Automated 2D and 3D Segmentation of AMD and DME Lesions in OCT

Age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss, and optical coherence tomography (OCT) is the standard modality for detecting and monitoring the subtle lesions that drive treatment decisions. Most deep-learning segmentation work for OCT is validated only in-domain, leaving generalization to clinical data collected under different acquisition protocols largely untested. This work develops and systematically ablates four lesion-segmentation pipelines -- 2D and 3D variants for AMD and DME -- reaching Dice scores of 0.76 to 0.82 with strong volumetric and surface calibration (r vol, r surf greater than or equal to 0.97 across all four pipelines) on an in-domain validation set. The ablation process establishes a full-volume, calibration-aware adoption standard that catches mechanisms an ordinary slice-level evaluation would keep, and identifies ensemble composition as the most consistent driver of improvement. To test generalization, the models are evaluated on OLIVES, an external clinical cohort with no lesion-level ground truth, using a proxy-metric framework built around biomarker AUROC, central subfield thickness (CST) correlation, and longitudinal concordance. Predictions track clinical biomarkers outside the training distribution, though less strongly than in-domain -- evidence for, not validation of, automated lesion-burden tracking as a clinical tool.

Simple, Safe, and Overlooked: Reclaiming Sustainable Domain Generalization with Statistical Color Matching

Hardware shifts, color variations, and changing patient characteristics between development and deployment routinely break trained medical image classifiers. Existing remedies fall short: standard color jittering provides insufficient diversity, while deep generative style transfer algorithms hallucinate features, destroy clinically relevant structures, and waste massive compute resources. To address this, we revisit classical statistical color matching and repurpose it as Colorist, a highly efficient data augmentation strategy that applies global mean-standard deviation matching directly in the RGB color space. We demonstrate that this training-free, fully interpretable approach safely generates structurally intact domain variations, outperforming deep generative models in structural fidelity and color alignment. Across out-of-distribution histopathology, peripheral blood, dermatology, and retinal datasets, it improves balanced accuracy by up to +9% over state-of-the-art domain generalization regularizers and by +13% over an unaugmented baseline. Moreover, by avoiding neural networks in the augmentation loop, Colorist preserves anatomical structure, minimizes carbon footprint, and integrates seamlessly into standard dataloaders. Together, these findings establish statistical matching as a safe, interpretable, yet overlooked alternative to deep architectures for clinical robustness. Source code is available at https://github.com/sdoerrich97/colorist.

Atrial Fibrillation Detection with Arbitrary Leads via a Codebook-Based Reconstruction-Classification Framework

\textbf{Background and Objective}: Reliable atrial fibrillation (AF) detection from electrocardiogram (ECG) signals remains challenging in real-world clinical settings due to variable lead configurations, cross-dataset domain shifts, and pervasive physiological and technical artifacts. So we develop a robust and generalizable deep learning model for accurate AF detection.\\ \textbf{Methods}: We propose the Dual-Codebook Graph Collaborative Network (DCGCNet), a novel end-to-end vector-quantized variational autoencoder that jointly performs AF classification and ECG reconstruction. DCGCNet introduces two key components: (1) a Local-Global Contrastive Module for learning noise-invariant representations, and (2) an Adaptive Codebook Vector Quantizer that dynamically refines codebook prototypes to better align with input data distributions, thereby preventing codebook collapse and enhancing generalization.\\ \textbf{Results}: DCGCNet achieves state-of-the-art performance in standard intra-dataset 12-lead evaluation and demonstrates exceptional cross-dataset generalization across seven diverse settings, consistently attaining AUC > 0.98 in all cases. Furthermore, it maintains high diagnostic accuracy under realistic noisy conditions, including baseline wander, powerline interference, and EMG artifacts.\\ \textbf{Conclusions}: DCGCNet establishes a new benchmark for robust, generalizable, and noise-resilient AF detection, showing strong potential for deployment in real-world clinical environments.

