Federated Learning (FL) with Differential Privacy (DP) is increasingly adopted to preserve data confidentiality in distributed machine learning. However, DP noise distorts learned representations and degrades explanation fidelity, limiting differentially private FL where trustworthy explanations are required, such as assistive clinical diagnosis. Prior work adapted DP noise with static feature-importance signals, restricting explainability to post hoc analysis and precluding noise calibration to explanation quality during training. We propose XCal-FL, a closed-loop, explainability-driven local training algorithm for image classification in cross-silo FL that dynamically calibrates DP noise from three complementary signals: (1) prediction logit variations, measuring causal influence on model confidence, (2) counterfactual margins, capturing decision-boundary sensitivity, and (3) saliency concentration, quantifying spatial coherence of model attention, while enforcing formal DP guarantees via adaptive privacy accounting. Experiments on three medical imaging datasets across varying FL configurations show that XCal-FL yields more accurate and interpretable global models, improving predictive performance by over 10\% and explanation fidelity by up to 5$\times$ over static-noise FL, and outperforming state-of-the-art adaptive DP methods in fidelity. XCal-FL also achieves higher privacy-budget efficiency, turning each unit of cumulative privacy loss into larger gains in both accuracy and explanation fidelity. Our analysis further reveals that, unlike predictive performance, which scales roughly linearly with privacy loss, explanation fidelity exhibits non-linear dynamics. These findings suggest explainability is a distinct dimension of the privacy trade-off that cannot be inferred from utility alone, with implications for training and privacy-budget allocation in decision-critical applications.
Deep learning models have achieved impressive performance in medical image diagnosis, yet their deployment in clinical settings remains constrained by limited explainability. Counterfactual images provide one means of auditing model behavior by showing how an image would need to change for a classifier to produce a different prediction. Existing approaches typically generate such explanations using auxiliary models, including generative adversarial networks and diffusion models. While often capable of producing visually realistic images, these methods explain one black-box model using another, making it difficult to separate the classifier's decision-making process from the inductive biases of the generator. We propose a novel counterfactual-generation framework that requires no generative model. Instead, counterfactuals are constructed directly from causal evidence extracted from the classifier. The resulting approach is deterministic, requires no additional model training, and enables controllable edits within user-specified regions of interest. Experiments on real-world medical imaging datasets demonstrate that the proposed method successfully changes classifier predictions while remaining closer to the original image than generative baselines, providing a more direct and transparent view of the classifier's decision boundary.
Diabetic retinopathy (DR) is a major cause of preventable blindness, creating a need for accurate and trustworthy automated screening. This study investigates an explainable DR classification framework using vision foundation models and multiple transfer learning strategies. Three backbones, DINOv2, CLIP, and Vision Transformer (ViT), were evaluated using full fine-tuning, linear probing, and Low-Rank Adaptation (LoRA). Models were trained and internally evaluated on the ODIR dataset and externally evaluated on APTOS to assess generalization. DINOv2-LoRA achieved the highest internal AUROC of 0.758, while DINOv2 full fine-tuning and ViT full fine-tuning achieved the highest external AUROC of 0.920. Calibration was further assessed using reliability analysis after isotonic regression. For explainability, Grad-CAM and HiResCAM were evaluated against expert-annotated lesion masks from the IDRiD dataset using Dice, Intersection over Union (IoU), and Pointing Game metrics. The results demonstrate that foundation models, particularly DINOv2, can provide strong predictive performance, while LoRA offers a parameter-efficient alternative to full fine-tuning. Quantitative evaluation of explanation maps further supports the assessment of whether model attention corresponds to clinically relevant retinal lesions.
Anja Witte, Maximilian Lennartz, Jan Baumbach +4cs.CV cs.LG
Vision Foundation Models (VFMs) are widely used in computational pathology but remain sensitive to domain shifts arising from variations in staining, tissue preparation, and scanner hardware. A key limitation is that VFM embeddings entangle biological with domain-specific information, hindering cross-domain generalization. We propose Explainable Probing of Cross-Domain Sparse Embeddings (EXPOSE), a framework that uses Sparse Autoencoders (SAEs) as an explainable bottleneck to identify and suppress domain-specific components in VFM embeddings. We train a sparse representation of VFM features, use a linear classifier to identify domain-specific latent dimensions, and mask these features prior to downstream relapse prediction without retraining the backbone model. Experiments on a large prostate cancer dataset with multiple acquisition domains show that SAE features capture both domain- and task-specific information, which are partially disentangled in the latent space. Removing domain-specific features improves cross-domain performance and increases embedding robustness as measured by the Domain Robustness Index (DoRI). Code is available at https://github.com/imsb-uke/expose .
