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01.
arXiv (CS.CL) 2026-06-15

Abstracting Cross-Domain Action Sequences into Interpretable Workflows

Sequential or time-stamped interaction logs provide objective records of digital application usage, yet their granularity and noise often obscure meaningful insights into people's work. Such insights are essential for improving digital products in ways grounded in real-world user interactions. Prior research has applied deep learning models to cluster user actions into high-level activities, but these approaches are highly sensitive to noise and struggle to generalize across applications. To address this limitation, we introduce WorkflowView, a framework that uses large language models (LLMs) to abstract low-level action sequences into high-level activities. We establish the effectiveness and generality of our approach across three distinct, challenging sequential tasks and diverse domains: (a) zero-shot task description reconstruction from browser logs (achieving high semantic similarity, $\mu_{sim} = 0.91$), (b) few-shot student dropout prediction using MOOC interaction logs (reaching weighted $F_1 = 0.90$ with only five few-shot examples), and (c) anonymized, privacy-preserving analysis of AI tool integration within document workflows in Microsoft Word. Our work demonstrates that LLM-based abstraction is a robust and efficient path forward for transforming low-level behavioral data into high-level, interpretable, and actionable insights. We also discuss practical considerations for deploying LLM-based inferences within logging infrastructures, including computational efficiency and user privacy.

02.
arXiv (CS.CL) 2026-06-15

"I Didn't Make the Micro Decisions": Measuring, Inducing, and Exposing Goal-Level AI Contributions in Collaboration

As large language models (LLMs) increasingly shape how users form, refine, and extend their goals, attributing contributions in human-AI collaboration becomes critical for users calibrating their own reliance and for evaluators assessing AI-assisted work. Yet existing methods focus on final artifacts, missing the process through which goals themselves are jointly shaped. We introduce a goal-level attribution framework, CoTrace, that decomposes explicit goals into verifiable requirements and traces both direct contributions and indirect influences across dialogue turns. Applying CoTrace to 638 real-world collaboration logs, we find that while models account for only 11-26% of goal-shaping contribution, they contribute substantially more on introducing lower-level concrete requirements, and make various kinds of indirect contributions. Through controlled simulations, we show that interaction design choices significantly affect model goal-shaping behavior. In a user study, exposing participants to goal-level analyses shifts their perceived contributions by nearly 2 points on a 5-point scale, revealing systematic miscalibration in how users understand their own AI-assisted work.

03.
arXiv (CS.CL) 2026-06-18

SciHorizon-GENE: Benchmarking LLM for Life Sciences Inference from Gene Knowledge to Functional Understanding

Large language models (LLMs) have shown growing promise in biomedical research, particularly for knowledge-driven interpretation tasks. However, their ability to reliably reason from gene-level knowledge to functional understanding, a core requirement for knowledge-enhanced cell atlas interpretation, remains largely underexplored. To address this gap, we introduce SciHorizon-GENE, a large-scale gene-centric benchmark constructed from authoritative biological databases. The benchmark integrates curated knowledge for over 190K human genes and comprises more than 540K questions covering diverse gene-to-function reasoning scenarios relevant to cell type annotation, functional interpretation, and mechanism-oriented analysis. Motivated by behavioral patterns observed in preliminary examinations, SciHorizon-GENE evaluates LLMs along four biologically critical perspectives: research attention sensitivity, hallucination tendency, answer completeness, and literature influence, explicitly targeting failure modes that limit the safe adoption of LLMs in biological interpretation pipelines. We systematically evaluate a wide range of state-of-the-art general-purpose and biomedical LLMs, revealing substantial heterogeneity in gene-level reasoning capabilities and persistent challenges in generating faithful, complete, and literature-grounded functional interpretations. Our benchmark establishes a systematic foundation for analyzing LLM behavior at the gene scale and offers insights for model selection and development, with direct relevance to knowledge-enhanced biological interpretation.

