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We introduce ProtoPathway, an interpretable-by-design multimodal framework for cancer survival prediction that unifies whole slide imaging and transcriptomics through encoders producing biologically grounded representations on both sides of the fusion. On the histopathology side, $K$ learnable morphological prototypes, trained end-to-end with the survival objective, serve as the slide representation itself: patches flow into prototype tokens via soft assignment, compressing variable-length patch sets into fixed task-adaptive tokens. On the genomic side, a bipartite graph neural network encodes gene expression within the Reactome pathway hierarchy, producing pathway embeddings that reflect both constituent genes and their broader biological context through bidirectional message passing over a shared gene--pathway graph. Cross-modal attention then operates over a compact prototype $\times$ pathway matrix in which prototypes query pathways, modeling the biological direction in which molecular programs give rise to tissue morphology. Because both axes carry stable task-learned identity, the attention matrix is itself an interpretability output, yielding native inference-time attribution across the full biological hierarchy, from genes through pathways and prototypes to spatial tissue maps. We evaluate on five TCGA cancer cohorts, demonstrating competitive or superior survival prediction with substantially improved biological interpretability and reduced computational cost, with interpretability claims validated through fold-stratified rank-based population-level analysis. Our source code, model weights, and Reactome pathways, together with a unified codebase reimplementing all multimodal survival baselines under identical preprocessing and evaluation, are available at: https://github.com/AmayaGS/ProtoPathway.

Multimodal survival prediction, a crucial yet challenging task, demands the integration of multimodal medical data (\eg Whole Slide Images (WSIs) and Genomic Profiles) to achieve accurate prognostic modeling. Given the inherent heterogeneity across modalities, the feature decoupling-fusion paradigm has emerged as a dominant approach. However, these methods have the following shortcomings: (1) fail to reduce the redundant information of modality features before decoupling, which negatively affects the feature decoupling and fusion effect;(2) lack the ability to model the fine-grained relationships of the features and capture the local information interactions between intra- and inter-modality features. To address these issues, we propose a \underline{H}ierarchical \underline{D}ecoupling-Fusion \underline{M}ixture-\underline{o}f-\underline{E}xperts (HDMoE) framework with two levels of MoE and \underline{R}andom \underline{F}eature \underline{R}eorganization (RFR) modules.In the first-level MoE, shared experts and routed experts are employed to remove redundant information and extract fine-grained specific features within each modality, while the second-level MoE facilitates fine-grained inter-modality feature decoupling. Besides, we design two RFR modules following each level of MoE to finely fuse intra- and inter-modality features, which can help the model capture more fine-grained relationships between modalities. Extensive experimental results on our private Liver Cancer (LC) and three TCGA public datasets confirm the effectiveness of our proposed method. Codes are available at https://github.com/ZJUMAI/HDMoE.

Precision oncology requires predicting which drugs will suppress a specific tumor from its molecular profile, but drug-blind sensitivity prediction has plateaued despite increasingly complex drug representations. Here we show that this stagnation reflects a metric artifact rather than a representational bottleneck. The standard benchmark, global Pearson r, is dominated by between-drug potency differences that a trivial drug-mean predictor captures without any cell-specific learning. Per-drug Pearson r, which isolates within-drug cell ranking, reveals that no drug encoding improves over cell-only features across four independent datasets. A controlled experiment channeling mechanism-of-action identity as either a drug feature or a training-distribution constraint identifies the cause. Supplying MoA as a feature yields negligible benefit, whereas using it to stratify training raises per-drug r substantially for targeted kinase inhibitors, because pan-cancer co-training suppresses pathway-specific sensitivity signals. Mechanism-stratified training and response matching from pilot observations provide two deployable strategies that together recover the principal sources of predictive gain in drug-blind sensitivity prediction.

Experienced physicians develop diagnostic expertise through clinical practice, acquiring not only disease knowledge but also the ability to differentiate confusable conditions. Current medical vision-language models (VLMs) lack this capability -- their parameters encode static knowledge that does not evolve across diagnostic encounters. We propose MedExpMem, an experience memory framework enabling VLM-based diagnostic agents to accumulate differential diagnosis expertise. Unlike retrieval-augmented generation, which retrieves encyclopedic disease descriptions, MedExpMem memorizes discriminative experience derived from the agent's own diagnostic failures and organizes them as pairwise differential notes encoding key discriminators, actionable decision rules and reasoning error patterns. The framework adopts a two-phase construction process mirroring physician learning: initial practice exposes knowledge gaps, and reflective re-diagnosis refines understanding. When encountering new cases, the agent retrieves experience memory to guide differential reasoning. We evaluate MedExpMem on a radiology benchmark spanning 11 subspecialties. Results demonstrate consistent accuracy improvements, maximum 7.0%, across diverse models and scales. Analytical experiments validate experience quality and robustness, demonstrating MedExpMem as a competitive method addresses medical adaptation needs beyond the reach of parameteric learning.

