Prognostic information is essential for decision-making in breast cancer management. Recently trials have predominantly focused on genomic prognostication tools, even though clinicopathological prognostication is less costly and more widely accessible. Machine learning (ML), transfer learning and ensemble integration offer opportunities to build robust prognostication frameworks. We evaluate this potential to improve survival prognostication in breast cancer by comparing de-novo ML, transfer learning from a pre-trained prognostic tool and ensemble integration. Data from the MA.27 trial was used for model training, with external validation on the TEAM trial and a SEER cohort. Transfer learning was applied by fine-tuning the pre-trained prognostic tool PREDICT v3, de-novo ML included Random Survival Forests and Extreme Gradient Boosting, and ensemble integration was realized through a weighted sum of model predictions. Transfer learning, de-novo RSF, and ensemble integration improved calibration in MA.27 over the pre-trained model (ICI reduced from 0.042 in PREDICT v3 to <=0.007) while discrimination remained comparable (AUC increased from 0.738 in PREDICT v3 to 0.744-0.799). Invalid PREDICT v3 predictions were observed in 23.8-25.8% of MA.27 individuals due to missing information. In contrast, ML models and ensemble integration could predict survival regardless of missing information. Across all models, patient age, nodal status, pathological grading and tumor size had the highest SHAP values, indicating their importance for survival prognostication. External validation in SEER, but not in TEAM, confirmed the benefits of transfer learning, RSF and ensemble integration. This study demonstrates that transfer learning, de-novo RSF, and ensemble integration can improve prognostication in situations where relevant information for PREDICT v3 is lacking or where a dataset shift is likely.

Current molecular generative models primarily focus on improving drug-target binding affinity and specificity, often neglecting the system-level phenotypic effects elicited by compounds. Transcriptional profiles, as molecule-level readouts of drug-induced phenotypic shifts, offer a powerful opportunity to guide molecular design in a phenotype-aware manner. We present PhenoMoler, a phenotype-guided molecular generation framework that integrates a chemistry large language model with expression profiles to enable biologically informed drug design. By conditioning the generation on drug-induced differential expression signatures, PhenoMoler explicitly links transcriptional responses to chemical structure. By selectively masking and reconstructing specific substructures-scaffolds, side chains, or linkers-PhenoMoler supports fine-grained, controllable molecular optimization. Extensive experiments demonstrate that PhenoMoler generates chemically valid, novel, and diverse molecules aligned with desired phenotypic profiles. Compared to FDA-approved drugs, the generated compounds exhibit comparable or enhanced drug-likeness (QED), optimized physicochemical properties, and superior binding affinity to key cancer targets. These findings highlight PhenoMoler's potential for phenotype-guided and structure-controllable molecular optimization.

Matched-pair experimental designs aim to detect treatment effects by pairing participants and comparing within-pair outcome differences. In many situations, the overall effect size across the entire population is small. Then, the focus naturally shifts to identifying and targeting high treatment-effect regions where the intervention is most effective. This paper proposes a matched-pair experimental design that sequentially and actively enrolls patients in high treatment-effect regions. Importantly, we frame the identification of the target region as a classification problem and propose an active learning framework tailored to matched-pair designs. Our design not only reduces the experimental cost of detecting treatment efficacy, but also ensures that the identified regions enclose the entire high-treatment-effect regions. Our theoretical analysis of the framework's label complexity and experiments in practical scenarios demonstrate the efficiency and advantages of the approach.

Predicting molecular properties is a critical component of drug discovery. Recent advances in deep learning--particularly Graph Neural Networks (GNNs)--have enabled end-to-end learning from molecular structures, reducing reliance on manual feature engineering. However, while GNNs and self-supervised learning approaches have advanced molecular property prediction (MPP), the integration of human prior knowledge remains indispensable, as evidenced by recent methods that leverage large language models (LLMs) for knowledge extraction. Despite their strengths, LLMs are constrained by knowledge gaps and hallucinations, particularly for less-studied molecular properties. In this work, we propose a novel framework that, for the first time, integrates knowledge extracted from LLMs with structural features derived from pre-trained molecular models to enhance MPP . Our approach prompts LLMs to generate both domain-relevant knowledge and executable code for molecular vectorization, producing knowledge-based features that are subsequently fused with structural representations. We employ three state-of-the-art LLMs--GPT -4o, GPT -4.1, and DeepSeek-R1--for knowledge extraction. Extensive experiments demonstrate that our integrated method outperforms existing approaches, confirming that the combination of LLM-derived knowledge and structural information provides a robust and effective solution for MPP .

The generation of high-quality candidate molecules remains a central challenge in AI-driven drug design. Current phenotype-based and target-based strategies each suffer limitations, either incurring high experimental costs or overlook system-level cellular responses. To bridge this gap, we propose ExMoIRL, a novel generative framework that synergistically integrates phenotypic and target-specific cues for de novo molecular generation. The phenotype-guided generator is first pretrained on expansive drug-induced transcriptional profiles and subsequently fine-tuned via multi-objective reinforcement learning (RL). Crucially, the reward function fuses docking affinity and drug-likeness scores, augmented with ranking loss, prior-likelihood regularization, and entropy maximization. The multi-objective RL steers the model toward chemotypes that are simultaneously potent, diverse, and aligned with the specified phenotypic effects. Extensive experiments demonstrate ExMoIRL's superior performance over state-of-the-art phenotype-based and target-based models across multiple well-characterized targets. Our generated molecules exhibit favorable drug-like properties, high target affinity, and inhibitory potency (IC50) against cancer cells. This unified framework showcases the synergistic potential of combining phenotype-guided and target-aware strategies, offering a more effective solution for de novo drug discovery.