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

Information-Theoretic Measures in AI: A Practical Decision Guide

arXiv:2604.23716v2 Announce Type: replace Abstract: Information-theoretic (IT) measures are ubiquitous in artificial intelligence: entropy drives decision-tree splits and uncertainty quantification, cross-entropy is the default classification loss, mutual information underpins representation learning and feature selection, and transfer entropy reveals directed influence in dynamical systems. A second, less consolidated family of measures, integrated information (Phi), effective information (EI), and autonomy, has emerged for characterizing agent complexity. Despite wide adoption, measure selection is often decoupled from estimator assumptions, failure modes, and safe inferential claims. This paper provides a practical decision framework for all seven measures, organized around three prescriptive questions for each: (i) what question does the measure answer and in which AI context; (ii) which estimator is appropriate for the data type and dimensionality; and (iii) what is the most dangerous misuse. The framework is operationalized in two complementary artifacts: a measure-selection flowchart and a master decision table. We cover both AI/ML and decision-making agent application domains per measure, with standardized Bridge Boxes linking IT quantities to cognitive constructs. Three worked examples illustrate the framework on concrete practitioner scenarios spanning representation learning, temporal influence analysis, and evolved agent complexity.

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

An Empirical Study on Learning Latent Representations for Emotional Speech Synthesis

For the last couple of years, the field of speech synthesis has improved dramatically thanks to deep learning. There are more and more deep learning-based TTS systems developed to make it possible to produce voices with high intelligibility and naturalness. Meanwhile, controlling the expressiveness is yet a big deal, generating speech in different styles or manners has received a lot of attention from community recently. This paper aims to give our solutions to deal with the task emotional speech synthesis (ESS) at VLSP 2022 which allows to generate humanlike natural-sounding voice from a given input text with desired emotional expression. By integrating speaker embedding, prosody bottleneck into FastSpeech 2, our systems can promisingly generate emotional speech of a single speaker (Sub-task 1), transfer speaking styles from another speaker to the target speaker with neutral non-expressive data while retaining the target speaker's identity (Sub-task 2).

06.
medRxiv (Medicine) 2026-06-22

Regional Service-System Conditions Associated with Facility-Linked Home-Based Specialist Care in Japan: A Claims-Based Ecological Study of Home Dialysis

Authors:

Background Complex chronic care is increasingly delivered in patients' homes while remaining linked to specialist facilities for training, monitoring, and backup care. Home dialysis provides a useful case because peritoneal dialysis (PD) and home hemodialysis (HHD) share a home-facility delivery structure but differ in technical and operational requirements. This study examined regional service-system conditions associated with the presence and scale of PD and HHD in Japan. Methods This ecological study used publicly available claims, administrative, census, and geospatial data harmonized to 334 Secondary Medical Areas. Regional indicators were organized into four domains: dialysis service delivery, implementation support for home-based care, hospital backup capacity, and living and sociodemographic context. Diffusion was examined using claims-based indicators of regional presence and post-presence scale, analyzed separately for PD and HHD with Firth penalized logistic regression and zero-truncated negative binomial regression, respectively. Results PD was observed in 271 regions and HHD in 109. Patterns of associated regional conditions differed by modality and stage. PD was associated mainly with existing dialysis-service organization, whereas HHD was associated with broader regional supports, including home-care delivery, living infrastructure, transition support, and hospital-system indicators. Conditions associated with presence differed from those associated with scale. Cross-modality associations suggested that shared regional factors may shape the distribution of both modalities. Conclusions Regional conditions for home dialysis diffusion in Japan differed by modality and stage. PD was linked mainly to existing dialysis-service organization, whereas HHD was linked to multi-domain regional support for technically demanding home treatment. Under standardized reimbursement, local service-system capacity may remain important for modality- and stage-specific diffusion of home dialysis.

