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01.
arXiv (CS.CL) 2026-06-18

ToolGrad: Efficient Tool-use Dataset Generation with Textual "Gradients"

Prior work synthesizes tool-use LLM datasets by first generating a user query, followed by complex tool-use annotations like depth-first search (DFS). This leads to inevitable annotation failures and low efficiency in data generation. We introduce ToolGrad, an agentic framework that inverts this paradigm. ToolGrad first constructs valid tool-use chains through an iterative process guided by textual "gradients", and then synthesizes corresponding user queries. This "answer-first" approach led to ToolGrad-500, a dataset generated with more complex tool use, lower cost, and almost 100% pass rate. Experiments show that ToolGrad models outperform those trained on expensive baseline datasets and proprietary LLMs. The ToolGrad source code, dataset, and models are available at https://github.com/zhongyi-zhou/toolgrad.

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

Rigel: Reverse-Engineering the Metal 4.1 Tensor Compute Path on the Apple M4 Max GPU

Apple's Metal 4.1 exposes a tensor compute path: the Metal Performance Primitives (MPP) matmul2d operation over cooperative_tensor fragments, whose interface is documented but whose hardware behavior is deliberately hidden. The specification states which data-type rows are supported, never whether they are hardware-accelerated, where the operation physically executes, what its accumulator width is, or how it partitions matrix fragments across threads. We present Rigel, an empirical characterization of this path on a single Apple M4 Max (a pre-neural-accelerator generation). Using a checksum-gated, provenance-tracked microbenchmark harness, Rigel recovers eleven facts the v4.1 specification hides or contradicts. The headline finding: the Metal 4.1 fp8 (E4M3) matmul2d is emulated, not accelerated: it sustains 0.94x the throughput of fp16 despite reading half the operand bytes, so on M4 it is a memory-footprint feature, not a performance feature. We further show, via a three-signal triangulation (throughput ceiling, comparison against simdgroup_matrix, and per-rail power attribution), that matmul2d executes entirely on the GPU shader cores with no dedicated matrix datapath and no evidence of Apple Neural Engine routing; that it accumulates in >=fp32; and we reconstruct the opaque 8x8 cooperative_tensor fragment layout Apple documents nowhere. Acting on the characterization, a hand-fused GEMM + bias + GELU kernel beats the decomposed path by +6.5-12.9% in the cache-resident regime. All findings are reproducible from committed MIT-licensed code and per-cell CSVs.

03.
arXiv (CS.CV) 2026-06-18

Investigation of Neural Network Methods for Reconstruction and Classification of Texture Images Under Conditions of Incomplete Information

The automated analysis of heterogeneous natural textures is frequently hindered by physical damage and data loss, presenting a significant challenge to computer vision. While deep learning has shown success in controlled environments, its application to complex geological materials under conditions of incomplete information remains underexplored. This study presents an integrated framework for the inpainting and classification of high-resolution core sample images. We propose an end-to-end pipeline that utilizes object detection for sample segmentation, followed by image inpainting using Generative Adversarial Networks (GANs) with Contextual Residual Aggregation (CRA) to reconstruct missing high-frequency details. Subsequently, we evaluate the performance of modern Transformer-based (Swin, ViT) and CNN architectures on the reconstructed data. Our experiments revealed a critical divergence between reconstruction quality and downstream utility: despite high structural fidelity (PSNR 28.7~dB, FID 74.01), classification accuracy plateaued at 53\%. To improve minority-class detection, we propose a confidence-based hybrid ensemble that raises MCA from 48\% to 58\%. These results highlight the limitations of current state-of-the-art generative models, which may produce visually plausible but semantically ambiguous features ("hallucinations") that confound classifiers. This work provides insights into the dependencies between image reconstruction quality and classification performance, offering a reproducible baseline for future research in non-destructive testing and material science. Given that cross-well accuracy remains in the 49–53\% range, we position the resulting system as a decision-support and screening tool for lithofacies interpretation rather than as a fully autonomous classifier. The code is available at https://github.com/GalymzhanAbdimanap/Lithology_recognition

