bluuebunny/crossref_metadata_2025 huggingface dataset:
Myopia-26, the female-limited form of early-onset high myopia is associated with retinal ganglion cell dysfunction and primary open angle glaucoma
Authors: Széll Noémi , Feher Tamas , Maróti Zoltán , Kalmár Tibor , Latinovics Dóra , Nagy István , Orosz Zsuzsanna Z. , Janáky Márta , Facskó Andrea , Sohajda Zoltán
Published: May 2020

Background: Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis Results: We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- and colour vision testing) and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. We found variously impaired visual fields in four affected myopic females and a carrier male. Abnormal pattern electroretinography responses were detected in both symptomatic and carrier patients. Conclusions: This is the first description of a Caucasian family displaying Myopia-26. Pattern electroretinography implies retinal ganglion cell dysfunction present in both sexes. In conjunction with the visual field loss, this suggests the development of age-related open angle glaucoma in addition to high myopia, both attributable to the rare genetic variant of ARR3. We present two hypotheses that could potentially explain the pathomechanism of this disease.
A novel multi-epitope recombinant protein for diagnosis of African swine fever
Authors: GAO ZHAN , SHAO JUNJUN , ZHANG GUANGLEI , GE SUDAN , CHANG YANYAN , XIAO LEI , CHANG HUIYUN
Published: May 2020

Background: African swine fever(ASF) is an acute, severe and highly fatal infectious disease of pigs. The disease spreads rapidly, causing huge economic losses to the pig industry in infected areas. The structural proteins p30 and p54 in African swine fever virus(ASFV) have been verified as diagnostic antigens.Methods: In this study, we constructed a novel multi-epitope fusion antigen gene based on P30 and P54 proteins, induced expression in a prokaryotic expression system and analyzed the reactivity of the recombinant fusion protein. The purified recombinant protein m35 was used as the coating antigen to establish an indirect enzyme-linked immunosorbent assay (ELISA) detection method for ASFV. 116 serum samples and positive sera of other swine diseases were detected by indirect ELISA.Results: Our results indicate that the m35 gene fragment with a length of 558bp was successfully constructed. SDS-PAGE and Western Blotting analysis showed that the protein had a band at 22kDa, proving its good reactogenicity. ROC analysis was performed to validate the assay, the area under the ROC curve is 0.9738 (95% confidence interval, 0.9336 to 1.014), and does not cross-react with other swine diseases.Conclusion: Our results show that its sensitivity and specificity were highly accurate. It is feasible to use this recombinant protein as a diagnostic antigen to distinguish ASFV infection.
Test anxiety and emotion regulation among undergraduate medical students in China: the mediating role of psychological resilience
Authors: Liu Yuguo , Pan Haiyan , Yang Runhuang , Wang Xingjie , Rao Jiawei , Zhang Xingshan , Pan Congcong
Published: May 2020

Background: Medical students experience a considerable amount of anxiety due to exams. Emotion regulation and psychological resilience are established protective factors of individual mental health, however, the investigations for the effects of anxiety were limited. The goal of the present study was to examine the relationship of psychological resilience and emotion regulation with test anxiety and the associated factors of them among medical students.Methods: In this cross-sectional survey, a simple random sampling methods was used to select the participants. Information from a sample of 1266 medical students was collected by self-reporting questionnaires. Logistic regression was applied to test the associations between test anxiety and emotion regulation, resilience. Bootstrap were conducted to explore the mediating role of resilience.Results: Our important results were that the prevalence of problematic test anxiety among medical students to be 71.4%, 33.7% was high test anxiety. Gender and academic performance correlated significantly with test anxiety, emotion regulation, and psychological resilience. There were correlations between test anxiety and various dimensions of emotion regulation and psychological resilience ( P<0.01 ). Emotion regulation and psychological resilience predicted emerging test anxiety. The mediating role of psychological resilience was identified for the effects of emotion regulation on test anxiety.Conclusions： Findings suggest that emotion regulation affected test anxiety through psychological resilience, which may provide insights for clinical psychologists, raise their awareness of the importance of cultivating and improving medical students' psychological resilience, and prompt them to offer psychological support to students with test anxiety as early as possible. The combination of curing and self-healing can solve the root cause of the problem and truly apply psychological research to improving the mental health of the general public.
Serum biomarkers of the calcium-deficient rats identified by metabolomics based on UPLC/Q-TOF MS/MS
Authors: Fanyu Meng , Lina Fan , Lin Sun , Qingli Yu , Wang Maoqing , Changhao Sun
Published: May 2020

