Clinical trials constitute a critical yet exceptionally challenging and costly stage of drug development (2.6B per drug), where protocols are encoded as complex natural language documents, motivating the use of AI systems beyond manual analysis. Existing AI methods accurately predict trial failure, but do not provide actionable remedies. To fill this gap, this paper proposes ClinicalReTrial, a multi-agent system that formulates clinical trial optimization as an iterative redesign problem on textual protocols. Our method integrates failure diagnosis, safety-aware modifications, and candidate evaluation in a closed-loop, reward-driven optimization framework. Serving the outcome prediction model as a simulation environment, ClinicalReTrial enables low-cost evaluation and dense reward signals for continuous self-improvement. We further propose a hierarchical memory that captures iteration-level feedback within trials and distills transferable redesign patterns across trials. Empirically, ClinicalReTrial turns 56.7% of failed protocols into predicted successes under the simulation environment, with a mean success probability gain of 7.4% at negligible cost (0.156 per trial). Extensive retrospective case studies further show that ClinicalReTrial recovers clinically meaningful modification patterns that align with real-world expert-driven protocol changes.

Scientific LLM agents have shown promise in literature reasoning, tool use, and experiment planning, but it remains unclear whether they can autonomously improve large, tightly coupled scientific machine-learning systems through executable code changes and computationally expensive validation. We study this question in protein folding, where progress requires coordinated architectural modifications, multi-objective evaluation, and domain-aware interpretation. We present AgentFold, a multi-agent framework that formulates folding-model development as a closed-loop search over executable code variants. Starting from ESMFold, AgentFold proposes hypotheses, implements and debugs code-level modifications, evaluates model variants, analyzes experimental outcomes, and stores both successful and failed interventions in structured memory. An MCTS-style policy allocates computational resources across high-scoring search branches. On an engineering-scale protein-folding codebase comprising more than 2,000 lines of code, AgentFold explores approximately 80 model variants using approximately 5,000 GPU-hours and 170 million LLM tokens. Under a matched computational budget, AgentFold improves the best lDDT by 7.5% over independent Codex proposals and outperforms a random-search control. Beyond model improvement, the resulting intervention traces reveal recurring empirical design patterns: stable gains tend to arise from early, soft, learnable priors and gated refinement, whereas direct geometric perturbations and geometry-conditioned feedback often destabilize training. The code and experimental resources are publicly available at https://github.com/lmqfly/AgentFold.

LLM-guided evolutionary search (Evolve systems) has reached state-of-the-art results on mathematical and combinatorial tasks, yet most existing systems report only the best of many runs and leave the run-to-run distribution undocumented. We ask how a fixed budget of LLM calls should be allocated, and how reliably a single run reaches the reported numbers. Sweeping the depth–breadth grid over five models and three tasks, we identify two empirical regularities: a fitness–compute envelope along which capability ordering largely collapses on effective FLOPs, and a bilinear depth–breadth fit with task-specific interaction; both are gated by model–task capability. Motivated by these regularities, we propose BaSE (Bandit-based Self-Evolving), a multi-armed bandit that allocates LLM calls across parallel trajectories. Without changing the model, prompt, or evaluator, BaSE improves mean fitness by 12.3% over the strongest island-protocol baseline across 8 (model, task) cells, with the largest gains on high-variance settings: a reliability gain from allocation alone.

Clinical trials are pivotal yet costly processes, often spanning multiple years and requiring substantial expenses, motivating predictive models to identify likely-to-fail drugs early and save resources. Recent approaches leverage deep learning to integrate multimodal data for clinical outcome prediction; however, they rely heavily on manually designed modality-specific encoders, limiting their adaptability to new modalities and ability to effectively share information across modalities. To address these challenges, we propose a multimodal mixture-of-experts (LIFTED) framework. Specifically, LIFTED transforms modality-specific data into natural language descriptions, encoded via unified, noise-resilient encoders. A sparse Mixture-of-Experts mechanism then identifies shared patterns across modalities, extracting consistent representations. Finally, another mixture-of-experts module dynamically integrates these modality representations, emphasizing critical information. Experiments show that LIFTED significantly outperforms baseline methods in predicting clinical trial outcomes across all phases, highlighting the effectiveness of our proposed approach.

Word embeddings have become a mainstream tool in statistical natural language processing. Practitioners often use pre-trained word vectors, which were trained on large generic text corpora, and which are readily available on the web. However, pre-trained word vectors oftentimes lack important words from specific domains. It is therefore often desirable to extend the vocabulary and embed new words into a set of pre-trained word vectors. In this paper, we present an efficient method for including new words from a specialized corpus, containing new words, into pre-trained generic word embeddings. We build on the established view of word embeddings as matrix factorizations to present a spectral algorithm for this task. Experiments on several domain-specific corpora with specialized vocabularies demonstrate that our method is able to embed the new words efficiently into the original embedding space. Compared to competing methods, our method is faster, parameter-free, and deterministic.