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01.
arXiv (CS.AI) 2026-06-11

Improving Detection of Rare Nodes in Hierarchical Multi-Label Learning

arXiv:2602.08986v2 Announce Type: replace-cross Abstract: In hierarchical multi-label classification, a persistent challenge is enabling model predictions to reach deeper levels of the hierarchy for more detailed or fine-grained classifications. This difficulty partly arises from the natural rarity of certain classes (or hierarchical nodes) and the hierarchical constraint that ensures child nodes are almost always less frequent than their parents. To address this, we propose a weighted loss objective for neural networks that combines node-wise imbalance weighting with focal weighting components, the latter leveraging modern quantification of ensemble uncertainties. By emphasizing rare nodes rather than rare observations (data points), and focusing on uncertain nodes for each model output distribution during training, we observe improvements in recall by up to a factor of five on benchmark datasets, along with statistically significant gains in $F_{1}$ score. We also show our approach aids convolutional networks on challenging tasks, as in situations with suboptimal encoders or limited data.

02.
arXiv (CS.AI) 2026-06-12

Learning What to Remember: Observability-Safe Memory Retention via Constrained Optimization for Long-Horizon Language Agents

arXiv:2606.10616v2 Announce Type: replace Abstract: Long-horizon language agents accumulate observations, reasoning traces, and retrieved facts that exceed their finite context windows, making memory retention a fundamental resource-allocation problem. Existing memory systems improve management through heuristic scoring, retrieval optimization, or learned compression, but largely treat retention as a local decision problem and do not explicitly model its long-term consequences under realistic observability constraints. To fill this gap, we formulate memory retention as a constrained stochastic optimization problem with explicit budget feasibility, evidence utility, and delayed costs including miss penalties, reacquisition delays, and stale-information risk. We then propose OSL-MR (Observability-Safe Learning for Memory Retention), a novel framework that enforces a strict separation between online-observable features and offline-available supervision (OAS). OSL-MR combines an evidence learner trained from realized evidence supervision with a Mixed-Score heuristic that serves both as a deployable online-safe baseline and as a structured inductive prior for learning. The resulting policy learns query-conditioned evidence value directly from interaction data while remaining deployable under the same observability constraints. Experiments on LOCOMO and LongMemEval show that OSL-MR consistently outperforms recency-based methods, Generative Agents-style scoring, and other heuristic baselines, particularly under tight memory budgets. The Mixed-Score prior further improves precision while preserving recall, and sensitivity analysis demonstrates robustness across a wide range of cost configurations.

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

Temporal Preference Optimization for Unsupervised Retrieval

arXiv:2606.17664v1 Announce Type: cross Abstract: Unsupervised dense retrievers offer scalability by learning semantic similarity from unlabeled documents via contrastive learning, but they struggle to capture the temporal relevance, retrieving semantically related but temporally misaligned documents-an important aspect when a document collection spans multiple time periods (e.g., retrieving documents from 2018-2025 for "Who is the president in 2019?" introduces temporal ambiguity). Existing methods rely on supervised training with explicit timestamps, which are not always feasible. We propose TPOUR (Temporal Preference Optimization for Unsupervised Retriever), which uses our novel training method Temporal Retrieval Preference Optimization (TRPO). TRPO reinterprets preference learning in the temporal dimension, guiding the retriever to favor temporally aligned documents. TPOUR further generalizes to unseen time periods via interpolation in a learned time embedding, enabling continuous temporal alignment. Experiments on temporal information retrieval (T-IR), TPOUR outperforms both unsupervised and supervised baselines. Compared to Qwen-Embedding-8B, despite being about 72.7x smaller, TPOUR Contriever improves average nDCG@5 by +4.04 (+12.15%) on explicit and +4.98 (+15.21%) on implicit queries. We provide our code at https://github.com/agwaBom/TPOUR.

