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

Deep Residual Injection for Full-Spectrum Forensic Signal Perception in Multimodal Large Language Models

Multimodal large language models (MLLMs) have been increasingly adopted in forensics for their robust semantic understanding. As AI-generated images become realistic, semantic-level inconsistencies alone are often insufficient for reliable detection. This motivates a critical question: whether MLLMs can achieve full-spectrum forensic signal perception, i.e., capturing low-level generator artifacts without sacrificing pre-trained semantic knowledge. We further perform a layer-wise analysis of forensic signal perception in MLLMs, showing that semantic information is primarily formed in the early-to-middle layers, whereas direct fine-tuning for artifact learning disrupts these semantic representations. Based on this insight, we propose Deep Visual Residual MLLM (Deep-VRM) to preserve early semantic processing while injecting artifact-specific visual signals as a residual path into an intermediate layer, where they are fused with semantic token representations and propagated through subsequent trainable layers. This enables later layers to jointly model semantic reasoning and signal-level forensic cues, and surprisingly, the model learns to adaptively leverage different levels of forensic signals depending on the input, achieving robust and generalizable detection performance. Extensive experiments show that our method achieves state-of-the-art across most benchmarks. The code and data are available at https://github.com/KQL11/Deep-VRM.

02.
arXiv (CS.AI) 2026-06-19

Confidence Calibration for Multimodal LLMs: An Empirical Study through Medical VQA

arXiv:2606.19950v1 Announce Type: cross Abstract: Multimodal Large Language Models (MLLMs) show great potential in medical tasks, but their elicited confidence often misaligns with actual accuracy, potentially leading to misdiagnosis or overlooking correct advice. This study presents the first comprehensive analysis of the relationship between accuracy and confidence in medical MLLMs. It proposes a novel method that combines Multi-Strategy Fusion-Based Interrogation (MS-FBI) with auxiliary expert LLM assessment, aiming to improve confidence calibration in Medical Visual Question Answering (VQA). Experiments demonstrate that our method reduces the Expected Calibration Error (ECE) by an average of 40\% across three Medical VQA datasets, significantly enhancing MLLMs' reliability. The findings highlight the importance of domain-specific calibration for MLLMs in healthcare, offering a more trustworthy solution for AI-assisted diagnosis.

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

First, do NOHARM: towards clinically safe large language models

arXiv:2512.01241v3 Announce Type: replace-cross Abstract: Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a 1,100-task benchmark of primary care-to-specialist consultation cases to measure the frequency and severity of harm from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 28 LLMs, recommendations carried the potential for severe harm in up to 22.6% of cases, with errors of omission accounting for more than 80% of severe errors. In a randomized trial of 101 generalist physicians, human benchmark performance significantly improved with AI assistance, yet physicians remained far from realizing the potential of AI tools, frequently ignoring essential advice surfaced by AI. Safety performance tracked general-intelligence and medical-knowledge benchmarks across the full range of models but decoupled at the frontier. Despite strong performance on existing evaluations, widely used AI models can produce medical advice with the potential for severe harm at non-trivial rates, highlighting the importance of explicit measurement of clinical safety.

05.
arXiv (CS.AI) 2026-06-15

Expert-Driven Survival Machines: Improving Stratification and Interpretability in Multiple Clinical Cohorts

arXiv:2606.14608v1 Announce Type: cross Abstract: Survival prediction plays a central role for healthcare providers and clinical researchers. Accurate risk stratification enables early intervention and improved patient management. Most existing deep survival models learn one common feature representation for all patients, which may hide important differences between patient subgroups. In contrast, a Mixture-of-Experts (MoE) framework allows different parts of the model to focus on different patient patterns, leading to more individualized representations. Therefore, in this work, we propose a mixture-of-experts enhanced adaptive deep clustering survival framework (AdaCSM) for modeling such heterogeneous survival patterns. We introduce a routing-based expert mechanism that enables conditional specialization within a parametric survival modeling framework. The proposed architecture allocates patients to specialized risk predictors dynamically while preserving the patient survival and subtype clustering objectives. We compare our method with state-of-the-art survival and deep clustering models on multiple real-world longitudinal clinical cohorts spanning diverse disease domains. The proposed method demonstrates improved predictive performance and leads to interpretable results in survival analysis.

