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01.
arXiv (CS.CL) 2026-06-16

Why Tree-Style Branching Matters for Thought Advantage Estimation in GRPO

Group Relative Policy Optimization (GRPO) trains Chain-of-Thought reasoning with verifiable rewards, but estimating thought-level advantages without value functions often suffers from high variance. Although tree-style branching is used in practice to reduce variance, it lacks a theoretical explanation of why it works and whether it is important or potentially necessary. We study thought-level advantage estimation in GRPO from a variance perspective under a minimal tree-style setting where multiple continuations are sampled for each thought. Using the multivariate delta method, we reveal a sampling-dimension asymmetry. Increasing sampled thoughts ($K$) leaves a strictly positive estimation-variance floor, whereas increasing continuations per thought ($M$) drives the leading-order estimation variance to zero at rate $1/M$. This implies that, within the fixed-temperature GRPO-style estimator without value models studied here, accurate thought-level advantage estimation cannot be achieved by scaling thought sampling alone, making continuation-level branching a principled and potentially necessary mechanism rather than a heuristic. Experiments further provide empirical evidence for its effectiveness and potential necessity, demonstrating improved optimization stability, training efficiency, and final performance not only in math but also across vision domains and under different model architectures and sizes.

02.
medRxiv (Medicine) 2026-06-18

Human Intuition vs. Computational Precision: Neurologists, Feature-based Models, and Deep Learning for Stroke Prognosis

Background: Prognostication in large vessel occlusion (LVO) stroke remains challenging. Although several prognostic models exist, their comparison to clinician performance, human-model interaction, and specific sources of human bias remain poorly understood. Methods: Using pre-treatment clinical and CT data from the MR CLEAN trial (n=500), six neurologists predicted three-month modified Rankin Scale (mRS) scores for 40 patients, both unaided and assisted by a validated feature-based model (MR PREDICTS). Human performance was benchmarked against MR PREDICTS and a multimodal, interpretable deep learning (DL) approach using raw imaging data. We explicitly assessed neurologists? ability to estimate model-required imaging features and identified systematic human biases. Models were additionally validated in a larger MR CLEAN trial cohort (n=404). Results: For predicting the full mRS distribution, standalone models achieved good ordinal agreement (MR PREDICTS quadratic weighted kappa (QWK) 0.51 [0.24 to 0.70]; DL model 0.49 [0.25 to 0.67]), significantly outperforming unaided neurologists (QWK 0.27 [0.10, 0.42]). Neurologists showed systematic overoptimism, predicting lower mRS scores than observed. Furthermore, there was poor accuracy in extracting imaging features. Raters? ASPECTS predictions deviated by 3.4 points from the confirmed scores, and collateral score accuracy was 44.6%. However, for predicting binary mRS (0-2 vs. 3-6), accuracy was comparable between unaided neurologists (64.17% [55.42% to 72.92%]) and models (MR PREDICTS 67.50% [52.50% to 82.50%]; DL model 63.16% [47.37% to 78.95%]). Model-assistance modestly improved and harmonized neurologists? predictions (QWK 0.41 [0.22 to 0.55]; binary accuracy 68.75% [58.33% to 78.34%]. Model performance remained robust in the larger cohort. Conclusions: Multimodal prognostic models outperform clinicians in predicting the full range of mRS outcomes, while human error in imaging assessment and systematic optimism bias are primary drivers of prognostic inaccuracy. End-to-end DL models eliminate human-input variability and hold strong potential as an automated second opinion to support prognostication and decision-making in acute LVO stroke.

