Matthew Flathers, Phuong Anh Nguyen, Jill Noorily +7cs.CL cs.AI cs.CY
General-purpose health benchmarks increasingly anchor claims about LLM medical performance, but they are not always resolved by clinical specialty, making domain-specific performance hard to isolate. Mental health is of acute public-health concern as millions of people turn to LLMs for psychological support, and most existing evaluations are bespoke academic benchmarks that are difficult to integrate into developer workflows. We introduce HealthBench-Psych and HealthBench-Psych-Hard. We screened HealthBench's 5,000 physician-rubric conversations for mental-health relevance with a transparent LLM-applied rubric, then validated the subset through two rounds of blinded clinician review with concealed known-exclude controls, yielding 610 conversations (12.2% of the corpus). Evaluating 20 frontier and open models under a cross-vendor panel of three LLM judges, we find a statistically tied frontier cluster, measurable refusal behavior in two models, and near-identical rankings across judges ($τ\ge 0.92$). We release the subset, pipeline, model responses, grades, and analysis code as a reusable resource.
Marie-Lisa Eich, Kai Standvoss, Timo Milbich +30cs.CV cs.AI cs.LG
Lung cancer tissue diagnostics is complex, as therapy decisions in precision oncology rely on the integration of histomorphological, immunohistochemical, and molecular features. Yet pathological assessment remains largely visual and semi-quantitative and shows interobserver variability, while existing artificial intelligence (AI) tools cover only selected tasks, rarely reach generalizable expert-level performance, and lack prospective clinical validation. To address these challenges, we developed and clinically validated LUCAID, an agentic AI system for precision lung cancer pathology. An integrative agent couples diagnostic reasoning with nine modules that cover the full routine workflow, from quality control, tumor detection and segmentation, histological subtyping, tumor microenvironment profiling, tumor cellularity quantification, and predictive biomarker scoring (PD-L1, MET, TROP-2) to automated structured report generation. LUCAID enables users to interactively query the module outputs and generate reports that contextualize the results. Against large-scale expert ground-truth annotations, the analysis modules achieved F1 scores of 0.82-0.95. In prospective clinical validation, LUCAID reached 93.0% concordance with an expert-panel adjudicated reference standard across clinically actionable decisions, compared with 68.3-81.1% for five experienced thoracic pathologists.
Missing or degraded sequences can limit prostate multiparametric MRI. We developed MSCNet, a sequence-conditioned cross-modal generative framework for reconstructing unavailable contrasts and restoring degraded acquisitions. Across ten completion tasks, task-specific MSCNet achieved mean structural similarity of 0.818 versus 0.798 for the strongest task-matched comparators; matched-capacity analyses showed larger differences in lesion fidelity and boundary preservation. In a blinded 1,000-case reader study, overall image quality met the prespecified non-inferiority criterion for DWI, ADC and T2W completion, but not T1W. In a separate 200-case diagnostic assessment, AUCs for clinically significant cancer were 0.860 with acquired images, 0.841 with MSCNet and 0.797 with baseline-generated images. A locked 186-case three-hospital cohort supported multicentre transportability. These retrospective results support quality-controlled cross-modal reconstruction as an adjunct to acquired prostate MRI.
3D body scanning has become an important tool in healthcare applications because of its rapid and non-invasive nature. While smartphone-based photogrammetric reconstruction provide a low-cost and accessible alternative to commercial 3D body scanners, their performance for whole-body scanning remains insufficiently validated. Thus, we designed this study to comprehensively validate the photogrammetric 3D scanning application by evaluating automatically extracted whole-body measurements and longitudinal body-shape monitoring. We evaluated a representative application, PolyCam, against the commercial depth-sensor-based Fit3D ProScanner using 144 pregnant participants scanned longitudinally throughout pregnancy. We designed an automatic circumference extraction pipeline to get measurements at four anatomical landmarks from paired 3D scans. A linear mixed-effects model was used to evaluate scanner effects and longitudinal body-shape changes. Measurement consistency was assessed using repeated PolyCam scans and tape measurements on a rigid mannequin. PolyCam demonstrated strong agreement with Fit3D, with average biases below 16 mm, intraclass correlation coefficients above 0.8, and Pearson correlation coefficients above 0.9 across all landmarks. Both systems captured comparable longitudinal body-shape changes. Mannequin experiments showed mean biases below 3.5 mm and no significant differences from tape measurements. These findings support smartphone photogrammetry as a potential accessible alternative to commercial body scanners and applicable for longitudinal 3D body-shape assessment.