Accurate classification of breast ultrasound images into benign, malignant, and normal categories is a critical clinical task complicated by speckle noise, acoustic shadowing, and inter-class visual ambiguity. Existing deep learning methods rely on single-stream architectures with generic augmentation that ignores ultrasound acquisition physics, and no prior method dedicates a stream to the lesion boundary features identified as the most diagnostically significant visual cue. We propose HADS-Net, a Hybrid Attention-Augmented Dual-Stream Network exploiting global texture and local boundary cues through two parallel pathways. Stream 1 applies physics-informed augmentation simulating speckle noise, acoustic shadowing, and gain variation before extracting features via pretrained EfficientNet-B3 projected to 512 dimensions. Stream 2 extracts Sobel edge maps processed by a lightweight CNN projected to the same 512-dimensional space. A cross-attention fusion module allows the texture stream to selectively query boundary features, producing a jointly optimised representation classified by an MLP trained with adaptive class-weighted focal loss. Five-fold stratified cross-validation with cosine annealing over 50 epochs is used, with the globally best checkpoint selected by lowest validation loss evaluated on a held-out test set. On the BUSI dataset, HADS-Net achieves 96.58% accuracy, macro ROC-AUC of 0.9978, macro F1 of 0.9654, and per-class F1-scores of 0.970, 0.951, and 0.976 for benign, malignant, and normal. No malignant lesion is misclassified as normal. These results confirm that modality-specific augmentation with cross-modal attention fusion is an effective strategy for ultrasound-based breast cancer diagnosis.

We present NeuroQA, a large-scale benchmark for visual question answering in 3D brain magnetic resonance imaging (MRI), with 56,953 QA pairs from 12,977 subjects across 12 datasets. It spans ages 5-104 and five clinical domains: Alzheimer's, Parkinson's, tumors, white matter disease, and neurodevelopment. Unlike prior medical Visual Question Answering (VQA) efforts that operate on 2D slices or rely on narrow diagnostic labels, NeuroQA pairs every item with a full 3D volume. It evaluates 11 clinically grounded reasoning skills across Yes/No, multiple-choice, and open-ended formats. Of the 203 templates, 131 are image-grounded (answerable from a 3-plane viewer) and 72 are image-informed (ground truth from quantitative volumetry or clinical instruments). To remove text-only shortcuts, we apply answer-distribution refinement, reducing closed-format text-only accuracy from $>$80% to 44.6%; image necessity is assessed separately through an image-grounding protocol released with the benchmark. A 38-rule deterministic pipeline and two rounds of expert review verify every QA pair against FreeSurfer measurements, metadata, or radiology report fields, with zero same-subject contradictions across templates. We conduct a clinician evaluation in which two clinicians independently assess 100 frozen test items on a three-plane viewer. On closed-format (Yes/No + multiple-choice) test-public items, the best zero-shot vision-language model and a supervised 3D CNN baseline reach 47.5% and 43.7% accuracy respectively, both below the 49.4% text-only majority-template floor. NeuroQA adopts a two-tier release with public QA pairs for open-access datasets and reproducible generation scripts for datasets restricted by data use agreements (DUAs), plus subject-level splits, a held-out private test set, and an online leaderboard.

Many complex systems combine dense background structure with sparse contextual information. We introduce a diffusion-based framework for analyzing how sparse condition-specific layers reshape diffusion geometry in multilayer hypergraphs. Each layer is represented as a weighted hypergraph, layers are coupled through shared entities, and random walks on the coupled system induce multiscale diffusion distances between nodes. We apply the framework to disease-conditioned gene networks by coupling a dense MSigDB functional gene-set layer to sparse disease-specific DGIdb drug-gene hypergraphs, with disease-associated drugs selected from DDDB and HumanNet-GSP used to define external gene weights. Across Bipolar Disorder, Schizophrenia, Leukemia, and Breast Cancer, the disease-specific layer contains less than 2 percent of genes in the coupled system, yet substantially changes diffusion distances and community structure. Centrality analysis suggests that this disproportionate effect arises because DGIdb-associated genes occupy influential positions in the MSigDB-derived functional network. The resulting diffusion-derived communities are stable under subsampling and show coherent post hoc functional enrichment, including signaling and neurotransmission categories in neuropsychiatric diseases and immune, translational, and metabolic categories in cancer-associated diseases. Community-level comparisons further reveal disease similarities not reducible to direct DGIdb gene overlap, including a Breast Cancer-Schizophrenia relationship consistent with recent biomedical evidence. These results show that sparse contextual layers can induce interpretable nonlocal changes in higher-order network geometry.

