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01.
arXiv (CS.LG) 2026-06-24

Model selection with proper scoring rules on data sets of time series

arXiv:2606.24715v1 Announce Type: cross Abstract: We consider the problem of model selection between probabilistic models on data sets of time series. Chosen a proper scoring rule, we denote by the term score the average value of the scoring rule on the test of an individual time series. For model selection, we need aggregating the values of the scores across multiple time series. Three summary statistics are commonly used for model selection: mean score, median score, and mean rank. Results in previous papers show that these statistics can yield conflicting decisions; we show how the conflicting conclusions are due to the skewness of the distribution of scores. We also show that as the test set of each time series of the data set increases, the different model selection criteria progressively converge to the same conclusion. However, for short tests sets, only the mean score identifies the true model as the best. We illustrate these phenomena with an analysis on intermittent time series, including the data set of the M5 competition, where we underline the importance of having a large test set. In such experiments, we further notice that model selection based on mean ranks remains unchanged using different scaling factors.

02.
arXiv (CS.CV) 2026-06-24

Open-Vocabulary BEV Segmentation with 3D-Aware Geometric Constraints

Bird's-eye view (BEV) perception fuses multi-camera images into a unified top-down representation for autonomous driving. Despite recent progress, state-of-the-art methods remain confined to closed-set scenarios, making them vulnerable to unpredictable real-world environments. In this work, we introduce open-vocabulary BEV segmentation (OVBS), which leverages vision-language models (VLMs) to recognize categories beyond the training set while maintaining precise BEV perception and real-time efficiency. A key challenge in OVBS lies in the 3D geometric inconsistency inherent in the ill-posed lifting of 2D VLM semantics into BEV. To address this, we propose OVBEVSeg, a geometry-aware OVBS framework that enhances efficient Gaussian splatting (GS)-based unprojection by leveraging robust 3D geometric constraints across three progressive stages: (1) 2D-to-BEV pseudo-labeling via reliable 3D projection for OV generalization; (2) joint 2D-BEV per-scene optimization with BEV structural constraints for 3D geometric consistency; and (3) 3D geometric distillation for online efficiency. On the nuScenes dataset, OVBEVSeg achieves state-of-the-art performance, outperforming closed-set methods by 15.3 mIoU on unseen categories. Remarkably, even with no novel-class ground-truth labels, it remains competitive with self- and semi-supervised baselines trained with up to 40% of ground-truth annotations. Furthermore, it achieves 2.5x faster inference with only 0.22x the memory consumption of projection-based methods. Project page: https://hchoi256.github.io/projects/ovbevseg/.

03.
arXiv (CS.LG) 2026-06-19

VIMPO: Value-Implicit Policy Optimization for LLMs

arXiv:2606.20008v1 Announce Type: new Abstract: Reinforcement learning with verifiable rewards has become a central tool for improving the reasoning ability of large language models, but current methods face a trade-off between simplicity and credit assignment. Group-relative methods such as GRPO avoid training a critic, but typically assign a trajectory-level advantage to every token. Actor-critic methods provide denser learning signals, but require a learned value function with its own training instability. We introduce VIMPO, a critic-free policy optimization method that derives a policy-implied value function from the optimality conditions of KL-regularized reinforcement learning. For autoregressive generation, the resulting value recurrence can be written in terms of policy-reference log-ratios and anchored by the terminal condition that no future reward remains at the end of a trajectory. This gives a simple value loss that incorporates outcome-level verifiable rewards without training a critic. The same derivation also yields a critic-free actor advantage, allowing VIMPO to separate reward incorporation through the value loss from policy improvement through a PPO-style actor update. On mathematical RLVR benchmarks, VIMPO improves over GRPO across MATH-500, AIME 2024, AIME 2025, and OlympiadBench, with especially larger gains on competition-style evaluations. Under noisy rewards, VIMPO retains a consistent advantage over GRPO, suggesting that policy-implied value optimization can provide finer credit assignment while preserving the practical simplicity of critic-free training.

