Daily Papers

Pathology foundation models (FMs) produce powerful tile-level representations which remain sensitive to scanner and staining variability, undermining deployment across laboratories. We develop a novel fine-tuning recipe that improves the robustness of pathology FMs to acquisition factors. Applied to ten different FMs, our fine-tuning strategy consistently improves robustness for every model as well as downstream performance, with no observed trade-off. On average, it raises the PathoROB robustness index by 23% (from 0.72 to 0.87) and increases the overall cross-benchmark performance by 43% on Patho-Bench, HEST and THUNDER combined, with individual gains reaching up to 72% in robustness (Phikon-v2) and 76% in performance (Midnight-12k). We publicly release the fine-tuned versions of Phikon-v2 (Phaet) and Midnight-12k (Mascaret) at https://huggingface.co/wearewaiv/models.

Sensitivity to staining variation remains a major barrier to deploying computational pathology (CPath) models as hematoxylin and eosin (H&E) staining varies across laboratories, requiring systematic assessment of how this variability affects model prediction. In this work, we developed a three-step protocol for evaluating robustness to H&E staining variation in CPath models. Step 1: Select reference staining conditions, Step 2: Characterize test set staining properties, Step 3: Apply CPath model(s) under simulated reference staining conditions. Here, we first created a new reference staining library based on the PLISM dataset. As an exemplary use case, we applied the protocol to assess the robustness properties of 306 microsatellite instability (MSI) classification models on the unseen SurGen colorectal cancer dataset (n=738), including 300 attention-based multiple instance learning models trained on the TCGA-COAD/READ datasets across three feature extractors (UNI2-h, H-Optimus-1, Virchow2), alongside six public MSI classification models. Classification performance was measured as AUC, and robustness as the min-max AUC range across four simulated staining conditions (low/high H&E intensity, low/high H&E color similarity). Across models and staining conditions, classification performance ranged from AUC 0.769-0.911 (Δ = 0.142). Robustness ranged from 0.007-0.079 (Δ = 0.072), and showed a weak inverse correlation with classification performance (Pearson r=-0.22, 95% CI [-0.34, -0.11]). Thus, we show that the proposed evaluation protocol enables robustness-informed CPath model selection and provides insight into performance shifts across H&E staining conditions, supporting the identification of operational ranges for reliable model deployment. Code is available at https://github.com/CTPLab/staining-robustness-evaluation .

Recent advancements in digital pathology have led to the development of numerous foundational models that utilize self-supervised learning on patches extracted from gigapixel whole slide images (WSIs). While this approach leverages vast amounts of unlabeled data, we have discovered a significant issue: features extracted from these self-supervised models tend to cluster by individual WSIs, a phenomenon we term WSI-specific feature collapse. This problem can potentially limit the model's generalization ability and performance on various downstream tasks. To address this issue, we introduce Stain Normalized Pathology Foundational Model, a novel foundational model trained on patches that have undergone stain normalization. Stain normalization helps reduce color variability arising from different laboratories and scanners, enabling the model to learn more consistent features. Stain Normalized Pathology Foundational Model is trained using 285,153,903 patches extracted from a total of 34,795 WSIs, combining data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Our experiments demonstrate that Stain Normalized Pathology Foundational Model significantly mitigates the feature collapse problem, indicating that the model has learned more generalized features rather than overfitting to individual WSI characteristics. We compared Stain Normalized Pathology Foundational Model with state-of-the-art models across six downstream task datasets, and our results show that Stain Normalized Pathology Foundational Model achieves excellent performance relative to the number of WSIs used and the model's parameter count. This suggests that the application of stain normalization has substantially improved the model's efficiency and generalization capabilities.

Identifying subtle phenotypic variations in cellular images is critical for advancing biological research and accelerating drug discovery. These variations are often masked by the inherent cellular heterogeneity, making it challenging to distinguish differences between experimental conditions. Recent advancements in deep generative models have demonstrated significant potential for revealing these nuanced phenotypes through image translation, opening new frontiers in cellular and molecular biology as well as the identification of novel biomarkers. Among these generative models, diffusion models stand out for their ability to produce high-quality, realistic images. However, training diffusion models typically requires large datasets and substantial computational resources, both of which can be limited in biological research. In this work, we propose a novel approach that leverages pre-trained latent diffusion models to uncover subtle phenotypic changes. We validate our approach qualitatively and quantitatively on several small datasets of microscopy images. Our findings reveal that our approach enables effective detection of phenotypic variations, capturing both visually apparent and imperceptible differences. Ultimately, our results highlight the promising potential of this approach for phenotype detection, especially in contexts constrained by limited data and computational capacity.

Most papers caution against using predictive models for disease stratification based on unselected radiomic features, as these features are affected by contouring variability. Instead, they advocate for the use of the Intraclass Correlation Coefficient (ICC) as a measure of stability for feature selection. However, the direct effect of segmentation variability on the predictive models is rarely studied. This study investigates the impact of segmentation variability on feature stability and predictive performance in radiomics-based prediction of Triple-Negative Breast Cancer (TNBC) subtype using Magnetic Resonance Imaging. A total of 244 images from the Duke dataset were used, with segmentation variability introduced through modifications of manual segmentations. For each mask, explainable radiomic features were selected using the Shapley Additive exPlanations method and used to train logistic regression models. Feature stability across segmentations was assessed via ICC, Pearson's correlation, and reliability scores quantifying the relationship between feature stability and segmentation variability. Results indicate that segmentation accuracy does not significantly impact predictive performance. While incorporating peritumoral information may reduce feature reproducibility, it does not diminish feature predictive capability. Moreover, feature selection in predictive models is not inherently tied to feature stability with respect to segmentation, suggesting that an overreliance on ICC or reliability scores for feature selection might exclude valuable predictive features.

Hematoxylin and Eosin (H&E) staining is widely regarded as the standard in pathology for diagnosing diseases and tracking tumor recurrence. While H&E staining shows tissue structures, it lacks the ability to reveal specific proteins that are associated with disease severity and treatment response. Immunohistochemical (IHC) stains use antibodies to highlight the expression of these proteins on their respective cell types, improving diagnostic accuracy, and assisting with drug selection for treatment. Despite their value, IHC stains require additional time and resources, limiting their utilization in some clinical settings. Recent advances in deep learning have positioned Image-to-Image (I2I) translation as a computational, cost-effective alternative for IHC. I2I generates high fidelity stain transformations digitally, potentially replacing manual staining in IHC. Diffusion models, the current state of the art in image generation and conditional tasks, are particularly well suited for virtual IHC due to their ability to produce high quality images and resilience to mode collapse. However, these models require extensive and diverse datasets (often millions of samples) to achieve a robust performance, a challenge in virtual staining applications where only thousands of samples are typically available. Inspired by the success of multitask deep learning models in scenarios with limited data, we introduce STAINDIFFUSER, a novel multitask diffusion architecture tailored to virtual staining that achieves convergence with smaller datasets. STAINDIFFUSER simultaneously trains two diffusion processes: (a) generating cell specific IHC stains from H&E images and (b) performing H&E based cell segmentation, utilizing coarse segmentation labels exclusively during training. STAINDIFFUSER generates high-quality virtual stains for two markers, outperforming over twenty I2I baselines.

Medical image segmentation exhibits intra- and inter-annotator variability due to ambiguous object boundaries, annotator preferences, expertise, and tools, among other factors. Lesions with ambiguous boundaries, e.g., spiculated or infiltrative nodules, or irregular borders per the ABCD rule, are particularly prone to disagreement and are often associated with malignancy. In this work, we curate IMA++, the largest multi-annotator skin lesion segmentation dataset, on which we conduct an in-depth study of variability due to annotator, malignancy, tool, and skill factors. We find a statistically significant (p<0.001) association between inter-annotator agreement (IAA), measured using Dice, and the malignancy of skin lesions. We further show that IAA can be accurately predicted directly from dermoscopic images, achieving a mean absolute error of 0.108. Finally, we leverage this association by utilizing IAA as a "soft" clinical feature within a multi-task learning objective, yielding a 4.2% improvement in balanced accuracy averaged across multiple model architectures and across IMA++ and four public dermoscopic datasets. The code is available at https://github.com/sfu-mial/skin-IAV.

Virtual immunohistochemistry (IHC) staining from hematoxylin and eosin (H&E) images can accelerate diagnostics by providing preliminary molecular insight directly from routine sections, reducing the need for repeat sectioning when tissue is limited. Existing methods improve realism through contrastive objectives, prototype matching, or domain alignment, yet the generator itself receives no direct guidance from pathology foundation models. We present UNIStainNet, a SPADE-UNet conditioned on dense spatial tokens from a frozen pathology foundation model (UNI), providing tissue-level semantic guidance for stain translation. A misalignment-aware loss suite preserves stain quantification accuracy, and learned stain embeddings enable a single model to serve multiple IHC markers simultaneously. On MIST, UNIStainNet achieves state-of-the-art distributional metrics on all four stains (HER2, Ki67, ER, PR) from a single unified model, where prior methods typically train separate per-stain models. On BCI, it also achieves the best distributional metrics. A tissue-type stratified failure analysis reveals that remaining errors are systematic, concentrating in non-tumor tissue. Code is available at https://github.com/facevoid/UNIStainNet.

Foundation models trained with self-supervised learning (SSL) on large-scale histological images have significantly accelerated the development of computational pathology. These models can serve as backbones for region-of-interest (ROI) image analysis or patch-level feature extractors in whole-slide images (WSIs) based on multiple instance learning (MIL). Existing pathology foundation models (PFMs) are typically pre-trained on Hematoxylin-Eosin (H&E) stained pathology images. However, images with special stains, such as immunohistochemistry, are also frequently used in clinical practice. PFMs pre-trained mainly on H\&E-stained images may be limited in clinical applications involving special stains. To address this issue, we propose StainNet, a specialized foundation model for special stains based on the vision transformer (ViT) architecture. StainNet adopts a self-distillation SSL approach and is trained on over 1.4 million patch images cropping from 20,231 publicly available special staining WSIs in the HISTAI database. To evaluate StainNet, we conduct experiments on an in-house slide-level liver malignancy classification task and two public ROI-level datasets to demonstrate its strong ability. We also perform few-ratio learning and retrieval evaluations, and compare StainNet with recently larger PFMs to further highlight its strengths. We have released the StainNet model weights at: https://huggingface.co/JWonderLand/StainNet.

Visual clustering is a common perceptual task in scatterplots that supports diverse analytics tasks (e.g., cluster identification). However, even with the same scatterplot, the ways of perceiving clusters (i.e., conducting visual clustering) can differ due to the differences among individuals and ambiguous cluster boundaries. Although such perceptual variability casts doubt on the reliability of data analysis based on visual clustering, we lack a systematic way to efficiently assess this variability. In this research, we study perceptual variability in conducting visual clustering, which we call Cluster Ambiguity. To this end, we introduce CLAMS, a data-driven visual quality measure for automatically predicting cluster ambiguity in monochrome scatterplots. We first conduct a qualitative study to identify key factors that affect the visual separation of clusters (e.g., proximity or size difference between clusters). Based on study findings, we deploy a regression module that estimates the human-judged separability of two clusters. Then, CLAMS predicts cluster ambiguity by analyzing the aggregated results of all pairwise separability between clusters that are generated by the module. CLAMS outperforms widely-used clustering techniques in predicting ground truth cluster ambiguity. Meanwhile, CLAMS exhibits performance on par with human annotators. We conclude our work by presenting two applications for optimizing and benchmarking data mining techniques using CLAMS. The interactive demo of CLAMS is available at clusterambiguity.dev.

Immunohistochemical (IHC) staining highlights the molecular information critical to diagnostics in tissue samples. However, compared to H&E staining, IHC staining can be much more expensive in terms of both labor and the laboratory equipment required. This motivates recent research that demonstrates that the correlations between the morphological information present in the H&E-stained slides and the molecular information in the IHC-stained slides can be used for H&E-to-IHC stain translation. However, due to a lack of pixel-perfect H&E-IHC groundtruth pairs, most existing methods have resorted to relying on expert annotations. To remedy this situation, we present a new loss function, Adaptive Supervised PatchNCE (ASP), to directly deal with the input to target inconsistencies in a proposed H&E-to-IHC image-to-image translation framework. The ASP loss is built upon a patch-based contrastive learning criterion, named Supervised PatchNCE (SP), and augments it further with weight scheduling to mitigate the negative impact of noisy supervision. Lastly, we introduce the Multi-IHC Stain Translation (MIST) dataset, which contains aligned H&E-IHC patches for 4 different IHC stains critical to breast cancer diagnosis. In our experiment, we demonstrate that our proposed method outperforms existing image-to-image translation methods for stain translation to multiple IHC stains. All of our code and datasets are available at https://github.com/lifangda01/AdaptiveSupervisedPatchNCE.

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Assessing resection margins is central to pathological specimen evaluation and has profound implications for patient outcomes. Current practice employs physical inking, which is applied variably, and cautery artifacts can obscure the true margin on histological sections. We present a virtual inking network (VIN) that autonomously localizes the surgical cut surface on whole-slide images, reducing reliance on inks and standardizing margin-focused review. VIN uses a frozen foundation model as the feature extractor and a compact two-layer multilayer perceptron trained for patch-level classification of cautery-consistent features. The dataset comprised 120 hematoxylin and eosin (H&E) stained slides from 12 human tonsil tissue blocks, resulting in ~2 TB of uncompressed raw image data, where a board-certified pathologist provided boundary annotations. In blind testing with 20 slides from previously unseen blocks, VIN produced coherent margin overlays that qualitatively aligned with expert annotations across serial sections. Quantitatively, region-level accuracy was ~73.3% across the test set, with errors largely confined to limited areas that did not disrupt continuity of the whole-slide margin map. These results indicate that VIN captures cautery-related histomorphology and can provide a reproducible, ink-free margin delineation suitable for integration into routine digital pathology workflows and for downstream measurement of margin distances.

Stain normalization algorithms aim to transform the color and intensity characteristics of a source multi-gigapixel histology image to match those of a target image, mitigating inconsistencies in the appearance of stains used to highlight cellular components in the images. We propose a new approach, StainFuser, which treats this problem as a style transfer task using a novel Conditional Latent Diffusion architecture, eliminating the need for handcrafted color components. With this method, we curate SPI-2M the largest stain normalization dataset to date of over 2 million histology images with neural style transfer for high-quality transformations. Trained on this data, StainFuser outperforms current state-of-the-art GAN and handcrafted methods in terms of the quality of normalized images. Additionally, compared to existing approaches, it improves the performance of nuclei instance segmentation and classification models when used as a test time augmentation method on the challenging CoNIC dataset. Finally, we apply StainFuser on multi-gigapixel Whole Slide Images (WSIs) and demonstrate improved performance in terms of computational efficiency, image quality and consistency across tiles over current methods.

