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May 8

BioHopR: A Benchmark for Multi-Hop, Multi-Answer Reasoning in Biomedical Domain

Biomedical reasoning often requires traversing interconnected relationships across entities such as drugs, diseases, and proteins. Despite the increasing prominence of large language models (LLMs), existing benchmarks lack the ability to evaluate multi-hop reasoning in the biomedical domain, particularly for queries involving one-to-many and many-to-many relationships. This gap leaves the critical challenges of biomedical multi-hop reasoning underexplored. To address this, we introduce BioHopR, a novel benchmark designed to evaluate multi-hop, multi-answer reasoning in structured biomedical knowledge graphs. Built from the comprehensive PrimeKG, BioHopR includes 1-hop and 2-hop reasoning tasks that reflect real-world biomedical complexities. Evaluations of state-of-the-art models reveal that O3-mini, a proprietary reasoning-focused model, achieves 37.93% precision on 1-hop tasks and 14.57% on 2-hop tasks, outperforming proprietary models such as GPT4O and open-source biomedical models including HuatuoGPT-o1-70B and Llama-3.3-70B. However, all models exhibit significant declines in multi-hop performance, underscoring the challenges of resolving implicit reasoning steps in the biomedical domain. By addressing the lack of benchmarks for multi-hop reasoning in biomedical domain, BioHopR sets a new standard for evaluating reasoning capabilities and highlights critical gaps between proprietary and open-source models while paving the way for future advancements in biomedical LLMs.

  • 3 authors
·
Jun 8, 2025

Symbolic Mixture-of-Experts: Adaptive Skill-based Routing for Heterogeneous Reasoning

Combining existing pre-trained expert LLMs is a promising avenue for scalably tackling large-scale and diverse tasks. However, selecting experts at the task level is often too coarse-grained, as heterogeneous tasks may require different expertise for each instance. To enable adaptive instance-level mixing of pre-trained LLM experts, we propose Symbolic-MoE, a symbolic, text-based, and gradient-free Mixture-of-Experts framework. Symbolic-MoE takes a fine-grained approach to selection by emphasizing skills, e.g., algebra in math or molecular biology in biomedical reasoning. We propose a skill-based recruiting strategy that dynamically selects the most relevant set of expert LLMs for diverse reasoning tasks based on their strengths. Each selected expert then generates its own reasoning, resulting in k outputs from k experts, which are then synthesized into a final high-quality response by an aggregator chosen based on its ability to integrate diverse reasoning outputs. We show that Symbolic-MoE's instance-level expert selection improves performance by a large margin but -- when implemented naively -- can introduce a high computational overhead due to the need for constant model loading and offloading. To address this, we implement a batch inference strategy that groups instances based on their assigned experts, loading each model only once. This allows us to integrate 16 expert models on 1 GPU with a time cost comparable to or better than prior multi-agent baselines using 4 GPUs. Through extensive evaluations on diverse benchmarks (MMLU-Pro, GPQA, AIME, and MedMCQA), we demonstrate that Symbolic-MoE outperforms strong LLMs like GPT4o-mini, as well as multi-agent approaches, with an absolute average improvement of 8.15% over the best multi-agent baseline. Moreover, Symbolic-MoE removes the need for expensive multi-round discussions, outperforming discussion baselines with less computation.

  • 5 authors
·
Mar 7, 2025 2

BiomedSQL: Text-to-SQL for Scientific Reasoning on Biomedical Knowledge Bases

Biomedical researchers increasingly rely on large-scale structured databases for complex analytical tasks. However, current text-to-SQL systems often struggle to map qualitative scientific questions into executable SQL, particularly when implicit domain reasoning is required. We introduce BiomedSQL, the first benchmark explicitly designed to evaluate scientific reasoning in text-to-SQL generation over a real-world biomedical knowledge base. BiomedSQL comprises 68,000 question/SQL query/answer triples grounded in a harmonized BigQuery knowledge base that integrates gene-disease associations, causal inference from omics data, and drug approval records. Each question requires models to infer domain-specific criteria, such as genome-wide significance thresholds, effect directionality, or trial phase filtering, rather than rely on syntactic translation alone. We evaluate a range of open- and closed-source LLMs across prompting strategies and interaction paradigms. Our results reveal a substantial performance gap: GPT-o3-mini achieves 59.0% execution accuracy, while our custom multi-step agent, BMSQL, reaches 62.6%, both well below the expert baseline of 90.0%. BiomedSQL provides a new foundation for advancing text-to-SQL systems capable of supporting scientific discovery through robust reasoning over structured biomedical knowledge bases. Our dataset is publicly available at https://huggingface.co/datasets/NIH-CARD/BiomedSQL, and our code is open-source at https://github.com/NIH-CARD/biomedsql.

  • 11 authors
·
May 23, 2025 2

SemEval-2023 Task 7: Multi-Evidence Natural Language Inference for Clinical Trial Data

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

  • 6 authors
·
May 4, 2023

Improving Medical Reasoning through Retrieval and Self-Reflection with Retrieval-Augmented Large Language Models

Recent proprietary large language models (LLMs), such as GPT-4, have achieved a milestone in tackling diverse challenges in the biomedical domain, ranging from multiple-choice questions to long-form generations. To address challenges that still cannot be handled with the encoded knowledge of LLMs, various retrieval-augmented generation (RAG) methods have been developed by searching documents from the knowledge corpus and appending them unconditionally or selectively to the input of LLMs for generation. However, when applying existing methods to different domain-specific problems, poor generalization becomes apparent, leading to fetching incorrect documents or making inaccurate judgments. In this paper, we introduce Self-BioRAG, a framework reliable for biomedical text that specializes in generating explanations, retrieving domain-specific documents, and self-reflecting generated responses. We utilize 84k filtered biomedical instruction sets to train Self-BioRAG that can assess its generated explanations with customized reflective tokens. Our work proves that domain-specific components, such as a retriever, domain-related document corpus, and instruction sets are necessary for adhering to domain-related instructions. Using three major medical question-answering benchmark datasets, experimental results of Self-BioRAG demonstrate significant performance gains by achieving a 7.2% absolute improvement on average over the state-of-the-art open-foundation model with a parameter size of 7B or less. Overall, we analyze that Self-BioRAG finds the clues in the question, retrieves relevant documents if needed, and understands how to answer with information from retrieved documents and encoded knowledge as a medical expert does. We release our data and code for training our framework components and model weights (7B and 13B) to enhance capabilities in biomedical and clinical domains.

  • 4 authors
·
Jan 26, 2024

Toward Reliable Biomedical Hypothesis Generation: Evaluating Truthfulness and Hallucination in Large Language Models

Large language models (LLMs) have shown significant potential in scientific disciplines such as biomedicine, particularly in hypothesis generation, where they can analyze vast literature, identify patterns, and suggest research directions. However, a key challenge lies in evaluating the truthfulness of generated hypotheses, as verifying their accuracy often requires substantial time and resources. Additionally, the hallucination problem in LLMs can lead to the generation of hypotheses that appear plausible but are ultimately incorrect, undermining their reliability. To facilitate the systematic study of these challenges, we introduce TruthHypo, a benchmark for assessing the capabilities of LLMs in generating truthful biomedical hypotheses, and KnowHD, a knowledge-based hallucination detector to evaluate how well hypotheses are grounded in existing knowledge. Our results show that LLMs struggle to generate truthful hypotheses. By analyzing hallucinations in reasoning steps, we demonstrate that the groundedness scores provided by KnowHD serve as an effective metric for filtering truthful hypotheses from the diverse outputs of LLMs. Human evaluations further validate the utility of KnowHD in identifying truthful hypotheses and accelerating scientific discovery. Our data and source code are available at https://github.com/Teddy-XiongGZ/TruthHypo.

  • 8 authors
·
May 20, 2025 2

BioGraphFusion: Graph Knowledge Embedding for Biological Completion and Reasoning

Motivation: Biomedical knowledge graphs (KGs) are crucial for drug discovery and disease understanding, yet their completion and reasoning are challenging. Knowledge Embedding (KE) methods capture global semantics but struggle with dynamic structural integration, while Graph Neural Networks (GNNs) excel locally but often lack semantic understanding. Even ensemble approaches, including those leveraging language models, often fail to achieve a deep, adaptive, and synergistic co-evolution between semantic comprehension and structural learning. Addressing this critical gap in fostering continuous, reciprocal refinement between these two aspects in complex biomedical KGs is paramount. Results: We introduce BioGraphFusion, a novel framework for deeply synergistic semantic and structural learning. BioGraphFusion establishes a global semantic foundation via tensor decomposition, guiding an LSTM-driven mechanism to dynamically refine relation embeddings during graph propagation. This fosters adaptive interplay between semantic understanding and structural learning, further enhanced by query-guided subgraph construction and a hybrid scoring mechanism. Experiments across three key biomedical tasks demonstrate BioGraphFusion's superior performance over state-of-the-art KE, GNN, and ensemble models. A case study on Cutaneous Malignant Melanoma 1 (CMM1) highlights its ability to unveil biologically meaningful pathways. Availability and Implementation: Source code and all training data are freely available for download at https://github.com/Y-TARL/BioGraphFusion. Supplementary information: Supplementary data are available at Bioinformatics online.

