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01.
medRxiv (Medicine) 2026-06-22

Rare loss-of-function variants in POLD1, PMS1 and FAN1 modify age at onset of motor symptoms in Huntington's disease

Huntington's disease is a rare neurodegenerative disease whose primary risk factors are inherited expansions of a CAG repeat tract in the HTT gene. Somatic expansion of these tracts leads to neuronal toxicity, neuronal death and clinical disease progression. To identify genetic factors with a major impact on disease onset and progression, we genome sequenced 18,825 individuals for the ENROLL-HD study. Our results show rare inactivating mutations in three genes, all involved in DNA damage repair, are major determinants of age of onset for motor symptoms (n=10,610) and other clinical manifestations. Heterozygote carriers of predicted loss-of-function (pLoF) variants in POLD1 and PMS1 developed motor symptoms an average 20 years (n=3; P=1x10-5) and 7 years (n=6; P=2x10-3) later than non-carriers, respectively. Conversely, heterozygote carriers of pLoF variants in FAN1 (n=30) developed symptoms 10 years earlier (P=2x10-10). Our findings highlight therapeutic strategies and help predict age of onset for at-risk individuals.

02.
arXiv (CS.LG) 2026-06-19

Adversarial Dependence Minimization

arXiv:2502.03227v2 Announce Type: replace Abstract: Minimally redundant representations are typically learned by minimizing feature covariance. However, covariance-based methods fail to eliminate all dependencies/redundancies, as linearly uncorrelated variables can still exhibit nonlinear relationships. To address this, we introduce ADM, a differentiable algorithm that minimizes statistical dependence between feature dimensions through an adversarial game: auxiliary networks identify dependencies, while the encoder removes them. We prove that mutual independence is achieved at the global optimum, empirically verify convergence, and study three potential applications: extending PCA to nonlinear decorrelation, improving generalization in image classification, and preventing dimensional collapse in self-supervised learning. By promoting statistically independent representations, ADM paves the way for learning more robust, compressed, and generalizable representations across diverse applications.

03.
medRxiv (Medicine) 2026-06-22

MinderCare: protocol for a mixed-methods evaluation of a digitally enabled dementia care service.

Introduction and aims Dementia is a growing public health challenge affecting millions of people worldwide. It is a progressive condition that increases the risk of infections, falls, hospital admissions, dependence in activities of daily living, safety issues such as wandering, care home transfers, and death. New ways of supporting people living with dementia (PLWD) at home are urgently needed. We describe the MinderCare study which evaluates a digitally enabled care model that integrates low-burden sensor-based remote monitoring within a nurse-led clinical service. Methods and analysis In this mixed-methods study, we will recruit 100 people with confirmed or suspected dementia living at home and deploy the Minder remote monitoring system for at least 12 months. A detailed characterisation of the cohort will be obtained, including cognition, frailty, participant and carer wellbeing, functioning, and quality of life. The feasibility, acceptability, sustainability, and resource requirements of the service will also be assessed. Low-cost sensors provide information about behaviour, environment and physiology from the home. Machine-learning algorithms have been used to develop digital biomarkers of infection, sleep, night-time behaviours, daily activities and routines, and the effects of clinical events and treatment. These will be assessed through clinical reports of sensor-derived data that include anomaly alerts provided to the clinical teams. Algorithms will be assessed for their clinical utility and acceptability. The comparative-effectiveness component will be designed as a target trial emulation using linked electronic health-record data to construct a time-indexed external usual-care control cohort. The primary comparative outcome will be Days Alive and Out of Hospital (DAOH) over 12 months from the activation-index date, with healthcare utilisation, costs, institutionalisation and mortality assessed as secondary outcomes. DAOH and estimated MinderCare effects will also be examined across prespecified strata of baseline inpatient utilisation. Ethics and dissemination Ethical approval has been granted by the North East Newcastle and North Tyneside 2 Research Ethics Committee, and the study has received confirmation of capacity and capability by the Imperial College Healthcare NHS Trust. Study findings will be disseminated to patients, health and social care professionals, and policymakers through peer-reviewed publications and conference presentations. Study registration number: ISRCTN14997677 and NIHR portfolio CPMSID 63023.

