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The standard surgical approach to the treatment of pediatric VUR is ureteral reimplantation. Although open surgery is still the standard benchmark for its long-term durability and high success rate, the development of minimally invasive techniques led to the creation of laparoscopic ureteral reimplantation. The high learning curve and technical difficulty needed for accurate intracorporeal suturing, however, have limited its widely adopted in clinical practice. Robotic platforms have since emerged as a promising alternative, offering enhanced dexterity and improved visualization, which facilitate complex suturing and achieve success rates comparable to open surgery. However, most available meta-analytical data are limited by high degrees of heterogeneity because previous studies have often combined laparoscopic and robotic procedures and have combined intravesical and extravesical reimplantation. This is a very general classification that can introduce systematic bias and mask underlying differences between modalities. Through this direct comparison of these two specific surgical approaches, the goal of this study is to isolate these variables to provide highly granular, clinically relevant evidence to inform surgical selection for modern practice. We conducted a comprehensive literature search across PubMed, Embase, Web of Science, and the Cochrane Library to identify clinical studies that directly compared the efficacy of RAUR via the extravesical approach with OUR for the treatment of VUR in pediatric patients. For the OUR group, no restriction was placed on the surgical approach, and both extravesical and intravesical techniques were included. The operative time, hospital stay, success rates, and postoperative complications such as urinary tract infection, urinary retention, and other complications were extracted for comparative analysis. A total of 473 patients from seven studies were analyzed. The results of the meta-analysis showed that there was no significant difference between the two groups in terms of total complications, but the RAUR group had significantly longer operative time (WMD&#x2009;=&#x2009;48.1 min, 95% CI [27.43, 68.76], p&#x2009;<&#x2009;0.05) and significantly shorter length of hospitalization (WMD = -0.54 days, 95% CI [-0.96, -0.13], p&#x2009;<&#x2009;0.05) when compared with the OUR group. When assessing surgical success rate, postoperative urinary tract infection, postoperative urinary retention, or overall complications, no significant differences were recorded between the two groups. In summary, these preliminary findings indicate that RAUR is associated with significantly longer operative time, which should be interpreted in the context of the learning curve. Although RAUR showed a statistically shorter hospital stay, the clinical benefit may be limited as most patients were discharged after overnight observation. Success and complication rates, including urinary tract infection and retention, were comparable to OUR, supporting the safety and efficacy of the robotic platform. Given equivalent key outcomes and expected experience accumulation, RAUR may be a viable alternative to OUR. However, owing to inherent confounding factors such as study design and surgical approach variations, these conclusions require further validation through high-quality multicenter randomized controlled trials.

Antibody-based therapeutics are a rapidly expanding class of treatments, with over 200 approved candidates and thousands in clinical trials. Computational pre-filtering using protein structure prediction models has the potential to reduce the cost of wet-lab screening, yet the relationship between model confidence measures and functional binding properties remains incompletely understood. Here, we evaluate whether confidence measures produced by contemporary open-source protein structure prediction models are suitable for in silico screening of nanobody-antigen interactions. We benchmark Boltz-2, Chai-1, IntFold, and AlphaFold3 using two complementary tasks: (i) ranking true nanobody-antigen binding complexes above non-binding bait pairs across 17 antigens, and (ii) detecting out-of-distribution sequences generated by alanine substitution of all complementarity-determining region residues. We further assess confidence measure sensitivity through progressive alanine mutagenesis on 13 nanobody-antigen complexes spanning the range of CDR3 lengths in our dataset and evaluate generalizability using data from a camelid immunization campaign against CD33. Boltz-2-derived confidence measures achieved the highest median performance for identifying true binders. Local confidence measures, including pLDDT and interface- or CDR-focused metrics, were most effective at detecting out-of-distribution sequences and exhibited the greatest sensitivity to mutations. No single confidence measure performed best across both tasks, and all evaluated protein structure prediction models showed limited generalization to previously unseen antigens. Our results suggest that robust in silico nanobody candidate selection should combine complementary global and local confidence measures rather than relying on a single metric. These findings provide practical guidance for integrating open-source protein structure prediction models into AI-driven nanobody discovery pipelines while highlighting the need for improved generalization across antigens.

