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

BBR-Net: Boundary-Balanced Replay for Continual Medical Image Segmentation

Continual learning for medical image segmentation remains challenging under domain shift because replay-based methods often preserve appearance information without explicitly modeling anatomical structure. This study investigates whether structural consistency governs knowledge retention in continual cardiac ultrasound segmentation. We propose the Boundary-Balanced Replay Network (BBR-Net), which selects replay samples using boundary-aware priority and class balance to preserve anatomically informative regions. The method is evaluated on CAMUS and CardiacNet under forward (CAMUS to CardiacNet) and reverse (CardiacNet to CAMUS) task orders. In the forward setting, BBR-Net retains source-task performance close to an offline joint-training reference, while markedly reducing catastrophic forgetting and preserving competitive target-task adaptation. Ablation results show that boundary-aware prioritization contributes to retention and improves the balance between source-task preservation and target-task adaptation when combined with class-aware sampling. In contrast, the reverse setting reveals that structure-aware replay fails when initial representations are learned from noisy and structurally inconsistent data. To isolate this effect, we conduct a controlled structural perturbation analysis by progressively corrupting source-task boundaries while keeping the dataset, architecture, and training protocol fixed. Forgetting increases consistently as structural reliability decreases, suggesting that replay effectiveness is strongly influenced by the quality of stored structural information, rather than by memory capacity alone. These findings indicate that preserving anatomical structure under domain shift is a central factor in continual medical image segmentation, and that replay mechanisms should account for structural reliability to support robust knowledge retention.

02.
arXiv (CS.CL) 2026-06-18

Lost in a Single Vector: Improving Long-Document Retrieval with Chunk Evidence Aggregation

Dense retrieval ranks one query vector against one document vector. On long documents, this interface can fail when a short but decisive span is weakened during document encoding before ranking. We study this failure mode as document-side early compression and introduce the Evidence Dilution Index (EDI) to measure how far a document-level representation falls below the strongest chunk-level evidence within the same gold document. Guided by this view, we propose DICE (Document Inference via Chunk Evidence), a training-free document-side strategy that splits documents into chunks, encodes them independently with a frozen model, and aggregates them back into a single vector while preserving the standard one-query-one-document interface. On LongEmbed, DICE improves retrieval across four backbones, with the largest gains on slices beyond 4k tokens: for Dream, Passkey >4k rises from 30.0 to 90.0 and Needle >4k from 23.3 to 74.0. Across 12,779 filtered samples, DICE yields lower EDI than the single-vector baseline in 92.8% of cases. These results establish document-level encoding as a practical and underexplored lever for long-document retrieval.

03.
PLOS Medicine 2026-05-08

Climate change and non-communicable diseases: An invisible syndemic

by Gokul Parameswaran, Sadeer Al-Kindi, Sanjay Rajagopalan Climate change accelerates non-communicable diseases (NCDs) through cascading environmental disruptions and is attributed to driving increased NCD-related mortality. Yet this syndemic remains invisible and underfunded. We detail why addressing the climate-NCD intersection is critical for improving health. In this Perspective, Sanjay Rajagopalan and colleagues discusses how climate change accelerates non-communicable diseases (NCDs) and exacerbates NCD-related mortality, and calls for greater visibility and funding to address this syndemic and improve human health.

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

From Privacy to Workflow Integrity: Communication-Graph Metadata in Autonomous Agent Interoperability

Authors:

