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01.
bioRxiv (Bioinfo) 2026-06-16

scIsoAgent enables autonomous isoform-resolved characterization and sequence-informed interpretation of long-read single-cell transcriptomes

Alternative isoform usage can alter gene function independently of total gene expression, creating a need to resolve transcript isoforms at single-cell resolution. Long-read single-cell RNA sequencing meets this need by linking cellular identity to transcript isoforms and sequence-level features. Realizing its full biological value requires reproducible workflows that connect specialized long-read analysis with biological interpretation. Existing large language model (LLM)-based biomedical agents support general omics analysis, but are not designed for isoform-resolved long-read single-cell workflows. Here, we present scIsoAgent, an autonomous LLM-powered scientific agent for long-read single-cell RNA-seq analysis. scIsoAgent turns heterogeneous long-read single-cell inputs into traceable isoform-resolved workflows, using stage-aware planning and persistent computational context to support both execution and interpretation. Across complementary evaluations, this design improved the continuity from analysis planning to executable, interactive workflows compared with general-purpose LLM baselines. In real-data reanalysis, scIsoAgent recovered major findings from published long-read single-cell resources and extended a representative differential transcript usage event into a sequence-informed functional hypothesis. By linking full-length isoform sequences with model-inferred transcript properties, scIsoAgent connects observed isoform usage with potential sequence-level functional consequences. These results demonstrate that autonomous scientific agents can transform fragmented long-read single-cell analysis into coherent, reproducible workflows for isoform-resolved discovery and biological interpretation.

03.
arXiv (CS.CL) 2026-06-24

CORE-BREW: LLR-Based Soft Decoding for Robust Multi-Bit LLM Watermarking

Reliable provenance for LLM outputs requires multi-bit watermarks that remain robust under editing while maintaining strict false-positive control. Existing ECC-based LLM watermarks rely largely on hard-decision decoding, discarding token-level reliability information. We propose CORE-BREW, a Constant-hit-Rate Embedding extension of block-wise BREW for robust multi-bit watermarking. CORE-BREW calibrates the watermark channel by targeting a fixed hit rate p-star, yielding closed-form per-token log-likelihood ratios (LLRs) for principled soft-decision decoding. It supports two detection modes: Strict-Safe, which preserves the bounded-distance designated-codeword acceptance region, and FPR-Calibrated, which uses likelihood-based scoring and lightweight list decoding to characterize the FPR-TPR trade-off. Experiments on open-source LLMs under token-level edits and paraphrasing demonstrate improved low-FPR discrimination and robustness over prior multi-bit watermarking baselines while maintaining comparable semantic quality.

04.
arXiv (CS.AI) 2026-06-18

Conflict-Aware Retriever Editing for Knowledge Injection Attacks on LLM-Based RAG Systems

arXiv:2606.18310v1 Announce Type: cross Abstract: Injecting malicious knowledge into retrieval-augmented generation (RAG) systems can manipulate retrieved evidence and mislead downstream generation, posing a serious security threat for AI applications. Existing RAG injection attacks mainly rely on manipulating external knowledge bases, such as crafting malicious corpus. However, the synthetic text crafted by such data-centric methods could be detectable, leading to the failure of attacks. Beyond corpus manipulation, open-source retrievers are increasingly exposing RAG systems to model-centric attacks. In this paper, we propose conflict-aware retriever editing, i.e., CAREATTACK, a model-centric retriever attack framework for malicious knowledge injection in RAG. Specifically, CAREATTACK consists two stages of conflict-aware retriever editing and attack-preserving anchor repair. Conflict-aware retriever editing adapts efficient closed-form parameter editing to the dense retrieval model, promoting malicious knowledge above benign competing passages and resolving potential parameter conflicts through graph-based conflict detection and parameter editing projection. Then, attack-preserving anchor repair performs lightweight calibration on the edited retriever to further eliminate the impact on non-target prompts while preserving the attack effectiveness for target prompts. We instantiate CAREATTACK on Qwen3-Embedding-0.6B and BGE-M3, and conduct evaluation on three benchmark datasets. Experimental results demonstrate our method substantially promote malicious passages into the retrieved knowledge of RAG systems and can perform attacks for batches of target prompts and passages, given the access of retrieval model parameters. Since most RAG systems are built upon open-source retrieval models, this work reveals a practical attack surface in RAG systems. Codes are public accessible at https://anonymous.4open.science/r/CareAttack-3F1C.