Burosumab has shown benefits in treating X-linked hypophosphatemia (XLH), a rare genetic bone disorder that causes rickets among pediatric patients. However, data in Chinese children with XLH are lacking. Therefore, we evaluated the effectiveness, safety, and pharmacokinetics of burosumab among Chinese children (aged 1-12&#xa0;yr) with XLH in this open-label, multi-center, single-arm, phase 4 study. Of the 28 patients enrolled (12 male, 16 female), 27 completed the study. All patients received s.c. injections of burosumab at a starting dose of 0.8&#xa0;mg/kg every 2&#xa0;wk for 64&#xa0;wk. The mean&#x2009;&#xb1;&#x2009;SD patient age was 5.68&#x2009;&#xb1;&#x2009;3.07&#xa0;yr. Burosumab treatment increased the serum phosphorus level by 0.96&#x2009;&#xb1;&#x2009;0.27&#xa0;mg/dL from baseline during the burosumab dose cycles (average of week 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64). The improvement from baseline (2.33&#x2009;&#xb1;&#x2009;0.24&#xa0;mg/dL) to week 64 (3.29&#x2009;&#xb1;&#x2009;0.30&#xa0;mg/dL) was significant (p&#x2009;<&#x2009;.05). The Radiograph Global Impression of Change was significantly improved at week 64 (1.90&#x2009;&#xb1;&#x2009;0.48; p&#x2009;<&#x2009;.0001 vs baseline), and the percentage predicted 6-min walking test among patients aged &#x2265;5&#xa0;yr with post-baseline values (n&#x2009;=&#x2009;16) was significantly increased from 67.32%&#x2009;&#xb1;&#x2009;8.27% at baseline to 71.91%&#x2009;&#xb1;&#x2009;8.25% at week 64 (p&#x2009;<&#x2009;.05). All patients experienced treatment-emergent adverse events; most were mild to moderate. In conclusion, burosumab treatment in Chinese children with XLH corrected serum phosphorus levels and improved clinical parameters with tolerable safety profiles.

Early relational health - the quality of caregiver-child interactions - is foundational for socio-emotional development and long-term wellbeing. The American Academy of Pediatrics has called for a paradigm shift toward relationship-centered care in pediatric primary care, yet a gap remains between this vision and real-world implementation. To map early relational health interventions implemented in pediatric primary care, summarize reported outcomes and identify implementation strategies, barriers, and facilitators. PubMed, CINAHL, and PsycINFO were searched for studies published between 2014 and 2024, supplemented by backward citation searching. A scoping review methodology following PRISMA-ScR guidelines was used. Data were charted and synthesized using descriptive and thematic analysis. Eighteen studies met inclusion criteria. Interventions were delivered in clinic, home, or hybrid settings and were commonly integrated into routine workflows. Reported outcomes included improvements in caregiver responsiveness, parenting self-efficacy, and child language and socio-emotional development. Implementation strategies included staff training, workflow integration, fidelity monitoring, and community partnerships. Key facilitators were contextual responsiveness, strong relational supports, and alignment with clinical processes. Barriers included small or homogeneous samples, reliance on parent-report outcomes, short follow-up periods, and resource constraints. Early relational health interventions are feasible and show promise in pediatric primary care when embedded into routine care and adapted to context. Addressing methodological and implementation challenges is essential to advancing relationship-centered pediatric practice. Open Science Framework (OSF) DOI: https://doi.org/10.17605/OSF.IO/ZCGVA.

Simulation is an established evidence-based tool in healthcare. It is widely used for medical education (simulation-based medical education [SBME]), quality improvement, capacity building, audit and feedback, and probing healthcare systems for latent safety threats. Implementation science (IS) currently subsumes these functions under broad taxonomy categories such as "conduct ongoing training" or "cyclical tests of change." This framing fails to capture simulation's distinct mechanisms and its unique potential to close the evidence-to-practice gap. We argue that the time has come for implementation scientists and the healthcare simulation community to come together around a shared question: does simulation, as it is already practiced in healthcare, meet the criteria for a discrete, named implementation strategy within taxonomies such as the Expert Recommendations for Implementing Change (ERIC)? Drawing on the ERIC definition of an implementation strategy as "methods or techniques used to enhance the adoption, implementation, and sustainability of a clinical program or practice," we argue that simulation in healthcare already functions in this role across at least three distinct domains: developing individual and team competencies (SBME); probing healthcare systems for latent hazards and driving quality improvement; and operationalizing evidence-based interventions (EBIs) and clinical decision supports (CDS) under realistic conditions. We specify simulation using established IS frameworks-including the Consolidated Framework for Implementation Research (CFIR), the EPIS framework (Exploration, Preparation, Implementation, Sustainment), and the PRISM (Practical, Robust Implementation and Sustainability Model)-and propose a research agenda at the intersection of these two fields. High-reliability industries including aviation, astronautics, and nuclear power provide useful analogies, but the healthcare simulation literature has developed a robust and distinct evidence base in its own right, exemplified by translational simulation paradigms. Simulation is not simply a training technique. It is a multi-mechanism, multi-level strategy with proven applications in healthcare education, QI, and systems change. Formally recognizing simulation within IS strategy taxonomies would sharpen conceptual clarity, enable more precise evaluation, and open a productive dialogue between two scientific communities whose work is more convergent than current frameworks suggest.

