Abstract:Healthcare models are transitioning from unimodal prediction toward multimodal reasoning over heterogeneous diagnostic inputs. In computational pathology, for complex tumor subtypes where morphology alone can be challenging to distinguish, pathology reports and molecular measurements may provide additional diagnostic evidence alongside whole-slide images, yet existing models often fail to clarify how diverse signals assemble into recognizable diagnostic concepts. We propose ConceptM$^3$oE (Concept Multimodal MoE), which embeds concept formation directly within interaction-aware mixture-of-experts (MoE) pathways. The architecture decomposes evidence into modality-specific, redundant, and synergistic experts, which are then projected into structured concept bottlenecks mapping latent features to a hierarchy of morphology and biomarker concepts. To prevent the information loss typical of interpretable bottlenecks, we utilize residual pathways within each expert to allow task-relevant signals to flow both through the concepts and directly to the final task prediction, so that high performance is maintained alongside interpretability. Across an institutional pediatric brain tumor cohort and a public glioma cohort, the framework delivers competitive performance to unconstrained models while producing reasoning traces validated by an independent neuropathologist. In data-limited regimes, ConceptM$^3$oE improves limited-data performance, increasing macro-F1 from 56.41% to 66.70% at small training sizes compared to non-concept-informed baselines, while also showing faster training convergence consistent with the regularizing effect of concept learning. This work offers a scalable path toward high-performance medical AI that is inherently verifiable and better aligned with the complex decision-making of clinical practice.
Abstract:Predicting how a cell will change its transcriptional state under a developmental signal or a genetic perturbation is the computational core of in-silico biology and the AI Virtual Cell program. Existing approaches either fit static control-to-treated maps that discard time, or solve multi-step ODE / Schrödinger-bridge problems on each dataset independently. We introduce Chreode, a one-step cell world model that predicts action-conditioned cell-state transitions through a structured residual transition operator. It shifts distributional evolution from inference time to training time, enabling single-pass generation while preserving a Waddington-inspired decomposition into downhill landscape flow, rotational in-tangent dynamics, and stochastic spread. The model is pretrained with a shared scVI encoder and a DiT-based dynamics backbone on a 2.4M-cell mouse embryonic atlas spanning 7 datasets. As a fine-tuning initialization, Chreode improves per-target Sinkhorn distance on Weinreb hematopoiesis and Veres islet differentiation over matched scratch models, PI-SDE, and PRESCIENT. As a transferable gene-state embedding for GEARS, the pretrained dynamics representation reduces shared-vocabulary DE20 mean squared error on Norman Perturb-seq from 0.2121 to 0.1858, a 12.4% relative improvement, without changing the GEARS training procedure. We interpret this transfer to perturbation prediction as evidence that pretrained developmental-trajectory dynamics encode differentiation primitives transferable to CRISPR-induced state shifts, since both involve cell-state transitions in a shared latent geometry. The pretrained backbone additionally produces zero-shot clonal fate scores on Weinreb that are competitive with strong dynamic-OT baselines.
Abstract:LLMs are vulnerable to prompt injection attacks. However, this vulnerability has been primarily demonstrated conceptually in academic studies or through a few anecdotal case studies. Its prevalence and impact in real-world LLM-based applications are largely unexplored. In this work, we present the first systematic study of prompt-injection attacks in a widely used application: LLM-based resume screening. Our analysis is based on approximately 200K real-world resumes collected over multiple years by hireEZ. We first design tailored methods to detect prompt injection in resumes. Manual validation on a small-scale dataset demonstrates that our detectors achieve high precision and outperform state-of-the-art general-purpose detectors. We then apply our detector to the full resume dataset and conduct a comprehensive measurement study of real-world prompt injection attacks. Our analysis reveals several intriguing findings: approximately 1% of resumes contain hidden prompt injections; the prevalence of such injected resumes has increased noticeably over the past one to two years; and more than 90% of injected prompts do not use explicit instructions. These results provide the first evidence of large-scale prompt injection in real-world LLM-based applications and lay the groundwork for future studies to understand and mitigate such attacks.