04.
arXiv (CS.CV) 2026-06-24

ObsGraph: Hierarchical Observation Representation for Embodied Reasoning and Exploration

Embodied reasoning and exploration are increasingly considered crucial abilities for robots operating in complex and unfamiliar environments. To accomplish tasks in such settings, an agent must identify and acquire the information necessary for the task through exploration. We propose ObsGraph, an observation-centric hierarchical scene graph that unifies scene representation, retrieval, and exploration. It retains visual evidence and organizes it into room-view-object layers: rooms provide coarse semantic anchors, views preserve contextual object covisibility, and objects store fine-grained details. On top of this representation, we perform coarse-to-fine hierarchical retrieval under a bounded budget, and crucially use retrieval outcomes to structure the exploration candidate space–activating room-level exploration, view refinement, or frontier exploration–thereby tightly coupling representation, retrieval, and adaptive multi-scale exploration. Experiments across embodied reasoning and exploration benchmarks demonstrate improved success and efficiency, highlighting the benefits of structured scene representation and more targeted information gathering driven by identified evidence gaps.

05.
arXiv (CS.CV) 2026-06-25

V-Zero: Answer-Label-Free On-Policy Distillation with Contrastive Evidence Gating for Fine-Grained Visual Reasoning

Fine-grained visual reasoning requires multimodal large language models (MLLMs) to identify task-relevant visual evidence and ground their reasoning in local image regions. Existing agentic methods typically rely on reinforcement learning with verifiable rewards or supervised fine-tuning on large-scale annotated reasoning traces, leading to costly exploration, hand-designed verification rules, or heavy dependence on textual supervision. A natural way to avoid such external answer labels is to learn from trajectories sampled by the student itself, which points to On-Policy Distillation (OPD). To understand what OPD can and cannot provide for visual reasoning, we revisit it as negative-free stop-gradient alignment. This perspective shows that, although OPD provides effective token-level correction, its ceiling is constrained by the absence of trajectory-level discrimination. Motivated by these observations, we propose V-Zero, an answer-label-free framework for visual reasoning with contrastive evidence gating. V-Zero uses no annotated textual answer labels; instead, during training it pairs a question-relevant regional crop with a negative visual view to evaluate student-sampled trajectories and gate dense token-level distillation. Experiments on multiple visual reasoning benchmarks show that V-Zero consistently improves fine-grained visual reasoning while preserving strong generalization. Notably, V-Zero is more than 5$\times$ faster than previous supervised fine-tuning methods and more than 10$\times$ faster than reinforcement learning baselines. Code and dataset will be released at https://github.com/eVI-group-SCU/V-Zero

06.
arXiv (CS.LG) 2026-06-25

When Does Synthetic Data Augmentation Improve Score-Based Imbalanced Classification?

arXiv:2606.26053v1 Announce Type: cross Abstract: Synthetic data augmentation is widely used to mitigate class imbalance, but its theoretical effects on score-based classification remain poorly understood. This paper develops a framework for characterizing when synthetic minority augmentation can improve threshold-integrated and threshold-optimized metrics, including AUROC, AUPRC, best-threshold balanced accuracy, and best-threshold \(\F_1\) score. We separate the effect of augmentation into two components: a change in effective class weighting and a discrepancy between the synthetic and true minority distributions. Under well-specified score models, the raw estimator already targets the likelihood-ratio ordering, which is population-optimal for the metrics considered. Consequently, augmentation cannot provide a fundamental population-level improvement beyond possible finite-sample variance reduction, and may introduce additional bias through synthetic distributional error. We further establish minimax lower bounds showing that the raw estimator already achieves the optimal metric-regret rate in the well-specified regime. Under misspecification, however, augmentation can play a qualitatively different role: by changing the effective class balance, it can alter the restricted-class projection and correct ranking errors induced by the raw imbalanced objective. We provide explicit improvement bounds quantifying the roles of approximation error, finite-sample estimation error, and synthetic distributional error. Simulation studies corroborate the theory, demonstrating limited gains under well-specification and nontrivial but nonmonotone improvements under misspecification.

07.
arXiv (quant-ph) 2026-06-19

Quantifying Imaginarity in Neutrino Systems

arXiv:2412.01871v2 Announce Type: replace-cross Abstract: It is a fundamental question why quantum mechanics employs complex numbers rather than solely real numbers. In this work, we conduct the first analysis of imaginarity quantification in neutrino flavor and spin-flavor oscillations. As quantum systems in coherent superposition, neutrinos are ideal candidates for quantifying imaginarity within the resource theoretic framework, using measures such as the $\ell_1$-norm and the relative entropy of imaginarity. We show that in the case of two-flavor mixing, these measures of imaginarity are nonzero. The measures of imaginarity reach their extreme values when the probabilistic features of quantum theory are fully maximized, i.e., both the transitional and survival probabilities are approximately equal. Our study reveals that the imaginarity, as a resource, can be harnessed not solely from the presence of a complex phase in the mixing matrix but also from the intrinsic quantum dynamics of time evolution itself. We further extend our analysis to explore the dynamics of three-flavor neutrino mixing, incorporating the effects of a nonzero $CP$ phase.

