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01.
Nature Medicine 2026-06-15

Plasma proteomic signatures of cellular aging predict human disease

作者:
Daisy Yi Ding↗

Aging is asynchronous across cells and organs. Here we tested whether plasma proteomics can be used to analyze cell type-specific aging. From analyses of over 7,000 plasma proteins measured in 60,542 individuals, we developed machine learning models to estimate the biological age of over 40 cell types spanning neuronal, immune, glial, endocrine, epithelial and musculoskeletal origins. We observed that 20–25% of individuals exhibited accelerated aging in a single cell type and 1–3% in 10 or more cell types. Cellular aging signatures were associated with disease status and predicted incident disease and mortality over 15 years of follow-up. Individuals with the APOE4 genotype showed older astrocytes but younger macrophages compared to APOE3 carriers, whereas the APOE2 genotype had inverse associations. Moreover, extreme astrocyte aging tripled the risk of incident Alzheimer’s Disease in individuals with two APOE4 alleles, while youthful astrocytes reduced risk. Individuals with extremely aged compared to youthful skeletal myocytes exhibited a 12.7-fold higher risk of developing amyotrophic lateral sclerosis. In individuals who smoked, extreme respiratory epithelial cell aging was associated with a 58% higher lung cancer risk compared to smoking alone. Specific cellular vulnerabilities and cumulative cellular aging burden influenced survival, with youthful immune and neuronal cell types conferring protective effects. Finally, we developed a polycellular aging risk score that stratified mortality risk across cohorts and proteomics platforms. These findings establish a framework for quantifying human physiology at cellular resolution, revealing heterogeneous aging trajectories and their impact on disease susceptibility and resilience. The biological age of individual cell types can be evaluated using plasma proteomics, revealing diverse aging profiles across more than 40 cell types and links between the accelerated aging of specific cell types and disease.

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03.
arXiv (CS.CV) 2026-06-25

ScalingAR: Scaling Confidence for Autoregressive Image Generation

作者:
Harold Haodong Chen↗Xianfeng Wu↗Wen-Jie Shu↗Rongjin Guo↗Disen Lan↗Harry Yang↗Ying-Cong Chen↗

Test-time strategies have shown remarkable success in improving large language models, but their application to next-token prediction (NTP) autoregressive (AR) image generation remains largely underexplored. Existing test-time scaling (TTS) methods for visual autoregressive models (VAR) rely on frequent partial decoding and external reward models, which are inefficient and often ineffective for NTP-based image generation due to the inherent instability of intermediate decoding results. To address these limitations, we propose ScalingAR, a novel test-time scaling framework tailored for NTP-based AR image generation. ScalingAR introduces token entropy as a confidence signal and operates at two complementary levels: (i) Profile Level, integrates intrinsic uncertainty and conditional utilization into a unified confidence state, and (ii) Policy Level, leverages this state for adaptive trajectory pruning and dynamic guidance scheduling. Without requiring early decoding or auxiliary rewards, ScalingAR achieves significant improvements across diverse benchmarks. Experiments show that ScalingAR (I) improves base models by $12.5\%$ on GenEval and $15.2\%$ on TIIF-Bench, (II) reduces visual token consumption by $62.0\%$ while outperforming baselines, and (III) enhances robustness, mitigating performance degradation by $26.0\%$ in challenging scenarios. These results establish ScalingAR as a robust and efficient test-time scaling solution for autoregressive image generation.

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04.
PLOS Computational Biology 2026-06-02

Linking reduced prefrontal microcircuit inhibition in schizophrenia to EEG biomarkers in silico

作者:
Sana Rosanally↗

by Sana Rosanally, Frank Mazza, Heng Kang Yao, Faraz Moghbel, Hannah Seo, Etay Hay Reduced cortical inhibition by parvalbumin-expressing (PV) interneurons in schizophrenia is thought to be associated with impaired processing in the prefrontal cortex and altered EEG signals such as oddball mismatch negativity (MMN). Recent studies also suggest loss of somatostatin (SST) interneuron inhibition. However, establishing the link between reduced interneuron inhibition and reduced MMN experimentally in humans is currently not possible. To overcome these challenges, we simulated spiking activity and EEG during baseline and oddball response in detailed models of human prefrontal microcircuits in health and schizophrenia, with reduced PV and SST interneuron inhibition as constrained by postmortem patient data. We showed that reduced PV interneuron inhibition can account for the decreased MMN amplitude seen in schizophrenia, with a threshold below which the amplitude effect was low as seen in at-risk patients. In contrast, reduced SST interneuron inhibition did not affect the MMN amplitude. We further showed that both types of inhibition loss were necessary to account for changes in resting EEG in schizophrenia, with reduced SST interneuron inhibition increasing broadband power, and reduced PV and SST interneuron inhibition both leading to a right shift from alpha to beta frequencies. Our study thus links reduced PV and SST interneuron inhibition in schizophrenia to distinct EEG biomarkers that can serve to improve stratification and early detection using non-invasive brain signals.

