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01.
arXiv (CS.CV) 2026-06-11

Moving Beyond Diffusion: Hierarchy-to-Hierarchy Autoregression for fMRI-to-Image Reconstruction

Reconstructing visual stimuli from fMRI signals is a central challenge bridging machine learning and neuroscience. Recent diffusion-based methods typically map fMRI activity to a single neural embedding, using it as static guidance throughout the entire generation process. However, this fixed guidance collapses hierarchical neural information and is misaligned with the stage-dependent demands of image reconstruction. In response, we propose MindHier, a coarse-to-fine fMRI-to-image reconstruction framework built on scale-wise autoregressive modeling. MindHier introduces three components: a Hierarchical fMRI Encoder to extract multi-level neural embeddings, a Hierarchy-to-Hierarchy Alignment scheme to enforce layer-wise correspondence with CLIP features, and a Scale-Aware Coarse-to-Fine Neural Guidance strategy to inject these embeddings into autoregression at matching scales. These designs make MindHier an efficient and cognitively aligned alternative to diffusion-based methods by enabling a hierarchical reconstruction process that synthesizes global semantics before refining local details, akin to human visual perception. Extensive experiments on the NSD dataset show that MindHier achieves superior semantic fidelity, 4.67$\times$ faster inference, and more deterministic results than the diffusion-based baselines.

02.
arXiv (CS.CV) 2026-06-12

VDE Bench: Evaluating The Capability of Image Editing Models to Modify Visual Documents

In recent years, image editing models have made significant progress, enabling users to manipulate visual content in a flexible and interactive manner through natural language instructions. However, an important yet underexplored research direction remains dense visual document image editing, which involves modifying textual content within images while faithfully preserving the original text style and background context. Existing methods primarily focus on English scenarios and images with relatively sparse text, and thus cannot adequately address dense, structurally complex documents or non-Latin scripts such as Chinese. To bridge this gap, we propose VDE Bench (Visual Doc Edit Bench), a rigorously human annotated and evaluated benchmark specifically designed to assess the performance of image editing models on bilingual Chinese-English and complex visual document editing tasks. The benchmark comprises a high quality dataset of 942 instruction based image editing samples, whose seed images encompass dense Chinese and English text documents including academic papers, posters, presentation slides, examination materials, and newspapers. Furthermore, we introduce a novel evaluation framework that systematically quantifies editing performance at the OCR parsing level, thereby enabling fine grained assessment of text modification accuracy. Based on this benchmark, we conduct a comprehensive evaluation of representative image editing models. Human verification demonstrates a high degree of consistency between human judgments and automated evaluation metrics. VDE Bench constitutes the first systematic benchmark for evaluating the performance of image editing models on bilingual dense text visual documents.

03.
arXiv (CS.CL) 2026-06-15

OdysSim: Building Foundation Models for Human Behavior Simulation

Large language models are increasingly deployed as human simulators for interactive evaluation and social simulation. Yet helpfulness-driven post-training pulls them toward a homogeneous, overly agreeable assistant register, creating a behavioral Sim2Real gap. We present OdysSim, the largest open systematic investigation of behavioral foundation models, i.e., models trained to simulate human behavior at scale. We propose SOUL, a taxonomy of five capability axes (CONV, SS, COG, ROLE, EVAL) that unifies 62 datasets and 23 benchmark tasks under one framework. Specifically, we curate the OdysSim corpus (21.4M interactions, 10B tokens, retrofitted with back-generated social contexts), construct the SOUL-Index benchmark, and develop an end-to-end training recipe combining midtraining, task-specific RL, and expert distillation. The resulting open 8B OSim model ranks first or tied-first on 8 of 23 tasks, outperforming any individual frontier model by this count, with the strongest gains on conversational and social tasks. Its outputs are also more human-like in length, formatting, and word choice, and it transfers zero-shot to out-of-distribution user simulation on $\tau$-bench, nearly matching real users on reaction alignment (93.2 vs. 93.5). We further show that LLM-as-judge RL induces reward-hacking patterns, and that our detectors can mitigate them during post-training. Together, our findings suggest that behavioral foundation models require rethinking the LLM training paradigm. We release all artifacts to support future research.

04.
arXiv (CS.CL) 2026-06-11

Reassessing High-Performing LLMs on Polish Medical Exams: True Competence or Bias-Driven Performance?