Virtual staining of histopathology images (e.g., H&E-IHC) is an emerging tool in digital pathology, enabling faster and cheaper workflows by synthesizing target stains from routinely acquired slides. Yet, the quality of virtual staining models is still predominantly assessed with generic metrics such as SSIM, PSNR, and LPIPS. Originally developed for natural images, these metrics are inherently misaligned with the domain-specific characteristics of histological data, failing to capture tissue morphology preservation and biomarker expression patterns. Consequently, a robust, domain-specific standard for quantifying similarity across diverse histological modalities remains a critical gap in the field. In this work, we formalize histology image similarity as a standalone problem and systematically evaluate a broad set of full-reference metrics against a dataset of H&E-IHC patch pairs annotated with expert similarity scores. We further analyze metrics sensitivity to controlled geometric distortions (shifts, rotations and non-rigid deformations) that mimic realistic registration errors between serial sections. Guided by these observations, we propose the Histology-Aware Perceptual Similarity (HAPS) metric. HAPS computes distances in the feature space of a frozen encoder pretrained on histopathology data, adding a linear head to aggregate feature-level differences into a final score that aligns with expert assessments. Finally, we demonstrate the practical value of HAPS for quality control of training data. By quantifying the similarity of training pairs in the MIST dataset and filtering low-scoring samples, we create a cleaner training set. Virtual staining models trained on this refined data outperform those trained on the original, unfiltered dataset.

Automatic report labeling facilitates the identification of clinical findings from unstructured text and enables large-scale annotation for medical imaging research. Existing rule-based labelers struggle with the diverse descriptions in clinical reports, while fine-tuning pre-trained language models (PLMs) requires large amounts of labeled data that are often unavailable in clinical settings. In this paper, we propose PromptRad, a knowledge-enhanced multi-label \textbf{prompt}-tuning approach for \textbf{rad}iology report labeling under low-resource settings. PromptRad reformulates multi-label classification as masked language modeling and incorporates synonyms from the UMLS Metathesaurus into a multi-word verbalizer to enrich category representations. By fine-tuning the PLM without additional classification layers, PromptRad requires substantially less labeled data than conventional fine-tuning. Experiments on liver CT (computed tomography) reports show that PromptRad outperforms dictionary-based and fine-tuning baselines with only 32 labeled training examples, and achieves competitive performance with GPT-4 despite using a much smaller model. Further analysis demonstrates that PromptRad captures complex negation patterns more effectively than existing methods, making it a promising solution for report labeling in data-scarce clinical scenarios. Our code is available at https://github.com/ila-lab/PromptRad.

Vision-language alignment using chest X-rays and radiology reports has emerged as an advanced paradigm for zero-shot classification and grounding of chest X-ray findings. However, standard contrastive learning typically treats radiographs and reports from different patients simply as negative pairs. This assumption introduces noisy negatives, as different patients frequently exhibit similar findings. Such noisy negatives cause semantic ambiguity and degrade performance in zero-shot understanding tasks. To address this challenge, we propose CoNNS, a concept-guided noisy-negative suppression framework. To support the negative suppression mechanism, unlike previous methods that use raw reports or templatized texts, we construct a hierarchical concept ontology using large language models. The ontology structures 41 key clinical concepts by explicitly modeling presence, attributes (location and characteristics), and texts (evidential segment and presence statement). Leveraging this ontology, we implement a cross-patient pair relabeling strategy comprising three steps: (1) Fine-Grained Breakdown to categorize pairs based on finding presence; (2) Noisy Negative Filtering to resolve semantic conflicts by removing false negatives; and (3) Hard Negative Mining to identify subtle attribute discrepancies using a lightweight language model. Finally, we propose a Concept-Aware NCE loss to align visual features with text while suppressing the identified noisy negatives. Extensive experiments across multi-granularity zero-shot grounding tasks and five zero-shot classification datasets validate that CoNNS outperforms existing state-of-the-art models. The code is available at https://github.com/DopamineLcy/conns.