Drug synergy prediction estimates whether two drugs produce a stronger joint effect than expected from their individual activities. For drug combination discovery, a single synergy score is often not enough: researchers also need to know which molecular regions jointly drive the prediction. We study motif-pair synergy explanation, which identifies pairs of chemically coherent regions, one from each drug, that jointly contribute to predicted synergy. Existing interpretable synergy models expose atom- or substructure-level signals, but their explanations are built into the predictor architecture, and none validates cross-drug region scores under repeated perturbations or feeds that evidence back to refine the explanation. A reliable motif-pair explanation should instead be chemically coherent, perturbation-stable, and aligned with predictor behavior. We introduce VINCENT (Validated Interaction Network for Cross-drug Explanation of Therapeutics), a post-training framework for a fixed interaction-aware synergy predictor. VINCENT extracts atom-pair evidence from attention and gradient signals, groups atoms into chemically coherent motifs, and validates candidate motif pairs through repeated local perturbations. The validated evidence is fed back to refine motif assignments, yielding explanations that satisfy these three criteria. On a 25-pair literature-annotated subset, VINCENT achieves a mean motif recall of 0.826 (95% CI: 0.78-0.87), compared with 0.49-0.66 for baselines. Across all 71 test pairs, its validated interaction scores yield a TP/TN separation of 3.36. These results show that closed-loop perturbation validation recovers literature-supported molecular regions more accurately than existing alternatives while producing cross-drug interaction scores that better reflect predictor behavior.
Md Abdullah Al Kafi, Walayat Hussain, Mousumi Karmakar +2cs.CV
Automated malaria diagnosis from stained blood-smear microscopy is dominated by deep convolutional neural networks that are accurate but computationally expensive, poorly interpretable, and rarely validated with patient-level rigor. We present EMFE (Efficient Mathematical Feature Extraction), a five-feature framework for classifying single red-blood-cell images as parasitized or uninfected using Gray World color normalization, adaptive green-channel thresholding, morphological spot detection, and classical machine learning. Using the NIH LHNCBC malaria dataset (27,558 images from 200 patients), we evaluate Random Forest, Histogram Gradient Boosting, and Support Vector Machine classifiers under patient-grouped nested cross-validation (K_outer=20, K_inner=3), ensuring that cells from each patient remain within a single fold. The optimized Random Forest achieves 94.6% pooled out-of-fold accuracy (95% CI [93.6, 95.7]), corroborated by an untouched 40-patient holdout test (94.3%) and a patient-level permutation test (p<0.001, 1,000 permutations). Ablation experiments quantify the contribution of individual features and pipeline stages. Hardware-matched comparisons with retrained DenseNet121, ResNet50, and MobileNetV2 models assess the accuracy-efficiency trade-off. Synthetic perturbations characterize three failure modes, while explainability analysis identifies spot saturation as the dominant discriminative feature. Patient-level aggregation further quantifies sensitivity-specificity trade-offs and false-positive accumulation. These results demonstrate a statistically rigorous, interpretable, and computationally lightweight alternative to deep learning, while explicitly quantifying its limitations.
Spatial multi-omics technologies jointly profile gene expression, surface proteins, and histology at each tissue spot, yet most spatial domain discovery methods provide only cluster assignments, without indicating assignment reliability, modality contributions, or why a domain decision should be trusted. We present OmicSync, a reliability-aware spatial multi-omics framework that couples unsupervised domain clustering with evidence-constrained LLM reasoning using model-derived per-spot signals, including assignment confidence, epistemic routing uncertainty, and modality-routing weights. These signals are converted into structured evidence dictionaries and used to generate standard, stepwise, counterfactual, contrastive, and uncertainty-focused explanations. OmicSync integrates a KAN-GCN backbone with spatial encoding, cross-modal fusion, uncertainty-aware routing, cell-type supervision, and missing-modality imputation. We further introduce OmicSync-R, which closes the reasoning-clustering loop by using automatically computed reasoning-quality scores as REINFORCE rewards, allowing reasoning coherence to shape the latent structure without backpropagating through the language model. Across four 10x CytAssist FFPE spatial proteomics benchmarks, OmicSync achieves the best average rank on Human Tonsil (1.44), Glioblastoma (1.78), and Tonsil Add-on (1.22), and second-best on Human Breast Cancer (2.33). OmicSync-R further improves ARI on Human Breast Cancer from 45.73 to 46.72 and outperforms existing methods on six of nine clustering metrics. Together, OmicSync and OmicSync-R enable reliability-aware, spot-level auditable spatial domain discovery guided by evidence-constrained reasoning.
