Guangzhi Xiong

Guangzhi Xiong, Qiao Jin, Xiao Wang et al.

The emergent abilities of large language models (LLMs) have demonstrated great potential in solving medical questions. They can possess considerable medical knowledge, but may still hallucinate and are inflexible in the knowledge updates. While Retrieval-Augmented Generation (RAG) has been proposed to enhance the medical question-answering capabilities of LLMs with external knowledge bases, it may still fail in complex cases where multiple rounds of information-seeking are required. To address such an issue, we propose iterative RAG for medicine (i-MedRAG), where LLMs can iteratively ask follow-up queries based on previous information-seeking attempts. In each iteration of i-MedRAG, the follow-up queries will be answered by a conventional RAG system and they will be further used to guide the query generation in the next iteration. Our experiments show the improved performance of various LLMs brought by i-MedRAG compared with conventional RAG on complex questions from clinical vignettes in the United States Medical Licensing Examination (USMLE), as well as various knowledge tests in the Massive Multitask Language Understanding (MMLU) dataset. Notably, our zero-shot i-MedRAG outperforms all existing prompt engineering and fine-tuning methods on GPT-3.5, achieving an accuracy of 69.68% on the MedQA dataset. In addition, we characterize the scaling properties of i-MedRAG with different iterations of follow-up queries and different numbers of queries per iteration. Our case studies show that i-MedRAG can flexibly ask follow-up queries to form reasoning chains, providing an in-depth analysis of medical questions. To the best of our knowledge, this is the first-of-its-kind study on incorporating follow-up queries into medical RAG. The implementation of i-MedRAG is available at https://github.com/Teddy-XiongGZ/MedRAG.

Sanchit Sinha, Guangzhi Xiong, Bohan Liu et al.

The effectiveness of Chain-of-Thought (CoT) prompting in Multimodal Large Language Models (MLLMs) remains uncertain: across several visual reasoning benchmarks, CoT prompting often degrades performance compared to direct prompting. In this paper, we provide a systematic analysis of CoT behavior in three modern MLLM families across model scales on datasets requiring step-wise visual evidence. Our analysis identifies two recurring failure modes: premature answer commitment and limited direct visual-token access during rationale generation. We further find that standard CoT-style Supervised Fine-Tuning (CoT-SFT) can mitigate these issues only partially, while often increasing reliance on textual priors and reducing counterfactual visual dependence. Motivated by these findings, we propose Attentive-CoT (Att-CoT), an attention-guided fine-tuning objective that encourages CoT trajectories to delay answer commitment while maintaining sustained visual-token access. Att-CoT can be plugged into any CoT-SFT training run without architectural changes. Experiments on three visual reasoning benchmarks across six MLLMs show that Att-CoT enhances CoT performance over standard fine-tuning.

Guangzhi Xiong, Qiao Jin, Sanchit Sinha et al.

Large Vision Language Models (LVLMs) show promise in medical applications, but their inability to faithfully ground responses in visual evidence raises serious concerns about clinical trustworthiness. While visual attribution methods are widely used to explain LVLM predictions, whether these explanations actually reflect the visual evidence underlying the model's decision is largely unverified, since ground-truth annotations for internal model reasoning are typically unavailable. We address this question for chest X-ray (CXR) reasoning by developing a causal evaluation framework that retains only CXR-VQA samples for which the expert-annotated region is verified, via counterfactual editing, to be causally responsible for the model's prediction. Using this framework across 11 attribution methods, six open-source LVLMs, and two output modes (direct answer and step-by-step reasoning), we find that existing attribution methods often fail to identify the evidence used by LVLMs. To address this failure, we propose MedFocus, a concept-based attribution method that localizes clinically meaningful anatomical regions via unbalanced optimal transport and measures their causal effect on model outputs through targeted interventions. MedFocus produces spatial, concept-level, and token-level attributions and substantially outperforms prior methods, taking a step toward more trustworthy attribution for medical LVLMs. Our data and code are available at https://github.com/gzxiong/medfocus/.

Guangzhi Xiong, Sanchit Sinha, Zhenghao He et al.