Background: We previously identified the urinary biomarkers to diagnose calcium deficiency and nutritional rickets by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS).To further confirm these biomarkers in vivo, we performed serum metabolomics analysis of calcium deficiency.Methods: A calcium-deficient rat model was established with a low-calcium diet for 12 weeks. Serum-metabolomics-based UPLC/Q-TOF MS/MS and multivariate statistical analysis was performed to identify the alterations in metabolites associated with calcium deficiency in rats.Results: Bone mineral density, serum parathyroid hormone and alkaline phosphatase were significantly decreased in the low-calcium diet group (LCG) compared to the normal calcium diet group (NCG). Serum metabolic-profiling analysis could definitively distinguish between the LCG and NCG andidentified25 calcium-deficient biomarkers. Three metabolites (indoxyl sulfate, phosphate, and taurine) of the 25 biomarkers were found in our previous urinary metabolomics study of rats with a calcium deficiency and nutritional rickets. The areas under the curve (AUCs) of these three biomarkers were greater than 0.8, and the combination of any two biomarkers was higher than 0.95.Conclusion: Dietary calcium deficiency induced the alterations of metabolites in the serum of rats, and the three identified biomarkers had relatively high diagnostic values for calcium deficiency in rats.hatase were significantly decreased in the low-calcium diet group (LCG) compared to the normal calcium diet group (NCG). Serum metabolic-profiling analysis could definitively distinguish between the LCG and NCG andidentified25 calcium-deficient biomarkers. Three metabolites (indoxyl sulfate, phosphate, and taurine) of the 25 biomarkers were found in our previous urinary metabolomics study of rats with a calcium deficiency and nutritional rickets. The areas under the curve (AUCs) of these three biomarkers were greater than 0.8, and the combination of any two biomarkers was higher than 0.95. Conclusion Dietary calcium deficiency induced the alterations of metabolites in the serum of rats, and the three identified biomarkers had relatively high diagnostic values for calcium deficiency in rats.
Prognostic model based on autophagy-related lncRNAs in gastric cancer
Authors: Cheng Mengqiu , Cao Wei , Chen Bo
Published: May 2020

Background: Gastric cancer (GC) is one of the most pravelent cancer in the world. Although increasing studies have indicated that autophagy-related long non-coding RNA (lncRNA) plays an essential role in the occurrence of GC, the prognosis of GC based on autophagy is still deficient.Method: Autophagy-related lncRNAs were obtained by using the correlation test with the autophagy-related gene. Data was downloaded from The Cancer Genome of Atlas stomach adenocarcinoma (TCGA-STAD) dataset. The prognostic autophagy-related lncRNAs significantly correlated with survival of TCGA-STAD dataset were obtained by using Kaplan-Meier and univariate Cox regression analysis. TCGA-STAD dataset was separated into a training set and a testing set randomly. The model was constructed based on the training set through the least absolute shrinkage and selection operator (LASSO) regression. The testing set and TCGA-STAD were used to validate the accuracy of the model. Every patient got a risk score (RS) and patients were separate into high-risk group and low-risk group due to the median RS. The prognostic network was built and the mRNAs in the system were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The signaling pathways that the differentially expressed genes (DEGs) between two types of risk group mainly participated in were distinguished through Gene Set Enrichment Analysis (GSEA). The individual’s survival rate was predicted through the nomogram.Results: 24 autophagy-related lncRNAs were found strongly associated with the survival of the TCGA-STAD dataset. Among them, 11 lncRNAs were selected to build the risk score model through LASSO regression. The multivariate Cox analysis showed that the RS could be an independent prognosis predictor. The Kaplan-Meier survival analysis and the Receiver Operating Characteristic (ROC) curve indicated the model had an excellent prediction effect. GO, and KEGG analysis revealed that the mRNAs in the prognostic network were mainly involved in the autophagy and ubiquitin-like protein ligase binding. GSEA analysis uncovered that the DEGs in high-risk group partially participated in the ECM receptor interaction and other signaling pathways.Conclusions: Our results indicated that the risk score model based on the autophagy-related lncRNAs performed well in the prediction of prognosis for patients with GC.
Identifying Research Priorities for Health Professions Education Research in Sub-Saharan Africa using a Modified Delphi Method
Authors: Schalkwyk Susan C van , Kiguli-Malwadde Elsie , Budak Jehan Z , Reid Michael JA , De Villiers Marietjie Rene
Published: May 2020

Background: Recent increases in health professions education (HPE) research in sub-Saharan Africa (SSA), though substantial, have predominantly originated from single institutions and remained uncoordinated. A shared research agenda can guide the implementation of HPE practices to ultimately influence the recruitment and retention of the health workforce. Thus, the authors aimed to generate and prioritise a list of research topics for HPE research (HPER) in SSA.Methods: A modified Delphi process was designed to prioritise a shared agenda. Members of the African Forum for Research and Education in Health (AFREhealth) technical working group (TWG) were asked to first list potential research topics. Then, members of the same TWG and attendees at the annual AFREhealth academic symposium held in Lagos, Nigeria in August 2019 rated the importance of including each topic on a 3-point Likert scale, through two rounds of consensus seeking. Consensus for inclusion was predefined as ≥ 70% of respondents rating the topic as “must be included.”Results: Health professions educators representing a variety of professions and 13 countries responded to the survey rounds. Twenty-three TWG members suggested 26 initial HPER topics; subsequently 90 respondents completed round one, and 51 completed round 2 of the modified Delphi. The final list of 12 research topics which met predetermined consensus criteria were grouped into three categories: (1) creating an enabling environment with sufficient resources and relevant training; (2) enhancing student learning; and (3) identifying and evaluating strategies to improve pedagogical practice.Conclusions: Establishing research priorities for HPE is important to ensure efficient and appropriate allocation of resources. This study serves as a reminder of how the prevailing context within which HPE, and by implication research in the field, is undertaken will inevitably influence choices about research foci. It further points to a potential advocacy role for research that generates regionally relevant evidence.
Aspartate transaminase/alanine transaminase ratio as a significant prognostic factor in patients with sepsis: a retrospective analysis
Authors: Zhao Pengyue , Yao Renqi , Ren Chao , Li Songyan , Li Yuxuan , Zhu Shengyu , Yao Yongming , Du Xiaohui
Published: May 2020

