Histopathological subtyping relies on the recognition of characteristic histological patterns. These patterns may be expressed by individual tissue structures or by the spatial distribution and co-occurrence of multiple structures, and they often span irregularly shaped tissue regions, termed semantic units in this work. However, conventional patch-based representations may fragment such units and fail to explicitly preserve their internal spatial organization, while efficiently modeling relationships among numerous spatially separated units remains challenging. To address these limitations, we propose the Semantic-Aware Subgraph State Space Model (SASG-SSM), a flexible and efficient framework for whole slide image (WSI) classification. Semantic-Aware Subgraphs (SASGs) first approximate irregularly shaped semantic units by adaptively grouping spatially connected patches guided by class-agnostic visual-semantic priors. By representing patches as graph nodes with adjacency edges, SASGs preserve their internal spatial organization rather than treating them as an unordered set. A Subgraph State Space Module (SG-SSM) subsequently combines a graph neural network encoder for intra-subgraph topology encoding with a Mamba-based state space encoder for efficient contextualization across large numbers of subgraphs. This module integrates local structural information within semantic units with global contextual information arising from their distribution and co-occurrence across the WSI, while efficiently modeling a large number of spatially distributed regions. Extensive experiments across four WSI subtyping datasets demonstrate consistent advantages over representative state-of-the-art methods. Further evaluations under small-cohort and few-shot settings demonstrate robustness and data efficiency under limited training data. Code will be released at https://github.com/HLSvois/SASG-SSM.
M. Tanveer, Ayush Singh Rana, Sanskriti Jain +5cs.LG
Electroencephalography (EEG) is a promising, non-invasive, and cost-effective modality for Alzheimer's disease (AD) detection, but deep learning methods are limited by small and imbalanced clinical datasets. Generative augmentation offers a solution, yet existing approaches rely on inefficient class-specific models or fail to capture complex spatial and temporal brain dynamics. To address this, we propose GraM-Diff, a unified classifier-guided Graph-Mamba diffusion framework for EEG synthesis. It embeds Graph Convolutional Networks within a diffusion U-Net to model inter-electrode connectivity and Bidirectional Mamba state-space blocks for linear-complexity long-range temporal modeling. Latent-space classifier guidance lets a single model generate both healthy and pathological EEG within a shared representation, avoiding fragmented per-cohort pipelines. Across four EEG-based AD benchmarks, synthetic augmentation improves classification, yields superior Context-FID and correlation scores over strong generative baselines, and enhances robustness in data-scarce settings.
Nadejda Drenska, Matthew Lemoine, Gowri Priya Sunkara +3cs.LG
Accurate estimation of body-composition outcomes, including body fat percentage (BFP), bone mineral density (BMD), and appendicular lean mass (ALM), is important for evaluating metabolic, skeletal, and muscular health. Direct assessment using dual-energy X-ray absorptiometry (DXA), however, requires specialized equipment and involves ionizing radiation. We propose a target-aware, state-adaptive $p$-Dirichlet energy-flow graph neural regression ($p$SADE-GNR) framework for estimating these outcomes from non-invasive anthropometric measurements. A neural encoder maps participant representations to hidden states that are propagated over an outcome-specific participant-similarity graph by a state-adaptive forward-Euler discretization of the graph $p$-Dirichlet energy flow. Graph distances weight each original or latent coordinate by its normalized absolute training-fold correlation with the outcome. Using clinical data from the Pennington Biomedical Research Center and five-fold cross-validation, the correlation-weighted model using the original standardized measurements achieved the lowest root mean squared error in all nine primary outcome-cohort combinations and outperformed previously reported support vector regression or least-squares support vector regression reference values in eight of nine comparisons. Autoencoder, variational-autoencoder, and Gaussian-mixture variational-autoencoder representations generally did not improve primary-outcome prediction or reduce computational cost. In an exploratory age-prediction analysis including ALM, BMD, and BFP as predictors, the correlation-weighted GMVAE model achieved the lowest mean error in all three cohorts. These results support target-aware, state-adaptive $p$-Dirichlet graph neural regression for non-invasive body-composition estimation.
