R-GenIMA: Integrating Neuroimaging and Genetics with Interpretable Multimodal AI for Alzheimer's Disease Progression

Early detection of Alzheimer's disease (AD) requires models capable of integrating macro-scale neuroanatomical alterations with micro-scale genetic susceptibility, yet existing multimodal approaches struggle to align these heterogeneous signals. We introduce R-GenIMA, an interpretable multimodal large language model that couples a novel ROI-wise vision transformer with genetic prompting to jointly model structural MRI and single nucleotide polymorphisms (SNPs) variations. By representing each anatomically parcellated brain region as a visual token and encoding SNP profiles as structured text, the framework enables cross-modal attention that links regional atrophy patterns to underlying genetic factors. Applied to the ADNI cohort, R-GenIMA achieves state-of-the-art performance in four-way classification across normal cognition (NC), subjective memory concerns (SMC), mild cognitive impairment (MCI), and AD. Beyond predictive accuracy, the model yields biologically meaningful explanations by identifying stage-specific brain regions and gene signatures, as well as coherent ROI-Gene association patterns across the disease continuum. Attention-based attribution revealed genes consistently enriched for established GWAS-supported AD risk loci, including APOE, BIN1, CLU, and RBFOX1. Stage-resolved neuroanatomical signatures identified shared vulnerability hubs across disease stages alongside stage-specific patterns: striatal involvement in subjective decline, frontotemporal engagement during prodromal impairment, and consolidated multimodal network disruption in AD. These results demonstrate that interpretable multimodal AI can synthesize imaging and genetics to reveal mechanistic insights, providing a foundation for clinically deployable tools that enable earlier risk stratification and inform precision therapeutic strategies in Alzheimer's disease.

Why Text Prevails: Vision May Undermine Multimodal Medical Decision Making

With the rapid progress of large language models (LLMs), advanced multimodal large language models (MLLMs) have demonstrated impressive zero-shot capabilities on vision-language tasks. In the biomedical domain, however, even state-of-the-art MLLMs struggle with basic Medical Decision Making (MDM) tasks. We investigate this limitation using two challenging datasets: (1) three-stage Alzheimer's disease (AD) classification (normal, mild cognitive impairment, dementia), where category differences are visually subtle, and (2) MIMIC-CXR chest radiograph classification with 14 non-mutually exclusive conditions. Our empirical study shows that text-only reasoning consistently outperforms vision-only or vision-text settings, with multimodal inputs often performing worse than text alone. To mitigate this, we explore three strategies: (1) in-context learning with reason-annotated exemplars, (2) vision captioning followed by text-only inference, and (3) few-shot fine-tuning of the vision tower with classification supervision. These findings reveal that current MLLMs lack grounded visual understanding and point to promising directions for improving multimodal decision making in healthcare.

Inferred global dense residue transition graphs from primary structure sequences enable protein interaction prediction via directed graph convolutional neural networks

Introduction Accurate prediction of protein-protein interactions (PPIs) is crucial for understanding cellular functions and advancing drug development. Existing in-silico methods use direct sequence embeddings from Protein Language Models (PLMs). Others use Graph Neural Networks (GNNs) for 3D protein structures. This study explores less computationally intensive alternatives. We introduce a novel framework for downstream PPI prediction through link prediction. Methods We introduce a two-stage graph representation learning framework, ProtGram-DirectGCN. First, we developed ProtGram. This approach models a protein's primary structure as a hierarchy of globally inferred n-gram graphs. In these graphs, residue transition probabilities define edge weights. Each edge connects a pair of residues in a directed graph. The probabilities are aggregated from a large corpus of sequences. Second, we propose DirectGCN, a custom directed graph convolutional neural network. This model features a unique convolutional layer. It processes information through separate path-specific transformations: incoming, outgoing, and undirected. A shared transformation is also applied. These paths are combined via a learnable gating mechanism. We apply DirectGCN to ProtGram graphs to learn residue-level embeddings. These embeddings are pooled via attention to generate protein-level embeddings for prediction. Results We first established the efficacy of DirectGCN on standard node classification benchmarks. Its performance matches established methods on general datasets. The model excels at complex, directed graphs with dense, heterophilic structures. When applied to PPI prediction, the full ProtGram-DirectGCN framework delivers robust predictive power. This strong performance holds even with limited training data.

