bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension
Authors: Yu Zhijie , Xiao Jun , Chen Xiao , Ruan Yi , Chen Yang , Zheng Xiaoyuan , Wang Qiang 
Published: January 2022

AbstractPulmonary arterial hypertension (PAH) is a progressive and rare disease without obvious clinical symptoms that shares characteristics with pulmonary vascular remodeling. Right heart failure in the terminal phase of PAH seriously threatens the lives of patients. This review attempts to comprehensively outline the current state of knowledge on PAH its pathology, pathogenesis, natural medicines therapy, mechanisms and clinical studies to provide potential treatment strategies. Although PAH and pulmonary hypertension have similar pathological features, PAH exhibits significantly elevated pulmonary vascular resistance caused by vascular stenosis and occlusion. Currently, the pathogenesis of PAH is thought to involve multiple factors, primarily including genetic/epigenetic factors, vascular cellular dysregulation, metabolic dysfunction, even inflammation and immunization. Yet many issues regarding PAH need to be clarified, such as the “oestrogen paradox”. About 25 kinds monomers derived from natural medicine have been verified to protect against to PAH via modulating BMPR2/Smad, HIF-1α, PI3K/Akt/mTOR and eNOS/NO/cGMP signalling pathways. Yet limited and single PAH animal models may not corroborate the efficacy of natural medicines, and those natural compounds how to regulate crucial genes, proteins and even microRNA and lncRNA still need to put great attention. Additionally, pharmacokinetic studies and safety evaluation of natural medicines for the treatment of PAH should be undertaken in future studies. Meanwhile, methods for validating the efficacy of natural drugs in multiple PAH animal models and precise clinical design are also urgently needed to promote advances in PAH.Graphical Abstract
Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains
Authors: Bigley Tarin M. , Xiong Monica , Ali Muhammad , Chen Yun , Wang Chao , Serrano Javier Remolina , Eteleeb Abdallah , Harari Oscar , Yang Liping , Patel Swapneel J. , Cruchaga Carlos , Yokoyama Wayne M. , Holtzman David M. 
Published: January 2022

AbstractBackgroundThe role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition.MethodsWe utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD.ResultsWe found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, −omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD.ConclusionAlthough MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.
DENA: training an authentic neural network model using Nanopore sequencing data of Arabidopsis transcripts for detection and quantification of N6-methyladenosine on RNA
Authors: Qin Hang , Ou Liang , Gao Jian , Chen Longxian , Wang Jia-Wei , Hao Pei , Li Xuan 
Published: January 2022

AbstractModels developed using Nanopore direct RNA sequencing data from in vitro synthetic RNA with all adenosine replaced by N6-methyladenosine (m6A) are likely distorted due to superimposed signals from saturated m6A residues. Here, we develop a neural network, DENA, for m6A quantification using the sequencing data of in vivo transcripts from Arabidopsis. DENA identifies 90% of miCLIP-detected m6A sites in Arabidopsis and obtains modification rates in human consistent to those found by SCARLET, demonstrating its robustness across species. We sequence the transcriptome of two additional m6A-deficient Arabidopsis, mtb and fip37-4, using Nanopore and evaluate their single-nucleotide m6A profiles using DENA.
Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)—study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial
Authors: Maláska Jan , Stašek Jan , Duška František , Balík Martin , Máca Jan , Hruda Jan , Vymazal Tomáš , Klementová Olga , Zatloukal Jan , Gabrhelík Tomáš , Novotný Pavel , Demlová Regina , Kubátová Jana , Vinklerová Jana , Svobodník Adam , Kratochvíl Milan , Klučka Jozef , Gál Roman , Singer Mervyn ,   on behalf of the REMED Study Group
Published: January 2022

Abstract
Background
Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids.

Methods
REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1–5, followed by dexamethasone 10 mg on days 6–10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic.

Discussion
We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety.