05.
arXiv (CS.CV) 2026-06-16

A Text Recognition Dataset from Sahidic Coptic Ancient Manuscripts

In this work, we target Handwritten Text Recognition (HTR) in low-resource scenarios, which arise from underrepresented languages, rare scripts, and degraded visual conditions typical of historical documents. We introduce SCAM (Sahidic Coptic Ancient Manuscripts), a new line-level dataset built from digitized ancient manuscripts written in the extinct Sahidic Coptic dialect. The dataset reflects a realistic and challenging setting, as it combines heterogeneous acquisition conditions across libraries with typical manuscript degradations such as ink fading, bleed-through, and material deterioration. In addition to visual complexity, SCAM poses significant linguistic challenges due to the scarcity of resources for Sahidic Coptic, its uncommon alphabet, and dialect-specific diacritics. To support research in low-resource HTR, we benchmark several state-of-the-art approaches based on different paradigms, highlighting their limitations and strengths in this setting. Our results underline the gap between current HTR performance on well-resourced modern scripts and historically grounded, low-resource scenarios, thus providing a reference point for future developments.

06.
arXiv (math.PR) 2026-06-18

A simple approach to the L{\o}kka-Zervos dichotomy for absolutely continuous dividend strategies

arXiv:2604.13302v3 Announce Type: replace-cross Abstract: We revisit the optimization problem solved in L{\o}kka & Zervos (2008), i.e., the maximization of dividends, in a Brownian risk model, with the possibility (not the obligation) of making capital injections. Following the approach introduced in Alvarez & Shepp (1998), Renaud & Simard (2021), Renaud et al. (2023), we consider instead absolutely continuous (AC) dividend strategies with an affine bound on the payment rates, while singular capital injections are still allowed. In addition, we incorporate a parameter for the cost of ruin or, said differently, a penalty at ruin in the performance function. We show that the solution is a so-called L{\o}kka-Zervos dichotomy: the surplus is never ruined by making bail-out payments, or no capital is injected and bankruptcy can occur; in either case, dividends are paid at full rate when the surplus is above a threshold. Our framework allows us to provide explicit conditions to express the dichotomy, either using the cost of capital injections or the cost of ruin as a criterion, which also exposes the underlying structure of the solution. In particular, for some values of the parameters, we show that it is optimal to liquidate. Moreover, we perform a numerical analysis highlighting the range of values generated under this AC affine-bound structure.

07.
arXiv (CS.CV) 2026-06-15

RT-VLA: Real-Time Vision-Language-Action Models via Knowledge Distillation

Vision-Language-Action (VLA) models have shown strong potential for end-to-end autonomous driving by jointly modeling visual perception, language reasoning, explainability and action prediction. However, their large vision-language backbones and reasoning modules introduce substantial inference latency and thereby prevent their deployment in the unforgiving reality of the road networks. We propose RT-VLA, a lightweight, distilled VLA model that transfers the driving and reasoning capabilities of the state-of-the-art SimLingo model into a compact student through multi-level supervised distillation. RT-VLA preserves language-based reasoning and supports post-hoc explanation through offline language analysis of safety-critical driving moments without adding latency to real-time control. Compared to the SimLingo teacher, RT-VLA maintains competitive closed-loop driving and language reasoning performance while reducing inference time by 44.8X in vision-only mode and 7.9X in vision+language mode. These results suggest that supervised distillation is a practical approach for building real-time, explainable VLA-style autonomous driving models.

