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01.
medRxiv (Medicine) 2026-06-15

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

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

02.
arXiv (CS.CL) 2026-06-16

AthDGC: An Open Diachronic Greek Treebank with Indo-European Parallels

AthDGC ("Athens-PROIEL") is an open, end-to-end workflow and dataset. It is, to the best of our knowledge, the first openly licensed dependency-parsed treebank of Greek that spans eight diachronic periods, namely Archaic, Classical, Koine, Late Antique, Byzantine, Late Byzantine, Early Modern, and Modern Greek, under a single PROIEL XML 2.0 schema, with verse-level cross-alignment of the New Testament to Latin (Vulgate), Gothic (Wulfila), Old Church Slavonic (Marianus), and Classical Armenian. AthDGC builds on the PROIEL Treebank Family (Haug and Johndal 2008; Eckhoff et al. 2018), which established the schema and the Koine-Greek reference set for the project. Annotation uses the Stanford Stanza PROIEL-trained workflow; sentence-level alignment uses LaBSE, a multilingual sentence-embedding model; word-level alignment uses multilingual-BERT attention through the AwesomeAlign procedure. The v0.4 release provides curated samples and the open-source toolkit; the full annotated corpus partitions remain under v0.5 audit on the Greek national HPC. Quantitative scale, per-witness verse counts, and per-period annotated-row counts are reported in the v0.5 release notes, after the audit pass completes. Concept DOI: 10.5281/zenodo.20439182.

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

Clustering and Pruning in Causal Data Fusion

arXiv:2505.15215v3 Announce Type: replace-cross Abstract: Data fusion, the process of combining observational and experimental data, can enable the identification of causal effects that would otherwise remain non-identifiable. Although identification algorithms have been developed for specific scenarios, do-calculus remains the only general-purpose tool for causal data fusion, particularly when variables are present in some data sources but not others. However, approaches based on do-calculus may encounter computational challenges as the number of variables increases and the causal graph grows in complexity. Consequently, there exists a need to reduce the size of such models while preserving the essential features. For this purpose, we propose pruning (removing unnecessary variables) and clustering (combining variables) as preprocessing operations for causal data fusion. We generalize earlier results on a single data source and derive conditions for applying pruning and clustering in the case of multiple data sources. We give sufficient conditions for inferring the identifiability or non-identifiability of a causal effect in a larger graph based on a smaller graph and show how to obtain the corresponding identifying functional for identifiable causal effects. Examples from epidemiology and social science demonstrate the use of the results.

04.
arXiv (CS.CL) 2026-06-16

Understanding Scam Trends and Rail Paths from Reddit Self-Disclosure Narratives

Online scam behavior is inherently multi-stage, and the lifecycle includes temporally ordered rails and events rather than isolated signals. Existing works analyze characteristics of scam types and rails, but they do not track scam trends across years. Moreover, the work on the relations between rails is hampered due to the lack of open-source datasets with annotations and coverage of different scam types. To address these gaps, we build a dataset to analyze the yearly trend of scam characteristics and rail paths using Reddit self-disclosure narratives from 2023 to 2025. We collect 21,304 posts from scam-related subreddits with at least one rail among identity, communication, platform, and payment for trend analysis by heuristic annotation. Then, we label 1,800 posts containing explicit or recoverable scam chains by an LLM-assisted method for scam path analysis. The method is evaluated with human annotation. Lastly, we run a topic model on the comments of the posts to analyze the community support behavior. The results reveal that scam processes are predominantly multi-rail. Across years, different scam types and rail components dominate. Different scam types vary systematically in path complexity. Reddit support behaviors have become more detailed over time. This work supports synthetic scam chain data simulation and AI-related scam risk assessment, though findings may not generalise to other platforms.

