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01.
arXiv (math.PR) 2026-06-12

Stochastic dominations for FK percolation and sharp thinning thresholds for the Ising energy field

arXiv:2606.13648v1 Announce Type: new Abstract: At first glance, one would imagine that the energy field of the Ising model, the set of edges whose endpoints share the same spin, is stochastically monotone as a function of the coupling constants. However, this is not generally the case. In this paper, we introduce two weaker notions of stochastic domination that make this result true: $p$–weak and $p$–weak$^\dagger$ domination. Both of these notions depend on a parameter $p$ and we find the optimal values $p$ and $p^\dagger$ so that these dominations hold. One of the key ingredient to obtain some of the results is a new stochastic domination relating FK percolations with different parameters $q,\tilde{q}\geq 1$ that is of independent interest.

03.
arXiv (CS.CV) 2026-06-16

A biological vision inspired framework for machine perception of abutting grating illusory contours

Higher levels of machine intelligence demand alignment with human perception and cognition. Deep neural networks (DNN) dominated machine intelligence have demonstrated exceptional performance across various real-world tasks. Nevertheless, recent evidence suggests that DNNs fail to perceive illusory contours like the abutting grating, a discrepancy that misaligns with human perception patterns. Departing from previous works, we propose a novel deep network called illusory contour perception network (ICPNet) inspired by the circuits of the visual cortex. In ICPNet, a multi-scale feature projection (MFP) module is designed to extract multi-scale representations. To boost the interaction between feedforward and feedback features, a feature interaction attention module (FIAM) is introduced. Moreover, drawing inspiration from the shape bias observed in human perception, an edge detection task conducted via the edge fusion module (EFM) injects shape constraints that guide the network to concentrate on the foreground. We assess our method on the existing AG-MNIST test set and the AG-Fashion-MNIST test sets constructed by this work. Comprehensive experimental results reveal that ICPNet is significantly more sensitive to abutting grating illusory contours than state-of-the-art models, with notable improvements in top-1 accuracy across various subsets. This work is expected to make a step towards human-level intelligence for DNN-based models.

04.
Science (Express) 2026-04-23

Structural N- and O-glycans revealed by high-resolution cryo-EM analysis of tubular mastigonemes | Science

作者: 未知作者

The chemical complexity and non-templated biosynthesis of glycans have posed significant challenges for establishing sequence-structure relationships. Here we report cryo-EM structures of tubular mastigonemes from a golden alga species, Ochromonas danica , in which a large number of N- and O-glycans are resolved at 1.8-2.2 Å resolution. Beyond high-mannose and complex N-glycans, we identify a non-canonical N-glycan on the Ala- Asn -Asp (A N D) motif. The surface spikes comprise dense O-glycans coating PSXX tetrapeptide repeats, with two glycans linked on trihydroxylated proline and one on serine per repeat. In addition to various types of sugars and their covalent modifiers, water molecules (>10% of resolved volume) and cations are clearly resolved and mediate the structural assembly. Our study establishes a framework for investigating glycan folding in high-order biological assemblies.

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

Towards Pareto-Optimal Tool-Integrated Agents with Pareto Ranking Policy Optimization

Recent advances in tool-integrated language agents have significantly improved their ability to solve complex reasoning tasks. However, existing alignment methods predominantly focus on maximizing task accuracy, while overlooking auxiliary objectives such as tool-use efficiency, which are essential for practical deployment. To address this gap, we introduce ParetoPO, a two-stage multi-objective optimization framework for aligning tool-using large language models (LLMs) under competing objectives. In the first stage, ParetoPO leverages hypervolume-guided dynamic scalarization to adapt reward weights based on global Pareto frontier progress. In the second stage, it replaces scalarized learning signals with Pareto-ranking-based advantage computation, promoting nondominated trajectories through dominance-aware credit assignment. This design enables fine-grained, action-level optimization across multiple conflicting objectives. Experimental results on mathematic reasoning and multi-hop QA tasks show that ParetoPO consistently discovers policies with superior accuracy-efficiency trade-offs compared to static and heuristic baselines.

