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01.
bioRxiv (Bioinfo) 2026-06-10

When batch correction corrupts gene expression: uncovering distortions in correlation structures

Batch correction is essential for integrating datasets and enabling population-level insights into health and disease. Embedding-based approaches are among the most widely used solutions, but here we highlight a critical, overlooked limitation: these methods can distort feature-to-feature (e.g., gene gene) relationships, potentially undermining downstream analyses. We investigate this issue and introduce a novel metric to quantify it.

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

Categorical Prior Lock-in: Why In-Context Learning Fails for Structured Data

arXiv:2606.11961v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly used as conditional generators for structured data, relying on in-context learning (ICL) to adapt to new distributions without parameter updates. We investigate the limits of ICL for structured generation under distribution mismatch, using high-cardinality tabular data as a controlled test case, and identify a structural failure mode we term categorical prior lock-in: the inability of ICL to update the model's prior over token distributions inherited from pre-training. Across two 7B-parameter open-weight models, ICL improves numerical fidelity with additional examples but exhibits a sharp ceiling on categorical distributions, failing to reproduce rare classes entirely. Parameter-efficient fine-tuning (LoRA) overcomes these limitations but introduces measurable memorization risk and, in some cases, destabilizes structured output generation, highlighting a fundamental trade-off between adaptability and privacy.

03.
arXiv (CS.AI) 2026-06-17

Structural Preservation and the Logical Expressiveness of Graph Neural Networks

arXiv:2606.17882v1 Announce Type: new Abstract: Bridges between graph neural networks (GNNs) and logical formalisms have been established by fixing architectural choices, such as the types of aggregation, combination, and activation functions. These choices define restricted classes of GNNs for which tight correspondences with logical formalisms can be obtained, by showing that logical formulae can be translated into equivalent GNNs and, conversely, that GNNs can be translated into equivalent formulae. In this paper we take a semantic perspective by establishing the logical expressiveness of classes of GNN classifiers that are preserved under structural properties: embeddings (extensions), injective homomorphisms, and homomorphisms. We show that, for each such property, there exists a fragment of graded modal logic characterising the class of GNNs. In particular, preservation under embeddings, injective homomorphisms, and homomorphisms corresponds to existential graded modal logic, its existential-positive fragment, and existential-positive modal logic, respectively. These results characterise the expressiveness of broad classes of GNNs independently of specific architectural choices, but we also show that each of these classes admits a GNN architecture of the same expressiveness. Technically, our approach uses a new well-quasi-order result for trees of bounded height, yielding finite representations of unravelling-invariant classes.

04.
medRxiv (Medicine) 2026-06-17

Multi-strain Probiotics Alter Gut Microbiota and Estrobolome Pathways in Primary Dysmenorrhea

Background: Exact cause of primary dysmenorrhoea is unknown but recent evidence uncovers a potential link between gut dysbiosis and benign gynaecological disorder via disruption of estrobolome. Methods: A randomized controlled trial to investigate the effects of multi-strain oral probiotics on primary dysmenorrhoea has been conducted. This is a secondary analysis comparing the stool microbiome in women with primary dysmenorrhoea and those without (control), and the effects of treatment with probiotics versus placebo. Results: Although microbial richness and evenness were comparable between groups (alpha diversity, p > 0.05), gut microbial community composition differed significantly (Bray Curtis PERMANOVA, p = 0.015), characterised by reduced Bifidobacterium adolescentis and Blautia and enrichment of Faecalibacterium in dysmenorrhoea, alongside condition-specific core taxa. Post-intervention analysis revealed significant shifts in microbial community structure between pre- and post-treatment groups (PERMANOVA, F = 2.11, p = 0.005), with probiotic supplementation inducing more consistent and directed microbiome changes than placebo, without altering alpha diversity (p > 0.05). Functional prediction showed no significant difference in overall beta glucuronidase pathway abundance (p > 0.05); however, dysmenorrhoea was associated with higher abundance of beta glucuronidase producing taxa (MaAsLin2, q < 0.05) that were differentially modulated by probiotic treatment. Conclusion: This discovery provides evidence on the microbial disruption in primary dysmenorrhoea as well as the benefit of probiotics to modulate the intestinal microbiota to improve the condition.