Chest radiography (CXR) remains the most widely used thoracic imaging modality, yet expert interpretation is constrained by a severe shortage of radiologists in Thailand and across Southeast Asia. Local adaptation of deep learning models to Thai data has been shown to substantially improve accuracy on Thai populations. Here we present the development and comprehensive validation of the chest radiograph analysis model in Inspectra CXR version 5, a deep learning system that performs multi-label thoracic disease classification and weakly supervised lesion localization within a single model. The architecture couples a DenseNet-121 backbone with Attend-and-Compare Modules (ACM) and a Probabilistic Class Activation Map (PCAM) aggregation layer, producing a per-condition classification score and heatmap simultaneously. The model was developed on 874,858 frontal chest radiographs with paired radiologist reports from Siriraj Hospital, Bangkok. On a held-out, radiologist-verified in-domain test set of 19,871 cases, it achieved a mean AUROC of 0.994 (mean sensitivity 92.4%, specificity 98.6%) across nine clinically important conditions. On an independent generalization set of 5,992 cases from 13 hospitals across Thailand, the mean AUROC was 0.970, indicating robust transfer across sites. For localization, evaluated on 4,549 radiologist-annotated cases, the model attained a mean lesion-localization fraction (LLF) of 77.9% at 0.59 non-lesion localizations per image. In a usability evaluation with five thoracic radiologists, the system reached a classification concordance of 93.6%, a localization concordance of 94.7%, and a mean System Usability Scale (SUS) score of 89. These results indicate that a locally developed, localization-capable CXR system can deliver high accuracy, generalize across heterogeneous Thai hospitals, and earn the trust of practicing radiologists.
Validating federated learning frameworks on real clinical data is an essential step between proof-of-concept demonstrations in controlled synthetic environments and deployment in real multicenter healthcare settings. A prior architectural study by the same authors (Tertulino and Alencar, 2026) demonstrated, on a synthetic six-feature benchmark, that server-side adaptive optimization acts as a temporal denoiser for Differential Privacy noise, answering an open challenge identified in the original pipeline work (Tertulino, 2025). That study used synthetically generated data and explicitly identified real-world validation as a priority future direction. The present work addresses this gap by validating the FedCVR framework on five publicly available real cardiovascular datasets (Framingham, Cleveland, Hungarian, Switzerland, and Long Beach VA), harmonized to the 13-attribute UCI Heart Disease schema and configured as a heterogeneous federated scenario with leave-one-institution-out cross-validation. Results demonstrate that FedCVR preserves its adaptive advantage on real data, achieving an F1-Score of 79.2% and AUC of 0.96 under the operational privacy budget (noise multiplier = 0.8, privacy budget epsilon approximately 4.2), while statistically outperforming standard FedAvg on all evaluated metrics (paired t-tests, all p <= 0.003, significant under the Bonferroni-corrected threshold). The measured privacy cost on real data confirms the graceful degradation pattern observed in the synthetic experiments, providing empirical evidence of the framework's clinical viability in genuine multicenter contexts.
