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01.
arXiv (CS.LG) 2026-06-17

Learn from Your Mistakes: Self-Correcting Masked Diffusion Models

arXiv:2602.11590v3 Announce Type: replace Abstract: Masked diffusion models (MDMs) have emerged as a promising alternative to autoregressive models, enabling parallel token generation while achieving competitive performance. Despite these advantages, MDMs face a fundamental limitation: once tokens are unmasked, they remain fixed, leading to error accumulation and ultimately degrading sample quality. We address this by proposing a framework that trains a model to perform both unmasking and correction. By reusing outputs from the MDM denoising network as inputs for corrector training, we train a model to recover from potential mistakes. During generation we apply additional corrective refinement steps between unmasking ones in order to change decoded tokens and improve outputs. We name our training and sampling method Progressive Self-Correction (ProSeCo) for its unique ability to iteratively refine an entire sequence, including already generated tokens. We conduct extensive experimental validation across multiple conditional and unconditional tasks, demonstrating that \method~yields better quality-efficiency trade-offs (up to ~4x faster sampling) and enables inference-time compute scaling to further increase sample quality beyond standard MDMs (up to ~1.2x improvement on benchmarks).

02.
arXiv (CS.AI) 2026-06-11

A Survey of Reasoning and Agentic Systems in Time Series with Large Language Models

arXiv:2509.11575v3 Announce Type: replace Abstract: Time series reasoning treats time as a first-class axis and incorporates intermediate evidence directly into the answer. This survey defines the problem and organizes the literature by reasoning topology with three families: direct reasoning in one step, linear chain reasoning with explicit intermediates, and branch-structured reasoning that explores, revises, and aggregates. The topology is crossed with the main objectives of the field, including traditional time series analysis, explanation and understanding, causal inference and decision making, and time series generation, while a compact tag set spans these axes and captures decomposition and verification, ensembling, tool use, knowledge access, multimodality, agent loops, and LLM alignment regimes. Methods and systems are reviewed across domains, showing what each topology enables and where it breaks down in faithfulness or robustness, along with curated datasets, benchmarks, and resources that support study and deployment (https://github.com/blacksnail789521/Time-Series-Reasoning-Survey). Evaluation practices that keep evidence visible and temporally aligned are highlighted, and guidance is distilled on matching topology to uncertainty, grounding with observable artifacts, planning for shift and streaming, and treating cost and latency as design budgets. We emphasize that reasoning structures must balance capacity for grounding and self-correction against computational cost and reproducibility, while future progress will likely depend on benchmarks that tie reasoning quality to utility and on closed-loop testbeds that trade off cost and risk under shift-aware, streaming, and long-horizon settings. Taken together, these directions mark a shift from narrow accuracy toward reliability at scale, enabling systems that not only analyze but also understand, explain, and act on dynamic worlds with traceable evidence and credible outcomes.

03.
arXiv (quant-ph) 2026-06-24

Universal Extraction of Quantum Critical Exponents and Phase Transitions via Tailored Hilbert Space

作者:

arXiv:2606.24312v1 Announce Type: cross Abstract: Finite-size scaling and the renormalization group form the central toolkit for analyzing quantum phase transitions (QPTs). In this Letter, we introduce a novel Hilbert-space tailoring scheme to probe quantum critical phenomena. Applied to the second-order QPT of the one-dimensional (1D) XY model, our method yields precise critical points and exponents on lattices containing merely 50 unit cells. We further establish the universal applicability of this framework via investigations of the Berezinskii-Kosterlitz-Thouless transition in the 1D XXZ chain: critical parameters are recovered with as few as 12 lattice sites. This technique may open an alternative, efficient route to universally characterize QPT across many-body lattice systems.

05.
medRxiv (Medicine) 2026-06-12

Does the method matter? Evaluating the effectiveness, efficiency and ease of hearing-aid gain self-adjustment