Single-nucleus transcriptomic atlases offer an unprecedented opportunity to connect cellular molecular states with Alzheimer's disease (AD) neuropathology, but whether these profiles encode reproducible, predictive information about pathological burden remains unclear. We present the SEA-AD DREAM Challenge, an open, international, model-to-data competition built on the Seattle Alzheimer's Disease Brain Cell Atlas to predict Alzheimer's disease neuropathological severity from single-nucleus RNA-sequencing data. Participants developed containerized models to predict categorical neuropathological staging, including overall Alzheimer's disease neuropathologic change, Braak stage, Thal phase, and CERAD score, as well as quantitative amyloid-&#x3b2; and phospho-tau burden measured by 6E10 and AT8 immunohistochemistry. Across 17 eligible teams from 15 countries, the crowdsourcing framework enabled systematic comparison of diverse computational approaches and surfaced a broad landscape of modeling strategies and candidate predictive features. Top-performing methods achieved near-perfect prediction of categorical staging, with the best submission reaching a quadratic weighted kappa of 1.0 for the Overall AD Neuropathological Change score (ADNC), and competitive prediction of quantitative pathological burden in held-out data, with a best concordance correlation coefficient of 0.48. Post hoc perturbation analyses revealed that top categorical-stage predictions relied heavily on donor-level metadata-driven signals rather than transcriptomic features, whereas quantitative pathology prediction was more robust and supported by transcriptomic and cell-type-associated features with potential biological relevance to AD progression. The challenge also introduced the first AI Agent Track in a DREAM Challenge, providing an early benchmark for autonomous and human-guided agentic model development in single-cell neuroscience. This work demonstrates that single-nucleus transcriptomes encode substantial information about Alzheimer's disease pathology, establishes a reproducible benchmark for molecular neuropathology prediction, and highlights critical principles for designing privacy-preserving, leakage-aware community challenges using deeply phenotyped human brain data.

Childhood cancer is an under-recognized public health priority in low- and middle-income countries. India bears a substantial share of the global burden, yet survival outcomes are poorly documented. This scoping review synthesizes survival outcomes across childhood cancers in India, assesses geographic disparities, and benchmarks against international standards to inform national policy and system strengthening. We searched PubMed, Scopus, Web of Science, and Embase (January 1994 to December 2023) for studies reporting survival outcomes among childhood cancers (0-18 years) in India. Two reviewers independently screened records, extracted data, and conducted descriptive synthesis by cancer type excluding case reports and registry summaries. Exploratory forest plots were created where &#x2265;3 studies reported comparable end points. The protocol was prospectively registered on Open Science Framework. Of 6,505 records screened, 182 studies (22,886 children) were included. Most were retrospective (78%) and single-center (94%), concentrated in four tertiary hospitals. Exploratory pooled estimates derived from descriptive analyses showed that the 5-year overall (OS) and event-free survival were 67.1% (95% CI, 56.9 to 77.2) and 59.2% (95% CI, 48.0 to 70.3) for ALL and 93.1% (95% CI, 91.7 to 94.4) and 85.3% (95% CI, 81.3 to 89.3) for Hodgkin lymphoma (HL). The pooled median OS for AML and Ewing sarcoma was 25.4 months (95% CI, 16.8 to 33.9) and 21.2 months (95% CI, 14.6 to 27.7), respectively, whereas the 3-year OS for neuroblastoma was 56.9% (95% CI, 45.7 to 68.0). Reporting was inconsistent, with frequent omission of CIs and heterogeneity across regions. Childhood cancer survival in India remains variable, with HL nearing global benchmarks, but leukemias and solid tumors show inferior outcomes. Strengthening national cancer registries, research infrastructure, and political commitment is critical for achieving equity in childhood cancer care.