Xiaocheng Fang, Haoyu Wang, Jieyi Cai +14cs.LG cs.AI
Complete digital 12-lead electrocardiograms (ECGs) are essential for AI-enabled cardiovascular assessment, yet many clinical ECG records, particularly those digitized from ECG images, remain incomplete because of short display formats, incomplete waveform digitization, lead loss, or signal corruption. We developed ImputeECG, a mask-conditioned one-dimensional Transformer autoencoder that completes 12-lead, 10-s ECGs while retaining all observed samples. The model was trained on PTB-XL and evaluated on PTB-XL and CPSC2018 under simulated incomplete settings, with additional real-world validation in a 43,633-record Kailuan clinical cohort after ECG image digitization. Metrics were computed over originally missing regions, with analyses of morphology and downstream diagnostic utility. On PTB-XL, ImputeECG reduced missing-region MAE by 41.7-51.0% and MSE by 54.0-63.7% versus the strongest baseline, with lower errors in R-peak timing, RR interval, QRS duration, QT interval, and P-wave, QRS-complex, and T-wave reconstruction. On CPSC2018, ImputeECG reduced MAE by 49.7-51.9%, supporting external generalization. In downstream multi-label classification, ImputeECG restored performance to 92.28% AUROC and 33.88% AUPRC in the most incomplete PTB-XL setting, approaching complete-ECG performance. On CPSC2018, completed ECGs achieved 94.75-95.89% AUROC and 78.83-81.86% AUPRC across settings. In Kailuan, ECG completion improved zero-shot sex prediction AUROC from 82.6% to 85.8% and reduced age prediction MAE from 10.72 to 9.87 years after image-based ECG digitization. These findings support ECG completion as a practical strategy for converting incomplete ECG records into AI-ready 12-lead, 10-s digital signals and extending the usable scope of ECG archives for digital cardiac assessment.
Wolf-Dieter Vogl, Hlynur Skulason, Oliver Leingang +3cs.CV
Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) requires precise monitoring of relevant structural biomarkers to assess disease stage, progression, and treatment response. This paper presents a fully automated, deep learning-based framework for the high-precision, pixel-wise segmentation of key biomarkers in optical coherence tomography (OCT) imaging: retinal pigment epithelium (RPE) loss, ellipsoid zone (EZ) loss, and EZ thinning. The proposed pipeline uses three specialized semantic segmentation models to delineate RPE loss, EZ boundaries (including interruptions), and Bruch's membrane. To ensure robustness and generalizability, the models were developed on a diverse dataset of 298 SD-OCT volumes representing the full phenotypic spectrum of AMD (GA:222, intermediate AMD: 40, neovascular AMD: 17, healthy: 19) and validated on an independent external dataset (n=43). The comprehensive evaluation was further strengthened using additional datasets to assess repeatability, inter-reader reliability, the impact of B-scan density on measurement accuracy, and subgroup performance stratified by lesion size. Results demonstrated high segmentation accuracy (Dice RPE loss: 0.88, Dice EZ loss: 0.87, Pearson's r > 0.99). Total EZ thickness measurements exhibited a sub-pixel average deviation of 2.15 $μm$, and segmentation reliability was confirmed by a strong reproducibility score (ICC > 0.98). By accurately and consistently quantifying outer photoreceptor degeneration and RPE loss, this fully automated framework provides a highly reliable tool for GA assessment in both clinical trials and routine real-world ophthalmic care.
Dominik Winter, Dominik Vonficht, Loïc Le Bescond +6eess.IV cs.AI q-bio.GN
H&E-stained whole-slide images offer cohort-scale availability and rich spatial context but lack molecular specificity, whereas bulk RNA-seq provides transcriptome-wide resolution at high cost with limited archival availability. We show that training a lightweight alignment module atop frozen histopathology and RNA-Seq foundation models enables open-vocabulary molecular prompting -- querying H&E slides with gene-set signatures to predict pathway activity without sequencing or end-to-end retraining. Using contrastive learning on a multi-cancer cohort (N=1,720), we achieve a 25-fold improvement in retrieval over baseline methods. Systematic analysis reveals a graduated predictability spectrum: morphologically grounded programs (cell-cycle programs, immune-related) are most reliably predicted (R^2>0.5), while predicting pathways with no morphological footprint remains challenging as expected. We validate clinical utility on the POSEIDON clinical trial: H&E-predicted squamous cell carcinoma scores recapitulate NSCLC subtype identity and predicted IFN-gamma mirror PD-L1 tumor-cell expression groups. Furthermore, genesets describing immune activation and fibrosis predict known tumor microenvironment archetypes from histology alone. We further validate generalization of our approach across unseen cohorts and demonstrate data-efficient domain adaptation, establishing a slide-native framework for molecular analysis on H&E images.