arXiv:2606.07150v2 Announce Type: replace-cross Abstract: Agent-interoperability protocols such as A2A and MCP standardize what agents say to one another but assume address-based transport. Whether over HTTP(S) or a content-protecting binding such as MLS-based SLIM, these transports protect message content yet leave the communication graph exposed: which agent contacts which, when, and how often. In agent systems this graph is more consequential than a privacy framing suggests. Endpoints are capability-labeled, workflows are structured and chained, and interactions are coupled to real actions, so an observer recovers more than past relationships: it can infer the pending workflow and, at machine speed, act on that inference before the workflow completes. The threat is therefore one of workflow integrity, not privacy alone. We formalize a threat model for the communication graph and locate what makes its metadata distinctively consequential: not stronger fingerprinting, which we measure to be comparable to other machine traffic, but exposure across independent trust domains, coupled to autonomous action. We define transport- and bootstrap-layer privacy properties, evaluate candidate transports, and give an A2A case study where a metadata-protecting binding surfaces the protocol's implicit identity assumptions. On a generative model anchored to a real capture and over a live A2A binding, a label-blind classifier recovers a task's class from passive metadata well above chance, and from only its opening; a defense-aware adversary does not overturn this, and only the full set of properties drives recovery toward chance. The leverage of acting on the leak is distinct from recoverability: under a fixed budget an adversary realizes most of a clairvoyant attacker's advantage from a workflow's opening, governed by precision over the top-ranked workflows rather than overall accuracy, so a defense suppresses it even while recovery stays above chance.

05.
arXiv (CS.CL) 2026-06-18

PreUnlearn: Auditing Collateral Knowledge Damage Before Large Language Model Unlearning

Machine unlearning for large language models (LLMs) aims to remove specified knowledge while preserving the rest of the model's capabilities. However, the boundary between knowledge to forget and knowledge to retain is often unclear, since related and even distant information may be entangled in the model. In this paper, we study LLM unlearning from a data-centric perspective and measure how unlearning effects propagate from the forget set to same-domain and distant-domain knowledge. We find a consistent decay pattern: collateral damage is strongest near the forget set, weakens with semantic distance, but does not disappear at domain boundaries. We further ask whether such damage can be audited before unlearning is executed. We formulate forget-set auditing as a pre-unlearning prediction task and analyze which data features are most predictive of downstream damage. Our results show that interaction features between the forget set and evaluation set provide the strongest signals, suggesting that collateral damage is partly reflected in data geometry before model updates occur. These findings position forget-set auditing as an early warning tool for identifying risky unlearning runs and designing more reliable unlearning procedures.

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

Stimulus Motion Perception Studies Imply Specific Neural Computations in Human Visual Stabilization

Even during fixation the human eye is constantly in low amplitude motion, jittering over small angles in random directions at up to 100Hz. This motion results in all features of the image on the retina constantly traversing a number of cones, yet objects which are stable in the world are perceived to be stable, and any object which is moving in the world is perceived to be moving. A series of experiments carried out over a dozen years revealed the psychophysics of visual stabilization to be more nuanced than might be assumed, say, from the mechanics of stabilization of camera images, or what might be assumed to be the simplest solution from an evolutionary perspective. The psychophysics revealed by the experiments strongly implies a specific set of operations on retinal signals resulting in the observed stabilization behavior. The presentation is in two levels. First is a functional description of the action of the mechanism that is very likely responsible for the experimentally observed behavior. Second is a more speculative proposal of circuit-level neural elements that might implement the functional behavior.

07.
arXiv (CS.LG) 2026-06-12

Simultaneous Latent Budget Trees for Stratified Classification

arXiv:2606.13295v1 Announce Type: cross Abstract: In the era of Explainable Artificial Intelligence, there is a renewed focus on single trees for their ease of interpretation. This paper introduces Simultaneous Latent Budget Trees, a probabilistic machine learning framework for classification trees in the presence of a stratification factor such as a temporal, spatial, or demographic variable, acting as a control variable or potential confounder. Standard tree growth procedures are not designed to optimize a conditional split rule. A model-based split rule is proposed in which child nodes are interpreted as latent components of a simultaneous mixture model, such as the Simultaneous Latent Budget Model and its constrained versions, fitted to the parent node. Mixing parameters drive the observations, differently for each group, to the child nodes whereas latent budgets parameters update the response classes profile of each level of the control variable. Parameters are estimated by least squares considering a neural network perspective of the model. An informative tree structure can be interactively visualized with interpretation aids on the node and the paths, including visual pruning and decision tree selection procedure. Suitable measures are proposed to handle an unbalanced response class distribution. The proposed methodology is applied to investigate gender-related differences in disease progression of Amyotrophic Lateral Sclerosis. The SLBT library with the various tree-based algorithms is available in the linked GitHub repository.