Mitotic figures are classified into typical and atypical variants, with atypical counts correlating strongly with tumor aggressiveness. Accurate differentiation is therefore essential for patient prognostication and resource allocation, yet remains challenging even for expert pathologists. Here, we leveraged Pathology Foundation Models (PFMs) pre-trained on large histopathology datasets and applied parameter-efficient fine-tuning via low-rank adaptation. In addition, we incorporated ConvNeXt V2, a state-of-the-art convolutional neural network architecture, to complement PFMs. During training, we employed a fisheye transform to emphasize mitoses and Fourier Domain Adaptation using ImageNet target images. Finally, we ensembled multiple PFMs to integrate complementary morphological insights, achieving competitive balanced accuracy on the Preliminary Evaluation Phase dataset.

Skin tone as a demographic bias and inconsistent human labeling poses challenges in dermatology AI. We take another angle to investigate color contrast's impact, beyond skin tones, on malignancy detection in skin disease datasets: We hypothesize that in addition to skin tones, the color difference between the lesion area and skin also plays a role in malignancy detection performance of dermatology AI models. To study this, we first propose a robust labeling method to quantify color contrast scores of each image and validate our method by showing small labeling variations. More importantly, applying our method to the only diverse-skin tone and pathologically-confirmed skin disease dataset DDI, yields DDI-CoCo Dataset, and we observe a performance gap between the high and low color difference groups. This disparity remains consistent across various state-of-the-art (SoTA) image classification models, which supports our hypothesis. Furthermore, we study the interaction between skin tone and color difference effects and suggest that color difference can be an additional reason behind model performance bias between skin tones. Our work provides a complementary angle to dermatology AI for improving skin disease detection.

To effectively optimize and personalize treatments, it is necessary to investigate the heterogeneity of treatment effects. With the wide range of users being treated over many online controlled experiments, the typical approach of manually investigating each dimension of heterogeneity becomes overly cumbersome and prone to subjective human biases. We need an efficient way to search through thousands of experiments with hundreds of target covariates and hundreds of breakdown dimensions. In this paper, we propose a systematic paradigm for detecting, surfacing and characterizing heterogeneous treatment effects. First, we detect if treatment effect variation is present in an experiment, prior to specifying any breakdowns. Second, we surface the most relevant dimensions for heterogeneity. Finally, we characterize the heterogeneity beyond just the conditional average treatment effects (CATE) by studying the conditional distributions of the estimated individual treatment effects. We show the effectiveness of our methods using simulated data and empirical studies.

Existing losses used in deep metric learning (DML) for image retrieval often lead to highly non-uniform intra-class and inter-class representation structures across test classes and data distributions. When combined with the common practice of using a fixed threshold to declare a match, this gives rise to significant performance variations in terms of false accept rate (FAR) and false reject rate (FRR) across test classes and data distributions. We define this issue in DML as threshold inconsistency. In real-world applications, such inconsistency often complicates the threshold selection process when deploying commercial image retrieval systems. To measure this inconsistency, we propose a novel variance-based metric called Operating-Point-Inconsistency-Score (OPIS) that quantifies the variance in the operating characteristics across classes. Using the OPIS metric, we find that achieving high accuracy levels in a DML model does not automatically guarantee threshold consistency. In fact, our investigation reveals a Pareto frontier in the high-accuracy regime, where existing methods to improve accuracy often lead to degradation in threshold consistency. To address this trade-off, we introduce the Threshold-Consistent Margin (TCM) loss, a simple yet effective regularization technique that promotes uniformity in representation structures across classes by selectively penalizing hard sample pairs. Extensive experiments demonstrate TCM's effectiveness in enhancing threshold consistency while preserving accuracy, simplifying the threshold selection process in practical DML settings.

Image-to-image translation (I2I) methods allow the generation of artificial images that share the content of the original image but have a different style. With the advances in Generative Adversarial Networks (GANs)-based methods, I2I methods enabled the generation of artificial images that are indistinguishable from natural images. Recently, I2I methods were also employed in histopathology for generating artificial images of in silico stained tissues from a different type of staining. We refer to this process as stain transfer. The number of I2I variants is constantly increasing, which makes a well justified choice of the most suitable I2I methods for stain transfer challenging. In our work, we compare twelve stain transfer approaches, three of which are based on traditional and nine on GAN-based image processing methods. The analysis relies on complementary quantitative measures for the quality of image translation, the assessment of the suitability for deep learning-based tissue grading, and the visual evaluation by pathologists. Our study highlights the strengths and weaknesses of the stain transfer approaches, thereby allowing a rational choice of the underlying I2I algorithms. Code, data, and trained models for stain transfer between H&E and Masson's Trichrome staining will be made available online.

Pathology Foundation Models (FMs) hold great promise for healthcare. Before they can be used in clinical practice, it is essential to ensure they are robust to variations between medical centers. We measure whether pathology FMs focus on biological features like tissue and cancer type, or on the well known confounding medical center signatures introduced by staining procedure and other differences. We introduce the Robustness Index. This novel robustness metric reflects to what degree biological features dominate confounding features. Ten current publicly available pathology FMs are evaluated. We find that all current pathology foundation models evaluated represent the medical center to a strong degree. Significant differences in the robustness index are observed. Only one model so far has a robustness index greater than one, meaning biological features dominate confounding features, but only slightly. A quantitative approach to measure the influence of medical center differences on FM-based prediction performance is described. We analyze the impact of unrobustness on classification performance of downstream models, and find that cancer-type classification errors are not random, but specifically attributable to same-center confounders: images of other classes from the same medical center. We visualize FM embedding spaces, and find these are more strongly organized by medical centers than by biological factors. As a consequence, the medical center of origin is predicted more accurately than the tissue source and cancer type. The robustness index introduced here is provided with the aim of advancing progress towards clinical adoption of robust and reliable pathology FMs.

Development of artificial intelligence (AI) techniques in medical imaging requires access to large-scale and diverse datasets for training and evaluation. In dermatology, obtaining such datasets remains challenging due to significant variations in patient populations, illumination conditions, and acquisition system characteristics. In this work, we propose S-SYNTH, the first knowledge-based, adaptable open-source skin simulation framework to rapidly generate synthetic skin, 3D models and digitally rendered images, using an anatomically inspired multi-layer, multi-component skin and growing lesion model. The skin model allows for controlled variation in skin appearance, such as skin color, presence of hair, lesion shape, and blood fraction among other parameters. We use this framework to study the effect of possible variations on the development and evaluation of AI models for skin lesion segmentation, and show that results obtained using synthetic data follow similar comparative trends as real dermatologic images, while mitigating biases and limitations from existing datasets including small dataset size, lack of diversity, and underrepresentation.

Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify several proteins expressed on the surface of cells, enabling cell classification, better understanding of the tumour micro-environment, more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, they are expensive and time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is much cheaper and easier to perform, but is not typically used in this case as it binds to DNA rather than to the proteins targeted by immunofluorescent techniques, and it was not previously thought possible to differentiate cells expressing these proteins based only on DNA morphology. In this work we show otherwise, training a deep convolutional neural network to identify cells expressing three proteins (T lymphocyte markers CD3 and CD8, and the B lymphocyte marker CD20) with greater than 90% precision and recall, from Hoechst 33342 stained tissue only. Our model learns previously unknown morphological features associated with expression of these proteins which can be used to accurately differentiate lymphocyte subtypes for use in key prognostic metrics such as assessment of immune cell infiltration,and thereby predict and improve patient outcomes without the need for costly multiplex immunofluorescence.

Domain generalization is critical for real-world applications of machine learning to microscopy images, including histopathology and fluorescence imaging. Artifacts in these modalities arise through a complex combination of factors relating to tissue collection and laboratory processing, as well as factors intrinsic to patient samples. In fluorescence imaging, these artifacts stem from variations across experimental batches. The complexity and subtlety of these artifacts make the enumeration of data domains intractable. Therefore, augmentation-based methods of domain generalization that require domain identifiers and manual fine-tuning are inadequate in this setting. To overcome this challenge, we introduce ContriMix, a domain generalization technique that learns to generate synthetic images by disentangling and permuting the biological content ("content") and technical variations ("attributes") in microscopy images. ContriMix does not rely on domain identifiers or handcrafted augmentations and makes no assumptions about the input characteristics of images. We assess the performance of ContriMix on two pathology datasets dealing with patch classification and Whole Slide Image label prediction tasks respectively (Camelyon17-WILDS and RCC subtyping), and one fluorescence microscopy dataset (RxRx1-WILDS). Without any access to domain identifiers at train or test time, ContriMix performs similar or better than current state-of-the-art methods in all these datasets, motivating its usage for microscopy image analysis in real-world settings where domain information is hard to come by. The code for ContriMix can be found at https://gitlab.com/huutan86/contrimix

Since their discovery, AGN light curves are known to be intrinsically variable. In the optical/UV band, this variability is consistent with correlated or red noise and is particularly well described by the damped random walk (DRW) model. In this work, we evaluate the feasibility of a new method for identifying spatially unresolved couples of AGN through a fully Bayesian time-domain analysis of the observed light curves (LCs). More specifically, we check whether observed LCs are better described by a single DRW, which we interpret as emitted by a single massive black hole (MBH), or a pair of independent DRWs, generated by a pair of MBHs. We test the method on mock LCs associated with a single MBH and pairs generated with different cadences and lengths of observational campaigns. We constrained the occurrence of false positives, that is, the percentage of single MBH LCs that show substantial evidence in favour of the unresolved MBH pair scenario, finding a fraction of 0.2% and 0.59% in the even and uneven sampling scenarios. We discuss how well the method recovers the model parameters, showing that about 51% and 7% of the simulated LCs have all the recovered parameters within 20% of their true values in our best scenario of evenly sampled LCs for the single MBH and MBH pair scenarios, respectively. We finally study the region of the parameter space in which the detection of an MBH pair is possible, finding that such objects can be correctly identified if the timescales of the process describing the noise are very different, with a ratio smaller than ~0.2, and the variability amplitudes are similar, with their ratio bigger than ~0.2. When limiting to such a region of the parameter space, the fraction of pairs with all the recovered parameters within 20% of the injected values increases up to about 14% and 8% for evenly and unevenly sampled LCs, respectively.

Reproducibility is essential for scientific research. However, in computer vision, achieving consistent results is challenging due to various factors. One influential, yet often unrecognized, factor is CUDA-induced randomness. Despite CUDA's advantages for accelerating algorithm execution on GPUs, if not controlled, its behavior across multiple executions remains non-deterministic. While reproducibility issues in ML being researched, the implications of CUDA-induced randomness in application are yet to be understood. Our investigation focuses on this randomness across one standard benchmark dataset and two real-world datasets in an isolated environment. Our results show that CUDA-induced randomness can account for differences up to 4.77% in performance scores. We find that managing this variability for reproducibility may entail increased runtime or reduce performance, but that disadvantages are not as significant as reported in previous studies.

In this article, we study the consistency of the template estimation with the Fr\'echet mean in quotient spaces. The Fr\'echet mean in quotient spaces is often used when the observations are deformed or transformed by a group action. We show that in most cases this estimator is actually inconsistent. We exhibit a sufficient condition for this inconsistency, which amounts to the folding of the distribution of the noisy template when it is projected to the quotient space. This condition appears to be fulfilled as soon as the support of the noise is large enough. To quantify this inconsistency we provide lower and upper bounds of the bias as a function of the variability (the noise level). This shows that the consistency bias cannot be neglected when the variability increases.

High-throughput screening techniques are commonly used to obtain large quantities of data in many fields of biology. It is well known that artifacts arising from variability in the technical execution of different experimental batches within such screens confound these observations and can lead to invalid biological conclusions. It is therefore necessary to account for these batch effects when analyzing outcomes. In this paper we describe RxRx1, a biological dataset designed specifically for the systematic study of batch effect correction methods. The dataset consists of 125,510 high-resolution fluorescence microscopy images of human cells under 1,138 genetic perturbations in 51 experimental batches across 4 cell types. Visual inspection of the images alone clearly demonstrates significant batch effects. We propose a classification task designed to evaluate the effectiveness of experimental batch correction methods on these images and examine the performance of a number of correction methods on this task. Our goal in releasing RxRx1 is to encourage the development of effective experimental batch correction methods that generalize well to unseen experimental batches. The dataset can be downloaded at https://rxrx.ai.

Single-channel 3D reconstruction is widely used in fields such as robotics and medical imaging. While these methods are good at reconstructing 3D geometry, their outputs are typically uncolored 3D models, making 3D colorization necessary for visualization. Recent 3D colorization studies address this problem by distilling 2D image colorization models. However, these approaches suffer from an inherent inconsistency of 2D image models. This results in colors being averaged during training, leading to monotonous and oversimplified results, particularly in complex 360° scenes. In contrast, we aim to preserve color diversity by generating a new set of consistently colorized training views, thereby suppressing the averaging process. Nevertheless, mitigating the averaging process introduces a new challenge: ensuring strict multi-view consistency across these colorized views. To achieve this, we propose \ourmethod, a pipeline designed to preserve color diversity by eliminating this guidance-averaging process with a `Local-Global' approach: we partition the scene into subscenes and explicitly tackle both inter-subscene and intra-subscene consistency using a fine-tuned multi-view diffusion model. We demonstrate our method achieves quantitatively and qualitatively more consistent and plausible 3D colorization on complex 360° scenes than existing methods.

Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1 - EPVS, 9 for Task 2 - Microbleeds and 6 for Task 3 - Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1 - EPVS and Task 2 - Microbleeds and not practically useful results yet for Task 3 - Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.

Typical neural network trainings have substantial variance in test-set performance between repeated runs, impeding hyperparameter comparison and training reproducibility. We present the following results towards understanding this variation. (1) Despite having significant variance on their test-sets, we demonstrate that standard CIFAR-10 and ImageNet trainings have very little variance in their performance on the test-distributions from which those test-sets are sampled, suggesting that variance is less of a practical issue than previously thought. (2) We present a simplifying statistical assumption which closely approximates the structure of the test-set accuracy distribution. (3) We argue that test-set variance is inevitable in the following two senses. First, we show that variance is largely caused by high sensitivity of the training process to initial conditions, rather than by specific sources of randomness like the data order and augmentations. Second, we prove that variance is unavoidable given the observation that ensembles of trained networks are well-calibrated. (4) We conduct preliminary studies of distribution-shift, fine-tuning, data augmentation and learning rate through the lens of variance between runs.