DRE: An Effective Dual-Refined Method for Integrating Small and Large Language Models in Open-Domain Dialogue Evaluation

Large Language Models (LLMs) excel at many tasks but struggle with ambiguous scenarios where multiple valid responses exist, often yielding unreliable results. Conversely, Small Language Models (SLMs) demonstrate robustness in such scenarios but are susceptible to misleading or adversarial inputs. We observed that LLMs handle negative examples effectively, while SLMs excel with positive examples. To leverage their complementary strengths, we introduce SLIDE (Small and Large Integrated for Dialogue Evaluation), a method integrating SLMs and LLMs via adaptive weighting. Building on SLIDE, we further propose a Dual-Refinement Evaluation (DRE) method to enhance SLM-LLM integration: (1) SLM-generated insights guide the LLM to produce initial evaluations; (2) SLM-derived adjustments refine the LLM's scores for improved accuracy. Experiments demonstrate that DRE outperforms existing methods, showing stronger alignment with human judgment across diverse benchmarks. This work illustrates how combining small and large models can yield more reliable evaluation tools, particularly for open-ended tasks such as dialogue evaluation.

Topo-VM-UNetV2: Encoding Topology into Vision Mamba UNet for Polyp Segmentation

Convolutional neural network (CNN) and Transformer-based architectures are two dominant deep learning models for polyp segmentation. However, CNNs have limited capability for modeling long-range dependencies, while Transformers incur quadratic computational complexity. Recently, State Space Models such as Mamba have been recognized as a promising approach for polyp segmentation because they not only model long-range interactions effectively but also maintain linear computational complexity. However, Mamba-based architectures still struggle to capture topological features (e.g., connected components, loops, voids), leading to inaccurate boundary delineation and polyp segmentation. To address these limitations, we propose a new approach called Topo-VM-UNetV2, which encodes topological features into the Mamba-based state-of-the-art polyp segmentation model, VM-UNetV2. Our method consists of two stages: Stage 1: VM-UNetV2 is used to generate probability maps (PMs) for the training and test images, which are then used to compute topology attention maps. Specifically, we first compute persistence diagrams of the PMs, then we generate persistence score maps by assigning persistence values (i.e., the difference between death and birth times) of each topological feature to its birth location, finally we transform persistence scores into attention weights using the sigmoid function. Stage 2: These topology attention maps are integrated into the semantics and detail infusion (SDI) module of VM-UNetV2 to form a topology-guided semantics and detail infusion (Topo-SDI) module for enhancing the segmentation results. Extensive experiments on five public polyp segmentation datasets demonstrate the effectiveness of our proposed method. The code will be made publicly available.

Adapting a Segmentation Foundation Model for Medical Image Classification

Recent advancements in foundation models, such as the Segment Anything Model (SAM), have shown strong performance in various vision tasks, particularly image segmentation, due to their impressive zero-shot segmentation capabilities. However, effectively adapting such models for medical image classification is still a less explored topic. In this paper, we introduce a new framework to adapt SAM for medical image classification. First, we utilize the SAM image encoder as a feature extractor to capture segmentation-based features that convey important spatial and contextual details of the image, while freezing its weights to avoid unnecessary overhead during training. Next, we propose a novel Spatially Localized Channel Attention (SLCA) mechanism to compute spatially localized attention weights for the feature maps. The features extracted from SAM's image encoder are processed through SLCA to compute attention weights, which are then integrated into deep learning classification models to enhance their focus on spatially relevant or meaningful regions of the image, thus improving classification performance. Experimental results on three public medical image classification datasets demonstrate the effectiveness and data-efficiency of our approach.

Zeus: Zero-shot LLM Instruction for Union Segmentation in Multimodal Medical Imaging

Medical image segmentation has achieved remarkable success through the continuous advancement of UNet-based and Transformer-based foundation backbones. However, clinical diagnosis in the real world often requires integrating domain knowledge, especially textual information. Conducting multimodal learning involves visual and text modalities shown as a solution, but collecting paired vision-language datasets is expensive and time-consuming, posing significant challenges. Inspired by the superior ability in numerous cross-modal tasks for Large Language Models (LLMs), we proposed a novel Vision-LLM union framework to address the issues. Specifically, we introduce frozen LLMs for zero-shot instruction generation based on corresponding medical images, imitating the radiology scanning and report generation process. {To better approximate real-world diagnostic processes}, we generate more precise text instruction from multimodal radiology images (e.g., T1-w or T2-w MRI and CT). Based on the impressive ability of semantic understanding and rich knowledge of LLMs. This process emphasizes extracting special features from different modalities and reunion the information for the ultimate clinical diagnostic. With generated text instruction, our proposed union segmentation framework can handle multimodal segmentation without prior collected vision-language datasets. To evaluate our proposed method, we conduct comprehensive experiments with influential baselines, the statistical results and the visualized case study demonstrate the superiority of our novel method.}

