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01.
medRxiv (Medicine) 2026-06-22

Evidence-guided AI regularization for suicidal ideation prediction in pediatric bipolar disorder

Background: Suicide prediction models in psychiatry often rely on purely data-driven feature selection, which can produce unstable and clinically opaque predictor sets in modest-sized samples. We developed Evidence-Based AI LASSO (EBAL), an evidence-guided regularization framework that incorporates curated clinical evidence into feature-specific penalty factors for interpretable prediction. Methods: Baseline data from 136 youth with confirmed bipolar spectrum disorder in the Greater Houston Area Bipolar Registry were analyzed using 20 candidate clinical predictors. Forty higher-level evidence documents on suicidality and related predictor domains were curated through a structured evidence synthesis workflow and indexed as an auditable evidence corpus. An open-weight large language model assigned feature-specific penalty factors using a prespecified scoring rubric, and these penalties were used to fit a weighted LASSO model. EBAL was compared with a standard evidence-agnostic LASSO using nested leave-one-out cross-validation. Results: For suicidal ideation, EBAL achieved an AUROC of 0.768, balanced accuracy of 0.757, sensitivity of 0.758, and specificity of 0.757. The standard LASSO achieved an AUROC of 0.760 and balanced accuracy of 0.715. EBAL improved balanced accuracy (+0.042, p=0.010) and Matthews correlation coefficient (+0.079, p=0.010), while retaining fewer stable predictors than standard LASSO (11/20 vs 18/20). The strongest positive predictors were current depressed mood, duration of mood disorder illness, and comorbid generalized anxiety disorder. For suicidal behavior, both models performed near chance and retained all candidate predictors. Limitations: The study was cross-sectional, single-site, and modest in sample size, with no external validation cohort. Conclusions: EBAL produced a sparser and more clinically coherent model for suicidal ideation in pediatric bipolar disorder, but did not improve prediction of suicidal behavior. These findings support evidence-guided regularization as a transparent strategy for aligning psychiatric prediction models with prior clinical knowledge while preserving interpretability.

02.
medRxiv (Medicine) 2026-06-25

Evaluating Generative Video AI for Standardized Psychiatric Patient Simulation With Graded Hygiene Deterioration.

Abstract Introduction: A clinician's initial assessment during the mental status examination (MSE) places substantial weight on a patient's general appearance, grooming, and hygiene. However, the logistical difficulty of producing simulated or standardized patient (SP) videos that systematically manipulate these characteristics limits the development of clinical AI tools and training curricula. This pilot study investigates the technical feasibility of using a video-generation diffusion model to re-animate modified reference images onto driving videos, enabling the creation of diverse patient presentations without the need for repeated filming. Methods: Utilizing an established publicly available dataset, we extracted reference images of three SPs and applied a text-to-image AI model to generate five appearance conditions: the unmodified baseline and four escalating hygiene-deterioration levels: mild, moderate, marked, and severe. We then used the Wan2.2-Animate-14B animate video generation AI model to re-animate these modified portraits onto the original driving footage. This factorial design varied several model parameters including; pose retargeting, classifier-free guidance scales, and generation modes, resulting in 180 unique videos. Quality was measured through Frechet Video Distance (FVD) for distributional fidelity and a physics-aware assessment performed by a multimodal large language model to evaluate physical plausibility. Results: Our analysis yielded two primary observations. First, compositing through replacement-mode achieved significantly higher temporal fidelity than animation-mode (mean FVD 8.6 vs. 19.4; Cohen's d = 1.84). Second, while distributional fidelity showed a monotonic decline as hygiene perturbation increased (Spearman rho = 0.48, p < 0.001), physics-aware scores did not follow a similar trend. This pattern is consistent with fine-motor artifacts arising from model-level generative constraints rather than from the severity of the appearance modification alone. Conclusions: These findings demonstrate that generating appearance-modulated clinical video libraries is technically achievable. Nevertheless, the persistence of fine-motor artifacts underscores the necessity of expert human oversight before these materials can be safely deployed in educational and translational settings. Keywords: Generative artificial intelligence; Standardized patients; Video diffusion models; Psychiatric simulation; Mental status examination; AI-generated video; Medical education; Digital psychiatry