04.
arXiv (CS.LG) 2026-06-15

How Task Structure Limits Multi-Agent Success: An Information-Theoretic Analysis

arXiv:2606.13733v1 Announce Type: cross Abstract: Multi-agent systems (MAS) were expected to overcome the limitation of single-agent systems (SAS) through collaboration. However, under typicality conditions on the task's constraint graph and bounded inter-agent communication, we prove that the success probability of a MAS is closely tied to the connectivity of task constraints, where each agent has limited information-processing capacity. Specifically, the success probability decays exponentially with an information bottleneck that emerges from partitioning the task's constraint graph among agents. We define this quantity as the minimum cut cost $C_{\min}$ of the potential constraint graph of each task. This information-theoretic bound applies to both open systems with external feedback and closed systems without. We validate our theory on both synthetic experiments and real-world empirical data from SWE-bench submissions. From our framework, effective MAS design should incorporate task-inherent constraints alongside engineering optimization, and when $\Cmin$ is high, practitioners should restructure tasks rather than simply scaling agents or communication.

05.
arXiv (CS.AI) 2026-06-24

AI-Driven Analytics of Team-Teaching Talk: Acoustic Patterns across Experience, Cohorts and the Learning Design

arXiv:2606.09831v2 Announce Type: replace-cross Abstract: As classroom cohorts expand, team teaching is increasingly used to integrate the expertise and pedagogical perspectives of multiple teachers. Yet, there is limited empirical understanding of how team teaching unfolds in practice, particularly regarding differences in teachers' contributions across experience levels, student cohorts, and learning task design. Prior research on team teaching has largely relied on retrospective self-reports or small-scale observations, offering limited insight into the micro-level processes through which team teaching is enacted. Teacher talk offers a scalable lens on these processes. While research in individual teaching contexts shows that acoustic features of speech (e.g., voice quality, intonation, and loudness) can shape student learning, evidence from team-teaching settings remains scarce. Moreover, capturing such features through manual observation or transcription is especially challenging in team-teaching classrooms, where multiple teachers speak across extended sessions and spatial locations, limiting scalability without automation. Grounded in spatial pedagogy theory and team-teaching research, this paper presents an AI-based speech processing approach to analyse classroom talk in team-teaching settings. We analysed 36 recorded undergraduate and postgraduate sessions involving 12 teachers. Spatial pedagogy behaviours were coded and acoustic features extracted to examine variation across teachers' experience, student cohorts, and the learning task design. The results reveal systematic differences, most notably in loudness dynamics: high-experience teachers, undergraduate classes and collaborative learning tasks exhibited greater loudness variation, suggesting more frequent modulation of volume to foreground key information and support classroom interaction and engagement.

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

Reasoning as Attractor Dynamics: Latent Memory Retrieval via Gibbs-Weighted Energy Minimization

arXiv:2606.24543v1 Announce Type: new Abstract: Large Language Models (LLMs) are traditionally viewed as autoregressive generators. However, from the perspective of collective computation, they function as high-dimensional Dense Associative Memories that store complex reasoning patterns as latent attractors. In this work, we investigate the energy landscape of mathematical reasoning. We posit that correct reasoning chains correspond to deep, wide attractor basins ("flat minima") in the model's output distribution, whereas hallucinations manifest as sharp, unstable local minima. To exploit this geometry, we introduce a retrieval mechanism based on a Gibbs measure of the trajectory's spectral entropy. By sampling multiple reasoning paths and weighting them by their inverse energy ($P \propto e^{-\beta E}$), we approximate the equilibrium distribution of the associative memory, effectively ``relaxing'' the system into a robust solution. Empirically, this physics-inspired mechanism improves Microsoft Phi-3.5 performance on GSM8K by 5.38\% (84.7\% $\to$ 90.1\%), demonstrating that inference is better modeled as a dynamic settling process into an attractor basin rather than greedy next-token prediction.

