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01.
medRxiv (Medicine) 2026-06-19

Validation of an Artificial Intelligence-Assisted Mobile Application for Dietary Oxalate Assessment in Kidney Stone Prevention

Background: Calcium oxalate nephrolithiasis is the most common type of kidney stone disease. Dietary oxalate intake is an important modifiable factor. Assessing dietary oxalate exposure in clinical practice poses challenges due to limitations of traditional dietary recall tools and variability in food composition data. Artificial intelligence (AI) applications in mobile health may offer scalable solutions for better dietary monitoring and kidney stone prevention. We examined the ability of StoneFree AI to estimate dietary oxalate from verbal and image-based food inputs. Objective: To evaluate the accuracy and limitations of StoneFree AI, for estimating dietary oxalate intake from verbal food descriptions and meal images, and to evaluate errors from entries that may inform future clinical use in kidney stone prevention. Methods: StoneFree AI is a cross-platform mobile application that uses a multimodal large language model (Google Gemini) to interpret verbal food descriptions and visual food images. The identified foods were mapped to oxalate values using the Harvard Oxalate Database. System performance was evaluated using 804 verbal food entries and 276 portion-size food images obtained from the ASA24 dietary assessment database. Verbal inputs were compared with reference oxalate values using absolute error and predefined agreement thresholds ({+/-}1, {+/-}5, {+/-}10 mg). Image-based inputs were evaluated against mutually exclusive primary error categories, including food identification, portion estimation, ingredient recognition, oxalate reference selection, and non-analyzable cases. Results: For verbal food entries, the AI system showed strong agreement with reference oxalate values. Overall, 82.1% of estimates were within {+/-}1 mg, 91.5% within {+/-}5 mg, and 94.5% within {+/-}10 mg of reference values. The mean absolute error was 3.32 mg, the median absolute error was 0.10 mg, and the concordance correlation coefficient (CCC) was 0.860. Image-based inputs showed a higher overall error rate of 63.0%, primarily due to food identification errors (33.0%), inaccurate portion estimation (11.0%), and ingredient recognition errors (9.8%). Most errors occurred with visually complex meals, such as mixed dishes and grain-based foods. Conclusions: AI-assisted estimation of dietary oxalate intake demonstrated high accuracy when structured verbal inputs were used but was less reliable for image-based meal analysis. These findings suggest AI-enabled mobile tools may support dietary monitoring for kidney stone prevention, particularly when user input is structured. Further refinement of computer vision models and prospective clinical validation are required before widespread clinical implementation.

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

Imbalanced Semi-Supervised Learning via Label Refinement and Threshold Adjustment

arXiv:2407.05370v3 Announce Type: replace Abstract: Semi-supervised learning (SSL) algorithms often struggle to perform well when trained on imbalanced data. In such scenarios, the generated pseudo-labels tend to exhibit a bias toward the majority class, and models relying on these pseudo-labels can further amplify this bias. Existing imbalanced SSL algorithms explore pseudo-labeling strategies based on either pseudo-label refinement (PLR) or threshold adjustment (THA), aiming to mitigate the bias through heuristic-driven designs. However, through a careful statistical analysis, we find that existing strategies are suboptimal: most PLR algorithms are either overly empirical or rely on the unrealistic assumption that models remain well-calibrated throughout training, while most THA algorithms depend on flawed metrics for pseudo-label selection. To address these shortcomings, we first derive the theoretically optimal form of pseudo-labels under class imbalance. This foundation leads to our key contribution: SEmi-supervised learning with pseudo-label optimization based on VALidation data (SEVAL), a unified framework that learns both PLR and THA parameters from a class-balanced subset of training data. By jointly optimizing these components, SEVAL adapts to specific task requirements while ensuring per-class pseudo-label reliability. Our experiments demonstrate that SEVAL outperforms state-of-the-art SSL methods, producing more accurate and effective pseudo-labels across various imbalanced SSL scenarios while remaining compatible with diverse SSL algorithms. The code is publicly available (https://github.com/ZerojumpLine/SEVAL).

