bluuebunny/crossref_metadata_2025 huggingface dataset:
Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis
Authors: Wang Yuli , Lv Fengyi , Huang Lintong , Zhang Hengwei , Li Bing , Zhou Weina , Li Xuan , Du Yifei , Pan Yongchu , Wang Ruixia
Published: October 2020

Background and aim: Periodontitis is a chronic inﬂammatory disease inducing the absorption of alveolar bone and leading to tooth loss. Human amnion–derived mesenchymal stem cells (HAMSCs) have been used for studying inﬂammatory processes. This study aimed to explore the role of long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) in HAMSC-driven osteogenesis in lipopolysaccharide (LPS)-induced human bone marrow mesenchymal stem cells (HBMSCs). Methods: The cells were incubated with a co-culture system. Reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were used to detect the oxidative stress level. Flow cytometry was performed to determine cell proliferation. The alkaline phosphatase (ALP) activity, Alizarin red assay, cell transfection, and rat mandibular defect model were used to evaluate the osteogenic differentiation. Quantitative real-time reverse transcription–polymerase chain reaction (RT-PCR), Western blot analysis, dual-luciferase reporter assay, and immunofluorescence staining were used to evaluate the molecular mechanisms.Results: This study showed that HAMSCs promoted the osteogenesis of LPS-induced HBMSCs, while the ANRIL level in HBMSCs decreased during co-culture. ANRIL had no significant influence on the proliferation of LPS-induced HBMSCs. However, its overexpression inhibited the HAMSC-driven osteogenesis in vivo and in vitro, whereas its knockdown reversed these effects. Mechanistically, this study found that downregulating ANRIL led to the overexpression of microRNA-125a (miR-125a), and further contributed to the competitive binding of miR-125a and adenomatous polyposis coli (APC), thus significantly activating the Wnt/β-catenin pathway. Conclusion: The study indicated that HAMSCs promoted the osteogenic differentiation of LPS-induced HBMSCs via the ANRIL/miR-125a/APC axis, and offered a novel approach for periodontitis therapy.
Working condition and health status of 6,317 front line public health workers during the COVID-19 epidemic across 5 provinces in China: a cross-sectional study
Authors: Li Jinghua , Xu Jingdong , Zhou Huan , You Hua , Wang Xiaohui , Li Yan , Liang Yuan , Li Shan , Ma Lina , Zeng Jing , Cai Huanle , Xie Jinzhao , Pan Chenghao , Hao Chun , Gilmour Stuart , Lau Joseph Tak-fai , Hao Yuantao , Xu Dong Roman , Gu Jing
Published: October 2020

Background: Public health workers at Chinese Center for Disease Control and Prevention (China CDC) and primary health care institutes (PHI) constitute one of the main workforces for implementing prevention and control measures to contain the COVID-19 epidemic, but their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of frontline public health workers in China during the epidemic.Methods: Between February 18 to March 1, 2020, we conducted a cross-sectional survey among 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We interviewed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardized measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results: The prevalence of depression, anxiety, and poor self-rated health was 21.3%, 19.0%, and 9.8%, respectively, among public health workers (27.1%, 20.6% and 15.0% among CDC workers; and 17.5%, 17.9% and 6.8% among PHI workers). The majority (71.6%) participated in both field and non-field work and gave immense efforts. Nearly 20.0% have worked all night for more than 3 days and 45.3% had worked during the whole period of Chinese New Year. Three risk factors and two protective factors were found independently associated with all three health outcomes in our final multivariate models, including working all night for >3 days (ORm=1.67~1.75, p<0.001), concerns about being infected at work (ORm=1.46~1.89, p<0.001), perceived troubles at work (ORm=1.10~1.28, p<0.001), starting COVID-19 prevention work after January 23 (ORm=0.78~0.82, p=0.002~0.008), and capability to persist for more than 1 month at the current work intensity (ORm=0.44~0.55, p<0.001).Conclusions: Chinese public health workers gave immense efforts and personal sacrifices to curb the COVID-19 epidemic and were exposed to risk of mental health problems. Efforts should be taken to improve the working condition and health status of public health workers to maintain the morale and effectiveness of public health workers in the fight against the epidemic.
Pilot Randomised Evaluation of Singing in Dementia (PRESIDE): protocol for a two-arm, parallel group randomised controlled feasibility study with waiting-list control
Authors: Dowson Becky , Schneider Justine , Guo Boliang , Bath Philip M , McDermott Orii , Haywood Lee J , Orrell Martin
Published: October 2020