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05.
arXiv (CS.CV) 2026-06-12

Navigating Gigapixel Pathology Images with Large Multimodal Models

作者:
Thomas A. Buckley↗Kian R. Weihrauch↗Katherine Latham↗Andrew Z. Zhou↗Padmini A. Manrai↗Arjun K. Manrai↗

Recent advances in large multimodal models have allowed for the development of interactive chat models that can converse and reason about pathology whole-slide images (WSIs). However, existing slide-level chat systems are often highly specialized, typically compressing WSIs into fixed slide-level embeddings or relying on multi-component pipelines, which can lose multi-scale detail and limit generalizability beyond the target task. We present GIANT (Gigapixel Image Agent for Navigating Tissue), a simple, training-free approach that lets general-purpose multimodal models navigate WSIs on their own, iteratively selecting multi-magnification crops and aggregating evidence over time. To evaluate generalizability in WSI question answering and to promote reproducibility, we introduce MultiPathQA, a benchmark suite spanning five clinical challenges and 934 questions over 868 unique WSIs. This includes a new set of 128 pathologist-authored multiple-choice questions designed to mirror real diagnostic search and multi-scale reasoning. Using GPT-5, GIANT outperforms models specialized for pathology question answering, achieving state-of-the-art performance on four out of five benchmarks.

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

Humor Style Drives Laughter, Topic Shapes Acceptability: Evaluating Bilingual Personal and Political Robot-Delivered AI Jokes

作者:
Anna-Maria Velentza↗Anne-Gwenn Bosser↗

arXiv:2606.13256v1 Announce Type: cross Abstract: Humor plays a central role in human social relationships, and recent advances in computational humor create new opportunities for integrating humor into human-robot interaction (HRI). While large language models (LLMs) can generate diverse forms of humor, it remains unclear how humor style, joke content, and language preference shape perceptions of robot-delivered humor in group settings. In this exploratory study, we employed a mixed factorial design in which participants evaluated AI-generated jokes delivered by a robot in a university classroom. We examined the effects of humor type (Affiliative, Self-Enhancing, Aggressive, Self-Defeating) and joke content (person-related vs. political) on perceived funniness and appropriateness, as well as preferred language. Results show that humor type significantly influences funniness, with Aggressive and Affiliative humor rated higher, while joke content primarily affects appropriateness, with person-related jokes preferred over political ones. Language preference was shaped by both joke content and participants' self-reported fluency and humor practices.

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07.
arXiv (quant-ph) 2026-06-24

Passive Polarization Stabilization for Robust Entanglement Distribution via Cross-Aligned Polarization Maintaining Fiber Pairs

作者:
Jin-Woo Kim↗Minchul Kim↗Jiho Park↗Junsang Oh↗Kyongchun Lim↗Byung-Seok Choi↗Chun Ju Youn↗

arXiv:2512.01229v2 Announce Type: replace Abstract: Maintaining stable entanglement distribution through perturbed fiber links is essential for practical quantum-optics experiments, yet it remains challenging because of polarization fluctuations and phase or temporal-delay variations. We demonstrate stable entangled-photon transmission using a cross-aligned polarization-maintaining fiber (CAPMF) structure composed of two polarization-maintaining fiber sections with mutually orthogonal principal axes. The CAPMF configuration passively compensates polarization fluctuations without real-time active polarization control. We theoretically analyze the CAPMF structure and experimentally verify its stabilization performance under external mechanical perturbations. In the experiment, the single-mode fiber configuration yields an average visibility of $0.7655$ and a CHSH value of $S=1.7714$, whereas the CAPMF configuration maintains an average visibility of $0.9843$ and a CHSH value of $S=2.6838$. These results show that CAPMF offers a simple and robust architecture for stabilizing fiber-interface sections in practical entanglement-distribution systems.