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

Enhancing Visual Feature Attribution via Weighted Integrated Gradients

arXiv:2505.03201v4 Announce Type: replace-cross Abstract: Integrated Gradients (IG) is a widely used attribution method in explainable AI, particularly in computer vision applications where reliable feature attribution is essential. A key limitation of IG is its sensitivity to the choice of baseline (reference) images. Multi-baseline extensions such as Expected Gradients (EG) assume uniform weighting over baselines, implicitly treating all baseline images as equally informative. In high-dimensional vision models, this assumption often leads to noisy or unstable explanations. This paper proposes Weighted Integrated Gradients (WG), a principled approach that evaluates and weights baselines to enhance attribution reliability. WG introduces an unsupervised criterion for baseline suitability, enabling adaptive selection and weighting of baselines on a per-input basis. The method preserves the core axiomatic properties of IG in a generalized weighted-baseline form. Under an expected, proxy-based fitness–relevance monotonicity assumption, WG provides a probabilistic justification for assigning larger weights to more informative baselines. Experiments on commonly used image datasets and models show that WG improves over EG under our protocol, with up to 36% gains across evaluated convolutional and Transformer architectures. These gains come with additional fitness-evaluation cost, so WG should be viewed as an attribution-fidelity trade-off rather than a faster alternative to EG. By moving beyond the assumption that all baselines contribute equally, Weighted Integrated Gradients offers a clearer and more reliable approach to explaining computer-vision models, improving both understanding and practical usability in explainable AI.

07.
arXiv (CS.LG) 2026-06-18

UST-GNN: A Unified Spatial–Topological Graph Neural Network Framework for Urban Analytics–Demonstrated through a Case Study on Urban Health Prediction

arXiv:2504.04739v3 Announce Type: replace Abstract: Understanding how social, demographic, environmental, and spatial factors jointly shape urban outcomes is essential for sustainable urban development and evidence-based policy. Traditional statistical approaches often struggle to capture complex non-linear relationships, while many machine learning methods overlook the joint roles of spatial autocorrelation and network topology in urban systems. Recent advances in GeoAI have addressed these challenges only partially, often treating spatial effects, graph structure, evaluation, and interpretability separately. We present UST-GNN, a unified spatial–topological graph neural network framework that integrates neighbourhood connectivity, heterogeneous urban features, and positional/locational embeddings into a single representation. Using the MedSAT dataset, which contains over 150 environmental and socio-demographic variables and six prescription outcomes across 4,835 neighbourhoods in Greater London, UST-GNN outperforms strong statistical, geographically enhanced, and graph Machine Learning baselines, improving out-of-sample $R^2$ by 8.4–13.2\% under strict spatial cross-validation. We further introduce a lightweight principal-component module to interpret learned node embeddings geographically and relate them to policy-relevant covariates. The resulting analyses recover established patterns, offer new perspectives on debated associations, and reveal novel predictors warranting further causal investigation. Together, these findings demonstrate the value of graph-based spatial machine learning for urban health analytics, environmental inequality assessment, and evidence-based urban policy. Beyond predictive gains, UST-GNN provides a unified GeoAI analytical pipeline that can be embedded into urban digital twin workflows for scenario testing, monitoring, and data-informed decision-making for healthier, more sustainable cities.

08.
arXiv (CS.CV) 2026-06-16

VinQA: Visual Elements Interleaved Long-form Answer Generation for Real-World Multimodal Document QA

Real-world documents combine text with tables, charts, photographs, and diagrams arranged in diverse layouts, yet existing research on multimodal large language models (MLLMs) for document QA predominantly produces text-only responses, underutilizing these visual elements. We introduce VinQA, a dataset for long-form answer generation where cited visual elements are explicitly interleaved with their supporting text and grounded in relevant document pages. To support this task, we study two encoding methods for feeding raw document page images into an MLLM, along with their visual-element citation mechanisms: (1) Page Encoding, which directly encodes full-page images with bounding boxes of visual elements and treats these boxed regions as citable units; and (2) Modality Encoding, which parses each page to extract text and crop visual elements, encodes them separately, and uses these cropped elements as citable units. In our experiments, we propose M-GroSE, a multimodal evaluation framework extending GroUSE to assess answers along four dimensions: completeness, answer relevancy, faithfulness, and unanswerability. We additionally report Visual Source F1 to directly measure visual citation accuracy. Although proprietary frontier models still achieve the best overall scores on the VinQA test split, fine-tuning open Qwen2.5-VL models on the training split substantially improves their performance and narrows this gap. Modality Encoding is initially more robust for complex documents with long text, many visual elements, and diverse citation requirements. After training on VinQA, however, Page Encoding reaches a comparable level, competing effectively even without the explicit parsing used in Modality Encoding. Finally, Visual G-Eval, an MLLM-based judge, confirms that fine-tuned models insert visual elements at semantically appropriate positions with faithful supporting text.