Vision-language models (VLMs) have achieved impressive performance across a wide range of multimodal reasoning tasks, but they often struggle to disentangle fine-grained visual attributes and reason about underlying causal relationships. In-context learning (ICL) offers a promising avenue for VLMs to adapt to new tasks, but its effectiveness critically depends on the selection of demonstration examples. Existing retrieval-augmented approaches typically rely on passive similarity-based retrieval, which tends to select correlated but non-causal examples, amplifying spurious associations and limiting model robustness. We introduce CIRCLES (Composed Image Retrieval for Causal Learning Example Selection), a novel framework that actively constructs demonstration sets by retrieving counterfactual-style examples through targeted, attribute-guided composed image retrieval. By incorporating counterfactual-style examples, CIRCLES enables VLMs to implicitly reason about the causal relations between attributes and outcomes, moving beyond superficial correlations and fostering more robust and grounded reasoning. Comprehensive experiments on four diverse datasets demonstrate that CIRCLES consistently outperforms existing methods across multiple architectures, especially on small-scale models, with pronounced gains under information scarcity. Furthermore, CIRCLES retrieves more diverse and causally informative examples, providing qualitative insights into how models leverage in-context demonstrations for improved reasoning. Our code is available at https://github.com/gzxiong/CIRCLES.

Guangzhi Xiong, Sanchit Sinha, Aidong Zhang

The trade-off between interpretability and accuracy remains a core challenge in machine learning. Standard Generalized Additive Models (GAMs) offer clear feature attributions but are often constrained by their strictly additive nature, which can limit predictive performance. Introducing feature interactions can boost accuracy yet may obscure individual feature contributions. To address these issues, we propose Neural Additive Experts (NAEs), a novel framework that seamlessly balances interpretability and accuracy. NAEs employ a mixture of experts framework, learning multiple specialized networks per feature, while a dynamic gating mechanism integrates information across features, thereby relaxing rigid additive constraints. Furthermore, we propose targeted regularization techniques to mitigate variance among expert predictions, facilitating a smooth transition from an exclusively additive model to one that captures intricate feature interactions while maintaining clarity in feature attributions. Our theoretical analysis and experiments on synthetic data illustrate the model's flexibility, and extensive evaluations on real-world datasets confirm that NAEs achieve an optimal balance between predictive accuracy and transparent, feature-level explanations. The code is available at https://github.com/Teddy-XiongGZ/NAE.

Guangzhi Xiong, Zhenghao He, Bohan Liu et al.

Retrieval-Augmented Generation (RAG) improves the factuality of large language models (LLMs) by grounding outputs in retrieved evidence, but faithfulness failures, where generations contradict or extend beyond the provided sources, remain a critical challenge. Existing hallucination detection methods for RAG often rely either on large-scale detector training, which requires substantial annotated data, or on querying external LLM judges, which leads to high inference costs. Although some approaches attempt to leverage internal representations of LLMs for hallucination detection, their accuracy remains limited. Motivated by recent advances in mechanistic interpretability, we employ sparse autoencoders (SAEs) to disentangle internal activations, successfully identifying features that are specifically triggered during RAG hallucinations. Building on a systematic pipeline of information-based feature selection and additive feature modeling, we introduce RAGLens, a lightweight hallucination detector that accurately flags unfaithful RAG outputs using LLM internal representations. RAGLens not only achieves superior detection performance compared to existing methods, but also provides interpretable rationales for its decisions, enabling effective post-hoc mitigation of unfaithful RAG. Finally, we justify our design choices and reveal new insights into the distribution of hallucination-related signals within LLMs. The code is available at https://github.com/Teddy-XiongGZ/RAGLens.

Sanchit Sinha, Guangzhi Xiong, Aidong Zhang

Interpretability of Deep Neural Networks using concept-based models offers a promising way to explain model behavior through human-understandable concepts. A parallel line of research focuses on disentangling the data distribution into its underlying generative factors, in turn explaining the data generation process. While both directions have received extensive attention, little work has been done on explaining concepts in terms of generative factors to unify mathematically disentangled representations and human-understandable concepts as an explanation for downstream tasks. In this paper, we propose a novel method CoLiDR - which utilizes a disentangled representation learning setup for learning mutually independent generative factors and subsequently learns to aggregate the said representations into human-understandable concepts using a novel aggregation/decomposition module. Experiments are conducted on datasets with both known and unknown latent generative factors. Our method successfully aggregates disentangled generative factors into concepts while maintaining parity with state-of-the-art concept-based approaches. Quantitative and visual analysis of the learned aggregation procedure demonstrates the advantages of our work compared to commonly used concept-based models over four challenging datasets. Lastly, our work is generalizable to an arbitrary number of concepts and generative factors - making it flexible enough to be suitable for various types of data.