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

Greedy Coordinate Diffusion: Effective and Semantically Coherent Adversarial Attacks via Diffusion Guidance

作者:
Bohdan Turbal↗Blossom Metevier↗Max Springer↗Aleksandra Korolova↗

arXiv:2606.15531v1 Announce Type: new Abstract: Fine-tuning aligned language models on benign tasks (e.g. math tutoring) systematically breaks safety guardrails, even when training data contains no harmful content. While mechanistic approaches have shed light on where alignment resides in model weights, they do not by provide a general formal framework for deriving guarantees about when fine-tuning degrades it – leaving the field without principled tools for predicting or preventing alignment collapse. We develop a local geometric framework through geometric analysis of parameter-space trajectories and apply it to understand the fragility of alignment in fine-tuning. While first-order analysis suggests orthogonal updates are safe, we prove this is illusory: the curvature of the fine-tuning loss induces second-order acceleration that can induce second-order drift into alignment-sensitive regions. We formalize a construct of our framework as the Alignment Instability Condition (AIC), three geometric properties that, when present, are sufficient to guarantee degradation. Our main result proves quartic onset of alignment degradation along gradient-flow trajectories, determined by how sharply alignment depends on specific parameters and how strongly tasks couple to these parameters. These findings yield formal sufficient conditions under which static first-order protection can fail under gradient descent. We further empirically validate the framework's foundations, showing that the Fisher Information Matrix provides a proxy for the degree of safety degradation across diverse fine-tuning.

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

Prior-Informed Flow Matching for Graph Reconstruction

作者:
Harvey Chen↗Nicolas Zilberstein↗Santiago Segarra↗

arXiv:2601.22107v2 Announce Type: replace Abstract: We introduce Prior-Informed Flow Matching (PIFM), a conditional flow model for graph reconstruction. Reconstructing graphs from partial observations remains a key challenge; classical embedding methods often lack global consistency, while modern generative models struggle to incorporate structural priors. PIFM bridges this gap by integrating embedding-based priors with continuous-time flow matching. Grounded in a permutation equivariant version of the distortion-perception theory, our method first uses a prior, such as GraphSAGE or node2vec, to form an informed initial estimate of the adjacency matrix based on local information. It then applies rectified flow matching to refine this estimate, transporting it toward the true distribution of clean graphs and learning a global coupling. Experiments on different datasets demonstrate that PIFM consistently enhances classical embeddings, outperforming them and state-of-the-art generative baselines in reconstruction accuracy.

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10.
arXiv (CS.CV) 2026-06-17

Reinforcing Dual-Path Reasoning in Spatial Vision Language Models

作者:
Yatai Ji↗An-Chieh Cheng↗Yang Fu↗Yukang Chen↗Han Zhang↗Zhaojing Yang↗Wei Huang↗Ka Chun Cheung↗Song Han↗Vidya Nariyambut Murali↗Pavlo Molchanov↗Jan Kautz↗…

Spatial VLMs have made substantial progress in geometric perception, yet complex spatial reasoning requiring multi-step inference over depth, distance, and scene relations remains challenging. Moreover, different spatial queries call for fundamentally different strategies: some are best addressed through purely linguistic, step-by-step deduction, while others require explicit 3D grounding before quantitative inference. We present Dual-Path Spatial Reasoning via Reinforcement Learning for Spatial VLMs (SR-REAL), a unified framework that equips a spatial VLM with two complementary reasoning paths: Language-Only Reasoning (LOR), which performs step-by-step linguistic deduction, and Detect-Then-Reason (DTR), which detects 3D geometric cues (e.g., centers or bounding boxes) via region tokens before explicit geometric inference. SR-REAL begins with a cold-start supervised fine-tuning stage that constructs LOR and DTR chain-of-thought supervision and exposes a region-to-3D interface, followed by RL that optimizes the policy model with accuracy and format rewards; for DTR, a discrete center-based detection reward further refines geometric alignment. Across diverse spatial benchmarks, SR-REAL significantly outperforms spatial VLM baselines: (i) a single RL-trained model supports both reasoning paths, with DTR excelling in region-aware tasks through precise 3D localization and LOR enhancing general spatial reasoning; (ii) jointly training both paths fosters mutual reinforcement; (iii) high-quality, blended cold-start data is crucial for stable RL optimization; and (iv) the model generalizes across datasets and domains without per-task tuning, demonstrating positive transfer between LOR and DTR.

