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01.
arXiv (CS.LG) 2026-06-19

Adaptive Distance-Aware Trunk Deep Operator Learning for Long-Span Roadway Bridges

arXiv:2606.20015v1 Announce Type: new Abstract: Long-span roadway bridges exhibit highly localized structural responses under vehicular loading, making repeated FE analysis computationally expensive for applications such as influence surface generation and structural digital twins. Existing SciML approaches struggle to accurately capture these localized responses. To address this challenge, this study proposes an adaptive-trunk DeepONet for localized structural response prediction in large-scale bridge systems. The framework dynamically constructs a load-dependent learning domain using a KNN strategy, allowing the network to focus on structural influence zones. The trunk network is further enhanced using distance-aware features that encode the geometric relationship between the load and structural nodes. A physics-based full-field reconstruction is incorporated through a stiffness-informed Schur complement formulation, enabling predictions at adaptive nodes to be extended to the entire structural domain. To enable scalable training, response data are generated using a reduced-order equivalent shell model that preserves the dominant global behavior while significantly reducing computational cost. The proposed framework is validated on both a benchmark bridge model and the real-world Mussafah Bridge. Results show that the method achieves FEM-level accuracy with relative errors below 5%, while reducing the total response evaluation time (including full-field reconstruction) by approximately 60x; excluding the post-processing reconstruction step, the AD-DeepONet inference is up to four orders of magnitude faster than FEM. In addition, the framework enables rapid generation of full-field responses, influence lines, and influence surfaces under arbitrary vehicular loading configurations, demonstrating strong potential for large-scale bridge analysis and digital twin applications.

02.
arXiv (quant-ph) 2026-06-12

Electric Field Distortions in Surface Ion Traps with Integrated Nanophotonics

arXiv:2503.20387v3 Announce Type: replace Abstract: The integration of photonic components into surface ion traps provides a scalable approach for trapped-ion quantum computing, sensing, and metrology, enabling compact systems with enhanced stability and precision. However, the introduction of optical apertures in the trap electrodes can distort the trapping electric field. This can lead to excess micromotion (EMM) and ion displacement which degrade the performance of quantum logic operations and optical clocks. In this work, we systematically investigate the electric field distortion in a surface ion trap with integrated waveguides and grating couplers using Finite Element Method (FEM) simulations. We analyze methods to reduce these distortions by exploiting symmetries and transparent conductive oxide materials.

03.
arXiv (CS.CV) 2026-06-11

Illumination-Robust Camera-Based Heart-Rate Estimation for Physiological Sensing in Robots

Physiological awareness is important for service, social, and assistive robots that interact with humans in everyday environments. Remote photoplethysmography (rPPG) enables non-contact heart-rate (HR) estimation from an RGB camera, making it a promising sensing modality for robot-mounted vision systems. However, illumination variation remains a major barrier to robust deployment. This paper presents an end-to-end spatial-temporal transformer framework for remote HR estimation on a new dataset with varied illumination. Our estimator integrates PRNet-based 3D face alignment, clip-level illumination augmentation, the Residual Temporal Standardization Module, and controlled hybrid temporal-frequency supervision. The training objective combines a Soft-Shifted Pearson waveform loss with a spectral Kullback-Leibler divergence loss, where a tuned weight ($\mathbf{\beta}$) controls the contribution of frequency-domain heart-rate guidance. Experiments on a static all-level mix protocol covering three illumination levels show that $\mathbf{\beta}=5$ provides the strongest result among the tested beta settings, achieving a best-run HR mean absolute error (MAE) of 0.79 bpm and an HR correlation of 0.982. Compared with the PhysFormer baseline evaluated on our dataset, our estimator reduces HR MAE by 93.6 %, while increasing HR correlation from 0.088 to 0.982, making it usable when illumination varies.