09.
arXiv (math.PR) 2026-06-18

Geometric obstructions to Lipschitz transport between weighted Hessian $\mathrm{CD}(\kappa,\infty)$ manifolds

arXiv:2606.11085v2 Announce Type: replace Abstract: We construct a weighted Riemannian manifold $(\mathbb R^2,g,\mu)$ satisfying $\mathrm{CD}(1/2,\infty)$, the curvature-dimension condition, with the following property: if $\gamma$ denotes a centered Gaussian measure on $\mathbb R^2$, then there is no Lipschitz map $T:(\mathbb R^2,\|\cdot\|) \to (\mathbb R^2,g)$ satisfying $T_\#\gamma=\mu$. Building on this, we prove a Weyl-type asymptotic law for the eigenvalues of the weighted Laplacian $-\Delta_{g,\mu}$ and show that they are asymptotically negligible when compared to the eigenvalues of $-\Delta_{\gamma}$. These results give strong counterexamples to two questions of E. Milman and complement the recent counterexample of Aryan.

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

The Truth Stays in the Family: Enhancing Contextual Grounding via Inherited Truthful Heads in Model Lineages

Recent advances in large language models (LLMs) have produced many specialized multimodal LLMs (MLLMs) that share common foundational LLMs, forming distinct model lineages. It remains unclear whether a fundamental behavioral link exists between the foundational LLMs and downstream variants. We investigate this question by quantifying head-level context-truthfulness scores. Across diverse LLM and MLLM lineages, including Vicuna-, Qwen2.5-, LLaMA2-, and Mistral-based models, we find that Truth Scores are strongly preserved within model families, even after instruction tuning or multimodal adaptation. We further show that this inheritance is consistent with attention-head weight preservation, and that context-truthful heads attend to query-relevant evidence. Building on this finding, we propose TruthProbe, a soft-gating strategy that amplifies context-truthful heads while preserving other head contributions. TruthProbe improves contextual truthfulness on HaluEval and reduces multimodal hallucination on POPE and CHAIR, with base-LLM Truth Scores transferring effectively to their fine-tuned LLM and MLLM descendants. Code is available at https://github.com/miso-choi/TruthProbe.

11.
arXiv (CS.AI) 2026-06-15

UltraSketchLLM: Sub-1-Bit LLM Compression via Sketch and Hardware-Friendly Operators

arXiv:2506.17255v2 Announce Type: replace-cross Abstract: Large language models (LLMs) require larger GPU memory size these days, necessitating efficient and extreme weight compression methods. Existing compression methods are either theoretically limited by 1 bit per weight or face severe performance degradation and inefficiency. To deploy LLMs in resource-constrained scenarios, we introduce UltraSketchLLM, compressing LLMs with data sketch. It reduces peak GPU memory footprint with a high compression rate down to 0.5 bit per weight. Combined with hardware-friendly implementation, UltraSketchLLM keeps tolerable performance degradation and extremely low latency overhead with 14.9x speedup compared to naive sketch solution.

12.
medRxiv (Medicine) 2026-06-17

Efficacy of a Gamified Digital Platform for Substance Use Education and Overdose Prevention Among College Students: a Pilot and Feasibility Study

Background: For US young adults aged 18-25 in the 2018-2024 period, fentanyl was involved in 78.2% of the 44,020 unintentional or undetermined-intent overdose deaths, most often co-involving stimulants and other non-opioid substances. While fatal overdose rates in this age group have fallen to their lowest recorded level, emergency medical services-attended non-fatal overdose events have reached record highs, shifting the decisive variable toward bystander recognition and response. College students report near-universal alcohol education but minimal education on the substances actually driving overdose mortality. Methods: We conducted a single-group pre-post evaluation of the DopaGE Portal, a gamified, mastery-based digital platform covering cocaine, MDMA, benzodiazepines, and opioid overdose response, deployed at a public university (UNL) and a multi-campus volunteer network (TACO). Paired pre/post surveys (N=42) measured self-efficacy (7 items; primary), behavioral intentions, risk perception, and knowledge/attitudes on 5-point scales, plus four factual knowledge questions. Paired t-tests, exact McNemar tests, and Benjamini-Hochberg correction across eight primary tests were applied. Institutional naloxone distribution at UNL was tracked as an ecological behavioral outcome. A mandated high-school cohort (N=94) provided supplementary acceptability data. Results: Self-efficacy increased from 2.82 to 4.46 (d=2.00, 95% CI 1.46-2.55; adjusted p