BackgroundAs the number of people living with dementia grows, so does the need to provide them with adequate psychosocial support. Many people with dementia live at home with family carers, who also require social and emotional support to cope with their role. Community group singing has received attention for its potential to support people with dementia and their carers. It is postulated that singing can improve cognitive function, strengthen the bonds between care partners, and help to establish social support networks. However, there is a lack of rigorous evidence of singing’s benefits for this population. This study aims to test the feasibility of a randomised controlled trial of community singing in dementia, to pave the way for a larger, conclusive study.MethodsThe PRESIDE study is designed as a two-arm, parallel group randomised trial with a waiting list control. Dyads consisting of a person with dementia (n=80) and their carer (n=80) will be recruited. Each dyad will be randomised either to attend 10 weeks of community group singing sessions straight away, or to wait for three months before attending the sessions. The singing sessions will be led by experienced professional musicians and will last about 90 minutes, including time for socialising. The primary outcome of this study is the attainment of feasibility criteria around recruitment, retention and the acceptability of the waiting list control. Secondary outcomes include the quality of life, mood, cognition, and musical engagement of the person with dementia, and quality of life, mood, and experiences/challenges of the carer. These data will be collected during home visits at baseline, and three and six months post-baseline. DiscussionDespite growing public interest in the positive effects of singing, and encouraging findings from qualitative and non-randomised quantitative studies, there is a lack of rigorous evidence. This is the first randomised controlled trial of community group singing for people with dementia in Europe, to our knowledge. If the results favour a full trial, conclusively demonstrating the effectiveness of group singing could positively affect the opportunities available to community-dwelling people with dementia and their carers.Trial RegistrationUnique identification number in ISRCTN registry: ISRCTN10201482 https://www.isrctn.com/ISRCTN10201482. Date registered: 12/05/2020
Physical Fitness and Cardiometabolic Risk in Seven to Nine Years Old Children
Authors: Weisstaub Gerardo , Gonzalez Maria Angelica , Hermoso Antonio Garcia , Salazar Gabriela
Published: October 2020

Background: Obesity and lower physical fitness levels in children are related to the development of cardiometabolic risk. The objective of the study was to determine the relationship of cardio-metabolic risk and physical fitness in school children from Santiago de Chile.Methods: Physical fitness was assessed as cardiorespiratory fitness and muscle strength. Fitness was measured using the six-minute-walk-test and muscle strength was assessed by hand grip and standing lung jump. Overweight (≥ 1 SD) and obesity (≥ 2 SD) were determined by body mass index. A cross sectional study was done in 452 children (185 boys and 267 girls), age range (7-9 years). Cardio-metabolic-risk (serum glucose, triglycerides, HDL, insulin) and waist for height ratio was expressed as z score. Data was analyzed using bivariate analysis and multiple and logistic regression.Results: A 21% were obese and 27% overweight. Children with high body fat and low cardiorespiratory fitness and muscle strength had an OR of 6.8-fold (IC 95% 3.4 to 13.9) cardiometabolic risk z-score, compared to those most fit.Conclusion: School children with higher body fat and lower physical fitness had increased cardio-metabolic-risk-score. No significant difference in cardio-metabolic risk in the non-obese children was found independent of their physical fitness.
Synthesis, Characterisation and Cytotoxicity of Gold Nanowires for Ultra-Sensitive Biosensor Development
Authors: Lah Nurul Akmal Che , Gray Robert , Trigueros Sonia
Published: October 2020

