Longitudinal radiology report generation (LRRG) requires identifying both current findings and their changes relative to a prior study. Existing methods jointly model diagnosis, attribute estimation, temporal comparison, and language generation within implicit representations, which can cause task interference, obscure the evidence underlying each decision, and limit error traceability. They also model progression states as independent labels, ignoring their ordered structure and thus treating missed changes and direction reversals equally. We present STRIVE, Multi-Agent Structured Temporal Reasoning with Integrated Verification for LRRG, which decomposes clinical reasoning into specialized Diagnosis, Attribute, and Temporal Change Agents that produce explicit intermediate evidence. In particular, the Temporal Change Agent is further post-trained using Progression-Aware GRPO, a verifiable, shaped reward that assigns partial credit to direction-preserving errors while scoring direction reversals lowest. STRIVE performs verification at two stages: a deterministic Consistency Gate reconciles the agent outputs before report generation, and a Validation Agent checks whether the generated report is supported by the aggregated clinical evidence. On Longitudinal-MIMIC, STRIVE attains the best clinical efficacy among recent methods and more than doubles Longitudinal Change Concordance (LCC), a measure of temporal agreement with the reference report, over the strongest baseline.
Ali Motahharynia, Mohammadreza Ghaffarzadeh-Esfahani, Mahsa Sheikholeslami +4q-bio.QM cs.AI cs.LG
Current computational approaches for drug design typically focus on generating molecules conditioned on specific targets or general molecular properties, often neglecting the influence of disease context on target behavior and therapeutic outcomes. To address this gap, we introduce DrugGen-2, a novel generative model that designs small molecules conditioned on both disease ontology and target protein sequences. DrugGen-2 was developed by fine-tuning a pre-trained GPT-2 model on a curated dataset of approved drugs linked to their diseases and targets, using a two-step strategy of supervised fine-tuning followed by reinforcement learning via group relative policy optimization (GRPO). This process was guided by reward functions optimizing for chemical validity, novelty, diversity, and high predicted binding affinity. When evaluated on five protein targets relevant to diabetic nephropathy, DrugGen-2 significantly outperformed baseline models (DrugGPT and DrugGen). It demonstrated a superior capacity to generate unique molecules, exhibited greater structural similarity to approved drugs, and achieved improved predicted binding affinities across all targets. Molecular docking analyses further supported these findings, identifying candidate ligands with strong binding potential, including compounds with predicted affinities (-9.917, -9.485, and -9.367) exceeding those of reference drugs such as enalapril for angiotensin-converting enzyme (-8.283). By integrating disease-specific context into molecular generation, DrugGen-2 advances AI-assisted drug discovery, offering a powerful tool for de novo design and drug repurposing that accounts for the complex interplay between diseases and molecular targets.