05.
arXiv (quant-ph) 2026-06-11

Energy-Modulated Time-Asymmetric Spontaneous Collapse: Forward-Backward Dynamics from Stochastic Ito Reversal and Bright Solitons

arXiv:2606.06452v3 Announce Type: replace Abstract: We present a rigorous theoretical framework for symmetry breaking and quantum irreversibility arising from stochastic Ito field reversal within a cubic-quintic nonlinear Schrodinger equation (CQ-NLSE) formalism. Starting from three physically motivated considerations, forward and backward nonlinear stochastic differential equations are derived via the Ito calculus. Kinematic time-reversal is shown to be fundamentally incompatible with the Ito stochastic structure, yielding the universal asymmetry-coupling parameter of 2/3. An energy-driven collapse operator proportional to the product of noise strength, local probability density, and excitation energy squared is introduced, amplifying the collapse in high-density, high-excitation regions. Exactly bright soliton solutions are obtained for a quasi-one-dimensional BEC of attractive Li-7 atoms, with forward and backward amplitude ratio of 1.870. Heat map analysis of the parameter planes reveals that the forward collapse operator grows monotonically in time while the backward counterpart decays, achieving a ratio approximately 1030, sharply distinguishing this framework from conventional symmetric collapse models.

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

Physics-informed generative AI for semiconductor manufacturing: Enforcing hard physical constraints in generative models by construction

arXiv:2606.11247v1 Announce Type: cross Abstract: Generative models are increasingly used to propose designs, data, and control actions for physical systems, yet many such systems are governed by hard physical constraints rather than by perceptual plausibility. Semiconductor manufacturing provides a demanding test case: generated masks, layouts, synthetic defect data, and process recipes must obey lithography, transport, reaction, and device-physics constraints, because physically invalid samples are not merely low quality but unusable. This Perspective argues that semiconductor manufacturing exposes a broader computational-science challenge, namely that generative AI for constrained physical domains must be physics-informed by construction, not corrected only through post-hoc filtering. We survey the emerging architectural toolkit, including physics-informed diffusion, PDE-constrained variational models, neural-operator priors, and conservation-law-respecting generative networks, and show how it connects to differentiable lithography, TCAD, process simulation, and autonomous experimentation. We identify four integration patterns between generative models and physics-based simulators, and we propose a research agenda centered on physics-fidelity benchmarks, differentiable simulator infrastructure, and multimodal foundation models for physical design and manufacturing. The central claim is analytical rather than rhetorical: where physical validity is the binding criterion of success, architectures that enforce it by construction should be expected to outperform those that filter for it after the fact, and the fab is the setting where this distinction is sharpest.

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

MOCHI: Motion Enhancement of Collaborative Human-object Interactions

Collaborative human-object interaction shows dynamic and complex movements that require mutual anticipation and continuous adjustment between participants and the shared object. Modeling such collaborative multi-human object interaction (MHOI) scenarios requires high-quality data acquisition as a foundational step; however, this is challenging due to the inherent complexity of MHOI where human-human and human-object interactions occur simultaneously. Such complexity leads to noisy MHOI captures characterized by several artifacts: contact misalignment between hands and objects, motion jitter and temporal inconsistencies in the captured sequences, and missing or incomplete finger-level articulation details. To address these challenges, we present MOCHI (MOtion Enhancement of Collaborative Human-object Interactions), a two-stage framework for enhancing noisy MHOI data. Our approach first generates physically plausible hand grasps through optimization from noisy body input, producing grasps that are both physically plausible and semantically consistent with the body pose, where these optimized grasps are extended into complete hand-object interaction sequences. Consequently, the full-body motion for all participants are refined through a diffusion-based noise optimization framework that uses single-person motion priors. During the optimization process, we introduce optimization objectives to encode human-object and human-human interaction information within these single-person priors. Experimental results demonstrate the effectiveness of our pipeline across diverse MHOI data, either acquired by existing capture methods or synthesized by generative models. We further show robustness of our system across varying numbers of participants and types of interactions, and demonstrate various applications including keyframe-based MHOI creation and data augmentation through varying object geometries.

