Expert Systems with Applications

IntroductionBlood glucose monitoring is essential for the management of diabetes mellitus. Continuous interstitial glucose (IG) monitoring systems are less invasive than capillary blood glucose (BG) measurements, but their agreement decreases at higher glucose levels. Artificial intelligence (AI) approaches, particularly recurrent neural networks such as long short-term memory (LSTM), have shown potential to model temporal glucose dynamics and correct inter-method discrepancies. Objective: To develop and validate an AI-based model capable of predicting capillary BG values from IG data, improving agreement between methods and enhancing glycemic status classification. Methods: This retrospective observational study analyzed 708 paired BG-IG measurements obtained from published anonymized datasets. Data preprocessing included Kalman filtering, robust normalization, temporal windowing, and class balancing via oversampling. An LSTM model with dual output was trained to perform both capillary glucose regression and glycemic status classification. Model performance was assessed using regression metrics (MAE, RMSE, R2), classification metrics (accuracy, F1-score), and agreement analysis (Bland-Altman). Results: The AI model substantially reduced the mean bias from +16.27 mg/dL to -2.08 mg/dL and achieved markedly narrower limits of agreement compared with raw BG-IG differences (-129.5 to +162.0 mg/dL vs. -47.3 to +43.2 mg/dL). Glycemic classification accuracy was high for hyperglycemia (94.6%), prediabetes (93.7%) and normoglycemia (100%), with lower performance observed for hypoglycemia (66.7%). Conclusion: LSTM-based AI modeling demonstrated strong capability to predict capillary BG from IG measurements and to correct inter-method discordance. These findings support the potential integration of AI-enhanced glucose estimation into clinical monitoring systems to improve therapeutic decision-making.

Artificial intelligence (AI) based segmentation has many medical applications but limited curated datasets challenge model training; this study compares the impact of dataset annotation quality and quantity on whole liver AI segmentation performance. We obtained 3,089 abdominal computed tomography scans with whole-liver contours from MD Anderson Cancer Center (MDA) and a MICCAI challenge. A total of 249 scans were withheld for testing of which 30, MICCAI challenge data, were reserved for external validation. The remaining scans were divided into mixed-curation and highly-curated groups, randomly sampled into sub-datasets of various sizes, and used to train 3D nnU-Net segmentation models. Dice similarity coefficients (DSC), surface DSC with 2mm margins (SD 2mm), the 95th percentile of Hausdorff distance (HD95), and 2D axial slice DSC (Slice DSC) were used to evaluate model performance. The highly curated, 244-scan model (DSC=0.971, SD 2mm=0.958, HD95=2.98mm) performed insignificantly different on 3D evaluation metrics to the mixed-curation 2,840-scan model (DSC=0.971 [p>.999], SD 2mm=0.958 [p>.999], HD95=2.87mm [p>.999]). The 710-scan mixed-curation (Slice DSC=0.929) significantly outperformed the highly curated, 244-scan model (Slice DSC=0.923 [p=0.012]) on the 30 external scans. Highly curated datasets yielded equivalent performance to datasets that were a full order of magnitude larger. The benefits of larger, mixed-curation datasets are evidenced in model generalizability metrics and local improvements. In conclusion, tradeoffs between dataset quality and quantity for model training are nuanced and goal dependent.

Predicting response to induction chemotherapy (IC) and overall survival (OS) is critical for optimizing treatment in patients with locally advanced nasopharyngeal carcinoma (LANPC). This study aimed to develop and validate a multi-task deep learning model integrating pretreatment MRI and whole slide images (WSIs) to predict IC response and OS in LANPC. Pretreatment MRI and WSIs from 404 patients with LANPC were retrospectively collected to construct a multi-task model (MoEMIL) for the simultaneous prediction of early IC response and OS. MoEMIL employed multi-instance learning to process WSIs, PyRadiomics and a convolutional neural network (ResNet50) to extract MRI features, and fused multimodal features through a multi-gate mixture-of-experts architecture. Clustering-constrained attention multiple instance learning and gradient-weighted class activation mapping were applied for visualization and interpretation. MoEMIL effectively stratified patients into good and poor IC response groups, achieving areas under the curve of 0.917, 0.869, and 0.801 in the train, validation, and test sets, respectively, and outperformed the deep learning radiomics model, the pathomics model and TNM staging. The model also stratified patients into high- and low-risk OS groups (P < 0.05). MoEMIL shows promise as a decision-support tool for early IC response prediction and prognostication in LANPC. Author SummaryWe have developed a deep learning model that integrates two types of medical images, including magnetic resonance imaging (MRI) and digital pathological slices, to simultaneously predict response to induction chemotherapy and prognosis in patients with locally advanced nasopharyngeal carcinoma. Current treatment decisions primarily rely on traditional tumor staging (TNM), which often fails to comprehensively reflect the complexity of the disease. Our model, named MoEMIL, was trained and tested on data from 404 patients across two hospitals and consistently outperformed both single-model approaches and TNM staging methods. By identifying patients who exhibit poor response to induction chemotherapy or higher prognostic risk, our tool can assist clinicians in achieving personalized treatment, enabling intensified management for high-risk patients and avoiding unnecessary side effects for low-risk patients. Additionally, we visualize the models reasoning process through heat map generation, which highlights the image regions exerting the greatest influence on prediction outcomes. This work represents a step toward more precise treatment for nasopharyngeal carcinoma; however, larger-scale prospective studies are required before the model can be integrated into routine clinical practice.

