When Cases Get Rare: A Retrieval Benchmark for Off-Guideline Clinical Question Answering

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

PBSBench: A Multi-Level Vision-Language Framework and Benchmark for Hematopathology Whole Slide Image Interpretation

Peripheral Blood Smear (PBS) is a critical microscopic examination in hematopathology that yields whole-slide imaging (WSI). Unlike solid tissue pathology, PBS interpretation focuses on individual cell morphologies rather than tissue architecture, making it distinct in both visual characteristics and diagnostic reasoning. However, current multimodal large language models (MLLMs) for pathology are primarily developed on solid-tissue WSIs and struggle to generalize to PBS. To bridge this gap, we construct PBSInstr, the first vision-language dataset for PBS interpretation, comprising 353 PBS WSIs paired with microscopic impression paragraphs and 29k cell-level image crops annotated with cell type labels and morphological descriptions. To facilitate instruction tuning, PBSInstr further includes 27k question-answer (QA) pairs for cell crops and 1,286 QA pairs for PBS slides. Building upon PBSInstr, we develop PBS-VL, a hematopathology-tailored vision-language model for multi-level PBS interpretation at both cell and slide levels. To comprehensively evaluate PBS understanding, we construct PBSBench, a visual question answering (VQA) benchmark featuring four question categories and six PBS interpretation tasks. Experiments show that PBS-VL outperforms existing general-purpose and pathology MLLMs, underscoring the value of PBS-specific data. We release our code, datasets, and model weights to facilitate future research. Our proposed framework lays the foundation for developing practical AI assistants supporting decision-making in hematopathology.

ClinicalTrialsHub: Bridging Registries and Literature for Comprehensive Clinical Trial Access

We present ClinicalTrialsHub, an interactive search-focused platform that consolidates all data from ClinicalTrials.gov and augments it by automatically extracting and structuring trial-relevant information from PubMed research articles. Our system effectively increases access to structured clinical trial data by 83.8% compared to relying on ClinicalTrials.gov alone, with potential to make access easier for patients, clinicians, researchers, and policymakers, advancing evidence-based medicine. ClinicalTrialsHub uses large language models such as GPT-5.1 and Gemini-3-Pro to enhance accessibility. The platform automatically parses full-text research articles to extract structured trial information, translates user queries into structured database searches, and provides an attributed question-answering system that generates evidence-grounded answers linked to specific source sentences. We demonstrate its utility through a user study involving clinicians, clinical researchers, and PhD students of pharmaceutical sciences and nursing, and a systematic automatic evaluation of its information extraction and question answering capabilities.

Slideflow: Deep Learning for Digital Histopathology with Real-Time Whole-Slide Visualization

Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40X magnification in 2.5 seconds per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.

Deep Learning Generates Synthetic Cancer Histology for Explainability and Education

Artificial intelligence (AI) methods including deep neural networks can provide rapid molecular classification of tumors from routine histology with accuracy that can match or exceed human pathologists. Discerning how neural networks make their predictions remains a significant challenge, but explainability tools can help provide insights into what models have learned when corresponding histologic features are poorly understood. Conditional generative adversarial networks (cGANs) are AI models that generate synthetic images and illustrate subtle differences between image classes. Here, we describe the use of a cGAN for explaining models trained to classify molecularly-subtyped tumors, exposing associated histologic features. We leverage cGANs to create class- and layer-blending visualizations to improve understanding of subtype morphology. Finally, we demonstrate the potential use of synthetic histology for augmenting pathology trainee education and show that clear, intuitive cGAN visualizations can reinforce and improve human understanding of histologic manifestations of tumor biology

Uncertainty-Informed Deep Learning Models Enable High-Confidence Predictions for Digital Histopathology

A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a novel, clinically-oriented approach to uncertainty quantification (UQ) for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without UQ, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that UQ thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts.