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01.
Nature Medicine 2026-06-15

Blood signatures of cell type-specific aging forecast disease risk and resilience

Authors: Unknown Author

By measuring thousands of proteins in blood samples from over 60,000 people, we built molecular ‘clocks’ to estimate how fast cells age. Our analyses show that cell types age at different rates within the same person. Accelerated aging of specific cell types is associated with increased disease risk, whereas slower aging of others is linked to protection and improved survival.

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

Edit Knowledge, Not Just Facts via Multi-Step Reasoning over Background Stories

Authors:
Ya Gao↗Kalle Kujanp\"a\"a↗Pekka Marttinen↗Harri Valpola↗Alexander Ilin↗

arXiv:2602.02028v2 Announce Type: replace Abstract: Enabling artificial intelligence systems, particularly large language models, to update knowledge and flexibly apply it during reasoning remains a central challenge. Existing knowledge editing approaches emphasize atomic facts, improving factual recall but often failing to integrate updated information into a coherent framework usable across contexts. In this work, we argue that knowledge update is fundamentally a reasoning problem rather than a memorization problem. Consequently, a model should be trained in situations where the new information is instrumental to solving a task, combined with pre-existing knowledge, and exercised through multi-step reasoning. Based on this insight, we propose a training strategy based on three principles. First, new knowledge is introduced as a coherent background story that contextualizes novel facts and explains their relation to existing knowledge. Second, models are trained using self-generated multi-hop questions that require multi-step reasoning involving the new information. Third, training is done using knowledge distillation, forcing a student model to internalize the teacher's reasoning behavior without access to the novel information. Experiments show that models trained with this strategy effectively leverage newly acquired knowledge during reasoning and achieve remarkable performance on challenging questions that require combining multiple new facts.

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03.
arXiv (CS.CV) 2026-06-16

Learned Image Compression for Vision-Language-Action Models

Authors:
Hyeonjun Kim↗Jegwang Ryu↗Sangbeom Ha↗Junhyeok Lee↗Jun-Hyuk Kim↗Hyemin Ahn↗Jaeho Lee↗

Vision-language-action (VLA) models increasingly rely on high-frequency multi-camera observations, making visual communication a major bottleneck for real-time robotic control in bandwidth-constrained or distributed deployment settings. Existing image and video codecs, however, are designed to preserve generic visual fidelity rather than the control performance of downstream VLA policies. In this work, we introduce SPARC (SPatially Adaptive Rate Control), a learned image compression framework tailored for VLA-driven robots. Our key observation is that the importance of visual information varies substantially across both camera views and spatial regions within an image. Based on this observation, SPARC employs a lightweight temporal mask selector that adaptively allocates bitrate over latent representations according to task relevance while leveraging temporal context. We further introduce a tilted rate loss that stabilizes training by reducing the tendency of entropy-based objectives to over-suppress rare yet task-critical visual patterns. Experiments on diverse robotic benchmarks, including RoboCasa365, VLABench, and LIBERO, show that SPARC consistently achieves stronger control performance than conventional image/video codecs and recent learned compression methods under the same bitrate budget. We additionally demonstrate real-world deployment benefits in remote-control settings, where our method substantially improves the bitrate-success tradeoff.

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

Quantization Robustness of Monotone Operator Equilibrium Networks

Authors:
James Li↗Philip H. W. Leong↗Thomas Chaffey↗

arXiv:2603.10562v2 Announce Type: replace-cross Abstract: Monotone operator equilibrium networks are implicit-layer models whose output is the unique equilibrium of a monotone operator, guaranteeing existence, uniqueness, and convergence. When deployed on low-precision hardware, weights are quantized, potentially destroying these guarantees. We analyze weight quantization as a spectral perturbation of the underlying monotone inclusion. Convergence of the quantized solver is guaranteed whenever the spectral-norm weight perturbation is smaller than the monotonicity margin; the displacement between quantized and full-precision equilibria is bounded in terms of the perturbation size and margin; and a condition number characterizing the ratio of the operator norm to the margin links quantization precision to forward error. MNIST experiments confirm a phase transition at the predicted threshold: three- and four-bit post-training quantization diverge, while five-bit and above converge. The backward-pass guarantee enables quantization-aware training, which recovers provable convergence at four bits.

