bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and characterization of a zebrafish gain-of-function ACOX1 Mitchell disease model
Authors: Raas Quentin , Wood Austin , Stevenson Tamara J. , Swartwood Shanna , Liu Suzanne , Kannan Rangaramanujam M. , Kannan Sujatha , Bonkowsky Joshua L. 
Published: January 2024

BackgroundMitchell syndrome is a rare, neurodegenerative disease caused by an ACOX1 gain-of-function mutation (c.710A&gt;G; p.N237S), with fewer than 20 reported cases. Affected patients present with leukodystrophy, seizures, and hearing loss. ACOX1 serves as the rate-limiting enzyme in peroxisomal beta-oxidation of very long-chain fatty acids. The N237S substitution has been shown to stabilize the active ACOX1 dimer, resulting in dysregulated enzymatic activity, increased oxidative stress, and glial damage. Mitchell syndrome lacks a vertebrate model, limiting insights into the pathophysiology of ACOX1-driven white matter damage and neuroinflammatory insults.MethodsWe report a patient presenting with rapidly progressive white matter damage and neurological decline, who was eventually diagnosed with an ACOX1 N237S mutation through whole genome sequencing. We developed a zebrafish model of Mitchell syndrome using transient ubiquitous overexpression of the human ACOX1 N237S variant tagged with GFP. We assayed zebrafish behavior, oligodendrocyte numbers, expression of white matter and inflammatory transcripts, and analysis of peroxisome counts.ResultsThe patient experienced progressive leukodystrophy and died 2 years after presentation. The transgenic zebrafish showed a decreased swimming ability, which was restored with the reactive microglia-targeted antioxidant dendrimer-N-acetyl-cysteine conjugate. The mutants showed no effect on oligodendrocyte counts but did display activation of the integrated stress response (ISR). Using a novel SKL-targeted mCherry reporter, we found that mutants had reduced density of peroxisomes.ConclusionsWe developed a vertebrate (zebrafish) model of Mitchell syndrome using transient ubiquitous overexpression of the human ACOX1 N237S variant. The transgenic mutants exhibited motor impairment and showed signs of activated ISR, but interestingly, there were no changes in oligodendrocyte counts. However, the mutants exhibited a deficiency in the number of peroxisomes, suggesting a possible shared mechanism with the Zellweger spectrum disorders.
Barriers, enablers and motivators of the “I’m an active Hero” physical activity intervention for preschool children: a qualitative study
Authors: Al-walah Mosfer A. , Donnelly Michael , Heron Neil 
Published: January 2024

BackgroundInsufficient physical activity (PA) in early childhood is linked to adverse health outcomes and a heightened risk of obesity. Successful PA programmes often require input from key stakeholders, such as parents and educators. However, research on stakeholders’ perspectives regarding PA programmes for preschool children is limited, impeding effective programme design and implementation.ObjectivesThis study aims to explore the perspectives of key stakeholders to gain insights into the challenges, facilitators, and motivators that influence the planning, execution, and sustainability of the “I'm an Active Hero (IAAH) intervention component,” a preschool-based initiative designed to promote PA among young children.MethodsSemi-structured interviews were conducted in Saudi Arabia with individual preschool principals (n = 2), and focus group discussions were held, respectively, with preschool staff members (n = 4, all female) and parents (4 mothers, 5 fathers).ResultsA thematic analysis identified four main themes: (1) Barriers to parental involvement in preschool PA interventions, such as time constraints, lack of flexibility, limited space, and a shortage of trained staff; (2) Risks and benefits of children's programme participation; (3) Motivators including rewards, non-financial incentives, and concerns about childhood obesity and a sedentary lifestyle; (4) Facilitating factors for overcoming barriers, including staff training, time reallocation, staff coordination, space optimization, non-financial incentives, and sustaining partnerships.ConclusionThis study's findings are crucial for childcare professionals, preschools, education authorities, and policymakers, offering valuable insights for future research. However, further collaboration with key stakeholders is essential to enhance individual attitudes and preschool policies for effective intervention implementation.
Chaihu Shugan prevents cholesterol gallstone formation by ameliorating the microbiota dysbiosis and metabolic disturbance in mice
Authors: Wang Wei , Zhang Kun , Liu Bin , Zhou Tong , Tang Yu , Li Yuliang 
Published: January 2024