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

Learning What to Predict: Downstream-Guided Task Design for Continued Pretraining

arXiv:2601.22108v2 Announce Type: replace-cross Abstract: Continued pretraining is optimized with fixed self-supervised tasks but selected by downstream performance, creating a coarse feedback loop in which practitioners evaluate checkpoints, change data mixtures or objectives, and restart runs, while individual updates remain blind to target capabilities. We ask whether a small set of verifiable downstream examples can provide step-level feedback without directly supervising the learner. We introduce V-pretraining, which decouples a learner trained only with a self-supervised loss from a lightweight task designer that constructs targets or views for unlabeled batches. Given the current learner and batch, V-pretraining scores a candidate construction by predicting the first-order reduction in downstream loss after the induced self-supervised update. The designer maximizes this value; the learner then applies the update with targets or views detached, so downstream labels never update learner parameters. We instantiate V-pretraining as adaptive top-K soft targets for language modeling and learned views or masks for self-supervised vision. Across both modalities, V-pretraining improves target capabilities without degrading generalization. Under wall-clock-matched continued pretraining, it improves GSM8K Pass@1 for Qwen models using 1,024 GSM8K examples only as feedback, including a +7.4 point single-run gain for Qwen2.5-0.5B. In vision, it improves DINOv3 transfer to ADE20K semantic segmentation and NYUv2 depth estimation while preserving ImageNet linear accuracy, suggesting that feedback-guided task construction can improve target capabilities without collapsing general-purpose representations.

08.
arXiv (CS.AI) 2026-06-19

Scaling Generative Foundation Models for Chest Radiography with Rectified Flow Transformers

arXiv:2606.19460v1 Announce Type: cross Abstract: We introduce the first generative foundation model for chest radiograph synthesis trained from scratch at the billion-parameter scale. Existing radiographic AI models often suffer from poor generalisation across patient subpopulations, institutions, and acquisition settings, resulting in limited real-world clinical utility. Controlled, high-fidelity synthesis of chest radiographs is a promising path toward diversifying clinical datasets and evaluating the robustness of diagnostic models. Therefore, we present the largest specialist generative foundation model for chest radiographs to date, with over 1.3B parameters, trained for 1.6T tokens on a curated, heterogeneous dataset comprising 1.2M radiographs and clinical expert-guided metadata. Our model supports controllable radiograph generation and editing across multiple demographic subgroups, acquisition views, and a dozen pathologies. Moreover, we significantly advance the state of the art in radiograph synthesis fidelity, producing images that are indistinguishable from real radiographs to clinical experts.

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

Exactly Solvable Quantum Model with Spin-Dependent Coulomb Interaction

arXiv:2501.05103v5 Announce Type: replace Abstract: In this work, we report an exactly solvable quantum model featuring a spin-dependent Coulomb interaction, described by the spin vector potential \(\vec{\mathcal{A}} = k (\vec{r} \times \vec{S}) / r^2\) together with a Coulomb-type scalar potential \(\varphi = \kappa / r\) . The model is governed by the Schrödinger-type Hamiltonian \(\mathcal{H}_S = \vec{\Pi}^2 / (2M) + q \varphi\) in nonrelativistic quantum mechanics and by the Dirac-type Hamiltonian \(\mathcal{H}_D = c \vec{\alpha} \cdot \vec{\Pi} + \beta M c^2 + q \varphi\) in relativistic quantum mechanics, where \(\vec{\Pi} = \vec{p} - (q/c)\vec{\mathcal{A}}\) is the canonical momentum. We demonstrate two main results: (i) Just as the Coulomb-type scalar potential \(\mathcal{S}_Maxwell = \{\vec{\mathcal{A}} = 0,\ \varphi = \kappa / r\}\) is a local exact solution of Maxwell's equations on $r\neq0$, the gauge potential \(\mathcal{S}_YM = \{\vec{\mathcal{A}} = k (\vec{r} \times \vec{S}) / r^2,\ \varphi = \kappa / r\}\) constitutes a local exact solution of the Yang–Mills equations on the punctured region $r\neq0$. (ii) Both Hamiltonians \(\mathcal{H}_S\) and \(\mathcal{H}_D\) can be solved exactly in the presence of this spin-dependent Coulomb interaction. The resulting energy spectra are derived, and they naturally reduce to those of the ordinary hydrogen atom when the spin-dependent terms are neglected. Finally, we clarify the quantization conditions and the fixed-background interpretation of the model.