03.
bioRxiv (Bioinfo) 2026-06-14

Cellfm-datasets: A Unified Data Infrastructure for Single-Cell and Spatial Transcriptomics Foundation Model Pretraining

Large-scale cell foundation models are increasingly limited not only by model architecture, but also by the data infrastructure required to repeatedly sample sparse transcriptomic profiles from out-of-core cohorts. AnnData/H5AD has become a standard exchange format for single-cell and spatial omics analysis, yet its HDF5-backed layout is not designed for high-frequency random mini-batch loading under multi-worker and distributed pretraining. We present Cellfm-datasets, a data infrastructure artifact that converts H5AD cohorts into a self-describing compressed sparse row (CSR) memmap layout and exposes the resulting corpus through Hugging Face Dataset and IterableDataset interfaces. The artifact stores a shared gene vocabulary, per-sample metadata, optional spatial coordinates, observation metadata, manifests, and checksums, and reconstructs sparse cell or group records at runtime without dense expansion. A unified sampling abstraction supports random-cell groups, manifest-defined biological regions, and coordinate-based spatial blocks, with deterministic sharding across distributed ranks and data-loader workers. Spatial demonstrations on P14 mouse brain transcriptomics sections illustrate region- and block-level sampling over real anatomical structures. In controlled benchmarks on a public heterogeneous ModelScope scRNA-seq subset, Cellfm-datasets reached 60,571 +/- 1,734 samples/s in single-core random loading, scaled to approximately 160,000 samples/s with eight workers, and maintained near-constant process-private memory while reading up to one million cells. By moving sparse single-cell and spatial corpora from model-specific loader code into reusable, validated, and framework-native dataset artifacts, this design may reduce the engineering burden of reproducible cell foundation model pretraining and make repeated training runs, model comparisons, and mixed-modality data reuse easier to standardize.

04.
arXiv (CS.LG) 2026-06-12

Central Limit Theorems for Stochastic Gradient Descent Quantile Estimators

arXiv:2503.02178v3 Announce Type: replace-cross Abstract: This paper develops asymptotic theory for quantile estimation via stochastic gradient descent (SGD) with a constant learning rate. The quantile loss function is neither smooth nor strongly convex. Beyond conventional perspectives and techniques, we view quantile SGD iteration as an irreducible, periodic, and positive recurrent Markov chain, which cyclically converges to its unique stationary distribution regardless of the arbitrarily fixed initialization. To derive the exact form of the stationary distribution, we analyze the structure of its characteristic function by exploiting the stationary equation. We also derive tight bounds for its moment generating function (MGF) and tail probabilities. Synthesizing the aforementioned approaches, we prove that the centered and standardized stationary distribution converges to a Gaussian distribution as the learning rate $\eta\rightarrow0$. This finding provides the first central limit theorem (CLT)-type theoretical guarantees for the quantile SGD estimator with constant learning rates. We further propose a recursive algorithm to construct confidence intervals of the estimators with statistical guarantees. Numerical studies demonstrate the effective finite-sample performance of the online estimator and inference procedure. The theoretical tools developed in this study are of independent interest for investigating general SGD algorithms formulated as Markov chains, particularly in non-strongly convex and non-smooth settings.

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

Are Tabular Foundation Models Robust to Realistic Query Distribution Shifts in Microbiome Data?

arXiv:2606.24995v1 Announce Type: cross Abstract: Tabular foundation models (TFMs) achieve strong performance on microbiome abundance data, yet their robustness under realistic distribution shift remains poorly characterized. We introduce a benchmark that evaluates the robustness of TFMs to biologically inspired perturbations across six gut microbiome datasets spanning four disease contexts. In this in-context learning setting, models receive unperturbed support sets as context and are evaluated on perturbed query samples. To isolate robustness beyond "shortcut" features, we preserve the most discriminative taxa and apply three controlled perturbation strategies: (i) removal of high-abundance (uninformative) taxa, (ii) sparsification via increased zero-inflation, and (iii) zero-imputation via spurious non-zero injections. Our results show that protecting discriminative features is insufficient to guarantee stability under support-query shift: across datasets, all perturbations degrade model performance, with zero-imputation consistently the most harmful, indicating that corrupting global feature structure can break generalization even when key taxa are retained. Sparsification disproportionately affects TFMs relative to a classical random forest baseline, suggesting greater sensitivity to zero-inflation-type shifts. The code is publicly available at: https://github.com/UMMISCO/metagenomics-fm/.