How does benzodiazepine use during an IVF cycle affect pregnancy outcomes? Benzodiazepine use was neither positively nor adversely associated with IVF pregnancy outcomes overall. Benzodiazepine use during oocyte retrieval, primarily with midazolam, and diazepam use at the time of embryo transfer (ET) have been reported to yield comparable procedural success rates to those of non-users, respectively. However, these studies focus on exposure at a single time point, necessitating a more comprehensive investigation of benzodiazepine use across the entire IVF treatment period. A retrospective cohort study was conducted using Korea's Health Insurance Review and Assessment (HIRA) database between October 2017 and June 2024. A total of 99&#xa0;484 women with a first completed IVF cycle were included. Benzodiazepine users were defined as individuals who had at least one prescription during an IVF cycle (from the last menstrual period to ET) (user group, n&#x2009;=&#x2009;28&#xa0;649). Non-users were defined as those who had no benzodiazepine prescriptions within 365&#x2009;days prior to ET to minimize exposure misclassification (non-user group, n&#x2009;=&#x2009;61&#xa0;433). The outcomes of interest were four IVF outcomes: clinical pregnancy rate, miscarriage rate, live birth rate, and preterm birth rate. To compare the two groups, propensity score overlap weighting was applied to adjust for potential imbalances in confounders. Relative risks (RRs) with 95% CIs were estimated using Poisson regression in the overlap-weighted at-risk population cohort for each outcome. Compared with non-users, benzodiazepine users had a lower prevalence of prior live birth and a higher prevalence of anxiety disorders, along with greater use of antidepressants before adjustment. The absolute event rates of each outcome were as follows: (i) clinical pregnancy rate: 36.0% of users versus 35.7% of non-users, (ii) miscarriage rate: 14.9% versus 15.2%, (iii) live birth rate: 99.3% versus 99.3%, (iv) preterm birth rate: 13.3% versus 11.6%. Most IVF outcomes were comparable between groups, though a marginally increased risk of preterm birth was observed among users (clinical pregnancy: adjusted RR 1.02 [95% CI 1.00 to 1.05]; miscarriage: 0.99 [0.91 to 1.08]; live birth: 1.00 [1.00 to 1.00]; preterm birth: 1.10 [0.99 to 1.21]). However, stratified analyses by cumulative dose showed no dose-response relationship (&#x2264;1.2&#x2009;mg and >2&#xa0;mg, respectively-preterm birth: 1.09 [0.99 to 1.21] and 1.01 [0.87 to 1.17]). Additionally, the point estimate was closer to the null among users prescribed both injectable and oral agents during the cycle (preterm birth: 1.04 [0.86 to 1.26]). The robustness of the main findings was supported by analyses accounting for benzodiazepine exposure during pregnancy and by multiple sensitivity analyses. Despite rigorous statistical adjustment, residual confounding by unmeasured factors and potential exposure misclassification due to discrepancies between prescription timing and actual medication use cannot be completely ruled out. This large population-based study found no association between benzodiazepine use throughout the IVF cycle and pregnancy outcomes. Although a small increase in preterm birth risk was observed, there was no evidence of a dose-response relationship or additional risk among patients with exposure to both oral and injectable formulations during the exposure assessment period. However, further studies are needed to evaluate the potential association. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2026-25474077); This research was supported by a grant (RS-2026-25511535) from Ministry of Food and Drug Safety in 2026. J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, GSK, Pfizer, Handok, JnJ, and SK Bioscience, outside the submitted work. N/A.

Understanding how Americans think about public health and the role of government institutions is crucial for informing effective health communication in a polarized political climate. We deployed an open-ended national survey of 1004 adults in October 2025 to assess public perceptions of these topics. Respondents associated the term "public health" with health for everyone (44%) and health of everyone (23%), alongside healthcare (20%) and other themes. The most common perceived government benefit was facilitating access to healthcare (39%)-particularly by addressing cost (16%). Among perceived government harms, more Republicans than Democrats cited overregulation (16% vs 8%, P < 0.01), limiting personal freedoms (16% vs 6%, P < 0.001), and inefficiency (10% vs 4%, P < 0.01); more Democrats than Republicans mentioned dismissing science (7% vs 2%, P < 0.01) and defunding (7% vs 2%, P = 0.02). Weighted analyses yielded minimal substantive differences from unweighted findings. Findings reveal both cross-partisan common ground in term associations and divergent concerns regarding government action. Public health messaging should leverage shared priorities and acknowledge partisan concerns about government roles.

Tandem repeat expansions have been implicated in various neurological conditions. Here, we present a novel hypermethylated CCG repeat expansion on Xp22 in the 5'UTR of BCLAF3 in males with neurodevelopmental disorders. We used patient-derived fibroblasts and neuronal models from a family with BCLAF3 repeat expansions to generate multiomic data and investigate downstream molecular consequences of the repeat expansion. To identify additional affected individuals with BCLAF3 repeat expansions, we screened methylation arrays (n&#x2009;=&#x2009;12,375) and short-read genomes (n&#x2009;=&#x2009;15,963) from probands with neurodevelopmental presentations. We also characterized BCLAF3 repeat expansions in the general population using long-read sequencing data (n&#x2009;=&#x2009;793) and population-level short-read sequencing data (n&#x2009;=&#x2009;410,076). Long-read sequencing validated hypermethylation of expanded repeats. Patient-derived cells showed repressed BCLAF3 RNA and protein expression. We show that the BCLAF3 CCG repeat expansion constitutes a previously uncharacterized fragile site (FRAXG) that shifts the surrounding chromatin compartment from open euchromatin to closed heterochromatin. Using our multiomic screening approaches, we identified three additional unrelated males and one related male cousin with long-read sequencing validated (n&#x2009;=&#x2009;2) or short-read sequencing predicted (n&#x2009;=&#x2009;2) repeat expansions. In one family, the BCLAF3 repeats segregate with more severe phenotypes than expected for the primary diagnoses. Long-read sequencing in three carrier mothers showed skewed X-inactivation against the repeat expansion, highlighting the potential deleterious effect of an allele with an expansion. Expansions were absent in long-read sequencing data from control populations. Assessment of the BCLAF3 repeat expansion in the UK Biobank indicates that it may be ~&#x2009;20X rarer than FMR1 repeat expansions. CCG repeat expansions in the 5'UTR of BCLAF3 likely constitute a novel genetic etiology associated with X-linked neurodevelopmental phenotypes in males. Future work will be essential to delineate the phenotypic spectrum and determine a disease pathomechanism.