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

ToolMenuBench: Benchmarking Tool-Menu Filtering Strategies for Reliable and Efficient LLM Agents

Authors:
Rahul Suresh Babu↗Laxmipriya Ganesh Iyer↗

arXiv:2606.15508v1 Announce Type: new Abstract: Tool-augmented large language model agents increasingly operate over large tool libraries, but existing evaluations often focus on whether a model can call a tool correctly rather than how the visible tool menu shapes reliability, efficiency, and safety-relevant risk exposure. We introduce ToolMenuBench, a benchmark for evaluating tool-menu construction in multi-step LLM agents. ToolMenuBench varies tool-menu size, distractor type, state-dependent task structure, and risk exposure, and reports both filter-level and downstream agent metrics, including visible-tool count, risky-tool exposure, task success, wrong-tool calls, premature actions, and token usage. In a controlled evaluation across seven model backends, three tool-menu sizes, six filtering methods, and seven evaluation settings, CMTF improves task success from 32.1% under all-tools exposure to 85.7%, while reducing average token usage by roughly 98%. Causal minimal tool filtering achieves the strongest overall tradeoff, reducing visible tools, wrong-tool calls, premature actions, and risky-tool exposure relative to unfiltered exposure, lexical filtering, state-aware filtering, and broader causal-path baselines. ToolMenuBench provides a reusable evaluation framework for studying the agent-interface problem: which tools should be visible, when they should be visible, and under what cost or risk constraints.

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

Topological Data Analysis for High-Dimensional Dynamic Process Monitoring

Authors:
Angan Mukherjee↗Tyler A. Soderstrom↗Michael J. Kurtz↗Victor M. Zavala↗

arXiv:2606.20443v1 Announce Type: cross Abstract: Real-time process monitoring requires methods that extract actionable information from high-dimensional time-series data. In this work, we present a new approach for process monitoring that combines tools of topological data analysis (TDA) and machine learning. In the proposed approach, we represent multivariate time-series data as manifolds and use topological descriptors to summarize the structure of such data; we then use a neural ordinary differential equation to learn the dynamic evolution of the topological structure of the system. Using real data from an industrial process, we show that this trajectory-based event detection approach is effective at detecting diverse types of events. We contrast this approach against reconstruction-based approaches such as principal component analysis and autoencoders and against a trajectory-based approach that uses Koopman autoencoders.

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07.
arXiv (CS.LG) 2026-06-18

Online Reward-Punishment Learning from Fixed-Channel Perceptual Event Streams without Environment Rewards

Authors:
Zirong Li↗

arXiv:2606.18963v1 Announce Type: new Abstract: We study online reward-punishment learning when the environment provides no scalar reward or evaluative label. At each step the agent receives only a fixed-channel perceptual packet, and quantities such as pain, energy, contact, damage, or cognitive error are treated as perceptual dimensions whose valence must be inferred from transition consequences. OHIRL separates four roles: M_psi learns next-packet prediction, D_omega models residual dynamics, C_eta is a fixed internal post-transition trajectory evaluator, and B_xi learns to use the resulting value evidence for later policy updates and action scoring. C_eta uses a recovery-positive and persistence/growth-negative residual-regulation orientation; a coefficient-origin audit shows that equal-unit, raw-equal, and random monotone variants preserve more than 92% of the released top-action rankings, while sign inversion preserves 0%. The reward-free protocol exposes observation transitions while withholding environment rewards, delayed external evaluators, success labels, and action-goodness labels. A conditional error decomposition separates B_xi evidence-estimation error from residual policy-optimization error. In a 2x2-XOR packet task, medicine and chili acquire opposite value under visual XOR contexts, and the same pain or spice increase can be positive or negative depending on consequence structure; B_xi reaches 0.952 balanced reward-sign accuracy. In a full online-interleaved audit, M_psi reaches holdout R2=0.907, B_xi reaches 0.940 sign accuracy, and the policy reaches 0.979 optimal-action accuracy, while immediate packet scores, prediction-error rewards, shuffled targets, zero reward, and error-reduction controls collapse. Hidden-reward CartPole and Taxi controls, public-context no-leakage audits, and module-role ablations further test information boundaries and component necessity.

