bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis
Authors: Salton Maayan , Engal Eden , Sharma Aveksha , Taqatqa Nadeen , Bentata Mercedes , Jaffe-Herman Shiri , Geminder Ophir , Lewis Reyut , Gotkine Marc , Eiges Rachel , Mouly Vincent , Drier Yotam 
Published: September 2023

Abstract
SMCHD1 is a non-canonical SMC protein and an epigenetic regulator. Mutations in SMCHD1 cause facioscapulohumeral muscular dystrophy type 2 (FSHD2), a genetic disorder characterized by progressive muscle weakness and wasting, believed to be caused by aberrant expression of DUX4 in muscle cells. Here we demonstrate a new role for SMCHD1 as a regulator of alternative splicing in various cell types. We show how SMCHD1 loss cause splicing alterations of DNMT3B which can lead to hypomethylation, DUX4 expression, and FSHD pathogenesis. Analyzing RNA-seq data from muscle biopsies of FSHD2 patients and Smchd1 knocked out cells, we found mis-splicing of hundreds of genes upon SMCHD1 loss. At least 20% of mis-spliced genes were associated with abnormalities of the musculature. Moreover, mis-spliced exons tend to be bound by SMCHD1, and bound exons demonstrate a slower elongation rate, suggesting SMCHD1 binding promotes exon exclusion by slowing RNAPII, and recruitment of the splicing factor RBM5. The mis-splicing of DNMT3B leads to hypomethylation of the D4Z4 region and to DUX4 overexpression. These results suggest that mis-splicing by SMCHD1 may play a major role in FSHD2 pathogenesis by promoting the mis-splicing of different targets including DNMT3B, and highlight the potential for targeting splicing as a therapeutic strategy.
Three predictive models for transthoracic device closure of atrial septal defect: a comprehensive comparative analysis
Authors: Ruan Weiqiang , Han Junyang , Xie Lin , Lin Ke 
Published: September 2023

Abstract
Background:
Atrial Septal Defect (ASD) is a common congenital heart disease. Although transthoracic occlusion of ASD is increasingly seen as a less invasive alternative to traditional surgery, the choice of procedure often relies on the surgeon's experience and the insights gained from transesophageal echocardiography (TEE) images, lacking concrete, quantifiable standards. This study aims to guide clinical surgical decisions by developing and comparing predictive models.
Methods:
We analyzed 312 patients with secundum atrial septal defects who underwent either transthoracic device closure or open surgical repair. By measuring and analyzing preoperative TEE data and utilizing statistical and programming software, we developed three predictive models: logistic regression, random forest, and multiple linear regression. The original data were divided into a training dataset and a testing dataset, with each model trained on the training dataset and validated on the testing dataset. The predictive performance of each model was then evaluated on both adult and pediatric data.
Results:
Each model exhibited remarkable predictive power. The prediction accuracies in the training dataset for the logistic regression model, random forest model, and multiple linear regression model were 0.892, 0.888, and 0.868, respectively. In the testing dataset, the prediction accuracies were 0.9194, 0.871, and 0.9194, respectively.
Conclusions:
This study developed three predictive models to guide clinical surgical decisions for ASD closure surgery. Among them, the multivariate linear regression model demonstrated significant predictive accuracy, offering the potential to streamline the clinical decision-making process. This model does not require complex computations and is capable of providing quick, real-time predictions.
Impact of Healthcare Accessibility on Suicide Rates in the European Union: A Cross-Sectional Correlation Study
Authors: Máčel Martin , Opelka Jakub , Němcová Hana , Labajová Alexa 
Published: September 2023

