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01.
medRxiv (Medicine) 2026-06-19

Extraction of Glaucoma Diagnosis, Type, and Severity from Clinical Notes using Secure Cloud-based Large Language Models

Purpose: To evaluate the performance of secure cloud-based large language models (LLMs) in extracting glaucoma diagnosis, type, and severity from free-text clinical notes in the electronic health record (EHR). Design: Retrospective chart review analysis. Participants: 1,250 subjects from the Bascom Palmer Ophthalmic Repository. Methods: Clinical notes of glaucoma-related encounters between 2014 and 2024 were extracted from the Bascom Palmer Ophthalmic Repository. Two fellowship-trained glaucoma specialists annotated clinical notes for glaucoma presence, type, and severity at the eye level. The dataset was split into development (10%), validation (10%), and test (80%) sets. Development and validation sets were used for prompt engineering and refinement, and the held-out test set was used for evaluation. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT-5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Azure AI Foundry within HIPAA-compliant containers. Model performance was assessed using standard metrics. Clinician-entered ICD-10 codes were also compared with adjudicated labels. Main Outcome Measures: Gwet AC1, accuracy, sensitivity, specificity, and F1-score. Results: Inter-grader agreement was high for glaucoma detection (Gwet AC1= 0.930 (95% CI: 0.917-0.945), type classification (Gwet AC1= 0.917 (95% CI: 0.904-0.930), and severity staging (Gwet AC1= 0.901 (95% CI: 0.884-0.916). For glaucoma diagnosis, LLMs demonstrated high overall accuracy, with Claude achieving 97.5%, DeepSeek 96.0%, GPT 96.2%, Grok 94.4%, and Qwen 95.5%. F1 scores for glaucoma detection ranged from 95.4% to 98.9% across models. For glaucoma type classification, accuracies were 97.1%, 94.2%, 94.2%, 94.0%, and 94.4% for Claude, DeepSeek, GPT, Grok, and Qwen, respectively. F1 scores for the most prevalent type (POAG) ranged from 96.3% to 98.9%. For severity staging, accuracies were 95.0%, 94.8%, 94.5%, 94.0%, and 95.2%, respectively, with F1 scores ranging from 89.7% to 96.3% across severity categories and models. ICD-10 codes demonstrated substantially lower performance for type and severity staging, with overall accuracies of 89.2% and 58.5%, respectively. Conclusions: Secure cloud-based LLMs accurately extracted glaucoma diagnosis, type, and severity information from free-text ophthalmology notes, achieving performance approaching expert clinician adjudication while substantially outperforming ICD-based phenotyping approaches, particularly for disease severity classification. These findings demonstrate the potential of LLMs to transform unstructured clinical documentation into scalable, research-ready phenotypic data for large-scale glaucoma cohort development and EHR-based ophthalmic research.

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

Stitching and dimensionality effects on large artificially generated volume datasets

Generating large images via deep learning requires patching input data to accommodate hardware memory limitations, then assembling output patches, a process that can introduce stitching artifacts when neighboring patches do not align at borders. While these artifacts are known to affect segmentation tasks, their impact on generative models for style-transfer remains poorly understood. We investigated three stitching approaches and two patch dimensionalities (2D vs 3D) using cycleGAN models trained on cryo-electron microscopy datasets. We evaluated both perceptual quality and performance on downstream mitochondria segmentation. Our key findings reveal that: (1) FID scores fail to detect subtle stitching artifacts that significantly impact downstream segmentation performance, (2) 3D models with artifact-free stitching marginally outperform 2D models on downstream tasks, though the improvement barely justifies the computational cost, and (3) 2D models train more stably due to larger batch sizes. Additionally, we demonstrate that ensembling predictions from three orthogonal directions can improve low-quality volumes but provides no benefit for high-quality outputs. These results demonstrate that maximizing generative model performance on large scientific datasets requires careful consideration and mitigation of stitching artifacts, and that perceptual metrics alone are insufficient for evaluating domain adaptation quality in biomedical imaging.