Large language models (LLMs) in medicine are mainly evaluated using multiple-choice question answering (MCQA), which can overestimate real clinical ability due to guessing strategies and answer biases. To address these limitations, we introduce an expanded and more challenging benchmark based on Polish medical exams, adding over 15,000 questions, two new domains, and four structural modifications that reduce MCQA-specific artifacts and better test reasoning. We evaluate 21 LLMs and show that evaluation design strongly affects results. Under our harder setup, the best model (Qwen3.5-122B) drops by 28.4 and 31 pp on English and Polish exams, respectively. Despite low evidence of data contamination, standard MCQA scores do not reliably reflect true medical competence. To facilitate further research, we make our benchmark publicly available.

05.
medRxiv (Medicine) 2026-06-15

Multidimensional nutritional assessment in Crohns disease: cross-sectional comparison of active disease and remission

Malnutrition is common in Crohns disease (CD), and its assessment requires multiple tools. Comprehensive evaluation of nutritional status in a population with CD, predominantly characterized by metabolic phenotype, was inadequately reported. This study evaluated the nutritional status of CD patients using anthropometric, clinical, and biochemical measures and compared patients with active disease with those in remission. This cross-sectional study included 127 adults with CD: 63 with active disease and 64 in remission. Disease activity was classified using the Crohns Disease Activity Index, the Simple Endoscopic Score for Crohns Disease, and magnetic resonance enterography. Nutritional assessment included body mass index (BMI), mid-upper arm circumference, calf circumference, triceps skinfold thickness, mid-arm muscle circumference, Mini Nutritional Assessment-Short Form (MNA-SF), and biochemical markers including hemoglobin, serum iron, folate, vitamin B12, albumin, and zinc. Malnutrition was defined using the Global Leadership Initiative on Malnutrition criteria. Overall, 47.2% of participants were malnourished. Malnutrition was significantly more frequent in active disease than in remission (81.0% vs. 14.1%, P

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

HOLMES: Evaluating Higher-Order Logical Reasoning in LLMs

arXiv:2606.23238v2 Announce Type: replace Abstract: Logical reasoning is essential for reliable AI, yet existing benchmarks are largely first-order-logic-centric, focusing on object-level deduction over fixed predicates. This misses many realistic scenarios where models must reason over rules, predicates, functions, constraints, and decision procedures themselves. We introduce HOLMES (Higher-Order Logic Meets real-world Explainable Symbolic reasoning), the first real-world benchmark for higher-order symbolic reasoning in LLMs, containing 1379 instances. Built on higher-order logic, HOLMES pairs natural-language problems with HOL formalizations, ground-truth answers, verifiable reasoning traces, and fine-grained controllable reasoning factors across law and finance. Experiments show that current LLMs still struggle on HOLMES, with an average accuracy of only 50.64% and the best model reaching 59.54%. Our analyses further reveal that high final-answer accuracy can mask shortcut reasoning in conflict-resolution settings, while performance drops sharply under scope-conditioned and compositional reasoning. These findings identify higher-order symbolic reasoning as a key bottleneck for building reliable and verifiable LLMs. The project code and dataset are publicly available at https://github.com/wuyucheng2002/HOLMES.

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

OmniOPSD: Rationale-Privileged On-Policy Self-Distillation for Affective Computing

Reinforcement learning for multimodal large language models (MLLMs) is often hindered by severe reward sparsity in complex reasoning tasks. This challenge is particularly pronounced in human-centered scenarios involving states, emotions, intentions, and behaviors, where heterogeneous multimodal signals and subjective human factors make high-quality chain-of-thought (CoT) annotations expensive and difficult to obtain. Although many multimodal datasets provide expert-annotated ground-truth labels, directly using these labels for supervised fine-tuning may encourage shortcut learning in multimodal perception and provides limited transparency for safety-critical human–AI interaction. To address these limitations, we propose OmniOPSD, a Rationale-Privileged On-Policy Self-Distillation framework that uses frontier-generated rationales as teacher-side privileged evidence rather than student imitation targets. OmniOPSD uses frontier-generated evidence-aware rationales only as training-time privileged evidence context for a local teacher. The student samples its own rollout from the original multimodal input, while the rationale-privileged teacher scores the same tokens and provides dense token-level supervision. Thus, the student learns on its own trajectory distribution without directly imitating frontier-model completions, and inference requires no labels, rationales, CoT annotations, or closed-source model access. Experiments on MER-UniBench show that OmniOPSD achieves state-of-the-art performance with an average score of $84.19$, and ablations further support the value of rationale-privileged teacher guidance.