Background: The study was performed to investigate the relationship between aspartate transaminase/alanine transaminase ratio (DRR) and long-term mortality among patients diagnosed with sepsis or septic shock. Methods: We conducted a retrospective study among adult septic patients who were admitted to surgical intensive care unit (ICU) of the Chinese People's Liberation Army (PLA) General Hospital from January 2014 to December 2018. Baseline characteristics were compared between survivors and non-survivors. We applied univariate as well as multivariate Cox regression analyses to evaluate DRR in relation to 180-day mortality. The potential prognostic value of DRR in predicting mortality rate was assessed by receiver operating curve (ROC) analysis. Besides, we conducted subgroup analysis by stratifying patients via optimal DRR cut-off value. Results: We included a total number of 183 patients in the current study, 44 (24%) patients died within 180-day hospitalization. Univariate and multivariate Cox analysis revealed that DRR was an independent predictor of 180-day mortality (hazard ratio [HR] 1.421, 95% confidence interval [CI] 1.073-1.883, P = 0.014). The predicting accuracy of 180-day mortality for DRR was presented as ROC with an area under the curve (AUC) of 0.708 (95% CI 0.629–0.786, P < 0.001). As we stratified all enrolled patients into two groups by using the optimal cut-off value of 1.29, we observed a significantly higher mortality in patients with relatively high DRR. Conclusions: An elevated DRR was associated with higher 180-day mortality among septic patients, and DRR might be an optimal marker for predicting the long-term mortality of sepsis. More prospective and randomized trials are needed to confirm the prognostic value of DRR.
Validation of the Palliative Prognostic Index, Performance Status–based Palliative Prognostic Index and Chinese Prognostic Scale in a Home Palliative Care Setting for Patients With Advanced Cancer in China
Authors: Zhou Jun , Xu Sitao , Cao Ziye , Tang Jing , Qin Ling , Zhou Fangping , He Yuzhen , Zhong Xueren , Hu Mingcai , Wang Yan , Lu Fengjuan , Bao Yongzheng , Dai Xiangheng , Wu Qiang
Published: May 2020

Background:Thepredictive value of theprognostic tool for patients with advanced cancer isuncertainin mainland China, especially in the home-based palliative care (HPC) setting. This study aimed to compare the accuracy of the Palliative Prognostic Index (PPI), the Performance Status–Based Palliative Prognostic Index (PS-PPI), and the Chinese Prognosis Scale (ChPS) for patients with advanced cancer in the HPC setting in mainland China.Methods:Patients with advanced cancer admitted to the hospice center of Yuebei People’s Hospital between January 2014 and December 2018 were retrospectively calculated the scores according to the three prognostic tools. The Kaplan-Meier method was used to compare survival times among different risk groups. Receiver operating characteristic curve analysis was used to assess the predictive value. The accuracy of 21-, 42- and 90-day survival was compared among the three prognostic tools.Results: A total of 1863 patients were included. Survival time among the risk groups of all prognostic tools was significantly different from each other except for the PPI. The AUROC of the ChPS was significantly higher than that of the PPI and PS-PPI for 7-, 14, 21-, 42-, 90-, 120-, 150- and 180-day survival (P <0.05). The AUROC of the PPI and PS-PPI were not significantly different from each other (P >0.05).Conclusions: The ChPS is more suitable than the PPI and PS-PPI for advanced cancer patients in the HPC setting. More researches are needed to verify the predictive value of the ChPS, PPI, and PS-PPI in the HPC setting in the future.
Impact on place of death in cancer patients: a causal exploration in southern Switzerland
Authors: Kern Heidi , Corani Giorgio , Huber David , Vermes Nicola , Zaffalon Marco , Varini Marco , Wenzel Claudia , Fringer André
Published: May 2020