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

Provably Efficient Regularized Online RLHF with Generalized Bilinear Preferences

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

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

Operator Learning for efficient Quantum Computation

arXiv:2606.20184v1 Announce Type: new Abstract: An efficient implementation of quantum algorithms is often hindered by the lack of efficient primitives for operators and state preparation. This limits both the ability of near-term quantum hardware to simulate complex problems and the potential of fault-tolerant algorithms to achieve practical quantum advantage. To address this, we propose a full-stack variational framework that transforms arbitrary operators to compact quantum circuits. The resulting variational circuits can be tailored to the connectivity and long-range interaction of the target hardware. The learning process employs backpropagation together with a cost function that efficiently optimizes unitary operators and non-unitary – dense or sparse – operators using only a single ancilla qubit for block encoding. Additionally, we introduce a regularization term that reduces the approximation error. The approach is validated for both quantum mechanical and engineering applications. In the former case, we learn propagators that arise in native quantum problems – such as quantum simulation and quantum chemistry – and achieve improved resource scaling in comparison to standard Suzuki-Trotter expansions. In the latter case, we demonstrate the approach's ability to implement the second-order central finite difference approximation of the Laplace operator – relevant for solving partial differential equations – while improving upon current error metrics. The final example deals with learning a dense, non-unitary operator that arises in the analysis of inviscid potential flow around an airfoil. This universality of the framework opens the door for solving general problems beyond prototypical engineering and quantum applications.

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

EngTrace: A Symbolic Benchmark for Verifiable Process Supervision of Engineering Reasoning

Large Language Models (LLMs) are increasingly entering specialized, safety-critical engineering workflows governed by strict quantitative standards and immutable physical laws, making rigorous evaluation of their reasoning capabilities imperative. However, existing benchmarks such as MMLU, MATH, and HumanEval assess isolated cognitive skills, failing to capture the physically grounded reasoning central to engineering, where scientific principles, quantitative modeling, and practical constraints must converge. To enable verifiable process supervision in engineering, we introduce EngTrace, a symbolic benchmark built on 90 parameterized templates, each generating unique, contamination-resistant problem instances, spanning three major engineering branches, nine core domains, and 20 distinct areas, yielding 1,350 test cases that stress-test generalization across diverse physical scenarios. Moving beyond outcome matching, we introduce a verifiable two-stage evaluation framework that uses a tiered protocol to validate intermediate reasoning traces alongside final answers through automated procedural checks and a heterogeneous AI Tribunal. Our evaluation of 27 leading LLMs reveals a distinct trade-off between numeric precision and trace fidelity, identifying a complexity cliff where abstract mathematical pre-training fails to translate into the integrative reasoning required for advanced engineering tasks.

09.
arXiv (quant-ph) 2026-06-16

Accelerating physics-informed neural networks for full waveform inversion using a hybrid quantum-classical finite-basis architecture

arXiv:2606.01110v2 Announce Type: replace-cross Abstract: Full waveform inversion (FWI) reconstructs heterogeneous material properties from receiver data but remains computationally demanding. Physics-informed neural networks (PINNs) and their domain-decomposed variants (FBPINNs) offer a mesh-free alternative but face convergence challenges when representing complex velocity fields. We present a hybrid quantum-classical FBPINN for acoustic FWI, bringing together quantum computing and classical machine learning, in which the decomposed wavefield network and the global velocity network are implemented as classical-to-quantum pipelines terminating in parameterized quantum circuits (PQCs). The PQCs are realized as differentiable JAX statevector simulators, enabling end-to-end automatic differentiation through the classical PINN, the quantum circuit, and the physics-informed loss. On a geophysical anomaly benchmark, the quantum hybrid reaches a lower L1 velocity error than the primary classical FBPINN baseline in approximately 8x fewer training iterations, despite using approximately 33% fewer trainable parameters, and it outperforms all 15 classical hyperparameter variants tested. A second benchmark (checkerboard) demonstrates the generality of the inversion pipeline, confirming that the quantum hybrid architecture can recover structured spatial variations beyond the localized anomaly benchmark. Our framework is broadly applicable to wave-based inverse problems beyond geophysics, including medical ultrasound tomography and non-destructive evaluation.