MammoMix: Leveraging Mixture of Experts for Robust Mammogram Breast Detection

Breast lesion detection in mammography remains a challenging task due to variations in image quality, lesion appearance, and population demographics across datasets. While current object detectors such as YOLO and DETR achieve strong results on individual datasets, their performance often degrades when trained on or applied across heterogeneous sources. To address this, we propose MammoMix, a novel framework based on Mixture-of-Experts (MoE) paradigm for robust and generalizable lesion detection. In MammoMix, each expert model is trained on a specific domain, allowing it to specialize in distinct characteristics of its source data. A gating mechanism adaptively weighs contributions from each expert based on input image, combining their outputs to enable domain-adaptive inference. To improve reliability, we further incorporate a calibration module, MoCAE, which adjusts confidence scores to reflect true predictive uncertainty. We evaluate MammoMix on 3 public mammography datasets: CSAW, DDSM, and DMID, covering diverse clinical settings. Results show that MammoMix outperforms baseline detectors in both average precision and reliability, particularly on datasets with greater variability. Our findings demonstrate that expert specialization and calibrated ensemble fusion significantly enhance model generalization and robustness. MammoMix offers a promising step toward dependable AI-assisted breast cancer screening across real-world clinical domains.

BreastMammo and DenseMammo: Benchmarks for Mammography Domain Generalization

Breast density classification is a critical component of breast cancer risk assessment, yet AI models often struggle to generalize across clinical sites due to vendor-specific acquisition styles. In this work, we introduce two new datasets, BreastMammo and DenseMammo, to facilitate robust multi-view mammography research. We propose a domain generalization framework that utilizes a foreground-only histogram matching protocol to resolve the domain shift issue arising from disparate clinical sources. Internal evaluation using a 5-fold cross-validation protocol demonstrates the efficacy of our approach, with the Swin Transformer backbone achieving a peak AUC of 98.32% for density classification. External evaluation on the TNMammo and LUMINA datasets demonstrates that the proposed approach consistently reduces domain shift, significantly outperforming prominent domain generalization paradigms, including MixStyle and Discrete-Fourier-Transform-based frameworks.

LoRSA: Toward Generalizable Parameter-Efficient Fine-Tuning for Biomedical Downstream Tasks

Parameter-efficient fine-tuning enables the adaptation of vision foundation models to biomedical tasks under limited computational resources, but a single low-rank update can constrain all task-specific changes to one narrow parameter subspace. This restriction may prevent the model from simultaneously representing globally shared task structure and localized residual directions required for generalization to unseen imaging domains. We introduce LoRSA, a global--residual adaptation framework that jointly learns a dense low-rank component and a dynamically structured-sparse low-rank component. The dense component captures globally coordinated task adaptation, while the structured component provides complementary residual corrections whose support evolves during training. We characterize the representational capacity, approximation properties, rank structure, and singular-subspace complementarity of this decomposition. We evaluate LoRSA for four-class breast-density classification using DINOv3-Base, with VinDr-Mammo as the source domain and MammosighTR and RSNA as unseen external domains. LoRSA remains competitive on the internal validation set and achieves the best external macro-F1 on both target datasets, improving upon the strongest competing method by 2.15 percentage points on MammosighTR and 3.09 percentage points on RSNA. Weight-matrix analysis further shows that approximately $92\%$ of the energy of each adaptation component lies outside the bilateral singular subspace of the other, indicating that the two components learn largely complementary update directions. These results suggest that organizing adaptation capacity into distinct global and residual paths can improve the external-domain generalization of parameter-efficiently adapted biomedical vision models.

Searching for Robust Augmentations to Improve Out-of-Domain Generalization in Dermoscopic Skin Cancer Classification

Background/Objectives: Dermoscopic skin-lesion classifiers lose accuracy when images arrive from a new clinic or a new device. We asked which data augmentations reduce that loss, and measured the effect under a protocol that keeps policy selection separate from policy evaluation. Methods: A ConvNeXt-Large binary malignant-versus-non-malignant classifier was trained on six dermoscopic sources (25,903 images); HAM10000 and ISIC 2016-2020 were held out of training entirely. Single augmentations, photometric combinations and eleven composite policies were ranked on a development split of 1511 held-out images. The winning policy was then evaluated on a confirmation set of 8073 held-out images that took no part in that ranking and from which we removed every image sharing a lesion identifier with the training data and every image contributed by an institution represented in training. Both policies were retrained with four random seeds each and compared with an exact permutation test. Results: The mix policy raised confirmation-set ROC-AUC from 0.787 to 0.826 (+0.039; per-seed ranges 0.772-0.797 and 0.815-0.840, non-overlapping; exact permutation p=0.029), with the same direction on each contributing source. At matched sensitivity the gain is larger in clinical terms: specificity rose from 0.612 to 0.713 at a sensitivity of 0.80, and from 0.284 to 0.397 at a sensitivity of 0.95. In-domain ROC-AUC was preserved (0.938 to 0.941). On an independent clinical cohort acquired with a different device at a different institution (472 images, 22 malignant), performance was maintained (0.934 versus 0.930). Conclusions: Augmentations that model the physical causes of domain shift improve cross-source transfer at no cost to in-domain accuracy, and the improvement survives a selection-disjoint, contamination-free evaluation.