08.
arXiv (CS.LG) 2026-06-24

Relatively Smart: A New Approach for Instance-Optimal Learning

arXiv:2603.01346v2 Announce Type: replace Abstract: We revisit the framework of Smart PAC learning, which seeks supervised learners which compete with semi-supervised learners that are provided full knowledge of the marginal distribution on unlabeled data. Prior work has shown that such marginal-by-marginal guarantees are possible for "most" marginals, with respect to an arbitrary fixed and known measure, but not more generally. We discover that this failure can be attributed to an "indistinguishability" phenomenon: There are marginals which cannot be statistically distinguished from other marginals that require different learning approaches. In such settings, semi-supervised learning cannot certify its guarantees from unlabeled data, rendering them arguably non-actionable. We propose relatively smart learning, a new framework which demands that a supervised learner compete only with the best "certifiable" semi-supervised guarantee. We show that such modest relaxation suffices to bypass the impossibility results from prior work. In the distribution-free setting, we show that the One-Inclusion Graph learner is relatively smart up to squaring the sample complexity, and show that no supervised learning algorithm can do better. For distribution-family settings, we show that relatively smart learning can be impossible or can require idiosyncratic learning approaches, and its difficulty can be non-monotone in the inclusion order on distribution families.

09.
arXiv (CS.CV) 2026-06-18

When AUC Misleads: Polarization-Aware Evaluation of Deepfake Detectors under Domain Shift

Recent advances in generative AI, such as diffusion models and face-swapping tools, have enabled the creation of highly realistic deepfakes, leading to real-world harms including financial fraud and non-consensual explicit content. In response, deepfake detection has become an active research area, with recent methods increasingly focusing on improving generalization to unseen manipulations. This is typically evaluated using the Area Under the ROC Curve (AUC) measured separately across multiple datasets. However, such an evaluation fails to reflect real-world scenarios where detectors face a mixture of data sources and varying artifact types. To address this limitation, we introduce a novel metric, Cross-dataset AUC (Cross-AUC) that averages per-domain AUCs with a measure of prediction polarization for taking into account the robustness to domain shift. The polarization extent is quantified by the Wasserstein Distance between class score distributions. Cross-AUC not only assesses the generalization capabilities of deepfake detectors under domain shifts more realistically, but it is also interpretable as it better explains the reason behind a drop in performance. Experiments performed on seven benchmark datasets demonstrate its practical relevance.

10.
medRxiv (Medicine) 2026-06-16

Diurnal variation in brain-derived tau and five other blood-based biomarkers for dementia and their association with cognitive performance

Blood-based biomarkers of dementia are a promising scalable tool for early diagnosis, tracking disease progression, and evaluating therapeutic efficacy. Utility of these biomarkers will not only be dependent on the reliability of their association with pathology but also contingent on their ability to track cognitive status. Previously, we demonstrated diurnal variation in several biomarkers (amyloid beta (A{beta}) 42 and 40, 42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and phosphorylated-Tau 217 (p-Tau217)) which has implications for their reliability. Here, we extend these observations to a larger cohort, include brain-derived tau (BD-Tau), which is assumed to be produced exclusively in the brain, and report endocrine measures of circadian rhythmicity. We not only assessed whether these biomarkers vary with time of day, but also whether they associate with daytime function and whether these associations vary with cognitive domain and number of repeated assessments. Data collected in 20 PLWA (72.4{+/-}5.9 years, mean{+/-}SD) and 19 controls (68.9{+/-}9.8 years) were analysed. Participants completed 14 days of home monitoring and one laboratory assessment of sleep and daytime function: mood, daytime sleepiness, reaction time, immediate and delayed memory recall, everyday memory errors. During the 27-hour residential laboratory session, 3-hourly blood samples were collected and analysed for the six blood-based biomarkers of dementia as well as melatonin and cortisol. Rhythmicity of melatonin and cortisol did not differ between groups. P-Tau217 and GFAP (p

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

Defending against Adaptive Prompt Injection Attacks via Reasoning-enabled Task Alignment