Trial registration
EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020
Blood flow restriction with different load levels in patients with knee osteoarthritis: protocol of a randomized controlled trial
Authors: Jardim Roger Andrey Carvalho , de Sousa Tamara Silva , dos Santos Wueyla Nicoly Nascimento , Matos Areolino Pena , Iosimuta Natália Camargo Rodrigues 
Published: January 2022

Abstract
Background
The effectiveness of blood flow restriction training (BFR) in elderly with knee osteoarthritis (OA) is comparable to performing high-intensity protocols (70 to 80% of 1 RM [repetition maximum]) that are known to be effective for improving the muscle strength of knee extensors, with the advantage of generating less particular rating of perceived exertion and pain immediately after training. However, despite being a promising alternative, little is known about the best way to apply the BFR, such as level of pressure and combination or not with other therapeutic modalities. The purpose of this study is to evaluate whether different levels of blood flow restriction with low load (BFR + LL) and no load (BFR + rest) are non-inferior to high-intensity resistance exercise (HIRE+BFRplacebo) for pain reduction in patients with knee OA.

Methods/design
This clinical trial is a non-inferiority, five-arm, randomized, active-controlled, single trial which will be carried out in 165 patients of both sexes with knee OA, aged 50 years and older. Participants will be randomly allocated into 5 exercise groups (40% of BFR + LL; 80% of BFR + LL; 40% of BFR + rest; 80% BFR + rest, and HIRE+BFR placebo). A mixed linear model will be used to examine the effect of group-by-time interaction on pain intensity on the WOMAC subscale (primary outcome) and on disease severity, physical functional data, balance data, quality of life, global perceived effect scale, and muscle strength (secondary outcomes). Participants will be analyzed for intention-to-treat, and the statistical assessor blinded to the groups. The collection of outcomes 72 h after completion of the 16 weeks of interventions will be the primary measurement point. Follow-up secondary timepoints will be collected at 20, 28, 40, 52, and 64 weeks after the end of interventions, except for pain during the training, which will be measured immediately at the end of each session. Only the comparison of the primary outcome between the HIRE group with each BFR group will be analyzed in the non-inferiority framework, the other comparisons between the BFR groups for the primary outcome, and all secondary outcomes will be interpreted in the superiority framework.

Discussion
The results of this clinical trial can point out more clearly to ways to optimize the BFR training with the minimum of pain immediately after training, which will allow the offer of an effective and more adherent strengthening training to patients with knee OA.

Trial registration
Registro Brasileiro de Ensaios Clínicos, RBR-93rx9q. Registered on 23 July 2020. Version 1.0.
Association between life-course cigarette smoking and metabolic syndrome: a discovery-replication strategy
Authors: Wang Jingya , Bai Yang , Zeng Zihang , Wang Jun , Wang Ping , Zhao Yongai , Xu Weili , Zhu Yun , Qi Xiuying 
Published: January 2022

Abstract
Background
The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples.

Methods
Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged ≥ 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS.

Results
In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64–2.47) and 1.76 (95%CI: 1.44–2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged < 70 years (Pinteraction = 0.015). We were able to replicate the association between cigarette smoking and MetS in an independent adult sample (second tertile vs. never: OR = 1.30, 95%CI: 1.04–1.63). The interaction of smoking with age was also replicated.

Conclusions
Life-course cigarette smoking is associated with an increased odds of MetS, especially among individuals who aged < 70 years.
Adherence and persistence rates of major antidiabetic medications: a review
Authors: Lee David Seung U. , Lee Howard 
Published: January 2022

AbstractThe objective of this paper was to review the adherence and persistence rates of major antidiabetic medication classes (i.e., metformin, sulfonylureas, sodium glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, insulin, glucagon-like peptide-1 receptor agonists, and thiazolidinediones) by summarizing the major findings of the studies published since 2017. In addition, we reported the potential causes for low adherence and persistence of antidiabetic medications. Based on the literature, the highest rate of adherence and persistence was consistently observed in metformin users. Second to metformin were sodium glucose cotransporter-2 inhibitors. Injectable therapies such as insulin and glucagon-like peptide-1 receptor agonists trailed low on the adherence and persistence rates. To the best of our knowledge, no studies published since the year 2017 analyzed the adherence and persistence of thiazolidinediones independently. The most frequently cited cause for low adherence and persistence was the severity of adverse events. Baseline characteristics (e.g., baseline HbA1c level), demographic information (e.g., age, gender, or ethnicity), and comorbidity profiles also had significant impacts on adherence and persistence in patients with type 2 diabetes mellitus.
Occupational performance of children with autism spectrum disorder and quality of life of their mothers
Authors: Beheshti Seyedeh Zeinab , Hosseini Seyed-Sirvan , Maroufizadeh Saman , Almasi-Hashiani Amir 
Published: January 2022