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11.
arXiv (quant-ph) 2026-06-25

Taxonomy of integrable and ground-state solvable models: Jastrow wave functions on graphs and parent Hamiltonians

作者:
Nilanjan Sasmal↗Adolfo del Campo↗

arXiv:2602.22315v2 Announce Type: replace Abstract: We introduce a family of many-body systems of distinguishable continuous-variable particles in which interparticle interactions are set by the adjacency matrix of a graph. The ground-state wave function of such systems is of a generalized Jastrow form involving the product of pair-correlation functions over the edge set of the graph. These systems describe quantum fluids when the graph is complete, and the pair function has a well-defined permutation symmetry. In general, they provide the continuous-variable generalization of spin systems on graphs, with broken permutation symmetry. The corresponding parent Hamiltonian is shown to include (a) two-body interactions determined by the graph adjacency matrix and (b) three-body interactions over all possible 2-paths on the graph. Employing elements of graph theory, we chart the landscape of models, recovering known instances in the literature and providing numerous new examples of ground-state solvable models for which the system Hamiltonian, ground-state wave function, and corresponding energy eigenvalue are specified.

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12.
medRxiv (Medicine) 2026-06-17

Womens intentions and motivations towards health behaviour change before pregnancy: a cross-sectional survey of pregnant women in Australia

作者:
Steel↗Schoenaker↗McIntyre↗Rogers↗Hall↗Adams↗

Introduction: The preconception period (i.e. the weeks and months before pregnancy) is a critical window during which parental health behaviours can influence pregnancy outcomes and the childs long-term health. Modifiable factors such as nutrition, physical activity, substance use, and environmental exposures play a key role, yet womens ability to adopt and sustain healthy behaviours is shaped by complex psychological, social and environmental influences. This study applies the Theory of Planned Behaviour to identify the beliefs underpinning womens preconception behaviours, with the aim of informing support for effective and sustained health behaviour change. Methods: An Australian national retrospective cross-sectional survey of pregnant women (18-49 years), recruited through social media platforms. The 92-item survey captured respondent socio-demographics, pregnancy status and health conditions, health behaviours, and beliefs regarding preconception health behaviours. Respondents level of pregnancy planning was categorised using the London Measure of Unplanned Pregnancy (LMUP). Items regarding preconception beliefs were structured in accordance with the Theory of Planned Behaviour, with a focus on regular exercise, healthy diet, and alcohol avoidance. These beliefs variables were analysed using structured equation modelling to identify paths between latent variables and the items used to estimate each concept. Results: The study was completed by 430 pregnant women of whom 72.7% had a planned pregnancy. Most had a partner, were university educated and in good health. Structural equation modelling showed intention strongly predicted exercise ({beta}=0.65), healthy diet ({beta}=0.54) and alcohol avoidance ({beta}=0.64). Perceived control and partner norms influenced intentions, whereas health professional norms had limited effect. Positive beliefs were associated with folate supplement use and smoking cessation. Conclusion: These findings highlight intention as a key driver of preconception health behaviours, with perceived control and partner influences playing a more significant role than individual beliefs or health professional input. Effective interventions should therefore address structural barriers and actively involve partners, while respecting womens autonomy. Overall, couples-focused, multi-level strategies are likely essential to support meaningful and sustained preconception health behaviour change.

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13.
arXiv (CS.CL) 2026-06-18

GraphPO: Graph-based Policy Optimization for Reasoning Models

作者:
Yuliang Zhan↗Xinyu Tang↗Jian Li↗Dandan Zheng↗Weilong Chai↗Jingdong Chen↗Jun Zhou↗Ge Wu↗Wenyue Tang↗Hao Sun↗

