bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autosomal dominant Emery-Dreifuss muscular dystrophy caused by a mutation in the lamin A/C gene identified by exome sequencing: a case report
Authors: Iskandar Kristy , Sunartini  , Astari Farida Niken , Gumilang Rizki Amalia , Ilma Nissya , Shartyanie Ni Putu , Adistyawan Guritno , Tan Grace , Gunadi  , Lai Poh San 
Published: October 2022

AbstractBackgroundEmery-Dreifuss Muscular Dystrophy (EDMD) is an uncommon genetic disease among the group of muscular dystrophies. EDMD is clinically heterogeneous and resembles other muscular dystrophies. Mutation of the lamin A/C (LMNA) gene, which causes EDMD, also causes many other diseases. There is inter and intrafamilial variability in clinical presentations. Precise diagnosis can help in patient surveillance, especially before they present with cardiac problems. Hence, this paper shows how a molecular work-out by next-generation sequencing can help this group of disorders.Case presentationA 2-year-10-month-old Javanese boy presented to our clinic with weakness in lower limbs and difficulty climbing stairs. The clinical features of the boy were Gower's sign, waddling gait and high CK level. His father presented with elbow contractures and heels, toe walking and weakness of limbs, pelvic, and peroneus muscles. Exome sequencing on this patient detected a pathogenic variant in theLMNAgene (NM_170707: c.C1357T: NP_733821: p.Arg453Trp) that has been reported to cause Autosomal Dominant Emery-Dreifuss muscular dystrophy. Further examination showed total atrioventricular block and atrial fibrillation in the father.ConclusionEDMD is a rare disabling muscular disease that poses a diagnostic challenge. Family history work-up and thorough neuromuscular physical examinations are needed. Early diagnosis is essential to recognize orthopaedic and cardiac complications, improving the clinical management and prognosis of the disease. Exome sequencing could successfully determine pathogenic variants to provide a conclusive diagnosis.
COVID-19 epidemiology and changes in health service utilization in Uganda’s refugee settlements during the first year of the pandemic
Authors: Altare Chiara , Kostandova Natalya , OKeeffe Jennifer , Omwony Emmanuel , Nyakoojo Ronald , Kasozi Julius , Spiegel Paul B. 
Published: October 2022

Abstract
Background
The COVID-19 pandemic has been characterized by multiple waves with varying rates of transmission affecting countries at different times and magnitudes. Forced displacement settings were considered particularly at risk due to pre-existing vulnerabilities. Yet, the effects of COVID-19 in refugee settings are not well understood. In this study, we report on the epidemiology of COVID-19 cases in Uganda’s refugee settlement regions of West Nile, Center and South, and evaluate how health service utilization changed during the first year of the pandemic.

Methods
We calculate descriptive statistics, testing rates, and incidence rates of COVID-19 cases in UNHCR’s line list and adjusted odds ratios for selected outcomes. We evaluate the changes in health services using monthly routine data from UNHCR’s health information system (January 2017 to March 2021) and apply interrupted time series analysis with a generalized additive model and negative binomial distribution, accounting for long-term trends and seasonality, reporting results as incidence rate ratios.

Findings
The first COVID-19 case was registered in Uganda on March 20, 2020, and among refugees two months later on May 22, 2020 in Adjumani settlement. Incidence rates were higher at national level for the general population compared to refugees by region and overall. Testing capacity in the settlements was lower compared to the national level. Characteristics of COVID-19 cases among refugees in Uganda seem to align with the global epidemiology of COVID-19. Only hospitalization rate was higher than globally reported. The indirect effects of COVID-19 on routine health services and outcomes appear quite consistent across regions. Maternal and child routine and preventative health services seem to have been less affected by COVID-19 than consultations for acute conditions. All regions reported a decrease in consultations for respiratory tract infections.

Interpretation
COVID-19 transmission seemed lower in settlement regions than the national average, but so was testing capacity. Disruptions to health services were limited, and mainly affected consultations for acute conditions. This study, focusing on the first year of the pandemic, warrants follow-up research to investigate how susceptibility evolved over time, and how and whether health services could be maintained.
Self-efficacy and oral health outcomes in a regional Australian Aboriginal population
Authors: Parker Eleanor Jane , Haag Dandara Gabriela , Spencer Andrew John , Roberts-Thomson Kaye , Jamieson Lisa Marie 
Published: October 2022