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

PhaseWin: An Efficient Search Algorithm for Faithful Visual Attribution

Visual attribution is a fundamental tool for interpreting modern vision and vision-language models, particularly when their decisions must be inspected, diagnosed, or audited. Its goal is to explain how a model's decision depends on local regions of the visual input, typically by assigning an importance ordering over candidate image regions. Given an image partitioned into $n$ regions, faithful attribution can be cast as an ordered subset-search problem, in which progressively inserting the selected regions should recover the target model response as early as possible. Exhaustive search over region subsets incurs exponential cost, while the widely used greedy search still requires a quadratic number of model evaluations, because every selection step rescores all remaining candidates. We propose PhaseWin, an efficient subset-search algorithm for faithful visual attribution. PhaseWin reorganizes greedy region selection into a phased window-search procedure: rather than re-evaluating the full candidate set at every step, it alternates between global candidate screening, adaptive pruning, and localized window refinement, while preserving the essential region-ranking behavior of greedy search. We analyze PhaseWin under monotone evidence-accumulation conditions and show that, under feature-level structural assumptions, it attains controllable linear evaluation complexity together with near-greedy faithfulness guarantees. Extensive experiments on image classification, object detection, visual grounding, and image captioning show that, among all compared attribution methods, PhaseWin reaches high faithfulness with the fewest forward passes, empirically realizing the predicted reduction from $O(n^2)$ to $O(n)$. The code is available at https://github.com/Qihuai27/phasewin-va.

04.
arXiv (CS.CL) 2026-06-17

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

05.
arXiv (CS.AI) 2026-06-19

Conditional Diffusion Guidance under Hard Constraint: A Stochastic Analysis Approach

arXiv:2602.05533v3 Announce Type: replace Abstract: We study conditional generation in diffusion models under hard constraints, where generated samples must satisfy prescribed events with probability one. Such constraints arise naturally in safety-critical applications and in rare-event simulation, where soft or reward-based guidance methods offer no guarantee of constraint satisfaction. Building on a probabilistic interpretation of diffusion models, we develop a principled conditional diffusion guidance framework based on Doob's h-transform, martingale representation and quadratic variation process. Specifically, the resulting guided dynamics augment a pretrained diffusion with an explicit drift correction involving the logarithmic gradient of a conditioning function, without modifying the pretrained score network. Leveraging martingale and quadratic-variation identities, we propose two novel off-policy learning algorithms based on a martingale loss and a martingale-covariation loss to estimate h and its gradient using only trajectories from the pretrained model. We provide non-asymptotic guarantees for the resulting conditional sampler in both total variation and Wasserstein distances, explicitly characterizing the impact of score approximation and guidance estimation errors. Numerical experiments demonstrate the effectiveness of the proposed methods in enforcing hard constraints and generating rare-event samples. The code of the numerical experiments can be found at https://github.com/ZhengyiGuo2002/CDG_Finance.

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

Rethinking the Role of Efficient Attention in Hybrid Architectures

Modern language models increasingly adopt hybrid architectures that combine full attention with efficient attention modules, such as sliding-window attention (SWA) and recurrent sequence mixers. However, how these efficient modules shape model capabilities remains poorly understood. To address this gap, we conduct a systematic analysis across hybrid architectures from three perspectives: scaling behavior, mechanism analysis, and architecture design. First, from a scaling perspective, we find that efficient-attention design primarily affects how fast long-context capability emerges, while different hybrids eventually converge to comparable long-context performance under sufficient training. Second, mechanistically, we show that long-range retrieval is mainly carried by full attention, whereas efficient attention shapes its optimization trajectory. This explains a counter-intuitive phenomenon we call Large-Window Laziness: larger SWA windows can delay the formation of retrieval heads in full-attention layers. Third, guided by this mechanism, we show that applying NoPE to only the full-attention layers of a small-window SWA hybrid substantially improves long-context performance with negligible impact on short-context performance.