Background Most terminally ill cancer patients prefer to die at home, but a majority die in institutional settings. Research questions about this discrepancy have not been fully answered. This study applies artificial intelligence and machine learning techniques to explore the complex network of factors and the cause-effect relationships affecting the place of death, with the ultimate aim of developing policies favouring home-based end-of-life care. Methods A data mining algorithm (a classifier) and a causal probabilistic model (a credal network) for data analysis were developed with information derived from expert knowledge that was merged with data from 116 deceased cancer patients in southern Switzerland. This data set was obtained via a retrospective clinical chart review. Results Dependencies of disease and treatment-related decisions demonstrate an influence on the place of death of 13%. Anticancer treatment in advanced disease prevents or delays communication about the end of life between oncologists, patients and families. Unknown preferences for the place of death represent a great barrier to a home death. A further barrier is the limited availability of family caregivers for terminal home care. The family’s preference for the last place of care has a high impact on the place of death of 51%, while the influence of the patient’s preference is low, at 14%. Approximately one-third of family systems can be empowered by health care professionals to provide home care through open end-of-life communication and good symptom management. Such intervention has an influence on the place of death of 17%. If families express a convincing preference for home care, the involvement of a specialist palliative home care service can increase the probability of home deaths by 24%. Conclusion Concerning death at home, open communication about dying is essential. Furthermore, for the patient preference for home care to be respected, the family’s decision for the last place of care seems key. Early initiation of family-centred palliative care and provision of specialist palliative home care for patients who wish to die at home are suggested. Keywords Cancer; End-of-life care; Palliative Home care; Place of death; Communication; Family caregivers; Patient preference; Bayesian networks; Credal networks; Bayesian classifiers
Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women with Alzheimer's Disease
Authors: Paranjpe Manish , Belonwu Stella , Wang Jason K , Oskotsky Tomiko , Gupta Aarzu , Taubes Alice , Zalokusky Kelly , Paranjpe Ishan , Glicksberg Benjamin S , Huang Yadong , Sirota Marina
Published: May 2020

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the United States. In spite of evidence of females having a greater lifetime risk of developing Alzheimer’s Disease (AD) and greater apolipoprotein E4-related (apoE4) AD risk compared to males, molecular signatures underlying these findings remain elusive. Methods: We took a meta-analysis approach to study gene expression in the brains of 1,084 AD patients and age-matched controls and whole blood from 645 AD patients and age-matched controls in seven independent datasets. Sex-specific gene expression patterns were investigated through use of gene-based, pathway-based and network-based approaches. The ability of a sex-specific AD gene expression signature to distinguish Alzheimer’s disease from healthy controls was assessed using a linear support vector machine model. Cell type deconvolution from whole blood gene expression data was performed to identify differentially regulated cells in males and females with AD.Results: Strikingly gene-expression, network-based analysis and cell type deconvolution approaches revealed a consistent immune signature in the brain and blood of female AD patients that was absent in males. In females, network-based analysis revealed a coordinated program of gene expression involving several zinc finger nuclease genes related to Herpes simplex viral infection whose expression was modulated by the presence of the apolipoprotein ε4 allele. Interestingly, this gene expression program was missing in the brains of male AD signature. Cell type deconvolution identified an increase in neutrophils and naïve B cells and a decrease in M2 macrophages, memory B cells, and CD8+ T cells in AD samples compared to controls in females. Interestingly, among males with AD, no significant differences in immune cell proportions compared to controls were observed. Machine learning-based classification of AD using gene expression from whole blood in addition to clinical features produced an improvement in classification accuracy upon stratifying by sex, achieving an AUROC of 0.91 for females and 0.80 for males. Conclusions: These results help identify sex and apoE4 genotype-specific transcriptomic signatures of AD and underscore the importance of considering sex in the development of biomarkers and therapeutic strategies for AD.
Tolerability of duloxetine in the elderly and in adults: a protocol and preliminary results of a systematic review and individual participant data meta-analysis of randomized placebo-controlled trials
Authors: ROY Jean-Charles , Rousseau Chloé , Jutel Alexis , Naudet Florian , Robert Gabriel
Published: May 2020

Background. Duloxetine is an antidepressant which benefits from a wide range of approval in elderly population while its safety of use in elderly population, compared to younger adults, is not clearly assessed. A comparison of tolerability of duloxetine between elderly and younger adults would help to rule on this issue. Methods and Design. This protocol outlines a systematic review and meta-analysis of individual participant data (IPD) of all double-blind randomized controlled trials comparing the number of serious adverse events among individuals taking duloxetine in comparison to placebo between participants at least 65 years and younger adults in conditions approved by the European Medical Agency (EMA) and the Food Drug Administration (FDA). Secondarily, will be compared the number of any adverse events, clinical efficacy and quality of life between elderly and younger adults under duloxetine, in comparison to placebo. Relevant studies were selected on ClinicalTrials.gov, Clinicaltrialsregister.eu, data sharing platforms, FDA and EMA websites, and from systematic reviews and meta-analyses of duloxetine on PubMed, following Cochrane’s recommendations. Sponsors and authors from eligible studies were invited to share IPD on data sharing platform or directly with our research team. As data cannot be aggregate into a unique database, a two step-approach meta-analysis will be undertaken. Qualitative results from available data. 77 eligible randomized controlled trials were identified, representing 25303 participants. From online available data, 35 trials were assessed as being at an overall low risk of bias, 31 trials at an unclear risk of bias and 1 at high risk of bias. Evaluation of risk of bias was not feasible for 10 studies. Conclusion. This study would represent the first meta-analysis investigating the safety of duloxetine in elderly population across all conditions approved by European and American regulatory authorities with an overall low risk of bias. Registration. PROSPERO: 2019 CRD42019130488.
Analysis of HIV-1 Molecular Transmission Network in Sexually Transmitted Population in Liaoning, China
Authors: Ma Ning , Chen Xing-hua , Zhao Yan , Kang Xu , Pan Shan , Yao Wen-qing
Published: May 2020