07.
Nature (Science) 2026-06-17

The EU needs to back its ambition to end animal testing with cash

作者: 未知作者

The European Union has declared that it wants to stop using animals in chemical safety testing. Its goal will need a timeline and a serious funding commitment. The European Union has declared that it wants to stop using animals in chemical safety testing. Its goal will need a timeline and a serious funding commitment.

08.
arXiv (CS.CL) 2026-06-17

AIPatient Arena: EHR-grounded evaluation of large language models in end-to-end clinical consultation workflows

Large language models (LLMs) are increasingly considered for use in clinical consultation tasks, yet most medical evaluations remain static, single-turn, or narrowly outcome-based, limiting their ability to reflect the sequential, uncertain, and interactive nature of real-world care. Here, we propose AIPatient Arena, an EHRs-grounded evaluation framework for assessing the clinical utility of LLMs across eight dimensions of clinical competence. The framework integrates EHR data into patient-specific knowledge graphs, enabling multi-turn physician-patient interactions. We applied AIPatient Arena on a primary cohort of 437 patients and two out-of-distribution validation cohorts of 119 and 67 patients. We observe that LLMs performed well in medical interview questioning skills (QS; mean scores, 4.43-4.99/5), ethical and professional conduct (ET; 4.38-4.93/5), and clarity and transparency of clinical explanations (EX; 3.80-4.72/5). Performance was moderate in information integration (II; 3.19-4.21/5) and medication safety and justification (MS; 3.13-3.78/5), but persistent weaknesses were observed in handling of ambiguous patient responses (HR; 2.57-3.32/5), information coverage (IC; 2.08-3.02/5), and diagnostic accuracy and reasoning (Dx; 2.63-3.55/5). Process-based evaluation revealed recurrent interaction failures, including repetitive questioning, omission of past medical history, and inadequate handling of uncertainty. Richer conversational context improved diagnostic reasoning but yielded limited gains in treatment planning. These findings indicate that final-answer accuracy alone is insufficient for evaluating clinical readiness and highlight the importance of assessing how models gather, interpret, and communicate information throughout a consultation. AIPatient Arena provides an EHR-grounded framework for workflow-oriented pre-deployment evaluation of medical LLMs.

09.
arXiv (CS.CL) 2026-06-11

Benchmarking Large Language Models for Safety Data Extraction

Accurate extraction of structured information from Safety Data Sheets (SDS) remains challenging in industrial safety due to heterogeneous document formats and the limitations of traditional rule-based methods. This study benchmarks state-of-the-art Large Language Models (LLMs) for automated SDS data extraction, comparing text-based and multimodal processing pipelines. We systematically evaluate four models: Gemini 1.5 Pro, GPT-4o, Claude 3.7 Sonnet, and Llama 3.1-70B, across three prompting strategies: zero-shot, few-shot, and chain-of-thought. The evaluation framework assessed accuracy, latency, and cost across more than 50,000 extracted data fields. Results show that text-based extraction consistently outperforms multimodal processing across all metrics. Gemini 1.5 Pro combined with a Chain-of-Thought prompt achieved the highest accuracy (84%), outperforming GPT-4o (81%) and Claude 3.7 Sonnet (79%). However, no model surpassed the 90% accuracy threshold commonly required for reliable real-world deployment. These findings indicate that general-purpose LLMs are not yet robust enough for unsupervised industrial use, though performance suggests strong potential with task-specific fine-tuning. Future research should focus on domain-adapted training, model calibration, and the integration of Human-in-the-Loop verification to ensure safety-critical reliability.