08.
arXiv (CS.CL) 2026-06-11

Beyond Third-Person Audits: Situated Interaction Auditing for User-Centered LLM Bias Research

Research on bias in large language models (LLMs) has predominantly focused on third-person audits, which study how models represent or evaluate demographic groups as external subjects. However, this paradigm overlooks a structural blind spot because the user is absent from the audit. In practice, LLMs are used in open-ended, personal interactions, during which the model implicitly represents the user and adjusts its responses accordingly. When identical requests yield different responses depending on who is asking, bias manifests not in how the model describes others but in how it treats its interlocutor. We propose Situated Interaction Auditing (SIA), a user-centered framework for studying how user profile signals – implicit sociodemographic markers, writing style, and stated identity – systematically shape LLM response quality, content, and tone. We demonstrate the framework through a case study that intersects gender and socioeconomic status signals across multiple task domains and outline a research agenda for SIA as a new mission for natural language processing.

09.
arXiv (CS.AI) 2026-06-15

A fully GPU-based workflow for building physics emulators of hypersonic flows

arXiv:2606.13742v1 Announce Type: cross Abstract: The ability to resolve complex physical phenomena with high fidelity and at low computational cost is central to addressing key challenges in modern engineering. A prime example lies in hypersonic flows, where the precise prediction of the full flowfield topology, in particular with respect to shock wave location and intensity, is critical. Yet supersonic and hypersonic flows continue to be a stumbling block for traditional reduced-order models and neural emulators that struggle to capture steep gradients in flow states with physical consistency in applications of industrial relevance. To that end, we introduce a fully GPU based workflow that integrates accelerated data generation with the training of neural emulators augmented by uncertainty quantification and physics-aware refinement. Our workflow is enabled by a differentiable high-fidelity solver (JAX-Fluids) which we employ for rapid dataset creation and residual-based improvement of the neural emulator to enhance physical consistency. Building on this framework, we first present a suite of model architectures and analyze their scaling behavior to expose their strengths and shortcomings. We then show that residual-based refinement enables training on cases where only mesh and input parameters are available, substantially reducing residuals and improving physical consistency. Together, differentiable simulation and residual-based refinement yield physics emulators that remain reliable beyond their training distribution, a key requirement for deploying surrogates in real-world engineering design loops.

10.
arXiv (math.PR) 2026-06-16

Experimentation for Different Scheduling Policies on Queues: Mixed Differences-in-Q Estimators Based on Little's Law

arXiv:2605.29641v2 Announce Type: replace-cross Abstract: In data centers, tasks are dispatched to various servers to evenly distribute the workload. When a data center considers implementing a new scheduling algorithm, it typically conducts an A/B test prior to deployment to assess the real-world impact of this new method. However, a straightforward A/B test might be interfered with so-called ``Markovian'' interference. We utilized the Differences-in-Q estimator, as developed by Farias et al. (2022), and introduced mixed Differences-in-Q estimators grounded in Little's Law. We show that our A/B testing methods significantly reduce bias and variance when testing various scheduling policies. Extensive simulations were conducted under scenarios like non-stationary arrival rates, heterogeneous service rates, and communication delays. These simulations highlight the robustness and efficacy of our A/B testing approach.

11.
Nature (Science) 2026-06-17

The ancestors of eukaryotic cells contained a mix of genes from various microbes

作者: 未知作者

Reconstruction of the ancestral gene repertoire of eukaryotic cells reveals traces of a series of close, long-term interactions with diverse microorganisms, and a role of viruses in gene exchange. The findings challenge the view that eukaryotic cells evolved from a simple merger of just two organisms. A series of gene-transfer events might have taken place in complex microbial communities.

