The clinical translation of Minibeam RT (MBRT) has recently started thanks to the first human treatments recently performed. However, despite experimental evidence, the impact of the dose distribution parameters involved on the magnitude of the effect itself and the underlying radiobiological mechanisms are still only partially understood. To address this issue, systematic investigations are needed through the implementation of advanced quantitative experiments with a multidisciplinary approach, which is the one proposed in the framework of the INFN funded MIRO (MInibeam RadiOtherapy) project. The aim of this work is to report on the on-going main activities recently carried out in the framework of the project, showing some of the main results achieved during the first 2 years of the project, in terms of: (i) facilities development and characterization; (ii) new dosimetric approaches; (iii) biological investigation of the effect; and (iv) development of the first tools for dose planning. The multidisciplinary approach adopted by this national Collaboration to tackle the main challenges of minibeam radiotherapy for a reliable and solid clinical translation is discussed. The facilities involved in the project are: (i) two facilities dedicated to low (up to 9 MeV) and medium (up to 18 MeV) energy electron minibeam studies, one of them also equipped with an electron FLASH LINAC to study possible synergistic effects with UHDR beams; (ii) one facility dedicated to proton minibeam studies, with energies from 70 to 140 MeV. Novel dosimetric approaches, are presented, mainly based on scintillators, silicon and silicon carbide detectors. Novel techniques for the analysis of biological samples are described, leveraging both integrated averaged data and spatially resolved analysis. Furthermore, a framework for biological modeling using a multiscale approach is presented. A dedicated dose-planning tool is currently under development to compare "virtual" minibeam plans with conventional ones and, consequently, to quantitatively investigate the potential for clinical translation. All the facilities were dosimetrically characterized, demonstrating the capability of producing controlled and reproducible electron and proton minibeams. These beams exhibited diverse physical parameters, including peak-to-valley ratios between 3 and 30 at the entrance and center-to-center distances between 2 and 3 mm. The developed detectors, specifically scintillators and silicon detectors, successfully measured the minibeam patterns with sub-millimeter resolution, while large-area silicon carbide detectors were used for average dose measurements. First in-vitro biological investigations performed with low energy minibeams clearly showed an enhanced survival fraction in the 16HBE healthy lung cells, while maintaining iso-effective cell killing in A549 cancer cells. Furthermore, a synergy was observed when combining UHDR electron beams with minibeams. The multidisciplinary approach was consolidated during these first 2 years of the MIRO project, as demonstrated by the results obtained both in terms of dosimetric characterization and biological investigations. The dedicated framework for modelling is being optimized to support the biological findings, allowing for a better interpretation of the results. The tool for dose planning, still under development, will allow the investigation of peculiar configurations to explore new frontiers in the perspective of future human trials.
Conventional underlying-cause surveillance shows a declining prostate cancer mortality trend in the United States. MCOD analysis, which also includes deaths where bone metastasis was co-documented as a contributing cause, may identify a different trajectory than single-cause coding. Objective: To characterize 25-year trends in prostate cancer mortality with co-documented bone metastasis, quantify divergence from underlying-cause surveillance, and project age-adjusted mortality rates (AAMRs) to 2040 across demographic and geographic subgroups. We queried CDC WONDER (1999-2024) for deaths with prostate cancer (ICD-10: C61) as the underlying cause and bone metastasis (C79.5) as a contributing cause. Joinpoint regression characterized temporal trends, and ARIMA and exponential smoothing models with RMSE/MAPE-based selection generated stratum-specific projections. Analyses were stratified by age, race/ethnicity, US Census region, and urbanization. In total, 73,429 deaths met the dual-code definition. The overall AAMR rose 93%, from 1.10 to 2.12 per 100,000 [average annual percent change (AAPC): +2.61%; 95% CI: 1.66-3.56; p < 0.000001]; however, this net increase followed an initial decline from 1999 to 2006 [annual percent change (APC): -5.57%] and reflected an acceleration to +12.91% annually during 2013-2018. Conventional underlying-cause surveillance showed an AAPC of -1.55%. Non-Hispanic Black or African American men had a mean AAMR 64% higher than non-Hispanic White men (1.89 vs. 1.15 per 100,000); in model-based projections, this ratio widened from 1.54 (2025) to 1.78 (2040). In 2024, men aged 65-85+ had a 17-fold higher AAMR than those aged 45-64. The overall AAMR is projected to reach 3.65 (95% CI: 0.88-6.43) by 2040, with wide prediction intervals reflecting substantial uncertainty. MCOD surveillance identified a sustained 25-year increase in co-documented prostate cancer and bone-metastasis deaths, diverging from the declining underlying-cause-only trend. The post-2013 acceleration predates the COVID-19 pandemic and persisted in sensitivity analyses. Rates were higher among older men, non-Hispanic Black or African American men, and non-metropolitan residents. As death-certificate-based measures, these estimates reflect documented bone metastasis rather than the true incidence of bone-metastatic disease and may be affected by evolving documentation and coding practices. Findings support incorporating MCOD-based metrics into national prostate cancer surveillance and targeted evaluation of care needs in higher-burden subgroups.