08.
arXiv (CS.CV) 2026-06-12

Measurement-Calibrated Multi-Camera Fusion for Vision-Based Indoor Localization

Indoor vision-based localization systems are affected by detection noise, occlusions, and limited camera coverage, leading to uncertainty at multiple stages of the pipeline. While multi-camera data fusion is widely used to mitigate these issues, it is typically treated as a black-box component and evaluated solely end-to-end, obscuring its mechanistic contributions. To address this gap, this work investigates whether explicitly characterizing single-camera localization errors can be leveraged to calibrate and optimize multi-camera data fusion. We introduce a measurement-calibrated fusion approach that integrates component-wise error quantification, specifically isolating homography calibration, human detection, and motion tracking. A component-wise evaluation is conducted to quantify error contributions from homography calibration, human detection, and motion tracking. Experimental results show that data fusion improves localization accuracy compared to single-camera baselines. While measurement-calibrated fusion provides only limited improvement in absolute accuracy over standard fusion, it substantially reduces trajectory variance and improves motion smoothness, which are critical for applications requiring stable and continuous motion estimates. These results highlight the value of explicit error characterization when designing data fusion strategies for vision-based indoor positioning systems.

09.
arXiv (math.PR) 2026-06-12

Averaging principles for nonautonomous multiscale McKean-Vlasov stochastic systems

arXiv:2606.12820v1 Announce Type: new Abstract: This paper investigates a class of nonautonomous multiscale McKean-Vlasov stochastic systems. By leveraging the nonautonomous Poisson equation, we rigorously establish both strong and weak averaging principles, accompanied by explicit convergence rates. Notably, the coefficients of the averaging equations derived in the general case retain dependence on the scaling parameter $\varepsilon$. However, under the additional assumptions that the fast-scale coefficients are either asymptotically convergent or time-periodic, we demonstrate that the slow component converges, in the strong or weak sense, to averaging equations with coefficients independent of $\varepsilon$.

10.
arXiv (CS.LG) 2026-06-18

Acceleration of an algebraic multigrid pressure solver using graph neural networks

arXiv:2606.19251v1 Announce Type: cross Abstract: Solving the pressure-Poisson equation remains the primary computational bottleneck in incompressible unstructured flow solvers primarily due to the inherent sensitivity of traditional linear solvers to mesh irregularities. This work introduces a data-driven algebraic multigrid (AMG) smoother that uses a modified graph convolutional isomorphism network (GCIN). The graph neural network predicts optimal polynomial coefficients to construct a sparse pseudo-inverse operator across diverse grid topologies. The coefficients are optimized to reduce the residual after each V-cycle iteration. By directly capturing the algebraic structure of the system from the sparse coefficient matrix, the proposed method maintains the solver's linearity while adapting to local anisotropies in unstructured grids. Our framework demonstrates significant performance gains by reducing the number of V-cycles required for a given tolerance and delivering wall-clock speedups from 4% to 37% across diverse benchmarks. Notably, the model exhibits robust generalization by maintaining efficiency on meshes up to 128 times larger than those seen in training, and by accelerating the solver's convergence on unseen industry-relevant problems such as the AirfRANS dataset.

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

Augmenting Dysarthric Speech Severity Assessment with MOS Supervision

arXiv:2606.18645v1 Announce Type: cross Abstract: Dysarthria is a speech disorder marked by reduced intelligibility and communicative effectiveness. Automatic utterance-level assessment of dysarthric speech can support scalable speech monitoring and therapy-related analysis. Yet training such systems is bottlenecked by the scarcity of clinically annotated dysarthric speech. This work proposes to augment dysarthric speech assessment using data from speech synthesis evaluations, specifically human-annotated utterances with Mean Opinion Score (MOS) labels from the QualiSpeech corpus. Experiments show that fine-tuning on speech synthesis assessment data consistently improves performance on both intelligibility and naturalness prediction, while joint training yields gains primarily on naturalness. These results suggest that synthesis artifacts and dysarthric speech share perceptual commonalities, and speech synthesis evaluation corpora offer a practical augmentation source that reduces reliance on scarce clinical annotations.

