bluuebunny/crossref_metadata_2025_split huggingface dataset:
A post-marketing pharmacovigilance study of triazole antifungals: adverse event data mining and analysis based on the FDA adverse event reporting system database
Authors: Tian Yalan , Jin Min , Ning Hong 
Published: January 2025

BackgroundTo explore and analyze post-marketing adverse drug event (ADE) signals for voriconazole, posaconazole, and isavuconazole, and to compare the safety differences among the three drugs, aiming to provide insights for rational clinical use.MethodsUsing the Open Vigil 2.1 online tool, extract adverse drug event (ADE) report data for voriconazole, posaconazole, and isavuconazole from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from the time the drugs were marketed up to the third quarter of 2023. Employ the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods for data mining. Filter out ADE signals detected by both the ROR and PRR methods, and categorize these ADE signals by System Organ Class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA 26.0).ResultsA total of 8,898 ADE reports with voriconazole as the primary suspect drug were retrieved, 1,948 for posaconazole, and 944 for isavuconazole. From the basic analysis of the adverse event reports, male patients (50.31%) outnumber female patients (32.11%). In terms of age, the majority of patients are over 45 years old (52.72%). The reports primarily come from the United States, Japan, France, China, and other countries. A total of 607 ADE signals were identified, with 402 for voriconazole, 159 for posaconazole, and 46 for isavuconazole. Voriconazole ADEs primarily involved the following SOCs: Investigations (9.45%), Eye Disorders (8.46%), and Nervous System Disorders (7.21%); Posaconazole ADEs primarily involved the following SOCs: Investigations (13.84%), General Disorders and Administration Site Conditions (11.95%), and Nervous System Disorders (6.29%); Isavuconazole ADEs primarily involved the following SOCs: General Disorders and Administration Site Conditions (15.22%), Hepatobiliary Disorders (10.87%), and Blood and Lymphatic System Disorders (10.87%).ConclusionVoriconazole, posaconazole, and isavuconazole all potentially pose safety risks related to hepatobiliary disorders and cardiac disorders. Additionally, voriconazole carries a higher safety risk for eye disorders and nervous system disorders. Newly discovered ADE signals not mentioned in the drug package inserts include voriconazole-induced rhabdomyolysis, posaconazole-induced peripheral neuropathy, and isavuconazole-induced visual impairment and mental confusion. These findings are significant for guiding rational clinical use of these medications.
hERG activators exhibit antitumor effects in breast cancer through calcineurin and β-catenin-mediated signaling pathways
Authors: Yu Yan , Zhu Chengchun , Wang Xiao , Shi Ying , Gao Yiping , Yu Zhiyi 
Published: January 2025

BackgroundBreast cancer remains a leading cause of mortality among women worldwide, with existing therapeutic options often accompanied by significant side effects and a persistent risk of disease recurrence. This highlights the need for novel drug candidates with new mechanisms of action by targeting alternative signaling pathways. While hERG channel is notoriously regarded as an off-target due to drug-induced cardiotoxicity, its therapeutic potential as a drug target remains largely unexplored.MethodsThis study investigated the role of hERG in breast cancer progression and its impact on patient survival. The anti-proliferative, anti-migratory, anti-invasive and pro-apoptotic effects of hERG activators were evaluated using the Cell Counting Kit-8, wound healing assay, transwell assay and cell apoptosis assay, respectively. Western blotting, Ca2+ imaging and immunofluorescence assays were employed to study their antitumor mechanisms of actions.ResultsWe identified two novel hERG activators, SDUY429 and SDUY436, which effectively inhibited the proliferation and migration of MDA-MB-231 and MCF-7 cells. In addition, SDUY436 demonstrated significant anti-invasive and pro-apoptotic effects in MDA-MB-231 cells. Mechanistically, the anti-proliferative activity of hERG activators were mediated through calcineurin activation via enhanced calcium ion influx, which facilitated the nuclear translocation of nuclear factor of activated T cells (NFAT) and upregulated p21Waf/Cip expression. Furthermore, both SDUY429 and SDUY436 remarkably suppressed the migration and invasion of MDA-MB-231 cells by downregulating the protein kinase B (AKT)/glycogen synthase kinase-3 beta (GSK3β)/β-catenin signaling pathway. The observed reduction in phospho-AKT-Ser473 (pAKTS473) expression resulted in the decreased levels of phospho-GSK3β-Ser9 (pGSK3βS9), thereby limiting the nuclear localization of β-catenin, which led to the inhibition of cell migration and invasion. Notably, combining SDUY429 or SDUY436 with the AKT inhibitor MK-2206 produced synergistic anti-proliferative effects.ConclusionThese findings suggest that hERG activators hold promise as new potential therapeutic agents for the treatment of breast cancer, paving the way for future investigations into their clinical applications.
Characterization of rectus femoris lesions in knee osteoarthritis at different stages and the effect of ultrasound-guided acupotomy
Authors: Yu Wen-Ying , Liu Jing , Lin Ze-Hao , Liu Hong , Zhang Liang-Zhi , Feng Xiang-Long , Xiu Zhong-Biao 
Published: January 2025