With the long-term goal of developing an ultra-sensitive microcantilever-based nano biosensor for versatile biomarker detection, new controlled bioreceptor-analytes systems are being explored to overcome the disadvantages of conventional ones. Gold nanowires (AuNWs) have been used as a probe to overcome the tolerance problem that occurs in response to changes in environmental conditions. However, the cytotoxicity of AuNWs is still unclear. Here, we examined the cytotoxicity of AuNWs systems using both commercial and as-synthesised AuNWs. In vitro experiments show that commercial AuNWs with an average quoted length of 6 µm are highly toxic against Gram-negative Escherichia coli (E. coli) at 50 µg/ml. However, this toxicity is due to the presence of CTAB surfactant not by the nanostructure. Conversely, the as-synthesised AuNWs with an average length of 9.5 µm show non-cytotoxicity even at the maximum viable concentration (330µg/ml). These findings may lead to the development of potentially life-saving cytotoxicity -free nano biosensors for an early diagnostic of potential diseases.
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome 
Authors: pandolfi laura , Tommaso Fossali , Vanessa Frangipane , Sara Bozzini , Monica Morosini , Maura D’Amato , Sara Lettieri , Mario Urtis , Alessandro Di Toro , Laura Saracino , Elena Percivalle , Stefano Tomaselli , Lorenzo Cavagna , Emanuela Cova , Francesco Mojoli , Paola Bergomi , Davide Ottolina , Daniele Lilleri , Guido Corsico Angelo , Eloisa Arbustini , Riccardo Colombo , Federica Meloni
Published: October 2020

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n=28) and to the Intermediate Medicine Ward (IMW) (n=5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels.Results: ICU patients showed a marked increase in neutrophils (1.24 x 105 ml-1 , 0.85-2.07), lower lymphocyte (0.97 x 105 ml-1, 0.024-0.34) and macrophages fractions (0.43 x 105 ml-1, 0.34-1.62) compared to IMW patients (0.095 x 105 ml-1, 0.05-0.73; 0.47 x 105 ml-1, 0.28-1.01 and 2.14 x 105 ml-1, 1.17-3.01, respectively) (p<0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p<0.01, IL8 p<0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p<0.1) or antivirals (p<0.05). Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
Quantitative DCE-MRI : An efficient diagnostic technique for evaluating early micro-environment permeability changes in ankylosing spondylitis
Authors: Yang Hui , Jiang Ling , Li Jiang , Zheng Xiuzhu , Yao Qianqian , Li Changqin , Zhu Jianzhong , Qin Jian
Published: October 2020

Background: In the management of early inflammatory joint of ankylosing spondylitis (AS), there is a need for reliable noninvasive quantitative monitoring biomarker to closely assess status of synovitis progression. Cognizant to this studies geared on improving techniques for quantitative evaluation of micro-environment permeability of the joint space are necessary. Such improved techniques may provide tissue perfusion as important biological parameters and can further help in understanding the origin of early changes associated with AS.Aims: To prospectively evaluate the diagnostic performance and determine longitudinal relationships of early micro-environment active in the joint space of the sacroiliac joint (SIJ) with a rat model by using quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Methods: Thirty wistar male rats were randomly assigned to the model (n= 15) or control (n = 15) group. All rats underwent DCE-MRI of SIJ region at fixed time points(12, 17 and 22 weeks),between September 2018 and October 2019. Differences in permeability parameters between the two groups at the same time point were compared by using an independent samples t test. Spearman correlations of DCE-MRI parameters with different time points in model group were analyzed. All statistical analyses were performed with software.Results: At 12 weeks, the Ktrans,Kep and Ve values in the model group were slightly lower than those in control group, but all the differences were not statistically significant (p>0.05).Compared with control group, the transfer constant (Ktrans)values increased significantly at 17 weeks and 22 weeks in model group, while the rate constant (Kep) and volume of extravascular extracellular space(Ve) significantly increased only at 22 weeks(p<0.05).The Ktrans,Kep and Ve were positively correlated with increasing time points (r=0.946, P＜0.01 for Ktrans; r=0.945, P＜0.01 for Kep; and r= 0.832, P＜0.01 for Ve).Conclusions: Quantitative DCE-MRI parameters are valuable for evaluating the early longitudinal relationship of micro-environment permeability changes in the joint space of SIJ.
Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection
Authors: Li Xiaoyi , Zhang Qifan , Zhang Wanyue , Ye Guofu , Ma Yanchen , Wen Chunhua , Gu Shuqin , Tang Libo , Li Yongyin
Published: October 2020

Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.
Hsa_circ_0004831 serves as a blood-based prognostic biomarker for colorectal cancer and its potentially circRNA-miRNA-mRNA regulatory network construction
Authors: Xing Linlin , Xia Mengyan , Jiao Xin , Fan Ling
Published: October 2020