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08.
arXiv (CS.CL) 2026-06-19

Granularity-Regulated Adaptive Computational Efficiency for Optimal Verification in Test-Time Scaling

Authors:
Ardit Krasniqi↗Luan Vejsiu↗Elira Dervishi↗

Test-time scaling (TTS) has emerged as a powerful paradigm for improving the reasoning performance of large language models (LLMs) by investing additional compute at inference time. A central component of TTS is the verifier, which selects or scores candidate solutions to guide the search process. While prior work has explored the benefit of verification, a fundamental question remains underexplored: what is the optimal granularity of verification under a given compute budget? Coarse-grained outcome reward models (ORMs) and fine-grained process reward models (PRMs) represent two extremes, yet neither alone achieves compute-optimality across all regimes. In this paper, we establish a unified theoretical framework, called GRACE (\underline{G}ranularity-\underline{R}egulated \underline{A}daptive \underline{C}omputational \underline{E}fficiency), that characterizes the optimal verification granularity as an explicit function of problem difficulty, verifier accuracy, and compute budget. We prove that there exists a phase transition: fine-grained verification dominates when either the compute budget is large or the problem is hard, whereas coarse-grained verification is preferred in the low-budget, easy-problem regime. Our theory unifies Best-of-$N$, beam search, and step-level MCTS within a single Pareto-optimality framework, and motivates an adaptive granularity strategy that provably achieves the compute-performance Pareto frontier. Empirical results on MATH-500, GSM8K, and AIME benchmarks corroborate all four theoretical claims, with our adaptive strategy outperforming fixed-granularity baselines by up to 3.1\% accuracy at matched compute.

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09.
arXiv (CS.CL) 2026-06-16

CoRA: Confidence-Rationale Alignment for Reliable Chain-of-Thought Reasoning

Authors:
Juming Xiong↗Weixin Liu↗Kevin Guo↗Congning Ni↗Junchao Zhu↗Chongyu Qu↗Chao Yan↗Katherine Brown↗Avinash Baidya↗Xiang Gao↗Bradley Malin↗Zhijun Yin↗…

Chain-of-thought (CoT) reasoning can improve LLM performance, but high answer confidence may be misleading when the accompanying CoT rationale is plausible yet incomplete or poorly supported. We study confidence–rationale alignment: whether a model's confidence in its committed answer is justified by its generated rationale. We introduce a GRPO-based reinforcement learning framework that jointly rewards answer correctness, committed-answer probability, and rubric-based rationale support, where the rubric assesses grounding, coherence, task match, and connection to the selected answer without revealing the gold answer to the judge. Across MedQA, MathQA, and OpenBookQA using three open-weight LLMs, our method reduces the confidence–rationale alignment error by up to 26.51% compared with untuned checkpoints, SFT, and correctness-only GRPO, while maintaining competitive accuracy and often improving calibration. These results show that reliable CoT reasoning requires not only confident answers, but rationales that substantively support them.

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10.
arXiv (CS.LG) 2026-06-11

Neuro-Relational Programs: Unifying Queries and Neural Computation over Structured Data

Authors:
Arie Soeteman↗Balder ten Cate↗Maurice Funk↗Benny Kimelfeld↗Carsten Lutz↗Moritz Sch\"onherr↗

arXiv:2606.11946v1 Announce Type: cross Abstract: The conventional approach to deep learning over relational databases applies neural models, such as Graph Neural Networks (GNNs), to a graph representation of the database. Recent approaches instead operate on databases directly, associating tuples with embeddings and extending query mechanisms to jointly process embeddings and relational content. Inspired by these developments, we introduce Neuro-Relational Programs (NRPs), a declarative query language for relational databases whose facts carry numeric vector embeddings. NRPs extend Datalog-style rules with operations that combine, aggregate, and transform embeddings, thereby interleaving relational reasoning and learnable neural components within a single formalism. This yields a general approach to neural computation over relational data: an NRP can be read both as a query plan with trainable components and as a neural architecture with relational structure built in. Natural syntactic fragments of NRPs recover existing architectures and query formalisms. Zero-ary NRPs correspond to non-adaptive query algorithms; monadic NRPs generalize GNN-style message passing and precisely capture Deep Homomorphism Networks, a connection that we extend to frontier-guarded NRPs over databases with row-ids. We characterize the expressive power of unrestricted NRPs with ReLU-FFN transformations by FOCQ, an extension of first-order logic with counting interpreted over real-weighted structures, yielding a precise connection with uniform TC$^0$ over ordered databases. Together, these results establish NRPs as a broad declarative framework for querying and neural computation over relational data.