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

Large Language Models as Optimizers: A Survey of Direct vs. Tool-Augmented Approaches and Their Performance Frontiers

arXiv:2606.15577v1 Announce Type: new Abstract: Large Language Models (LLMs) are increasingly involved in complex mathematical optimization, even if the pragmatic user who triggers them is unaware of it. After all, many real-world problems reduce to the search for better or the best solutions. The field of LLM-as-optimizer has three paradigms: direct optimization, tool-augmented optimization, and tool-creating optimization. Direct optimization uses iterative prompting and heuristic generation to navigate solution spaces. Tool-augmented optimization translates natural language problems into formal specifications and orchestrates external solvers. Tool-creating optimization goes further, using LLMs to discover reusable algorithms or heuristics that can be deployed at zero marginal LLM cost. We describe current performance frontiers based on the benchmarks from the literature. We identify the critical reasoning gap in current architectures and argue for trade-offs between the future potential of direct optimization and the auditability of tool-augmented optimization. Even future, more powerful models might opt for tool-making to improve operational efficiency for repetitive families of problems.

11.
arXiv (CS.CV) 2026-06-25

ESTANet: Efficient Online Error Detection in Procedural Videos via Prediction Inconsistency

An efficient and accurate system for detecting errors in procedural tasks is crucial for supporting human needs in daily life, as it can provide instant notifications and guide people to correct mistakes. In this work, we study real-time online error detection in procedural videos from a simple but overlooked perspective: the prediction behavior of action detectors themselves. Instead of designing complex architectures or specialized supervision, we observe that action detectors naturally exhibit different prediction characteristics depending on their sensitivity to input dynamics and temporal context. We therefore propose ESTANet (Error-Sensitive and Temporally-vArying Network), a lightweight framework that detects errors by exploiting inconsistencies among action predictions produced by a small set of action detectors. We construct standard and error-sensitive action detectors that behave similarly on correct executions but respond differently when errors occur. Meanwhile, detectors operating with different temporal contexts further amplify prediction inconsistencies when the procedure deviates from the intended sequence. During inference, we detect errors by aggregating mismatches between standard and error-sensitive predictions through majority voting to flag frames that contain errors. Extensive experiments on EgoPER, Assembly-101-O, and EPIC-Tent-O demonstrate that ESTANet achieves state-of-the-art performance in online error detection while maintaining real-time efficiency with a lightweight architecture. Our results highlight that leveraging the intrinsic properties of action detectors can yield a powerful and practical solution for online error detection without increasing architectural design complexity.

12.
arXiv (CS.AI) 2026-06-11

Skill-Augmented AI Agents for Medical Research Analysis: An Exploratory Multi-Model Human Evaluation in an NSCLC Transcriptomic Biomarker Task