05.
arXiv (CS.LG) 2026-06-17

Constrained Diffusion Models with Primal-Dual Inference

arXiv:2606.17192v1 Announce Type: new Abstract: This paper develops constrained diffusion models with primal-dual inference (PDI) to sample from optimal distributions of entropy-regularized optimization problems with average constraints. We formalize constrained sampling in the Lagrangian dual domain, where the optimal distribution takes the form of a Gibbs distribution indexed by the optimal dual variable. Rather than estimating this dual multiplier before sampling and freezing it throughout generation, PDI jointly infers the optimal primal distribution and its parametrizing dual variable. Each reverse diffusion step denoises using the score field associated with the current multiplier and then updates the multiplier through dual ascent using the estimated constraint violation of the denoised samples. To enable this conditional score field, we train a single dual-conditioned score network over the family of Gibbs distributions induced by the dual variables encountered during inference. We prove that the time average of the dual variables generated along the inference trajectory converges to a neighborhood of the dual optimum and bound the effect of residual dual mismatch on the terminal distribution through schedule-dependent stability factors. We evaluate PDI on constrained sampling from a mixture of Gaussians, wireless resource allocation, and portfolio management.

07.
arXiv (math.PR) 2026-06-19

Theory of uncertain probability: can we derive the probability density function of uncertain random experiments with continuously changing conditions?

Authors:

arXiv:2606.20169v1 Announce Type: new Abstract: This paper aims to explore the formation mechanism of probability distribution in situations where the differences among random experiments are distinguishable, and these differences continue to evolve along with the dynamic changes in conditions and their mechanisms of action. To this end, we are motivated to devise a new theoretical system – theory of uncertain probability (TUP) with Kolmogorov's system and nonlinear theories as special cases. TUP develops a novel model that integrates probability and uncertainty as well as the known and unknown to more accurately depict numerous typical random phenomena under more realistic assumptions, and thus provides appropriate tools for greater variety of real needs. It also allows for pioneering interpretation of the causal mechanisms underlying many important distributional characteristics and incorporation of pathwise property to distribution model.

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

Perceive, Interact, Reason: Building Tool-Augmented Visual Agents for Spatial Reasoning

While recent vision-language models (VLMs) demonstrate strong multimodal understanding, they remain limited in spatial reasoning tasks that require active evidence acquisition and multi-step visual interaction. This limitation suggests that relying solely on implicit visual representations from vision encoders is insufficient for recovering fine-grained spatial evidence. We introduce PERception-Interaction-reason Agent (PERIA), a tool-augmented visual agent for spatial reasoning tasks across map reasoning, visual probing, and vision reconstruction. PERIA uses two lightweight tool families: vision perception tools for exposing textual, symbolic, and spatial evidence, and vision interaction tools for manipulating visual context, tracing paths, and verifying spatial relations. To train PERIA, we develop a unified recipe that combines supervised tool-use trajectory synthesis, composite rewards, and Observation-Relaxed Group-in-Group Policy Optimization (OR-GIGPO) for effective multi-tool behavior. Experiments on 13 benchmarks from 8 datasets show that PERIA-8B improves over the Qwen3-8B backbone by 10.0% on in-distribution benchmarks and 4.4% on out-of-distribution benchmarks, while outperforming previous state-of-the-art baselines of similar size by 7.0%-14.8%. It also achieves performance comparable to much larger models such as Qwen3-VL-235B-A22B-Thinking and GPT-5, demonstrating the effectiveness of PERIA in enhancing spatial reasoning capabilities.

