Hairong Wang

Xuan Wang, Zhongling Xu, Gopi Kannedhara et al.

Healthcare models are transitioning from unimodal prediction toward multimodal reasoning over heterogeneous diagnostic inputs. In computational pathology, for complex tumor subtypes where morphology alone can be challenging to distinguish, pathology reports and molecular measurements may provide additional diagnostic evidence alongside whole-slide images, yet existing models often fail to clarify how diverse signals assemble into recognizable diagnostic concepts. We propose ConceptM$^3$oE (Concept Multimodal MoE), which embeds concept formation directly within interaction-aware mixture-of-experts (MoE) pathways. The architecture decomposes evidence into modality-specific, redundant, and synergistic experts, which are then projected into structured concept bottlenecks mapping latent features to a hierarchy of morphology and biomarker concepts. To prevent the information loss typical of interpretable bottlenecks, we utilize residual pathways within each expert to allow task-relevant signals to flow both through the concepts and directly to the final task prediction, so that high performance is maintained alongside interpretability. Across an institutional pediatric brain tumor cohort and a public glioma cohort, the framework delivers competitive performance to unconstrained models while producing reasoning traces validated by an independent neuropathologist. In data-limited regimes, ConceptM$^3$oE improves limited-data performance, increasing macro-F1 from 56.41% to 66.70% at small training sizes compared to non-concept-informed baselines, while also showing faster training convergence consistent with the regularizing effect of concept learning. This work offers a scalable path toward high-performance medical AI that is inherently verifiable and better aligned with the complex decision-making of clinical practice.

Joakim Nguyen, Jian Yu, Jinrui Fang et al.

Accurate diagnosis of pediatric brain tumors, starting with histopathology, presents unique challenges for deep learning, including severe data scarcity, class imbalance, and fine-grained morphologic overlap across diagnostically distinct subtypes. While pathology foundation models have advanced patch-level representation learning, their effective adaptation to weakly supervised pediatric brain tumor classification under limited data remains underexplored. In this work, we introduce an expert-guided contrastive fine-tuning framework for pediatric brain tumor diagnosis from whole-slide images (WSI). Our approach integrates contrastive learning into slide-level multiple instance learning (MIL) to explicitly regularize the geometry of slide-level representations during downstream fine-tuning. We propose both a general supervised contrastive setting and an expert-guided variant that incorporates clinically informed hard negatives targeting diagnostically confusable subtypes. Through comprehensive experiments on pediatric brain tumor WSI classification under realistic low-sample and class-imbalanced conditions, we demonstrate that contrastive fine-tuning yields measurable improvements in fine-grained diagnostic distinctions. Our experimental analyses reveal complementary strengths across different contrastive strategies, with expert-guided hard negatives promoting more compact intra-class representations and improved inter-class separation. This work highlights the importance of explicitly shaping slide-level representations for robust fine-grained classification in data-scarce pediatric pathology settings.

Mufhumudzi Muthivhi, Terence L. van Zyl, Hairong Wang

Context-aware recommendation systems improve upon classical recommender systems by including, in the modelling, a user's behaviour. Research into context-aware recommendation systems has previously only considered the sequential ordering of items as contextual information. However, there is a wealth of unexploited additional multi-modal information available in auxiliary knowledge related to items. This study extends the existing research by evaluating a multi-modal recommendation system that exploits the inclusion of comprehensive auxiliary knowledge related to an item. The empirical results explore extracting vector representations (embeddings) from unstructured and structured data using data2vec. The fused embeddings are then used to train several state-of-the-art transformer architectures for sequential user-item representations. The analysis of the experimental results shows a statistically significant improvement in prediction accuracy, which confirms the effectiveness of including auxiliary information in a context-aware recommendation system. We report a 4% and 11% increase in the NDCG score for long and short user sequence datasets, respectively.

Hairong Wang, Lingchao Mao, Zihan Zhang et al.

Liver cancer is a leading cause of mortality worldwide, and accurate Computed Tomography (CT)-based tumor segmentation is essential for diagnosis and treatment. Manual delineation is time-intensive, prone to variability, and highlights the need for reliable automation. While deep learning has shown promise for automated liver segmentation, precise liver tumor segmentation remains challenging due to the heterogeneous nature of tumors, imprecise tumor margins, and limited labeled data. We present SmoothSegNet, a novel deep learning framework that addresses these challenges with the three key designs: (1) A novel knowledge-informed label smoothing technique that distills knowledge from clinical data to generate smooth labels, which are used to regularize model training, reducing the overfitting risk and enhancing model performance; (2) A global and local segmentation framework that breaks down the main task into two simpler sub-tasks, allowing optimized preprocessing and training for each; and (3) Pre- and post-processing pipelines customized to the challenges of each subtask aimed to enhance tumor visibility and refines tumor boundaries. We apply the proposed model on a challenging HCC-TACE-Seg dataset and show that SmoothSegNet outperformed various benchmarks in segmentation performance, particularly at smaller tumors (<10cm). Our ablation studies show that the three design components complementarily contribute to the model improved performance. Code for the proposed method are available at https://github.com/lingchm/medassist-liver-cancer.