  • 6 authors
·
Jul 19, 2025

K-Paths: Reasoning over Graph Paths for Drug Repurposing and Drug Interaction Prediction

Drug discovery is a complex and time-intensive process that requires identifying and validating new therapeutic candidates. Computational approaches using large-scale biomedical knowledge graphs (KGs) offer a promising solution to accelerate this process. However, extracting meaningful insights from large-scale KGs remains challenging due to the complexity of graph traversal. Existing subgraph-based methods are tailored to graph neural networks (GNNs), making them incompatible with other models, such as large language models (LLMs). We introduce K-Paths, a retrieval framework that extracts structured, diverse, and biologically meaningful paths from KGs. Integrating these paths enables LLMs and GNNs to effectively predict unobserved drug-drug and drug-disease interactions. Unlike traditional path-ranking approaches, K-Paths retrieves and transforms paths into a structured format that LLMs can directly process, facilitating explainable reasoning. K-Paths employs a diversity-aware adaptation of Yen's algorithm to retrieve the K shortest loopless paths between entities in an interaction query, prioritizing biologically relevant and diverse relationships. Our experiments on benchmark datasets show that K-Paths improves the zero-shot performance of Llama 8.1B's F1-score by 12.45 points on drug repurposing and 13.42 points on interaction severity prediction. We also show that Llama 70B achieves F1-score gains of 6.18 and 8.46 points, respectively. K-Paths also improves the supervised training efficiency of EmerGNN, a state-of-the-art GNN, by reducing KG size by 90% while maintaining strong predictive performance. Beyond its scalability and efficiency, K-Paths uniquely bridges the gap between KGs and LLMs, providing explainable rationales for predicted interactions. These capabilities show that K-Paths is a valuable tool for efficient data-driven drug discovery.

  • 7 authors
·
Feb 18, 2025

OncoReason: Structuring Clinical Reasoning in LLMs for Robust and Interpretable Survival Prediction

Predicting cancer treatment outcomes requires models that are both accurate and interpretable, particularly in the presence of heterogeneous clinical data. While large language models (LLMs) have shown strong performance in biomedical NLP, they often lack structured reasoning capabilities critical for high-stakes decision support. We present a unified, multi-task learning framework that aligns autoregressive LLMs with clinical reasoning for outcome prediction on the MSK-CHORD dataset. Our models are trained to jointly perform binary survival classification, continuous survival time regression, and natural language rationale generation. We evaluate three alignment strategies: (1) standard supervised fine-tuning (SFT), (2) SFT with Chain-of-Thought (CoT) prompting to elicit step-by-step reasoning, and (3) Group Relative Policy Optimization (GRPO), a reinforcement learning method that aligns model outputs to expert-derived reasoning trajectories. Experiments with LLaMa3-8B and Med42-8B backbones demonstrate that CoT prompting improves F1 by +6.0 and reduces MAE by 12%, while GRPO achieves state-of-the-art interpretability and predictive performance across BLEU, ROUGE, and BERTScore. We further show that existing biomedical LLMs often fail to produce valid reasoning traces due to architectural constraints. Our findings underscore the importance of reasoning-aware alignment in multi-task clinical modeling and set a new benchmark for interpretable, trustworthy LLMs in precision oncology.

  • 4 authors
·
Oct 20, 2025

Rapid Biomedical Research Classification: The Pandemic PACT Advanced Categorisation Engine

This paper introduces the Pandemic PACT Advanced Categorisation Engine (PPACE) along with its associated dataset. PPACE is a fine-tuned model developed to automatically classify research abstracts from funded biomedical projects according to WHO-aligned research priorities. This task is crucial for monitoring research trends and identifying gaps in global health preparedness and response. Our approach builds on human-annotated projects, which are allocated one or more categories from a predefined list. A large language model is then used to generate `rationales' explaining the reasoning behind these annotations. This augmented data, comprising expert annotations and rationales, is subsequently used to fine-tune a smaller, more efficient model. Developed as part of the Pandemic PACT project, which aims to track and analyse research funding and clinical evidence for a wide range of diseases with outbreak potential, PPACE supports informed decision-making by research funders, policymakers, and independent researchers. We introduce and release both the trained model and the instruction-based dataset used for its training. Our evaluation shows that PPACE significantly outperforms its baselines. The release of PPACE and its associated dataset offers valuable resources for researchers in multilabel biomedical document classification and supports advancements in aligning biomedical research with key global health priorities.

  • 14 authors
·
Jul 14, 2024

TxAgent: An AI Agent for Therapeutic Reasoning Across a Universe of Tools

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

  • 8 authors
·
Mar 13, 2025 3

MicroVQA++: High-Quality Microscopy Reasoning Dataset with Weakly Supervised Graphs for Multimodal Large Language Model

Multimodal Large Language Models are increasingly applied to biomedical imaging, yet scientific reasoning for microscopy remains limited by the scarcity of large-scale, high-quality training data. We introduce MicroVQA++, a three-stage, large-scale and high-quality microscopy VQA corpus derived from the BIOMEDICA archive. Stage one bootstraps supervision from expert-validated figure-caption pairs sourced from peer-reviewed articles. Stage two applies HiCQA-Graph, a novel heterogeneous graph over images, captions, and QAs that fuses NLI-based textual entailment, CLIP-based vision-language alignment, and agent signals to identify and filter inconsistent samples. Stage three uses a MultiModal Large Language Model (MLLM) agent to generate multiple-choice questions (MCQ) followed by human screening. The resulting release comprises a large training split and a human-checked test split whose Bloom's level hard-sample distribution exceeds the MicroVQA benchmark. Our work delivers (i) a quality-controlled dataset that couples expert literature with graph-based filtering and human refinement; (ii) HiCQA-Graph, the first graph that jointly models (image, caption, QA) for cross-modal consistency filtering; (iii) evidence that careful data construction enables 4B-scale MLLMs to reach competitive microscopy reasoning performance (e.g., GPT-5) and achieve state-of-the-art performance among open-source MLLMs. Code and dataset will be released after the review process concludes.

  • 5 authors
·
Nov 14, 2025 2

From LLM Reasoning to Autonomous AI Agents: A Comprehensive Review

Large language models and autonomous AI agents have evolved rapidly, resulting in a diverse array of evaluation benchmarks, frameworks, and collaboration protocols. However, the landscape remains fragmented and lacks a unified taxonomy or comprehensive survey. Therefore, we present a side-by-side comparison of benchmarks developed between 2019 and 2025 that evaluate these models and agents across multiple domains. In addition, we propose a taxonomy of approximately 60 benchmarks that cover general and academic knowledge reasoning, mathematical problem-solving, code generation and software engineering, factual grounding and retrieval, domain-specific evaluations, multimodal and embodied tasks, task orchestration, and interactive assessments. Furthermore, we review AI-agent frameworks introduced between 2023 and 2025 that integrate large language models with modular toolkits to enable autonomous decision-making and multi-step reasoning. Moreover, we present real-world applications of autonomous AI agents in materials science, biomedical research, academic ideation, software engineering, synthetic data generation, chemical reasoning, mathematical problem-solving, geographic information systems, multimedia, healthcare, and finance. We then survey key agent-to-agent collaboration protocols, namely the Agent Communication Protocol (ACP), the Model Context Protocol (MCP), and the Agent-to-Agent Protocol (A2A). Finally, we discuss recommendations for future research, focusing on advanced reasoning strategies, failure modes in multi-agent LLM systems, automated scientific discovery, dynamic tool integration via reinforcement learning, integrated search capabilities, and security vulnerabilities in agent protocols.

  • 3 authors
·
Apr 28, 2025

MicroVQA: A Multimodal Reasoning Benchmark for Microscopy-Based Scientific Research

Scientific research demands sophisticated reasoning over multimodal data, a challenge especially prevalent in biology. Despite recent advances in multimodal large language models (MLLMs) for AI-assisted research, existing multimodal reasoning benchmarks only target up to college-level difficulty, while research-level benchmarks emphasize lower-level perception, falling short of the complex multimodal reasoning needed for scientific discovery. To bridge this gap, we introduce MicroVQA, a visual-question answering (VQA) benchmark designed to assess three reasoning capabilities vital in research workflows: expert image understanding, hypothesis generation, and experiment proposal. MicroVQA consists of 1,042 multiple-choice questions (MCQs) curated by biology experts across diverse microscopy modalities, ensuring VQA samples represent real scientific practice. In constructing the benchmark, we find that standard MCQ generation methods induce language shortcuts, motivating a new two-stage pipeline: an optimized LLM prompt structures question-answer pairs into MCQs; then, an agent-based `RefineBot' updates them to remove shortcuts. Benchmarking on state-of-the-art MLLMs reveal a peak performance of 53\%; models with smaller LLMs only slightly underperform top models, suggesting that language-based reasoning is less challenging than multimodal reasoning; and tuning with scientific articles enhances performance. Expert analysis of chain-of-thought responses shows that perception errors are the most frequent, followed by knowledge errors and then overgeneralization errors. These insights highlight the challenges in multimodal scientific reasoning, showing MicroVQA is a valuable resource advancing AI-driven biomedical research. MicroVQA is available at https://huggingface.co/datasets/jmhb/microvqa, and project page at https://jmhb0.github.io/microvqa.