10.
arXiv (CS.LG) 2026-06-12

How Useful is Causal Invariance for Domain Adaptation in Finite-Sample Settings?

arXiv:2606.12680v1 Announce Type: new Abstract: Machine learning models often degrade when they are deployed on a target distribution that differs from the source distributions they were trained on. Recent work in causality-based domain generalization has shown how shared causal structure between domains can induce invariant predictors, e.g., models on a subset of features which have stable risk across structured domain shifts. However, the extent to which such population-level causal invariances can lead to gains in finite-sample settings remains underexplored. In particular, in practice we often have access to a few labeled target samples, a setting called supervised domain adaptation (sDA). In this paper, we explore when (full or partial) causal knowledge can provably improve supervised domain adaptation. As a first step, we study linear regression, where full or partial causal knowledge specifies a collection of invariant or possibly invariant feature subsets, each yielding a source-trained candidate predictor. We derive matching upper and lower bounds showing that finite-sample gains are governed by the target-risk margins separating the candidates, together with the finite-source estimation error. When these margins are sufficiently large relative to $n_Q$, an adaptive aggregation procedure can match the best candidate predictor while avoiding negative transfer relative to target-only learning. On the other hand, when the margins are too small, no algorithm can reliably exploit the candidate collection to obtain faster finite-sample rates. We further connect these margins to structural shift magnitude in linear SCMs and validate the theory on real-world causal benchmarks.

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

Language Models as Interfaces, Not Oracles: A Hybrid LLM-ML System for Pediatric Appendicitis

Large language models (LLMs) can make clinical decision support more accessible by interpreting free-text documentation, but their direct use as diagnostic engines is limited by sensitivity to prompts, information order, and plausible but incorrect outputs. Structured machine-learning models offer more stable risk prediction, yet they require tabular inputs that are difficult to integrate with narrative clinical workflows. We present ClaMPAPP (Clinical Language-assisted Machine-learning Pipeline for Appendicitis), a hybrid system that uses an LLM as an interface rather than as the final decision-maker. ClaMPAPP extracts schema-constrained clinical features from note-like narratives, applies deterministic plausibility checks, and passes validated features to an XGBoost classifier trained on clinical, laboratory, and ultrasound variables. We evaluated ClaMPAPP on two independent pediatric appendicitis cohorts from German hospitals and compared it with end-to-end LLM baselines, including open-source and proprietary models. To preserve ground truth while testing free-text input, narratives were generated from structured electronic health records through template rendering and constrained LLM rewriting, with additional sentence-order permutation to assess positional robustness. ClaMPAPP achieved the strongest overall diagnostic performance in both internal and external validation while minimizing missed appendicitis cases, the key safety concern in acute triage. End-to-end LLMs showed unstable sensitivity-specificity trade-offs and greater degradation under narrative reordering. These results support an LLM-as-interface, ML-as-predictor design that separates natural-language usability from predictive inference and provides a more auditable pathway for clinical decision support.

12.
arXiv (quant-ph) 2026-06-15

Calibrated Helstrom geometry on the Bloch ball via Connes spectral distance

arXiv:2606.13824v1 Announce Type: new Abstract: We show that the equal-prior Helstrom trace-distance geometry of qubit states is recovered from Connes spectral distance in a finite scalar-qubit-scalar model. The two scalar reference sectors couple isotropically to the qubit block through identity Dirac links, so that the full Bloch ball, including mixed states, inherits its standard chordal trace-distance geometry from the finite spectral metric. The scalar-sector distances serve a distinct calibration role: they determine the individual link lengths, satisfy a Pythagorean consistency relation, and reconstruct the middle-sector scale.