Introduction: Cholesterol gallstone (CGS) is a biliary tract disorder requiring treatment in approximately 20% of patients. The efficacy of Chaihu Shugan in preventing CGS recurrence after successful treatment remains uncertain.Methods: We examined the in vivo preventive efficacy of Chaihu Shugan using a CGS mouse model and used multi-omics to study the interplay between gut microbiota, metabolism, and gene expression.Results: The intestinal microbiota was severely dysregulated during the formation of CGS, showing a marked decrease in the abundance of beneficial microbiota, especially Lactobacillus and Akkermansia. Chaihu Shugan prevented CGS formation by restoring the composition of the gut microbiota and reversing the metabolic disturbances caused by dysbiosis. This preventive effect of Chaihu Shugan was paralleled by changes in the expression of metabolism-related genes in the liver. A network pharmacology analysis of Chaihu Shugan revealed that obacunone may be the key active metabolite in regulating bile acid metabolism. Multi-omics and correlation analyses elucidated the interplay between gut microbiota, metabolism, and gene alterations in the dose-dependent effect of Chaihu Shugan.Conclusion: Our data show that Chaihu Shugan can prevent CGS and indicate its mechanisms of action.
Contrastive analysis on the safety of brand and generic nebivolol: a real-world pharmacovigilance study based on the FDA adverse event reporting system
Authors: Wang Hongli , Zhong Guizun , Ji Huanhuan , Chen Siqi , Xie Qinqin , Shen Zhengze , Jia Yuntao 
Published: January 2024

Background:The equivalence of generic drugs to their brand-name counterparts is a controversial issue. Current literature indicates disparities between the generic nebivolol (GN) and the brand nebivolol (BN).Aim:The study is designed to investigate the safety difference between GN and BN and provide reference information for clinical practice.Methods:We reviewed adverse event (AE) reports that recorded nebivolol as the primary suspect drug in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2022, conducted a disproportional analysis to detect signals for the GN and BN respectively, and compared the AE heterogeneity between them using the Breslow-Day test.Results:A total of 2613 AE reports of nebivolol were recorded in the FAERS database from 2004 to 2022, of which 2,200 were classified as BN, 346 as GN, and 67 unclassifiable AE reports were excluded. The signals of 37 AEs distributed in cardiac, gastrointestinal, psychiatric, and nervous systems were detected in disproportional analysis. 33 out of 37 AEs were positive signals, with 21 not previously listed on the drug label, indicating an unrecognized risk with nebivolol. In the heterogeneity analysis of AE signals between GN and BN, the GN generally showed a higher AE signal value than BN, especially 15 AEs distributed in the cardiac, neurological, and psychiatric systems that showed statistically significantly higher risk by taking GN.Conclusion:Our study shows some previously overlooked adverse effects of nebivolol. It suggests that the risk of GN’s adverse effects may be higher than those in BN, which deserves further attention and investigation by healthcare professionals, regulators, and others.
From genomic spectrum of NTRK genes to adverse effects of its inhibitors, a comprehensive genome-based and real-world pharmacovigilance analysis
Authors: Cui Zhiwei , Zhai Zhen , Xie De , Wang Lihui , Cheng Feiyan , Lou Siyu , Zou Fan , Pan Rumeng , Chang Shixue , Yao Haoyan , She Jing , Zhang Yidan , Yang Xinyuan 
Published: January 2024