Yin Fang, Qiao Jin, Guangzhi Xiong et al.

Cell type annotation is a key task in analyzing the heterogeneity of single-cell RNA sequencing data. Although recent foundation models automate this process, they typically annotate cells independently, without considering batch-level cellular context or providing explanatory reasoning. In contrast, human experts often annotate distinct cell types for different cell clusters based on their domain knowledge. To mimic this workflow, we introduce the CellPuzzles task, where the objective is to assign unique cell types to a batch of cells. This benchmark spans diverse tissues, diseases, and donor conditions, and requires reasoning across the batch-level cellular context to ensure label uniqueness. We find that off-the-shelf large language models (LLMs) struggle on CellPuzzles, with the best baseline (OpenAI's o1) achieving only 19.0% batch-level accuracy. To fill this gap, we propose Cell-o1, a 7B LLM trained via supervised fine-tuning on distilled reasoning traces, followed by reinforcement learning with batch-level rewards. Cell-o1 achieves state-of-the-art performance, outperforming o1 by over 73% and generalizing well across contexts. Further analysis of training dynamics and reasoning behaviors provides insights into batch-level annotation performance and emergent expert-like reasoning. Code and data are available at https://github.com/ncbi-nlp/cell-o1.

Guangzhi Xiong, Eric Xie, Corey Williams et al.

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 scientific 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.

Sanchit Sinha, Guangzhi Xiong, Zhenghao He et al.

Modern vision-language models (VLMs) deliver impressive predictive accuracy yet offer little insight into 'why' a decision is reached, frequently hallucinating facts, particularly when encountering out-of-distribution data. Neurosymbolic frameworks address this by pairing black-box perception with interpretable symbolic reasoning, but current methods extract their symbols solely from task labels, leaving them weakly grounded in the underlying visual data. In this paper, we introduce a multi-agent system - Concept-RuleNet that reinstates visual grounding while retaining transparent reasoning. Specifically, a multimodal concept generator first mines discriminative visual concepts directly from a representative subset of training images. Next, these visual concepts are utilized to condition symbol discovery, anchoring the generations in real image statistics and mitigating label bias. Subsequently, symbols are composed into executable first-order rules by a large language model reasoner agent - yielding interpretable neurosymbolic rules. Finally, during inference, a vision verifier agent quantifies the degree of presence of each symbol and triggers rule execution in tandem with outputs of black-box neural models, predictions with explicit reasoning pathways. Experiments on five benchmarks, including two challenging medical-imaging tasks and three underrepresented natural-image datasets, show that our system augments state-of-the-art neurosymbolic baselines by an average of 5% while also reducing the occurrence of hallucinated symbols in rules by up to 50%.

Guangzhi Xiong, Qiao Jin, Zhiyong Lu et al.

While large language models (LLMs) have achieved state-of-the-art performance on a wide range of medical question answering (QA) tasks, they still face challenges with hallucinations and outdated knowledge. Retrieval-augmented generation (RAG) is a promising solution and has been widely adopted. However, a RAG system can involve multiple flexible components, and there is a lack of best practices regarding the optimal RAG setting for various medical purposes. To systematically evaluate such systems, we propose the Medical Information Retrieval-Augmented Generation Evaluation (MIRAGE), a first-of-its-kind benchmark including 7,663 questions from five medical QA datasets. Using MIRAGE, we conducted large-scale experiments with over 1.8 trillion prompt tokens on 41 combinations of different corpora, retrievers, and backbone LLMs through the MedRAG toolkit introduced in this work. Overall, MedRAG improves the accuracy of six different LLMs by up to 18% over chain-of-thought prompting, elevating the performance of GPT-3.5 and Mixtral to GPT-4-level. Our results show that the combination of various medical corpora and retrievers achieves the best performance. In addition, we discovered a log-linear scaling property and the "lost-in-the-middle" effects in medical RAG. We believe our comprehensive evaluations can serve as practical guidelines for implementing RAG systems for medicine.

Zihan Guan, Qiao Jin, Guangzhi Xiong et al.

