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

Beyond Logprobs: A Multi-Signal Confidence Engine for LLM-Based Document Field Extraction

Authors:

In high-stakes document processing pipelines, including financial reconciliation, compliance verification, and procurement automation, an LLM extraction that is silently wrong is more dangerous than one that is visibly absent. The central challenge is not extraction accuracy alone but reliable confidence estimation: knowing, field by field, whether an extraction can be trusted for automation or deferred to human review. Token-level log-probabilities, verbalized confidence, and multi-sample self-consistency all collapse toward all-positive behaviour at practical thresholds, offering no reliable separation between trustworthy and untrustworthy extractions. We present ExtractConf, a cross-domain, field-agnostic confidence engine that grounds confidence estimation in two structurally different readings of the same document. A field-guided Hunter call extracts each field under schema-slot completion pressure; a document-guided Mapper call scans holistically and surfaces values grounded in document content. This asymmetry yields different failure modes: Hunter hallucinates values for absent fields, while Mapper misses visually non-salient ones. Their disagreement is independently informative. ExtractConf fuses cross-call disagreement, LLM-internal uncertainty, OCR, image quality, and spatial layout into a classifier requiring no domain-specific rules or retraining. On DocILE (55-field invoices, 26% failure rate), it achieves 0.928 ROC AUC and reduces selective prediction risk by 70% over logprob-mean. At 80% coverage, accuracy reaches 99.1%, enabling a practical human-in-the-loop workflow. Zero-shot transfer to CORD receipts achieves 0.858 AUC; lightweight Lasso recalibration reduces ECE by 89% and Brier by 43%, confirming the signals generalise across document domains.

02.
arXiv (CS.CV) 2026-06-11

A Comprehensive Ecosystem for Open-Domain Customized Video Generation

Recent progress in video generation has shown impressive visual synthesis capabilities. However, open-domain customized video generation remains limited by the lack of large-scale, annotated datasets capturing diverse identity-specific attributes. To address this, we introduce PexelsCustom-1M, the first publicly available million-scale dataset for identity-preserving video generation, containing one million curated triplets across 8,000+ categories. Leveraging this, we propose CustoMDiT, a parameter-efficient framework that adapts a pretrained multimodal Diffusion Transformer into a customized video generator with only 8% additional learnable parameters. Our method surpasses prior state-of-the-art. However, benchmarks such as DreamBooth cover only 100 classes, which is insufficient for real-world applications. To overcome this, we construct OpenCustom, a new benchmark with 1,000+ categories, created via cross-dataset knowledge fusion from ImageNet and MS-COCO. Extensive experiments confirm the advantages of both our dataset and model. We will open-source the entire ecosystem–including dataset, pipeline, benchmark, and implementations–to support further research.

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

MVM-IOD: An Industrial Object-Centric Benchmark Dataset for the Evaluation of 3D Reconstruction Methods

3D object reconstruction, and camera pose estimation in industrial applications are challenging tasks, as errors are costly while the computation time is often limited. The complexity of typical industrial objects further complicates these tasks. Most of the existing datasets in this context do not depict realistic industrial scenarios. Therefore, we introduce the Machine Vision Metrology Industrial Object Dataset (MVM-IOD). Images of typical industrial objects are captured systematically, by moving a camera, mounted at the end effector of an industrial robot arm, on a hemisphere around the objects. MVM-IOD contains reference camera poses and reference 3D point clouds, the acquired RGB images of 9 objects and 2 background choices resulting in 18 scenes, which allows evaluation of all image based methods that compute a 3D reconstruction, camera poses, or novel views of a scene. Based on MVM-IOD, we extensively evaluate current SOTA 3D reconstruction and camera pose estimation methods, such as Structure from Motion, Multi-View Stereo, recent feed forward methods (Visual Geometry Grounded Transformer, {\pi}3), and 2D Gaussian Splatting and report our findings as a baseline for future research. The experiments show that capture setups like ours generate out-of distribution images for feed forward methods, leading to suboptimal point clouds and camera poses. However, these out-of-distribution images can be shifted closer to the training distribution by applying simple preprocessing steps. Consequently, in certain industrial applications, feed forward methods should be used with caution.