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

Model soups need only one ingredient

arXiv:2602.09689v2 Announce Type: replace Abstract: Fine-tuning large pre-trained models on a target distribution often improves in-distribution (ID) accuracy, but at the cost of out-of-distribution (OOD) robustness as representations specialize to the fine-tuning data. Weight-space ensembling methods, such as Model Soups, mitigate this effect by averaging multiple checkpoints, but they are computationally prohibitive, requiring the training and storage of dozens of fine-tuned models. In this paper, we introduce MonoSoup, a simple, data-free, hyperparameter-free, post-hoc method that achieves a strong ID-OOD balance using only a single checkpoint. Our method applies Singular Value Decomposition (SVD) to each layer's update and decomposes it into high-energy directions that capture task-specific adaptation and low-energy directions that introduce noise but may still encode residual signals useful for robustness. MonoSoup then uses entropy-based effective rank to automatically re-weigh these components with layer-wise coefficients that account for the spectral and geometric structure of the model. Experiments on CLIP models fine-tuned on ImageNet and evaluated under natural distribution shifts, as well as on Qwen language models tested on mathematical reasoning and multiple-choice benchmarks, show that this plug-and-play approach is a practical and effective alternative to multi-checkpoint methods, retaining much of their benefits without their computational overhead.

05.
arXiv (CS.CL) 2026-06-18

SAGE: Stochastic Prompt Optimization via Agent-Guided Exploration

Context engineering has emerged as a primary lever for improving AI systems without parameter updates. Recent work showing that textual gradients do not function as real gradients motivates treating automatic prompt optimization (APO) as black-box search. We introduce SPO (Stochastic Prompt Optimization), a framework for stochastic search over prompt space, and compare three strategies of increasing sophistication: error-informed random search, a genetic algorithm with evolutionary operators, and SAGE (SPO via Agent-Guided Exploration), a multi-agent pipeline with diagnostic code execution. Across three benchmarks, no single strategy dominates; effectiveness depends on the interaction of landscape structure with error type. We further deploy SAGE on a mental-health chatbot under a continuous optimization paradigm, where it compounds eight cycles of individually-noisy A/B tests into a statistically robust gain in next-day retention. We argue that coupling qualitative diagnosis with quantitative validation is what makes agentic optimization effective for open-ended task-oriented dialogue.

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

Efficient upsampling for tensor-network and quantum-state encoded functions

arXiv:2601.03885v2 Announce Type: cross Abstract: Both tensor trains (TTs) and quantum states provide compressed representations of grid-structured data with potentially exponential compression power. We present a unified framework for upsampling data encoded in vector amplitudes, with efficient realizations in both classical TT and quantum settings. Starting from an \(n\)-core TT or an \(n\)-qubit state on a coarse grid with \(2^n\) points, the construction produces an \((n+m)\)-core TT or \((n+m)\)-qubit state on a finer grid with \(2^{n+m}\) points. In the TT setting, it supports interpolation, quasi-interpolation, augmentation, and synthesis through efficient low-rank contractions, with the added \(m\) cores retaining constant rank. For function-value encodings, the resulting interpolation satisfies an \(\ell^2\)-error bound independent of the number of added grid points, achieves exponential compression at fixed accuracy, and has a logarithmic complexity in the number of grid points. In the quantum setting, the refined state is prepared by a \(\mathrm{poly}(n,m)\)-size circuit using \(\log(p+1)\) ancillas, where \(p\) controls the smoothness of the quasi-interpolant; the corresponding error scales quadratically with the initial grid spacing. We validate our framework for tensor networks in one-, two-, and three-dimensional examples, including functions, derivatives, airfoil masks, and synthetic random fields such as three-dimensional turbulence. In particular, fractal fields can be generated directly in TT format with logarithmic memory and runtime. These results open a practical route to multiscale solvers, generative models, and geometry-aware algorithms on tensor-network and quantum platforms, with potential applications in scientific simulation, imaging, and real-time graphics.