12.
arXiv (CS.CV) 2026-06-16

Learning a Sampling-Free Variational DNN Plugin from Tiny Training Sets to Refine OOD Segmentation With Uncertainty Estimation

Deep neural networks (DNNs) frequently fail to generalize to out-of-distribution (OOD) medical images because of variations in scanners and acquisition protocols. Retraining DNN models to address these distribution shifts is often impractical due to the high cost of acquiring and annotating new medical datasets. To address this, we introduce VarDeepPCA, a novel lightweight variational DNN framework designed to restore/refine degraded segmentation maps by leveraging intrinsic geometric priors. Unlike existing approaches that require target-domain data or extensive pre-training, our VarDeepPCA explicitly learns a distribution of valid anatomical geometries using only small in-distribution (ID) datasets. Theoretically, our novel variational learning framework leverages a reinterpretation of the softmax mapping to implicitly perform exact distribution modeling, thereby enabling computationally efficient, sampling-free learning and inference. This also enables VarDeepPCA to provide uncertainty estimates associated with its restored segmentation maps. We empirically validate our framework across 4 distinct clinical applications, using 14 publicly available datasets, involving segmentation of the myocardium, neuroretinal rim, prostate, and fetal head. Comparisons against 15 existing methods demonstrate that VarDeepPCA consistently restores segmentation maps produced by the existing methods on OOD data to (i) significantly improve anatomical plausibility of geometries and clinical utility of the segmentations, and (ii) significantly reduce errors, without needing any more training data than that used by existing methods.

13.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

作者:

Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation1–3. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein–protein interactions and coordinated intracellular trafficking4–13. Despite its central role in immunity and relevance as therapeutic target14, the sequence elements that govern STING (in)activation in cells remain incompletely understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2′3′-cGAMP15–18 or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts. A massively parallel assay systematically charts the sequence-function landscape of the STING signalling protein, and the findings define molecular principles that tune STING activity and show its functional potential across immune contexts.

14.
arXiv (CS.AI) 2026-06-24

HiPath: Hierarchical Vision-Language Alignment for Structured Pathology Report Prediction

arXiv:2603.19957v2 Announce Type: replace-cross Abstract: Pathology reports are structured, multi-granular documents encoding diagnostic conclusions, histological grades, and ancillary test results across one or more anatomical sites; yet existing pathology vision-language models (VLMs) reduce this output to a flat label or free-form text. We present HiPath, a lightweight VLM framework built on frozen UNI2 and Qwen3 backbones that treats structured report prediction as its primary training objective. Three trainable modules totalling 15M parameters address complementary aspects of the problem: a Hierarchical Patch Aggregator (HiPA) for multi-image visual encoding, Hierarchical Contrastive Learning (HiCL) for cross-modal alignment via optimal transport, and Slot-based Masked Diagnosis Prediction (Slot-MDP) for structured diagnosis generation. Trained on 749K real-world Chinese pathology cases from three hospitals, HiPath achieves 68.9% strict and 74.7% clinically acceptable accuracy with a 97.3% safety rate, outperforming all baselines under the same frozen backbone. Cross-hospital evaluation confirms generalisation with only a 3.4pp drop in strict accuracy while maintaining 97.1% safety.

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

Skill-Guided Continuation Distillation for GUI Agents

arXiv:2606.18890v1 Announce Type: new Abstract: Improving GUI agents typically relies on behavior cloning on expert trajectories. However, as the current policy deviates from the expert policy, it inevitably encounters policy-induced off-trajectory states during closed-loop execution, i.e., states that fall outside the expert trajectories. Since expert trajectories provide no demonstrations for these unseen states, such states receive no effective supervision, leaving the policy unable to select the correct action. To close this supervision gap, we propose Skill-Guided Continuation Distillation (SGCD), an iterative self-improvement framework. SGCD first runs the plain policy without skill guidance for a few steps to reach realistic off-trajectory states. From these states, a skill-guided policy then completes the task and produces successful continuations, which are mixed with expert trajectories to supply supervision over policy-induced off-trajectory states. The skills are extracted from both successful and failed rollouts, consisting of Continuation Plans, Critical Targets, Failure Traps, and Success Criteria. On OSWorld-Verified, SGCD improves the success rate of three base models from the low-30\% range to over 50\%, demonstrating its effectiveness and generality.