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

PrologMCP: A Standardized Prolog Tool Interface for LLM Agents

arXiv:2606.14935v1 Announce Type: new Abstract: Frontier reasoning-tuned language models still fail on deductive tasks at depth, and the cost of improved performance through extended internal reasoning scales poorly. Symbolic delegation offers a complementary route: a language model translates the problem, while a solver performs the inference. However, current autoformalization pipelines for logic programming are typically bespoke integrations tied to particular tasks or agents. We introduce PrologMCP, a task-agnostic, open-source server that exposes Prolog as a stateful tool through the Model Context Protocol (MCP). Its compact tool interface, structured error reporting, and per-session isolation make the translate-run-inspect-repair loop a reusable primitive for MCP-capable agents. We evaluate a formalizer agent enhanced with PrologMCP against standard and reasoning LLMs (Claude Sonnet 4.6, GPT-4.1, and o4-mini) on two subsets of PARARULE-Plus: a general-purpose sample and a more challenging one targeting a specific failure mode of natural-language reasoning. On the general sample, the formalizer matches or exceeds reasoning LLMs (accuracy 1.00 vs.\ 1.00 / 0.998), with the largest gains over standard models (0.762 for GPT-4.1). On the challenging subset, the formalizer remains near-perfect (1.00 / 0.99) while reasoning LLMs drop to 0.95 / 0.94. These results suggest that delegating inference to Prolog via MCP is a robust and inspectable alternative to extended natural-language reasoning.

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

Sensorimotor World Models: Perception for Action via Inverse Dynamics

arXiv:2606.20104v1 Announce Type: cross Abstract: Perception for action suggests that representations of the world should be shaped not by visual fidelity alone, but by their relevance for actions. At the same time, latent JEPA-style world models advocate learning compact predictive states from high-dimensional observations to facilitate the prediction of future states, but end-to-end training of these models is nontrivial because representations may collapse if our only goal is to construct a latent state that is easy to predict. We introduce a sensorimotor world model (SMWM): a latent world model trained end-to-end with inverse dynamics regularization. This single regularizer addresses both issues: it prevents representation collapse and induces action-aligned representations. By forcing latent states to preserve information about the action underlying a transition, it biases the model toward the controllable degrees of freedom of the environment while discarding uncontrollable distractors. This yields stable latent world models trained from offline, reward-free trajectories, without frozen encoders, exponential moving averages, or complex latent regularizers. Empirically, SMWM learns compact, interpretable latent spaces and enables competitive planning performance across simple 2D and 3D control tasks.

05.
arXiv (quant-ph) 2026-06-12

Improving Variational Counterdiabatic Driving with Weighted Actions and Computer Algebra

arXiv:2505.18367v4 Announce Type: replace Abstract: Variational counterdiabatic (CD) driving is a disciplined and widely used method to robustly control quantum many-body systems by mimicking adiabatic processes with high fidelity and reduced duration. Central to this technique is a universal structure of the adiabatic gauge potential (AGP) over a parameterized Hamiltonian. Here, we reveal that introducing a new degree of freedom into the theory of the AGP can significantly improve variational CD driving. Specifically, we find that the algebraic characterization of the AGP is not unique, and we exploit this nonuniqueness to develop the weighted variational method for deriving a refined driving protocol. This approach extends the conventional method in two aspects: it assigns customized weights to matrix elements relevant to specific problems, and it effectively incorporates nonlocal information into local driving coefficients. We also develop an efficient numerical algorithm to compute the refined driving protocol using computer algebra. Our framework is broadly applicable and, in principle, it can replace any previous use of variational CD driving. We demonstrate its practicality by applying it to adiabatic evolution along the ground state of a parameterized Hamiltonian. This proposal outperforms the conventional method in terms of fidelity, as confirmed by extensive numerical simulations on quantum Ising models.

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

3D Masked Autoencoders are Robust Learners of Volumetric and Multimodal Cellular Representations for Microscopy

Self-supervised learning in fluorescence microscopy often relies on 2D projections, despite the inherently three-dimensional nature of cells. We present a systematic comparison of 2D and 3D masked autoencoders (MAE-2D vs. MAE-3D) on volumetric microscopy data. Under matched architectures and training protocols, MAE-3D consistently outperforms 2D max-projection and slice-based variants on downstream single-cell tasks. We further align visual representations with a pretrained protein language model (ESM2) and show that cross-modal supervision yields larger gains for volumetric models. Channel cross-attention and frequency-domain regularization are critical for leveraging 3D spatial context. On a protein–protein interaction task, MAE-3D achieves a ROC–AUC of 0.865, outperforming prior methods by up to +0.025. For protein localization, our best 3D model attains state-of-the-art AUC$_{micro}$ (0.952) and F1$_{micro}$ (0.742), improving over previous approaches by +0.003 and +0.010 absolute, respectively. Overall, these results demonstrate the advantages of native 3D modeling and multimodal alignment for representation learning in single-cell microscopy.