Abstract
Background.
Suicide is a global and devastating phenomenon with severe society-wide consequences. One of the fundamental goals of researchers, policymakers, and health and social service professionals is to predict suicidal behaviour and prevent it. This study aimed to explore the relationship between the accessibility of healthcare, its financing by the state and the suicide rate in the states of the European Union. We aim to identify which part of the healthcare system, or the interplay between them, is critical to suicide prevention.
Methods.
We used freely available data from Eurostat, the statistical agency of the European Union, which processes and freely publishes demographic, economic, and social data from all European Union states. From the available data, we identified those that best indicate the availability and funding of health care in each state. These are the following factors: number of psychiatrists, number of general practitioners, length of psychiatric hospitalisation, number of psychiatric beds, unmet medical needs of citizens, government funding of healthcare and suicide rate. We included data from 2011 to 2019, the latest fully published datasets at the time of this study's writing.
Results.
Our statistical model demonstrated exceptional explanatory power, accounting for 25% of the suicide rate variance within European Union states, a substantial number for a phenomenon as complex as suicide. A significantly protective effect was found between the number of psychiatrists, percentage of inhabitants self-reporting fully met medical examination needs and suicide rate. Notably, the reported met medical needs can serve as an indirect yet significant indicator of the accessibility and quality of a healthcare system. Moreover, the significant positive effect between reported unmet medical needs and the suicide rate highlights the profound impact of healthcare accessibility on overall well-being and mental health.
Conclusions.
Our findings might serve as a basis for policies aiming to lower suicide rates in European countries by enhancing access to and funding of healthcare. We consider it crucial that interventions trying to reduce suicide rates focus not only on the quantity of resources and personnel that go into the healthcare system but also on their education, supervision, and care for their own physical and mental health.
Mendelian Randomization Analysis Reveals Causal Relationship Between Obstetric-related Diseases and COVID-19
Authors: Fang Yan , Fang Dajun 
Published: September 2023

Abstract
Background: Several observational studies demonstrated that pregnant individuals with COVID-19 had a higher risk of preeclampsia and preterm birth. We aimed to determine whether women with COVID-19 diagnosis had adverse pregnancy outcomes.
Methods: A two-sample Mendelian randomization (MR) analysis in this study was used to evaluate the casual relationships between COVID-19 infection and obstetric-related diseases based on genome-wide association studies (GWAS) dataset. Inverse-variance weighted (IVW), MR-Egger and MR-PRESSO were used to infer the connection and estimate the pleiotropy respectively.
Results: The significant connection was observed between COVID-19 and placental disorders with betaIVW of 1.57 and odds ratio of 4.81 (95% confidence interval [CI]:1.05-22.05, p =0.04). However, there were no associations between COVID-19 infection and gestational diabetes mellitus (GDM) (OR= 1.12; 95% CI:0.85-1.45, p =0.41), other disorders of amniotic fluid and membranes (OR= 0.90; 95% CI:0.61-1.32, p =0.59), Intrahepatic Cholestasis of Pregnancy (ICP) (OR= 1.42; 95% CI:0.85-2.36, p =0.18), birth weight (OR= 1.02; 95% CI:0.99-1.05, p =0.19), gestational hypertension (OR= 1.00; 95% CI:1.00-1.00, p =0.85), spontaneous miscarriages (OR= 1.00; 95% CI:0.96-1.04, p =0.90) and stillbirth (OR= 1.00; 95% CI:0.98-1.01, p =0.62).
Conclusion: There was no direct causal relationship between COVID-19 infection and maternal and neonatal poor outcomes. Our study could alleviate the anxiety of pregnant women under the COVID-19 pandemic conditions partly.
Altitude-dependent Variation in Lipoprotein Profile as a Predictor of Hypoxic Pulmonary Arterial Hypertension in COPD Patients: An Analysis Across Gradient Altitudes
Authors: Zhong-Ping Wang , Geng Yu-Mei , Hua Mao , Ge Ri-Li , Bai Zhenzhong 
Published: September 2023

