Thoracic aortic aneurysm (TAA) is a significant public health concern. We aimed to identify drug targets and understand the pathogenic mechanisms of TAA.

We employed 4907 circulating proteins as exposure data from a large-scale protein quantitative trait loci study involving 35 559 Icelanders. We used findings from the FinnGen study as the outcome data. We conducted bidirectional Mendelian randomization analysis and colocalization analysis to pinpoint potential therapeutic targets for TAA and validated the results in the UK Biobank database. We validated findings with plasma transcriptomics and single-cell sequencing to uncover the pathological mechanisms of TAA. Western blots and immunofluorescence staining examined potential drug targets in aortic tissues.

Mendelian randomization results suggest that LTBP4 (latent transforming growth factor β-binding protein 4) is significantly associated with the risk of TAA. Plasma transcriptomics showed significantly increased LTBP4 expression in patients with TAA (log fold change=0.69, adjusted P=7.04×10^-4), with an area under the curve of 0.76. The single-cell sequencing analysis highlighted the predominant expression of LTBP4 in fibroblasts and the central role of LTBP4 in the functional regulation of the transforming growth factor β pathway. In vitro experiments demonstrate that the expression of LTBP4 protein is significantly increased in TAA tissue. Immunofluorescence staining indicates that LTBP4 is primarily localized in the extracellular matrix of the medial layer of the aorta.

This study presents an innovative integration of Mendelian randomization with multi-omics and in vitro experiments, identifying LTBP4 as a candidate therapeutic target for TAA. It also underscores the role of LTBP4 in regulating the transforming growth factor β signaling pathway within the pathogenic mechanism of TAA, particularly within fibroblast cells.

To identify barriers and facilitators to implementing guideline-recommended cognitive rehabilitation within the Veterans Health Administration (VHA) Polytrauma/Traumatic Brain Injury System of Care (PSC) and to systematically identify implementation strategies targeting these determinants.

Qualitative study using semi-structured interviews informed by the Consolidated Framework for Implementation Research (CFIR), followed by CFIR-Expert Recommendations for Implementing Change (CFIR-ERIC) mapping to identify implementation strategies aligned with identified determinants.

VHA PSC.

PSC providers involved in delivery of cognitive rehabilitation for Veterans with traumatic brain injury (TBI; n = 14), including referring providers and cognitive rehabilitation specialists.

None.

CFIR-based implementation determinants and implementation strategies aligned with identified determinants, identified using CFIR-ERIC query results.

Barriers and facilitators to implementing guideline-recommended cognitive rehabilitation were identified across multiple CFIR domains. Key barriers included perceived misalignment between manualized treatments and individualized Veteran needs, intervention complexity, limited staffing and organizational prioritization, gaps in provider knowledge of evidence-based practices, and lack of systematic implementation planning and evaluation. Facilitators were primarily concentrated within the inner setting and included interdisciplinary collaboration, support for provider training, and leadership prioritization of cognitive rehabilitation. CFIR-ERIC mapping identified 23 discrete implementation strategies aligned with these determinants. The most aligned strategies included identifying and preparing champions, assessing readiness and barriers, developing an implementation blueprint, capturing and sharing local knowledge, and conducting local needs assessments.

Implementation of guideline-recommended cognitive rehabilitation within the PSC is shaped by multi-level determinants. Findings underscore the need for coordinated, multi-component implementation strategies that extend beyond training alone and are tailored to the organizational context of the PSC. This work provides a strong foundation for future implementation efforts capable of expanding access to evidence-based cognitive rehabilitation for Veterans with TBI.

Selective participation in research studies hampers researchers' ability to draw valid and generalizable inferences from analyses. Quantifying and adjusting for selective participation are desirable but can be challenging given the paucity of data for non-participants.

We used individual-level information from population registers to predict baseline and continued participation in the Norwegian Mother, Father and Child Cohort Study (MoBa). Inverse probability weights were computed from logistic regression models with elastic-net regularization. We predicted selective participation and attrition in 296 987 mothers, of whom 29% returned the first MoBa questionnaire and 12.5% returned a follow-up questionnaire 8 years later. To quantify bias, we computed sample characteristics and exposure-outcome associations in the target population and stratified samples. To compare approaches for adjusting for bias, we computed weighted sample estimates by using three sets of weights.

Unweighted sample estimates were systematically different from target-population values, indicating bias due to selective participation. Baseline participation weights substantially reduced the impact of selection bias on mean values by 93% and associations by 75%. Attrition weights reduced attrition bias on mean values by 78% and associations by 50% but were less effective for reducing participation bias (22% and 14% respectively).

