bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study
Authors: Yun Jae-Seung , Jung Sang-Hyuk , Shivakumar Manu , Xiao Brenda , Khera Amit V. , Won Hong-Hee , Kim Dokyoon 
Published: July 2022

AbstractBackgroundFew studies have examined associations between genetic risk for type 2 diabetes (T2D), lifestyle, clinical risk factors, and cardiovascular disease (CVD). We aimed to investigate the association of and potential interactions among genetic risk for T2D, lifestyle behavior, and metabolic risk factors with CVD.MethodsA total of 345,217 unrelated participants of white British descent were included in analyses. Genetic risk for T2D was estimated as a genome-wide polygenic risk score constructed from > 6 million genetic variants. A favorable lifestyle was defined in terms of four modifiable lifestyle components, and metabolic health status was determined according to the presence of metabolic syndrome components.ResultsDuring a median follow-up of 8.9 years, 21,865 CVD cases (6.3%) were identified. Compared with the low genetic risk group, participants at high genetic risk for T2D had higher rates of overall CVD events, CVD subtypes (coronary artery disease, peripheral artery disease, heart failure, and atrial fibrillation/flutter), and CVD mortality. Individuals at very high genetic risk for T2D had a 35% higher risk of CVD than those with low genetic risk (HR 1.35 [95% CI 1.19 to 1.53]). A significant gradient of increased CVD risk was observed across genetic risk, lifestyle, and metabolic health status (Pfor trend > 0.001). Those with favorable lifestyle and metabolically healthy status had significantly reduced risk of CVD events regardless of T2D genetic risk. This risk reduction was more apparent in young participants (≤ 50 years).ConclusionsGenetic risk for T2D was associated with increased risks of overall CVD, various CVD subtypes, and fatal CVD. Engaging in a healthy lifestyle and maintaining metabolic health may reduce subsequent risk of CVD regardless of genetic risk for T2D.
Heterogeneity in prevalence of subclinical Plasmodium falciparum and Plasmodium vivax infections but no parasite genomic clustering in the Chittagong Hill Tracts, Bangladesh
Authors: Huwe Tiffany , Kibria Mohammad Golam , Johora Fatema Tuj , Phru Ching Swe , Jahan Nusrat , Hossain Mohammad Sharif , Khan Wasif Ali , Price Ric N. , Ley Benedikt , Alam Mohammad Shafiul , Koepfli Cristian 
Published: July 2022

Abstract
Background
Malaria remains endemic in Bangladesh, with the majority of cases occurring in forested, mountainous region in the Chittagong Hill Tracts (CHT). This area is home to Bengali and diverse groups of indigenous people (Pahari) residing largely in mono-ethnic villages.

Methods
1002 individuals of the 9 most prominent Pahari and the Bengali population were randomly selected and screened by RDT and qPCR. Parasites were genotyped by msp2 and deep sequencing of 5 amplicons (ama1-D3, cpmp, cpp, csp, and msp7) for Plasmodium falciparum (n = 20), and by microsatellite (MS) typing of ten loci and amplicon sequencing of msp1 for Plasmodium vivax (n = 21). Population structure was analysed using STRUCTURE software. Identity-by-state (IBS) was calculated as a measure of parasite relatedness and used to generate relatedness networks.

Results
The prevalence of P. falciparum and P. vivax infection was 0.7% by RDT (P. falciparum 6/1002; P. vivax 0/1002, mixed: 1/1002) and 4% by qPCR (P. falciparum 21/1002; P. vivax 16/1002, mixed: 5/1002). Infections were highly clustered, with 64% (27/42) of infections occurring in only two Pahari groups, the Khumi and Mro. Diversity was high; expected heterozygosity was 0.93 for P. falciparum and 0.81 for P. vivax. 85.7% (18/21) of P. vivax and 25% (5/20) of P. falciparum infections were polyclonal. No population structure was evident for either species, suggesting high transmission and gene flow among Pahari groups.