04.
arXiv (CS.LG) 2026-06-19

Evaluating Universal Machine Learning Force Fields Against Experimental Measurements

arXiv:2508.05762v2 Announce Type: replace-cross Abstract: Universal machine learning force fields (UMLFFs) promise to revolutionize materials science by enabling rapid atomistic simulations across the periodic table. However, their evaluation has been limited to computational benchmarks that may not reflect real-world performance. We introduce UniFFBench, a comprehensive evaluation framework featuring the MinX dataset – a diverse collection of 1,500+ mineral systems spanning 85 elements, extreme thermodynamic conditions (0–5000 K, 0–1000 GPa), and structural complexity, including partial occupancy and disorder. This diversity, combined with experimental reference values for validation, enables assessment of UMLFF generalization across chemical space and conditions substantially beyond typical training scenarios. Our systematic evaluation of six state-of-the-art UMLFFs reveals a substantial ``reality gap'': models achieving impressive performance on computational benchmarks often fail when confronted with experimental complexity. Even the best-performing models exhibit higher density prediction error than the threshold required for practical applications. We observe disconnects between simulation stability and mechanical property accuracy, with prediction errors correlating with training data representation rather than the modeling method.

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

State-Grounded Multi-Agent Synthetic Data Generation for Tool-Augmented LLMs

Training tool-augmented LLM agents requires large corpora of multi-turn, tool-grounded conversational data that is expensive to annotate, privacy-constrained in production settings, and largely absent from public datasets. We present StateGen, a synthetic data generation platform that produces scored, reasoning-trace-rich training conversations by orchestrating a four-role LLM loop: a persona-conditioned user simulator, an agent under test, a state-grounded tool simulator, and a multi-axis LLM judge. The key architectural contribution is an authoritative state manager that maintains a structured world-state object across turns, enforcing a backend-is-truth invariant that eliminates the dominant class of tool-call hallucinations by construction. StateGen extends naturally to hierarchical multi-agent settings by declaring sub-agents as tools, all sharing a single state object. We report results on 64,698 evaluated conversations across three production corpora: tool-call hallucination scores reach 9.66/10, the system supports persona-driven variation via a 23-dimensional trait vector, and a cleanly separated train and golden evaluation set split confirms the data is not memorization bait (per-criterion gap analysis). Comparison with eight external systems shows that no single publicly available platform combines multi-turn generation, state-grounded tool simulation, hierarchical multi-agent support, and built-in judge scoring.

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

Multi-Turn Reflective Masking Elicits Reasoning in Mask Diffusion Models

While reasoning on autoregressive (AR) models is often performed by chain-of-thought reasoning and reflection, their refinement of previous outputs still relies on fully sequential generation, even when only local edits are needed. In contrast, the masking mechanism in Mask Diffusion Models (MDMs) naturally supports explicit local edits on previous outputs, allowing selective refinement without discarding previous answers and generating another from scratch. While this property more closely aligns with how humans correct mistakes by iterative local refinement, existing MDMs do not support multi-turn masking and denoising. We propose Reflective Masking (RM), which elicits such an intrinsic reasoning capability in MDMs via lightweight post-training. RM provides a native test-time scaling, where an MDM iteratively revisits and revises its prior outputs based on evolving context. To exploit insights from previous turns like AR reasoning, we further introduce History Reference, a parameter-free mechanism that leverages intermediate denoising states during revision. Our approach requires no architectural changes and is easily applicable to existing MDMs. Across diverse tasks and modalities, including text generation, Sudoku, and image editing, Reflective Masking consistently outperforms standard masking-based baselines and demonstrates strong generality, positioning RM as a fundamental primitive for reasoning on MDMs.

07.
arXiv (CS.CL) 2026-06-17

Compositional Skill Routing for LLM Agents: Decompose, Retrieve, and Compose

作者:

