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01.
arXiv (CS.AI) 2026-06-16

LearnOpt: Recovering the Latent Cognitive Structure of Standardized Examinations via Knowledge Graphs and Constrained Optimization

arXiv:2606.15349v1 Announce Type: cross Abstract: Standardized examinations are typically treated as uniform syllabus coverage problems. We argue they are better understood as adversarial systems with stable latent cognitive structures diverging systematically from official syllabi. We introduce LearnOpt, which recovers this structure from historical question papers and generates personalized, time-bounded study plans. Applied to nine years of NEET questions (2016-2024, n=1,496), LearnOpt builds an exam knowledge graph from LLM-tagged questions, extracts a five-category latent skill distribution, and formulates study planning as a knapsack-variant optimization over prerequisite-aware subgraphs with Bayesian Knowledge Tracing. Central finding: NEET's latent skill distribution is stable within a syllabus regime (consecutive-year KL divergence 0.004-0.032 for 2016-2021, non-significant under permutation testing) but shifts significantly with NCERT's 2023 syllabus rationalization: pooling 2016-2021 (n=1,072) vs 2023-2024 (n=392) gives KL=0.040 (p=0.0005), with Elimination/Negation questions rising from ~20-29% to ~31-35%. Latent structure, while not permanently stationary, is piecewise stable, with shifts detectable and attributable to curricular events. Within either regime, subject predicts skill profile more strongly than year. An optimization evaluation, using one real and two synthetic mastery profiles, shows the skill-weighted objective produces a modest but real reordering of recommended topics over a mastery-conditioned frequency baseline. Applying the pipeline to JEE Advanced reveals a profile dominated by Multi-concept Integration (80.9% vs. 33.3% for NEET), with a JEE-vs-NEET divergence (KL=0.505) exceeding NEET's largest cross-subject divergence: exam tier shapes latent cognitive structure more than subject, which shapes it more than time within a regime. Code, knowledge graph, and annotated dataset are released publicly.

02.
arXiv (CS.CL) 2026-06-15

"I Didn't Make the Micro Decisions": Measuring, Inducing, and Exposing Goal-Level AI Contributions in Collaboration

As large language models (LLMs) increasingly shape how users form, refine, and extend their goals, attributing contributions in human-AI collaboration becomes critical for users calibrating their own reliance and for evaluators assessing AI-assisted work. Yet existing methods focus on final artifacts, missing the process through which goals themselves are jointly shaped. We introduce a goal-level attribution framework, CoTrace, that decomposes explicit goals into verifiable requirements and traces both direct contributions and indirect influences across dialogue turns. Applying CoTrace to 638 real-world collaboration logs, we find that while models account for only 11-26% of goal-shaping contribution, they contribute substantially more on introducing lower-level concrete requirements, and make various kinds of indirect contributions. Through controlled simulations, we show that interaction design choices significantly affect model goal-shaping behavior. In a user study, exposing participants to goal-level analyses shifts their perceived contributions by nearly 2 points on a 5-point scale, revealing systematic miscalibration in how users understand their own AI-assisted work.

03.
arXiv (CS.CL) 2026-06-15

Detecting Historical Turning Points in Italian Media: A Complex Systems Approach to a Diachronic News Corpus

The increasing availability of large-scale textual corpora has opened new possibilities for data-driven, quantitative approaches to historical analysis using Natural Language Processing (NLP). However, diachronic corpora with historical relevance from the pre-digital era remain scarce and often incomplete. We present a quantitative approach to historical analysis based on the reconstruction and exploration of a diachronic corpus of around 600,000 articles from the Italian newspaper "La Repubblica", covering all the articles published from the 1st of January 1985 to the 31st of December 2000 - a period of major political, social, and geopolitical change in Italy and globally. Using NLP techniques, we analyze the text at both lexical and semantic levels; we then apply tools from complex systems and statistical physics to trace shifts in media discourse over time. This allows us to detect key transition periods, such as the transition from the First Republic to the Second Republic in Italy, or major international conflicts like the Gulf War or the Kosovo War, without relying on prior labeling. The results show how combining computational linguistics with ideas from complex systems can offer new quantitative insight into historical changes, opening up new paths for studying the dynamics of media and society through large-scale textual data.

