bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol consumption and the risk of liver disease: a nationwide, population-based study
Authors: Moon Sang Yi , Son Minkook , Kang Yeo Wool , Koh Myeongseok , Lee Jong Yoon , Baek Yang Hyun 
Published: November 2023

IntroductionAlthough most patients with alcohol-related liver disease (ALD) have a history of prolonged and heavy drinking, there is no clear threshold defining the level of alcohol consumption that leads to ALD. We aimed to evaluate the correlation between average alcohol consumption and the risk of liver disease and to determine the threshold for clinically significant alcohol consumption.Materials and methodsUsing the Korean National Health Insurance database, we identified participants who underwent a health-screening program in 2010 and 2011 and retrospectively analyzed their data until 2019. To diagnose and categorize the extracted participants, we used the International Classification of Diseases version 10 and Fatty Liver Index. The primary outcome was to determine the incidence of newly diagnosed liver-related diseases during the observation period and compare the incidence of liver-related diseases among non-drinkers and drinkers based on the amount of alcohol consumption.ResultsA total of 53,006 patients were enrolled and followed-up for a median of 8.4 years, during which 1,509 cases of liver-related diseases occurred. The participants were divided into five groups: no alcohol consumption (n = 31,359), 1st quartile (n = 5,242), 2nd quartile (n = 5,704), 3rd quartile (n = 5,337), and 4th quartile (n = 5,364). The corresponding number of glasses of alcohol consumed per week for each quantile (Q1, Q2, Q3, and Q4) was labeled 2.5 ± 1.1 standard units (1 standard unit = 8 g alcohol), 5.4 ± 1.9 standard units, 11.5 ± 3.3 standard units, and 27.9 ± 18.2 standard units, respectively. Compared with non-drinkers, the risk of liver-related disease was found to be higher in Q1 drinkers (adjusted hazard ratio [aHR], 1.09; 95% CI, 0.90–1.33), Q2 drinkers (aHR, 1. 10; 95% CI, 0.91–1.32), Q3 drinkers (aHR, 1.33; 95% CI, 1.11–1.59), and Q4 drinkers (aHR, 1.47; 95% CI, 1.24–1.75).ConclusionWe report that our study has shown that drinking more than 11.5 ± 3.3 standard units/week (92 ± 26.4 g/week) significantly increases the risk of developing liver-related diseases. Therefore, as a preventive measure to reduce the risk of developing liver disease, alcohol consumption should be limited beyond traditionally recommended levels.
Associations between microstructural tissue changes, white matter hyperintensity severity, and cognitive impairment: an intravoxel incoherent motion imaging study
Authors: Lin Huihua , Dai Xiaomin , Su Jiawei , Yang Shengsheng , Zheng Yonghong , Ma Mingping , Yu Shun 
Published: November 2023

IntroductionWhite matter hyperintensities (WMHs) are a common age- and vascular risk factor-related disease and have been recognized to play an important role in cognitive impairment. However, it is still unclear what the mechanism of this effect is. In this study, intravoxel incoherent motion (IVIM) was employed to assess the microvasculature and parenchymal microstructure changes of WMHs and explore their relationship with cognitive function.MethodsForty-nine WMH patients and thirty-one healthy controls underwent IVIM imaging, a diffusion technique that provides parenchymal diffusivity D, intravascular diffusivity D*, and perfusion fraction f . The IVIM dual exponential model parameters were obtained in specific regions of interest, including deep white matter hyperintensities (DWMHs), periventricular white matter hyperintensities (PWMHs), and normal-appearing white matter (NAWM). The independent-sample t-test or Mann–Whitney U-test was utilized to compare IVIM parameters between patients and controls. The Kruskal–Wallis test or one-way analysis of variance was used to compare IVIM parameters among DWMH, PWMH, and NAWM for patients. The Wilcoxon two-sample test or independent-sample t-test was used to assess the differences in IVIM parameters based on the severity of WMH. The multivariate linear regression analysis was conducted to explore the factors influencing cognitive scores.ResultsWMH patients exhibited significantly higher parenchymal diffusivity D than controls in DWMH, PWMH, and NAWM (all p &lt; 0.05). IVIM parameters in the three groups (DWMH, PWMH, and NAWM) were significantly different for patients (all p &lt; 0.001). The severe WMH group had a significantly higher parenchymal diffusivity D (DWMH and PWMH) than mild WMH (both p &lt; 0.05). The multiple linear regression analysis identified D in DWMH and PWMH as influencing cognitive function scores (all p &lt; 0.05).ConclusionIVIM has the potential to provide a quantitative marker of parenchymal diffusivity for assessing the severity of WMH and may serve as a quantitative marker of cognitive dysfunction in WMH patients.
Experimental verification and identifying biomarkers related to insomnia
Authors: Wang Qianfei , Liu Dong , Gao Tianci , Tao Yulei , Li Xin , Liu Yuan , Liu Zhiliang , Mei Jianqiang , Chen Fenqiao 
Published: November 2023

