Abstract:Predicting single-cell transcriptomic responses to genetic perturbations is central to functional genomics and virtual-cell modeling. Existing approaches, however, typically predict an entire expression profile as a whole, leaving the order in which individual gene responses are generated unmodeled. To address this problem, we introduce \textbf{$D^{2}R^{2}$} (\textbf{D}iscrete \textbf{D}iffusion with \textbf{R}egulation \textbf{R}einforcement), which reformulates perturbation prediction as regulation-guided gene-wise progressive generation. A Masked Discrete Diffusion Model represents expression as ordinal tokens and reconstructs a fully masked profile step by step, allowing generated gene responses to condition those that remain masked. A Regulatory Policy Module initializes the generation policy from a gene regulatory network inferred from control cells and adapts it to the perturbation and current partially generated state. Then, group-relative policy optimization refines only the ordering policy using final perturbation-effect agreement as reward. Across Norman19 and VCC-H1, $D^{2}R^{2}$ achieves the best performance on all five metrics on Norman19 and remains competitive on H1. Controlled ablations holding the generator and generation budget fixed show that biological-prior ordering improves over random ordering and is more reliable than uncertainty-based heuristics, whereas reversing the biological-prior ordering degrades every metric. Biological analyses further show that the refined policy prioritizes regulatory genes early while promoting perturbation-specific transcription factors and responsive genes. These results establish gene generation order as an effective, controllable, and biologically interpretable dimension of single-cell perturbation prediction.
Abstract:Reinforcement Fine-Tuning (RFT) has enabled medical Multimodal Large Language Models (MLLMs) to produce Chain-of-Thought (CoT) reasoning for visual question answering, yet these models suffer from $\textit{confidence miscalibration}$---a systematic gap between expressed certainty and actual diagnostic accuracy that undermines clinical trust. We propose $\textbf{CARE}$, a $\textbf{C}$onfidence-$\textbf{A}$ware medical $\textbf{RE}$asoning framework that jointly optimizes accuracy and calibration through a dual-stage pipeline. First, a scalable Medical-CoT synthesis provides structured cold-start data for Supervised Fine-Tuning. Second, Group Relative Policy Optimization (GRPO) with a novel $\textbf{Confidence-Aware Reward (CAR)}$ mechanism ties the model's confidence to diagnostic correctness within the reward signal. Across three Medical VQA benchmarks, $\textbf{CARE}$ achieves the highest diagnostic accuracy while obtaining the lowest Expected Calibration Error and Hallucination Rate, establishing a foundation for trustworthy clinical decision support. Our code is available at https://github.com/anotherbricki/CARE.
Abstract:Ultrasound imaging is widely used in clinical diagnostics due to its real-time capability and radiation-free nature. However, existing vision-language pre-training models, such as CLIP, are primarily designed for other modalities, and are difficult to directly apply to ultrasound data, which exhibit heterogeneous anatomical structures and diverse diagnostic attributes. To bridge this gap, we construct US-365K, a large-scale ultrasound image-text dataset containing 365k paired samples across 52 anatomical categories. We establish Ultrasonographic Diagnostic Taxonomy (UDT) containing two hierarchical knowledge frameworks. Ultrasonographic Hierarchical Anatomical Taxonomy standardizes anatomical organization, and Ultrasonographic Diagnostic Attribute Framework formalizes nine diagnostic dimensions, including body system, organ, diagnosis, shape, margins, echogenicity, internal characteristics, posterior acoustic phenomena, and vascularity. Building upon these foundations, we propose Ultrasound-CLIP, a semantic-aware contrastive learning framework that introduces semantic soft labels and semantic loss to refine sample discrimination. Moreover, we construct a heterogeneous graph modality derived from UDAF's textual representations, enabling structured reasoning over lesion-attribute relations. Extensive experiments with patient-level data splitting demonstrate that our approach achieves state-of-the-art performance on classification and retrieval benchmarks, while also delivering strong generalization to zero-shot, linear probing, and fine-tuning tasks.