arXiv:2606.11830v1 Announce Type: new Abstract: Background. Large language models and AI agents are increasingly used to support biomedical research, but native model outputs may omit key analytical steps, misuse methods, or overstate conclusions. We evaluated whether autonomous access to a medical research skill package was associated with higher-quality AI-generated transcriptomic research-analysis outputs compared with native AI without skills. Methods. We conducted an exploratory multi-model human evaluation using a non-small cell lung cancer immunotherapy biomarker task. Six model backbones were tested. The evaluation included 21 anonymized outputs: 9 native-AI outputs and 12 skill-augmented outputs generated through an AI agent implementation represented by OpenClaw. Four non-expert biomedical reviewers and two blinded experts evaluated each output, with two ratings from each reviewer type. The primary outcome was expert-rated overall quality. Results. Skill-augmented outputs showed directionally higher expert overall quality than native-AI outputs (mean 5.50 vs 5.11; difference=0.39; bootstrap 95\% CI, -0.04 to 0.90; Welch p=0.156). Non-expert reviewer quality showed the same direction (mean 4.72 vs 4.47; difference=0.26; bootstrap 95\% CI, -0.25 to 0.80; Welch p=0.373). Expert agreement was limited (single-rating ICC=-0.15), and model-specific effects were descriptive and heterogeneous. Conclusions. Autonomous skill access showed a directional quality signal in this exploratory sample, but the signal was smaller than expert-rating noise and should not be interpreted as confirmatory evidence. The findings primarily motivate larger evaluations of skill-augmented AI agents with stronger reliability controls, platform replication, and biological-validity assessment.

13.
medRxiv (Medicine) 2026-06-12

The Clinical Characteristics and mortality outcomes of Atrial fibrillation complicating Heart failure with reduced ejection fraction: A prospective study from South Africa

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

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

A Five-Plane Reference Architecture for Runtime Governance of Production AI Agents

Authors:

arXiv:2606.12320v1 Announce Type: new Abstract: Enterprise security was built to govern data boundaries: the protected surface was data at rest and in transit, and the controls – access control, data-loss prevention, perimeter inspection – governed crossings of that boundary. Production AI agents dissolve this assumption. An agent reads context, calls tools, invokes connectors, and modifies systems of record on an enterprise's behalf, so risk moves inside the workflow, into sequences of individually-permitted actions that may transform a business process no one authorized. Existing policy engines do not extend to this regime: they evaluate request-time decisions against atomic principals, where agentic systems require stateful evaluation against composite principals whose authority attenuates through delegation chains. We present a reference architecture for the runtime governance of production agents, built from four composable primitives: a five-plane decomposition (a reasoning plane that adjudicates intent, and four enforcement planes – network, identity, endpoint, data – that realize the decision), stop-anywhere mediation, composite principals with capability attenuation, and audit as a structured evidence substrate. We define a taxonomy of six interruption primitives that generalize allow and deny, state and argue for four correctness invariants, and demonstrate the foreclosure of seven production-agent threats across five concrete workflows. A reference implementation of the policy-engine core supplies measured evidence: attenuation correctness and evidence reconstructability hold on every trial, adjudication runs in single-digit microseconds, and the audit substrate's tamper-evidence behaves exactly as designed. We are explicit about scope: the architecture governs delegated action, not model behavior, and a full-system evaluation against a live agent benchmark is the invited next step.

15.
arXiv (CS.AI) 2026-06-12

Real-Time Execution with Autoregressive Policies

arXiv:2606.13355v1 Announce Type: cross Abstract: Real-time execution, enabled by asynchronous inference that ensures both smooth action trajectories and fast reactivity, is critical for realistic deployments of large-scale Vision-Language-Action models. However, recent work on real-time execution primarily focuses on variants of diffusion policies, even though it is more critical for autoregressive policies given their slower rollout speed in synchronous inference. In contrast, we demonstrate that autoregressive policies can achieve real-time execution by adjusting the tokenization horizon and applying constrained decoding, thereby guaranteeing strict latency bounds that enable multi-trajectory decoding to maximize performance. Across simulated and real-world environments, we find that the autoregressive policy consistently outperforms its equivalent-level flow-matching policy counterpart while achieving significantly improved task completion speeds from synchronous inference. Coupled with the inherent advantages of autoregressive policies, such as faster convergence and better generalizability in instruction-following, these results confirm that autoregressive policies can remain a competitive policy type supporting real-time execution.