Background: Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC. Methods: The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831. Results: Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.Conclusions: The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.
Diagnostic Value of Serum HER2 Levels in Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Shamshirian Amir , Aref Amir Reza , Yip George W. , Warkiani Majid Ebrahimi , Heydari Keyvan , Bazaz Sajad Razavi , Hamzehgardeshi Zeinab , Shamshirian Danial , Moosazadeh Mahmood , Alizadeh-Navaei Reza
Published: October 2020

Background:Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods.Methods:We performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).Results:Fourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82-65.28), but reasonable specificity of 79.27 (95%CI 73.02-85.51), accuracy of 72.06 (95%CI 67.04-77.08) and AUC of 0.79 (95%CI 0.66-0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16-68.20), NPV (NPV: 76.93, 95%CI 69.56-84.31), PLR (PLR: 2.10, 95%CI 1.69-2.50) and NLR (NLR: 0.58, 95%CI 0.44-0.71).Conclusion:Our findings revealed that although serum HER-2 levels showed low sensitivity for breast cancer diagnosis, its specificity, accuracy and AUC were reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.
CDX2 and Reg IV expression and correlation in gastric cancer
Authors: Chai Dandan , Du Huifen , Li Kesheng , Zhang Xueliang , Li Xiaoqin , Zhao Xiaoning , Lian Xiaowen , Xu Yang
Published: October 2020

Background: Ectopic expression of CDX2 is associated with the development and progression of gastric cancer. Previous studies showed that CDX2 may be an upstream regulator of Reg IV expression in gastric cancer, and our previous report showed that Reg IV upregulated SOX9 expression and enhanced cell migration and invasion in gastric cancer cells. However, the regulatory roles of CDX2 have not been clarified in gastric cancer, and the correlation between CDX2 and Reg IV requires further study. Methods: CDX2 and Reg IV were examined in gastric cancer specimens and paired adjacent tissues via real-time PCR and immunohistochemistry (IHC). The association between CDX2 and Reg IV was assessed using the χ 2 -test and Spearman’s rank correlation. To verify their relationship, knockdown and exogenous expression of CDX2 or Reg IV were performed in AGS and MKN-45 gastric cancer cells, and their expression was subsequently analyzed via a real-time PCR and western blotting. Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression. Results: A positive correlation was observed between CDX2 and Reg IV expression at the mRNA and protein levels in gastric cancer tissues. CDX2 silencing significantly downregulated Reg IV expression, and CDX2 overexpression significantly upregulated Reg IV expression in AGS and MKN-45 cells. Neither Reg IV silencing nor overexpression had any effect on CDX2 protein expression in AGS or MKN-45 cells, even though both affected the expression of CDX2 mRNA. Functionally, CDX2 silencing significantly inhibited cell migration and invasion, and CDX2 overexpression significantly promoted cell migration and invasion in AGS and MKN-45 cells. Conclusions: Our findings demonstrate that CDX2 expression was positively correlated with that of Reg IV in gastric cancer, and CDX2 promoted cell migration and invasion through upregulation of Reg IV expression in AGS and MKN-45 cells.
DLDTI: A learning-based framework for drug-target interaction identification using neural networks and network representation
Authors: Zhao Yihan , Zheng Kai , Guan Baoyi , Guo Mengmeng , Song Lei , Gao Jie , Qu Hua , Wang Yuhui , Shi Dazhuo , Zhang Ying
Published: October 2020