IntroductionInsomnia is the most common form of sleep deprivation (SD) observed in clinics. Although there are differences between insomnia and SD, they have similar symptoms and the same animal model. Currently, there is a lack of microarray data on insomnia. Therefore, for now, we are going to apply the SD data to insomnia. Although many studies have explained the possible mechanisms associated with insomnia, no previous studies have considered the key genes associated with insomnia or the relationship between insomnia and immune cells. In this study, we analyzed the relationship between key genes and immune cells by identifying biomarkers for the diagnosis of insomnia. Next, we verified the efficacy of these biomarkers experimentally.MethodsFirst, we downloaded four microarrays (GSE11755, GSE12624, GSE28750, and GSE48080) from the Gene Expression Omnibus (GEO) database, which included data from 239 normal human blood samples and 365 blood specimens from patients with SD. Then, we analyzed two groups of differentially expressed genes (DEGs) and used Support Vector Machine Recursive Feature Elimination (SVM-RFE) analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model to investigate these key genes. Next, we used CIBERSORT to investigate the composition of 22 immune cell components of key genes in SD patients. Finally, the expression levels of key biomarkers in sleep-deprived patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 50 DEGs were identified: six genes were significantly upregulated, and 44 genes were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Salmonella infection, NOD-like receptor (NLR) signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and Th17 cell differentiation were significant. Based on machine learning, we identified C2CD2L, SPINT2, APOL3, PKNOX1, and A2M as key genes for SD; these were confirmed by receiver operating characteristic (ROC) analysis. Immune cell infiltration analysis showed that C2CD2L, SPINT2, APOL3, PKNOX1, and A2M were related in different degrees to regulatory T cells (Tregs), follicular T helper cells, CD8 cells, and other immune cells. The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not.DiscussionIn summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.
Relationships among gut microbes, the interleukin family, and hypertension: a mediation Mendelian randomization study
Authors: Zhao Shiyao , Zhang Jing , Ding Fuxia , Sun Shougang 
Published: November 2023

PurposeObservational studies have increasingly recognized the influence of gut microbes on blood pressure modulation. Despite these findings, a direct causal link between gut flora and hypertension remains unestablished due to inherent confounders and the challenges of reverse causality in observational research. In this study, we sought to elucidate the causal relationship between specific gut flora and hypertension and its intermediary mediators.MethodsWe employed a two-sample Mendelian randomization (MR) and mediation MR analysis, analyzing 211 species of gut bacteria, with a focus on the interleukin family as potential mediators and hypertension as the primary outcome. The central methodological technique was inverse variance-weighted estimation, supplemented by various other estimators.ResultsOur findings revealed that two bacterial species positively correlated with hypertension risk, while five exhibited a negative association. Further validation was conducted using sensitivity analyses. Notably, our mediation MR results suggest interleukin-1 receptor type 2 (IL-1R2) as a mediator for the effect of the genus Clostridium innocuum group on hypertension, accounting for a mediation proportion of 14.07% [mediation effect: (b = 0.0007, 95%CI: 0.0002–0.0011); proportion mediation = 14.07% (4.26–23.40%)].ConclusionOur research confirms a genetic causal relationship between specific gut microbes and hypertension, emphasizing the potential mediating role of interleukin-1 receptor type 2 (IL-1R2) and offering insights for clinical hypertension interventions.
Risk factors associated with multiple organ damage in childhood-onset systemic lupus erythematosus
Authors: Puengpipattrakul Thanaporn , Lerkvaleekul Butsabong , Pirojsakul Kwanchai , Vilaiyuk Soamarat 
Published: November 2023