12.
arXiv (CS.CV) 2026-06-18

Moving Beyond Diversity: Visual Token Pruning as Subspace Reconstruction for Efficient VLMs

Despite their remarkable performance, Vision Language Models (VLMs) incur substantial computational overhead due to the large number of visual tokens. While diversity maximization has become a dominant strategy for token reduction, existing methods rely on cosine-based normalized similarity that discards magnitude information, failing to faithfully approximate the original feature representation and leading to suboptimal performance, particularly on compositional multi-skill reasoning tasks. In this paper, we introduce SPARE, a subspace reconstruction method that reformulates token pruning as a column subset selection problem and explicitly minimizes reconstruction error. By iteratively selecting tokens with large projection residuals, SPARE performs reconstruction-driven pruning beyond angular diversity. Moreover, we reveal a counterintuitive anti-relevance phenomenon: tokens with lower image-text relevance score can better preserve contextual information. Based on this finding, we incorporate anti-relevance into SPARE as an additional selection criterion to promote context-aware token selection. Extensive experiments across multiple VLMs and benchmarks demonstrate that SPARE consistently achieves state-of-the-art performance, with strong gains on compositional tasks. When applied to LLaVA, SPARE removes up to 94% of visual tokens while retaining 95% of the baseline performance, all in a fully training-free manner.

13.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

14.
arXiv (CS.AI) 2026-06-16

Can Artificial Intelligence Accelerate Technological Progress? Researchers' Perspectives on AI in Manufacturing and Materials Science

arXiv:2511.14007v3 Announce Type: replace-cross Abstract: Artificial intelligence (AI) raises expectations of substantial increases in rates of technological progress, but such anticipations are often not connected to detailed ground-level studies of AI use in innovation processes. Accordingly, it remains unclear how and to what extent AI can accelerate innovation. To help to fill this gap, we explore and assess results from 32 interviews with U.S.-based academic manufacturing and materials sciences researchers experienced with AI and machine learning (ML) techniques. We found that AI was primarily used for modeling of materials and manufacturing processes, facilitating cheaper and more rapid search of design spaces for materials and manufacturing processes alike. Benefits included cost, time, and computation savings in technology development. However, AI/ML tools were unreliable outside design spaces for which dense data were already available; they required skilled and judicious application in tandem with older research techniques; and concerns were raised about the potential to detrimentally circumvent opportunities for disruptive theoretical advancement. Based on these results, we suggest there is reason for optimism about acceleration in sustaining innovations through the use of AI/ML; but that support for conventional empirical, computational, and theoretical research is required to maintain the likelihood of further disruptive advances in manufacturing and materials.

15.
Nature (Science) 2026-06-12

Daily briefing: How Venus flytraps snap shut

Authors:

Softening cells enable flytraps to shut with astonishing speed. Plus, the cutting-edge science happening at the World Cup and why scientists shouldn’t ignore the Pope’s AI message. Softening cells enable flytraps to shut with astonishing speed. Plus, the cutting-edge science happening at the World Cup and why scientists shouldn’t ignore the Pope’s AI message.

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

No-Free-Fairness: Fundamental Limits and Trade-offs in Learning Systems

Authors:

arXiv:2606.17810v1 Announce Type: cross Abstract: In this paper, we establish a set of theoretical impossibility results, termed the No-Free-Fairness theorems, that identify three fundamental sources of disparity in learning systems. First, we show that when a task exhibits irreducible cost on a subgroup, any decision rule must trade off overall performance with disparity, yielding an inherent fairness–cost frontier. Second, we prove that even in ideal, noise-free settings where a perfectly fair and accurate solution exists, finite-sample learning alone induces nontrivial subgroup disparity, ruling out distribution-free fairness guarantees. More seriously, enforcing strict relative fairness creates a statistical bottleneck: achieving low cost may require exponentially many samples. Third, we show that limitations of the model class can independently induce disparity: if the model cannot represent accurate solutions for a subgroup, fairness remains unattainable regardless of data or training procedure. Overall, these results demonstrate that unfairness is not solely a consequence of biased data or suboptimal optimization, but arises from the intrinsic structure of decision problems, the constraints of finite data, and the expressivity of models. Our framework applies broadly beyond standard supervised learning, and suggests that achieving fairness requires explicit trade-offs and should be treated as a core design consideration.