10.
arXiv (CS.CV) 2026-06-18

Semantic Router: On the Feasibility of Hijacking MLLMs via a Single Adversarial Perturbation

Multimodal Large Language Models (MLLMs) are increasingly deployed in stateless systems, such as autonomous driving and robotics. This paper investigates a novel threat: Semantic-Aware Hijacking. We explore the feasibility of hijacking multiple stateless decisions simultaneously using a single universal perturbation. We introduce the Semantic-Aware Universal Perturbation (SAUP), which acts as a semantic router, "actively" perceiving input semantics and routing them to distinct, attacker-defined targets. To achieve this, we conduct theoretical and empirical analysis on the geometric properties in the latent space. Guided by these insights, we propose the Semantic-Oriented (SORT) optimization strategy and annotate a new dataset with fine-grained semantics to evaluate performance. Extensive experiments on three representative MLLMs demonstrate the fundamental feasibility of this attack, achieving a 66% attack success rate over five targets using a single frame against Qwen.

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

CD-RCM: Generalizable Continuous-Depth Novel View Synthesis for Reflectance Confocal Microscopy

Reflectance confocal microscopy (RCM) provides noninvasive, cellular-resolution "optical biopsies" of human skin in vivo by acquiring en-face images at successive depths, forming a sparse z-stack. Due to optical limitations, these stacks are anisotropic 3D volumes with lateral resolution (0.5 $\mu$m) $\sim$6 times higher compared to axial resolution, which is defined by the optical sectioning (3 $\mu$m), limiting the interpretation of tissue. Our goal is to provide continuous-depth visualization by interpolating intermediate sections and making the 3D volume isotropic. Such a representation permits arbitrary-direction sectioning, including histopathology-like cross-sectional examination, without requiring per-patient optimization. To that end, we introduce the first RCM-specific novel-view synthesis (NVS) approach, CD-RCM, a feedforward model that predicts realistic, unseen depths from sparsely sampled RCM stacks. Classical neural rendering methods focus on reconstruction from surface-level multi-view observations. In contrast to surface-level camera views, RCM can acquire optically sectioned en-face images of tissue beyond the surface up to 200 $\mu$m. However, during visualization of the RCM stacks, observations of the shallower sections (towards the surface) obscure the deeper ones. This unique axial imaging geometry and layer-dependent anatomical organization motivated our development of a tailored architectural and training framework that explicitly accounts for RCM's depth-resolved, occlusive imaging physics. Experiments demonstrate that CD-RCM achieves high-fidelity novel-view synthesis with sub-second inference time.

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

VietFashion: Benchmarking Sketch-Text Composed Image Retrieval for Cultural Outfits

Cultural garments pose a unique challenge for visual retrieval systems, as their identity often depends on subtle structural and symbolic details that are poorly captured by standard AI models. We introduce VietFashion, a new benchmark for sketch-text composed image retrieval centered on the Ao Dai, a traditional Vietnamese garment. VietFashion enables designers and researchers to retrieve culturally meaningful outfits using a combination of hand-drawn sketches, which convey garment structure, and textual descriptions, which encode cultural semantics. The dataset is initialized with 650 sketches and expanded using generative models to produce over 21,000 photorealistic images with aligned captions. Textual prompts that describe detailed outfit attributes, which are extracted from fashion magazines to ensure authenticity and diversity. To better reflect the inherent ambiguity of design intent, VietFashion adopts a multi-target retrieval setting, where a single query may correspond to multiple valid results. We establish standardized evaluation protocols and benchmark state-of-the-art composed image retrieval methods. Experimental results reveal significant performance gaps in modeling fine-grained cultural semantics and multi-modal composition, positioning VietFashion as a challenging benchmark for fine-grained fashion retrieval. The dataset is publicly available at: https://hng0303.github.io/VietFashion.