AbstractBackgroundPerceived self-efficacy has been associated with psychological well-being, health behaviours and health outcomes. Little is known about the influence of self-efficacy on oral health outcomes for Aboriginal adults in Australia, a population experiencing high levels of oral health conditions. This study examines associations between oral health-related self-efficacy and oral health outcomes in a regional Aboriginal Australian population and investigates whether the associations persist after adjusting for sociodemographic characteristics and other general and oral health-related psychosocial factors.MethodsCross-sectional data were obtained from the baseline questionnaire of the Indigenous Oral Heath Literacy Project, South Australia. Oral health-related self-efficacy was measured using a six item scale, with total sum scores dichotomised into high/low self-efficacy. Oral health outcomes included self-rated oral health and oral health impacts, measured using the Oral Health Impact Profile (OHIP-14). Generalized linear models with a log-Poisson link function were used to estimate Prevalence Ratios (PR) of poor self-rated oral health according to levels of oral health-related self-efficacy. Multivariable linear regressions were used to estimate the association between oral health-related self-efficacy and OHIP-14 scores. Blocks of confounders were subsequently added into the models, with the final model including all factors.ResultsComplete data were available for 252 participants (63%) aged 18 to 82 years (mean age of 37.6 years). Oral health-related self-efficacy was associated with poor self-rated oral health, with a 43% (PR = 1.43 (95% CI 1.09, 1.88)) greater prevalence of poor self-rated oral health among those with low self-efficacy. Oral health-related self-efficacy was associated with OHIP-14 severity scores, with a score over six points higher for those with low self-efficacy (B = 6.27 95% CI 2.71, 9.83). Although addition of perceived stress into the models attenuated the relationship, associations remained in the final models.ConclusionLower levels of oral health-related self-efficacy were associated with a higher prevalence of poor self-rated oral health and greater impacts of oral health among Aboriginal adults in regional South Australia. These associations persisted after controlling for sociodemographic and psychosocial confounders, suggesting that increasing self-efficacy may provide an opportunity for improving oral health outcomes for Aboriginal adults.
Monte Carlo cross-validation for a study with binary outcome and limited sample size
Authors: Shan Guogen 
Published: October 2022

AbstractCross-validation (CV) is a resampling approach to evaluate machine learning models when sample size is limited. The number of all possible combinations of folds for the training data, known as CV rounds, are often very small in leave-one-out CV. Alternatively, Monte Carlo cross-validation (MCCV) can be performed with a flexible number of simulations when computational resources are feasible for a study with limited sample size. We conduct extensive simulation studies to compare accuracy between MCCV and CV with the same number of simulations for a study with binary outcome (e.g., disease progression or not). Accuracy of MCCV is generally higher than CV although the gain is small. They have similar performance when sample size is large. Meanwhile, MCCV is going to provide reliable performance metrics as the number of simulations increases. Two real examples are used to illustrate the comparison between MCCV and CV.
Transcription factor FfMYB15 regulates the expression of cellulase gene FfCEL6B during mycelial growth of Flammulina filiformis
Authors: Liu Zongqi , Deng Bing , Yuan Hui , Zhang Benfeng , Liu Jingyu , Meng Junlong , Chang Mingchang 
Published: October 2022

AbstractBackgroundCellulose degradation can determine mycelial growth rate and affect yield during the growth ofFlammulina filiformis. The degradation of cellulose requires the joint action of a variety of cellulases, and some cellulase-related genes have been detected in mushrooms. However, little is known about the transcriptional regulatory mechanisms of cellulose degradation.ResultsIn this study, FfMYB15 that may regulate the expression of cellulase geneFfCEL6BinF. filiformiswas identified. RNA interference (RNAi) showed thatFfCEL6Bpositively regulated mycelial growth. Gene expression analyses indicated that the expression patterns ofFfCEL6BandFfMYB15in mycelia cultured on the 0.9% cellulose medium for different times were similar with a correlation coefficient of 0.953. Subcellular localization and transcriptional activity analyses implied that FfMYB15 was located in the nucleus and was a transcriptional activator. Electrophoretic mobility shift assay (EMSA) and dual-luciferase assays demonstrated that FfMYB15 could bind and activateFfCEL6Bpromoter by recognizing MYB cis-acting element.ConclusionsThis study indicated thatFfCEL6Bplayed an active role in mycelial growth ofF. filiformisand was regulated by FfMYB15.
The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy
Authors: Croft Wayne , Evans Richard P. T. , Pearce Hayden , Elshafie Mona , Griffiths Ewen A. , Moss Paul 
Published: October 2022

AbstractImmune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy.
Identification of a necroptosis-related prognostic gene signature associated with tumor immune microenvironment in cervical carcinoma and experimental verification
Authors: Sun Kai , Huang Cheng , Li Jing-zhang , Luo Zhan-xiong 
Published: October 2022