Background: Drug repositioning, the strategy of unveiling novel targets of existing drugs could reduce costs and accelerate the pace of drug development. To elucidate the novel molecular mechanism of known drugs, considering the long time and high cost of experimental determination, the efficient and feasible computational methods to predict the potential associations between drugs and targets are of great aid.Methods: A novel calculation model for drug-target interaction (DTI) prediction based on network representation learning and convolutional neural networks, called DLDTI， was generated. The proposed approach simultaneously fuses the topology of complex networks and diverse information from heterogeneous data sources, and copes with the noisy, incomplete, and high-dimensional nature of large-scale biological data by learning the low-dimensional and rich depth features of drugs and proteins. The low-dimensional feature vectors were used to train DLDTI to obtain the optimal mapping space and to infer new DTIs by ranking candidates according to their proximity to the optimal mapping space. More specifically, based on the results from the DLDTI, we experimentally validate the predicted targets of tetramethylpyrazine (TMPZ) on atherosclerosis progression in vivo.Results: The experimental results show that the DLDTI model achieves promising performance under 5-fold cross-validations with AUC values of 0.9172, which is higher than the methods using different classifiers or different feature combination methods mentioned in this paper. For the validation study of TMPZ on atherosclerosis, a total of 288 targets were identified and 190 of them were involved in platelet activation. The pathway analysis indicated signaling pathways, namely PI3K/Akt, cAMP and calcium pathways might be the potential targets. Effects and molecular mechanism of TMPZ on atherosclerosis were experimentally confirmed in animal models.Conclusions: DLDTI model can serve as a useful tool to provide promising DTI candidates for experimental validation. Based on the predicted results of DLDTI model, we found TMPZ could attenuate atherosclerosis by inhibiting signal transductions in platelets. The source code and datasets explored in this work are available at https://github.com/CUMTzackGit/DLDTI.
Pharmacokinetics and Dialytic Clearance of Apixaban During In Vitro Continuous Renal Replacement Therapy
Authors: Andrews Lauren , Benken Scott , Tan Xing , Wenzler Eric
Published: October 2020

Objective: To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Design: In vitro pharmacokinetic (PK) study.Setting: University research laboratory.Subjects: Not applicable. Interventions: Apixaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with analogous post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types (M150 and HF1400), flow rates (2 and 4 L/h), and point of CVVH replacement fluid dilution (pre, post, and pre/post filter). Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma PK parameters for apixaban were estimated via noncompartmental analysis in WinNonlin. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way ANOVA models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was then utilized to provide dosing estimations for flow rates from 0.5-5 L/h. Measurements and Main Results: Mean adsorption to the HF1400 and M150 filters differed significantly at 38% and 13%, respectively, while mean (±SD) percent protein binding was 70.81±0.01%. Effect of CVVH point of replacement fluid dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 2.5-7.5 mg BID may be needed for flow rates ranging from 0.5-5 L/h, respectively. Conclusion: For CRRT flow rates most commonly employed in clinical practice, the standard labeled 5 mg BID dose of apixaban is predicted to achieve target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.
Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data
Authors: Yuan Xinlu , Diao Jianjun , Du Anqing , Wen Song , Zhou Ligang , Pan Yangbin
Published: October 2020

Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously. Methods: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development. Conclusions: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.
TMEFF2 Promoter Hypermethylation Is an Unfavorable Prognostic Marker in Gliomas
Authors: Xie Sidi , Zhang Yunxiao , Peng Tao , Guo Jinglin , Cao Yongfu , Guo Jing , Shi Xiaofeng , Li Yaqin , Liu Yawei , Qi Songtao , Wang Hai
Published: October 2020

Background: Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) is a transmembrane protein in the tomoregulin family. Little research has been performed to determine whether TMEFF2 methylation is a prognostic marker in adult diffuse gliomas. Methods: In this study, we investigated TMEFF2 expression in surgical glioma tissue samples. In addition, we conducted bisulfite amplicon sequencing (BSAS) and methylation-specific PCR (MSP) to evaluate TMEFF2 methylation in glioblastoma (GBM) cells. Subsequently, we investigated the biological function of TMEFF2 in GBM cells. Moreover, we explored the prognostic significance of TMEFF2 in gliomas by analysing a cohort dataset from TCGA. Results: Immunohistochemistry analysis of 75 paired glioma tumour and peritumoural tissues demonstrated that glioma tumour tissues expressed lower TMEFF2 levels than peritumoural tissues (P<0.001). TMEFF2 promoter methylation levels were increased in glioblastoma cells compared with SVG p12 cells (P<0.001). Inhibition of methylation reduced TMEFF2 methylation and increased its expression in LN229 and T98G cells (P<0.05). Knockdown of TMEFF2 expression significantly promoted the proliferation of U87MG cells and primary GBM cells (P<0.05). TMEFF2 methylation is negatively associated with IDH1, ATRX and TP53 mutations, and the subtype of glioma harbouring combined IDH1/ATRX/TP53 mutations was associated with low TMEFF2 methylation levels. Survival analysis confirmed that low TMEFF2 methylation levels are associated with good prognosis in glioma patients. Conclusions: Our results suggest that TMEFF2 DNA methylation might be associated with glioma tumour progression and could serve as a valuable prognostic marker for adult diffuse gliomas.
How Specific is Alcohol-Specific Self-Control? A Longitudinal Study of the Mediating Role of Alcohol-Specific Self-Control in the Relation between General Self-Control and Adolescent Alcohol Use
Authors: Geurts Suzanne , Koning Ina , Finkenauer Catrin
Published: October 2020