08.
arXiv (CS.AI) 2026-06-17

Combating Data Laundering in LLM Training

arXiv:2604.01904v3 Announce Type: replace-cross Abstract: Post-hoc unauthorized-training data detection for large language models (LLMs) typically assumes a query-with-originals regime: rights holders query a target LLM with raw proprietary data and assess whether the model assigns them stronger memorization-based detection signals, e.g., higher confidence or lower loss, than held-out non-training reference texts. We show that this regime becomes brittle under data laundering, where the target LLM is trained on semantics-preserving but stylistically or structurally transformed surrogates of proprietary data to obfuscate provenance. Since training-time exposure occurs in the laundered form, memorization signals may no longer appear on the originals, collapsing the candidate-reference signal separation that standard detectors rely on. We counter this threat by studying laundering-aware detection with raw proprietary data, a held-out reference corpus, and query access to the target LLM, while the laundering transformation is undisclosed. Since exact recovery of the laundered corpus is infeasible, we infer a detection-useful synthesis process via an auxiliary LLM that maps originals into training-like queries. To make this search tractable, we introduce Synthesis Data Reversion (SDR), which constrains the unbounded space of natural-language transformations through a goal-details abstraction: a high-level transformation goal, e.g., "lyrical rewriting", and fine-grained details, e.g., "with vivid imagery". SDR identifies the most likely goal and iteratively refines details so synthesized queries elicit stronger target-model detection signals. Evaluated on the MIMIR benchmark against diverse laundering practices and target LLM families (Pythia, Llama2, and Falcon), SDR consistently restores detection signals, offering a practical auditing layer against data laundering.

09.
arXiv (CS.LG) 2026-06-15

Lyapunov-Based Sample Complexity Analysis for Weakly-Coupled MDPs

arXiv:2606.14095v1 Announce Type: new Abstract: We study the sample complexity of learning in average-reward weakly-coupled Markov decision processes (WCMDPs) and Restless Bandits (RBs) under a generative model. Naive reduction to a tabular MDP leads to high complexity bounds as the state-action space is exponentially large in the number of arms $N$. By exploiting the weakly coupled structure, we show that near-optimal policies can be learned with sample and computational complexities that are polynomial in $N$. Specifically, we analyze the plug-in approach, which applies an efficient planning algorithm to an empirical model estimated from data. For fully heterogeneous WCMDPs, we establish the first finite-sample PAC guarantee with polynomial complexity and an $O(1/\sqrt{N})$ optimality gap. For homogeneous RBs, we further prove that a smaller optimality gap is achievable under mild structural assumptions. A primary technical contribution of our work is a novel Lyapunov-based analysis framework. Unlike classical approaches that rely on the difficult-to-control bias function, our framework uses an explicitly constructed Lyapunov function along with a drift transfer technique between the true and empirical models. A key step of independent interest in our framework is a fine-grained perturbation analysis for the underlying linear programming (LP) relaxation, which provides a general tool for analyzing LP-based policies and weakly-coupled systems.

10.
arXiv (quant-ph) 2026-06-17

An energy-based uncertainty principle and low-energy state preparation

作者:

arXiv:2603.15495v2 Announce Type: replace Abstract: Preparing low-energy states of many-body Hamiltonians is a central challenge in quantum computing, quantum complexity, and condensed matter physics. Existing approaches often get trapped in suboptimal states such as high-energy eigenstates or, more generally, low-variance states that resist further energy reduction. In this work, we explore a different perspective: instead of optimizing with respect to a single Hamiltonian, we leverage the fact that many systems admit families of Hamiltonians that share similar low-energy subspaces but differ at higher energies. We show that this redundancy can be turned into an algorithmic resource by establishing an energy-based uncertainty principle, which implies that these Hamiltonians cannot simultaneously admit low-variance states at higher energies. This suggests a simple strategy of alternating energy-lowering steps across such Hamiltonians, which we investigate numerically on several models. We also introduce a sparse variant where the uncertainty principle yields quadratically larger variance at higher energies, leading to more pronounced energy change. Overall, this work suggests a range of open questions at the interface of random matrix theory, local Hamiltonians and low-energy state preparation, aimed at understanding when such approaches are practical and how they can be analyzed rigorously.

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

Comparing Human Gaze and Vision-Language Model Attention in Safety-Relevant Environments