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

Policy-aware Vector Search: A Vision for Fine Grained Access Control in Vector Databases

Authors:
Lakshmi Sahithi Yalamarthi↗Primal Pappachan↗

arXiv:2606.19803v1 Announce Type: cross Abstract: Vector databases are increasingly used in security sensitive contexts with Retrieval Augmented Generation and organizational AI pipelines; however, their security capabilities remain limited. Specifically, Fine-grained Access Control (FGAC) which is required to ensure that data access adheres to user-specific policies is not fully supported in modern vector databases. Unlike relational databases, vector databases combine structured and unstructured attributes to provide semantic, approximate query results, which complicates FGAC implementation. This creates an inherent tension between enforcing FGAC policies correctly, achieving high ANN search recall and maintaining low query latency. In this paper, we present a vision for Policy-aware Vector Search by formalizing the FGAC policy model in vector databases as well as the enforcement problem. We compare various enforcement strategies, present preliminary findings, and identify key open challenges for future research in policy-aware vector search.

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

Earth Science Foundation Models: From Perception to Reasoning and Discovery

Authors:
Xiangyu Zhao↗Bo Liu↗Yuehan Zhang↗Zelin Song↗Wanghan Xu↗Feng Liu↗Fengxiang Wang↗Ben Fei↗Fenghua Ling↗Wangxu Wei↗Wenlong Zhang↗Xiao-Ming Wu↗…

arXiv:2605.12542v2 Announce Type: replace-cross Abstract: Large foundation models (FMs) are transforming Earth science by integrating heterogeneous multimodal data, such as multi-platform imagery, gridded reanalysis data, diverse geophysical and geochemical observations, and domain-specific text, to support tasks ranging from basic perception to advanced scientific discovery. This paper provides a unified review of Earth science foundation models (Earth FMs) through two complementary dimensions: depth, which traces the evolution of model capabilities from perception to multimodal reasoning and agentic scientific workflows, and breadth, which summarizes their expanding applications across the atmosphere, hydrosphere, lithosphere, biosphere, anthroposphere, and cryosphere, as well as coupled Earth system processes. Using this framework, we review representative multimodal Earth foundation models and compile more than 200 datasets and benchmarks spanning diverse Earth science tasks and modalities. We further discuss key challenges in multimodal data heterogeneity, scientific reliability and continual updating, scalability and sustainability, and the transition from foundation models to agentic and embodied Earth intelligence, and outline future directions toward more integrated, trustworthy, and actionable AI Earth scientists. Overall, this paper offers a structured roadmap for understanding the development of Earth foundation models from both capability depth and application breadth.

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13.
arXiv (CS.AI) 2026-06-11

Sovereign Assurance Boundary: Certificate-Bound Admission for Agentic Infrastructure

Authors:
Jun He↗Deying Yu↗

arXiv:2606.11632v1 Announce Type: cross Abstract: Agentic infrastructure introduces a critical control-plane authorization problem: non-deterministic reasoning systems can propose high-stakes mutations to production resources, yet existing security mechanisms – such as identity and access management (IAM), policy engines, consensus protocols, and audit logs – either enforce static, context-unaware permissions or merely record actions post-execution. This paper introduces the Sovereign Assurance Boundary (SAB), a certificate-bound runtime admission layer for autonomous execution authority. SAB intercepts agent proposals at an assurance airlock, compiles them into typed execution contracts $C$, and binds these contracts to cryptographic evidence digests $H(E)$ and policy versions. The contracts are then routed through consequence-aware certification paths. Upon successful admission, the system emits a signed Sovereign Assurance Certificate ($\Omega$) that is strictly scoped to a specific execution identity, revocation epoch, and validity window. Finally, a sovereign execution broker verifies $\Omega$ and performs fresh pre-execution revocation and drift checks before invoking infrastructure APIs. We detail the airlock-broker architecture, formalize its admission and revocation invariants, and report preliminary feasibility measurements from a Go prototype evaluated over 2,500 admission attempts. Ultimately, this broker-enforced model prevents autonomous reasoning from directly mutating state, transforming delegated execution authority into a cryptographically verifiable, evidence-bound, revocable, and replayable runtime artifact.