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

EARS: Explanatory Abstention for Reliable Sub-Agent Modeling in Large-scale Multi-Agent Systems

In large-scale enterprise settings, centralized multi-agent systems (MAS) are increasingly adopted, in which a coordinator delegates user requests to lightweight, domain-specialized sub-agents. While this architecture improves modularity, scalability, and cost efficiency, its reliability depends not only on accurate routing but also on sub-agents' ability to calibrate their responses to capability constraints. In particular, sub-agents built on smaller fine-tuned models often struggle with such calibration, leading them to over-answer ambiguous, underspecified, misrouted, or unsupported requests and produce hallucinated outputs instead of actionable feedback. To address this challenge, we present EARS (Explanatory Abstention for Reliable Sub-Agent Modeling), a production-oriented framework that reframes sub-agent abstention as an inter-agent communication protocol: a sub-agent does not merely abstain, but exposes an actionable failure state to the coordinator. EARS curates human-agent interaction data using an ensemble of calibrated LLM-as-a-Judge models, producing structured abstention labels and rationales under a taxonomy of sub-agent failure modes. These data are used to fine-tune sub-agents to detect failure conditions and return rationales for coordinator-level clarification, rerouting, or fallback. We evaluate EARS in a large-scale production e-commerce assistant supporting enterprise business intelligence workflows. EARS improves the overall response pass rate from 68.5% to 78.9%, demonstrating that sub-agent-side explanatory abstention improves MAS reliability.

05.
arXiv (CS.LG) 2026-06-11

FlexiBrain: Resolution-Agnostic Voxel-Level Encoding for Native fMRI

arXiv:2606.11500v1 Announce Type: cross Abstract: The success of large-scale deep learning models in neuroscience is fundamentally constrained by severe data heterogeneity. Native fMRI data aggregated from diverse sources exhibit substantial variation in both spatial and temporal resolutions. Consequently, most existing frameworks rely on lengthy, rigid preprocessing pipelines that enforce uniformity across datasets. This practice introduces two critical limitations: (1) potential degradation of subject-specific anatomical information; (2) significant computational overhead, often requiring hours of processing per subject. Here, we propose FlexiBrain, a resolution-agnostic voxel-level encoding framework for native fMRI based on Mamba-JEPA. FlexiBrain defines patch sizes in real-world physical units and employs a dynamic patch resizing, thereby bypassing destructive spatial standardization while enabling direct ingestion of data in native space. We instantiate the framework using an efficient Mamba-JEPA backbone to model high-dimensional 4D fMRI signals. Across five diverse downstream neuroscience tasks, FlexiBrain consistently outperforms recent state-of-the-art methods, achieving gains of up to 12 percentage points without external data augmentation. Importantly, FlexiBrain functions as a seamless plug-in module, substantially reducing preprocessing costs and accelerating the development of robust voxel-level fMRI foundation models. Code is available at https://github.com/OneMore1/FlexiBrain.

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

Gaming-Resistant Insurance Contracts for Autonomous AI Agents: Strategy-Proof Toll Mechanism Design

arXiv:2606.16326v1 Announce Type: cross Abstract: Paper A defines a time-consistent actuarial runtime that prices each side-effect-bearing action against a contractually fixed safe default and gates execution against a reserve budget. It treats the operator as passive. This paper makes the operator strategic. We characterise a five-attack space for autonomous AI-agent insurance contracts and prove when the actuarial runtime is gaming-resistant. Two attack surfaces – post-toll safe-default selection and within-boundary action splitting – are closed by Paper A's minimal-authority and no-splitting clauses. The remaining three require new contract clauses. First, common-control aggregation prevents cross-boundary re-routing from reducing toll below the boundary potential applied to total exposure. Second, interface failures such as invalid JSON are contract-relevant events, not safety wins: treating them as zero-toll safe defaults can reward unreliable models, while escalation fees reverse the incentive. We validate this interface-compliance theorem on committed cross-model traces from the companion empirical paper. Third, a model-identity menu with a componentwise-minimum penalty schedule makes truthful reporting of the deployed model weakly dominant. We then compose these clauses with Paper A's runtime guarantees to obtain joint incentive compatibility over the five-attack space. Finally, a two-parameter premium family discharges operator individual rationality and weak budget balance at the truthful equilibrium. The result is an incentive-compatibility layer for actuarial control of autonomous-agent side effects.