07.
arXiv (CS.AI) 2026-06-24

Invariant Graph Representations for Continuous-Time Dynamic Graphs Under Distribution Shifts

arXiv:2405.19062v2 Announce Type: replace-cross Abstract: Continuous-Time Dynamic Graphs (CTDGs) enable fine-grained modeling of evolving relational systems. However, most existing CTDG representation learning methods are tailored to in-distribution settings and exhibit limited robustness under out-of-distribution (OOD) shifts. Although recent causal approaches learn invariant representations via interventions, they are primarily designed for static or discrete-time graphs and become computationally prohibitive for CTDGs due to the combinatorial explosion of structural and temporal variations. To address these challenges, we propose CIR, a framework grounded in a novel structural causal model termed the ICCM. To avoid exhaustive interventions, we leverage the Normalized Weighted Geometric Mean (NWGM) to efficiently approximate interventional predictions. We further instantiate ICCM within a practical deep learning architecture that jointly captures invariant structural and temporal patterns through dedicated subgraph extractors, and maintains an environment memory bank to model distributional shifts across evolving contexts. Extensive experiments demonstrate that CIR consistently outperforms existing methods under diverse OOD scenarios.

08.
medRxiv (Medicine) 2026-06-18

Personalizing Suicide Risk Assessment: Machine Learning Extraction of Cross-Modal Interactions Between Psychosocial and Demographic Factors in Veterans

Background: Veterans face an elevated risk of suicide compared to the general population, motivating national efforts to develop predictive models that can guide proactive care. Current models used by the U.S. Department of Veterans Affairs (VA) rely primarily on structured electronic health record (EHR) data, though clinical notes contain rich contextual information that can be quantified using natural language processing (NLP) to derive psychosocial variables that may improve risk detection. Machine learning methods, particularly classification and regression trees (CART), can also uncover interactions between clinical and psychosocial variables, enabling identification of patient characteristics that modify suicide risk factors. However, integrating structured and unstructured data presents challenges because NLP features often greatly outnumber traditional clinical variables, potentially biasing interaction discovery. In prior work, we addressed this imbalance by introducing a weighted CART framework that balances structured variables with NLP-derived psychosocial features from semantic lexicons (SEANCE). While effective, semantic approaches summarize language into predefined constructs and may overlook important lexical variation present in clinical narratives. Methods: In this study, we extend that framework by replacing semantic features with a high-dimensional bag-of-words (BoW) representation of clinical notes and by evaluating models across cohorts defined by structured suicide risk stratification (low, medium, high) and varying temporal lookback windows. Using a cohort of 27,241 veterans, we analyzed clinical documentation collected up to 30, 90, or 270 days prior to death (or a matched index date for controls), enabling temporally flexible risk modeling. XGBoost models were trained to balance structured and unstructured features and identify cross-modal interactions between textual and clinical variables. Results: When incorporated into generalized linear models, these interactions improved predictive performance, particularly among low- and medium-risk patients, and substantially reduced the performance gap between interpretable and more complex models. Notably, the BoW representation outperformed our prior semantic index-based approach. Discussion and Conclusions: Together, these findings demonstrate the utility of interpretable NLP methods for uncovering clinically meaningful interactions between psychosocial and demographic factors in suicide risk and establish a strong benchmark for future deep learning approaches aimed at capturing richer contextual and temporal information from clinical narratives.