  • 23 authors
·
Mar 17, 2025 2

Interactive Medical Image Analysis with Concept-based Similarity Reasoning

The ability to interpret and intervene model decisions is important for the adoption of computer-aided diagnosis methods in clinical workflows. Recent concept-based methods link the model predictions with interpretable concepts and modify their activation scores to interact with the model. However, these concepts are at the image level, which hinders the model from pinpointing the exact patches the concepts are activated. Alternatively, prototype-based methods learn representations from training image patches and compare these with test image patches, using the similarity scores for final class prediction. However, interpreting the underlying concepts of these patches can be challenging and often necessitates post-hoc guesswork. To address this issue, this paper introduces the novel Concept-based Similarity Reasoning network (CSR), which offers (i) patch-level prototype with intrinsic concept interpretation, and (ii) spatial interactivity. First, the proposed CSR provides localized explanation by grounding prototypes of each concept on image regions. Second, our model introduces novel spatial-level interaction, allowing doctors to engage directly with specific image areas, making it an intuitive and transparent tool for medical imaging. CSR improves upon prior state-of-the-art interpretable methods by up to 4.5\% across three biomedical datasets. Our code is released at https://github.com/tadeephuy/InteractCSR.

  • 10 authors
·
Mar 9, 2025

Not All Large Language Models (LLMs) Succumb to the "Reversal Curse": A Comparative Study of Deductive Logical Reasoning in BERT and GPT Models

The "Reversal Curse" refers to the scenario where auto-regressive decoder large language models (LLMs), such as ChatGPT, trained on "A is B" fail to learn "B is A", demonstrating a basic failure of logical deduction. This raises a red flag in the use of GPT models for certain general tasks such as constructing knowledge graphs, considering their adherence to this symmetric principle. In our study, we examined a bidirectional LLM, BERT, and found that it is immune to the reversal curse. Driven by ongoing efforts to construct biomedical knowledge graphs with LLMs, we also embarked on evaluating more complex but essential deductive reasoning capabilities. This process included first training encoder and decoder language models to master the intersection (cap) and union (cup) operations on two sets and then moving on to assess their capability to infer different combinations of union (cup) and intersection (cap) operations on three newly created sets. The findings showed that while both encoder and decoder language models, trained for tasks involving two sets (union/intersection), were proficient in such scenarios, they encountered difficulties when dealing with operations that included three sets (various combinations of union and intersection). Our research highlights the distinct characteristics of encoder and decoder models in simple and complex logical reasoning. In practice, the choice between BERT and GPT should be guided by the specific requirements and nature of the task at hand, leveraging their respective strengths in bidirectional context comprehension and sequence prediction.

  • 3 authors
·
Dec 6, 2023

Towards Generalist Biomedical AI

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

  • 32 authors
·
Jul 26, 2023

Domain-Specific Language Model Pretraining for Biomedical Natural Language Processing

Pretraining large neural language models, such as BERT, has led to impressive gains on many natural language processing (NLP) tasks. However, most pretraining efforts focus on general domain corpora, such as newswire and Web. A prevailing assumption is that even domain-specific pretraining can benefit by starting from general-domain language models. In this paper, we challenge this assumption by showing that for domains with abundant unlabeled text, such as biomedicine, pretraining language models from scratch results in substantial gains over continual pretraining of general-domain language models. To facilitate this investigation, we compile a comprehensive biomedical NLP benchmark from publicly-available datasets. Our experiments show that domain-specific pretraining serves as a solid foundation for a wide range of biomedical NLP tasks, leading to new state-of-the-art results across the board. Further, in conducting a thorough evaluation of modeling choices, both for pretraining and task-specific fine-tuning, we discover that some common practices are unnecessary with BERT models, such as using complex tagging schemes in named entity recognition (NER). To help accelerate research in biomedical NLP, we have released our state-of-the-art pretrained and task-specific models for the community, and created a leaderboard featuring our BLURB benchmark (short for Biomedical Language Understanding & Reasoning Benchmark) at https://aka.ms/BLURB.

  • 9 authors
·
Jul 30, 2020 1

Libra: Leveraging Temporal Images for Biomedical Radiology Analysis

Radiology report generation (RRG) is a challenging task, as it requires a thorough understanding of medical images, integration of multiple temporal inputs, and accurate report generation. Effective interpretation of medical images, such as chest X-rays (CXRs), demands sophisticated visual-language reasoning to map visual findings to structured reports. Recent studies have shown that multimodal large language models (MLLMs) can acquire multimodal capabilities by aligning with pre-trained vision encoders. However, current approaches predominantly focus on single-image analysis or utilise rule-based symbolic processing to handle multiple images, thereby overlooking the essential temporal information derived from comparing current images with prior ones. To overcome this critical limitation, we introduce Libra, a temporal-aware MLLM tailored for CXR report generation using temporal images. Libra integrates a radiology-specific image encoder with a MLLM and utilises a novel Temporal Alignment Connector to capture and synthesise temporal information of images across different time points with unprecedented precision. Extensive experiments show that Libra achieves new state-of-the-art performance among the same parameter scale MLLMs for RRG tasks on the MIMIC-CXR. Specifically, Libra improves the RadCliQ metric by 12.9% and makes substantial gains across all lexical metrics compared to previous models.

  • 4 authors
·
Nov 28, 2024 1

Tabular LLMs for Interpretable Few-Shot Alzheimer's Disease Prediction with Multimodal Biomedical Data

Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.

GALAX: Graph-Augmented Language Model for Explainable Reinforcement-Guided Subgraph Reasoning in Precision Medicine

In precision medicine, quantitative multi-omic features, topological context, and textual biological knowledge play vital roles in identifying disease-critical signaling pathways and targets. Existing pipelines capture only part of these-numerical omics ignore topological context, text-centric LLMs lack quantitative grounded reasoning, and graph-only models underuse node semantics and the generalization of LLMs-limiting mechanistic interpretability. Although Process Reward Models (PRMs) aim to guide reasoning in LLMs, they remain limited by unreliable intermediate evaluation, and vulnerability to reward hacking with computational cost. These gaps motivate integrating quantitative multi-omic signals, topological structure with node annotations, and literature-scale text via LLMs, using subgraph reasoning as the principle bridge linking numeric evidence, topological knowledge and language context. Therefore, we propose GALAX (Graph Augmented LAnguage model with eXplainability), an innovative framework that integrates pretrained Graph Neural Networks (GNNs) into Large Language Models (LLMs) via reinforcement guided by a Graph Process Reward Model (GPRM), which generates disease-relevant subgraphs in a step-wise manner initiated by an LLM and iteratively evaluated by a pretrained GNN, enabling process-level supervision without explicit intermediate reasoning annotations. As an application, we also introduced Target-QA, a benchmark combining CRISPR-identified targets, multi-omic profiles, and biomedical graph knowledge across diverse cancer cell lines, which enables GNN pretraining for supervising step-wise graph construction and supports long-context reasoning over text-numeric graphs (TNGs), providing a scalable and biologically grounded framework for explainable, reinforcement-guided subgraph reasoning toward reliable and interpretable target and pathway discovery in precision medicine.

  • 7 authors
·
Sep 25, 2025

Enhancing Domain-Specific Retrieval-Augmented Generation: Synthetic Data Generation and Evaluation using Reasoning Models

Retrieval-Augmented Generation (RAG) systems face significant performance gaps when applied to technical domains requiring precise information extraction from complex documents. Current evaluation methodologies relying on document-level metrics inadequately capture token-resolution retrieval accuracy that is critical for domain-related documents. We propose a framework combining granular evaluation metrics with synthetic data generation to optimize domain-specific RAG performance. First, we introduce token-aware metrics Precision Omega and Intersection-over-Union (IoU) that quantify context preservation versus information density trade-offs inherent in technical texts. Second, we develop a reasoning model-driven pipeline using instruction-tuned LLMs (DeepSeek-R1, DeepSeek-R1 distilled variants, and Phi-4) to generate context-anchored QA pairs with discontinuous reference spans across three specialized corpora: SEC 10-K filings (finance), biomedical abstracts (PubMed), and APT threat reports (cybersecurity). Our empirical analysis reveals critical insights: smaller chunks (less than 10 tokens) improve precision by 31-42% (IoU = 0.071 vs. baseline 0.053) at recall costs (-18%), while domain-specific embedding strategies yield 22% variance in optimal chunk sizing (5-20 tokens). The DeepSeek-R1-Distill-Qwen-32B model demonstrates superior concept alignment (+14% mean IoU over alternatives), though no configuration universally dominates. Financial texts favor larger chunks for risk factor coverage (Recall = 0.81 at size = 20), whereas cybersecurity content benefits from atomic segmentation, Precision Omega = 0.28 at size = 5. Our code is available on https://github.com/aryan-jadon/Synthetic-Data-Generation-and-Evaluation-using-Reasoning-Model

  • 3 authors
·
Feb 21, 2025

SciHorizon-GENE: Benchmarking LLM for Life Sciences Inference from Gene Knowledge to Functional Understanding

Large language models (LLMs) have shown growing promise in biomedical research, particularly for knowledge-driven interpretation tasks. However, their ability to reliably reason from gene-level knowledge to functional understanding, a core requirement for knowledge-enhanced cell atlas interpretation, remains largely underexplored. To address this gap, we introduce SciHorizon-GENE, a large-scale gene-centric benchmark constructed from authoritative biological databases. The benchmark integrates curated knowledge for over 190K human genes and comprises more than 540K questions covering diverse gene-to-function reasoning scenarios relevant to cell type annotation, functional interpretation, and mechanism-oriented analysis. Motivated by behavioral patterns observed in preliminary examinations, SciHorizon-GENE evaluates LLMs along four biologically critical perspectives: research attention sensitivity, hallucination tendency, answer completeness, and literature influence, explicitly targeting failure modes that limit the safe adoption of LLMs in biological interpretation pipelines. We systematically evaluate a wide range of state-of-the-art general-purpose and biomedical LLMs, revealing substantial heterogeneity in gene-level reasoning capabilities and persistent challenges in generating faithful, complete, and literature-grounded functional interpretations. Our benchmark establishes a systematic foundation for analyzing LLM behavior at the gene scale and offers insights for model selection and development, with direct relevance to knowledge-enhanced biological interpretation.