07.
arXiv (CS.AI) 2026-06-11

The Impossibility of Eliciting Latent Knowledge

arXiv:2606.12268v1 Announce Type: new Abstract: Advanced AI systems have extensive knowledge of their environments; in fact, their knowledge may (far) exceed that of their developers or users. Consequently, a desirable property for an AI system is that it is honest – that it accurately reports its beliefs about the world. Designing an AI system to be honest may be difficult, especially if we want to ask it questions about latent variables in the environment – variables which are hidden from the human interacting with it. This gives rise to the problem of eliciting latent knowledge (ELK): the problem of training an AI agent to honestly report its beliefs. In this paper, we make ELK formally precise using Causal Influence Diagrams (CIDs). CIDs can be used to describe the relationship between an agent's training environment and its subjective representation of the world. We use CIDs to formalise the distinction between observable and latent variables, to specify what exactly it means for an agent to be honest, and to formally define goal misgeneralisation. We show that, under certain circumstances, developers can incentivise an agent to honestly answer questions by providing correct feedback during training. However, a natural, but undesirable, way for an agent to generalise is to provide answers which humans would evaluate as true, rather than honest answers. We prove an impossibility theorem stating: There is no feedback-based training strategy that depends only on agent behaviour and with certainty produces an honest agent, even if feedback is perfect during training.

08.
arXiv (math.PR) 2026-06-16

Super-Arrhenius relaxation of the triangular plaquette model in any dimension

arXiv:2606.16259v1 Announce Type: new Abstract: Consider the following plaquette model from statistical physics: a lamp lies at every vertex of the triangular lattice and a switch lies at every even vertex of the (bipartite) dual hexagonal lattice. Each switch toggles the three lamps on its face. The energy of a configuration is the number of ON lamps. For the Glauber dynamics associated with the Gibbs measure defined by this Hamiltonian at any inverse temperature $\beta>0$, we show that, in any dimension $d\ge 2$, the infinite volume relaxation time satisfies \[e^{\beta^2/C}/C \le T_{\mathrm{rel}}\le Ce^{e^{C\beta}}\] for some $C>0$. Our result entails that the Gibbs measure is unique. The $e^{\beta^2}$ scaling was conjectured by Newman and Moore in 1999 and matches the behaviour of supercritical rooted kinetically constrained models such as the East model, thus recovering fragile glass phenomenology in the absence of kinetic constraints. More precisely, we show that, on a torus of side length $2^k$, when $\beta\to\infty$ and $k/\beta\to0$, we have $T_{\mathrm{rel}}=e^{2\beta k(1+o(1))}$. Quite surprisingly, however, we also prove that, on non-periodic finite domains of size $n\le e^{\beta/C}$ for large $C>0$, we have the much larger asymptotics $\ln T_{\mathrm{rel}}=\beta n^{\Theta(1)}$. The main ingredients of the proofs are new results in extremal and enumerative combinatorics and rely on renormalisation ideas for the dynamics and its groundstates also known as the Ledrappier subshift. We note consequences of our results to geometric group theory (more precisely to the complexity of the word problem for the Baumslag finitely presented group) and to ergodic theory.

09.
arXiv (math.PR) 2026-06-16

Eyring-Kramers asymptotics for infinite-dimensional stochastic gradient systems

arXiv:2606.16083v1 Announce Type: new Abstract: We study small-noise asymptotics for a class of reversible stochastic evolution equations in infinite dimensions. The dynamics are of the form \[ dX_t=-A\nabla F(X_t)\,dt+\sqrt{2\beta^{-1}A}\,dW_t, \] where $F$ is a regular multi-well potential, $A$ is a selfadjoint mobility operator, $W$ is a cylindrical Brownian motion and $\beta\gg 1$ is the inverse noise strength. The invariant measure is a Gibbs perturbation of a Gaussian reference measure, and the resulting framework covers, in particular, the stochastic Allen-Cahn and stochastic Cahn-Hilliard equations on bounded intervals. In the double-well case, we derive a sharp asymptotic formula for the first nonzero eigenvalue of the generator. This gives an infinite-dimensional Eyring-Kramers law for the spectral gap, with exponential rate determined by the communication height and leading prefactor determined by the local quadratic behavior at the relevant minima and saddle points. Our approach provides a general strategy for lifting finite-dimensional Eyring-Kramers analysis to infinite-dimensional stochastic gradient systems.

