Dialogue to Question Generation for Evidence-based Medical Guideline Agent Development

Evidence-based medicine (EBM) is central to high-quality care, but remains difficult to implement in fast-paced primary care settings. Physicians face short consultations, increasing patient loads, and lengthy guideline documents that are impractical to consult in real time. To address this gap, we investigate the feasibility of using large language models (LLMs) as ambient assistants that surface targeted, evidence-based questions during physician-patient encounters. Our study focuses on question generation rather than question answering, with the aim of scaffolding physician reasoning and integrating guideline-based practice into brief consultations. We implemented two prompting strategies, a zero-shot baseline and a multi-stage reasoning variant, using Gemini 2.5 as the backbone model. We evaluated on a benchmark of 80 de-identified transcripts from real clinical encounters, with six experienced physicians contributing over 90 hours of structured review. Results indicate that while general-purpose LLMs are not yet fully reliable, they can produce clinically meaningful and guideline-relevant questions, suggesting significant potential to reduce cognitive burden and make EBM more actionable at the point of care.

LLM-MINE: Large Language Model based Alzheimer's Disease and Related Dementias Phenotypes Mining from Clinical Notes

Accurate extraction of Alzheimer's Disease and Related Dementias (ADRD) phenotypes from electronic health records (EHR) is critical for early-stage detection and disease staging. However, this information is usually embedded in unstructured textual data rather than tabular data, making it difficult to be extracted accurately. We therefore propose LLM-MINE, a Large Language Model-based phenotype mining framework for automatic extraction of ADRD phenotypes from clinical notes. Using two expert-defined phenotype lists, we evaluate the extracted phenotypes by examining their statistical significance across cohorts and their utility for unsupervised disease staging. Chi-square analyses confirm statistically significant phenotype differences across cohorts, with memory impairment being the strongest discriminator. Few-shot prompting with the combined phenotype lists achieves the best clustering performance (ARI=0.290, NMI=0.232), substantially outperforming biomedical NER and dictionary-based baselines. Our results demonstrate that LLM-based phenotype extraction is a promising tool for discovering clinically meaningful ADRD signals from unstructured notes.

ECG-MoE: Mixture-of-Expert Electrocardiogram Foundation Model

Electrocardiography (ECG) analysis is crucial for cardiac diagnosis, yet existing foundation models often fail to capture the periodicity and diverse features required for varied clinical tasks. We propose ECG-MoE, a hybrid architecture that integrates multi-model temporal features with a cardiac period-aware expert module. Our approach uses a dual-path Mixture-of-Experts to separately model beat-level morphology and rhythm, combined with a hierarchical fusion network using LoRA for efficient inference. Evaluated on five public clinical tasks, ECG-MoE achieves state-of-the-art performance with 40% faster inference than multi-task baselines.

MIRAGE: Knowledge Graph-Guided Cross-Cohort MRI Synthesis for Alzheimer's Disease Prediction

Reliable Alzheimer's disease (AD) diagnosis increasingly relies on multimodal assessments combining structural Magnetic Resonance Imaging (MRI) and Electronic Health Records (EHR). However, deploying these models is bottlenecked by modality missingness, as MRI scans are expensive and frequently unavailable in many patient cohorts. Furthermore, synthesizing de novo 3D anatomical scans from sparse, high-dimensional tabular records is technically challenging and poses severe clinical risks. To address this, we introduce MIRAGE, a novel framework that reframes the missing-MRI problem as an anatomy-guided cross-modal latent distillation task. First, MIRAGE leverages a Biomedical Knowledge Graph (KG) and Graph Attention Networks to map heterogeneous EHR variables into a unified embedding space that can be propagated from cohorts with real MRIs to cohorts without them. To bridge the semantic gap and enforce physical spatial awareness, we employ a frozen pre-trained 3D U-Net decoder strictly as an auxiliary regularization engine. Supported by a novel cohort-aggregated skip feature compensation strategy, this decoder acts as a rigorous structural penalty, forcing 1D latent representations to encode biologically plausible, macro-level pathological semantics. By exclusively utilizing this distilled "diagnostic-surrogate" representation during inference, MIRAGE completely bypasses computationally expensive 3D voxel reconstruction. Experiments demonstrate that our framework successfully bridges the missing-modality gap, improving the AD classification rate by 13% compared to unimodal baselines in cohorts without real MRIs.

Position: General Alignment Has Hit a Ceiling; Edge Alignment Must Be Taken Seriously

Large language models are being deployed in complex socio-technical systems, which exposes limits in current alignment practice. We take the position that the dominant paradigm of General Alignment, which compresses diverse human values into a single scalar reward, reaches a structural ceiling in settings with conflicting values, plural stakeholders, and irreducible uncertainty. These failures follow from the mathematics and incentives of scalarization and lead to \textbf{structural} value flattening, \textbf{normative} representation loss, and \textbf{cognitive} uncertainty blindness. We introduce Edge Alignment as a distinct approach in which systems preserve multi dimensional value structure, support plural and democratic representation, and incorporate epistemic mechanisms for interaction and clarification. To make this approach practical, we propose seven interdependent pillars organized into three phases. We identify key challenges in data collection, training objectives, and evaluation, outlining complementary technical and governance directions. Taken together, these measures reframe alignment as a lifecycle problem of dynamic normative governance rather than as a single instance optimization task.