07.
arXiv (CS.AI) 2026-06-19

Modularity-Free Conflict-Averse Training for Generalized PINNs

arXiv:2606.20156v1 Announce Type: new Abstract: Physics-informed neural networks (PINNs) have become a powerful framework for solving PDEs by embedding physical laws into differentiable objectives. Despite their advances, training PINNs remains fragile: recent conflict-averse optimization schemes alleviate gradient interference between residual and boundary losses, but we show that their effectiveness deteriorates as model capacity increases. In this paper, we identify a capacity-induced failure mode, where overparameterized networks undergo functional modularity, self-partitioning into task-exclusive modules that suppress cross-objective interaction and hinder convergence toward Pareto-stationary points. To address this issue, we propose a novel framework, Modular-Sparsity Synchronization (ModSync), which integrates structural optimization into conflict-averse training by penalizing task-exclusive connections while preserving interaction-promoting pathways. Extensive experiments across diverse PDE benchmarks demonstrate that ModSync consistently prevents capacity-driven failures, sustains robust cross-objective coupling, and achieves state-of-the-art accuracy. Codes are available at \url{https://github.com/heejokong/ModSync}.

08.
arXiv (CS.AI) 2026-06-18

Learning from Own Solutions: Self-Conditioned Credit Assignment for Reinforcement Learning with Verifiable Rewards

arXiv:2606.18810v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has driven substantial progress in training LLMs for reasoning tasks, but representative methods such as GRPO assign uniform credit across all tokens, wasting gradient on routine tokens while under-crediting pivotal reasoning steps. Existing token-level credit assignment methods require resources beyond the model's own rollouts. GRPO variants rely on process reward models or ground-truth answers. Knowledge distillation assigns credit through per-token divergence but requires external teachers (On-Policy Distillation) or privileged information (On-Policy Self Distillation). However, these dependencies limit applicability in the pure RLVR setting. We observe that conditioning the model on its own verified trajectories induces a measurable per-token KL divergence between the original and conditioned distributions, and prove that distilling from a self-teacher constructed by verified trajectories leads to infeasible weighted-average solutions when multiple verified trajectories exist. We propose SC-GRPO (Self-Conditioned GRPO), which uses KL divergence mentioned before as a multiplicative weight on GRPO gradients. Across five benchmarks spanning math, code, and agentic tasks, SC-GRPO consistently outperforms 8.1% over GRPO and 5.9% over DAPO with stronger OOD performance. Moreover, SC-GRPO achieves higher performance than OPD.

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

Understanding Scam Trends and Rail Paths from Reddit Self-Disclosure Narratives

Online scam behavior is inherently multi-stage, and the lifecycle includes temporally ordered rails and events rather than isolated signals. Existing works analyze characteristics of scam types and rails, but they do not track scam trends across years. Moreover, the work on the relations between rails is hampered due to the lack of open-source datasets with annotations and coverage of different scam types. To address these gaps, we build a dataset to analyze the yearly trend of scam characteristics and rail paths using Reddit self-disclosure narratives from 2023 to 2025. We collect 21,304 posts from scam-related subreddits with at least one rail among identity, communication, platform, and payment for trend analysis by heuristic annotation. Then, we label 1,800 posts containing explicit or recoverable scam chains by an LLM-assisted method for scam path analysis. The method is evaluated with human annotation. Lastly, we run a topic model on the comments of the posts to analyze the community support behavior. The results reveal that scam processes are predominantly multi-rail. Across years, different scam types and rail components dominate. Different scam types vary systematically in path complexity. Reddit support behaviors have become more detailed over time. This work supports synthetic scam chain data simulation and AI-related scam risk assessment, though findings may not generalise to other platforms.

10.
Science (Express) 2026-06-18

Dynamic asymmetric strain imprinted into substrates by an oxide thin film | Science

Authors: Unknown Author

In film-substrate systems, the substrate role is often considered to be limited to providing static mechanical constraints. Dynamic film-substrate interactions when a structural change in the film modifies the substrate are generally disregarded. Using combined X-ray and electron microscopies, we observed that the electrically induced filament in a VO 2 film created strong asymmetric strain in the underlying Al 2 O 3 substate. This asymmetric substrate strain fed back into the film and defined the filament expansion direction, revealing the importance of film-substrate dynamic interactions in determining film functionality. Furthermore, the strain imprint propagated at least tens of microns deep into the substrate, exceeding the film thickness more than 200 times, potentially enabling substrate functionalization as an active mechanical coupling media in 3D-integrated microelectronics architectures.