Heart failure (HF), a common comorbidity of chronic obstructive pulmonary disease (COPD), is associated with an increased risk of death among patients with COPD. However, no systematic assessment has quantified the population-level burden of comorbid COPD and HF, hereafter referred to as COPD-HF comorbidity, worldwide. This study assessed the global, regional, and national burden of COPD-HF comorbidity from 1990 to 2021 and projected this burden to 2050. Data on the non-fatal burden of COPD-HF comorbidity, including prevalence and years lived with disability (YLDs), were obtained from the Global Burden of Disease Study 2021. Temporal trends in age-standardized rates (ASRs) for COPD-HF comorbidity from 1990 to 2021 were examined using joinpoint models. Bayesian age-period-cohort models were used to project ASRs to 2050. From 1990 to 2021, the absolute numbers of prevalent cases and YLDs for COPD-HF comorbidity increased globally, and the ASRs for prevalence and YLDs also increased. These upward trends were projected to continue to 2050. The burden of COPD-HF comorbidity was consistently higher in men than in women and higher in older adults than in younger individuals. By severity level, the burden of COPD-HF comorbidity was mainly attributable to the treated and severe subtypes of HF. The burden varied substantially across regions, with low-development regions having the highest age-standardized burden. The global non-fatal burden of COPD-HF comorbidity was substantial from 1990 to 2021 and may continue to increase to 2050. Public health interventions targeting COPD-HF comorbidity may help reduce this burden.
Hearing loss (HL) constitutes a significant hazard to the health and social welfare, yet there is a lack of data on its burden in young adults (YAs) aged 15-39 yr. This study aimed to delineate the global temporal trends and predict the future burden of HL in YAs. Using data from the Global Burden of Disease study 2021, we analyzed the prevalent cases and age-standardized prevalence rates (ASPR) of HL in YAs by age, sex, and Socio-demographic Index(SDI). The age-period-cohort (APC) model was used to assess trends, while the Bayesian Age-Period-Cohort (BAPC) model projected future epidemiological trajectories. Globally, HL prevalent cases in YAs increased from 171.77 million (95% CI: 145.95-200.16) in 1992 to 256.16 million (95% CI: 222.49-293.87) in 2021. The ASPR rose from 7862.80 to 8474.66 per 100,000 over this period, with males consistently showing higher rates than females. APC analysis revealed age-dependent increases in hearing loss risk, adverse period effects in recent years (2012-2021), and a peak relative risk in the 1997-2006 birth cohort. The BAPC model projects 291.37 million (95% CI: 182.25-400.49) prevalent cases by 2040. The global burden of HL in YAs is rising, particularly since the relative risk of HL has continued to grow during the last 10 years, highlighting the need for further research and intervention.