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

The Language You Ask In: Language-Conditioned Ideological Divergence in LLM Analysis of Contested Political Documents

Authors:
Oleg Smirnov↗

Large language models (LLMs) are increasingly deployed as analytical tools across multilingual contexts, yet their outputs may carry systematic biases conditioned by the language of the prompt. This study presents an experimental comparison of LLM-generated political analyses of a Ukrainian civil society document, using semantically equivalent prompts in Russian and Ukrainian administered to two frontier models from different developers, ChatGPT 5.2 and Claude Opus 4.5. Despite identical source material and parallel query structures, both models diverged along the same axis: Russian-language outputs leaned toward delegitimizing framings, characterizing civil society actors as externally funded elites constraining a democratic mandate, while Ukrainian-language outputs treated the same actors as legitimate stakeholders in democratic contestation. The magnitude of this divergence, however, was model-dependent. ChatGPT's Russian output reproduced vocabulary characteristic of Russian state discourse; Claude Opus's stayed in a mainstream critical idiom and hedged its judgments in both languages. These findings demonstrate that prompt language alone can systematically shift the ideological orientation of an unchanged model analyzing identical content. The shift is a general property of multilingual LLMs whose severity, and whose alignment with propaganda narratives, varies across systems. The implications reach AI deployment in polarized information environments, cross-lingual research, and AI governance in multilingual societies.

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

Gender Bias in LLM Hiring Decisions: Evidence from a Japanese Context and Evaluation of Mitigation Strategies

Authors:
Serena A. Hoffstedde↗Machiko Hirota↗Akshara Nadayanur Sathis Kanna↗Rihito Kotani↗Ujwal Kumar↗Gabriele Trovato↗Phan Xuan Tan↗

Large language models (LLMs) are increasingly deployed in hiring workflows, yet most research on gender bias in LLM hiring decisions has focused on English-language, Western-format resumes. This study examines whether pro-female gender bias extends to a Japanese corporate context and evaluates two practical mitigation strategies. Using a counterfactual resume design with 60 Japanese rirekisho-format resumes, 12 name pairs selected on linguistically grounded gender-signal criteria, and five state-of-the-art LLMs (Claude Sonnet 4.6, GPT-4o, DeepSeek-V3, Gemini 2.5 Flash, Llama 3.3 70B), we conducted 43,200 API calls across baseline, prompt instruction, and privacy filter conditions. A crossed random-effects linear mixed model confirms a significant pro-female bias across all five models, replicating Western findings in a non-Western context. A prompt-level gender-neutrality instruction produces no meaningful reduction in bias. A name-reliance analysis formally identifies the candidate name as the primary gender channel: removing the name from the prompt reduces the female effect by nearly its full magnitude. An unexpected incompatibility between the privacy filter and GPT-4o's content safety filter, resulting in a 42% refusal rate, highlights a practical deployment challenge for name anonymization in LLM-assisted recruitment pipelines.

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16.
arXiv (CS.AI) 2026-06-19

SIMBA: ABidirectional Retrieval Forward Simulation Framework for Modeling FY-4A GIIRS Hyperspectral Infrared Radiances Toward NWP Applications

Authors:
Jingdong Shen↗Fu Wang↗Qifeng Lu↗Hao Huang↗Chunqiang Wu↗Chi Yang↗Xiaofang Liu↗