arXiv:2606.15441v1 Announce Type: cross Abstract: Indirect prompt injection attacks hijack LLM-based agents by embedding malicious instructions in third-party data that the agent retrieves during task execution. Existing defenses report near-zero attack success rate on static benchmarks, yet recent adaptive evaluations show that these results collapse once the attacker is allowed to optimize against the deployed defense. In this work, we trace this collapse to two failure modes. First, existing defense methods are confined to recognizing specific attack patterns, rather than assessing whether the intent of every embedded instruction is relevant to the user task. Second, training-based defenses, which otherwise offer the strongest safety-utility trade-off, assemble their adversarial examples from a handful of hand-crafted templates, and the resulting defender fails to generalize outside that narrow strategy distribution. To address these gaps, we propose RETA, a training-based method that grounds defense decisions on the user tasks rather than attacker-controlled data. At each tool-output step, the defender undertakes chain-of-thought reasoning verifying that its actions are consistent with the user task. Leveraging red-teaming, a simulated attacker synthesizes adversarial training data and receives a dictionary-learning diversity reward, achieving broad coverage of injection-reformulation strategies. Together, these allow the defender to be optimized via multi-objective reinforcement learning and achieve better safety-utility trade-off. Across six black-box adaptive attacks, RETA keeps every per-attack ASR below 10%, with average ASR of 2.92% and 3.75% on the two target models, while preserving most utility under attack and on clean inputs.

12.
arXiv (CS.CV) 2026-06-24

Token-to-Token Alignment of Text Embeddings for Semantic Blending

In modern generative models, images are specified and controlled through text prompts. In practice, images are generated from sequences of tokens derived from these prompts. However, the space of token sequences lacks a consistent accessible structure: semantically similar images may correspond to sequences that differ in wording, ordering, and placement of concepts, while similar token sequences may encode very different semantics. This apparent lack of structure makes it difficult to perform smooth transitions in this space, hindering applications such as image blending and continuous control of edits. We argue that this limitation stems not from the absence of semantic structure, but from misalignment between representations. To address this misalignment, we introduce Token-to-Token alignment, a framework that establishes explicit semantic correspondence between tokens across prompts. Our approach transforms prompts into a structured representation in which semantically corresponding concepts are mapped to consistent positions across prompts, and then aligns their token embeddings based on semantic similarity. Concretely, the method consists of two stages: a structural alignment that rephrases prompts into a shared structured form, followed by an embedding-level alignment that matches token representations across prompts. With this alignment in place, simple linear interpolation becomes a meaningful operation, producing smooth and coherent semantic transitions and enabling applications such as blending and continuous editing. Our results show that text embedding spaces in text-to-image models implicitly encode a continuous semantic structure that becomes accessible once representations are properly aligned, suggesting that semantic control can be achieved by organizing existing representations rather than modifying the generative model.

13.
arXiv (CS.LG) 2026-06-12

Generalized Schrödinger Bridge on Graphs

arXiv:2602.04675v2 Announce Type: replace Abstract: Transportation on graphs is a fundamental challenge across many domains, where decisions must respect topological and operational constraints. Despite the need for actionable policies, existing graph-transport methods lack this expressivity. They rely on restrictive assumptions, fail to generalize across sparse topologies, and scale poorly with graph size and time horizon. To address these issues, we introduce Generalized Schrödinger Bridge on Graphs (GSBoG), a novel scalable data-driven framework for learning executable controlled continuous-time Markov chain (CTMC) policies on arbitrary graphs under state cost augmented dynamics. Notably, GSBoG learns trajectory-level policies, avoiding dense global solvers and thereby enhancing scalability. This is achieved via a likelihood optimization approach, satisfying the endpoint marginals, while simultaneously optimizing intermediate behavior under state-dependent running costs. Extensive experimentation on challenging real-world graph topologies shows that GSBoG reliably learns accurate, topology-respecting policies while optimizing application-specific intermediate state costs, highlighting its broad applicability and paving new avenues for cost-aware dynamical transport on general graphs.

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

Human genetic evidence is associated with drug approval across therapeutic areas: an observational analysis of 26,278 target-disease pairs with temporal validation and feature ablation

Genetic evidence is enriched among approved drug targets: in an observational analysis of 26,278 target-disease pairs from Open Targets and ChEMBL, targets with any genetic association had a 3.25-fold higher approval rate than those without (OR = 3.25, 95% CI 2.79-3.79, p = 1.91e-42). A target-level analysis accounting for non-independence of pairs sharing the same gene gave OR = 2.79 (bootstrap 95% CI 2.22-3.53); the oncology pair-level OR of 6.72 attenuates to 2.71 at the target level, illustrating how non-independence inflates area-specific estimates. The enrichment replicated in post-2015 approvals (OR = 3.51, p = 1.72e-8). Feature ablation across six evidence types revealed that literature mining alone accounts for most classifier performance (AUPRC = 0.099 versus 0.109 for all features), consistent with temporal leakage from post-approval publications. Excluding literature, remaining evidence types retain above-baseline signal (AUPRC = 0.084, 1.63x baseline). Sensitivity analyses bracket the pair-level OR between 3.25 and 4.93. Genetic evidence alone yields only a 1.0-percentage-point absolute AUPRC gain and the best model has poor calibration; the classifier has limited practical predictive value. We catalogue 1,433 genetically supported Phase 1/2 pairs as a hypothesis-generating resource. All findings are observational.