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

Regression Language Models for Code

We study code-to-metric regression: predicting numeric outcomes of code executions, a challenging task due to the open-ended nature of programming languages. While prior methods have resorted to heavy and domain-specific feature engineering, we show that a single unified Regression Language Model (RLM) using a frozen LLM encoder can simultaneously predict directly from text, (i) the memory footprint of code across multiple high-level languages such as Python and C++, (ii) the latency of Triton GPU kernels, and (iii) the accuracy and speed of trained neural networks represented in ONNX. In particular, a relatively small 300M parameter RLM based on T5Gemma, obtains >0.9 Spearman-rank on competitive programming submissions from APPS, and a single unified model achieves >0.5 average Spearman-rank across 24 different programming languages from CodeNet. Furthermore, the RLM can obtain the highest average Kendall-Tau of 0.46 on five classic NAS design spaces previously dominated by graph neural networks, and simultaneously predict architecture latencies on numerous hardware platforms.

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

From Frames to Temporal Graphs: In-Context Egocentric Action Recognition with Vision-Language Models

Action reasoning in egocentric video requires capturing fine-grained transitions of hand-object interactions, a task where general-purpose Vision-Language Models (VLMs) often struggle when operating directly on raw pixels. We propose to decouple visual perception from symbolic reasoning by converting videos into Temporal Action Graphs. In a multi-stage prompting pipeline, we first generate dense natural language narratives over short temporal windows as a semantic bottleneck, then formalize them into structured, open-vocabulary graph representations. On the EGTEA and Epic-Kitchens-100 datasets, the symbolic representation unlocks efficient in-context learning: few-shot graph demonstrations yield substantial accuracy gains over zero-shot frame and graph-based inference alike. Even in the zero-shot setting, graph-based reasoning remains competitive with pixel-based inference despite potential pretraining contamination favoring the latter. Across 11 open-weight VLMs from 6 model families ranging from 2B to 235B parameters, our findings indicate that current VLMs are more effective as symbolic reasoners than as direct visual observers. By projecting video into the language domain, we provide a scalable, fine-tuning-free alternative to end-to-end approaches that better leverages these models' latent reasoning strengths. The code will be made public.

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

Schattor: Schatten-family methods for deep learning optimization

arXiv:2606.15702v1 Announce Type: cross Abstract: Modern deep learning optimization features heterogeneous parameter structures, noisy gradients, and highly nonconvex landscapes, posing significant challenges for both algorithm design and theoretical analysis. Motivated by the limitations of SGD and the success of adaptive optimizers, we propose {\it Schattor}, a family of adaptive first-order methods based on Schatten norms. Schattor unifies SGD and the recently proposed matrix-variate adaptive optimizer Muon within a single Schatten-norm-based framework. We establish dimension-free stationarity guarantees for methods in the Schattor family for stochastic matrix optimization problems via a novel matrix martingale moment bound. We also develop multi-block extensions that adaptively balance block-wise optimization progress and prove dimension-free stationarity guarantees in this more general setting.

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

ParaScale: Scale-Calibrated Camera-Motion Transfer via a Gauge-Invariant Parallax Number

作者:

arXiv:2606.19805v1 Announce Type: cross Abstract: Transferring the camera motion of a reference video to a freshly generated one lets creators reuse cinematic moves. Yet reference and target often live at incompatible scales – a sweep across a galaxy versus a nudge across a desk – and naively reusing the recovered trajectory yields either imperceptible or violently exaggerated motion. We trace this to a geometric fact: translation-induced image motion scales as ||T||/Z, so a monocular trajectory is meaningful only up to a depth-scale gauge. We distill this into the Parallax Number Pi = ||Delta T|| / Zbar, a dimensionless, gauge-invariant descriptor of how strongly a camera move is felt, and prove that it – not the raw trajectory – is the quantity that scale-faithful transfer must preserve. ParaScale is a plug-and-play module that reads Pi off any reference video and re-realizes it against the target scene's own depth, per frame, leaving rotation untouched. Sitting between pose extraction and pose injection, it requires no retraining and drops into any pose-conditioned generator. We further introduce the Parallax Consistency Error (PCE), a scale-symmetric metric that – unlike the similarity-aligned TransErr – exposes scene-scale mismatch. Across scale regimes spanning four orders of magnitude and multiple backbones, ParaScale keeps the realized parallax on the identity line and cuts PCE by more than 3x over uncalibrated transfer with no loss of visual fidelity.