ObjectivePrevious studies have shown that approximately 39%–65% of patients with childhood-onset systemic lupus erythematosus (cSLE) have damage in at least one organ. Data on risk factors for organ damage in cSLE remain limited, especially in Asian populations. This study was conducted to evaluate the incidence of cSLE and identify the risk factors for accumulated organ damage in patients with cSLE.MethodsThis was a retrospective study. Patients aged &lt;18 years who were diagnosed with cSLE between 2008 and 2020 were enrolled. Information on baseline characteristics, treatment, and disease activity assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was collected from diagnosis until the most recent visits were reviewed from medical records. Disease damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).ResultsA total of 134 patients with a mean age at diagnosis of 11.2 ± 2.9 years were enrolled. The median duration of treatment was 4.7 (interquartile range 2.8–7.1) years. Forty patients (29.9%) had irreversible organ damage (SDI &gt; 1) with an incidence rate of 5.7 events per 100 person-years. The most frequent type of organ damage was ocular (11.1%), followed by musculoskeletal (8.9%) and neurological (7.4%). High disease activity at diagnosis (SLEDAI-2K ≥ 12) (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.32–7.68), infection (OR 3.73, 95% CI 1.60–8.67), and mycophenolate mofetil use (OR 3.62, 95% CI 1.45–9.03) were predictors of organ damage. The median time to disease damage in patients with SLEDAI-2K scores ≥12 at diagnosis was 6.5 years (95% CI 5.77–7.36; P = 0.004).ConclusionPhysicians should be aware of organ damage in patients with cSLE, particularly those with high disease activity at initial presentation, those who are receiving mycophenolate mofetil therapy, and those with an infection.
Pricing and reimbursement mechanisms for advanced therapy medicinal products in 20 countries
Authors: Rejon-Parrilla Juan Carlos , Espin Jaime , Garner Sarah , Kniazkov Stanislav , Epstein David 
Published: November 2023

Introduction: Advanced Therapy Medicinal Products are a type of therapies that, in some cases, hold great potential for patients without an effective current therapeutic approach but they also present multiple challenges to payers. While there are many theoretical papers on pricing and reimbursement (P&amp;R) options, original empirical research is very scarce. This paper aims to provide a comprehensive international review of regulatory and P&amp;R decisions taken for all ATMPs with centralized European marketing authorization in March 2022.Methods: A survey was distributed in July 2022 to representatives of 46 countries.Results: Responses were received from 20 countries out of 46 (43.5%). 14 countries reimbursed at least one ATMP. Six countries in this survey reimbursed no ATMPs.Conclusion: Access to ATMPs is uneven across the countries included in this study. This arises from regulatory differences, commercial decisions by marketing authorization holders, and the divergent assessment processes and criteria applied by payers. Moving towards greater equality of access will require cooperation between countries and stakeholders, for example, through the WHO Regional Office for Europe’s Access to Novel Medicines Platform.
Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research
Authors: Nie Jingjing , Xia Hailun , Liu Ya-Nan , Yu Yige , Xu Ren-Ai 
Published: November 2023

As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID‐19) today, arbidol often involves drug–drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 μM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was non-competitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice.
Self-regulatory employability attributes and competency: the strengthening role of grit
Authors: Ismail Sadika , Potgieter Ingrid L. , Coetzee Melinde 
Published: November 2023

IntroductionThis study examines grit as psychological mindsets that explain the link between self-regulatory employability attributes and perceived employability competency expectations in a sample of South African adults (N = 308).MethodsA quantitative, cross-sectional research design approach was used to collect primary data.ResultsResults of a mediation analysis through structural equation modelling revealed grit as an important mechanism to strengthen the association between employability attributes (career agility, cultural ingenuity, proactive career resilience) and employability competency expectations (autonomy/leadership skills and personal employability qualities).DiscussionThis study makes an important contribution to the role of learning and training through understanding the role of grit in enhancing prospects of employability. This study further adds to the grit literature, highlighting the role that grit plays in the contemporary employment context. Practical implications include supportive practices that strengthen individual workers’ grit when confronted with the turbulent changes of today’s work world.
Assessment of knowledge, attitudes, and practices regarding menstruation and menstrual hygiene among early-reproductive aged women in Bangladesh: a cross-sectional survey
Authors: Siddique Abu Bakkar , Deb Nath Sudipto , Mubarak Mahfuza , Akter Amena , Mehrin Sanjida , Hkatun Mst Jemi , Parvine Liza Antara , Amin M. Ziaul 
Published: November 2023