07.
arXiv (CS.CV) 2026-06-17

Effective Gaussian Management for High-fidelity Object Reconstruction

This paper proposes an effective Gaussian management framework for high-fidelity scene reconstruction of both appearance and geometry. Unlike recent Gaussian Splatting (GS) pipelines that treat all primitives uniformly during optimization, our framework explicitly manages the attribute activation, representation and pruning of Gaussian. Specifically, our framework first introduces GauSep, a novel densification strategy that selectively activates Gaussian color or normal attributes to alleviate destructive gradient conflicts arising from dual supervision. We further propose GauRep, an adaptive Gaussian representation that dynamically adjusts spherical harmonics (SHs) orders and performs task-decoupled pruning to reduce redundancy at both the individual and global levels. To provide reliable geometric supervision for above mangement process, we additionally introduce CoRe, an regularized surface reconstruction module that distills robust normal fields from an SDF branch to the Gaussian representation through a confidence mechanism. Notably, the proposed Gaussian management is compatible with various reconstruction architectures and can be seamlessly integrated to improve performance while reducing size of the model. Extensive experiments demonstrate that our approach achieves superior or comparable performance in appearance and geometry reconstruction compared with state-of-the-art methods, while using significantly fewer parameters.

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

EG-VQA: Benchmarking Verifiable Video Question Answering with Grounded Temporal Evidence

arXiv:2606.24797v1 Announce Type: cross Abstract: Recent advances in Video Large Language Models (Video-LLMs) have yielded promising performance on video question answering (VideoQA). Nevertheless, existing benchmarks are predominantly evaluated through answer correctness, while the grounding of predictions in relevant video evidence remains largely unexamined. This disconnect between answer generation and evidence understanding motivates the construction of the Evidence-Grounded Video Question Answering Benchmark (EG-VQA), an open-ended evaluation protocol in which each QA pair is explicitly annotated with supporting temporal evidence, thereby requiring joint reasoning and precise evidence localization. EG-VQA is comprised of 2,067 videos and 11,838 QA pairs with fine-grained evidence annotations. To evaluate predicted evidence, Evidence-Grounded F1 (EG-F1) is introduced as a unified metric in which temporal alignment and semantic consistency against ground-truth evidence are jointly measured. Experimental evaluation reveals that even strong proprietary models struggle to accurately ground their predictions, exposing a fundamental discrepancy between answer correctness and faithful evidence localization. To bridge this gap, EG-Reasoner, an evidence-grounded reasoning model trained with explicit supervision, is proposed. State-of-the-art performance is achieved among open-source models, with results competitive against proprietary systems, particularly pronounced gains are observed on reasoning-intensive tasks such as counterfactual questions. These findings demonstrate that scaling alone is insufficient for robust video understanding and that structured evidence supervision is essential for the development of more reliable and interpretable VideoQA systems.

09.
arXiv (CS.AI) 2026-06-17

Evaluating Interactive 2D Visualization as a Sample Selection Strategy for Biomedical Time-Series Data Annotation

arXiv:2603.26592v2 Announce Type: replace-cross Abstract: Reliable machine-learning models in biomedical settings depend on accurate labels, yet annotating biomedical time-series data remains challenging. Algorithmic sample selection may support annotation, but evidence from studies involving real human annotators is scarce. Consequently, we compare three sample selection methods for annotation: random sampling (RND), farthest-first traversal (FAFT), and a graphical user interface-based method enabling exploration of complementary 2D visualizations (2DVs) of high-dimensional data. We evaluated the methods across four classification tasks in infant motility assessment (IMA) and speech emotion recognition (SER). Twelve annotators, categorized as experts or non-experts, performed data annotation under a limited annotation budget, and post-annotation experiments were conducted to evaluate the sampling methods. Across all classification tasks, 2DV performed best when aggregating labels across annotators. In IMA, 2DV most effectively captured rare classes, but also exhibited greater annotator-to-annotator label distribution variability resulting from the limited annotation budget, decreasing classification performance when models were trained on individual annotators' labels; in these cases, FAFT excelled. For SER, 2DV outperformed the other methods among expert annotators and matched their performance for non-experts in the individual-annotator setting. A failure risk analysis revealed that RND was the safest choice when annotator count or annotator expertise was uncertain, whereas 2DV had the highest risk due to its greater label distribution variability. Furthermore, post-experiment interviews indicated that 2DV made the annotation task more interesting and enjoyable. Overall, 2DV-based sampling appears promising for biomedical time-series data annotation, particularly when the annotation budget is not highly constrained.