13.
arXiv (CS.CV) 2026-06-16

HAFMat: Hybrid Priors Guided Adaptive Fusion for Single-Image Human Material Estimation

Physically based rendering (PBR) material estimation is a fundamental appearance decomposition task with broad applications in virtual content creation, relighting, and digital human rendering. However, estimating PBR materials from a single human image remains highly ill-posed, since illumination, geometry, and reflectance are heavily entangled in the observed appearance. To mitigate this ambiguity, we propose HAFMat, a hybrid-prior-guided framework for single-image human material estimation. Our method introduces guidance maps that encode complementary cues, including appearance, body geometry, structure, and prior material predictions from pre-trained models. A key observation is that these guidance cues are heterogeneous: some cues mainly provide texture-level constraints, while others convey higher-level semantic information. To exploit this property, we design a Multi-layer Adaptive Feature Fusion Mechanism, which adaptively fuses guidance features with decoder features at different stages. This design enables texture-dominant and semantic-dominant cues to guide material decoding at appropriate levels, leading to more accurate and physically plausible material estimation. Extensive experiments on both synthetic and real data demonstrate that our method achieves state-of-the-art performance in material estimation and downstream relighting.

14.
arXiv (CS.CV) 2026-06-11

UniReason-Med: A Shared Grounded Reasoning Interface for 2D-to-3D Transfer in Medical VQA

We study whether grounded reasoning supervision from abundant 2D medical images can improve 3D medical VQA when both input types are aligned through a common reasoning interface. We introduce UniReason-Med, a single-checkpoint framework that processes either a 2D image or a slice-serialized 3D volume at inference time, generating interleaved textual reasoning and localized visual evidence through shared box syntax, region-token injection, and a common grounded reasoning policy. To train this interface, we construct UniMed-CoT, a 220K instruction-tuning dataset with interleaved textual reasoning and grounded visual evidence, including 170K 2D and 50K 3D samples. Through supervised fine-tuning followed by outcome-level reinforcement learning, UniReason-Med learns to generate grounded reasoning traces without IoU/Dice-based localization rewards during RL. Data-mixture and component ablations show that joint 2D+3D grounded supervision substantially improves 3D reasoning over 3D-only training, while grounding and region-token injection consistently benefit both 2D and 3D tasks. These results suggest that a shared grounded reasoning interface can transfer reasoning structure from 2D images to slice-serialized volumetric medical understanding. The code and data are publicly available at https://github.com/IQuestLab/unireason-med.

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

Dual Cross-Attention Siamese Transformer for Rectal Tumor Regrowth Assessment in Watch-and-Wait Endoscopy

Increasing evidence supports watch-and-wait (WW) surveillance for patients with rectal cancer who show clinical complete response (cCR) at restaging following total neoadjuvant treatment (TNT). However, accurate methods to early detect local regrowth (LR) from follow-up endoscopy images during WW are essential to manage care and prevent distant metastases. Hence, we developed a Siamese Swin Transformer with Dual Cross-Attention (SSDCA) to combine longitudinal endoscopic images at restaging and follow-up and distinguish cCR from LR. SSDCA leverages pretrained Swin Transformers to extract domain agnostic features and enhance robustness to imaging variations. Dual cross attention is implemented to emphasize features from the paired scans without requiring any spatial alignment to predict response. SSDCA as well as Swin-based baselines were trained using image pairs from 135 patients and evaluated on a held-out set of image pairs from 62 patients. SSDCA produced the best balanced accuracy (81.76% $\pm$ 0.04), sensitivity (90.07% $\pm$ 0.08), and specificity (72.86% $\pm$ 0.05). Robustness analysis showed stable performance irrespective of artifacts including blood, stool, telangiectasia, and poor image quality. UMAP clustering of extracted features showed maximal inter-cluster separation (1.45 $\pm$ 0.18) and minimal intra-cluster dispersion (1.07 $\pm$ 0.19) with SSDCA, confirming discriminative representation learning. Code and weights available at: https://github.com/Jotanator/SSDCA

