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

Can Agents Distinguish Visually Hard-to-Separate Diseases in a Zero-Shot Setting? A Pilot Study

The rapid progress of multimodal large language models (MLLMs) has led to increasing interest in agent-based systems. While most prior work in medical imaging concentrates on automating routine clinical workflows, we study an underexplored yet clinically significant setting: distinguishing visually hard-to-separate diseases in a zero-shot setting. We benchmark representative agents on two imaging-only proxy diagnostic tasks, (1) melanoma vs. atypical nevus and (2) pulmonary edema vs. pneumonia, where visual features are highly confounded despite substantial differences in clinical management. We introduce a multi-agent framework based on contrastive adjudication. Experimental results show improved diagnostic performance (an 11-percentage-point gain in accuracy on dermoscopy data) and reduced unsupported claims on qualitative samples, although overall performance remains insufficient for clinical deployment. We acknowledge the inherent uncertainty in human annotations and the absence of clinical context, which further limit the translation to real-world settings. Within this controlled setting, this pilot study provides preliminary insights into zero-shot agent performance in visually confounded scenarios.

02.
arXiv (CS.CL) 2026-06-16

A Practical Evaluation Method for Long-Form Simultaneous Speech-to-Speech Translation

Simultaneous speech-to-speech translation (SimulS2ST) enables real-time cross-lingual communication, but existing evaluation has focused largely on short or pre-segmented speech rather than long-form, continuous input. Prior approaches are difficult to reproduce and make assumptions that do not hold for end-to-end systems. We present a practical evaluation method for long-form SimulS2ST. Given source speech, pre-segmented source transcripts, and reference translations, we run automatic speech recognition (ASR) and forced alignment on the generated target speech to recover token-level timestamps, then apply a sentence-embedding-based aligner to match the target text to its corresponding source sentences. This enables sentence-level computation of latency and quality metrics, including YAAL and xCOMET, which are then aggregated into final system-level scores. Experiments on representative SimulS2ST systems show that the method is effective in practice and reveal that current systems suffer from substantial latency accumulation on long speech.

03.
Science (Express) 2026-04-23

Structural N- and O-glycans revealed by high-resolution cryo-EM analysis of tubular mastigonemes | Science

作者: 未知作者

The chemical complexity and non-templated biosynthesis of glycans have posed significant challenges for establishing sequence-structure relationships. Here we report cryo-EM structures of tubular mastigonemes from a golden alga species, Ochromonas danica , in which a large number of N- and O-glycans are resolved at 1.8-2.2 Å resolution. Beyond high-mannose and complex N-glycans, we identify a non-canonical N-glycan on the Ala- Asn -Asp (A N D) motif. The surface spikes comprise dense O-glycans coating PSXX tetrapeptide repeats, with two glycans linked on trihydroxylated proline and one on serine per repeat. In addition to various types of sugars and their covalent modifiers, water molecules (>10% of resolved volume) and cations are clearly resolved and mediate the structural assembly. Our study establishes a framework for investigating glycan folding in high-order biological assemblies.

04.
arXiv (CS.AI) 2026-06-16

Inference-time Policy Steering via Vision and Touch

arXiv:2606.14981v1 Announce Type: cross Abstract: Inference-time steering adapts pre-trained generative robot policies during deployment by verifying candidate actions before execution. While prior methods typically perform this verification only with visual observations, vision alone is often insufficient for contact-rich manipulation, where success depends on both global task progress and subtle local interactions such as contact force. We introduce ViTaL, a visuo-tactile inference-time steering framework that formulates multimodal guidance as a bi-level optimization problem. At the high level, visual sampling-and-verification performs long-horizon mode selection, deciding what behavior the robot should execute. At the low level, tactile-guided diffusion editing refines the selected action sequence over a shorter horizon to satisfy local contact requirements. To support outcome-based steering, ViTaL learns a visuo-tactile latent world model and employs semantically aligned visual and tactile verifiers, including a novel text-conditioned tactile reward that scores predicted tactile futures directly in latent space. Across three real-world contact-rich manipulation tasks, ViTaL improves overall success by 51% over the base policy, outperforms unimodal steering by at least 33%, and exceeds naive multimodal fusion by at least 20%. Website: https://yilin-wu98.github.io/vital_website.