10.
arXiv (quant-ph) 2026-06-12

More efficient Clifford+T synthesis for small-angle rotations and application to Trotterization

arXiv:2605.31544v2 Announce Type: replace Abstract: Clifford+T synthesis of rotation gates is an important routine in fault-tolerant quantum compilation. While Clifford+T synthesis is scalable, it has a high overhead of tens of T gates per rotation in practice, translating to high resource estimates for many fault-tolerant algorithms. However, these well-known results, including those using probabilistic mixtures [Quantum 7, 1208 (2023)], are independent of the rotation angle $\theta$, requiring $O(\log 1/\delta)$ T gates. We show that it is possible to do much better for small angles, reducing the T cost to $\tilde{O}(\theta^2/\delta)$, and returning to existing $O(\log1/\delta)$ results in the worst case. This is particularly important since many algorithms, such as Trotterization, are dominated by small-angle rotations. Further, we perform a detailed theoretical and numerical study of quasi-probabilities, which can further reduce the total T cost of large circuits by orders of magnitude with only a small overhead in sample complexity. We also develop a scheme based on quasi-probability mixtures of Clifford+T fallback channels. We derive new $\theta$-dependent formulas that can be used for resource estimation of fault-tolerant quantum algorithms. As an application of our results, we show that the gate cost of Trotterization circuits compiled to a Clifford+T gate set is constant in the small Trotter step size limit, and can be reduced by orders of magnitude even for large step sizes. The cost of fault-tolerant Trotterization for a variety of applications should be re-examined in light of these results. Our work dispels the widely-stated claim that Clifford+T rotation synthesis has a high cost independent of $\theta$, and further develops a scalable quasi-probability method for rotation synthesis. We also expect our results to bring forward useful early fault-tolerant quantum computing by reducing required magic state resources.

12.
arXiv (CS.CV) 2026-06-16

Task-Instructed Causal Routing of Vision Foundation Models for Multi-Task Learning

Vision foundation models (VFMs) have demonstrated strong robustness and transferability across a wide range of visual tasks. However, each model typically encodes strong inductive biases shaped by its pre-training objective and data domain, resulting in fragmented yet complementary visual knowledge. As a result, a single model often struggles to capture the diverse visual representations required across multiple dense prediction tasks. To address this limitation, we propose TIGER (Task-Instruction-Guided Expert Routing), a framework that coordinates multiple heterogeneous VFMs for multi-task dense prediction. Instead of naively aggregating expert features, TIGER leverages natural-language task instructions to guide a routing network that assigns token-level expert weights conditioned on task semantics, enabling adaptive integration of complementary expert features. TIGER further introduces a counterfactual loss that aligns routing decisions with each expert's causal contribution by measuring prediction changes when experts are excluded, encouraging more reliable and interpretable routing. We evaluate TIGER on two multi-task dense prediction benchmarks, NYUD-v2 and Pascal Context, where it consistently outperforms recent multi-task learning baselines while keeping all VFMs frozen. These results demonstrate that combining instruction-guided expert routing with counterfactual causal alignment enables effective coordination of heterogeneous vision foundation models.

13.
arXiv (CS.CV) 2026-06-15

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

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

14.
arXiv (CS.CL) 2026-06-17

LLM Features Can Hurt GNNs: Concatenation Interference on Homophilous Graph Benchmarks

Adding LLM-generated node features to graph neural networks (GNNs) is widely reported to improve accuracy on standard benchmarks. We document a contrasting observation: when LLM features are introduced through pure input concatenation (rather than joint training, distillation, or prompt-conditioning), they can systematically degrade accuracy on the same homophilous benchmarks where end-to-end LLM pipelines succeed. With an MLP backbone on the Planetoid public split and bag-of-words original features, concatenating SBERT-encoded GPT-4o-mini TAPE features reduces PubMed test accuracy by -17.0 +/- 0.3 pp and Cora by -4.3 +/- 0.6 pp (CiteSeer -0.6 +/- 0.8 pp, within seed noise). The drop attenuates as we relax each condition (GCN / GCNII / GAT backbones, random splits, smaller encoders) and reverses on medium-homophily WikiCS (+4.4 pp) and ogbn-arxiv (+11.7 pp). To predict when concatenation helps versus hurts, we report a simple measure of LLM-alone discriminability, Delta_sig. Across 9 datasets Delta_sig correlates with the concatenation cost more strongly than homophily at point estimate (r^2 = 0.38 vs. 0.06; N=9, bootstrap CIs overlap). The bootstrap-best change-point is tau = 13.8 pp, and the rule "Delta_sig