Conclusions
High subclinical infection prevalence and genetic diversity mirror ongoing transmission. Control activities should be specifically directed to Pahari groups at greatest risk.
Tissue Doppler derived biphasic velocities during the pre and post-ejection phases: patterns, concordance and hemodynamic significance in health and disease
Authors: Omar Alaa Mabrouk Salem , Botero Diana Maria Ronderos , Caraballo Javier Arreaza , Kim Ga Hee , Khachatoorian Yeraz , Kliewer Jaclyn , Rahman Mohamed Ahmed Abdel , Rifaie Osama , Bella Jonathan N. , Argulian Edgar , Contreras Johanna 
Published: July 2022

Abstract
Background
Pre-(PRE) and post-ejection (POE) velocities by mitral annular tissue Doppler (TD) are biphasic and may be related to myocardial deformations. We investigated the predominance and concordance of TD-PRE and POE velocities and their effect on myocardial functions in controls and in heart failure (HF) patients.

Methods
Retrospectively, 84 HF patients [57.6 years, 28(33%) females, NYHA: 2.3 ± 0.6, EF: 55 ± 15%, 52(62%) preserved EF, and 32(38%) reduced EF], 42 normal young controls, and 26 asymptomatic age matched controls were included. Echocardiography was done and from mitral annular tissue Doppler recordings, the biphasic PRE and POE velocity signals were identified and compared between groups.

Results
While controls had almost always predominantly positive PRE and negative POE, HF had more negative PRE and positive POE. Moreover, almost all controls exhibited normal concordance (positive PRE and negative POE). HF exhibited more abnormal concordance which was significantly associated with worse NYHA, and parameters of diastolic and systolic functions. Opposite PRE and POE velocities correlated significantly in all groups (PREp vs POEn: young:r = 0.52, p < 0.001, age controls:r = 0.79, p < 0.001, HFpEF: r = 0.56, p < 0.001, HFrEF: r = 0.42, p = 0.018; PREn vs POEp: young: r = 0.25,p = 0.1, age controls: r = 0.42, p = 0.04, HFpEF: r = 0.43, p = 0.004, HFrEF: r = 0.61, p < 0.001) and the ratios PRE-P/N and POE-N/P correlated significantly with E/e’ in HF only.

Conclusions
In physiological state, TD signals are predominantly positive during PRE and negative during POE. Opposite PRE and POE velocities corelate, representing the PRE-generation and POE-reversal of shortening–stretch relationships, the attenuation of which in HF may be related to elevated LV filling pressures. In HF, partially or completely reversed concordance of PRE and POE is associated with progressive worsening of clinical and hemodynamic profiles.
Fucoidan-derived carbon dots against Enterococcus faecalis biofilm and infected dentinal tubules for the treatment of persistent endodontic infections
Authors: Tang Shang , Zhang Hui , Mei Li , Dou Keke , Jiang Yuying , Sun Zhanyi , Wang Shuai , Hasanin Mohamed Sayed , Deng Jing , Zhou Qihui 
Published: July 2022

AbstractEnterococcus faecalis (E. faecalis) biofilm-associated persistent endodontic infections (PEIs) are one of the most common tooth lesions, causing chronic periapical periodontitis, root resorption, and even tooth loss. Clinical root canal disinfectants have the risk of damaging soft tissues (e.g., mucosa and tongue) and teeth in the oral cavity, unsatisfactory to the therapy of PEIs. Nanomaterials with remarkable antibacterial properties and good biocompatibility have been developed as a promising strategy for removing pathogenic bacteria and related biofilm. Herein, carbon dots (CDs) derived from fucoidan (FD) are prepared through a one-pot hydrothermal method for the treatment of PEIs. The prepared FDCDs (7.15 nm) with sulfate groups and fluorescence property are well dispersed and stable in water. Further, it is found that in vitro FDCDs display excellent inhibiting effects on E. faecalis and its biofilm by inducing the formation of intracellular and extracellular reactive oxygen species and altering bacterial permeability. Importantly, the FDCDs penetrated the root canals and dentinal tubules, removing located E. faecalis biofilm. Moreover, the cellular assays show that the developed FDCDs have satisfactory cytocompatibility and promote macrophage recruitment. Thus, the developed FDCDs hold great potential for the management of PEIs.
Graphical Abstract
Huc-MSCs-derived exosomes attenuate inflammatory pain by regulating microglia pyroptosis and autophagy via the miR-146a-5p/TRAF6 axis
Authors: Hua Tong , Yang Mei , Song Honghao , Kong Erliang , Deng Mengqiu , Li Yongchang , Li Jian , Liu Zhixiao , Fu Hailong , Wang Yue , Yuan Hongbin 
Published: July 2022