16.
arXiv (math.PR) 2026-06-11

Marked random graphs with given degree sequence: large deviations on the local topology

arXiv:2401.00351v2 Announce Type: replace Abstract: We investigate the behavior of the empirical neighborhood distribution of marked graphs in the framework of local weak convergence. Here we extend known results by considering uniform random graphs with given degree sequences and i.i.d. marks on half-edges and vertices. We establish a large deviation principle for such families of empirical measures. The proof builds on Bordenave and Caputo's seminal 2015 paper, and Delgosha and Anantharam's 2019 introduction of BC entropy, relying on combinatorial lemmas that allow one to construct suitable approximations of measures supported on marked trees. Possible applications of these results are in the study of interacting diffusions on top of random graphs.

17.
arXiv (quant-ph) 2026-06-19

Recursive perturbation approach to time-convolutionless master equations: Explicit construction of generalized Lindblad generators for arbitrary open systems

arXiv:2506.04095v2 Announce Type: replace Abstract: We develop a recursive perturbative expansion for the time-convolutionless (TCL) generator of an open quantum system in a generalized Lindblad form. This formulation provides a systematic approach to derive the generator at arbitrary order while preserving a Lindblad-like structure, without imposing assumptions on the system or environment beyond an initially uncorrelated state. The generator is written, at all orders, in a canonical form, which also corresponds to the minimal dissipation condition, which uniquely specifies the decomposition of the generator into Hamiltonian and dissipative contributions. To validate the method and show its effectiveness in addressing non-Markovian dynamics and strong-coupling effects, we compute the generator explicitly up to fourth order.

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

Comparing Commercial Depth Sensor Accuracy for Medical Applications

Depth estimation has numerous medical and surgical applications. We benchmark four depth sensors on a porcine bone specimen, a porcine belly specimen, and a silicone kidney phantom using stylus-sampled references. These objects contain several real-world challenges, including homogeneous surfaces, specular surfaces, and subsurface scattering. The comparison includes stereo, structured-light, and time-of-flight sensors at a distance of approximately 50 cm. Specifically, the Intel RealSense D405 (Intel RealSense, United States), PMD Flexx2 (pmdtechnologies, Germany), Stereolabs ZED 2i (Stereolabs, France), and Zivid 2M+ 60 (Zivid, Norway) are compared. The Zivid 2M+ 60 performed best across all objects and metrics considered in this work. The ZED ranked second for real tissue, but last on the phantom.

20.
arXiv (CS.AI) 2026-06-24

AI Tokenomics: The Economics of Tokens, Computation, and Pricing in Foundation Models

作者:

arXiv:2606.24616v1 Announce Type: new Abstract: Tokens have become the practical accounting unit for modern foundation model services, linking information processing, computation, memory use, energy expenditure, pricing, and economic value. This paper develops a framework for AI tokenomics: the study of how tokens are generated, consumed, priced, allocated, and optimized across AI systems. We connect token-level technical costs to workflow-level production functions, enterprise resource allocation, measurement and instrumentation methods, and emerging market-design questions. The framework shows that token expenditure and economic value are distinct: value depends on marginal productivity, workflow position, hidden reasoning activity, risk, and downstream propagation effects. The paper concludes by identifying open research directions in hidden-token measurement, empirical calibration, token productivity, dynamic allocation, and token-based markets.

21.
arXiv (CS.CL) 2026-06-25

Constituency Structure over Eojeol in Korean Treebanks

The design of Korean constituency treebanks raises a central representational question concerning the choice of terminal units. Although Korean words are morphologically complex, treating morphemes as constituency terminals can obscure the distinction between word-internal morphology and phrase-level syntactic structure, and can create mismatches with eojeol-based dependency resources. This paper argues for an eojeol-based constituency representation, with morphological segmentation and fine-grained POS information encoded in a separate, non-constituent layer. A comparative analysis shows that, under explicit normalization assumptions, the Sejong, Penn Korean, and KAIST treebanks can be compared over a shared eojeol-based constituency backbone. Building on this result, we outline an eojeol-based annotation scheme that preserves interpretable constituency, supports cross-treebank comparison and constituency-dependency alignment, and provides a surface-form terminal layer for future end-to-end Korean constituency parsing.