Diffusion models trained on different, non-overlapping subsets of a dataset often produce strikingly similar outputs when given the same noise seed. We trace this consistency to a simple linear effect: the shared Gaussian statistics across splits already predict much of the generated images. To formalize this, we develop a random matrix theory (RMT) framework that quantifies how finite datasets shape the expectation and variance of the learned denoiser and sampling map in the linear setting. For expectations, sampling variability acts as a renormalization of the noise level through a self-consistent relation σ^2 mapsto κ(σ^2), explaining why limited data overshrink low-variance directions and pull samples toward the dataset mean. For fluctuations, our variance formulas reveal three key factors behind cross-split disagreement: anisotropy across eigenmodes, inhomogeneity across inputs, and overall scaling with dataset size. Extending deterministic-equivalence tools to fractional matrix powers further allows us to analyze entire sampling trajectories. The theory sharply predicts the behavior of linear diffusion models, and we validate its predictions on UNet and DiT architectures in their non-memorization regime, identifying where and how samples deviates across training data split. This provides a principled baseline for reproducibility in diffusion training, linking spectral properties of data to the stability of generative outputs.

Blazars, a class of active galactic nuclei (AGN) powered by supermassive black holes, are known for their remarkable variability across multiple timescales and wavelengths. With advancements in both ground- and space-based telescopes, our understanding of AGN central engines has significantly improved. However, the mechanisms driving this variability remain elusive, and continue to fascinate both theorists and observers alike. The primary objective of this study is to constrain the X-ray variability properties of the TeV blazar PKS 2155-304. We conduct a comprehensive X-ray spectral and timing analysis, focusing on both long-term and intra-day variability. This analysis uses data from 22 epochs of XMM-Newton EPIC-pn observations, collected over 15 years (2000-2014). To investigate the variability of the source, we applied both timing and spectral analyses. For the timing analysis, we estimated fractional variability, variability amplitude, minimum variability timescales, flux distribution, and power spectral density (PSD). In the spectral analysis, we fitted the X-ray spectra using power-law, log-parabola, and broken power-law (BPL) models to determine the best-fitting parameters. Additionally, we studied the hardness ratio (HR). We observed moderate intra-day variability in most of the light curves. Seven out of the twenty-two observations showed a clear bimodal flux distribution, indicating the presence of two distinct flux states. Our analysis revealed a variable power-law PSD slope. Most HR plots did not show significant variation with flux, except for one observation (OBSID 0124930501), where HR increased with flux (Count/s). The fitted X-ray spectra favored the BPL model for the majority of observations. The findings of this work shed light on the intraday variability of blazars, providing insights into the non-thermal jet processes that drive the observed flux variations.

Ensemble disagreement is widely used as a proxy for epistemic uncertainty in medical image segmentation. In practice, many studies form ensembles via K-fold cross-validation (CV), yet refer to them as ``deep ensembles'' (DE). Because CV members are trained on different data subsets, their disagreement mixes seed-driven variability with data-exposure effects, which can change how uncertainty should be interpreted. We audit recent segmentation uncertainty studies and find that terminology--implementation mismatches are common. We then compare a standard 5-fold CV ensemble to a 5-member DE (fixed training set, different random seeds) under otherwise identical configurations on three multi-rater segmentation datasets spanning three modalities. We evaluate uncertainty for calibration, failure detection, ambiguity modeling, and robustness under distribution shift. DE match segmentation accuracy while improving calibration and failure detection, whereas CV ensembles sometimes correlate more strongly with inter-rater variability on the studied datasets. Thus, ensemble construction should be chosen to match the research question: DE for reliability-oriented use (e.g., selective referral/failure detection) and CV ensembles as a proxy for ambiguity. We provide a lightweight nnU-Net modification enabling DE training within the default pipeline.

Developing self-supervised learning (SSL) models that can learn universal and transferable representations of H&E gigapixel whole-slide images (WSIs) is becoming increasingly valuable in computational pathology. These models hold the potential to advance critical tasks such as few-shot classification, slide retrieval, and patient stratification. Existing approaches for slide representation learning extend the principles of SSL from small images (e.g., 224 x 224 patches) to entire slides, usually by aligning two different augmentations (or views) of the slide. Yet the resulting representation remains constrained by the limited clinical and biological diversity of the views. Instead, we postulate that slides stained with multiple markers, such as immunohistochemistry, can be used as different views to form a rich task-agnostic training signal. To this end, we introduce Madeleine, a multimodal pretraining strategy for slide representation learning. Madeleine is trained with a dual global-local cross-stain alignment objective on large cohorts of breast cancer samples (N=4,211 WSIs across five stains) and kidney transplant samples (N=12,070 WSIs across four stains). We demonstrate the quality of slide representations learned by Madeleine on various downstream evaluations, ranging from morphological and molecular classification to prognostic prediction, comprising 21 tasks using 7,299 WSIs from multiple medical centers. Code is available at https://github.com/mahmoodlab/MADELEINE.

In biological research, fluorescence staining is a key technique to reveal the locations and morphology of subcellular structures. However, it is slow, expensive, and harmful to cells. In this paper, we model it as a deep learning task termed subcellular structure prediction (SSP), aiming to predict the 3D fluorescent images of multiple subcellular structures from a 3D transmitted-light image. Unfortunately, due to the limitations of current biotechnology, each image is partially labeled in SSP. Besides, naturally, subcellular structures vary considerably in size, which causes the multi-scale issue of SSP. To overcome these challenges, we propose Re-parameterizing Mixture-of-Diverse-Experts (RepMode), a network that dynamically organizes its parameters with task-aware priors to handle specified single-label prediction tasks. In RepMode, the Mixture-of-Diverse-Experts (MoDE) block is designed to learn the generalized parameters for all tasks, and gating re-parameterization (GatRep) is performed to generate the specialized parameters for each task, by which RepMode can maintain a compact practical topology exactly like a plain network, and meanwhile achieves a powerful theoretical topology. Comprehensive experiments show that RepMode can achieve state-of-the-art overall performance in SSP.

The galaxy population is strongly bimodal in both colour and morphology, and the two measures correlate strongly, with most blue galaxies being late-types (spirals) and most early-types, typically ellipticals, being red. This observation has led to the use of colour as a convenient selection criteria to make samples which are then labelled by morphology. Such use of colour as a proxy for morphology results in necessarily impure and incomplete samples. In this paper, we make use of the morphological labels produced by Galaxy Zoo to measure how incomplete and impure such samples are, considering optical (ugriz), NUV and NIR (JHK) bands. The best single colour optical selection is found using a threshold of g-r = 0.742, but this still results in a sample where only 56% of red galaxies are smooth and 56% of smooth galaxies are red. Use of the NUV gives some improvement over purely optical bands, particularly for late-types, but still results in low purity/completeness for early-types. No significant improvement is found by adding NIR bands. With any two bands, including NUV, a sample of early-types with greater than two-thirds purity cannot be constructed. Advances in quantitative galaxy morphologies have made colour-morphology proxy selections largely unnecessary going forward; where such assumptions are still required, we recommend studies carefully consider the implications of sample incompleteness/impurity.

This dataset represents almost all the harmful diseases for rice in Bangladesh. This dataset consists of 1106 image of five harmful diseases called Brown Spot, Leaf Scaled, Rice Blast, Rice Turngo, Steath Blight in two different background variation named field background picture and white background picture. Two different background variation helps the dataset to perform more accurately so that the user can use this data for field use as well as white background for decision making. The data is collected from rice field of Dhaka Division. This dataset can use for rice leaf diseases classification, diseases detection using Computer Vision and Pattern Recognition for different rice leaf disease.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability. To help drive forward research and innovation for automatic nuclei recognition in CPath, we organise the Colon Nuclei Identification and Counting (CoNIC) Challenge. The challenge encourages researchers to develop algorithms that perform segmentation, classification and counting of nuclei within the current largest known publicly available nuclei-level dataset in CPath, containing around half a million labelled nuclei. Therefore, the CoNIC challenge utilises over 10 times the number of nuclei as the previous largest challenge dataset for nuclei recognition. It is important for algorithms to be robust to input variation if we wish to deploy them in a clinical setting. Therefore, as part of this challenge we will also test the sensitivity of each submitted algorithm to certain input variations.

Chromosome analysis is vital for diagnosing genetic disorders and guiding cancer therapy decisions through the identification of somatic clonal aberrations. However, developing an AI model are hindered by the overwhelming complexity and diversity of chromosomal abnormalities, requiring extensive annotation efforts, while automated methods remain task-specific and lack generalizability due to the scarcity of comprehensive datasets spanning diverse resource conditions. Here, we introduce CHROMA, a foundation model for cytogenomics, designed to overcome these challenges by learning generalizable representations of chromosomal abnormalities. Pre-trained on over 84,000 specimens (~4 million chromosomal images) via self-supervised learning, CHROMA outperforms other methods across all types of abnormalities, even when trained on fewer labelled data and more imbalanced datasets. By facilitating comprehensive mapping of instability and clonal leisons across various aberration types, CHROMA offers a scalable and generalizable solution for reliable and automated clinical analysis, reducing the annotation workload for experts and advancing precision oncology through the early detection of rare genomic abnormalities, enabling broad clinical AI applications and making advanced genomic analysis more accessible.

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Accurate histopathologic interpretation is key for clinical decision-making; however, current deep learning models for digital pathology are often overconfident and poorly calibrated in out-of-distribution (OOD) settings, which limit trust and clinical adoption. Safety-critical medical imaging workflows benefit from intrinsic uncertainty-aware properties that can accurately reject OOD input. We implement the Spectral-normalized Neural Gaussian Process (SNGP), a set of lightweight modifications that apply spectral normalization and replace the final dense layer with a Gaussian process layer to improve single-model uncertainty estimation and OOD detection. We evaluate SNGP vs. deterministic and MonteCarlo dropout on six datasets across three biomedical classification tasks: white blood cells, amyloid plaques, and colorectal histopathology. SNGP has comparable in-distribution performance while significantly improving uncertainty estimation and OOD detection. Thus, SNGP or related models offer a useful framework for uncertainty-aware classification in digital pathology, supporting safe deployment and building trust with pathologists.

Diffusion models are the state of the art in text-to-image generation, but their perceptual variability remains understudied. In this paper, we examine how prompts affect image variability in black-box diffusion-based models. We propose W1KP, a human-calibrated measure of variability in a set of images, bootstrapped from existing image-pair perceptual distances. Current datasets do not cover recent diffusion models, thus we curate three test sets for evaluation. Our best perceptual distance outperforms nine baselines by up to 18 points in accuracy, and our calibration matches graded human judgements 78% of the time. Using W1KP, we study prompt reusability and show that Imagen prompts can be reused for 10-50 random seeds before new images become too similar to already generated images, while Stable Diffusion XL and DALL-E 3 can be reused 50-200 times. Lastly, we analyze 56 linguistic features of real prompts, finding that the prompt's length, CLIP embedding norm, concreteness, and word senses influence variability most. As far as we are aware, we are the first to analyze diffusion variability from a visuolinguistic perspective. Our project page is at http://w1kp.com.

Is it possible to perform linear regression on datasets whose labels are shuffled with respect to the inputs? We explore this question by proposing several estimators that recover the weights of a noisy linear model from labels that are shuffled by an unknown permutation. We show that the analog of the classical least-squares estimator produces inconsistent estimates in this setting, and introduce an estimator based on the self-moments of the input features and labels. We study the regimes in which each estimator excels, and generalize the estimators to the setting where partial ordering information is available in the form of experiments replicated independently. The result is a framework that enables robust inference, as we demonstrate by experiments on both synthetic and standard datasets, where we are able to recover approximate weights using only shuffled labels. Our work demonstrates that linear regression in the absence of complete ordering information is possible and can be of practical interest, particularly in experiments that characterize populations of particles, such as flow cytometry.

Building Virtual Cells that can accurately simulate cellular responses to perturbations is a long-standing goal in systems biology. A fundamental challenge is that high-throughput single-cell sequencing is destructive: the same cell cannot be observed both before and after a perturbation. Thus, perturbation prediction requires mapping unpaired control and perturbed populations. Existing models address this by learning maps between distributions, but typically assume a single fixed response distribution when conditioned on observed cellular context (e.g., cell type) and the perturbation type. In reality, responses vary systematically due to unobservable latent factors such as microenvironmental fluctuations and complex batch effects, forming a manifold of possible distributions for the same observed conditions. To account for this variability, we introduce PerturbDiff, which shifts modeling from individual cells to entire distributions. By embedding distributions as points in a Hilbert space, we define a diffusion-based generative process operating directly over probability distributions. This allows PerturbDiff to capture population-level response shifts across hidden factors. Benchmarks on established datasets show that PerturbDiff achieves state-of-the-art performance in single-cell response prediction and generalizes substantially better to unseen perturbations. See our project page (https://katarinayuan.github.io/PerturbDiff-ProjectPage/), where code and data will be made publicly available (https://github.com/DeepGraphLearning/PerturbDiff).

Addressing fairness in lesion classification from dermatological images is crucial due to variations in how skin diseases manifest across skin tones. However, the absence of skin tone labels in public datasets hinders building a fair classifier. To date, such skin tone labels have been estimated prior to fairness analysis in independent studies using the Individual Typology Angle (ITA). Briefly, ITA calculates an angle based on pixels extracted from skin images taking into account the lightness and yellow-blue tints. These angles are then categorised into skin tones that are subsequently used to analyse fairness in skin cancer classification. In this work, we review and compare four ITA-based approaches of skin tone classification on the ISIC18 dataset, a common benchmark for assessing skin cancer classification fairness in the literature. Our analyses reveal a high disagreement among previously published studies demonstrating the risks of ITA-based skin tone estimation methods. Moreover, we investigate the causes of such large discrepancy among these approaches and find that the lack of diversity in the ISIC18 dataset limits its use as a testbed for fairness analysis. Finally, we recommend further research on robust ITA estimation and diverse dataset acquisition with skin tone annotation to facilitate conclusive fairness assessments of artificial intelligence tools in dermatology. Our code is available at https://github.com/tkalbl/RevisitingSkinToneFairness.