Abstract
Background
The heterogeneity of the spectrum of lipoproteins plays an important role in pulmonary hypertension, which mainly focuses on arterial types of pulmonary hypertension (PAH), but is little understood for the hypoxic pulmonary hypertension (HPH).
Objectives
Here, we explore the impact of altitude-induced hypoxia and lipoprotein levels on the occurrence and development of Chronic Obstructive Pulmonary Disease combined with Pulmonary Hypertension (COPD-PH) in high-altitude residents.
Methods
Clinical data from 245 COPD-PH patients admitted to Qinghai University Affiliated Hospital (2018–2022) were retrospectively analyzed. Patients were divided into middle (1500m-<2500m; 119 cases) and high-altitude (2500m-<4500m; 126 cases) groups, with a control group comprising 100 health-check participants from the same altitudes. Main variables included Pulmonary Arterial Systolic Pressure (PASP), Total Cholesterol (TC), Triglycerides (TG), High-Density Lipoprotein Cholesterol (HDL), and Low-Density Lipoprotein Cholesterol (LDL).
Results
Differences in Body Mass Index (BMI), PASP, TC, TG, HDL, LDL, and lipoprotein ratios between the control and COPD-PH groups were statistically significant (P < 0.05). Multivariate logistic regression revealed serum TC, HDL ≤ 1.13 mmol/L, and TC/HDL ≥ 3.52 as independent predictors of COPD-PH. In the COPD-PH group, PASP negatively correlated with BMI, TC, and HDL but positively correlated with age, altitude, and TC/HDL.
Conclusions
Low-oxygen conditions at high altitude are closely related to the severity of pulmonary artery pressure in COPD-PH patients and can influence the occurrence and development of COPD-PH by affecting serum TC and TC/HDL levels. Gender differences in COPD-PH occurrence and prognosis may be linked to TC, HDL, and TC/HDL, suggesting PAH is a gender-bimodal disease primarily affecting females.
Managing Pratylenchus brachyurus in subsequent soybean crops following maize-brachiaria intercropping in greenhouse conditions
Authors: Bicalho Anderson Cascione Gripp , Santiago Débora Cristina , Machado Andressa Cristina Zamboni 
Published: September 2023

Abstract
This study aimed to evaluate how intercropping maize and brachiaria impacts the population dynamics of Pratylenchus brachyurus in subsequent soybean crops, both in greenhouse and field conditions. A secondary objective was to assess the effectiveness of two seed treatment nematicides in this crop system. The research involved ten sites where soybeans were grown after the maize-brachiaria intercropping, alongside fields with single maize or brachiaria cultivation for comparison. In addition, two experiments were conducted in pots in greenhouse. The treatments included maize-brachiaria intercropping with maize treated or non-treated with nematicides, followed by soybean treated or non-treated with the same nematicides, all in the presence of P. brachyurus. Nematode population analyses were conducted for both the intercropped maize and brachiaria, as well as the subsequent soybean plants. The findings indicated that P. brachyurus was the predominant nematode in the root samples, with higher representation observed in the presence of maize-brachiaria intercropping. In both experiments, fluopyram exhibited superior efficacy against the lesion nematode compared to B. firmus when applied to soybean after intercropping of maize and brachiaria. Importantly, intercropping maize and brachiaria without nematicides led to the persistence of P. brachyurus populations, potentially causing issues in subsequent soybean crops. The data suggests that incorporating brachiaria in intercropping with maize contributes to the proliferation of P. brachyurus. However, the study demonstrated that this negative impact could be mitigated by implementing chemical and/or biological nematicides throughout the crop season. Hence, while intercropping systems involving maize-brachiaria may worsen problems caused by P. brachyurus in infested fields, appropriate nematicide application can effectively manage nematode populations and minimize potential harm to crops.
Epidemiology of adverse events and near misses in public exercise facilities: A prospective cohort study
Authors: Hirata Akihiro , Oguma Yuko , Saito Yoshinobu , Ito Tomoya , Kondo Keisuke , Takemoto Yoshiteru , Nishigaya Tatsunori , Shiobara Sachi 
Published: September 2023