Background: Although accumulating studies indicate that alcohol-specific self-control can be useful in predicting adolescent alcohol use, little is known about its specificity. This longitudinal study aimed to advance our understanding of domain-specific self-control by examining whether alcohol-specific self-control mediates the effect of general self-control on adolescent alcohol use or has generalizing effects by also mediating the effect of general self-control on other behavior requiring self-control (adolescent digital media use and smoking).Methods: Data from 906 adolescents aged 11-14 years who were enrolled in the Dutch study Prevention of Alcohol Use in Students were used. Data were collected using online questionnaires at four annual measurements. Results: Structural equation modelling revealed that higher alcohol-specific self-control fully mediated the effect of higher general self-control on alcohol use. Alcohol-specific self-control did not mediate the effect of higher general self-control on digital media use, but did partially mediate the effect of higher general self-control on smoking. Conclusions: These results suggest that alcohol-specific self-control is domain-specific, but not necessarily substance-specific. The domain-specificity of alcohol-specific self-control provides evidence for its theoretical relevance for the explanation of adolescent alcohol use. It also suggests leverage points for intervention programs focusing on improving alcohol-specific self-control to reduce adolescent alcohol use. Trial registration. The trial protocol (NTR649) was approved by the Medical Ethical Committee.
Multipolar mapping for catheter ablation of premature ventricular complexes originating from papillary muscles in the structurally normal heart: A case series
Authors: Cai Chi , Wang Jing , Niu Hongxia , Hua Wei , Chu Jianmin , Zhang Shu
Published: October 2020

Background: Previous studies on radiofrequency catheter ablation of premature ventricular complexes (PVCs) arising from the left ventricle (LV) papillary muscles (PM) show a modest procedural success rate with higher recurrence rate. Our study sought to explore the utility of using a multipolar mapping with a steerable linear duodecapolar catheter for ablating the PM PVCs.Methods：Detailed endocardial multipolar mapping was performed using a steerable linear duodecapolar catheter in 6 consecutive PM PVCs patients with structurally normal heart. The clinical features and procedural data as well as success rate were analysed.Results: LV endocardial electroanatomic mapping was performed in all patients via a retrograde aortic approach using a duodecapolar mapping catheter. All patients displayed a PVC burden with 16.2 ± 5.4%. Duodecapolar catheter mapping demonstrated highly efficiency with an average procedure time (95.8 ± 7.4 minutes) and fluoroscopy time (14.2 ± 1.5 minutes). The mean number of ablation applications points was 6.8 ± 1.9 with an average overall ablation duration of 6.1 ± 3.0 minutes. The values of earliest activation time during mapping using duodecapolar catheter were 37.8 ± 7.2 ms. All patients demonstrated acute successful ablation, and the PVC burden in all patients after an average follow-up of 8.5 ± 2.0 months was only 0.7%. There were no complications during the procedures and after follow-up.Conclusion: Mapping and ablation of PM PVCs using a duodecapolar catheter facilitated the identification of earliest activation potentials and pace mapping, and demonstrated a high success rate during follow-up.
Individual Approach for Treatment of Primary Intestinal Lymphangiectasia in Children: Single-center Experience and Systemic Review
Authors: Kwon Yiyoung , KIM Mi Jin , Kim Eun Sil , Choe Yon Ho
Published: October 2020