Large language models can arrive at the same answer through reasoning paths that are unstable, contradictory, or difficult to rank consistently -- a failure mode especially prevalent in multi-step deductive reasoning. Existing methods assess reliability primarily through output dispersion -- measuring how much sampled answers differ -- but this discards a complementary signal: whether the model can consistently rank competing reasoning candidates. We propose structural uncertainty, a consistency-aware framework derived from the stability of self-preference-induced rankings over sampled reasoning solutions. Given a query, we generate multiple candidate solutions and ask the model to judge pairwise preferences among its own outputs. We aggregate self-preferences into ranking distributions via Bradley-Terry modeling with PageRank, and decompose the signal into two entropy-based components: across-trial ranking instability and within-trial candidate ambiguity. Across five LLMs and eight benchmarks, structural signals provide information complementary to answer dispersion: on logical and mathematical reasoning tasks, the combination improves identification of unreliable instances, while on factual retrieval the structural signal collapses toward uniformity, diagnosing a regime boundary where reasoning-level consistency evaluation is uninformative. The two components relate differently to accuracy: within-trial ambiguity correlates positively with correctness -- consistent with settings where multiple plausible solution paths remain competitive -- while across-trial instability correlates negatively, signaling unreliable reasoning. Structural uncertainty is best understood not as a universal confidence estimator, but as a regime-sensitive evaluator of logical reasoning consistency.

Multi-site neuroimaging analysis is fundamentally confounded by scanner-induced covariate shifts, where the marginal distribution of voxel intensities P(x) varies non-linearly across acquisition protocols while the conditional anatomy P(y|x) remains constant. This is particularly detrimental to radiomic reproducibility, where acquisition variance often exceeds biological pathology variance. Existing statistical harmonization methods (e.g., ComBat) operate in feature space, precluding spatial downstream tasks, while standard deep learning approaches are theoretically bounded by local effective receptive fields (ERF), failing to model the global intensity correlations characteristic of field-strength bias. We propose SA-CycleGAN-2.5D, a domain adaptation framework motivated by the HΔH-divergence bound of Ben-David et al., integrating three architectural innovations: (1) A 2.5D tri-planar manifold injection preserving through-plane gradients nabla_z at O(HW) complexity; (2) A U-ResNet generator with dense voxel-to-voxel self-attention, surpassing the O(L) receptive field limit of CNNs to model global scanner field biases; and (3) A spectrally-normalized discriminator constraining the Lipschitz constant (K_D le 1) for stable adversarial optimization. Evaluated on 654 glioma patients across two institutional domains (BraTS and UPenn-GBM), our method reduces Maximum Mean Discrepancy (MMD) by 99.1% (1.729 to 0.015) and degrades domain classifier accuracy to near-chance (59.7%). Ablation confirms that global attention is statistically essential (Cohen's d = 1.32, p < 0.001) for the harder heterogeneous-to-homogeneous translation direction. By bridging 2D efficiency and 3D consistency, our framework yields voxel-level harmonized images that preserve tumor pathophysiology, enabling reproducible multi-center radiomic analysis.

Phylogenetic comparative methods may fail to produce meaningful results when either the underlying model is inappropriate or the data contain insufficient information to inform the inference. The ability to measure the statistical power of these methods has become crucial to ensure that data quantity keeps pace with growing model complexity. Through simulations, we show that commonly applied model choice methods based on information criteria can have remarkably high error rates; this can be a problem because methods to estimate the uncertainty or power are not widely known or applied. Furthermore, the power of comparative methods can depend significantly on the structure of the data. We describe a Monte Carlo based method which addresses both of these challenges, and show how this approach both quantifies and substantially reduces errors relative to information criteria. The method also produces meaningful confidence intervals for model parameters. We illustrate how the power to distinguish different models, such as varying levels of selection, varies both with number of taxa and structure of the phylogeny. We provide an open-source implementation in the pmc ("Phylogenetic Monte Carlo") package for the R programming language. We hope such power analysis becomes a routine part of model comparison in comparative methods.

Human medical data can be challenging to obtain due to data privacy concerns, difficulties conducting certain types of experiments, or prohibitive associated costs. In many settings, data from animal models or in-vitro cell lines are available to help augment our understanding of human data. However, this data is known for having low etiological validity in comparison to human data. In this work, we augment small human medical datasets with in-vitro data and animal models. We use Invariant Risk Minimisation (IRM) to elucidate invariant features by considering cross-organism data as belonging to different data-generating environments. Our models identify genes of relevance to human cancer development. We observe a degree of consistency between varying the amounts of human and mouse data used, however, further work is required to obtain conclusive insights. As a secondary contribution, we enhance existing open source datasets and provide two uniformly processed, cross-organism, homologue gene-matched datasets to the community.

Despite advances in generation quality, current text-to-image (T2I) models often lack diversity, generating homogeneous outputs. This work introduces a framework to address the need for robust diversity evaluation in T2I models. Our framework systematically assesses diversity by evaluating individual concepts and their relevant factors of variation. Key contributions include: (1) a novel human evaluation template for nuanced diversity assessment; (2) a curated prompt set covering diverse concepts with their identified factors of variation (e.g. prompt: An image of an apple, factor of variation: color); and (3) a methodology for comparing models in terms of human annotations via binomial tests. Furthermore, we rigorously compare various image embeddings for diversity measurement. Notably, our principled approach enables ranking of T2I models by diversity, identifying categories where they particularly struggle. This research offers a robust methodology and insights, paving the way for improvements in T2I model diversity and metric development.

Deep learning (DL) has become the dominant approach for medical image segmentation, yet ensuring the reliability and clinical applicability of these models requires addressing key challenges such as annotation variability, calibration, and uncertainty estimation. This is why we created the Calibration and Uncertainty for multiRater Volume Assessment in multiorgan Segmentation (CURVAS), which highlights the critical role of multiple annotators in establishing a more comprehensive ground truth, emphasizing that segmentation is inherently subjective and that leveraging inter-annotator variability is essential for robust model evaluation. Seven teams participated in the challenge, submitting a variety of DL models evaluated using metrics such as Dice Similarity Coefficient (DSC), Expected Calibration Error (ECE), and Continuous Ranked Probability Score (CRPS). By incorporating consensus and dissensus ground truth, we assess how DL models handle uncertainty and whether their confidence estimates align with true segmentation performance. Our findings reinforce the importance of well-calibrated models, as better calibration is strongly correlated with the quality of the results. Furthermore, we demonstrate that segmentation models trained on diverse datasets and enriched with pre-trained knowledge exhibit greater robustness, particularly in cases deviating from standard anatomical structures. Notably, the best-performing models achieved high DSC and well-calibrated uncertainty estimates. This work underscores the need for multi-annotator ground truth, thorough calibration assessments, and uncertainty-aware evaluations to develop trustworthy and clinically reliable DL-based medical image segmentation models.

Analyzing outcomes in long-term cancer survivor studies can be complex. The effects of predictors on the failure process may be difficult to assess over longer periods of time, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. In this manuscript, we compare seven different survival models that estimate the hazard rate and the effects of proportional and non-proportional covariates. In particular, we focus on an extension of the the multi-resolution hazard (MRH) estimator, combining a non-proportional hierarchical MRH approach with a data-driven pruning algorithm that allows for computational efficiency and produces robust estimates even in times of few observed failures. Using data from a large-scale randomized prostate cancer clinical trial, we examine patterns of biochemical failure and estimate the time-varying effects of androgen deprivation therapy treatment and other covariates. We compare the impact of different modeling strategies and smoothness assumptions on the estimated treatment effect. Our results show that the benefits of treatment diminish over time, possibly with implications for future treatment protocols.

Derived from diffusion models, MangaNinjia specializes in the task of reference-guided line art colorization. We incorporate two thoughtful designs to ensure precise character detail transcription, including a patch shuffling module to facilitate correspondence learning between the reference color image and the target line art, and a point-driven control scheme to enable fine-grained color matching. Experiments on a self-collected benchmark demonstrate the superiority of our model over current solutions in terms of precise colorization. We further showcase the potential of the proposed interactive point control in handling challenging cases, cross-character colorization, multi-reference harmonization, beyond the reach of existing algorithms.

In industrial settings, surface defects on steel can significantly compromise its service life and elevate potential safety risks. Traditional defect detection methods predominantly rely on manual inspection, which suffers from low efficiency and high costs. Although automated defect detection approaches based on Convolutional Neural Networks(e.g., Mask R-CNN) have advanced rapidly, their reliability remains challenged due to data annotation uncertainties during deep model training and overfitting issues. These limitations may lead to detection deviations when processing the given new test samples, rendering automated detection processes unreliable. To address this challenge, we first evaluate the detection model's practical performance through calibration data that satisfies the independent and identically distributed (i.i.d) condition with test data. Specifically, we define a loss function for each calibration sample to quantify detection error rates, such as the complement of recall rate and false discovery rate. Subsequently, we derive a statistically rigorous threshold based on a user-defined risk level to identify high-probability defective pixels in test images, thereby constructing prediction sets (e.g., defect regions). This methodology ensures that the expected error rate (mean error rate) on the test set remains strictly bounced by the predefined risk level. Additionally, we observe a negative correlation between the average prediction set size and the risk level on the test set, establishing a statistically rigorous metric for assessing detection model uncertainty. Furthermore, our study demonstrates robust and efficient control over the expected test set error rate across varying calibration-to-test partitioning ratios, validating the method's adaptability and operational effectiveness.

We conducted more than 1.3 million comparisons of iris patterns encoded from images collected at two Nigerian universities, which constitute the newly available African Human Iris (AFHIRIS) database. The purpose was to discover whether ethnic differences in iris structure and appearance such as the textural feature size, as contrasted with an all-Chinese image database or an American database in which only 1.53% were of African-American heritage, made a material difference for iris discrimination. We measured a reduction in entropy for the AFHIRIS database due to the coarser iris features created by the thick anterior layer of melanocytes, and we found stochastic parameters that accurately model the relevant empirical distributions. Quantile-Quantile analysis revealed that a very small change in operational decision thresholds for the African database would compensate for the reduced entropy and generate the same performance in terms of resistance to False Matches. We conclude that despite demographic difference, individuality can be robustly discerned by comparison of iris patterns in this West African population.

Vision-language models in pathology enable multimodal case retrieval and automated report generation. Many of the models developed so far, however, have been trained on pathology reports that include information which cannot be inferred from paired whole slide images (e.g., patient history), potentially leading to hallucinated sentences in generated reports. To this end, we investigate how the selection of information from pathology reports for vision-language modeling affects the quality of the multimodal representations and generated reports. More concretely, we compare a model trained on full reports against a model trained on preprocessed reports that only include sentences describing the cell and tissue appearances based on the H&E-stained slides. For the experiments, we built upon the BLIP-2 framework and used a cutaneous melanocytic lesion dataset of 42,433 H&E-stained whole slide images and 19,636 corresponding pathology reports. Model performance was assessed using image-to-text and text-to-image retrieval, as well as qualitative evaluation of the generated reports by an expert pathologist. Our results demonstrate that text preprocessing prevents hallucination in report generation. Despite the improvement in the quality of the generated reports, training the vision-language model on full reports showed better cross-modal retrieval performance.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

The recent 'Mpox' outbreak, formerly known as 'Monkeypox', has become a significant public health concern and has spread to over 110 countries globally. The challenge of clinically diagnosing mpox early on is due, in part, to its similarity to other types of rashes. Computer-aided screening tools have been proven valuable in cases where Polymerase Chain Reaction (PCR) based diagnosis is not immediately available. Deep learning methods are powerful in learning complex data representations, but their efficacy largely depends on adequate training data. To address this challenge, we present the "Mpox Skin Lesion Dataset Version 2.0 (MSLD v2.0)" as a follow-up to the previously released openly accessible dataset, one of the first datasets containing mpox lesion images. This dataset contains images of patients with mpox and five other non-mpox classes (chickenpox, measles, hand-foot-mouth disease, cowpox, and healthy). We benchmark the performance of several state-of-the-art deep learning models, including VGG16, ResNet50, DenseNet121, MobileNetV2, EfficientNetB3, InceptionV3, and Xception, to classify mpox and other infectious skin diseases. In order to reduce the impact of racial bias, we utilize a color space data augmentation method to increase skin color variability during training. Additionally, by leveraging transfer learning implemented with pre-trained weights generated from the HAM10000 dataset, an extensive collection of pigmented skin lesion images, we achieved the best overall accuracy of 83.59pm2.11%. Finally, the developed models are incorporated within a prototype web application to analyze uploaded skin images by a user and determine whether a subject is a suspected mpox patient.

Recently, a myriad of conditional image generation and editing models have been developed to serve different downstream tasks, including text-to-image generation, text-guided image editing, subject-driven image generation, control-guided image generation, etc. However, we observe huge inconsistencies in experimental conditions: datasets, inference, and evaluation metrics - render fair comparisons difficult. This paper proposes ImagenHub, which is a one-stop library to standardize the inference and evaluation of all the conditional image generation models. Firstly, we define seven prominent tasks and curate high-quality evaluation datasets for them. Secondly, we built a unified inference pipeline to ensure fair comparison. Thirdly, we design two human evaluation scores, i.e. Semantic Consistency and Perceptual Quality, along with comprehensive guidelines to evaluate generated images. We train expert raters to evaluate the model outputs based on the proposed metrics. Our human evaluation achieves a high inter-worker agreement of Krippendorff's alpha on 76% models with a value higher than 0.4. We comprehensively evaluated a total of around 30 models and observed three key takeaways: (1) the existing models' performance is generally unsatisfying except for Text-guided Image Generation and Subject-driven Image Generation, with 74% models achieving an overall score lower than 0.5. (2) we examined the claims from published papers and found 83% of them hold with a few exceptions. (3) None of the existing automatic metrics has a Spearman's correlation higher than 0.2 except subject-driven image generation. Moving forward, we will continue our efforts to evaluate newly published models and update our leaderboard to keep track of the progress in conditional image generation.

With the advent of novel cancer treatment options such as immunotherapy, studying the tumour immune micro-environment (TIME) is crucial to inform on prognosis and understand potential response to therapeutic agents. A key approach to characterising the TIME may be through combining (1) digitised microscopic high-resolution optical images of hematoxylin and eosin (H&E) stained tissue sections obtained in routine histopathology examinations with (2) automated immune cell detection and classification methods. In this work, we introduce a workflow to automatically generate robust single cell contours and labels from dually stained tissue sections with H&E and multiplexed immunofluorescence (IF) markers. The approach harnesses the Segment Anything Model and requires minimal human intervention compared to existing single cell databases. With this methodology, we create Immunocto, a massive, multi-million automatically generated database of 6,848,454 human cells and objects, including 2,282,818 immune cells distributed across 4 subtypes: CD4^+ T cell lymphocytes, CD8^+ T cell lymphocytes, CD20^+ B cell lymphocytes, and CD68^+/CD163^+ macrophages. For each cell, we provide a 64times64 pixels^2 H&E image at 40times magnification, along with a binary mask of the nucleus and a label. The database, which is made publicly available, can be used to train models to study the TIME on routine H&E slides. We show that deep learning models trained on Immunocto result in state-of-the-art performance for lymphocyte detection. The approach demonstrates the benefits of using matched H&E and IF data to generate robust databases for computational pathology applications.