04.
bioRxiv (Bioinfo) 2026-06-18

Accounting for allelic diversity and multicopy gene detection improves the accuracy of antibiotic resistance genotypic determination

Background Genomic prediction of antimicrobial resistance (AMR) relies on the accurate detection of resistance genes or allelic variants of core genes from raw or assembled genomes sequences. For several bacterial species and antibiotics, AMR genotype-phenotype discrepancies are common, indicating that important sources of error remain unresolved. For Enterococcus faecium, we focused on identifying the sources of discrepancies for tetracycline resistance, for which genotypic detection had shown particularly low accuracy. We investigated the effect of structural variation in antibiotic resistance genes (ARGs), including gene duplications, truncations, interruptions, and mixed configurations of complete and partial gene copies, as a source of genotype-phenotype discrepancies from short-read data. We conduct further extended investigations to other antibiotic families and into another bacterial species: Escherichia coli. Methods We analyzed collections of E. faecium and E. coli genomes, integrating high-quality complete assemblies, simulated Illumina short reads, and matched AMR phenotypic data. The integrity, copy number, and allelic diversity of ARGs were examined for multiple antibiotic classes, and their impact on ARG detection and accuracy of AMR determination was assessed using several commonly used bioinformatic tools (SRST2, ARIBA and AMRFinderPlus). Results For E. faecium, after ruling out the effect of specific tet allelic variants on tetracycline susceptibility, we found that the integrity and copy number of tet(M) had a major effect on detection accuracy. Duplicated and incomplete ARGs are also common in E. faecium genomes, particularly for macrolides (erm(B)) and aminoglycosides (ant(6)-Ia and aph(3')-IIIa). In E. coli, similar patterns were observed for tet(A), erm(B) and aminoglycoside-associated genes (aph(3')-IIIa and ant(6)-Ia). Across ARGs in both species, short-read mapping methods wrongly reported interrupted genes as complete in some instances, while assembly-based methods often failed to resolve complete copies of duplicated genes. Detection accuracy improved when tools were adapted to account for gene integrity and when extended AMR databases incorporating species-specific alleles were included. Conclusions Our findings reveal that bioinformatic limitations in dealing with ARG copy number and completeness, and in accounting for allelic variation, underly a substantial source of genotype-phenotype errors, highlighting the need for improved AMR databases and bioinformatic tools that consider these factors to achieve reliable genomic prediction of AMR.

05.
arXiv (math.PR) 2026-06-15

Hierarchical symmetry selects log-Poisson cascades: classification, uniqueness, and stability

arXiv:2604.01632v2 Announce Type: replace Abstract: Within i.i.d. multiplicative cascades, a single axiom – the hierarchical symmetry, a linear contraction on incremental scaling exponents – is shown to be necessary and sufficient for the cascade multiplier to be log-Poisson. We prove: (1) a characterization theorem determining the log-Poisson law with explicit parameters, within the class of all multipliers with finite lattice moments; (2) a classification theorem locating the log-Poisson class inside the log-infinitely-divisible family and identifying the mechanism by which every rival sub-family fails the symmetry; (3) a stability theorem with sharp constants – $(1+\beta)^{1/2}$ when the limiting increment is known, $\sqrt{2}$ when it is fitted – and (4) an unconditional propagation theorem transferring the bound to the multiplier distribution at the sharp rate $\Theta(\sqrt{\varepsilon})$, with a matching lower bound. Beyond independence, the classification extends exactly at the level of asymptotic statistics (limiting cumulant generating function, large deviations, multifractal spectrum) and provably not at the level of laws: an explicit stationary ergodic Markov multiplier satisfies the symmetry exactly with a non-log-Poisson marginal, while exchangeable multipliers collapse to the i.i.d. log-Poisson cascade and finite-state Markov multipliers cannot satisfy the symmetry at all. In the continuous category of exactly scale-invariant log-infinitely-divisible multifractal random measures, no finite moment window of structure-function exponents identifies the cascade class, whereas at the level of the scale-invariance generator the symmetry selects exactly the Barral-Mandelbrot compound Poisson cascade, with scale-ratio-free stability constants. The proofs reduce to second-moment identities on [0,1] via the change of variables $u = e^{kx}$, boundedness of the multiplier, and multiplicative couplings.