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

Enhancing Underwater Light Field Images via Global Geometry-aware Diffusion Process

This work studies the challenging problem of acquiring high-quality underwater images via 4-D light field (LF) imaging. To this end, we propose GeoDiff-LF, a novel diffusion-based framework built upon SD-Turbo to enhance underwater 4-D LF imaging by leveraging its spatial-angular structure. GeoDiff-LF consists of three key adaptations: (1) a modified U-Net architecture with convolutional and attention adapters to model geometric cues, (2) a geometry-guided loss function using tensor decomposition and progressive weighting to regularize global structure, and (3) an optimized sampling strategy with noise prediction to improve efficiency. By integrating diffusion priors and LF geometry, GeoDiff-LF effectively mitigates color distortion in underwater scenes. Extensive experiments demonstrate that our framework outperforms existing methods across both visual fidelity and quantitative performance, advancing the state-of-the-art in enhancing underwater imaging. The code will be publicly available at https://github.com/linlos1234/GeoDiff-LF.

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

Contactless 3D Human Body Measurement Using Depth Cameras for Smart Health Monitoring

Contactless body measurement technologies are becoming increasingly significant for smart health monitoring, digital health applications, and remote patient assessment. Traditional anthropometric measurements typically necessitate physical contact and trained personnel, which may constrain scalability in remote healthcare settings. In this study, we introduce a depth camera-based framework for estimating human body measurements utilizing 3D point cloud data. An Orbbec Astra 2 depth camera was employed to capture RGB images, depth maps, and 3D point clouds of participants. The captured point cloud was processed using Python-based tools, including Open3D, NumPy, and OpenCV, to segment the human body from the background. Key anthropometric measurements, such as height and arm span, were computed. The measurements were obtained through a combination of spatial filtering and landmark selection on the 3D point cloud, followed by the projection of the computed measurements onto the corresponding RGB image using camera intrinsic parameters. In addition to linear measurements, the approximate body volume and visible surface area were estimated using voxel-based occupancy analysis and mesh-based surface reconstruction methods. The experimental results from a single depth capture demonstrated that accurate body measurements and geometric estimates could be obtained from depth camera data without physical contact. This study provides a foundation for future real-time systems that integrate depth sensing with intelligent health monitoring and generative AI models for smart healthcare applications.

19.
arXiv (CS.CL) 2026-06-15

Achieving Precise Text-To-Cypher Via Grounded Knowledge Graph Data Generation

Property Graphs are rapidly being adopted as database frameworks for representing heterogeneous data sources. To enable precise access to the information contained in them we need conversational interfaces based on Text-To-Cypher (Text2Cypher) parsers. This paper presents an automatic synthetic data generation method that can be leveraged to fine-tune small LLMs for this task. We conduct experiments on all the major Text-To-Cypher benchmarks, demonstrating that with our synthetic data generation approach we can significantly increase the performance of small LLMs, allowing them to compete with much larger proprietary models. This means that in settings in which models must be locally deployed we can ensure data-sovereignty without sacrificing accuracy and without costly annotation campaigns.