Mindstate Design Labs, backed by Silicon Valley power players, has created what its CEO calls "the least psychedelic psychedelic that's psychoactive." While there's growing evidence that psychedelic drugs can effectively treat severe mental health conditions, especially in cases where traditional treatments have failed, they still come with downsides. Their hallucinogenic effects can be scary and overwhelming, with dosing sessions lasting several hours. Good treatment is heavily reliant on the individual's mindset going into a session and the environment in which they receive it. And though it's rare, psychedelics can sometimes worsen existing mental illness.

Fragment-Based Drug Discovery (FBDD) is a popular approach in early drug development, but designing effective linkers to combine disconnected molecular fragments into chemically and pharmacologically viable candidates remains challenging. Further complexity arises when fragments contain structural redundancies, like duplicate rings, which cannot be addressed by simply adding or removing atoms or bonds. To address these challenges in a unified framework, we introduce FragmentGPT, which integrates two core components: (1) a novel chemically-aware, energy-based bond cleavage pre-training strategy that equips the GPT-based model with fragment growing, linking, and merging capabilities, and (2) a novel Reward Ranked Alignment with Expert Exploration (RAE) algorithm that combines expert imitation learning for diversity enhancement, data selection and augmentation for Pareto and composite score optimality, and Supervised Fine-Tuning (SFT) to align the learner policy with multi-objective goals. Conditioned on fragment pairs, FragmentGPT generates linkers that connect diverse molecular subunits while simultaneously optimizing for multiple pharmaceutical goals. It also learns to resolve structural redundancies-such as duplicated fragments-through intelligent merging, enabling the synthesis of optimized molecules. FragmentGPT facilitates controlled, goal-driven molecular assembly. Experiments and ablation studies on real-world cancer datasets demonstrate its ability to generate chemically valid, high-quality molecules tailored for downstream drug discovery tasks.

Large Language Model (LLM)-based agents have emerged as a new paradigm that extends LLMs' capabilities beyond text generation to dynamic interaction with external environments. By integrating reasoning with perception, memory, and tool use, agents are increasingly deployed in diverse domains like web navigation and household robotics. A critical challenge, however, lies in ensuring agent generalizability - the ability to maintain consistent performance across varied instructions, tasks, environments, and domains, especially those beyond agents' fine-tuning data. Despite growing interest, the concept of generalizability in LLM-based agents remains underdefined, and systematic approaches to measure and improve it are lacking. In this survey, we provide the first comprehensive review of generalizability in LLM-based agents. We begin by emphasizing agent generalizability's importance by appealing to stakeholders and clarifying the boundaries of agent generalizability by situating it within a hierarchical domain-task ontology. We then review datasets, evaluation dimensions, and metrics, highlighting their limitations. Next, we categorize methods for improving generalizability into three groups: methods for the backbone LLM, for agent components, and for their interactions. Moreover, we introduce the distinction between generalizable frameworks and generalizable agents and outline how generalizable frameworks can be translated into agent-level generalizability. Finally, we identify critical challenges and future directions, including developing standardized frameworks, variance- and cost-based metrics, and approaches that integrate methodological innovations with architecture-level designs. By synthesizing progress and highlighting opportunities, this survey aims to establish a foundation for principled research on building LLM-based agents that generalize reliably across diverse applications.

"Our focus is really on what we can do to pull the doctor out of the visit," says Akido's CTO. Imagine this: You've been feeling unwell, so you call up your doctor's office to make an appointment. At the appointment, you aren't rushed through describing your health concerns; instead, you have a full half hour to share your symptoms and worries and the exhaustive details of your health history with someone who listens attentively and asks thoughtful follow-up questions. You leave with a diagnosis, a treatment plan, and the sense that, for once, you've been able to discuss your health with the care that it merits. AI companies have stopped warning you that their chatbots aren't doctors Once cautious, OpenAI, Grok, and others will now dive into giving unverified medical advice with virtually no disclaimers. You might not have spoken to a doctor, or other licensed medical practitioner, at all.

Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and AI systems can expand access to fundus photography screening. Current FDA-cleared systems primarily provide binary referral outputs, where this minimal output may limit clinical trust and utility. Yet, determining the most effective output format to enhance clinician-AI performance is an empirical challenge that is difficult to assess at scale. We evaluated multimodal large language models (MLLMs) for DR detection and their ability to simulate clinical AI assistance across different output types. Two models were tested on IDRiD and Messidor-2: GPT-4o, a general-purpose MLLM, and MedGemma, an open-source medical model. Experiments included: (1) baseline evaluation, (2) simulated AI assistance with synthetic predictions, and (3) actual AI-to-AI collaboration where GPT-4o incorporated MedGemma outputs. MedGemma outperformed GPT-4o at baseline, achieving higher sensitivity and AUROC, while GPT-4o showed near-perfect specificity but low sensitivity. Both models adjusted predictions based on simulated AI inputs, but GPT-4o's performance collapsed with incorrect ones, whereas MedGemma remained more stable. In actual collaboration, GPT-4o achieved strong results when guided by MedGemma's descriptive outputs, even without direct image access (AUROC up to 0.96). These findings suggest MLLMs may improve DR screening pipelines and serve as scalable simulators for studying clinical AI assistance across varying output configurations. Open, lightweight models such as MedGemma may be especially valuable in low-resource settings, while descriptive outputs could enhance explainability and clinician trust in clinical workflows.