Jingyu Li, Lingchao Mao, Hairong Wang et al.

Background: Alzheimer's disease and related dementias (ADRD) are progressive neurodegenerative conditions where early detection is vital for timely intervention and care. Spontaneous speech contains rich acoustic and linguistic markers that may serve as non-invasive biomarkers for cognitive decline. Foundation models, pre-trained on large-scale audio or text data, produce high-dimensional embeddings encoding contextual and acoustic features. Methods: We used the PREPARE Challenge dataset, which includes audio recordings from over 1,600 participants with three cognitive statuses: healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's Disease (AD). We excluded non-English, non-spontaneous, or poor-quality recordings. The final dataset included 703 (59.13%) HC, 81 (6.81%) MCI, and 405 (34.06%) AD cases. We benchmarked a range of open-source foundation speech and language models to classify cognitive status into the three categories. Results: The Whisper-medium model achieved the highest performance among speech models (accuracy = 0.731, AUC = 0.802). Among language models, BERT with pause annotation performed best (accuracy = 0.662, AUC = 0.744). ADRD detection using state-of-the-art automatic speech recognition (ASR) model-generated audio embeddings outperformed others. Including non-semantic features like pause patterns consistently improved text-based classification. Conclusion: This study introduces a benchmarking framework using foundation models and a clinically relevant dataset. Acoustic-based approaches -- particularly ASR-derived embeddings -- demonstrate strong potential for scalable, non-invasive, and cost-effective early detection of ADRD.

Licheng Xiao, Hairong Wang, Nam Ling

In this paper, we build autoencoder based pipelines for extreme end-to-end image compression based on Ballé's approach, which is the state-of-the-art open source implementation in image compression using deep learning. We deepened the network by adding one more hidden layer before each strided convolutional layer with exactly the same number of down-samplings and up-samplings. Our approach outperformed Ballé's approach, and achieved around 4.0% reduction in bits per pixel (bpp), 0.03% increase in multi-scale structural similarity (MS-SSIM), and only 0.47% decrease in peak signal-to-noise ratio (PSNR), It also outperforms all traditional image compression methods including JPEG2000 and HEIC by at least 20% in terms of compression efficiency at similar reconstruction image quality. Regarding encoding and decoding time, our approach takes similar amount of time compared with traditional methods with the support of GPU, which means it's almost ready for industrial applications.

Joshua Bruton, Hairong Wang

The effective receptive field of a fully convolutional neural network is an important consideration when designing an architecture, as it defines the portion of the input visible to each convolutional kernel. We propose a neural network module, extending traditional skip connections, called the translated skip connection. Translated skip connections geometrically increase the receptive field of an architecture with negligible impact on both the size of the parameter space and computational complexity. By embedding translated skip connections into a benchmark architecture, we demonstrate that our module matches or outperforms four other approaches to expanding the effective receptive fields of fully convolutional neural networks. We confirm this result across five contemporary image segmentation datasets from disparate domains, including the detection of COVID-19 infection, segmentation of aerial imagery, common object segmentation, and segmentation for self-driving cars.

Jian Yu, Joakim Nguyen, Jinrui Fang et al.

Accurate classification of pediatric central nervous system tumors remains challenging due to histological complexity and limited training data. While pathology foundation models have advanced whole-slide image (WSI) analysis, they often fail to leverage the rich, complementary information found in clinical text and tissue microarchitecture. To this end, we propose PathMoE, an interpretable multimodal framework that integrates H\&E slides, pathology reports, and nuclei-level cell graphs via an interaction-aware mixture-of-experts architecture built on state-of-the-art foundation models for each modality. By training specialized experts to capture modality uniqueness, redundancy, and synergy, PathMoE employs an input-dependent gating mechanism that dynamically weights these interactions, providing sample-level interpretability. We evaluate our framework on two dataset-specific classification tasks on an internal pediatric brain tumor dataset (PBT) and external TCGA datasets. PathMoE improves macro-F1 from 0.762 to 0.799 (+0.037) on PBT when integrating WSI, text, and graph modalities; on TCGA, augmenting WSI with graph knowledge improves macro-F1 from 0.668 to 0.709 (+0.041). These results demonstrate significant performance gains over state-of-the-art image-only baselines while revealing the specific modality interactions driving individual predictions. This interpretability is particularly critical for rare tumor subtypes, where transparent model reasoning is essential for clinical trust and diagnostic validation.