The existing methods for evaluating the medical knowledge of Large Language Models (LLMs) are largely based on atemporal examination-style benchmarks, while in reality, medical knowledge is inherently dynamic and continuously evolves as new evidence emerges and treatments are approved. Consequently, evaluating medical knowledge without a temporal context may provide an incomplete assessment of whether LLMs can accurately reason about time-specific medical knowledge. Moreover, most medical data are historical, requiring the models not only to recall the correct knowledge, but also to know when that knowledge is correct. To bridge the gap, we built TempoMed-Bench, the first-of-its-kind benchmark for evaluating the temporal awareness of the LLMs in the medical domain through evolving guideline knowledge. Based on the TempoMed-Bench, our evaluation analysis first reveals that LLMs lack temporal awareness in medical knowledge through the key findings: (1) model performance on up-to-date medical knowledge exhibits a gradual linear decline over time rather than a sharp knowledge-cutoff behavior, suggesting that parametric medical knowledge is not strictly bounded by knowledge cutoffs; (2) LLMs consistently struggle more with recalling outdated historical medical knowledge than with up-to-date recommendations: accuracy of historical knowledge is only 25.37%-53.89% of up-to-date knowledge, indicating potential knowledge forgetting effects during training; and (3) LLMs often exhibit temporally inconsistent behaviors, where predictions fluctuate irregularly across neighboring years. We also show that the temporal awareness problem is a challenge that cannot be easily solved when integrated with agentic search tools (-3.15%-14.14%). This work highlights an important yet underexplored challenge and motivates future research on developing LLMs that can better encode time-specific medical knowledge.

Qiao Jin, Yin Fang, Lauren He et al.

Assessing whether an article supports an assertion is essential for hallucination detection and claim verification. While large language models (LLMs) have the potential to automate this task, achieving strong performance requires frontier models such as GPT-5 that are prohibitively expensive to deploy at scale. To efficiently perform biomedical evidence attribution, we present Med-V1, a family of small language models with only three billion parameters. Trained on high-quality synthetic data newly developed in this study, Med-V1 substantially outperforms (+27.0% to +71.3%) its base models on five biomedical benchmarks unified into a verification format. Despite its smaller size, Med-V1 performs comparably to frontier LLMs such as GPT-5, along with high-quality explanations for its predictions. We use Med-V1 to conduct a first-of-its-kind use case study that quantifies hallucinations in LLM-generated answers under different citation instructions. Results show that the format instruction strongly affects citation validity and hallucination, with GPT-5 generating more claims but exhibiting hallucination rates similar to GPT-4o. Additionally, we present a second use case showing that Med-V1 can automatically identify high-stakes evidence misattributions in clinical practice guidelines, revealing potentially negative public health impacts that are otherwise challenging to identify at scale. Overall, Med-V1 provides an efficient and accurate lightweight alternative to frontier LLMs for practical and real-world applications in biomedical evidence attribution and verification tasks. Med-V1 is available at https://github.com/ncbi-nlp/Med-V1.

Sanchit Sinha, Guangzhi Xiong, Aidong Zhang

Compositional reasoning remains a persistent weakness of modern vision language models (VLMs): they often falter when a task hinges on understanding how multiple objects, attributes, and relations interact within an image. Multiple research works have attempted to improve compositionality performance by creative tricks such as improving prompt structure, chain of thought reasoning, etc. A more recent line of work attempts to impart additional reasoning in VLMs using well-trained Large Language Models (LLMs), which are far superior in linguistic understanding than VLMs to compensate for the limited linguistic prowess of VLMs. However, these approaches are either resource-intensive or do not provide an interpretable reasoning process. In this paper, we present 'COCO-Tree' - a novel approach that augments VLM outputs with carefully designed neurosymbolic concept trees learned from LLMs to improve VLM's linguistic reasoning. COCO-Tree's beam search-inspired reasoning process boosts compositionality performance and provides a rationale behind VLM predictions. Empirical results on four compositionality benchmarks, Winoground, EqBench, ColorSwap, and SugarCrepe, in seven different open-source VLMs with varying sizes, demonstrate that COCO-Tree significantly improves compositional generalization by 5-10% over baselines.

Zhenghao He, Sanchit Sinha, Guangzhi Xiong et al.