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

Post-Hoc Merging is Not Enough: Many-Shot Model Merging with Loss-Gap Balancing

arXiv:2606.16501v1 Announce Type: new Abstract: Model merging has become a practical post-training strategy for building a single multi-task large language model (LLM) by combining multiple task-specialized models. However, most existing approaches rely on post-hoc merging, in which task-specific models are merged only once after training. This one-shot aggregation often suffers from task interference, leading to information erasure across individual tasks. In this work, we show that replacing post-hoc merging with an iterative many-shot merging protocol is effective in improving multi-task performance. Building on this insight, we propose METIS, Mitigating Erasure from Task Interference for Stable many-shot merging. METIS is a loss-aware many-shot merging method that addresses information erasure in post-hoc merging through task-wise loss-gap weighting and consensus-based masking. Notably, METIS exhibits significant performance improvement on the worst-performing task, effectively mitigating information erasure. (Project page: https://imkyungjin.github.io/METIS/)

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

GASE: Gaussian Splatting-Based Automated System for Reconstructing Embodied-Simulation Environments

Training embodied agents in the real world requires skilled operators and expensive hardware. Simulation environments offer a compelling alternative by enabling large-scale, cost-effective data augmentation. Consequently, rapidly constructing high-fidelity simulation scenes with a minimal sim-to-real gap has become a critical objective in robot learning. While reconstruction-based methods provide superior visual quality, current workflows are hindered by inefficient data acquisition and subpar foreground object extraction. We thus propose GASE, a highly automated system for simulation scene construction. GASE leverages multi-view video streams from panoramic camera arrays to enable rapid environment scanning. To ensure high-quality asset generation, our pipeline introduces a camera-pose-based strategy that robustly extracts objects across frames in the 2D domain, followed by high-fidelity scene inpainting. Foreground objects and the static background are then reconstructed independently and seamlessly imported into physics simulators for policy training. Extensive experiments demonstrate that GASE outperforms existing 3D Gaussian-based methods in segmentation accuracy by over 10\% while achieving state-of-the-art inpainting quality. Furthermore, real-robot deployments across manipulation and navigation tasks maintains a performance gap of less than 10\% compared to policies trained purely on real-world data. These results confirm that GASE provides an efficient and highly effective solution for bridging the sim-to-real gap. Code will be released.

12.
arXiv (CS.CL) 2026-06-19

S2D2: Fast Decoding for Diffusion LLMs via Training-Free Self-Speculation

Block-diffusion language models offer a promising path toward faster-than-autoregressive generation by combining block-wise autoregressive decoding with within-block parallel denoising. However, in the few-step regime needed for practical acceleration, standard confidence-thresholded decoding is often brittle: aggressive thresholds hurt quality, while conservative thresholds require unnecessary denoising steps. Existing approaches that address this issue either require additional training or incur extra test-time compute. We present S2D2, a training-free self-speculative decoding framework for block-diffusion language models. Our key observation is that a block-diffusion model becomes autoregressive when the block size is reduced to one, allowing the same pretrained model to act as both drafter and verifier. S2D2 inserts a speculative verification step into standard block-diffusion decoding and uses lightweight routing policies to decide when verification is worth its cost. This yields a hybrid decoding trajectory in which diffusion proposes tokens in parallel, while the autoregressive mode acts as a local sequence-level critic. Across three mainstream block-diffusion families, S2D2 consistently improves the accuracy-speed tradeoff over strong confidence-thresholding baselines. On SDAR, we observe up to $4.7\times$ speedup over autoregressive decoding, and up to $1.57\times$ over a tuned dynamic decoding baseline while improving accuracy by up to $4.5$ points. On LLaDA2.1-Mini, S2D2 remains complementary to built-in self-correction, including a conservative setting where it is $4.4\times$ faster than the static baseline with slightly higher accuracy.

13.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

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

LOKI: Memory-Free Null-Space Constrained Lifelong Knowledge Editing

arXiv:2606.19679v1 Announce Type: cross Abstract: Lifelong knowledge editing aims to efficiently and sequentially update language models over time, as new knowledge becomes available or when the model makes mistakes, while preserving acceptable performance on past knowledge. One unresolved challenge is that existing methods modify a fixed set of layers for all new knowledge samples, reducing flexibility and increasing catastrophic forgetting. Another is requiring access to previous knowledge and extensive pre-processing to obtain data statistics. To address these challenges, we introduce LOKI, a novel approach that uses dynamic layer selection based on the Hilbert-Schmidt Independence Criterion and projects gradient updates onto the null-space of the model weights, bypassing the requirement for previous knowledge access. We show that LOKI achieves superior performance to existing approaches across a wide variety of experiments, achieving up to a 14\% improvement in average accuracy.

