Understanding how chemical perturbations propagate through biological systems is essential for robust molecular property prediction. While most existing methods focus on chemical structures alone, recent advances highlight the crucial role of cellular responses such as morphology and gene expression in shaping drug effects. However, current cell-aware approaches face two key limitations: (1) modality incompleteness in external biological data, and (2) insufficient modeling of hierarchical dependencies across molecular, cellular, and genomic levels. We propose CHMR (Cell-aware Hierarchical Multi-modal Representations), a robust framework that jointly models local-global dependencies between molecules and cellular responses and captures latent biological hierarchies via a novel tree-structured vector quantization module. Evaluated on nine public benchmarks spanning 728 tasks, CHMR outperforms state-of-the-art baselines, yielding average improvements of 3.6% on classification and 17.2% on regression tasks. These results demonstrate the advantage of hierarchy-aware, multimodal learning for reliable and biologically grounded molecular representations, offering a generalizable framework for integrative biomedical modeling. The code is in https://github.com/limengran98/CHMR.

Emerging from NASA's spacecraft simulations in the 1960s, digital twin technology has advanced through industrial adoption to spark a healthcare transformation. A digital twin is a dynamic, data-driven virtual counterpart of a physical system, continuously updated through real-time data streams and capable of bidirectional interaction. In medicine, digital twin integrates imaging, biosensors, and computational models to generate patient-specific simulations that support diagnosis, treatment planning, and drug development. Representative applications include cardiac digital twin for predicting arrhythmia treatment outcomes, oncology digital twin for tracking tumor progression and optimizing radiotherapy, and pharmacological digital twin for accelerating drug discovery. Despite rapid progress, major challenges, including interoperability, data privacy, and model fidelity, continue to limit widespread clinical integration. Emerging solutions such as explainable AI, federated learning, and harmonized regulatory frameworks offer promising pathways forward. Looking ahead, advances in multi-organ digital twin, genomics integration, and ethical governance will be essential to ensure that digital twin shifts healthcare from reactive treatment to predictive, preventive, and truly personalized medicine.

Randomized controlled trials (RCTs) have been the cornerstone of clinical evidence; however, their cost, duration, and restrictive eligibility criteria limit power and external validity. Studies using real-world data (RWD), historically considered less reliable for establishing causality, are now recognized to be important for generating real-world evidence (RWE). In parallel, artificial intelligence and machine learning (AI/ML) are being increasingly used throughout the drug development process, providing scalability and flexibility but also presenting challenges in interpretability and rigor that traditional statistics do not face. This Perspective argues that the future of evidence generation will not depend on RCTs versus RWD, or statistics versus AI/ML, but on their principled integration. To this end, a causal roadmap is needed to clarify inferential goals, make assumptions explicit, and ensure transparency about tradeoffs. We highlight key objectives of integrative evidence synthesis, including transporting RCT results to broader populations, embedding AI-assisted analyses within RCTs, designing hybrid controlled trials, and extending short-term RCTs with long-term RWD. We also outline future directions in privacy-preserving analytics, uncertainty quantification, and small-sample methods. By uniting statistical rigor with AI/ML innovation, integrative approaches can produce robust, transparent, and policy-relevant evidence, making them a key component of modern regulatory science.

Drug shortages pose critical risks to patient care and healthcare systems worldwide, yet the effectiveness of regulatory interventions remains poorly understood due to information asymmetries in pharmaceutical supply chains. We propose \textbf{ShortageSim}, addresses this challenge by providing the first simulation framework that evaluates the impact of regulatory interventions on competition dynamics under information asymmetry. Using Large Language Model (LLM)-based agents, the framework models the strategic decisions of drug manufacturers and institutional buyers, in response to shortage alerts given by the regulatory agency. Unlike traditional game theory models that assume perfect rationality and complete information, ShortageSim simulates heterogeneous interpretations on regulatory announcements and the resulting decisions. Experiments on self-processed dataset of historical shortage events show that ShortageSim reduces the resolution lag for production disruption cases by up to 84\%, achieving closer alignment to real-world trajectories than the zero-shot baseline. Our framework confirms the effect of regulatory alert in addressing shortages and introduces a new method for understanding competition in multi-stage environments under uncertainty. We open-source ShortageSim and a dataset of 2,925 FDA shortage events, providing a novel framework for future research on policy design and testing in supply chains under information asymmetry.

The disconnect between AI-generated molecules with desirable properties and their synthetic feasibility remains a critical bottleneck in computational discovery of drugs and materials. While generative AI has accelerated the proposal of candidate molecules, many of these structures prove challenging or impossible to synthesize using established chemical reactions. Here, we introduce SynTwins, a novel retrosynthesis-guided molecule design framework that finds synthetically accessible molecular analogs by emulating expert chemists' strategies in three steps: retrosynthesis, searching similar building blocks, and virtual synthesis. Using a search algorithm instead of a stochastic data-driven generator, SynTwins outperforms state-of-the-art machine learning models at exploring synthetically accessible analogs while maintaining high structural similarity to original target molecules. Furthermore, when integrated into existing molecular property-optimization frameworks, our hybrid approach produces synthetically feasible analogs with minimal loss in property scores. Our comprehensive benchmarking across diverse molecular datasets demonstrates that SynTwins effectively bridges the gap between computational design and experimental synthesis, providing a practical solution for accelerating the discovery of synthesizable molecules with desired properties for a wide range of applications.