Abstract:Chain-of-thought (CoT) reasoning improves the problem-solving ability of large language models (LLMs), but generated reasoning traces may not faithfully reflect the model's actual decision process. Existing CoT unfaithfulness detectors mainly rely on external signals from generated rationales, such as textual plausibility or answer consistency, while overlooking evidence from the model's internal computation. Although recent circuit tracing methods provide a way to obtain model-internal evidence by tracing how information flows through model components during reasoning, constructing full reasoning circuits for long CoTs is costly and difficult to scale. To address these challenges, we propose Circuit-guided Internal-External Discrepancy Scorer (CIE-Scorer), a framework for instance-level CoT unfaithfulness detection. The key idea is that faithful reasoning traces should align with the model's computational process, whereas unfaithful traces may diverge from it. CIE-Scorer efficiently traces compact sentence-level circuits from informative reasoning tokens, constructs internal and external reasoning graphs, and measures their discrepancy using Fused Gromov--Wasserstein distance. Experiments on four datasets from FaithCoT-Bench show that CIE-Scorer achieves state-of-the-art performance while reducing the cost of circuit construction, demonstrating the effectiveness of combining mechanistic interpretability signals with external reasoning traces for CoT unfaithfulness detection.
Abstract:Mixture-of-Experts Large Language Models (MoE-LLMs) achieve strong performance but incur substantial memory overhead due to massive expert parameters. Mixed-precision quantization mitigates this cost by allocating expert-wise bit-widths based on their importance, approaching the accuracy-memory Pareto frontier and enabling extreme low-bit quantization. However, existing methods rely on layer-wise importance estimation and overlook router shifts induced by quantization, resulting in suboptimal allocation and routing. In this work, we propose Global Expert-level Mixed-precision Quantization (GEMQ) to overcome these limitations via (1) a global linear-programming formulation that captures model-wide expert importance based on quantization error analysis, and (2) efficient router fine-tuning to adapt routing to quantized experts. These components are integrated into a progressive quantization framework that iteratively refines importance estimation and allocation. Experiments demonstrate that GEMQ significantly reduces memory and accelerates inference with minimal accuracy degradation. Source code is available at https://github.com/jndeng/GEMQ .
Abstract:Accurate diagnosis of pediatric brain tumors, starting with histopathology, presents unique challenges for deep learning, including severe data scarcity, class imbalance, and fine-grained morphologic overlap across diagnostically distinct subtypes. While pathology foundation models have advanced patch-level representation learning, their effective adaptation to weakly supervised pediatric brain tumor classification under limited data remains underexplored. In this work, we introduce an expert-guided contrastive fine-tuning framework for pediatric brain tumor diagnosis from whole-slide images (WSI). Our approach integrates contrastive learning into slide-level multiple instance learning (MIL) to explicitly regularize the geometry of slide-level representations during downstream fine-tuning. We propose both a general supervised contrastive setting and an expert-guided variant that incorporates clinically informed hard negatives targeting diagnostically confusable subtypes. Through comprehensive experiments on pediatric brain tumor WSI classification under realistic low-sample and class-imbalanced conditions, we demonstrate that contrastive fine-tuning yields measurable improvements in fine-grained diagnostic distinctions. Our experimental analyses reveal complementary strengths across different contrastive strategies, with expert-guided hard negatives promoting more compact intra-class representations and improved inter-class separation. This work highlights the importance of explicitly shaping slide-level representations for robust fine-grained classification in data-scarce pediatric pathology settings.
