Zhengyun Zhao

Zheng Yuan, Qiao Jin, Chuanqi Tan et al. · tsinghua

Vision-and-language multi-modal pretraining and fine-tuning have shown great success in visual question answering (VQA). Compared to general domain VQA, the performance of biomedical VQA suffers from limited data. In this paper, we propose a retrieval-augmented pretrain-and-finetune paradigm named RAMM for biomedical VQA to overcome the data limitation issue. Specifically, we collect a new biomedical dataset named PMCPM which offers patient-based image-text pairs containing diverse patient situations from PubMed. Then, we pretrain the biomedical multi-modal model to learn visual and textual representation for image-text pairs and align these representations with image-text contrastive objective (ITC). Finally, we propose a retrieval-augmented method to better use the limited data. We propose to retrieve similar image-text pairs based on ITC from pretraining datasets and introduce a novel retrieval-attention module to fuse the representation of the image and the question with the retrieved images and texts. Experiments demonstrate that our retrieval-augmented pretrain-and-finetune paradigm obtains state-of-the-art performance on Med-VQA2019, Med-VQA2021, VQARAD, and SLAKE datasets. Further analysis shows that the proposed RAMM and PMCPM can enhance biomedical VQA performance compared with previous resources and methods. We will open-source our dataset, codes, and pretrained model.

Sheng Yu, Zheng Yuan, Jun Xia et al. · tsinghua

Biomedical knowledge graphs (BioMedKGs) are essential infrastructures for biomedical and healthcare big data and artificial intelligence (AI), facilitating natural language processing, model development, and data exchange. For decades, these knowledge graphs have been developed via expert curation; however, this method can no longer keep up with today's AI development, and a transition to algorithmically generated BioMedKGs is necessary. In this work, we introduce the Biomedical Informatics Ontology System (BIOS), the first large-scale publicly available BioMedKG generated completely by machine learning algorithms. BIOS currently contains 4.1 million concepts, 7.4 million terms in two languages, and 7.3 million relation triplets. We present the methodology for developing BIOS, including the curation of raw biomedical terms, computational identification of synonymous terms and aggregation of these terms to create concept nodes, semantic type classification of the concepts, relation identification, and biomedical machine translation. We provide statistics on the current BIOS content and perform preliminary assessments of term quality, synonym grouping, and relation extraction. The results suggest that machine learning-based BioMedKG development is a viable alternative to traditional expert curation.

Bingning Wang, Haizhou Zhao, Huozhi Zhou et al.

The current generation of large language models (LLMs) is typically designed for broad, general-purpose applications, while domain-specific LLMs, especially in vertical fields like medicine, remain relatively scarce. In particular, the development of highly efficient and practical LLMs for the medical domain is challenging due to the complexity of medical knowledge and the limited availability of high-quality data. To bridge this gap, we introduce Baichuan-M1, a series of large language models specifically optimized for medical applications. Unlike traditional approaches that simply continue pretraining on existing models or apply post-training to a general base model, Baichuan-M1 is trained from scratch with a dedicated focus on enhancing medical capabilities. Our model is trained on 20 trillion tokens and incorporates a range of effective training methods that strike a balance between general capabilities and medical expertise. As a result, Baichuan-M1 not only performs strongly across general domains such as mathematics and coding but also excels in specialized medical fields. We have open-sourced Baichuan-M1-14B, a mini version of our model, which can be accessed through the following links.

Zheng Yuan, Zhengyun Zhao, Haixia Sun et al.

This paper proposes CODER: contrastive learning on knowledge graphs for cross-lingual medical term representation. CODER is designed for medical term normalization by providing close vector representations for different terms that represent the same or similar medical concepts with cross-lingual support. We train CODER via contrastive learning on a medical knowledge graph (KG) named the Unified Medical Language System, where similarities are calculated utilizing both terms and relation triplets from KG. Training with relations injects medical knowledge into embeddings and aims to provide potentially better machine learning features. We evaluate CODER in zero-shot term normalization, semantic similarity, and relation classification benchmarks, which show that CODERoutperforms various state-of-the-art biomedical word embedding, concept embeddings, and contextual embeddings. Our codes and models are available at https://github.com/GanjinZero/CODER.

Huaiyuan Ying, Zhengyun Zhao, Yang Zhao et al.