13.
bioRxiv (Bioinfo) 2026-06-11

An AI-Powered Trisomy 21 Research Assistant

Down syndrome, caused by trisomy 21, increases the risk of diverse co-occurring conditions. With more than 34,000 related publications indexed in PubMed as of early 2026, keeping pace with this expanding literature is challenging. While general-purpose large language models are widely used for information retrieval, they often rely on broad training data rather than specific evidence. Retrieval-augmented generation (RAG) improves rigor and reliability of responses by linking model outputs to source texts. In research, source texts are peer-reviewed articles. Standard implementations treat all manuscript sections equally, allowing background text to rank as highly as experimental results. To focus model outputs on experimentally supported responses, we developed the T21 Research Assistant, a section-aware RAG system that prioritizes Results sections to ground responses in primary experimental evidence. The system draws exclusively from 1,789 open-access Down syndrome publications from PubMed Central, including 327 NIH INCLUDE-funded studies, and uses a multistage pipeline for query validation, retrieval, reranking, synthesis, and citation verification. Built on NVIDIA Nemotron models, it generates structured, cited responses. Evaluation using expert-curated questions demonstrated strong performance, achieving a BERTScore F1 of 0.712 and recall of 0.758, comparable to or exceeding leading proprietary and open-source models. T21 Research Assistant is available at: https://bioinformatics.cuanschutz.edu/t21-res-assi/

14.
arXiv (quant-ph) 2026-06-24

Clifford Volume and Free Fermion Volume: Complementary Scalable Benchmarks for Quantum Computers

arXiv:2512.19413v2 Announce Type: replace Abstract: As quantum computing advances toward the late-NISQ and early fault-tolerant eras, scalable and platform-independent benchmarks are essential for quantifying computational capacity in a classically verifiable manner. We introduce two volumetric benchmarks, Clifford Volume and Free Fermion Volume, that assess quantum hardware by testing the execution of random Clifford and free fermion operations. These two groups of unitaries possess a combination of properties that make them ideal for benchmarking: (i) each is individually efficient to simulate classically, enabling verification at scale; (ii) together they form a universal gate set; (iii) they serve as essential algorithmic primitives in practical applications (including shadow tomography and quantum chemistry); and (iv) their definitions are formulated abstractly, without explicit reference to hardware-specific features such as qubit connectivity or native gate sets. This framework thus enables scalable and fair cross-platform comparisons and tracks meaningful computational advancement. We demonstrate the practical feasibility of these benchmarks through extensive numerical simulations across realistic noise parameters and through experimental validation on Quantinuum's H2-1 trapped-ion quantum computer, which achieves a Clifford Volume of 34.

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

When AI Meets Finance (StockAgent): Large Language Model-based Stock Trading in Simulated Real-world Environments

arXiv:2407.18957v5 Announce Type: replace-cross Abstract: Can AI Agents simulate real-world trading environments to investigate the impact of external factors on stock trading activities (e.g., macroeconomics, policy changes, company fundamentals, and global events)? These factors, which frequently influence trading behaviors, are critical elements in the quest for maximizing investors' profits. Our work attempts to solve this problem through large language model based agents. We have developed a multi-agent AI system called StockAgent, driven by LLMs, designed to simulate investors' trading behaviors in response to the real stock market. The StockAgent allows users to evaluate the impact of different external factors on investor trading and to analyze trading behavior and profitability effects. Additionally, StockAgent avoids the test set leakage issue present in existing trading simulation systems based on AI Agents. Specifically, it prevents the model from leveraging prior knowledge it may have acquired related to the test data. We evaluate different LLMs under the framework of StockAgent in a stock trading environment that closely resembles real-world conditions. The experimental results demonstrate the impact of key external factors on stock market trading, including trading behavior and stock price fluctuation rules. This research explores the study of agents' free trading gaps in the context of no prior knowledge related to market data. The patterns identified through StockAgent simulations provide valuable insights for LLM-based investment advice and stock recommendation. The code is available at https://github.com/MingyuJ666/Stockagent.