Background: Intestinal lymphangiectasia is a rare disease. Thus, prospective studies are impossible, and therapy is still controversial. Several medicines are suggested for treatment but there are no existing indications for drug choice and treatment guidelines. We experienced seven patients with primary intestinal lymphangiectasia who showed clinical improvement with different treatments. Aim: We aimed to introduce the action mechanism of each drug and treatment overview in a single-center experience and a systemic review of second-line therapy for primary intestinal lymphangiectasia.Method: Children under 18 years old diagnosed with intestinal lymphangiectasia from June 2000 to June 2020 were included in the study. Capsule endoscopy, MR lymphangiography, or whole-body MRI for investigating the extent of abnormal lymphatic vessels in addition to endoscopy and biopsy were conducted. The individual treatment approaches depended upon the lymphangiectasis locations involved.Results: Only one patient showed a response to dietary therapy. One patient was successfully cured after two therapeutic lymphatic embolization. Octreotide was tried for two patients who had extensive lymphangiectasis. Lymphangiectasis recurred when octreotide was used for three months in one patient, and there was no effect in the other patient. Sirolimus was tried for four patients. Two of them had abnormal lymphatic lesions only in the intestine, and the others had extensive lymphangiectasis. The former group showed clinical improvement after 3 – 4 months of sirolimus treatment, whereas the latter group showed clinical improvement only after one month of sirolimus treatment.Conclusion: Intervention is a potential therapeutic option for patients with focal abnormal lymphatic lesions. Octreotide is not an optimal choice for patients with extensive lymphangiectasis. Sirolimus is an effective and safe drug and can be the first drug of choice for patients with extensive lymphangiectasis.
Body Image Perception and Body Composition in Early Adolescents: A Longitudinal Study of an Italian Cohort
Authors: Toselli Stefania , Grigoletto Alessia , Zaccagni Luciana , Rinaldo Natascia , Badicu Georgian , Grosz Wilhelm Robert , Campa Francesco
Published: October 2020

Background: Adolescence is a period of life in which students face physical and psychological changes that can destabilise them, and that is characterised by specific health and developmental needs and rights. The aim of this study was to evaluate the longitudinal association between anthropometric, weight status, body composition changes, and body image perception, keeping into account sex and maturity differences in adolescents. Methods: A sample of 134 children (64 males and 70 females) attending secondary school in the Emilia Romagna region (northern Italy) have been followed longitudinally for three consecutive years. Sports practice was assessed by questionnaire, and maturity status was detected. Anthropometric measurements, body composition, and body image perception were carried out. The discrepancy between the actual figure and the ideal figure was used to determine the degree of body image dissatisfaction, while improper perception of weight status was evaluated by means of Feel weight status minus Actual weight status Inconsistency (FAI).Results: A high percentage of the sample (about 90% in both sexes) practiced sport during the three years. In males, since they were approaching the PHV, leg length growth was prevalent. In females, height increment was lower than the one observed in males, such as the sitting height increment was higher than that of leg length. Connected with sexual dimorphism is also the trend of skinfold thicknesses, which generally showed a decrease in males and increase in females during the three years. Percentage of body fat followed the same trend. In both sex, body image perception did not show significant variations with age, and FAI score indicated no inconsistency in weight status perception. A difference in the perception of body image was observed in subjects of different weight status categories in each class. Conclusions: As demonstrated by the present study, the body image perception did not seem to change with age, but associations were found between body image perception and weight status. Monitoring perception in young adolescents, as well as taking into account their maturity and weight status is a priority to prevent nutritional disorders.
Dynamic Changes of the Colonic Microbiota in Rat during Severe Acute Pancreatitis
Authors: Wang sizhen , Tong Zhihui , Li Weiqin , Li Qiurong , Li Jieshou
Published: October 2020

Background: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. To date, the pathophysiology of the underlying bacterial translocation is poorly understood. Increased gut permeability and gut flora dysbiosis may be the initial phenomenon in this process. The present study investigated the colonic microbiota alteration pattern as well as observed colonic epithelium change in rats with SAP. Method: Denaturing gradient gel electrophoresis (DGGE) was used to monitor the colonic microbiota of control rats and experimental rats that 2, 6,and 12 hours following severe acute pancreatitis which was induced by retrograde injection of sodium taurocholate into biliopancreatic duct. Colonic samples and its contents at 1 cm distal to the cecal-colonic junction was harvested for morphological studies, streptavidin-peroxidase immunohistochemistry examination.Results: Denaturing gradient gel electrophoresis of colonic microbiota showed that gut flora pattern changed early after severe acute pancreatitis, differed significantly at 6 hours of model was induced, and then started to recover towards normal pattern. The specific dysbiosis were characterized by Escherichia coli proliferation and Lachnospiraceae and Lactobacilli reduction. As shown by immunohistochemical staining, greatly reduced expressions of ZO-1 protein were detected in rats with SAP. And the structures of junctional complexes were disrupted and the gaps between cell junctions were wider after the SAP induced.Conclusions: Severe acute pancreatitis results in colonic flora dysbiosis. And tight junction in rats with SAP was disrupted in the intestinal epithelium. Both of them may be a key factor contributing to bacterial translocations in rats with SAP.
Association between triglyceride-glucose index and risk of incident diabetes: a secondary analysis based on a Chinese cohort study
Authors: Li Xiaoli , Li Guilong , Cheng Tiantian , Liu Jing , Song Guangyao , Ma Huijuan
Published: October 2020