15.
bioRxiv (Bioinfo) 2026-06-19

Accurate detection of tumor clonality and ongoing expansion mode from genomic data

Recent evidence shows that despite considerable effort, currently available algorithms for estimating intra-tumor heterogeneity (ITH) remain limited. We developed DECODE (Deciphering Cancer Origin from DNA Evolution), a novel mutation clustering method that incorporates the impact of sample-specific sequencing coverage and mutation calling biases. On synthetic data, DECODE outperformed existing methods across multiple clonality metrics and accurately detected and characterized the neutral tail in the site frequency spectrum (SFS), which encodes the tumor's ongoing expansion mode. In acute myeloid leukemia, accounting for the neutral tail enabled DECODE to yield more parsimonious clonal decompositions that align more closely with known subclonal dynamics that drive relapse. Applied to data from The Cancer Genome Atlas, DECODE not only detected a neutral SFS tail in most samples across tumor types but also uncovered a clinically meaningful link between ITH and survival in low-grade glioma. By jointly inferring clonality and expansion mode, DECODE provides two complementary and prognostically relevant readouts of tumor evolution from single tumor genomic samples.

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

BRITE: A Benchmark for Reliable and Interpretable T2V Evaluation on Implausible Scenarios

The rapid advancement of photorealistic Text-to-Video (T2V) generation brings in an urgent need for up-to-date evaluation methods. Existing benchmarks largely overlooked implausible scenarios and do not measure audio-visual alignment. We introduce BRITE, the first framework that unifies (1) implausible prompting, (2) fine-grained assessment of audio-visual consistency, and (3) QA-based interpretable evaluation into a comprehensive T2V benchmark. Unlike fully automated Multimodal LLM-based pipelines, which are prone to hallucination and prompt ambiguity, BRITE guarantees reliability through a rigorous human-in-the-loop protocol for benchmark creation. Evaluating five state-of-the-art models (Sora 2, Veo 3.1, Runway Gen4.5, Pixverse V5.5, and Qwen3Max), we reveal a critical performance gap: while models excel at static object composition, they exhibit significant degradation in object-action binding and audio-visual synchronization. Our framework offers the community a reliable, interpretable benchmark and evaluation framework that can detect and locate limitations in the next generation of T2V models, especially for off-manifold prompts

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

MOCHA: Multi-modal Objects-aware Cross-arcHitecture Alignment

arXiv:2509.14001v5 Announce Type: replace-cross Abstract: Personalized object detection aims to adapt a general-purpose detector to recognize user-specific instances from only a few examples. Lightweight models often struggle in this setting due to their weak semantic priors, while large vision-language models (VLMs) offer strong object-level understanding but are too computationally demanding for real-time or on-device applications. We introduce MOCHA (Multi-modal Objects-aware Cross-arcHitecture Alignment), a distillation framework that transfers multimodal region-level knowledge from a frozen VLM teacher into a lightweight vision-only detector. MOCHA extracts fused visual and textual teacher's embeddings and uses them to guide student training through a dual-objective loss that enforces accurate local alignment and global relational consistency across regions. This process enables efficient transfer of semantics without the need for teacher modifications or textual input at inference. MOCHA consistently outperforms prior baselines across four personalized detection benchmarks under strict few-shot regimes, yielding a +10.1 average improvement, with minimal inference cost.