03.
medRxiv (Medicine) 2026-06-24

Association Between Intermittent Water Supply and Helicobacter pylori Prevalence: A Global Ecological Study

Background: Helicobacter pylori is a major global pathogen with recognized potential for waterborne transmission. Intermittent water supply affects over one billion worldwide and may promote H. pylori contamination of municipal sources. Whether water supply discontinuity contributes to population-level H. pylori burden has not been examined globally. Materials and Methods: We conducted a cross-sectional ecological analysis of 79 countries with matched utility-level water infrastructure data and country-level H. pylori prevalence estimates from a published global meta-analysis. The primary exposure was continuity of water supply (hours/day). Secondary exposures included non-revenue water percentage (NRW %), pipe breaks per utility, and operating cost coverage ratio. Unadjusted and adjusted linear regression models with heteroscedasticity-consistent standard errors were estimated, controlling for basic sanitation coverage and log-transformed population density. A sensitivity analysis used a population-based measure of water availability on demand. Results: Greater water supply continuity was independently associated with lower H. pylori prevalence in both unadjusted ({beta} = -0.987, 95% CI -1.669 to -0.305, p = 0.005) and adjusted models ({beta} = -1.125, 95% CI -1.876 to -0.375, p = 0.004). Higher NRW % and lower operating cost coverage were each associated with higher H. pylori prevalence after adjustment. Pipe breaks were not significant in regression models though the Spearman correlation was in the expected direction. Sensitivity analysis produced consistent findings. Conclusion: IWS and broader water infrastructure deterioration are associated with higher H. pylori prevalence at the country level. These findings implicate water supply continuity as a potentially relevant environmental determinant of H. pylori transmission and suggest a role for water system investment within long-term gastric cancer prevention strategies.

04.
medRxiv (Medicine) 2026-06-18

Early-life Urban Environment, Nutrition, and Pubertal Timing in Southern Europe: An Exposome Analysis

Background: Urban environmental and lifestyle factors during early life may influence pubertal timing, but the combined effects of multiple environmental exposures within an exposome analytical framework remain poorly understood. Objective: To examine the association between early-life urban environmental exposures and pubertal timing, and to explore whether these exposures interact with early-life nutritional factors, namely breastfeeding duration and childhood diet quality. Methods: Data from two European population-based birth cohorts were analysed: Generation XXI (G21, Portugal; n=5263; 51.5% girls) and INfancia y Medio Ambiente (INMA, Spain; n=1019; 50.1% girls). Urban environmental exposures including indicators of air pollution, traffic, built environment, and natural spaces were estimated at 4 early-life stages at both cohorts: pregnancy (INMA only), birth, 1 year, and 4-5 years of age. Pubertal development timing was assessed using Tanner staging and/or the Pubertal Development Scale (PDS), and age at menarche was self-reported. Exposome-Wide Association Study (ExWAS) models and unsupervised clustering followed by ordinal logistic regression models were used to examine single- and multi-exposure associations, respectively. Regression models were fitted adjusting for relevant child characteristics, maternal factors, and household socioeconomic conditions, and corrected for multiple testing. Results: Individuals living in more unfavourable urban environments characterised by higher building density, air pollution, and lower access to natural spaces showed earlier pubertal timing according to multiple outcomes, across multiple early-life exposure periods, and in both cohorts. In the G21 cohort, these environmental profiles were associated with earlier age at menarche, particularly for exposures at 1-1.5 and 4-5 years (e.g., 1-1.5y: {beta}=-0.172, FDR-adjusted p-value=0.041), while in the INMA cohort, boys exposed to more unfavourable environmental profiles showed more advanced pubertal development, also particularly for exposures at 1-1.5 and 4-5 years of age (e.g., 1-1.5y; {beta}=0.572, FDR-adjusted p-value=0.008). Among environmental domains, air pollution and traffic were the factors most consistently associated with pubertal timing. Regarding early-life nutritional factors, longer duration of exclusive breastfeeding was associated with a lower Tanner stage among girls in G21. No significant interactions between breastfeeding duration and environmental exposure clusters were observed. Conclusion: Early-life urban environmental exposures, particularly air pollution and traffic, may influence pubertal timing. Exclusive breastfeeding may have a protective role against earlier pubertal development. These findings highlight the importance of improving urban environmental conditions and promoting breastfeeding to support healthy developmental trajectories.