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

Phase Transitions in Attention: A Bayesian Theory of Copy Head Emergence

arXiv:2606.12058v1 Announce Type: cross Abstract: Attention is the key mechanism underlying in-context learning in transformers, and attention patterns have been observed empirically to emerge abruptly during training. We present a Bayesian theory of feature learning in attention; we then focus on how the copy subcircuit in the first layer of an induction head is learned by analyzing a single-layer softmax attention network trained on a copy task. We derive a closed-form posterior over the attention matrix and reduce it to a low-dimensional order parameter space. This reduction reveals a phase transition in the amount of training data, which we verify using both Bayesian sampling and standard training with Adam. We contrast our results with linear attention and find that softmax attention exhibits a first-order phase transition while in linear attention an initial second-order phase transition is followed by a smooth, continuous evolution toward the structured attention pattern (crossover). Our work provides a first-principles theoretical account of the abrupt emergence of the copy subcircuit, reminiscent of the one observed in training large language models.

09.
Nature (Science) 2026-06-23

How should I respond to race-based exclusion in my lab?

作者:

A researcher in Europe feels left out of their team and held to different standards from their colleagues. How can they challenge exclusion without risking their position? A researcher in Europe feels left out of their team and held to different standards from their colleagues. How can they challenge exclusion without risking their position?

10.
arXiv (quant-ph) 2026-06-24

M{\o}lmer-S{\o}rensen gates in trapped-ions chains in the presence of correlated noise

arXiv:2606.23951v1 Announce Type: new Abstract: We analyze the impact of correlated laser frequency noise on M{\o}lmer-S{\o}rensen gates in qubit registers based on trapped-ion chains. Using perturbation theory, we calculate gate fidelities in the presence of noise with arbitrary power spectral density for different chain lengths and ion positions in the chain. With our approach, we account for simultaneous excitation of multiple phonon modes during gate operation. We find out that the impact of medium-frequency laser noise depends considerably on the positions of the ions in the chain. In contrast, low-frequency noise has similar effect for different chain lengths and ion positions.

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

When Plausible Is Not Realistic: Evaluating Human Mobility in LLM-Based Urban Simulation

LLM-based generative agents are increasingly used in urban simulators, yet it remains unclear whether they reproduce empirically realistic human mobility patterns or merely generate plausible mobility narratives. We introduce a validation framework for evaluating the mobility of generative agents of LLM-based urban simulators against real-world mobility data. For this, we use mobility laws, temporal rhythms, network motifs, semantic activity transitions, and behavioral mobility profiles. Using datasets from the Greater Paris region and Shanghai, we evaluate AgentSociety and CitySim across multiple dimensions of mobility realism. Our analysis reveals a substantial gap between narrative plausibility and empirical mobility realism. Although the simulators capture some high-level semantic activity distributions, they struggle to reproduce core spatial and temporal constraints, including realistic trip-length distributions, origin-destination flows, dwell times, and transition dynamics. We further observe that realistic mobility diversity is unstable across default prompting configurations and may require explicit profile-aware initialization. To support reproducible evaluation, we also contribute scalable and open LLM-driven infrastructure for regional-scale map generation, observability-enhanced simulation, mobility-metric computation, and traffic simulation. Our findings highlight the need for rigorous empirical validation of LLM-based urban simulators and provide practical tools for building more realistic and reproducible urban simulation systems.

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

Schützen: Evaluating LLM Safety in Bulgarian and German Contexts

Large language models are increasingly deployed across professional domains, bringing hard-to-predict risks, including the generation of harmful or disrespectful content. Although substantial progress has been made in developing safety evaluation datasets, existing resources remain overwhelmingly English- and Chinese-centric. This limitation is particularly pronounced when evaluating languages that operate within shared sociocultural, legal, and ethical contexts. To address this gap, we introduce Sch\"{u}tzen: a German–Bulgarian safety dataset designed to assess model answerability under risk, covering both a low-resource language (Bulgarian) and a high-resource language (German). Experiments with multilingual and language-specific LLMs reveal pronounced cross-language differences in safety behavior, highlighting the necessity of tailored, region-specific evaluation resources to support the responsible deployment of LLMs in Germany and Bulgaria. Datasets and code are available at https://github.com/xnlp-lab/Schutzen. Warning: this paper contains examples that may be offensive, harmful, or biased.