  • 7 authors
·
Jan 19

Dragonfly: Multi-Resolution Zoom Supercharges Large Visual-Language Model

Recent advances in large multimodal models (LMMs) suggest that higher image resolution enhances the fine-grained understanding of image details, crucial for tasks such as visual commonsense reasoning and analyzing biomedical images. However, increasing input resolution poses two main challenges: 1) It extends the context length required by the language model, leading to inefficiencies and hitting the model's context limit; 2) It increases the complexity of visual features, necessitating more training data or more complex architecture. We introduce Dragonfly, a new LMM architecture that enhances fine-grained visual understanding and reasoning about image regions to address these challenges. Dragonfly employs two key strategies: multi-resolution visual encoding and zoom-in patch selection. These strategies allow the model to process high-resolution images efficiently while maintaining reasonable context length. Our experiments on eight popular benchmarks demonstrate that Dragonfly achieves competitive or better performance compared to other architectures, highlighting the effectiveness of our design. Additionally, we finetuned Dragonfly on biomedical instructions, achieving state-of-the-art results on multiple biomedical tasks requiring fine-grained visual understanding, including 92.3% accuracy on the Path-VQA dataset (compared to 83.3% for Med-Gemini) and the highest reported results on biomedical image captioning. To support model training, we curated a visual instruction-tuning dataset with 5.5 million image-instruction samples in the general domain and 1.4 million samples in the biomedical domain. We also conducted ablation studies to characterize the impact of various architectural designs and image resolutions, providing insights for future research on visual instruction alignment. The codebase and model are available at https://github.com/togethercomputer/Dragonfly.

  • 6 authors
·
Jun 3, 2024

MedReason: Eliciting Factual Medical Reasoning Steps in LLMs via Knowledge Graphs

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

  • 15 authors
·
Apr 1, 2025

Medical Reasoning with Large Language Models: A Survey and MR-Bench

Large language models (LLMs) have achieved strong performance on medical exam-style tasks, motivating growing interest in their deployment in real-world clinical settings. However, clinical decision-making is inherently safety-critical, context-dependent, and conducted under evolving evidence. In such situations, reliable LLM performance depends not on factual recall alone, but on robust medical reasoning. In this work, we present a comprehensive review of medical reasoning with LLMs. Grounded in cognitive theories of clinical reasoning, we conceptualize medical reasoning as an iterative process of abduction, deduction, and induction, and organize existing methods into seven major technical routes spanning training-based and training-free approaches. We further conduct a unified cross-benchmark evaluation of representative medical reasoning models under a consistent experimental setting, enabling a more systematic and comparable assessment of the empirical impact of existing methods. To better assess clinically grounded reasoning, we introduce MR-Bench, a benchmark derived from real-world hospital data. Evaluations on MR-Bench expose a pronounced gap between exam-level performance and accuracy on authentic clinical decision tasks. Overall, this survey provides a unified view of existing medical reasoning methods, benchmarks, and evaluation practices, and highlights key gaps between current model performance and the requirements of real-world clinical reasoning.

  • 7 authors
·
Mar 16

Med-R^3: Enhancing Medical Retrieval-Augmented Reasoning of LLMs via Progressive Reinforcement Learning

In medical scenarios, effectively retrieving external knowledge and leveraging it for rigorous logical reasoning is of significant importance. Despite their potential, existing work has predominantly focused on enhancing either retrieval or reasoning capabilities of the models in isolation, with little attention given to their joint optimization, which leads to limited coordination between the two processes. Additionally, current methods rely heavily on supervised fine-tuning (SFT), which can cause models to memorize existing problem-solving pathways, thereby restricting their generalization ability when confronted with novel problem contexts. Furthermore, while some studies have explored to improve retrieval-augmented reasoning in general domains via reinforcement learning, their reward function designs do not adequately capture the specific demands of the medical domain. To address these challenges, we introduce **Med-R^3**, a **Med**ical **R**etrieval-augmented **R**easoning framework driven by progressive **R**einforcement learning. In this framework, we first develop the model's ability to perform logical reasoning over medical problems. Subsequently, on the basis of this foundation, we adaptively optimize the retrieval capability to better align with the characteristics of knowledge corpus and external information utilization throughout the reasoning process. Finally, we conduct joint optimization of the model's retrieval and reasoning coordination. Extensive experiments indicate that **Med-R^3** could achieve state-of-the-art performances, with LLaMA3.1-8B-Instruct + Med-R^3 surpassing closed-sourced GPT-4o-mini by 3.93\% at a comparable parameter scale, while Qwen2.5-14B augmented with Med-R^3 shows a more substantial gain of 13.53\%.

  • 10 authors
·
Jul 31, 2025

X-Reasoner: Towards Generalizable Reasoning Across Modalities and Domains

Recent proprietary models (e.g., o3) have begun to demonstrate strong multimodal reasoning capabilities. Yet, most existing open-source research concentrates on training text-only reasoning models, with evaluations limited to mainly mathematical and general-domain tasks. Therefore, it remains unclear how to effectively extend reasoning capabilities beyond text input and general domains. This paper explores a fundamental research question: Is reasoning generalizable across modalities and domains? Our findings support an affirmative answer: General-domain text-based post-training can enable such strong generalizable reasoning. Leveraging this finding, we introduce X-Reasoner, a vision-language model post-trained solely on general-domain text for generalizable reasoning, using a two-stage approach: an initial supervised fine-tuning phase with distilled long chain-of-thoughts, followed by reinforcement learning with verifiable rewards. Experiments show that X-Reasoner successfully transfers reasoning capabilities to both multimodal and out-of-domain settings, outperforming existing state-of-the-art models trained with in-domain and multimodal data across various general and medical benchmarks (Figure 1). Additionally, we find that X-Reasoner's performance in specialized domains can be further enhanced through continued training on domain-specific text-only data. Building upon this, we introduce X-Reasoner-Med, a medical-specialized variant that achieves new state of the art on numerous text-only and multimodal medical benchmarks.

  • 12 authors
·
May 6, 2025 3

MedCalc-Bench: Evaluating Large Language Models for Medical Calculations

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

  • 17 authors
·
Jun 17, 2024

Fleming-R1: Toward Expert-Level Medical Reasoning via Reinforcement Learning

While large language models show promise in medical applications, achieving expert-level clinical reasoning remains challenging due to the need for both accurate answers and transparent reasoning processes. To address this challenge, we introduce Fleming-R1, a model designed for verifiable medical reasoning through three complementary innovations. First, our Reasoning-Oriented Data Strategy (RODS) combines curated medical QA datasets with knowledge-graph-guided synthesis to improve coverage of underrepresented diseases, drugs, and multi-hop reasoning chains. Second, we employ Chain-of-Thought (CoT) cold start to distill high-quality reasoning trajectories from teacher models, establishing robust inference priors. Third, we implement a two-stage Reinforcement Learning from Verifiable Rewards (RLVR) framework using Group Relative Policy Optimization, which consolidates core reasoning skills while targeting persistent failure modes through adaptive hard-sample mining. Across diverse medical benchmarks, Fleming-R1 delivers substantial parameter-efficient improvements: the 7B variant surpasses much larger baselines, while the 32B model achieves near-parity with GPT-4o and consistently outperforms strong open-source alternatives. These results demonstrate that structured data design, reasoning-oriented initialization, and verifiable reinforcement learning can advance clinical reasoning beyond simple accuracy optimization. We release Fleming-R1 publicly to promote transparent, reproducible, and auditable progress in medical AI, enabling safer deployment in high-stakes clinical environments.

  • 7 authors
·
Sep 18, 2025

Proactive Reasoning-with-Retrieval Framework for Medical Multimodal Large Language Models

Incentivizing the reasoning ability of Multimodal Large Language Models (MLLMs) is essential for medical applications to transparently analyze medical scans and provide reliable diagnosis. However, existing medical MLLMs rely solely on internal knowledge during reasoning, leading to hallucinated reasoning and factual inaccuracies when encountering cases beyond their training scope. Although recent Agentic Retrieval-Augmented Generation (RAG) methods elicit the medical model's proactive retrieval ability during reasoning, they are confined to unimodal LLMs, neglecting the crucial visual information during reasoning and retrieval. Consequently, we propose the first Multimodal Medical Reasoning-with-Retrieval framework, Med-RwR, which actively retrieves external knowledge by querying observed symptoms or domain-specific medical concepts during reasoning. Specifically, we design a two-stage reinforcement learning strategy with tailored rewards that stimulate the model to leverage both visual diagnostic findings and textual clinical information for effective retrieval. Building on this foundation, we further propose a Confidence-Driven Image Re-retrieval (CDIR) method for test-time scaling when low prediction confidence is detected. Evaluation on various public medical benchmarks demonstrates Med-RwR's significant improvements over baseline models, proving the effectiveness of enhancing reasoning capabilities with external knowledge integration. Furthermore, Med-RwR demonstrates remarkable generalizability to unfamiliar domains, evidenced by 8.8% performance gain on our proposed EchoCardiography Benchmark (ECBench), despite the scarcity of echocardiography data in the training corpus. Our data, model, and codes will be made publicly available at https://github.com/xmed-lab/Med-RwR.