15.
arXiv (CS.AI) 2026-06-16

Quantifying the Impact of Lossy Compression on Neural Generative Surrogate Modeling

arXiv:2606.15959v1 Announce Type: cross Abstract: Neural networks are used as generative surrogate models for scientific discovery, which are trainable approximations of scientific simulations. These models enable users to replace time-consuming numerical simulations with learned alternatives, providing quick solutions. However, high-fidelity generative surrogate models require massive training datasets, which can create storage and I/O challenges. Lossy compression is a promising way to reduce this burden, but compression errors may affect the model quality in subtle ways, making it challenging to quantify their impact. In this work, we examine how lossy compression of training data impacts the quality of generative surrogate models. We begin by characterizing the uncertainty inherent in training neural networks, showing that identical training configurations can produce different models. By exploiting this variability, we propose a method to estimate how much compression-induced error a surrogate model can tolerate without affecting its accuracy. Evaluation of two application simulations demonstrates that our approach significantly reduces memory/storage requirements and speeds up training while producing high-quality surrogate models. These results show that lossy compression saves data storage up to 23.7x and 39x with negligible impact on the quality of the surrogate model. Meanwhile, reducing the size of the training data set also enhances the data loading speed and reduces the training time by up to 3x.

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

RoboNaldo: Accurate, Stable and Powerful Humanoid Soccer Shooting via Motion-Guided Curriculum Reinforcement Learning

arXiv:2606.11092v2 Announce Type: replace-cross Abstract: Elite humanoid soccer shooting requires whole-body stability, high-impulse whole-body interactions, and accuracy to targets. Motion tracking-driven reinforcement learning (RL) provides stability in whole-body movement coordination, but a fixed reference makes it hard to adapt to varied ball positions and strike timings; in contrast, task reward-driven RL struggles to explore and discover valid kicks from scratch. We therefore introduce RoboNaldo, a three-stage motion-guided curriculum RL framework for high-impulse humanoid interaction. A single human-kick reference is used as a scaffold and progressively shifts optimization towards shooting performance. The curriculum first learns a stable whole-body kicking prior, then adapts the kick to free-kick settings where the ball is stationary at random positions, and finally extends it to moving-ball shooting through a locomotion-command and kick-trigger interface. A high-level heuristic planner controls this interface during training, while alternative high-level controllers can drive the same low-level policy at inference. In simulation, RoboNaldo demonstrates free-kick shot error 48.6% lower and shoot velocity 2.96x than prior work baselines. In real world on a Unitree G1 with onboard perception, RoboNaldo attains 0.73 m and 0.86 m average target shooting error from 3 m away in free-kick and moving-ball cases, accordingly. And the post-contact ball velocity reaches 13.10 m/s, which is 59-71% of reported professional open-play shot speed. Project page: https://opendrivelab.com/RoboNaldo.

17.
medRxiv (Medicine) 2026-06-22

Population-Scale, Genotype-First Characterization of Monogenic Diabetes in 374,973 Multi-Ancestry Individuals from the All of Us Research Program