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

Measuring Semantic Progress in Multi-turn Dialogue via Information Gain

Evaluating multi-turn dialogue is challenging because quality emerges across turns rather than within individual responses. We focus on a key dimension of information-seeking dialogue: semantic progress, defined as the accumulation of new, question-relevant, and non-redundant information over the course of a conversation. We formalize semantic progress as question-conditioned uncertainty reduction and introduce an information-theoretic metric that approximates it in embedding space. Our main estimator uses a tractable Gaussian formulation with closed-form updates, while a complementary maximum-entropy argument shows why log-determinant structure arises more broadly when only second-order embedding information is retained. This formulation yields desirable theoretical properties, including monotonicity, additive decomposition of total information gain across turns, and diminishing returns for redundant evidence. Unlike LLM-as-a-judge approaches, our metric requires no autoregressive inference at evaluation time and is fully reproducible for a fixed embedding model. Experiments on MT-Bench, Chatbot Arena, and UltraFeedback show that the proposed metric achieves competitive agreement with human judgments despite targeting only semantic progress, with improved alignment on MT-Bench and UltraFeedback compared to several LLM-based judges. Notably, the method remains effective with lightweight embedding models under CPU-only execution, indicating that semantic progress can be captured without reliance on large model capacity.

19.
bioRxiv (Bioinfo) 2026-06-12

A Graph-based QSAR Modeling Pipeline for Predicting In vitro PubChem Assays and In vivo Human Hepatotoxicity: Mechanistic Analysis of Caspase-3/7 Activation

Background: Caspase-3 and -7 are key effector caspases in the apoptotic pathway, a form of programmed cell death, and their activities serve as a well-established biomarker for evaluating environmental chemical toxicity and informing chemical risk assessment. Loss of mitochondrial membrane potential is a key event in the activation of Caspase-3/7 signaling and the subsequent induction of apoptosis. Therefore, simultaneous assessment of mitochondrial membrane potential and Caspase-3/7 activity enables elucidation of the mechanisms and pathways through which apoptosis is initiated. Rapid and accurate assessment of the potential toxicity of environmental chemicals and drugs remains a major challenge. Quantitative Structure Activity Relationship (QSAR) modeling have been widely used for toxicity prediction. Graph-based approaches encode compounds directly as molecular graphs, allowing structure-activity relationships to be learnt from molecular topology without the information loss in binary fingerprints. While advanced graph models such as graph transformers (GTs) have shown outstanding performance in many domains, they have not been fully leveraged in QSAR modeling on Caspase and mitochondrial toxicity. Methods: We propose a QSAR modeling pipeline that encompasses assay data preprocessing, feature representations (fingerprints and molecular graphs), and benchmarking machine learning (ML) models, including classic ML models, graph neural networks (GNNs), GTs, and their consensus ensembles. Based on in vitro Caspase and mitochondrial assays in PubChem, we applied the pipeline to predict Caspase-3/7 activation and mitochondrial membrane potential (MMP). Beyond in vitro assays, we also built in vivo QSAR modeling for FDA Drug-Induced Liver Injury (DILI) gold standard on human hepatotoxicity. Moreover, mechanistic analysis on Caspase-3/7 activation was conducted by comparing with MMP disruption to identify chemical substructures that may be responsible for dual activations. We also investigated cell-line-specific responses by identifying structural motifs that selectively induce Caspase-3/7 activation in individual cell lines.Results:Experimental evaluations show that GTs and GNNs outperformed classic ML models when the number of active compounds is large, such as MMP disruption, while classic ML models and GTs performed good for highly imbalance data with limited active compounds, such as Caspase-3/7 activation. For DILI prediction, the full consensus model achieved the highest AUC 0.69 and Graphormer had the highest F1 score 0.79, both surpassing the previous best model with AUC 0.63 and F1 0.65 with a large margin.Our mechanistic analysis shows that phenolic compounds bearing a para-hydroxyphenyl motif, as well as members of the lipophilic chain family with long alkyl chains can trigger the collapse of MMP, leading to the activation of caspases-3 and -7. Human embryonic kidney (HEK293) was the only cell line with a distinct structural motif: 1,1-dichloroethane and chlorobenzene. Human neuroblastoma (SK-N-SH) is uniquely impacted by an epoxide fragment and rat hepatoma (H-4-II-E) is uniquely impacted by a tetramethylcyclohexene motif and an acetaldehyde fragment.Conclusions:The proposed pipeline for QSAR modeling, including data preprocessing, feature representations, and incorporation of advanced graph ML approaches, is highly effective in predicting not only on Caspase-3/7 activation and membrane potential collapse, but also on FDA DILI human hetatotoxicity. As future research directions, we will leverage extra information, e.g., biological activity and findings in existing toxicity literature, and recent advances in large language models and agentic AI to further improve the predictive performance and enable a sensitive and specific framework for assessing human hepatotoxicity of environmental compounds.