In conventional hearing-aid personalisation, clinicians cannot hear what their patients hear, and patients cannot often reliably detect or describe what they hear. Self-adjustment avoids this issue but requires user controls that adjust hearing-aid signal processing parameters to be effective, efficient and easy. In this study, we explored (a) the roles of interface complexity and stimulus type in the self-adjustment of hearing-aid gain, and (b) how well individuals can adjust one sound to match another to assess the same interfaces and stimuli. Adult hearing-aid users with mild to moderate symmetrical sensorineural hearing loss repeatedly adjusted the gain (a) to their preference from individual prescription (n = 41) and (b) to match their previous preferences from a random starting point (n = 32) using three interfaces representing different bass/mid/treble configurations and three stimuli (music, speech and speech-in-noise). The large interindividual variability in self-adjusted gains clustered into three patterns of deviation from initial prescription: increased relative bass, overall gain reduction, and close to initial prescription. There were no substantial effects of interface nor stimulus on self-adjustment reliability (median {sigma} = 2.8 dB), whereas absolute sound-matching error increased with increasing interface complexity and centre frequency. Neither individual matching accuracy nor questionnaire responses predicted either self-adjusted gains or reliability. Overall, these results show that many - but not all - hearing-aid users can adjust gains with reasonable reliability, and while it can be difficult to predict the behaviour from the individual, the individual applies a similar self-adjustment behaviour across different interfaces and stimuli.

06.
arXiv (CS.CL) 2026-06-24

Reinforcement Learning Towards Broadly and Persistently Beneficial Models

As AI systems are deployed across increasingly diverse and high-stakes settings, model alignment must generalize beyond the tasks and domains seen during training. This is especially important for reinforcement learning (RL), which can introduce unexpected misalignment through reward hacking, deception, or other unintended strategies. We study whether RL on beneficial behavior, instantiated in realistic domains, can produce broad and persistent alignment generalization beyond the training distribution. We construct a dataset of realistic situations designed to measure and train beneficial traits, such as truthfulness, fairness, risk awareness, and corrigibility, spanning varied domains, including health, science, and education. We then train models with RL on this dataset and evaluate them on more than 50 independent benchmarks of alignment and beneficial behavior. Compared to a compute-matched baseline, beneficial trait RL improves performance on over 80% of these out-of-distribution benchmarks. We observe substantial out-of-distribution alignment transfer: a beneficial-behavior RL intervention entirely limited to one domain, health, produces broad improvements on non-health alignment evaluations, including reduced reward hacking, deception, and general misalignment. Finally, we study alignment persistence: whether behavior remains robustly aligned under attempts to steer models towards misalignment. Models trained with beneficial trait RL show improved persistence, including greater resistance to adversarial prompting and harmful finetuning; further work is required to isolate the sources of these effects. These results suggest that RL to reinforce beneficial behavior in realistic domains can produce models that are more robustly aligned with human flourishing.

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

Benchmarking LLM Agents on Meta-Analysis Articles from Nature Portfolio

Meta-analysis is a demanding form of evidence synthesis that combines literature retrieval, PI/ECO-guided study selection, and statistical aggregation. Its structured, verifiable workflow makes it an ideal substrate for evaluating systematic scientific reasoning, yet existing benchmarks lack ground truth across the full retrieval-screening-synthesis pipeline. We introduce MetaSyn, a dataset of 442 expert-curated meta-analyses from Nature Portfolio journals. Each entry pairs a research question with PI/ECO criteria, a retrieval corpus of 140k PubMed articles, verified positive studies, hard negatives that are topically similar but PI/ECO-ineligible, and complete search strategies and date bounds. Benchmarking twelve pipeline configurations (nine RAG variants and a protocol-driven agent) reveals a critical screening bottleneck: despite a retrieval ceiling of 90.9% recall at K=200, no system recovers more than 52.7% of ground-truth included literature. Current LLMs fail to reliably separate eligible studies from PI/ECO-failing distractors in pools of comparable topical relevance. Stage-attributed metrics capture where systems succeed and fail; a single end-to-end score does not.

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

An Integrated System for Real-Time Student Assessment and Career Guidance Using Neural Networks in Computing Disciplines

arXiv:2606.15831v1 Announce Type: new Abstract: Many undergraduate students in Computer Science (CS) and Software Engineering (SWE) struggle to identify suitable career paths, particularly when their academic performance, abilities, and interests do not fully align. To address this issue, this study proposes an AI-driven Student Assessment and Career Prediction System that integrates a Career Guidance Expert (CGE) system with a Web-Based Student Assessment (WBSA) platform. Within the integrated framework, CGE enhances personalized career recommendations using AI while also assisting students after graduation in identifying suitable jobs, research domains, and higher study opportunities aligned with their skills and interests. The WBSA platform further strengthens interaction between students and faculty through assessments, personalized tasks, mentorship activities, and a secure real-time chat application. The CGE system employs a Multilayer Perceptron (MLP) model trained on real-world academic and extracurricular data collected using the snowball sampling method from the students of universities, achieving a validation accuracy of 94.71% in predicting personalized career paths. A pre-survey was conducted across universities to evaluate the proposed model before deployment. The WBSA system was developed as a modern web application using technologies such as Node.js, Next.js, and PostgreSQL to ensure scalability, responsiveness, and secure data management. The overall system is supported by a secure cloud-based infrastructure, the platform provides reliable performance while assisting graduates to select suitable career path in IT sector. In addition, a post-survey involving both students and faculty was conducted to gather feedback and further improve the overall effectiveness and usability of the system.