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

A Mathematical Theory of Value: a synthesis on goal-directed agency under resource constraints

作者:

arXiv:2606.12502v1 Announce Type: cross Abstract: We propose that value – the quantity goal-directed agents create, destroy, and exchange – is a lawful structural quantity in the same category as information. Following Shannon's method, we make one ruthless abstraction: value is the rate at which an agent converts a resource into goal-progress, relative to a frame fixed by its goal. A scale-invariance axiom forces a logarithmic measure, $V=\sum_i k_i \ln e_i$; compounding of a reinvested resource forces the same form via the ergodicity argument of Peters (2019). The two routes are kin rather than independent; their agreement is a consistency check, not an over-determination. We derive a coding theorem of value: $\Delta G \le I(X;Y)$, achieved by Bayes-proportional allocation; realized value decomposes as $G=D(q\|r)-D(q\|p)$, identifying misalignment with measurable waste. For populations, value is frame-relative while price is frame-independent; a fleet that pools its resource and fuses its perception inherits the ceiling $G_{\mathrm{fleet}} \le I(X;Y_{1:m}) \le H(X)$ (a corollary; an earlier sum-form claim was wrong and is corrected in v5). A dynamical layer yields an is/ought asymmetry from which alignment emerges as a control-stability condition with a closed-form residual. We test the single-frame laws on live language models in a pre-registered scale-up: perception mutual information tracks realized capability rather than parameter count (Spearman $\rho = 0.977$ pooled over 30 model$\times$domain points), out-of-sample $\Delta G$ tracks $I(X;Y)$, and over-confidence is measurable dissipation; a further pre-registered test shows the bridge is shape-invariant across four task shapes ($n=42$, slope 0.953). None of the mechanisms is individually new – generalized Kelly, Armstrong & Mindermann (2018), classical control; the contribution is their unification and the governance mapping (incentive design over oversight) that follows.

14.
arXiv (CS.LG) 2026-06-12

Toward General Digraph Contrastive Learning: A Dual Spatial Perspective

arXiv:2510.16311v2 Announce Type: replace Abstract: Graph Contrastive Learning (GCL) has emerged as a powerful tool for extracting consistent representations from graphs, independent of labeled information. However, existing methods predominantly focus on undirected graphs, disregarding the pivotal directional information that is fundamental and indispensable in real-world networks (e.g., social networks and recommendations).In this paper, we introduce S2-DiGCL, a novel framework that emphasizes spatial insights from complex and real domain perspectives for directed graph (digraph) contrastive learning. From the complex-domain perspective, S2-DiGCL introduces personalized perturbations into the magnetic Laplacian to adaptively modulate edge phases and directional semantics. From the real-domain perspective, it employs a path-based subgraph augmentation strategy to capture fine-grained local asymmetries and topological dependencies. By jointly leveraging these two complementary spatial views, S2-DiGCL constructs high-quality positive and negative samples, leading to more general and robust digraph contrastive learning. Extensive experiments on 7 real-world digraph datasets demonstrate the superiority of our approach, achieving SOTA performance with 4.41% improvement in node classification and 4.34% in link prediction under both supervised and unsupervised settings.

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

FLiP: Towards understanding and interpreting multimodal multilingual sentence embeddings

This paper presents factorized linear projection (FLiP) models for understanding pretrained sentence embedding spaces. We train FLiP models to recover the lexical content from multilingual (LaBSE), multimodal (SONAR) and API-based (Gemini) sentence embedding spaces in several high- and mid-resource languages. We show that FLiP can recall more than 75% of lexical content from the embeddings, significantly outperforming existing non-factorized baselines. Using this as a diagnostic tool, we uncover the modality and language biases across the selected sentence encoders and provide practitioners with intrinsic insights about the encoders without relying on conventional downstream evaluation tasks. Our implementation is public https://github.com/BUTSpeechFIT/FLiP.