06.
medRxiv (Medicine) 2026-06-16

Higher Population Coverage with Typhoid Conjugate Vaccine is Needed to Induce Herd Protection: Evidence from a Cluster-Randomized Trial in Urban Bangladesh

Introduction: A cluster randomized trial (CRT) in Bangladesh found that Vi-tetanus toxoid (Vi-TT) vaccine conferred 85% protection to vaccinees at 18 months of follow-up; however, it failed to confer significant herd protection to non-vaccinees. Methods: In the CRT, children aged 9 months to

07.
arXiv (CS.LG) 2026-06-17

A Diffusion Approximation for Temporal-Difference Learning with Linear Features under Markovian Noise

arXiv:2606.18183v1 Announce Type: cross Abstract: Temporal difference (TD) learning with linear function approximation is a core method for policy evaluation. Its classical continuous-time description is an ordinary differential equation (ODE), which captures the asymptotic mean dynamics but neglects stochastic fluctuations determining the error floor. We introduce a stochastic differential equation (SDE) approximation for linear TD(0) under Markovian noise. The resulting model distinguishes the contraction dynamics governed by the projected Bellman operator from the influence of Markovian sampling. As a consequence, the model explains the constant-stepsize error floor through the interaction between Markovian long-run covariance and the contraction geometry of the projected Bellman operator.

08.
arXiv (CS.CV) 2026-06-16

BioAutoML-NAS: An End-to-End AutoML Framework for Multimodal Insect Classification via Neural Architecture Search on Large-Scale Biodiversity Data

Insect classification is important for agricultural management and ecological research, as it directly affects crop health and production. However, this task remains challenging due to the complex characteristics of insects, class imbalance, and large-scale datasets. To address these issues, we propose BioAutoML-NAS, the first BioAutoML model using multimodal data, including images, and metadata, which applies neural architecture search (NAS) for images to automatically learn the best operations for each connection within each cell. Multiple cells are stacked to form the full network, each extracting detailed image feature representations. A multimodal fusion module combines image embeddings with metadata, allowing the model to use both visual and categorical biological information to classify insects. An alternating bi-level optimization training strategy jointly updates network weights and architecture parameters, while zero operations remove less important connections, producing sparse, efficient, and high-performing architectures. Extensive evaluation on the BIOSCAN-5M dataset demonstrates that BioAutoML-NAS achieves 96.81% accuracy, 97.46% precision, 96.81% recall, and a 97.05% F1 score, outperforming state-of-the-art transfer learning, transformer, AutoML, and NAS methods by approximately 16%, 10%, and 8% respectively. Further validation on the Insects-1M dataset obtains 93.25% accuracy, 93.71% precision, 92.74% recall, and a 93.22% F1 score. These results demonstrate that BioAutoML-NAS provides accurate, confident insect classification that supports modern sustainable farming.

09.
medRxiv (Medicine) 2026-06-12

Heterogeneity of Treatment Effect of Aspirin and Clinically Significant Bleeding in Older Adults

Aim: The global population of older adults is growing, and older age is linked to higher bleeding risk. Although guidelines discourage aspirin for primary prevention in healthy older adults due to bleeding harms outweighing benefits, many continue taking it without a clear indication. It remains unclear whether all older adults face uniform aspirin-related bleeding risk or if certain subgroups are more vulnerable. Methods: We analyzed data from 19,114 ASPREE trial participants to develop machine learning models using 116 baseline variables. Random forest (RF) and random survival forest (RSF) models predicted 5-year bleeding risk, and participants were stratified into low, intermediate, and high-risk groups based on the 20th and 80th percentiles of predicted risk. We assessed heterogeneity of treatment effect (HTE) by testing treatment-by-risk group interactions on the relative scale using Fine-Gray models, and on the absolute scale using observed 5-year cumulative incidence rates. Results: Over a median follow-up of 4.7 years, 626 major bleeding events occurred. The RF model had moderate discrimination (AUC = 0.65, 95% CI: 0.63-0.67) and good calibration (Brier = 0.032, 95% CI: 0.029-0.034). Statistically significant HTE was observed on the relative scale, with the greatest relative increase in bleeding risk seen in the low-risk group (subdistribution hazard ratio = 2.26, 95% CI: 1.27-4.01). On the absolute scale, low-risk participants experienced higher bleeding with aspirin (absolute risk difference (ARD) = 1.17%, 95% CI: 0.37-1.95), but heterogeneity in ARDs was not statistically significant (Cochran's Q p > 0.45). Similar findings were observed when using the RSF model. Conclusion: Participants at lowest baseline bleeding risk experienced the greatest relative increase in bleeding risk with aspirin therapy. We found statistically significant heterogeneity in treatment effects on the relative but not absolute scale. These findings support an individualized, risk-based approach to aspirin therapy decision-making in older adults.

