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01.
arXiv (CS.CV) 2026-06-19

WeGenBench: A Multidimensional Diagnostic Benchmark towards Text-to-Image Model Optimization

Recent text-to-image generation models have demonstrated remarkable capabilities in synthesizing highly realistic images from text inputs alone. Although existing benchmarks can evaluate the generation capabilities of various models to some extent, they struggle to comprehensively and accurately measure performance across multiple dimensions, often failing to reveal the inherent deficiencies of models in specific categories. To address these limitations, we propose WeGenBench, a novel benchmark designed for the comprehensive, multi-perspective evaluation of text-to-image generation capabilities. Our benchmark comprises a total of 4,000 test prompts across two primary categories, meticulously balanced between Chinese and English to evaluate bilingual and cross-cultural generation capabilities. Beyond macroscopic scene classification, we annotate each prompt with multi-dimensional tags tailored to the distinct content and challenges of each language, thereby refining the generation tasks into more specific sub-categories. Through a cross-dimensional evaluation mechanism leveraging both scene classifications and multi-dimensional tags, WeGenBench can precisely pinpoint model shortcomings in specific generation categories. Furthermore, to measure generation quality more accurately, we design and validate several novel evaluation metrics by integrating Vision-Language Models (VLMs), which assess model performance on domain-specific tasks from three core aspects. Crucially, our approach yields both the assessment outcomes and the detailed reasoning trajectories, facilitating a rigorous verification of the accuracy and soundness of the evaluation results. Finally, we conduct systematic benchmarking on current state-of-the-art methods and provide an in-depth analysis of the limitations present in existing models.

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

When Does Trajectory-Level Supervision Permit Efficient Offline Reinforcement Learning?

arXiv:2606.18531v1 Announce Type: cross Abstract: Offline reinforcement learning is typically analyzed under process-level reward supervision, yet many sequential decision datasets record only trajectory-level outcomes. We develop a statistical theory for offline policy optimization from such outcome-level supervision. We first study the canonical setting where the target remains the expected cumulative reward, but each offline trajectory provides only a scalar label whose conditional mean is the cumulative return. We propose OPAC, a pessimistic actor-critic algorithm that learns a latent reward model and optimizes a policy from trajectory-level labels. We prove a high-probability guarantee of order $\widetilde O(H^2\sqrt{C_{sa}(\pi^\star)/n})$ and a matching lower bound, characterizing the sharp statistical cost of replacing process-level rewards with one trajectory-level label. We then extend the principle to preference-based feedback, preserving the leading horizon and concentrability dependence up to preference-model constants. Finally, we study generalized outcome-based offline RL, where both the supervision and the objective are trajectory-level quantities induced by a nonlinear aggregation of latent per-step rewards. This problem is not learnable in general: for all-success objectives, any offline learner may require $\Omega(2^H)$ trajectories even with deterministic transitions and constant concentrability. We then identify a tractable regime through two structural coefficients, $\kappa_\mu(\sigma)$ and $\chi_\mu(\sigma)$, capturing information loss in outcome aggregation and generalized Bellman updates, under which generalized OPAC achieves polynomial sample complexity. Together, our results delineate when outcome-level supervision enables sample-efficient offline control and when missing process-level rewards create fundamental statistical barriers.

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

Mordal: Automated Pretrained Model Selection for Vision Language Models

Incorporating multiple modalities into large language models (LLMs) is a powerful way to enhance their understanding of non-textual data, enabling them to perform multimodal tasks. Vision language models (VLMs) form the fastest growing category of multimodal models because of their many practical use cases, including in healthcare, robotics, and accessibility. Unfortunately, even though different VLMs in the literature demonstrate impressive visual capabilities in different benchmarks, they are handcrafted by human experts; there is no automated framework to create task-specific multimodal models. We introduce Mordal, an automated multimodal model search framework that efficiently finds the best VLM for a user-defined task without manual intervention. Mordal achieves this both by reducing the number of candidates to consider during the search process and by minimizing the time required to evaluate each remaining candidate. Our evaluation shows that Mordal can find the best VLM for a given problem using $8.9\times$–$11.6\times$ lower GPU hours than grid search. We have also discovered that Mordal achieves about 69\% higher weighted Kendall's $\tau$ on average than the state-of-the-art model selection method across diverse tasks.