Convolutional Neural Networks have demonstrated dermatologist-level performance in the classification of melanoma from skin lesion images, but prediction irregularities due to biases seen within the training data are an issue that should be addressed before widespread deployment is possible. In this work, we robustly remove bias and spurious variation from an automated melanoma classification pipeline using two leading bias unlearning techniques. We show that the biases introduced by surgical markings and rulers presented in previous studies can be reasonably mitigated using these bias removal methods. We also demonstrate the generalisation benefits of unlearning spurious variation relating to the imaging instrument used to capture lesion images. Our experimental results provide evidence that the effects of each of the aforementioned biases are notably reduced, with different debiasing techniques excelling at different tasks.

Tissue segmentation is a routine preprocessing step to reduce the computational cost of whole slide image (WSI) analysis by excluding background regions. Traditional image processing techniques are commonly used for tissue segmentation, but often require manual adjustments to parameter values for atypical cases, fail to exclude all slide and scanning artifacts from the background, and are unable to segment adipose tissue. Pen marking artifacts in particular can be a potential source of bias for subsequent analyses if not removed. In addition, several applications require the separation of individual cross-sections, which can be challenging due to tissue fragmentation and adjacent positioning. To address these problems, we develop a convolutional neural network for tissue and pen marking segmentation using a dataset of 200 H&E stained WSIs. For separating tissue cross-sections, we propose a novel post-processing method based on clustering predicted centroid locations of the cross-sections in a 2D histogram. On an independent test set, the model achieved a mean Dice score of 0.981pm0.033 for tissue segmentation and a mean Dice score of 0.912pm0.090 for pen marking segmentation. The mean absolute difference between the number of annotated and separated cross-sections was 0.075pm0.350. Our results demonstrate that the proposed model can accurately segment H&E stained tissue cross-sections and pen markings in WSIs while being robust to many common slide and scanning artifacts. The model with trained model parameters and post-processing method are made publicly available as a Python package called SlideSegmenter.

Despite the remarkable progress in generative modelling, current diffusion models lack a quantitative approach to assess image quality. To address this limitation, we propose to estimate the pixel-wise aleatoric uncertainty during the sampling phase of diffusion models and utilise the uncertainty to improve the sample generation quality. The uncertainty is computed as the variance of the denoising scores with a perturbation scheme that is specifically designed for diffusion models. We then show that the aleatoric uncertainty estimates are related to the second-order derivative of the diffusion noise distribution. We evaluate our uncertainty estimation algorithm and the uncertainty-guided sampling on the ImageNet and CIFAR-10 datasets. In our comparisons with the related work, we demonstrate promising results in filtering out low quality samples. Furthermore, we show that our guided approach leads to better sample generation in terms of FID scores.

Unlike color photography images, which are consistently encoded into RGB channels, biological images encompass various modalities, where the type of microscopy and the meaning of each channel varies with each experiment. Importantly, the number of channels can range from one to a dozen and their correlation is often comparatively much lower than RGB, as each of them brings specific information content. This aspect is largely overlooked by methods designed out of the bioimage field, and current solutions mostly focus on intra-channel spatial attention, often ignoring the relationship between channels, yet crucial in most biological applications. Importantly, the variable channel type and count prevent the projection of several experiments to a unified representation for large scale pre-training. In this study, we propose ChAda-ViT, a novel Channel Adaptive Vision Transformer architecture employing an Inter-Channel Attention mechanism on images with an arbitrary number, order and type of channels. We also introduce IDRCell100k, a bioimage dataset with a rich set of 79 experiments covering 7 microscope modalities, with a multitude of channel types, and channel counts varying from 1 to 10 per experiment. Our proposed architecture, trained in a self-supervised manner, outperforms existing approaches in several biologically relevant downstream tasks. Additionally, it can be used to bridge the gap for the first time between assays with different microscopes, channel numbers or types by embedding various image and experimental modalities into a unified biological image representation. The latter should facilitate interdisciplinary studies and pave the way for better adoption of deep learning in biological image-based analyses. Code and Data to be released soon.

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis suffers from limited reproducibility and diagnostic variability. To overcome these limitations, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on over 353 million multi-scale images from 210,043 H&E-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, protein expression status prediction, gene mutation prediction, and prognosis evaluation. We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.70% sensitivity across nine independent medical institutions. This work not only advances AI-driven precision pathology for GI diseases but also bridge critical gaps in histopathological practice.

Social scientists are now using large language models to create "silicon samples" - synthetic datasets intended to stand in for human respondents, aimed at revolutionising human subjects research. However, there are many analytic choices which must be made to produce these samples. Though many of these choices are defensible, their impact on sample quality is poorly understood. I map out these analytic choices and demonstrate how a very small number of decisions can dramatically change the correspondence between silicon samples and human data. Configurations (N = 252) varied substantially in their capacity to estimate (i) rank ordering of participants, (ii) response distributions, and (iii) between-scale correlations. Most critically, configurations were not consistent in quality: those that performed well on one dimension often performed poorly on another, implying that there is no "one-size-fits-all" configuration that optimises the accuracy of these samples. I call for greater attention to the threat of analytic flexibility in using silicon samples.

Timely and accurate lymphoma diagnosis is essential for guiding cancer treatment. Standard diagnostic practice combines hematoxylin and eosin (HE)-stained whole slide images with immunohistochemistry, flow cytometry, and molecular genetic tests to determine lymphoma subtypes, a process requiring costly equipment, skilled personnel, and causing treatment delays. Deep learning methods could assist pathologists by extracting diagnostic information from routinely available HE-stained slides, yet comprehensive benchmarks for lymphoma subtyping on multicenter data are lacking. In this work, we present the first multicenter lymphoma benchmarking dataset covering four common lymphoma subtypes and healthy control tissue. We systematically evaluate five publicly available pathology foundation models (H-optimus-1, H0-mini, Virchow2, UNI2, Titan) combined with attention-based (AB-MIL) and transformer-based (TransMIL) multiple instance learning aggregators across three magnifications (10x, 20x, 40x). On in-distribution test sets, models achieve multiclass balanced accuracies exceeding 80% across all magnifications, with all foundation models performing similarly and both aggregation methods showing comparable results. The magnification study reveals that 40x resolution is sufficient, with no performance gains from higher resolutions or cross-magnification aggregation. However, on out-of-distribution test sets, performance drops substantially to around 60%, highlighting significant generalization challenges. To advance the field, larger multicenter studies covering additional rare lymphoma subtypes are needed. We provide an automated benchmarking pipeline to facilitate such future research.

Image-based or morphological profiling is a rapidly expanding field wherein cells are "profiled" by extracting hundreds to thousands of unbiased, quantitative features from images of cells that have been perturbed by genetic or chemical perturbations. The Cell Painting assay is the most popular imaged-based profiling assay wherein six small-molecule dyes label eight cellular compartments and thousands of measurements are made, describing quantitative traits such as size, shape, intensity, and texture within the nucleus, cytoplasm, and whole cell (Cimini et al., 2023). We have created the Cell Painting Gallery, a publicly available collection of Cell Painting datasets, with granular dataset descriptions and access instructions. It is hosted by AWS on the Registry of Open Data (RODA). As of January 2024, the Cell Painting Gallery holds 656 terabytes (TB) of image and associated numerical data. It includes the largest publicly available Cell Painting dataset, in terms of perturbations tested (Joint Undertaking for Morphological Profiling or JUMP (Chandrasekaran et al., 2023)), along with many other canonical datasets using Cell Painting, close derivatives of Cell Painting (such as LipocyteProfiler (Laber et al., 2023) and Pooled Cell Painting (Ramezani et al., 2023)).

In recent years, the advent of foundation models (FM) for digital pathology has relied heavily on scaling the pre-training datasets and the model size, yielding large and powerful models. While it resulted in improving the performance on diverse downstream tasks, it also introduced increased computational cost and inference time. In this work, we explore the distillation of a large foundation model into a smaller one, reducing the number of parameters by several orders of magnitude. Leveraging distillation techniques, our distilled model, H0-mini, achieves nearly comparable performance to large FMs at a significantly reduced inference cost. It is evaluated on several public benchmarks, achieving 3rd place on the HEST benchmark and 5th place on the EVA benchmark. Additionally, a robustness analysis conducted on the PLISM dataset demonstrates that our distilled model reaches excellent robustness to variations in staining and scanning conditions, significantly outperforming other state-of-the art models. This opens new perspectives to design lightweight and robust models for digital pathology, without compromising on performance.

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

Rapid progress in computational pathology is increasingly driven by vision foundation models pretrained on vast histopathology datasets. While recent efforts have prioritized training on an ever-larger amount of patches, we take an alternative approach focused on data diversity. Our foundation model, Athena, was initialized from a pretrained model and trained on just 115 million tissue patches, several times fewer than recent histopathology foundation models. Rather than relying on patch volume or complex sampling heuristics, we maximize data diversity by randomly selecting only a moderate number of patches per whole-slide image from our diverse internal repository, which spans multiple countries, institutions, and scanner types. Evaluated on a single patch-level benchmark and four slide-level downstream tasks (two molecular and two morphological), Athena approaches the state-of-the-art and even surpasses several models trained on substantially larger datasets. This indicates that diversity across whole-slide images, rather than patch quantity alone, drives learning in histopathology foundation models.

In this paper, we show that paint markings are a feasible approach to automatize the analysis of behavioral assays involving honey bees in the field where marking has to be as lightweight as possible. We contribute a novel dataset for bees re-identification with paint-markings with 4392 images and 27 identities. Contrastive learning with a ResNet backbone and triplet loss led to identity representation features with almost perfect recognition in closed setting where identities are known in advance. Diverse experiments evaluate the capability to generalize to separate IDs, and show the impact of using different body parts for identification, such as using the unmarked abdomen only. In addition, we show the potential to fully automate the visit detection and provide preliminary results of compute time for future real-time deployment in the field on an edge device.

Point-based interactive colorization techniques allow users to effortlessly colorize grayscale images using user-provided color hints. However, point-based methods often face challenges when different colors are given to semantically similar areas, leading to color intermingling and unsatisfactory results-an issue we refer to as color collapse. The fundamental cause of color collapse is the inadequacy of points for defining the boundaries for each color. To mitigate color collapse, we introduce a lasso tool that can control the scope of each color hint. Additionally, we design a framework that leverages the user-provided lassos to localize the attention masks. The experimental results show that using a single lasso is as effective as applying 4.18 individual color hints and can achieve the desired outcomes in 30% less time than using points alone.

Machine learning models are often used to inform real world risk assessment tasks: predicting consumer default risk, predicting whether a person suffers from a serious illness, or predicting a person's risk to appear in court. Given multiple models that perform almost equally well for a prediction task, to what extent do predictions vary across these models? If predictions are relatively consistent for similar models, then the standard approach of choosing the model that optimizes a penalized loss suffices. But what if predictions vary significantly for similar models? In machine learning, this is referred to as predictive multiplicity i.e. the prevalence of conflicting predictions assigned by near-optimal competing models. In this paper, we present a framework for measuring predictive multiplicity in probabilistic classification (predicting the probability of a positive outcome). We introduce measures that capture the variation in risk estimates over the set of competing models, and develop optimization-based methods to compute these measures efficiently and reliably for convex empirical risk minimization problems. We demonstrate the incidence and prevalence of predictive multiplicity in real-world tasks. Further, we provide insight into how predictive multiplicity arises by analyzing the relationship between predictive multiplicity and data set characteristics (outliers, separability, and majority-minority structure). Our results emphasize the need to report predictive multiplicity more widely.

Rare diseases collectively affect an estimated 3.5% to 5.9% of the population, yet more than 70% of patients are misdiagnosed and many endure years of evaluation before a diagnosis is reached, because early presentations are nonspecific and relevant expertise is scarce and unevenly distributed. Artificial intelligence could provide support, but existing systems address isolated stages of care, overwhelmingly diagnosis. They typically depend on the results of downstream investigations, and they treat the variability between models as noise to be eliminated. Here we present RareLens, a system that supports clinical decision-making across the entire rare disease trajectory by exploiting this variability. When heterogeneous large language models evaluate the same case, they generate divergent but complementary reasoning, which RareLens aligns and calibrates into a single convergent, actionable decision at each stage. Four coordinated modules perform primary-visit risk screening, diagnosis, treatment planning and prognosis. Developed and evaluated on RareBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, at each stage. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external study spanning 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both substantially outperformed unaided physicians. These findings indicate that aligning divergent model reasoning, rather than scaling a single model, offers a generalizable strategy for high-uncertainty clinical decision-making.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intraclass variability. In this work, we propose an approach that combine Separable-HoverNet and Instance-YOLOv5 to indentify colon nuclei small and unbalanced. Our approach can achieve mPQ+ 0.389 on the Segmentation and Classification-Preliminary Test Dataset and r2 0.599 on the Cellular Composition-Preliminary Test Dataset on ISBI 2022 CoNIC Challenge.

We present a systematic study of the BVRI colours of novae over the course of their eruptions. Where possible, interstellar reddening was measured using the equivalent widths of Diffuse Interstellar Bands (DIBs). Some novae lack spectra with sufficient resolution and signal-to-noise ratios; therefore, we supplement as necessary with 3D and 2D dust maps. Utilising only novae with DIB- or 3D-map-based E(B-V), we find an average intrinsic (B-V)_0 colour of novae at V-band light curve peak of 0.18 with a standard deviation of 0.31, based on a sample of 23 novae. When the light curve has declined by 2 magnitudes (t_2), we find an average (B-V)_0 = -0.02 with a standard deviation of 0.19. These average colours are consistent with previous findings, although the spreads are larger than previously found due to more accurate reddening estimates. We also examined the intrinsic (R-I)_0 and (V-R)_0 colours across our sample. These colours behave similarly to (B-V)_0, except that the (V-R)_0 colour gets redder after peak, likely due to the contributions of emission line flux. We searched for correlations between nova colours and t_2, peak V-band absolute magnitude, and GeV gamma-ray luminosity, but find no statistically significant correlations. Nova colours can therefore be used as standard "crayons" to estimate interstellar reddening from photometry alone, with 0.2--0.3 mag uncertainty. We present a novel Bayesian strategy for estimating distances to Galactic novae based on these E(B-V) measurements, independent of assumptions about luminosity, built using 3D dust maps and a stellar mass model of the Milky Way.