10.
medRxiv (Medicine) 2026-06-10

Exploratory Assessment of Pulsed-Wave Doppler Representations of Lung Sounds Using Deep Learning: An In-Vitro Phantom Study

The increasing availability of portable ultrasound systems motivates exploration of novel approaches to respiratory signal assessment. In this in-vitro study, we investigate whether pulsed-wave (PW) Doppler ultrasound can capture structured spectral patterns from replayed lung sound recordings. Digitized respiratory sounds were replayed through a tissue-mimicking ultrasound phantom, generating 1,478 PW Doppler spectral images from recordings associated with healthy subjects and several externally labeled disease categories. Exploratory classification experiments using a ResNet-18 architecture demonstrated that these Doppler representations contain learnable differences under controlled conditions. These findings motivate further investigation into PW Doppler as a potential representation of respiratory acoustics.

11.
medRxiv (Medicine) 2026-06-10

Resolving Diagnostic Discordance in Group 2 Pulmonary Hypertension Through Staged Physiologic Testing: Insights From PVDOMICS

Background World Symposium on Pulmonary Hypertension (WSPH) Group 2 pulmonary hypertension (PH) is a clinically integrated phenotype attributed to left heart disease, whereas pre- versus post-capillary classification is operationalized primarily by pulmonary capillary wedge pressure (PCWP). Although current recommendations emphasize contextual interpretation and provocative testing for intermediate PCWP values, the relationship between PCWP-based classification and underlying phenotype has not been systematically evaluated. We aim to quantify phenotype-hemodynamic discordance across the PCWP spectrum and evaluate a staged physiology-guided framework incorporating inhaled nitric oxide (iNO), ventricular geometry, and provocative testing. Methods We studied 1,032 participants from the NHLBI-sponsored PVDOMICS cohort with multidisciplinary adjudicated phenotypes integrating clinical, imaging, physiologic, and hemodynamic data. Stage-specific PCWP thresholds classified pre- versus post-capillary physiology at rest, during iNO, and during provocation (fluid challenge or invasive cardiopulmonary exercise testing [iCPET]). Echocardiographic right ventricular-to-left ventricular (RV/LV) ratio was evaluated as a marker of ventricular interdependence. Restricted cubic spline and staged concordance analyses defined certainty-based PCWP ranges and incremental diagnostic yield. Results Adjudicated Group 2 phenotype was present in 37.0% of participants. Resting PCWP demonstrated good discrimination (AUC 0.86), but substantial bidirectional phenotype-hemodynamic discordance persisted across intermediate PCWP ranges. At a resting PCWP of 12 mmHg, 25% of participants classified as pre-capillary had adjudicated Group 2 PH, whereas at 18 mmHg, 35% classified as post-capillary remained discordant non-Group 2. Concordance did not approach 90% until PCWP values were 24 mmHg. Dynamic testing incrementally improved concordance within these overlap zones. Nearly half of adjudicated Group 2 PH participants (46.5%) were not identified by resting PCWP alone; incorporation of iNO and provocative testing increased cumulative Group 2 identification by 63.4% and improved sensitivity from 79.9% to 83.7%. Model discrimination improved from an AUC of 0.863 to 0.908 (likelihood-ratio P

12.
arXiv (CS.CV) 2026-06-11

FOCUS on Contamination: Hydrology-Informed Noise-Aware Learning for Geospatial PFAS Mapping