Reinforcement Learning with Verifiable Rewards (RLVR) has become a standard paradigm for enhancing the capability of large reasoning models. RLVR typically samples responses independently and optimizes the policy using from final answers. This paradigm has two limitations. First, independently responses often contain similar intermediate reasoning steps, causing redundant exploration and wasted computation. Second, sparse final-answer rewards make it hard to identify useful steps. Tree-based methods partly address this problem by sharing prefixes and comparing branches from the same prefix to provide fine-grained signals. However, tree branches are still expanded independently. When different branches reach similar reasoning states, they cannot share information and repeat similar exploration. Moreover, tree-based methods ignore such dispersion and only perform local comparisons within separate branches, which can lead to higher variance in advantage estimation. To address this challenge, we propose GraphPO (Graph-based Policy Optimization), a novel RL framework that represents rollouts as a directed acyclic graph, with reasoning steps as edges and semantic states summarized from the reasoning paths as nodes. GraphPO merges semantically equivalent reasoning paths into equivalence classes, allowing them to share suffixes and reallocating budget away from redundant expansions to diverse exploration. Furthermore, we assign efficiency advantages to incoming edges and correctness advantages to outgoing edges, thereby improving inference efficiency while deriving process supervision from outcome. Theory shows that GraphPO reduces advantage-estimation variance and enhances reasoning efficiency. Experiments on three LLMs across reasoning and agentic search benchmarks show that GraphPO consistently outperforms chain- and tree-based baselines with the same token budgets or response budgets.

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14.
Nature (Science) 2026-06-08

Fifty years since a simple equation described the chaos of biology

作者:
Michael P. H. Stumpf↗

An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics. An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics.

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15.
arXiv (CS.AI) 2026-06-25

Adapt Only When It Pays: Budgeted Decision-Loss Priority for Delayed Online Time-Series Adaptation

作者:
Xibai Wang↗

arXiv:2606.25068v1 Announce Type: cross Abstract: Online time-series forecasters receive labels only after horizon-dependent delays, while every adaptation step spends limited compute. We study when an online learner should update, not how to adapt at every opportunity, and introduce ADOWIP: a residual-adapter framework with sealed delay queues, exact budget accounting, and auditable update telemetry. Its main scheduler is an observed decision-loss priority gate that updates only after feedback is revealed, when downstream loss, optionally penalized by prediction MSE, exceeds a calibrated empirical quantile and budget remains. We prove hard-budget feasibility, projected-OGD regret for a convex linear accepted-update subproblem, and stability plus conditional finite-sample gate-selection statements. On public ETT capacity-planning tasks, a frozen calibration/evaluation split selects a gate that lowers held-out decision loss against always, fixed-period, and drift-triggered exact-update baselines under matched compute. Secondary threshold/load-index ETT suites are mixed: 33 of 41 selected contrasts clear the stricter cross-artifact Holm family, and the 8 nonpassing rows are explicitly excluded from primary claims. The same protocol improves an external UCI Bike capacity proxy with 20/0 held-out wins, and a fixed gate passes three full-year Capital Bikeshare station-rebalancing contrasts. Probe-based and finance experiments remain negative, delimiting the current scope of decision-prioritized adaptation.

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16.
arXiv (CS.AI) 2026-06-24

It's Complicated: On the Design and Evaluation of AI-Powered AAC Interfaces

作者:
Blade Frisch↗Will Wade↗Dylan Gaines↗Michelle Kinsella↗Betts Peters↗Tamara Broderick↗Keith Vertanen↗

arXiv:2606.24854v1 Announce Type: cross Abstract: Artificial intelligence (AI) can enhance what people who use augmentative and alternative communication (AAC) are able to do with their systems. However, evaluating AI-powered AAC interfaces can be difficult. People are intersectional beings and current evaluation metrics can struggle to capture the multifaceted and nuanced desires people may have for their AAC. We explore the complicated nature of six AAC problem spaces, explore how AI might be used in these spaces, and suggest more robust methods of evaluation that take the intersectional nuances of people into account. We also discuss broader issues that arise across these problem spaces and how they could be addressed using our proposed evaluation methods.

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17.
arXiv (CS.AI) 2026-06-19

Automating SKILL.md Generation for Computer-Using Agents via Interaction Trajectory Mining

作者:
Yuexing Hao↗Xiaomin Li↗

arXiv:2606.20363v1 Announce Type: new Abstract: Explicit skill libraries make computer-using agents easier to inspect, but it remains unclear whether such libraries can be mined from interaction data in a way that improves downstream policies. We study this question through a three-stage pipeline that segments GUI trajectories, clusters segments into candidate skills, and trains a skill-aware policy from the resulting annotations. The mined clusters are readable on the source benchmark: five of eight clusters have at least 0.95 purity against InteraSkill Workflows labels. However, readability does not imply transfer. GRPO improves IW skill-step accuracy only from 18.5\% to 20.5\%, leaves BrowseComp+ essentially unchanged, and underperforms trivial frequency priors on key source-domain metrics. We therefore present the method as a diagnostic study: trajectory mining can expose inspectable skill structure, but the current boundary detector, orderless segment representation, and offline reward model are insufficient for reliable cross-domain policy improvement.