16.
medRxiv (Medicine) 2026-06-22

Evidence-guided AI regularization for suicidal ideation prediction in pediatric bipolar disorder

Background: Suicide prediction models in psychiatry often rely on purely data-driven feature selection, which can produce unstable and clinically opaque predictor sets in modest-sized samples. We developed Evidence-Based AI LASSO (EBAL), an evidence-guided regularization framework that incorporates curated clinical evidence into feature-specific penalty factors for interpretable prediction. Methods: Baseline data from 136 youth with confirmed bipolar spectrum disorder in the Greater Houston Area Bipolar Registry were analyzed using 20 candidate clinical predictors. Forty higher-level evidence documents on suicidality and related predictor domains were curated through a structured evidence synthesis workflow and indexed as an auditable evidence corpus. An open-weight large language model assigned feature-specific penalty factors using a prespecified scoring rubric, and these penalties were used to fit a weighted LASSO model. EBAL was compared with a standard evidence-agnostic LASSO using nested leave-one-out cross-validation. Results: For suicidal ideation, EBAL achieved an AUROC of 0.768, balanced accuracy of 0.757, sensitivity of 0.758, and specificity of 0.757. The standard LASSO achieved an AUROC of 0.760 and balanced accuracy of 0.715. EBAL improved balanced accuracy (+0.042, p=0.010) and Matthews correlation coefficient (+0.079, p=0.010), while retaining fewer stable predictors than standard LASSO (11/20 vs 18/20). The strongest positive predictors were current depressed mood, duration of mood disorder illness, and comorbid generalized anxiety disorder. For suicidal behavior, both models performed near chance and retained all candidate predictors. Limitations: The study was cross-sectional, single-site, and modest in sample size, with no external validation cohort. Conclusions: EBAL produced a sparser and more clinically coherent model for suicidal ideation in pediatric bipolar disorder, but did not improve prediction of suicidal behavior. These findings support evidence-guided regularization as a transparent strategy for aligning psychiatric prediction models with prior clinical knowledge while preserving interpretability.

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

The Holistic Storage of Verb+Up Phrases in Text-based and Audio-based Language Models

A crucial aspect of linguistic capability is the ability to trade off between stored representations and abstract knowledge: one must retrieve learned representations, but also generate novel ones by applying productive rules. While recent work has examined abstract knowledge in language models, holistic storage of multi-word units has received far less attention. We probe internal representations in text-based LLMs and an ASR model, testing whether V+up phrasal verbs develop distinct representations as a function of frequency and predictability. All models show evidence of holistic storage driven by frequency and predictability, further supporting usage-based theories of language.

18.
arXiv (CS.AI) 2026-06-12

Competition and Diversity in Generative AI

arXiv:2412.08610v3 Announce Type: replace-cross Abstract: Recent evidence, both in the lab and in the wild, suggests that the use of generative artificial intelligence reduces the diversity of content produced. The use of the same or similar AI models appears to lead to more homogeneous behavior. Our work begins with the observation that there is a force pushing in the opposite direction: competition. When producers compete with one another (e.g., for customers or attention), they are incentivized to create novel or unique content. We explore the impact competition has on both content diversity and overall social welfare. Through a formal game-theoretic model, we show that competitive markets select for diverse AI models, mitigating monoculture. We further show that a generative AI model that performs well in isolation (i.e., according to a benchmark) may fail to provide value in a competitive market. Our results highlight the importance of evaluating generative AI models across the breadth of their output distributions, particularly when they will be deployed in competitive environments. We validate our results empirically by using language models to play Scattergories, a word game in which players are rewarded for answers that are both correct and unique. Overall, our results suggest that homogenization due to generative AI is unlikely to persist in competitive markets, and instead, competition in downstream markets may drive diversification in AI model development.

19.
arXiv (quant-ph) 2026-06-16

Generalized symmetries, invariant solutions and conservation laws in the Jaynes-Cummings model

arXiv:2606.15538v1 Announce Type: cross Abstract: In this work, we investigate the Jaynes–Cummings model (JCM) using Lie symmetry analysis and conservation-law theory. The dynamics is formulated as a system of partial differential equations by projecting the von Neumann equation onto the atomic degrees of freedom and representing the field mode through its characteristic function. We determine the admitted point and generalized symmetries and construct invariant solutions satisfying the physical conditions imposed by quantum mechanics. The conventional dressed-state dynamics is recovered while a second class of solutions with radial dependence expressed through Heun polynomials is obtained for coupled atom–field configurations. We also apply the generating functions methodology to derive local conservation laws of the JCM differential system. Besides recovering the conservation of the total number of excitations, we obtain additional conserved currents involving atomic populations, coherence, reduced-state purity, and moments of the field characteristic function. In particular, we derive a balance equation for a combination of atomic purity and coherence whose evolution is controlled by the atom–field coupling and is linked to atom–field correlation and entanglement dynamics. The symmetry structure further generates generalized symmetries and an infinite hierarchy of conservation laws.