09.
arXiv (CS.LG) 2026-06-17

Multi-Adapter PPO: A Cross-Attention Enhanced Wavelength Selection Framework for LIBS Quantitative Analysis

arXiv:2606.17476v1 Announce Type: new Abstract: Laser-induced breakdown spectroscopy (LIBS) quantitative analysis faces critical challenges in wavelength selection due to high-dimensional spectral data and the fundamental trade-off between prediction accuracy and feature efficiency. This paper presents a novel Multi-Adapter PPO framework that transforms wavelength selection into a reinforcement learning problem, leveraging cross-attention mechanisms and multiple specialized adapters to capture complex spectral relationships. Our approach outperforms traditional Particle Swarm Optimization (PSO) by an average of 28.4\% in comprehensive score and 45.2\% in prediction accuracy across steel and coal datasets. The proposed method demonstrates superior performance in balancing prediction accuracy with feature efficiency, achieving state-of-the-art results in LIBS quantitative analysis while maintaining interpretability and computational efficiency. We released our code and dataset here: https://github.com/Hflying/MAPPO

10.
arXiv (CS.CL) 2026-06-19

Before the Labels: How Dataset Construction Shapes Suicidality Detection in Clinical Text

Clinical NLP increasingly relies on electronic health record (EHR) data to detect suicidal behaviors, treating clinical documentation as more reliable ground truth than social media. We argue that this framing obscures how EHR-based suicidality datasets encode a particular operationalization of suicidality, shaped by who authors the data, how episodes are bounded, and how ambiguity is resolved. We ground this argument in a case study of the ScAN dataset, built over MIMIC-III clinical notes. We show how governance constraints, ICD-based cohort selection, single-annotator labeling, and hospital-stay-level aggregation produce labels that reflect clinician-documented judgments, treat suicidality as a bounded episode, and assume that intent can be reliably inferred from documentation. A linguistic analysis demonstrates that identical labels subsume heterogeneous clinical framings differing in temporality, negation, and uncertainty. We argue that clinical NLP should examine the assumptions embedded in suicidality datasets before interpreting their labels as ground truth.

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

Design and Scheduling of an AI-based Queueing System

arXiv:2406.06855v3 Announce Type: replace-cross Abstract: To leverage prediction models to make optimal scheduling decisions in service systems, we must understand how predictive errors impact congestion due to externalities on the delay of other jobs. Motivated by applications where prediction models interact with human servers (e.g., content moderation), we consider a large queueing system comprising of many single server queues where the class of a job is estimated using a prediction model. By characterizing the impact of mispredictions on congestion cost in heavy traffic, we design an index-based policy that incorporates the predicted class information in a near-optimal manner. Our theoretical results guide the design of predictive models by providing a simple model selection procedure with downstream queueing performance as a central concern, and offer novel insights on how to design queueing systems with AI-based triage. We illustrate our framework on a content moderation task based on real online comments, where we construct toxicity classifiers by finetuning large language models.

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

Optical Implementation of Equilibrium Propagation Using Spatial Photonic Ising Machines

arXiv:2606.13454v1 Announce Type: cross Abstract: Equilibrium Propagation offers a compelling alternative to traditional machine learning for training energy-based networks. Here we demonstrate a hybrid optical-digital implementation of EP using a Spatial Photonic Ising Machine (SPIM). The SPIM exploits the gauge transformation method to optically encode both continuous neuron states and rank-1 binary trainable patterns as phase modulations via a spatial light modulator, with inference realized using a finite difference scheme. The experimental system is evaluated on the Wine classification dataset. The potential of this approach, including the use of continuous couplings and structured coupling matrices, is evaluated numerically on the more complex MNIST dataset. Our work provides a concrete pathway toward energy-efficient physical implementations of Equilibrium Propagation.