Fracture detection and its clinical interpretability see notable improvements when deep vision models are integrated with agentic AI architectures. While deep learning models achieve high diagnostic performance, their black-box nature limits clinical adoption. We propose FRAC-MAS, an agentic AI system for automated, explainable, and safe bone fracture detection. The framework combines a stacked ensemble of four vision models with conformal prediction to produce statistically grounded differential diagnoses, while a multi-agent workflow performs independent verification, retrieves clinical guidelines, and generates patient-friendly reports. A pipeline-depth ablation study confirms that our multi-agent critic triages 86.6% of cases into a high-confidence auto-confirmed cohort while escalating uncertain cases, outperforming a single-agent baseline. Patient preference studies against Llama, MedGemma, and Gemini further demonstrate significantly more comprehensible clinical reports. These results suggest that integrating multi-agent critics with conformal guarantees enables safer radiology triage while preserving clinician oversight. More broadly, FRAC-MAS demonstrates how cooperative agentic architectures can serve as auditable, human-in-the-loop decision support systems for safety-critical healthcare. Our code is available at https://github.com/hardik1712/FRAC-MAS, and the website is available at https://frac-mas.vercel.app.
Fairness in medical imaging is commonly evaluated through subgroup performance metrics, yet it remains unclear whether models rely on consistent visual evidence across demographic groups. This work introduces the Explanation Consistency Score (ECS), a fairness-aware metric based on Jensen-Shannon divergence that quantifies the similarity of attribution maps across subgroups. Using diabetic retinopathy screening as a case study, ECS is evaluated globally and within disease severity. Experiments reveal that while predictive performance differs across ethnic groups, explanation consistency remains relatively high and shows no significant association with performance disparities. These findings suggest that predictive fairness and explanation consistency capture complementary dimensions of model behavior, motivating fairness evaluations that extend beyond predictive performance.
Fahad Ahammed, Omar Faruq Shikdar, Navid Zaman +3cs.CV cs.LG
Appendicitis is one of the most common abdominal emergencies worldwide and requires prompt diagnosis and treatment to prevent life-threatening conditions. However, accurately differentiating complicated cases, such as perforation or abscess formation, from uncomplicated appendicitis remains a significant clinical challenge. Among other methods, ultrasound is a safer and more cost-efficient diagnostic technique because of the lack of radiation exposure. In this research, an advanced system capable of automatically detecting complicated appendicitis from ultrasound images was developed. A dataset consisting of 4679 ultrasound images with 5 classes, namely perforated, abscess, acute, appendicolith, and normal, was used for the proposed model training and testing. Four pretrained deep learning models, DenseNet201, InceptionV3, ConvNextTiny, and VGG19, have been employed for detecting and classifying complicated appendicitis. In the initial configuration, InceptionV3 achieved the second highest accuracy, with a value of 69.21%. Owing to suboptimal performance with raw images, further optimization techniques, including image preprocessing, hyperparameter tuning, model fine-tuning, and image sharpening, were applied. These enhancements significantly improved the model's performance, with an accuracy of 95.58% for InceptionV3. The model performance is then explained with gradient-weighted class activation mapping (Grad-CAM), which creates a heatmap of the regions responsible for the model's prediction of the infected areas. This could make crosschecking with experts much easier.
Generative models promise a route to explainable clinical AI: rather than probe a classifier, model the distributions of healthy and diseased patients and read explanations off the geometry between them. We build such a system - an optimal-transport rectified flow trained between two clinical distributions - and use it to ask a pointed question the field too rarely tests: do the resulting explanation heatmaps actually localize disease? On tabular tumour biomarkers (Breast Cancer Wisconsin) a single flow yields per-patient counterfactuals, an unsupervised malignancy score (AUROC 0.91; 0.93 +/- 0.01 across five seeds), and a label-free attribution that agrees with a supervised classifier (r ~ 0.5) - a compact, honest interpretability engine, though it never out-predicts logistic regression. Moving to chest X-rays, we show the transport heatmap is a population-level signal, not a localiser; a reconstruction-based, identity-preserving variant does localize synthetic lesions (pointing game 0.52), yet on real RSNA radiologist boxes it collapses to chance while only supervised Grad-CAM stays above it. The central result is a synthetic-to-real gap: label-free heatmaps that look compelling on planted lesions are not evidence of real localisation. We contribute a reusable optimal-transport recipe for generative explanations and a controlled benchmark for stress-testing whether they localize.