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

SciOrch: Learning to Orchestrate Expert LLMs for Solving Frontier Multimodal Scientific Reasoning Tasks

Frontier scientific reasoning remains a major challenge for large language models (LLMs), where even the strongest commercial systems fall short of expert-level performance. A closer look at model behavior reveals substantial complementarity that single-model evaluation hides: different frontier models excel on different question types, and no single model captures the full picture. We present SciOrch, a framework that trains a lightweight 8B model to orchestrate frontier LLMs for scientific reasoning. The orchestrator decomposes each question, delegates sub-problems to selected commercial models through API calls, and synthesizes a final answer. Training such an orchestrator is fundamentally harder than conventional agentic RL: each action triggers an API call that is expensive in both dollar cost and latency, making standard online rollouts infeasible. We address this with MCTS-based approach, producing diverse orchestration trajectories, extracting per-node single-turn samples, and optimizing the orchestrator with GRPO-style training. On a 240-question test set spanning SGI-Reasoning and Scientists' First Exam, SciOrch reaches 56.66% average accuracy, outperforming the strongest single commercial model by 3.74% and the strongest multi-agent baseline by 3.33%. It also attains the best accuracy on both SGI and SFE with less than half the API cost of typical multi-agent methods.

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

Atlas H&E-TME: Scalable AI-Based Tissue Profiling at Expert Pathologist-Level Accuracy

Hematoxylin and eosin (H&E) staining is the cornerstone of histopathology, yet scalable, quantitative analysis of H&E whole-slide images (WSIs) remains a central challenge in computational pathology. We present Atlas H&E-TME, an AI-based system built on the Atlas family of pathology foundation models that predicts tissue quality, tissue region, and cell type labels across multiple cancer types, yielding over 4,500 quantitative readouts per slide at cell-level resolution. A key challenge to validating such systems is overcoming morphological ambiguity inherent to H&E-only ground truth and the limited scalability of more informed references drawing on modalities such as immunohistochemistry (IHC). We address this with a dual validation framework combining biologically grounded depth with technical and morphological breadth. For depth, we propose an IHC-informed multi-pathologist consensus protocol that substantially improves inter-rater agreement over conventional H&E-only annotation. This yields a molecularly grounded reference against which we compare Atlas H&E-TME and pathologists working from H&E alone. For breadth, we benchmark Atlas H&E-TME on over 200,000 high-confidence H&E-only pathologist annotations across 1,500+ cases spanning eight cancer types and their most common metastatic sites, with subtypes covering >90% of clinical cases per cancer type, drawn from 25+ sources and 8+ scanner models. Benchmarked against the IHC-informed consensus, Atlas H&E-TME matches or exceeds pathologist H&E-only performance and generalizes consistently and robustly across this broad morphological and technical scope. In doing so, Atlas H&E-TME turns the H&E slide – the most ubiquitous data in pathology – into a scalable, quantitative window into the tumor and its microenvironment, laying a foundation for the next generation of tissue-based biomarkers in translational and clinical research.

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

Mem-World: Memory-Augmented Action-Conditioned World Models for Persistent Robot Manipulation

Action-conditioned world models have emerged as a promising paradigm for robot learning, offering a scalable alternative to costly real-world experimentation by generating action-consistent video rollouts. However, persistent world modeling remains challenging in manipulation: frequent end-effector occlusions and rapid wrist-camera motion make the current observation insufficient for predicting future views, causing models to forget or hallucinate scene details seen in earlier frames. Existing memory retrieval strategies often fail to identify informative history in dynamic manipulation scenarios. To address this limitation, we propose Mem-World, a memory-augmented multi-view action-conditioned world model. At its core, we present W-VMem, a 4D wrist-view-centered surfel-indexed memory that anchors historical observations to temporally evolving surface elements. By explicitly modeling when and where scene elements are observed, W-VMem enables geometry-aware retrieval of relevant history frames conditioned on future actions. During generation, relevant history frames are selected via surfel-based rendering and scoring, providing informative and non-redundant context for prediction. Extensive experiments show that Mem-World generates persistent rollouts in complex manipulation scenarios, enables more reliable policy evaluation than Ctrl-World, improving the Pearson correlation with real-world performance by 14.5\%, and supports effective policy improvement through synthetic data generation, increasing success rates from 58\% to 72\% on long-horizon tasks.