The risk of mosquito-borne diseases is expected to increase due to climate change, and thus it is needed to forecast how mosquito abundance would vary in response to dynamic climatic conditions. Both short-term prediction and long-term projection are essential for supporting timely mosquito control and mitigating vector-borne disease risk. This study developed a machine learning-based forecasting framework to support an early warning system for short-term mosquito abundance prediction and to project long-term mosquito abundance. Short-term prediction was conducted using machine learning models (MLMs) with short-term meteorological forecast data. Long-term projection was made by future climate data (∼2100) under SSP1-2.6 and SSP2-4.5. Results showed that MLMs using short-term meteorological forecast data produced mosquito abundance comparable to those using observational data (R2 difference of 0.03), demonstrating the reliability of short-term predictions. In addition, it outperformed the current monitoring system with R2 improvements of 0.20-0.48 across all landscape type. These results indicate that reliable forecasts of mosquito abundance can be provided in advance, enabling public health agencies to implement mosquito control measures before mosquito abundance increases. SHapley Additive exPlanations analysis indicated that the previous day's mosquito abundance and maximum temperature were the most influential ecological and meteorological predictors. Under climate change scenarios, mosquito abundance was expected to decrease due to higher temperatures. In contrast, the rate of increase in mosquito abundance during spring is expected to rise, indicating a temporal shift in mosquito occurrence. These seasonal shifts suggest that mosquito surveillance and vector control may need to begin earlier to mitigate mosquito-borne disease risk. Overall, the proposed framework provides a practical decision-support tool for mosquito surveillance, vector-borne disease risk mitigation, and One Health preparedness under climate change.
There is growing emphasis on the importance of active partner engagement in research and the design, planning, and implementation of new programs. Indeed, the science of engagement is gaining is receiving more attention from researchers, being formally included in research studies more often, and increasingly being required by funders. Financial costs and economic implications are well-known drivers of successful adoption, implementation, and sustainment of evidence-based programs; however, partner engagement costs are often excluded from economic evaluations even when elements of engagement may be relevant to sustainment and replication. Resource constraints in both research and practice highlight the need to better understand engagement costs to ensure that scarce resources are put towards the richest engagement activities. As part of the Rapid and Rigorous Patient-Centered Program (R2P2) in Colorado, we designed an approach to systematically document and analyze partner engagement costs across four prototype projects. We describe this approach, summarize needed adaptations, share an interactive data collection template, synthesize the relevant engagement costs during implementation, replication, and sustainment, and discuss lessons learned. Our experiences in R2P2 in costing initial engagement activities across four diverse projects offer direction for future research and practice that balances high-quality partner engagement with efficiency in addressing resource constraints facing researchers and practitioners.
With climate and biodiversity crises intensifying, integrated solutions are urgently needed. Rewilding offers a promising approach to ecosystem restoration and climate adaptation. However, challenges regarding land-use, societal conflicts and governance can hinder its implementation. This paper discusses the elements of transformative thinking that can support rewilding implementation and establishment as an innovative approach to ecological recovery. We draw on the lessons learned from over 30 years of rewilding in the Gelderse Poort, the Netherlands. The floodplains in this area have been transformed from a predominantly dry, agricultural landscape into a dynamic riverine nature landscape with a broader range of socio-economic services in a peri-urban area and densely populated region. We describe how a readiness to embrace uncertainty, supportive policies, dedicated champions and innovative funding partnerships were crucial for this rewilding project. We explore how these lessons can inform rewilding efforts in Europe to deliver both climate resilience and biodiversity benefits.
This work is a result of a pilot study integrated in an international project of collaboration and consists in the developing a comprehensive methodological framework to investigate the multifactorial nature of corrosion in hospitals across Spain, Romania and Turkey. By integrating multidisciplinary perspectives from engineering, materials science and law, the program prepares participants to address corrosion challenges through both technical competence and regulatory awareness. This pilot study conducted at Dr. Negrin Hospital (Spain) validated the methodology, involving 3 hospital professionals and 11 students with 3 academic staff from the University of Las Palmas de Gran Canaria. The study included environmental monitoring, laboratory experiments on electrochemical behavior and protective strategies against corrosion. Representative functional zones (including operating rooms, sterilization units, HVAC systems, intensive care units and patient wards) were instrumented with environmental monitoring devices to record pollutants, temperature, humidity and particulate matter. Metal coupons made of stainless steel, carbon steel, aluminum and zinc were exposed under simulated hospital conditions to assess corrosion rates. Data analysis combined quantitative and qualitative approaches to ensure methodological feasibility and reliability. The results emphasize that corrosion in healthcare settings has significant technical, economic and legal implications. Preventive strategies and continuous monitoring can reduce maintenance costs, enhance patient safety and ensure regulatory compliance. Ultimately, this work underscores the importance of multidisciplinary education and international collaboration in developing sustainable corrosion management practices for modern healthcare infrastructure.