Background: Health datasets from clinical sources do not reflect the breadth and diversity of disease in the real world, impacting research, medical education, and artificial intelligence (AI) tool development. Dermatology is a suitable area to develop and test a new and scalable method to create representative health datasets. Methods: We used Google Search advertisements to invite contributions to an open access dataset of images of dermatology conditions, demographic and symptom information. With informed contributor consent, we describe and release this dataset containing 10,408 images from 5,033 contributions from internet users in the United States over 8 months starting March 2023. The dataset includes dermatologist condition labels as well as estimated Fitzpatrick Skin Type (eFST) and Monk Skin Tone (eMST) labels for the images. Results: We received a median of 22 submissions/day (IQR 14-30). Female (66.72%) and younger (52% < age 40) contributors had a higher representation in the dataset compared to the US population, and 32.6% of contributors reported a non-White racial or ethnic identity. Over 97.5% of contributions were genuine images of skin conditions. Dermatologist confidence in assigning a differential diagnosis increased with the number of available variables, and showed a weaker correlation with image sharpness (Spearman's P values <0.001 and 0.01 respectively). Most contributions were short-duration (54% with onset < 7 days ago ) and 89% were allergic, infectious, or inflammatory conditions. eFST and eMST distributions reflected the geographical origin of the dataset. The dataset is available at github.com/google-research-datasets/scin . Conclusion: Search ads are effective at crowdsourcing images of health conditions. The SCIN dataset bridges important gaps in the availability of representative images of common skin conditions.

Machine learning models for medical image analysis often suffer from poor performance on important subsets of a population that are not identified during training or testing. For example, overall performance of a cancer detection model may be high, but the model still consistently misses a rare but aggressive cancer subtype. We refer to this problem as hidden stratification, and observe that it results from incompletely describing the meaningful variation in a dataset. While hidden stratification can substantially reduce the clinical efficacy of machine learning models, its effects remain difficult to measure. In this work, we assess the utility of several possible techniques for measuring and describing hidden stratification effects, and characterize these effects on multiple medical imaging datasets. We find evidence that hidden stratification can occur in unidentified imaging subsets with low prevalence, low label quality, subtle distinguishing features, or spurious correlates, and that it can result in relative performance differences of over 20% on clinically important subsets. Finally, we explore the clinical implications of our findings, and suggest that evaluation of hidden stratification should be a critical component of any machine learning deployment in medical imaging.

How does the accuracy of deep neural network models trained to classify clinical images of skin conditions vary across skin color? While recent studies demonstrate computer vision models can serve as a useful decision support tool in healthcare and provide dermatologist-level classification on a number of specific tasks, darker skin is underrepresented in the data. Most publicly available data sets do not include Fitzpatrick skin type labels. We annotate 16,577 clinical images sourced from two dermatology atlases with Fitzpatrick skin type labels and open-source these annotations. Based on these labels, we find that there are significantly more images of light skin types than dark skin types in this dataset. We train a deep neural network model to classify 114 skin conditions and find that the model is most accurate on skin types similar to those it was trained on. In addition, we evaluate how an algorithmic approach to identifying skin tones, individual typology angle, compares with Fitzpatrick skin type labels annotated by a team of human labelers.

Uncertainty estimation is essential for the safe clinical deployment of medical image segmentation systems, enabling the identification of unreliable predictions and supporting human oversight. While prior work has largely focused on pixel-level uncertainty, landmark-based segmentation offers inherent topological guarantees yet remains underexplored from an uncertainty perspective. In this work, we study uncertainty estimation for anatomical landmark-based segmentation on chest X-rays. Inspired by hybrid neural network architectures that combine standard image convolutional encoders with graph-based generative decoders, and leveraging their variational latent space, we derive two complementary measures: (i) latent uncertainty, captured directly from the learned distribution parameters, and (ii) predictive uncertainty, obtained by generating multiple stochastic output predictions from latent samples. Through controlled corruption experiments we show that both uncertainty measures increase with perturbation severity, reflecting both global and local degradation. We demonstrate that these uncertainty signals can identify unreliable predictions by comparing with manual ground-truth, and support out-of-distribution detection on the CheXmask dataset. More importantly, we release CheXmask-U (huggingface.co/datasets/mcosarinsky/CheXmask-U), a large scale dataset of 657,566 chest X-ray landmark segmentations with per-node uncertainty estimates, enabling researchers to account for spatial variations in segmentation quality when using these anatomical masks. Our findings establish uncertainty estimation as a promising direction to enhance robustness and safe deployment of landmark-based anatomical segmentation methods in chest X-ray. A fully working interactive demo of the method is available at huggingface.co/spaces/matiasky/CheXmask-U and the source code at github.com/mcosarinsky/CheXmask-U.

The J-region Asymptotic Giant Branch (JAGB) is an overdensity of stars in the near-infrared, attributed to carbon-rich asymptotic giant branch stars, and recently used as a standard candle for measuring extragalactic distances and the Hubble constant. Using JWST in Cycle 2, we extend JAGB measurements to 6 hosts of 9 Type Ia supernovae (SNe Ia) (NGC 2525, NGC 3147, NGC 3370, NGC 3447, NGC 5468, and NGC 5861), with two at D sim 40 Mpc, all calibrated by the maser host NGC 4258. We investigate the effects of incompleteness and find that we are unable to recover a robust JAGB measurement in one of the two most distant hosts at R sim 40 Mpc, NGC 3147. We compile all JWST JAGB observations in SNe Ia hosts, 15 galaxies hosting 18 SNe Ia, from the SH0ES and CCHP programs and employ all literature measures (mode, mean, median, model). We find no significant mean difference between these distances and those from HST Cepheids, -0.03pm0.02 (stat) pm 0.05 (sys) mag. We find a difference of 0.11 pm 0.02 mag between JAGB mode measurements in the CCHP analyses of two fields in NGC 4258, a feature also seen in two SH0ES fields (see field-to-field variations in Li et al. 2024a), indicating significant field-to-field variation of JAGB measurements in NGC 4258 which produce a large absolute calibration uncertainty. Variations are also seen in the shape of the JAGB LF across galaxies so that different measures produce different values of the Hubble constant. We look for but do not (yet) find a standardizing relation between JAGB LF skew or color dependence and the apparent variation. Using the middle result of all JAGB measures to calibrate SNe Ia yields a Hubble constant of H_0 = 73.3 pm 1.4 (stat) pm 2.0 (sys) km/s/Mpc with the systematic dominated by apparent differences across NGC 4258 calibrating fields or their measures.

The progress in the generation of synthetic images has made it crucial to assess their quality. While several metrics have been proposed to assess the rendering of images, it is crucial for Text-to-Image (T2I) models, which generate images based on a prompt, to consider additional aspects such as to which extent the generated image matches the important content of the prompt. Moreover, although the generated images usually result from a random starting point, the influence of this one is generally not considered. In this article, we propose a new metric based on prompt templates to study the alignment between the content specified in the prompt and the corresponding generated images. It allows us to better characterize the alignment in terms of the type of the specified objects, their number, and their color. We conducted a study on several recent T2I models about various aspects. An additional interesting result we obtained with our approach is that image quality can vary drastically depending on the latent noise used as a seed for the images. We also quantify the influence of the number of concepts in the prompt, their order as well as their (color) attributes. Finally, our method allows us to identify some latent seeds that produce better images than others, opening novel directions of research on this understudied topic.

Histopathology image analysis is fundamental to digital pathology, with hematoxylin and eosin (H&E) staining as the gold standard for diagnostic and prognostic assessments. While H&E imaging effectively highlights cellular and tissue structures, it lacks sensitivity to birefringence and tissue anisotropy, which are crucial for assessing collagen organization, fiber alignment, and microstructural alterations--key indicators of tumor progression, fibrosis, and other pathological conditions. To bridge this gap, we construct a polarization imaging system and curate a new dataset of over 13,000 paired Polar-H&E images. Visualizations of polarization properties reveal distinctive optical signatures in pathological tissues, underscoring its diagnostic value. Building on this dataset, we propose PolarHE, a dual-modality fusion framework that integrates H&E with polarization imaging, leveraging the latter ability to enhance tissue characterization. Our approach employs a feature decomposition strategy to disentangle common and modality specific features, ensuring effective multimodal representation learning. Through comprehensive validation, our approach significantly outperforms previous methods, achieving an accuracy of 86.70% on the Chaoyang dataset and 89.06% on the MHIST dataset. These results demonstrate that polarization imaging is a powerful and underutilized modality in computational pathology, enriching feature representation and improving diagnostic accuracy. PolarHE establishes a promising direction for multimodal learning, paving the way for more interpretable and generalizable pathology models.

In recent years, text-driven image editing has made significant progress. However, due to the inherent ambiguity and discreteness of natural language, color editing still faces challenges such as insufficient precision and difficulty in achieving continuous control. Although linearly interpolating the embedding vectors of different textual descriptions can guide the model to generate a sequence of images with varying colors, this approach lacks precise control over the range of color changes in the output images. Moreover, the relationship between the interpolation coefficient and the resulting image color is unknown and uncontrollable. To address these issues, we introduce a color mapping module that explicitly models the correspondence between the text embedding space and image RGB values. This module predicts the corresponding embedding vector based on a given RGB value, enabling precise color control of the generated images while maintaining semantic consistency. Users can specify a target RGB range to generate images with continuous color variations within the desired range, thereby achieving finer-grained, continuous, and controllable color editing. Experimental results demonstrate that our method performs well in terms of color continuity and controllability.

A central statistical problem in population genetics is to infer evolutionary and biological parameters such as the strength of natural selection and allele age from DNA samples extracted from a contemporary population. That all samples come only from the present-day has long been known to limit statistical inference; there is potentially more information available if one also has access to ancient DNA so that inference is based on a time-series of historical changes in allele frequencies. We introduce a Markov Chain Monte Carlo (MCMC) method for Bayesian inference from allele frequency time-series data based on an underlying Wright--Fisher diffusion model of evolution, through which one can infer the parameters of essentially any selection model including those with frequency-dependent effects. The chief novelty is that we show this method to be exact in the sense that it is possible to augment the state space explored by MCMC with the unobserved diffusion trajectory, even though the transition function of this diffusion is intractable. Through careful design of a proposal distribution, we describe an efficient method in which updates to the trajectory and accept/reject decisions are calculated without error. We illustrate the method on data capturing changes in coat colour over the past 20,000 years, and find evidence to support previous findings that the mutant alleles ASIP and MC1R responsible for changes in coat color have experienced very strong, possibly overdominant, selection and further provide estimates for the ages of these genes.

The VIP Cup offers a unique experience to undergraduates, allowing students to work together to solve challenging, real-world problems with video and image processing techniques. In this iteration of the VIP Cup, we challenged students to balance personalization and generalization when performing biomarker detection in 3D optical coherence tomography (OCT) images. Balancing personalization and generalization is an important challenge to tackle, as the variation within OCT scans of patients between visits can be minimal while the difference in manifestation of the same disease across different patients may be substantial. The domain difference between OCT scans can arise due to pathology manifestation across patients, clinical labels, and the visit along the treatment process when the scan is taken. Hence, we provided a multimodal OCT dataset to allow teams to effectively target this challenge. Overall, this competition gave undergraduates an opportunity to learn about how artificial intelligence can be a powerful tool for the medical field, as well as the unique challenges one faces when applying machine learning to biomedical data.

Deep Neural Networks achieve high performance in vision tasks by learning features from regions of interest (ROI) within images, but their performance degrades when deployed on out-of-distribution (OOD) data that differs from training data. This challenge has led to OOD detection methods that aim to identify and reject unreliable predictions. Although prior work shows that OOD detection performance varies by artefact type, the underlying causes remain underexplored. To this end, we identify a previously unreported bias in OOD detection: for hard-to-detect artefacts (near-OOD), detection performance typically improves when the artefact shares visual similarity (e.g. colour) with the model's ROI and drops when it does not - a phenomenon we term the Invisible Gorilla Effect. For example, in a skin lesion classifier with red lesion ROI, we show the method Mahalanobis Score achieves a 31.5% higher AUROC when detecting OOD red ink (similar to ROI) compared to black ink (dissimilar) annotations. We annotated artefacts by colour in 11,355 images from three public datasets (e.g. ISIC) and generated colour-swapped counterfactuals to rule out dataset bias. We then evaluated 40 OOD methods across 7 benchmarks and found significant performance drops for most methods when artefacts differed from the ROI. Our findings highlight an overlooked failure mode in OOD detection and provide guidance for more robust detectors. Code and annotations are available at: https://github.com/HarryAnthony/Invisible_Gorilla_Effect.

Pathology is the study of microscopic inspection of tissue, and a pathology diagnosis is often the medical gold standard to diagnose disease. Pathology images provide a unique challenge for computer-vision-based analysis: a single pathology Whole Slide Image (WSI) is gigapixel-sized and often contains hundreds of thousands to millions of objects of interest across multiple resolutions. In this work, we propose PathoLogy Universal TransfOrmer (PLUTO): a light-weight pathology FM that is pre-trained on a diverse dataset of 195 million image tiles collected from multiple sites and extracts meaningful representations across multiple WSI scales that enable a large variety of downstream pathology tasks. In particular, we design task-specific adaptation heads that utilize PLUTO's output embeddings for tasks which span pathology scales ranging from subcellular to slide-scale, including instance segmentation, tile classification, and slide-level prediction. We compare PLUTO's performance to other state-of-the-art methods on a diverse set of external and internal benchmarks covering multiple biologically relevant tasks, tissue types, resolutions, stains, and scanners. We find that PLUTO matches or outperforms existing task-specific baselines and pathology-specific foundation models, some of which use orders-of-magnitude larger datasets and model sizes when compared to PLUTO. Our findings present a path towards a universal embedding to power pathology image analysis, and motivate further exploration around pathology foundation models in terms of data diversity, architectural improvements, sample efficiency, and practical deployability in real-world applications.

Most super-resolution (SR) models struggle with real-world low-resolution (LR) images. This issue arises because the degradation characteristics in the synthetic datasets differ from those in real-world LR images. Since SR models are trained on pairs of high-resolution (HR) and LR images generated by downsampling, they are optimized for simple degradation. However, real-world LR images contain complex degradation caused by factors such as the imaging process and JPEG compression. Due to these differences in degradation characteristics, most SR models perform poorly on real-world LR images. This study proposes a dataset generation method using undertrained image reconstruction models. These models have the property of reconstructing low-quality images with diverse degradation from input images. By leveraging this property, this study generates LR images with diverse degradation from HR images to construct the datasets. Fine-tuning pre-trained SR models on our generated datasets improves noise removal and blur reduction, enhancing performance on real-world LR images. Furthermore, an analysis of the datasets reveals that degradation diversity contributes to performance improvements, whereas color differences between HR and LR images may degrade performance. 11 pages, (11 figures and 2 tables)

Many colour maps provided by vendors have highly uneven perceptual contrast over their range. It is not uncommon for colour maps to have perceptual flat spots that can hide a feature as large as one tenth of the total data range. Colour maps may also have perceptual discontinuities that induce the appearance of false features. Previous work in the design of perceptually uniform colour maps has mostly failed to recognise that CIELAB space is only designed to be perceptually uniform at very low spatial frequencies. The most important factor in designing a colour map is to ensure that the magnitude of the incremental change in perceptual lightness of the colours is uniform. The specific requirements for linear, diverging, rainbow and cyclic colour maps are developed in detail. To support this work two test images for evaluating colour maps are presented. The use of colour maps in combination with relief shading is considered and the conditions under which colour can enhance or disrupt relief shading are identified. Finally, a set of new basis colours for the construction of ternary images are presented. Unlike the RGB primaries these basis colours produce images whereby the salience of structures are consistent irrespective of the assignment of basis colours to data channels.