Abstract
Background
This study aims to identify the demographics of new users of training rooms in public exercise facilities in Fujisawa City, Kanagawa Prefecture, Japan, as well as determine the incidence and frequency of adverse events and near misses of users exercising in the training room.
Methods
This prospective cohort study was conducted between October 2021 and December 2022. The participants were 1,235 (739 male and 496 female) new users of training rooms in three public exercise facilities in Fujisawa City who agreed to respond to the survey questionnaire comprising questions on demographics (age, sex, height, weight, exercise habits, underlying medical conditions, preworkout health check created based on Physical Activity Readiness Questionnaire +: PAR-Q་), frequency of training room use, and occurrence of adverse events and near misses during exercise. Participant demographics were elicited at baseline using a questionnaire. Furthermore, data on the frequency of use and adverse events/near misses were reported by staff.
Results
The study found that 54.4% of the male and 72.9% of the female users of public exercise facilities did not report any exercise habits. The proportion of individuals with underlying medical conditions and persons included in one or more of the seven-item preexercise health check was higher in older age groups than in younger groups for both males and females. During the observation period, participants did not experience any adverse events or near misses. However, all training room users experienced a total of six adverse events, five of which were falls, of which four occurred in users aged 60 years or older.
Conclusions
The findings of this study suggest consideration of preexisting health conditions, the use of a standardized preexercise health check, and the education of trainers at public exercise facilities in Japan to avoid the occurrence of adverse events and near misses during exercise, particularly for those with underlying medical conditions and those in the older age group.
Effectiveness of gamified digital interventions in mental health prevention and health promotion among adults: A systematic review
Authors: Aschentrup Leona , Steimer Pia Anna , Dadaczynski Kevin , Call Timothy Mc , Fischer Florian , Wrona Kamil J. 
Published: September 2023

Abstract
Background
Though still a young field of research, gamified digital interventions have demonstrated potential in exerting a favorable impact on health and overall well-being. With the increasing use of the internet and digital devices, the integration of game elements presents novel opportunities for preventing mental disorders and enhancing mental health. Hence, this systematic review aims to assess the effectiveness of gamified interventions focusing on preventing mental disorders or promoting mental health among adults.
Methods
Based on a systematic literature research across four databases (MEDLINE, Embase, PsycInfo and Web of Science), 7,953 studies were initially identified. After removing duplicates and screening titles, abstracts and full texts, 16 studies were identified as suitable for inclusion in a narrative synthesis of findings. We included interventional studies encompassing an intervention and a control group aiming to investigate the effectiveness of the use of gamified digital mental health interventions and the use of gamified digital elements.
Results
Overall, positive effects of gamified interventions on mental health-related outcomes were identified. In particular, beneficial consequences for psychological well-being and depressive symptoms were observed. However, further outcomes, such as resilience, anxiety, stress or satisfaction with life, showed heterogenous findings. Most game elements used were reward, sensation and progress, whilst the quantity of elements was not consistent and, therefore, no substantiated conclusion can be drawn. Further, the outcomes, measurements and analyses differed greatly between the 16 included studies making comparisons difficult.
Conclusion
In summary, this systematic review demonstrates the potential of integrating digital game elements on mental health and well-being with still a great gap of research. A taxonomy is needed to adequately address relevant game elements in the field of mental health promotion and prevention of mental disorders. Therefore, future studies should explicitly focus on the mechanisms of effect and apply rigorous study designs.
CRISPR/Cas9-mediated suppression of A4GALT rescues endothelial cell dysfunction in a Fabry disease vasculopathy model derived from human induced pluripotent stem cells
Authors: Shin Yoo Jin , Chae Seung Yun , Lee Hanbi , Fang Xianying , Cui Sheng , Lim Sun Woo , Lee Kang In , Lee Jae Young , Li Can , Yang Chul Woo , Chung Byung Ha 
Published: September 2023