16.
Nature (Science) 2026-06-09

A unicellular relative links aggregative multicellularity to animal origins

Authors:

How animals evolved complex multicellularity from their unicellular ancestors remains unanswered. Unicellular relatives of animals exhibit simple multicellularity through clonal division, formation of multinucleate coenocytes, or aggregation. 1 Therefore, animal multicellularity may have evolved from one (or a combination) of these behaviours. Aggregation has classically been dismissed as a means to complex multicellularity. 2 However, aggregation occurs in many extant animal cells and has also been recently described in three close unicellular relatives of animals (the choanoflagellates Salpingoeca rosetta and Choanoeca flexa, and the filasterean Capsaspora owczarzaki). 3-5 It is unclear whether aggregation in these species is derived or ancestral, and its relevance for animal origins remains unknown. To fill this gap, we investigated whether an additional close unicellular relative of animals can undergo aggregation. We discovered that the marine free-living bacterivorous filasterean Ministeria vibrans 6 forms homogeneous aggregates with reproducible kinetics that have long-term stability, and that improved feeding and mating may be evolutionary drivers of this aggregation. Notably, we found that homologs of many animal multicellularity genes involved in cell adhesion, signalling, and transcriptional regulation were deployed during the aggregation process, indicating that they may have been used for aggregation in the unicellular ancestors of animals before being co-opted into animal multicellular development. Thus, our results imply that aggregative multicellularity was key to the development of the multicellular animal genetic toolkit.

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

Large Language Models for Agentic NetOps and AIOps: Architectures, Evaluation, and Safety

arXiv:2605.12729v2 Announce Type: replace-cross Abstract: Large language models are increasingly being used to support network operations (NetOps) and artificial intelligence for IT operations (AIOps), including incident investigation, root-cause analysis, configuration synthesis, and limited self-healing. In both NetOps and AIOps, this shift is changing how tasks are managed. Agent-based operations work as workflows, from gathering evidence to taking action, following permissions, policies, and checks, and providing rollback options when necessary. This is crucial because operational decisions can have instant impacts. To make the argument concrete, we organise the relevant literature around the hierarchy of autonomy, tool scope, evidence traces, and assurance contracts. These contracts define what an agent may observe, propose, and execute. They also define the checks that must pass before any action is allowed. A consistent pattern appears across work on telemetry query recommendation, diagnosis, root-cause analysis, configuration synthesis, change planning, and limited self-healing. Operational reliability does not come chiefly from the model itself. It depends on the machinery around the model. We also argue that evaluation should go beyond static question answering. Agentic NetOps and AIOps systems require workflow-centred evaluation, including trace quality, bounded tool use, safe proposal generation, replay in sandboxed environments, and canary trials with rollback-aware scoring. Without these measures, a system may appear robust yet remain too fragile. Finally, we examine security, privacy, and governance risks that become acute when agents sit close to operational control surfaces. Taken together, the survey concludes that progress in intelligent NetOps and AIOps will depend on treating autonomy as a constrained operational control problem, whose outputs must be reliable, auditable, and securely deployable.

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

SMART: Scalable Mesh-free Aerodynamic Simulations from Raw Geometries using a Transformer-based Surrogate Model

Machine learning-based surrogate models have emerged as more efficient alternatives to numerical solvers for physical simulations over complex geometries, such as car bodies. Many existing models incorporate the simulation mesh as an additional input, thereby reducing prediction errors. However, generating a simulation mesh for new geometries is computationally costly. In contrast, mesh-free methods, which do not rely on the simulation mesh, typically incur higher errors. Motivated by these considerations, we introduce SMART, a neural surrogate model that predicts physical quantities at arbitrary query locations using only a point-cloud representation of the geometry, without requiring access to the simulation mesh. The geometry and simulation parameters are encoded into a shared latent space that captures both structural and parametric characteristics of the physical field. A physics decoder then attends to the encoder's intermediate latent representations to map spatial queries to physical quantities. Through this cross-layer interaction, the model jointly updates latent geometric features and the evolving physical field. Extensive experiments show that SMART is competitive with and often outperforms existing methods that rely on the simulation mesh as input, demonstrating its capabilities for industry-level simulations.