04.
medRxiv (Medicine) 2026-06-15

Supporting people to access social security payments through the Special Rules for End of Life: a qualitative study of the perspectives of patients, carers and health care professionals

Background: People living with terminal illness face a double financial burden from additional costs and loss of earning for themselves and their carers. Social security benefits are intended to help alleviate some of this financial pressure, and in the UK and other countries people are eligible for fast-tracked access to financial support via the Special Rules for End of Life. One in 3 people who are eligible miss out on this support, yet there is limited evidence on the reasons for this take-up deficit. Objectives: The aim of this study is to understand the barriers and facilitators to claiming benefits for terminally ill people from the perspectives of patients, carers, and health care professionals. Methods: This is a qualitative study combining i) focus groups with healthcare professionals recruited via professional networks and social media, and ii) interviews with patients and carers recruited in hospital and hospice settings. We analysed the data using Practical Thematic Analysis Results: Fifty-five multidisciplinary healthcare professionals participated in 11 focus groups, and we interviewed 10 patients and carers. We constructed five descriptive themes to summarise the data: Navigating priorities and uncertainty; positive impacts alongside a sense of shame and stigma; talking about money, difficulties and dividends; everybodys, yet nobodys, responsibility; and sticking points in the system. Conclusion: The themes reveal several challenges that may contribute to people not taking up this financial support. However, discussions about access to benefits were also seen as a core part of holistic care, a positive way to offer support and a gateway to other discussions about end-of-life care preferences and decisions. Recommendations for policy and practice include evaluating the adoption of a diagnostic rather than a prognostic eligibility criteria, integrating discussions about benefits into existing processes such as advance care planning, and improving education and support for clinicians.

05.
arXiv (CS.LG) 2026-06-15

Time Series Causal Discovery via Context-Conditioned and Causality-Augmented Pretraining

arXiv:2605.26759v2 Announce Type: replace Abstract: Causal discovery from time series is critical for many real-world applications, such as tracing the root causes of anomalies. Existing approaches typically rely on dataset-specific optimization, making it difficult to transfer their causal discovery capabilities to new time series governed by diverse causal mechanisms. In this paper, we propose PTCD, a novel Pretraining framework for Time-series Causal Discovery, which improves cross-task generalization through context-conditioned modeling and transferable causal augmentation. To model complex temporal causal dependencies, PTCD employs a dual-scale iterative attention mechanism to capture window-level causal relationships, and a Gaussian mixture with a context-level routing mechanism to handle heterogeneous exogenous distributions. To further address distribution shifts across causal graphs, PTCD adopts a pretraining paradigm on synthetic datasets that integrates intervention-based learning and a causal mixup strategy, promoting stable causal discovery and stronger generalization. Extensive experiments on multiple real-world out-of-distribution (OOD) datasets demonstrate that PTCD excels in both causal discovery and root cause identification.

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

Not What, But How: A Framework for Auditing LLM Responses across Positioning, Generalization, Anthropomorphism, and Maxims

Large language models (LLMs) are being increasingly used to answer subjective, information-seeking questions, where users are sensitive to how responses are communicated, not just whether the answers are correct. Existing LLM evaluations for subjective cultural queries largely focus on factual correctness, ignoring how the response is framed. To this end, we introduce FRANZ, an automated FRAmework for respoNse characteriZation to conduct communicative audit of LLM responses along four dimensions: cultural positioning, use of generalizing language, anthropomorphic cues, and adherence to conversational maxims. To enable this evaluation, we contribute SQUARE - a corpus of 376k subjective questions sourced from 57 subreddits, and mapped to 7 countries and 19 question categories. We demonstrate FRANZ's applicability by scoring responses from three open-weight LLMs. We observe that LLMs show statistically significant differences in the frequency with which they employ each response characteristic. Unlike single-dimensional audits, FRANZ reveals that insider positioning and anthropomorphism are positively coupled, with the degree of coupling varying by country, providing a diagnostic lens for identifying framing divergences.