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

Entity Labels Are Not Entity Signals: A Framework for Observable Relevance in Document Re-Ranking

Entity-aware document retrieval uses query-associated entities as ranking signals, assuming that semantically relevant entities are also useful retrieval signals. We show this assumption is insufficient- and explain why. Unlike terms, which are ground-truth observations, entity links are hypotheses produced by an imperfect linker: an entity can be topically central yet provide no discriminative signal if the linker fires indiscriminately across relevant and non-relevant documents. We formalize this as a distinction between Conceptual Entity Relevance (CER)- whether an entity is topically related to a query- and Observable Entity Relevance (OER)- whether its observed presence in a collection discriminates relevant from non-relevant documents. Across four collections and annotation sources including human entity judgments, CER and OER exhibit near-chance agreement ($\kappa \approx 0$), while OER operationalizations agree substantially ($\kappa \approx 0.5$), confirming CER as the systematic outlier. CER-based supervision selects topically plausible but weakly discriminative entities, pruning fewer than 4% of non-relevant documents on some collections. Aligning supervision with OER improves non-relevant pruning by up to 10x and open-world MAP by 0.051 over BM25. Our findings motivate a shift from conceptual to observable notions of entity relevance in entity-aware retrieval.

18.
medRxiv (Medicine) 2026-06-22

Paired plasma and EV-enriched plasma proteomics reveal nonredundant sepsis-associated host-response signatures in critical illness

Background: Plasma proteomics may identify host-response signatures in sepsis, but it is unclear whether extracellular vesicle (EV)-enriched plasma provides distinct or redundant information compared with plasma. We compared paired plasma and EV-enriched plasma proteomes in critically ill patients with sepsis and critically ill non-sepsis controls (CINS). Methods: In this prospective observational study, paired plasma and EV-enriched plasma samples were analyzed from 56 critically ill adults, including 40 patients with sepsis and 16 CINS patients. Protein abundance was quantified using liquid chromatography-tandem mass spectrometry. Analyses compared proteomic depth, protein overlap, global concordance between compartments, and differential protein abundance between CINS and sepsis. Exploratory Gene Ontology enrichment was performed as a supplementary analysis. Results: EV-enriched plasma expanded proteomic detection, identifying 2,476 filtered proteins compared with 506 in plasma. Only 386 proteins were detected in both compartments, while 2,090 were unique to EV-enriched plasma and 120 were unique to plasma. Among shared proteins, plasma and EV-enriched plasma showed modest global concordance across critically ill patients (Spearman coeff = 0.322, p = 9.19 x 10^-11), with similar findings in sepsis alone. Differential abundance analysis identified 11 sepsis-associated proteins in plasma and 22 in EV-enriched plasma. Only SAA1, SAA2, and IGFBP6 were significant in both compartments. Exploratory pathway analysis supported acute-phase and inflammatory enrichment in plasma sepsis-associated proteins, while EV-enriched signals were directionally plausible but did not meet prespecified FDR thresholds. Conclusion: Plasma and EV-enriched plasma proteomics capture related but nonredundant sepsis-associated host-response information in critically ill patients.

19.
arXiv (CS.CV) 2026-06-12

SAM-Deep-EIoU: Selective Mask Propagation for Multi-Object Tracking

Multi-object tracking has a heavy-tailed difficulty distribution: most frames are easy for a lightweight base tracker, while a small fraction are intrinsically hard. Video object segmentation (VOS) models can often preserve identity through the hard frames where the base tracker fails, but they are much more expensive in compute and memory. We propose selective mask propagation, a tracking algorithm that dispatches from a base tracker to a VOS model only on windows where an assignment-uncertainty signal fires. The base tracker's output is modified only when the VOS model makes a confident prediction that contradicts the base tracker's identity assignment; weak or inconclusive predictions preserve the base output. The method is training-free, treats both the base tracker and the VOS model as black boxes, and can benefit from replacing the VOS component with a more capable model. On DanceTrack, selective mask propagation improves three different base trackers. On SportsMOT, where identity preservation is central to sports analytics, SAM3-Deep-EIoU with global track association achieves state-of-the-art performance on the benchmark with 86.8 HOTA.