Alexis Ivan Escamilla-Lopez, Gilberto Ochoa-Ruiz, Salvador Hinojosa +1cs.CV
The interpretation of endoscopic imagery in ulcerative colitis is complex and subjective, with variability in human assessment and subtle mucosal inflammation. Although deep learning has advanced automated analysis, most vision-language models rely on global visual embeddings that overlook the localized and relational nature of pathological evidence, limiting clinical reliability and interpretability. We introduce LUX (Lesion-aware Unified eXplainable captioning), a graph-conditioned vision-language architecture for explainable endoscopic image captioning. LUX constructs a lesion-centric scene graph from Grad-CAM and CBAM activation maps, representing pathological regions as nodes and encoding their spatial and clinical relationships. These graph embeddings are integrated into the cross-attention layers of a T5 decoder, enabling generated words to attend to specific lesion nodes rather than only to global image features. This provides direct alignment between linguistic content and pathological evidence, supporting token-level interpretability and relational reasoning. LUX outperforms strong baseline and state-of-the-art medical captioning models across BLEU, METEOR, ROUGE-L, and CIDEr, with particularly strong gains in CIDEr. It also reduces hallucinated clinical findings and improves lesion-level grounding through stronger correspondence between generated tokens and localized pathological regions.
\textbf{Background and Objective}: Reliable atrial fibrillation (AF) detection from electrocardiogram (ECG) signals remains challenging in real-world clinical settings due to variable lead configurations, cross-dataset domain shifts, and pervasive physiological and technical artifacts. So we develop a robust and generalizable deep learning model for accurate AF detection.\\ \textbf{Methods}: We propose the Dual-Codebook Graph Collaborative Network (DCGCNet), a novel end-to-end vector-quantized variational autoencoder that jointly performs AF classification and ECG reconstruction. DCGCNet introduces two key components: (1) a Local-Global Contrastive Module for learning noise-invariant representations, and (2) an Adaptive Codebook Vector Quantizer that dynamically refines codebook prototypes to better align with input data distributions, thereby preventing codebook collapse and enhancing generalization.\\ \textbf{Results}: DCGCNet achieves state-of-the-art performance in standard intra-dataset 12-lead evaluation and demonstrates exceptional cross-dataset generalization across seven diverse settings, consistently attaining AUC > 0.98 in all cases. Furthermore, it maintains high diagnostic accuracy under realistic noisy conditions, including baseline wander, powerline interference, and EMG artifacts.\\ \textbf{Conclusions}: DCGCNet establishes a new benchmark for robust, generalizable, and noise-resilient AF detection, showing strong potential for deployment in real-world clinical environments.
Cognitive distortion detection is a key task in computational mental health, yet existing approaches often overlook the psychological structure of distorted thoughts. We propose MTI-GNN (Multi-Perspective Triad Interaction Graph Neural Network), which models Beck's cognitive triad---negative views of the self, world, and future---as complementary perspectives for classification. An LLM decomposes each utterance into the three perspectives, from which perspective-specific similarity graphs are constructed and encoded by a Multi-Perspective GNN. A Triad Interaction module models cross-perspective dependencies through sequential source-conditioned updates and feature-wise gating, while Prototype-Guided Perspective Fusion performs label-conditioned aggregation. Label-expanded supervision incorporates all available distortion annotations during training. We evaluate MTI-GNN on 9,764 samples from four Korean, English, and Chinese datasets spanning ten distortion categories. MTI-GNN significantly outperforms all supervised variants and exceeds eight prompted generative models under zero-shot and few-shot settings. Leave-one-perspective-out ablations show that all three perspectives contribute significantly, while human expert evaluation provides preliminary evidence of their alignment with the intended cognitive dimensions.
