A Survey of Scientific Large Language Models: From Data Foundations to Agent Frontiers

Scientific Large Language Models (Sci-LLMs) are transforming how knowledge is represented, integrated, and applied in scientific research, yet their progress is shaped by the complex nature of scientific data. This survey presents a comprehensive, data-centric synthesis that reframes the development of Sci-LLMs as a co-evolution between models and their underlying data substrate. We formulate a unified taxonomy of scientific data and a hierarchical model of scientific knowledge, emphasizing the multimodal, cross-scale, and domain-specific challenges that differentiate scientific corpora from general natural language processing datasets. We systematically review recent Sci-LLMs, from general-purpose foundations to specialized models across diverse scientific disciplines, alongside an extensive analysis of over 270 pre-/post-training datasets, showing why Sci-LLMs pose distinct demands -- heterogeneous, multi-scale, uncertainty-laden corpora that require representations preserving domain invariance and enabling cross-modal reasoning. On evaluation, we examine over 190 benchmark datasets and trace a shift from static exams toward process- and discovery-oriented assessments with advanced evaluation protocols. These data-centric analyses highlight persistent issues in scientific data development and discuss emerging solutions involving semi-automated annotation pipelines and expert validation. Finally, we outline a paradigm shift toward closed-loop systems where autonomous agents based on Sci-LLMs actively experiment, validate, and contribute to a living, evolving knowledge base. Collectively, this work provides a roadmap for building trustworthy, continually evolving artificial intelligence (AI) systems that function as a true partner in accelerating scientific discovery.

Cross-view Generalized Diffusion Model for Sparse-view CT Reconstruction

Sparse-view computed tomography (CT) reduces radiation exposure by subsampling projection views, but conventional reconstruction methods produce severe streak artifacts with undersampled data. While deep-learning-based methods enable single-step artifact suppression, they often produce over-smoothed results under significant sparsity. Though diffusion models improve reconstruction via iterative refinement and generative priors, they require hundreds of sampling steps and struggle with stability in highly sparse regimes. To tackle these concerns, we present the Cross-view Generalized Diffusion Model (CvG-Diff), which reformulates sparse-view CT reconstruction as a generalized diffusion process. Unlike existing diffusion approaches that rely on stochastic Gaussian degradation, CvG-Diff explicitly models image-domain artifacts caused by angular subsampling as a deterministic degradation operator, leveraging correlations across sparse-view CT at different sample rates. To address the inherent artifact propagation and inefficiency of sequential sampling in generalized diffusion model, we introduce two innovations: Error-Propagating Composite Training (EPCT), which facilitates identifying error-prone regions and suppresses propagated artifacts, and Semantic-Prioritized Dual-Phase Sampling (SPDPS), an adaptive strategy that prioritizes semantic correctness before detail refinement. Together, these innovations enable CvG-Diff to achieve high-quality reconstructions with minimal iterations, achieving 38.34 dB PSNR and 0.9518 SSIM for 18-view CT using only \textbf{10} steps on AAPM-LDCT dataset. Extensive experiments demonstrate the superiority of CvG-Diff over state-of-the-art sparse-view CT reconstruction methods. The code is available at https://github.com/xmed-lab/CvG-Diff.

MOC: Meta-Optimized Classifier for Few-Shot Whole Slide Image Classification

Recent advances in histopathology vision-language foundation models (VLFMs) have shown promise in addressing data scarcity for whole slide image (WSI) classification via zero-shot adaptation. However, these methods remain outperformed by conventional multiple instance learning (MIL) approaches trained on large datasets, motivating recent efforts to enhance VLFM-based WSI classification through fewshot learning paradigms. While existing few-shot methods improve diagnostic accuracy with limited annotations, their reliance on conventional classifier designs introduces critical vulnerabilities to data scarcity. To address this problem, we propose a Meta-Optimized Classifier (MOC) comprising two core components: (1) a meta-learner that automatically optimizes a classifier configuration from a mixture of candidate classifiers and (2) a classifier bank housing diverse candidate classifiers to enable a holistic pathological interpretation. Extensive experiments demonstrate that MOC outperforms prior arts in multiple few-shot benchmarks. Notably, on the TCGA-NSCLC benchmark, MOC improves AUC by 10.4% over the state-of-the-art few-shot VLFM-based methods, with gains up to 26.25% under 1-shot conditions, offering a critical advancement for clinical deployments where diagnostic training data is severely limited. Code is available at https://github.com/xmed-lab/MOC.