arXiv:2606.19943v1 Announce Type: cross Abstract: Hyperspectral infrared observations are an important data source for numerical weather prediction (NWP) because they provide rich information on the vertical structure of atmospheric temperature and humidity. However, most existing deep learning methods mainly focus on one-way retrieval from radiances to atmospheric profiles, while the reverse radiance simulation process and the consistency between atmospheric state space and radiance observation space are insufficiently considered. In this study, we propose SIMBA, a unified bidirectional retrieval-forward simulation framework for FY-4A GIIRS hyperspectral infrared radiance modeling toward NWP applications. The framework jointly performs atmospheric profile retrieval and radiance reconstruction, introduces a cycle-consistency constraint to strengthen the coupling between the two processes, and employs a bidirectional Mamba state-space module to capture long-range dependencies along pressure levels. Using collocated FY-4A GIIRS observations and ERA5 reanalysis data, the proposed method is evaluated for temperature retrieval, specific humidity retrieval, long-wave radiance reconstruction, and medium-wave radiance reconstruction. Experimental results show that SIMBA outperforms several representative deep learning baselines across both retrieval and reconstruction tasks, while ablation experiments confirm the contribution of the bidirectional design and cycle-consistency mechanism. These results demonstrate that the proposed framework is effective for joint atmospheric profile retrieval and hyperspectral infrared radiance modeling, and suggest potential for future Jacobian-related analysis and NWP-oriented extensions.

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17.
arXiv (CS.CL) 2026-06-15

The Linguistics Olympiads: Towards a New Corpus for Linguistics Research?

Authors:
Vlad A. Neacsu↗

Linguistics olympiad problems (LOPs) are a category of self-sufficient puzzles consisting of a scaled-down corpus representative of certain linguistic phenomena, from which the solver must deduce a primitive set of rules of the language and then translate a new set of elements. The linguistics olympiads (LOs) have become a worldwide phenomenon with 43 different territories taking part in the International Linguistics Olympiad (IOL) 2025. While the typology and solving strategies of LOPs have been analysed, their scientific facet and connections to academic linguistics have yet to be explored. LOPs are directly connected to many linguistic fields, e.g., linguistic typology, linguistic relativity, and linguistics fieldwork. Recently, LOPs have become a research focus as benchmarks for large language models, thus highlighting their usefulness in computational linguistics. Nevertheless, they have not yet been integrated into mainstream linguistics research. This paper attempts to open new directions of including this particular type of puzzle in academic research by offering a structured evaluation of LOPs as linguistic data sources and proposes criteria for their responsible use in academic research. Starting from a set of over 1800 LOPs, this study critically examines the potential of LOPs as a novel corpus for linguistics research by discussing their strengths and limitations as tools, as well as the areas of linguistics into which these problems could fit. This work forms the foundation for a broader initiative aimed at bridging the gap between LOs and academic linguistics, by establishing a robust theoretical framework for LOPs.

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

IVIE: A Neuro-symbolic Approach to Incremental and Validated Generation of Interactive Fiction Worlds

Authors:
Micaela Vaucher↗Santiago Silveira↗Santiago G\'ongora↗Luis Chiruzzo↗

Computational creativity in Interactive Fiction faces a fundamental tension: Large Language Models (LLM) may produce creative narratives but struggle with world coherence, while symbolic systems ensure consistency but lack creative flexibility. We present IVIE (Incremental & Validated Interactive Experiences), a neuro-symbolic approach to generating complete and playable interactive fiction worlds from scratch. Building upon PAYADOR's neuro-symbolic framework, IVIE implements a four-stage incremental generation pipeline that delegates creative decisions–setting and character creation, puzzle design–to LLMs while grounding the world state through symbolic validation. The system generates worlds with interconnected locations, functional items, non-player characters, and coherent puzzles, all structured around a central goal-oriented architecture. Human evaluation shows the approach generates immersive, thematically coherent worlds with high player engagement. Results seem to indicate that the neuro-symbolic approach successfully balances flexibility with narrative coherence: symbolic validation grounds LLM generation without eliminating generative freedom. However, challenges remain: LLM inconsistencies occasionally bypass puzzle constraints, and objective validation gaps allow some structurally impossible goals. We identify key design considerations for future neurosymbolic interactive storytelling systems, particularly regarding LLM capabilities and their limitations.