LLM agents increasingly rely on external skills – reusable tool specifications – but real-world tasks often require composing multiple skills, not just selecting one. We formalize this as the Compositional Skill Routing problem: given a complex user query and a large skill library, decompose the query into atomic sub-tasks, retrieve the appropriate skill for each sub-task, and compose an executable plan. We present SkillWeaver, a decompose-retrieve-compose framework combining an LLM task decomposer, a bi-encoder skill retriever with FAISS indexing, and a dependency-aware DAG planner. To support evaluation, we introduce CompSkillBench, a benchmark of 300 compositional queries over 2,209 real MCP server skills spanning 24 functional categories, sourced from the public MCP ecosystem. Our experiments reveal that task decomposition quality is the primary bottleneck: standard LLM decomposition reaches only 34.2% category recall at the step level. To address this, we propose Iterative Skill-Aware Decomposition (SAD), a retrieval-augmented feedback loop that iteratively aligns decomposition with available skills. SAD improves decomposition accuracy from 51.0% to 67.7% (+32.7%, Wilcoxon p < 10^-6) in a single iteration; DA-conditioned analysis confirms that correct granularity is the prerequisite for effective retrieval (CatR@1 rises from 34% to 41% when DA=1). SkillWeaver reduces context window consumption by over 99%, and transfer experiments confirm generalization (+35.6% relative DA gain even when target categories are absent from the retrieval pool).

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

Planning with the Views via Scene Self-Exploration

Can VLMs predict how each camera move changes the view, and plan many such moves ahead? We call this capability view planning, requiring (1)understanding how a single action transforms the view, and (2)composing many such transformations across multi-turn plans to identify a target view. We probe both abilities in our proposed ViewSuite, a 3D point-cloud environment on real ScanNet scenes. Across 13 frontier VLMs, a critical planning gap emerges: they possess basic view-action knowledge but fail to compose it across multi-turn plans, with the gap widening as viewpoint distance grows. To close this gap, we propose an iterative framework that alternates self-exploration with view graph distillation. The key insight is that all exploration trajectories, regardless of their outcome, collectively form a view graph that compactly captures how viewpoints connect across a scene. Distilling this graph into diverse supervised tasks reshapes the policy distribution and overcomes the sparse rewards that stall pure RL. This improves Qwen2.5-VL-7B from 2.5% to 47.8% on interactive view planning, surpassing GPT-5.4 Pro (18.5%) and Gemini 3.1 Pro (21.4%). Self-exploration emerges as a promising path toward VLMs that can actively reason and plan in 3D space. Code and Data are at https://viewsuite.github.io.

09.
arXiv (CS.CL) 2026-06-24

ModTGCN: Modularity-aware Graph Neural Networks for Text Classification

Graph-based text classification models typically rely on local neighborhood aggregation and overlook global community structure, despite semantic document graphs exhibiting strong class-consistent clustering. Ignoring this can blur class boundaries and lead to over-smoothing. We propose ModTGCN, a modularity-aware graph neural network for text classification that jointly optimizes cross-entropy and a modularity-based auxiliary objective to promote class-coherent document communities while preserving discriminative representations. The modularity term is computed on a document-document similarity graph derived from transformer embeddings (pretrained or fine-tuned). To improve scalability, we decouple the original heterogeneous TextGCN graph into separate document-word and word-word components, achieving 2x-10x faster training. We further study graph construction strategies, label-aware edge reweighting, and supervision choices for modularity optimization. Experiments on five benchmarks show consistent gains, with larger improvements on complex, low homophily datasets such as Ohsumed and 20NG.

11.
arXiv (CS.LG) 2026-06-16

Beyond the Blood Draw: Explainable Machine Learning for Non-Invasive Dysglycemia Risk Screening

arXiv:2606.16056v1 Announce Type: new Abstract: Dysglycemia, encompassing both prediabetes and diabetes, affects huge numbers of adults worldwide, yet many of them remain undiagnosed. We developed and validated machine-learning (ML) models for non-invasive screening of dysglycemia risk that require no laboratory tests. Pooling data from the National Health and Nutrition Examination Survey (NHANES) 2017–2023 (n=14,352), we trained six ML models with stratified 5-fold cross-validation and compared them with two established clinical risk scores. LightGBM achieved the highest area under the receiver operating characteristic curve (AUC=0.820, 95% CI: 0.806–0.835), outperforming the Finnish Diabetes Risk Score (0.745) and American Diabetes Association Risk Test (0.783). SHAP analysis identified age, race/ethnicity, and waist-to-height ratio as the most influential predictors. Subgroup analyses confirmed consistent performance across demographic strata (AUC: 0.735–0.832). These results demonstrate the feasibility of explainable, laboratory-free dysglycemia screening for deployment in community settings and self-tracking health applications.