Amos Muench, Jonathan Thielmann, Reduan Achtibat +9cs.CV
Recent advances in pathology foundation models have enabled accurate prediction of spatial transcriptomics (ST) from routine H&E images. However, existing explainability methods for vision transformer (ViT)-based models are largely limited to local heatmaps and do not reveal how morphological concepts contribute to ST predictions. Here, we introduce an explainable framework that combines relevance propagation and concept discovery to link transcriptional programs to tissue morphology. We developed a ViT-based framework for virtual ST from H&E images that combines ViT-aware layer-wise relevance propagation with relaxed archetypal TopK sparse autoencoder-based concept discovery. This approach provides both local explanations and global insights into the morphological patterns associated with transcriptional programs. We applied the framework to colorectal cancer ST data from the HEST-1k cohort and evaluated its generalizability in TCGA COAD. Our architecture accurately predicts clinically relevant ST signatures and accompanying molecular phenotypes. Measured and predicted gene expression profiles reveal substantial spatial heterogeneity of the colorectal cancer subtypes iCMS2 and iCMS3 across a large number of samples. Spatially resolved and aggregated iCMS classification achieve weighted F1 scores of 0.872 and 0.819 (0.770 in TCGA COAD), respectively, and both stratify patient outcome. Beyond prediction, our framework establishes a relevance-based concept atlas linking molecular phenotypes to histopathological representations. Comparison of activation- with relevance-derived concepts demonstrates that relevances provide a more direct link between tissue morphology and downstream predictions. We establish a general strategy for concept-based explanation of spatial prediction, and our framework is readily applicable to a broad range of ViT-based pathology models.
Automated five-stage diabetic retinopathy (DR) grading requires more than high accuracy alone. Medical-grade deployment calls for lesion-aware preprocessing, ordinal predictions, calibrated uncertainty, and explainability to support reliable diagnostic systems. We present a unified pipeline that addresses these requirements using a Ben-Graham-green-channel CLAHE feature representation, an EfficientNetV2-L ordinal regressor, and Monte Carlo dropout for uncertainty-driven referral. Grad-CAM provides visual explanations aligned with clinically relevant lesions. The proposed method achieves a QWK of 91.31% on the APTOS-2019 official test split, placing it within the near-perfect agreement band (>80%). At a 20% referral rate, 293 of 366 images are automatically graded with a QWK of 90.40%. More complex cases are referred for specialist assessment, demonstrating a practical trade-off among grading quality, automation, and patient safety in robust, reliable, and deployment-ready medical diagnostic systems.
Dorian Rząsa, Bartosz Zabdyr, Krzysztof Piekarz +7cs.CV
Explainability is essential for deploying deep learning models in high-stakes medical applications. Existing explainability methods for volumetric imaging predominantly operate in voxel space, overlooking the structured representations introduced by recent advances in 3D scene modeling. We present COGENT (Counterfactual Gaussian Explanations), a framework that generates counterfactual explanations directly in the parameter space of Gaussian-based volumetric representations. Built upon MedGS and the Sybil lung cancer risk prediction model, COGENT optimizes selected Gaussian primitives through a differentiable rendering pipeline, enabling gradients from the downstream predictor to identify representation components that most influence model decisions. Unlike conventional pixel- or voxel-level attribution methods, our approach formulates explainability as a counterfactual optimization problem over an explicit 3D scene representation, producing sparse and spatially localized explanations while preserving anatomical consistency. We evaluate COGENT on lung CT scans using quantitative comparisons with existing explainability methods together with qualitative analysis by medical experts. The results demonstrate that representation-space counterfactual optimization provides clinically meaningful explanations while offering a new perspective on interpreting volumetric deep learning models.
Inadequate target--disease linkage accounts for 40--50\% of Phase~II efficacy failures, so anticipating which programmes will advance would let sponsors back the hypotheses most likely to reach patients. What a programme can be judged on is the evidence that supported its linkage \emph{when it entered the clinic}. No existing biomedical knowledge graph allows that evidence profile to be assembled as of a past date. We present the Temporal Heterogeneous Biomedical Knowledge Graph (THBKG), which describes and predicts therapeutic target--disease links through time: 110,396 entities and 11.1M edges across nineteen relation types, each edge carrying the year its evidence changed, so a pair's profile can be recovered as it stood when its own decision fell due. On this graph we define a decision-aligned benchmark that predicts, for a target--disease pair entering Phase~II, whether it advances to Phase~III on evidence datable before that decision. Graph propagation over the THBKG outranks every direct-evidence reference scored under the same decision-aligned protocol, reaching a relative success of 4.3--4.5 at the top ten pairs per therapeutic area. The gain concentrates on the 72.8\% of pairs with no direct target--disease evidence at their decision point, where a direct-edge model has nothing to read: the encoders still rank five- to sixfold above chance, recovering the signal by propagating over the intervening biology. Adapting a path-based explainer to the decision-time subgraph decomposes each prediction into the evidence landscape behind the hypothesis for explainable prediction. We release the THBKG as a continually updated substrate for studying therapeutic target hypotheses by retrospective validation.