OBJECTIVE To characterize the prevalence and penetrance of maturity-onset diabetes of the young (MODY) in a multi-ancestry population using a genotype-first design. RESEARCH DESIGN AND METHODS We analyzed whole-genome sequencing and clinical data from 374,973 unrelated All of Us participants (42.0% non-European ancestry). We identified pathogenic or likely pathogenic (P/LP) variants in 10 established MODY genes and assessed carrier prevalence, diabetes penetrance, and glycemic profiles. We evaluated age-dependent diabetes risk by comparing carriers with non-carriers stratified by type 2 diabetes polygenic risk score (T2D PRS). RESULTS We identified 370 carriers of P/LP MODY gene variants (0.099%; 1 in 1,013), with similar carrier prevalence among European- and African-ancestry participants (0.105% in both groups). Diabetes penetrance was incomplete (13.4% by age 40; 43.5% by age 60) and varied by etiology: highest for GCK (56.0% by age 60), intermediate for HNF genes (HNF1A/HNF1B/HNF4A; 45.4%), and lowest for non-GCK/HNF genes (ABCC8/INS/KCNJ11/NEUROD1/PDX1/RFX6; 29.0%). In multivariable Cox models using non-carriers in the middle 80% of the T2D PRS as the reference, non-GCK/HNF gene variant carriers had modestly increased diabetes risk (HR, 1.57), similar to non-carriers in the top 10% of T2D PRS (HR, 1.64). These associations were observed in both European- and non-European-ancestry individuals. HbA1c profiles differed by etiology, with stable mild hyperglycemia in GCK variant carriers and greater variability among HNF and non-GCK/HNF gene variant carriers. CONCLUSIONS MODY gene variants showed incomplete, etiology-dependent penetrance across ancestries. Carriers of P/LP variants in lower-penetrance genes had diabetes risk comparable to that of non-carriers with high polygenic susceptibility.

18.
arXiv (CS.CL) 2026-06-16

Understanding the Behaviors of Environment-aware Information Retrieval

Recent retrieval-augmented generation (RAG) approaches have demonstrated strong capability in handling complex queries, yet current research overlooks a critical challenge: different retrievers require fundamentally different query formulation strategies for optimal performance. In this work, we present the first systematic analysis of how LLMs can learn to adapt their query formulation strategies for different retrievers via reinforcement learning (RL). Our empirical study reveals that RL effectively teaches an LLM to tailor its queries to specific retriever characteristics. We discover that different retrievers exhibit surprisingly distinct optimal query styles (e.g., descriptive vs. question-like), suggesting strategies learned for one retriever ineffective for another. We further show that performance can be enhanced by incorporating retriever-specific human guidance and by scaling model size. To facilitate learning over multi-retrieval-step trajectories, we introduce a branching-based rollout technique that improves training stability. Our work provides the first empirical evidence and actionable insights for building truly retriever-aware RAG systems. Code and resources are available at https://github.com/LCO-Embedding/Envs-aware-Information-Retrieval.

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

ScaffoldAgent: Utility-Guided Dynamic Outline Optimization for Open-Ended Deep Research

arXiv:2606.20122v1 Announce Type: new Abstract: Open-ended deep research (OEDR) requires systems to acquire knowledge through multi-round retrieval and generate coherent long-form reports. The outline plays a central role as a structural scaffold that coordinates retrieval, evidence organization, and generation. However, existing methods either fix the outline before writing or refine it with local heuristics, leading to scaffold drift under continuous information accumulation and delayed feedback for evaluating outline modifications. We propose ScaffoldAgent, a utility-guided dynamic outline optimization framework for OEDR. ScaffoldAgent models outline evolution as a structured decision process with three operations: Expansion, Contraction, and Revision, enabling controlled updates to the report scaffold. It further introduces a utility-guided feedback mechanism that estimates the downstream value of each outline operation from retrieval gain, structural coherence, and trial-generation quality. The resulting utility signal guides node selection, operation scheduling, and termination during inference. Experiments on DeepResearch Bench and DeepResearch Gym show that ScaffoldAgent consistently improves long-form report generation and factual grounding over existing deep research agents.

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

A Hybrid GNN-FEM Framework for Phase-Field Fracture Simulation. Physics-Preserving Hybridization for Generalizable Surrogate Modeling