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

On Sequence-to-Sequence Models for Automated Log Parsing

Context: Log parsing is a critical standard operating procedure in software systems, enabling monitoring, anomaly detection, and failure diagnosis. However, automated log parsing remains challenging due to heterogeneous log formats, distribution shifts between training and deployment data, and the brittleness of rule-based approaches. Objectives: This study aims to systematically evaluate how sequence modelling architecture, representation choice, sequence length, and training data availability influence automated log parsing performance and computational cost. Methods: We conduct a controlled empirical study comparing four sequence modelling architectures: Transformer, Mamba state-space, monodirectional LSTM, and bidirectional LSTM models. In total, 396 models are trained across multiple dataset configurations and evaluated using relative Levenshtein edit distance with statistical significance testing. Results: Transformer achieves the lowest mean relative edit distance (0.111), followed by Mamba (0.145), mono-LSTM (0.186), and bi-LSTM (0.265), where lower values are better. Mamba provides competitive accuracy with substantially lower computational cost. Character-level tokenization generally improves performance, sequence length has negligible practical impact on Transformer accuracy, and both Mamba and Transformer demonstrate stronger sample efficiency than recurrent models. Conclusion: Overall, Transformers reduce parsing error by 23.4%, while Mamba is a strong alternative under data or compute constraints. These results also clarify the roles of representation choice, sequence length, and sample efficiency, providing practical guidance for researchers and practitioners.

21.
arXiv (CS.AI) 2026-06-18

UBP2: Uncertainty-Balanced Preference Planning for Efficient Preference-based Reinforcement Learning

arXiv:2606.19328v1 Announce Type: cross Abstract: Preference-based RL provides an approach to learning reward models from pairwise comparisons of behaviors, bypassing the need for explicit reward design. However, existing methods typically rely on passive data collection and suffer from poor sample efficiency, especially during the early stages of learning. We introduce a model-based approach that actively directs exploration by jointly reasoning over uncertainties in the reward, dynamics, and value functions. Our method, Uncertainty-Balanced Preference Planning (UBP2), uses ensembles of reward, dynamics, and value function models to evaluate candidate trajectories according to a unified score that combines expected reward, terminal value, and epistemic uncertainty. Planning under this objective yields an explicit tradeoff between exploitation and information acquisition without requiring ad hoc exploration heuristics. Under standard regularity assumptions, we establish sublinear regret guarantees for both finite-horizon and infinite-horizon settings. Empirically, experiments on the Meta-World benchmark show UBP2 achieves substantially higher sample efficiency than model-free preference-based methods and non-optimistic model-based baselines.

22.
medRxiv (Medicine) 2026-06-15

Repurposing cardiovascular disease risk models to predict incident and co-occurring cardiovascular, cardiometabolic and neurocognitive outcomes.

Background: Cardiovascular disease (CVD), cardiometabolic and neurocognitive conditions share risk factors and frequently co-occur. We evaluated whether four established CVD risk prediction models (QRISK3, PCE, SCORE2, SCORE2-OP) can be repurposed to predict 10-year risk of these conditions and their co-occurrence with CVD. Methods: The models were recalibrated using 20% of the UK Biobank (UKB) and evaluated in the remaining 80%. We performed external validation using data from Clinical Practice Research Datalink (CPRD) Aurum, assessing model discrimination (c-statistics) and calibration (intercept and slope). We used permuted feature importance to determine the influence of each individual predictor in the models. Results: Depending on the model, the c-statistics for incident CVD ranged from 0.71 to 0.74 in the UKB test set (16,137 events). Discrimination was equal to or higher than CVD when evaluated against non-traditional CVD outcomes: 0.74 to 0.77 for heart failure (3,471 events), 0.72 to 0.73 for atrial fibrillation (9,213 events), 0.73 to 0.75 for peripheral arterial disease (1,927 events) and 0.80 to 0.82 for abdominal aortic aneurysm (595 events). For the multimorbidity endpoints, model discrimination ranged from 0.74 for the composite of CVD and T2DM (SCORE2-OP) to 0.83 for the composite of CVD and dementia or Parkinson's disease (QRISK3). When considering the onset of any cardiovascular, cardiometabolic, or neurocognitive outcome discrimination ranged from 0.71 to 0.72. The repurposed models slightly underestimated the predicted risk in the CPRD compared to the UKB: average difference in calibration intercept was at most -0.64. After age and sex, smoking status and systolic blood pressure contributed most to model predictions. Conclusions: Repurposed CVD models can be used to identify 10-year risk of many CVD-related conditions and their multimorbidity. These may be used to support risk-based approaches to prevention and screening. The repurposed models have been made available at: https://repurposed-cvd-risk-models.shinyapps.io/cvd_cmd_dementia_app/ Keywords: Risk prediction; cardiovascular disease; cardiometabolic disease; dementia; disease prevention.