A Cyclic Adaptation-Generalization Framework with Uncertainty-Guided Self-Paced Learning for Long-Term Brain-Machine Interfaces

Brain-Machine Interfaces (BMIs), which link the brain to external devices, hold great potential in rehabilitation, human performance augmentation, and human-centered robotics. However, invasive BMIs face a critical challenge for long-term deployment due to neural drift, which degrades decoding performance over time and necessitates frequent recalibration. Existing methods designed to mitigate neural drift typically rely on either domain adaptation (DA) or domain generalization (DG) alone and often fail to capture fine-grained distribution shifts across neural subdomains, resulting in limited performance. To overcome these limitations, we propose Uncertainty-guided Self-paced Cycling (UnSPC), a robust framework that synergizes DA and DG for target domain refining under an Uncertainty-guided Self-paced Pseudo-labeling (UnSPL) mechanism. To handle subdomain neural drift across domains, UNSPL is proposed to iteratively mine reliable pseudo-labeled samples with a noise-robust ranking strategy for further fine-tuning. Leveraging these high-quality samples, we introduce a novel Cycling Adaptation and Generalization (CycAG) strategy, which integrates DA and DG within an iterative cycle to progressively mitigate both global and subdomain drift. This cyclic process enables effective alignment to evolving target distributions while preserving robust and transferable representations, thereby mitigating performance degradation under long-term neural drifts. Extensive experiments on multiple neural decoding datasets demonstrate the effectiveness and robustness of UnSPC. To our knowledge, our proposed UnSPC is the first to cyclically integrate DA and DG with pseudo-labeling, paving the way toward stable long-term BMI controls.

Multimodal Domain Generalization for Depression Detection: An Attention-Based BiLSTM Network with Domain-Adversarial Training

Automatic depression detection with deep learning has shown promise but often suffers from limited generalization due to domain shift arising from inter-speaker variability. To address this critical issue, we present the first patient-independent multimodal depression detection framework that incorporates domain generalization (DG), jointly leveraging both acoustic and textual modalities. The proposed model integrates bidirectional Long Short-Term Memory (BiLSTM) with intra- and cross-modal attention mechanisms, accompanied by segment-level fusion for decision-making. Generalization is further enhanced by applying a gradient reversal layer inspired by Domain-Adversarial Training of Neural Networks (DANN), which promotes domain-invariant representations by adversarially limiting the model's ability to identify individual speakers, effectively reducing patient-specific bias. Conducting experiments on the Androids-Corpus dataset with a 5-fold cross-validation (CV) protocol, various pairings of audio and text feature extractors were evaluated over different segment durations, determining MelSpec and ItalianBERT as the optimal baseline at a 30-second segment duration. The addition of DG to this baseline yields a 2.5% increase in accuracy and 3.3% in F1-score, achieving 93.2% accuracy, 93.2% precision, 96.2% recall, and 94.2% F1-score, surpassing all existing benchmarks. Extensive ablation studies assess the impact of multimodal fusion, deep architectural choices, and DG, highlighting their combined contribution to robust and generalizable depression detection.

RED-Sphere: Hyperspherical Residual Edge Debiasing for Cross-Population Fundus Disease Domain Generalization