This study explored the knowledge, awareness, and lived experiences of Indigenous youth ice hockey players across Canada with respect to concussion. Using a community-engaged approach grounded in Two-Eyed Seeing, we examined how intersections of culture, sport, and healthcare shape concussion education, disclosure, and recovery. Sport-related concussions (SRCs) are a significant health concern in Canada, with Indigenous youth disproportionately affected by injuries due to systemic inequities in healthcare access, culturally relevant education, and historical mistrust of medical institutions. Despite the high prevalence of concussions in ice hockey, limited research has examined Indigenous athletes' perspectives on concussion knowledge, reporting, and recovery. We explored these issues among 48 Indigenous hockey players aged 15-24 from across Canada. Participants completed an online questionnaire that included both open-ended and closed-ended items, addressing concussion awareness, education, and recovery experiences. Thematic analysis revealed that while athletes generally recognized concussion symptoms, many delayed or avoided reporting injuries due to stigma and fear of being sidelined. Access to concussion education varied, with urban athletes more likely to have encountered formal resources, such as the Concussion Awareness Training Tool (CATT), while others relied on informal knowledge from peers, coaches, or family. Recovery experiences for many participants highlighted the importance of traditional healing methods, including smudging, sweat lodges, and Elder guidance, which were valued, but often absent in formal care pathways. In centring Indigenous voices, this work contributes to growing efforts to support Indigenous self-determination in concussion recovery through holistic and community-based approaches within sport and healthcare systems. R&#xe9;SUM&#xe9;: OBJECTIF: Nous avons voulu explorer les connaissances, les perceptions et l&#x2019;exp&#xe9;rience v&#xe9;cue de jeunes joueurs autochtones de hockey sur glace au Canada en ce qui a trait aux commotions. &#xc0; l&#x2019;aide d&#x2019;une approche faisant appel aux communaut&#xe9;s, ancr&#xe9;e dans la &#xab; vision &#xe0; deux yeux&#xbb;, nous avons cherch&#xe9; &#xe0; d&#xe9;terminer si la confluence de la culture, du sport et des soins de sant&#xe9; a des effets sur les informations, la divulgation et le r&#xe9;tablissement en lien avec les commotions. Les commotions li&#xe9;es au sport sont un important probl&#xe8;me de sant&#xe9; au Canada, et les jeunes Autochtones sont d&#xe9;mesur&#xe9;ment victimes de blessures en raison d&#x2019;iniquit&#xe9;s syst&#xe9;miques dans l&#x2019;acc&#xe8;s aux soins de sant&#xe9; et &#xe0; l&#x2019;enseignement culturellement appropri&#xe9; et de la m&#xe9;fiance historique des peuples autochtones envers les &#xe9;tablissements m&#xe9;dicaux. Malgr&#xe9; la forte pr&#xe9;valence des commotions dans le hockey sur glace, peu d&#x2019;&#xe9;tudes portent sur les points de vue d&#x2019;athl&#xe8;tes autochtones sur la connaissance et le signalement des commotions et sur le r&#xe9;tablissement de ceux qui en sont victimes. M&#xe9;THODES: Nous avons explor&#xe9; ces questions avec 48 joueurs de hockey autochtones de 15 &#xe0; 24 ans venant de tout le Canada. Les participants ont rempli un questionnaire en ligne comportant &#xe0; la fois des questions ouvertes et ferm&#xe9;es sur les perceptions, les informations et le r&#xe9;tablissement li&#xe9;s aux commotions. R&#xe9;SULTATS: L&#x2019;analyse th&#xe9;matique a r&#xe9;v&#xe9;l&#xe9; que les athl&#xe8;tes savaient g&#xe9;n&#xe9;ralement reconna&#xee;tre les sympt&#xf4;mes de commotion courants, mais que beaucoup retardaient ou &#xe9;vitaient le signalement de leurs blessures en raison de la stigmatisation qui s&#x2019;y rattache et de peur d&#x2019;&#xea;tre mis sur la touche. L&#x2019;acc&#xe8;s aux informations sur les commotions variait; les athl&#xe8;tes urbains &#xe9;taient plus susceptibles d&#x2019;avoir trouv&#xe9; des ressources officielles, comme l&#x2019;outil Concussion Awareness Training Tool (CATT), tandis que les autres se fiaient aux connaissances informelles de leurs pairs, de leur entra&#xee;neur ou de leur famille. Les exp&#xe9;riences de r&#xe9;tablissement de nombreux participants &#xe9;taient centr&#xe9;es sur l&#x2019;importance des m&#xe9;thodes de gu&#xe9;rison traditionnelles, dont la purification par la fum&#xe9;e, les sueries et les conseils d&#x2019;a&#xee;n&#xe9;s, m&#xe9;thodes qui &#xe9;taient appr&#xe9;ci&#xe9;es, mais souvent absentes des parcours de soins officiels. CONCLUSION: En mettant les voix autochtones au premier plan, cette &#xe9;tude contribue aux efforts croissants pour appuyer l&#x2019;autod&#xe9;termination autochtone dans le r&#xe9;tablissement &#xe0; la suite de commotions au moyen d&#x2019;approches holistiques et communautaires dans les syst&#xe8;mes du sport et des soins de sant&#xe9;.

