bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Is it Possible to Model the Impact of Calorie-Reduction Interventions on Childhood Obesity at a Population Level and Across the Range of Deprivation: Evidence from the Avon Longitudinal Study of Parents and Children (ALSPAC)
Authors: Russell Simon James , Hope Steven , Croker Helen , Packer Jessica , Viner Russell M 
Published: May 2020

Abstract
Background Simulated interventions using observational data have the potential to inform policy and public health interventions where randomised controlled trials are not feasible. National childhood obesity policy is one such area. Overweight and obesity are primarily caused by energy-rich and low-nutrient diets that contribute to a positive net energy imbalance. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated whether causal modelling techniques could be applied to simulate the potential impact of policy-relevant calorie-reduction interventions on population prevalence and inequalities in obesity in childhood.Methods Predicted probabilities of obesity at age 11 (UK90 cut offs) were estimated from logistic marginal structural models (MSM) accounting for observed calorie consumption at age 7 and confounding, overall and by maternal occupational social class. A series of population intervention scenarios were modelled to simulate daily calorie-reduction interventions that differed in effectiveness, targeting mechanism and programme uptake level.Results 18.3% of children were living with obesity at age 11 years, after accounting for confounding and observed calorie intake. MSM produced usable estimates of obesity reduction. A universal simulation to lower median intake to the estimated average requirement (EAR) (a 6.1% reduction in daily calories) with 75% uptake reduced overall obesity prevalence by 0.6%; there was little impact on inequalities. A targeted intervention to limit consumption to the EAR for children with above average intake reduced population obesity prevalence at 11 years by 1.5% but inequalities remained broadly unchanged. A targeted intervention for children of low-income families reduced prevalence and was found to slightly reduce inequalities.Conclusions MSMs allow estimation of effects of simulated calorie-reduction interventions on childhood obesity prevalence and inequalities, although estimates are limited by the accuracy of reported calorie intake. Further work is needed to understand causal pathways and opportunities for intervention.
Personality and sleep evaluation of patients with tinnitus in Japan
Authors: Inagaki Yozo , Suzuki Noriomi , Oishi Naoki , Goto Fumiyuki , Shinden Seiichi , Ogawa Kaoru 
Published: May 2020

Abstract
Background
In Japan, there have been no examinations of tinnitus with respect to personality traits, and only a few studies have investigated sleep disorders in tinnitus. Understanding the association of these with one another can aid in selecting and developing effective treatment options for patients with tinnitus. This study aimed to clarify the relationship between tinnitus severity, personality, and sleeping disorders, in patients with chronic tinnitus in Japan.
Methods
We retrospectively evaluated the personality factors of 56 patients presenting with tinnitus using the NEO Five-Factor Inventory (NEO-FFI), which examines five personality characteristics, including Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. We also evaluated tinnitus severity using the Tinnitus Handicap Inventory, sleep disorders using the Pittsburgh Sleep Quality Index (PSQI), depression using the Self-Rating Depression Scale, and anxiety using the State Trait Anxiety Inventory.
Results
There was a positive correlation between Neuroticism and tinnitus severity (r = 0.548, P < 0.001). Sleep disorders were observed in 73.2% of patients; however, there was no correlation between the PSQI score and tinnitus severity or between PSQI score and scores of the five NEO-FFI items.
Conclusions
Understanding the relationship between personality and tinnitus severity could lead to better management of tinnitus. Sleep disorders are frequently experienced by patients with chronic tinnitus, regardless of tinnitus severity or personality.
Diversification of Leech Proboscis Structure According to Prey Ingestion Behavior
Authors: Kwak Hee-Jin , Kim Jung-Hyeuk , Kim Joo-Young , Jeon Donggu , Lee Doo-Hyung , Yoo Shinja , Kim Jung , Eyun Seong-il , Park Soon Cheol , Cho Sung-Jin 
Published: May 2020

Abstract
Background Adaptive radiation is a phenomenon in which various organs, depending on their diet and circumstance, are diversified morphologically or functionally as animals adapt to the environment. Although previous studies on changes caused by various external pressures have been well studied, the evidence for variation in invertebrates is not well known. We used freshwater leeches as an invertebrate model to observe their specific trophic niche and diversity of ingestion organ. Our results show convergent evolution according to structural changes through a representative species Alboglossiphonia sp., and the origin from common ancestor due to the remaining fluid ingestion behavior of the larval stages as a vestige.Results We identified the feeding behavior of rhynchobdellid leeches, which have the proboscis. Alboglossiphonia sp. swallows the entire prey using its proboscis, whereas proboscis leeches exhibit typical fluid-sucking behavior. We observed that proboscis of fluid-sucking leeches encompasses compartmentalized and dense muscle layers. In contrast, macrophagous leeches have relatively simple esophagus structures. To address whether the different feeding behaviors were intrinsic, we investigated the behavioral pattern and muscle arrangement in the earlier developmental stage of rhynchobdellid leeches. Interestingly, juveniles of the macrophagous leech as well as fluid-sucking leeches have the proboscis with the compartmentalized muscle layers and exhibit fluid-sucking behaviorsConclusions Animals have adapted various ways to obtain the energy needed for their survival. Diversification and evolution of ingestion methods across species further exhibit the functional morphology of the ingestion organ. However, information on ingestion behavior and internal structure is still lack and unclear, especially in invertebrate models. Our results suggest that the proboscis leeches have originated from the common fluid-sucking glossiphoniid ancestor and species diversification has led to modifications in the structure of the feeding tube. Together, leeches represent a comparative model for esophagus development according to the ingestion pattern based on diverse muscular arrangement in proboscis.