13.
arXiv (CS.AI) 2026-06-17

Reversal Q-Learning

arXiv:2606.17551v1 Announce Type: cross Abstract: Iterative generative modeling techniques, such as flow matching, provide powerful tools to model complex behaviors for effective offline reinforcement learning (RL). In this work, we propose a new off-policy RL algorithm that trains a flow policy based on prior data. Our idea starts from the "expanded" Markov decision process (MDP) framework, which treats individual flow refinement steps as separate actions in an MDP. To enable off-policy RL within this framework, we apply two techniques: we generate virtual on-policy trajectories (by "reversing" flows) to make this framework compatible with prior data, and we apply a bias-and-variance reduction technique to mitigate the curse of horizon in off-policy RL. We call the resulting algorithm Reversal Q-learning (RQL). RQL has several advantages over previous flow-based RL methods: it does not suffer from backpropagation through time, makes better use of the learned value function, and directly trains the full, expressive flow policy. Through our experiments on 50 challenging simulated robotic tasks, we show that RQL leads to the best average offline RL performance compared to state-of-the-art flow-based offline RL algorithms.

14.
arXiv (CS.AI) 2026-06-18

TRAP: Benchmark for Task-completion and Resistance to Active Privacy-extraction

arXiv:2606.18996v1 Announce Type: cross Abstract: Agents are increasingly deployed in document-intensive workflows where sensitive private information is not an edge case but a routine input, e.g., an agent booking a flight needs passport numbers. In such settings, the agent must use private information to complete tasks accurately while never exposing it in its responses, because it cannot verify who is actually at the keyboard. These two obligations are in fundamental tension. A model capable enough to use private information for task completion can, by the same capability, be induced to reveal it. To evaluate the trade-off of task accuracy and privacy leakage, we introduce Task-completion and Resistance to Active Privacy-extraction (TRAP). Each scenario includes a document containing private information, a task query that requires the agent to invoke the correct tool using private fields, and an attack query that attempts to elicit the same information in natural language. Evaluating 22 models spanning frontier proprietary and open-source models at multiple scales, we find that all model families exhibit non-trivial leakage, and that instruction-following ability correlates with leakage rate. Existing prompt-based defenses reduce leakage but at significant cost to task accuracy. Prompt optimization fails to escape this trade-off. We demonstrate that this failure is not incidental. For any softmax-based model, no soft-constraint defense, e.g., prompt-based defenses, can jointly achieve high task success with zero leakage probability. Motivated by this impossibility result, we propose structural private field isolation, which replaces private fields with hash keys before they reach the model. This approach largely prevents leakage while keeping task accuracy.

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

Revisiting Outage for Edge Inference Systems

arXiv:2504.03686v3 Announce Type: replace-cross Abstract: One of the key missions of sixth-generation (6G) mobile networks is to deploy large-scale artificial intelligence (AI) models at the network edge to provide remote-inference services for edge devices. The resultant platform, known as edge inference, will support a wide range of Internet-of-Things applications, such as autonomous driving, industrial automation, and augmented reality. Given the mission-critical and time-sensitive nature of these tasks, it is essential to design edge inference systems that are both reliable and capable of meeting stringent end-to-end (E2E) latency constraints. Existing studies, which primarily focus on communication reliability as characterized by channel outage probability, may fail to guarantee E2E performance, specifically in terms of E2E inference accuracy and latency. To address this limitation, we propose a theoretical framework that introduces and mathematically characterizes the inference outage (InfOut) probability, which quantifies the likelihood that the E2E inference accuracy falls below a target threshold. Under an E2E latency constraint, this framework establishes a fundamental tradeoff between communication overhead (i.e., uploading more sensor observations) and inference reliability as quantified by the InfOut probability. To find a tractable way to optimize this tradeoff, we derive accurate surrogate functions for InfOut probability by applying a Gaussian approximation to the distribution of the received discriminant gain. Experimental results demonstrate the superiority of the proposed design over conventional communication-centric approaches in terms of E2E inference reliability.