BackgroundPoor menstrual hygiene practices during menstruation increases the risk of reproductive tract infections, absenteeism, and negative impact on school performance. Despite being a global problem, there is a lack of knowledge and misconceptions about menstrual hygiene among women of all ages, especially in developing countries like Bangladesh. The study aims to assess the knowledge, attitudes, and practices toward menstrual hygiene among early reproductive-aged women in Bangladesh to help policymakers and planners take effective initiatives.MethodologyA cross-sectional survey was conducted between July and December 2022 in Dhaka, Rajshahi, Chittagong, Sylhet, and Barisal regions of Bangladesh. A convenience sampling technique was utilized to recruit a total of 1,214 participants (100% female; mean age: 22.87 ± 2.64 years). A semi-structured questionnaire including informed consent, socio-demographic information, as well as questions regarding knowledge (6-item), attitudes (7-item), and practices (6-item) toward menstruation and menstrual hygiene practices, was used to conduct the survey. All analyses were performed using the STATA (Version 15.0) and Statistical Package for the Social Sciences (SPSS version 25.0).ResultThe mean scores of the knowledge, attitudes, and practices were 4.9 ± 1.51 (out of 6), 12.58 ± 1.58 (out of 14), and 8.80 ± 1.87 (out of 12), respectively. The higher scores of knowledge, attitudes, and practices were significantly associated with several socio-demographic and menstruation-related factors (education, family type, type of menstruation, duration of menstruation, etc.).ConclusionThis study identified several key factors associated with improved knowledge, attitudes, and practices related to menstrual hygiene, including higher education levels, student status, younger age, non-alcohol consumption, and regular menstrual cycles. To enhance menstrual hygiene practices among women, it is crucial to implement targeted interventions that address knowledge disparities and tackle social and environmental influences.
Influencing factors of early childhood teachers’ disaster preparedness
Authors: Lee Young-Ran , Park Sun-Nam , Lee Mi-Ran , Nam Eunjeong 
Published: November 2023

BackgroundThe risk of disasters and infectious diseases continues to persist in modern times. Children are a vulnerable group in disaster prevention and management due to their limited ability to cope on their own. Hence, the role and disaster preparedness capacity of early childhood teachers (ECTs) is vital for children’s protection.ObjectivesThis study aims to explore how ECTs can improve their personal resilience to adapt to and overcome disasters as part of early childhood education and care (ECEC). To this end, this study examined the effects of ECTs’ self-efficacy, resilience, disaster awareness, COVID-19 stress, and work-related stress on their disaster preparedness.ResultsAccording to the outcomes of disaster preparedness of ECTs based on their general and job characteristics, full-time employees and principals scored significantly higher in work-related disaster preparedness (WrDP) compared to part-time workers and general and assistant teachers, respectively. Resilience and WrDP were identified as influencing factors of general disaster preparedness (GdP), with an explanatory power of 26.4%. GdP and self-efficacy were identified as influencing factors of WrDP, with an explanatory power of 25.7%.DiscussionAccording to the findings, ECTs’ self-efficacy and GdP must be improved, followed by developing strategies to strengthen their resilience and WrDP. Doing so would ensure the safety and disaster preparedness of ECTs and infants who have low self-care capacity.
Determinants of Residential Satisfaction During the Initial Stage of the COVID-19 Pandemic: The Case of Xiangyang City, China
Authors: Yuan Dinghuan , Yu Haoyuan , Lin Wenyi , Zha Lisi 
Published: November 2023

Objectives: To explore the impacts of psychological character strengths, self-efficacy, and the number of confirmed COVID-19 cases on residential satisfaction at the initial stage of the COVID-19 pandemic in China.Methods: To achieve the study aim, we collected data from 281 observations from Xiangyang City, China, via an online survey. Data were analyzed using linear regression.Results: Character strengths and the number of confirmed COVID-19 cases significantly impacted residential satisfaction. While self-efficacy did not directly impact residential satisfaction, it moderated the relationship between the number of confirmed COVID-19 cases and residential satisfaction. The control variables of social trust and shared value positively impacted residential satisfaction, and their influence on residential satisfaction was higher than that of character strengths. The sociodemographic variables of marriage, age, educational attainment, and housing area per capita also impacted residential satisfaction significantly. However, strong ties and weak ties became insignificant variables due to social distancing strategies.Conclusion: The study findings offer insights for local governments to enhance residential satisfaction in the community to avoid social panic during unpredictable threats or future pandemics.
The Mulberry Juice Fermented by Lactiplantibacillus plantarum O21: The Functional Ingredient in the Formulations of Fruity Jellies Based on Different Gelling Agents
Authors: Szydłowska Aleksandra , Zielińska Dorota , Sionek Barbara , Kołożyn-Krajewska Danuta 
Published: November 2023

This study aimed to investigate the effects of adding probiotics, prebiotics, and different types of jelly agents on a few key quality attributes of potentially functional mulberry jellies throughout a 10-day storage period at 4 °C. Mullbery juice was separately fermented at 37 °C for 24 h using Lactiplantibacillus plantarum O21; it was a favorable matrix for the proliferation of probiotics. Lactic acid fermentation positively affected the total anthocyanin concentration of investigated products. Also, antioxidant capacities of mulberry juices were improved by L. plantarum O21 fermentation. The results showed that the applied prebiotic–inulin addition and agar–agar addition, as a gelling agent in recipes of potentially functional mulberry jellies, were proved to be beneficial technological solutions, both in fresh and stored products, and obtained an appropriate, high number of LAB bacteria, good sensory quality, and beneficial antioxidant properties.