Medical image classifiers are often trained within one source population, yet clinical deployment requires robustness to patients whose appearance, acquisition style, and disease prevalence differ from the source cohort. Existing fairness and robustness methods often require group supervision or treat appearance variation as an undifferentiated nuisance, which is insufficient when population-correlated low-level cues and lesion evidence share edge and texture structure. We study a strict source-only cross-population setting, where external populations are unseen during optimization, validation, scheduling, hyperparameter and model selection. We propose RED-Sphere, a plug-and-play robustness framework for image classification under unseen population shifts. It estimates shortcut-sensitive nuisance responses with an edge and feature energy prior, attenuates dominant responses through residual soft gating, regularizes masked nuisance views with counterfactual-inspired consistency and separation losses, and predicts labels with normalized spherical prototypes. It favours angular semantic evidence over source-correlated activation magnitude while preserving lesion structure. Although demonstrated on 2D Scanning Laser Ophthalmoscopy (SLO) fundus classification for Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR), RED-Sphere is not tied to retinal anatomy: the same principle can be adapted with modality-specific nuisance priors wherever appearance shortcuts and semantic evidence are entangled. Under a strict White-only Harvard-FairVision protocol, RED-Sphere improves held-out macro-F1 across all 20 task and backbone comparisons, with average gains of 1.28 and 2.98 F1 points on AMD and DR. Gains in AUC and PR-AUC, visual diagnostics, ablations, and sensitivity analyses further support stronger external semantic alignment and more stable angular disease geometry.

SleepBand: Single-Source Domain Generalization for Sleep Staging via Physiologically Structured Spectral Modeling

Generalizing sleep staging models to unseen datasets is challenging, and typical domain generalization (DG) methods often rely on multiple source domains or domain labels that are rarely available in practice. We tackle the stricter and more practical setting of single-source domain generalization: training on a single labeled source dataset, without domain labels or access to target data. We present SleepBand, a physiology-guided framework that embeds oscillatory priors via a learnable Morlet filter bank and a structured integration-and-recalibration pipeline. This anchors representations to domain-invariant sleep rhythms (e.g., slow waves, spindles), reducing reliance on dataset-specific artefacts. On five public datasets, SleepBand achieves state-of-the-art SDG performance and remains competitive under leave-one-domain-out (multi-source) DG. Analyses show that the learned filters align with canonical neurophysiology and that robustness stems from focusing on narrowband, physiologically meaningful cues. Our results suggest that principled, physiology-aware inductive biases are a promising path for robust single-domain sleep staging. Code is available at https://github.com/lzcn/sleep-band

The Good, the Bad, and the Brittle: Benchmarking Robustness and Generalisation of Histopathology Foundation Models

How robust and generalisable are pathology foundation models and have their scaling limites been reached? We benchmarked twelve pathology foundation models (PFMs) and ResNet baselines using our Robustness Evaluation and Enhancement Toolbox (REET) across eleven clinically realistic perturbations and a dissimilarity-driven Non-Redundant K-fold validation (NR-Kfold) protocol. We introduce a Perturbation Performance Index (PPI) to summarise accuracy trends under controlled perturbation sweeps and analyse robustness scaling with parameter count. We show that PFMs consistently outperform CNNs in both robustness and domain generalisation, yet model scaling shows diminishing returns: mid-sized models such (UNI2/Virchow-2 etc.) achieve comparable or greater resilience than larger systems. NR-Kfold analysis further reveals systematic accuracy loss and increased variability when training-test similarity is broken, underscoring the need for explicit distribution-shift evaluation. These findings suggest that the next generation of pathology foundation models must prioritise data quality, multimodality information and domain alignment over parameter count to achieve genuine clinical reliability.

Trust the Prior (or Not): Uncertainty-Aware Abdominal Aortic Aneurysm Segmentation

Robust segmentation of intraluminal thrombus is critical for risk assessment in Abdominal Aortic Aneurysm, yet it remains challenging due to heterogeneous thrombus features and low contrast with surrounding non-enhanced tissues. Domain shifts induced by different Computed Tomography Angiography (CTA) protocols further inhibit multi-center generalization of deep learning models. To address these challenges, we propose a patient-specific framework that integrates discriminative learning with anatomically informed priors. Our approach introduces two key components: (1) a patient-specific intensity normalization based on a Gaussian Mixture Model of local anatomy, and (2) an Uncertainty-Gated Anatomical Attention module that incorporates spatial priors while adaptively modulating their influence according to voxel-wise confidence. This design allows for anatomical guidance in ambiguous regions while suppressing unreliable priors. The proposed method achieves state-of-the-art performance on in-distribution test data and substantially outperforms existing alternatives in generalization to external multi-center CTA data, while remaining interpretable through an explicit separation of visual and anatomical evidence.