07.
arXiv (CS.CL) 2026-06-16

Evaluating the Robustness of Proof Autoformalization in Lean 4

Proof autoformalization aims to translate a mathematical informal proof written in natural language into a formal proof in a formal language such as Lean~4. Several works have developed LLM-based models for proof autoformalization. However, existing evaluations have typically focused on translating well-formed informal proofs from curated datasets. We argue that a robust proof autoformalizer must remain faithful even for informal proofs that diverge from these idealized ones, and we present the first study on the robustness of proof autoformalization models. We formulate two categories of perturbations and evaluate robustness under each: a global perturbation paraphrases the informal proof in a different style, under which the formalization should remain consistent; a local perturbation alters a value, symbol, or proof step, possibly in a counterfactual way, and a robust formalization should faithfully reflect the perturbation rather than reverting to the original one or inferring a different one on its own. We build a benchmark with both perturbations on miniF2F and MATH-500, and automatically measure how stable a proof autoformalization's correctness is under global perturbations and how faithfully its output reflects local perturbations. We evaluate seven recent models, all of which are sensitive to global perturbations and mostly fail to remain faithful under local perturbations. Code and data are available via https://github.com/ucr-rai/robust-proof-autoformalization.

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

TUNI: Unifying Pre-training and Fine-tuning with Modality-Aware Mutual Learning and Rectification for RGB-T Semantic Segmentation

RGB-thermal (RGB-T) semantic segmentation improves the environmental perception of autonomous platforms in challenging conditions. Prevailing RGB-T segmentation frameworks suffer from suboptimal multi-modal feature extraction and fusion, unbalanced modality dependency, and inadequate utilization of thermal information. To address these challenges, we propose TUNI, a unified pre-training and fine-tuning framework for efficient and real-time RGB-T semantic segmentation. It pre-trains an RGB-T encoder that incorporates an RGB-T local module that selectively emphasizes salient consistent and distinct local features across modalities, thereby integrating cross-modal feature extraction and fusion in a unified manner. To alleviate the modality bias issue during RGB-T pre-training, modality-inverted contrastive mutual learning is introduced to enable knowledge exchange between two RGB-dominated and thermal-dominated encoders. In the fine-tuning phase, modality rectification learning fully exploits residual thermal information by focusing on correct yet divergent prediction regions between two modality-specific decoders. We further develop three TUNI variants, covering lightweight, balanced, and high-performance requirements. Extensive experiments on five RGB-T semantic segmentation datasets demonstrate that TUNI achieves superior accuracy, generalization, and compactness compared with 15 state-of-the-art models. The code is available at https://github.com/xiaodonguo/TUNI-v2.

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

Learning in the Recurrent State: Gradient Descent with Linear Recurrent Networks

arXiv:2410.11687v3 Announce Type: replace-cross Abstract: Linear recurrent networks (LRNNs) offer linear-time sequence modeling, but standard recurrent updates do not directly expose the supervised products needed for in-context gradient descent. We propose a sufficient constructive inductive bias for LRNNs: equip a diagonal recurrent state with multiplicative readout and a short sliding-window cross-product self-attention update. The resulting architecture, Gradient-based Recurrent In-context Learner (GRIL), can implement minibatch gradient descent on a task-specific linear predictor during a single forward pass. The same design extends to multi-step updates and cross-entropy classification, with a limited MLP-based extension to non-linear regression. Empirically, trained GRILs recover the behavior and parameters predicted by the construction on synthetic ICL tasks, and the same architectural bias yields useful performance on Long Range Arena and language modelling. These results present windowed cross-product self-attention as a practical, testable inductive bias for LRNNs that learn in context through gradient-descent-like updates.