20.
arXiv (quant-ph) 2026-06-15

Efficient Simulation of Szegedy Quantum Walk Formulations and Algorithms

arXiv:2606.14226v1 Announce Type: new Abstract: Quantum walks provide a versatile framework for quantum algorithms across a wide range of applications. We develop efficient classical simulation methods for Szegedy quantum walks that avoid explicit construction of the full unitary evolution operator. Unlike previous approaches restricted to a particular walk formulation, our framework is built from fundamental update and reflection operators, enabling the simulation of a broader class of Szegedy walk formulations. We further extend these methods to phase-estimation-based algorithms coupled to the walk, including implementations suitable for large sparse graphs. The resulting methods achieve optimal $O(N^2)$ complexity for dense graphs with $N$ nodes. For sparse graphs, the computational cost scales linearly with the number of edges, which is $O(N)$ in many cases. We implement the framework in the Python package SQWLib and illustrate its capabilities through simulations of representative algorithms, including quantum simulated annealing and quantum search on graphs. These results provide a practical tool for studying Szegedy-walk-based algorithms numerically beyond purely analytical treatments.

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

Reward as An Agent for Embodied World Models

arXiv:2606.19990v1 Announce Type: new Abstract: While RL has become a promising tool for refining world models, existing methods largely rely on conservative rollouts near the training distribution, limiting exploration, behavioral diversity, and richer dynamic discovery. In this work, we challenge this conservative paradigm. We argue that the core limitation is not exploration itself, but the lack of reliable verification strategies to support broader exploration. Without reliable verification, expanded exploration becomes highly susceptible to reward hacking, where policies exploit imperfect rewards without achieving genuine improvement. To evaluate this motivation, we instantiate our method in embodied world models, where physical plausibility, and task completion provide a rigorous testbed for scalable RL under complex dynamics. On the verification side, we introduce Reward as an Agent, an agentic reward framework that actively evaluates generated behaviors to provide robust reward signals and mitigate reward hacking under distribution shifts. On the exploration side, we introduce Dynamic-Aware Rollout Diversification through DynDiff-GRPO, which explicitly expands action-space exploration to diversify trajectories, broaden state-action coverage, and encourage richer embodied behaviors beyond conservative rollout regimes. By unifying Reward as an Agent with DynDiff-GRPO, we enable RL on a more reliable reward foundation with substantially diversified sampling, effectively mitigating reward hacking while yielding significant accuracy gains across multiple open-source world models, thereby demonstrating that broader exploration can scale successfully when grounded in robust verification.

22.
medRxiv (Medicine) 2026-06-22

Multisite Real-World Validation of an Electronic Health Record-Integrated Generative Artificial Intelligence Tool for Venous Thromboembolism Risk Stratification