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

Age of LLM: A Strategic 1v1 Benchmark for Reasoning, Diplomacy and Reliability of Large Language Models under Fog of War

作者:

We introduce Age of LLM, a turn-based 1v1 benchmark in which two LLMs face off on a 13x7 grid to destroy the enemy base. Three stressors are deliberate: fog of war, full diplomacy (messages, ceasefires, ultimatums; uranium kept secret), and a reliability dimension where every turn must follow a strict JSON schema and an illegal action is silently discarded. The engine is private and each match uses a fresh random map seed and opponent, mitigating the data contamination that affects public benchmarks. Models receive a (near) rule-only prompt with no build-order advice (two tactical seed phrases were present during data collection; see Section 2.7). We benchmark 15 reasoning models across 54 matches and 5,258 actions. Findings: (1) the nuclear rush dominates (78% on the rules-coherent v0.11+ sub-corpus; 85% corpus-wide) with a sole-launcher signature that is largely mechanical under secret-simultaneous launch rules, not a cognitive deterrence failure; (2) military conquest is rare but faster (12.3 vs 18.9 turns); (3) diplomacy is prolific yet almost never consummated; (4) ~58% of illegal actions are fog/state errors, making the illegal-action rate a measure of belief-tracking; (5) – the least established, and the only one we label exploratory – a weak link associates reliability with winning. The corpus is small, unbalanced and not side-swapped, so the ranking is a preliminary descriptive view, not a contribution. Beyond ranking, the turn-by-turn traces of actions and messages make the corpus a lens on how LLMs reason under adversarial uncertainty – their belief-tracking, spontaneous deception, and per-model cognitive "personas" – which we frame as a future research direction. We release the replay format, an isometric viewer and all replays; engine source on request.

16.
arXiv (CS.AI) 2026-06-24

THEIA: Learning Complete Kleene Three-Valued Logic in a Pure-Neural Modular Architecture

arXiv:2604.11284v5 Announce Type: replace-cross Abstract: We present THEIA, a 2.75M-parameter modular neural architecture that learns the complete Kleene three-valued logic (K3) truth table from task data without external symbolic inference or hand-encoded K3 gate primitives. Across 5 seeds it passes all 39 K3 rules at >99% per-rule accuracy. K3 learnability is not the central finding: Transformer baselines also pass all 39 rules, and flat MLPs match THEIA on Phase-1 accuracy within 0.04pp. The contributions are two properties of the learned system. (1) Uncertainty-verdict asymmetric propagation. THEIA preserves Has-Unknown at every upstream boundary (80.0/91.1/90.8/99.7% across Arith/Order/Set/Logic vs. ~52% majority) while final-verdict decodability stays at or below a 73.4% U-vs-non-U oracle reference under linear and nonlinear probes. Activation patching on non-absorbent T->U cases flips 4,898/4,898 OR and 4,719/4,719 AND pairs across 5 seeds, ruling out residual shortcuts. (2) Reliability spectrum under discretized end-to-end training, on tasks decomposable along the engine boundaries. A mod-3 sequential composition task generalizes from 5- to 500-step evaluation at 99.96+-0.04% (5 seeds). Under identical Gumbel-softmax training, flat MLPs collapse to chance by 50 steps; a 2x2 ResMLP grid reaches >=99% on only 3/20 (config, seed) trials; a pre-LN Transformer reaches 99.24+-0.34%. Straight-through discretization prevents 0.999^500 compounding; the architectural separator is sustaining Phase-1 accuracy under Phase-3 training, where flat MLPs fail. Auxiliary: under per-architecture development defaults (not optimizer-controlled), THEIA reaches 12/12 Kleene coverage 6.5x faster than a parameter-comparable 8L Transformer; this narrows to ~3.6x with Transformer-standard tuning and 4.93x with the same recipe on both. Ratios are config-specific, not asymptotic.