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

ModTGCN: Modularity-aware Graph Neural Networks for Text Classification

Graph-based text classification models typically rely on local neighborhood aggregation and overlook global community structure, despite semantic document graphs exhibiting strong class-consistent clustering. Ignoring this can blur class boundaries and lead to over-smoothing. We propose ModTGCN, a modularity-aware graph neural network for text classification that jointly optimizes cross-entropy and a modularity-based auxiliary objective to promote class-coherent document communities while preserving discriminative representations. The modularity term is computed on a document-document similarity graph derived from transformer embeddings (pretrained or fine-tuned). To improve scalability, we decouple the original heterogeneous TextGCN graph into separate document-word and word-word components, achieving 2x-10x faster training. We further study graph construction strategies, label-aware edge reweighting, and supervision choices for modularity optimization. Experiments on five benchmarks show consistent gains, with larger improvements on complex, low homophily datasets such as Ohsumed and 20NG.

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

Prototype-Based Semantic Consistency Alignment for Domain Adaptive Retrieval

arXiv:2512.04524v4 Announce Type: replace-cross Abstract: Domain adaptive retrieval aims to transfer knowledge from a labeled source domain to an unlabeled target domain, enabling effective retrieval while mitigating domain discrepancies. However, existing methods encounter several fundamental limitations: 1) neglecting class-level semantic alignment and excessively pursuing pair-wise sample alignment; 2) lacking either pseudo-label reliability consideration or geometric guidance for assessing label correctness; 3) directly quantizing original features affected by domain shift, undermining the quality of learned hash codes. In view of these limitations, we propose Prototype-Based Semantic Consistency Alignment (PSCA), a two-stage framework for effective domain adaptive retrieval. In the first stage, a set of orthogonal prototypes directly establishes class-level semantic connections, maximizing inter-class separability while gathering intra-class samples. During the prototype learning, geometric proximity provides a reliability indicator for semantic consistency alignment through adaptive weighting of pseudo-label confidences. The resulting membership matrix and prototypes facilitate feature reconstruction, ensuring quantization on reconstructed rather than original features, thereby improving subsequent hash coding quality and seamlessly connecting both stages. In the second stage, domain-specific quantization functions process the reconstructed features under mutual approximation constraints, generating unified binary hash codes across domains. Extensive experiments validate PSCA's superior performance across multiple datasets.

18.
PLOS Computational Biology 2026-06-22

GrassSV – hybrid method to detect structural variants in high throughput DNA-seq data

by Dominik Witczak, Krzysztof Sychla, Julia Wysocka, Artur Laskowski, Wojciech Frohmberg, Marta Glowacka, Alicja Dzik, Piotr Lukasiak, Jacek Blazewicz, Aleksandra Swiercz Genetic diversity is crucial for populations to adapt and survive in dynamic environments. This diversity arises from genetic mutations, which manifest in the genome as structural variants (SVs). Several types of SVs exist, but not all are equally easy to detect. Current SV detection tools tend to specialize in certain SV types or require the use of multiple tools to obtain a comprehensive variant profile, which increases computational cost and complexity. While some methods excel at identifying breakpoints, they often struggle with accurately classifying variant types, and their precision depends strongly on data quality and sequencing technology. At present, the majority of available genomic data originates from high-quality short reads, which remain the most affordable sequencing technology. In this manuscript, we introduce GrassSV, a novel and computationally efficient method that employs a hybrid pattern-matching approach to detect all major classes of structural variants using short-read sequencing data. GrassSV integrates depth-of-coverage analysis with contig-based pattern recognition to ensure both sensitivity and precision while minimizing false positives and runtime. Its robustness was demonstrated on the human Genome in a Bottle dataset, as well as on synthetic data derived from the yeast genome, where it achieved high accuracy across all SV types at a lower computational cost compared to existing methods. This makes GrassSV a practical alternative to multi-tool pipelines typically required for comprehensive SV detection. GrassSV is available at https://github.com/Domomod/GrassSV under GPL-3.0 license and the benchmark at: https://github.com/Domomod/GrassBenchmark.