17.
arXiv (CS.CL) 2026-06-18

Attention as Frustrated Synchronization

A network of oscillators that synchronizes perfectly computes nothing further, so an attention architecture built from synchronization must locate its computation in structured departures from agreement. We introduce the Frustrated Synchronization Network (FSN), whose token states are phases on a torus and whose entire value pathway is one learned complex coupling kernel over harmonics and a one-step delay. Each component of the kernel is a frustration in the sense of the synchronization literature. The complex phases are static Kuramoto-Sakaguchi frustration angles, the signed harmonics are repulsive Daido components, and the delay term, which couples each token to the successors of the tokens it attends to, is algebraically identical to Kuramoto-Sakaguchi coupling whose frustration angle is the data's own transition, so next-token prediction is implemented as synchronization frustrated by the data. At matched one-million-parameter and training budgets on character-level text and code, the FSN's validation loss is below a tuned RoPE-SwiGLU transformer's at every epoch measured, and the comparison survives training the baseline to convergence: every thirty-epoch enwik8 seed finishes below the transformer's converged fifty-epoch loss of 1.611, and the FSN's completed fifty-epoch runs converge to 1.5953 +/- 0.0014. A variant with every feed-forward block replaced by mean-field coupling to learned collective modes, leaving no multilayer perceptron in the stack, tracks the transformer. On natural text the unfrustrated base layer falls behind the converged transformer at every copy depth, worst on long-range copy events; the kernel reverses the deficit at every depth of four and beyond. Headline comparisons are at the one-million-parameter scale; a scale ladder is complete through four million parameters with the advantage persisting, and remaining arms are marked as in progress.

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

Pix2Pix-Hybrid: Structure-Guided Conditional Synthesis of Hajj Crowd Images with Multi-Channel Conditioning and Weak Attribute Supervision

Developing accurate crowd-counting models for Hajj pilgrimage scenes remains challenging because domain-specific annotated images are scarce and data collection during large gatherings raises privacy concerns. To address these limitations, this paper proposes Pix2Pix-Hybrid (P2P-H), a hybrid conditional GAN for structure-guided Hajj crowd-image synthesis and data augmentation. P2P-H builds on Pix2Pix and employs a U-Net generator conditioned on eight input channels that jointly encode structural cues (edges and grayscale) and contextual attributes (crowd density and time of day). To capture detailed textures in dense scenes, the framework integrates two multi-scale PatchGAN discriminators operating at different resolutions. The training procedure combines adversarial, perceptual, and feature-matching objectives with adaptive data augmentation and stabilization strategies. The model was trained on 993 real Hajj frames collected from 60 publicly available video sources, with conditioning attributes derived automatically to reduce manual labeling effort. Using this framework, we constructed CrowdH, a synthetic dataset of 10,000 high-resolution Hajj crowd images. Experimental results show that P2P-H improves structure-preserving conditional synthesis quality compared with Pix2Pix and StyleGAN2-ADA baselines and shows favorable transfer to other crowd datasets. To assess downstream utility, we further constructed CrowdH-Mix-469, an annotated mixed real-synthetic dataset comprising 384 real Hajj images and 85 selected synthetic images,and evaluated five crowd-counting models under real-only and real-plus-synthetic training. The selected synthetic data reduced MAE across all five models, with the strongest gain observed for CSRNet.