The rapid global expansion of digital technologies has reshaped everyday life across generations, yet the role of smartphones in older immigrants' social well-being remains insufficiently understood. Drawing on the sociotechnical perspective that ageing and technology are co-constituted, our study examines how Mandarin-speaking older immigrants in Canada use smartphones to overcome social isolation and sustain social participation. Data were obtained from 102 qualitative interviews conducted across seven Canadian cities as part of the Inclusive Communities for Older Immigrants (ICOI) project. The data were analysed using a hybrid deductive-inductive thematic analysis. Three overarching themes were identified: experiences of social isolation, shaped by linguistic, cultural, and seasonal barriers; smartphones as tools for social connection; and smartphones as facilitators of social participation, enabling both online engagement and the coordination of in-person activities. Study findings demonstrate that smartphones operate not merely as communication devices but as sociotechnical infrastructures that sustain belonging, enable local and transnational connectivity, and support mutual aid among older immigrants. At the same time, they complement rather than replace in-person interaction, with many participants preferring face-to-face social engagement when feasible. This study contributes to critical gerontology and migration scholarship by illustrating how digital technologies address social isolation among older immigrants and highlights the need for culturally and linguistically tailored digital inclusion initiatives that promote equitable ageing in diverse societies.
Gaining clinical trial design and management experience can be challenging for students in class. Opportunities for students to participate in designing and implementing a "from scratch" design are essential to succeeding after graduating. Limited materials are available that provide meaningful opportunities for learners to practice and implement adaptive trial design. As a solution, we developed an open-source case study framework that instructors can use directly in a course to give students hands-on experience with Bayesian adaptive trial design and implementation. We developed an open case study (DRIVE trial) project, which offers an instructor-ready framework organized into seven components. Each component is designed to map onto a distinct stage of a clinical trial and include materials that instructors can adapt to match their course level and chosen scientific questions. These components are tied together by a worked example in which, after comparing multiple study designs, a Bayesian adaptive design with response adaptive randomization was chosen and implemented throughout the framework. The framework provides instructors with a complete, ready-to-use template for bringing adaptive trial experience into the classroom without building a case study from scratch. The study's significance lies in its broader implications for biostatistics student training and experience. The trial underscored the effectiveness of comparing study designs and the necessity for collaboration when implementing a clinical trial. This offers valuable practical training and resources for future biostatisticians, serving as a template across various fields. Supplementary materials for this article can be found online (https://github.com/BayesPhase/DRIVE).
ATP-binding cassette transporter A1 (ABCA1) has been associated with Alzheimer's disease (AD), but the mechanisms by which it impacts disease risk are unknown. ABCA1 is known to bind apolipoprotein E (ApoE) and catalyze apolipoprotein lipidation. We explored whether genetic variants altering ABCA1 function interact with APOE isoforms to modify AD risk. Using data from the Alzheimer's Disease Sequencing Project (ADSP), UK Biobank, and the Alzheimer Disease European Sequencing consortium, we assessed the impact of ABCA1 variants on AD risk in APOE subgroups and tested for statistical interactions with APOE ε2 and ε4 in an all-APOE cohort. We first examined damaging nonsynonymous ABCA1 variants previously associated with AD. We then constructed a measure of predicted ABCA1 activity based on HDL-associated variants and tested its association with AD risk. Finally, we explored potential pathogenic mechanisms of missense variants of interest. Damaging nonsynonymous ABCA1 variants had differential AD risk effects between APOE genotype groups and exhibited interaction effects with APOE ε2 and ε4. Predicted ABCA1 activity based on HDL-associated variants was associated with reduced AD risk and interacted with APOE ε4. Replication analyses suggested similar differences in effect size of ABCA1 variants between APOE groups and had concordant effect directions, although not statistically significant, in the APOE interaction model. ABCA1 missense variants N1800H and E1172D were strongly associated with plasma HDL and interacted with APOE in AD risk. In cell-based assays, ABCA1-N1800H showed plasma membrane localization defects potentially driven by misfolding. Genetic modifiers of ABCA1 activity interact with APOE isoforms to alter AD risk. ANN NEUROL 2026.