05.
arXiv (CS.CV) 2026-06-16

A Multi-Center Benchmark for Abdominal Disease Diagnosis and Report Generation from Non-Contrast CT

Multiphasic contrast-enhanced CT (CECT) is widely used for abdominal lesion characterization, yet it carries inherent risks of contrast-induced nephropathy, escalates acquisition burden, and heavily contributes to radiologist workload. To address these challenges, we introduce a novel multi-center benchmark for multi-organ abdominal disease diagnosis and automated radiology report generation, which learns to synthesize contrast-enhanced findings from single-phase non-contrast CT (NCCT). To support this, we curated a large-scale dataset of paired NCCT-CECT studies and their corresponding contrast-enhanced radiology reports from two centers, partitioned into internal sets and an external validation cohort. Under a unified evaluation protocol, we benchmarked five contemporary deep learning architectures encompassing chest-specific, abdomen-specific, and general-purpose multimodal domains. Extensive experiments demonstrate that NCCT retains diagnostic signals, achieving an average multi-organ AUC of 69.1% on the internal cohort and 63.1% on the external cohort, respectively. By releasing this dataset and standardized benchmark publicly, this study aims to catalyze future research into safer, resource-efficient, and globally accessible contrast-free abdominal imaging workflows. Code is available at: https://github.com/xmed-lab/TriALS-Report.

06.
arXiv (CS.AI) 2026-06-11

MODF-SIR: A Multi-agent Omni-modal Distilled Framework for Social Intelligence Reasoning

arXiv:2606.12018v1 Announce Type: new Abstract: We propose a multi-agent collaborative framework built upon a lightweight Multimodal Large Language Model (MLLM), specifically designed for social intelligence reasoning. A key feature of our approach is that both the training and inference phases are augmented via knowledge distillation. Within this architecture, multi-modal data pertinent to social intelligence is precisely localized. Furthermore, relevant long-tail events are identified, extracted, and rendered as formatted, explicit text. This formatting strategy prevents critical long-tail information from being overshadowed by head events and environmental noise during the tokenization process. Specifically, we integrate Test-Time Adaptation (TTA) across the entire reasoning pipeline, encompassing the extraction and representation of long-tail events, Chain-of-Thought (CoT) prompting, and self-reflection. This TTA mechanism is also distillation-enhanced, utilizing Low-Rank Adaptation (LoRA) to fine-tune the foundation model exclusively for instance-level reasoning. Extensive evaluations against various open-source and proprietary AI models across multiple benchmarks demonstrate the effectiveness of the proposed framework. With around 30% of training data from IntentTrain, we achieve state-of-the-art results. Codes are available at https://github.com/eeee-sys/MODF-SIR, demo is available at https://huggingface.co/spaces/Harry-1234/MODF-SIR, LoRA is available at https://huggingface.co/Harry-1234/MODF-SIR and the dataset for training router is available at https://huggingface.co/datasets/Harry-1234/IntentRouterTrain.

07.
arXiv (CS.LG) 2026-06-19

Activation- and Influence-Aware Ranks (AIR): Function-Preserving SVD Compression for LLMs

arXiv:2606.19993v1 Announce Type: new Abstract: We present Activation- and Influence-Aware Ranks (AIR), an SVD-based LLM compression framework that guides each weight matrix's low-rank approximation with a backward-signal influence metric. Starting from the activation-aware optimum of SVD-LLM(W), AIR runs a single closed-form alternating least squares (ALS) sweep that integrates influence element-wise under a monotone-descent guarantee. AIR is layer-local and composes orthogonally with end-to-end methods: alone it exceeds ACIP, and AIR+LoRA outperforms it further. AIR improves perplexity over SVD-LLM(W) by >18% at

08.
arXiv (CS.AI) 2026-06-15

Low-Burden LLM-Based Preference Learning: Personalizing Assistive Robots from Natural Language Feedback for Users with Paralysis

arXiv:2604.01463v2 Announce Type: replace-cross Abstract: Physically Assistive Robots require personalized behaviors to ensure user safety and comfort. However, traditional preference learning methods, like exhaustive pairwise comparisons, cause substantial physical and cognitive fatigue for users with severe motor impairments. To solve this, we propose a low-burden, offline framework that translates unstructured natural language feedback directly into deterministic robotic control policies. To safely bridge the gap between ambiguous human speech and robotic code, our pipeline uses Large Language Models (LLMs) grounded in the Occupational Therapy Practice Framework. This clinical reasoning decodes subjective user reactions into explicit physical and psychological needs, which are then mapped into transparent decision trees. Before deployment, an automated "LLM-as-a-Judge" verifies the code's structural safety. We validated this system in a simulated meal preparation study with 10 adults with paralysis. Results show our natural language approach significantly reduces user workload compared to traditional baselines. Additionally, occupational therapists confirmed the generated policies are safe and accurately reflect user preferences.