Background In recent years, with the development of molecular epidemiology, molecular transmission networks based on evolutionary theory and sequence analysis have been widely used in the study of HIV-1 transmission kinetics and precision intervention in high-risk populations ,especially HIV − 1 Long-term monitoring of drug resistance and real-time prevention interventions. To analyze the characteristics of HIV-1 molecular transmission network in Liaoning, China .Methods A study on HIV infected persons with STIs in Liaoning Province from 2003 to 2019. HIV-1 RNA was extracted, amplified and sequenced, and a phylogenetic tree was constructed to determine the subtype using the well matched pol gene region sequence. The gene distance between sequences was calculated, the threshold was determined, and the propagation network was constructed.Results 109 samples of pol gene region were obtained, The main subtype of HIV-1 was CRF01, followed by B, CRF07, BC, etc.12.8% of them were resistant to HIV.At the threshold of 0.55% gene distance, 60.6% of them entered the HIV-1 molecular transmission network. Workers, sample source VCT, other testing, subtype B and drug resistance are the factors influencing the access to HIV-1 molecular transmission network.The subtype of CRF01 _ AE propagated in the molecular network to form six clusters. In the network, the difference of connection degree between different subtypes was statistically significant .Conclusion Liaoning Province should build a molecular transmission network and carry out long-term monitoring, so as to take targeted measures to block the spread of HIV and achieve accurate prevention and control.
Modification of transcriptional factor ACE3 enhances protein production in Trichoderma reesei in the absence of cellulase gene inducer.
Authors: Luo Yun , Valkonen Mari , Jackson Raymond E. , Palmer Jonathan M. , Bhalla Aditya , Nikolaev Igor , Saloheimo Markku , Ward Michael
Published: May 2020

The authors have removed this preprint from Research Square.
Consolidated bioprocessing of lignocellulose for production of glucaric acid by an artificial microbial consortium
Authors: Li Chaofeng , Lin Xiaofeng , Ling Xing , Li Shuo , Fang Hao
Published: May 2020

Background

The biomanufacturing of D-glucaric acid has been attracted increasing interest and the industrial yeast Saccharomyces cerevisiae is regarded as an excellent host for D-glucaric acid production.

Results

Here we constructed the biosynthetic pathway of D-glucaric acid in S. cerevisiae INVSc1 whose opi1 was knocked out and obtained two engineered strains, LGA-1 and LGA-C, producing record breaking titers of D-glucaric acid, 9.53 ± 0.46 g/L and 11.21 ± 0.63 g/L D-glucaric acid from 30 g/L glucose and 10.8 g/L myo -inositol in the mode of fed-batch fermentation, respectively. Due to the genetic stability and the outperformance in subsequent applications, however, LGA-1 was a preferable strain. As one of the top chemicals from biomass, there have been no reports on D-glucaric acid production from lignocellulose, which is the most abundant renewable on earth. Therefore, the biorefinery processes of lignocellulose for D-glucaric acid production including separated hydrolysis and fermentation (SHF), simultaneous saccharification and fermentation (SSF) and consolidated bioprocessing (CBP) were investigated in this work and CBP by an artificial microbial consortium composed of Trichoderma reesei Rut-C30 and S. cerevisiae LGA-1 was found to have relatively high D-glucaric acid titers and yields after 7 d fermentation, 0.54 ± 0.12 g/L D-glucaric acid from 15 g/L Avicel, and 0.45 ± 0.06 g/L D-glucaric acid from 15 g/L steam exploded corn stover (SECS), respectively.

Conclusions

In attempts to design the microbial consortium for more efficient CBP the team consisted of the two members, T. reesei Rut-C30 and S. cerevisiae LGA-1, was found to be the best with excellent work distribution and collaboration. This desirable and promising approach for direction production of D-glucaric acid from lignocellulose deserves extensive and in-depth research.
Age-related Changes of Microbiota in Midlife Associated with Reduced Saccharolytic Potential: An In Vitro Study
Authors: Zhu Liying , Chen Junkui , Pi Xionge , Li Jinjun , Liu Wei , Ding Qunfang , Wang Xin , Jia Weiguo
Published: May 2020

Background: Gut microbiota diversity and abundance are critical in maintaining human health, and subject to significantly reduce in seniors. Gut microbiota are reported to be stable across the long adulthood in general, but lack of careful examination, especially for the midlife people.Results: To characterize the gut microbiota in midlife, we investigated the faecal microbiota between two groups of healthy people, young, 20-39 years old, n=15; and midlife, 40-60 years old, n=15. Metabolic responses of the microbiota were studied through in vitro batch fermentation model. Despite no difference was observed in the diversity indies between the two age groups, a wide range taxonomic changes were found in the faecal microbiota. Furthermore, substantial Bifidobacterium reduction was also found in both faecal and fermented samples. The level of SCFAs in both faecal and starch fermented samples is similar in both groups. However, when fermentation was performed with inulin as the sole carbon source, the acetate concentration and inulin degradation rate decreased while the gas production increased in midlife group, suggesting a deficiency of saccharolytic potential in midlife, especially for non-digestible carbohydrate. Conclusions: Our data demonstrate that gut microbiota begin to change as early as in midlife. The reduction in Bifidobacterium dominates the change of the microbiota composition in midlife resulting in attenuated saccharolytic capability of inulin, leading to insufficient acetate production which might be associated with healthy problems in this transition period from young to elderly.
Homozygous and compound heterozygous rare variants in VPS13C contribute to Lewy body diseases
Authors: Smolders Stefanie , Philtjens Stéphanie , Crosiers David , Sieben Anne , Hens Elisabeth , Heeman Bavo , Mossevelde Sara Van , Pals Philippe , Asselbergh Bob , Dias Roberto Dos Santos , Vermeiren Yannick , Vandenberghe Rik , Engelborghs Sebastiaan , Deyn Peter P. De , Martin Jean-Jacques , Cras Patrick , Annaert Wim , Broeckhoven Christine Van
Published: May 2020