19.
arXiv (CS.CL) 2026-06-12

BLUEmed: Retrieval-Augmented Multi-Agent Debate for Clinical Error Detection

Terminology substitution errors in clinical notes, where one medical term is replaced by a linguistically valid but clinically different term, pose a persistent challenge for automated error detection in healthcare. We introduce BLUEmed, a multi-agent debate framework augmented with hybrid Retrieval-Augmented Generation (RAG) that combines evidence-grounded reasoning with multi-perspective verification for clinical error detection. BLUEmed decomposes each clinical note into focused sub-queries, retrieves source-partitioned evidence through dense, sparse, and online retrieval, and assigns two domain expert agents distinct knowledge bases to produce independent analyses; when the experts disagree, a structured counter-argumentation round and cross-source adjudication resolve the conflict, followed by a cascading safety layer that filters common false-positive patterns. We evaluate BLUEmed on a clinical terminology substitution detection benchmark under both zero-shot and few-shot prompting with multiple backbone models spanning proprietary and open-source families. Experimental results show that BLUEmed achieves the best accuracy (69.13%), ROC-AUC (74.45%), and PR-AUC (72.44%) under few-shot prompting, outperforming both single-agent RAG and debate-only baselines. Further analyses across six backbone models and two prompting strategies confirm that retrieval augmentation and structured debate are complementary, and that the framework benefits most from models with sufficient instruction-following and clinical language understanding.

20.
arXiv (CS.LG) 2026-06-12

Accelerating Speculative Diffusions via Block Verification

arXiv:2606.13426v1 Announce Type: new Abstract: Speculative decoding speeds up LLM inference by using a draft model to generate tokens, with an acceptance-rejection scheme that ensures that the output matches the target distribution. Adapting this to continuous diffusions is difficult because speculative sampling requires drawing from a residual distribution. While straightforward in discrete spaces, efficiently sampling this residual in continuous space is non-trivial. Consequently, existing diffusion adaptations either use computationally inefficient sampling techniques or rely on an alternative scheme. In this work, we introduce a novel scheme that efficiently implements the original speculative sampling mechanism for diffusion models. Our approach offers a critical advantage over current methods: it enables us to adapt block verification from LLMs to diffusions – which provably improves the acceptance rate of drafts. Furthermore, we formalize and analyze the Free Drafter, a heuristic self-speculative drafter for diffusions that requires no training. By enabling block verification, our Free Drafter yields up to a 6.3% speedup over existing speculative methods with no additional training and negligible overhead beyond the existing parallel verification pass.

21.
arXiv (CS.CV) 2026-06-15

Manga109-v2026: Revisiting Manga109 Annotations for Modern Manga Understanding

Manga is a culturally distinctive multimodal medium and one of the most influential forms of Japanese popular culture. As AI systems increasingly target manga understanding, OCR, and translation, Manga109 has become a foundational dataset for manga-related AI research. However, the current Manga109 dataset contains inaccurate transcriptions and coarse annotations, which do not align well with modern OCR and multimodal manga understanding tasks. In this work, we revisit the dialogue text annotations of Manga109 and identify five categories of annotation issues, including inaccurate transcriptions, missing text regions, overlapping dialogue and onomatopoeia, and under-segmented speech balloons. To address these issues, we combine OCR-based issue detection and manual revision to construct Manga109-v2026, revising approximately 29,000 dialogue annotations. Our revisions better align Manga109 with modern OCR and multimodal manga understanding systems while preserving expressive structures characteristic of manga.

22.
arXiv (CS.CL) 2026-06-17

A Framework for Evaluating Agentic Skills at Scale

Agent skills – structured, reusable knowledge artifacts that augment LLM agent capabilities – have been rapidly adopted in industry, yet their cross-domain impact and use across commercial and open-source models remain under-studied, and no reusable methodology exists for evaluating an individual skill. In this work, we present an evaluation framework that lets a skill author construct realistic tasks to rigorously assess the aspects of a skill that matter most to them, and that estimates skill utility by solving those tasks. Further, we apply our evaluation approach at scale to 500 real-world skills, generating 1,000 tasks derived from the skills' content, along with instruction-following and goal-completion scoring rubrics. Using these metrics, we evaluate how 19 agent-model configurations, both proprietary and open-source, perform on the tasks. Our results show that models vary widely in how closely they adhere to the instructions encoded in skills, leading to substantial differences in their performance gains. Furthermore, we show that access to a skill significantly changes model behavior compared to the no-skill setup, providing an essential mechanism for encoding opinionated workflows into LLM agents. We release our evaluation dataset to support future work on agent skills.