09.
medRxiv (Medicine) 2026-06-16

Efficacy of Ergothioneine Supplementation on Postpartum Fatigue, Sleep Quality, and Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Postpartum asthenia, characterized by severe fatigue, sleep disturbances, and physiological stress, lacks effective targeted interventions. Ergothioneine (EGT) is a unique, naturally occurring antioxidant that actively accumulates in mitochondria, offering a compelling therapeutic rationale for systemic recovery. This study aimed to evaluate the efficacy of EGT in accelerating postpartum functional restoration and alleviating fatigue. Methods: This single-center, randomized, double-blind, placebo-controlled trial enrolled 40 postpartum women (SF-36 total score [≤] 70) who had ceased breastfeeding. Participants were randomized (1:1) to receive either 120 mg/day of EGT or a matched placebo for 30 days. Efficacy was assessed using the SF-36, Pittsburgh Sleep Quality Index (PSQI), Fatigue Scale-14 (FS-14), and Traditional Chinese Medicine (TCM) asthenia scale. To rigorously evaluate the treatment effects, advanced statistical modeling, including Linear Mixed-Effects Models (LMM) and Analysis of Covariance (ANCOVA) adjusted for baseline covariates, was employed. Results: All 40 participants completed the trial. The EGT group demonstrated robust and accelerated functional recovery. Notably, significant improvements in sleep quality (p = 0.0361) and systemic fatigue (p = 0.0059) were observed as early as Day 15. Importantly, EGT yielded a statistically significant between-group superiority in alleviating mental fatigue compared to placebo at Day 15 (p = 0.0313). By Day 30, the EGT cohort exhibited substantial within-group improvements across all primary metrics, including SF-36 (+35.94%, p = 0.0006) and FS-14 (-27.78%, p = 0.0011). Furthermore, as an additional physiological benefit, EGT induced a selective and significant reduction in hepatic transaminases (ALT: -30.42%; AST: -17.44%) within normal limits, a trend not observed in the placebo group. EGT was exceptionally well-tolerated with no treatment-related adverse events. Conclusions: EGT supplementation (120 mg/day) safely accelerates postpartum functional recovery, offering rapid relief from mental fatigue and sleep disturbances within 15 days, while concurrently optimizing hepatic physiological status. These preliminary clinical signals warrant confirmation in larger, adequately powered cohorts. Trial Registration: ChiCTR2500114171; Prospectively registered on 2025-12-08.

10.
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.

11.
arXiv (quant-ph) 2026-06-17

A polynomial-time approximation scheme for minimum-weight decoding of topological codes

arXiv:2606.18145v1 Announce Type: new Abstract: Two-dimensional topological translationally invariant (2D TTI) stabilizer codes lie at the heart of fault-tolerant quantum computation, but using them requires solving the decoding problem. Minimum-weight decoding of these codes was recently shown to be NP-hard, even in basic settings, such as the color code with Pauli $Z$ errors and the toric code with Pauli $X$, $Y$ and $Z$ errors. Here, we prove that minimum-weight decoding of 2D TTI codes nonetheless admits a polynomial-time approximation scheme (PTAS), i.e., for any constant $\varepsilon>0$, a recovery operator of weight within a multiplicative factor of $1+\varepsilon$ of the minimum can be found in polynomial time. Our approach builds on Arora's PTAS for Euclidean problems, such as the traveling salesman problem, and applies when decoding can be cast in terms of point-like excitations connected by string-like errors. It therefore extends beyond two dimensions, covering certain higher-dimensional topological codes and quantum memories, including the toric code with phenomenological or circuit-level noise.