Automated radiology report generation from chest X-ray (CXR) images has the potential to improve clinical efficiency and reduce radiologists' workload. However, most datasets, including the publicly available MIMIC-CXR and CheXpert Plus, consist entirely of free-form reports, which are inherently variable and unstructured. This variability poses challenges for both generation and evaluation: existing models struggle to produce consistent, clinically meaningful reports, and standard evaluation metrics fail to capture the nuances of radiological interpretation. To address this, we introduce Structured Radiology Report Generation (SRRG), a new task that reformulates free-text radiology reports into a standardized format, ensuring clarity, consistency, and structured clinical reporting. We create a novel dataset by restructuring reports using large language models (LLMs) following strict structured reporting desiderata. Additionally, we introduce SRR-BERT, a fine-grained disease classification model trained on 55 labels, enabling more precise and clinically informed evaluation of structured reports. To assess report quality, we propose F1-SRR-BERT, a metric that leverages SRR-BERT's hierarchical disease taxonomy to bridge the gap between free-text variability and structured clinical reporting. We validate our dataset through a reader study conducted by five board-certified radiologists and extensive benchmarking experiments.

While current multimodal models are proficient at open-ended visual editing, executing precise single-answer edits remains an important obstacle. To probe this challenge, we introduce PaintBench, a dynamically scalable benchmark targeting 20 fundamental precise visual editing operations across four categories: geometric transformation, structural manipulation, color change, and symbolic reasoning. Procedural generation with configurable complexity enables an effectively infinite, contamination-resistant evaluation suite, and deterministic pixel-level evaluation eliminates reliance on bias-prone judge models. Across 11 image editing models, we find overall low performance, with the current highest-performing industry leader scoring only 17.1% (mIoU). Task decomposition reveals especially challenging operation types (geometric transformation, most structural manipulation, formula-based color change) and model-specific specializations. Fine-grained benchmark diagnostics further show performance degradations induced by scene variations in object count, background complexity, color scheme, and edit-region size. To test generalization of PaintBench scores to applied task performance, we create a procedural, deterministic evaluation for data visualization editing (TinyGrafixBench) and find strong linear correlation with PaintBench scores (R^2 = 0.91, p < 0.001). Altogether, PaintBench provides a rigorous foundation for measuring and driving progress in precise multimodal visual editing.

The raw-RGB colors of a camera sensor vary due to the spectral sensitivity differences across different sensor makes and models. This paper focuses on the task of mapping between different sensor raw-RGB color spaces. Prior work addressed this problem using a pairwise calibration to achieve accurate color mapping. Although being accurate, this approach is less practical as it requires: (1) capturing pair of images by both camera devices with a color calibration object placed in each new scene; (2) accurate image alignment or manual annotation of the color calibration object. This paper aims to tackle color mapping in the raw space through a more practical setup. Specifically, we present a semi-supervised raw-to-raw mapping method trained on a small set of paired images alongside an unpaired set of images captured by each camera device. Through extensive experiments, we show that our method achieves better results compared to other domain adaptation alternatives in addition to the single-calibration solution. We have generated a new dataset of raw images from two different smartphone cameras as part of this effort. Our dataset includes unpaired and paired sets for our semi-supervised training and evaluation.

Large language models (LLMs) are increasingly deployed in settings where reasoning, such as multi-step problem solving and chain-of-thought, is essential. Yet, current evaluation practices overwhelmingly report single-run accuracy while ignoring the intrinsic uncertainty that naturally arises from stochastic decoding. This omission creates a blind spot because practitioners cannot reliably assess whether a method's reported performance is stable, reproducible, or cost-consistent. We introduce ReasonBENCH, the first benchmark designed to quantify the underlying instability in LLM reasoning. ReasonBENCH provides (i) a modular evaluation library that standardizes reasoning frameworks, models, and tasks, (ii) a multi-run protocol that reports statistically reliable metrics for both quality and cost, and (iii) a public leaderboard to encourage variance-aware reporting. Across tasks from different domains, we find that the vast majority of reasoning strategies and models exhibit high instability. Notably, even strategies with similar average performance can display confidence intervals up to four times wider, and the top-performing methods often incur higher and less stable costs. Such instability compromises reproducibility across runs and, consequently, the reliability of reported performance. To better understand these dynamics, we further analyze the impact of prompts, model families, and scale on the trade-off between solve rate and stability. Our results highlight reproducibility as a critical dimension for reliable LLM reasoning and provide a foundation for future reasoning methods and uncertainty quantification techniques. ReasonBENCH is publicly available at https://github.com/au-clan/ReasonBench .

Prior work on a social web highlighter located individuality in selection -- which documents a person chooses to highlight -- but measured it cross-sectionally. We ask the temporal question: is a reader's selection signature a trait or a state? We freeze each reader's first six months of highlighting as a profile and track its own-vs-other advantage on their later selections at growing gaps (to 24+ months), with negatives drawn from the same calendar era -- so supply drift cannot masquerade as personal drift -- at a coarse global level and at a fine level whose negatives and controls come from the reader's own interest neighborhood; the anchor cell reproduces the prior cross-sectional level (+0.188 vs +0.169), validating the harness. Four results. Within the same users, the fine-layer advantage shows no statistically detectable paired decline at any horizon (6-12 month retention R = 1.00 [0.85, 1.18], n = 212; the farthest bin is compatible with a modest decline; the only contrast whose interval excludes zero is the coarse layer at 12-24 months, about 13%). The signal is not reducible to repeated domains (~90% survives excluding all profile sources). Within-person drift is slow (a recent-half profile beats the old half by +0.042). Prospectively, personal profiles -- even one built from a reader's earliest documents, median 20 months before evaluation -- rank their next reads at roughly 3x the AP of every simple non-personal prior tested. We use "trait" operationally (a stable signature under continued engagement); the scope is heavy, long-tenured readers of one platform, and exposure is not separable from choice.

Deep learning methods for unsupervised registration often rely on objectives that assume a uniform noise level across the spatial domain (e.g. mean-squared error loss), but noise distributions are often heteroscedastic and input-dependent in real-world medical images. Thus, this assumption often leads to degradation in registration performance, mainly due to the undesired influence of noise-induced outliers. To mitigate this, we propose a framework for heteroscedastic image uncertainty estimation that can adaptively reduce the influence of regions with high uncertainty during unsupervised registration. The framework consists of a collaborative training strategy for the displacement and variance estimators, and a novel image fidelity weighting scheme utilizing signal-to-noise ratios. Our approach prevents the model from being driven away by spurious gradients caused by the simplified homoscedastic assumption, leading to more accurate displacement estimation. To illustrate its versatility and effectiveness, we tested our framework on two representative registration architectures across three medical image datasets. Our method consistently outperforms baselines and produces sensible uncertainty estimates. The code is publicly available at https://voldemort108x.github.io/hetero_uncertainty/.

Supervised low-level vision models rely on pixel-wise losses against paired references, yet paired training sets exhibit per-pair photometric inconsistency, say, different image pairs demand different global brightness, color, or white-balance mappings. This inconsistency enters through task-intrinsic photometric transfer (e.g., low-light enhancement) or unintended acquisition shifts (e.g., de-raining), and in either case causes an optimization pathology. Standard reconstruction losses allocate disproportionate gradient budget to conflicting per-pair photometric targets, crowding out content restoration. In this paper, we investigate this issue and prove that, under least-squares decomposition, the photometric and structural components of the prediction-target residual are orthogonal, and that the spatially dense photometric component dominates the gradient energy. Motivated by this analysis, we propose Photometric Alignment Loss (PAL). This flexible supervision objective discounts nuisance photometric discrepancy via closed-form affine color alignment while preserving restoration-relevant supervision, requiring only covariance statistics and tiny matrix inversion with negligible overhead. Across 6 tasks, 16 datasets, and 16 architectures, PAL consistently improves metrics and generalization. The implementation is in the appendix.

Human image datasets used to develop and evaluate technology should represent the diversity of human phenotypes, including skin tone. Datasets that include skin tone information frequently rely on manual skin tone ratings based on the Fitzpatrick Skin Type (FST) or the Monk Skin Tone (MST) scales in lieu of the actual measured skin tone of the image dataset subjects. However, perceived skin tone is subject to known biases and skin tone appearance in digital images can vary substantially depending on the capture camera and environment, confounding manual ratings. Surprisingly, the relationship between skin-tone ratings and measured skin tone has not been explored. To close this research gap, we measured the relationship between skin tone ratings from existing scales (FST, MST) and skin tone values measured by a calibrated colorimeter. We also propose and assess a novel Colorimetric Skin Tone (CST) scale developed based on prior colorimetric measurements. Using experiments requiring humans to rate their own skin tone and the skin tone of subjects in images, we show that the new CST scale is more sensitive, consistent, and colorimetrically accurate. While skin tone ratings appeared to correct for some color variation across images, they introduced biases related to race and other factors. These biases must be considered before using manual skin-tone ratings in technology evaluations or for engineering decisions.

Accurate dermatological diagnosis naturally necessitates equitable performance across diverse populations, yet a systematic lack of expertly annotated images, especially for underrepresented skin tones and rare diseases, impedes progress toward measurably fair methods. We introduce cgDDI (Controllable Generation of Diverse Dermatological Imagery), a hybrid framework that (1) synthesizes realistic healthy skin samples without disturbing other input properties, (2) maps single-sample rare lesions onto novel skin-tones and locations non-parametrically, and (3) allows for efficient parametric generation with as few as 10 training samples. The framework supports both human and automated segmentation masking, enabling scalability to datasets without pre-made lesion masks. We grow a 656-image dataset by more than 400x and validate across two datasets: biopsy-confirmed Diverse Dermatology Images (DDI) and expert-verified Fitzpatrick17k (F17k). On the DDI benchmark, we achieve malignancy classification accuracy of 86.4% under synthetic-only training and 90.9% state-of-the-art performance with real data fine-tuning, alongside leading fairness metrics. Cross-dataset experiments show +13.9% accuracy improvements on unseen F17k data despite minimal disease overlap. We openly release 266k+ synthetic images, code, and generative models to further support fairness research at https://github.com/hectorcarrion/ControllableGenDDI.

Small sample sizes are common in many disciplines, which necessitates pooling roughly similar datasets across multiple institutions to study weak but relevant associations between images and disease outcomes. Such data often manifest shift/imbalance in covariates (i.e., secondary non-imaging data). Controlling for such nuisance variables is common within standard statistical analysis, but the ideas do not directly apply to overparameterized models. Consequently, recent work has shown how strategies from invariant representation learning provides a meaningful starting point, but the current repertoire of methods is limited to accounting for shifts/imbalances in just a couple of covariates at a time. In this paper, we show how viewing this problem from the perspective of Category theory provides a simple and effective solution that completely avoids elaborate multi-stage training pipelines that would otherwise be needed. We show the effectiveness of this approach via extensive experiments on real datasets. Further, we discuss how this style of formulation offers a unified perspective on at least 5+ distinct problem settings, from self-supervised learning to matching problems in 3D reconstruction.

Recent years have seen impressive advances in text-to-image generation, with image generative or unified models producing high-quality images from text. Yet these models still struggle with fine-grained color controllability, often failing to accurately match colors specified in text prompts. While existing benchmarks evaluate compositional reasoning and prompt adherence, none systematically assess color precision. Color is fundamental to human visual perception and communication, critical for applications from art to design workflows requiring brand consistency. However, current benchmarks either neglect color or rely on coarse assessments, missing key capabilities such as interpreting RGB values or aligning with human expectations. To this end, we propose GenColorBench, the first comprehensive benchmark for text-to-image color generation, grounded in color systems like ISCC-NBS and CSS3/X11, including numerical colors which are absent elsewhere. With 44K color-focused prompts covering 400+ colors, it reveals models' true capabilities via perceptual and automated assessments. Evaluations of popular text-to-image models using GenColorBench show performance variations, highlighting which color conventions models understand best and identifying failure modes. Our GenColorBench assessments will guide improvements in precise color generation. The benchmark will be made public upon acceptance.

Jointly identifying a mixture of discrete and continuous factors of variability without supervision is a key problem in unraveling complex phenomena. Variational inference has emerged as a promising method to learn interpretable mixture representations. However, posterior approximation in high-dimensional latent spaces, particularly for discrete factors remains challenging. Here, we propose an unsupervised variational framework using multiple interacting networks called cpl-mixVAE that scales well to high-dimensional discrete settings. In this framework, the mixture representation of each network is regularized by imposing a consensus constraint on the discrete factor. We justify the use of this framework by providing both theoretical and experimental results. Finally, we use the proposed method to jointly uncover discrete and continuous factors of variability describing gene expression in a single-cell transcriptomic dataset profiling more than a hundred cortical neuron types.

Patient education materials for solid-organ transplantation vary substantially across U.S. centers, yet no systematic method exists to quantify this heterogeneity at scale. We introduce a framework that grounds the same patient questions in different centers' handbooks using retrieval-augmented language models and compares the resulting answers using a five-label consistency taxonomy. Applied to 102 handbooks from 23 centers and 1,115 benchmark questions, the framework quantifies heterogeneity across four dimensions: question, topic, organ, and center. We find that 20.8% of non-absent pairwise comparisons exhibit clinically meaningful divergence, concentrated in condition monitoring and lifestyle topics. Coverage gaps are even more prominent: 96.2% of question-handbook pairs miss relevant content, with reproductive health at 95.1% absence. Center-level divergence profiles are stable and interpretable, where heterogeneity reflects systematic institutional differences, likely due to patient diversity. These findings expose an information gap in transplant patient education materials, with document-grounded medical question answering highlighting opportunities for content improvement.