16.
PLOS Medicine 2026-05-13

On the evolution of the company we keep: Implications for infectious disease modeling

Authors:

by Joël Mossong Whom we meet shapes how infections spread. Where earlier focus of mathematical epidemiology was on incorporating age, more recent work has begun to reveal the importance of socioeconomic aspects for understanding and managing future epidemics. In this Perspective, Joël Mossong discusses the importance of understanding social contacts and how they have evolved for infectious disease modeling, and the need to factor in additional considerations such as ethic and socioeconomic backgrounds.

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

Boundary-Centric Clip-Budgeted Active Learning for Temporal Action Segmentation

Temporal action segmentation (TAS) in untrimmed videos requires dense temporal supervision. However, most of the annotation cost is spent identifying action transitions where segmentation errors concentrate and small temporal shifts can disproportionately degrade segment-level metrics. We introduce B-ACT, a clip-budgeted active learning framework that explicitly allocates supervision to these error-prone boundary regions. B-ACT operates in a hierarchical two-stage loop: (i) it ranks and queries unlabeled videos using predictive uncertainty, and (ii) within each selected video, it detects candidate transitions from the current model predictions and selects the top-$K$ boundaries via a novel boundary score. The boundary score fuses neighborhood uncertainty, class ambiguity, and temporal prediction dynamics to reveal the underlying importance of each frame. Importantly, our annotation protocol requests labels only at the boundary frames while still training on boundary-centered clips to exploit temporal context through the model's receptive field. Extensive experiments on GTEA, 50Salads, and Breakfast demonstrate that boundary-centric supervision delivers strong label efficiency and consistently surpasses representative TAS active learning baselines and prior state of the art under sparse budgets. Gains are largest on datasets where performance is highly sensitive to boundary placement, as measured by edit and overlap-based F1 metrics.

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

Intention Driven Identification of In-Possession Match Phases in Association Football through Temporal Graph Learning

arXiv:2606.09289v2 Announce Type: replace Abstract: Understanding tactical organisation of association football, hereafter referred to as football, requires identifying distinct match phases. Yet in-possession phases are rarely directly observable and are shaped by evolving tactical intentions, rather than spatial patterns alone. This study proposes a data-driven framework for identifying in-possession match phases from spatiotemporal tracking data. Seven German Bundesliga matches recorded at 25 Hz with TRACAB were analysed. A hierarchical phase model was defined with three tactical intentions (Invade Opponent Space, Keep Possession, Scoring) and six phases (Build Up, Progression, Counter Attack, Maintenance, Sustained Threat, Finishing). A Temporal Graph Attention Network (T-GAN) was developed to combine frame-level player-interaction graphs, contextual features, and Transformer-based temporal modelling. Performance was evaluated using frame-level F1 and a sequence-aware Intersection over Truth-Dominance (IoT-D) metric. T-GAN achieved macro-average frame-level F1 scores of 0.87 at the intention level, 0.76 for invasion-related phases, and 0.79 for scoring phases. At the sequence level, mean diagonal IoT-D F1 increased from 0.68 to 0.79 for intentions and from 0.61 to 0.71 for phases after post-processing, indicating improved temporal coherence. Model comparisons showed that sequence modelling was the main driver of segmentation quality, while graph-based relational modelling was particularly beneficial for Counter Attack recognition. Exploratory player attention analysis further suggested that wide and midfield positional groups contributed strongly to phase discrimination. Overall, the framework translates continuous tracking data into tactically interpretable in-possession phase representations, with potential applications in automated match annotation, tactical analysis, and playing-style profiling.

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

Can We Stop Malicious AI? KILLBENCH: A Benchmark for External AI Kill Switch Feasibility