AbstractBackgroundChronic inflammatory pain significantly reduces the quality of life and lacks effective interventions. In recent years, human umbilical cord mesenchymal stem cells (huc-MSCs)-derived exosomes have been used to relieve neuropathic pain and other inflammatory diseases as a promising cell-free therapeutic strategy. However, the therapeutic value of huc-MSCs-derived exosomes in complete Freund's adjuvant (CFA)-induced inflammatory pain remains to be confirmed. In this study, we investigated the therapeutic effect and related mechanisms of huc-MSCs-derived exosomes in a chronic inflammatory pain model.MethodsC57BL/6J male mice were used to establish a CFA-induced inflammatory pain model, and huc-MSCs-derived exosomes were intrathecally injected for 4 consecutive days. BV2 microglia cells were stimulated with lipopolysaccharide (LPS) plus adenosine triphosphate (ATP) to investigate the effect of huc-MSCs-derived exosomes on pyroptosis and autophagy. Bioinformatic analysis and rescue experiments were used to demonstrate the role of miR-146a-5p/ TRAF6 in regulating pyroptosis and autophagy. Western blotting, RT-qPCR, small interfering RNA and Yo-Pro-1 dye staining were performed to investigate the related mechanisms.ResultsHuc-MSCs-derived exosomes alleviated mechanical allodynia and thermal hyperalgesia in CFA-induced inflammatory pain. Furthermore, huc-MSCs-derived exosomes attenuated neuroinflammation by increasing the expression of autophagy-related proteins (LC3-II and beclin1) and inhibiting the activation of NLRP3 inflammasomes in the spinal cord dorsal horn. In vitro, NLRP3 inflammasome components (NLRP3, caspase1-p20, ASC) and gasdermin D (GSDMD-F, GSDMD-N) were inhibited in BV2 cells pretreated with huc-MSCs-derived exosomes. Western blot and Yo-Pro-1 dye staining demonstrated that 3-MA, an autophagy inhibitor, weakened the protective effect of huc-MSCs-derived exosomes on BV2 cell pyroptosis. Importantly, huc-MSCs-derived exosomes transfected with miR-146a-5p mimic promoted autophagy and inhibited BV2 cell pyroptosis. TRAF6, as a target gene of miR-146a-5p, was knocked down via small-interfering RNA, which increased pyroptosis and inhibited autophagy.ConclusionHuc-MSCs-derived exosomes attenuated inflammatory pain via miR-146a-5p/TRAF6, which increased the level of autophagy and inhibited pyroptosis.Graphical Abstract
Van-mediated self-aggregating photothermal agents combined with multifunctional magnetic nickel oxide nanoparticles for precise elimination of bacterial infections
Authors: Du Ting , Cao Jiangli , Xiao Zehui , Liu Jiaqi , Wei Lifei , Li Chunqiao , Jiao Jingbo , Song Zhiyong , Liu Jifeng , Du Xinjun , Wang Shuo 
Published: July 2022

AbstractBuilding a novel and efficient photothermal antibacterial nanoplatform is a promising strategy for precise bacterial elimination. Herein, a nanocomposite NiO NPs@AuNPs@Van (NAV) for selective MRSA removal was constructed by electrostatic self-assembly of highly photothermal magnetic NiO NPs and vancomycin (Van)-modified gold nanoparticles (AuNPs). In the presence of MRSA and under NIR irradiation, Van-mediated AuNPs can self-aggregate on MRSA surface, generating photothermal effect in situ and killing 99.6% MRSA in conjunction with magnetic NiO NPs. Additionally, the photothermal efficiency can be improved by magnetic enrichment due to the excellent magnetism of NAV, thereby enhancing the bactericidal effect at a lower experimental dose. In vitro antibacterial experiments and full-thickness skin wound healing test demonstrated that this combination therapy could effectively accelerate wound healing in MRSA-infected mice, increase collagen coverage, reduce IL-6 and TNF-α content, and upregulate VEGF expression. Biological safety experiments confirmed that NAV has good biocompatibility in vivo and in vitro. Overall, this work reveals a new type of nanocomposite with enhanced photothermal antibacterial activity as a potential nano-antibacterial agent for treating bacteria-infected wounds.
IGF2 reduces meiotic defects in oocytes from obese mice and improves embryonic developmental competency
Authors: Wan Yanling , Muhammad Tahir , Huang Tao , Lv Yue , Sha Qianqian , Yang Shuang , Lu Gang , Chan Wai-yee , Ma Jinlong , Liu Hongbin 
Published: July 2022