In this sample, characteristics and effect estimates are substantially different from target-population values. Participation weights were relatively effective at reducing bias due to selective participation but attrition weights were not. Estimates from studies that use attrition weights may still contain non-negligible selection bias-particularly if the baseline sample is not representative of the target population. Future studies should prioritize opportunities for deriving sampling weights for participation as well as attrition.

Chronic diseases affect up to 15% of adolescents, and their prevalence continues to rise. As adolescence and chronic diseases interact in complex and evolving ways, ensuring comprehensive care and facilitating a successful transition to adult services are major challenges for pediatric services. It is essential to take psychosocial aspects into account to promote autonomy and continuity of care during this vulnerable period.

To assess how psychosocial dimensions are evaluated and documented among adolescents with chronic illnesses in specialized pediatric services, and to explore healthcare professionals' views on barriers to addressing sensitive issues.

We conducted a retrospective analysis of paper and electronic medical records of adolescents transferred to adult care between December 2015 and February 2021 from two pediatric units (Gastroenterology and Urological & Digestive Surgery). Psychosocial data were extracted using a form. In parallel, 27 healthcare professionals (16 physicians, 11 nurses) completed a self-administered questionnaire about their practices and the perceived obstacles to discussing psychosocial issues.

Forty-six patient records were analyzed (35% female). The median follow-up time was 19 years [IQR 10-20] in Surgery and 7 years [IQR 5-12] in Gastroenterology, with a total of 16 diagnoses. Home (96%), education (93%), and activities (87%) were the most frequently recorded domains, while substance use (26%), sexuality (30%), and mental health (32%) were rarely noted. Sexuality was documented significantly more often in girls than boys (75% vs 7%, p < 0.001). Reported barriers included lack of time (62%), privacy concerns (56%), and the assumption that another professional would address the issue (44%).

Although psychosocial assessment is recognized as essential, it remains irregularly performed and documented. Implementing validated and structured tools could help standardize practice, improve multidisciplinary communication, and ultimately facilitate the transition of adolescent to adult care.

Treatment-resistant depression (TRD) is associated with severe depression, low quality of life (QoL) and reduced work productivity, which may increase risk of relapse, suicide and suboptimal response to treatment. Esketamine nasal spray plus a newly-initiated oral antidepressant (esketamine + OAD) has been shown to improve depression symptoms, QoL and productivity in patients with TRD; however real-world evidence is limited. This was a descriptive, exploratory post-hoc subgroup analysis of patients with TRD who received esketamine + OAD treatment over 16 weeks through an Early Access Program in Australia and New Zealand. This analysis aimed to describe response to esketamine + OAD (≥50% decrease in Hamilton Depression Rating Scale Index [HAMD-17] score at Week 16), including changes in depression severity, QoL and work productivity. QoL was assessed using the Assessment of QoL-8D (AQoL-8D) questionnaire and work productivity was assessed using the Workplace Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP). Overall, 28 (33.3%) participants were identified as responders. Responders experienced mean improvements in HAMD-17 (71.2%), AQoL-8D (29.5%) and WPAI:SHP (≥11.9%) from Baseline to Week 16. The greatest improvement among AQoL-8D domains was observed in mental health (32.9%). The largest improvement in WPAI:SHP was seen in overall work productivity loss (35.9%). These findings describe concurrent improvements in symptoms, QoL and self-reported functioning among responders. Results should be interpreted with caution due to limitations conferred by the post-hoc design, short follow-up, small population sizes and missing data.

Cladribine tablets are an oral immune reconstitution therapy with demonstrated efficacy and durable disease control in relapsing-remitting multiple sclerosis (RRMS). While global evidence supports their use, region-specific guidance adapted to healthcare variability, access constraints, and real-world practice in North-West Africa (NWA) remains limited.

To develop expert-based, region-specific consensus recommendations on the optimal use of cladribine tablets in RRMS in the NWA region.

A modified Delphi methodology was conducted during a face-to-face advisory board meeting in May 2025 in Tunisia. Senior neurologists with expertise in multiple sclerosis from across NWA reviewed available evidence, discussed key clinical questions, and voted on consensus statements addressing treatment positioning, early use, switching strategies, long-term management, safety, and special populations. Consensus was predefined as agreement by ≥75% of voting experts.

All consensus statements met the predefined threshold after discussion and refinement, achieving high to unanimous agreement. Experts endorsed cladribine tablets as a high-efficacy option for treatment-naïve patients with moderate-to-high disease activity and as a switch option following suboptimal response to platform therapies and in selected patients previously treated with high-efficacy therapies. Benefits include early initiation, durable disease control without continuous immunosuppression, and suitability for patients with limited access to hospital-based care. Expert consensus recommendations also addressed long-term management beyond Year 4, retreatment strategies, safety monitoring, pregnancy planning, and use in older patients, recognizing that some areas are supported mainly by emerging real-world evidence and expert clinical experience.