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

Generative models for decision-making under distributional shift

arXiv:2604.04342v2 Announce Type: replace Abstract: Many data-driven decision problems are formulated using a nominal distribution estimated from historical data, while performance is ultimately determined by a deployment distribution that may be shifted, context-dependent, partially observed, or stress-induced. This tutorial presents modern generative models, particularly flow- and score-based methods, as mathematical tools for constructing decision-relevant distributions. From an operations research perspective, their primary value lies not in unconstrained sample synthesis but in representing and transforming distributions through transport maps, velocity fields, score fields, and guided stochastic dynamics. We present a unified framework based on pushforward maps, continuity, Fokker-Planck equations, Wasserstein geometry, and optimization in probability space. Within this framework, generative models can be used to learn nominal uncertainty, construct stressed or least-favorable distributions for robustness, and produce conditional or posterior distributions under side information and partial observation. We also highlight representative theoretical guarantees, including forward-reverse convergence for iterative flow models, first-order minimax analysis in transport-map space, and error-transfer bounds for posterior sampling with generative priors. The tutorial provides a principled introduction to using generative models for scenario generation, robust decision-making, uncertainty quantification, and related problems under distributional shift.

13.
arXiv (CS.LG) 2026-06-19

Improved Stochastic Optimization of LogSumExp

arXiv:2509.24894v4 Announce Type: replace-cross Abstract: The LogSumExp function, dual to the Kullback-Leibler (KL) divergence, plays a central role in many important optimization problems, including entropy-regularized optimal transport (OT) and distributionally robust optimization (DRO). In practice, when the number of exponential terms inside the logarithm is large or infinite, optimization becomes challenging since computing the gradient requires differentiating every term. We propose a novel convexity- and smoothness-preserving approximation to LogSumExp that can be efficiently optimized using stochastic gradient methods. This approximation is rooted in a sound modification of the KL divergence in the dual, resulting in a new $f$-divergence called the Safe KL divergence. Our experiments and theoretical analysis of the LogSumExp-based stochastic optimization, arising in DRO and continuous OT, demonstrate the advantages of our approach over existing baselines.

14.
arXiv (CS.CV) 2026-06-19

GenTrack: A New Generation of Multi-Object Tracking

This paper introduces a novel multi-object tracking (MOT) method, dubbed GenTrack, whose main contributions include: first-a hybrid tracking approach employing both stochastic and deterministic manners to robustly handle unknown and time-varying numbers of targets, particularly in maintaining target identity (ID) consistency and managing nonlinear dynamics, second-leveraging particle swarm optimization (PSO) with some proposed fitness measures to guide stochastic particles toward their target distribution modes, enabling effective tracking even with weak and noisy object detectors, third-integration of social interactions among targets to enhance PSO-guided particles as well as improve continuous updates of both strong (matched) and weak (unmatched) tracks, thereby reducing ID switches and track loss, especially during occlusions, fourth-a GenTrack-based redefined visual MOT baseline incorporating a comprehensive state and observation model based on space consistency, appearance, detection confidence, track penalties, and social scores for systematic and efficient target updates, and five-the first ever publicly available source-code reference implementation with minimal dependencies, featuring three variants, including GenTrack Simple, Strengthen, and Super, facilitating flexible reimplementation. Experimental results have shown that GenTrack provides superior performance on standard benchmarks and real-world scenarios compared to state-of-the-art trackers, with integrated implementations of baselines for fair comparison. Potential directions for future work are also discussed. The source-code reference implementations of both the proposed method and compared-trackers are provided on GitHub: https://github.com/SDU-VelKoTek/GenTrack

