Cleaner Speech, Weaker Generalization: Revisiting Pitt-Derived Benchmarks for Alzheimer's Disease Detection

Speech-based Alzheimer's disease (AD) detection increasingly relies on speech-enhanced and curated versions of the Pitt Corpus, where speech enhancement, sample selection, and demographic balancing are often treated as beneficial preprocessing steps. However, whether these transformations improve real-world AD detection or instead affect model generalization and prediction behavior remains unclear. In this work, we revisit the role of speech preprocessing and dataset curation across widely used benchmarks for speech-based AD detection. We evaluate the speech quality of different datasets, the cross-dataset generalization of multiple deep learning models under matched and mismatched enhancement settings, and the behavior of several recent large audio-language models (LALMs). Experimental results show that across multiple supervised speech models, speech-enhanced datasets often improve in-domain performance while reducing robustness in cross-domain evaluation. Matched enhancement between training and test data alleviates, but does not eliminate, this degradation. LALMs show a similar sensitivity: enhanced datasets induce stronger class imbalance and prediction shifts than unprocessed data. These results suggest that speech preprocessing and dataset curation can substantially influence downstream AD detection behavior, indicating that ``cleaner'' speech datasets are not necessarily more reliable for real-world AD detection.

Why ML-based cough models do not generalize: a systematic cross-dataset evaluation for tuberculosis screening

Cough acoustics are promising for non-invasive tuberculosis (TB) screening, yet whether machine learning (ML) models capture disease-related acoustics or artifacts of data collection remains unresolved. We evaluated the cross-dataset generalizability of classical ML and deep learning (DL) cough-based TB classifiers across three independent datasets. Despite moderate within-dataset performance (ROC-AUC up to $0.755 \pm 0.056$), both pipelines fail to generalize, with external performance frequently below 0.6, indicating a possible limitation of the data. We further observed audio representations are organized by recording device and dataset rather than TB status, predicted TB probability tracks country-level prevalence in CODA, and device mismatch degrades transfer while device-diverse training improves it. Additionally, a clinical-variable baseline generalizes more consistently (ROC-AUC $0.655 - 0.711$), indicating acquisition-specific variability is a stronger driver of poor generalizability than population shift. High within-dataset performance is not enough. External validation is essential before cough-based TB models are clinically ready.

Multi-Stage Prompt-Guided Feature Modulation for Generalizable Brain Tumor Segmentation

Accurate brain tumor segmentation from magnetic resonance imaging (MRI) is essential for diagnosis, treatment planning, surgical guidance, and disease monitoring. However, developing automated segmentation models that generalize across diverse tumor characteristics, imaging protocols, acquisition sites, and patient populations remains challenging. Variations in tumor morphology and imaging distributions can substantially degrade performance outside the training domain. Consequently, improving the robustness and generalization of deep learning-based segmentation models has become a key objective in medical image analysis. To improve segmentation robustness, we propose Multi-Stage Dynamic Prompt nnU-Net, a prompt-conditioned extension of nnU-Net. Three independent dynamic prompt modules are inserted into the deepest encoder stages. Each module contains a learnable bank of ten 256-dimensional prompt vectors and uses globally pooled encoder features to generate image-specific prompt representations. These representations are projected into feature-wise scaling $(γ)$ and shifting $(β)$ parameters that modulate encoder feature maps through Feature-wise Linear Modulation (FiLM), enabling adaptive feature conditioning at multiple semantic levels. Evaluation on the BraTS GOAT validation dataset demonstrated that the proposed Multi-Stage Dynamic Prompt nnU-Net outperformed the baseline nnU Net across the majority of evaluated metrics and tumor subregions. The proposed model achieved average lesion-wise Dice scores of 76.16% (ET), 80.04% (TC), and 86.42% (WT), compared with 74.38%, 78.14% and 84.01% for the baseline model. The results demonstrate that multi-stage dynamic prompt conditioning improves segmentation accuracy and boundary delineation for brain tumor segmentation.

Do Medical Foundation Models Generalize on the African Brain?

Medical foundation models (FMs) are increasingly used for brain MRI analysis. However, their evaluation remains dominated by high-resource datasets, leaving generalization to African cohorts underexplored. We assess whether FMs generalize equally to African and non-African brain MRI data across two tasks: dementia classification using a Nigerian dataset and brain tumor segmentation using BraTS-Africa. We evaluate two generalist FMs (BrainIAC, 3DINO) and two segmentation-specific FMs (MedSAM2, Medical-SAM2) against a from-scratch baseline. For classification, FMs provide limited gains (highest ROC-AUC of 0.86 with BrainIAC), whereas for segmentation they consistently improve performance, reaching up to 0.86 Dice with MedSAM2. Performance differences between African and non-African cohorts are inconsistent and appear more related to dataset size than data origin. These results suggest that FMs do not exhibit an inherent bias against African cohorts, and highlight the limited availability and diversity of African neuroimaging datasets as the main barrier to robust evaluation and deployment.