Objective: Biomedical Knowledge Graphs play a pivotal role in various biomedical research domains. Concurrently, term clustering emerges as a crucial step in constructing these knowledge graphs, aiming to identify synonymous terms. Due to a lack of knowledge, previous contrastive learning models trained with Unified Medical Language System (UMLS) synonyms struggle at clustering difficult terms and do not generalize well beyond UMLS terms. In this work, we leverage the world knowledge from Large Language Models (LLMs) and propose Contrastive Learning for Representing Terms via Explanations (CoRTEx) to enhance term representation and significantly improves term clustering. Materials and Methods: The model training involves generating explanations for a cleaned subset of UMLS terms using ChatGPT. We employ contrastive learning, considering term and explanation embeddings simultaneously, and progressively introduce hard negative samples. Additionally, a ChatGPT-assisted BIRCH algorithm is designed for efficient clustering of a new ontology. Results: We established a clustering test set and a hard negative test set, where our model consistently achieves the highest F1 score. With CoRTEx embeddings and the modified BIRCH algorithm, we grouped 35,580,932 terms from the Biomedical Informatics Ontology System (BIOS) into 22,104,559 clusters with O(N) queries to ChatGPT. Case studies highlight the model's efficacy in handling challenging samples, aided by information from explanations. Conclusion: By aligning terms to their explanations, CoRTEx demonstrates superior accuracy over benchmark models and robustness beyond its training set, and it is suitable for clustering terms for large-scale biomedical ontologies.

Huaiyuan Ying, Hongyi Yuan, Jinsen Lu et al.

Electronic Health Records (EHRs) hold immense potential for advancing healthcare, offering rich, longitudinal data that combines structured information with valuable insights from unstructured clinical notes. However, the unstructured nature of clinical text poses significant challenges for secondary applications. Traditional methods for structuring EHR free-text data, such as rule-based systems and multi-stage pipelines, are often limited by their time-consuming configurations and inability to adapt across clinical notes from diverse healthcare settings. Few systems provide a comprehensive attribute extraction for terminologies. While giant large language models (LLMs) like GPT-4 and LLaMA 405B excel at structuring tasks, they are slow, costly, and impractical for large-scale use. To overcome these limitations, we introduce GENIE, a Generative Note Information Extraction system that leverages LLMs to streamline the structuring of unstructured clinical text into usable data with standardized format. GENIE processes entire paragraphs in a single pass, extracting entities, assertion statuses, locations, modifiers, values, and purposes with high accuracy. Its unified, end-to-end approach simplifies workflows, reduces errors, and eliminates the need for extensive manual intervention. Using a robust data preparation pipeline and fine-tuned small scale LLMs, GENIE achieves competitive performance across multiple information extraction tasks, outperforming traditional tools like cTAKES and MetaMap and can handle extra attributes to be extracted. GENIE strongly enhances real-world applicability and scalability in healthcare systems. By open-sourcing the model and test data, we aim to encourage collaboration and drive further advancements in EHR structurization.

Zecheng Wang, Deyuan Liu, Chunshan Li et al.

Standard negative log-likelihood (NLL) for Supervised Fine-Tuning (SFT) applies uniform token-level weighting. This rigidity creates a two-fold failure mode: (i) overemphasizing low-probability targets can amplify gradients on noisy supervision and disrupt robust priors, and (ii) uniform weighting provides weak sharpening when the model is already confident. Existing methods fail to resolve the resulting plasticity--stability dilemma, often suppressing necessary learning signals alongside harmful ones. To address this issue, we unify token-level SFT objectives within a generalized deformed-log family and expose a universal gate $\times$ error gradient structure, where the gate controls how much the model trusts its current prediction. By employing the Cayley transform, we map the model's continuously evolving uncertainty onto a continuous focus trajectory, which enables seamless interpolation between scenarios involving uncertain novel concepts and those involving well-established knowledge. We then introduce Dynamic Entropy Fine-Tuning (DEFT), a parameter-free objective that modulates the trust gate using distribution concentration (Rényi-2 entropy) as a practical proxy for the model's predictive state. Extensive experiments and analyses demonstrate that DEFT achieves a better balance between exploration and exploitation, leading to improved overall performance.

Zhengyun Zhao, Huaiyuan Ying, Yue Zhong et al.