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

UniMM: A Unified Mixture Model Framework for Multi-Agent Simulation

arXiv:2501.17015v2 Announce Type: replace Abstract: Simulation plays a crucial role in assessing autonomous driving systems, where the generation of realistic multi-agent behaviors is a key aspect. In multi-agent simulation, the primary challenges include behavioral multimodality and closed-loop distributional shifts. In this study, we formulate a unified mixture model (UniMM) framework for generating multimodal agent behaviors, which can cover the mainstream methods including regression-based mixture models and discrete NTP models. Furthermore, we introduce a closed-loop sample generation approach tailored for mixture models to mitigate distributional shifts. Within the UniMM framework, we recognize critical configurations from both the model and data perspectives. We conduct a systematic examination of various model configurations, and comprehensively characterize their effects. Moreover, our investigation into the data configuration highlights the pivotal role of closed-loop samples in achieving realistic simulations. To extend the benefits of closed-loop samples across a broader range of mixture models, we further introduce a temporal disentanglement-and-alignment mechanism to address the shortcut learning and off-policy learning issues. Leveraging insights from our exploration, the distinct variants proposed within the UniMM framework, including discrete, anchor-free, and anchor-based models, all achieve state-of-the-art performance on the WOSAC benchmark.

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

Bridging Spatial And Frequency Views For Disaster Assessment: Benefits And Limitations

Rapid assessment of building damage from satellite imagery is essential for effective disaster response and recovery. While most deep learning methods rely on spatial-domain features, frequency-domain representations can capture complementary structural cues such as debris patterns and collapse-induced textures. This study presents a controlled comparison of spatial-domain, frequency-domain, and dual-domain deep learning approaches for multi-class building damage classification using post-disaster imagery from the xView2 (xBD) dataset. To ensure fairness, all models are built on an EfficientNet-B0 backbone and trained under identical settings, differing only in their input representations and fusion strategies. Performance is evaluated using accuracy, macro F1-score, per-class metrics, and confusion matrices. Results show that dual-domain models provide measurable improvements over single-domain approaches. The dual spatial configuration achieves the highest test accuracy (0.4688) and lowest loss, while the spatial-only model attains the best macro F1-score (0.4254), indicating more balanced class performance. In contrast, frequency-only models perform worst and exhibit overfitting, suggesting limited generalization. Despite these gains, all models struggle to detect subtle damage levels, particularly the Minor class, due to class imbalance and fine-grained visual ambiguity. While dual-domain approaches improve detection of severe damage, challenges remain. These findings highlight the benefits and limitations of hybrid representations and motivate future work on data balancing, advanced fusion, and regularization.

13.
arXiv (CS.LG) 2026-06-19

On the QUEST for Uncertainty Quantification via Highest Density Regions

arXiv:2606.19569v1 Announce Type: new Abstract: Uncertainty quantification (UQ) is essential for reliable decision-making in safety-critical applications in probabilistic machine learning. For regression problems, dominant scalar UQ approaches - notably, those based on proper scoring rules - measure uncertainty via pointwise predictive risk. This can lead to counterintuitive results when the target statistic is not the conditional expectation. We propose an alternative framework, in which uncertainty is characterised by the volume of the most probable subset of a distribution's support. QUEST (Quantifying Uncertainty via highest dEnSiTy regions) is a novel approach to UQ based on the concentration of Lebesgue measure at a distribution's peak(s), evaluated at one or more values of a robustness parameter $\alpha$. We establish connections between our measures and classical statistics from information theory and economics. We show that, unlike popular alternatives based on proper scoring rules, QUEST measures of epistemic and aleatoric uncertainty satisfy a set of axioms adapted from the UQ literature, including monotonicity under distributional spread and invariance to location shifts. Selective prediction benchmarks confirm that QUEST performs favourably against standard measures such as variance and differential entropy.