Diffmv: A Unified Diffusion Framework for Healthcare Predictions with Random Missing Views and View Laziness

Advanced healthcare predictions offer significant improvements in patient outcomes by leveraging predictive analytics. Existing works primarily utilize various views of Electronic Health Record (EHR) data, such as diagnoses, lab tests, or clinical notes, for model training. These methods typically assume the availability of complete EHR views and that the designed model could fully leverage the potential of each view. However, in practice, random missing views and view laziness present two significant challenges that hinder further improvements in multi-view utilization. To address these challenges, we introduce Diffmv, an innovative diffusion-based generative framework designed to advance the exploitation of multiple views of EHR data. Specifically, to address random missing views, we integrate various views of EHR data into a unified diffusion-denoising framework, enriched with diverse contextual conditions to facilitate progressive alignment and view transformation. To mitigate view laziness, we propose a novel reweighting strategy that assesses the relative advantages of each view, promoting a balanced utilization of various data views within the model. Our proposed strategy achieves superior performance across multiple health prediction tasks derived from three popular datasets, including multi-view and multi-modality scenarios.

UniEval: Unified Holistic Evaluation for Unified Multimodal Understanding and Generation

The emergence of unified multimodal understanding and generation models is rapidly attracting attention because of their ability to enhance instruction-following capabilities while minimizing model redundancy. However, there is a lack of a unified evaluation framework for these models, which would enable an elegant, simplified, and overall evaluation. Current models conduct evaluations on multiple task-specific benchmarks, but there are significant limitations, such as the lack of overall results, errors from extra evaluation models, reliance on extensive labeled images, benchmarks that lack diversity, and metrics with limited capacity for instruction-following evaluation. To tackle these challenges, we introduce UniEval, the first evaluation framework designed for unified multimodal models without extra models, images, or annotations. This facilitates a simplified and unified evaluation process. The UniEval framework contains a holistic benchmark, UniBench (supports both unified and visual generation models), along with the corresponding UniScore metric. UniBench includes 81 fine-grained tags contributing to high diversity. Experimental results indicate that UniBench is more challenging than existing benchmarks, and UniScore aligns closely with human evaluations, surpassing current metrics. Moreover, we extensively evaluated SoTA unified and visual generation models, uncovering new insights into Univeral's unique values.

Leveraging Segment Anything Model for Source-Free Domain Adaptation via Dual Feature Guided Auto-Prompting

Source-free domain adaptation (SFDA) for segmentation aims at adapting a model trained in the source domain to perform well in the target domain with only the source model and unlabeled target data.Inspired by the recent success of Segment Anything Model (SAM) which exhibits the generality of segmenting images of various modalities and in different domains given human-annotated prompts like bounding boxes or points, we for the first time explore the potentials of Segment Anything Model for SFDA via automatedly finding an accurate bounding box prompt. We find that the bounding boxes directly generated with existing SFDA approaches are defective due to the domain gap.To tackle this issue, we propose a novel Dual Feature Guided (DFG) auto-prompting approach to search for the box prompt. Specifically, the source model is first trained in a feature aggregation phase, which not only preliminarily adapts the source model to the target domain but also builds a feature distribution well-prepared for box prompt search. In the second phase, based on two feature distribution observations, we gradually expand the box prompt with the guidance of the target model feature and the SAM feature to handle the class-wise clustered target features and the class-wise dispersed target features, respectively. To remove the potentially enlarged false positive regions caused by the over-confident prediction of the target model, the refined pseudo-labels produced by SAM are further postprocessed based on connectivity analysis. Experiments on 3D and 2D datasets indicate that our approach yields superior performance compared to conventional methods. Code is available at https://github.com/xmed-lab/DFG.

AI-Enabled Accurate Non-Invasive Assessment of Pulmonary Hypertension Progression via Multi-Modal Echocardiography

Echocardiographers can detect pulmonary hypertension using Doppler echocardiography; however, accurately assessing its progression often proves challenging. Right heart catheterization (RHC), the gold standard for precise evaluation, is invasive and unsuitable for routine use, limiting its practicality for timely diagnosis and monitoring of pulmonary hypertension progression. Here, we propose MePH, a multi-view, multi-modal vision-language model to accurately assess pulmonary hypertension progression using non-invasive echocardiography. We constructed a large dataset comprising paired standardized echocardiogram videos, spectral images and RHC data, covering 1,237 patient cases from 12 medical centers. For the first time, MePH precisely models the correlation between non-invasive multi-view, multi-modal echocardiography and the pressure and resistance obtained via RHC. We show that MePH significantly outperforms echocardiographers' assessments using echocardiography, reducing the mean absolute error in estimating mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) by 49.73% and 43.81%, respectively. In eight independent external hospitals, MePH achieved a mean absolute error of 3.147 for PVR assessment. Furthermore, MePH achieved an area under the curve of 0.921, surpassing echocardiographers (area under the curve of 0.842) in accurately predicting the severity of pulmonary hypertension, whether mild or severe. A prospective study demonstrated that MePH can predict treatment efficacy for patients. Our work provides pulmonary hypertension patients with a non-invasive and timely method for monitoring disease progression, improving the accuracy and efficiency of pulmonary hypertension management while enabling earlier interventions and more personalized treatment decisions.