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

Gaussian Process Prior Variational Autoencoder for Endoscopic Videos

Endoscopic video analysis is essential for gastrointestinal diagnosis and computer-assisted interventions, but video sequences are routinely degraded by specular reflections, motion artifacts, and missing frames. These transient corruptions can distract clinicians, reduce image interpretability, and disrupt downstream tasks such as 3D reconstruction and navigation. Effective restoration therefore requires methods that exploit temporal continuity rather than treating frames in isolation. We introduce a Gaussian Process Prior Variational Autoencoder (GPVAE) framework for endoscopic video restoration that replaces the standard factorized latent prior with a temporal Gaussian process prior, enabling interpolation of missing frames with uncertainty-aware reconstruction. The framework combines endoscopy-specific encoders, including a convolutional EndoVAE backbone and pretrained Vision Transformer encoders from GastroNet-5M, with two scalable GP approximations: Hierarchical Prior Approximation (HPA) and Sparse Precision Approximation (SPA). Specular reflections are handled using a DUCKNet-based masking pipeline that excludes corrupted pixels from the reconstruction objective. On the C3VDv2 colonoscopy dataset, the best GPVAE variants reduced image reconstruction RMSE by 21.9\% on average, and by up to 26.1\%, relative to matched VAE baselines. Downstream trajectory RMSE was reduced by 12.7\% on average across classical visual odometry and a pretrained PoseNet, at an average increase of 27.3\% in training time per epoch. Finally, the GP posterior provides per-frame uncertainty estimates that reflect temporal support and offer a confidence signal for restored frames.

13.
Nature (Science) 2026-06-08

GPR15-guided CD8<sup>+</sup> T regulatory cells control intestinal inflammation

Authors:

Inflammatory bowel disease (IBD) causes chronic suffering from gastrointestinal inflammation and dysfunction that can progress to colon cancer1,2. The disease prevalence is increasing and there is an urgent need to better understand its pathogenic mechanisms to improve treatment. We show that GPR15, a G protein-coupled receptor (GPCR) expressed in immune cells and previously described as an entry co-factor for human and simian immunodeficiency viruses3, is a marker and homing receptor for a subset of intramucosal GPR15-guided regulatory CD8+ T lymphocytes (CD8+ TIGR). Deleterious GPR15 gene variants in humans cause defective homing of CD8+ TIGR and are associated with severe early-onset IBD. Moreover, CD8+ TIGR cells are reduced in the intestinal mucosa of sporadic IBD patients. In mice, GPR15 deficiency impairs colonic homing of CD8+ TIGR cells, leading to accumulation of inflammatory macrophages and increased susceptibility to colitis. CD8+ TIGR cells potently kill macrophages activated by intestinal damage or disease using Fas ligand (FasL) and TNF-related weak inducer of apoptosis (TWEAK). The identification of CD8+ TIGR cells yields new insights into organ-specific immune regulation and potential therapeutics for IBD.

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

Investigating Human-Model Discrepancies in Speech Quality Assessment via Acoustic and Prosodic Perturbations

Mean opinion score (MOS) prediction models are widely used as proxy metrics in text-to-speech (TTS) research, yet their ability to capture quality differences beyond acoustic fidelity remains unclear. We investigate this via controlled perturbations on speech: acoustic degradation, prosodic errors, and manipulation of speaker-specific characteristics such as pitch and speaking rate. We obtained MOS predictions for these speech samples from both human listeners and the model, and analyzed the differences in their perceptual characteristics. Results show that most models track acoustic degradation well, while all are insensitive to prosodic errors despite large subjective score drops. For speaker characteristics, models exhibit a double dissociation: strong mean fundamental frequency (F0) biases absent in human ratings, yet insensitivity to speaking rate and F0 variability that humans notice. These findings highlight limitations of scalar MOS prediction beyond acoustic fidelity.