Concept Activation Vectors (CAVs) provide a powerful approach for interpreting deep neural networks by quantifying their sensitivity to human-defined concepts. However, when computed independently at different layers, CAVs often exhibit inconsistencies, making cross-layer comparisons unreliable. To address this issue, we propose the Global Concept Activation Vector (GCAV), a novel framework that unifies CAVs into a single, semantically consistent representation. Our method leverages contrastive learning to align concept representations across layers and employs an attention-based fusion mechanism to construct a globally integrated CAV. By doing so, our method significantly reduces the variance in TCAV scores while preserving concept relevance, ensuring more stable and reliable concept attributions. To evaluate the effectiveness of GCAV, we introduce Testing with Global Concept Activation Vectors (TGCAV) as a method to apply TCAV to GCAV-based representations. We conduct extensive experiments on multiple deep neural networks, demonstrating that our method effectively mitigates concept inconsistency across layers, enhances concept localization, and improves robustness against adversarial perturbations. By integrating cross-layer information into a coherent framework, our method offers a more comprehensive and interpretable understanding of how deep learning models encode human-defined concepts. Code and models are available at https://github.com/Zhenghao-He/GCAV.

Nicholas Wan, Qiao Jin, Joey Chan et al.

Although large language models (LLMs) have been assessed for general medical knowledge using licensing exams, their ability to support clinical decision-making, such as selecting medical calculators, remains uncertain. We assessed nine LLMs, including open-source, proprietary, and domain-specific models, with 1,009 multiple-choice question-answer pairs across 35 clinical calculators and compared LLMs to humans on a subset of questions. While the highest-performing LLM, OpenAI o1, provided an answer accuracy of 66.0% (CI: 56.7-75.3%) on the subset of 100 questions, two human annotators nominally outperformed LLMs with an average answer accuracy of 79.5% (CI: 73.5-85.0%). Ultimately, we evaluated medical trainees and LLMs in recommending medical calculators across clinical scenarios like risk stratification and diagnosis. With error analysis showing that the highest-performing LLMs continue to make mistakes in comprehension (49.3% of errors) and calculator knowledge (7.1% of errors), our findings highlight that LLMs are not superior to humans in calculator recommendation.

Sikun Guo, Amir Hassan Shariatmadari, Guangzhi Xiong et al.

Large Language Models (LLMs) have transformed how people interact with artificial intelligence (AI) systems, achieving state-of-the-art results in various tasks, including scientific discovery and hypothesis generation. However, the lack of a comprehensive and systematic evaluation framework for generating research ideas using LLMs poses a significant obstacle to understanding and assessing their generative capabilities in scientific discovery. To address this gap, we propose IdeaBench, a benchmark system that includes a comprehensive dataset and an evaluation framework for standardizing the assessment of research idea generation using LLMs. Our dataset comprises titles and abstracts from a diverse range of influential papers, along with their referenced works. To emulate the human process of generating research ideas, we profile LLMs as domain-specific researchers and ground them in the same context considered by human researchers. This maximizes the utilization of the LLMs' parametric knowledge to dynamically generate new research ideas. We also introduce an evaluation framework for assessing the quality of generated research ideas. Our evaluation framework is a two-stage process: first, using GPT-4o to rank ideas based on user-specified quality indicators such as novelty and feasibility, enabling scalable personalization; and second, calculating relative ranking based "Insight Score" to quantify the chosen quality indicator. The proposed benchmark system will be a valuable asset for the community to measure and compare different LLMs, ultimately advancing the automation of the scientific discovery process.

Guangzhi Xiong, Eric Xie, Amir Hassan Shariatmadari et al.

Large language models (LLMs) have demonstrated remarkable capabilities in various scientific domains, from natural language processing to complex problem-solving tasks. Their ability to understand and generate human-like text has opened up new possibilities for advancing scientific research, enabling tasks such as data analysis, literature review, and even experimental design. One of the most promising applications of LLMs in this context is hypothesis generation, where they can identify novel research directions by analyzing existing knowledge. However, despite their potential, LLMs are prone to generating ``hallucinations'', outputs that are plausible-sounding but factually incorrect. Such a problem presents significant challenges in scientific fields that demand rigorous accuracy and verifiability, potentially leading to erroneous or misleading conclusions. To overcome these challenges, we propose KG-CoI (Knowledge Grounded Chain of Ideas), a novel system that enhances LLM hypothesis generation by integrating external, structured knowledge from knowledge graphs (KGs). KG-CoI guides LLMs through a structured reasoning process, organizing their output as a chain of ideas (CoI), and includes a KG-supported module for the detection of hallucinations. With experiments on our newly constructed hypothesis generation dataset, we demonstrate that KG-CoI not only improves the accuracy of LLM-generated hypotheses but also reduces the hallucination in their reasoning chains, highlighting its effectiveness in advancing real-world scientific research.