The commercial pork production sector prioritizes genetic improvements in lean meat percentage to enhance profitability and meet consumer preferences. The Pietrain pig, a premier terminal sire breed renowned for its exceptional muscularity and leanness, serves as an ideal model to decipher the genetic underpinnings of these traits. This study investigated two key measures of leanness, backfat thickness and loin muscle depth, in two distinct Pietrain populations to elucidate the genetic architecture underlying these traits. We estimated genetic parameters and performed a meta-analysis of genome-wide association studies, identifying ABCD4, LTBP2, NUMB, and SLC30A9 as candidate genes. To further investigate these associations, we integrated information on molecular quantitative trait loci from the PigGTEx project and single-cell transcriptomic resources. This integrative approach prioritized ABCD4 as a key candidate gene regulating backfat thickness. Functional validation in 3T3-L1 preadipocytes revealed a novel dual regulatory role for ABCD4: its knockdown suppressed cell proliferation while simultaneously stimulating adipogenic differentiation, as demonstrated by the upregulation of key markers. Our findings positioned ABCD4 as a critical modulator of fat deposition, likely through its influence on the core adipogenic transcriptional network. By establishing an analytical framework that integrates large-scale sequencing data from Pietrain pigs with functional validation, our study addresses a key gap in understanding the genetic basis of leanness and provides novel insights for precision breeding.
Contraceptive implants are highly effective long-acting reversible contraceptives (LARCs), yet early discontinuation remains a major challenge globally and in Nigeria, undermining family planning (FP) goals. Community Pharmacists (CPs) and Patent and Proprietary Medicine Vendors (PPMVs) have been trained through the IntegratE Project, to expand access to implant, but evidence on discontinuation patterns among their clients is limited. This retrospective descriptive study analyzed 874 routine service delivery records of women aged 15-49 years who sought implant removal services from trained CPs and Tier 2/3 PPMVs between July 2023 and June 2025 across four Nigerian states (Enugu, Kaduna, Kano, and Lagos). Early discontinuation was defined as removal within two years of insertion. Descriptive statistics summarized socio-demographic and service-related characteristics, while bivariate and multivariate logistic regression identified predictors of early removal. Overall, 28.4% (n = 248) of implant users who discontinued discontinued early, with similar proportions for Implanon (29.5%) and Jadelle (25.7%%). More than half (57.6%) of early discontinuers removed their implants within 12 months of insertion. Side effects (38.9%) and desire for pregnancy (37.2%) were the most reported reasons for discontinuation whether early or not, while partner disapproval accounted for 15.4%. Adjusted analysis showed women aged 35-39 years were less likely to discontinue early compared with those aged 25-29 years [Adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI): 0.31-0.80; p = 0.004]. Geographic variation was noted, with lower odds in Enugu (AOR = 0.53; 95% CI: 0.30-0.91; p = 0.02). Side effects (AOR = 3.01; 95% CI: 1.89-4.78; p < 0.001) and partner disapproval (AOR = 2.31; 95% CI: 1.25-4.26; p = 0.007) were significant predictors. Almost one-third of discontinuers served by CPs and PPMVs did so early that is at less than 24 months, primarily driven by side effects and partner opposition. Strengthening counselling, managing side-effects, and engaging male partners are critical to improving continuation and advancing Nigeria's FP goals.