Dohyun Ku, Min Gu Kwak, Francisco J. Pasquel +1cs.LG
Metabolomics knowledge is distributed across heterogeneous resources and remains difficult to translate into predictive representations. We developed MetaboLLM, a metabolomics-specialized large language model adapted through continual pretraining, supervised fine-tuning, and structured retrieval, together with MetaboLLM-GIN, which converts generated biochemical descriptions into metabolite graphs for patient-level prediction using a graph isomorphism network. Across four backbone families, MetaboLLM outperformed corresponding base and medically adapted models on metabolomics knowledge, relational, and description tasks, and transferred to an external public benchmark. MetaboLLM-GIN achieved the highest AUC for stress hyperglycemia prediction after coronary artery bypass grafting (0.8616) and postmenopausal hormone-regimen classification (0.8123), outperforming conventional models, alternative graph constructions, and graphs generated from unadapted or non-retrieval LLM configurations. Model interpretation further produced biologically meaningful findings in both applications. These results show that domain-specialized language models can organize heterogeneous biochemical knowledge into predictive and interpretable metabolite graph representations.
Abdulkadir Külçe, Alihan Esen, Cağla Fikir +4cs.AI cs.CL
This paper presents ECHO (Enhanced Care \& Health Observer), a locally-deployable conversational health assistant for long-term chronic care management. ECHO integrates three complementary software modules developed under shared supervision as a unified system. The core module is an agentic chatbot built on a ReAct loop orchestrated via LangGraph, equipped with 17 clinical tools and a temporal knowledge graph for persistent cross-session memory; it achieves a 94.9\% tool-execution pass rate across a 59-scenario benchmark with GPT-5 Mini. A two-stage hybrid safety layer intercepts all incoming queries: a rule-based layer handles explicit crisis signals and jailbreak attempts in under 1ms, while a signed graph neural network (GNN) with APPNP-style propagation classifies boundary cases by clinical intent, achieving 88.8\% accuracy and 90.6\% unsafe recall on a 2,537-query annotated Turkish health dataset while outperforming zero-shot LLM baselines including Llama 3.3 70B. A multimodal speech assessment module combining Whisper acoustic encoding and BERT text encoding with cross-attention fusion estimates emotion, depression, and pain, reaching a mean macro F1 of 0.652. The full system is implemented as a web application that can run entirely on consumer hardware, with no patient data transmitted to external services, supporting compliance with GDPR and KVKK.
Hao Ding, Daniel Semchin, Paul M. Thompson +1cs.CV cs.LG
Predicting how a subcortical structure's shape will evolve from a few prior scans could support prognosis and clinical-trial enrichment. Existing longitudinal mesh predictors either extrapolate shape trajectories via high-dimensional embeddings or regress vertex deformations directly. We instead predict the surface's intrinsic geometry in continuous time: a single per-structure graph network predicts the future per-vertex first fundamental form (metric tensor) for an arbitrary causal multiple-visit history and an arbitrary prediction horizon, conditioned on a Fourier encoding of the lead time. The predicted metric is decoded into a surface by a differentiable As-Rigid-As-Possible solver, and the model is trained end-to-end on the rigid-aligned vertex error. Training through the reconstruction keeps the decoded prediction a valid surface and consistently improves it. On 14 subcortical structures from the ADNI dataset, the proposed mesh evolution model (MT-GNN) predicts best among the evaluated methods at every horizon ($-2.29\%$ mean vertex error vs. the temporal mean, $p{=}6.1{\times}10^{-5}$, beating it on 14/14 structures), ahead of geodesic shape regression (DCM, $-0.19\%$) and a mesh transformer (TransforMesh, $-0.45\%$; $p{=}1.2{\times}10^{-4}$), with the lead widening as the horizon grows.