19.
medRxiv (Medicine) 2026-06-22

T Cell Receptor repertoire analysis reveals antigenic convergence and immunotherapeutic opportunities in Prostate Cancer

Background: The T-cell receptor {beta} (TCR{beta}) repertoire reflects antigen-driven adaptive immune responses and provides insight into tumor-immune interaction. In prostate cancer (PCa), the immunosuppressive tumor microenvironment limits effective T-cell activation, and the antigenic drivers shaping intratumoral TCR repertoires remains poorly defined. This study aimed to characterize matched tumor and peripheral TCR{beta} repertoires from treatment-naive PCa patients and to identify shared clonotypes and antigenic specificities associated with disease severity. Methods: Next-generation sequencing was used to profile TCR{beta} repertoires from matched tumor biopsies and peripheral blood mononuclear cells obtained from treatment-naive PCa patients. Repertoires clonality, diversity, and was assessed using established metrics. Antigenic convergence was evaluated using GLIPH2 to identify shared CDR3{beta} motifs and predicted tumor-associated antigen (TAA) recognition, followed by functional validation using IFN-{gamma} ELISpot and T-cell expansion assays. Results: Tumor-derived TCR{beta} repertoires displayed reduced richness and increased clonality compared with peripheral blood mononuclear cells, consistent with local antigen-driven expansion. High-grade tumors demonstrated greater interpatient clonotype sharing and motif-level convergence, indicative of recognition of common TAAs. GLIPH2 analysis associated expanded clonotypes with epitopes derived from prostate-specific G-protein coupled receptor (PSGR), prostate-specific membrane antigen (PSMA), and prostate-specific antigen (PSA). Functional validation confirmed that peptide pools containing PSGR- and PSMA-derived epitopes induced IFN-{gamma} production and antigen-specific T-cell proliferation in vitro. Conclusions: These findings reveal an oligoclonal, antigen-driven intratumoral TCR{beta} landscape and identify PSGR and PSMA as immunogenic, potentially actionable targets. Integration of TCR profiling with antigen discovery pipelines may support the development of TCR-based biomarkers and precision immunotherapeutic strategies in prostate cancer.

20.
arXiv (CS.CV) 2026-06-16

Attention-Based Prototype Calibration for Multi-Rater Few-Shot Medical Image Segmentation

Few-shot medical image segmentation methods typically assume a single ground-truth annotation, overlooking systematic variability across expert raters commonly observed in clinical datasets. We propose an attention-based prototype calibration framework for few-shot multi-rater segmentation that models rater-specific deviations from a consensus representation in prototype space. A lightweight yet principled attention operator directly refines rater prototypes without modifying the backbone feature extractor, making the approach fully compatible with existing prototype-based few-shot segmentation methods. This design preserves semantic consistency while enabling personalized segmentation outputs with minimal computational overhead. Experiments on multi-rater medical imaging datasets demonstrate consistent improvements over baseline prototype approaches, highlighting the effectiveness of structured prototype calibration for modeling annotation variability. Our code is available at https://github.com/truong2710-cyber/JAPC.

21.
arXiv (CS.AI) 2026-06-16

Active Inference with a Self-Prior in the Mirror-Mark Task

arXiv:2604.09673v2 Announce Type: replace-cross Abstract: The mirror self-recognition test evaluates whether a subject touches a mark on its own body that is visible only in a mirror, and is widely used as an indicator of self-awareness. In this study, we present a computational model in which this behavior emerges spontaneously through a single mechanism, the self-prior, without any external reward. The self-prior, implemented with a Transformer, learns the density of familiar multisensory experiences; when a novel mark appears, the discrepancy from this learned distribution drives mark-directed behavior through active inference. A simulated infant, relying solely on vision and proprioception without tactile input, discovered a sticker placed on its own face in the mirror and removed it in approximately 70% of cases without any explicit instruction. Expected free energy decreased significantly after sticker removal, confirming that the self-prior operates as an internal criterion for distinguishing self from non-self. Cross-modal sampling further demonstrated that the self-prior captures visual–proprioceptive associations, functioning as a probabilistic body schema. These results provide a concise computational account of the key behavior observed in the mirror test and suggest that the free energy principle can serve as a unifying hypothesis for investigating the developmental origins of self-awareness. Code is available at: https://github.com/kim135797531/self-prior-mirror