10.
arXiv (CS.AI) 2026-06-16

Orcheo: A Modular Full-Stack Platform for Conversational Search

arXiv:2602.14710v2 Announce Type: replace-cross Abstract: Conversational search (CS) requires a complex software engineering pipeline that integrates query reformulation, ranking, and response generation. CS researchers currently face two barriers: the lack of a unified framework for efficiently sharing contributions with the community, and the difficulty of deploying end-to-end prototypes needed for user evaluation. We introduce Orcheo, an open-source platform designed to bridge this gap. Orcheo offers three key advantages: (i) A modular architecture promotes component reuse through single-file node modules, facilitating sharing and reproducibility in CS research; (ii) Production-ready infrastructure bridges the prototype-to-system gap via dual execution modes, secure credential management, and execution telemetry, with built-in AI coding support that lowers the learning curve; (iii) Starter-kit assets include 45+ off-the-shelf components for query understanding, ranking, and response generation, enabling the rapid bootstrapping of complete CS pipelines. We describe the framework architecture and validate Orcheo's utility through case studies that highlight modularity and ease of use. Orcheo is released as open source under the MIT License at https://github.com/AI-Colleagues/orcheo.

11.
arXiv (quant-ph) 2026-06-15

Link-Free Multi-Node Timing Synchronization for Scalable Quantum Networking

arXiv:2606.14077v1 Announce Type: new Abstract: Precise timing synchronization is essential for distributed quantum networking, enabling entanglement distribution, quantum teleportation, and entanglement swapping across remote nodes. Existing synchronization architectures rely on dedicated timing-distribution infrastructure, most notably White Rabbit networks, which constrain topology, scalability, and deployment in free-space and satellite environments. Here we demonstrate link-free synchronization of quantum network nodes using independently operating miniature rubidium atomic clocks and computational post-processing. We validate the approach on a deployed metropolitan-scale telecom fiber network spanning three geographically separated nodes. Following drift correction, atomic-clock-based synchronization achieves timing performance approaching that of a White Rabbit benchmark and remains stable over continuous 8-hour operation. As a stringent test of quantum-network functionality, we observe Hong-Ou-Mandel interference across spatially separated nodes with visibility exceeding 70%, statistically equivalent to that obtained using dedicated White Rabbit timing links. To the best of our knowledge, this represents the first observation of quantum interference across a deployed metropolitan-scale telecom fiber network synchronized entirely without dedicated timing-transfer infrastructure. These results establish atomic-clock-based synchronization as a scalable, topology-independent alternative to conventional timing-distribution architectures and a practical pathway toward terrestrial, airborne, and space-based quantum networks where dedicated timing links are unavailable.

12.
arXiv (CS.AI) 2026-06-11

When Researchers Say Mental Model/Theory of Mind of AI, What Are They Really Talking About?

arXiv:2510.02660v2 Announce Type: replace-cross Abstract: When researchers claim AI systems possess ToM or mental models, they are fundamentally discussing behavioral predictions and bias corrections rather than genuine mental states. This position paper argues that the current discourse conflates sophisticated pattern matching with authentic cognition, missing a crucial distinction between simulation and experience. While recent studies show LLMs achieving human-level performance on ToM laboratory tasks, these results are based only on behavioral mimicry. More importantly, the entire testing paradigm may be flawed in applying individual human cognitive tests to AI systems, but assessing human cognition directly in the moment of human-AI interaction. I suggest shifting focus toward mutual ToM frameworks that acknowledge the simultaneous contributions of human cognition and AI algorithms, emphasizing the interaction dynamics, instead of testing AI in isolation.