Thuy Nuong Tran, Ömer Sümer, Evangelia Christodoulou +15cs.CV
The global elimination of cervical cancer is a key public health goal set by the World Health Organization (WHO), with screening programs reducing mortality by up to 80%. However, access to experts and biopsy services is limited in low- to middle-income countries (LMICs). Deep learning (DL)-based algorithms offer promising support for screening, but most existing approaches have been developed and validated on private datasets from single countries. We present the first DL-based approach to cervical cancer screening validated on data from multiple countries. Technically, we phrase the problem of detecting and classifying lesions in colposcopy images as a multi-task learning problem, in which we simultaneously perform image-level classification and lesion segmentation. Our model was trained on a private data set of acid stain colposcopy images with manually generated lesion segmentation masks and corresponding histopathological results, employing extensive data augmentation to address image variability. In an in-distribution validation with pathology results serving as ground truth, our algorithm outperformed medical experts (Balanced Accuracy: 0.68 vs 0.64) in CIN1- (Cervical intraepithelial neoplasia grade 1 or lower) versus CIN2+ (grade 2 or higher) classification. External validation on four colposcopy data sets from four countries featuring radical differences in prevalence and patient characteristics yielded superior performance of our method compared to baseline methods. Performance variability across countries was high with AUC values ranging from 0.54 - 0.80. Overall, algorithm performance varied with age, transformation zone (cervical area most prone to lesion development), presence of comorbidities and pathognomonic signs, with comorbidities having by far the largest negative effect. Future work should focus on improving model robustness and generalizability.
Elena S. Kozachok, Sergey S. Seregin, Aleksandr V. Kozachok +2cs.CV cs.AI
Purpose. To compare deep learning architectures and classification schemes for dermoscopic images of skin neoplasms and assess their generalization on transfer from open international datasets to independent clinical datasets of Russian practice. Methods. Four architectures (ViT-B/16, Swin-S, ConvNeXt-S, EfficientNetV2-S) were compared in three schemes: binary (malignant/benign), single-stage four-class (benign, MEL, SCC, BCC), and a two-stage cascade (binary triage, then three-class differentiation MEL/SCC/BCC). All models used ImageNet-pretrained weights and a single augmentation protocol on aggregated open ISIC Archive data, and were evaluated on an internal held-out sample and two clinical datasets (Melanoscope AI mobile system; Sechenov University). Results. Internally the binary stage attains ROC-AUC 0.952-0.966; on Sechenov University it drops to 0.797-0.893, sensitivity to 0.53-0.67, and ECE rises from 0.02 to 0.27-0.39 with underestimation of malignancy, quantifying a generalization gap in ranking and calibration. Paired tests confirm one inter-architecture result on clinical data: the deficit of ViT-B/16 at the binary stage (p<0.05); at the differentiation stage no architecture has a proven advantage. The cascade raises macro F1 over single-stage four-class classification for most architectures, but significantly only for ViT-B/16, by recovering malignant lesions assigned to the dominant benign class. On ISIC MILK10k, direct 11-class classification yields mean-class sensitivity 0.525. Conclusion. A tunable triage threshold gives sensitivity control not attainable in standard single-stage (argmax) classification and better reproduces clinical differential-diagnosis logic. The persistent generalization gap mandates external clinical validation and recalibration before deployment.
Lisa Herzog, Oliver Dürr, Pascal Bühler +4stat.AP cs.LG
Personalized medicine in acute ischemic stroke requires moving beyond average treatment effects (ATE) to individualized treatment effect (ITE) estimates to support treatment decisions. In acute ischemic stroke, mechanical thrombectomy has been shown to be more effective on average than lysis in randomized controlled trials (RCTs), such as the MR CLEAN study. We aim to identify which individual patients benefit most from mechanical thrombectomy compared to lysis. The outcome of interest is the modified Rankin Scale (mRS) at three months, an ordinal measure of functional disability (0: no symptoms, 6: death). We demonstrate that causal transformation models on directed acyclic graphs (TRAM-DAG) can be used for ITE estimation after being fitted on observational MAGIC multi-center stroke patient data. To ensure comparability with the MR CLEAN population, which we use for validation, we train the TRAM-DAG on a MAGIC sub-population with NIHSS at admission >= 6, corresponding to one inclusion criterion of MR CLEAN. The fitted model is then used to estimate ITEs for stroke patients in the MR CLEAN population. While these ITE estimates cannot be confirmed experimentally, we show that their average is consistent with the trial's reported ATE. Furthermore, the ITE estimates correctly rank trial patients by their observed frequency of a good outcome (mRS at three months <= 2). These findings support the use of causal models like TRAM-DAG for personalized decision-making in stroke care and highlight their ability to bridge the gap between observational evidence and clinical trials.