15.
arXiv (CS.AI) 2026-06-24

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

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

16.
arXiv (quant-ph) 2026-06-24

Quantum mechanics over real numbers fully reproduces standard quantum theory

arXiv:2604.19482v3 Announce Type: replace Abstract: Standard quantum mechanics employs complex Hilbert spaces, but whether complex numbers are fundamental or merely convenient has long been debated. For decades, real-valued equivalents were considered mathematically possible but cumbersome. However, a highly cited 2021 result claimed that any quantum theory based on real numbers is experimentally falsifiable via network Bell experiments. Yet, it remains an open question whether this falsification applies to all real-valued theories. Here we show that this conclusion rests on an incomplete real formulation, and we present a rigorous real-valued framework that perfectly reproduces all predictions of standard quantum mechanics. We demonstrate that the standard real tensor product ($\otimes_{\mathbb{R}}$) used in previous no-go theorems is algebraically incompatible with the rich structure of conventional quantum mechanics. We present a real framework based on K\"{a}hler space and prove that it is exactly isomorphic to established quantum mechanics via an explicit bijection $\gamma$. The isomorphism extends to composite systems through a symplectic composition rule $\otimes^{\ks}$ that replaces the Kronecker product. Consequently, our formulation achieves the maximal $\mathrm{CHSH}_{3}$ violation of $6\sqrt{2}$ using purely real variables, demonstrating that the no-go theorem is specific to a particular real representation of states and operators and to the composition rule $\otimes_\mathbb{R}$ built upon it, neither of which extends to the present K\"{a}hler framework. These results demonstrate that complex numbers are not fundamentally required by nature; rather, they encode a deeper real geometric structure that governs quantum interference and entanglement, settling this long debate.

17.
arXiv (CS.AI) 2026-06-11

Planning under Distribution Shifts with Causal POMDPs

arXiv:2602.23545v2 Announce Type: replace Abstract: In the real world, planning is often challenged by distribution shifts. As such, a model of the environment obtained under one set of conditions may no longer remain valid as the distribution of states or the environment dynamics change, which in turn causes previously learned strategies to fail. In this work, we propose a theoretical framework for planning under partial observability using Partially Observable Markov Decision Processes (POMDPs) formulated using causal knowledge. By representing shifts in the environment as interventions on this causal POMDP, the framework enables evaluating plans under hypothesized changes and actively identifying which components of the environment have been altered. We show how to maintain and update a belief over both the latent state and the underlying domain, and we prove that the value function remains piecewise linear and convex (PWLC) in this augmented belief space. Preservation of PWLC under distribution shifts has the advantage of maintaining the tractability of planning via $\alpha$-vector-based POMDP methods.

18.
arXiv (quant-ph) 2026-06-16

On-Demand Coherent Mapping of Telecom Optical States onto Erbium Hyperfine Spins

arXiv:2606.15009v1 Announce Type: new Abstract: Optical quantum memories operating directly at telecom wavelengths are a key enabling technology for long-distance quantum networks, yet on-demand storage onto long-lived ground-state spins in this spectral region has remained elusive due to the challenge of coherently transferring optical excitations to hyperfine spin states. Here we demonstrate spin-wave storage in $^{167}$Er$^{3+}$:Y$_2$SiO$_5$ at 0.8 K and 1.1 T, establishing the core operational primitive required for on-demand telecom quantum memories. Using classical optical control pulses, we coherently transfer collective optical excitations to erbium hyperfine states with transfer efficiency exceeding 12%, enabling on-demand retrieval. We measure a hyperfine population lifetime of 25 s and demonstrate spin-wave storage for up to 25 $\mu$s. By identifying hyperfine inhomogeneous broadening as the dominant present limitation, our measurements define a clear pathway toward second-scale storage through improved spectral tailoring and dynamical decoupling. The results highlight the application of erbium-based solid-state memories for scalable fiber-compatible quantum repeater architectures.

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

Sentinel: Decoding Context Utilization via Attention Probing for Efficient LLM Context Compression

Retrieval-augmented generation (RAG) often suffers from long and noisy retrieved contexts. Existing context compression methods typically rely on heuristic relevance estimation or supervised compression models rather than on how LLMs utilize retrieved context during inference. We propose Sentinel, a lightweight sentence-level compression framework that decodes inference-time contextual utilization behaviors from head-wise attention patterns of frozen LLMs. To ground supervision in retrieval-dependent answering behavior, Sentinel trains a lightweight probe using QA examples where the model succeeds only when retrieved context is available. Sentinel performs compression using only a single non-autoregressive forward pass without dedicated compression training or autoregressive scoring. Empirically, we find that effective contextual utilization signals remain accessible even in compact proxy models. On LongBench, Sentinel with a 0.5B proxy model achieves up to 5$\times$ compression while attaining question-answering performance competitive with compression methods built on 7B-scale models. Despite being trained only on English QA data, Sentinel also generalizes effectively to Chinese and out-of-domain settings.