Language models (LMs) offer strong textual representations for electronic health records (EHRs), but they encode patient sequences in isolation and provide limited explainability. Graph neural networks (GNNs) complement LMs by incorporating inter-patient relationships and enabling reference-patient attribution, yet they rely on high-quality patient representations. We propose Patients-like-me (PLM), a unified LM--GNN framework that integrates local patient semantics with global cohort structure. To train PLM efficiently, we introduce a Variational Expectation-Maximization algorithm that alternates LM and GNN updates under a supervised variational objective. Extensive experiments on MIMIC-III and MIMIC-IV show that PLM consistently outperforms state-of-the-art methods, with improvements generalizing across encoder-only and decoder-only LM backbones. These gains are achieved with only modest additional computational overhead. PLM also provides reference-patient explanations by retrieving influential similar patients, while edge-masking experiments confirm that the highest-ranked references have the greatest impact on model predictions.
Abdallah Lamane, Abdul Rahman Diab, Ren-Chin Wu +1cs.CV cs.AI
Attention-based multiple instance learning (ABMIL) is the predominant approach for slide-level prediction in computational pathology, yet its attention maps provide only local explanations: they indicate where a model focuses but not which histological features drive its predictions or how the model behaves across a patient cohort. We present Semantic Attention Global Explanations (SAGE), a post-hoc framework that extracts global, language-grounded explanations from a frozen ABMIL model. Using a pathology vision-language model, SAGE scores image patches against a dictionary of 25 histological concepts, aggregates these scores according to the model's learned attention, and quantifies how each concept relates to prediction risk across a cohort. Applied to survival prediction using seven TCGA cancer cohorts and three foundation models, SAGE recovered established prognostic features, such as the adverse association of necrosis, while revealing cancer-specific biology, including a favorable angiogenic signature in renal cell carcinoma consistent with known molecular subtypes. Ablation studies demonstrated that these associations depend on the model's learned attention rather than concept prevalence alone, and that the concept dictionary captures much of the prognostic information encoded by the foundation model features. Through semantically-grounded explanations, SAGE provides a scalable, model-agnostic framework for understanding what ABMIL survival models learn, enabling pathologists to interpret model behavior at the cohort level and offering the potential for biomarker identification.
Abdullah Mamun, Shovito Barua Soumma, Hassan Ghasemzadehcs.AI cs.LG
Ensuring trust in AI systems is essential for the safe and ethical integration of machine learning systems into high-stakes domains such as digital health. Key dimensions, including robustness, explainability, fairness, accountability, and privacy, need to be addressed throughout the AI lifecycle, from problem formulation and data collection to model deployment and human interaction. While various contributions address different aspects of trustworthy AI, a focused synthesis on robustness and explainability, especially tailored to the healthcare context, remains limited. This review addresses that need by organizing recent advancements into an accessible framework, highlighting both technical and practical considerations. We present a structured overview of methods, challenges, and solutions, aiming to support researchers and practitioners in developing reliable and explainable AI solutions for digital health. This review article is organized into three main parts. First, we introduce the pillars of trustworthy AI and discuss the technical and ethical challenges, particularly in the context of digital health. Second, we explore application-specific trust considerations across domains such as intensive care, neonatal health, and metabolic health, highlighting how robustness and explainability support trust. Lastly, we present recent advancements in techniques aimed at improving robustness under data scarcity and distributional shifts, as well as explainable AI methods ranging from feature attribution to gradient-based interpretations and counterfactual explanations. This paper is further enriched with detailed discussions of the contributions toward robustness and explainability in digital health, the development of trustworthy AI systems in the era of LLMs, and various evaluation metrics for measuring trust and related parameters such as validity, fidelity, and diversity.
Wearable sensors capture fine-grained motion patterns that support rich behavioral understanding, yet most existing methods reduce these signals to activity labels. Recent LM-based approaches generate natural-language explanations for sensor data, but their reasoning is weakly grounded in the underlying signal, leading to fluent yet unverifiable explanations. We introduce TRACE-TS (Traceable Reasoning with Attribution-Grounded Evidence), a framework for structured and signal-grounded reasoning over wearable time series. TRACE-TS uses attribution from an expert classifier to identify salient spatio-temporal sensor regions, uses them to construct DAG reasoning traces with explicit evidence provenance, and trains a compact language model to generate these traces through gated cross-attention over sensor memory tokens. At inference, the adapted model jointly outputs the activity prediction and its reasoning trace, without requiring attribution computation or teacher guidance. We introduce Semantic Node Match(SNM), an LLM-as-judge metric that diagnoses reasoning fidelity at the observation, inference, and synthesis levels, localizing hallucinated observations and broken evidence chains missed by standard NLG metrics. Across seven wearable benchmarks, TRACE-TS achieves the best average accuracy and F1 among all evaluated methods (84.43%/81.24%), and outperforms the best LLM-based baseline by 17.96% in F1. Our code is available at https://github.com/SparshRastogi/TRACE-TS.