Abstract
Objectives
Limited studies were found to investigate the occupational performance of autistic children and their parents’ quality of life. Therefore, this study aimed to investigate occupational performance of children with Autism Spectrum Disorder (ASD) and QoL of their mothers.

Results
In this study, 88 participants were selected from autism centers in Arak, Iran, 2020. The Canadian Occupational Performance Measure (COPM) and the parent version of Quality of Life in Autism Questionnaire (QoLA-P) were used to assess the occupational performance of ASD children and their mothers QoL. QoLA-P consists of parts A which is related to the quality of life and part-B related to the problems that these children have and are related to the parents or their caregivers. Regarding occupational performance, the first priority of mothers is self-care with frequency 64.8%. The finding suggested a significant correlation between total function score of COPM and the score of part-A (r = 0.227, p = 0.033) of QoLA-P. Also, the results revealed a significant correlation between the total satisfaction score of COPM and the score of part-A (r = 0.236, p = 0.026) and part-B of QoLA-P questionnaire (r = 0.231, p = 0.030). The mothers’ first priority is self-care and, the total satisfaction and function score of COPM showed a significant correlation with mothers’ QoL.
Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury
Authors: Li Xiangling , Guan Yanjun , Li Chaochao , Zhang Tieyuan , Meng Fanqi , Zhang Jian , Li Junyang , Chen Shengfeng , Wang Qi , Wang Yi , Peng Jiang , Tang Jinshu 
Published: January 2022

AbstractVarious immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.
Automation of literature screening using machine learning in medical evidence synthesis: a diagnostic test accuracy systematic review protocol
Authors: Zhang Yuelun , Liang Siyu , Feng Yunying , Wang Qing , Sun Feng , Chen Shi , Yang Yiying , He Xin , Zhu Huijuan , Pan Hui 
Published: January 2022

Abstract
Background
Systematic review is an indispensable tool for optimal evidence collection and evaluation in evidence-based medicine. However, the explosive increase of the original literatures makes it difficult to accomplish critical appraisal and regular update. Artificial intelligence (AI) algorithms have been applied to automate the literature screening procedure in medical systematic reviews. In these studies, different algorithms were used and results with great variance were reported. It is therefore imperative to systematically review and analyse the developed automatic methods for literature screening and their effectiveness reported in current studies.

Methods
An electronic search will be conducted using PubMed, Embase, ACM Digital Library, and IEEE Xplore Digital Library databases, as well as literatures found through supplementary search in Google scholar, on automatic methods for literature screening in systematic reviews. Two reviewers will independently conduct the primary screening of the articles and data extraction, in which nonconformities will be solved by discussion with a methodologist. Data will be extracted from eligible studies, including the basic characteristics of study, the information of training set and validation set, and the function and performance of AI algorithms, and summarised in a table. The risk of bias and applicability of the eligible studies will be assessed by the two reviewers independently based on Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Quantitative analyses, if appropriate, will also be performed.

Discussion
Automating systematic review process is of great help in reducing workload in evidence-based practice. Results from this systematic review will provide essential summary of the current development of AI algorithms for automatic literature screening in medical evidence synthesis and help to inspire further studies in this field.