Qiao Jin, Nicholas Wan, Robert Leaman et al.

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

Guangzhi Xiong, Qiao Jin, Xiao Wang et al.

Retrieval-augmented generation (RAG) has shown great promise for knowledge-intensive tasks and recently advanced with agentic RAG, where language agents engage in multi-round interactions with external knowledge sources for adaptive information retrieval. However, existing agentic RAG methods often depend on ad-hoc prompt engineering and lack a unified optimization framework. We introduce RAG-Gym, a comprehensive platform that systematically explores three optimization dimensions: (1) prompt engineering, (2) actor tuning, and (3) critic training. For prompt engineering, we propose Re$^2$Search, a novel agent incorporating reasoning reflection that significantly outperforms standard prompts. In actor tuning, we evaluate three popular post-training algorithms with fine-grained process supervision and identify direct preference optimization as the most effective. We further demonstrate that a trained critic can enhance inference by selecting higher-quality intermediate reasoning steps. Together, these findings lead to the optimized Re$^2$Search++ agent, which surpasses most recent methods like Search-R1 by a relative increase of 3.2% to 11.6% in average F1. Finally, we examine the impact of different reward sources and analyze scaling properties in training and inference, offering practical insights for agentic RAG optimization. The project homepage is available at https://rag-gym.github.io.

Yifan Yang, Qiao Jin, Robert Leaman et al.

The remarkable capabilities of Large Language Models (LLMs) make them increasingly compelling for adoption in real-world healthcare applications. However, the risks associated with using LLMs in medical applications have not been systematically characterized. We propose using five key principles for safe and trustworthy medical AI: Truthfulness, Resilience, Fairness, Robustness, and Privacy, along with ten specific aspects. Under this comprehensive framework, we introduce a novel MedGuard benchmark with 1,000 expert-verified questions. Our evaluation of 11 commonly used LLMs shows that the current language models, regardless of their safety alignment mechanisms, generally perform poorly on most of our benchmarks, particularly when compared to the high performance of human physicians. Despite recent reports indicate that advanced LLMs like ChatGPT can match or even exceed human performance in various medical tasks, this study underscores a significant safety gap, highlighting the crucial need for human oversight and the implementation of AI safety guardrails.

Sanchit Sinha, Guangzhi Xiong, Aidong Zhang

With the wide proliferation of Deep Neural Networks in high-stake applications, there is a growing demand for explainability behind their decision-making process. Concept learning models attempt to learn high-level 'concepts' - abstract entities that align with human understanding, and thus provide interpretability to DNN architectures. However, in this paper, we demonstrate that present SOTA concept learning approaches suffer from two major problems - lack of concept fidelity wherein the models fail to learn consistent concepts among similar classes and limited concept interoperability wherein the models fail to generalize learned concepts to new domains for the same task. Keeping these in mind, we propose a novel self-explaining architecture for concept learning across domains which - i) incorporates a new concept saliency network for representative concept selection, ii) utilizes contrastive learning to capture representative domain invariant concepts, and iii) uses a novel prototype-based concept grounding regularization to improve concept alignment across domains. We demonstrate the efficacy of our proposed approach over current SOTA concept learning approaches on four widely used real-world datasets. Empirical results show that our method improves both concept fidelity measured through concept overlap and concept interoperability measured through domain adaptation performance.

Sanchit Sinha, Guangzhi Xiong, Aidong Zhang

As Vision Transformers (ViTs) are increasingly adopted in sensitive vision applications, there is a growing demand for improved interpretability. This has led to efforts to forward-align these models with carefully annotated abstract, human-understandable semantic entities - concepts. Concepts provide global rationales to the model predictions and can be quickly understood/intervened on by domain experts. Most current research focuses on designing model-agnostic, plug-and-play generic concept-based explainability modules that do not incorporate the inner workings of foundation models (e.g., inductive biases, scale invariance, etc.) during training. To alleviate this issue for ViTs, in this paper, we propose ASCENT-ViT, an attention-based, concept learning framework that effectively composes scale and position-aware representations from multiscale feature pyramids and ViT patch representations, respectively. Further, these representations are aligned with concept annotations through attention matrices - which incorporate spatial and global (semantic) concepts. ASCENT-ViT can be utilized as a classification head on top of standard ViT backbones for improved predictive performance and accurate and robust concept explanations as demonstrated on five datasets, including three widely used benchmarks (CUB, Pascal APY, Concept-MNIST) and 2 real-world datasets (AWA2, KITS).