05.
arXiv (CS.AI) 2026-06-19

Latent Confounded Causal Discovery via Lie Bracket Geometry

arXiv:2606.19610v1 Announce Type: cross Abstract: Recent work on Kan-Do-Calculus (KDC) has established that the boundary between passive observation and active intervention in causal inference is a category-theoretic bi-adjunction, with interventions modeled by left Kan extensions and conditioning by right Kan extensions. This paper introduces two causal discovery algorithms under latent confounding, building on the information-geometric and categorical consequences of KDC. In smooth statistical settings, Radon-Nikodym derivatives between observational and interventional measures induce local causal vector fields; failures of these fields to close under Lie brackets become computable Frobenius residuals, which we interpret as witnesses of failed visible integrability and possible latent or unmodeled structure. Our first algorithm, BRIDGE (Bracket Residuals for Interventional Discovery and Geometric Estimation), combines an interventional density or Radon-Nikodym-ratio engine with a geometric screen that proposes a high-recall family of admissible arrows, identifies non-closing visible pairs as latent-obstruction candidates, and passes the reduced family to downstream score-based or differentiable discovery routines. The second algorithmic contribution, Spectral Kan-Do Flow Matching (SKFM), learns amortized intervention fields and factors latent curvature spectrally, exposing the direct Lie-space endpoint toward which BRIDGE points. A detailed set of experiments show that both algorithms are capable of discovering causal models with latent confounders while collapsing the super-exponential space of possible DAGs by many orders of magnitude. This paper introduces a new paradigm in causal discovery, where latent structure is inferred directly from the geometry of intervention-induced flows.

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

MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

Molecular dynamics (MD) is the canonical in-silico method for atomistic molecular science, simulating molecular behavior from first-principle physics. Designing an MD pipeline for a new system requires substantial expert knowledge: running it on even one molecule is expensive, ruling out trial-and-error. We automate this expert pipeline-design process with an LLM agent. Unlike existing MD agents that orchestrate a predefined tool set, we treat pipeline design as open-ended code generation in which the agent's behavior is reshaped online by verbal reward. Specifically, we build MDForge, an LLM agent whose in-context update rule densifies the sparse reward via a multi-agent debate among physics experts. On three SAMPL host-guest binding free-energy benchmarks, MDForge automatically designs MD pipelines competitive with human experts. Deployed on a library of unseen candidate guests, its CB[7] pipeline discovers a novel binder that wet-lab competition NMR confirms is a high-affinity, picomolar CB[7] binder. Our data and code are available at https://github.com/Zehong-Wang/MDForge.

07.
arXiv (CS.LG) 2026-06-16

Tail-Shape Estimation in LLM Evaluation Is Fragile: A Protocol for Diagnosing False Positives

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arXiv:2606.16511v1 Announce Type: new Abstract: Recent work motivates moving large language model (LLM) evaluation from mean-based to tail-aware metrics, including conditional value-at-risk and tail-index estimates of reward-model error. We ask whether the canonical extreme-value-theory tail-index parameter, which isolates how heavy a tail is from how large the tail mass is, adds discriminative information beyond the mean and a standard tail-magnitude statistic in LLM evaluation. We pre-register a protocol covering admissibility, goodness-of-fit, threshold-stability, and effect-size requirements for any positive tail-shape claim. The protocol is the contribution of this paper; the empirical study below is a demonstration of what its gates catch. Applied to a standard LLM toxicity-evaluation setup under two structurally different scorer families, the protocol catches three distinct modes of false positives that a naive analysis would have published, and rejects the headline tail-shape claim on both scorers. We conclude that tail-shape estimation in the LLM toxicity-evaluation setups we examined is more fragile than the recent literature suggests, and recommend the protocol as a starting point for tail-index claims in similar setups.