SouLLMate: An Application Enhancing Diverse Mental Health Support with Adaptive LLMs, Prompt Engineering, and RAG Techniques

Mental health issues significantly impact individuals' daily lives, yet many do not receive the help they need even with available online resources. This study aims to provide diverse, accessible, stigma-free, personalized, and real-time mental health support through cutting-edge AI technologies. It makes the following contributions: (1) Conducting an extensive survey of recent mental health support methods to identify prevalent functionalities and unmet needs. (2) Introducing SouLLMate, an adaptive LLM-driven system that integrates LLM technologies, Chain, Retrieval-Augmented Generation (RAG), prompt engineering, and domain knowledge. This system offers advanced features such as Risk Detection and Proactive Guidance Dialogue, and utilizes RAG for personalized profile uploads and Conversational Information Extraction. (3) Developing novel evaluation approaches for preliminary assessments and risk detection via professionally annotated interview data and real-life suicide tendency data. (4) Proposing the Key Indicator Summarization (KIS), Proactive Questioning Strategy (PQS), and Stacked Multi-Model Reasoning (SMMR) methods to enhance model performance and usability through context-sensitive response adjustments, semantic coherence evaluations, and enhanced accuracy of long-context reasoning in language models. This study contributes to advancing mental health support technologies, potentially improving the accessibility and effectiveness of mental health care globally.

Interpretable Spatio-Temporal Embedding for Brain Structural-Effective Network with Ordinary Differential Equation

The MRI-derived brain network serves as a pivotal instrument in elucidating both the structural and functional aspects of the brain, encompassing the ramifications of diseases and developmental processes. However, prevailing methodologies, often focusing on synchronous BOLD signals from functional MRI (fMRI), may not capture directional influences among brain regions and rarely tackle temporal functional dynamics. In this study, we first construct the brain-effective network via the dynamic causal model. Subsequently, we introduce an interpretable graph learning framework termed Spatio-Temporal Embedding ODE (STE-ODE). This framework incorporates specifically designed directed node embedding layers, aiming at capturing the dynamic interplay between structural and effective networks via an ordinary differential equation (ODE) model, which characterizes spatial-temporal brain dynamics. Our framework is validated on several clinical phenotype prediction tasks using two independent publicly available datasets (HCP and OASIS). The experimental results clearly demonstrate the advantages of our model compared to several state-of-the-art methods.

Constrained Multiview Representation for Self-supervised Contrastive Learning

Representation learning constitutes a pivotal cornerstone in contemporary deep learning paradigms, offering a conduit to elucidate distinctive features within the latent space and interpret the deep models. Nevertheless, the inherent complexity of anatomical patterns and the random nature of lesion distribution in medical image segmentation pose significant challenges to the disentanglement of representations and the understanding of salient features. Methods guided by the maximization of mutual information, particularly within the framework of contrastive learning, have demonstrated remarkable success and superiority in decoupling densely intertwined representations. However, the effectiveness of contrastive learning highly depends on the quality of the positive and negative sample pairs, i.e. the unselected average mutual information among multi-views would obstruct the learning strategy so the selection of the views is vital. In this work, we introduce a novel approach predicated on representation distance-based mutual information (MI) maximization for measuring the significance of different views, aiming at conducting more efficient contrastive learning and representation disentanglement. Additionally, we introduce an MI re-ranking strategy for representation selection, benefiting both the continuous MI estimating and representation significance distance measuring. Specifically, we harness multi-view representations extracted from the frequency domain, re-evaluating their significance based on mutual information across varying frequencies, thereby facilitating a multifaceted contrastive learning approach to bolster semantic comprehension. The statistical results under the five metrics demonstrate that our proposed framework proficiently constrains the MI maximization-driven representation selection and steers the multi-view contrastive learning process.