To understand the experience of fatigue and cognitive impairment in adults with symptomatic primary sclerosing cholangitis (PSC) as an essential first step towards developing PSC-specific symptom measures. Purposeful sampling was used to identify 17 symptomatic adults from the PSC Symptom Assessment Project who met general trial eligibility criteria for in-depth concept elicitation interviews focused on key PSC symptoms. Of these, twelve were interviewed in-depth about fatigue and eleven about cognitive impairment. Interviews were conducted virtually, audio-recorded, transcribed and analysed. The Theory of Unpleasant Symptoms guided the development of a PSC symptom conceptual framework. Participants were on average 42 years old, 57% male, 71% White and 57% had inflammatory bowel disease. Half experienced fatigue and cognitive impairment daily, while others described varying frequencies of these symptoms. Most participants described fatigue getting progressively worse throughout the day, often requiring naps. Fatigue interfered with domestic duties, job responsibilities and family/social activities. Fatigue impacted mental health with frustration, sadness and guilt. Participants with cognitive impairment reported it ranged from mild to severe, with some unable to live independently or maintain employment. Working memory, verbal fluency, attention and processing speed were impacted. Fatigue and cognitive impairment frequently co-occurred but could occur separately. PSC-related fatigue and cognitive impairment impact daily, work-related, emotional and social functioning in symptomatic adults. These qualitative findings inform the customization of PSC-specific fatigue and cognitive function measures with strong content validity that is necessary for use in PSC research and clinical trials. In‐depth interviews with symptomatic patients with PSC found that fatigue and cognitive impairment have a significant impact on patients' lives. These data inform the design of PSC‐specific fatigue and cognitive impairment instruments.
The East African immigrant community in San Diego has proactively sought multi-generational, nutrition-focused strategies for the prevention and management of cardiometabolic disease. Existing studies on Somali immigrants in the U.S. Midwest document elevated rates of diabetes (4.5-21.1%), overweight/obesity, and dyslipidemia, while qualitative evidence indicates that dietary acculturation, particularly within the first decade of migration, is associated with decreased consumption of traditional foods and increased exposure to sodium- and sugar-dense processed foods. This community case study describes the long-standing community-academic partnership between United Women of East Africa Support Team (UWEAST) and the University of California, San Diego Herbert Wertheim School of Public Health Anderson Lab, operationalized through the Healthy Eating with Spices and Herbs to Manage Hypertension (HAWAASH) research project series and formative phase of HAWAASH2. Guided by Community Based Participatory Research (CBPR) and community-driven research principles, the partnership prioritized social participation, empowerment, and capacity building through shared governance, community-led recruitment, multilingual engagement strategies, and culturally responsive implementation practices. Using a convenience sampling approach with an iterative mixed-methods formative design, 60 community members and seven key informants contributed to shaping the design of a future culturally tailored nutrition intervention. Activities were conducted at the UWEAST community hub in City Heights, San Diego. Grounded theory-guided thematic analysis identified five themes from community member interviews and four themes from key informant interviews, encompassing cultural food identity, structural barriers to healthy eating, dietary acculturation experiences, community social assets, and readiness for nutrition programming. This case study highlights practical strategies, lessons learned, and contextual constraints relevant to advancing equitable, community-driven nutrition initiatives among underrepresented immigrant populations. Detailed findings on measurement tool acceptability and proof-of-concept intervention plausibility are reported in companion manuscripts.
Community engagement is essential to research. Community Advisory Boards (CABs) are frequently consulted to inform recruitment and engagement strategies. In our experience, a gap emerged between CAB recommendations and implementation, largely due to limitations in research infrastructure, funding, and team capacity. Researchers may underappreciate why providing contextual details about studies that relate to resources or constraints, can lead to tailored recommendations. In response, our institutional CAB now incorporates researcher input before and after consultations to clarify programmatic and institutional limitations. This ongoing, bidirectional dialogue supports more pragmatic, tailored recommendations that better align with research team capacity while advancing shared goals.