12.
arXiv (CS.LG) 2026-06-24

Posterior Sampling Reinforcement Learning with Gaussian Processes for Continuous Control: Sublinear Regret Bounds for Unbounded State Spaces

arXiv:2603.08287v2 Announce Type: replace-cross Abstract: We analyze the Bayesian regret of the Gaussian process posterior sampling reinforcement learning (GP-PSRL) algorithm. Posterior sampling is a heuristic for decision-making under uncertainty that has been used to develop successful algorithms for a variety of continuous control problems. However, theoretical work on GP-PSRL is limited. All known regret bounds either have a sub-optimal growth rate, require strong smoothness assumptions, or fail to properly account for the fact that the set of possible system states is unbounded. Through a recursive application of the Borell-Tsirelson-Ibragimov-Sudakov inequality, we show that, with high probability, the states actually visited by the algorithm are contained within a ball of near-constant radius. We then use the chaining method to control the regret suffered by GP-PSRL under weak smoothness conditions. Our main result is a Bayesian regret bound of the order $\widetilde{\mathcal{O}}(H\sqrt{\gamma_TT})$, where $H$ is the horizon, $T$ is the number of time steps and $\gamma_T$ is the expected information gain. With this result, we resolve the limitations with prior theoretical work on PSRL, and provide the theoretical foundation and tools for analyzing PSRL in complex settings.

13.
arXiv (CS.CL) 2026-06-16

Compositional Reasoning Depth Predicts Clinical AI Failure: Empirical Evidence Consistent with Transformer Compositionality Limits in Electronic Health Record Question Answering

作者:

Aggregate accuracy benchmarks conceal a systematic structure in how large language models fail at electronic health record (EHR) question answering: questions requiring more inferential steps produce disproportionately more errors. Motivated by theoretical results on transformer compositionality limits, we introduce a pre-specified hop-count taxonomy – the number of distinct reasoning steps required to answer a clinical question from an EHR – as a principled predictor of model failure. We annotate 313 clinician-generated MedAlign EHR question-answer pairs across four hop levels and evaluate 301 questions in a within-model ablation (claude-sonnet-4-6, zero-shot vs. extended thinking) and cross-architecture replications (gpt-4o and gpt-5.4-2026-03-05, zero-shot). All three models, spanning two providers and two OpenAI generations (GPT-4 and GPT-5), show monotone accuracy decline with hop count: Claude Sonnet zero-shot falls from 30.6% (hop=1) to 17.6% (hop=4) (Cochran-Armitage z=-2.30, p=0.011; OR per hop 0.72, 95% CI [0.56,0.92], p=0.008); GPT-4o replicates this (37.8% to 14.7%; OR 0.58 [0.45,0.75], p

14.
arXiv (quant-ph) 2026-06-15

Compact graphs and quantum automorphisms

arXiv:2606.13928v1 Announce Type: new Abstract: Compact graphs are graphs for which the fractional automorphism polytope has no genuinely fractional vertices. This paper proposes a quantum analogue of this idea by evaluating the fundamental magic unitary of the quantum automorphism group on states, which we show to produce a closed convex set of doubly stochastic matrices sitting between the classical automorphism polytope and the full fractional automorphism polytope. Our main result is that the natural quantum analogue of compactness is classical, that is, a quantum compact graph is classically compact. We also relate this set to the quantum orbital algebra and obtain a hierarchy of classical and quantum compactness pseudo notions. The framework recovers familiar consequences of compactness through commutants and suggests quantum analogues of generous transitivity and distance-transitivity. We also isolate examples and open problems indicating where quantum symmetries may strictly refine the classical compactness theory.

15.
bioRxiv (Bioinfo) 2026-06-23

Model-based inference of gene expression noise from single-cell RNA-sequencing data

The heterogeneity of expression levels among genetically identical cells, termed gene expression noise, is a property of the gene expression process whose importance in the biology of organisms and their evolution is increasingly recognized. Measuring gene expression noise requires single-cell expression data, as obtained from single-cell RNA sequencing (scRNASeq). Its estimation, however, is challenging owing to (i) the presence of technical noise in addition to biological noise, and (ii) the heterogeneity of cell types in the sampled population. We propose a maximum-likelihood framework to infer biological noise from scRNASeq data, while accounting for technical noise, dropout probabilities, and distinct cell sequencing depths. We demonstrate the parameter identifiability using simulations and that the resulting noise estimates are uncorrelated from the mean gene expression, and therefore do not need extra correction in downstream analyses, easing intra- and inter- genome comparisons. Using two technical replicates of scRNASeq data from the wild yeast *Saccharomyces paradoxus*, we show that expression noise can be inferred in a reproducible manner.