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

MentisOculi: Revealing the Limits of Reasoning with Mental Imagery

作者:
Jana Zeller↗Thadd\"aus Wiedemer↗Fanfei Li↗Thomas Klein↗Prasanna Mayilvahanan↗Matthias Bethge↗Felix Wichmann↗Ryan Cotterell↗Wieland Brendel↗

Frontier models are transitioning from multimodal large language models (MLLMs) that merely ingest visual information to unified multimodal models (UMMs) capable of native interleaved generation. This shift has sparked interest in using intermediate visualizations as a reasoning aid, akin to human mental imagery. Central to this idea is the ability to form, maintain, and manipulate visual representations in a goal-oriented manner. To evaluate and probe this capability, we develop MentisOculi, a procedural, stratified suite of multi-step reasoning problems amenable to visual solution, tuned to challenge frontier models. Evaluating visual strategies ranging from latent tokens to explicit generated imagery, we find they generally fail to improve performance. Analysis of UMMs specifically exposes a critical limitation: While they possess the textual reasoning capacity to solve a task and can sometimes generate correct visuals, they suffer from compounding generation errors and fail to leverage even ground-truth visualizations. Our findings suggest that despite their inherent appeal, visual thoughts do not yet benefit model reasoning. MentisOculi establishes the necessary foundation to analyze and close this gap across diverse model families.

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19.
arXiv (CS.CV) 2026-06-11

MedCTA: A Benchmark for Clinical Tool Agents

作者:
Tajamul Ashraf↗Hyewon Jeong↗Fida Mohammad Thoker↗Bernard Ghanem↗

To make clinically grounded decisions, medical AI agents are expected to go beyond simple recognition and be capable of tool retrieval, evidence acquisition, and integration. Existing benchmarks largely evaluate isolated perception or single-turn question answering, and therefore provide limited visibility into failures of planning, tool recruitment, and rollout reliability. We introduce MedCTA, a benchmark for evaluating medical tool agents on clinician-validated, step-implicit tasks grounded in realistic multimodal clinical inputs, including radiology images, pathology slides, and reports. MedCTA comprises 107 real-world clinical tasks with clinician-verified executable trajectories over 5 deployed tools, and supports process-aware evaluation of tool selection, argument validity, execution stability, trajectory fidelity, and outcome quality. We benchmark 18 open- and closed-source multimodal models and find that even frontier systems remain brittle in multi-step clinical tool use: autonomous rollouts are dominated by protocol failures, premature stopping, and incorrect tool recruitment, while gold-standard tool routing yields large but still incomplete gains. These results show that strong backbone perception does not translate into reliable agentic behavior in clinical settings. MedCTA provides a rigorous testbed for auditing, diagnosing, and advancing trustworthy medical AI agents. The dataset and evaluation suite are available at https://ivul-kaust.github.io/MedCTA/

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20.
arXiv (CS.CL) 2026-06-18

Learning User Simulators with Turing Rewards

作者:
Yingshan Susan Wang↗Cedegao E. Zhang↗Linlu Qiu↗Zexue He↗Pengyuan Li↗Alex Pentland↗Roger P. Levy↗Yoon Kim↗

Learning to simulate human users in interactive settings could advance the training of agent assistants, evaluation of personalization systems, research in the social sciences, and more. Existing approaches generally do so by training a large language model (LLM) to match a single ground truth response, either by maximizing the log probability or by using a similarity reward. We instead propose {Turing-RL}: a Turing-Test-based reinforcement learning approach for training user simulator models. {Turing-RL} uses a discriminative Turing reward with an LLM judge to score how indistinguishable a generated response is from the real user's given the user's history, and the user simulator LLM learns to produce responses indistinguishable from what the user could have said with such rewards. Across two different domains–conversational chat and Reddit forum discussion–we find that {Turing-RL} consistently outperforms baseline methods on both LLM and human evaluation metrics. Our study suggests that optimizing for indistinguishability, rather than response matching, is effective for learning user simulators.