13.
bioRxiv (Bioinfo) 2026-06-16

Accelerating String Comparison in RLZ Compressed Sequences via LCE Jumps

Relative Lempel-Ziv (RLZ) is an effective compression method for large, repetitive collections; however, the fundamental primitives required to elevate it from a passive archival format to a tractable representation for compressed construction have yet to be fully established. In this paper, we introduce an algorithmic framework for structurally comparing and lexicographically sorting sequences of RLZ factors. We characterize when direct factor comparisons are necessary and when they can be bypassed using RLZ specific shortcuts. We further introduce a method for extending truncated factors into right-maximal matches, enabling the recovery of matching statistics from the RLZ parse. Experimentally, RLZ sorting achieved speedups of up to 3.93x over character-based sorting. Together, these results advance the use of the RLZ format as a foundation for compressed construction.

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

Improved Knowledge Distillation for Land-Use Image Classification

In the present article, an improved Knowledge Distillation (KD) framework has been proposed for efficient compression of deep convolutional neural networks for land-use image classification task. Motivated by the need to achieve competitive classification accuracy while reducing computational complexity, a teacher-student learning paradigm is adopted in which a VGG16 network transfers knowledge to a lightweight MobileNetV2 model. The proposed framework integrates hard supervision from ground truth labels with a soft supervision strategy that combines Kullback-Leibler divergence and Cosine Similarity losses. Experiments conducted on three land-use datasets show that the proposed KD-based method yields improved performance, and achieves an accuracy of 99.04%, outperforming both baseline student training and single-loss distillation approaches, while retaining substantial model compression.

15.
Nature (Science) 2026-06-17

A prototype differential atom interferometer for fundamental physics

Gravitational waves and ultralight dark matter are among the most compelling frontiers in fundamental physics, motivating proposals for very-long-baseline atom interferometerssuch as AION1, MAGIS2, AICE3 and AEDGE4 that aim to detect at frequencies at which ground-based5 and space-borne6 laser interferometers lose sensitivity. Very-long-baseline atom interferometers look for signals by comparing the quantum phase evolution of widely separated atomic ensembles interrogated by a common laser. However, their performance depends critically on suppressing noise sources, particularly laser phase noise. The experimental validation of such noise rejection remains an important challenge. Here we demonstrate a prototype differential atom interferometer based on the single-photon clock transition of fermionic 87Sr. Thus, we obtain a gradiometer configuration with a species intrinsically suited to kilometre-scale and space-baseline operation. The instrument operates at the standard quantum limit7 with no excess noise beyond atom shot noise. The differential configuration maintains quantum-limited sensitivity in the presence of several radians of artificially injected laser phase noise per shot, which emulates the conditions expected in a very-long-baseline atom interferometer. We also demonstrate the recovery of coherent oscillatory signals across a broad frequency range under fully phase-randomized conditions, a capability that is inaccessible to a single interferometer operating in the same regime. These results provide an experimental validation of the noise-immune measurement principle underlying very-long-baseline atom interferometers and mark an important step towards next-generation quantum sensors for gravitational-wave detection and searches for ultralight dark matter8,9. A prototype differential atom interferometer operates at the standard quantum limit with no excess noise beyond atom shot noise, achieving performance in line with the specifications for future long-baseline atom interferometers.

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

A Perception vs. Distortion Perspective on Score-Based Generative Channel Estimation

arXiv:2606.16815v1 Announce Type: cross Abstract: Driven by their remarkable success in computer vision and inverse problem solving, score-based models are increasingly applied to wireless communications, where they show promise across a range of physical-layer tasks. However, despite this growing interest, the current literature often lacks a rigorous analysis of when score-matching offers a tangible advantage over traditional discriminative learning. This paper aims to address this gap through the use-case of channel estimation, a fundamental inverse problem in wireless systems. We present a theoretically grounded interpretation of score-based channel estimation through the lens of the perception-distortion tradeoff, identifying the conditions where score matching excels as well as its key limitations. In particular, by modeling downstream wireless tasks (e.g., capacity maximization) as functionals of the channel estimation process, we quantify the excess risk incurred by standard distortion-minimization approaches. Extensive numerical results show that under high predictive uncertainty, the large excess risk gap can be offset by score-based estimation, enabling near Bayesian-optimal precoding via the learned posterior, whereas in the low predictive uncertainty regime, discriminative distortion-minimization approaches are preferable due to lower complexity and more efficient use of model capacity.