As a common image editing operation, image composition (object insertion) aims to combine the foreground from one image and another background image, resulting in a composite image. However, there are many issues that could make the composite images unrealistic. These issues can be summarized as the inconsistency between foreground and background, which includes appearance inconsistency (e.g., incompatible illumination), geometry inconsistency (e.g., unreasonable size), and semantic inconsistency (e.g., mismatched semantic context). Image composition task could be decomposed into multiple sub-tasks, in which each sub-task targets at one or more issues. Specifically, object placement aims to find reasonable scale, location, and shape for the foreground. Image blending aims to address the unnatural boundary between foreground and background. Image harmonization aims to adjust the illumination statistics of foreground. Shadow (resp., reflection) generation aims to generate plausible shadow (resp., reflection) for the foreground. These sub-tasks can be executed sequentially or parallelly to acquire realistic composite images. To the best of our knowledge, there is no previous survey on image composition (object insertion). In this paper, we conduct comprehensive survey over the sub-tasks and combinatorial task of image composition (object insertion). For each one, we summarize the existing methods, available datasets, and common evaluation metrics. We have also contributed the first image composition toolbox libcom, which assembles 10+ image composition related functions (e.g., image blending, image harmonization, object placement, shadow generation, generative composition). The ultimate goal of this toolbox is solving all the problems related to image composition with simple `import libcom'.

Text-to-image diffusion models have demonstrated remarkable capability in generating realistic images from arbitrary text prompts. However, they often produce inconsistent results for compositional prompts such as "two dogs" or "a penguin on the right of a bowl". Understanding these inconsistencies is crucial for reliable image generation. In this paper, we highlight the significant role of initial noise in these inconsistencies, where certain noise patterns are more reliable for compositional prompts than others. Our analyses reveal that different initial random seeds tend to guide the model to place objects in distinct image areas, potentially adhering to specific patterns of camera angles and image composition associated with the seed. To improve the model's compositional ability, we propose a method for mining these reliable cases, resulting in a curated training set of generated images without requiring any manual annotation. By fine-tuning text-to-image models on these generated images, we significantly enhance their compositional capabilities. For numerical composition, we observe relative increases of 29.3% and 19.5% for Stable Diffusion and PixArt-α, respectively. Spatial composition sees even larger gains, with 60.7% for Stable Diffusion and 21.1% for PixArt-α.

Mitotic figure (MF) detection in histopathology images is challenging due to large variations in slide scanners, staining protocols, tissue types, and the presence of artifacts. This paper presents a collection of training techniques - a bag of tricks - that enable robust, real-time MF detection across diverse domains. We build on the efficient RTMDet single stage object detector to achieve high inference speed suitable for clinical deployment. Our method addresses scanner variability and tumor heterogeneity via extensive multi-domain training data, balanced sampling, and careful augmentation. Additionally, we employ targeted, hard negative mining on necrotic and debris tissue to reduce false positives. In a grouped 5-fold cross-validation across multiple MF datasets, our model achieves an F1 score between 0.78 and 0.84. On the preliminary test set of the MItosis DOmain Generalization (MIDOG) 2025 challenge, our single-stage RTMDet-S based approach reaches an F1 of 0.81, outperforming larger models and demonstrating adaptability to new, unfamiliar domains. The proposed solution offers a practical trade-off between accuracy and speed, making it attractive for real-world clinical adoption.

Benchmarks measure whether a model is correct. They do not measure whether a model is reliable. This distinction is largely academic for single-shot inference, but becomes critical for agentic AI systems, where a single rephrased prompt can trigger cascading failures in multi-step execution. Yet this form of instability is not captured by existing evaluations. Hallucinations live in variance: they arise when semantically equivalent prompts activate inconsistent internal pathways, producing divergent outputs. Consistent but incorrect outputs reflect bias or missing knowledge; confident guessing reflects calibration failure. Neither constitutes hallucination under this definition. When error is variance-dominated, reducing redundant pathways improves reliability without adding knowledge. We formalize this through Semantic Stability (SS), measured via Paraphrase Consistency (PC@k): generate k paraphrases, greedy decode each, compute mode agreement. SS is a diagnostic for variance-driven unreliability, not a method for improving correctness. We show that a dense Qwen3-0.6B agrees with itself only 23.8% of the time; at 32% sparsity, agreement jumps to 55.9%. A phase diagram reveals the sweet spot where variance reduction outpaces bias accumulation, and regimes where stability collapses onto wrong answers.

This paper presents a smartphone-based imaging system capable of quantifying the concentration of an assortment of biological/chemical assay samples. The main objective is to construct an image database which characterizes the relationship between color information and concentrations of the biological/chemical assay sample. For this aim, a designated optical setup combined with image processing and data analyzing techniques was implemented. A series of experiments conducted on selected assays, including fluorescein, RNA Mango, homogenized milk and yeast have demonstrated that the proposed system estimates the concentration of fluorescent materials and colloidal mixtures comparable to currently used commercial and laboratory instruments. Furthermore, by utilizing the camera and computational power of smartphones, eventual development can be directed toward extremely compact, inexpensive and portable analysis and diagnostic systems which will allow experiments and tests to be conducted in remote or impoverished areas.

We consider the problem of performing Bayesian inference in probabilistic models where observations are accompanied by uncertainty, referred to as "uncertain evidence." We explore how to interpret uncertain evidence, and by extension the importance of proper interpretation as it pertains to inference about latent variables. We consider a recently-proposed method "distributional evidence" as well as revisit two older methods: Jeffrey's rule and virtual evidence. We devise guidelines on how to account for uncertain evidence and we provide new insights, particularly regarding consistency. To showcase the impact of different interpretations of the same uncertain evidence, we carry out experiments in which one interpretation is defined as "correct." We then compare inference results from each different interpretation illustrating the importance of careful consideration of uncertain evidence.

Accurate cell segmentation in pathology images typically requires dense pixel-wise annotations, which are costly and time-consuming to obtain. This challenge is especially important for emerging biological imaging modalities and multiplexed datasets with variable channel configurations, where expert-labeled data are scarce. In this work, we introduce ImPartial, a deep learning framework designed to achieve state-of-the-art segmentation performance in low-annotation regimes using sparse scribbles and limited supervision. ImPartial augments the segmentation objective via self-supervised multi-channel quantized imputation. This approach leverages the observation that perfect pixel-wise reconstruction or denoising of the image is not needed for accurate segmentation, and thus, introduces a self-supervised classification objective that better aligns with the overall segmentation goal. We demonstrate that ImPartial achieves performance at par with fully supervised models while requiring substantially fewer annotations. Extensive experiments on benchmark multiplexed cellular imaging and single-plex clinical brightfield immunohistochemistry datasets show consistent improvements over strong baselines with only partial annotations. All benchmark datasets and code are available via our Github: https://github.com/nadeemlab/ImPartial.

Inverse problems aim to determine parameters from observations, a crucial task in engineering and science. Lately, generative models, especially diffusion models, have gained popularity in this area for their ability to produce realistic solutions and their good mathematical properties. Despite their success, an important drawback of diffusion models is their sensitivity to the choice of variance schedule, which controls the dynamics of the diffusion process. Fine-tuning this schedule for specific applications is crucial but time-costly and does not guarantee an optimal result. We propose a novel approach for learning the schedule as part of the training process. Our method supports probabilistic conditioning on data, provides high-quality solutions, and is flexible, proving able to adapt to different applications with minimum overhead. This approach is tested in two unrelated inverse problems: super-resolution microscopy and quantitative phase imaging, yielding comparable or superior results to previous methods and fine-tuned diffusion models. We conclude that fine-tuning the schedule by experimentation should be avoided because it can be learned during training in a stable way that yields better results.

Diffusion models have recently demonstrated their effectiveness in generating extremely high-quality images and are now utilized in a wide range of applications, including automatic sketch colorization. Although many methods have been developed for guided sketch colorization, there has been limited exploration of the potential conflicts between image prompts and sketch inputs, which can lead to severe deterioration in the results. Therefore, this paper exhaustively investigates reference-based sketch colorization models that aim to colorize sketch images using reference color images. We specifically investigate two critical aspects of reference-based diffusion models: the "distribution problem", which is a major shortcoming compared to text-based counterparts, and the capability in zero-shot sequential text-based manipulation. We introduce two variations of an image-guided latent diffusion model utilizing different image tokens from the pre-trained CLIP image encoder and propose corresponding manipulation methods to adjust their results sequentially using weighted text inputs. We conduct comprehensive evaluations of our models through qualitative and quantitative experiments as well as a user study.

Point-interactive image colorization aims to colorize grayscale images when a user provides the colors for specific locations. It is essential for point-interactive colorization methods to appropriately propagate user-provided colors (i.e., user hints) in the entire image to obtain a reasonably colorized image with minimal user effort. However, existing approaches often produce partially colorized results due to the inefficient design of stacking convolutional layers to propagate hints to distant relevant regions. To address this problem, we present iColoriT, a novel point-interactive colorization Vision Transformer capable of propagating user hints to relevant regions, leveraging the global receptive field of Transformers. The self-attention mechanism of Transformers enables iColoriT to selectively colorize relevant regions with only a few local hints. Our approach colorizes images in real-time by utilizing pixel shuffling, an efficient upsampling technique that replaces the decoder architecture. Also, in order to mitigate the artifacts caused by pixel shuffling with large upsampling ratios, we present the local stabilizing layer. Extensive quantitative and qualitative results demonstrate that our approach highly outperforms existing methods for point-interactive colorization, producing accurately colorized images with a user's minimal effort. Official codes are available at https://pmh9960.github.io/research/iColoriT

Recent work found that LLMs are sensitive to a wide range of arbitrary prompt dimensions, including the type of delimiters, answer enumerators, instruction wording, and more. This throws into question popular single-prompt evaluation practices. We present DOVE (Dataset Of Variation Evaluation) a large-scale dataset containing prompt perturbations of various evaluation benchmarks. In contrast to previous work, we examine LLM sensitivity from an holistic perspective, and assess the joint effects of perturbations along various dimensions, resulting in thousands of perturbations per instance. We evaluate several model families against DOVE, leading to several findings, including efficient methods for choosing well-performing prompts, observing that few-shot examples reduce sensitivity, and identifying instances which are inherently hard across all perturbations. DOVE consists of more than 250M prompt perturbations and model outputs, which we make publicly available to spur a community-wide effort toward meaningful, robust, and efficient evaluation. Browse the data, contribute, and more: https://slab-nlp.github.io/DOVE/

Image colorization is a challenging problem due to multi-modal uncertainty and high ill-posedness. Directly training a deep neural network usually leads to incorrect semantic colors and low color richness. While transformer-based methods can deliver better results, they often rely on manually designed priors, suffer from poor generalization ability, and introduce color bleeding effects. To address these issues, we propose DDColor, an end-to-end method with dual decoders for image colorization. Our approach includes a pixel decoder and a query-based color decoder. The former restores the spatial resolution of the image, while the latter utilizes rich visual features to refine color queries, thus avoiding hand-crafted priors. Our two decoders work together to establish correlations between color and multi-scale semantic representations via cross-attention, significantly alleviating the color bleeding effect. Additionally, a simple yet effective colorfulness loss is introduced to enhance the color richness. Extensive experiments demonstrate that DDColor achieves superior performance to existing state-of-the-art works both quantitatively and qualitatively. The codes and models are publicly available at https://github.com/piddnad/DDColor.

Recent advances in Conditional Diffusion Models have led to substantial capabilities in various domains. However, understanding the impact of variations in the initial seed vector remains an underexplored area of concern. Particularly, latent-based diffusion models display inconsistencies in image generation under standard conditions when initialized with suboptimal initial seed vectors. To understand the impact of the initial seed vector on generated samples, we propose a reliability evaluation framework that evaluates the generated samples of a diffusion model when the initial seed vector is subjected to various synthetic shifts. Our results indicate that slight manipulations to the initial seed vector of the state-of-the-art Stable Diffusion (Rombach et al., 2022) can lead to significant disturbances in the generated samples, consequently creating images without the effect of conditioning variables. In contrast, GLIDE (Nichol et al., 2022) stands out in generating reliable samples even when the initial seed vector is transformed. Thus, our study sheds light on the importance of the selection and the impact of the initial seed vector in the latent-based diffusion model.

The complexity and variability inherent in high-resolution pathological images present significant challenges in computational pathology. While pathology foundation models leveraging AI have catalyzed transformative advancements, their development demands large-scale datasets, considerable storage capacity, and substantial computational resources. Furthermore, ensuring their clinical applicability and generalizability requires rigorous validation across a broad spectrum of clinical tasks. Here, we present PathOrchestra, a versatile pathology foundation model trained via self-supervised learning on a dataset comprising 300K pathological slides from 20 tissue and organ types across multiple centers. The model was rigorously evaluated on 112 clinical tasks using a combination of 61 private and 51 public datasets. These tasks encompass digital slide preprocessing, pan-cancer classification, lesion identification, multi-cancer subtype classification, biomarker assessment, gene expression prediction, and the generation of structured reports. PathOrchestra demonstrated exceptional performance across 27,755 WSIs and 9,415,729 ROIs, achieving over 0.950 accuracy in 47 tasks, including pan-cancer classification across various organs, lymphoma subtype diagnosis, and bladder cancer screening. Notably, it is the first model to generate structured reports for high-incidence colorectal cancer and diagnostically complex lymphoma-areas that are infrequently addressed by foundational models but hold immense clinical potential. Overall, PathOrchestra exemplifies the feasibility and efficacy of a large-scale, self-supervised pathology foundation model, validated across a broad range of clinical-grade tasks. Its high accuracy and reduced reliance on extensive data annotation underline its potential for clinical integration, offering a pathway toward more efficient and high-quality medical services.

Computational pathology (CPath) digitizes pathology slides into whole slide images (WSIs), enabling analysis for critical healthcare tasks such as cancer diagnosis and prognosis. However, WSIs possess extremely long sequence lengths (up to 200K), significant length variations (from 200 to 200K), and limited supervision. These extreme variations in sequence length lead to high data heterogeneity and redundancy. Conventional methods often compromise on training efficiency and optimization to preserve such heterogeneity under limited supervision. To comprehensively address these challenges, we propose a pack-based MIL framework. It packs multiple sampled, variable-length feature sequences into fixed-length ones, enabling batched training while preserving data heterogeneity. Moreover, we introduce a residual branch that composes discarded features from multiple slides into a hyperslide which is trained with tailored labels. It offers multi-slide supervision while mitigating feature loss from sampling. Meanwhile, an attention-driven downsampler is introduced to compress features in both branches to reduce redundancy. By alleviating these challenges, our approach achieves an accuracy improvement of up to 8% while using only 12% of the training time in the PANDA(UNI). Extensive experiments demonstrate that focusing data challenges in CPath holds significant potential in the era of foundation models. The code is https://github.com/FangHeng/PackMIL