20.
arXiv (quant-ph) 2026-06-11

Controlled ion-ion interactions and cavity-enhanced emission of a coherent dinuclear Eu$^{3+}$ complex

arXiv:2606.11947v1 Announce Type: new Abstract: Molecular rare-earth-ion complexes offer unique opportunities for quantum technologies by combining the intrinsic coherence properties of rare-earth ions with chemically tunable molecular environments. A crucial capability is the realization of multi-qubit architectures with defined qubit couplings to enable two-qubit quantum gates. Here, we investigate the optical coherence properties and excitation-induced interactions of two Eu$^{3+}$-based molecular complexes, comparing a mononuclear reference system with a dinuclear analogue in which two Eu$^{3+}$ ions are positioned at a well-defined intramolecular distance of about 7 Angstrom. Using cryogenic ensemble spectroscopy, including spectral hole burning, free-induction decay, and photon echo measurements at temperatures down to 100 mK, we demonstrate long optical coherence times $T_{2,o}$ of up to 9 $\mu$s. As a key step toward scalable multi-qubit architectures, a control-target sequence was implemented to probe conditional ion-ion interactions, revealing a stronger interaction-induced dephasing in the dinuclear complex. Finally, we show the integration of the dinuclear complex into a fiber-based optical microcavity, and observe an 380-fold emission enhancement of the $\mathrm{}^5\mathrm{D}_0\rightarrow\mathrm{}^7\mathrm{F}_0$ transition. Together, these results position molecular rare-earth complexes as versatile and chemically tunable building blocks for scalable quantum technologies.

21.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

22.
medRxiv (Medicine) 2026-06-18

Cost analysis of overseas versus domestic vaccination of US-bound refugees

Context: To ensure healthy resettlement and protect US health security, the Vaccination Program for US-bound Refugees (VPR) offers some recommended vaccines to refugees overseas before resettlement to the United States. The selected vaccines and number of doses vary by country of departure. VPR was found to be cost-saving in 2018 but had since expanded to more sites. Objective: Assess VPR's current costs and impact on post-arrival domestic vaccination needs and costs. Setting and Participants: A model-based analysis of the Federal government costs for VPR and post-arrival (US) vaccination of resettled refugees separated across five regions: Africa, Asia, the Middle East and North Africa/Republic of Turkiye and Middle East, Europe, and the Americas using fiscal year 2024 data. Design: We quantified and compared full vaccination costs for refugees under two scenarios: (1) 'No VPR' and (2) 'VPR'. Refugees would receive no vaccines overseas and be fully vaccinated after US arrival under 'No VPR'. Under 'VPR', refugees receive one or two doses of selected vaccines overseas before completing vaccination schedules after arrival. Main Outcomes: Costs were reported in 2023 US dollars for 'VPR' and 'No VPR' scenarios and further subdivided by grouping countries/sites depending on whether the International Organization for Migration (IOM) provides vaccination services for refugees (IOM sites) versus non-IOM providers (non-IOM sites). Results: 'VPR' resulted in average net cost savings of $147 per person or $14.7 million per 100,000-refugee cohort compared to providing all vaccines after US arrival ('No VPR'). 'VPR' was cost-saving across most regions, except for IOM sites in Europe, where a net cost of $44 per person was observed. Net cost savings per person were highest for IOM sites in Africa ($333). Conclusions: VPR remains a cost-saving strategy, while protecting US-bound refugees' health and US health security by preventing disease outbreaks during resettlement.

23.
arXiv (math.PR) 2026-06-15

Universality for Products of Random Matrices with i.i.d. Entries and the Fuss–Catalan Number