20.
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.

21.
arXiv (quant-ph) 2026-06-16

Interaction and non-Hermiticity controlled transmission in extended Su-Schrieffer-Heeger models

arXiv:2606.15245v1 Announce Type: cross Abstract: We study the transport characteristics of an extended version of the Su-Schrieffer-Heeger (SSH) model with next-nearest-neighbor (NNN) interactions and non-Hermitian onsite energies. We observed that transport in such a system is significantly modified by the NNN interaction and the non-Hermitian terms. The transmission coefficient exhibits oscillatory behavior as the strength of the NNN interaction varies in a fixed-length chain. Moreover, the transmission coefficient also shows oscillation with system size for a fixed strength of the NNN interaction. We find that novel oscillatory behavior of the transmission coefficient, arising form the NNN interaction, is a unique feature of such a model and has not been reported previously. The presence of the non-Hermitian terms also enhances/reduces the transmission coefficient depending on the values of the other system parameters like intra-, inter- and NNN hopping. It appears from our study that both the NNN interaction and the non-Hermiticity introduce significant changes in the transport properties of the extended SSH chain, which are not observed in the standard Hermitian nearest-neighbour variant of the SSH model.

22.
bioRxiv (Bioinfo) 2026-06-21

Expanding the GUSome: Structure-guided identification and characterization of gut microbial β-glucuronidases

The gut microbiome-encoded {beta}-glucuronidase (GUS) enzymes have a significant effect on human physiology through their deglucuronidation activity on endogenous and exogenous glucuronides. GUS activity also significantly influences the pharmacokinetics, efficacy and toxicity of various drugs including chemotherapeutic drugs. Given their crucial role in drug metabolism, GUS enzymes have emerged as promising targets for therapeutic intervention. Here, we have identified and characterized 79 unique GUS enzymes through a structure-guided approach. Structural modelling of these GUS enzymes revealed a conserved core and active-site residues with significant variations in the number and nature of the C-terminal domains. A new classification system based on the number and type of additional C-terminal domains is presented for the GUS proteins. Further, GUS enzymes have been categorized into different loop categories linked to their substrate preferences. The relationship between domain architecture and loop-type is explored by sequence similarity network analysis. We could successfully express, purify and validate GUS processing capability of a panel of identified GUS proteins. The nature of oligomer organization has been deciphered by SEC and DLS studies. Further, we have identified additional GUS enzymes capable of processing SN-38G, glucuronidated form of anticancer drug, irinotecan. These newly identified GUS enzymes will offer valuable insights into gut microbial GUS diversity and their role in understanding the population-specific drug-induced adverse effects on human health.

23.
arXiv (CS.AI) 2026-06-12

From Digital to Physical: Digital Agents as Autonomous Coaches for Physical Intelligence

arXiv:2601.21570v2 Announce Type: replace Abstract: The field of Embodied AI is witnessing a rapid evolution toward general-purpose robotic systems, fueled by high-fidelity simulation and large-scale data collection. However, this scaling capability remains severely bottlenecked by a reliance on labor-intensive manual oversight from intricate reward shaping to hyperparameter tuning across heterogeneous backends. Inspired by LLMs' success in software automation and science discovery, we introduce \textsc{EmboCoach-Bench}, a benchmark evaluating the capacity of LLM agents to autonomously engineer embodied policies. Spanning 32 expert-curated RL and IL tasks, our framework posits executable code as the universal interface. We move beyond static generation to assess a dynamic closed-loop workflow, where agents leverage environment feedback to iteratively draft, debug, and optimize solutions, spanning improvements from physics-informed reward design to policy architectures such as diffusion policies. Extensive evaluations yield three critical insights: (1) autonomous agents can qualitatively surpass human-engineered baselines by 26.5\% in average success rate; (2) agentic workflow with environment feedback effectively strengthens policy development and substantially narrows the performance gap between open-source and proprietary models; and (3) agents exhibit self-correction capabilities for pathological engineering cases, successfully resurrecting task performance from near-total failures through iterative simulation-in-the-loop debugging. Ultimately, this work establishes a foundation for self-evolving embodied intelligence, accelerating the paradigm shift from labor-intensive manual tuning to scalable, autonomous engineering in embodied AI field.