AbstractBackgroundMaternal obesity is a global issue that has devastating effects across the reproductive spectrum such as meiotic defects in oocytes, consequently worsening pregnancy outcomes. Different studies have shown that such types of meiotic defects originated from the oocytes of obese mothers. Thus, there is an urgent need to develop strategies to reduce the incidence of obesity-related oocyte defects that adversely affect pregnancy outcomes. Multiple growth factors have been identified as directly associated with female reproduction; however, the impact of various growth factors on female fertility in response to obesity remains poorly understood.MethodsThe immature GV-stage oocytes from HFD female mice were collected and cultured in vitro in two different groups (HFD oocytes with and without 50 nM IGF2), however; the oocytes from ND mice were used as a positive control. HFD oocytes treated with or without IGF2 were further used to observe the meiotic structure using different analysis including, the spindle and chromosomal analysis, reactive oxygen species levels, mitochondrial functional activities, and early apoptotic index using immunofluorescence. Additionally, the embryonic developmental competency and embryos quality of IGF2-treated zygotes were also determined.ResultsIn our findings, we observed significantly reduced contents of insulin-like growth factor 2 (IGF2) in the serum and oocytes of obese mice. Our data indicated supplementation of IGF2 in a culture medium improves the blastocyst formation: from 46% in the HFD group to 61% in the HFD + IGF2-treatment group (50 nM IGF2). Moreover, adding IGF2 to the culture medium reduces the reactive oxygen species index and alleviates the frequency of spindle/chromosome defects. We found increased mitochondrial functional activity in oocytes from obese mice after treating the oocytes with IGF2: observed elevated level of adenosine triphosphate, increased mitochondrial distribution, higher mitochondrial membrane potentials, and reduced mitochondrial ultrastructure defects. Furthermore, IGF2 administration also increases the overall protein synthesis and decreases the apoptotic index in oocytes from obese mice.ConclusionsCollectively, our findings are strongly in favor of adding IGF2 in culture medium to overcome obesity-related meiotic structural-developmental defects by helping ameliorate the known sub-optimal culturing conditions that are currently standard with assisted reproduction technologies.
A loss-of-function variant in SSFA2 causes male infertility with globozoospermia and failed oocyte activation
Authors: Huang Gelin , Zhang Xueguang , Yao Guanping , Huang Lin , Wu Sixian , Li Xiaoliang , Guo Juncen , Wen Yuting , Wang Yan , Shang Lijun , Li Na , Xu Wenming 
Published: July 2022

AbstractGlobozoospermia (OMIM: 102530) is a rare type of teratozoospermia (< 0.1%). The etiology of globozoospermia is complicated and has not been fully revealed. Here, we report an infertile patient with globozoospermia. Variational analysis revealed a homozygous missense variant in theSSFA2gene (NM_001130445.3: c.3671G > A; p.R1224Q) in the patient. This variant significantly reduced the protein expression of SSFA2. Immunofluorescence staining showed positive SSFA2 expression in the acrosome of human sperm. Liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS) and Coimmunoprecipitation (Co-IP) analyses identified that GSTM3 and Actin interact with SSFA2. Further investigation revealed that for the patient, regular intracytoplasmic sperm injection (ICSI) treatment had a poor prognosis. However, Artificial oocyte activation (AOA) by a calcium ionophore (A23187) after ICSI successfully rescued the oocyte activation failure for the patient with theSSFA2variant, and the couple achieved a live birth. This study revealed that SSFA2 plays an important role in acrosome formation, and the homozygous c.3671G > A loss-of-function variant inSSFA2caused globozoospermia.SSFA2may represent a new gene in the genetic diagnosis of globozoospermia, especially the successful outcome of AOA-ICSI treatment for couples, which has potential value for clinicians in their treatment regimen selections.
Environmental and practice factors associated with children’s device-measured physical activity and sedentary time in early childhood education and care centres: a systematic review
Authors: Martin Anne , Brophy Rachel , Clarke Joanne , Hall Charlotte J. S. , Jago Russell , Kipping Ruth , Reid Tom , Rigby Benjamin , Taylor Hilary , White James , Simpson Sharon A. 
Published: July 2022

Abstract
Background
Early childhood education and care (ECEC) settings offer a potentially cost-effective and sustainable solution for ensuring children have opportunities to meet physical activity (PA) and sedentary time (ST) guidelines. This paper systematically reviewed the association between childcare environment and practice and children’s PA and ST.