14.
arXiv (CS.CV) 2026-06-18

Technical Report for ICRA 2026 GOOSE 2D Fine-Grained Semantic Segmentation Challenge: Leveraging DINOv3 for Robust Outdoor Scene Understanding in Field Robotics

The GOOSE 2D Fine-Grained Semantic Segmentation Challenge at the ICRA 2026 Workshop on Field Robotics evaluates dense semantic segmentation of off-road imagery over a fine-grained taxonomy of 64 classes and 11 evaluated non-void coarse categories. We present the first-place solution to this challenge. Our solution comprises two complementary improvements: (a) a network-level design that combines a self-supervised DINOv3 ViT-L/16 backbone, a ViT-Adapter, and a Mask2Former mask-classification decoder, together with a coarse-category auxiliary loss on the global [CLS] token; and (b) an inference-time aggregation strategy based on multi-scale and horizontal-flip test-time augmentation and an ensemble of the top three checkpoints selected using Codabench scores. Our method achieves an official composite score of 76.57%, consisting of 69.32% fine-class mIoU and 83.81% category-level mIoU, and ranks first on the final phase leaderboard: www.codabench.org/competitions/14257/#/results-tab.

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

Vision-language models for chest radiography do not always need the image

Medical vision-language models report strong chest radiograph accuracy, and this is increasingly read as evidence that they use the image. That inference is unsafe: a model exploiting finding-name priors scores like one that reads the scan, and no standard benchmark separates them. We introduce a causal audit that intervenes on the image, occluding the relevant region, occluding an irrelevant one, and swapping in another patient's same-label scan, and combines three behavioral metrics to test whether a correct answer depends on the image. Across nine systems, a text-only model with no image access reaches within 5.7 accuracy points of the best multimodal one, and a 119-billion-parameter multimodal model is statistically indistinguishable from a 7-billion text-only baseline. The audit splits the cohort into three models that ignore the image, one that is unstable, and five that use it selectively, for a subset of findings; the categories hold across a second dataset, resolution, and prompt phrasing. Against board-certified radiologists, a text-only model is statistically indistinguishable from a radiologist's accuracy while grounding at zero, whereas the image-using models ground at radiologist-comparable rates. Reported confidence flags ungrounded answers only when a model uses the image. Grounding audits, not accuracy, should gate clinical deployment.

16.
arXiv (quant-ph) 2026-06-12

Quantum Reference Fields Transformations in Linearized Quantum Gravity

arXiv:2606.09344v1 Announce Type: cross Abstract: Diffeomorphism invariance is a central feature of general relativity. Without external reference structures, matter and geometry must be specified relationally, with respect to internal subsystems serving as reference frames. In quantum gravity, these reference systems must themselves be treated as quantum, motivating the use of quantum reference frames. In this work, we address how such a relational description could be formulated within linearized quantum gravity. To this purpose, we introduce quantum reference fields, i.e. sets of four dynamical scalar fields whose stress-energy tensors enter the gravitational constraints. These fields extend the notion of quantum reference frames to local field-theoretic reference systems, allowing matter and gravitational degrees of freedom to be described relationally with respect to physical quantum systems. By generalizing the perspective-neutral construction of quantum reference frames, we show that relational, gauge invariant observables admit reduced descriptions in the perspective of each quantum reference field, and we derive the unitary transformations relating them. The resulting unitary maps implement local quantum coordinate changes between different internal perspectives, and act on the linearized gravitational field with an analogous structure to a linearized diffeomorphism, but with the classical gauge parameter replaced by a physical quantum field. Finally, we construct a relational von Neumann-type measurement scheme, showing how the corresponding reduced observables can be accessed operationally from the perspective of a quantum reference field.

17.
arXiv (math.PR) 2026-06-16

Sharp One-Dimensional Sub-Gaussian Comparison in Convex Order

Authors:

arXiv:2604.26819v2 Announce Type: replace Abstract: We prove that any random variable $X$ whose moment generating function is point-wise upper bounded by that of $ G \sim \mathcal{N}(0,1) $ must be dominated by $ G/\mathbb{E}[|G|] $ in convex order, meaning $ \mathbb{E}[f(X)] \le \mathbb{E}[f(G/\mathbb{E}[|G|])] $ for all convex $f$. This is sharp as witnessed by $ X \sim \mathrm{Unif}(\{-1,1\}) $ and $ f(x) = |x| $.

