRNAs and non-hub isoforms. Surprisingly, for many genes, their corresponding isoforms were assigned to different co-expressed modules, and they exhibited more divergent mRNA structures including presence and absence of miRNA binding sites, suggesting functional divergence for many isoforms is escalated by both structural and expression divergence. The gene function enrichment analysis of miRNA targeted reveals that miRNAs are involved in regulation of lotus growth and development by regulating plant hormone-related pathway genes. CONCLUSION. Taken together, we carry out a comprehensive and deep analysis between miRNA and mRNA transcriptome to study coordination of interaction between miRNAs with different splicing isoforms. Our study on lotus highlights not only the complicate interactions between the miRNAs and transcript isoforms but also functional divergence of many transcript isoforms from the same locus in plant.
Persistent postoperative pain and healthcare costs associated with instrumented and non-instrumented spinal surgery: a case-control study
Authors: Weir Sharada , Samnaliev Mihail , Kuo Tzu-Chun , Tierney Travis S. , Manca Andrea , Taylor Rod S. , Bruce Julie , Eldabe Sam , Cumming David 
Published: December 2019

Abstract
Purpose. To compare rates of persistent postoperative pain (PPP) after lumbar spine surgery—commonly known as Failed Back Surgery Syndrome—and healthcare costs for instrumented lumbar spinal fusion versus decompression/discectomy. Methods. UK population-based healthcare data from the Hospital Episode Statistics (HES) database from NHS Digital and the Clinical Practice Research Datalink (CPRD) were queried to identify patients with PPP following lumbar spinal surgery. Rates of PPP were calculated by type of surgery (instrumented and non-instrumented). Total healthcare costs associated with the surgery and covering the 24 month period after index hospital discharge were estimated using standard methods for classifying health care encounters into major categories of health care resource utilization (i.e., inpatient hospital stays, outpatient clinic visits, accident and emergency attendances, primary care encounters, and medications prescribed in primary care) and applying the appropriate unit costs (expressed in 2013 GBP). Results. Increasing the complexity of surgery with instrumentation was not associated with an increased rate of PPP. However, 2-year healthcare costs following discharge after surgery are significantly higher among patients who underwent instrumented surgery compared with decompression/discectomy. Conclusions. Although there is a not insubstantial risk of ongoing pain following spine surgery, with 1-in-5 patients experiencing PPP within two years of surgery, the choice of surgical procedure does not, by itself, appear to be a driving factor.
The efficacy and safety of Ojeok-san plus Saengmaek-san for gastro-esophageal reflux-induced chronic cough: a protocol for a pilot, randomized, double-blind, placebo-controlled trial
Authors: Lee Beom-Joon , Lee Jun-Hwan , Bhang Yeon Hee , Kim Kwan-Il , Kim Jaehyo , Ahn Junmo , Jung Hwan-Su , Yang Changsop , Ko Seok-Jae , Bu Youngmin , Park Jae-Woo , Park Kyoung Sun , Jung Hee-Jae 
Published: December 2019

Abstract
Background Gastro-esophageal reflux disease (GERD) is a major cause of chronic cough. GERD-induced chronic cough is difficult to diagnose because some patients do not complain of any gastrointestinal (GI) reflux symptoms. Although chronic cough due to GERD is highly prevalent, no effective treatment is currently available, especially for GERD-related cough without GI symptoms. As the herbal medicines Ojeok-san and Saengmaek-san can effectively treat GERD and cough, we aim to evaluate the efficacy and safety of a combination of these components for relieving chronic cough due to GERD. Methods This is a study protocol of a randomized, double-blind, placebo-controlled, single-center pilot trial. After one-week run-in period, a total of 30 patients with GERD-induced chronic cough will be randomly allocated to an intervention group (n=15) or placebo group (n=15). Participants will receive 5.76 g of Ojeok-san plus Saengmaek-san or a placebo three times per day for 6 weeks. The primary outcome measures, the frequency and severity of cough, will be recorded using a cough diary. The secondary outcome measures will include a cough visual analog scale, the Leicester Cough Questionnaire (Korean version), Gastrointestinal Symptom Rating Scale, Hull Airway Reflux (hypersensitivity) Questionnaire, Pattern Identification for Chronic Cough Questionnaire, Pattern Identification for Gastroesophageal Reflux Disease, and safety testing. Adverse events will also be reported. Discussion This will be the first clinical trial to explore herbal medicines for the GERD-related chronic cough, including patients without GI reflux symptoms. This study will provide useful evidence regarding the efficacy and safety of Ojeok-san plus Saengmaek-san treatment. In addition, this trial will offer scientific basis for the combination of herbal medicines. This finding will also serve as an important data for conducting a larger-scale clinical trial on GERD-induced chronic cough. Trial registration This trial has been registered with Clinical Research Information Service (CRIS) of South Korea (http://cris.nih.go.kr; registration number: KCT0003115). Registered August 28, 2018.