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with significant public health impacts, yet large-scale monitoring remains severely limited due to the high cost and logistical challenges of field sampling. The lack of samples leads to difficulty simulating their spread with physical models and limited scientific understanding of PFAS transport in surface waters. Yet, rich geospatial and satellite-derived data describing land cover, hydrology, and industrial activity are widely available. We introduce FOCUS, a geospatial deep learning framework for PFAS contamination mapping that integrates sparse PFAS observations with large-scale environmental context, including priors derived from hydrological connectivity, land cover, source proximity, and sampling distance. These priors are integrated into a principled, noise-aware loss, yielding a robust training objective under sparse labels. Across extensive ablations, robustness analyses, and real-world validation, FOCUS consistently outperforms baselines including sparse segmentation, Kriging, and pollutant transport simulations, while preserving spatial coherence and scalability over large regions. Our results demonstrate how AI can support environmental science by providing screening-level risk maps that prioritize follow-up sampling and help connect potential sources to surface-water contamination patterns in the absence of complete physical models.

13.
arXiv (CS.CV) 2026-06-15

Explaining RhythmFormer: A Systematic XAI Analysis of Periodic Sparse Attention for Remote Photoplethysmography

Remote photoplethysmography (rPPG) transformers achieve low heart-rate error on benchmarks, yet their decisions remain opaque–a growing concern as rPPG moves toward clinical heart rate estimation. Existing rPPG XAI is dominated by qualitative heatmap inspection without quantitative faithfulness metrics or physiology-grounded validation, leaving a gap between visual plausibility and auditable evidence. We address this gap. First, we adapt four attribution methods (raw attention, rollout, flow, Beyond Intuition) to RhythmFormer's bi-level routing attention with top-$k$ selection. Second, we introduce a skin coverage metric quantifying how much attribution mass falls on skin regions. Third, we adapt the SaCo faithfulness coefficient from its original classification setting to rPPG regression by using the MAE between original and perturbed predicted rPPG waveforms as the perturbation impact. Applying these tools, we quantify a multi-hop leakage effect under sparse top-$k$ routing: attention rollout and flow almost completely restores the connections that individual refined-attention layers explicitly set to zero. Beyond Intuition mitigates this via its value-projection-weighted rollout and gradient-supported mask, attaining the highest median refined skin coverage ($0.83$ vs. $0.57$ for vanilla rollout) and faithfulness ($F=0.92$) among the evaluated methods on UBFC-rPPG. Validation across diverse datasets and model variants is needed. A case study on a low-SaCo outlier further shows all four methods recovering consistently once an artefactual region is replaced, suggesting consistent SaCo behavior across attribution families in this illustrative case. Together, these metrics move XAI for rPPG toward auditable numerical evidence about spatial alignment and perturbation faithfulness, i.e. trustworthy rPPG XAI.

14.
bioRxiv (Bioinfo) 2026-06-17

AMaNITA: an end-to-end workflow for native tRNA nanopore sequencing data analysis

Transfer RNA (tRNA) molecules serve as essential adapters during protein translation. While direct RNA sequencing (DRS) via Oxford Nanopore Technologies has emerged as a powerful platform for systematic tRNAome profiling, we currently lack a simple and robust statistical framework for nanopore tRNA data analyses. Here, we address this gap by developing AMaNITA (Abundance, Modifications, and Nanopore Intensity Toolbox Application), an end-to-end bioinformatic workflow that enables simplified, robust, and scalable analyses of nanopore native tRNA sequencing datasets. AMaNITA streamlines the entire analytical trajectory: from upstream processing (basecalling, mapping, filtering, batch effect correction) to downstream assessment of differential tRNA abundance and modification stoichiometry. The workflow generates an interactive HTML report for data exploration and analysis, allowing the user to download the source data files and resulting plots. AMaNITA can be executed using Singularity from the command line, without requiring installation of dependencies.