Self-Supervised Consistency Enhanced Disentangled Learning for Neural Decoding Generalization in Brain-Machine Interface

Brain-Machine Interfaces (BMIs) provide a direct communication pathway between the brain and external devices, enabling humans to control assistive and robotic technologies, with potential applications in rehabilitation, human motor augmentation, and human-centered robotics. However, due to neural drift, the performance of BMIs decreases over time, posing challenges for long-term viability, particularly for invasive BMIs (iBMIs). Existing solutions suffer from two main drawbacks: (i) difficulty in learning robust neural representations, and (ii) neglecting that neural drift varies across motor parameters (e.g., velocity, direction, and speed). To overcome these limitations, we propose Self-Supervised Consistency enhanced Disentangled Learning (SSCDL), a neural decoding generalization framework built on two key innovations. We first design a backbone model named Consistency enhanced Neural Decoder (CND), using a novel teacher-student consistency constraint with simulated neural signal perturbations to learn robust representations invariant to neural drift. Then, we employ three dedicated CNDs under the Complementary-Disentangled Generalization (CDG) mechanism, which disentangles motor signals into velocity, direction, and speed with inspiration from neural preference theory. This disentangled learning enables SSCDL to capture invariant neural representations from diverse neural preference perspectives, significantly enhancing cross-day generalization. Extensive experimental results show that SSCDL delivers state-of-the-art decoding performance, exhibiting high robustness and cross-day stability. These capabilities underscore its strong potential for long-term interaction in human-centric robotic and fine-grained assistive applications.

SHFormer: Dynamic Spectral Filtering Convolutional Neural Network and High-pass Kernel Generation Transformer for Adaptive MRI Reconstruction

Attention Mechanism (AM) selectively focuses on essential information for imaging tasks and captures relationships between distant pixel neighborhoods to compute feature representations. Accelerated MRI reconstruction benefits from AM, as the imaging process involves Fourier domain measurements that influence image representation non-locally. However, AM-based models are more adept at capturing low-frequency information with limited capacity for high-frequency representations, restricting models to smooth reconstruction. Additionally, AM-based models need mode-specific retraining for multimodal MRI data, as their knowledge is restricted to local contextual variations that may be inadequate to capture transferable features across heterogeneous domains. To address these challenges, we propose a neuromodulation-based discriminative multi-spectral AM for scalable MRI reconstruction that can (i) propagate context-aware high-frequency details for high-quality reconstruction, and (ii) capture features reusable across deviated unseen domains in multimodal MRI. The proposed network consists of a spectral filtering CNN to capture mode-specific transferable features and a dynamic high-pass kernel generation transformer focusing on high-frequency details. We evaluate our model on comparative studies in supervised and self-supervised learning, diffusion model-based training, closed-set and open-set generalization under heterogeneous MRI data, and interpretation-based analysis. Our method offers scalable, high-quality reconstruction with best improvement margins of ~1 dB in PSNR and ~0.01 in SSIM under unseen scenarios. Code: https://github.com/sriprabhar/SHFormer

GenDiff: A Dose and Anatomy Aware Diffusion Model with Structural Prior Refinement for Low-Dose CT Reconstruction and Generalization

Computed tomography (CT) is a critical imaging modality for clinical diagnosis, but reducing radiation dose inevitably introduces severe noise and structured artifacts that degrade image quality. Existing deep learning-based low-dose CT (LDCT) reconstruction methods are typically optimized for fixed dose levels or specific anatomical regions, limiting their robustness and generalization in realistic clinical settings. We propose GenDiff, a generalizable diffusion-based framework for LDCT reconstruction that jointly models continuous radiation dose and anatomical information within a unified reconstruction network. The proposed framework integrates a Dose-Anatomy Encoder to learn acquisition-aware embeddings, a dose- and anatomy-conditioned cold diffusion backbone for iterative refinement, a physics-consistency update to enforce fidelity to the CT forward model, and a Structural Prior Refinement Module (SPRM) that preserves anatomical structures while suppressing dose-dependent artifacts. Extensive experiments on multi-anatomy clinical datasets, including unseen ultra-low-dose conditions as well as out-of-distribution phantom and animal datasets, demonstrate that GenDiff consistently outperforms state-of-the-art convolutional neural network and diffusion-based reconstruction methods. The proposed approach achieves superior reconstruction quality while maintaining strong robustness across different dose levels, anatomical regions, and acquisition domains, making it a promising solution for practical low-dose CT imaging.