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

Optimizing Agentic Reasoning with Retrieval via Synthetic Semantic Information Gain Reward

arXiv:2602.00845v3 Announce Type: replace Abstract: Agentic reasoning enables large reasoning models (LRMs) to dynamically acquire external knowledge, but yet optimizing the retrieval process remains challenging due to the lack of dense, principled reward signals. In this paper, we introduce InfoReasoner, a unified framework that incentivizes effective information seeking via a synthetic semantic information gain reward. Theoretically, we redefine information gain as uncertainty reduction over the model's belief states, establishing guarantees, including non-negativity, telescoping additivity, and channel monotonicity. Practically, to enable scalable optimization without manual retrieval annotations, we propose an output-aware intrinsic estimator that computes information gain directly from the model's output distributions using semantic clustering via bidirectional textual entailment. This intrinsic reward guides the policy to maximize epistemic progress, enabling efficient training via Group Relative Policy Optimization (GRPO). Experiments across seven question-answering benchmarks demonstrate that InfoReasoner consistently outperforms strong retrieval-augmented baselines, achieving up to 5.4% average accuracy improvement. Our work provides a theoretically grounded and scalable path toward agentic reasoning with retrieval. The code is available at https://github.com/dl-m9/InfoReasoner

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

D2H-AD: A Hybrid Model Utilizing Hyperdimensional Computing for Advanced Anomaly Detection

arXiv:2606.13754v1 Announce Type: new Abstract: Anomaly detection is a fundamental component of intelligent systems with applications in healthcare, cybersecurity, smart grids, and IoT environments. Although conventional machine learning and deep learning methods have demonstrated effectiveness in identifying anomalies, they often rely on large labeled datasets, incur high computational costs, and face scalability challenges in edge and high-dimensional settings. This paper presents D2H-AD, a novel anomaly detection framework based on Hyperdimensional Computing (HDC), a brain-inspired paradigm that represents information using high-dimensional distributed vectors. Unlike existing HDC-based methods, D2H-AD integrates distance-based similarity and density-aware encoding within a unified framework, improving anomaly representation and detection performance. Ablation studies show that hyperdimensional encoding alone yields up to 5.4% higher ROC-AUC than applying the same density-distance scoring directly in the original feature space. Furthermore, D2H-AD consistently outperforms five established baselines, namely HDAD, ODHD, One-Class SVM, Isolation Forest, and Autoencoders, across all evaluated datasets. The framework is lightweight, interpretable, and computationally efficient, making it suitable for resource-constrained and real-time applications. We validate D2H-AD on five benchmark datasets and demonstrate superior F1-score and ROC-AUC performance, together with robustness to class imbalance, noise, and data complexity. In addition to improved accuracy, D2H-AD offers scalability, a small memory footprint, and low-latency operation enabled by binary computations and a compact design. These properties make it particularly attractive for TinyML and edge AI deployments. The proposed framework highlights the potential of HDC for accurate, interpretable, and energy-efficient anomaly detection in dynamic environments.

20.
arXiv (CS.LG) 2026-06-16

Next-Latent Prediction Transformers Learn Compact World Models

arXiv:2511.05963v4 Announce Type: replace Abstract: Transformers replace recurrence with a memory that grows with sequence length and self-attention that enables ad-hoc lookups over past tokens. Consequently, they lack an inherent incentive to compress history into compact latent states with consistent transition rules. This often leads to learning solutions that generalize poorly. We introduce Next-Latent Prediction (NextLat), which extends standard next-token training with self-supervised predictions in the latent space. Specifically, NextLat trains a transformer to learn latent representations that are predictive of its next latent state given the next token. Theoretically, we show that these latents provably converge towards belief states, compressed information about the history necessary to predict the future. This simple auxiliary objective injects a recurrent inductive bias into transformers while leaving their architecture, parallel training efficiency, and inference unchanged. NextLat effectively encourages transformers to form compact internal world models with coherent belief states and transition dynamics – crucial properties not guaranteed by standard next-token prediction alone. Empirically, across benchmarks in world modeling, reasoning, planning, and language modeling, NextLat demonstrates significant gains over standard next-token prediction and other baselines in downstream accuracy, representation compression, and lookahead planning. Furthermore, NextLat enables variable-length self-speculative decoding, accelerating inference by up to 3.3x in language modeling. NextLat offers a simple yet effective paradigm for learning compact, predictive representations in transformers that generalize better. Our code is available at https://github.com/JaydenTeoh/NextLat.