20.
medRxiv (Medicine) 2026-06-18

Digital self-efficacy as a potential intermediary between vision impairment and daily internet use among older adults: A cross-sectional analysis of HINTS 2024

Background: Older adults with vision impairment often experience barriers to using digital technology. The indirect associations between vision impairment and digital access and skills via digital self-efficacy and frustration among older adults remain largely unknown. Objective: This study aimed to 1) explore factors associated with digital access, skills, self-efficacy, and frustration among older adults with vision impairment; 2) examine associations between vision impairment and digital access, skills, self-efficacy, and frustration among older adults; and 3) examine whether digital self-efficacy and frustration may help explain associations between vision impairment and digital access and skills among older adults. Methods: This was a cross-sectional study using nationally representative data from the Health Information National Trends Survey (HINTS) 2024. Respondents aged 60 and older were included. Vision impairment was assessed using a self-reported item. Outcomes included self-reported digital access, skills, self-efficacy, and frustration. Survey-weighted multivariable logistic regression and generalized structural equation modeling were conducted, adjusting for age, sex, race/ethnicity, education, and the number of comorbidities. Results: Among 3,149 older adults (mean [SD] age, 70.7 [10.0] years; 45.6% female), 7.1% (n=223) reported vision impairment. Among older adults with vision impairment, 65.6% (95% CI, 53.5% to 75.9%) used the internet daily, and 79.5% (95% CI, 66.8% to 88.2%) used a smartphone in the past 12 months. In multivariable logistic regression analyses among older adults with vision impairment, older age was associated with lower odds of daily internet use (OR, 0.84; 95% CI, 0.79 to 0.90), smartphone use (OR, 0.85; 95% CI, 0.75 to 0.97), wearable device use (OR, 0.88; 95% CI, 0.79 to 0.97), and using the internet to send a message to a healthcare provider (OR, 0.87; 95% CI, 0.80 to 0.93). Older adults who self-identified as racial and ethnic minority groups (e.g., Black/African American, Hispanic) had lower odds of daily internet use (OR, 0.15; 95% CI, 0.05 to 0.50) and using the internet to send a message to a healthcare provider (OR, 0.17; 95% CI, 0.04 to 0.73) compared with Non-Hispanic White older adults. Vision impairment was associated with lower odds of daily internet use (OR, 0.60; 95% CI, 0.37 to 0.99) and digital self-efficacy (OR, 0.53; 95% CI, 0.32 to 0.86). Digital self-efficacy was associated with higher odds of daily internet use (OR, 2.95; 95% CI, 2.04 to 4.26). Generalized structural equation modeling identified an indirect association between vision impairment and daily internet use via digital self-efficacy (coefficient, -0.68; 95% CI, -1.24 to -0.12). Conclusions: Findings suggest that reduced digital self-efficacy may help explain the observed association between vision impairment and daily internet use among older adults. Interventions targeting digital self-efficacy, including accessible interface designs, personalized coaching, and peer support, may help bridge the digital divide among older adults with vision impairment.

21.
bioRxiv (Bioinfo) 2026-06-11

Hyper3D-lite: count-preserving representation auditing for long-read multi-contact genome data

Authors:

Long-read and single-molecule sequencing technologies are rapidly increasing molecule-level data, with platforms such as Oxford Nanopore, PacBio HiFi, and Roche sequencing-by-expansion advancing at different technology readiness levels. In the specific context of Pore-C and HiPore-C multi-contact chromatin-conformation assays, long-read multi-contact 3D genome assays preserve molecule-level contact context, but common downstream pairwise projections can expand one multi-contact molecule into many pair records. This creates a representation problem: apparent contact evidence can increase through the counting frame before biological interpretation begins. Hyper3D-lite addresses this problem as a representation-first audit tool for read-to-fragment-style long-read multi-contact inputs. It compares all-pair projection with CPB, a count-preserving statistical accounting reference point, and separates broad software outputs from conservative higher-order candidate calls.

22.
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.