This Delphi consensus provides practical, region-specific guidance to optimize the use of cladribine tablets in RRMS across NWA, aiming to harmonize treatment practices and improve long-term outcomes.

The climate crisis plays a central role in the displacement of millions each year in Sub-Saharan Africa (SSA). Few studies have explored the burden of poor health outcomes among climate-related migrants (CRMs) in SSA. This scoping review aimed to summarize this limited body of literature and identify gaps for future research.

A protocol was developed and registered with OSF before performing the literature search. Four databases were systematically searched, identifying 392 unique records. After screening the titles and abstracts of these articles for relevance, 18 articles were sought for full-text review to assess alignment with the pre-defined inclusion criteria. Ten articles were reviewed in depth and summarized to identify key themes.

Included articles originated from Western, Eastern, and Southern Africa and focused primarily on flooding, droughts, and environmental degradation. The five key health outcomes identified were (i) poor mental health and solastalgia, (ii) poor physical health, (iii) loss of financial livelihood, (iv) reduced access to healthcare, and (v) poor social health. Sense of place was also observed to be disrupted, as CRMs reported feelings of solastalgia.

CRMs experience significant and wide-ranging health and place-based struggles. These outcomes are deeply connected and contribute to many quality-of-life challenges. This study highlights a critical research gap in understanding how displacement and climate change contribute to poor health outcomes and disruptions to sense of place, especially in SSA.

Autistic people with an eating disorder (ED) report more negative experiences of ED treatment and are at greater risk of requiring higher intensity services. Current ED treatment options do not fully meet underpinning drivers of autistic people's experiences of EDs. There remains little guidance or understanding on how autism-informed adaptations are implemented. This paper aims to explore clinician-perceived barriers and enablers to implementing autism-affirming adaptations in UK ED services.

Semi-structured interviews were conducted with 12 clinicians in multidisciplinary roles across UK ED services who were beginning to implement autism-affirming care. Data were analysed using critical realist thematic analysis.

Clinicians described many barriers associated with implementing autism-affirming care underpinned by longstanding beliefs about the risks of accommodating ED behaviours. This contributed to anxiety about making adaptations to care and the potential to over- or under-accommodate autistic needs. An underlying assumption that evidence-based practice solely equates to manualised treatment for EDs constrained adaptation. A commitment to individualised formulation and care, regardless of diagnosis, and valuing a diverse multidisciplinary team were key enablers. System-level barriers included siloed autism and ED resources and training.

Autism-affirming adaptations challenge some core underpinning messages historically embedded in siloed ED services.

This review overviews the research base for obsessive-compulsive disorder (OCD) among three historically understudied populations; Latino/Latin Americans, Black/African Americans, and Sexual and Gender Minority individuals.

Findings suggest that while core OCD symptoms are broadly similar across groups, sociocultural factors such as discrimination, minority stress, stigma, family context, spirituality, and access to care significantly influence symptom presentation, severity, and treatment utilization. Recent studies have evaluated assessment tools and provided evidence supporting exposure and response prevention, while emphasizing the importance of culturally responsive assessment and treatment. Large-scale initiatives are also improving representation in OCD research and addressing longstanding disparities in knowledge and care. OCD presents similarly across diverse populations, but cultural and contextual factors shape symptom expression and treatment experiences. Future research should prioritize representative samples, culturally informed assessment, and greater access to evidence-based care.

There is a paucity of longitudinal research comparing early-life mental health in rural and metropolitan communities. Living in rural areas is associated with limited access to specialist care, as well as additional stresses such as natural disasters. To address health disparities for rural communities it is critical to understand variance in predictors and outcomes for child mental health. Data was obtained on 595 women and their children, recruited before 20 weeks of pregnancy and followed up until their child was 3-4 years of age. Rurality was assessed using the Modified Monash Model (MM Model) with 432 children in metropolitan cities MM1, and 163 in rural communities MM2-7. Child mental health was measured using the Preschool Age Psychiatric Assessment and the Child Behavior Checklist at 3-4 years of age. This study found no differences in rates of child mental health disorders at 3-4 years. Rural mothers with untreated depression were more likely to report internalising and externalising symptoms in their children. Compared to rural families, metropolitan families were twice as likely to access childcare and kindergarten across the first 4 years. Parenting stress showed no differences, although rural children spent more time with their mother and had less screen time. While there were no significant differences in child mental health, there were differences in childcare and kindergarten attendance. Whether this occurred due to preference or access is unclear. Furthermore, children of mothers with untreated depression in rural communities had elevated symptoms suggesting vulnerability to poorer mental health.