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

Small LLMs: Pruning vs. Training from Scratch

Pruning promises a shortcut to strong small language models. In this work, we examine this promise by pruning Llama-3.1-8B at pruning ratios of 0.5–0.8 with six methods spanning depth, width, and sparse granularities, under two controlled token-matched settings. (1) With the same training token budget, pruned initialization consistently outperforms random initialization. This shows that the parent model provides a strong starting point, although the advantage narrows as the training token budget grows and as the pruning ratio rises, nearly vanishing at the highest pruning ratio we study. (2) When training from scratch is instead given the full token budget consumed by the whole pipeline, pruning at finer granularities still retains an advantage, while coarser structured pruning can be matched or surpassed. This suggests that the parent model transfers knowledge that additional training tokens alone cannot fully recover, but only at fine granularity. Taken together, our results yield a clear recommendation: with a large pretrained model in hand and a limited training token budget, pruning is better than training from scratch; when the training budget is not limited, training from scratch can be competitive for coarser pruning, so a large pretrained parent is not always necessary.

07.
arXiv (CS.LG) 2026-06-16

Information Leakage Detection through Approximate Bayes-optimal Prediction

arXiv:2401.14283v4 Announce Type: replace-cross Abstract: In today's data-driven world, the proliferation of publicly available information raises security concerns due to the information leakage (IL) problem. IL involves unintentionally exposing sensitive information to unauthorized parties via observable system information. Conventional statistical approaches rely on estimating mutual information (MI) between observable and secret information for detecting ILs, face challenges of the curse of dimensionality, convergence, computational complexity, and MI misestimation. Though effective, emerging supervised machine learning based approaches to detect ILs are limited to binary system sensitive information and lack a comprehensive framework. To address these limitations, we establish a theoretical framework using statistical learning theory and information theory to quantify and detect IL accurately. Using automated machine learning, we demonstrate that MI can be accurately estimated by approximating the typically unknown Bayes predictor's log-loss and accuracy. Based on this, we show how MI can effectively be estimated to detect ILs. Our method performs superior to state-of-the-art baselines in an empirical study considering synthetic and real-world OpenSSL TLS server datasets.

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

A Turbo-Inference Strategy for Object Detection and Instance Segmentation

Object detection and instance segmentation tasks are closely related. Existing top-down instance segmentation methods usually follow a detect-then-segment paradigm, where an initial detector is used to recognize and localize objects with bounding boxes, followed by the segmentation of an instance mask within each bounding box. In such methods, the detection accuracy directly influences the subsequent segmentation performance. However, previous research has seldom explored the impact of the instance segmentation task on object detection. In this paper, we present a turbo-inference strategy for the top-down methods that leverages the complementary information between detection and segmentation tasks iteratively. Specifically we design two modules: turbo-detection head and turbo-segmentation head, which facilitate communication between the tasks. The two modules form a closed loop that interlaces the detection and segmentation results without retraining the model. Comprehensive experiments on the COCO, iFLYTEK, and Cityscapes datasets demonstrate that our method substantially enhances both detection and segmentation accuracies with a certain increase in computational cost. The proposed method represents a tradeoff between prediction accuracy and inference speed. Codes are available at https://github.com/zhaozhen2333/Turbo-Learning.git.

09.
bioRxiv (Bioinfo) 2026-06-10

A Unified Spatial AI Framework for Cross-Domain Tissue-State Analysis in Trauma, Oral, and Cardiovascular Pathology

作者:

Objective: To develop a cross-domain spatial AI framework for identifying conserved tissue-state organisation across trauma, oral disease, and cardiovascular tissue using spatial transcriptomic data. Methods: Four public spatial transcriptomic datasets spanning wound healing, periodontitis, oral squamous cell carcinoma, and cardiac tissue were integrated using recurrence modelling, graph-based spatial learning, fuzzy tissue-state analysis, and tensor decomposition. Cross-domain coupling, spatial fragmentation, recurrence structure, and permutation-based topological validation were evaluated. Results: Six conserved fuzzy tissue states were identified, dominated by extracellular matrix remodelling, fibroblast/stromal activation, endothelial signalling, and inflammatory pathways. Latent embedding analysis demonstrated strong overlap between trauma and oral domains, while cardiovascular tissue exhibited more compact spatial organisation. Oral inflammatory tissue showed the highest fragmentation, whereas cardiovascular tissue demonstrated greater recurrence coherence. Tensor decomposition identified conserved stromal-remodelling programmes across domains. Permutation testing confirmed significantly elevated graph modularity and reduced spatial entropy relative to null distributions. Conclusion: The proposed framework identified conserved spatial tissue-state architecture linking wound healing, oral pathology, and cardiovascular tissue despite differences in tissue origin, pathology, and acquisition technology. Significance: These findings demonstrate the potential of spatial AI for investigating conserved stromal and inflammatory microenvironmental organisation across clinically related disease systems and may support spatial biology research in trauma–oral–systemic health.