23.
Nature Medicine 2026-06-25

Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling

Immune-checkpoint inhibitors benefit a subset of patients with advanced cancer, and the metabolic determinants of response remain unclear. Here, using targeted metabolomics and metagenomics, we profiled 4,336 plasma samples from 1,714 patients across five tumor types and 16 cohorts spanning Europe and North America, longitudinally sampled during five immune-checkpoint inhibitor-based treatment modalities, including fecal microbiota transplantation. A multimodal machine-learning framework integrating 154 metabolites with clinical variables identified five metabolites, age, body mass index and renal function as predictors of 12-month progression-free survival. The model achieved areas under the curve of 0.88 in training and 0.73 in validation cohorts of 105 and 30 patients, respectively and generalized across seven external cohorts. Histidine was a favorable prognostic feature of survival, whereas long-chain fatty acids and succinate were negatively associated with outcome. Histidine supplementation enhanced antitumor immunity in mice. Histidine-rich diets improved progression-free survival in patients lacking dysbiotic microbiome signatures associated with histidine catabolism. Mass-spectrometry-based metabolomic analysis of plasma samples from multiple cohorts of patients treated with immunotherapy across five distinct tumor types, followed by machine learning enabled identification of metabolic signatures, as well as functional exploration, reveals association of increased plasma histidine levels with prolonged survival and its potential for therapeutic intervention.

24.
bioRxiv (Bioinfo) 2026-06-11

Tumour evolution as ground truth for cancer whole-genome sequencing

Cancer genomes are shaped by evolutionary processes that couple mutagenesis, clonal selection, chromosomal instability, spatial growth and treatment response into structured genomic patterns, yet current benchmarking strategies largely ignore this evolutionary dependency. Here, we present SCOUT, a large-scale synthetic whole-genome sequencing resource of over 200 samples, designed for systematic benchmarking of tumour genomic analysis and evolutionary inference under controlled evolutionary ground truth. Unlike conventional task-specific simulations, SCOUT models tumour evolution as a latent generative process that simultaneously shapes mutations, copy-number alterations, variant allele frequencies, mutational signatures and clonal architectures. SCOUT recapitulates key features of solid and haematological malignancies, including driver mutations, chromosomal instability, intratumour heterogeneity, spatial sampling and treatment-associated evolutionary dynamics in tumour and matched-normal longitudinal and multi-region sequencing designs. Using SCOUT, we benchmarked widely used methods for somatic variant detection, copy-number analysis, mutational signature inference and tumour evolutionary reconstruction. Across analytical tasks, performance deteriorated in low-purity, highly subclonal and structurally complex tumours, while spatial sampling bias and hypermutation generated spurious evolutionary signals that confounded tumour interpretation across multiple inference layers. Evolutionary simulations further distinguished lineage-restricted genetic bottlenecks from multi-lineage resistance dynamics associated with tumour plasticity. Tumour purity consistently exerted a stronger effect on inference accuracy than sequencing depth. Together, our results establish evolutionary ground truth as a prerequisite for reproducible benchmarking and biologically interpretable analysis of cancer whole-genome sequencing data.

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arXiv (CS.AI) 2026-06-24

Quant Convergence: Bridging Classical Value Investing and Modern Factor Models for Systematic Equity Selection

arXiv:2606.24575v1 Announce Type: new Abstract: Modern finance relies heavily on complex machine learning models to find patterns in the stock market. However, as these AI models get more complicated, they often memorize short-term market noise instead of finding companies with real, lasting value. We designed this research to test if Benjamin Graham's classic value investing rules could act as a mathematical "low-pass filter" to keep these modern models in check. We built three different sets of features - pure Graham rules, modern market factors, and a mix of both - and tested them against highly complex models (XGBoost and AutoGluon) using 20 years of S&P 500 data. By applying a strict buy-and-hold strategy over a four-year test period (March 2022 to March 2026), the results showed that more complex algorithms do not always win. While the AutoGluon model captured high returns (222.68%), it suffered a substantial 39.78% drop because it bought volatile tech stocks right before the market crashed. On the other hand, the pure Graham Random Forest achieved the highest overall return (232.13%) with much less risk (1.38 Calmar Ratio). Furthermore, the Combined Random Forest successfully mixed momentum with Graham's rules, making a 202.91% return while keeping the lowest maximum drop (34.53%) of any model tested. Ultimately, this research proves that Graham's "margin of safety" isn't outdated; it is actually a highly effective way to prevent modern AI from taking on too much risk.