  • 4 authors
·
Oct 21, 2025

Med-REFL: Medical Reasoning Enhancement via Self-Corrected Fine-grained Reflection

Large reasoning models have recently made significant strides in mathematical and code reasoning, yet their success has not transferred smoothly to the medical domain. While multiple factors contribute to this disparity, a critical issue is the inadequate focus on the quality of intermediate reflection steps, which is particularly crucial in high-stakes medical scenarios. To address this challenge, we propose Med-REFL, a \textbf{Med}ical \textbf{R}easoning \textbf{E}nhancement via self-corrected \textbf{F}ine-grained ref\textbf{L}ection. Our method leverages a tree-of-thought approach to decompose medical questions into fine-grained reasoning paths, quantitatively evaluating each step and its subsequent reflections. These assessments enable automatic construction of direct preference optimization data, reducing reliance on expensive expert annotations while guiding models to identify and correct reasoning errors. Experimental results on the MedQA-USMLE benchmark demonstrate Med-REFL achieves consistent improvements, with average gains up to 4.11\%. Notably, it further boosts the state-of-the-art performance of 7B/8B models by an additional 4.13\%. Furthermore, Med-REFL exhibits strong generalization capabilities and robustness across several challenging medical question-answering datasets. Our work illustrates that prioritizing reflection quality leads to more accurate and trustworthy reasoning in medical AI applications. Checkpoints, code, and data can be found https://github.com/TianYin123/Med-REFL{here}.

  • 5 authors
·
Jun 11, 2025 1

Citrus: Leveraging Expert Cognitive Pathways in a Medical Language Model for Advanced Medical Decision Support

Large language models (LLMs), particularly those with reasoning capabilities, have rapidly advanced in recent years, demonstrating significant potential across a wide range of applications. However, their deployment in healthcare, especially in disease reasoning tasks, is hindered by the challenge of acquiring expert-level cognitive data. In this paper, we introduce Citrus, a medical language model that bridges the gap between clinical expertise and AI reasoning by emulating the cognitive processes of medical experts. The model is trained on a large corpus of simulated expert disease reasoning data, synthesized using a novel approach that accurately captures the decision-making pathways of clinicians. This approach enables Citrus to better simulate the complex reasoning processes involved in diagnosing and treating medical conditions.To further address the lack of publicly available datasets for medical reasoning tasks, we release the last-stage training data, including a custom-built medical diagnostic dialogue dataset. This open-source contribution aims to support further research and development in the field. Evaluations using authoritative benchmarks such as MedQA, covering tasks in medical reasoning and language understanding, show that Citrus achieves superior performance compared to other models of similar size. These results highlight Citrus potential to significantly enhance medical decision support systems, providing a more accurate and efficient tool for clinical decision-making.

  • 12 authors
·
Feb 25, 2025

Quantifying the Reasoning Abilities of LLMs on Real-world Clinical Cases

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.

  • 10 authors
·
Mar 6, 2025

Towards LogiGLUE: A Brief Survey and A Benchmark for Analyzing Logical Reasoning Capabilities of Language Models

Logical reasoning is fundamental for humans yet presents a substantial challenge in the domain of Artificial Intelligence. Initially, researchers used Knowledge Representation and Reasoning (KR) systems that did not scale and required non trivial manual effort. Recently, the emergence of large language models (LLMs) has demonstrated the ability to overcome various limitations of formal Knowledge Representation (KR) systems. Consequently, there is a growing interest in using LLMs for logical reasoning via natural language. This work strives to understand the proficiency of LLMs in logical reasoning by offering a brief review of the latest progress in this area; with a focus on the logical reasoning datasets, tasks, and the methods adopted to utilize LLMs for reasoning. To offer a thorough analysis, we have compiled a benchmark titled LogiGLUE. This includes 24 varied datasets encompassing deductive, abductive, and inductive reasoning. We have standardized these datasets into Seq2Seq tasks to facilitate straightforward training and evaluation for future research. Utilizing LogiGLUE as a foundation, we have trained an instruction fine tuned language model, resulting in LogiT5. We study single task training, multi task training, and a chain of thought knowledge distillation fine tuning technique to assess the performance of model across the different logical reasoning categories. By this comprehensive process, we aim to shed light on the capabilities and potential pathways for enhancing logical reasoning proficiency in LLMs, paving the way for more advanced and nuanced developments in this critical field.

  • 8 authors
·
Oct 1, 2023

MME-Reasoning: A Comprehensive Benchmark for Logical Reasoning in MLLMs

Logical reasoning is a fundamental aspect of human intelligence and an essential capability for multimodal large language models (MLLMs). Despite the significant advancement in multimodal reasoning, existing benchmarks fail to comprehensively evaluate their reasoning abilities due to the lack of explicit categorization for logical reasoning types and an unclear understanding of reasoning. To address these issues, we introduce MME-Reasoning, a comprehensive benchmark designed to evaluate the reasoning ability of MLLMs, which covers all three types of reasoning (i.e., inductive, deductive, and abductive) in its questions. We carefully curate the data to ensure that each question effectively evaluates reasoning ability rather than perceptual skills or knowledge breadth, and extend the evaluation protocols to cover the evaluation of diverse questions. Our evaluation reveals substantial limitations of state-of-the-art MLLMs when subjected to holistic assessments of logical reasoning capabilities. Even the most advanced MLLMs show limited performance in comprehensive logical reasoning, with notable performance imbalances across reasoning types. In addition, we conducted an in-depth analysis of approaches such as ``thinking mode'' and Rule-based RL, which are commonly believed to enhance reasoning abilities. These findings highlight the critical limitations and performance imbalances of current MLLMs in diverse logical reasoning scenarios, providing comprehensive and systematic insights into the understanding and evaluation of reasoning capabilities.

  • 11 authors
·
May 27, 2025 3

MedVLM-R1: Incentivizing Medical Reasoning Capability of Vision-Language Models (VLMs) via Reinforcement Learning

Reasoning is a critical frontier for advancing medical image analysis, where transparency and trustworthiness play a central role in both clinician trust and regulatory approval. Although Medical Visual Language Models (VLMs) show promise for radiological tasks, most existing VLMs merely produce final answers without revealing the underlying reasoning. To address this gap, we introduce MedVLM-R1, a medical VLM that explicitly generates natural language reasoning to enhance transparency and trustworthiness. Instead of relying on supervised fine-tuning (SFT), which often suffers from overfitting to training distributions and fails to foster genuine reasoning, MedVLM-R1 employs a reinforcement learning framework that incentivizes the model to discover human-interpretable reasoning paths without using any reasoning references. Despite limited training data (600 visual question answering samples) and model parameters (2B), MedVLM-R1 boosts accuracy from 55.11% to 78.22% across MRI, CT, and X-ray benchmarks, outperforming larger models trained on over a million samples. It also demonstrates robust domain generalization under out-of-distribution tasks. By unifying medical image analysis with explicit reasoning, MedVLM-R1 marks a pivotal step toward trustworthy and interpretable AI in clinical practice. Inference model is available at: https://huggingface.co/JZPeterPan/MedVLM-R1.

  • 9 authors
·
Mar 18, 2025 3

Beyond Distillation: Pushing the Limits of Medical LLM Reasoning with Minimalist Rule-Based RL

Improving performance on complex tasks and enabling interpretable decision making in large language models (LLMs), especially for clinical applications, requires effective reasoning. Yet this remains challenging without supervised fine-tuning (SFT) on costly chain-of-thought (CoT) data distilled from closed-source models (e.g., GPT-4o). In this work, we present AlphaMed, the first medical LLM to show that reasoning capability can emerge purely through reinforcement learning (RL), using minimalist rule-based rewards on public multiple-choice QA datasets, without relying on SFT or distilled CoT data. AlphaMed achieves state-of-the-art results on six medical QA benchmarks, outperforming models trained with conventional SFT+RL pipelines. On challenging benchmarks (e.g., MedXpert), AlphaMed even surpasses larger or closed-source models such as DeepSeek-V3-671B and Claude-3.5-Sonnet. To understand the factors behind this success, we conduct a comprehensive data-centric analysis guided by three questions: (i) Can minimalist rule-based RL incentivize reasoning without distilled CoT supervision? (ii) How do dataset quantity and diversity impact reasoning? (iii) How does question difficulty shape the emergence and generalization of reasoning? Our findings show that dataset informativeness is a key driver of reasoning performance, and that minimalist RL on informative, multiple-choice QA data is effective at inducing reasoning without CoT supervision. We also observe divergent trends across benchmarks, underscoring limitations in current evaluation and the need for more challenging, reasoning-oriented medical QA benchmarks.

  • 9 authors
·
May 23, 2025 2

Incentivizing Tool-augmented Thinking with Images for Medical Image Analysis

Recent reasoning based medical MLLMs have made progress in generating step by step textual reasoning chains. However, they still struggle with complex tasks that necessitate dynamic and iterative focusing on fine-grained visual regions to achieve precise grounding and diagnosis. We introduce Ophiuchus, a versatile, tool-augmented framework that equips an MLLM to (i) decide when additional visual evidence is needed, (ii) determine where to probe and ground within the medical image, and (iii) seamlessly weave the relevant sub-image content back into an interleaved, multimodal chain of thought. In contrast to prior approaches limited by the performance ceiling of specialized tools, Ophiuchus integrates the model's inherent grounding and perception capabilities with external tools, thereby fostering higher-level reasoning. The core of our method is a three-stage training strategy: cold-start training with tool-integrated reasoning data to achieve basic tool selection and adaptation for inspecting key regions; self-reflection fine-tuning to strengthen reflective reasoning and encourage revisiting tool outputs; and Agentic Tool Reinforcement Learning to directly optimize task-specific rewards and emulate expert-like diagnostic behavior. Extensive experiments show that Ophiuchus consistently outperforms both closed-source and open-source SOTA methods across diverse medical benchmarks, including VQA, detection, and reasoning-based segmentation. Our approach illuminates a path toward medical AI agents that can genuinely "think with images" through tool-integrated reasoning. Datasets, codes, and trained models will be released publicly.