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

Toward Calibrated Mixture-of-Experts Under Distribution Shift

arXiv:2606.20544v1 Announce Type: new Abstract: Calibration aligns a model's predictive uncertainty with the frequencies of its empirical outcomes and is important for understanding and trusting reported probabilities. Recent work shows that enforcing calibration at the level of individual predictors can improve ensemble accuracy and calibration, with mixture-of-experts (MoE) models showing strong empirical improvements in particular; however, the conditions under which calibration helps MoE are not well understood. In this work, we study how MoE models behave under distribution shift, focusing on how routing mechanisms interact with expert-level calibration. We show that expert calibration is sufficient to ensure calibration of the overall model under a broad class of distribution shifts in hard-routed models, but is insufficient for calibrating soft-routed models. To address this, we propose an adversarial reweighting that penalizes calibration errors of the routed aggregate under distribution shift, and we demonstrate that it improves the accuracy-calibration tradeoff both on average and on difficult subsets of the data, across model classes, prediction tasks, and distribution shifts.

18.
arXiv (quant-ph) 2026-06-19

Unveiling coherent dynamics in non-Markovian open quantum systems: exact expression and recursive perturbation expansion

arXiv:2506.04097v2 Announce Type: replace Abstract: We introduce a systematic framework to derive the effective Hamiltonian governing the coherent dynamics of non-Markovian open quantum systems. By applying the minimal dissipation principle, we uniquely isolate the coherent contribution to the time-local generator of the reduced dynamics. We derive a general expression for the effective Hamiltonian and develop a recursive perturbative expansion that expresses it in terms of system-bath interaction terms and bath correlation functions. This expansion provides a systematic tool for analyzing energy renormalization effects across different coupling regimes. Applying our framework to paradigmatic spin systems, we reveal how environmental correlations influence energy shifts and eigenbasis rotations, offering new insights into strong-coupling effects and non-Markovian quantum thermodynamics.

19.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

20.
Nature (Science) 2026-06-17

Towards autonomous medical artificial intelligence agents

Authors:

Large language models (LLMs) show great potential for clinical decision-making, yet most applications remain narrow, task-specific chat tools rather than systems integrated into clinical workflows1,2. However, building physician copilots will require models that operate within the electronic health record (EHR), with governed access to patient data and the ability to initiate permitted EHR actions within defined safety constraints. Yet it remains unproven whether such a system can manage patient cases with physician-level performance. Here we show that MIRA (Medical Intelligence for Reasoning and Action), an autonomous artificial intelligence agent operating in a sandboxed EHR environment, can navigate a large clinical action space to obtain patient histories; order and interpret laboratory, imaging and microbiology tests; generate differential diagnoses; and formulate treatment plans such as prescribing medications, scheduling surgical procedures and planning admissions. In simulations on real patient cases spanning multiple diagnoses, MIRA outperformed physicians in diagnostic accuracy and made guideline-concordant, medication-safe and appropriate admission decisions. Compared with previous LLM applications that addressed isolated subtasks or provided free-text advice, these results suggest that an EHR-integrated artificial intelligence agent can turn clinical intent into structured, actionable EHR operations, possibly making it a more effective decision-support partner for physicians. Further work is needed to establish generalization, safety and governance through prospective, real-world studies. A large language model artificial intelligence agent operating in a sandboxed electronic health record system can autonomously&nbsp;take patient histories, order tests, interpret findings, diagnose conditions and propose treatments, outperforming experienced clinicians while adhering to safety standards and clinical guidelines.