22.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

Authors:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

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

Secure Coding Drift in LLM-Assisted Post-Quantum Cryptography Development: A Gamified Fix

arXiv:2606.19474v1 Announce Type: cross Abstract: The transition to Post Quantum Cryptography (PQC) introduces considerable implementation complexity, requiring strict adherence to constant-time execution, side channel resistance, and precise parametrisation. Simultaneously, large language models (LLMs) are heavily embedded in software development workflows, including cryptographic engineering. While LLMs improve productivity, evidence shows that they frequently generate insecure or suboptimal code, particularly in security critical domains. This paper introduces Secure Coding Drift in PQC, a novel socio technical vulnerability model capturing the gradual degradation of secure coding practices due to sustained reliance on LLM-generated code. Unlike prior work that focuses on static vulnerabilities, we conceptualise security risk as a longitudinal behavioural phenomenon rising from human AI interaction. To mitigate this, we propose a gamified, LLM augmented secure coding framework that embeds adversarial evaluation, behavioural feedback, and security scoring into development workflows. Our approach reframes LLMs from passive assistants into active security co-pilots, contributing toward safer PQC implementation in AI mediated environments.

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

Imitating What Works: Simulation-Filtered Modular Policy Learning from Human Videos

The ability to learn manipulation skills by watching videos of humans has the potential to unlock a new source of highly scalable data for robot learning. Here, we tackle prehensile manipulation, in which tasks involve grasping an object before performing various post-grasp motions. Human videos offer strong signals for learning the post-grasp motions, but they are less useful for learning the prerequisite grasping behaviors, especially for robots without human-like hands. A promising way forward is to use a modular policy design, leveraging a dedicated grasp generator to produce stable grasps. However, arbitrary stable grasps are often not task-compatible, hindering the robot's ability to perform the desired downstream motion. To address this challenge, we present Perceive-Simulate-Imitate (PSI), a framework for training a modular manipulation policy using human video motion data processed by paired grasp-trajectory filtering in simulation. This simulation step extends the trajectory data with grasp suitability labels, which allows for supervised learning of task-oriented grasping capabilities. We show through real-world experiments that our framework can be used to learn precise manipulation skills efficiently without any robot data, resulting in significantly more robust performance than using a grasp generator naively.

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

Multi-Bitwidth Quantization for LLMs Using Additive Codebooks

As large language models (LLMs) are increasingly deployed across heterogeneous hardware with varying resource constraints, the ability to adaptively manage the trade-off between performance and efficiency without retraining is critical. We propose Drop-by-Drop, a novel multi-bitwidth post-training quantization framework that enables inference-time precision control over LLM weights from a single trained model. Our method is theoretically grounded in information theory and successive refinement. We establish that LLM weights, which commonly follow a Gaussian distribution, can be optimally reconstructed with increasing fidelity as additional bits are incorporated, under a weighted mean squared error distortion motivated by LLM loss functions. To realize this in practice, Drop-by-Drop incorporates Matryoshka-style supervision into the loss function, exploiting the structure of additive codebooks. Drop-by-Drop produces a single model where ordered subsets of codebooks yield accurate partial reconstructions at each precision level. This approach significantly reduces storage and memory overhead by allowing a single checkpoint to serve multiple bitwidths, while maintaining competitive perplexity and accuracy across major architectures, such as Qwen, LLaMA, Gemma, and Mistral.