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

DLawBench: Evaluating LLMs Through Multi-Turn Legal Consultation

Lawyer-client consultation is a critical starting point for legal services. Effective legal assistance hinges on eliciting sufficient and truthful information from clients in order to devise strategies that best protect their interests. This task requires Large Language Models (LLMs) not only to perform robust legal reasoning, but also to strategically elicit material facts through multi-turn interactions and effectively guide clients with diverse personalities. Yet existing legal benchmarks overlook this interactive capability. To fill this gap, we introduce DLawBench, a diagnostic benchmark for real-world legal consultation. Drawing on realistic client behavior, we characterize lawyer-client interactions into four types: Cooperative, Dependent, Withdrawn, and Adversarial. Using dialogues grounded in real cases, DLawBench evaluates whether LLMs can effectively conduct legal consultation under realistic conditions. DLawBench comprises 461 cases from Chinese and U.S. law, 5,532 paired fact entries, 3,411 inquiry rubrics, and 3,348 issue-resolution rubrics, and evaluates 26 representative LLMs. Systematic experiments show substantial headroom: the best-performing model, GPT-5.5, achieves only 0.562 on consultation-grounded legal reasoning. More importantly, DLawBench exposes both sycophancy in legal consultation and a paradox: models perform worse when clients need guidance most.

09.
arXiv (CS.AI) 2026-06-19

PCBSchemaGen: Reward-Guided LLM Code Synthesis for Printed Circuit Boards (PCB) Schematic Design with Structured Verification

arXiv:2602.00510v2 Announce Type: replace Abstract: Most LLM code-synthesis benchmarks rely on unit tests as the reward oracle, but PCB schematic design has none: correctness is defined by structured physical constraints over real IC packages and pin-level assignments, per-task golden references are unavailable, and SPICE simulation does not validate schematic-level correctness. We introduce PCBSchemaGen, a training-free inference-time framework that turns a frozen LLM into a verifiable, repairable PCB schematic generator. The framework induces a domain schema from IC datasheets to ground LLM decoding, pairs it with a deterministic 5-layer continuous-reward verifier with pin-level error localization, and refines candidates through a Thompson Sampling arm-acquiring bandit. We evaluate on 2 PCB benchmarks covering 227 real-IC tasks across 22 unified circuit domains, including a public-schematic-derived suite that serves as a fully held-out generalization test (verifier, KG library, and prompts frozen before any evaluation). Under our framework, an open-weight 31B model (Gemma-4-31B) passes 81.3% of PCBBench tasks on average, and the same framework transfers across both benchmarks with zero verifier code changes; a Circuitron-style inference-time prompting baseline on the same Gemma-4-31B backbone collapses on hard system-level designs. This suggests inference-time refinement under a deterministic structural verifier is a general recipe for reference-free LLM code synthesis in domains without unit-test oracles. Our benchmarks and deterministic verifier are publicly available at https://github.com/HZou9/PCBSchemaGen_v2.

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

Sinkhorn-CPD: Robust point cloud registration via unbalanced entropic optimal transport

Coherent Point Drift (CPD) is widely used for rigid point cloud registration because of its soft correspondences and closed-form parameter updates. However, CPD's target-side marginal constraint forces every observation, including outliers, to receive exactly unit probability mass. This assumption degrades registration accuracy under heavy outliers and partial overlap. Optimal transport (OT) methods can handle missing mass through unbalanced formulations, but require hand-tuned annealing schedules. In this paper, we propose Sinkhorn-CPD, which replaces CPD's target-side marginal constraint with dual Kullback-Leibler penalties, allowing the algorithm to discard outliers on both sides. The resulting formulation is a fully unbalanced entropic optimal transport problem, which can be efficiently solved by generalized Sinkhorn iterations. Moreover, Sinkhorn-CPD preserves the closed-form Procrustes and variance updates of CPD. In our method, the variance sigma^2 plays the role of the entropic regularization parameter, which induces an automatic annealing schedule from diffuse to sharp correspondences without manual temperature tuning. Experiments on synthetic, cross-category, and scan-to-CAD benchmarks show that Sinkhorn-CPD achieves state-of-the-art accuracy, with strong robustness to outliers and partial overlap.