09.
arXiv (CS.AI) 2026-06-12

Fantastic Scientific Agents and How to Build Them: AgentBuild for Rietveld Refinement

arXiv:2606.12834v1 Announce Type: new Abstract: As scientific workflows shift from deterministic executables to LLM-based agents, the development practices on offer, such as fine-tuning, reinforcement learning, and prompt-and-go, bury the scientist's judgment. We propose treating agent construction as a workflow stage and introduce AgentBuild, which builds a scientific agent from a contract the scientist authors. The contract is a version-controlled rubric, a difficulty-graded curriculum, and a curated external knowledge base. A rubric-driven judge gates a meta-optimizer coding agent that edits the agent within a declared boundary, so the build compiles the agent, not the scientist's judgment. We instantiate this for Rietveld refinement of X-ray diffraction data through GSAS-II behind MCP and A2A, where a blank-harness construction run progresses through a lithium lanthanum zirconium oxide (LLZO) signal-to-noise ladder, reaches the 4 hour scan as a frontier case, and exposes the workflow-scope limits that remain. The same rubric that rewards credible fits also scores trajectory scope, making the frontier a contract failure rather than a pattern-fitting failure. As base models evolve, re-running AgentBuild is a re-tune, not a rebuild, and the scientist's authored contract remains the durable asset.

10.
arXiv (CS.CV) 2026-06-16

MatchLM2Lite: A Scalable MLLM-to-Lite Framework for Reproduced Content Identification

Content moderation is critical for online video platforms to ensure content safety, protect creators, and sustain positive user experiences. Beyond filtering harmful content, platforms must guarantee content authenticity at scale so that users are exposed to diverse, original videos rather than low-value reproductions. We present MatchLM2Lite, a real-time, production-grade reproduced content identification (RCI) system that leverages the powerful understanding of a multimodal large language model (MLLM) distilled into a small and fast-inference model. Our system jointly models video, audio, and text signals, operating on pairs of videos to produce fine-grained reproduction scores. The system comprises two modules, MatchLM and MatchLite, and a two-stage training recipe. First, our high-capacity MLLM, MatchLM, serves as a teacher model to define the upper bound of RCI performance. Its capabilities are then distilled into a compact student model, MatchLite. This design allows MatchLite to deliver low-latency, high-throughput inference on video pairs while preserving much of MatchLM's accuracy, making it suitable for integration into real-time recommendation systems. MatchLM achieves an F1-score improvement of +8.57 compared to our previous production model. After knowledge distillation, MatchLite retains a +6.55 gain in F1-score while reducing computational cost by 35x. Deployed at scale, MatchLM2Lite enables efficient, pairwise multimodal RCI, stably serving online traffic at high queries per second (QPS) with an end-to-end latency below 30 seconds. This system has reduced the reproduced video view rate on our platform by 2.5% without degrading user engagement, demonstrating its effectiveness in a large-scale production environment.

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

Learning on a Razor's Edge: Identifiability and Singularity of Polynomial Neural Networks

arXiv:2505.11846v3 Announce Type: replace Abstract: We study function spaces parametrized by neural networks, referred to as neuromanifolds. Specifically, we focus on deep Multi-Layer Perceptrons (MLPs) and Convolutional Neural Networks (CNNs) with an activation function that is a sufficiently generic polynomial. First, we address the identifiability problem, showing that, for almost all functions in the neuromanifold of an MLP, there exist only finitely many parameter choices yielding that function. For CNNs, the parametrization is generically one-to-one. As a consequence, we compute the dimension of the neuromanifold. Second, we describe singular points of neuromanifolds. We characterize singularities completely for CNNs, and partially for MLPs. In both cases, they arise from sparse subnetworks. For MLPs, we prove that these singularities often correspond to critical points of the mean-squared error loss, which does not hold for CNNs. This provides a geometric explanation of the sparsity bias of MLPs. All of our results leverage tools from algebraic geometry.