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

ActWorld: From Explorable to Interactive World Model via Action-Aware Memory

Interactive world models aim to simulate environment dynamics under real-time user actions. However, their action vocabulary is largely confined to navigation: most actions correspond to motion (e.g., walk, turn, look around), while interaction with objects in the scene (e.g., pick up plates, open doors, or trigger physical responses) is either absent, restricted to game domains, or relegated to prompt-to-full-video scenarios. The resulting worlds are visually explorable but not truly actionable. In this work, we present ActWorld, an interactive world model that extends prior navigation-centric generators to support mid-rollout object interaction within a chunk-autoregressive framework. We argue that the navigation-interaction gap stems from two bottlenecks. First, a data bottleneck: the lack of human-object interaction data with accurate, dense labels. Second, a memory bottleneck: recency-biased history compression in existing world models discards the event-transition frames that causally determine subsequent object states, leading to an action-forgetting pathology. On the data side, we construct a 100K interaction video dataset, each annotated with per-chunk captions via chain-of-thought reasoning. On the model side, we introduce a hierarchical action-aware memory design that routes history compression by interaction importance, complemented by a persistent memory bank that maintains event-update and object-identity tokens across long rollouts. Experiments show that ActWorld supports both flexible navigation and rich object interaction within a single model, substantially improving interaction fidelity over navigation-only baselines without sacrificing viewpoint control. Project page is available at https://interactwm.github.io/ActWorld.

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

Infant Spontaneous Movement Noise Improves Exploration in Deep RL

arXiv:2606.16590v1 Announce Type: cross Abstract: Exploration in deep reinforcement learning (RL) is commonly implemented as temporally uncorrelated white noise. However, recent works show that temporally correlated colored noise can improve exploration efficiency by producing smooth trajectories with better coverage of the state space. We inquire whether action noise inspired by infant spontaneous movements can also improve exploration in deep RL. We find that the power spectral densities of babies' end-effector velocities follow a colored noise process where the spectral exponent increases with age. Inspired by this developmental pattern, we introduce a mechanism that progressively increases the temporal auto-correlation of exploration noise during RL training, matching the infant statistics. Experiments across several RL environments show that infant-inspired noise produces structured exploratory behavior and can improve learning efficiency compared to conventional exploration strategies. These findings suggest that human motor and cognitive development can provide useful guidance for designing learning mechanisms in artificial agents. Our code is available at https://github.com/trieschlab/baby-noise-rl.

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

Equivariant Representation Learning via Class-Pose Decomposition

arXiv:2207.03116v4 Announce Type: replace Abstract: We introduce a general method for learning representations that are equivariant to symmetries of data. Our central idea is to decompose the latent space into an invariant factor and the symmetry group itself. The components semantically correspond to intrinsic data classes and poses respectively. The learner is trained on a loss encouraging equivariance based on supervision from relative symmetry information. The approach is motivated by theoretical results from group theory and guarantees representations that are lossless, interpretable and disentangled. We provide an empirical investigation via experiments involving datasets with a variety of symmetries. Results show that our representations capture the geometry of data and outperform other equivariant representation learning frameworks.

25.
arXiv (CS.CL) 2026-06-24

A specialized reasoning large language model for accelerating rare disease diagnosis: a randomized AI physician assistance trial

Rare diseases affect millions of individuals worldwide, yet timely diagnosis remains a major public health challenge due to scarcity of specialized clinical expertise. While large language models (LLMs) show promise to support rare disease diagnosis, current models are constrained by insufficient clinical deployability, limited clinically grounded evidence, and scarcity of training data. Here we present RaDaR (Rare Disease navigatoR), an open-source, compact reasoning LLM (32B parameters) for rare disease diagnosis. RaDaR was trained with 49,170 publicly available free-text cases and 104,666 synthetic cases with reasoning-enhanced training. RaDaR showed the strongest performance among evaluated open-source models, including the 671B DeepSeek-R1, across public benchmarks and four external validation centers. In a retrospective cohort, RaDaR prioritized the final diagnosis before documented clinical suspicion in 61.06 percent of cases, corresponding to a potential lead time of 1.87 months and 50.18 percent of the within-center interval. In a randomized physician-assistance trial, RaDaR assistance improved physicians' rare-disease diagnostic accuracy by 21.44 percentage points compared with internet search alone. Synthetic-data ablations suggested that phenotype-anchored narratives provide useful training signal for long-tail rare diseases, with a monotonic scaling trend within the tested data range. Together, RaDaR and its development and validation framework provide a deployable rare-disease reasoning model and a reproducible development framework for diagnostic AI under data scarcity.