Mufhumudzi Muthivhi, Terence L van Zyl, Hairong Wang

Sequential recommendation models aim to learn from users evolving preferences. However, current state-of-the-art models suffer from an inherent popularity bias. This study developed a novel framework, BiCoRec, that adaptively accommodates users changing preferences for popular and niche items. Our approach leverages a co-attention mechanism to obtain a popularity-weighted user sequence representation, facilitating more accurate predictions. We then present a new training scheme that learns from future preferences using a consistency loss function. BiCoRec aimed to improve the recommendation performance of users who preferred niche items. For these users, BiCoRec achieves a 26.00% average improvement in NDCG@10 over state-of-the-art baselines. When ranking the relevant item against the entire collection, BiCoRec achieves NDCG@10 scores of 0.0102, 0.0047, 0.0021, and 0.0005 for the Movies, Fashion, Games and Music datasets.

Lingchao Mao, Hairong Wang, Leland S. Hu et al.

Cancer remains one of the most challenging diseases to treat in the medical field. Machine learning has enabled in-depth analysis of rich multi-omics profiles and medical imaging for cancer diagnosis and prognosis. Despite these advancements, machine learning models face challenges stemming from limited labeled sample sizes, the intricate interplay of high-dimensionality data types, the inherent heterogeneity observed among patients and within tumors, and concerns about interpretability and consistency with existing biomedical knowledge. One approach to surmount these challenges is to integrate biomedical knowledge into data-driven models, which has proven potential to improve the accuracy, robustness, and interpretability of model results. Here, we review the state-of-the-art machine learning studies that adopted the fusion of biomedical knowledge and data, termed knowledge-informed machine learning, for cancer diagnosis and prognosis. Emphasizing the properties inherent in four primary data types including clinical, imaging, molecular, and treatment data, we highlight modeling considerations relevant to these contexts. We provide an overview of diverse forms of knowledge representation and current strategies of knowledge integration into machine learning pipelines with concrete examples. We conclude the review article by discussing future directions to advance cancer research through knowledge-informed machine learning.

Lujia Wang, Hairong Wang, Fulvio D'Angelo et al.

Glioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcomes. We proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA, and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. The classification accuracy of each gene was compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity. This study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.

Lujia Wang, Hairong Wang, Yi Su et al.

Ordinal learning (OL) is a type of machine learning models with broad utility in health care applications such as diagnosis of different grades of a disease (e.g., mild, modest, severe) and prediction of the speed of disease progression (e.g., very fast, fast, moderate, slow). This paper aims to tackle a situation when precisely labeled samples are limited in the training set due to cost or availability constraints, whereas there could be an abundance of samples with imprecise labels. We focus on imprecise labels that are intervals, i.e., one can know that a sample belongs to an interval of labels but cannot know which unique label it has. This situation is quite common in health care datasets due to limitations of the diagnostic instrument, sparse clinical visits, or/and patient dropout. Limited research has been done to develop OL models with imprecise/interval labels. We propose a new Hybrid Ordinal Learner (HOL) to integrate samples with both precise and interval labels to train a robust OL model. We also develop a tractable and efficient optimization algorithm to solve the HOL formulation. We compare HOL with several recently developed OL methods on four benchmarking datasets, which demonstrate the superior performance of HOL. Finally, we apply HOL to a real-world dataset for predicting the speed of progressing to Alzheimer's Disease (AD) for individuals with Mild Cognitive Impairment (MCI) based on a combination of multi-modality neuroimaging and demographic/clinical datasets. HOL achieves high accuracy in the prediction and outperforms existing methods. The capability of accurately predicting the speed of progression to AD for each individual with MCI has the potential for helping facilitate more individually-optimized interventional strategies.

John M. Statheros, Hairong Wang, Richard Klein

The interpretation of chest X-rays (CXRs) poses significant challenges, particularly in achieving accurate multi-label pathology classification and spatial localization. These tasks demand different levels of annotation granularity but are frequently constrained by the scarcity of region-level (dense) annotations. We introduce CLARiTy (Class Localizing and Attention Refining Image Transformer), a vision transformer-based model for joint multi-label classification and weakly-supervised localization of thoracic pathologies. CLARiTy employs multiple class-specific tokens to generate discriminative attention maps, and a SegmentCAM module for foreground segmentation and background suppression using explicit anatomical priors. Trained on image-level labels from the NIH ChestX-ray14 dataset, it leverages distillation from a ConvNeXtV2 teacher for efficiency. Evaluated on the official NIH split, the CLARiTy-S-16-512 (a configuration of CLARiTy), achieves competitive classification performance across 14 pathologies, and state-of-the-art weakly-supervised localization performance on 8 pathologies, outperforming prior methods by 50.7%. In particular, pronounced gains occur for small pathologies like nodules and masses. The lower-resolution variant of CLARiTy, CLARiTy-S-16-224, offers high efficiency while decisively surpassing baselines, thereby having the potential for use in low-resource settings. An ablation study confirms contributions of SegmentCAM, DINO pretraining, orthogonal class token loss, and attention pooling. CLARiTy advances beyond CNN-ViT hybrids by harnessing ViT self-attention for global context and class-specific localization, refined through convolutional background suppression for precise, noise-reduced heatmaps.