Pediatric abdominal aortic aneurysms (AAAs) are rare and differ fundamentally from adult degenerative disease in etiology, presentation, and management. We performed a systematic review to characterize the causes, clinical features, treatment strategies, and outcomes of pediatric AAAs. A PRISMA-compliant systematic review was conducted using PubMed/MEDLINE, Embase, and Web of Science from inception through March 2025. Studies reporting AAAs in patients &#x2264;18 years were included. Case reports and case series were eligible. Data extracted included demographics, aneurysm characteristics, etiology, presentation, management approach, complications, and outcomes. Seventy-seven studies encompassing 87 pediatric patients met inclusion criteria. The median age at presentation was 13 months [IQR: 1-96 months], with some cases identified in the prenatal period. Etiologies were idiopathic congenital (50.6%), mycotic (26.4%), genetic disorders (17.2%), and vasculitis (5.7%). Nearly half of aneurysms were detected incidentally, including 8 identified prenatally. Thirteen patients (15%) presented with rupture. Most aneurysms were infrarenal (81.6%), with a mean diameter of 4.6 cm. Open surgical repair was the predominant treatment (74 patients), most commonly using prosthetic grafts. Overall mortality was 17.2%, with deaths primarily associated with rupture or postoperative complications. Survival was favorable in non-ruptured patients undergoing repair. Pediatric AAAs represent a heterogeneous and clinically significant entity distinct from adult disease. Early recognition in high-risk populations and timely surgical intervention are critical. Given the absence of pediatric-specific guidelines, multicenter collaboration and long-term surveillance data are needed to inform evidence-based management strategies.

Greater understanding of relationships between social factors and pain responses can provide new modifiable targets for pain interventions in adolescents. This observational preliminary exploratory study aims to examine the associations between experimental pain sensitivity and social factors in healthy adolescents. Sixty-three healthy girls (age 11.9&#x2009;&#xb1;&#x2009;1.3) completed comprehensive quantitative sensory testing assessments of ten experimental pain measures as well as three open-ended self-identity qualitative questions and the Patient-Reported Outcomes Measurement Information System peer-relationships family-relationships surveys. Linguistic Inquiry Word Count (LIWC) was used to quantify the proportion of socially oriented words. Higher LIWC scores indicate a greater emphasis on social aspects in responses. Associations between experimental pain measures and social variables were examined using 10 regression models and 20 correlations. Most associations were not statistically significant. Contrary to the hypothesis, a greater use of socially oriented language (higher LIWC social score) was associated with greater pain sensitivity reflected by lower cold pain thresholds (p&#x2009;=&#x2009;0.013) and higher heat pain ratings (p&#x2009;=&#x2009;0.020). As hypothesized, greater social scores were related to greater pain inhibitory responses, with LIWC scores related to the conditioned pain modulation response (p&#x2009;=&#x2009;0.020), and better peer relationships were related to greater offset analgesia response (r&#x2009;=&#x2009;-0.276, p&#x2009;=&#x2009;0.048). No other significant associations were observed. Social experiences may have a minor effect on experimental pain sensitivity and modulation in healthy adolescent girls. These findings suggest that, in this population, social experiences may have only a minor influence on experimental pain responses relative to other biopsychosocial factors. This exploratory study identified only very few associations, suggesting that social experiences may have a minor effect on experimental pain sensitivity in healthy adolescent girls. However, the few associations observed may point towards a possible association between greater inhibitory response and greater social support from family and peers, which could guide future studies investigating the role of social factors in pain modulation during adolescence.