10.
arXiv (CS.CV) 2026-06-16

Timestep Rescheduling in Diffusion Inversion

Diffusion inversion, which maps images back to the Gaussian latent space of a diffusion model, is a critical task for image reconstruction and editing. While DDIM enables fast deterministic inversion, it inherently introduces deviations that accumulate into noticeable inversion errors. Existing methods often address this by solving a fixed-point problem but largely overlook how the selection of the diffusion timestep in the noise scheduler influences inversion fidelity. In this work, we reveal that the deviation scale in diffusion inversion is strongly dependent on the timestep size, and exhibits a parabolic trend, with larger errors concentrated at both small and large timesteps. Based on this finding, we propose a simple yet effective nonuniform timestep scheduler that integrates a global rescaling with a local dynamic programming based rescheduling, enabling a strategic allocation of computational effort that minimizes the overall inversion error and preserves higher inversion accuracy. Our method serves as an off-the-shelf enhancement for existing inversion techniques and requires no extra parameters or computational overhead. Through extensive experiments, we verify that integrating our scheduler consistently boosts the performance of existing inversion methods, achieving superior results in image reconstruction and editing.

11.
arXiv (CS.AI) 2026-06-16

MADAR: An Address-Free Processor

arXiv:2606.15535v1 Announce Type: cross Abstract: In a modern processor, computing is the cheap part. Most of its area and energy go to addressing – moving operands to and from a register file and cache, and running the tags, ports, miss queues, and bypass networks that find a value where it was left. MADAR deletes that machinery by abolishing the address. All state circulates in rings of slots that advance one position per clock; instructions and data ride in the same slots; a value is named by its place in an orbit – a \rp{} coordinate – not by an address; a fixed station computes when a circulating instruction sweeps past its operands, on a schedule set at compile time; and a hierarchy of rings of increasing period replaces the cache hierarchy, movement between them scheduled rather than triggered by a miss. No prior circulating-store, dataflow, or statically scheduled machine combines all four of these. We define the execution model, validate it in a cycle-accurate register-transfer-level implementation, show it compilable – a constructive scheduler emits programs cross-checked against the implementation – and price it with a first-order energy model. The payoff is clearest for AI acceleration: the multiply-accumulate at the heart of every matmul and convolution compiles to a streaming form whose energy per operation stays flat as the reduction grows, and the operand reuse that makes matrix multiplication efficient is carried by the ring-period hierarchy – the memory hierarchy doing by rotation what a cache does by tags. MADAR is a new design point for any computation whose data movement is known before the program runs.

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

Evaluating Large Language Models Abilities for Addressee, Turn-change, and Next Speaker Prediction in Meetings

We investigate turn-taking in multimodal multi-party conversations using large language models (LLMs). We construct an evaluation framework for three tasks: addressee detection, turn-change prediction, and next speaker prediction. We compare supervised models trained for these tasks, text-based LLMs, multimodal LLMs (MM-LLMs), and human subjects. Experiments on the AMI corpus showed that LLMs outperformed supervised models and humans in next speaker prediction, despite not being trained on the target domain and without access to audio or visual information. An MM-LLM performed better than text-based LLMs on addressee detection and turn-change prediction but remained below human performance, indicating difficulty leveraging raw audio-visual signals. Ablation analyses revealed that conversational context was critical, particularly for next speaker prediction. We observed that human and LLM prediction patterns were similar, and intervals with frequent turn changes were difficult for both.

13.
arXiv (quant-ph) 2026-06-12

Geometric Algebra Quantum Gate Decomposition

arXiv:2606.12480v1 Announce Type: new Abstract: Quantum gates are usually described through matrix and tensor-product formalisms that often obscure their geometric structure. In this work, we formulate the Pauli and Clifford groups within the complex Geometric Algebra (GA) framework. We show that the Pauli group is naturally identified with the group of blades up to a global phase, thereby providing a geometric interpretation of Pauli operators and their commutation relations in terms of oriented subspaces. We further prove that Clifford operators are generated by products of {\pi}/4-Pauli rotors and introduce a greedy Pauli rotor decomposition algorithm whose empirical behavior suggests unexpectedly compact decompositions for Clifford operators. Finally, we show that Clifford+T universality admits a natural geometric interpretation through {\pi}/8-rotors within this framework.