21.
bioRxiv (Bioinfo) 2026-06-20

Evaluation of Trypanosoma brucei Phosphofructokinase Allosteric Inhibition: An In-Silico Study

Human African trypanosomiasis, caused by a protozoan parasite Trypanosoma brucei, is a neglected tropical disease for which well-tolerated, conveniently administered, and highly efficacious medicines are still missing. Previously, T. brucei Phosphofructokinase was targeted by small-molecule inhibitor development efforts. This approach has shown promise both in vitro and in vivo. In this study, we have used these wet-lab results, evaluated the compounds already characterised by Molecular Dynamics simulations, found relationships between in silico and wet-lab data and used these observations to evaluate compounds that we selected through several different approaches of virtual screens. We observed that inhibitor-ATP interactions are highly predictive of the inhibitory activity. Several compounds selected through virtual screens have outperformed previously characterised compounds.

22.
medRxiv (Medicine) 2026-06-23

Post Hoc Localization of Beam F3 Stimulation Targets: An MRI-Derived Geodesic Approach for Refined TMS E-Field Simulations

Background: Transcranial magnetic stimulation (TMS) targeting the left dorsolateral prefrontal cortex (dlPFC) is an established treatment option in major depressive disorder. One of the most common approaches for targeting the dlPFC is the Beam F3 method, which determines the stimulation site (F3Beam) as a function of external cranial measurements. Precise knowledge of the individual stimulation site is essential for imaging-based analyses of TMS effects. However, due to the method's reliance on individual anatomy, retrospective identification of F3Beam targets across cohorts is challenging, limiting the analysis of existing datasets. We developed a scalable method to reconstruct subject-specific F3Beam target locations for e-field simulations based on structural imaging. Methods: High-resolution three-dimensional (3D) T1-weighted MRI was used to generate individual scalp meshes via the ''Simulation of Non-Invasive Brain Stimulation'' (SimNIBS) software. Subject-specific anatomical distances and coordinates of interest were measured geodesically using a Python-based script to reconstruct the individual F3Beam targets. Validation included a retrospective comparison between digital geodesic measurements and manual cranial measurements in 20 patients and a prospective comparison with MR-visible scalp markers in 2 healthy controls. To assess the impact of our targeting algorithm on e-field simulations, volumetric e-field maps based on three potential targets (F3Beam, F3MNI, F3Geo) were generated in SimNIBS and compared using voxel-wise statistics in SPM12. Results: Retrospective analysis revealed a systematic bias towards higher in vivo measurements compared to digital geodesic measurements, though deviations in the final distances determining F3Beam (xBeam and yBeam) were minimal ({Delta}xBeam: 0.11 {+/-} 0.08 cm; {Delta}yBeam: 0.14 {+/-} 0.21 cm). Prospective validation demonstrated that F3Beam coordinates better matched in vivo coil positions than group-template-derived targets (F3MNI). Group-level analysis showed method-dependent clustering of coil positions with corresponding voxel-wise e-field differences. Conclusions: Individualized geodesic measurements may enable accurate, scalable and retrospective identification of Beam F3 targets and coil orientations. This approach may yield more accurate e-field simulations than group-template based targeting and provides a practical method for retrospective analysis of existing TMS treatment cohorts. This could be leveraged to identify response predictors or imaging-based biomarkers of treatment response.