Spermiogenesis is a highly specialized differentiation process involving by extensive nuclear remodeling and cytoplasmic reorganization. Disruption of these events is a major cause of male infertility, however the genetic determinants underlying human spermiogenic failure remain incompletely understood. NUP210L, which encodes a testis-enriched nucleoporin, has recently been implicated in male infertility, although direct evidence in humans is limited and murine models do not fully recapitulate the human phenotype. To investigate the genetic basis and spermiogenic consequences of a homozygous NUP210L variant in a patient with severe oligoasthenoteratozoospermia (OAT), and to evaluate its impact on fertilization. A consanguineous family with an affected male proband was studied. Whole-exome sequencing followed by Sanger validation was performed to identify the causative variant. Comprehensive sperm analyses, including light and transmission electron microscopy, immunofluorescence, Western blotting, and chromomycin A3 staining, were conducted to assess ultrastructure, protein localization, and chromatin remodeling. Fertilization outcomes of intracytoplasmic sperm injection (ICSI) with or without artificial oocyte activation (AOA) were evaluated. A homozygous in-frame deletion in NUP210L (c.1501_1503del, p.Ser501del) was identified. Patient sperm exhibited marked spermiogenic defects, including impaired chromatin condensation, acrosomal abnormalities, mitochondrial sheath disorganization, and fibrous sheath dysplasia. Although NUP210L protein levels were preserved, immunofluorescence revealed abnormal accumulation and mislocalization, suggesting functional impairment rather than loss of expression. Chromomycin A3 staining indicated significant histone retention, consistent with defective nuclear remodeling. Notably, the sperm-specific oocyte activation factor PLCζ was undetectable, consistent with total fertilization failure (TFF) following conventional ICSI. In contrast, ICSI combined with AOA successfully restored fertilization and enabled blastocyst development. This study identifies a homozygous NUP210L variant associated with severe spermiogenic defects and impaired sperm function. The findings support a role for NUP210L in human spermiogenesis that is not fully recapitulated in murine models. The successful rescue of fertilization by AOA further suggests that NUP210L-related defects are associated with impaired oocyte activation, providing human-based evidence that nucleoporin dysfunction contributes to male infertility.
This study aimed to develop and validate the Thai AI Literacy Scale for Nursing Students (TAILS-NS). A cross-sectional study was conducted across multiple nursing institutions in Thailand from March to May 2026 to address the absence of a validated artificial intelligence (AI) literacy instrument for nursing students in Thai or Southeast Asian contexts. A total of 410 nursing students participated, yielding a response rate of 94.5%. The TAILS-NS was developed through item generation, expert content-validity assessment using the item-objective congruence index, and a 2-phase pilot study, resulting in a 40-item instrument comprising a 15-item knowledge test and 25 Likert-scale items across 6 domains. Exploratory factor analysis using maximum likelihood estimation and confirmatory factor analysis using the weighted least squares mean and variance-adjusted estimator, as well as internal consistency, convergent validity, and discriminant validity, were assessed. An independent validation sample (n=157) was recruited for cross-validation confirmatory factor analysis. Raw data are available as a supplement. Exploratory factor analysis supported a 6-factor structure: AI awareness, skills, ethics and professionalism, positive attitude, AI anxiety, and readiness. Confirmatory factor analysis showed acceptable model fit, although the root mean square error of approximation (RMSEA) indicated marginal fit (comparative fit index [CFI]=0.919, Tucker-Lewis index [TLI]=0.906, RMSEA=0.090). Reliability of the knowledge subscale was acceptable (Kuder-Richardson Formula 20=0.758). Internal consistency was excellent (α=0.810-0.934; total α=0.974; ω=0.989). Average variance extracted exceeded 0.50 for all factors, supporting convergent validity. Most heterotrait-monotrait ratios were below 0.90, supporting discriminant validity. Cross-validation confirmed factorial replicability (CFI=0.917, TLI=0.904). The TAILS-NS provides evidence of validity and reliability for measuring AI literacy among Thai nursing students and may serve as a standardized tool for curriculum evaluation. Future studies should expand the AI anxiety subscale and explore cross-cultural applicability in Southeast Asian nursing contexts.