  • 7 authors
·
Dec 16, 2025 1

WiNGPT-3.0 Technical Report

Current Large Language Models (LLMs) exhibit significant limitations, notably in structured, interpretable, and verifiable medical reasoning, alongside practical deployment challenges related to computational resources and data privacy. This report focused on the development of WiNGPT-3.0, the 32-billion parameter LLMs, engineered with the objective of enhancing its capacity for medical reasoning and exploring its potential for effective integration within healthcare IT infrastructures. The broader aim is to advance towards clinically applicable models. The approach involved a multi-stage training pipeline tailored for general, medical, and clinical reasoning. This pipeline incorporated supervised fine-tuning (SFT) and reinforcement learning (RL), leveraging curated Long Chain-of-Thought (CoT) datasets, auxiliary reward models, and an evidence-based diagnostic chain simulation. WiNGPT-3.0 demonstrated strong performance: specific model variants achieved scores of 66.6 on MedCalc and 87.1 on MedQA-USMLE. Furthermore, targeted training improved performance on a clinical reasoning task from a baseline score of 58.1 to 62.5. These findings suggest that reinforcement learning, even when applied with a limited dataset of only a few thousand examples, can enhance medical reasoning accuracy. Crucially, this demonstration of RL's efficacy with limited data and computation paves the way for more trustworthy and practically deployable LLMs within clinical workflows and health information infrastructures.

  • 13 authors
·
May 22, 2025

LINC: A Neurosymbolic Approach for Logical Reasoning by Combining Language Models with First-Order Logic Provers

Logical reasoning, i.e., deductively inferring the truth value of a conclusion from a set of premises, is an important task for artificial intelligence with wide potential impacts on science, mathematics, and society. While many prompting-based strategies have been proposed to enable Large Language Models (LLMs) to do such reasoning more effectively, they still appear unsatisfactory, often failing in subtle and unpredictable ways. In this work, we investigate the validity of instead reformulating such tasks as modular neurosymbolic programming, which we call LINC: Logical Inference via Neurosymbolic Computation. In LINC, the LLM acts as a semantic parser, translating premises and conclusions from natural language to expressions in first-order logic. These expressions are then offloaded to an external theorem prover, which symbolically performs deductive inference. Leveraging this approach, we observe significant performance gains on FOLIO and a balanced subset of ProofWriter for three different models in nearly all experimental conditions we evaluate. On ProofWriter, augmenting the comparatively small open-source StarCoder+ (15.5B parameters) with LINC even outperforms GPT-3.5 and GPT-4 with Chain-of-Thought (CoT) prompting by an absolute 38% and 10%, respectively. When used with GPT-4, LINC scores 26% higher than CoT on ProofWriter while performing comparatively on FOLIO. Further analysis reveals that although both methods on average succeed roughly equally often on this dataset, they exhibit distinct and complementary failure modes. We thus provide promising evidence for how logical reasoning over natural language can be tackled through jointly leveraging LLMs alongside symbolic provers. All corresponding code is publicly available at https://github.com/benlipkin/linc

  • 7 authors
·
Oct 23, 2023

Medical Adaptation of Large Language and Vision-Language Models: Are We Making Progress?

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

  • 4 authors
·
Nov 6, 2024

MedVLThinker: Simple Baselines for Multimodal Medical Reasoning

Large Reasoning Models (LRMs) have introduced a new paradigm in AI by enabling models to ``think before responding" via chain-of-thought reasoning. However, the absence of open and reproducible recipes for building reasoning-centric medical LMMs hinders community-wide research, analysis, and comparison. In this paper, we present MedVLThinker, a suite of simple yet strong baselines. Our fully open recipe consists of: (1) systematic data curation for both text-only and image-text medical data, filtered according to varying levels of reasoning difficulty, and (2) two training paradigms: Supervised Fine-Tuning (SFT) on distilled reasoning traces and Reinforcement Learning with Verifiable Rewards (RLVR) based on final answer correctness. Across extensive experiments on the Qwen2.5-VL model family (3B, 7B) and six medical QA benchmarks, we find that RLVR consistently and significantly outperforms SFT. Additionally, under the RLVR framework, a key, counter-intuitive finding is that training on our curated text-only reasoning data provides a more substantial performance boost than training on multimodal image-text data. Our best open 7B model, trained using the RLVR recipe on text-only data, establishes a new state-of-the-art on existing public VQA benchmarks, surpassing all previous open-source medical LMMs. Furthermore, scaling our model to 32B achieves performance on par with the proprietary GPT-4o. We release all curated data, models, and code to provide the community with a strong, open foundation for future research in multimodal medical reasoning.

  • 5 authors
·
Aug 4, 2025

Enhancing Step-by-Step and Verifiable Medical Reasoning in MLLMs

Multimodal large language models (MLLMs) have begun to demonstrate robust reasoning capabilities on general tasks, yet their application in the medical domain remains in its early stages. Constructing chain-of-thought (CoT) training data is essential for bolstering the reasoning abilities of medical MLLMs. However, existing approaches exhibit a deficiency in offering a comprehensive framework for searching and evaluating effective reasoning paths towards critical diagnosis. To address this challenge, we propose Mentor-Intern Collaborative Search (MICS), a novel reasoning-path searching scheme to generate rigorous and effective medical CoT data. MICS first leverages mentor models to initialize the reasoning, one step at a time, then prompts each intern model to continue the thinking along those initiated paths, and finally selects the optimal reasoning path according to the overall reasoning performance of multiple intern models. The reasoning performance is determined by an MICS-Score, which assesses the quality of generated reasoning paths. Eventually, we construct MMRP, a multi-task medical reasoning dataset with ranked difficulty, and Chiron-o1, a new medical MLLM devised via a curriculum learning strategy, with robust visual question-answering and generalizable reasoning capabilities. Extensive experiments demonstrate that Chiron-o1, trained on our CoT dataset constructed using MICS, achieves state-of-the-art performance across a list of medical visual question answering and reasoning benchmarks. Codes are available at GitHub - manglu097/Chiron-o1: Enhancing Step-by-Step and Verifiable Medical Reasoning in MLLMs

  • 9 authors
·
Jun 20, 2025 3

Bridging the Gap in Ophthalmic AI: MM-Retinal-Reason Dataset and OphthaReason Model toward Dynamic Multimodal Reasoning

Multimodal large language models (MLLMs) have recently demonstrated remarkable reasoning abilities with reinforcement learning paradigm. Although several multimodal reasoning models have been explored in the medical domain, most of them focus exclusively on basic reasoning, which refers to shallow inference based on visual feature matching. However, real-world clinical diagnosis extends beyond basic reasoning, demanding reasoning processes that integrate heterogeneous clinical information (such as chief complaints and medical history) with multimodal medical imaging data. To bridge this gap, we introduce MM-Retinal-Reason, the first ophthalmic multimodal dataset with the full spectrum of perception and reasoning. It encompasses both basic reasoning tasks and complex reasoning tasks, aiming to enhance visual-centric fundamental reasoning capabilities and emulate realistic clinical thinking patterns. Building upon MM-Retinal-Reason, we propose OphthaReason, the first ophthalmology-specific multimodal reasoning model with step-by-step reasoning traces. To enable flexible adaptation to both basic and complex reasoning tasks, we specifically design a novel method called Uncertainty-Aware Dynamic Thinking (UADT), which estimates sample-level uncertainty via entropy and dynamically modulates the model's exploration depth using a shaped advantage mechanism. Comprehensive experiments demonstrate that our model achieves state-of-the-art performance on both basic and complex reasoning tasks, outperforming general-purpose MLLMs, medical MLLMs, RL-based medical MLLMs, and ophthalmic MLLMs by at least 24.92\%, 15.00\%, 21.20\%, and 17.66\%. Project Page: https://github.com/lxirich/OphthaReason{link}.

  • 9 authors
·
Aug 22, 2025

A Preliminary Study of o1 in Medicine: Are We Closer to an AI Doctor?

Large language models (LLMs) have exhibited remarkable capabilities across various domains and tasks, pushing the boundaries of our knowledge in learning and cognition. The latest model, OpenAI's o1, stands out as the first LLM with an internalized chain-of-thought technique using reinforcement learning strategies. While it has demonstrated surprisingly strong capabilities on various general language tasks, its performance in specialized fields such as medicine remains unknown. To this end, this report provides a comprehensive exploration of o1 on different medical scenarios, examining 3 key aspects: understanding, reasoning, and multilinguality. Specifically, our evaluation encompasses 6 tasks using data from 37 medical datasets, including two newly constructed and more challenging question-answering (QA) tasks based on professional medical quizzes from the New England Journal of Medicine (NEJM) and The Lancet. These datasets offer greater clinical relevance compared to standard medical QA benchmarks such as MedQA, translating more effectively into real-world clinical utility. Our analysis of o1 suggests that the enhanced reasoning ability of LLMs may (significantly) benefit their capability to understand various medical instructions and reason through complex clinical scenarios. Notably, o1 surpasses the previous GPT-4 in accuracy by an average of 6.2% and 6.6% across 19 datasets and two newly created complex QA scenarios. But meanwhile, we identify several weaknesses in both the model capability and the existing evaluation protocols, including hallucination, inconsistent multilingual ability, and discrepant metrics for evaluation. We release our raw data and model outputs at https://ucsc-vlaa.github.io/o1_medicine/ for future research.