15.
arXiv (CS.AI) 2026-06-12

ReSum: Synergizing LLM Reasoning and Summarization with Reinforcement Learning

arXiv:2606.13316v1 Announce Type: new Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) is a central technique for improving long-horizon reasoning in Large Language Models (LLMs). However, existing RLVR methods often encourage unnecessarily long reasoning rollouts, which can degrade reasoning coherence and exhaust the available context budget. Existing approaches to long-context organization often depend on external mechanisms to organize rollouts, rather than enabling the model to manage its own reasoning trajectory. To address this limitation, we propose ReSum, a novel RLVR framework that enables LLMs to compress and organize their reasoning trajectories through self-summarization. Our pilot studies show that self-summarization stabilizes generation by lowering token-level entropy, and that introducing a ``summarization'' phrase can substantially mitigate errors propagated from an incorrect rollout prefix. Motivated by these findings, ReSum adopts a summarization-aware adaptive rollout mechanism that contrastively evaluates whether self-summarization benefits the ongoing reasoning process. Specifically, when the model spontaneously triggers self-summarization, ReSum masks the summarization phrase to create a contrastive branch; for non-summarization positions, it instead randomly injects the phrase to create a matched branch. We further design a summarization-aware advantage to enable finer-grained comparison between contrastive rollout trajectories. Extensive experiments show that ReSum improves performance at an average of 4\% while reducing rollout length by 18.6\%.

16.
medRxiv (Medicine) 2026-06-16

Risk beliefs, intensive digital information and demand for a new preventative health product in public clinics: Evidence from an experiment in Zimbabwe.

Demand for preventative health care is weak in low-income settings. In a field experiment in a low-income, high-risk setting, we evaluated whether demand for a new bio-medical preventative health product, offered free at public health clinics, responds to digital feedback-based intensive information on health risks and benefits of prevention along with a clinic referral enabling access to the product. In our sample of women aged 18-24 years, we find a large correction in risk beliefs sustained six months after the intervention. Against a background of very low baseline usage, within six months we find a 5.8 percentage point increase in take up of the prevention method, a level of uptake which is very large relative to the control group. Reassuringly, there is no meaningful difference in up-take amongst baseline high- risk and low-risk individuals.

17.
arXiv (CS.CL) 2026-06-12

PRISM: Prosody-Integrated Multi-Agent Reasoning Framework for Empathetic Spoken Dialogue

Empathetic spoken dialogue systems require not only semantically appropriate responses but also emotionally aligned prosodic expression. However, cascade pipelines often discard acoustic cues during speech-to-text conversion, while end-to-end speech models lack interpretable control over emotion and knowledge integration. To address these challenges, we propose PRISM, a multi-agent framework for empathetic spoken dialogue that decouples speech perception, response generation, and speech synthesis into coordinated components. PRISM introduces a prosody-to-language translation mechanism to stabilize large language model reasoning and enables on-demand invocation of external knowledge tools for empathetic dialogue generation. Experimental results demonstrate that PRISM achieves consistent improvements in empathy, prosodic appropriateness, and text response generation quality across objective and subjective metrics. Our code is available at: https://github.com/Bxzfrm/PRISM.

18.
arXiv (CS.CL) 2026-06-15

MASLab: A Unified and Comprehensive Codebase for LLM-based Multi-Agent Systems

LLM-based multi-agent systems (MAS) have demonstrated significant potential in enhancing single LLMs to address complex and diverse tasks in practical applications. Despite considerable advancements, the field lacks a unified codebase that consolidates existing methods, resulting in redundant re-implementation efforts, unfair comparisons, and high entry barriers for researchers. To address these challenges, we introduce MASLab, a unified, comprehensive, and research-friendly codebase for LLM-based MAS. (1) MASLab integrates over 20 established methods across multiple domains, each rigorously validated by comparing step-by-step outputs with its official implementation. (2) MASLab provides a unified environment with various benchmarks for fair comparisons among methods, ensuring consistent inputs and standardized evaluation protocols. (3) MASLab implements methods within a shared streamlined structure, lowering the barriers for understanding and extension. Building on MASLab, we conduct extensive experiments covering 10+ benchmarks and 8 models, offering researchers a clear and comprehensive view of the current landscape of MAS methods. MASLab will continue to evolve, tracking the latest developments in the field, and invite contributions from the broader open-source community.