The Austin-based startup will test its high-bandwidth device to help restore speech in people with extremely limited movement. Brain implant developer Paradromics has received approval from the US Food and Drug Administration to test its device in an early-stage human trial, the company announced Thursday. The Austin-based company is aiming to give a digital voice to people who have lost the ability to speak due to severe motor impairment. The trial will assess the long-term safety of the Paradromics device, as well as its ability to enable synthesized speech and text communication. Paradromics is one of several companies--which include Neuralink, Synchron, Precision Neuroscience, and Cognixion --working on technology to control computers and other devices using brain waves.

Scientific databases aggregate vast amounts of quantitative data alongside descriptive text. In biochemistry, molecule screening assays evaluate candidate molecules' functional responses against disease targets. Unstructured text that describes the biological mechanisms through which these targets operate, experimental screening protocols, and other attributes of assays offer rich information for drug discovery campaigns but has been untapped because of that unstructured format. We present Assay2Mol, a large language model-based workflow that can capitalize on the vast existing biochemical screening assays for early-stage drug discovery. Assay2Mol retrieves existing assay records involving targets similar to the new target and generates candidate molecules using in-context learning with the retrieved assay screening data. Assay2Mol outperforms recent machine learning approaches that generate candidate ligand molecules for target protein structures, while also promoting more synthesizable molecule generation.

Chimeric antigen receptor T-cell (CAR-T) therapy represents a paradigm shift in cancer treatment, yet development timelines of 8-12 years and clinical attrition rates exceeding 40-60% highlight critical inefficiencies in target selection, safety assessment, and molecular optimization. We present Bio AI Agent, a multi-agent artificial intelligence system powered by large language models that enables autonomous CAR-T development through collaborative specialized agents. The system comprises six autonomous agents: Target Selection Agent for multi-parametric antigen prioritization across >10,000 cancer-associated targets, Toxicity Prediction Agent for comprehensive safety profiling integrating tissue expression atlases and pharmacovigilance databases, Molecular Design Agent for rational CAR engineering, Patent Intelligence Agent for freedom-to-operate analysis, Clinical Translation Agent for regulatory compliance, and Decision Orchestration Agent for multi-agent coordination. Retrospective validation demonstrated autonomous identification of high-risk targets including FcRH5 (hepatotoxicity) and CD229 (off-tumor toxicity), patent infringement risks for CD38+SLAMF7 combinations, and generation of comprehensive development roadmaps. By enabling parallel processing, specialized reasoning, and autonomous decision-making superior to monolithic AI systems, Bio AI Agent addresses critical gaps in precision oncology development and has potential to accelerate translation of next-generation immunotherapies from discovery to clinic.

Drug-target interaction (DTI) prediction is of great significance for drug discovery and drug repurposing. With the accumulation of a large volume of valuable data, data-driven methods have been increasingly harnessed to predict DTIs, reducing costs across various dimensions. Therefore, this paper proposes a $\textbf{L}$arge $\textbf{L}$anguage $\textbf{M}$odel and $\textbf{M}$ulti-$\textbf{M}$odel data co-powered $\textbf{D}$rug $\textbf{T}$arget $\textbf{I}$nteraction prediction framework, named LLM$^3$-DTI. LLM$^3$-DTI constructs multi-modal data embedding to enhance DTI prediction performance. In this framework, the text semantic embeddings of drugs and targets are encoded by a domain-specific LLM. To effectively align and fuse multi-modal embedding. We propose the dual cross-attention mechanism and the TSFusion module. Finally, these multi-modal data are utilized for the DTI task through an output network. The experimental results indicate that LLM$^3$-DTI can proficiently identify validated DTIs, surpassing the performance of the models employed for comparison across diverse scenarios. Consequently, LLM$^3$-DTI is adept at fulfilling the task of DTI prediction with excellence. The data and code are available at https://github.com/chaser-gua/LLM3DTI.

The National Comprehensive Cancer Network (NCCN) provides evidence-based guidelines for cancer treatment. Translating complex patient presentations into guideline-compliant treatment recommendations is time-intensive, requires specialized expertise, and is prone to error. Advances in large language model (LLM) capabilities promise to reduce the time required to generate treatment recommendations and improve accuracy. We present an LLM agent-based approach to automatically generate guideline-concordant treatment trajectories for patients with non-small cell lung cancer (NSCLC). Our contributions are threefold. First, we construct a novel longitudinal dataset of 121 cases of NSCLC patients that includes clinical encounters, diagnostic results, and medical histories, each expertly annotated with the corresponding NCCN guideline trajectories by board-certified oncologists. Second, we demonstrate that existing LLMs possess domain-specific knowledge that enables high-quality proxy benchmark generation for both model development and evaluation, achieving strong correlation (Spearman coefficient r=0.88, RMSE = 0.08) with expert-annotated benchmarks. Third, we develop a hybrid approach combining expensive human annotations with model consistency information to create both the agent framework that predicts the relevant guidelines for a patient, as well as a meta-classifier that verifies prediction accuracy with calibrated confidence scores for treatment recommendations (AUROC=0.800), a critical capability for communicating the accuracy of outputs, custom-tailoring tradeoffs in performance, and supporting regulatory compliance. This work establishes a framework for clinically viable LLM-based guideline adherence systems that balance accuracy, interpretability, and regulatory requirements while reducing annotation costs, providing a scalable pathway toward automated clinical decision support.