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21.
arXiv (CS.CL) 2026-06-25

Natural Ungrokking: Asymmetric Control of Which Rules Survive Pretraining

作者:
Juliana Li↗Diya Sreedhar↗

Midway through an ordinary pretraining run, a small language model learns the pronoun-gender rule: cued with a girl's name ("Sue cried because"), it resolves the next pronoun to she, generalizing to held-out probes (0.94 by step 925). By step 3,500 the same model scores near zero on the same probes, although the rule's evidence is still in the training data. We call this within-run reversal natural ungrokking: the corpus decides, with no trace in the loss curve, which learned rules a model keeps. Which rules survive is predictable from one corpus statistic: how often the training stream shows the rule winning. Across un-intervened runs (two corpora, three budgets, three seeds), support frequency decides a rule's fate; the data-to-parameter ratio only modulates how deeply a doomed rule falls. The same emerge-then-collapse dynamics appear in public Pythia checkpoints, collapse depth ordered by model scale as predicted. The forgetting is a displacement: a competing surface pattern out-competes the rule, and the log-probability margin between them crosses zero within 100 training steps of the behavioral collapse. Control over this fate is asymmetric: the same edit that destroys a rule on demand cannot restore it. Flipping support to counter-evidence in place kills the rule with monotone dose-response in two unrelated rules; but injecting support back, even to 450 times the level that naturally sustains it, buys no recovery. Every confirmatory threshold and prediction was pre-registered before the data it governed was read.

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22.
medRxiv (Medicine) 2026-06-23

Socioeconomic Determinants of Guideline-Concordant Therapy for Early-Stage Non-Small Cell Lung Cancer: A Population-Based Analysis from Appalachian and Non-Appalachian Ohio, 2004-2015

作者:
Martin↗Waugh↗

Purpose: To examine the relative contributions of insurance, county-level poverty, and other socioeconomic factors, as compared with Appalachian geography, to receipt of guideline-concordant therapy for early-stage non-small cell lung cancer (NSCLC) in Appalachian and non-Appalachian Ohio. Methods: Retrospective population-based cohort study using the Ohio Cancer Incidence Surveillance System. We identified adults diagnosed with early-stage NSCLC between 2004 and 2015 (N=26,756). The primary outcome was receipt of guideline-concordant local therapy (surgery or definitive radiation). Rural-urban classification used USDA Rural-Urban Continuum Codes. Multivariable logistic regression and Cox proportional hazards models assessed predictors of treatment and survival, with E-values, race-stratified models, and propensity score weighting as sensitivity analyses. Findings: Median age was 71 years; 50.3% were male, 83.8% non-Hispanic White, and 20.4% Appalachian. Overall, 83.6% received guideline-concordant local therapy (59.6% surgery, 24.0% radiation). In adjusted analysis, Medicaid (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI] 0.44-0.63; adjusted risk ratio [RR] 0.94, 0.91-0.96), county-level poverty >20% (OR 0.77, 95% CI 0.68-0.87; RR 0.96, 0.95-0.98), and unmarried status were independently associated with lower therapy receipt, whereas Appalachian residence was associated with modestly higher receipt (OR 1.17, 95% CI 1.06-1.29; RR 1.02, 1.01-1.04). Therapy rates converged across regions over the study period (year x Appalachian interaction p20% (HR 1.13, 95% CI 1.07-1.20). Conclusions: Socioeconomic factors, particularly Medicaid insurance and county-level poverty, were the patient characteristics most strongly associated with lower receipt of guideline-concordant therapy, whereas Appalachian residence was not a barrier. Findings support targeted interventions addressing insurance-related and poverty-related barriers to lung cancer care in high-poverty communities regardless of geographic designation.