Methods
Three electronic databases were searched, and citation tracking of eligible studies performed between June–July 2020 (updated March 2022). Studies were eligible when (i) participants attended ECEC settings, (ii) they reported the association between use of outdoor space, including factors of time, availability, play, size and equipment, and children’s device-measured PA and ST, and (iii) where applicable, they compared the exposure to use of indoor space. Risk of bias was assessed using the Critical Appraisal Skills Program (CASP) tools. A synthesis was performed using effect direct plots and charts to visualise effect sizes.

Results
Of 1617 reports screened, 29 studies met the inclusion criteria. Studies provided data on outdoor versus indoor time (n = 9; 960 children), outdoor versus indoor play (n = 3; 1104 children), outdoor play space (n = 19; 9596 children), outdoor space use external to ECEC (n = 2; 1148 children), and portable (n = 7; 2408 children) and fixed (n = 7; 2451 children) outdoor equipment. Time spent outdoors versus indoors was associated with increased moderate-to-vigorous PA (MVPA), light PA (LPA) and total PA, while the association with ST was inconclusive. The mean (standard deviation) levels of outdoor MVPA (4.0 ± 3.2 to 18.6 ± 5.6 min/h) and LPA (9.9 ± 2.6 to 30.8 ± 11.8 min/h) were low, and ST high (30.0 ± 6.5 to 46.1 ± 4.3 min/h). MVPA levels doubled when children played outdoors versus indoors. Outdoor play space, and outdoor portable equipment, were associated with increased MVPA. A dose-response relationship for outdoor play area size was observed, demonstrating increased MVPA with areas ≥505m2 (5436 ft2), but no further increases when areas were > 900m2 (9688 ft2). No studies reported on injuries in outdoor settings.

Conclusions
ECEC policies and practices should promote not only outdoor time but also the availability of resources such as portable play equipment and sufficient size of outdoor play areas that enable children to be physically active for sustained periods while outdoors.

Systematic review registration
International prospective register of systematic reviews (PROSPERO) Registration Number: CRD42020189886.
Identification of ENO1 as a prognostic biomarker and molecular target among ENOs in bladder cancer
Authors: Huang Zhengnan , Yan Yilin , Wang Tengjiao , Wang Zeyi , Cai Jinming , Cao Xiangqian , Yang Chenkai , Zhang Fang , Wu Gang , Shen Bing 
Published: July 2022

AbstractBackgroundEnolase is an essential enzyme in the process of glycolysis and has been implicated in cancer progression. Though dysregulation of ENOs has been reported in multiple cancers, their prognostic value and specific role in bladder cancer (BLCA) remain unclear.MethodsMultiple databases were employed to examine the expression of ENOs in BLCA. The expression of ENO1 was also validated in BLCA cell lines and tissue samples by western blotting and immunohistochemistry. Kaplan–Meier analysis, ROC curve, univariate and multivariate Cox regression were performed to evaluate the predictive capability of the ENO1. Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) analysis were employed to perform the biological processes enrichment. Function experiments were performed to explore the biological role of ENO1 in BLCA. The correlation of ENO1 with immune cell infiltration was explored by CIBERSORT.ResultsBy analyzing three ENO isoforms in multiple databases, we identified that ENO1 was the only significantly upregulated gene in BLCA. High expression level of ENO1 was further confirmed in BLCA tissue samples. Aberrant ENO1 overexpression was associated with clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ENO1 depletion inhibited cancer cell aggressiveness. Furthermore, the expression level of ENO1 was correlated with the infiltration levels of immune cells and immune-related functions.ConclusionsTaken together, our results indicated that ENO1 might serve as a promising prognostic biomarker for prognosticating prognosis associated with the tumor immune microenvironment, suggesting that ENO1 could be a potential immune-related target against BLCA.