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

Reliable Error Estimation for PINNs: Lower and Upper A Posteriori Bounds

arXiv:2606.12050v1 Announce Type: new Abstract: Physics-informed neural networks (PINNs) combine machine learning with physical laws to solve differential equations. While existing results provide rigorous a posteriori upper bounds for PINN prediction errors, complete certification also requires complementary lower information in order to obtain computable two-sided error enclosures. In this paper, we derive computable a posteriori lower bounds for PINN errors in ordinary differential equations on suitable certified state-space domains under a localized strong monotonicity condition. We combine these estimates with complementary localized upper bounds under a one-sided Lipschitz condition, which is weaker than the global Lipschitz assumption used in previous work and can yield sharper upper error bands. The resulting bounds depend only on the neural-network approximation, the ODE residual, and local monotonicity and growth constants, and therefore do not require access to the exact solution. For linear time-invariant and time-varying systems, we further derive explicit formulas in terms of the minimal and maximal eigenvalues of the symmetric part of the system matrix. We also discuss the distinction between soft and hard enforcement of initial conditions in PINNs and explain why exact enforcement can make the scalar lower certificate uninformative. To recover nontrivial lower information in the linear setting, we use a signed-residual finite-probe certificate based on coordinate unit vectors. We also formulate a certificate-informed training strategy in which the propagated upper certificate is used as an auxiliary regularizer, while lower certificates remain post-training diagnostics. Altogether, the proposed framework provides rigorous and practically computable error certificates for PINN approximations of ODEs, while making explicit the domains and model classes for which the assumptions can be verified.

20.
medRxiv (Medicine) 2026-06-15

Anti-Platelet Factor 4 Antibody Clonal Heterogeneity and MGUS Status in HIT

Background Monoclonal gammopathy of thrombotic significance (MGTS) is a recently described chronic prothrombotic condition characterized by monoclonal anti-PF4 antibodies that are detected above the polyclonal antibody background in patient sera (i.e. present as monoclonal gammopathy of undetermined significance, MGUS). Due to conflicting data in the published literature on antibody clonality in heparin-induced thrombocytopenia (HIT), we evaluated clonality and abundance of anti-PF4 antibodies in HIT, including investigating whether an MGUS, if present in HIT, represents the causative anti-PF4 antibody. Methods Blood samples from 15 patients with HIT were subject to Platelet Factor 4-dependent antigen-based and functional tests. The unmanipulated serum antibody repertoire and isolated anti-PF4 antibodies were subjected to mass spectrometric evaluation. Results Two of the 15 HIT patients had an IgG MGUS. Notably, anti-PF4 antibodies were not synonymous with the MGUS antibody in either of the two patients. Eight of the 15 patients demonstrated monoclonal anti-PF4 antibodies, however, none of the anti-PF4 antibodies were detectable as an MGUS upon evaluation of the entire serum antibody repertoire, reflecting their low abundance. In the seven patients with multiple anti-PF4 antibodies, non-monoclonality was confirmed by analysis of deglycosylated antibody heavy chains. Conclusions Anti-PF4 HIT antibodies are monoclonal in approximately 50% of HIT patients, however, antibody abundance is low such that they are not detectable over the polyclonal IgG background (i.e. are MGUS-negative), differentiating HIT from MGTS. This observation helps explain the transient nature of HIT relative to the persistent prothrombotic state seen in MGTS.

21.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

22.
arXiv (CS.LG) 2026-06-17

Provably Efficient Regularized Online RLHF with Generalized Bilinear Preferences

arXiv:2602.23116v3 Announce Type: replace Abstract: We consider the problem of regularized best-response max-regret minimization in online RLHF under general preferences and bandit feedback. While various regularizers are utilized to robustify alignment, known polylogarithmic regret guarantees remain heavily specific to KL. To investigate whether such fast rates extend beyond KL, we adopt the Generalized Bilinear Preference Model (GBPM) – capturing intransitive preferences over $d$-dimensional item-wise features via a rank-$2r$ skew-symmetric matrix – to isolate the impact of generic regularization. Crucially, under GBPM, we prove that the dual gap of any greedy policy is bounded by the squared estimation error, derived using only strong convexity and skew-symmetry. Under a feature coverage assumption, we establish a generic polylogarithmic regret of $\tilde{\mathcal{O}}(\eta d^4 C_{\min}^{-1} (\log T)^2 \wedge d^2 C_{\min}^{-1/2} \sqrt{T})$ with Greedy Sampling, and a dimension-wise improved regret (for well-conditioned arm-sets) of $\tilde{\mathcal{O}}(C_{\min}^{-2} \sqrt{\eta r T} \wedge r^{1/3} C_{\min}^{-4/3} T^{2/3})$ with Explore-Then-Commit, where $\eta^{-1}$ is the regularization coefficient, $T$ is the time horizon, and $C_{\min}$ is an arm-set dependent quantity. This demonstrates that ``fast'' regrets are not KL-specific, but rather a fundamental consequence of generic strongly convex geometry.