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

TSAssistant: A Human-in-the-Loop Agentic Framework for Automated Target Safety Assessment

Authors:
Xiaochen Zheng↗Zhiwen Jiang↗David Tokar↗Yexiang Cheng↗Alvaro Serra↗Melanie Guerard↗Klas Hatje↗Tatyana Doktorova↗

Target Safety Assessment (TSA) requires systematic integration of genetic, transcriptomic, target homology, pharmacological, and clinical data to evaluate potential safety liabilities of therapeutic targets. This process is labor-intensive and expert-dependent, posing challenges in scalability and reproducibility. We present TSAssistant, a human-in-the-loop multi-agent framework that decomposes TSA report generation into a workflow of specialized subagents: Research Subagents that each ground and cite a single TSA domain, and Synthesis Subagents that integrate findings across domains. Subagents retrieve and synthesize evidence from curated biomedical sources through standardized tool interfaces and produce individually citable, evidence-grounded sections, with behavior shaped by a hierarchical instruction architecture that separates coordination logic from domain expertise and user intent. To complement these soft constraints, programmatic execution hooks and persistent memory stores enforce hard constraints across the workflow, while an interactive refinement loop allows experts to review and revise individual sections with full conversational context preserved across iterations. Rather than a single holistic comparison, we decompose report quality into reproducibility, evidential grounding, task-level accuracy, and controllability under expert oversight, finding high reproducibility and grounding, substantial agreement with the human reference, and net-positive expert-driven refinement.

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20.
arXiv (math.PR) 2026-06-17

Limit theorems for descents and inversions of shelf-shuffles

Authors:
Alexander Clay↗

arXiv:2510.00343v2 Announce Type: replace Abstract: We prove central limit theorems for the number of descents and inversions of permutations produced by shelf-shuffles. These are a model for casino card shuffling machines. We show the asymptotic normality of the number of descents in two limiting regimes depending on the ratio of cards to shelves. On the other hand, we study the inversions by employing a modification of the techniques from Islak's analysis of the statistics of riffle shuffles. In particular, we obtain a bound for the rate of convergence for inversions that is independent of the number of shelves.

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21.
arXiv (CS.LG) 2026-06-12

Individual Control Barrier Functions-Guided Diffusion Model for Safe Offline Multi-Agent Reinforcement Learning

Authors:
Qingyun Guo↗Junyi Shi↗Jianuo Huang↗Tianyu Shi↗

arXiv:2606.12640v1 Announce Type: new Abstract: Offline reinforcement learning allows control policies to be learned directly from data without online interaction, making it suitable for safety-critical tasks. Recent studies have applied diffusion models to offline reinforcement learning to leverage their strong capacity for modeling complex data distributions. However, existing approaches primarily focus on single-agent settings, leaving the safety challenges in multi-agent environments largely unexplored. In this work, we propose a safe offline multi-agent reinforcement learning algorithm that embeds neural individual control barrier functions into the diffusion model to enhance safety during trajectory generation, with control policies recovered through inverse dynamics. We evaluate our algorithm across diverse benchmarks, demonstrating substantial safety improvements while maintaining competitive rewards.

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22.
medRxiv (Medicine) 2026-06-15

Non-Parametric Ancestry Adjustment for Polygenic Scores

Authors:
Mas Montserrat↗Barrabes↗Bustamante↗C. D↗Ioannidis↗A. G↗

Modern polygenic risk scores (PRS) exhibit shifts correlated with ancestry, leading to erroneous predictions for non-European individuals when models are trained on predominantly European cohorts. Such shifts arise from, among other factors, (1) algorithmic limitations in the ability of PRS model training to detect causal variants, rather than nearby variants with ancestry-dependent correlations to the causal one, (2) under-representation of alleles with higher prevalence in non-European populations in the association study training, and (3) gene-by-environment interactions where the environment is correlated with genetic ancestry. Current ancestry-adjustment methodologies often discretize individuals into population categories and apply a simple affine mapping to reduce these genetic ancestry biases. However, such approaches provide suboptimal adjustments, particularly for admixed individuals. In this work, we introduce a detailed theoretical characterization of ancestry-dependent biases and propose novel methods based on non-parametric neighborhood techniques that provide more accurate empirical results and admit statistical consistency guarantees. Extensive experiments using the UK Biobank demonstrate the effectiveness of the proposed methods.