15.
medRxiv (Medicine) 2026-06-19

Performance of family history-based colorectal cancer screening criteria by race and age at diagnosis in the Disparities and Cancer Epidemiology (DANCE) study

Importance: Family history (FH) and age are the primary criteria employed for early colorectal cancer (CRC) risk stratification. We evaluated how well these criteria identify individuals diagnosed with CRC across age and racial groups. Objective: To evaluate the performance of FH and age based screening criteria for identifying individuals with CRC, with attention to differences by race and age at diagnosis. Design, Setting, and Participants: This case control and case only analysis used data from the Disparities and Cancer Epidemiology (DANCE) cohort, a population based study of invasive CRC cases diagnosed from 2013 to 2022, recruited through the Metropolitan Detroit Cancer Surveillance System and the Louisiana Tumor Registry. Analyses included 1,158 non-Hispanic Black (NHB) and non-Hispanic White (NHW) CRC cases and 1,434 cancer-free controls from the Inflammation Health and Lung Epidemiology (INHALE) study, enrolled from the same Detroit catchment area. Data were analyzed in 2025. Exposures: Self reported cancer FH among first-degree (FD) relatives and grandparents, summarized into three FH-based screening criteria: at least one FD relative with CRC (colon early-screening criterion), any FH of Lynch syndrome related cancers, and meeting NCCN criteria for Lynch syndrome genetic testing. Main Outcomes and Measures: Proportion of cases meeting each FH based screening criterion stratified by race and age at diagnosis (

16.
medRxiv (Medicine) 2026-06-11

Association between depressive symptoms and physical function among participants with heart disease in the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Background: Depression and heart disease frequently co-occur in the aging population and are associated with functional decline and poor health outcomes. Understanding how depressive symptoms relate to different aspects of physical function among adults with heart disease may help identify high-risk subgroups. Objective: To examine the association of depressive symptoms with self-reported and observed physical function measures among participants with heart disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and assess whether associations differ by sex and race?sex groups. Methods: We conducted a cross-sectional analysis using data from REGARDS study second in-home visit (2013?2016). Depressive symptoms were measured with the 10-item Center for Epidemiologic Studies Depression scale (CES D 10), considering scores ?10 as clinically significant. Physical function measures were instrumental activities of daily living (IADL), activities of daily living (ADL), chair stand time (5 repetitions), and gait speed. Linear regression models estimated associations of depressive symptoms with function, adjusting for sociodemographic, health behavior, antidepressant medications, body mass index, and social support. Effect modification by sex and race?sex group was evaluated. Results: Among 3,055 participants, 11.7% had CES D 10 ?10. Compared to CES-D-10 scores

17.
arXiv (CS.CL) 2026-06-16

LLM-based Visual Code Completion for Aerospace Geometric Design

Recent advances in both Large Language Models (LLMs) and Vision Language Models (VLMs) have seen a step change in their ability to perform visual code completion, but the aerospace industry, which prioritizes safety and explainabilty over rapid LLM adoption, currently has no publicly announced LLM-based geometric design copilot systems in commercial use by aerospace Original Equipment Manufacturers (OEMs). This paper presents a LLM-based visual programming copilot application for aerospace engineering design tasks, using a visual programming variant of the ReAct methodology and GPT 5.4. In addition to the copilot, we describe Wingbuilder, a new Grasshopper plugin library with custom components for aerospace-specific geometry abstraction, and an associated Aerospace Visual Programming Dataset (AVPD) with 18 aerospace expert designed tasks at different levels of difficulty alongside ground truth solutions. We evaluate our copilot application with a user trial involving two experienced aerospace engineers from a large aircraft manufacturing company. We find our copilot visual programming ReAct methodology was successful in generating suggestions that participants found helpful, but slow ReAct inference times limit its usefulness to more complex time-consuming tasks where waiting for good copilot solution suggestion was worthwhile. Participants reported they liked the tool and would be willing to use it in the future.

18.
medRxiv (Medicine) 2026-06-10

Developmental Associations Linking Childhood Trauma and Early Cannabis Use to Adolescent DNA Methylation and Psychotic-Like Experiences

Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.