As AI adoption accelerates across human society, the problem of aligning AI models with human preferences remains a grand challenge. Currently, the AI alignment field is deeply divided between behavioral and representational approaches, resulting in narrowly aligned models that are more vulnerable to increasingly deceptive misalignment threats. In the face of this fragmentation, we propose an integrated vision for the future of the field. Drawing on related lessons from immunology and cybersecurity, we lay out a set of design principles for the development of integrated alignment frameworks that combine the complementary strengths of diverse alignment approaches through deep integration and adaptive coevolution. We highlight the importance of strategic diversity-deploying orthogonal alignment and misalignment detection approaches to avoid homogeneous pipelines that risk being "doomed to success." We also recommend steps for greater unification of the AI alignment research field itself, through cross-collaboration, open model weights, and shared community resources.

Adolescents and young adults (AYAs) with type 1 diabetes (T1D) face a heightened risk of care gaps and preventable complications during the transition from pediatric to adult care. AYAs from low-income families are more likely to experience poor outcomes. Care guidelines for T1D now recommend a transition program beginning several years prior to anticipated independence. However, existing transition programs often require substantial resources, limiting their scalability and accessibility. We used a human-centered design approach to develop and refine a low-cost, virtual intervention to support T1D transitions among publicly insured AYAs. Guided by the "3I" model (inspiration, ideation, implementation) of IDEO, we conducted semistructured interviews with 26 providers and staff across 4 University of California medical centers to identify challenges and opportunities for improving transition care. We then completed customer discovery interviews with 36 adopters and influencers, including AYAs, endocrinologists, and diabetes educators, to identify priorities and needs and create value propositions. The resulting intervention was tested with 3 cohorts (n=25) of publicly insured AYAs aged 17 to 21 years receiving pediatric diabetes care at an academic medical center. The intervention consisted of two 75-minute virtual group sessions led by a diabetes educator and peer mentors with lived experience. Feasibility, acceptability, and appropriateness were assessed via validated surveys and qualitative interviews. Core functions of the intervention included education and discussion on "adulting with diabetes" and navigating the health care system, interactive creation of a transition plan, mentors sharing their experiences with diabetes, open discussion among peers, opportunities to ask questions, and provision of resources based on individual needs. Facilitators and mentors reported high feasibility (mean 4.25, SD 0.52) and appropriateness (mean 4.43, SD 0.53). Qualitative interviews highlighted peer support and lived-experience mentorship as core drivers of engagement. Attendance was highest among participants enrolled closer to session dates. Participant feedback informed ongoing adaptations to content and delivery across cohorts, including timing of the intervention, use of the chat function, multiple text reminders before intervention sessions, and specific topics of interest. This human-centered virtual transition intervention addressed priorities identified by AYAs, peer mentors, and clinicians, including peer support, judgment-free discussion, and self-advocacy. While engagement and attendance varied across cohorts, findings support further refinement and evaluation of the intervention in diverse settings.

Quantification of retinal and avascular areas in the rat oxygen induced retinopathy (OIR) model is traditionally performed using time-intensive manual methods that may be subject to inter-rater variability. We developed and validated two open-source, semi-automated Fiji (Fiji is Just ImageJ) macros to measure total retinal area (RA) and avascular area (AA) in rat 50/10 OIR retinal flat mounts. Concordance correlation coefficients demonstrated high agreement between macro-derived and manual measurements for RA (0.988), AA (0.985), and AA/RA (0.983), with minimal bias observed. While inter-user variability was higher for macro-based AA measurements compared to manual methods, averaging results from two users improved precision. These semi-automated tools reduce analysis time and training burden while maintaining strong agreement with gold standard measurements. Although limited by user input requirements and single-laboratory validation, these macros provide accessible, standardized methods for retinal quantification and have the potential to improve reproducibility and efficiency in OIR research.