  • 9 authors
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Sep 23, 2024 2

CasiMedicos-Arg: A Medical Question Answering Dataset Annotated with Explanatory Argumentative Structures

Explaining Artificial Intelligence (AI) decisions is a major challenge nowadays in AI, in particular when applied to sensitive scenarios like medicine and law. However, the need to explain the rationale behind decisions is a main issue also for human-based deliberation as it is important to justify why a certain decision has been taken. Resident medical doctors for instance are required not only to provide a (possibly correct) diagnosis, but also to explain how they reached a certain conclusion. Developing new tools to aid residents to train their explanation skills is therefore a central objective of AI in education. In this paper, we follow this direction, and we present, to the best of our knowledge, the first multilingual dataset for Medical Question Answering where correct and incorrect diagnoses for a clinical case are enriched with a natural language explanation written by doctors. These explanations have been manually annotated with argument components (i.e., premise, claim) and argument relations (i.e., attack, support), resulting in the Multilingual CasiMedicos-Arg dataset which consists of 558 clinical cases in four languages (English, Spanish, French, Italian) with explanations, where we annotated 5021 claims, 2313 premises, 2431 support relations, and 1106 attack relations. We conclude by showing how competitive baselines perform over this challenging dataset for the argument mining task.

  • 6 authors
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Oct 7, 2024

Med-R1: Reinforcement Learning for Generalizable Medical Reasoning in Vision-Language Models

Vision-language models (VLMs) have advanced reasoning in natural scenes, but their role in medical imaging remains underexplored. Medical reasoning tasks demand robust image analysis and well-justified answers, posing challenges due to the complexity of medical images. Transparency and trustworthiness are essential for clinical adoption and regulatory compliance. We introduce Med-R1, a framework exploring reinforcement learning (RL) to enhance VLMs' generalizability and trustworthiness in medical reasoning. Leveraging the DeepSeek strategy, we employ Group Relative Policy Optimization (GRPO) to guide reasoning paths via reward signals. Unlike supervised fine-tuning (SFT), which often overfits and lacks generalization, RL fosters robust and diverse reasoning. Med-R1 is evaluated across eight medical imaging modalities: CT, MRI, Ultrasound, Dermoscopy, Fundus Photography, Optical Coherence Tomography (OCT), Microscopy, and X-ray Imaging. Compared to its base model, Qwen2-VL-2B, Med-R1 achieves a 29.94% accuracy improvement and outperforms Qwen2-VL-72B, which has 36 times more parameters. Testing across five question types-modality recognition, anatomy identification, disease diagnosis, lesion grading, and biological attribute analysis Med-R1 demonstrates superior generalization, exceeding Qwen2-VL-2B by 32.06% and surpassing Qwen2-VL-72B in question-type generalization. These findings show that RL improves medical reasoning and enables parameter-efficient models to outperform significantly larger ones. With interpretable reasoning outputs, Med-R1 represents a promising step toward generalizable, trustworthy, and clinically viable medical VLMs.

  • 5 authors
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Mar 18, 2025

Proceedings of the First International Workshop on Next-Generation Language Models for Knowledge Representation and Reasoning (NeLaMKRR 2024)

Reasoning is an essential component of human intelligence as it plays a fundamental role in our ability to think critically, support responsible decisions, and solve challenging problems. Traditionally, AI has addressed reasoning in the context of logic-based representations of knowledge. However, the recent leap forward in natural language processing, with the emergence of language models based on transformers, is hinting at the possibility that these models exhibit reasoning abilities, particularly as they grow in size and are trained on more data. Despite ongoing discussions about what reasoning is in language models, it is still not easy to pin down to what extent these models are actually capable of reasoning. The goal of this workshop is to create a platform for researchers from different disciplines and/or AI perspectives, to explore approaches and techniques with the aim to reconcile reasoning between language models using transformers and using logic-based representations. The specific objectives include analyzing the reasoning abilities of language models measured alongside KR methods, injecting KR-style reasoning abilities into language models (including by neuro-symbolic means), and formalizing the kind of reasoning language models carry out. This exploration aims to uncover how language models can effectively integrate and leverage knowledge and reasoning with it, thus improving their application and utility in areas where precision and reliability are a key requirement.

  • 5 authors
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Oct 6, 2024

R2MED: A Benchmark for Reasoning-Driven Medical Retrieval

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED

  • 3 authors
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May 20, 2025

Are Large Language Models Really Good Logical Reasoners? A Comprehensive Evaluation and Beyond

Logical reasoning consistently plays a fundamental and significant role in the domains of knowledge engineering and artificial intelligence. Recently, Large Language Models (LLMs) have emerged as a noteworthy innovation in natural language processing (NLP), exhibiting impressive achievements across various classic NLP tasks. However, the question of whether LLMs can effectively address the task of logical reasoning, which requires gradual cognitive inference similar to human intelligence, remains unanswered. To this end, we aim to bridge this gap and provide comprehensive evaluations in this paper. Firstly, to offer systematic evaluations, we select fifteen typical logical reasoning datasets and organize them into deductive, inductive, abductive and mixed-form reasoning settings. Considering the comprehensiveness of evaluations, we include three representative LLMs (i.e., text-davinci-003, ChatGPT and BARD) and evaluate them on all selected datasets under zero-shot, one-shot and three-shot settings. Secondly, different from previous evaluations relying only on simple metrics (e.g., accuracy), we propose fine-level evaluations from objective and subjective manners, covering both answers and explanations. Additionally, to uncover the logical flaws of LLMs, problematic cases will be attributed to five error types from two dimensions, i.e., evidence selection process and reasoning process. Thirdly, to avoid the influences of knowledge bias and purely focus on benchmarking the logical reasoning capability of LLMs, we propose a new dataset with neutral content. It contains 3,000 samples and covers deductive, inductive and abductive settings. Based on the in-depth evaluations, this paper finally forms a general evaluation scheme of logical reasoning capability from six dimensions. It reflects the pros and cons of LLMs and gives guiding directions for future works.

  • 6 authors
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Jun 16, 2023

A Survey of Frontiers in LLM Reasoning: Inference Scaling, Learning to Reason, and Agentic Systems

Reasoning is a fundamental cognitive process that enables logical inference, problem-solving, and decision-making. With the rapid advancement of large language models (LLMs), reasoning has emerged as a key capability that distinguishes advanced AI systems from conventional models that empower chatbots. In this survey, we categorize existing methods along two orthogonal dimensions: (1) Regimes, which define the stage at which reasoning is achieved (either at inference time or through dedicated training); and (2) Architectures, which determine the components involved in the reasoning process, distinguishing between standalone LLMs and agentic compound systems that incorporate external tools, and multi-agent collaborations. Within each dimension, we analyze two key perspectives: (1) Input level, which focuses on techniques that construct high-quality prompts that the LLM condition on; and (2) Output level, which methods that refine multiple sampled candidates to enhance reasoning quality. This categorization provides a systematic understanding of the evolving landscape of LLM reasoning, highlighting emerging trends such as the shift from inference-scaling to learning-to-reason (e.g., DeepSeek-R1), and the transition to agentic workflows (e.g., OpenAI Deep Research, Manus Agent). Additionally, we cover a broad spectrum of learning algorithms, from supervised fine-tuning to reinforcement learning such as PPO and GRPO, and the training of reasoners and verifiers. We also examine key designs of agentic workflows, from established patterns like generator-evaluator and LLM debate to recent innovations. ...

  • 12 authors
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Apr 11, 2025

Eliciting Medical Reasoning with Knowledge-enhanced Data Synthesis: A Semi-Supervised Reinforcement Learning Approach

While large language models hold promise for complex medical applications, their development is hindered by the scarcity of high-quality reasoning data. To address this issue, existing approaches typically distill chain-of-thought reasoning traces from large proprietary models via supervised fine-tuning, then conduct reinforcement learning (RL). These methods exhibit limited improvement on underrepresented domains like rare diseases while incurring substantial costs from generating complex reasoning chains. To efficiently enhance medical reasoning, we propose MedSSR, a Medical Knowledge-enhanced data Synthesis and Semi-supervised Reinforcement learning framework. Our framework first employs rare disease knowledge to synthesize distribution-controllable reasoning questions. We then utilize the policy model itself to generate high-quality pseudo-labels. This enables a two-stage, intrinsic-to-extrinsic training paradigm: self-supervised RL on the pseudo-labeled synthetic data, followed by supervised RL on the human-annotated real data. MedSSR scales model training efficiently without relying on costly trace distillation. Extensive experiments on Qwen and Llama demonstrate that our method outperforms existing methods across ten medical benchmarks, achieving up to +5.93% gain on rare-disease tasks. Our code is available at https://github.com/tdlhl/MedSSR.