Do Diabetic Foot Ulcer Segmentation Models Generalize? A Cross-Dataset Benchmark of CNN and Transformer Architectures

Deep learning models for diabetic foot ulcer (DFU) segmentation routinely report high accuracy, but they are almost always trained and tested on the same dataset, leaving their behaviour on data from a different clinical source largely unmeasured. We benchmark three representative segmentation architectures -- U-Net and DeepLabV3+ (convolutional) and SegFormer-B2 (Transformer) -- under an identical, leakage-screened protocol: training on the combined FUSeg/AZH wound data and evaluating, without fine-tuning, on two independent external datasets (DFUC2022 and Medetec). All models achieve strong in-domain performance (Dice 0.80--0.83) but degrade substantially across datasets. The degradation is, however, architecture-dependent: SegFormer-B2 generalizes best on both external sets (DFUC2022 Dice 0.557, Medetec Dice 0.786), outperforming both convolutional models, while the more complex DeepLabV3+ generalizes worse than the simpler U-Net. Per-image failure analysis on 2,160 images across both external test sets confirms that SegFormer-B2 produces the fewest catastrophic failures on DFUC2022 (31.1%), compared with U-Net (38.5%) and DeepLabV3+ (43.0%). The consistent ranking across two independent external sources, confirmed by Wilcoxon signed-rank tests (p < 0.001 on both datasets), indicates that architecture family, not model complexity, drives cross-hospital generalization.

Mitigating Batch Effects in Histopathology via Language-Mediated Robust Embedding Generation

Pathology foundation models (PFMs) have demonstrated strong potential across clinical and scientific applications, yet their performance is often hindered by batch effects, which are non-biological variations across tissue source institutions (TSIs) that distort learned feature representations and impair generalization. Conventional mitigation strategies, such as stain normalization, offer limited success in addressing these high-dimensional, complex artifacts. We present GLMP (General-purpose LLM-Mediated Pathology model), a novel framework that generates robust numerical embeddings from histology image patches through an intermediate textual representation. By leveraging pretrained general-purpose multimodal large language models (MLLMs) and text encoders, GLMP effectively prioritizes biologically meaningful signals over TSI-specific artifacts, thereby improving cross-institutional generalization. To our knowledge, GLMP is the first pathology model to use text descriptions of histological features as an intermediate representation for generating numerical embeddings from histology images. Our results highlight the untapped potential of broad-domain, non-specialized MLLMs in computational pathology and introduce a new paradigm for building versatile, generalizable, and robust pathology models.

GEN-Guard: Correcting Generalization Failures for Deployable Federated Surgical AI

Federated Learning (FL) in surgical video AI enables collaborative model training without sharing sensitive data. However, standard evaluation practices - selecting the "best" global model based only on validation data from participating hospitals - can lead to suboptimal deployment choices. We identify this critical failure mode as performance leakage, where the selected model overfits internal federation data and fails to generalize to unseen institutions. We propose GEN-Guard, a practical post-hoc framework to detect and correct generalization failures in federated surgical AI. It integrates Generalization Detection via Client-Blocked Evaluation (CBE), which validates performance on isolated client distributions to prevent performance leakage, and Generalization Correction through Disagreement-Aware Distillation (DAD), which learns adaptive feature-level corrections for cross-institutional robustness. Both components operate after standard FL convergence while providing robust support for zero-shot adaptation to unseen environments. We first quantify the severity of performance leakage, observing Model Selection Failures (MSFs) exceeding 80% under standard evaluation. GEN-Guard is evaluated on two multi-center clinical challenges: surgical phase recognition in laparoscopic cholecystectomy and polyp segmentation in colonoscopy. Across both datasets, GEN-Guard consistently corrects these failures, improving in-federation F1 scores by up to 2 points, unseen-institution performance by up to 3 points, and worst-case institutional performance by 3-9 points. Performance leakage represents a systematic and previously under-recognized risk in federated surgical AI. GEN-Guard provides a practical solution for detecting and correcting such failures. By improving cross-institutional robustness and zero-shot generalization, it strengthens the reliability of FL for real-world surgical deployment.

SpeechDx: A Multi-Task Benchmark for Clinical Speech AI

Speech offers a uniquely informative window into health by simultaneously engaging neurological, motor, respiratory, and vocal systems. Current clinical speech AI methods have largely progressed through isolated condition-specific studies, making results difficult to compare and generalization difficult to assess. We introduce SpeechDx, a large-scale benchmark for clinical speech AI spanning 12 datasets and 27 tasks across diverse health conditions. To enable evaluation across shared clinical mechanisms, SpeechDx structures tasks by the stage of speech production they disrupt: conceptualization, formulation, and articulation. The benchmark tests generalization by including tasks with limited labeled data and evaluating the same health condition across multiple datasets, distinguishing clinically meaningful patterns from dataset artefacts. We systematically evaluate 12 state-of-the-art audio encoders across all tasks and under zero-shot cross-condition transfer. Results show that large-scale speech models represent the strongest overall baselines, domain-specific models improve performance only on closely matched tasks, and no current representation generalizes reliably across the clinical speech landscape. SpeechDx establishes a shared evaluation framework for tracking progress toward general-purpose clinical speech representations