AbstractCervical carcinoma (CC) has been associated with high morbidity, poor prognosis, and high intratumor heterogeneity. Necroptosis is the significant cellular signal pathway in tumors which may overcome tumor cells’ apoptosis resistance. To investigate the relationship between CC and necroptosis, we established a prognostic model based on necroptosis-related genes for predicting the overall survival (OS) of CC patients. The gene expression data and clinical information of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients were obtained from The Cancer Genome Atlas (TCGA). We identified 43 differentially expressed necroptosis-related genes (NRGs) in CESC by examining differential gene expression between CESC tumors and normal tissues, and 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene ontology (GO) and KEGG enrichment analysis illustrated that the genes identified were mainly related to cell necrosis, extrinsic apoptosis, Influenza A, I − kappaB kinase/NF − kappaB, NOD − like receptor, and other signaling pathways. Subsequently, least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate Cox regression analyses were used to screen for NRGs that were correlated with patient prognosis. A prognostic signature that includes CAMK2A, CYBB, IL1A, IL1B, SLC25A5, and TICAM2 was established. Based on the prognostic model, patients were stratified into either the high-risk or low-risk subgroups with distinct survival. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive accuracy of the model. In relation to different clinical variables, stratification analyses were performed to demonstrate the associations between the expression levels of the six identified NRGs and the clinical variables in CESC. Immunohistochemical (IHC) validation experiments explored abnormal expressions of these six NRGs in CESC. We also explored the relationship between risk score of this necroptosis signature and expression levels of some driver genes in TCGA CESC database and Gene Expression Omnibus (GEO) datasets. Significant relationships between the six prognostic NRGs and immune-cell infiltration, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints in CESC were discovered. In conclusion, we successfully constructed and validated a novel NRG signature for predicting the prognosis of CC patients and might also play a crucial role in the progression and immune microenvironment in CC.
Caveolin-1 accelerates hypoxia-induced endothelial dysfunction in high-altitude cerebral edema
Authors: Xue Yan , Wang Xueting , Wan Baolan , Wang Dongzhi , Li Meiqi , Cheng Kang , Luo Qianqian , Wang Dan , Lu Yapeng , Zhu Li 
Published: October 2022

Abstract
Background
High-altitude cerebral edema (HACE) is a serious and potentially fatal brain injury that is caused by acute hypobaric hypoxia (HH) exposure. Vasogenic edema is the main pathological factor of this condition. Hypoxia-induced disruptions of tight junctions in the endothelium trigger blood‒brain barrier (BBB) damage and induce vasogenic edema. Nuclear respiratory factor 1 (NRF1) acts as a major regulator of hypoxia-induced endothelial cell injury, and caveolin-1 (CAV-1) is upregulated as its downstream gene in hypoxic endothelial cells. This study aimed to investigate whether CAV-1 is involved in HACE progression and the underlying mechanism.

Methods
C57BL/6 mice were exposed to HH (7600 m above sea level) for 24 h, and BBB injury was assessed by brain water content, Evans blue staining and FITC-dextran leakage. Immunofluorescence, transmission electron microscope, transendothelial electrical resistance (TEER), transcytosis assays, and western blotting were performed to confirm the role and underlying mechanism of CAV-1 in the disruption of tight junctions and BBB permeability. Mice or bEnd.3 cells were pretreated with MβCD, a specific blocker of CAV-1, and the effect of CAV-1 on claudin-5 internalization under hypoxic conditions was detected by immunofluorescence, western blotting, and TEER. The expression of NRF1 was knocked down, and the regulation of CAV-1 by NRF1 under hypoxic conditions was examined by qPCR, western blotting, and immunofluorescence.

Results
The BBB was severely damaged and was accompanied by a significant loss of vascular tight junction proteins in HACE mice. CAV-1 was significantly upregulated in endothelial cells, and claudin-5 explicitly colocalized with CAV-1. During the in vitro experiments, hypoxia increased cell permeability, CAV-1 expression, and claudin-5 internalization and downregulated tight junction proteins. Simultaneously, hypoxia induced the upregulation of CAV-1 by activating NRF1. Blocking CAV-1-mediated intracellular transport improved the integrity of TJs in hypoxic endothelial cells and effectively inhibited the increase in BBB permeability and brain water content in HH animals.

Conclusions
Hypoxia upregulated CAV-1 transcription via the activation of NRF1 in endothelial cells, thus inducing the internalization and autophagic degradation of claudin-5. These effects lead to the destruction of the BBB and trigger HACE. Therefore, CAV-1 may be a potential therapeutic target for HACE.
Impact of personal and environmental factors affecting exclusive breastfeeding practices in the first six months during the COVID-19 pandemic in Thailand: a mixed-methods approach
Authors: Nuampa Sasitara , Ratinthorn Ameporn , Patil Crystal L. , Kuesakul Kornkanok , Prasong Sudhathai , Sudphet Metpapha 
Published: October 2022

Abstract
Background
Exclusive breastfeeding (EBF) for six months is recommended as one of the most important ways to support child health and survival, particularly during the COVID-19 pandemic. However, breastfeeding women encountered several obstacles during the pandemic. The purpose of this study was to conduct a survey to document breastfeeding practices, EBF rates and associated factors with six month exclusive breastfeeding during the second wave of the coronavirus outbreak in Thailand.