Systematic review registration
PROSPERO CRD42020170815 (28 April 2020).
Microbial and metabolomic mechanisms mediating the effects of dietary inulin and cellulose supplementation on porcine oocyte and uterine development
Authors: Men Zhaoyue , Cao Meng , Gong Yuechan , Hua Lun , Zhang Ruihao , Zhu Xin , Tang Lianchao , Jiang Xuemei , Xu Shengyu , Li Jian , Che Lianqiang , Lin Yan , Feng Bin , Fang Zhengfeng , Wu De , Zhuo Yong 
Published: January 2022

Abstract
Background
Dietary fiber (DF) is often eschewed in swine diet due to its anti-nutritional effects, but DF is attracting growing attention for its reproductive benefits. The objective of this study was to investigate the effects of DF intake level on oocyte maturation and uterine development, to determine the optimal DF intake for gilts, and gain microbial and metabolomic insight into the underlying mechanisms involved.

Methods
Seventy-six Landrace × Yorkshire (LY) crossbred replacement gilts of similar age (92.6 ± 0.6 d; mean ± standard deviation [SD]) and body weight (BW, 33.8 ± 3.9 kg; mean ± SD) were randomly allocated to 4 dietary treatment groups (n = 19); a basal diet without extra DF intake (DF 1.0), and 3 dietary groups ingesting an extra 50% (DF 1.5), 75% (DF 1.75), and 100% (DF 2.0) dietary fiber mixture consisting of inulin and cellulose (1:4). Oocyte maturation and uterine development were assessed on 19 d of the 2nd oestrous cycle. Microbial diversity of faecal samples was analysed by high-throughput pyrosequencing (16S rRNA) and blood samples were subjected to untargeted metabolomics.

Results
The rates of oocytes showing first polar bodies after in vitro maturation for 44 h and uterine development increased linearly with increasing DF intake; DF 1.75 gilts had a 19.8% faster oocyte maturation rate and a 48.9 cm longer uterus than DF 1.0 gilts (P <  0.05). Among the top 10 microbiota components at the phylum level, 8 increased linearly with increasing DF level, and the relative abundance of 30 of 53 microbiota components at the genus level (> 0.1%) increased linearly or quadratically with increasing DF intake. Untargeted metabolic analysis revealed significant changes in serum metabolites that were closely associated with microbiota, including serotonin, a gut-derived signal that stimulates oocyte maturation.

Conclusions
The findings provide evidence of the benefits of increased DF intake by supplementing inulin and cellulose on oocyte maturation and uterine development in gilts, and new microbial and metabolomic insight into the mechanisms mediating the effects of DF on reproductive performance of replacement gilts.
Mapping short tandem repeats for liver gene expression traits helps prioritize potential causal variants for complex traits in pigs
Authors: Wu Zhongzi , Gong Huanfa , Zhou Zhimin , Jiang Tao , Lin Ziqi , Li Jing , Xiao Shijun , Yang Bin , Huang Lusheng 
Published: January 2022

Abstract
Background
Short tandem repeats (STRs) were recently found to have significant impacts on gene expression and diseases in humans, but their roles on gene expression and complex traits in pigs remain unexplored. This study investigates the effects of STRs on gene expression in liver tissues based on the whole-genome sequences and RNA-Seq data of a discovery cohort of 260 F6 individuals and a validation population of 296 F7 individuals from a heterogeneous population generated from crosses among eight pig breeds.

Results
We identified 5203 and 5868 significantly expression STRs (eSTRs, FDR < 1%) in the F6 and F7 populations, respectively, most of which could be reciprocally validated (π1 = 0.92). The eSTRs explained 27.5% of the cis-heritability of gene expression traits on average. We further identified 235 and 298 fine-mapped STRs through the Bayesian fine-mapping approach in the F6 and F7 pigs, respectively, which were significantly enriched in intron, ATAC peak, compartment A and H3K4me3 regions. We identified 20 fine-mapped STRs located in 100 kb windows upstream and downstream of published complex trait-associated SNPs, which colocalized with epigenetic markers such as H3K27ac and ATAC peaks. These included eSTR of the CLPB, PGLS, PSMD6 and DHDH genes, which are linked with genome-wide association study (GWAS) SNPs for blood-related traits, leg conformation, growth-related traits, and meat quality traits, respectively.

Conclusions
This study provides insights into the effects of STRs on gene expression traits. The identified eSTRs are valuable resources for prioritizing causal STRs for complex traits in pigs.