Edoardo Coppola, Stefano Fiorini, Pietro Liò +2cs.LG
Point-of-care cardiac devices such as smartwatches and handheld ECG recorders typically capture 1--2 leads, yet existing ECG foundation models are architecturally constrained to fixed 12-lead inputs, degrading or failing under these reduced configurations. We introduce LAEF (Lead-Agnostic ECG Foundation), a 7M-parameter ECG foundation model that can natively process any lead subset without zero-padding or architectural modification. LAEF represents ECGs as variable-size spatiotemporal graphs with physiologically motivated intra- and inter-lead connectivity, processed by a Graph Attention Network that scales naturally with active lead count.Pre-trained on 9.2M 12-lead ECGs via masked node modelling with stochastic lead sampling, LAEF learns representations robust to lead configuration. Across 18 downstream datasets, LAEF is on par with specialized 12-lead baselines over 12$\times$ larger at full lead availability. Under direct point-of-care-oriented diagnostics (1--2 leads), it outperforms all zero-padded alternatives on 17 out of 18 datasets with with a single randomly sampled lead and on 14 out of 18 with 2 leads, with an average AUROC gain of +3.2 points. Representation analysis links this advantage to architectural lead-agnosticism, and a lead-importance study across 164 cardiovascular conditions shows population-level performance is stable across single standard input leads while still recovering established clinically lead-condition associations.
Spatially resolved omics studies increasingly combine transcriptomic and epigenomic assays, yet downstream analysis is often still performed using single-modality pipelines. We present LATTICE (Latent Alignment of Tissue-level and Transcriptomic Information for Cross-modal Embedding), a graph-based self-supervised framework that learns spot-level representations from harmonized multimodal features. LATTICE integrates five aligned modality blocks per Visium spot: Visium RNA, scMultiome RNA, scMultiome ATAC, spatial ATAC, and spatial CUT\&Tag. These modalities capture spatial transcriptomic measurements, single-cell inferred regulatory activity, and in situ chromatin and histone states within a unified lattice representation. LATTICE constructs a spatial neighborhood graph and trains a TransformerConv encoder using masked reconstruction, cross-modal alignment, and spatial smoothness objectives. On a private 11-sample melanoma cohort from an anonymized clinical collaborator comprising 54{,}912 total spots, LATTICE demonstrated stable optimization behavior, reproducible embeddings across analysis seeds, and complete multimodal integration across all samples. Adding scMultiome RNA to Visium RNA alone substantially improved concordance with Space Ranger clusters across 11 runs (adjusted Rand index [ARI] +0.157, normalized mutual information [NMI] +0.143, and spatial contiguity +0.174). Additional modalities further improved spatial contiguity and multimodal utility score (MUS), although they sometimes reduced agreement with RNA-derived reference labels, likely because the learned embeddings captured chromatin and regulatory structure beyond transcriptomic similarity alone. These results position LATTICE as a practical and empirically grounded framework for multimodal spatial omics integration, while also highlighting the need for stronger supervision and broader external benchmarking.
We present a physics-inspired classical digital twin of brain-computer- interface (BCI) data: a graph neural network constrained to a band-stratified, metriplectic port-Hamiltonian form, with parameters learned from scalp EEG recorded during rest and motor imagery. The port-Hamiltonian structure is a modelling choice - it buys passivity, a certified steady-state power balance, and a clean separation of storage, routing and dissipation - not a claim about what the brain is. The state pairs each channel's instantaneous phase with its angular frequency, and stored energy decomposes over the five canonical frequency bands. A phase-locking prior measured from the same recordings gates the learned connectome, and a metriplectic formulation places the twin at a non- equilibrium steady state sustained by a metabolic port. Fitted to $1{,}109{,}250$ phasor samples from the PhysioNet EEG Motor Movement/Imagery database under a leakage-free split, the twin reaches a held-out reconstruction error of $1.30\times10^{-4}$. Scored free-running against invariants it did not author, the verdict is mixed: it reproduces near-critical avalanche branching ($σ\approx1$) but not the aperiodic $1/f$ slope or the long-range temporal correlations of the recordings. Skew-symmetry and non-negative dissipation hold by construction rather than by penalty, making the twin a structure-preserving substrate on which closed-loop neuromodulation can be designed and tested.