Kai Standvoss, Miriam Hägele, Rosemarie Krupar +25cs.CV cs.AI cs.LG
Hematoxylin and eosin (H&E) staining is the cornerstone of histopathology, yet scalable, quantitative analysis of H&E whole-slide images (WSIs) remains a central challenge in computational pathology. We present Atlas H&E-TME, an AI-based system built on the Atlas family of pathology foundation models that predicts tissue quality, tissue region, and cell type labels across multiple cancer types, yielding over 4,500 quantitative readouts per slide at cell-level resolution. A key challenge to validating such systems is overcoming morphological ambiguity inherent to H&E-only ground truth and the limited scalability of more informed references drawing on modalities such as immunohistochemistry (IHC). We address this with a dual validation framework combining biologically grounded depth with technical and morphological breadth. For depth, we propose an IHC-informed multi-pathologist consensus protocol that substantially improves inter-rater agreement over conventional H&E-only annotation. This yields a molecularly grounded reference against which we compare Atlas H&E-TME and pathologists working from H&E alone. For breadth, we benchmark Atlas H&E-TME on over 200,000 high-confidence H&E-only pathologist annotations across 1,500+ cases spanning eight cancer types and their most common metastatic sites, with subtypes covering >90% of clinical cases per cancer type, drawn from 25+ sources and 8+ scanner models. Benchmarked against the IHC-informed consensus, Atlas H&E-TME matches or exceeds pathologist H&E-only performance and generalizes consistently and robustly across this broad morphological and technical scope. In doing so, Atlas H&E-TME turns the H&E slide -- the most ubiquitous data in pathology -- into a scalable, quantitative window into the tumor and its microenvironment, laying a foundation for the next generation of tissue-based biomarkers in translational and clinical research.
Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.
Pranav Mahajan, Amanda Wall, Eleonora Maria Camerone +7cs.HC cs.AI cs.CV
Chronic pain diminishes quality of life by decreasing functional ability, yet objectively measuring this functional impact remains challenging in real-world settings. While optical motion capture provides high precision for assessing altered movement quality, it is costly and restricted to laboratory environments. We aimed to develop and validate Quantitative Movement Testing (QMT), a computer vision pipeline extracting 3D kinematic biomarkers from standard monocular smartphone video, balancing clinical accessibility with biomechanical accuracy. We validated the QMT pipeline, utilising deep learning-based 3D pose-estimation, against gold-standard optical motion capture in healthy controls (N=13). Following leave-one-subject-out calibration to correct systematic bias, we deployed QMT in two prospective clinical cohorts to assess real-world utility: a pre- and post-intervention trial for fibromyalgia patients, and a 30-day longitudinal at-home monitoring study of chronic sciatica patients and healthy controls. In laboratory validation, QMT extracted clinical kinematic metrics with high agreement to optical motion capture, yielding strong correlations (r > 0.85) and low mean absolute errors. QMT demonstrated high test-retest reliability (r > 0.86) in fibromyalgia patients and successfully tracked day-to-day movement fluctuations in chronic sciatica. While real-world home settings introduced higher measurement variance than lab settings, QMT found group-level differences between healthy controls and sciatica patients based entirely on remote recordings. Monocular 3D pose estimation offers a scalable alternative to traditional assessments. QMT provides an objective, accessible biomarker for tracking disease progression and treatment response in clinical trials, though further research is needed to optimise reliability in home environments.
Xiaoyi Ji, Renata Zelic, Oskar Aspegren +11cs.CV cs.AI
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.