Semantic-Anchored Evidential Fusion for Domain-Robust Whole-Slide Survival Analysis

Whole-slide images (WSIs) are widely used for computational cancer prognosis. However, most existing methods primarily focus on in-domain performance and fail to generalize across clinical centers. This limitation stems from their reliance on pixel-derived representations that are highly susceptible to domain-specific artifacts caused by staining protocols and scanner hardware. We hypothesize that high-level pathology semantics, such as tumor grade and micro-environmental architecture, provide a domain-invariant semantic representation that mirrors the robust diagnostic logic of human pathologists. Therefore, we propose a Semantic-Anchored Evidential Fusion Survival (SAEFS) framework, where SAEFS derives semantic anchors from WSIs via Visual Question Answering (VQA), employs a dual-stream WSI evidence extraction architecture, uses Dirichlet-based Subjective Logic to model uncertainty, and fuses semantic and visual evidence through a cautious conjunction rule to avoid overconfident fusion from correlated sources. Trained exclusively on one source domain and evaluated zero-shot across four unseen domains, SAEFS consistently outperforms state-of-the-art models both in prediction accuracy and reliability, improving the average C-index by 10.2%. Quantitative analyses further show that VQA-derived semantic features exhibit significantly lower cross-center divergence than pixel-derived features, highlighting their robustness for cross-center clinical applications.

UniPET: a universal network for high-quality PET image denoising across varied dose reduction factors

Most existing deep learning-based PET image denoising methods assume a fixed and known dose reduction factor (DRF) for low-dose PET images. However, these methods encounter significant performance degradation when the DRF varies beyond the assumed one in practical applications. To address the challenge posed by varied DRFs, several preliminary studies focus on the task of universal PET image denoising, aiming to train a universal model over low-dose data across DRFs. Nonetheless, these vanilla universal models often struggle with misaligned styles present in different DRF data, leading to the \textit{style elimination issue} with a significant over-smoothing effect. To deal with this issue, we innovatively introduce domain generalization to PET image denoising and propose a universal PET image denoising network (UniPET) to achieve high-quality PET image denoising across diverse DRFs. UniPET comprises two primary innovations: a style alignment network (SAN) and a region-aware learning strategy (RALS). Specifically, SAN utilizes style alignment techniques derived from domain generalization to align and recover styles across different DRFs, ensuring the model's generalizability across various DRFs while effectively preserving styles. Furthermore, to enhance style recovery, RALS distinguishes between flat and stylized regions, exclusively conducting adversarial learning on the latter, thereby more effectively guiding the model's focus towards learning stylized regions. It is demonstrated that our proposed UniPET can adaptively recover different DRF styles and achieve high-quality PET image denoising across DRFs. Comprehensive experiments show that UniPET exhibits comparable performance to individual DRF-specific models at specific DRFs and realizes state-of-the-art performance in universal PET image denoising quantitatively, perceptually, and clinically.

Mitosis Detection in the Wild: Multi-Tumor and Context-Aware Generalization in the MIDOG 2025 Challenge

Automated mitosis detection is a well-established task in computational pathology. While previous benchmarks focused on scanner-induced domain shift, clinical "real-world" application requires models to be robust across the vast variance to be expected in the histological landscape. The MItosis DOmain Generalization (MIDOG) 2025 challenge was designed to evaluate algorithmic performance across unprecedented biological and contextual diversity. We curated a test dataset of 365 cases, encompassing 12 distinct human, canine and feline tumor types, digitized across multiple scanning platforms. Moving beyond hand-selected hotspots, the challenge required detection also in random tissue areas (representative of the whole slide detection situation) and challenging areas (areas rich in hard negatives). In the second track, we introduced the classification of atypical mitotic figures (AMFs). There were 18 teams submitting to the detection track, with F1 scores ranging up to 0.740. In the AMF detection track, we had 21 submissions with balanced accuracy values up to 0.908. Our analysis reveals that while most models perform reliably in traditional hotspots, significant performance degradation occurs in challenging ROIs, where false positive rates tripled. Furthermore, performance varied significantly across the 12 tumor types, highlighting "blind spots" in current state-of-the-art architectures when encountering rare or highly pleomorphic malignancies. Moreover, we evaluated the effectiveness of ensembling and found a mean increases of 1.5 and 1.3 percentage points in F1 score and balanced accuracy, respectively. In contrast, TTA showed no relevant improvement. MIDOG 2025 demonstrates that "in the wild" mitosis detection remains a significant hurdle. The transition from hotspot-only evaluation to a multi-contextual framework provides a more realistic proxy for clinical reliability.