11.
arXiv (CS.AI) 2026-06-18

DRIFT: Refining Instruction Data via On-Policy Data Attribution

arXiv:2606.18307v1 Announce Type: cross Abstract: Optimizing the training data distribution for Supervised Fine-Tuning (SFT) dictates the capability of Large Language Models (LLMs). While existing data curation methods excel at accelerating training under constrained budgets, they are less suited to elevating the capability upper bound. The challenge here is no longer to identify a smaller subset that preserves performance, but to refine the data distribution toward instances most capable of improving the final model. To address this problem, we explore instance-level data attribution using Influence Functions (IF). We identify that standard IF formulations struggle in this setting due to two structural limitations: a proximity gap caused by off-policy validation targets, and a severe bias towards gradient norm. We propose DRIFT (Data Refinement via On-Policy Influence Functions for Supervised Fine-Tuning). Instead of relying on external reference data, DRIFT utilizes the model's on-policy rollouts as validation targets, which empirically minimizes the parameter proximity gap and better aligns with the local neighborhood assumption of IF. It further applies signed weighting based on trajectory correctness and debiases influence scores against the gradient hacking issue, allowing a small set of validation queries to act as reliable anchors for attributing the full dataset. Experiments on 7B-parameter instruction and reasoning models show that DRIFT consistently raises the performance ceiling on both, outperforming existing data curation baselines.

13.
arXiv (CS.CL) 2026-06-12

Select to Think: Unlocking SLM Potential with Local Sufficiency

Small language models (SLMs) offer efficient deployment, yet they often lag behind their larger counterparts (LLMs) in reasoning. Existing remedies either invoke an LLM at points of reasoning divergence, incurring substantial latency and cost, or rely on standard distillation, which is limited by the SLM's capacity to accurately mimic the LLM's complex generative distribution. We address this dilemma by identifying local sufficiency: at divergence points, the LLM's preferred token often resides within the SLM's top-K next-token predictions, even when failing to emerge as the SLM top-1 choice. We therefore propose Select to Think (S2T), which reframes the LLM's role from open-ended generation to selection among the SLM's proposals, simplifying the supervision signal to discrete candidate rankings. Leveraging this, we introduce S2T-Local, which distills the selection logic into the SLM, empowering it to perform autonomous re-ranking without inference-time LLM dependency. Empirically, a 1.5B SLM's top-8 candidates contain the 32B LLM's choice with a 95% hit rate, and S2T-Local improves the 1.5B SLM's Math Avg. over greedy decoding by 24.1% relative gain, matching the efficacy of 8-path self-consistency with single-trajectory efficiency.

14.
arXiv (CS.CV) 2026-06-18

URDF Synthesis from RGB-D Sequences via Differentiable Joint Inference and Energy-Consistent Verification

作者:

Reconstructing simulation-ready digital twins of articulated objects from sensor observations remains constrained by two persistent gaps: (i) part-level geometric reconstruction is decoupled from kinematic-parameter estimation, and (ii) the recovered models often violate basic dynamic invariants such as energy conservation, leading to drift when the URDF is replayed in physics simulators. We present KinemaForge, a constraint-driven pipeline that jointly infers part-level shape, joint topology, and joint parameters from short RGB-D sequences and validates the result against an energy-consistent verifier built on differentiable rigid-body dynamics. The pipeline introduces three components: a kinematic constraint graph that encodes joint-part incidences as soft edges; a differentiable screw-axis solver that backpropagates from rendered observations through Featherstone's articulated-body algorithm to joint parameters; and an energy residual loss that penalises non-physical free responses of the reconstructed model. Across five PartNet-Mobility categories and an internal RGB-D benchmark, KinemaForge reduces the average joint-axis error from 4.52 degrees to 2.83 degrees (-37.4%) over the strongest geometric baseline (PARIS) and from 5.30 degrees to 2.83 degrees (-46.6%) over the interaction-based Ditto baseline, lowers long-horizon simulation drift by 64% (vs. PARIS) over 50 s rollouts, and yields URDFs whose closed-loop manipulation success rate improves by 14.6 percentage points over Ditto in our preliminary evaluation. Code and reconstruction data will be released upon acceptance.