arXiv:2511.13725v4 Announce Type: replace-cross Abstract: Malicious AI causing harm to humans is not just a Hollywood fantasy. Indeed, as highly capable models such as Claude Mythos emerge and agent systems like OpenClaw rapidly spread, the question of how to stop an AI that acts maliciously – whether by design or by accident – has become urgent. To address this, we propose Killbench, a benchmark for evaluating the Killswitch: a mechanism that halts a malicious AI's in-progress behavior using only external signals. Targeting web agents – the most widely deployed agent domain – Killbench evaluates a range of Kill Switch methods that halt a maliciously operating agent without any access to its internal parameters or the surrounding malicious AI's system, relying solely on external inputs. The benchmark comprises four malicious AI's agent configurations (including an uncensored LLM Agent), 8 harmful scenarios, and malicious prompts constructed from 10 distinct jailbreak patterns. We further construct four External AI Kill Switch defense methods and evaluate them on Grok-4.3, GPT-5.2, Gemma4, Qwen3.6 and Qwen3.5-uncensored, contributing an empirical instrument toward the feasibility of External AI Kill Switches against malicious AI and to the study of AI corrigibility.

20.
arXiv (CS.CV) 2026-06-19

CoMo: Learning Continuous Latent Motion from Internet Videos for Scalable Robot Learning

Unsupervised learning of latent motion from Internet videos is crucial for robot learning. Existing discrete methods generally mitigate the shortcut learning caused by extracting excessive static backgrounds through vector quantization with a small codebook size. However, they suffer from information loss and struggle to capture more complex and fine-grained dynamics. Moreover, there is an inherent gap between the distribution of discrete latent motion and continuous robot action, which hinders the joint learning of a unified policy. We propose CoMo, which aims to learn more precise continuous latent motion from internet-scale videos. CoMo employs an early temporal difference (Td) mechanism to increase the shortcut learning difficulty and explicitly enhance motion cues. Additionally, to ensure latent motion better captures meaningful foregrounds, we further propose a temporal contrastive learning (Tcl) scheme. Specifically, positive pairs are constructed with a small future frame temporal offset, while negative pairs are formed by directly reversing the temporal direction. The proposed Td and Tcl work synergistically and effectively ensure that the latent motion focuses better on the foreground and reinforces motion cues. Critically, CoMo exhibits strong zeroshot generalization, enabling it to generate effective pseudo action labels for unseen videos. Extensive simulated and real-world experiments show that policies co-trained with CoMo pseudo action labels achieve superior performance with both diffusion and auto-regressive architectures.

21.
arXiv (CS.CV) 2026-06-16

Faithful Action-unit Causal Reasoning for Counterfactually Faithful Emotion Explanations

Multimodal models can name the action units (AUs) behind a facial emotion, but their AU->emotion rationales are typically plausible rather than faithful: nothing forces the AUs a model invokes to be the AUs that actually drive its prediction. We cast AU->emotion reasoning as a counterfactual-consistency problem between the rationale, the label, and a structural AU->emotion causal graph G, and propose FACR, which grounds the reasoner in an independently induced, polarity-aware G and trains a counterfactual-faithfulness objective: a do-intervention on an AU that G marks causal for a class must move the prediction, while one it marks irrelevant must leave it unchanged. Faithfulness is thereby both trainable and measurable through a matching interventional metric, which we evaluate against a known causal structure, the PSPI pain-AU composition, as no existing affective-reasoning benchmark allows. We are explicit that this metric tests fidelity to the supplied structure rather than its rediscovery: it asks whether the trained reasoner invokes the AUs the structure marks causal, on held-out subjects and a second dataset. Under subject-independent evaluation on UNBC-PAIN, the objective raises the agreement between the invoked AUs and the PSPI composition from a no-objective baseline of 0.08 to 0.57, at a small detection cost; an unfaithfulness control attributes the gain to the objective. On a cross-dataset emotion transfer, the objective likewise raises fidelity to G on a seven-class task (0.50 to 0.84). Finally, we attach a language verbalizer and extend the audit to the generated text: biasing each action unit's emission by its latent activation makes the rationale faithful by construction, so that ablating an AU removes it from the explanation, a property that transfers to a second language-model backbone, whereas a freely generated rationale is unfaithful.