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23.
arXiv (CS.CL) 2026-06-16

Do You Really Need a GPU to Guard Your LLM? CPU-Class Classifiers and Multi-Stage Pipelines for Safety Enforcement at Scale

作者:
Vasudev Majhi↗Dhruv Gupta↗Advait Singh↗Matthew Barker↗Dhruv Kumar↗

Safety classifiers that screen LLM inputs for jailbreak attempts have become standard deployment components, yet almost all production systems rely on GPU-based models: fine-tuned transformers and LLM-as-a-judge pipelines. These approaches impose significant per-query latency and infrastructure cost. Very little research has asked whether CPU-based classifiers, such as support vector machines and gradient-boosted trees trained on TF-IDF features, can match their accuracy across the conditions that production deployments encounter. We evaluate five CPU classifier families, Mamba-130M as an SSM-based GPU classifier, and transformer-based GPU models (DeBERTa-v3 and Gemma-2B with LoRA) across nine jailbreak sources and three regimes: in-distribution (D1), out-of-distribution (D2), and adversarially obfuscated (D3). On D1, the best CPU classifier matches the best transformer GPU model at roughly one-fifth the deployment cost. On D2, CPU classifiers fail via confident miscalibration, producing high-confidence false negatives that bypass escalation entirely. On D3, CPU classifiers outperform transformer GPU models by more than 26 percentage points in F1. Based on these complementary failure modes, we design GuardChain, a three-stage safety pipeline (Regex -> CPU -> GPU) that routes each prompt to the cheapest stage capable of a confident decision. The CPU stage alone resolves 80\% of in-distribution prompts at near-peak accuracy, and the GPU stage recovers the out-of-distribution failures. For practitioners deploying LLM safety at scale, this work provides evidence that GPU-class infrastructure is unnecessary for the majority of traffic.

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24.
medRxiv (Medicine) 2026-06-24

Biochemical fingerprinting of human scalp hair reveals endocannabinoid related compounds as potential biomarker indicators of altered mitochondrial bioenergetics in immune cells from female patients with major depressive disorder

作者:
Bondy↗De Punder↗Salinas-Manrique↗Hennessy↗Stoll↗Hill↗M. M↗Dietrich↗D. E↗Karabatsiakis↗

Major depressive disorder (MDD) is a severe psychiatric disorder that affects more than 350 million people worldwide, yet its biomolecular mechanisms are incompletely understood, and clinically applicable markers remain elusive. To shed new light on the underlying pathophysiology of MDD across multiple research disciplines, we first used a biochemical fingerprinting approach with human hair (the first 3 cm cut from the scalp) to identify changes in the total set of detectable metabolites and lipids (metabolipidomics) using quadrupole time-of-flight mass spectrometry (qToF-MS). In this study, we focused on endocannabinoid (ECB)-related lipid compounds and identified 7 candidate markers that differed between depressed and non-depressed female participants. Two phosphatidylinositols, namely PI 24:0 and PI 37:4, showed dose-dependent associations with the severity of depressive symptoms. Finally, to bridge hair findings with previously reported results in blood, we tested associations between changes in identified ECB-related compounds and parameters of mitochondrial respiratory activity in peripheral blood mononuclear cells. We found 17 significant associations, with the strongest effects for the lipids PI 24:0, MGDG-O 16:3, PG 12:0, and PI 37:4. Our approach not only identified novel associations between endocannabinoid (ECB)-related lipid dysregulation and impaired mitochondrial energy metabolism in MDD but also revealed ECB-related lipids as a possible surrogate marker of impaired bioenergetic metabolism in MDD, at least in immune cells. More research is needed to replicate these findings, ideally by testing reversibility in longitudinal intervention studies and by including both sexes in larger cohorts.

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

Cross-Lingual Exploration for Parametric Knowledge

作者:
Elisha Diskind↗Itamar Trainin↗Uri Shaham↗Leshem Choshen↗Idan Szpektor↗Omri Abend↗

Parametric knowledge in Large Language Models is not equally accessible across languages. As a result, standard inference techniques often struggle to surface localized facts, leading to failures in cross-lingual knowledge transfer and consistency. In this work, we investigate techniques for accessing hidden factual knowledge by exploring cross-lingual prompting strategies. We identify four inherent dimensions of cross-lingual exploration that directly govern parametric knowledge retrieval and evaluate them on multilingual factual benchmarks covering 17 typologically diverse languages. Our results demonstrate that cross-lingual exploration significantly improves knowledge transfer and factual recall, representing a more efficient compute Pareto frontier than native-language scaling. Furthermore, we observe corresponding improvements in cross-lingual consistency, exceeding what can be explained by accuracy gains alone. Overall, our work establishes multilingual prompt exploration as a highly effective inference-time strategy for unlocking latent parametric knowledge.

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