Yizhi Dong, Yuhe Ke, Hairil Rizal Abdullah +4cs.LG
Postoperative adverse events, including mortality and morbidity, remain a major global burden, many of which are preventable through early identification of high-risk patients and targeted perioperative care. Accurate risk stratification is therefore essential. With the growing availability of large-scale electronic health records (EHRs), machine learning (ML) provides a data-driven approach to model complex clinical patterns. However, existing studies vary widely in design, and methodological practices remain fragmented. This scoping review characterizes ML pipelines for surgical risk stratification and outcome prediction using EHR data. We reviewed 190 studies covering the ML workflow, including data preprocessing, algorithm selection, model evaluation, and explainability. Most studies relied on single-center private datasets with limited data modalities, while the scarcity of open-access surgical datasets constrained reproducibility and generalizability. Reporting of key preprocessing steps, including missing data handling, feature selection, and class imbalance, was often incomplete. Conventional ML models and simple neural networks predominated, whereas deep learning and multimodal approaches remained uncommon. Benchmark datasets and standardized evaluation protocols were largely absent, hindering cross-study comparisons. Only about one-third of studies incorporated explainability methods. This review identifies methodological gaps limiting clinically robust postoperative ML tools and provides a structured reference to support more rigorous, reproducible, and clinically meaningful ML development for perioperative care.
Detecting anomalies in longitudinal clinical profiles is clinically important but difficult: abnormal evidence is often sparse, patient histories have unequal length, and expert explanations are costly. We propose INCLAIR, a framework that scores each observation against multiple historical contexts, aggregates evidence at the profile level, and generates grounded natural-language explanations under limited expert supervision. Under stated within-profile exchangeability assumptions, the complete mean subsequence score takes an order-$l$ U-statistic form, yielding a variance decomposition and an incomplete-subset approximation that controls combinatorial inference cost independently of profile length. The same analysis shows that mean aggregation attenuates localized anomalies by a factor set by the anomaly support and profile length, motivating validation-selected top-$k$ pooling. Across three clinical datasets, INCLAIR consistently outperforms state-of-the-art baselines. We further validate practical relevance through a case study on longitudinal steroid profiles, comparing INCLAIR's predictions and explanations against domain-expert assessments supported by DNA analysis. The results show that INCLAIR enables clinically actionable anomaly detection under limited expert supervision.
The Mpox outbreak remains a serious public health issue, with the WHO (World Health Organization) reporting increasing cases in some regions. Research on Mpox is vital for several reasons, including vaccine development, diagnostic improvement, viral evolution studies, and preventing future outbreaks. However, the large amount of research being published makes it difficult to organize and analyze information efficiently. This study focuses on using multilabel classification to categorize 14590 Mpox research articles into key topics such as outbreaks, vaccination, and epidemiology. Among the different AI models tested, BERT performed the best, achieving 97.05% accuracy, 97.67% micro F1 score, and 96.46% macro F1 score. To better understand how the model makes decisions, SHAP was used to analyze significant word features and patterns. The results show that BERT can help automate the classification of Mpox research, making it easier for researchers, policymakers, and healthcare workers to quickly find relevant information, saving time and improving public health efforts.
Krithi Shailya, Ananya Lakshmi Ravi, Venkatanathan K. V. +4cs.CV cs.AI
Computer vision models have become highly effective for medical applications, yet their black-box nature continues to undermine clinician trust. In clinical workflows, chest X-ray classifiers are increasingly paired with Vision-Language Models (VLMs) to generate natural-language explanations. However, these systems add linguistic fluency without addressing the underlying opacity of the visual model. With the emergence of Kolmogorov-Arnold Networks (KANs), whose spline-based components provide inherently interpretable functional units, we investigate whether this architectural transparency can be leveraged to produce more trustworthy textual explanations. We introduce KANEx, the first ever framework that leverages the symbolic transparency of KANs to ground VLM reasoning. This interpretability also made it possible to design KAN-Map, a novel heatmap generation method derived directly from KAN models rather than gradient approximations. We feed these grounded contexts into downstream VLMs for enhanced explainability. Benchmarked on the MIMIC-CXR dataset, we demonstrate that KAN-based architectures with ResNet/ViT baselines demonstrate improved semantic similarity while producing significantly more faithful saliency maps. KAN architectures improve visual localization and downstream reasoning quality by 10%. Our findings suggest that grounding linguistic explanations and visual attributions in mathematically interpretable units is a necessary step toward trustworthy medical AI.