21.
PLOS Medicine 2026-05-15

Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study

Authors:

by Zhi-Hui Luo, Na Wang, Jingwei Zhao, Fei Long, Si Wu, Wei Zhong, Wei-Ming Chen, Bicheng Wang, Kun Wang, Yufeng Yuan, Jingjiao Zhou, Chunhui Yuan, Fubing Wang Background Microvascular invasion (MVI) is closely related to the recurrence and metastasis of hepatocellular carcinoma (HCC), but the underlying cellular mechanism remains largely elusive. This study aims to elucidate the regional cellular discrepancy between MVI-positive (MVI+) and MVI-negative (MVI−) HCC by integrating Spatial transcriptomics (ST) and spatial metabolomics (SM). Methods and findings ST and SM were performed on six tissue samples from four patients (including 2 MVI+, 2 MVI−, and 2 paratumor tissues), with the integration of 79 public single-cell RNA sequencing datasets of HCC. Patient identity was used as a covariate in the linear equation for regional differentially expressed gene analysis with the ST data. Clinical validation was conducted through multiplex immunofluorescence staining in 79 patients, together with external validation in the cancer genome atlas (TCGA)-liver hepatocellular carcinoma (LIHC) cohort (n = 299) and an independent microarray dataset (n = 62). For cell-type-specific metabolic profiling, spatial transcriptomic-metabolic registration was performed. The functional roles of key metabolites were further validated in vitro using inflammatory cancer-associated fibroblasts (iCAFs) derived from hepatic stellate cells (HSCs) and primary CAFs through co-culture models and various functional assays assessing cell proliferation, migration, and invasion. In the tumor lesion, a malignant STMN1+HMGN2+GPC3+ cell subtype enriched in MVI+ HCC was identified, which exhibited enhanced proliferative activity and was associated with poor prognosis. This finding was further confirmed in a local cohort of 79 patients, where multiplex immunofluorescence staining for the three genes (STMN1, HMGN2, and GPC3) showed significantly higher expression in the MVI+ group than in the MVI− group (p = 0.046). Integrated SM analysis further revealed that this cell population underwent metabolic reprogramming characterized by suppressed glycerolipid metabolism. In the tumor capsule, iCAFs-related genes were downregulated in MVI+ cases, and iCAFs were located distally from the tumor boundary. Spatial metabolite mapping showed a strong correlation between taurine and iCAFs, and functional assays demonstrated that taurine promotes HCC proliferation and migration by suppressing iCAF activity. One limitation of this study is the small sample size of spatial omics data, which hinders a more complete molecular functional analysis of the STMN1+HMGN2+GPC3+ cell subtype and iCAFs in MVI+ HCC. Larger-scale ST cohorts are required to further validate and expand the findings of this study. Conclusions This integrative spatial atlas proposes a hypothesis that there exists a highly proliferative and metabolically reprogrammed malignant cell subtype in the tumor lesion of MVI+ HCC, and that taurine in the tumor capsule modulates iCAF activity to influence tumor progression. The exploratory results provide mechanistic insights into MVI-related HCC progression and offer potential avenues for targeted therapeutic intervention of MVI+ HCC.