Introduction: The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has facilitated the development of precision oncology. Two first-generation NTRK inhibitors (larotrectinib and entrectinib) are currently approved for the treatment of patients with solid tumors harboring NTRK gene fusions. Nevertheless, comprehensive NTRK profiling at the pan-cancer genomic level and real-world studies pertaining to the adverse events of NTRK inhibitors are lacking.Methods: We characterize the genome of NTRK at the pan-cancer level through multi-omics databases such as The Cancer Genome Atlas (TCGA). Through the FDA Adverse Event Reporting System (FAERS) database, we collect reports of entrectinib and larotrectinib-induced adverse events and perform a pharmacovigilance analysis using various disproportionality methods.Results:NTRK1/2/3 expression is lower in most tumor tissues, while they have higher methylation levels. NTRK gene expression has prognostic value in some cancer types, such as breast invasive carcinoma (BRCA). The cancer type with highest NTRK alteration frequency is skin cutaneous melanoma (SKCM) (31.98%). Thyroid carcinoma (THCA) has the largest number of NTRK fusion cases, and the most common fusion pair is ETV6-NTRK3. Adverse drug events (ADEs) obtained from the FAERS database for larotrectinib and entrectinib are 524 and 563, respectively. At the System Organ Class (SOC) level, both drugs have positive signal value for “nervous system disorder”. Other positive signals for entrectinib include “cardiac disorders”, “metabolism and nutrition disorders”, while for larotrectinib, it is “hepatobiliary disorders”. The unexpected signals are also listed in detail. ADEs of the two NTRK inhibitors mainly occur in the first month. The median onset time of ADEs for entrectinib and larotrectinib was 16 days (interquartile range [IQR] 6–86.5) and 44 days ([IQR] 7–136), respectively.Conclusion: Our analysis provides a broad molecular view of the NTRK family. The real-world adverse drug event analysis of entrectinib and larotrectinib contributes to more refined medication management.
The crisis is over, long live the crisis: mental health in emerging adulthood during the course of the COVID-19 pandemic
Authors: Wirkner Janine , Brakemeier Eva-Lotta 
Published: January 2024

IntroductionAs a multidimensional stressor, the COVID-19 pandemic posed a significant threat to mental health, with studies showing younger age groups to be particularly vulnerable. Thus, this study aimed to monitor mental health, potential risk/protective factors, and pandemic-related variables among young university students during the pandemic.MethodsStudents of the University of Greifswald (M age = 23.0 years, 73.9% female) participated in five cross-sectional online surveys in December 2020 (N = 1,127), March 2021 (N = 760), June/July 2021 (N = 531), December 2021 (N = 1,226), and December 2022 (N = 814). Sociodemographic data, depression and anxiety severity, loneliness, quality of life, coping strategies, resilience, self-esteem, and emotion regulation were measured. First, results from December 2020 were compared to pre-pandemic normative data. Second, the time course during the pandemic was analyzed. Third, linear models were calculated to examine the influence of risk and protective factures on depression and anxiety severity.ResultsHigher levels of depression, anxiety, and loneliness, as well as lower levels of self-esteem, physical and mental health, social relationships and well-being were found in December 2020 compared to pre-pandemic. Levels of depression and anxiety severity peaked in December 2022. Female sex, loneliness, and previous mental treatment showed associations with higher depression and anxiety severity, while higher self-esteem, resilience and use of reappraisal strategies appeared to act as protective factors.DiscussionThe study indicates the pandemic’s detrimental impact on students’ mental health and quality of life. Identified risk and protective factors provide guidance for tailored prevention and treatment, as well as the design of measures for future pandemics and other crisis.
Psychometric characteristics of the career adapt-abilities scale in Thai undergraduate students: a multiple indicators multiple causes model
Authors: Khampirat Buratin 
Published: January 2024