arXiv:2606.14450v1 Announce Type: cross Abstract: Let \((w_{ij})_{i,j\ge1}\) be a single infinite array of independent identically distributed real- or complex-valued entries of mean zero, variance \(\sigma^2\), and finite fourth moment. Set \(W_n=(w_{ij})_{1\le i,j\le n}\) and \(X_n=n^{-1/2}W_n\). For every fixed \(k\ge1\), we identify the almost sure limiting operator norm of several fixed products built from this family. Define the \(k\)-th freeness coefficient by \[ \gamma_k:=\sqrt{\frac{(k+1)^{k+1}}{k^k}}. \] Then we prove \[ \|X_n^k\|\to\sigma^k\gamma_k \qquad almost surely. \] The same limit holds for products sampled with replacement from any fixed finite pool of independent copies of \(X_n\); in particular, it holds for the product of \(k\) independent copies. Thus, the freeness coefficient captures the non-commuting characteristic between large random matrices %powers and independent or fixed-pool sampled products under the finite fourth moment assumption. The improvement of the classical Bai–Yin-type power estimate from the scale \(\sigma^k(k{+}1)\) to \(\sigma^k \sqrt{k{+}1}\) is a direct corollary of our result. The main technical challenge is to prove the upper bound using a high-moment expansion of %the upper bound is proved by a high-moment expansion of \(\E\Tr((X_n^kX_n^{*k})^m)\). The leading zero-defect trace words are tree-like and are counted by the Fuss–Catalan number \[ F_{k,m}= \frac1{km+1}\binom{(k+1)m}{m}. \] The combinatorial tool helps to devise a defect-sensitive global enumeration: if \(L=km\) and \[ r=(L+1-v)+(L-q), \] then the number of admissible word classes with defect \(r\) is at most \(F_{k,m}(Cm)^{Dr}\). This polynomial-in-\(m\) loss, with degree proportional to the defect, is summable in the logarithmic moment range.

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

Reward-SQL: Boosting Text-to-SQL via Stepwise Execution-Aware Reasoning and Process-Supervised Rewards

Recent advances in large language models (LLMs) trained with reinforcement learning (RL) have improved Text-to-SQL performance. However, RL-based approaches still struggle with complex queries due to two key limitations: insufficient stepwise execution-aware reasoning grounded in database feedback, and the lack of process-level rewards for guiding reasoning optimization. To address these issues, we propose CoCTE, a divide-and-conquer and execution-aware reasoning framework that progressively composes SQL queries through intermediate view validation and structured Common Table Expressions (CTEs), improving both accuracy and interpretability. To realize a CoCTE reasoning process, we develop Reward-SQL, a unified approach with three stages: (1) model initialization, which equips LLMs with structured CoCTE reasoning capabilities; (2) process reward design, which delivers fine-grained, execution-aware supervision; and (3) process-supervised RL and inference, which integrates process rewards into training and guides the inference stage by process rewards. This paper addresses the core challenges in Reward-SQL and makes the following contributions. We introduce a process reward model (PRM) that combines execution-aware trajectory scoring with entropy-based step weighting, providing dense and interpretable supervision across reasoning steps. We integrate PRM into both RL training and inference stages, stabilizing optimization and improving trajectory exploration with process-level signals. Experiments show that Reward-SQL significantly outperforms baselines with comparable model sizes, and exhibits strong cross-domain generalization.

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

Large-Scale OD Matrix Estimation with A Deep Learning Method

arXiv:2310.05753v2 Announce Type: replace Abstract: The estimation of origin-destination (OD) matrices is a crucial aspect of Intelligent Transport Systems (ITS). It involves adjusting an initial OD matrix by regressing the current observations like traffic counts of road sections (e.g., using least squares). However, the OD estimation problem lacks sufficient constraints and is mathematically underdetermined. To alleviate this problem, some researchers incorporate a prior OD matrix as a target in the regression to provide more structural constraints. However, this approach is highly dependent on the existing prior matrix, which may be outdated. Others add structural constraints through sensor data, such as vehicle trajectory and speed, which can reflect more current structural constraints in real-time. Our proposed method integrates deep learning and numerical optimization algorithms to infer matrix structure and guide numerical optimization. This approach combines the advantages of both deep learning and numerical optimization algorithms. The neural network(NN) learns to infer structural constraints from probe traffic flows, eliminating dependence on prior information and providing real-time performance. Additionally, due to the generalization capability of NN, this method is economical in engineering. We conducted tests to demonstrate the good generalization performance of our method on a large-scale synthetic dataset. Subsequently, we verified the stability of our method on real traffic data. Our experiments provided confirmation of the benefits of combining NN and numerical optimization.