Abstract:Large language models (LLMs) achieve high accuracy in medical diagnosis when all clinical information is provided in a single turn, yet how they behave under multi-turn evidence accumulation closer to real clinical reasoning remains unexplored. We introduce MINT (Medical Incremental N-Turn Benchmark), a high-fidelity, multi-turn medical diagnosis benchmark comprising 1,035 cases with clinically labeled evidence shards, controlled turn granularity, and information-preserving decomposition. Through systematic evaluation of 11 LLMs on MINT, we uncover three persistent behavioral patterns that significantly impact diagnostic decisions: (1) intent to answer, models rush to answer before sufficient evidence has been observed, with over 55% of answers committed within the first two turns; (2) self-correction, incorrect-to-correct answer revisions occur at up to 10.6 times the rate of correct-to-incorrect flips, revealing a latent capacity for self-correction that premature commitment forecloses; and (3) strong lures, clinically salient information such as laboratory results trigger premature answering even when models are explicitly instructed to wait. We translate these findings into clinically actionable guidance: deferring the diagnostic question to later turns reduces premature answering and improves accuracy at the first point of commitment by up to 62.6%, while reserving salient clinical evidence for later turns prevents a catastrophic accuracy drop of up to 23.3% caused by premature commitment. Our work provides both a controlled evaluation framework and concrete recommendations for improving the reliability of LLMs in multi-turn medical diagnosis.
Abstract:Multimodal self-supervised pretraining offers a promising route to cancer prognosis by integrating histopathology whole-slide images, gene expression, and pathology reports, yet most existing approaches require fully paired and complete inputs. In practice, clinical cohorts are fragmented and often miss one or more modalities, limiting both supervised fusion and scalable multimodal pretraining. We propose PRIME, a missing-aware multimodal self-supervised pretraining framework that learns robust and transferable representations from partially observed cohorts. PRIME maps heterogeneous modality embeddings into a unified token space and introduces a shared prototype memory bank for latent-space semantic imputation via patient-level consensus retrieval, producing structurally aligned tokens without reconstructing raw signals. Two complementary pretraining objectives: inter-modality alignment and post-fusion consistency under structured missingness augmentation, jointly learn representations that remain predictive under arbitrary modality subsets. We evaluate PRIME on The Cancer Genome Atlas with label-free pretraining on 32 cancer types and downstream 5-fold evaluation on five cohorts across overall survival prediction, 3-year mortality classification, and 3-year recurrence classification. PRIME achieves the best macro-average performance among all compared methods, reaching 0.653 C-index, 0.689 AUROC, and 0.637 AUROC on the three tasks, respectively, while improving robustness under test-time missingness and supporting parameter-efficient and label-efficient adaptation. These results support missing-aware multimodal pretraining as a practical strategy for prognosis modeling in fragmented clinical data settings.
Abstract:The recent success of reinforcement learning (RL) in large reasoning models has inspired the growing adoption of RL for post-training Multimodal Large Language Models (MLLMs) to enhance their visual reasoning capabilities. Although many studies have reported improved performance, it remains unclear whether RL training truly enables models to learn from visual information. In this work, we propose the Hallucination-as-Cue Framework, an analytical framework designed to investigate the effects of RL-based post-training on multimodal reasoning models from the perspective of model hallucination. Specifically, we introduce hallucination-inductive, modality-specific corruptions that remove or replace essential information required to derive correct answers, thereby forcing the model to reason by hallucination. By applying these corruptions during both training and evaluation, our framework provides a unique perspective for diagnosing RL training dynamics and understanding the intrinsic properties of datasets. Through extensive experiments and analyses across multiple multimodal reasoning benchmarks, we reveal that the role of model hallucination for RL-training is more significant than previously recognized. For instance, we find that RL post-training under purely hallucination-inductive settings can still significantly improve models' reasoning performance, and in some cases even outperform standard training. These findings challenge prevailing assumptions about MLLM reasoning training and motivate the development of more modality-aware RL-based training designs.
Abstract:Large language model (LLM) agents struggle to autonomously evolve coordination strategies in dynamic environments, largely because coarse global outcomes obscure the causal signals needed for local policy refinement. We identify this bottleneck as a multi-agent credit assignment problem, which has long been studied in classical multi-agent reinforcement learning (MARL) but remains underaddressed in LLM-based systems. Building on this observation, we propose LangMARL, a framework that brings credit assignment and policy gradient evolution from cooperative MARL into the language space. LangMARL introduces agent-level language credit assignment, pioneers gradient evolution in language space for policy improvement, and summarizes task-relevant causal relations from replayed trajectories to provide dense feedback and improve convergence under sparse rewards. Extensive experiments across diverse cooperative multi-agent tasks demonstrate improved sample efficiency, interpretability, and strong generalization.