Methods
A mixed-methods design that included a cross-sectional survey (n = 390) and semi-structured in-depth interviews (n = 15) was carried out between August and November 2021. Participants were women aged ≥ 15 years who had given birth within 6–12 months before data collection and delivered in three public hospitals in the top three provinces with the most severe COVID-19 outbreaks.

Results
The median duration of EBF was four months (interquartile range, IQR: 1–6 months) and 37.4% of women exclusively breastfed for six months. From binary logistic regression models, several personal factors were associated with exclusive breastfeeding for six months including being a housewife (AOR 2.848; 95% CI 1.512, 5.367), perceived sufficiency of family income (AOR 2.502; 95% CI 1.362, 4.594), working from home/business (AOR 2.071; 95% CI 1.074, 3.995), breastfeeding intention (AOR 1.162; 95% CI 1.116, 1.210), and maternal age (AOR 0.932; 95% CI 0.882, 0.986). From qualitative interviews, women who were able to exclusively breastfed during the outbreak explained five themes that were a protective shield; I have to save money, I could spend all my time with my baby and breastfeed, spousal support is valuable, and opportunity to avoid the obstructed beliefs about exclusive breastfeeding.

Conclusions
Mothers with higher socioeconomic status and who were unemployed/worked from home and had support structures in place were able to successfully EBF during the COVID-19 outbreak. Healthcare providers can better support breastfeeding if they provide informational support and allow family members to participate in breastfeeding programs, especially spouses who provided key emotional and tangible support during pandemic.
scGWAS: landscape of trait-cell type associations by integrating single-cell transcriptomics-wide and genome-wide association studies
Authors: Jia Peilin , Hu Ruifeng , Yan Fangfang , Dai Yulin , Zhao Zhongming 
Published: October 2022

AbstractBackgroundThe rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes.ResultsscGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets. We demonstrated scGWAS in 40 genome-wide association studies (GWAS) datasets (average sample sizeN≈ 154,000) using 18 scRNA-seq datasets from nine major human/mouse tissues (totaling 1.08 million cells) and identified 2533 trait and cell-type associations, each with significant modules for further investigation. The module genes were validated using disease or clinically annotated references from ClinVar, OMIM, and pLI variants.ConclusionsWe showed that the trait-cell type associations identified by scGWAS, while generally constrained to trait-tissue associations, could recapitulate many well-studied relationships and also reveal novel relationships, providing insights into the unsolved trait-tissue associations. Moreover, in each specific cell type, the associations with different traits were often mediated by different sets of risk genes, implying disease-specific activation of driving processes. In summary, scGWAS is a powerful tool for exploring the genetic basis of complex diseases at the cell type level using single-cell expression data.
Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway
Authors: Chen Yan , Pan Xiaoli , Zhao Jing , Li Chunyan , Lin Yupei , Wang Yu , Liu Xu , Tian Mei 
Published: October 2022

Abstract
Objectives
This study aims to investigate the effects of Icariin (ICA) on interleukin-1β (IL-1β)-induced osteoarthritis (OA) and its potential mechanism of action.

Methods
SW1353 chondrocytes were pretreated with ICA for 2 h, followed by stimulation with IL-1β to mimic OA. Expression levels of matrix metalloproteinases (MMP-3) and collagen II were determined using real-time PCR and Western blot assays. Autophagy activation (by ICA) or inhibition (by shRNA) was determined based on the expression levels of ULK1, Beclin-1, LC3-II/I, and p62, using Western blot analysis. The phosphorylation levels of PI3K, Akt, mTOR, and ULK1 were also detected using Western blot analysis.

Results
IL-1β increased MMP-3 overproduction, induced collagen II degradation, and reduced the level of autophagy-associated proteins, including ULK1, Beclin-1, and LC3-II/I. In contrast, ICA pretreatment attenuated IL-1β-induced MMP-3 overproduction, increased collagen II expression, and induced expression of autophagy-related proteins. ICA also decreased PI3K, Akt, and mTOR phosphorylation, increased the production of ULK1, and induced autophagy. Short hairpin RNA-mediated knockdown of ULK1 led to activation of the PI3K/Akt/mTOR pathway, which reversed the protective effects of ICA.

Conclusions
Our findings indicate that ICA can induce autophagy by regulating the PI3K/AKT/mTOR/ULK1 signaling pathway. This study suggests that ICA may be effective for treating OA.