End user co-design in the personal digital health technology space is underdeveloped. Clinical uptake of personal digital health technologies has been poor, highlighting a need to cocreate solutions with end users. The study aimed to describe an "end user" co-design framework in the development of 5 prototype personal health apps for patients with different rare or complex diseases. A patient-led, user-centered, collaborative personal health app plus wearable plug-in co-design methodology was developed. Five prototype apps were developed for end users with long COVID-19, pancreatitis, primary ciliary dyskinesia, sarcoidosis, and valosin-containing protein disease by a multidisciplinary partnership including patients, app design and development experts, user experience experts, clinicians, and patient-driven organizations. Phase 1 involved a 6-month co-design process with 5 modules involving patient-driven organizations that included the codevelopment of specifications through group workshops and independent exercises that defined the goals, content, features, and user experience of each app. Phase 2 involved app build-out, internal alpha testing, and beta study preparations. Phase 3 involved a usability beta testing study in which end users used the app and associated wearable/smart devices (Oura ring, Lumia ear device, Empatica EmbracePlus, and MIR Spirobank Spirometer) for up to 5 months. Participant feedback was documented continuously and systematically, centering on the following themes: functionality, usability, harms, benefits, self-explorations, and beta testing study details related to retention and adherence. While unique app goals were codeveloped by each disease group, a central goal across groups was to develop a personal health app enabling users to track subjective, self-reported symptoms, objective measures of health, and unique modifiers of symptoms. A total of 239 end user participants participated in the beta testing pilot study. Enrollment and retention rates were high, ranging from 94% to 100% and 92.2% to 100%, respectively. All active participants gave some form of feedback: there were 257 unique participant suggestions of how to specifically modify or improve the study app experience. Participant feedback themes commonly centered around customization to reduce daily burden and improve personal tailoring of the app. Participants' desires surrounding symptom displays were heterogeneous. Personal health app co-design is rooted in a complex digital landscape that requires a significant amount of up-front effort and time. However, the up-front investment of time can result in rich and diverse end user feedback that could save time in the app development trajectory to implementation. This paper provides a co-design framework and the building blocks of 5 prototype personal health apps with publicly available open-source code on GitHub. These prototypes could be leveraged for improving understanding of, communicating symptoms of, and providing n-of-1 suggestions for rare or complex diseases, providing benefit to patient communities and individual patients.

Systematic clinical phenotyping using Human Phenotype Ontology (HPO) is central to rare disease diagnosis. However, current disease prioritization (ranking candidate diseases from HPO for a patient) methods face key challenges: they often fail to account for the hierarchical structure of HPO terms, ignore dependencies among correlated terms, and do not adjust for batch effects arising from systematic differences in phenotype documentation across cohorts, institutions, or clinicians. We aim to develop a scalable and statistically principled framework to address these limitations for rare disease prediction and patient stratification. We developed PhenoSS, a Gaussian copula-based framework that models disease-specific marginal prevalence of HPO terms while capturing their joint dependencies through a multivariate normal distribution. Phenotype frequencies were estimated using external curated resources, including OARD (Open Annotations for Rare Diseases) and HPO annotations. PhenoSS supports both pair-wise phenotype similarity calculation for patient clustering and posterior odds estimation for patient-specific disease prioritization. A batch-effect correction module mitigates systematic phenotyping differences across datasets. Across diverse simulation scenarios, PhenoSS demonstrated robust disease-prediction performance and consistently improved accuracy after batch-effect correction. In real electronic health record data, PhenoSS identified clinically meaningful patient clusters and effectively distinguished patients with different rare diseases. In disease prioritization tasks, PhenoSS achieved competitive performance with existing methods, particularly for patients exhibiting sparse or noisy phenotype annotations. PhenoSS provides a statistically interpretable framework for modeling phenotypic heterogeneity in rare disease research and is adaptable to other structured clinical vocabularies such as SNOMED-CT and ICD codes.

This study aims to elucidate the clinical characteristics, management, and prognosis of anterior urethral valves (AUV) in children. A retrospective analysis was performed on 8 pediatric AUV patients (2015-2025), examining their clinical presentation, imaging and renal function data, surgical management, and reoperation rates. Prognosis was evaluated during follow-up. Among the eight patients, four were diagnosed with AUV (one including posterior urethral valves (PUV)), and four had AUV combined with diverticula (one also associated with PUV). All diagnoses were confirmed by retrograde cystography and/or cystoscopy. Associated findings included bladder trabeculation in four cases and vesicoureteral reflux in four. Three patients had renal impairment. Treatment included cystoscopic electrocoagulation of the urethral valves, or a combination of valve resection, diverticulectomy, and urethral reconstruction. Postoperatively, five patients recovered completely, while one experienced occasional urinary tract infections (UTI). Two patients required reoperation; they continue to exhibit vesicoureteral reflux and renal impairment, and remain under close observation. AUV can be definitively diagnosed via cystoscopy or voiding cystourethrogram (VCUG). Surgical intervention, including endoscopic valve ablation or open urethroplasty, yields favorable outcomes. However, the prognosis for patients with pre-existing renal impairment remains poor. Consequently, close monitoring and long-term follow-up are imperative.