22.
bioRxiv (Bioinfo) 2026-06-16

RetroMol: Parsing a shared encoding from natural products and their biosynthetic gene clusters

Natural products such as polyketides and nonribosomal peptides (NRPs) are important sources of bioactive compounds, including many antibiotics. Many of them are assembled by modular enzyme complexes and further modified and diversified by tailoring reactions encoded by biosynthetic gene clusters (BGCs). Although natural products and their coding BGCs describe different data modalities of the same biochemical process, a unified language to jointly describe their biochemistry is lacking. Here we introduce a sequence-based representation of the core biosynthesis of modular natural products, which we call primary sequences, that bridges chemical structures and BGCs. We also present RetroMol, an algorithm that parses either natural product structures or their encoding BGCs into their primary sequences of natural product building blocks. RetroMol allows for similarity scoring between natural products and BGCs, enabling the retrieval of compounds, BGCs, and a combination of the two, based on their biosynthetic similarity. This can, for instance, be used to retrieve biosynthetically similar but structurally dissimilar compounds, or link natural products to candidate coding BGCs in large experimental datasets. We demonstrate the latter by rediscovering the nocardichelin B BGC as a proof of principle. We also exemplify the utility of biosynthetic similarity by showing various pairs of biosynthetically similar compounds with low structural similarity. Together, these results establish primary sequences as a shared biosynthetic encoding for natural product comparison and BGC prioritization.

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

Leadership as Coordination Control: Behavioral Signatures and the Recovery-Advantage Boundary in Multi-Agent LLM Teams

Authors:

Team science holds that leadership is contingent: it helps only under specific conditions, and capable, autonomous teams may need none at all. We ask the analogous question for multi-agent LLM teams: under what measurable conditions does process-level coordination control add value, and do those conditions match what team science predicts? We use behavioral signatures (majority lock-in, exploration, recovery from an incorrect round-0 consensus) and per-action ablations, clean because each controller is an explicit action set, not a monolithic prompt. We operationalize three classical leadership styles (transactional, transformational, situational) as controllers over a shared action vocabulary (explore, revise, accept, synthesize). A matched controller with the same actions but an arbitrary rule recovers no better than majority voting, so the theory-derived rule, not the vocabulary, does the work. Across four task regimes and three open-weight model families, no controller dominates by accuracy, as the contingency view predicts: transactional control matches a shared round-0 vote on all 12 (model, regime) combinations to within 1.3pp, and gains appear only on the one combination where the round-0 majority is unreliable (llama-4-scout social; situational +8pp over flat). A recovery-advantage account, tested with four boundary probes, says a controller beats plain interaction only where the round-0 majority is unreliable, the task is recoverable, and undirected interaction does not already repair it. These regions map onto contingency theory (leadership substitutes, path-goal redundancy, the situational readiness gap), so a largely null accuracy result is what the theory predicts, not a failure of the controllers. We read process-level coordination control as a contingency to be measured and theory-mapped, not a leaderboard to be topped.

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

HyMaTE: A Hybrid Mamba and Transformer Model for EHR Representation Learning

arXiv:2509.24118v2 Announce Type: replace Abstract: Electronic health Records (EHRs) have become a cornerstone in modern-day healthcare. They are a crucial part for analyzing the progression of patient health; however, their complexity, characterized by long, multivariate sequences, sparsity, and missing values poses significant challenges in traditional deep learning modeling. While Transformer-based models have demonstrated success in modeling EHR data and predicting clinical outcomes, their quadratic computational complexity and limited context length hinder their efficiency and practical applications. On the other hand, State Space Models (SSMs) like Mamba present a promising alternative offering linear-time sequence modeling and improved efficiency for handling long sequences, but focus mostly on mixing sequence-level information rather than channel-level data. To overcome these challenges, we propose HyMaTE (A Hybrid Mamba and Transformer Model for EHR Representation Learning), a novel hybrid model tailored for representing longitudinal data, combining the strengths of SSMs with advanced attention mechanisms. By testing the model on predictive tasks on multiple clinical datasets, we demonstrate HyMaTE's ability to capture an effective, richer, and more nuanced unified representation of EHR data. Additionally, the interpretability of the outcomes achieved by self-attention illustrates the effectiveness of our model as a scalable and generalizable solution for real-world healthcare applications. Codes are available at: https://github.com/healthylaife/HyMaTE.