Background

Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are clinically, pathologically and etiologically overlapping disorders. They are included in the Lewy body disease (LBD) continuum characterized by α-synuclein-positive Lewy body pathology in neurons. Homozygous PTC mutations in Vacuolar Protein Sorting 13 homolog C gene (VPS13C) are associated with early-onset PD.
Methods

Whole genome sequencing of two affected siblings and healthy parents of family A with onset age below 50 years and DLB pathology confirmed at autopsy. Targeted resequencing of the VPS13C coding region in 844 LBD patients and 664 control individuals. Phasing cis-trans location of the compound heterozygous VPS13C variants. Analysis of VPS13C protein expression in lymphoblast cells and brain lysates. Immunohistochemistry and live cell labeling in HeLa and SH-SY5Y cells overexpressing wild type or mutant VPS13C.
Results

In the two affected siblings of family A, we identified compound heterozygous rare variants located in trans in VPS13C Rare VPS13C variants (MAF ≤ 1%), are significantly associated (p = 0.0233) in the LBD patient cohort using optimized sequence kernel association test (SKAT-O). We identified 11 carriers of compound heterozygous variants and 1 carrier of homozygous variants in VPS13C. Trans location of the variants in compound heterozygous carriers was confirmed in 4 and cis location in 3 patients. The frequency of patient carriers with bi-allelic variants mimicking recessive inheritance is 1.07% (9/844). In post-mortem brain tissue of two unrelated DLB carriers of compound trans heterozygous variants, we observed a reduction of VPS13C protein expression. Overexpressing of wild type or mutant VPS13C, in HeLa and SH-SY5Y cells, demonstrated that the mutations abolish the endosomal/lysosomal localization of VPS13C.
Conclusions

Our data indicate that rare alleles are associated with LBD, and when present bi-allelic in patients, these combinations have variable effects on expression and functioning of VPS13C. Apart from the recessive PTC mutations, some combinations of rare missense mutations might mimic recessive inheritance and explain part of the sporadic LBD patients. We propose that homozygous or compound heterozygous rare missense variants in VPS13C reducing VPS13C protein expression can contribute to risk of LBD.
A functionalized polydopamine theranostic nanoprobe for efficient imaging of miRNA-21 and in vivo synergetic cancer therapy
Authors: Mao Wenjie , Zheng Haifeng , Xie Jinrong , Shi Xiaorui , Du Yarong , Wang Fu
Published: May 2020

Background: MicroRNAs (miRNAs) are emerging as vital biomarkers since their abnormal expression is associated with various disease types including cancer. Therefore, it is essential to develop a sensitive and specific platform to monitor the dynamic expression of miRNAs for early clinical diagnosis and treatment. In this study, we designed a functionalized polydopamine (PDA)-based theranostic nanoprobe for efficient detection of miR-21 and in vivo synergistic cancer therapy.Methods: PDA was synthesized from dopamine hydrochloride and functionalized with polyethylene glycol (PEG). PDA-PEG nanoparticles were loaded with FITC-labeled hairpin DNA (hpDNA) and an anticancer drug doxorubicin (DOX). The measurement of miRNA-21 expression was reflected by the fluorescence quenching and release assay. The cellular toxicity of nanoprobe was assessed by Cell Counting Kit-8 (CCK-8) assay. Furthermore, the diagnosis and therapy effect of nanoparobe were investigated in xenograft tumor models.Results: PDA-PEG nanoparticles showed good stability in different solutions and effectively quench the fluorescence of FITC-labeled hpDNA. The presence of miR-21 induced the dissociation of hpDNA from PDA-PEG and subsequent the recovery of fluorescence signals. Upon cellular uptake of these nanoprobes, a dose-dependent fluorescence activation and synergetic cytotoxic effect were observed due to the release of DOX and inhibition of miR-21 function. Furthermore, PDA-PEG-DOX-hpDNA nanoparticles can afford long-term monitoring of miR-21 and combined therapeutic efficacy in the nude mice bearing 4T1 tumors.Conclusions: Our results demonstrate the capability of PDA-PEG-DOX-hpDNA as a theranostic nanoprobe for continuously tracking of miRNAs and synergetic cancer therapy.
SNP rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering RNA-Binding Protein ELAVL1
Authors: Xie Weijia , Wang Youhao , Zhang Yao , Xiang Ying , Wu Na , Wu Long , Li Chengying , Cai Tongjian , Ma Xiangyu , Yu Zubin , Bai Li , Li Yafei
Published: May 2020