Background: Recent studies have suggested the triglyceride-glucose index (TyG index) may serve as a suitable substitute for insulin resistance. However, evidence for the relationship between TyG index and risk of diabetes remains limited. This study sought to explore the association of baseline TyG index with risk of developing diabetes in Chinese adults.Methods: This retrospective cohort study was conducted using data from the health screening program in China. A total of 201,298 non-diabetic individuals were included. TyG index was calculated as Ln [fasting plasma glucose (mg/dL) × fasting triglyceride level (mg/dL) / 2]. Diabetes was defined as fasting plasma glucose ≥126 mg/dL and/or self-reported diabetes. Cox proportion-hazard model was employed to evaluate the independent impact of baseline TyG index on future diabetes risk. Sensitivity and subgroup analyses were implemented to verify the reliability of results. Notably, data were downloaded from the DATADRYAD website, and used only for secondary analyses.Results: During an average follow-up of 3.12 years, among 201,298 individuals aged ≥20 years, 3,389 subjects developed diabetes. After adjusting for potential confounders, elevated TyG index were independently correlated with greater risk of incident diabetes (hazard ratio (HR), 3.34; 95% confidence interval (CI), 3.11–3.60). Compared with the lowest quartile (Q1), increasing TyG index (Q2, Q3, and Q4) was related to increased HR estimates of incident diabetes [HR (95% CI), 1.83 (1.49–2.26); 3.29 ( 2.70–4.01), and 6.26 (5.15–7.60), respectively]. Moreover, a nonlinear relationship was observed between TyG index and risk of diabetes and the slope of the curve increased accompanying the rise of TyG index. Subgroup analysis revealed the positive association was stronger among subjects with age < 40 years, body mass index ≥18.5 kg/m2 and < 24 kg/m2, or systolic blood pressure <140 mmHg, or in females.Conclusions: Elevated TyG index is independently correlated with increased risk of incident diabetes in Chinese adults, indicating it may represent a reliable predictor of diabetes in high-risk populations.
Role of the Media in Health-Related Awareness Campaigns on Perceptions of COVID-19: A Pre-Post Study in the General Population of Pakistan
Authors: Rehman Atta Ur , Zakar Rubeena , Zakar Muhammaz Zakria , Hani Ume , Fischer Florian
Published: October 2020

Background: In January 2020, the World Health Organization declared the COVID-19 outbreak a global public health emergency. Medical preparedness and community education are the most valuable preventive tools for combatting this pandemic. The objective of this study was to assess the role of media public health awareness campaigns on the knowledge of the general population about COVID-19 in Rawalpindi, Pakistan.Methods: A quantitative study using a pre-post design among 384 respondents was conducted. To recruit study participants, a systematic random sampling technique was used. A structured questionnaire was administered to the participants twice: The first response (t1) from participants was filled in during the first week in February 2020 before any confirmed cases were reported in the country, and the second response (t2) was completed one month after the first case detection in Pakistan (March 2020). Media health awareness campaigns were launched just after the detection of the first case in Pakistan. Data was analysed by computing descriptive statistics and paired t-tests to measure the level of association between variables.Results: Exposure to the media and knowledge relating to COVID-19, particularly its symptoms and frequent handwashing as a preventive measure, increased over time. Whereas only a quarter of respondents judged the isolation of suspected cases in quarantine to be important to prevent the spread of infection in society at t1, more than half did so at t2. The same increase was visible in relation to the statement that a lockdown helps to follow social distancing. Socio-demographic characteristics were not significantly associated with knowledge (gains). However, more frequent use of electronic media is associated with greater knowledge gains from t1 to t2.Conclusions: The findings of this study provide evidence that awareness and knowledge related to COVID-19 symptoms and preventive measures increased significantly over time. The increased frequency of following the media indicates that health awareness campaigns are important for enhancing the knowledge of the general public regarding COVID-19.