12.
arXiv (CS.CL) 2026-06-16

RoTRAG: Rule of Thumb Reasoning for Conversation Harm Detection with Retrieval-Augmented Generation

Detecting harmful content in multi turn dialogue requires reasoning over the full conversational context rather than isolated utterances. However, most existing methods rely mainly on models internal parametric knowledge, without explicit grounding in external normative principles. This often leads to inconsistent judgments in socially nuanced contexts, limited interpretability, and redundant reasoning across turns. To address this, we propose RoTRAG, a retrieval augmented framework that incorporates concise human written moral norms, called Rules of Thumb (RoTs), into LLM based harm assessment. For each turn, RoTRAG retrieves relevant RoTs from an external corpus and uses them as explicit normative evidence for turn level reasoning and final severity classification. To improve efficiency, we further introduce a lightweight binary routing classifier that decides whether a new turn requires retrieval grounded reasoning or can reuse existing context. Experiments on ProsocialDialog and Safety Reasoning Multi Turn Dialogue show that RoTRAG consistently improves both harm classification and severity estimation over competitive baselines, with an average relative gain of around 40% in F1 across benchmark datasets and an average relative reduction of 8.4% in distributional error, while reducing redundant computation without sacrificing performance.

13.
arXiv (CS.AI) 2026-06-19

LoRDO: Distributed Low-Rank Optimization with Infrequent Communication

arXiv:2602.04396v2 Announce Type: replace-cross Abstract: Distributed training of foundation models via $\texttt{DDP}$ is limited by interconnect bandwidth. While infrequent communication strategies reduce synchronization frequency, they remain bottlenecked by the memory and communication requirements of optimizer states. Low-rank optimizers can alleviate these constraints; however, in the local-update regime, workers lack access to the full-batch gradients required to compute low-rank projections, which degrades performance. We propose $\texttt{LoRDO}$, a principled framework unifying low-rank optimization with infrequent synchronization. We first demonstrate that, while global projections based on pseudo-gradients are theoretically superior, they permanently restrict the optimization trajectory to a low-rank subspace. To restore subspace exploration, we introduce a full-rank quasi-hyperbolic update. $\texttt{LoRDO}$ achieves near-parity with low-rank $\texttt{DDP}$ in language modeling and downstream tasks at model scales of $125$M–$720$M, while reducing communication by $\approx 10 \times$. Finally, we show that $\texttt{LoRDO}$ improves performance even more in very low-memory settings with small rank/batch size.

14.
arXiv (CS.AI) 2026-06-11

Sample-Efficient Hypergradient Estimation for Decentralized Bi-Level Reinforcement Learning

arXiv:2603.14867v4 Announce Type: replace-cross Abstract: Many strategic decision-making problems, such as environment design for warehouse robots, can be naturally formulated as bi-level reinforcement learning (RL), where a leader agent optimizes its objective while a follower solves a Markov decision process (MDP) conditioned on the leader's decisions. In many situations, a fundamental challenge arises when the leader cannot intervene in the follower's optimization process; it can only observe the optimization outcome. We address this decentralized setting by deriving the hypergradient of the leader's objective, i.e., the gradient of the leader's strategy that accounts for changes in the follower's optimal policy. Unlike prior hypergradient-based methods that require extensive data for repeated state visits or rely on gradient estimators whose complexity can increase substantially with the high-dimensional leader's decision space, we leverage the Boltzmann covariance trick to derive an alternative hypergradient formulation. This enables efficient hypergradient estimation solely from interaction samples, even when the leader's decision space is high-dimensional. Additionally, to our knowledge, this is the first method that enables hypergradient-based optimization for 2-player Markov games in decentralized settings. Experiments highlight the impact of hypergradient updates and demonstrate our method's effectiveness in both discrete and continuous state tasks.