17.
arXiv (CS.LG) 2026-06-18

Knockoffs-based False Discovery Rate Control and Simplification for Deep Neural Networks

arXiv:2606.04404v2 Announce Type: replace-cross Abstract: The deep neural network is a widely used framework in machine learning that has been widely applied in various fields. However, deep neural networks often involve a large number of parameters and inputs, many of which may be irrelevant to the goal or true output. These parameters and input variables not only increase computational complexity, but also contribute to additional computational cost. One solution to this problem is knockoff methods, which have proven successful in controlling false discovery rates in high-dimensional regression. Building on the knockoff methods and using the regularised neural network, this paper proposes three variable screening methods under the condition of controlling false discovery rates: one layer filter, multiple layers filter, and variable weight aggregation filter. In comparison with existing algorithms, we find that our algorithms show satisfactory performance.

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

Deep Learning of Solver-Aware Turbulence Closures from Nudged LES Dynamics

arXiv:2604.23874v3 Announce Type: replace-cross Abstract: The differentiable physics paradigm may be leveraged as an a-posteriori approach for discovering turbulence closure models by embedding a neural network parameterization directly inside the solver and optimizing it given potentially sparse target data. This addresses a key limitation of a-priori learning where direct numerical simulation (DNS) data is used to approximate the subgrid stress with the assumption of a low-pass filter. Closures trained in this a-priori manner frequently lead to unstable deployments due to the mismatch between the assumed filter and the effect of numerical discretizations and coarse-graining. In comparison, while typically stable during deployment, a-posteriori learning incurs high computational costs due to the need to backpropagate through a large eddy simulation (LES) solver. Furthermore, a-posteriori methods are challenging to apply broadly since they require significant modification of existing solvers. Finally, both approaches are limited when generalization is desired across different numerical schemes with their implicit filtering characteristics. In this work, we present a deep-learning approach for turbulence closure modeling built on the continuous data assimilation framework. Our approach enables the a-priori training of closures using sparsely observed DNS data without modifying or differentiating through the LES solver, while preserving stability during deployment for the recovery of invariant statistics. We focus on the model's ability to adapt to different discretizations by explicitly conditioning it on the numerical scheme. We use two- and three-dimensional canonical cases to test our framework and show that the learned correction systematically tracks the discretization error of the coarse solver.

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

End-to-End Radar and Communication Modulation Recognition with Neuromorphic Computing

arXiv:2606.24075v1 Announce Type: cross Abstract: Although deep learning-based methods can achieve high accuracy in automatic modulation recognition (AMR) tasks, their high computational cost makes it difficult to strike a balance between accuracy and power consumption, thereby limiting their application on resource-constrained platforms. Neuromorphic architectures that perform spike-driven inference with modest energy budgets have recently been explored for vision and timeseries tasks. Motivated by these works, we propose EMRFormer, a novel end-to-end spiking nerural network (SNN) architecture that applies spike-driven transformer to the constraints of neuromorphic hardware for AMR. The model incorporates an adaptive spike encoder and Integer Leaky Integrate-and-Fire neurons to mitigate the degradation of effective information and enhance SNN representational capacity. By integrating spike-separable Convolution Neural Networks (SSCNN) into Spike-Driven Transformers (SpikeFormer), EMRFormer effectively extracts multi-scale temporal features from the raw IQ waveforms. We validate our approach across various mainstream datasets, the experimental results show that EMRFormer achieves state-of-the-art interms of accuracy, outperforming all the baselines. Furthermore, the model maintains strong performance in low signal-to-noise(SNR) environments and reduces theoretical energy consumption by over 90%. Finally, we evaluate our model on a KA200 neuromorphic chip. The results show that our model achieves up to 5 times reduction in power compared to running on a 3090 GPU or an Orin NX. This work demonstrates a promising pathway for AMR on resource-constrained devices.