IntroductionChronic injury to the rectus femoris muscle induces and exacerbates the progression of knee osteoarthritis (KOA). However, the lesion characteristics of the rectus femoris muscle in KOA at different stages have not been fully characterized. The aim of this study was to analyze the pattern of lesion characteristics of the rectus femoris muscle at different stages of KOA and to investigate the mechanism by which ultrasound-guided acupotomy operations can prevent and control KOA.MethodsEarly, middle, and late-stage rabbit KOA models were constructed using the modified Videman method. Ultrasonography was used to record the elastic modulus and cross-sectional area of the rectus femoris muscle, and morphology was used to observe the ultramicroscopic changes in the rectus femoris muscle and assess the degree of fibrosis. Additionally, ultrasound-guided acupotomy operations were performed on the rabbit model of late-stage KOA, and alterations in the key molecular markers of rectus femoris fibrosis were determined using Western Blot and qPCR methods.ResultsAs the disease progressed, the elastic modulus of the rectus femoris muscle in KOA rabbits gradually increased, the cross-sectional area gradually decreased, and the degree of fibrosis increased. In contrast, the degree of fibrosis in the rectus femoris muscle improved after ultrasound-guided acupotomy intervention.ConclusionThese findings highlight the gradual increase in the modulus of elasticity, the gradual decrease in cross-sectional area, and the increased fibrosis of the rectus femoris muscle in KOA rabbits as the disease progressed. Ultrasoundguided acupotomy operations have been shown to have a protective effect on KOA cartilage and to delay the progression of KOA by ameliorating pathological changes in the rectus femoris muscle. The mechanism may involve reducing chronic injury to the rectus femoris muscle and protecting joint homeostasis by attenuating the degree of rectus femoris fibrosis.
Deep application of controlled-release urea increases the yield and saponin content of Panax notoginseng by regulating soil nitrate distribution
Authors: Su Yun-xia , Zhao Ping , Jia Li-jie , Cao Yuan-feng , Liu Guan-ze , Chen Jun-wen , Yang Sheng-chao , Zhou Yan-li , Long Guang-qiang 
Published: January 2025