23.
arXiv (CS.CV) 2026-06-16

BBR-Net: Boundary-Balanced Replay for Continual Medical Image Segmentation

Continual learning for medical image segmentation remains challenging under domain shift because replay-based methods often preserve appearance information without explicitly modeling anatomical structure. This study investigates whether structural consistency governs knowledge retention in continual cardiac ultrasound segmentation. We propose the Boundary-Balanced Replay Network (BBR-Net), which selects replay samples using boundary-aware priority and class balance to preserve anatomically informative regions. The method is evaluated on CAMUS and CardiacNet under forward (CAMUS to CardiacNet) and reverse (CardiacNet to CAMUS) task orders. In the forward setting, BBR-Net retains source-task performance close to an offline joint-training reference, while markedly reducing catastrophic forgetting and preserving competitive target-task adaptation. Ablation results show that boundary-aware prioritization contributes to retention and improves the balance between source-task preservation and target-task adaptation when combined with class-aware sampling. In contrast, the reverse setting reveals that structure-aware replay fails when initial representations are learned from noisy and structurally inconsistent data. To isolate this effect, we conduct a controlled structural perturbation analysis by progressively corrupting source-task boundaries while keeping the dataset, architecture, and training protocol fixed. Forgetting increases consistently as structural reliability decreases, suggesting that replay effectiveness is strongly influenced by the quality of stored structural information, rather than by memory capacity alone. These findings indicate that preserving anatomical structure under domain shift is a central factor in continual medical image segmentation, and that replay mechanisms should account for structural reliability to support robust knowledge retention.

24.
arXiv (CS.AI) 2026-06-18

An In-depth Study of LLM Contributions to the Bin Packing Problem

arXiv:2510.27353v2 Announce Type: replace Abstract: Recent studies have suggested that Large Language Models (LLMs) could provide interesting ideas contributing to mathematical discovery. This claim was motivated by reports that LLM-based genetic algorithms produced heuristics offering new insights into the online bin packing problem under uniform and Weibull distributions. In this work, we reassess this claim through a detailed analysis of the heuristics produced by LLMs, examining both their behavior and interpretability. Despite being human-readable, these heuristics remain largely opaque even to domain experts. Building on this analysis, we propose a new class of algorithms tailored to these specific bin packing instances. The derived algorithms are significantly simpler, more efficient, more interpretable, and more generalizable, suggesting that the considered instances are themselves relatively simple. We then discuss the limitations of the claim regarding LLMs' contribution to this problem, which appears to rest on the mistaken assumption that the instances had previously been studied. Our findings instead emphasize the need for rigorous validation and contextualization when assessing the scientific value of LLM-generated outputs.

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arXiv (CS.CV) 2026-06-17

MOCHI: Motion Enhancement of Collaborative Human-object Interactions

Collaborative human-object interaction shows dynamic and complex movements that require mutual anticipation and continuous adjustment between participants and the shared object. Modeling such collaborative multi-human object interaction (MHOI) scenarios requires high-quality data acquisition as a foundational step; however, this is challenging due to the inherent complexity of MHOI where human-human and human-object interactions occur simultaneously. Such complexity leads to noisy MHOI captures characterized by several artifacts: contact misalignment between hands and objects, motion jitter and temporal inconsistencies in the captured sequences, and missing or incomplete finger-level articulation details. To address these challenges, we present MOCHI (MOtion Enhancement of Collaborative Human-object Interactions), a two-stage framework for enhancing noisy MHOI data. Our approach first generates physically plausible hand grasps through optimization from noisy body input, producing grasps that are both physically plausible and semantically consistent with the body pose, where these optimized grasps are extended into complete hand-object interaction sequences. Consequently, the full-body motion for all participants are refined through a diffusion-based noise optimization framework that uses single-person motion priors. During the optimization process, we introduce optimization objectives to encode human-object and human-human interaction information within these single-person priors. Experimental results demonstrate the effectiveness of our pipeline across diverse MHOI data, either acquired by existing capture methods or synthesized by generative models. We further show robustness of our system across varying numbers of participants and types of interactions, and demonstrate various applications including keyframe-based MHOI creation and data augmentation through varying object geometries.