23.
arXiv (CS.LG) 2026-06-19

Computational Methods and Challenges in Cell-Free DNA Analysis for Multi-Cancer Early Detection

arXiv:2606.20174v1 Announce Type: new Abstract: Cell-free DNA (cfDNA) is a promising avenue for non-invasive multicancer early detection (MCED), in that, it can enable multiple cancer detection simultaneously from a single blood draw, with particular sensitivity to cancers that currently lack established screening programs. Here we review the computational methods developed between 2022 and 2025 for cfDNA-based MCED. We focus on how fragmentomics and epigenetic features are extracted and analyzed to detect cancer at early stages. We first briefly outline the biological basis of cfDNA signals, then review classical statistical and machine learning approaches alongside deep learning frameworks including autoencoder-based models. For each method we discuss biological interpretability, validation strategy, and readiness for clinical integration. Furthermore, we categorize the current challenges into technical, computational, and methodological while outlining open problems in the field. This review shows that multimodal ensemble approaches have the strongest promise for clinical integration and the highest readiness. However, for better assessment of future work and side-by-side comparison, standardization of evaluation protocols and reporting results will be crucial.

24.
bioRxiv (Bioinfo) 2026-06-15

Inferring Cell Fate Trajectories in Time-Resolved Metabolic RNA Labeling data

Single-cell RNA sequencing provides high-resolution snapshots of cellular states but lacks direct information about transcriptional dynamics. Metabolic RNA labeling addresses this limitation by distinguishing newly synthesized RNA, offering insight into the direction of cell state changes, and providing valuable information when attempting to recover the underlying continuous dynamics from static snapshots of cell distributions. However, existing trajectory inference methods do not fully exploit this additional signal. Here, we propose FLOWSATATE, a framework for single-cell trajectory inference that leverages time-resolved RNA labeling within an Optimal Transport setting. We model cell dynamics as a gradient flow in an inferred potential landscape parameterized by a neural network, integrating both total and labeled RNA across time points. The learned potential enables identification of key genes and transcription factors driving cell fate decisions and supports prediction of future cellular states. We benchmark our approach on its ability to generalize unseen data and recover coherent trajectories. We also apply it to study colorectal cancer response to demethylation treatment as well as neuronal differentiation of embryonic stem cells.

25.
medRxiv (Medicine) 2026-06-15

Entity-Aware Generation of Synthetic Clinical Progress Notes for Prostate Cancer using Large Language Model

Objectives: This study investigates large language models (LLMs) for clinical entity projection across substantial textual transformation. Specifically, we evaluate whether entities annotated in Spanish prostate cancer case reports can be preserved and explicitly projected when the source narratives are transformed into hospital-style clinical progress notes. Entity projection is treated as a generation-driven task, allowing paraphrase, condensation and narrative reorganisation, providing that clinically relevant entities remain recoverable as structured annotations. Methods: A corpus of 109 Spanish prostate cancer case reports was annotated using a silver-standard pipeline combining Spanish biomedical named-entity recognition with rule-based prostate-specific antigen (PSA) and Gleason extractors. The resulting silver-standard annotations were validated on a subset of generated notes against a gold-standard consensus produced by medical experts in prostate cancer. Four LLMs were evaluated for note generation and entity projection: GPT-5.4 Nano, Qwen 3.5:35B-A3B, GLM5 and Claude Sonnet 4.6. Entity-to-Entity (E2E) generation used XML-annotated cases as RAG-supported input, whereas Text-to-Entity (T2E) generation required models to generate and annotate notes directly from plain text cases. Zero-shot and few-shot prompting were tested. Projection quality was measured using precision, recall and F1-score, and complemented by LLM-as-a-judge evaluation using Kimi K2.6. Results: E2E consistently outperformed T2E, indicating that explicit entity-enriched in- put substantially facilitates entity preservation and localisation. GLM5 achieved the best E2E zero-shot result (F1 = 0.915), followed by Claude Sonnet 4.6 (F1 = 0.896). In T2E, few-shot prompting improved performance, with Claude Sonnet 4.6 reaching the highest score (F1 =0.718). Age, Gleason, Disease, Procedure, Duration and negation-related entities were robustly projected, whereas PSA and Dose showed less stable behaviour. Conclusion: LLMs can generate clinically plausible synthetic prostate cancer evolution notes while preserving a substantial proportion of source entities, particularly when explicit semantic annotations are provided as input. However, the lower and more variable performance observed in T2E highlights the difficulty of jointly generating clinical narratives and projecting entities without source-side information, especially for numerical and measure-related entities.