Recent advances in computational pathology have led to the emergence of numerous foundation models. These models typically rely on general-purpose encoders with multi-instance learning for whole slide image (WSI) classification or apply multimodal approaches to generate reports directly from images. However, these models cannot emulate the diagnostic approach of pathologists, who systematically examine slides at low magnification to obtain an overview before progressively zooming in on suspicious regions to formulate comprehensive diagnoses.

Alzheimer's disease (AD) is marked by cognitive decline along with the widespread of tau aggregates across the brain cortex. Due to the challenges of imaging pathology spreading flows in vivo, however, quantitative analysis on the cortical pathways of tau propagation and its interaction with the cascade of amyloid-beta (Aβ) plaques lags behind the experimental insights of underlying pathophysiological mechanisms. To address this challenge, we present a physics-informed neural network, empowered by mean-field theory, to uncover the biologically meaningful spreading pathways of tau aggregates between two longitudinal snapshots. Following the notion of'prion-like' mechanism in AD, we first formulate the dynamics of tau propagation as a mean-field game (MFG), where the spread of tau aggregate at each location (aka.

Pathology foundation models (PFMs) have emerged as powerful tools for analyzing whole slide images (WSIs). However, adapting these pretrained PFMs for specific clinical tasks presents considerable challenges, primarily due to the availability of only weak (WSI-level) labels for gigapixel images, necessitating multiple instance learning (MIL) paradigm for effective WSI analysis. This paper proposes a novel approach for single-GPUTask Adaptation of PFMs (TAPFM) that uses vision transformer (ViT) attention for MIL aggregation while optimizing both for feature representations and attention weights. The proposed approach maintains separate computational graphs for MIL aggregator and the PFM to create stable training dynamics that align with downstream task objectives during end-to-end adaptation. Evaluated on mutation prediction tasks for bladder cancer and lung adenocarcinoma across institutional and The Cancer Genome Atlas (TCGA) cohorts, TAPFM consistently outperforms conventional approaches, with H-Optimus-0 (TAPFM) outperforming the benchmarks. TAPFM effectively handles multi-label classification of actionable mutations as well. Thus, TAPFM makes adaptation of powerful pre-trained PFMs practical on standard hardware for various clinical applications.

Multimodal Large Language Models (LLMs) hold promise for biomedical reasoning, but current benchmarks fail to capture the complexity of real-world clinical workflows. Existing evaluations primarily assess unimodal, decontextualized question-answering, overlooking multi-agent decision-making environments such as Molecular Tumor Boards (MTBs). MTBs bring together diverse experts in oncology, where diagnostic and prognostic tasks require integrating heterogeneous data and evolving insights over time. Current benchmarks lack this longitudinal and multimodal complexity. We introduce MTBBench, an agentic benchmark simulating MTB-style decision-making through clinically challenging, multimodal, and longitudinal oncology questions. Ground truth annotations are validated by clinicians via a co-developed app, ensuring clinical relevance. We benchmark multiple open and closed-source LLMs and show that, even at scale, they lack reliability--frequently hallucinating, struggling with reasoning from time-resolved data, and failing to reconcile conflicting evidence or different modalities. To address these limitations, MTBBench goes beyond benchmarking by providing an agentic framework with foundation model-based tools that enhance multi-modal and longitudinal reasoning, leading to task-level performance gains of up to 9.0% and 11.2%, respectively. Overall, MTBBench offers a challenging and realistic testbed for advancing multimodal LLM reasoning, reliability, and tool-use with a focus on MTB environments in precision oncology.

Despite theoretical advantages, causal methods for Gene Regulatory Network (GRN) inference from single-cell RNA-seq data consistently fail to match or outperform correlation-based baselines in many realistic benchmarks, a persistent puzzle which casts doubt on the value of causality for this task. We argue that existing benchmarks are insufficiently controlled to answer this question because they evaluate on real or semi-real data where multiple pathologies co-occur, confounding failure modes, and obscuring the specific conditions under which different inference methods excel or fail. To address this gap, we introduce a controlled diagnostic framework that isolates seven biologically motivated pathologies (dropout, latent confounders, cell-type mixing, feedback loops, network density, sample size, and pseudotime drift) and measure how six representative methods spanning three inference paradigms degrade as each pathology intensifies. Across 6,120 controlled experiments, we find that causal methods genuinely dominate in clean and structurally favorable regimes, but specific pathologies (notably dropout and latent confounders) selectively neutralize their advantages. We further introduce an errortype decomposition that reveals methods with similar aggregate accuracy commit qualitatively different errors. To probe whether single-pathology effects persist when multiple stressors co-occur, we perform an interaction sweep over the three most impactful pathologies and find that their joint effects are sub-additive, while also exposing density-conditional cross-overs invisible to single-dial analysis. Our findings offer a nuanced understanding of when and why different methods succeed or fail for GRN inference, providing actionable insights for method development and practical guidance for practitioners.3

Magnification shift is a major obstacle to robust histopathology classification, because models trained on one imaging scale often generalize poorly to another. Here, we evaluated this problem on the BreaKHis dataset using a strict patient-disjoint leave-one-magnification-out protocol, comparing supervised baseline, baseline augmented with DCGAN-generated patches, and a gradient-reversal domain-general model designed to preserve discriminative information while suppressing magnification-specific variation. Across held-out magnifications, the domain-general model achieved the strongest overall discrimination and its clearest gain was observed when 200X was held out. By contrast, GAN augmentation produced inconsistent effects, improving some folds but degrading others, particularly at 400X. The domain-general model also yielded the lowest Brier score at 0.063 vs 0.089 at baseline. Sparse embedding analysis further revealed that domain-general training reduced average signature size more than three-fold (306 versus 1,074 dimensions) while preserving equivalent predictive performance (AUC: 0.967 vs 0.965; F1: 0.930 vs 0.931). It also increased cross-fold signature reproducibility from near-zero Jaccard overlap in the baseline to 0.99 between the 100X and 200X folds. These findings show that calibrated, compact, and transferable representations can be learned without added architectural complexity, with clear implications for the reliable deployment of computational pathology models across heterogeneous acquisition settings.

Varied number of bit split: To generate the samples in this split, we first sampled the number ofbits, then sampled each bitindividually from auniform Bernoulli distribution. Variednumberofonessplit: Here, we fixed the number of bits at30. NaturalLanguageParityDataset: Inorder totapinto thenatural language understanding capabilities of pretrained language models, we situated the parity task as a"coin flip problem". We trained baseline models with the same parameter count on a modified version of the variable assignment dataset where the order of the operations were randomly shuffled. We used greedy decoding in all of our experiments (including few-shot scratchpad ones).