Human visual attention plays an important role in how people perceive and respond to environments containing potential risks. This study investigates whether large vision-language models can identify the same regions of a scene that attract human attention in safety-relevant environments. Eye-tracking data were collected from ten participants viewing 33 scene images representing environments with varying levels of potential risk using Pupil Invisible wearable glasses. Gaze coordinates were mapped onto stimulus images to generate population-averaged human gaze heatmaps. In parallel, GPT-4o was prompted through the OpenAI Vision Application Programming Interface (API) to generate spatial predictions of visual attention, which were converted into saliency maps for comparison with human gaze patterns. Spatial alignment between human gaze heatmaps and model-generated saliency maps was evaluated using four complementary metrics: Pearson correlation (r = 0.515 +- 0.117), Normalised Scanpath Saliency (NSS = 0.988 +- 0.323), Kullback-Leibler divergence (KL = 1.766 +- 0.844), and Area Under the Receiver Operating Characteristic Curve using the Judd formulation (AUC-Judd = 0.806 +- 0.076). A cross-model comparison with Gemini Pro, Gemini Flash, and Claude showed that all models exceeded the AUC-Judd chance baseline of 0.5 and achieved positive NSS scores. Gemini Pro demonstrated the strongest spatial localisation according to three of the four metrics, whereas GPT-4o produced the closest distributional match to human attention as measured by KL divergence. These findings suggest that large vision-language models can identify regions that broadly correspond to where humans direct visual attention in safety-relevant scenes without requiring eye-tracking training data. The results highlight the potential of vision-language models as a scalable tool for approximating human attentional patterns.

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

Accurate and Resource-Efficient Federated Continual Learning

arXiv:2606.11480v1 Announce Type: new Abstract: Federated continual learning (FCL) must learn from distributed task streams under limited resources, such as communication, computation, memory, and label availability. Existing FCL methods often rely on repeated local optimization, replay, and full supervision. Analytic alternatives avoid iterative training and replay, but using high-dimensional random features to improve accuracy requires a second-order feature statistic, the Gram matrix, which has a quadratic communication cost in the random feature size $M$. We propose FedRAN, a resource-aware analytic FCL framework that replaces gradient-based updates with compact random feature statistics. Each client transmits a truncated-SVD summary of its Gram matrix, reducing the dominant second-order upload from quadratic to linear in $M$ for fixed rank. The server performs a two-level QR-SVD subspace merge, spatially across clients and temporally across tasks, and solves a ridge classifier in closed form. FedRAN further supports label scarcity through prototype-based pseudo-labeling. Across CIFAR-100, ImageNet-R, and VTAB datasets, FedRAN improves average accuracy by up to 4.8 percentage points over the strongest baseline, uses 30.6-121.8$\times$ less per-client communication than optimization-based FCL, and is 190.3$\times$ faster on average than gradient-based baselines; with only 20% labels, pseudo-labeling improves average accuracy by up to 6.61 points. These results show that FedRAN enables accurate and resource-efficient FCL under communication, computation, and label constraints. The source code is available at https://github.com/JebacyrilArockiaraj/Fed-RAN-SSL.

13.
medRxiv (Medicine) 2026-06-16

AI-assisted continuous-time modelling of metastatic breast cancer reveals subtype-specific spatiotemporal organ interactions

Metastatic breast cancer is one of the leading causes of premature mortality among women worldwide. A major barrier to optimal care is the marked heterogeneity in both the temporal dynamics of metastatic spread and the organ-specific spatial distribution of metastases. Existing analyses do not adequately capture this complexity, as they either neglect temporal dependencies or assume independence between metastasic sites. As a result, it remains unclear how established metastases influence subsequent organ-specific dissemination. We address this question using patient-level longitudinal trajectories from a large multicentre real-world metastatic breast cancer registry, combined with an AI-assisted disease-progression modelling framework based on continuous-time Markov chains that represent combinations of metastatic sites and the non-uniform and practice-driven timing of radiologic response assessments, as encountered in routine clinical care. We present a stochastic model determined by progression rates, which are parameterised to capture baseline organ-specific transition risks, patient-level covariates, and pairwise inter-organ interaction effects. High-dimensional treatment information is incorporated using an large language model based encoding. We find that metastatic spread follows non-independent, subtype-specific spatiotemporal patterns, with subtype-specific inter-organ interaction patterns that shape progression. Visceral metastases, particularly lung and liver metastasis, are associated with an increased hazard of subsequent brain metastasis, with effects varying across hormone receptor-positive, HER2-positive, and triple-negative subtypes. Together, these findings define a clinically relevant spatiotemporal architecture of metastatic progression in breast cancer. This framework enables refined mechanism-informed risk stratification and provides a data-driven rationale for targeted and risk-adapted – rather than symptom-triggered – surveillance strategies.

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

Modeling Sarcastic Speech: Semantic and Prosodic Cues in a Speech Synthesis Framework

Sarcasm is a pragmatic phenomenon in which speakers convey meanings that diverge from literal content, relying on an interaction between semantics and prosodic expression. However, how these cues jointly contribute to the recognition of sarcasm remains poorly understood. We propose a computational framework that models sarcasm as the integration of semantic interpretation and prosodic realization. Semantic cues are derived from an LLaMA 3 model fine-tuned to capture discourse-level markers of sarcastic intent, while prosodic cues are extracted through semantically aligned utterances drawn from a database of sarcastic speech, providing prosodic exemplars of sarcastic delivery. Using a speech synthesis testbed, perceptual evaluations show that semantic and prosodic cues enhance perceived sarcasm, with the combined system achieving the best downstream F1 while maintaining high subjective sarcasm ratings. These findings highlight the complementary roles of semantics and prosody in pragmatic interpretation and illustrate how modeling can shed light on the mechanisms underlying sarcastic communication.

15.
arXiv (CS.CV) 2026-06-16

Ellipse Meets Bit-Planes: A Novel Approach to RNFL based Glaucoma Detection Using Advanced Image Processing and Deep Learning

This work proposes an integrated pipeline for automatic glaucoma detection method from easily available colour fundas images based on an adaptive algorithm for ellipse-based polar transformation, to enhance the analysis of the Retinal Nerve Fiber Layer (RNFL) as the primary biomarker for observing glaucomatous changes, regardless of optic disc and macula position. Utilizing this transformation, we introduce two distinct frameworks tailored to different operational needs. The first framework, a deep learning-inspired feature fusion approach, achieves a 99.3% detection rate, ideal for settings where high precision is essential, despite higher computational demands. The second framework employs a novel image-processing algorithm based on bit-plane slicing, offering 92.31% accuracy and optimized for environments requiring rapid inference with minimal resource consumption. Both frameworks provide scalable and cost-effective solutions for early glaucoma detection. This study highlights the potential of RNFL-based diagnostic tools in addressing the global challenge of glaucoma, particularly in underserved regions.

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

Harnessing cortical geometry, wiring, and function as inductive biases for recurrent neural networks

arXiv:2606.14975v1 Announce Type: cross Abstract: How the wiring and functional organization of cortex shape recurrent computation remains a central question in both neuroscience and machine learning. Here, we leverage data released through the Machine Intelligence from Cortical Networks (MICrONS) program–a functional connectomics resource spanning multiple areas of mouse visual cortex, in which dense calcium imaging is co-registered with high-resolution electron microscopy reconstruction from the same animal–to build biologically grounded recurrent neural networks. Using neuronal spatial coordinates, anatomical connectivity, and function-derived relationships from nearly 12,000 coregistered excitatory neurons, we initialize recurrent weights and impose communication-aware spatial constraints during learning. Across three cognitive decision-making tasks, networks constrained by cortical structure and function consistently outperform baseline and partially constrained models. Functional weight initialization provides the largest gain, while real spatial embedding yields robust additional improvements across conditions. These biologically grounded networks also develop low-entropy, modular, and small-world organization, and retain strong performance even when recurrence is restricted to positive weights. Together, our results show that the machinery of cortex–its geometry, wiring, and functional structure–can be harnessed as a powerful inductive basis for building recurrent networks that learn more effectively while converging toward key organizational principles of biological computation.

17.
arXiv (CS.CV) 2026-06-11

Cross-Modal Benchmarking for Robotic Perception in Natural Environments

Natural environments present a complex challenge to robotics perception systems. Current models, particularly vision foundation models, are largely trained on structured, urban environments leading to weaknesses in their perception for field robotics tasks. We showcase the limitations of current models using our recently released WildCross benchmark, a new cross-modal benchmark for place recognition and metric depth estimation in large-scale natural environments. WildCross comprises over 476K sequential RGB frames with semi-dense depth and surface normal annotations, each aligned with accurate 6DoF pose and synchronized dense lidar submaps. In this work, we provide an expanded analysis of the benchmark results from the recent WildCross benchmark, with particular emphasis on expanded metric depth estimation experiments. Access to the code repository and dataset for this work can be found at https://csiro-robotics.github.io/WildCross.

18.
arXiv (quant-ph) 2026-06-17

A matching decomposition algorithm for simulating quantum walk Hamiltonians

arXiv:2601.11418v3 Announce Type: replace Abstract: In this work, we present a new algorithm for generating quantum circuits that efficiently implement continuous time quantum walks on arbitrary simple sparse graphs. The algorithm, called matching decomposition, works by decomposing a continuous-time quantum walk Hamiltonian into a collection of exactly implementable Hamiltonians corresponding to matchings in the underlying graph followed by a novel graph compression algorithm that merges edges in the graph. We develop a greedy matching heuristic and a compression-aware matching heuristic, both of which can be used in the quantum circuit algorithm. Lastly, we convert the walks to a circuit and Trotterize over these components. The dynamics of the walker on each edge in the matching can be implemented in the circuit model as sequences of CX and CRx gates. We do not use Pauli decomposition when implementing walks along each matching. Furthermore, we compare greedy (compression-aware) matching decomposition to a standard Pauli-based simulation pipeline and find that greedy (compression-aware) matching decomposition consistently yields substantial resource reductions, requiring up to 43$\%$ (70\%) fewer controlled gates and up to 54$\%$ (75\%) shallower circuits than Pauli decomposition across multiple graph families. Finally, we also present examples and theoretical results for when matching decomposition can exactly simulate a continuous-time quantum walk on a graph.

19.
arXiv (CS.CL) 2026-06-16

When Cognitive Graphs Meet LLMs: BDEI Cognitive Pathways for Panic Emotional Arousal Prediction

Predicting individual panic emotional arousal timing before manifestation is essential for proactive emergency intervention. Existing methods incorporate cognitive elements but none explicitly model the emotional arousal process, making them ill-suited for emotional arousal timing prediction. We argue that grounding prediction in appraisal emotion theory is necessary because it explicitly models this process, but three problems must be solved. (1) Appraisal theory posits that emotion arises from simultaneous evaluation across multiple threat dimensions, yet no prior work fuses these inputs into risk perception. (2) Existing cognitive models lack an Emotion node, decoupling threat appraisal from emotional arousal and forcing emotions to be inferred indirectly from behaviors. (3) Given their generalizable cognitive reasoning, current approaches adopt LLMs as the primary decision-maker, yet overlook the fragility and hallucination-proneness of their outputs. To address these issues, we introduce PanicCognitivePath (PCP), a framework that addresses all three. A Psychological Safety Distance (PSD) model, grounded in psychological distance theory, maps four-domain signals into a unified risk metric as the entry condition for subsequent cognitive reasoning. An explicit Emotion node grounded in appraisal emotion theory is introduced into BDI, forming a Belief-Desire-Emotion-Intention (BDEI) pathway. Agents whose risk metric exceeds the PSD threshold enter this pathway, coupling threat appraisal directly to emotional arousal. The BDEI pathway governs all state transitions while the LLM is confined to parameter estimation for the Belief-to-Desire transition, confining hallucinations to a single step and preventing error propagation. Experiments on Hurricane Sandy show PCP improves arousal timing accuracy by 10.68% over baselines, reduces peak count error to 7.07%.

20.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

21.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

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

Treatment Response Optimized Clinical Decision Support AI System via Digital Twin Simulation

arXiv:2606.17405v1 Announce Type: new Abstract: Clinical decision support AI systems (CDSASs) must adapt to evolving patient conditions in real-time while adhering to strict safety constraints. We present an online adaptive framework that integrates Treatment Effect (TE) estimation to quantify clinical benefits, a patient Digital Twin (DT) to simulate treatment trajectories, and Reinforcement Learning (RL) for sequential decision-making. The AI system is initially trained on historical medical records and operates in a continuous learning loop. To ensure safety, a rule-based module monitors vital signs and blocks contraindicated treatments. Cases with strong internal model disagreement are flagged for clinician review, simulated in our experiments via a pre-trained outcome model. We validate our framework using both a synthetic clinical simulator and a real-world ovarian cancer dataset from The Cancer Genome Atlas (TCGA). In both simulated and clinical settings, our method demonstrated superior effectiveness and stability in recommending treatments compared to standard computational baselines. Furthermore, the AI system maintains low latency and requires expert consultation for only a minority of cases in our experimental validation, demonstrating its potential as a safe, clinician-supervised tool for personalized medicine that continuously improves through practical use.