arXiv:2606.19378v1 Announce Type: new Abstract: Scientific machine learning (SciML) has emerged as a promising approach for accelerating simulations of complex physical systems, yet achieving physically consistent and generalizable predictions for nonlinear, history-dependent problems remains a central challenge. In this study, we propose a hybrid GNN–FEM framework for efficient and generalizable phase-field fracture modeling. While phase-field approaches provide a robust variational framework for simulating complex crack evolution, their high computational cost limits practical applications because they require solving coupled, nonlinear, and history-dependent systems within an incremental finite element procedure. To address this challenge, a graph neural network surrogate is integrated into the conventional staggered scheme, replacing the phase-field update at each load increment while retaining the FEM-based displacement solver to enforce mechanical equilibrium and boundary conditions. By preserving the incremental solution structure, the framework remains consistent with history-dependent fracture evolution without requiring the surrogate to approximate the full solution trajectory. This selective surrogate strategy emphasizes the identification of a physically meaningful and incrementally structured learning target, rather than relying on brute-force data generation to learn the full fracture process. The proposed framework achieves strong generalization across varying geometries, loading conditions, material properties, and discretizations through dimensionless feature design, a graph-based formulation on mesh-based domains, and a physics-informed loss derived from the governing phase-field equation. Numerical experiments demonstrate that the hybrid approach reduces computational cost while maintaining accuracy compared with conventional FEM, and exhibits robust predictive performance across diverse problem settings.

21.
arXiv (CS.CL) 2026-06-19

Creating Multilingual Mental Health Dialogue Datasets: Limits of Persona-Based Localization via Nationality and Language

AI and large language models (LLMs) have emerged as promising tools to address global mental health challenges. Despite the global nature of these challenges, there remains a critical shortage of high-quality datasets for training and evaluating such systems. To mitigate this gap, researchers increasingly generate synthetic clinical personas to simulate user data and test digital mental health support systems. However, most validated personas rely on English-centric contexts. This paper investigates whether similar persona-based methods can be used to generate multilingual mental health datasets. We modified nationality and language parameters in personas to generate clinical dialogues in Mandarin, Bengali, and Hindi. We then examined how different LLMs perform when evaluating the depression severity of these generated multilingual datasets against the baseline in English. Our findings indicate that just adding nationality and language parameters in personas might not be adequate, as it can introduce clinical inconsistency across languages. LLM judge models often exhibit inaccuracies in assessing depression severity in non-English texts, with performance varying across different models. This exposes the systemic limitations of applying English-centric personas to multilingual contexts. Ultimately, our work highlights the urgent need for culturally responsive data generation to ensure equitable mental health systems globally.

22.
medRxiv (Medicine) 2026-06-15

Quantitative Gait Categorization in Parkinson's Disease with and without Freezing of Gait

Background: Freezing of gait (FOG) is a disabling and often underrecognized feature of Parkinsons disease (PD). Objective gait analysis may improve characterization of this motor symptom. Objective: To compare quantitative 3D gait parameters in PD with FOG (PDF) and PD without FOG (PDNF) in a routine clinical cohort. Methods: We retrospectively analyzed a sequential sample of 180 patients with PD referred for motion analysis between 2020 and 2024. All patients underwent 3D motion capture in the off-medication state. Eighteen gait outcomes spanning pace, rhythm, postural control, variability, and asymmetry domains were derived from steady-state walking tasks. FOG status was determined using physician documentation and Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS) items. Group differences between PDF (n=99) and PDNF (n=81) were evaluated using independent samples t-tests, with outcomes adjusted for disease duration and corrected for multiple comparisons. A secondary analysis among PDF compared those in Hoehn and Yahr (H&Y) stage [≥]III to those in H&Y [≤]II. Results: PDF had longer disease duration, higher OFF MDS-UPDRS III scores, and higher Hoehn and Yahr stage than PDNF but were similar in age and sex. After adjusting for disease duration and multiplicity, PDF demonstrated reduced step length, stride length, and forward velocity, and greater cadence variability, while most postural control, and asymmetry measures were comparable between groups. Among PDF, advanced H&Y stage was associated with impaired pace and rhythm, similar to previous reports among PD in general. Conclusion: In this large, sequential, clinically referred cohort, FOG was associated with more advanced PD and specific impairments in pace and gait variability. These findings support comprehensive 3D gait analysis as an objective tool to better delineate FOG-related gait abnormalities and identify features that may predict FOG, informing targeted interventions.