Nils Gumpfer, Michael Guckert, Samuel Sossalla +2cs.CY cs.LG
Explainable AI (XAI) is used to assess whether artificial intelligence models rely on meaningful patterns, yet explanations that appear plausible for individual predictions may systematically misrepresent model behavior. This is particularly problematic in medicine, where models may rely on irrelevant signal characteristics rather than disease-specific patterns without being recognizable. We address this challenge using electrocardiogram (ECG) data, for which clinical guidelines provide explicit knowledge about diagnostically relevant signal regions. We introduce a global, guideline-grounded framework that aggregates explanations across heartbeats to evaluate them against clinically defined regions of interest. Using four binary classifiers trained on PTB-XL, we assess 13 gradient-based methods across two categories of patterns: low-amplitude segments and high-amplitude QRS morphology. Our results reveal a systematic failure of methods transferred from computer vision. Their explanations often follow signal amplitude rather than clinical relevance, with mean Spearman correlations up to 0.69, leading them to overlook diagnostically decisive low-amplitude regions. For ischemia, LRP-$ε$ assigns only 4.6% of relevance to the ST segment, compared with 63.8% for LRP-SIGN. Nine of 13 methods fall below chance for at least one condition, indicating inconsistent reliability across patterns. These findings show that global, domain-grounded evaluation can uncover systematic explanation failures not obvious from sample-level heatmaps.
Acoustic biomarkers show promise for detecting Alzheimer's Disease (AD), yet whether the cues driving diagnostic AI align with those salient to human listeners is underexplored across languages and genders, where pathological markers and perceptual strategies differ. We train models to predict clinical AD status (pathology) and human perceptual scores across Mandarin and Greek, male and female speakers. Using SHAP for interpretability and statistical models for validation, we compare feature importance by subgroup. Results reveal a context-dependent divergence: pathological-perceptual alignment is significant for Mandarin and female speakers but disappears for Greek and male speakers, where pathology models did not exceed chance; this is a failure mode that population-specific auditing surfaces. Global Explainable AI (XAI) explanations can mask critical demographic divergences, highlighting the need for population-specific explainability auditing for equitable deployment of clinical speech AI.
Jakub Rymarski, Adam Rempała, Bartłomiej Sobieski +1cs.CV cs.AI cs.CL
Vision-Language Models (VLMs) are demonstrating significant capabilities in medical tasks like radiology analysis, yet providing faithful and interpretable explanations remains a key consideration for their responsible deployment in clinical settings. However, existing explanation methods, such as the widely used FIxLIP framework, often struggle with the fine-grained nature of modern tokenizers. The tokenization problem fragments clinical concepts---splitting terms like "saddle embolus" into scattered, meaningless subwords---which leads to noisy, semantically incoherent cross-modal attributions. Such fragmentation also results in a combinatorial explosion of interaction possibilities, obscuring the model's true reasoning. To address this, we introduce ParseFIxLIP, an extension that incorporates the Tree-Gram Parsing into the Banzhaf interaction game used by FIxLIP. This semantically informed strategy utilizes dependency parsing trees to define explanation players by grouping related text tokens into semantically coherent units. Our smart_depth grouping strategy, merging tokens according to spaCy token dependency tree, successfully mitigates concept fragmentation, yielding substantially more interpretable cross-modal interactions by unifying complex medical concepts. Quantitatively, while baselines struggled with the high dimensionality of long captions, our parsing approach maintained statistical robustness and semantic parsimony. Qualitative analysis on BiomedCLIP, validated on medical imagery (ROCOv2) and general examples, confirms that the approach accurately captures the synergistic influence of grouped words on model predictions. In conclusion, our work offers intuitive and clinically relevant insights into VLM decision-making, fulfilling the critical need for coherent explanations in the medical domain.
Francesca Pia Panaccione, Carlo Sgaravatti, Marco Venerecs.LG cs.AI cs.CV
Integrating heterogeneous biomedical data, including clinical metadata, histopathology images, and molecular profiles, is crucial for comprehensive disease understanding. However, gene expression data acquisition remains constrained by high costs and privacy concerns, limiting its use in multimodal research and AI-driven applications. We present MultiModal Molecular Generation (M$^3$-Gen), a novel framework for the generation of gene expression profiles by conditioning a Generative Adversarial Network on histopathology images and clinical metadata. M$^3$-Gen learns a unified latent representation from the clinical variables and the images, leveraging contrastive learning, and exploits the embeddings of the two modalities to guide a generative model in producing biologically coherent gene expression profiles. Evaluations on the TCGA dataset demonstrate that M$^3$-Gen generates realistic and functionally meaningful gene expression data. Importantly, by integrating multiple modalities in an attention-based mechanism, M$^3$-Gen provides intrinsic explainability: it allows the identification of which regions of the histopathology images most strongly influenced the generation of specific gene expression profiles, making the model's decisions interpretable by design.