Traceable Latent Variable Discovery Based on Multi-Agent Collaboration

Revealing the underlying causal mechanisms in the real world is crucial for scientific and technological progress. Despite notable advances in recent decades, the lack of high-quality data and the reliance of traditional causal discovery algorithms (TCDA) on the assumption of no latent confounders, as well as their tendency to overlook the precise semantics of latent variables, have long been major obstacles to the broader application of causal discovery. To address this issue, we propose a novel causal modeling framework, TLVD, which integrates the metadata-based reasoning capabilities of large language models (LLMs) with the data-driven modeling capabilities of TCDA for inferring latent variables and their semantics. Specifically, we first employ a data-driven approach to construct a causal graph that incorporates latent variables. Then, we employ multi-LLM collaboration for latent variable inference, modeling this process as a game with incomplete information and seeking its Bayesian Nash Equilibrium (BNE) to infer the possible specific latent variables. Finally, to validate the inferred latent variables across multiple real-world web-based data sources, we leverage LLMs for evidence exploration to ensure traceability. We comprehensively evaluate TLVD on three de-identified real patient datasets provided by a hospital and two benchmark datasets. Extensive experimental results confirm the effectiveness and reliability of TLVD, with average improvements of 32.67% in Acc, 62.21% in CAcc, and 26.72% in ECit across the five datasets.

Alternating Reinforcement Learning for Rubric-Based Reward Modeling in Non-Verifiable LLM Post-Training

Standard reward models typically predict scalar scores that fail to capture the multifaceted nature of response quality in non-verifiable domains, such as creative writing or open-ended instruction following. To address this limitation, we propose Rubric-ARM, a framework that jointly optimizes a rubric generator and a judge using reinforcement learning from preference feedback. Unlike existing methods that rely on static rubrics or disjoint training pipelines, our approach treats rubric generation as a latent action learned to maximize judgment accuracy. We introduce an alternating optimization strategy to mitigate the non-stationarity of simultaneous updates, providing theoretical analysis that demonstrates how this schedule reduces gradient variance during training. Extensive experiments show that Rubric-ARM achieves state-of-the-art performance among baselines on multiple benchmarks and significantly improves downstream policy alignment in both offline and online reinforcement learning settings.

Transferable Graph Condensation from the Causal Perspective

The increasing scale of graph datasets has significantly improved the performance of graph representation learning methods, but it has also introduced substantial training challenges. Graph dataset condensation techniques have emerged to compress large datasets into smaller yet information-rich datasets, while maintaining similar test performance. However, these methods strictly require downstream applications to match the original dataset and task, which often fails in cross-task and cross-domain scenarios. To address these challenges, we propose a novel causal-invariance-based and transferable graph dataset condensation method, named \textbf{TGCC}, providing effective and transferable condensed datasets. Specifically, to preserve domain-invariant knowledge, we first extract domain causal-invariant features from the spatial domain of the graph using causal interventions. Then, to fully capture the structural and feature information of the original graph, we perform enhanced condensation operations. Finally, through spectral-domain enhanced contrastive learning, we inject the causal-invariant features into the condensed graph, ensuring that the compressed graph retains the causal information of the original graph. Experimental results on five public datasets and our novel \textbf{FinReport} dataset demonstrate that TGCC achieves up to a 13.41\% improvement in cross-task and cross-domain complex scenarios compared to existing methods, and achieves state-of-the-art performance on 5 out of 6 datasets in the single dataset and task scenario.

Imaging-anchored Multiomics in Cardiovascular Disease: Integrating Cardiac Imaging, Bulk, Single-cell, and Spatial Transcriptomics

Cardiovascular disease arises from interactions between inherited risk, molecular programmes, and tissue-scale remodelling that are observed clinically through imaging. Health systems now routinely generate large volumes of cardiac MRI, CT and echocardiography together with bulk, single-cell and spatial transcriptomics, yet these data are still analysed in separate pipelines. This review examines joint representations that link cardiac imaging phenotypes to transcriptomic and spatially resolved molecular states. An imaging-anchored perspective is adopted in which echocardiography, cardiac MRI and CT define a spatial phenotype of the heart, and bulk, single-cell and spatial transcriptomics provide cell-type- and location-specific molecular context. The biological and technical characteristics of these modalities are first summarised, and representation-learning strategies for each are outlined. Multimodal fusion approaches are reviewed, with emphasis on handling missing data, limited sample size, and batch effects. Finally, integrative pipelines for radiogenomics, spatial molecular alignment, and image-based prediction of gene expression are discussed, together with common failure modes, practical considerations, and open challenges. Spatial multiomics of human myocardium and atherosclerotic plaque, single-cell and spatial foundation models, and multimodal medical foundation models are collectively bringing imaging-anchored multiomics closer to large-scale cardiovascular translation.

EpiQAL: Benchmarking Large Language Models in Epidemiological Question Answering for Enhanced Alignment and Reasoning

Reliable epidemiological reasoning requires synthesizing study evidence to infer disease burden, transmission dynamics, and intervention effects at the population level. Existing medical question answering benchmarks primarily emphasize clinical knowledge or patient-level reasoning, yet few systematically evaluate evidence-grounded epidemiological inference. We present EpiQAL, the first diagnostic benchmark for epidemiological question answering across diverse diseases, comprising three subsets built from open-access literature. The subsets respectively evaluate text-grounded factual recall, multi-step inference linking document evidence with epidemiological principles, and conclusion reconstruction with the Discussion section withheld. Construction combines expert-designed taxonomy guidance, multi-model verification, and retrieval-based difficulty control. Experiments on ten open models reveal that current LLMs show limited performance on epidemiological reasoning, with multi-step inference posing the greatest challenge. Model rankings shift across subsets, and scale alone does not predict success. Chain-of-Thought prompting benefits multi-step inference but yields mixed results elsewhere. EpiQAL provides fine-grained diagnostic signals for evidence grounding, inferential reasoning, and conclusion reconstruction.