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

EgoSAT: A Comprehensive Benchmark of Egocentric Streaming Interaction Understanding

We introduce EgoSAT, the first comprehensive benchmark for egocentric video reasoning in streaming settings, designed to evaluate the capabilities of modern vision-language models (VLMs). The benchmark targets streaming interaction understanding, where video frames arrive sequentially and models must continuously interpret evolving visual context. EgoSAT unifies several previously distinct tasks within a single streaming framework. In this formulation, queries about completed events correspond to retrospective reasoning, queries about ongoing activities require online understanding, and queries about future actions involve prospective anticipation. This unified setting requires models to reason about the past, present, and future while operating under the constraint that only previously observed frames are available. EgoSAT contains 1,997 unique videos spanning 165 hours of egocentric footage and around 4,800 high-quality question-answer pairs, carefully designed to probe reasoning across varying temporal contexts. Using this benchmark, we evaluate a diverse set of both open-weight and closed-weight VLMs, providing a systematic assessment of their ability for streaming interaction understanding. By distinguishing answerability and conducting diagnostics on confidence of models, we find existing models not only struggle with prospective and retrospective modeling, but also exhibit severe mis-calibration: confidence often fails to track inherent answerability, leading to dangerous "confidently wrong" behaviors. Project page: https://leiyj23.github.io/EgoSAT/

18.
arXiv (CS.CL) 2026-06-24

Predicting Poets' Origins from Verse: A Computational Analysis of Regional Linguistic Fingerprints in the Complete Tang Poems

We ask whether the geographic origin of Tang-dynasty poets leaves a detectable linguistic trace in their work. Aggregating every poem attributed to each author in the Complete Tang Poems (Quan Tang Shi) and linking poets to their administrative circuit of origin via the China Biographical Database (CBDB), we build a poet-level corpus of 357 poets across the ten Tang circuits and frame origin prediction as multi-class classification. Using character $n$-gram TF-IDF together with interpretable domain features (imagery, season, and allusion), classical and neural models predict a poet's broad region (South vs.\ North) at $0.69$ accuracy, well above the $0.53$ majority baseline, and finer circuit-level origin above chance. Beyond classification, three findings emerge. (i) Linguistic distance between circuits grows with geographic distance (Mantel $r=0.40$, $p\approx0.09$ over nine circuits), evidence of a distance-decay effect in poetic language. (ii) The signal interacts with time: South/North separability is at chance in the High Tang and strongest in the Late Tang, consistent with court-driven homogenization at the empire's height followed by regional divergence. (iii) The model's confident errors are historically meaningful – in the Early Tang, every misclassification is a southern poet read as northern, reflecting the prestige of the northern court idiom. We further show that, when given the whole corpus through a hierarchical frozen-encoder representation, a classical-Chinese transformer (GuwenBERT) only matches – not beats – simple TF-IDF, and that combining them adds nothing, indicating that character $n$-grams already capture the regional signal. Our results position interpretable machine learning as a hypothesis generator for literary history.

19.
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.

20.
arXiv (CS.CV) 2026-06-18

Experimental Analysis of Neural Network-Based Image Classification on the CIFAR-10 Dataset

An experimental investigation of neural image classification on the CIFAR-10 benchmark is presented through fully connected and convolutional network formulations. The analysis emphasizes the complete learning pipeline: image vectorization, normalization, one-hot class encoding, supervised loss minimization, learning-rate selection, mini-batch training, convolutional feature extraction, max-pooling, and validation-based generalization assessment. A convolutional architecture with six convolutional layers and three max-pooling stages is evaluated for ten training epochs using a batch size of 128 and an Adam optimizer with a learning rate of 0.001. The validation accuracy reaches approximately 74.77%, while the validation loss begins to increase after the middle of training despite continued reduction in training loss. The resulting behavior illustrates the practical difference between representation learning and memorization, and it provides a compact experimental baseline for future studies on regularization, data augmentation, deeper architectures, and reproducible image-classification education.