23.
arXiv (CS.CV) 2026-06-16

Sub-Semantic Image Segmentation

Images can be segmented based on visual cues (i.e., texture segmentation) or into objects (i.e., semantic segmentation). We propose a new category of sub-semantic image segmentation that blurs the line between the two. In sub-semantic image segmentation, language is not used to name whole objects. Instead, it is used to partition an image into stable appearance patterns that can be described by language. To do that, we couple a general-purpose vision-language model to SAM 3, a promptable segmentation backbone whose native text pathway can ground rich descriptions into masks. Simple coupling fails for a number of reasons that we identify in the paper, and we overcome them by introducing DETECTURE that resolves three concrete failure modes – language leakage between texture regions, prompt competition inside the segmentation backbone, and semantic distortion at the language-to-mask interface. Since there is no dataset of sub-semantic image segmentation, we introduce one, termed TextureADE. The new dataset is derived from the ADE20K dataset using a system we designed. We compare DETECTURE to a number of baselines and find that it achieves the strongest performance on several datasets using different metrics. Code is available at https://github.com/Scientific-Computing-Lab/TextureDetecture.

24.
bioRxiv (Bioinfo) 2026-06-14

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers and infectious diseases, where highly antigen-specific TCR recognition is crucial for adaptive immunity against tumors and pathogens. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing reactive TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences with state-of-the-art fidelity to native binding TCRs through a denoising diffusion process. Furthermore, incorporating the interface geometry features generated TCR-pMHC complexes with superior structural plausibility. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs for immunotherapy. In vitro activation assays validated that TCRDiff-generated TCRs specifically recognize the MAGE-A3 epitope with minimized off-target cross-reactivity. Together, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

25.
medRxiv (Medicine) 2026-06-22

Brain-gut axis imaging, motion correction with 11C-carfentanil total-body PET

Background: Mu-opioid receptors (MORs) are expressed throughout the body including in the brain and gastrointestinal (GI) tract. Total-body PET imaging of the brain and GI tract offers a promising approach for cross-sectional in vivo evaluation of the MOR brain-GI axis. However, intestinal motility and bladder filling introduce motion throughout the GI tract over the scan window. Here we establish analysis methodology to account for motion for dynamic imaging of the brain-GI axis, to further characterize peripheral MORs throughout the body and provide a framework for semi-automatic total-body PET modeling. Methods: 4 subjects underwent 90-min dynamic [11C]-carfentanil (cfn) total-body PET acquisitions at baseline, after intravenous naloxone (central antagonist) administration, and after orally administered loperamide (peripheral agonist and P-glycoprotein substrate). Thalamic MOR availability was measured using the Logan reference tissue model. Using CT-based segmentation, the GI tract was subdivided into anatomical segments, in addition to other peripheral organs (e.g., liver, psoas muscle). Frame-by-frame semi-automatic motion correction was performed with three distinct reference frames (11-14 min post-injection, p.i., 35-40 min p.i., and 85-90 min p.i.). The performance of these three were compared to manual correction. Compartment modeling and Logan graphical analysis were performed to estimate relevant kinetic parameters (K1, VT, VTLogan). Results: Across the 4 subjects and regions, kinetic parameter estimates were highly correlated (r>0.7) for K1, VT and VT Logan when comparing semi-automatic (reference frame at 35-40 min p.i.) and manual correction. With semi-automatic motion correction, graphical-based estimation of VTLogan in the gastrointestinal tract was significantly decreased with loperamide relative to baseline (p