14.
arXiv (CS.AI) 2026-06-15

Sorries Are Not the Hard Part: An Expert-Review Case Study of a Semi-Autonomous Formalization

arXiv:2606.13925v1 Announce Type: new Abstract: Large language models can often close proof gaps in interactive theorem provers, but a verified theorem is not the same thing as a reusable library contribution. We study this distinction through a detailed case study: a semi-autonomous formalization of Grothendieck's vanishing theorem. The initial version compiles with no sorries, but an expert review found serious problems in definitions, theorem generality, file organization, and the API. We then ran a review-driven refactor and compression process and obtained a second expert review. The before-and-after comparison shows a sharp split: agents adapted well to local, mechanically checkable feedback, but remained weak at choosing definitions and designing APIs. We argue that autoformalization should be evaluated not only by closed sorries, but by whether the resulting formalization survives expert review.

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

A Convex Quasilinearization Method for Solving Nonlinear PDEs with Physics-Informed Neural Networks

arXiv:2606.18175v1 Announce Type: cross Abstract: We present a numerical method for the forward solution of nonlinear partial differential equations (PDEs) in which Bellman-Kalaba quasilinearization reduces the nonlinear problem to a sequence of linear subproblems, each discretized by collocation onto a trial space that is linear in its parameters and solved by a single direct linear least-squares QR factorization. The trial space, which we term Linear-in-Learnables (LiL), comprises representations whose trainable parameters enter linearly, including random-feature extreme learning machines, spectral polynomial bases, and trigonometric expansions, each implemented as a physics-informed neural network. The method thus replaces the nonconvex gradient-based training that limits standard PINNs with a convex per-step solve. We establish local Newton-Kantorovich convergence of the outer iteration to a residual-limited neighborhood under an explicit smallness condition, with the limiting accuracy governed by the best-approximation residual of the trial space rather than by an optimization tolerance. The method, denoted LiL-Q, is assessed on seven benchmarks spanning scalar nonlinear PDEs (Bratu, viscous Burgers, Buckley-Leverett), coupled systems (plane-strain elasticity and the incompressible Navier-Stokes equations in two and three spatial dimensions), and steady-state Darcy flow with heterogeneous permeability. Across these problems, LiL-Q converges in single-digit outer iterations in most cases, even at the coarsest basis sizes and independent of the parameter count. When the exact solution lies in the span of the trial space, the method recovers it to machine precision in a single solve. On the Navier-Stokes benchmarks, it matches or exceeds published PINN solvers with up to two orders of magnitude fewer trainable parameters, without gradient-based optimization.

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

A Lightweight Fiducial-Based Pipeline for 3D Hyperspectral Mapping of ex-vivo Lumpectomy Specimens

Hyperspectral Imaging (HSI) is a promising modality for intraoperative assessment of resection margins in Breast-Conserving Surgery (BCS), but its clinical translation requires aligning the inherently 2D spectral information onto the 3D shape of the excised tissue so that suspicious regions can be precisely localized for targeted follow-up. We present a fully automated, calibration-free pipeline that produces a 3D hyperspectral point cloud of an ex-vivo lumpectomy specimen from a set of consumer-camera RGB images and a single top-down HSI acquisition. The 3D geometry is reconstructed with a deep-learning Structure-from-Motion backbone, stabilized in a metric reference frame by a custom bundle adjustment that enforces consistency on the corners of four ArUco markers placed around the specimen. The HSI cube is then registered to the reconstruction without recovering the HSI camera pose: the markers, visible in both modalities, define 16 corner correspondences that drive a planar homography, and 3D coordinates are recovered by lookup on an orthographically rendered depth map. Evaluated on two ex-vivo lumpectomy specimens, the pipeline achieves a median 3D registration error below 1~mm and a 2D reprojection error below 0.02 mm, with a total per-specimen processing time under 4 minutes on accelerated hardware. These results support the feasibility of integrating HSI-guided spatial localization into intraoperative margin assessment workflows for breast-conserving surgery.