23.
arXiv (CS.CL) 2026-06-11

Verifiable Environments Are LEGO Bricks: Recursive Composition for Reasoning Generalization

Reinforcement Learning (RL) with verifiable environments has emerged as a powerful approach for enhancing the reasoning capabilities of Large Language Models (LLMs). While prior research demonstrates that scaling environment quantity improves RL performance, existing manual or individual construction methods suffer from linear scaling limits, thereby hindering scalable reasoning generalization. This paper introduces RACES (Recursive Automated Composition for Environment Scaling), a framework that conceptualizes verifiable environments as composable building blocks that can be recursively assembled. The key insight is that when the codomain (output type) of one environment matches the domain (input type) of another, they can be automatically fused into a new verifiable environment, enabling recursive composition. RACES is implemented with 300 individual environments and defines a set of composition operators (\textsc{SEQUENTIAL}, \textsc{PARALLEL}, \textsc{SORT}, and \textsc{SELECT}) that induce diverse reasoning patterns. Extensive experiments show that RL training on these composite environments consistently enhances reasoning generalization. Specifically, RACES improves DeepSeek-R1-Distill-Qwen-14B by an average of 3.1 points (from 48.2 to 51.3) and boosts Qwen3-14B performance from 58.8 to 61.1 on six benchmarks, which are unseen during the construction of training environments. Moreover, RACES achieves performance comparable to training on 300 individual environments using only 50 base environments, demonstrating significant efficiency in environment utilization.

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

Dual Cross-Attention Siamese Transformer for Rectal Tumor Regrowth Assessment in Watch-and-Wait Endoscopy

Increasing evidence supports watch-and-wait (WW) surveillance for patients with rectal cancer who show clinical complete response (cCR) at restaging following total neoadjuvant treatment (TNT). However, accurate methods to early detect local regrowth (LR) from follow-up endoscopy images during WW are essential to manage care and prevent distant metastases. Hence, we developed a Siamese Swin Transformer with Dual Cross-Attention (SSDCA) to combine longitudinal endoscopic images at restaging and follow-up and distinguish cCR from LR. SSDCA leverages pretrained Swin Transformers to extract domain agnostic features and enhance robustness to imaging variations. Dual cross attention is implemented to emphasize features from the paired scans without requiring any spatial alignment to predict response. SSDCA as well as Swin-based baselines were trained using image pairs from 135 patients and evaluated on a held-out set of image pairs from 62 patients. SSDCA produced the best balanced accuracy (81.76% $\pm$ 0.04), sensitivity (90.07% $\pm$ 0.08), and specificity (72.86% $\pm$ 0.05). Robustness analysis showed stable performance irrespective of artifacts including blood, stool, telangiectasia, and poor image quality. UMAP clustering of extracted features showed maximal inter-cluster separation (1.45 $\pm$ 0.18) and minimal intra-cluster dispersion (1.07 $\pm$ 0.19) with SSDCA, confirming discriminative representation learning. Code and weights available at: https://github.com/Jotanator/SSDCA

25.
arXiv (CS.CL) 2026-06-16

Why Tree-Style Branching Matters for Thought Advantage Estimation in GRPO

Group Relative Policy Optimization (GRPO) trains Chain-of-Thought reasoning with verifiable rewards, but estimating thought-level advantages without value functions often suffers from high variance. Although tree-style branching is used in practice to reduce variance, it lacks a theoretical explanation of why it works and whether it is important or potentially necessary. We study thought-level advantage estimation in GRPO from a variance perspective under a minimal tree-style setting where multiple continuations are sampled for each thought. Using the multivariate delta method, we reveal a sampling-dimension asymmetry. Increasing sampled thoughts ($K$) leaves a strictly positive estimation-variance floor, whereas increasing continuations per thought ($M$) drives the leading-order estimation variance to zero at rate $1/M$. This implies that, within the fixed-temperature GRPO-style estimator without value models studied here, accurate thought-level advantage estimation cannot be achieved by scaling thought sampling alone, making continuation-level branching a principled and potentially necessary mechanism rather than a heuristic. Experiments further provide empirical evidence for its effectiveness and potential necessity, demonstrating improved optimization stability, training efficiency, and final performance not only in math but also across vision domains and under different model architectures and sizes.