Guillermo Rubiños Rodríguez, Martín Ottavianelli, Mateo Alonso +4quant-ph cs.AI cs.LG
Numerous studies have analyzed the use of hybrid quantum-classical convolutional neural networks as a promising alternative to classical deep learning. However, network components on quantum hardware impose fundamental limitations, while the scalability of quantum circuits leads to trainability issues. In this work, we investigate whether small, classically-emulated quantum circuit components can play a meaningful role within complex models, offering an alternative to purely classical convolutional architectures. To this end, we present a systematic study of the effectiveness of a Hybrid Quantum-inspired Convolutional Neural Network (HQiCNN) compared with a parameter-matched classical Convolutional Neural Network (CNN) that differs only in an intermediate dense neural layer. Both models are evaluated on two real-world medical datasets while systematically varying the different hyperparameters, ensuring a fair model comparison that is both dataset and hyperparameter independent. The results show that no architecture consistently dominates the other: the HQiCNN achieves its largest gains in intermediate-data regimes, whereas the CNN reaches the highest accuracies for the largest training sets in both datasets. Furthermore, removing entanglement produces comparable performance while enabling substantially better scalability of quantum simulations, and richer observable sets become beneficial only when sufficient training data are available. Finally, we propose two SHAP-based explainability tools for comparing the predictions between both models, $|SHAP|$IoU and $EMD_{pos}$ metric, to demonstrate that both architectures consistently attend to anatomically plausible regions. Thus, we provide a comprehensive benchmark showing that, under certain conditions, hybrid quantum-inspired models are an alternative that can offer benefits in practical tasks such as medical image classification.
Automated detection of vision impairing retina-based ocular conditions from fundus images is important for early screening, timely referral and reducing dependency on specialist-only assessment, for which neural network-based deep learning (DL) models have been widely utilized. However, explainability of the DL frameworks remains a major bottleneck for clinical adoption, particularly when model decisions are not linked to retinal regions that are clinically meaningful. To address this issue, this study presents CounterFundus, a novel CycleGAN-driven counterfactual explainability framework, integrating EfficientNet-B5-based retinal disease detection with visually interpretable disease-to-normal fundus image translation. For each pathological image, the counterfactual yielded by the CycleGAN generator represents an estimated healthy counterpart and the resultant difference map is utilized to localize disease-associated retinal changes. Unlike conventional post-hoc saliency methods, CounterFundus provides counterfactual explanations through visually plausible disease-to-normal retinal translation. Thereafter, to quantify the spatial agreement between counterfactual difference maps and classifier saliency, the Counterfactual-Classifier Alignment Score (CCAS) is introduced, embedding Spearman correlation, binary IoU and pointing accuracy into a single assessment protocol. To this end, EigenCAM-aligned evaluation demonstrates that the generated counterfactual explanations remain spatially consistent with classifier-relevant retinal evidence across all CCAS dimensions. Along with that, ablation studies further confirm that CCAS-filtered counterfactual augmentation improves the downstream classification performance in fundus images, establishing CounterFundus as a clinically-grounded, explainable artificially intelligence (XAI) framework for retinal disease detection.
The electrocardiogram (ECG) is a cornerstone of cardiac as- sessment, yet clinical deployment of deep learning models remains con- strained by limited interpretability and the hallucination risk of large language models (LLMs). Existing CNN+Grad-CAM+multimodal LLM frameworks can generate ECG reports, but their explanations are often only weakly grounded in established diagnostic criteria, reducing trust- worthiness and reproducibility. We propose a guide-grounded multimodal framework that explicitly anchors report generation in curated clinical knowledge. A convolutional neural network (CNN) and Grad-CAM first produce class probabilities and class-specific heatmaps from 12-lead ECG images. In parallel, authoritative ECG textbooks and guideline materials are distilled offline into a structured ECG Interpretation Guide, which is injected as a fixed knowledge block for every sample. Conditioned on the ECG image, Grad-CAM overlay, CNN-derived fact pack, and the in- jected guide, a multimodal LLM generates structured diagnostic reports with guideline-consistent terminology and criteria usage. Experiments on the full PTB-XL test set demonstrate that guide grounding improves se- mantic quality and perceived consistency of generated reports while pre- serving competitive classification performance. In particular, our method increases the average BERTScore of generated impressions from 0.818 to 0.953 relative to a strong CNN+Grad-CAM+MLLM baseline, indicat- ing closer alignment with reference reports. These findings suggest that injecting a distilled interpretation guide into the multimodal prompting pipeline offers a practical pathway to reduce hallucinations and enhance the clinical plausibility of LLM-based ECG explanations, bringing ex- plainable cardiac diagnosis closer to real-world deployment.