How Post-Training Shapes Biological Reasoning Models

Scientific reasoning models for biology combine language models with foundation models trained on multimodal biological data, including DNA, RNA, and proteins. These models are built through post-training, yet how each stage shapes reasoning and generalization remains poorly understood. We study when post-training improves performance and when it induces over-specialization. Across genomics, transcriptomics, and proteins, we train and evaluate more than 100 biological reasoning models under controlled variation in backbone, continued pre-training (CPT), supervised fine-tuning (SFT), and reinforcement learning (RL), measuring both in-domain (ID) and out-of-domain (OOD) performance. We find that each post-training stage reshapes generalization in a distinct way rather than contributing uniform gains. CPT improves downstream performance by aligning models with biological language. SFT consistently increases ID performance but causes OOD performance to peak early and decline as models fit the training distribution. RL, when applied to strong SFT checkpoints with aligned rewards, improves OOD performance and partially recovers generalization. These results show that biological reasoning does not improve monotonically with additional supervision or compute. Instead, performance depends on how training stages are composed. Under fixed post-training budgets, the strongest ID-OOD trade-off comes from brief SFT, larger RL allocations, and asymmetric adaptation capacity across stages.

New Benchmarking Shows Limited Generalization Power of TCR Antigenic Epitope Prediction Models

Accurate computational prediction of T cell receptor (TCR) antigen specificity would transform the study of T cell biology and enable scalable immune engineering, yet existing models lack sufficient sensitivity and specificity for broad applications. A major limitation is the absence of rigorously defined, unseen benchmark datasets that allow unbiased evaluation of model performance and generalizability. Here, we describe two complementary classes of datasets that meet this criterion and argue that they provide both a robust framework for model assessment and a foundation for next-generation TCR-antigen prediction algorithm development.

Why Do Self-Harm Prediction Models Struggle to Generalise? Lexical and Semantic Variations in Emergency Department Triage Notes

Self-harm presentations to emergency departments (EDs) are strongly associated with higher suicide risk. NLP models have shown robust performance in detecting self-harm from triage notes within single hospitals, yet performance often declines across institutions. To examine potential causes, we compare ED triage notes from two hospitals by analyzing lexical characteristics, highly associated predictive features, and salient topics. Our results reveal variation in lexical expression and feature importance related to self-harm across hospitals, despite consistent core themes such as self-poisoning and self-injury. These documentation differences are associated with reduced cross-site performance. Our findings provide insight into how institutional variation affects the identification of self-harm in clinical text and highlight potential methods to improve model generalisability.

Validation of an AI-based end-to-end model for prostate pathology using long-term archived routine samples

Artificial intelligence (AI) is becoming a clinical tool for prostate pathology, but generalization across variations in sample preparation and preservation over prolonged time periods remains poorly understood. We evaluated GleasonAI, an end-to-end attention-based multiple instance learning model, on an independent validation cohort comprising 10,366 biopsy cores from 1,028 patients across 14 Swedish regions, using archival diagnostic specimens from the ProMort cohorts collected between 1998-2015. The model achieved an overall quadratic-weighted kappa of 0.86 for core-level ISUP grading, comparable to several experienced pathologists and consistent across geographic regions. Notably, performance remained stable across the 17-year collection period, demonstrating robustness to time-related variation in archival material, a property not consistently observed with foundation model-based approaches, with exploratory analysis demonstrating a significant prognostic gradient across AI-assigned grade groups for prostate cancer-specific mortality. These findings support the generalizability of the AI grading model and demonstrate the potential of pathology archives as a large-scale resource for AI development, validation, and retrospective prognostic research.

Meta-Ensemble Learning with Diverse Data Splits for Improved Respiratory Sound Classification

Training reliable respiratory sound classification models remains challenging due to the limited size and subject diversity of datasets. Ensemble methods can improve robustness, but when base models are trained on identical data, models tend to overfit and produce highly correlated predictions, thereby reducing the effectiveness of ensembling. In this work, we investigate a meta-ensemble learning methodology that enhances prediction diversity by training base models on diverse data splits and combining their outputs through a trained meta-model. Specifically, we train base models on the ICBHI dataset using two data split settings: fixed 80-20% split and five-fold cross-validation split, under two data granularity settings: patient- and sample-level. The resulting diversity in base model predictions enables the meta-model to better generalize. Our approach achieves new state-of-the-art performance on the ICBHI benchmark, reaching a Score of 66.49% and showing improved generalization on two out-of-distribution datasets, indicating its potential applicability to real-world clinical data.