15.
arXiv (CS.CV) 2026-06-16

FUSE: Quantifying Uncertainty in Vision-Language Models by Bayesian Fusing Epistemic and Aleatoric Uncertainty

Vision-language models (VLMs) are playing an increasingly important role across multiple domains. In many applications, such as robotics, it is crucial to quantify the uncertainty in the output of these models. } We develop FUSE, a probabilistic framework for capturing two complementary sources of uncertainty in vision-language modeling: (i) aleatoric embedding-level uncertainty derived from input data vision-language ambiguity, and (ii) epistemic model-level uncertainty estimated from the semantic response diversity of VLMs. Our approach formulates a Bayesian fusion mechanism that analytically combines these uncertainty sources to produce a scalar measure of uncertainty. This measure can be used to reliably predict the model's output correctness for downstream applications. We demonstrate that our method outperforms baselines and achieves SOTA uncertainty calibration.

16.
bioRxiv (Bioinfo) 2026-06-10

APOSM: Pairwise preference learning improves generative small-molecule design

Small-molecule lead refinement is constrained by the cost of synthesizing and assaying candidates, making the surrogate models that prioritize compounds for experimental testing central to the design process. The reliability of such surrogates is limited by the noise and sparsity of screening measurements. We show that training the surrogate on pairwise comparisons between candidate molecules, rather than on absolute predicted scores, yields a substantially more reliable signal for active candidate selection in this regime. We develop APOSM, an active-learning algorithm that combines a fragment-based generator, a pairwise message-passing graph neural network surrogate, and probabilistic ranking inside a batched acquisition loop. On the Practical Molecular Optimization benchmark and a GPCR ligand rediscovery task, APOSM improves target attainment and sampling efficiency over unguided fragment-based optimization, the Graph-GA genetic algorithm, and a pointwise-regression ablation, with the largest gains on tasks where absolute scores are hardest to calibrate.

17.
arXiv (math.PR) 2026-06-17

Optimal Impulse Control for Cyber Risk Management

arXiv:2410.17706v2 Announce Type: replace-cross Abstract: We explore an optimal impulse control problem wherein an electronic device owner strategically calibrates protection levels against cyber attacks. Utilizing epidemiological compartment models, we qualitatively characterize the dynamics of cyber attacks within the network. We determine the optimal protective measures against effective hacking by formulating and solving a stochastic control problem with optimal switching. We demonstrate that the value function for the cluster owner constitutes a viscosity solution to a system of coupled variational inequalities associated with a fully coupled reflected backward stochastic differential equation (BSDE). Furthermore, we devise a comprehensive algorithm alongside a verification procedure to ascertain the optimal timing for network protection across various cyber attack scenarios. Our findings are illustrated through numerical approximations employing deep Galerkin methods for partial differential equations (PDEs). We visualize the optimal protection strategies in the context of two distinct attack scenarios: (1) a constant cyber attack, (2) an exogenous cyber attack strategy modeled with a Poisson process.

18.
arXiv (CS.LG) 2026-06-15

Utility-Constrained Policy Optimization

arXiv:2606.14029v1 Announce Type: new Abstract: Constrained MDPs (CMDPs) are a widely adopted framework for incorporating safety into RL agents; however, the framework does not support risk-sensitive constraints. This can be problematic: For example, CMDPs allow for optimal solutions that, in order to satisfy the risk-neutral constraints, mix infrequent catastrophic behaviors and frequent, overly conservative ones. Moreover, prior empirical results suggest that enforcing stricter, risk-sensitive constraints can improve performance even under risk-neutral evaluation. The natural framework to incorporate risk-sensitive constraints is utility-constrained MDPs (UCMDPs), but no practical solutions for this problem existed. In this work, we introduce a simple yet powerful methodology for UCMDPs and constrained RL. Besides allowing for risk-sensitive constraints, our framework does not require us to fix constraint limits in advance of training the agent, provided that a sensible range is known. This increases policy flexibility and, in practice, allows for adjustments to these limits at no extra training cost. Besides benefiting from the generality of the framework, our agent shows strong performance in practice, consistently matching or outperforming existing baselines in several Safety Gymnasium benchmark tasks.