Abstract
Backgrounds: The objective of this study was to investigate the efficacy of CRISPR/Cas9-mediated A4GALT suppression in rescuing endothelial dysfunction in Fabry disease (FD) endothelial cells (FD-ECs) derived from human induced pluripotent stem cells (hiPSCs).
Methods: We differentiated hiPSCs (WT (wild-type), WTC-11), GLA-mutant hiPSCs (GLA-KO, CMC-Fb-002), and CRISPR/Cas9-mediated A4GALT-KO hiPSCs (GLA/A4GALT-KO, Fb-002-A4GALT-KO) into ECs and compared FD phenotypes and endothelial dysfunction. We also analyzed the effect of A4GALT suppression on reactive oxygen species (ROS) formation and transcriptome profiles through RNA sequencing.
Results: GLA-mutant hiPSC-ECs (GLA-KO and CMC-Fb-002) showed downregulated expression of EC markers and significantly reduced α-GalA expression with increased Gb-3 deposition and intra-lysosomal inclusion bodies. However, CRISPR/Cas9-mediated A4GALT suppression in GLA/A4GALT-KO and Fb-002-A4GALT-KO hiPSC-ECs increased expression levels of EC markers and rescued these FD phenotypes. GLA-mutant hiPSC-ECs failed to form tube-like structure in tube formation assays with, showing significantly decreased migration of cells into the scratched wound area. In contrast, A4GALT suppression improved tube formation and cell migration capacity. Western blot analysis revealed that MAPK and AKT phosphorylation levels were downregulated whereas SOD and catalase were upregulated in GLA-KO hiPSC-ECs. However, suppression of A4GALT restored these protein alterations. RNA sequencing analysis demonstrated significant transcriptome changes in GLA-mutant EC, especially in angiogenesis, cell death, and cellular response to oxidative stress. However, these were effectively restored in GLA/A4GALT-KO hiPSC-ECs.
Conclusions: CRISPR/Cas9-mediated A4GALT suppression rescued FD phenotype and endothelial dysfunction in GLA-mutant hiPSC-ECs, presenting a potential therapeutic approach for FD-vasculopathy.
Construction and evaluation of neonatal respiratory failure risk prediction model for neonatal respiratory distress syndrome
Authors: Lei Yupeng , Qiu Xia , Zhou Ruixi 
Published: September 2023

Abstract
Background
Neonatal respiratory distress syndrome (NRDS) is a common respiratory disease in preterm infants, often accompanied by respiratory failure. The aim of this study was to establish and validate a nomogram model for predicting the probability of respiratory failure in NRDS patients.
Methods
Patients diagnosed with NRDS were extracted from the MIMIC-ⅳ database. The patients were randomly assigned to a training and a validation cohort. Univariate and stepwise Cox regression analyses were used to determine the prognostic factors of NRDS. A nomogram containing these factors was established to predict the incidence of respiratory failure in NRDS patients. The area under the receiver operating characteristic curve (AUC), receiver operating characteristic curve (ROC), calibration curves and decision curve analysis were used to determine the effectiveness of this model.
Results
The study included 2,705 patients with NRDS. Univariate and multivariate stepwise Cox regression analysis showed that the independent risk factors for respiratory failure in NRDS patients were gestational age, pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), hemoglobin, blood culture, infection, neonatal intracranial hemorrhage, Pulmonary surfactant (PS), parenteral nutrition and respiratory support. Then, the nomogram was constructed and verified.
Conclusions
This study identified the independent risk factors of respiratory failure in NRDS patients and used them to construct and evaluate respiratory failure risk prediction model for NRDS. The present findings provide clinicians with the judgment of patients with respiratory failure in NRDS and help clinicians to identify and intervene in the early stage.
Well-dispersed fluorine-doped tin oxide nanoparticles on the one dimensional network structure of carbon nanofibers for enabling ultrafast lithium storage
Authors: Yoon Seon-Hee , Sung Ki-Wook , Ahn Hyo-Jin 
Published: September 2023

Abstract
The growing environmental concerns have spurred a surge in the interest in eco-friendly energy storage devices. Because of their advantages, such as high energy density and long cycle life, Li-ion batteries (LIBs) are used in electronic devices and electric vehicles (EVs). However, the specific capacity and ultrafast cycling performance of the LIBs used in EVs require further improvement. In this study, well-dispersed fluorine-doped tin oxide (FTO) nanoparticles (NPs) were deposited on carbon nanofibers (CNFs) using horizontal ultrasonic spray pyrolysis deposition to obtain a CNF/FTO electrode. The F atoms in tin oxide increased its electrical conductivity. The one-dimensional CNF network structure enhanced the electrical conductivity of the electrode. The abundant active sites in nanosized FTO facilitated Li-ion diffusion. The well-dispersed FTO NPs on the CNF matrix prevented the agglomeration of the electrode material and substantial volume changes in the electrode during its cycling. At a current density of 100 mA/g, the CNF/FTO electrode exhibited a superior discharge capacity of 487.96 mAh/g with a capacity retention of 66.7% and even at an ultrafast current density of 2000 mA/g, it demonstrated excellent performance with a discharge capacity of 289.3 mAh/g and a capacity retention of 93.6% after 500 cycles of operation.