The purpose of this study was to compare the efficacy of different non-pharmacological multicomponent interventions in community-dwelling older adults with frailty or prefrailty and to determine the most effective non-pharmacological multicomponent interventions. Frailty or prefrailty is highly prevalent among community-dwelling older adults and contributes to significant distress among older adults and increases the caregiver burden. Non-pharmacological multicomponent interventions are recommended for first-line management; however, the comparative efficacy among interventions remains unclear. A systematic electronic literature search was performed in the PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL, Chinese National Knowledge Infrastructure (CNKI), Wanfang, VIP and Sinomed databases up to July 1, 2025. Randomized controlled trials (RCTs) evaluating the efficacy of non-pharmacological multicomponent interventions compared with routine care or other interventions in community-dwelling older adults with frailty or prefrailty were included. A random effects model based on restricted maximum likelihood (REML) estimation was used for the network meta-analysis. Efficacy was assessed via standardized mean differences with 95% credible intervals, and interventions were ranked via surface under the cumulative ranking curve (SUCRA) probabilities. Twenty-two RCTs were included in the analysis. For overall frailty level, exercise + cognitive intervention achieved the highest rank (SUCRA = 84.7%), followed by exercise + cognitive + social support intervention (SUCRA = 83%) and exercise + nutritional intervention (SUCRA = 72%). With respect to motor ability, exercise + nutrition + psychological intervention was the most effective intervention (SUCRA = 77.1%). Non-pharmacological multicomponent interventions have a positive effect on improving the physical condition of community-dwelling older adults with frailty or prefrailty. Nurses and care managers should actively prioritize the integration of the above two interventions into personalized frailty or prefrailty care plans, maximizing the efficacy of non-pharmacological management. Exercise + cognitive intervention is likely the most effective non-pharmacological multicomponent intervention for reducing the frailty level, and exercise + nutrition + psychological intervention is likely the most effective non-pharmacological multicomponent intervention for improving motor ability in community-dwelling older adults with frailty or prefrailty. The study identified the best non-pharmacological multicomponent interventions to improve frailty or prefrailty in community-dwelling older adults, providing a basis for the development of practical interventions in later gerontological nursing practice. PROSPERO: CRD420251115805.
The triglyceride-glucose(TyG) index, a surrogate marker of insulin resistance, has been linked to cardiac dysfunction; however, its underlying associated pathways in patients with type 2 diabetes mellitus(T2DM) remain unclear. This study used cardiac magnetic resonance(CMR) to explore the association of TyG index with subclinical left ventricular(LV) myocardial dysfunction and whether imaging indicators statistically mediate this relationship. In this retrospective cross-sectional study, a total of 235 T2DM patients who underwent CMR examination were included and assigned to three groups based on the tertiles of their TyG indexes as follows: low(< 8.73, n = 78), moderate(8.73-9.36, n = 79), and high TyG index(≥ 9.36, n = 78) groups. LV geometry, function, myocardial energetic efficiency index (MEEi), resting first-pass perfusion, and global peak strain in radial(GRPS), circumferential(GCPS), and longitudinal(GLPS) directions were measured. Univariate and multivariate linear regression models and exploratory mediation analysis were used to analyze the associations of TyG index on LV global strain. Compared with the low and moderate TyG index groups, the high TyG index group had significantly higher LV remodeling index, lower LV global function index, lower MEEi, impaired resting myocardial perfusion, and reduced LV global peak strain (all p ≤ 0.002). Multivariate analysis showed that TyG index remained independently associated with reduced LV strain after adjusting for confounders (GRPS β = -0.261; GCPS β = 0.271; GLPS β = 0.381; all p < 0.001). And MEEi and upslope were also independently associated with reduced LV GRPS and GLPS (all p < 0.05). Further mediation analysis revealed the statistically mediated proportions of the association between the TyG index and LV global strain were 8.2-8.6% for MEEi and 4.3% to 12.5% for upslope. In model comparison analyses, the TyG index demonstrated substantially better model fit than either component alone across all strain directions (all Akaike Information Criterion difference > 150). In patients with T2DM, a higher TyG index is independently associated with decreased LV global strain, and this relationship is statistically mediated by reduced MEEi and impaired resting perfusion upslope. These findings generate hypotheses regarding myocardial energetics and resting perfusion as potential pathways associated with diabetic myocardial dysfunction that warrant prospective investigation.