15.
arXiv (CS.AI) 2026-06-19

Spatial-Aware Reduction Framework: Towards Efficient and Faithful Visual State Space Models

arXiv:2606.19932v1 Announce Type: cross Abstract: Mamba demonstrates strong efficiency in modeling long visual sequences. However, when token reduction is applied to structurally enhanced Mamba variants, these models exhibit a severe performance collapse. We attribute this degradation to the spatially agnostic nature of existing reduction methods, which violate the two-dimensional structural premise required by the selective scanning mechanism. In this work, we propose STORM, a spatial-aware token reduction framework designed to maintain structural integrity throughout the compression process. STORM reformulates reduction into a structured operation on spatial units, enforcing localized constraints to maintain both grid topology and neighborhood coherence. As a plug-and-play module, STORM equips existing reduction pipelines with explicit spatial awareness without any training. Empirical results demonstrate that STORM achieves state-of-the-art pruning accuracy across diverse vision Mamba backbones under training-free settings. Notably, STORM delivers a substantial accuracy recovery on VMamba, outperforming prior methods by up to 63.3\% in top-1 accuracy. Meanwhile, STORM incurs only a 1.0\% accuracy drop on PlainMamba, achieving performance comparable to ViT.

16.
medRxiv (Medicine) 2026-06-22

Longitudinal multi-omics characterization of the malignant evolution in multirelapsing glioblastoma

Linking glioblastoma (GBM) evolution to clinical progression is challenged by multiple factors, including tumor location for repeated sample collection, and short patient survival. In a single individual, we collected and analysed samples from 11 operations distributed across 31 months of multi-relapsing and multifocal GBM, including terminal leptomeningeal progression. All samples shared genomic ancestry of the retinoblastoma protein 1 (RB1) and neurofibromin 1 (NF1) mutations while advanced progression and extracranial metastases featured mutations of tuberous sclerosis complex 2 (TSC2), PBRM1, CD22 and Fanconi anemia supplementation group I (FANCI), correlated with clinical resistance to immunotherapies and DNA-damaging agents. Single-cell analytics revealed distinct yet reversible shifts in response to the precision medicine arsenal. GBM parenchymal dissemination and extracranial progression were associated with strengthening of neuron-like cell phenotypes. Our multidimensional study describes GBM evolution over a rarely reported time scale, and provides a valuable resource linking genetic, molecular, cellular and clinical progressions.

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

Distilling latent electrostatics from foundation machine learning interatomic potentials

arXiv:2606.15001v1 Announce Type: cross Abstract: Foundation machine learning interatomic potentials (MLIPs) have enabled atomistic simulations across broad regions of chemical and materials space, but many remain computationally expensive and lack explicit electrostatics, limiting their use for systems governed by long-range interactions and electrical response. Previously, we introduced Latent Ewald Summation (LES), which learns latent atomic charges and long-range electrostatics from density functional theory (DFT) energy and force labels alone. Here, we use LES to extract electrostatics that are latent in foundation models: energies and forces predicted by a teacher model are used to train a lightweight LES-augmented student MLIP, with optional fine-tuning on additional DFT data. The resulting models reduce computational cost while providing access to Born effective charge tensors, and infrared spectra. We benchmark student models distilled from a broad set of foundation MLIPs, including UMA, MACE, Orb, eSEN, GemNet-OC, PET, and EquiformerV2-based models, against experimental infrared spectra for liquid water, concentrated hydrochloric acid, and the anatase TiO2(101)-water interface. Across these systems, electrostatic response can be extracted from most foundation MLIPs. The benchmark further shows that the underlying DFT level and dataset used to train the teacher model play a larger role than architecture in determining electrostatic and spectroscopic accuracy. For the TiO2-water interface, fine-tuning with a modest amount of higher-level DFT data improves structural and infrared predictions. LES-based distillation therefore provides a practical route for converting foundation MLIPs into efficient, electrically responsive models, while also testing the physical fidelity encoded in foundation models.

19.
arXiv (quant-ph) 2026-06-17

Photon anti-bunching in high harmonic generation

arXiv:2606.17620v1 Announce Type: new Abstract: Photon anti-bunching is the direct evidence for the existence of photons without having a classical counterpart. Unlike bunching of photons, which can have a semi-classical description, the effect of photon anti-bunching can only be understood with quantized electromagnetic fields. However, for the process of high harmonic generation (HHG), where many photons of the driving field are upconverted to a single photon of higher energy, there is yet no clear evidence for the presence of individual photon emission. The key result of this work is the prediction of photon anti-bunching in the process of HHG, marking it the first theoretical discovery of non-classicality in the temporal correlations of HHG photons. While other non-classical signatures in HHG, such as sub-Poissonian statistics or squeezing, have been discussed for an ensemble of photons, the anti-bunching signature reported here is a signature of a single photon. This is achieved by using the recently developed Heisenberg picture approach for quantum optical HHG, revealing clear anti-bunching signatures in the intensity correlation function across the entire harmonic spectrum.