Zhenghao He, Guangzhi Xiong, Boyang Wang et al.

Internal activations of diffusion models encode rich semantic information, but interpreting such representations remains challenging. While Sparse Autoencoders (SAEs) have shown promise in disentangling latent representations, existing SAE-based methods for diffusion model understanding rely on unsupervised approaches that fail to align sparse features with human-understandable concepts. This limits their ability to provide reliable semantic control over generated images. We introduce CASL (Concept-Aligned Sparse Latents), a supervised framework that aligns sparse latent dimensions of diffusion models with semantic concepts. CASL first trains an SAE on frozen U-Net activations to obtain disentangled latent representations, and then learns a lightweight linear mapping that associates each concept with a small set of relevant latent dimensions. To validate the semantic meaning of these aligned directions, we propose CASL-Steer, a controlled latent intervention that shifts activations along the learned concept axis. Unlike editing methods, CASL-Steer is used solely as a causal probe to reveal how concept-aligned latents influence generated content. We further introduce the Editing Precision Ratio (EPR), a metric that jointly measures concept specificity and the preservation of unrelated attributes. Experiments show that our method achieves superior editing precision and interpretability compared to existing approaches. To the best of our knowledge, this is the first work to achieve supervised alignment between latent representations and semantic concepts in diffusion models.

Zhenghao He, Guangzhi Xiong, Bohan Liu et al.

Chain-of-Thought (CoT) prompting has improved the reasoning performance of large language models (LLMs), but it remains unclear why it works and whether it is the unique mechanism for triggering reasoning in large language models. In this work, we study this question by directly analyzing and intervening on the internal representations of LLMs with Sparse Autoencoders (SAEs), identifying a small set of latent features that are causally associated with LLM reasoning behavior. Across multiple model families and reasoning benchmarks, we find that steering a single reasoning-related latent feature can substantially improve accuracy without explicit CoT prompting. For large models, latent steering achieves performance comparable to standard CoT prompting while producing more efficient outputs. We further observe that this reasoning-oriented internal state is triggered early in generation and can override prompt-level instructions that discourage explicit reasoning. Overall, our results suggest that multi-step reasoning in LLMs is supported by latent internal activations that can be externally activated, while CoT prompting is one effective, but not unique, way of activating this mechanism rather than its necessary cause.

Sanchit Sinha, Guangzhi Xiong, Aidong Zhang

The rising need for explainable deep neural network architectures has utilized semantic concepts as explainable units. Several approaches utilizing disentangled representation learning estimate the generative factors and utilize them as concepts for explaining DNNs. However, even though the generative factors for a dataset remain fixed, concepts are not fixed entities and vary based on downstream tasks. In this paper, we propose a disentanglement mechanism utilizing a variational autoencoder (VAE) for learning mutually independent generative factors for a given dataset and subsequently learning task-specific concepts using a structural causal model (SCM). Our method assumes generative factors and concepts to form a bipartite graph, with directed causal edges from generative factors to concepts. Experiments are conducted on datasets with known generative factors: D-sprites and Shapes3D. On specific downstream tasks, our proposed method successfully learns task-specific concepts which are explained well by the causal edges from the generative factors. Lastly, separate from current causal concept discovery methods, our methodology is generalizable to an arbitrary number of concepts and flexible to any downstream tasks.

Nikhil Khandekar, Qiao Jin, Guangzhi Xiong et al.

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.

Qiao Jin, Zheng Yuan, Guangzhi Xiong et al.

Automatic Question Answering (QA) has been successfully applied in various domains such as search engines and chatbots. Biomedical QA (BQA), as an emerging QA task, enables innovative applications to effectively perceive, access and understand complex biomedical knowledge. There have been tremendous developments of BQA in the past two decades, which we classify into 5 distinctive approaches: classic, information retrieval, machine reading comprehension, knowledge base and question entailment approaches. In this survey, we introduce available datasets and representative methods of each BQA approach in detail. Despite the developments, BQA systems are still immature and rarely used in real-life settings. We identify and characterize several key challenges in BQA that might lead to this issue, and discuss some potential future directions to explore.