23.
arXiv (CS.CL) 2026-06-18

PragReST: Self-Reinforcing Counterfactual Reasoning for Pragmatic Language Understanding

Natural language understanding often depends on meanings that are implied rather than explicitly stated, requiring pragmatic reasoning. Despite strong performance on math and logical reasoning, large language models (LLMs) still struggle with making pragmatic inferences, often choosing literal interpretations. To improve LLM pragmatic reasoning, we introduce PragReST, a self-supervised framework that constructs pragmatic QA data, generates counterfactual reasoning traces, and trains models to internalize them through supervised fine-tuning and reinforcement learning, without human-labeled training data or distillation from a stronger teacher. Across four pragmatic benchmarks (PragMega, Ludwig, MetoQA, and AltPrag), PragReST improves over backbone models, task-specific pragmatic tuning baselines, and non-counterfactual variants of the same pipeline. On accuracy-based benchmarks, PragReST improves over the instruct backbone by 5.37 and 5.50% (absolute) for Qwen3-8B and Qwen3-14B, respectively. Our error analysis and ablations underscore the importance of counterfactual reasoning: PragReST primarily reduces errors caused by failures to contrast observed utterances with plausible alternatives, and removing counterfactual reasoning substantially reduces performance. Moreover, our training preserves out-of-domain performance on general-knowledge and mathematical reasoning benchmarks.

24.
arXiv (CS.LG) 2026-06-17

Continual Self-Improvement with Lightweight Experiential Latent Memories

arXiv:2606.17803v1 Announce Type: new Abstract: Large language models achieve strong reasoning performance by scaling inference-time compute, yet remain fundamentally stateless, discarding the rich, self-produced reasoning traces generated during this process. We investigate whether models can instead learn online from this experience, converting transient computation (reasoning traces) into persistent reusable knowledge, and without external supervision or access to future data. We show that In-Context Learning (ICL) over raw reasoning traces fails to generalize, reflecting a fundamental limitation of token-level reuse: individual traces lack the abstraction needed for transfer, even after refinement (e.g. self-reflection). In contrast, drawing inspiration from recent works on unsupervised reinforcement learning, we find that lightweight per-instance training with self-generated test-time signals (majority voting) as rewards yields substantial gains, often surpassing full-dataset offline training, motivating a shift from raw traces to learned latent representations. Building on this insight, we propose an online method that distills inference-time compute spent on encountered problems into compact modular latent memories capturing the underlying reasoning structure. These memories are stored and retrieved for future inputs, enabling continual improvement while avoiding catastrophic forgetting through modular design. Importantly, our method is highly efficient, parametrized as extremely lightweight soft prompt memories (~0.001% of model parameters) and trained with only a few gradient steps, yet achieving performance competitive with full parametric updates and offline training. Across challenging mathematical reasoning benchmarks, our approach significantly outperforms zero-shot and raw data ICL baselines, while transferring effectively across datasets.

25.
arXiv (quant-ph) 2026-06-17

Singular Vector Finite Element Basis Functions for Tetrahedra in Complex Electromagnetic Geometries

arXiv:2606.18140v1 Announce Type: cross Abstract: Electromagnetic finite element method (FEM) implementations using traditional basis functions struggle to accurately represent field behavior near singular features such as conducting wedges. To combat this, specialized singular basis functions have been introduced to directly model the singular fields in these regions, leading to substantially improved performance. While these efforts have been pursued extensively in 2D, few functions have been developed for 3D elements. In this work, we develop basis functions for this in tetrahedra. Unlike prior functions, these basis functions are additive, meaning they are included alongside the standard vector basis functions to achieve more robust performance. Further, these functions are designed to be adaptable to tetrahedra touching several unique singular features by using combinations of basis functions singular with respect to each node and edge in the element, making them applicable to highly complex geometries. Higher-order interpolatory versions of the basis functions for modeling singular behavior with greater accuracy are also provided. These basis functions lead to substantial improvements in accuracy relative to the standard basis functions, and allow otherwise expensive simulations to be performed at far lower costs. As an application example, we perform simulations to extract critical quantities for designing superconducting qubits that significantly depend on the behavior of singular fields. In Ansys HFSS, this took 21.27 hours and a peak memory usage of 6.23 TB with 800 processors available, while using our singular basis functions achieved comparable results in 196 seconds while using 27.24 GB of memory and only 16 processors. Due to these benefits, our singular basis functions could be applied to enable design optimization of electromagnetic geometries with dominantly singular behavior, such as superconducting qubits.