IntroductionThe deep application of controlled-release urea (CRU) offers potential advantages for crops with extended growth periods. However, its effects on P. notoginseng yield and quality, a medicinal plant with a prolonged nutrient acquisition duration, remain unclear.MethodsIn this study, we conducted a two-year field plot experiment to investigate the effect of CRU on P. notoginseng with three placement depths (0, 6, and 12 cm denoted as R0, R6, and R12, respectively) at an application dosage of 250 kg N ha-1 with biochar addition (R6B) and 20% N reduction (R6R) based on the R6, with conventional fertilization (250 kg N ha-1, common urea) serving as the control (CK).ResultsOur results indicated that yields increased by 27.1–37.6% with R0, R6, R12, and R6B, while remaining stable with R6R compared to CK. Simultaneously, the total saponin content in the roots of R6, R6B, and R6R was improved by 14.3–38.1%, compared to CK. The distribution depth of soil NO3⁻-N and plant roots increased with the depth of CRU application, with a high overlap in time and space, indicating P. notoginseng N uptake peaked when CRU was applied at a depth of 6 cm (R6). Structural equation modeling indicated that soil NO3⁻-N supply in specific microareas directly affected the N uptake and increased total saponin content by increasing root length and surface area, thus boosting yield.ConclusionThis study identifies that the deep application of CRU at a depth of 6 cm has the potential to enhance both yield and quality of P. notoginseng and highlights that the spatial-temporal matching of soil NO₃⁻-N and plant roots was the key to applying CRU to ensure high yield and quality.
Does the therapeutic alliance process explain the results of the Egokitzen post-divorce intervention program?
Authors: Alvarez Irati , Herrero Marta , Martínez-Pampliega Ana 
Published: January 2025

ObjectiveThe objective of this study was to explain the relationship between therapeutic alliance and the changes observed in the parents’ psychological symptomatology after participation in the Egokitzen program, analyzing the mediating role of emotion regulation.MethodsThe study involved 117 divorced parents and 40 therapists.ResultsIt has been observed that the early development and maintenance of the therapeutic alliance influence the parents’ psychological symptomatology after the intervention, through emotion regulation.ConclusionThe study reinforce the role of the therapeutic alliance as a determining factor in the success of group interventions. This effect has turned out to be indirect through emotion regulation, highlighting the importance of emotional management.
Students’ cross-domain mindset profiles and academic achievement in Finnish lower-secondary education
Authors: Laurell Jenni , Puusepp Ita , Hakkarainen Kai , Tirri Kirsi 
Published: January 2025

IntroductionThis study uses a person-centered approach to explore Finnish lower-secondary school students’ (N = 1106) mindsets across intelligence, giftedness, and creativity. It further investigates the relationship between mindsets profiles, school achievement in various subjects, and gender differences, aiming to address the domain-specificity of the three ability domains.MethodsA self-reported questionnaire was used to measure students’ mindsets, with latent profile analysis (LPA) identifying distinct profiles. School achievement was assessed through academic grades in core and arts subjects, while gender differences in profile membership were examined via logistic regression.ResultsFour mindset profiles emerged: Growth, Fixed, Mixed, and Opposing. Most students exhibited consistent “general” mindsets across domains, except those in the Opposing profile, who combined a growth mindset for intelligence and creativity with a fixed mindset for giftedness. Students in the Opposing profile outperformed others in mathematics and foreign languages, while those in the Growth profile excelled across other subjects. The Fixed profile was linked to the lowest achievement, except in reading, foreign languages, and music, where Mixed and Fixed profiles performed similarly. Girls were more likely to belong to the Growth profile, while boys dominated the Fixed and Opposing profiles.DiscussionThe findings highlight the cross-domain nature of mindsets but reveal unique domain-specific variations, particularly for giftedness. These differences influenced academic outcomes, underscoring the nuanced role of mindsets in student achievement. Gender disparities in mindset profiles align with observed differences in school performance.ConclusionBy identifying distinct mindset profiles, this study emphasizes the complexity of students’ beliefs and possible educational implications. Future research should explore qualitative aspects of mindset formation across ability-related constructs, its broader motivational frameworks, and their relation to students’ academic outcomes.
The efficacy of telemedicine interventions on quality of life and depression in individuals with spinal cord injury: a systematic review and meta-analysis
Authors: Tan YinHu , Liang Xue , Ming Wei , Xing HuiMin , Liang Yan , Wang Yang , Onodu Emmanuel Onyebuchi 
Published: January 2025