ObjectiveThis study aimed to evaluate the psychometric properties of the Career Adapt-abilities Scale (CAAS) and analyze the relationships between sociodemographic variables and career adaptability using the MIMIC model with DIF.MethodsIn this cross-sectional study, the CAAS, consisting of four sub-scales—concern, control, curiosity, and confidence—each comprising six items, was administered to 620 undergraduate students from 34 universities in Thailand. Among the participants, women constituted 66.77%, while men accounted for 32.58% (Mean Age = 20.33). To explore the influence of sociodemographic characteristics on specific CAAS item responses, a Multiple-Indicators, Multiple-Causes model with Differential Item Functioning (MIMIC-model with DIF) was employed.ResultsThe findings revealed robust internal consistency and reliability in the CAAS. Both the four-factor and second-order factor models exhibited excellent fit indices, emphasizing the significance of each item within the measure. Sociodemographic characteristics did not demonstrate a significant direct effect on the four CAAS subscales, it is worth noting the exception regarding paternal education. Paternal education was found to have a statistical significance impact on two specific CAAS items: “looking for opportunities to grow as a person” and “becoming curious about new opportunities.”ConclusionThese findings underscore the intricate influence of paternal education on specific aspects of career adaptability, suggesting that certain dimensions of career adaptability may be shaped by factors extending beyond the conventional sociodemographic variables examined in this study. Future research could delve deeper into the complex interplay of sociodemographic factors and individual attributes to provide a more holistic perspective on career adaptability in Thailand.
The effect of occupational coping self-efficacy on presenteeism among ICU nurses in Chinese public hospitals: a cross-sectional study
Authors: Wu Jijun , Li Yuxin , Lin Qin , Zhang Jiquan , Liu Zhenfan , Liu Xiaoli , Rong Xian , Zhong Xiaoli 
Published: January 2024

BackgroundNurses are the largest occupational group in the health field, with inestimable value in realizing universal health coverage, and nurses’ physical and mental health has become an ordinary global reality. Compared with explicit absence, nurses’ presenteeism has a more lasting impact and significant harm and loss. It has become an essential factor affecting nurses’ physical and mental health, declining quality of healthcare services, and elevated healthcare-related risks. There is a lack of research exploring whether occupational coping self-efficacy influences nurses’ presenteeism behavior, especially in less-developed regions of China.ObjectiveThis study aimed to investigate the current status of ICU nurses’ occupational coping self-efficacy and presenteeism in public hospitals in western China and to explore the impact of ICU nurses’ occupational coping self-efficacy on presenteeism.MethodsA cross-sectional research design selected 722 ICU nurses in western China from January to February 2023 as survey respondents. A general information questionnaire, Occupational Coping Self-Efficacy Scale (OCSE-N), and Stanford Presenteeism Scale (SPS-6) were used. SPSS 21.0 software was used for statistical analysis. Pearson correlation analysis and multivariate hierarchical regression were used to explore the influence of ICU nurses’ occupational coping self-efficacy on presenteeism.ResultsA total of 722 ICU nurses completed the questionnaire. The OCSE-N score of ICU nurses was (22.24 ± 6.15), and the SPS-6 score was (16.83 ± 4.24). The high presenteeism was 67.23%. Correlation analysis showed that in ICU nurses, OCSE-N total score was negatively correlated with SPS-6 total score (r = −0.421, p &lt; 0.05), indicating that the higher the level of occupational coping self-efficacy, the lower the presenteeism. Multiple hierarchical regression analysis showed that occupational coping self-efficacy strongly predicted presenteeism, accounting for approximately 18.35% of the total variance.ConclusionThere is a correlation between ICU nurses’ occupational coping self-efficacy and presenteeism, and nurses’ occupational coping self-efficacy affects presenteeism differently. Managers should pay attention to nurses’ occupational coping self-efficacy to promote nurses’ presenteeism reduction.
The relationship between Internet use and loneliness of middle-aged and older adult people: the moderating effect of residence
Authors: Li Qiusha , Yang Chunxiao , Zhao Zixuan , Yang Chenxiao , Chen Zhongming , Huang Dongmei , Yin Wenqiang 
Published: January 2024