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

Dynamic In-Group Persona Generation for Enhancing Human-AI Rapport

arXiv:2606.18256v1 Announce Type: cross Abstract: LLM-based chatbots are increasingly applied in interpersonal domains such as counseling and peer support, where establishing human-AI rapport is crucial yet remains challenging. In this work, we introduce a novel approach for conditioning LLMs with in-group personas, which (i) first identifies a user's primary concern and brief personal context (e.g., a computer science undergraduate worried about future career prospects), and (ii) generates a synthetic in-group persona that shares a similar primary concern while differing in background and narrative details, such as age or profession (e.g., a junior researcher at an AI startup). Furthermore, we conduct a human-subject study to systematically evaluate the effectiveness of in-group persona agents in enhancing human-AI rapport. We compare our approach against two baseline conditions: a conventional agent without persona conditioning and an agent exhibiting minimal self-disclosure (e.g., "I've felt that too"). Results from post-task questionnaires assessing rapport and user experience indicate that the in-group persona agent significantly improves perceived rapport and personal relevance compared to the baselines, and also yields more positive user experience-most notably higher engagement.

21.
arXiv (CS.AI) 2026-06-17

ARVO: Atlas of Reproducible Vulnerabilities for Open-Source Software

arXiv:2606.17283v1 Announce Type: cross Abstract: Achieving reproducibility, quantity, and diversity in vulnerability datasets has long been viewed as an inherent three-way trade-off, where improving one dimension often comes at the cost of the others. In practice, reproducibility has been the dimension most often neglected. This has limited what can be automatically extracted from historical bug datasets, and has reduced their utility for downstream security research. In this work, we propose a method to produce a new security dataset which ensures reproducibility for diverse vulnerabilities at scale by identifying the key obstacles to large-scale bug reproduction and addressing them with general solutions. Using this method, we introduce full reproducibility to the largest open source software vulnerability dataset (OSS-Fuzz) and construct the ARVO dataset (an Atlas of Reproducible Vulnerabilities in Open-source software). ARVO is a large-scale dataset consisting of over 6,100 real-world vulnerabilities across 311 projects. Focusing on reproducibility, ARVO differs from existing datasets by providing each vulnerability in a form that can be consistently rebuilt, triggered, and analyzed across versions. Reproducibility also enables automatic identification of the corresponding patch for each vulnerability and supports direct interaction with vulnerabilities after code changes, capabilities that existing large-scale datasets do not provide. In our evaluation, ARVO successfully reproduces 81% of vulnerabilities and achieves 89.4% accuracy on the located patches. We also discuss ARVO's influence on both upstream practices and downstream security research.

22.
arXiv (CS.LG) 2026-06-15

Where Black-box Drug-Target Interaction Prediction Models Look: Cross-Method Explainability

arXiv:2606.14245v1 Announce Type: new Abstract: Drug-target interaction (DTI) and affinity (DTA) predictors increasingly achieve strong benchmark scores, yet their internal use of sequence, fingerprint, and graph features often remains opaque. We present an interpretability audit of BridgeDPI architecture on three different datasets including Gao, Human, and C.elegans. This study combines gradient-based attributions – integrated gradients, saliency, layer-wise relevance propagation, SmoothGrad, and SmoothGrad-IG – with feature-wise occlusion ablation and strict intersection consensus across methods to reduce single-explainer bias. We summarize sensitivity and signed effects at raw inputs, at the bridge similarity scaffold, and through the graph convolution, including edge-level sensitivities and targeted edge removals. The results show that explainability is most informative when treated as model criticism: it reveals modality dominance, padding and special-token artifacts, dataset-dependent cooperative versus suppressive effects across layers, and chemistry-consistent fragment and composition motifs where methods agree. These analyses do not substitute for structural or experimental ground truth, yet they can provide testable hypotheses for downstream validation in computational drug discovery pipelines. More broadly, applying modern XAI to contemporary DTI/DTA models is still an early pass over the rich structure implicit in trained weights and data – yet even this first layer of scrutiny already helps researchers relate predictions to drug- and target-side representations and to prioritize external validation.