22.
arXiv (CS.AI) 2026-06-11

Multimodal Ordinal Modeling of Alzheimer's Disease Severity Using Structural MRI and Clinical Data

arXiv:2606.11794v1 Announce Type: cross Abstract: Neurodegenerative diseases such as Alzheimer's disease (AD) require accurate and scalable tools for assessing disease severity, yet current clinical staging remains time-intensive and prone to variability. We propose an attention-enhanced multimodal machine learning framework with ordinal regression for automated and interpretable AD severity staging. The framework integrates T1-weighted MRI with demographic and genetic variables and compares unimodal and multimodal architectures using ordinal and non-ordinal prediction heads. Models were trained and validated using cohort-stratified splits derived from the ADNI, AIBL, and NIFD datasets. A strictly held-out test set was constructed using subjects excluded from all training, validation, preprocessing, and hyperparameter tuning procedures, with subject-level splitting employed throughout to prevent data leakage. Among unimodal approaches, the T1-weighted MRI model achieved slightly higher adjacent-stage accuracy (0.963) and agreement with clinical staging (QWK 0.444) than the tabular model (QWK 0.433). Integrating imaging, demographic, and genetic information improved overall performance. The multimodal non-ordinal baseline achieved the lowest prediction error (MAE 0.340), whereas the ordinal multimodal model achieved the highest adjacent-stage accuracy (0.970) and strongest agreement with clinical staging (QWK 0.549). These findings indicate that ordinal formulations better capture the ordered structure of the CDR scale and yield predictions more consistent with clinical staging. Explainability analyses using Grad CAM++ and SHAP demonstrated anatomically and clinically plausible model behavior, supporting transparent decision-making. Overall, attention-based multimodal learning with ordinal regression represents a robust, interpretable, and scalable approach for automated AD severity staging and AI-assisted clinical decision support.

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

APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization

arXiv:2606.12991v1 Announce Type: new Abstract: Cyclic peptides represent a promising class of therapeutic compounds in modern drug discovery, often offering improved stability and binding affinity. However, the de novo design of cyclic peptides remains challenging because methods must identify pocket-adaptive cyclization patterns and linkage sites while simultaneously controlling drug-relevant properties. This challenge is particularly pronounced for recent generative models trained predominantly on linear peptide data, which may fail to capture cyclization-specific constraints. To address the limitation, we introduce APCyc, a target-aware de novo cyclic peptide generation framework that explicitly models cyclization and jointly optimizes multiple essential physicochemical properties. By using an expanded residue vocabulary and explicitly encoding cyclization-site and linkage-type information, APCyc learns cyclization-aware representations and leverages Bayesian posterior guidance to steer sampling toward cyclic peptides satisfying multiple property objectives. Experimental results demonstrate that our model learns target-dependent cyclization preferences, and enables effective and controllable multi-property optimization for cyclic peptide design. The source code of this paper is available at https://github.com/HKUSTGZ-ML4Health-Lab/APCyc.

24.
arXiv (CS.CL) 2026-06-19

Prompt, Plan, Extract: Zero-Shot Agentic LLMs Workflows for Lung Pathology Extraction from Clinical Narratives

Information extraction from pathology reports is essential for cancer staging, tumor registry population. Yet key data remains embedded in narrative reports, making manual extraction labor-intensive and error-prone. Traditional supervised Natural Language Processing pipelines address this through fully supervised Named Entity Recognition and Relation Extraction, but require expensive manual annotation and suffer cascading failures when upstream entities are missed. In this study, we developed a zero-shot, agentic workflow, and evaluated five open-source generative Large Language Models (LLMs) to populate 13 College of American Pathologists synoptic fields from lung resection pathology reports. We compared them against a state-of-the-art supervised GatorTron NER-RE baseline using a novel, registry-aligned evaluation framework. The baseline achieved Micro-F1of 0.960, while the best zero-shot model (GPT-OSS-20B) achieved Micro-F1 of 0.893 (recall: 0.949), accurately extracting complex relations like Pathologic Stage without task-specific training. These results suggest that open-source, zero-shot agentic LLMs are a low-cost solution for extracting lung pathology information.

25.
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.