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

Cross-Modal Masked Compositional Concept Modeling for Enhancing Visio-Linguistic Compositionality

Contrastively trained vision-language models like CLIP, have made remarkable progress in learning joint image-text representations, but still face challenges in compositional understanding. They often exhibit a "bag-of-words" behavior–struggling to capture the object relations, attribute-object bindings, and word order dependencies. This limitation arises not only from the reliance on global, single-vector representations for optimization, but also from the insufficient exploitation and modeling of the rich compositional information inherently present in paired image text data. In this work, we propose MACCO (MAsked Compositional Concept MOdeling), a framework that masks compositional concepts in one modality and reconstructs them conditioned on the full contextual information from the other, enabling the model to capture and align cross-modal compositional structures more effectively. To facilitate this process, we introduce two auxiliary objectives that jointly align and regularize masked features both inter-modally and intra-modally. Extensive experiments on five compositional benchmarks, along with in-depth analyses, demonstrate that our approach not only significantly enhances compositionality in VLMs but also improves their ability to capture syntactic structure and linguistic information. Additionally, the improved compositionality also benefits text-to-image generation and multimodal large language model. Code is available at https://github.com/hiker-lw/MACCO.

18.
arXiv (quant-ph) 2026-06-17

Active Quantum Reservoir Engineering: Using a Qubit to Manipulate its Environment

arXiv:2505.16898v4 Announce Type: replace Abstract: Quantum reservoir engineering leverages dissipative processes to achieve desired behavior, with applications ranging from entanglement generation to quantum error correction. Therein, a structured environment acts as an entropy sink for the system and no time-dependent control over the system is required. We develop a theoretical framework for active reservoir engineering, where time-dependent control over a quantum system is used to manipulate its environment. In this case, the system may act as an entropy sink for the environment. Our framwork captures the dynamical interplay between system and environment, and provides an intuitive picture of how finite-size effects and system-environment correlations allow for manipulating the environment by repeated initialization of the quantum system. We illustrate our results with two examples: a superconducting qubit coupled to an environment of two-level systems and a semiconducting quantum dot coupled to nuclear spins. In both scenarios, we find qualitative agreement with previous experimental results, illustrating how active control can unlock new functionalities in open quantum systems.

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

Distill Once, Adapt Life-Long: Exploring Dataset Distillation for Continual Test-Time Adaptation

Continual Test-Time Adaptation (CTTA) aims to maintain model performance under evolving target domains by adapting online without labeled data. However, practical deployments often cannot retain the source dataset due to privacy or licensing constraints, and purely source-free CTTA methods tend to become unstable under long-term distribution shift, suffering from compounding self-training errors and catastrophic forgetting. We introduce DO-ALL (Distill Once, Adapt Life-Long), a plug-and-play framework that revisits source information in a compact and privacy-conscious form via Dataset Distillation (DD). Before deployment, DO-ALL performs DD to produce a small set of synthetic distilled anchors that summarize the source distribution. During adaptation, each target sample is matched with its most semantically aligned anchor, which provides a stable reference for various CTTA via source replay, representation alignment, and manifold-smoothing regularization. DO-ALL can be seamlessly integrated into existing CTTA algorithms, consistently improving long-term robustness across CIFAR100-C, ImageNet-C, and the CCC benchmark. This demonstrates the potential of leveraging DD to enable stable and continuous adaptation without retaining raw source data. The code is available at https://github.com/blue-531/DOALL.

20.
arXiv (CS.LG) 2026-06-15

Machine Learning for Biomedical Raman Spectroscopy: From Spectral Acquisition to Clinical Translation

arXiv:2606.14169v1 Announce Type: new Abstract: Raman spectroscopy provides label-free, chemically specific characterization of biological systems and has become an important tool for cancer diagnosis, molecular subtyping, microbiological identification, and intraoperative decision support. Biomedical Raman spectra are, however, high-dimensional, noisy, and affected by fluorescence background, acquisition variability, and biological heterogeneity, making robust computational analysis essential. This review examines the role of machine learning across the biomedical Raman spectroscopy pipeline, from preprocessing and signal correction to unsupervised structure discovery, supervised diagnosis and molecular stratification, representation and transfer learning, explainability, biomarker discovery, and multimodal integration with imaging, pathology, and molecular profiling. Emphasis is placed on the use of machine learning not only for diagnostic classification, but also for biologically interpretable and clinically actionable analysis. We also discuss the main barriers to clinical translation, including limited dataset sizes, inter-instrument variability, inconsistent preprocessing, insufficient external validation, reproducibility concerns, and limited sharing of software, data, and metadata. We argue that progress will require methodological advances together with standardization, robust validation, explainability, and deployment-ready analytical frameworks. By integrating methodological, biomedical, and translational perspectives, this review outlines key directions for developing reliable and clinically deployable Raman-AI systems.