23.
medRxiv (Medicine) 2026-06-12

Mathematical analysis of the overall survival after chemoradiotherapy of limited-stage small cell lung cancer and the effect of dose/fractionation

The purpose of this work is to analyze the 2-year overall survival (OS2y) of limited-stage small cell lung cancer (LS-SCLC) treated with chemoradiotherapy (CRT), aiming at characterizing the response of LS-SCLC, and in particular the /{beta} value and proliferation parameters. Through a systematic analysis of the literature, we collated a dataset containing 57 entries (3363 patients) of response of LS-SCLC treated with CRT. Radiotherapy schedules ranged from hyper- to hypofractionation. Four radiobiological models to describe the OS2y were investigated, with progressive levels of complexity including the effect of radiotherapy, chemotherapy, treatment year and toxicity. The Akaike Information Criterion (AIC) was used to compare models, and the profile likelihood methodology to compute confidence intervals. Model 4, which includes the effect of radiotherapy, chemotherapy, treatment year and dose-dependent toxicity, provided the best fits of the experimental data (lowest AIC value). While being the best model, model 4 still fails to provide a good prediction of the OS2y, in particular failing to predict the survival of the schedules achieving the lower/higher survivals. The radiobiological analysis of the dose-response of LS-SCLC to CRT does not allow to narrowly constrain the value of response parameters. We attribute this limitation to the large heterogeneity of this disease. Nonetheless, our analysis shows a large /{beta} value (>9 Gy, 95% CI), which implies a low fractionation effect in the radiotherapy of LS-SCLC. and an accelerated proliferation of tumor cells, {lambda}' > 1.6 Gy/day (95% CI), after a kick-off time of ~4-5 weeks, which supports the use of accelerated protocols to avoid the effect of tumor proliferation on the clinical outcome.

24.
arXiv (CS.CL) 2026-06-11

FORT-Searcher: Synthesizing Shortcut-Resistant Search Tasks for Training Deep Search Agents

Training deep search agents requires verifiable questions whose answers remain unavailable until sufficient evidence has been acquired through search. Existing synthesis methods often increase apparent difficulty by enriching graph structures, but structural complexity alone does not guarantee realized search difficulty: the intended search process can collapse through a cheaper identifying route. We formalize this gap with a shortcut-aware difficulty framework and identify four actionable shortcut risks: evidence co-coverage, single-clue selectivity, exposed constants, and prior-knowledge binding. To diagnose their realized effects, we use trajectory signatures including solving cost, answer hit time, and prior-shortcut rate. Guided by this framework, we introduce FORT, a Framework of Shortcut-Resistant Training-Data Synthesis. FORT constructs shortcut-resistant training data by controlling shortcut risks across entity selection, evidence graph construction, question formulation, and adversarial refinement. Experiments show that FORT induces longer pre-answer search and fewer shortcut patterns than existing open-source deep search datasets. Using the resulting trajectories, we train FORT-Searcher with supervised fine-tuning (SFT) only, and it achieves the best overall performance among comparable-size open-source search agents on challenging deep search benchmarks. Relevant resources will be made available at https://github.com/RUCAIBox/FORT-Searcher.

25.
arXiv (CS.AI) 2026-06-12

Intelligence as Managed Autonomy: Failure, Escalation, and Governance for Agentic AI Systems

arXiv:2605.27628v2 Announce Type: replace Abstract: As autonomous and agentic AI systems scale in robotic and human-machine environments, managing hallucination and persistent but unjustified action remains an open challenge. Rather than attributing these failures solely to model or alignment limitations, this paper explores the architectural vulnerability of unbounded autonomy - the presumption that an agent should continue operating regardless of rising uncertainty. It introduces a theory of managed autonomy that defines intelligent behavior through the formal capacity to detect epistemic drift, suspend reasoning, attempt recovery, and ultimately surrender control when reliability diminishes. We instantiate this theory via the SMARt (Self-Managing Multi-tier Autonomous Reasoning with Regulated/Revoked transitions) model, a four-layer framework featuring Stable, Meta-cognitive, Assisted, and Regulated states. By developing a timed, guarded Petri net formulation, we establish theoretically bounded properties for the system, demonstrating how architecture can formally mandate escalation, constrain invalid outputs, and ensure governance reachability under specified conditions. We further analyze how incorporating domain-specific trigger sets across varied operational settings (e.g., healthcare, robotics, etc.) can systematically preserve safety, assuming completeness and soundness criteria are met. Because these triggers are designed to be adaptive, the SMARt model accommodates the safe, controlled expansion of an agent's operational scope over time. We conclude that formalizing failure management within the autonomy lifecycle is a crucial step toward realizing reliable and governed artificial intelligence.