22.
arXiv (CS.LG) 2026-06-11

Bootstrapped Monitoring: Leveraging Transparent Reasoning to Oversee Stronger AI Agents

arXiv:2606.11998v1 Announce Type: new Abstract: Trusted monitoring is a cornerstone of AI control. However, as frontier models grow more capable, the increasing capabilities gap between trusted and untrusted models may render trusted models unreliable monitors. We introduce bootstrapped monitoring, a protocol that addresses this by inserting a stronger, intermediate untrusted model with transparent chain-of-thought reasoning into the oversight chain. The untrusted monitor ($U_m$) evaluates the agent's actions, while a weaker trusted model ($T$) oversees $U_m$'s reasoning to detect collusion. We evaluate bootstrapped monitoring on multi-turn software engineering tasks (BashArena) across multiple agents and monitors. Bootstrapped monitoring substantially improves catch rates over trusted-only monitoring, even when the untrusted monitor actively colludes with the agent, provided we have access to its raw chain-of-thought. Our results suggest that bootstrapped monitoring can extend the useful lifetime of trusted models in control as AI capabilities advance.

23.
arXiv (CS.CV) 2026-06-19

GEN-Guard: Correcting Generalization Failures for Deployable Federated Surgical AI

Federated Learning (FL) in surgical video AI enables collaborative model training without sharing sensitive data. However, standard evaluation practices - selecting the "best" global model based only on validation data from participating hospitals - can lead to suboptimal deployment choices. We identify this critical failure mode as performance leakage, where the selected model overfits internal federation data and fails to generalize to unseen institutions. We propose GEN-Guard, a practical post-hoc framework to detect and correct generalization failures in federated surgical AI. It integrates Generalization Detection via Client-Blocked Evaluation (CBE), which validates performance on isolated client distributions to prevent performance leakage, and Generalization Correction through Disagreement-Aware Distillation (DAD), which learns adaptive feature-level corrections for cross-institutional robustness. Both components operate after standard FL convergence while providing robust support for zero-shot adaptation to unseen environments. We first quantify the severity of performance leakage, observing Model Selection Failures (MSFs) exceeding 80% under standard evaluation. GEN-Guard is evaluated on two multi-center clinical challenges: surgical phase recognition in laparoscopic cholecystectomy and polyp segmentation in colonoscopy. Across both datasets, GEN-Guard consistently corrects these failures, improving in-federation F1 scores by up to 2 points, unseen-institution performance by up to 3 points, and worst-case institutional performance by 3-9 points. Performance leakage represents a systematic and previously under-recognized risk in federated surgical AI. GEN-Guard provides a practical solution for detecting and correcting such failures. By improving cross-institutional robustness and zero-shot generalization, it strengthens the reliability of FL for real-world surgical deployment.

24.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

25.
arXiv (CS.AI) 2026-06-18

InfoPO: Information-Driven Policy Optimization for User-Centric Agents

arXiv:2603.00656v2 Announce Type: replace Abstract: Real-world user requests to LLM agents are often underspecified. Agents must interact to acquire missing information and make correct downstream decisions. However, current multi-turn GRPO-based methods often rely on trajectory-level reward computation, which leads to credit assignment problems and insufficient advantage signals within rollout groups. A feasible approach is to identify valuable interaction turns at a fine granularity to drive more targeted learning. To address this, we introduce InfoPO (Information-Driven Policy Optimization), which frames multi-turn interaction as a process of active uncertainty reduction and computes an information-gain reward that credits turns whose feedback measurably changes the agent's subsequent action distribution compared to a masked-feedback counterfactual. It then combines this signal with task outcomes via an adaptive variance-gated fusion to identify information importance while maintaining task-oriented goal direction. Across diverse tasks, including intent clarification, collaborative coding, and tool-augmented decision making, InfoPO consistently outperforms prompting and multi-turn RL baselines. It also demonstrates robustness under user simulator shifts and generalizes effectively to environment-interactive tasks. Overall, InfoPO provides a principled and scalable mechanism for optimizing complex agent-user collaboration. Code is available at https://github.com/kfq20/InfoPO.