Multi-Modal Explainable Medical AI Assistant for Trustworthy Human-AI Collaboration

Generalist Medical AI (GMAI) systems have demonstrated expert-level performance in biomedical perception tasks, yet their clinical utility remains limited by inadequate multi-modal explainability and suboptimal prognostic capabilities. Here, we present XMedGPT, a clinician-centric, multi-modal AI assistant that integrates textual and visual interpretability to support transparent and trustworthy medical decision-making. XMedGPT not only produces accurate diagnostic and descriptive outputs, but also grounds referenced anatomical sites within medical images, bridging critical gaps in interpretability and enhancing clinician usability. To support real-world deployment, we introduce a reliability indexing mechanism that quantifies uncertainty through consistency-based assessment via interactive question-answering. We validate XMedGPT across four pillars: multi-modal interpretability, uncertainty quantification, and prognostic modeling, and rigorous benchmarking. The model achieves an IoU of 0.703 across 141 anatomical regions, and a Kendall's tau-b of 0.479, demonstrating strong alignment between visual rationales and clinical outcomes. For uncertainty estimation, it attains an AUC of 0.862 on visual question answering and 0.764 on radiology report generation. In survival and recurrence prediction for lung and glioma cancers, it surpasses prior leading models by 26.9%, and outperforms GPT-4o by 25.0%. Rigorous benchmarking across 347 datasets covers 40 imaging modalities and external validation spans 4 anatomical systems confirming exceptional generalizability, with performance gains surpassing existing GMAI by 20.7% for in-domain evaluation and 16.7% on 11,530 in-house data evaluation. Together, XMedGPT represents a significant leap forward in clinician-centric AI integration, offering trustworthy and scalable support for diverse healthcare applications.

Concept-Based Unsupervised Domain Adaptation

Concept Bottleneck Models (CBMs) enhance interpretability by explaining predictions through human-understandable concepts but typically assume that training and test data share the same distribution. This assumption often fails under domain shifts, leading to degraded performance and poor generalization. To address these limitations and improve the robustness of CBMs, we propose the Concept-based Unsupervised Domain Adaptation (CUDA) framework. CUDA is designed to: (1) align concept representations across domains using adversarial training, (2) introduce a relaxation threshold to allow minor domain-specific differences in concept distributions, thereby preventing performance drop due to over-constraints of these distributions, (3) infer concepts directly in the target domain without requiring labeled concept data, enabling CBMs to adapt to diverse domains, and (4) integrate concept learning into conventional domain adaptation (DA) with theoretical guarantees, improving interpretability and establishing new benchmarks for DA. Experiments demonstrate that our approach significantly outperforms the state-of-the-art CBM and DA methods on real-world datasets.

Reinforced Correlation Between Vision and Language for Precise Medical AI Assistant

Medical AI assistants support doctors in disease diagnosis, medical image analysis, and report generation. However, they still face significant challenges in clinical use, including limited accuracy with multimodal content and insufficient validation in real-world settings. We propose RCMed, a full-stack AI assistant that improves multimodal alignment in both input and output, enabling precise anatomical delineation, accurate localization, and reliable diagnosis through hierarchical vision-language grounding. A self-reinforcing correlation mechanism allows visual features to inform language context, while language semantics guide pixel-wise attention, forming a closed loop that refines both modalities. This correlation is enhanced by a color region description strategy, translating anatomical structures into semantically rich text to learn shape-location-text relationships across scales. Trained on 20 million image-mask-description triplets, RCMed achieves state-of-the-art precision in contextualizing irregular lesions and subtle anatomical boundaries, excelling in 165 clinical tasks across 9 modalities. It achieved a 23.5% relative improvement in cell segmentation from microscopy images over prior methods. RCMed's strong vision-language alignment enables exceptional generalization, with state-of-the-art performance in external validation across 20 clinically significant cancer types, including novel tasks. This work demonstrates how integrated multimodal models capture fine-grained patterns, enabling human-level interpretation in complex scenarios and advancing human-centric AI healthcare.