19.
arXiv (CS.CL) 2026-06-19

CogniFold: Always-On Proactive Memory via Cognitive Folding

Existing agent memory remains predominantly reactive and retrieval-based, lacking the capacity to autonomously organize experience into persistent cognitive structure. Toward genuinely autonomous agents, we introduce CogniFold, a brain-inspired "always-on" agent memory designed for the next generation of proactive assistants. CogniFold continuously folds fragmented event streams into self-emerging cognitive structures, bootstrapping progressively higher-level cognition from incoming events and accumulated knowledge. We ground this by extending Complementary Learning Systems (CLS) theory from two layers (hippocampus, neocortex) to three, adding a prefrontal intent layer. Emulating the prefrontal cortex as the locus of intentional control and decision-making, CogniFold achieves this through graph-topology self-organization: cognitive structures proactively assemble under the stream, merge when semantically similar, decay when stale, relink through associative recall, and surface intents when concept-cluster density crosses a threshold. We evaluate structural formation using CogEval-Bench, demonstrating that CogniFold uniquely produces memory structures that match cognitive expectations and concept emergence. Furthermore, across eight downstream benchmarks – two probing long-term conversational memory (LoCoMo, LongMemEval) and six spanning other cognitive domains – we validate that CogniFold simultaneously performs robustly on conventional memory tasks. Our code is available at https://github.com/OpenNorve/CogniFold.

20.
arXiv (CS.CL) 2026-06-11

LLMpedia: A Transparent Framework to Materialize an LLM's Encyclopedic Knowledge at Scale

Benchmarks like MMLU suggest flagship language models approach factuality saturation above 90\%. LLMpedia shows this picture is incomplete. We materialize ${\sim}$1.3M encyclopedia articles entirely from parametric memory across three model families, then audit every claim against Wikipedia and curated web evidence. For \texttt{gpt-5-mini}, the verifiable true rate is 68.4\% on Wikipedia-covered subjects - more than 21\,pp below MMLU - and the gap is driven by unverifiability (30.5\%), not refutation (1.2\%). Beyond Wikipedia, frontier articles audited against curated web evidence reach 57.6\%; Wikipedia covers only 56.7\% of model-surfaced subjects, and three model families overlap in just 7.3\% of subject choices. In a retrieval-trap benchmark inspired by prior analysis of Grokipedia, LLMpedia is more factual at roughly half the textual similarity to Wikipedia. Every prompt, article, and verdict is released. Data, code, interface: https://llmpedia.net.

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

What sentiment analysis can't see: Measuring whether customers were helped, and what went wrong, across 70,000 support conversations

Most companies read their customer support data at scale using sentiment analysis, which measures how customers sound rather than whether they were satisfied with the result. We tested a richer alternative on 70,450 support conversations from a leading online fundraising platform: alongside tone, we used GPT-5.4 to estimate each customer's satisfaction and to flag whether they reported a concrete problem, then validated all three readings against the 1-to-5 ratings customers left on the conversations they rated. The satisfaction estimate tracked those ratings far better than sentiment did, correlating at 0.47 against 0.36 and flagging unhappy customers with far fewer false alarms. The structured read also sees what sentiment cannot: tone and satisfaction disagree in 44% of conversations, a single "Neutral" label hides everything from quietly satisfied customers to ones who quietly gave up, and the largest group of all is "tolerated friction," customers who are satisfied but still reporting a fixable problem, a standing issue that no sentiment-based dashboard can surface. The broader finding is that LLM-based annotation can capture far more than the tonality of a customer's language, offering strong potential for new business metrics grounded instead in the customer's state (whether they were satisfied) and the cause of their problem extracted directly from the raw textual data of interactions and feedback.