ObjectiveThe purpose of this systematic review and meta-analysis is to examine the impact of telemedicine interventions on the quality of life (QoL) and depression in individuals with spinal cord injury (SCI).MethodsA literature search was conducted in four electronic databases (PubMed, Web of Science, EMBASE, and the Cochrane Library) from their inception to February 1, 2024. Two authors independently screened the studies and extracted the data. Cochrane’s bias risk tool for randomized controlled trials was used to examine the methodological quality of the included studies. A meta-analysis was conducted using Review Manager (version 5.4) to synthesize the results of the included studies.ResultsA total of 10 trials with 728 participants were included in the review. The results of the meta-analysis showed that telemedicine interventions significantly improved QoL [Standardized Mean Difference (SMD)=0.72, 95% Confidence Interval (CI) (0.11, 1.32), P=0.02] and reduced depression scores [SMD=-0.18, 95% CI (-0.31, -0.05), P=0.006].ConclusionsTelemedicine interventions are a feasible method to support people with SCI, and can mitigate depression and enhance quality of life. In the future, studies should involve larger sample sizes and extended follow-up periods to validate these findings and to identify the most effective telemedicine interventions for improving the overall health outcomes of individuals with SCI.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024508702.
A protocol for mobilising novel finance models for collaborative health promotion and disease prevention initiatives: taking a smart capacitating investment approach in the Invest4Health project
Authors: Lane Joanna , Edwards Rhiannon T. , Babarczy Balázs , Whiteley Holly , Oruganti Vidya , Rutten-van Mölken Maureen , Costongs Caroline , Jani Anant R. , Wordsworth Sarah , Maassen Alison , Tsiachristas Apostolos , Davies Jacob , Stavenow Bengt , van Vliet Jolanda , Wright Steve , Papartyte Lina , Camaradou Jennifer Catherine , Koleva-Kolarova Rositsa 
Published: January 2025

BackgroundThe prevalence of preventable non-communicable disease (NCD) underpins the need for a life-course and cross-sectoral approach to population health that is grounded in health promotion and disease prevention. European Union (EU) countries typically spend 6 to 13% of gross domestic product (GDP) on health care, yet less than 3% of this is dedicated to prevention. The extent to which spending in other sectors prevents avoidable ill-health is largely unknown. The lack of fiscal space post-COVID-19 means shifting from models of care built around treatment to those with greater emphasis on prevention will require innovative, evidence-based investment within and between sectors. The term “smart capacitating investment” (SCI) has previously been used to understand how to best boost social infrastructure investment in education, health, transport and housing across the EU. Here we take that idea further by exploring the applicability of SCI to public health financing to improve population health and well-being.AimTo explore and develop innovative SCI models and tools that enable collaboration and investment across health ecosystems for enhanced health promotion and disease prevention, test them in diverse real-world settings, and create a roadmap for large-scale implementation.MethodsThe Invest4Health (I4H) project brings together transdisciplinary expertise in epidemiology, public health, health economics, population science, business management, finance, implementation and social sciences, digital health innovation, and regional health systems. The project consists of eight work packages which span the exploration and conceptualisation of SCI in public health; the characterisation of SCI-compatible business and finance models; piloting and evaluation of these models in four European testbeds (Sweden, Germany, Spain and Wales UK); and exploring the opportunities for sustainable replication and scaling of SCI and future research.DiscussionWe present an introduction to the I4H project, the concept of SCI applied to public health, plus key points for discussion internationally.
Socio-economic inequalities in access to COVID-19 tests in France in 2020: evidence from the EPICOV socio-epidemiological cohort
Authors: Geoffard Pierre-Yves , Jusot Florence , Sireyjol Antoine , Warszawski Josiane , Bajos Nathalie 
Published: January 2025