Min Gu Kwak, Yeonju Lee, Hairong Wang et al.

Brain tumors are among the most clinically significant neurological diseases and remain a major cause of morbidity and mortality due to their aggressive growth and structural heterogeneity. As tumors expand, they induce substantial anatomical deformation that disrupts both local tissue organization and global brain architecture, complicating diagnosis, treatment planning, and surgical navigation. Yet a subject-specific reference of how the brain would appear without tumor-induced changes is fundamentally unobtainable in clinical practice. We present BrainNormalizer, an anatomy-informed diffusion framework that reconstructs pseudo-healthy MRIs directly from tumorous scans by conditioning the generative process on boundary cues extracted from the subject's own anatomy. This boundary-guided conditioning enables anatomically plausible pseudo-healthy reconstruction without requiring paired non-tumorous and tumorous scans. BrainNormalizer employs a two-stage training strategy. The pretrained diffusion model is first adapted through inpainting-based fine-tuning on tumorous and non-tumorous scans. Next, an edge-map-guided ControlNet branch is trained to inject fine-grained anatomical contours into the frozen decoder while preserving learned priors. During inference, a deliberate misalignment strategy pairs tumorous inputs with non-tumorous prompts and mirrored contralateral edge maps, leveraging hemispheric correspondence to guide reconstruction. On the BraTS2020 dataset, BrainNormalizer achieves strong quantitative performance and qualitatively produces anatomically plausible reconstructions in tumor-affected regions while retaining overall structural coherence. BrainNormalizer provides clinically reliable anatomical references for treatment planning and supports new research directions in counterfactual modeling and tumor-induced deformation analysis.

Xi Mao, Zhendong Wang, Jingyu Li et al.

Early detection of Alzheimer's disease (AD) is crucial because its neurodegenerative effects are irreversible, and neuropathologic and social-behavioral risk factors accumulate years before diagnosis. Identifying higher-risk individuals earlier enables prevention, timely care, and equitable resource allocation. We predict cognitive performance from social determinants of health (SDOH) using the NIH NIA-supported PREPARE Challenge Phase 2 dataset derived from the nationally representative Mex-Cog cohort of the 2003 and 2012 Mexican Health and Aging Study (MHAS). Data: The target is a validated composite cognitive score across seven domains-orientation, memory, attention, language, constructional praxis, and executive function-derived from the 2016 and 2021 MHAS waves. Predictors span demographic, socioeconomic, health, lifestyle, psychosocial, and healthcare access factors. Methodology: Missingness was addressed with a singular value decomposition (SVD)-based imputation pipeline treating continuous and categorical variables separately. This approach leverages latent feature correlations to recover missing values while balancing reliability and scalability. After evaluating multiple methods, XGBoost was chosen for its superior predictive performance. Results and Discussion: The framework outperformed existing methods and the data challenge leaderboard, demonstrating high accuracy, robustness, and interpretability. SHAP-based post hoc analysis identified top contributing SDOH factors and age-specific feature patterns. Notably, flooring material emerged as a strong predictor, reflecting socioeconomic and environmental disparities. Other influential factors, age, SES, lifestyle, social interaction, sleep, stress, and BMI, underscore the multifactorial nature of cognitive aging and the value of interpretable, data-driven SDOH modeling.

Joshua Bruton, Hairong Wang

Dictionary learning and sparse coding have been widely studied as mechanisms for unsupervised feature learning. Unsupervised learning could bring enormous benefit to the processing of hyperspectral images and to other remote sensing data analysis because labelled data are often scarce in this field. We propose a method for clustering the pixels of hyperspectral images using sparse coefficients computed from a representative dictionary as features. We show empirically that the proposed method works more effectively than clustering on the original pixels. We also demonstrate that our approach, in certain circumstances, outperforms the clustering results of features extracted using principal component analysis and non-negative matrix factorisation. Furthermore, our method is suitable for applications in repetitively clustering an ever-growing amount of high-dimensional data, which is the case when working with hyperspectral satellite imagery.