Background: Guiding risk-appropriate inpatient thromboprophylaxis requires venous thromboembolism (VTE) risk stratification; however, reliable risk determination remains inconsistent in routine care. Health systems increasingly pilot artificial intelligence (AI) tools, yet few studies demonstrate rigorous evaluation in the context of a learning health system (LHS). We evaluated the performance of a pilot electronic health record (EHR)-integrated generative AI (GenAI) system, inHealth General Reasoner (iHGR), for VTE risk stratification versus clinician order set classifications and physician-adjudicated chart review. Methods: This multisite retrospective validation study included adult inpatient admissions at Johns Hopkins Medicine between June 21, 2025, and Dec 18, 2025 (checklist-based order set from June 21, 2025 - November 19, 2025, and clinician judgement-based order set from November 29 - December 18, 2025). From 758 eligible admissions, we randomly sampled 500 balanced by site and order set periods. iHGR and clinician-selected order set classifications were compared with the reference standard (RS). Primary outcomes were iHGR sensitivity and specificity. Secondary analyses compared the order sets with the same RS to evaluate workflow comparators and error patterns. Results: iHGR achieved 81.8% sensitivity (95% CI 77.3-85.6) and 70.9% specificity (63.6-77.3). The checklist-based order set had 61.3% sensitivity (53.7-68.5) and 86.2% specificity (77.4-91.9). The clinician judgement-based order set had 78.1% sensitivity (71.3-83.7) and 65.4% specificity (54.3-75.0). False-negative iHGR classifications were associated with missed narrative risk factors. Conclusion: iHGR showed higher sensitivity for VTE risk than checklist-based order sets and clinician judgement without introducing systematic bias. In silico evaluation of pilot AI systems within LHSs can identify clinically important performance trade-offs and implementation targets before operational scale-up. Narrative clinical data abstraction remained a key limitation, supporting the use of GenAI to support rather than supplant clinician judgement.

23.
arXiv (CS.CL) 2026-06-12

Unsafer in Many Turns: Benchmarking and Defending Multi-Turn Safety Risks in Tool-Using Agents

LLM-based agents are becoming increasingly capable, yet their safety lags behind. This creates a gap between what agents can do and should do. This gap widens as agents engage in multi-turn interactions and employ diverse tools, introducing new risks overlooked by existing benchmarks. To systematically scale safety testing into multi-turn, tool-realistic settings, we propose a principled taxonomy that transforms single-turn harmful tasks into multi-turn attack sequences. Using this taxonomy, we construct MT-AgentRisk (Multi-Turn Agent Risk Benchmark), the first benchmark to evaluate multi-turn tool-using agent safety. Our experiments reveal substantial safety degradation: the Attack Success Rate (ASR) increases by 16% on average across open and closed models in multi-turn settings. To close this gap, we propose ToolShield, a training-free, tool-agnostic, self-exploration defense: when encountering a new tool, the agent autonomously generates test cases, executes them to observe downstream effects, and distills safety experiences for deployment. Experiments show that ToolShield effectively reduces ASR by 30% on average in multi-turn interactions. Our code is available at https://github.com/CHATS-lab/ToolShield.

24.
medRxiv (Medicine) 2026-06-12

Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk

Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 significant cell-type-specific CpG sites in 106 loci and 68 risk genes in 40 loci, including 26 previously unreported loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-{beta} signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.

25.
arXiv (CS.AI) 2026-06-19

REVEAL++: Differentiable Phenotypic Grouping for Vision-Language Retinal Modeling of Alzheimer's Disease Risk

arXiv:2606.19522v1 Announce Type: new Abstract: The retina offers a noninvasive window into neurodegenerative disease, capturing subtle structural patterns associated with a risk of future cognitive decline. Vision-language alignment frameworks such as REVEAL have shown that pairing retinal fundus images with structured clinical risk narratives improves early prediction of Alzheimer's disease (AD). A key design choice in these approaches is the use of phenotypic grouping, where individuals with similar risk profiles are treated as multi-positive pairs during contrastive learning. However, existing methods operationalize phenotypic similarity as a discrete construct, relying on hard group assignments that impose rigid supervision and decouple group formation from representation learning. We propose a continuous formulation of phenotypic structure within contrastive learning. Rather than assigning samples to fixed clusters, we model inter-subject similarity as a differentiable weighting function derived from intra-modality embedding similarities in both retinal images and risk profiles. These weights define soft multi-positive relationships through a continuous aggregation operator, enabling graded supervision that reflects the spectrum nature of disease risk. We further introduce a soft-target contrastive objective that jointly learns cross-modal alignment and phenotypic structure in an end-to-end manner. Evaluated on UK Biobank retinal imaging data for incident AD prediction, the proposed framework consistently outperforms discrete group-based contrastive learning and standard vision-language baselines. By treating phenotypic similarity as a learnable, continuous signal rather than a fixed grouping rule, our approach provides a principled and robust foundation for population-scale neurodegenerative risk modeling from multi-modal retinal and clinical data.