BackgroundTesting for COVID-19 has been strongly recommended for individuals experiencing COVID-19-like symptoms or those with a close relative who tested positive. In France, tests were free of charge until mid-October 2021 and became widely available after June 2020. Our main objective was to investigate whether access to COVID-19 testing in France was associated with socio-economic conditions, considering gender and ethno-racial status.MethodsA random population-based cohort survey was conducted in France in May 2020 and November 2020, including 95,388 participants aged 18 and over. We used logistic regressions to identify how having been tested in 2020 was associated with socio-economic status and exposure factors among two groups of individuals. The first group consisted of individuals who had no close relative test positive but reported experiencing COVID-19-like symptoms, such as cough, fever, dyspnea, or sudden onset of ageusia, dysgeusia, or anosmia (N = 12,729). The second group included individuals, with or without symptoms, who reported that a close relative had tested positive for COVID-19 (N = 5,360).FindingsIn both groups, testing was more frequent among individuals living in urban areas. For individuals who had no close relative test positive but reported COVID-19-like symptoms, women were 1.04 (95%CI [1.01–1.06]) more likely than men to be tested, and testing decreased with age up to 35. Individuals holding a university degree were (1.08 [1.04–1.12]) more likely than those who only completed high school to be tested, as well as those in one of the three top income deciles with reference to the bottom decile (OR 1.07, [1.02–1.13] for the top decile). Ethno-racial status was not significantly associated with testing. For respondents who had a close relative test positive, testing was strongly associated with having experienced some symptoms, especially after September 1 (OR 1.34, 95%CI [1.30–1.39]). However, there was no link between testing and income, education, or ethno-racial status.InterpretationWhen an individual experiences symptoms but has no close relative who is positive, the motivation to test to avoid transmitting the virus to relatives by isolating oneself is particularly strong. This strategy makes sense when there are actual possibilities to isolate, which may explain why higher income and education positively impact the propensity to test. For individuals who had a close relative test positive, most socio-economic variables were no longer related to testing once infection risk was controlled for. The availability of tests at no cost is not sufficient in itself to eliminate socio-economic inequalities in testing.
Prevalence and characteristics of HPV vaccine hesitancy among parents of adolescent females across Saudi Arabia
Authors: Othman Sahar , Ghamri Ranya , Alhamadah Wala , Alsatty Anwaar , Khesfaty Dhuha , Alghamdi Ohoud , Arbaein Ragad , Baglagel Alaa M. , Khayyat Jumana , Almalki Bushra 
Published: January 2025

PurposeVaccination against human papillomavirus (HPV) is pivotal in preventing HPV-related diseases, including cervical cancer. However, vaccine hesitancy and their related factors among parents of adolescent females present a significant obstacle to achieving high vaccination rates. HPV vaccine hesitancy among parents of adolescents and their related factors have been studied at the regional level in Saudi Arabia, but national-level data are not available. Therefore, this study aims to assess the prevalence and characteristics of HPV vaccine hesitancy among parents of adolescent females in Saudi Arabia.Materials and methodsThis cross-sectional study was conducted in Saudi Arabia among parents of adolescent females aged 11–17 years between November and December 2022. The participants completed a self-administered online questionnaire containing the validated Vaccine Hesitancy Scale (VHS), which was originally developed in 2015 by the WHO’s Strategic Advisory Group of Experts (SAGE) on immunization. Descriptive statistics, univariate binomial regression, and multivariate binary logistic regression were employed for statistical analysis.ResultsAmong the 667 participants who completed the questionnaire, 34% were hesitant about immunizing their adolescent daughters with the HPV vaccine. A few demographic variables were significantly associated with vaccine hesitancy, including lower household income and living in the southern region. In addition, lack of recommendation by their healthcare provider and inconvenience related to immunization with the vaccine were also associated with higher levels of hesitancy.ConclusionHPV vaccine hesitancy remains high among parents of adolescent females in Saudi Arabia. More effort needs to be directed toward educating parents, especially during doctor’s visits, in order to increase the acceptance and vaccination rates.