Alzheimer's disease (AD) is a common neurodegenerative disorder, and early diagnosis is of great significance for delaying disease progression and enabling timely intervention. Mild cognitive impairment (MCI), which represents an intermediate clinical stage between cognitively normal aging and AD. Structural magnetic resonance imaging (sMRI) provides detailed characterization of anatomical structures and plays an important role in AD-related brain analysis. However, existing sMRI-based brain network methods typically rely on a single graph construction strategy, limiting their ability to jointly capture spatial relationships and morphological similarities between brain regions. To address these issues, this paper proposes an sMRI-based multi-view masked graph neural network model (MVMGNN) for AD diagnosis. A joint node-edge masking mechanism is proposed to simultaneously select radiomics feature dimensions and structural connections, reducing redundancy during graph learning. Furthermore, a patient-level cross-view gated fusion mechanism is proposed to integrate multi-view representations. Experimental results on the ADNI dataset demonstrate that MVMGNN outperforms several competing approaches in AD classification. Interpretability analysis further demonstrates that MVMGNN is able to identify key brain regions associated with AD, providing useful insights into discriminative patterns in sMRI-based brain networks.Our implementation is publicly available at https://github.com/chenzhao2023/MVMGNN_AD
Graph Neural Networks (GNNs) have been widely used to capture spatial functional connectivity patterns to improve electroencephalography (EEG)-based depression recognition performance. However, the functional connectivity of brain networks in patients with depression exhibits an inherent hierarchical structure, making it difficult to capture accurate connection patterns. To address these issues, this paper proposes a novel model named Sample-Adaptive Hyperbolic Graph Neural Network (SA-HGNN), which aims to accurately extract the authentic hierarchical structure of depression-affected brain networks. Specifically, the proposed model comprises three core modules. First, a Sample-Adaptive Graph Construction module dynamically constructs personalized brain network topologies to capture more complex spatial relationships within the brain network. Second, hyperbolic graph convolution is employed to overcome the representation bottlenecks of Euclidean space, leveraging hyperbolic geometry to precisely capture latent hierarchical relationships within the brain network. Finally, an Attention Pooling module adaptively filters out highly redundant noise channels in EEG signals, effectively mitigating the interference of inherent noise on the authentic hierarchical topology. Extensive experiments on public EEG datasets demonstrate the superior performance of our method across resting-state and task-related paradigms, validating its robustness to noise and efficacy in capturing abnormal functional connectivity patterns in brain networks of patients with depression.
Casey Meisenzahl, Jon Heiselman, Michael Holtz +3cs.CV cs.AI eess.IV
Accurate intraoperative liver registration is challenging due to substantial soft-tissue deformation yet sparse intraoperative measurements. Biomechanical models regularize this ill-posedness with prior knowledge but exhibit persistent prediction bias due to simplifying assumptions, while data-driven learning solutions struggle with data efficiency, generalization, and physical plausibility. We propose a hybrid registration framework that adapts a biomechanical prior using sparse intraoperative correspondences. Rather than learning a full deformation field, we learn a residual deformation function that corrects linear biomechanical predictions, modeled as a graph neural diffusion function with geometry-aware attention over the 3D liver mesh. To enable long-range information transfer of sparse observations, we take a novel perspective of sparse intraoperative measurements as \textit{context} samples where input-output pairs of the residual deformation function are fully observed, casting the problem into learning-to-learn this residual function from intraoperative context samples with feedforward meta-learners. Experiments on a deformable liver phantom dataset demonstrate improved registration accuracy and generalization compared to rigid, biomechanical, and data-driven baselines, particularly for out-of-distribution geometries and deformations.
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that affects millions of older adults, with prevalence expected to rise significantly in the coming years. Early diagnosis, particularly during the mild cognitive impairment (MCI) stage, is critical for timely intervention. Structural Magnetic Resonance Imaging (sMRI) has emerged as a key modality for detecting AD-related brain changes, but traditional graph-based approaches often struggle with modality and inter-site heterogeneity, limiting diagnostic performance. In this paper, we propose Graph Matching Network for Alzheimer's Disease Diagnosis (GMN4AD), designed to model interactions between heterogeneous brain graphs derived from neuroimaging data. Unlike conventional methods that treat each brain graph independently, GMN4AD leverages graph matching to capture cross-graph relationships, enhancing diagnostic precision. Furthermore, we introduce a test-time domain adaptation strategy that combines contrastive learning to mitigate domain shifts during inference. Extensive experiments on three public AD datasets demonstrate that GMN4AD achieves superior performance compared to state-of-the-art methods, offering a robust and generalizable solution for AD diagnosis.