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23.
arXiv (CS.AI) 2026-06-15

FreoStream:Enhancing Stream Guardrails via Future-Aware Reasoning and Safety-Aligned Optimization

Authors:
Jianwei Wang↗Guoyang Shen↗Yanhong Wu↗Haoran Li↗Hao Peng↗Huiping Zhuang↗Cen Chen↗Ziqian Zeng↗

arXiv:2606.13737v1 Announce Type: cross Abstract: Stream guardrails enable token-level safety detection before full responses are generated. However, they often make overly conservative judgements and block those sensitive but safe tokens, which is known as over-refusal. Due to lack of full context, they also fail to detect implicitly harmful content from jailbreaking. To address these challenges, we propose FreoStream, a novel streaming guardrail framework. Specifically, FreoStream fine-tunes a LoRA module to perform Future-Aware Reasoning when the base guardrail detects unsafe tokens. The reasoning process follows a Future-Reason-Judge paradigm: predict the future, reason about the full context and give the final judgement. This design can effectively reduce over-refusal by incorporating the future information. Moreover, we introduce the Safety-Aligned Optimization module that extracts the safety-aligned component from the reasoning gradients to update the base guardrail model, thereby enhancing streaming safety detection. Extensive experiments on various safety benchmarks demonstrate that FreoStream achieves lower over-refusal rates and better jailbreak defense compared to existing streaming guardrails.

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24.
bioRxiv (Bioinfo) 2026-06-15

SMLMFlow: Improving Structural Resolution in Single Molecule Localization Microscopy with Flow Matching

Authors:
Bauer↗Panconi↗Cunha↗Latron↗Sage↗Peters↗Griffie↗

While Single Molecule Localization Microscopy (SMLM) aims to generate precise coordinates of molecular targets in cells, the resulting point clouds are inherently blurred by additive noise sources across the experimental, imaging, and processing workflow. This blurring often limits SMLM's ability to accurately quantify complex assembled structures required to address biological issues, despite reported localization precision down to a couple of nanometers. Here, we present SMLMFlow, a machine learning framework for improving structural resolution in SMLM datasets that combines a graph neural network and a hierarchical transformer with flow matching. We show that SMLMFlow improves structural resolution and downstream quantification across different structures, including filaments and protein nano-clusters, and generalizes to new unseen photophysics models.

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25.
medRxiv (Medicine) 2026-06-17

Clinical Study Protocol of the 'Biomarkers of Severity of COVID-19 Patients' (BIOMARCOVID) Project

Authors:
Dinh↗T.-A↗Leroy↗Brandolini-Bunlon↗Berthier↗Trocme↗Varoquaux↗Plazy↗Vilotitch↗Terra↗Toussaint↗Bosson↗…

Introduction The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide, in certain areas exceeding hospital capacities and human resources. This has underscored the importance of having better tools to predict the outcome of potentially severe respiratory infections such as SARS-CoV-2. Predicting COVID-19 severity may allow physicians to better manage ICU beds and increase the chances of patient survival through appropriate management. During the toughest months of the pandemic, most physicians tried to identify patients that might develop severe forms based primarily on clinical features on admission (e.g., BMI, age). In this context, significant research has focused on identifying comorbidities, clinical manifestations, and routine blood biomarkers to predict disease severity. However, despite the demonstrated value of untargeted metabolomics in assessing severity, limited data exist on its use for identifying novel metabolite biomarkers that could improve both the sensitivity and specificity of outcome prediction. Our goal is to identify metabolite biomarkers that could enhance the predictive accuracy of standard medical biology data and clinical parameters. Methods and analysis This is a retrospective, observational, monocentric cohort study conducted at the Centre Hospitalier Universitaire Grenoble Alpes (CHUGA). The maximum number of eligible patients admitted for PCR-confirmed COVID-19 between March and December 2020 will be included. Severity outcome is defined using the WHO 10-category ordinal scale (mild: categories 4-5; severe: >5). Blood samples were collected within 48 hours of admission and analyzed for 62 routine blood tests and untargeted multiplatform LC-MS/MS metabolomics across four national platforms. Statistical analysis will include logistic regression with variable selection for the primary aim, and multi-block chemometric integration of clinical, biological, and metabolomics data as a secondary aim. Ethics and dissemination A study steering committee has been formed to ensure the accuracy of the collected data by thoroughly reviewing it prior to the data lock. All aspects of the study comply with ethical standards, including approval by the CHUGA institutional review board and adherence to CNIL Reference Methodology MR004 for the protection of participants' rights, privacy, and confidentiality. This study is registered on the French Health Data Hub (number F20210218154851). Results will be disseminated through peer-reviewed publications, presentations at national and international scientific and clinical conferences, and reports shared with key healthcare system stakeholders.

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