20.
arXiv (CS.CL) 2026-06-17

Security and Privacy Prompts in the Wild: What Users Ask LLMs and How LLMs Respond

Large language models (LLMs) are widely used to fulfill users' information needs; users ask LLMs about the weather, pose educational questions, and consult them for legal assistance. One particularly understudied area is digital security and privacy (S&P), where users may seek LLMs' help on how to secure their online accounts or protect their computers from cyber attacks. To the best of our knowledge, no prior study has collected or analyzed the S&P questions users ask LLMs; prior research on LLM response quality relied on expert-authored S&P misconceptions or FAQs rather than user queries. Drawing from WildChat, a dataset of 3.2M user-LLM conversations collected in the wild, our study identifies 14,727 S&P prompts and categorizes them into nine categories covering a wide range of S&P topics. From the S&P prompts, we sampled 450 and performed a thematic analysis to characterize the S&P questions users ask LLMs. Separate from the thematic analysis, we curated 270 advice-seeking S&P prompts, where users ask for recommendations, guidance, or specific S&P information. We measured LLM response quality and consistency when posing the prompt to LLMs 10 times. We found that commercial LLMs outperform open-weight models (GPT 5.5 provided "good enough" responses on 98% of prompts; Llama 4 on 47%). However, among prompts that received high-quality responses on average, commercial models sometimes produce contradictory responses across runs, risking confusing or misleading users.

21.
bioRxiv (Bioinfo) 2026-06-08

TRACEY: an updated resource for SNARE protein domain annotation with improved HMMs and expanded sequence coverage

Motivation: SNARE proteins catalyse membrane fusion across the eukaryotic endomembrane system, from synaptic vesicle exocytosis to intracellular trafficking, endosomal and vacuolar transport, and autophagy, and their accurate domain annotation depends on the quality of profile models and the sequence diversity behind them. The original SNARE domain classification predates the recent expansion of eukaryotic sequence data, leaving its HMM profiles and subgroup coverage unable to resolve divergent and lineage-specific paralogs. Results: We present an updated release of TRACEY built on a resynchronized, non-redundant collection of 18,915 curated SNARE proteins spanning 1,188 species, together with a consolidated set of 83 HMM profiles, including 43 models for newly defined subgroups, reconstructed through an iterative, mixture-model-driven procedure. In direct comparison with the legacy models, at least ~75% of sequences in every overlapping group scored better with the new HMMs, indicating systematic gains in domain detection. A redesigned web interface adds multiparameter querying, FASTA download, and direct scanning of user-submitted sequences against the curated profiles. Availability and implementation: TRACEY is freely available at https://tracey.unil.ch.

22.
arXiv (CS.CV) 2026-06-17

Response-Aware Multimodal Learning for Post-Treatment Visual Acuity Forecasting

Long-term visual acuity (VA) forecasting after anti-VEGF therapy is important for counseling and follow-up planning in diabetic macular edema (DME), yet remains challenging when only early post-treatment findings are available. While prior OCT-based methods mainly focus on short-term response or single-endpoint prediction, multi-horizon VA forecasting from early longitudinal data remains insufficiently under-explored. In this study, we assembled a real-world cohort of 188 anti-VEGF–treated DME patients with paired baseline and month-1 OCT scans, along with tabular OCT-derived biomarkers and non-imaging clinical variables. Using only these early data, we formulate a multi-horizon VA forecasting problem aimed at predicting visual outcomes at 3, 6, 12, 18, and 24 months, reflecting clinically meaningful follow-up intervals. We propose ReVA, a response-aware multimodal framework that combines baseline and month-1 OCT features with tabular variables to capture disease status and early treatment response. ReVA integrates spatial OCT attention, dependency-aware tabular encoding, and cross-modal fusion to predict patient-specific long-term VA trajectories. The proposed framework achieves MAE=0.1246, RMSE=0.1621, and R^2=0.6064 for 24-month VA prediction, with consistent performance across all forecast horizons. Our findings show that incorporating early treatment-response signals enables clinically meaningful long-term visual acuity forecasting, supporting data-driven decision support for routine anti-VEGF management. Code and pretrained models will be released on https://github.com/nguyenpbui/ReVA.

23.
medRxiv (Medicine) 2026-06-24

Deleterious mitochondrial heteroplasmy drives high-risk clonal hematopoiesis and hematological malignancy