21.
arXiv (CS.AI) 2026-06-11

Risk Under Pressure: Compute-Aware Evaluation of Adversarial Robustness in Language Models

arXiv:2606.11409v1 Announce Type: cross Abstract: Adversarial robustness evaluations of large language models (LLMs) typically report attack success rate (ASR) under fixed query budgets, implicitly treating all attacks as equally costly. In practice, the computational expense of different attack strategies can vary by orders of magnitude. Consequently, ASR at a fixed budget can obscure the true effort required to jailbreak a model, thereby making it hard to determine whether an attack's cost justifies its payoff to the attacker. We propose a compute-aware evaluation framework based on computational pressure, measured in cumulative floating-point operations (FLOPs), as a proxy for adversarial effort. We introduce risk-compute curves, which map compute budgets to attack risk, and derive two metrics that summarize the average pressure required for a given attack to succeed. Across ten models spanning three families and four different stages in language model training and alignment, evaluated with three attack strategies (gradient-based, iterative refinement, and template-based) on two jailbreak robustness benchmarks, we find: (1) alignment training has non-monotonic effects on compute-space robustness; (2) scaling model size reduces gradient-based attack effectiveness but has limited impact on cheaper template-based attacks; (3) gradient-based attacks optimized on a surrogate model can transfer to a separate target model, providing a way to reduce attacker costs; (4) compute cost varies by up to ${\approx}5{\times}$ across harm categories within a single model; and (5) safety-aligned RL increases aggregate cost while leaving some categories disproportionately accessible. We release our framework to enable compute-aware risk assessment and evaluation.

22.
arXiv (CS.CV) 2026-06-16

Dual-branch Prompting for Multimodal Machine Translation

Multimodal Machine Translation (MMT) typically enhances text-only translation by incorporating aligned visual features. Despite the remarkable progress, state-of-the-art MMT approaches often rely on paired image-text inputs at inference and are sensitive to irrelevant visual noise, which limits their robustness and practical applicability. To address these issues, we propose D2P-MMT, a diffusion-based dual-branch prompting framework for robust vision-guided translation. Specifically, D2P-MMT requires only the source text and a reconstructed image generated by a pre-trained diffusion model, which naturally filters out distracting visual details while preserving semantic cues. During training, the model jointly learns from both authentic and reconstructed images using a dual-branch prompting strategy, encouraging rich cross-modal interactions. To bridge the modality gap and mitigate training-inference discrepancies, we introduce a distributional alignment loss that enforces consistency between the output distributions of the two branches. Extensive experiments on the Multi30K dataset demonstrate that D2P-MMT achieves superior translation performance compared to existing state-of-the-art approaches. Our code is publicly available at https://github.com/MentaY/DDP.

23.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

作者:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.

24.
arXiv (CS.AI) 2026-06-17

Lean4Agent: Formal Modeling and Verification for Agent Workflow and Trajectory

arXiv:2606.06523v2 Announce Type: replace Abstract: Equipping Large Language Models (LLMs) to execute reliable multi-step workflows has become a central challenge in artificial intelligence. Despite recent advances in LLMs' agentic capabilities, most agent systems still lack formal methods for specifying, verifying, and debugging their workflow and execution trajectories. This challenge mirrors a long-standing problem in mathematics, where the ambiguity of natural languages (NLs) motivates the development of formal languages (FLs). Inspired by this paradigm, we propose **Lean4Agent**, to the best of our knowledge, the first framework that uses Lean4, a dependent-type FL to model and verify agent behavior. **Lean4Agent** launches **FormalAgentLib**, an extensible Lean4 library for formally modeling and verifying agent workflows' semantic consistency under explicit assumptions, and enabling localization of execution-time failures revealed by trajectories. Building on **FormalAgentLib**, we further develop **LeanEvolve**, which applies results in **FormalAgentLib** to revise workflows to enhance its capability. Extensive experiments on a hard problem subset of SWE-Bench-Verified and a subset of ELAIP-Bench across 5 leading LLMs indicate that the verification-passing workflows outperform the failing ones by an average of **11.94%**, and **LeanEvolve** further improves SWE performance by **7.47%** on average. Furthermore, **Lean4Agent** establishes a foundation for a new field of using expressive dependent-type FL to formally model and verify agent behavior.

25.
arXiv (CS.AI) 2026-06-17

Learning Cardiac Electrophysiology Digital Twins Through Agentic Discovery of Hybrid Structure

arXiv:2606.18154v1 Announce Type: new Abstract: Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.