A Sliced-Wasserstein Framework on Correlation Matrices for EEG Decoding

Electroencephalography (EEG) offers noninvasive, millisecond resolution recordings of neuronal activity and is widely used in neuroscience and healthcare. Many EEG decoding pipelines rely on covariance descriptors for their robustness to noise, but such representations are sensitive to channel-wise scaling. Recent studies have therefore advocated full-rank correlation matrices as a scale-invariant alternative for EEG decoding. In this paper, we study Sliced-Wasserstein (SW) discrepancies for probability distributions on the manifold of full-rank correlation matrices. We adopt the pullback-Euclidean formulation of SW, referred to as Pullback Euclidean Metric Sliced-Wasserstein (PEMSW), and instantiate it under two recently introduced correlation geometries, \textit{i.e.}, the Off-Log Metric (OLM) and Log-Scaled Metric (LSM). This yields two Correlation Sliced-Wasserstein (CorSW) discrepancies with closed-form slicing coordinates and efficient computation through one-dimensional Wasserstein distances. Building on CorSW, we further develop a domain generalization (DG) framework for EEG decoding. Experiments on three EEG datasets demonstrate improved generalization under distribution shifts, with low training overhead and no additional inference cost. The source code is available at github.com/ChenHu-ML/CorSW.

Biological Spatial Priors Regularize Foundation Model Representations for Cross-Site MSI Generalization in Colorectal Cancer

Predicting microsatellite instability (MSI) status from routine hematoxylin and eosin (H&E) whole slide images (WSIs) offers a practical alternative to molecular testing, but models trained at one institution tend to generalize poorly to slides acquired at a different site. Foundation model representations, despite their generality, still encode site-specific texture alongside the conserved biological morphology underlying MSI. We investigate whether tile-level spatial priors derived from known MSI histology can guide these representations toward more site-invariant features. We introduce a biologically motivated spatial prior based on peripheral distance encoding, reflecting the Crohn's-like peripheral lymphocytic reaction at the tumor invasive margin, and evaluate a secondary local immune neighborhood encoding reflecting the lymphocyte-to-tumor ratio in each tile's immediate spatial neighborhood. Both priors are injected into a TransMIL aggregator before self-attention, allowing the transformer to integrate spatial biological context with UNI2-h or Virchow2 features across all attention layers. We evaluate six foundation model and MIL aggregator combinations as a reference, then assess the effect of each spatial prior. Training on TCGA-COAD (137 slides) and evaluating externally on TCGA-READ (50 slides) without retraining, peripheral distance encoding achieves MSI AUC 0.959 +/- 0.012 on COAD and MSS specificity 1.000 on READ, compared to 0.957 and 0.939 for the strongest reference configuration. Local immune neighborhood encoding achieves comparable internal AUC but lower cross-site specificity, suggesting margin proximity encodes a more site-invariant biological signal than local immune density. Results suggest biologically grounded spatial priors act as regularizers that reduce reliance on site-specific imaging patterns.

Magnification-Invariant Image Classification via Domain Generalization and Stable Sparse Embedding Signatures

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

Robust and Clinically Reliable EEG Biomarkers: A Cross Population Framework for Generalizable Parkinson's Disease Detection

Developing robust and clinically reliable EEG biomarkers requires evaluation frameworks that explicitly address cross population generalization in multi site settings such as Parkinsons disease (PD) detection. Models trained under i.i.d. assumptions often capture population specific artifacts rather than disease relevant neural structure, leading to poor generalization across clinical cohorts. EEG further amplifies this challenge due to low signal to noise ratio and heterogeneous acquisition conditions. We propose a population aware evaluation framework to assess the robustness and clinical reliability of EEG biomarkers under distribution shift. Using an n gram expansion strategy, we enumerate all cross population train test configurations across five independent cohorts, resulting in 75 directional evaluations. A nested cross validation design with integrated channel selection ensures prospective biomarker identification without population leakage. Results show that cross population transfer is asymmetric and that both accuracy and biomarker stability improve with increasing training population diversity, achieving up to 94.1% accuracy on held out cohorts. A theoretical analysis based on mixture risk optimization and hypothesis space contraction explains these trends, showing that multi population training promotes population robust representations. This work establishes a principled framework for learning robust, generalizable, and clinically reliable EEG biomarkers for multi site biomedical applications.