23.
arXiv (quant-ph) 2026-06-15

Extending Covariant Fluctuation Theorems into Quantum Regime through Quasiprobability Approach

arXiv:2606.14519v1 Announce Type: cross Abstract: The covariant formulation of stochastic thermodynamics requires treating the stochastic work as a 4-vector, posing significant challenges for quantum systems due to the non-commutativity. We introduce a new quasiprobability distribution for the work 4-vector, which combines the Wigner and Margenau-Hill quasiprobabilities. This extends the covariant fluctuation theorems from classical to quantum regime. We illustrate our findings with a scalar field driven by classical particles with a generalized version of trace formula. Our work establishes a quasiprobability approach to studying relativistic quantum thermodynamics in a covariant way.

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

CRIS: Cross-Plane Self-Supervised Isotropic Restoration for Anisotropic Volumetric Imaging Across Modalities

Anisotropic volumetric acquisitions are common in clinical MRI and volume electron microscopy (vEM), where sparse through-plane sampling creates thick slices or sections that degrade orthogonal reformats and downstream analysis. We present CRIS, a cross-plane self-supervised framework for isotropic restoration without paired isotropic ground truth. CRIS casts 3D restoration as 2D stripe completion on orthogonal reformats of an isotropic grid: high-resolution in-plane slices are synthetically degraded and periodically masked for training, while at inference blank slices define the isotropic grid, two orthogonal reformats are restored, and predictions are fused by multi-view averaging. We evaluate CRIS on two MRI cohorts and two microscopy benchmarks up to 8x anisotropy. On brain MRI, CRIS achieves 32.921 +/- 0.436 dB PSNR and 0.9631 +/- 0.0027 SSIM, outperforming interpolation, SMORE4, SIMPLE, SA-INR, and ATME, and gives the best segmentation consistency (Dice 0.940 +/- 0.004, ASSD 0.245 +/- 0.014 mm, HD99 1.275 +/- 0.061 mm). On reference-free abdominal MRI, CRIS reduces FID/KID to 48.714/0.023. On vEM, CRIS outperforms interpolation, NIIV, and vEMINR, reaching 29.133 dB/0.834 3D PSNR/SSIM at 4x, 27.123 dB/0.734 on EPFL at 8x, and 21.915 dB/0.699 on noisy hemibrain data. In a robustness experiment, one variable-gap CRIS model evaluated across gap factors 3–7 and coronal, axial, and sagittal degradations maintained higher PSNR/SSIM than interpolation (36.36–31.14 dB and 0.977–0.932 vs. 33.07–27.85 dB and 0.951–0.853). These results support CRIS as a modality-flexible route to isotropic restoration without paired isotropic targets or configuration-specific retraining. Code is available at https://github.com/adi-hatav/CRIS.

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PLOS Computational Biology 2026-06-15

Fung-AI: An AI/ML-driven pipeline for antifungal peptide discovery

by Daniel S. Berman, Libby M. Lewis, Tom D. Curtis, Olivia N. Tiburzi, Daniel F. Q. Smith, Arturo Casadevall, Laura J. Dunphy Emerging fungal pathogens represent a concerning threat to both global health and food security. In this study, we aimed to address our rising vulnerability to fungal pathogens through the development of the Fung-AI pipeline: an AI/ML-driven approach for antifungal discovery. A generative adversarial network (GAN) was trained to generate novel candidate antifungal peptide sequences. Next, in silico antifungal and hemolytic classifiers were built to further prioritize AI-generated peptides for experimental validation. From a pool of ~10,000 candidates, thirteen peptides were selected for testing over two-stages of experimentation. Five peptides were found to display mild antifungal activity against the wheat pathogen, Fusarium graminearum, with minimal inhibitory concentrations (MICs) ranging from 250 µg/mL to 500 µg/mL. Four of the five peptides also showed activity against the human pathogen, Candida albicans (MIC: 500 µg/mL). Two of our AI-generated antifungal peptides additionally demonstrated low cytotoxicity in HepG2 human liver carcinoma cells (LC50 > 704.2 µg/mL) indicating that they may be useful as scaffolds for future optimization for therapeutic applications. None of our peptides were found to considerably inhibit the emerging pathogen C. auris, suggesting the need for pathogen-specific down-selection of candidate peptides. Overall, we present a proof-of-principle, generative-AI-based approach for the rapid design of de novo antifungal peptides.