22.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

23.
medRxiv (Medicine) 2026-06-15

Modelling the public-health impact of indoor air quality interventions on respiratory virus transmission

Respiratory virus transmission occurs in indoor settings where ventilation, occupancy, and dwell time determine exposure levels. Improving indoor air quality (IAQ) therefore could help reduce disease burden associated with respiratory viruses, yet its population-level impact remains poorly quantified. Here, we develop an individual-based transmission modelling framework that links within-location airborne dynamics to individual infection risk and population-level spread, whilst explicitly incorporating heterogeneity in ventilation and baseline indoor air quality across locations. We use this modelling approach to evaluate IAQ-improving interventions (air-quality interventions or AQIs), using hypothetical endemic and pandemic pathogen archetypes with properties similar to SARS-CoV-2 and influenza, and evaluate how effects on key epidemiological metrics (such as annualized incidence and epidemic final size) depend on AQI coverage, efficacy and allocation strategy. At 20% AQI intervention coverage and 80% efficacy, annualized incidence was reduced by approximately 7.2% for an endemic 'SARS-CoV-2-like' respiratory virus, and 17.0% for an endemic 'influenza-like' virus; at 60% coverage (80% efficacy) the reductions were 26.3% and 56.4%, respectively. Targeting AQI installation to the highest-risk locations outperformed random allocation: for SARS-CoV-2-like transmission, 20% coverage at 80% efficacy cut absolute incidence by 10.8% when targeted versus 7.2% when random; for influenza-like transmission, this comparison was 28.9% versus 17.0%. In epidemic scenarios, random installation at 40% coverage and 60% efficacy reduced final size by 23.7% (influenza-like) versus 6.3% (SARS-CoV-2-like). These results support treating clean indoor air as core public-health infrastructure and prioritising risk-based deployment of IAQ-improving interventions to maximise population-level benefit within budgetary and operational constraints.

24.
arXiv (CS.CV) 2026-06-19

Prediction of Alzheimer's Disease Risk Factors from Retinal Images via Deep Learning: Development and Validation of Biologically Relevant Morphological Associations in the UK Biobank

The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for continuous factors, outperforming most of the morphometry-machine learning models. Saliency-based score consistently highlighted biologically meaningful regions, particularly the optic nerve head and retinal vasculature. It also aligned with present morphometric variations. Several saliency-based scores differed significantly between incident AD and matched controls, suggesting potential overlap between retinal correlates of risk factors and preclinical AD-associated changes. CFP encodes retinal signatures linked to AD risk factors. Although not diagnostic, DL-derived retinal representations may uncover biologically meaningful risk-related structural changes mirroring the potential AD vulnerability.

25.
arXiv (CS.CV) 2026-06-16

An Adaptive Data cleaning Framework for Noisy Label Detection

Deep neural networks (DNNs) excel in computer vision tasks given large annotated datasets. In real-world applications, however, labels are often corrupted by ambiguity, human error, or dynamic environments. Over-parameterized DNNs easily memorize these noisy labels during training, degrading model accuracy and generalization. Existing data-cleaning and sample-selection strategies often rely on manually specified thresholds, prior knowledge of the noise ratio, or a single metric (either learning dynamics or geometric structure), making them unstable in complex data regimes. This paper proposes a self-adaptive data-cleaning framework that integrates local, global, and learning dynamics cues for robust noisy-label detection. Samples are mapped into a unified low-dimensional feature space through a modular feature concatenation paradigm. We provide two instantiations: a 2D metric integrating class-adaptive KNN-based local disagreement with k-means-based global centroid distance, and a 3D multi-metric that additionally incorporates a z-normalized score. Unlike conventional 1D Gaussian Mixture Models applied to a single scalar metric, our framework performs multi-metric clustering on the feature space to adaptively partition samples into clean-dominant and noise-dominant components without requiring manual thresholds or noise priors. Experiments on CIFAR-10, MNIST, and ImageNet-100 with 5% to 40% symmetric label noise show high recall across settings, including near-perfect recall (>=98%) on ImageNet-100 at 40% noise. Subsequent training yields accuracy gains across evaluated settings, especially under severe corruption on ImageNet-100. These findings suggest that multi-metric integration provides a threshold-free, practical, and low-tuning strategy for noisy label detection.