20.
Nature (Science) 2026-06-11

‘Footballers are not superheroes’: we must tackle the mental and physical pressures of elite sport

作者:

As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge. As the men’s football World Cup gets under way, how the game weighs on the health of athletes still isn’t talked about enough, says player-turned-medic Vincent Gouttebarge.

21.
arXiv (CS.LG) 2026-06-19

Recurrent neural networks approximate continuous functions

arXiv:2606.20325v1 Announce Type: new Abstract: Classical approximation theorems ask for a new neural network whenever the target accuracy is improved. This paper studies the opposite possibility: can the network be chosen once and for all, and can accuracy be bought only by letting it run longer? We prove that this is possible for every continuous function on [-1,1]. More precisely, each such function is uniformly approximated by the time evolution of a single ReLU recurrent neural network with fixed weights and fixed hidden dimension. The mechanism behind the construction is a new intermediate model, the Turing machine with neural units (TMNU). This model retains the algorithmic freedom needed to implement polynomial approximation schemes, while remaining rigid enough to be simulated by RNNs with explicit bounds on hidden dimension and weight magnitude. The resulting convergence rates reflect the underlying polynomial approximation rates. We complement the construction with minimax lower bounds showing that runtime is not merely a proof artifact, but an unavoidable resource in this fixed-network approximation paradigm.

22.
medRxiv (Medicine) 2026-06-16

High-Risk Anti-Seizure Medication Use in Childbearing-Age People with Epilepsy in a Taenia solium Endemic Region

Background: People of childbearing potential with epilepsy in regions endemic for Taenia solium, where neurocysticercosis (NCC) is highly prevalent, represent a vulnerable population due to the elevated burden of epilepsy and resource limitations. Clinical practice in these settings remains poorly characterized. This study characterized anti-seizure medication (ASM) prescribing patterns by medication risk profiles among people of childbearing potential with epilepsy in Northern Peru, a region highly endemic for T. solium. Methods: Participants were drawn from a prospective, population-based epilepsy cohort in Tumbes, Peru (2006 to 2020). The analytic population included females with epilepsy aged 15 to 49 years. The primary outcome was pregnancy-associated ASM risk of congenital malformations and adverse neurodevelopmental outcomes. ASMs were classified as ''Established Low Risk'' (lamotrigine, levetiracetam), ''Possible Risk/Inadequate Data'' (carbamazepine, phenobarbital, phenytoin), and ''Established High Risk'' (valproic acid). Prescription patterns were examined in relation to demographic and clinical characteristics. Results: Among 1,975 individuals with epilepsy, 685 were people of childbearing potential. Approximately 34.9% met criteria for probable or definite NCC. Most ASM prescriptions were in the ''Possible Risk/Inadequate Data'' category (87.0%), and 12.8% received ''Established High Risk'' medications. In multivariable analysis, high-risk prescribing was associated with prior ASM use and polytherapy. Discussion: People of childbearing potential with epilepsy were predominantly treated with carbamazepine, phenytoin, phenobarbital, and valproate, reflecting local ASM availability. Despite evidence supporting lamotrigine and levetiracetam in pregnancy, prescribing patterns reflect local formulary constraints. These findings highlight a gap between guideline recommendations and real-world prescribing in resource-limited settings, underscoring the need for context-specific treatment strategies.

23.
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.

25.
arXiv (CS.LG) 2026-06-11

Prediction-Powered Risk Monitoring of Deployed Models for Detecting Harmful Distribution Shifts

arXiv:2602.02229v2 Announce Type: replace Abstract: We study the problem of monitoring model performance in dynamic environments where labeled data are limited. To this end, we propose prediction-powered risk monitoring (PPRM), a semi-supervised risk-monitoring approach based on prediction-powered inference (PPI). PPRM constructs anytime-valid lower bounds on the running risk by combining synthetic labels with a small set of true labels. Harmful shifts are detected via a threshold-based comparison with an upper bound on the nominal risk, satisfying assumption-free finite-sample guarantees on the type-I error. We demonstrate the effectiveness of PPRM through extensive experiments on image classification, large language model (LLM), and telecommunications monitoring tasks.