Abstract Mitochondrial DNA (mtDNA) heteroplasmy, the coexistence of multiple mtDNA variants within cells, accumulates with age and is associated with hematological malignancies and mortality. However, whether predicted deleterious heteroplasmies causally contribute to cancer or merely represent passenger mutations remains unresolved. Here, leveraging ~36,000 first-degree relative pairs from the UK Biobank and All of Us Research Program cohorts, we deconvolute overall heteroplasmy metrics into those that are shared across family members (representing inherited variants) and those that are not (representing de novo variants) to establish a Mendelian randomization framework for assessing causality. We show that shared heteroplasmies exhibit strong purifying selection, with reduced predicted deleteriousness compared to not shared variants, and that 90% of an individual's deleterious heteroplasmy burden is somatically acquired. Critically, shared deleterious heteroplasmy burden, fixed at conception and thus temporally upstream of potential confounders, is significantly associated with hematological malignancies (RR=2.81, 95% CI 1.29-6.13), with effect sizes concordant with the not shared heteroplasmy burden. Furthermore, shared deleterious heteroplasmy specifically associates with high-risk clonal hematopoiesis of indeterminate potential (CHIP), particularly spliceosome mutations, suggesting mitochondrial dysfunction promotes clonal expansion of specific CHIP subtypes. Finally, we identify ultra-rare individual mtDNA variants associated with hematological malignancies, a hallmark of driver mutations. These findings establish mtDNA heteroplasmies, including inherited variants, as causal contributors to hematological malignancy risk and demonstrate that most disease-relevant burden is acquired during life, identifying potential opportunities for prevention and therapeutic intervention in individuals at elevated risk for hematological cancer, particularly of myeloid origin.

24.
arXiv (CS.AI) 2026-06-25

UC-Search: Risk-Aware Test-Time Search for Delayed Constrained Time-Series Control

作者:

arXiv:2606.25274v1 Announce Type: cross Abstract: Time-series models are usually scored as forecasters, yet deployed systems often require delayed decisions under uncertainty and hard feasibility constraints. UC-Search is a model-agnostic test-time wrapper: a backbone emits forecasts or action scores, a feasibility automaton rolls candidate paths forward, and bounded search returns the first action of a risk-adjusted feasible trajectory. We instantiate UC-Beam and a UCT-style UC-MCTS diagnostic, using epistemic, aleatoric, and propagated uncertainty mainly as path-risk terms. A myopic-collapse/separation theorem states when search reduces to one-step risk-greedy and when delayed feasible-set coupling can create non-myopic value. Primary evidence comes from a predeclared public $9$-family, $33$-series delayed-control suite with six held-out starts per series: UC-Pareto is positive versus validation-selected CEM, MPPI, and risk-aware random at the normalized threshold ($+3.1675/+2.3328/+2.5038$), and remains positive in a compute-matched audit ($+2.8466/+2.7418/+2.7429$). ETT/LTSF delayed-inventory validation supports the same compute-frontier claim. A 48-series raw M4 standard periodic-review lost-sales inventory audit is positive versus the strongest classic base-stock control ($+13556.7547$), CEM ($+64900.2207$), and risk-random ($+52881.6042$), while MPPI remains family-mixed. FI-2010, official-forecast adapters, SB3/FQI controls, direction/capacity/intervention checks, and synthetic mechanism tests are reported as boundary or mechanism evidence rather than broad dominance claims.

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

PhysGuard: Fisher-Guided Gradient Projection for Sim-to-Real Neural PDE Surrogates

arXiv:2606.16602v1 Announce Type: new Abstract: Neural operator models trained on simulation data often lose accuracy when applied to experimental measurements due to the sim-to-real gap. Standard fine-tuning with limited real data can reduce this gap, but it may also damage the core physics-relevant representations learned during pretraining. Although knowledge-preserving adaptation has been widely investigated in vision or language tasks, it remains unclear whether these methods are suitable for neural operators whose architectures and protected knowledge are fundamentally different. Neural operators need to preserve core-scale physical structures rather than semantic or visual features. We propose PhysGuard, a physics-preserving framework for accurate sim-to-real adaptation of neural operators. Specifically, PhysGuard uses the empirical Fisher Information Matrix computed on simulation data to identify physics-critical parameter directions, then restricts fine-tuning updates to directions that do not interfere with them. A layer-wise Gram-matrix formulation makes this efficient for models with millions of parameters, while an adaptive threshold automatically determines the protected subspace size. A spectral probe experiment shows that the dominant Fisher directions are strongly associated with low-frequency output structures. Experiments on benchmark across four neural operator architectures and different physical systems show that PhysGuard performs strongly on most evaluation metrics compared to baselines. The benefits are most evident under severe domain shift, where it reduces low-frequency error by up to 32\% compared to standard fine-tuning while maintaining adaptability. Our code is available at https://github.com/ZhouChaunge/PhysGuard.