  • 6 authors
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Apr 12 2

M3CoTBench: Benchmark Chain-of-Thought of MLLMs in Medical Image Understanding

Chain-of-Thought (CoT) reasoning has proven effective in enhancing large language models by encouraging step-by-step intermediate reasoning, and recent advances have extended this paradigm to Multimodal Large Language Models (MLLMs). In the medical domain, where diagnostic decisions depend on nuanced visual cues and sequential reasoning, CoT aligns naturally with clinical thinking processes. However, Current benchmarks for medical image understanding generally focus on the final answer while ignoring the reasoning path. An opaque process lacks reliable bases for judgment, making it difficult to assist doctors in diagnosis. To address this gap, we introduce a new M3CoTBench benchmark specifically designed to evaluate the correctness, efficiency, impact, and consistency of CoT reasoning in medical image understanding. M3CoTBench features 1) a diverse, multi-level difficulty dataset covering 24 examination types, 2) 13 varying-difficulty tasks, 3) a suite of CoT-specific evaluation metrics (correctness, efficiency, impact, and consistency) tailored to clinical reasoning, and 4) a performance analysis of multiple MLLMs. M3CoTBench systematically evaluates CoT reasoning across diverse medical imaging tasks, revealing current limitations of MLLMs in generating reliable and clinically interpretable reasoning, and aims to foster the development of transparent, trustworthy, and diagnostically accurate AI systems for healthcare. Project page at https://juntaojianggavin.github.io/projects/M3CoTBench/.

  • 10 authors
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Jan 13

BMMR: A Large-Scale Bilingual Multimodal Multi-Discipline Reasoning Dataset

In this paper, we introduce BMMR, a large-scale bilingual, multimodal, multi-disciplinary reasoning dataset for the community to develop and evaluate large multimodal models (LMMs). BMMR comprises 110k college-level questions spanning 300 UNESCO-defined subjects, spanning diverse formats-multiple-choice, fill-in-the-blank, and open-ended QA-and sourced from both print and digital media such as books, exams, and quizzes. All data are curated and filtered via a human-in-the-loop and scalable framework, and each instance is paired with a high-quality reasoning path. The dataset is organized into two parts: BMMR-Eval that comprises 20,458 high-quality instances to comprehensively assess LMMs' knowledge and reasoning across multiple disciplines in both Chinese and English; and BMMR-Train that contains 88,991 instances to support further research and development, extending the current focus on mathematical reasoning to diverse disciplines and domains. In addition, we propose the process-based multi-discipline verifier (i.e., BMMR-Verifier) for accurate and fine-grained evaluation of reasoning paths. Extensive experiments on 24 models reveal that (i) even SOTA models (e.g., o3 and Gemini-2.5-Pro) leave substantial headroom on BMMR-Eval; (ii) reasoning models exhibit discipline bias and outperform LMMs only on specific subjects; (iii) open-source models still trail their proprietary counterparts; and (iv) fine-tuning on BMMR-Train narrows this gap. Additionally, we conduct reasoning-chain analyses using BMMR-Verifier and other in-depth studies, uncovering the challenges LMMs currently face in multidisciplinary reasoning. We will release the data, and we hope our work can offer insights and contributions to the community.

  • 15 authors
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Jul 4, 2025 1

One Sample to Rule Them All: Extreme Data Efficiency in RL Scaling

The reasoning ability of large language models (LLMs) can be unleashed with reinforcement learning (RL) (OpenAI, 2024; DeepSeek-AI et al., 2025a; Zeng et al., 2025). The success of existing RL attempts in LLMs usually relies on high-quality samples of thousands or beyond. In this paper, we challenge fundamental assumptions about data requirements in RL for LLMs by demonstrating the remarkable effectiveness of one-shot learning. Specifically, we introduce polymath learning, a framework for designing one training sample that elicits multidisciplinary impact. We present three key findings: (1) A single, strategically selected math reasoning sample can produce significant performance improvements across multiple domains, including physics, chemistry, and biology with RL; (2) The math skills salient to reasoning suggest the characteristics of the optimal polymath sample; and (3) An engineered synthetic sample that integrates multidiscipline elements outperforms training with individual samples that naturally occur. Our approach achieves superior performance to training with larger datasets across various reasoning benchmarks, demonstrating that sample quality and design, rather than quantity, may be the key to unlock enhanced reasoning capabilities in language models. Our results suggest a shift, dubbed as sample engineering, toward precision engineering of training samples rather than simply increasing data volume.

  • 9 authors
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Jan 6 3

Are Your Reasoning Models Reasoning or Guessing? A Mechanistic Analysis of Hierarchical Reasoning Models

Hierarchical reasoning model (HRM) achieves extraordinary performance on various reasoning tasks, significantly outperforming large language model-based reasoners. To understand the strengths and potential failure modes of HRM, we conduct a mechanistic study on its reasoning patterns and find three surprising facts: (a) Failure of extremely simple puzzles, e.g., HRM can fail on a puzzle with only one unknown cell. We attribute this failure to the violation of the fixed point property, a fundamental assumption of HRM. (b) "Grokking" dynamics in reasoning steps, i.e., the answer is not improved uniformly, but instead there is a critical reasoning step that suddenly makes the answer correct; (c) Existence of multiple fixed points. HRM "guesses" the first fixed point, which could be incorrect, and gets trapped there for a while or forever. All facts imply that HRM appears to be "guessing" instead of "reasoning". Leveraging this "guessing" picture, we propose three strategies to scale HRM's guesses: data augmentation (scaling the quality of guesses), input perturbation (scaling the number of guesses by leveraging inference randomness), and model bootstrapping (scaling the number of guesses by leveraging training randomness). On the practical side, by combining all methods, we develop Augmented HRM, boosting accuracy on Sudoku-Extreme from 54.5% to 96.9%. On the scientific side, our analysis provides new insights into how reasoning models "reason".

  • 2 authors
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Jan 15

Bottom-up Domain-specific Superintelligence: A Reliable Knowledge Graph is What We Need

Language models traditionally used for cross-domain generalization have recently demonstrated task-specific reasoning. However, their top-down training approach on general corpora is insufficient for acquiring abstractions needed for deep domain expertise. This may require a bottom-up approach that acquires expertise by learning to compose simple domain concepts into more complex ones. A knowledge graph (KG) provides this compositional structure, where domain primitives are represented as head-relation-tail edges and their paths encode higher-level concepts. We present a task generation pipeline that synthesizes tasks directly from KG primitives, enabling models to acquire and compose them for reasoning. We fine-tune language models on the resultant KG-grounded curriculum to demonstrate domain-specific superintelligence. While broadly applicable, we validate our approach in medicine, where reliable KGs exist. Using a medical KG, we curate 24,000 reasoning tasks paired with thinking traces derived from diverse medical primitives. We fine-tune the QwQ-32B model on this curriculum to obtain QwQ-Med-3 that takes a step towards medical superintelligence. We also introduce ICD-Bench, an evaluation suite to quantify reasoning abilities across 15 medical domains. Our experiments demonstrate that QwQ-Med-3 significantly outperforms state-of-the-art reasoning models on ICD-Bench categories. Further analysis reveals that QwQ-Med-3 utilizes acquired primitives to widen the performance gap on the hardest tasks of ICD-Bench. Finally, evaluation on medical question-answer benchmarks shows that QwQ-Med-3 transfers acquired expertise to enhance the base model's performance. While the industry's approach to artificial general intelligence (AGI) emphasizes broad expertise, we envision a future in which AGI emerges from the composable interaction of efficient domain-specific superintelligent agents.

  • 3 authors
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Jul 18, 2025

Evaluating Relational Reasoning in LLMs with REL

Relational reasoning is the ability to infer relations that jointly bind multiple entities, attributes, or variables. This ability is central to scientific reasoning, but existing evaluations of relational reasoning in large language models often focus on structured inputs such as tables, graphs, or synthetic tasks, and do not isolate the difficulty introduced by higher-arity relational binding. We study this problem through the lens of Relational Complexity (RC), which we define as the minimum number of independent entities or operands that must be simultaneously bound to apply a relation. RC provides a principled way to vary reasoning difficulty while controlling for confounders such as input size, vocabulary, and representational choices. Building on RC, we introduce REL, a generative benchmark framework spanning algebra, chemistry, and biology that varies RC within each domain. Across frontier LLMs, performance degrades consistently and monotonically as RC increases, even when the total number of entities is held fixed. This failure mode persists with increased test-time compute and in-context learning, suggesting a limitation tied to the arity of the required relational binding rather than to insufficient inference steps or lack of exposure to examples. Our results identify a regime of higher-arity reasoning in which current models struggle, and motivate re-examining benchmarks through the lens of relational complexity.

  • 5 authors
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Apr 13

BioMedGPT-Mol: Multi-task Learning for Molecular Understanding and Generation

Molecules play a crucial role in biomedical research and discovery, particularly in the field of small molecule drug development. Given the rapid advancements in large language models, especially the recent emergence of reasoning models, it is natural to explore how a general-purpose language model can be efficiently adapted for molecular science applications. In this work, we introduce BioMedGPT-Mol, a molecular language model designed to support molecular understanding and generation tasks. By curating and unifying existing public instruction datasets, we have assembled a large-scale, comprehensive, and high-quality training dataset. The model is then fine-tuned through a meticulously designed multi-task learning framework. On a consolidated benchmark derived from LlaSMol, TOMG-Bench, and MuMOInstruct, BioMedGPT-Mol achieves remarkable performance. Our experimental results demonstrate that a general-purpose reasoning model can be effectively and efficiently post-trained into a professional molecular language model through a well-structured multi-task curriculum. Leveraging these capabilities, we further apply the model to multi-step retrosynthetic planning, achieving state-of-the-art performance on RetroBench and demonstrating its superior efficacy as an end-to-end retrosynthetic planner. We anticipate that our approach can be extended to other biomedical scientific domains.

  • 3 authors
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Dec 4, 2025