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

Progressive Pixel-Neighborhood Deformable Cross-Attention for Multispectral Object Detection

Effective cross-modal feature alignment and interaction are central challenges in multispectral object detection. Although global cross-attention provides strong long-range modeling ability, its quadratic complexity with respect to feature size limits deployment on resource-constrained platforms. We therefore propose Progressive Pixel-Neighborhood Deformable Cross-Attention for multispectral feature fusion, termed PNAFusion. The proposed framework is motivated by two observations: weak misalignment between visible and thermal images is usually concentrated around local neighborhoods, and semantic correspondence across modalities often follows non-linear spatial mappings that fixed receptive fields cannot model well. To address these issues, PNAFusion incorporates local spatial priors into its architectural design to concentrate feature interaction and alignment on the most relevant neighborhoods. Specifically, a Pixel-Neighborhood Cross-Attention (PNCA) module is introduced to avoid redundant global feature matching and suppress background noise. Meanwhile, an Adaptive Deformable Alignment (ADA) module captures non-linear spatial correspondences through learned pixel-wise offsets. These components are further integrated through an iterative feedback mechanism to progressively refine cross-modal feature alignment. Experiments on FLIR, M3FD, and DroneVehicle show that PNAFusion achieves 84.2, 90.5, and 85.5 mAP@0.5, respectively, under the YOLOv5 detector, and further reaches 86.8 mAP@0.5 on FLIR and 90.8 mAP@0.5 on M3FD when transferred to Co-DETR. Efficiency analysis indicates that PNAFusion reduces allocated GPU memory by 33.0\% compared with ICAFusion and reduces theoretical FLOPs from 194.8 G to 156.4 G, although the deformable sampling and iterative refinement introduce additional latency. Our code will be available at https://github.com/DanielQiuTian/PNAFusion.

25.
arXiv (CS.CV) 2026-06-12

Flex4DHuman: Flexible Multi-view Video Diffusion for 4D Human Reconstruction

We present Flex4DHuman, a multi-view video diffusion model that transforms a monocular or sparse multi-view video of a dynamic subject into synchronized dense multi-view videos using only relative camera-pose conditioning. Unlike prior human-centric methods that rely on skeletons, depth maps, normals, or rendered target-view geometry, Flex4DHuman requires no explicit geometry priors and instead conditions generation through relative camera-pose positional encoding. The generated videos can be directly ingested by downstream reconstruction pipelines to create dynamic 4D Gaussian splats. Built on the Wan 2.1 1.3B text-to-video model, Flex4DHuman preserves the backbone architecture and encodes camera and view information through a five-axis positional encoding that extends spatio-temporal RoPE with view indices and continuous SE(3) relative camera geometry. A three-stage curriculum progressively trains the model for pose following, flexible reference-to-target view generation, and temporal rollout. To support temporal rollout, we train with clean historical target-view tokens. We also add multi-view captions to enable test-time text control. Combined with an off-the-shelf 4D Gaussian Splatting stage, our framework lifts monocular static-camera videos into dynamic 4D Gaussian splats. Experiments on DNA-Rendering and ActorsHQ show that Flex4DHuman surpasses prior state-of-the-art methods, while the same formulation generalizes to animal categories after mixed human-animal training. These capabilities make Flex4DHuman a practical step toward scalable 4D content creation from casual monocular videos for simulation, gaming, AR/VR, and video re-shooting.