Electronic Health Records (EHRs) are pivotal in clinical practices, yet their retrieval remains a challenge mainly due to semantic gap issues. Recent advancements in dense retrieval offer promising solutions but existing models, both general-domain and biomedical-domain, fall short due to insufficient medical knowledge or mismatched training corpora. This paper introduces \texttt{DR.EHR}, a series of dense retrieval models specifically tailored for EHR retrieval. We propose a two-stage training pipeline utilizing MIMIC-IV discharge summaries to address the need for extensive medical knowledge and large-scale training data. The first stage involves medical entity extraction and knowledge injection from a biomedical knowledge graph, while the second stage employs large language models to generate diverse training data. We train two variants of \texttt{DR.EHR}, with 110M and 7B parameters, respectively. Evaluated on the CliniQ benchmark, our models significantly outperforms all existing dense retrievers, achieving state-of-the-art results. Detailed analyses confirm our models' superiority across various match and query types, particularly in challenging semantic matches like implication and abbreviation. Ablation studies validate the effectiveness of each pipeline component, and supplementary experiments on EHR QA datasets demonstrate the models' generalizability on natural language questions, including complex ones with multiple entities. This work significantly advances EHR retrieval, offering a robust solution for clinical applications.

Zhengyun Zhao, Hongyi Yuan, Jingjing Liu et al.

Electronic Health Record (EHR) retrieval plays a pivotal role in various clinical tasks, but its development has been severely impeded by the lack of publicly available benchmarks. In this paper, we introduce a novel public EHR retrieval benchmark, CliniQ, to address this gap. We consider two retrieval settings: Single-Patient Retrieval and Multi-Patient Retrieval, reflecting various real-world scenarios. Single-Patient Retrieval focuses on finding relevant parts within a patient note, while Multi-Patient Retrieval involves retrieving EHRs from multiple patients. We build our benchmark upon 1,000 discharge summary notes along with the ICD codes and prescription labels from MIMIC-III, and collect 1,246 unique queries with 77,206 relevance judgments by further leveraging powerful LLMs as annotators. Additionally, we include a novel assessment of the semantic gap issue in EHR retrieval by categorizing matching types into string match and four types of semantic matches. On our proposed benchmark, we conduct a comprehensive evaluation of various retrieval methods, ranging from conventional exact match to popular dense retrievers. Our experiments find that BM25 sets a strong baseline and performs competitively to the dense retrievers, and general domain dense retrievers surprisingly outperform those designed for the medical domain. In-depth analyses on various matching types reveal the strengths and drawbacks of different methods, enlightening the potential for targeted improvement. We believe that our benchmark will stimulate the research communities to advance EHR retrieval systems.

Zhengyun Zhao, Qiao Jin, Fangyuan Chen et al.

Objective: Retrieval-based Clinical Decision Support (ReCDS) can aid clinical workflow by providing relevant literature and similar patients for a given patient. However, the development of ReCDS systems has been severely obstructed by the lack of diverse patient collections and publicly available large-scale patient-level annotation datasets. In this paper, we aim to define and benchmark two ReCDS tasks: Patient-to-Article Retrieval (ReCDS-PAR) and Patient-to-Patient Retrieval (ReCDS-PPR) using a novel dataset called PMC-Patients. Methods: We extract patient summaries from PubMed Central articles using simple heuristics and utilize the PubMed citation graph to define patient-article relevance and patient-patient similarity. We also implement and evaluate several ReCDS systems on the PMC-Patients benchmarks, including sparse retrievers, dense retrievers, and nearest neighbor retrievers. We conduct several case studies to show the clinical utility of PMC-Patients. Results: PMC-Patients contains 167k patient summaries with 3.1M patient-article relevance annotations and 293k patient-patient similarity annotations, which is the largest-scale resource for ReCDS and also one of the largest patient collections. Human evaluation and analysis show that PMC-Patients is a diverse dataset with high-quality annotations. The evaluation of various ReCDS systems shows that the PMC-Patients benchmark is challenging and calls for further research. Conclusion: We present PMC-Patients, a large-scale, diverse, and publicly available patient summary dataset with the largest-scale patient-level relation annotations. Based on PMC-Patients, we formally define two benchmark tasks for ReCDS systems and evaluate various existing retrieval methods. PMC-Patients can largely facilitate methodology research on ReCDS systems and shows real-world clinical utility.