Accurate prediction of protein-protein interaction sites (PPIS) is essential for understanding cellular processes, disease mechanisms, and therapeutic target discovery. Graph-based deep learning has advanced PPIS prediction by incorporating residue-level structural context. However, most graph-based models still rely on fixed propagation schemes that treat all residues similarly, despite the structural and functional heterogeneity of protein interfaces. Such propagation may limit the ability to adapt information diffusion to local geometric environments, making it difficult to distinguish true interaction sites from structurally similar non-interacting neighbors. We present SGAP-PPIS, a structure-guided adaptive propagation model for PPIS prediction. Rather than using a fixed propagation mechanism, SGAP-PPIS leverages multi-scale geometric states from an equivariant graph neural network to generate residue-wise propagation coefficients. This design allows each residue to adaptively balance local feature preservation and neighborhood diffusion according to its geometric microenvironment. Experimental results show that SGAP-PPIS achieves competitive performance among the state-of-the-art methods on Test\_60. Ablation studies show that geometry-conditioned adaptive propagation, scale-aligned geometric guidance, and multi-step propagation-state representation jointly drive these improvements.
Eliya Naomi Aharon, Meytal Grimland, Avi Segal +4cs.CL
Effective mental health counseling is a complex, theory-driven process requiring the simultaneous integration of psychological frameworks, real-time distress signals, and strategic intervention planning. This level of clinical reasoning is critical for safety and therapeutic effectiveness but is often missing in general-purpose Large Language Models (LLMs). We introduce SAGE (Strategy-Aware Graph-Enhanced), a novel framework designed to bridge the gap between structured clinical knowledge and generative AI. SAGE constructs a heterogeneous graph that unifies conversational dynamics with a psychologically grounded layer, explicitly anchoring interactions in a theory-driven lexicon. Our architecture first employs a Next Strategy Classifier to identify the optimal therapeutic intervention. Subsequently, a Graph-Aware Attention mechanism projects graph-derived structural signals into soft prompts, conditioning the LLM to generate responses that maintain clinical depth. Validated through both automated metrics and expert human evaluation, SAGE outperforms baselines in strategy prediction and recommended response quality. By providing actionable intervention recommendations, SAGE serves as a cutting-edge decision-support tool designed to augment human expertise in high-stakes crisis counseling.
Automatic depression detection from conversational interactions holds significant promise for scalable screening but remains hindered by severe data scarcity and a lack of clinical interpretability. Existing approaches typically rely on black-box deep learning architectures that struggle to model the subtle, temporal evolution of depressive symptoms or account for participant-specific heterogeneity. In this work, we propose PsyGAT (Psychological Graph Attention Network), a psychologically grounded framework that models conversational sessions as dynamic temporal graphs. We introduce Psychological Expression Units (PEUs) to explicitly encode utterance-level clinical evidence, structuring the session graph to capture transitions in psychological states rather than mere semantic dependencies. To address the critical class imbalance in depression datasets, we employ clinically approved persona-based data augmentation, enable robust model learning. Additionally, we integrate session-level personality context directly into the graph structure to disentangle trait-based behavior from acute depressive symptoms. PsyGAT achieves state-of-the-art performance, surpassing both strong graph-based baselines and closed-source LLMs like GPT-5, achieving 89.99 and 71.37 Macro F1 scores in DAIC-WoZ and E-DAIC, respectively. We further introduce Causal-PsyGAT, an interpretability module that identifies symptom triggers. Experiments show a 20% improvement in MRR for identifying causal indicators, effectively bridging the gap between depression monitoring and clinical explainability. The full augmented dataset is publicly available at https://doi.org/10.6084/m9.figshare.31801921.