Background: Single nucleotide polymorphisms (SNPs) and long non-coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNPs, we aimed to find novel functional lncRNAs as candidate targets in non-small cell lung cancer (NSCLC). Methods: Case-control analyses were performed in 626 cases and 736 controls matched up on sex and age. The lncRNA OSER1-AS1 was identified near a lung cancer risk-associated SNP rs4142441. Kaplan–Meier survival analysis was performed to investigate the association between OSER1-AS1 expression and overall survival. The influence of rs4142441 on the expression level of OSER1-AS1 was confirmed using Luciferase assays. Subsequently, the biological function of OSER1-AS1 was assessed in vitro by cell proliferation, migration, and invasion experiments through gain- and loss-of-function approaches, and in vivo by subcutaneous tumor model and tail vein injection lung metastasis model. ChIP and RIP experiments were carried out to investigate the interaction between transcription factors, RNA-binding proteins, and OSER1-AS1.Results: OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in NSCLC patients. Gain- and loss-of-function studies revealed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and metastasis mouse model confirmed that OSER1-AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1-AS1 was repressed by MYC, and the 3’-end of OSER1-AS1 was competitively targeted by microRNA hsa-miR-17-5p and RNA-binding protein ELAVL1. Conclusion: Our results indicated that OSER1-AS1 exerted tumor-suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mRNAs. Our findings characterized OSER1-AS1 as a new tumor suppressive lncRNA in NSCLC, suggesting that OSER1-AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.
Knockdown long noncoding RNA SLC8A1-AS1 attenuate cell invasion and migration in glioma via suppression of Wnt-β catenin signaling pathways
Authors: He Ling , Yang Hui , Zhu Xiao-long , Zhang Yan , Lv Kun
Published: May 2020

Background: Glioma, as the most common aggressive malignant tumor in the central nervous system, is still an insurmountable disease in neural system. The potential mechanism of its carcinogenesis remains largely unclear. Methods: In the present study, we identified dysregulated lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) as associated with glioma based on The Cancer Genome Atlas （TCGA）data. Validation experiment was conducted to confirm a high expression level of lncRNA SLC8A1-AS1 in glioma tissues. Results: Down-regulation of lncRNA SLC8A1-AS1 suppressed proliferation, clone formation, migration and invasion of glioma cells in vitro and in vivo. Moreover, lncRNA SLC8A1-AS1 silencing decreased the activity of the Wnt/β-catenin pathway and suppressed the epithelial to mesenchymal transition (EMT) in glioma cells. Conclusions: Collectively, these findings provide a novel insights into the function and mechanism of lncRNA SLC8A1-AS1 in the pathogenesis of glioma and highlight its potential as a therapeutic target for glioma intervention.
Long noncoding RNA LINC00968 inhibits lung adenocarcinoma progression through sponging miR-22-5p and further restoring CDC14A
Authors: Wu Chao , Bian Xuzhao , Zhang Liyuan , Wu Yang , Pei Tianli , Han Xinpeng
Published: May 2020

Background: Lung adenocarcinoma (LUAD) is a high aggressive human cancer which usually diagnosed at advanced stages. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) are crucial participants in LUAD progression. Methods: The mRNA levels of LINC00968, miR-22-5p and cell division cycle 14A (CDC14A) were measured using quantitative real-time PCR. Cell proliferation was evaluated using cell counting kit-8 and flow cytometry. Cell migration and cell invasion were assessed by wound healing and transwell assay, respectively. The interactions between LINC00968 and miR-22-5p were validated by RNA immunoprecipitation, RNA pull down and luciferase reporter assay. Results: We found that lncRNA LINC00968 was significantly down-regulated in LUAD tissues and cell lines. LINC00968 level was positively correlated to survival rate, and negatively correlated to tumor node metastasis stage, tumor size and lymph node metastasis of LUAD patients. LINC00968 over-expression in LUAD cells inhibited cell proliferation and induced cell cycle arrest at G1 phase. LINC00968 over-expression also suppressed migration, invasion and epithelial mesenchymal transition (EMT) as evidenced by elevated E-cadherin, decreased N-cadherin, TWIST and SNAIL levels. We further validated that LINC00968 localized in cytoplasma and acted as an upstream of microRNA miR-22-5p, which was up-regulated in LUAD tissues and cell lines. Besides, elevated miR-22-5p expression abolished the effect of LINC00968 over-expression on LUAD progression including in vivo tumor growth. In addition, we first validated that cell division cycle 14A (CDC14A), which was down-regulated in LUAD tissues, was a downstream target of miR-22-5p. We over-expressed CDC14A in LUAD cells and miR-22-5p induced LUAD progression was partially reversed. Conclusion: our study demonstrated that LINC00968 inhibited proliferation, migration and invasion of LUAD by sponging miR-22-5p and further restoring CDC14A. This novel regulatory network might provide us with promising diagnostic and therapeutic target in LUAD treatment.
The relationship between mental health self-efficacy and mental well-being in England, UK: A Cross-sectional study
Authors: Lemmel Frederike Katharina , Jones Rebecca , Johnson Sonia , Jolly Anita , Miller Miriam , Henderson Claire
Published: May 2020