ObjectivesThe proportion of middle-aged and older adult people exposed to the Internet continues to grow. Internet use may have an impact on the mental health of the older adult, especially loneliness. This study analyzed the relationship between Internet use and presence of loneliness.MethodsA total of 550 person aged 45 years and above were randomly selected from a province in eastern China at the end of 2022. The outcome variable was presence of loneliness, as measured by self-report. Descriptive analysis, chi-square test and binary logistic analysis were used to analyze the data.Results58.3% of respondents use the Internet. Internet use could reduce the possible of reported loneliness in middle-aged and older adult people (OR = 0.652, 95%CI: 0.465, 0.940), and residence played a moderating role in the relationship between them. Middle-aged and older adults who used the Internet for 1–3 h (OR = 0.464, 95%CI: 0.275, 0.784) and 3–5 h (OR = 0.484, 95%CI: 0.247, 0.946) were less likely to felt lonely than those who used the Internet for less than 1 h per day. In addition, middle-aged and older adult people using the Internet to contact relatives and friends (OR = 0.488, 95%CI:0.292, 0.818), read the news (OR = 0.485, 95%CI:0.277, 0.848), assets management (OR = 0.297, 95%CI:0.109, 0.818) were less likely to report loneliness, while those who made online payment (OR = 3.101, 95%CI:1.413, 6.807) were more likely to report loneliness.ConclusionThere is a significant negative correlation between Internet use and presence of loneliness, but different Internet duration and content have different effects on loneliness in middle-aged and older adult people. We should pay attention to the impact of Internet use on loneliness in middle-aged and older adult people.
Towards human-centered AI and robotics to reduce hospital falls: finding opportunities to enhance patient-nurse interactions during toileting
Authors: Rafferty Hannah , Cretaro Cameron , Arfanis Nicholas , Moore Andrew , Pong Douglas , Tulk Jesso Stephanie 
Published: January 2024

Introduction: Patients who are hospitalized may be at a higher risk for falling, which can result in additional injuries, longer hospitalizations, and extra cost for healthcare organizations. A frequent context for these falls is when a hospitalized patient needs to use the bathroom. While it is possible that “high-tech” tools like robots and AI applications can help, adopting a human-centered approach and engaging users and other affected stakeholders in the design process can help to maximize benefits and avoid unintended consequences.Methods: Here, we detail our findings from a human-centered design research effort to investigate how the process of toileting a patient can be ameliorated through the application of advanced tools like robots and AI. We engaged healthcare professionals in interviews, focus groups, and a co-creation session in order to recognize common barriers in the toileting process and find opportunities for improvement.Results: In our conversations with participants, who were primarily nurses, we learned that toileting is more than a nuisance for technology to remove through automation. Nurses seem keenly aware and responsive to the physical and emotional pains experienced by patients during the toileting process, and did not see technology as a feasible or welcomed substitute. Instead, nurses wanted tools which supported them in providing this care to their patients. Participants envisioned tools which helped them anticipate and understand patient toileting assistance needs so they could plan to assist at convenient times during their existing workflows. Participants also expressed favorability towards mechanical assistive features which were incorporated into existing equipment to ensure ubiquitous availability when needed without adding additional mass to an already cramped and awkward environment.Discussion: We discovered that the act of toileting served more than one function, and can be viewed as a valuable touchpoint in which nurses can assess, support, and encourage their patients to engage in their own recovery process as they perform a necessary and normal function of life. While we found opportunities for technology to make the process safer and less burdensome for patients and clinical staff alike, we believe that designers should preserve and enhance the therapeutic elements of the nurse-patient interaction rather than eliminate it through automation.
Quantifying soil carbon sequestration from regenerative agricultural practices in crops and vineyards
Authors: Villat Jessica , Nicholas Kimberly A. 
Published: January 2024

IntroductionRegenerative agriculture commonly aims to increase soil carbon sequestration, with potential benefits for human and ecosystem health, climate mitigation, and biodiversity. However, the effectiveness of various regenerative practices at increasing carbon sequestration is unclear.MethodsThis study identified and quantified the yearly soil carbon sequestration rate of regenerative practices in arable cropland and vineyard ecosystems through a literature review. We examined N=345 soil carbon sequestration measures across seven regenerative practices – agroforestry, cover cropping, legume cover cropping, animal integration, non-chemical fertilizer, non-chemical pest management, and no tillage.ResultsOur findings indicate that all seven practices effectively increased the carbon sequestration rate. There were no statistically significant differences among the practices. Combining these practices may further enhance soil carbon sequestration.DiscussionWe propose a sequence of regenerative practices that farmers can adopt, balancing ease of implementation and carbon sequestration effectiveness. To address under-studied practices, we recommend further research, including long-term monitoring studies and randomized controlled trials in perennial systems. Our recommendations aim to enhance the implementation and effectiveness of regenerative practices while mitigating the current challenge of limited sample sizes for quantifying carbon sequestration.