Background. Mental well-being is an essential concept in research and public health as it is recognised as an indicator of population mental health and quality of life. Previous studies have provided evidence that general self-efficacy is positively related to mental well-being. The aim of this study is to examine whether higher help-seeking self-efficacy and higher psychological well-being self-efficacy respectively, are associated with increased mental well-being.Methods. In this cross-sectional study 1795 adults from the general English population were recruited from a market research panel to fill out an online questionnaire between 24th September 2018 and 05th October 2018. Two simple linear regression analyses were used to investigate the relationship between each of help-seeking self-efficacy and psychological well-being self- efficacy as exposure variables and mental well-being as the outcome. Multiple imputation by chained equations was used to handle missing data.Results. No evidence was found for an association between either help-seeking self-efficacy or psychological well-being self-efficacy and mental well-being.Conclusions. These findings do not provide evidence that improving help-seeking or psychological well-being self-efficacy could lead to improving well-being. Methodological limitations, such as unmeasured confounders might be responsible for the lack of evidence in this study. Having a mental health condition is a potential negative confounder that might not have been measured adequately.
Improvement of Parent’s Awareness, Knowledge, Perception, and Acceptability of HPV Vaccination After an Educational Intervention
Authors: Sitaresmi Mei Neni , Rozanti Nisrina Maulida , Wahab Abdul
Published: May 2020

Background
Regardless of the disease burden of Human Papilloma Virus (HPV), the vaccine has not been included in the Indonesia National Immunization Program. Since 2017 there was a demonstration program of the HPV vaccination in Yogyakarta Province. This vaccine was given to female elementary school students in 5th and 6th grades. This study aimed to assess whether an educational intervention about the risks of HPV and the vaccine increases the parental awareness, knowledge, and perceptions toward HPV and the vaccine acceptability.
Methods
We conducted a pre-post educational intervention study in July 2017 before the implementation of the HPV vaccination demonstration program, in Kulon Progo District, Yogyakarta Province. Parents of female elementary school students grades 5th and 6th were selected using a school-based proportional random sampling. A pediatric resident provided a structured-educational intervention program. Parents were required to complete validated self-administered questionnaires before and after the intervention program.
Results
A total of 506 parents participated. Before the educational intervention program, parents' awareness of HPV infection and the vaccines were low. Only 49.2% of parents had heard HPV infection, and 48.8% had never heard about the vaccine. After the educational intervention, there were significant improvements in parent’s awareness, knowledge, and perceptions of HPV infection, cervical cancer, and HPV vaccination (all p < 0.001). HPV vaccine's acceptability increased from 74.3–87.4% (p < 0.001). There was a significant correlation between increasing HPV vaccine acceptability with the improvement of awareness, knowledge, and perception toward HPV infection, cervical cancer and HPV vaccination (r = 0.32 to 0.53, p < 0.001). After the educational intervention, better knowledge and positive perceptions of HPV vaccination were predictive of HPV vaccine's acceptability with OR 1.90 (95%CI:1.40–2.57) and OR 1.31(95%CI:1.05–1.63), respectively.
Conclusions
A structured educational intervention program conducted by qualified health providers is effective in improving parental awareness, knowledge, and perceptions toward HPV as well as the acceptability of the vaccine. There was a significant correlation between improving the parental knowledge and perceptions of HPV vaccine with increasing acceptability of the HPV vaccine.
Joint Effect of Alcohol use and Tobacco Smoke on All-Cause Mortality and Premature Death in China: A Cohort Study
Authors: Zhang Hongli , Xueyuan Bi , Nanbo Zheng , Li Chao , Kangkang Yan
Published: May 2020

Background Tobacco smoke and alcohol use were associated with several diseases, study on joint effect of smoke and drink was rare.Objective This study aims to investigate the joint effect of tobacco smoke and alcohol use on all-cause mortality and premature death in a contemporary cohort.Methods China Health and Retirement Longitudinal Study (CHARLS) was an ongoing nationally representative survey for subjects aged over 45 years in China, which performed every 2 years for total of 3 waves from 2011 to 2015 in China. We used weighted logistic regression model to estimate the joint effect of tobacco smoke and alcohol use on total mortality and premature death.Results After adjusting for the confounders, the odd ratios (ORs) value of all-cause mortality were 1.47 (95%CI: 1.03–2.08) and 1.51 (95%CI: 1.09–2.10) in smoker and non-drinker and smoker and drinker separately. Compared with non-smoker and non-drinker, smoker and drinker increased the odds of premature death by 3.14 (95%CI: 1.56–6.34). In the subgroup analysis, there was a 5-fold (OR = 4.95; 95%CI: 2.00-12.27) increase in the odds of premature death for female smoker and drinker.Conclusion This study found a joint effect of tobacco smoke and alcohol use on all-cause mortality and premature death among a contemporary and nationally representative data in China. Our results suggested the joint effect was more pronounced in women, but further research was needed.