Brain tumors are one of the most life-threatening diseases, requiring precise and timely detection for effective treatment. Traditional methods for brain tumor detection rely heavily on manual analysis of MRI scans, which is time-consuming, subjective, and prone to human error. With advancements in deep learning, Convolutional Neural Networks (CNNs) have become popular for medical image analysis. However, CNNs are limited in their ability to capture spatial hierarchies and pose variations, which reduces their accuracy, particularly for tasks like brain tumor segmentation where precise spatial relationships are crucial. This research introduces a hybrid Capsule Neural Network (CapsNet) and ResNet50 model designed to overcome the limitations of traditional CNNs by capturing both spatial and pose information in MRI scans. The proposed model leverages ResNet50 for feature extraction and CapsNet for handling spatial relationships, leading to more accurate segmentation. The study evaluates the model on the BraTS2020 dataset and compares its performance to state-of-the-art CNN architectures, including U-Net and pure CNN models. The hybrid model, featuring a custom 5-cycle dynamic routing algorithm to enhance capsule agreement for tumor boundaries, achieved 98% accuracy and an F1-score of 0.87, demonstrating superior performance in detecting and segmenting brain tumors. This study pioneers the systematic evaluation of the ResNet50 + CapsNet hybrid on the BraTS2020 dataset, with a tailored class weighting scheme addressing class imbalance, improving effectiveness in identifying irregularly shaped tumors and smaller regions in identifying irregularly shaped tumors and smaller tumor regions. The study offers a robust solution for automating brain tumor detection. Future work will explore the use of Capsule Networks alone for brain tumor detection in MRI data and investigate alternative Capsule Network architectures, as well as their integration into clinical decision support systems.

Evolutionary cancer therapy (ECT) applies principles of evolutionary game theory to prolong the effectiveness of cancer treatment by curbing the development of treatment resistance. It was shown to increase time to progression while decreasing the cumulative drug dose. ECT individually tailors treatment schedules for patients based on their cancer dynamics and, thus, requires regular follow-up and precise measurements of the cancer burden. The current literature on ECT often overlooks clinical realities, such as rather long intervals between tests, possible appointment delays and measurement errors, in the development of the treatment protocols. In this study, we assess the clinical feasibility of ECT for metastatic non-small cell lung cancer (NSCLC). We create virtual patients with cancer dynamics described by the polymorphic Gompertzian model, based on data from the START-TKI clinical trial. We assess the effects of longer test intervals, measurement error and appointment delays on the expected time to progression under the evolutionary therapy protocols. We show that a higher containment level, although it increases time to progression in the models predictions, may lead to premature treatment failure in the presence of measurement error and appointment delay. Further, we show that the ECT protocol with a single containment bound is more robust to the clinical realities than the protocol with two bounds. Finally, we show that a dynamically adjusted treatment protocol can be beneficial for individual patients, but requires a thorough follow-up. This study contributes to the design of a clinical trial and the future clinical implementation of evolutionary therapy for NSCLC.

Bladder cancer presents significant clinical challenges due to its complex immune microenvironment and highly heterogeneous response to treatments. To create accurate, individualized models of disease progression, we first construct a system of Ordinary Differential Equations (ODEs) that captures tumor-immune interactions. We address the challenge of estimating unknown parameters by performing a rigorous comparative analysis of two heuristic optimization methods: Differential Evolution (DE), a robust global optimization algorithm, and Physics-Informed Neural Networks (PINN), a novel machine learning framework that embeds ODE constraints into its loss function. Our findings provide a critical evaluation of the computational efficiency and accuracy of each method for parameterizing biological ODE systems. This study validates the power of hybrid machine learning approaches in mathematical oncology, yielding a data-driven model of bladder cancer progression with direct potential for optimizing personalized treatment strategies. Author summaryBladder cancer remains a major global health threat, characterized by highly unpredictable responses to treatment and a high likelihood of recurrence. To better predict how a patients disease will progress, researchers use mathematical models that simulate the "war" between cancer cells and the immune system. However, these models are only useful if they can be accurately tuned to a specific patients data--a process called parameter estimation. This task is notoriously difficult because clinical data is often sparse and noisy, making it hard to find the right settings for the model. In this study, we developed a novel computational framework that combines a traditional "survival of the fittest" optimization algorithm (Differential Evolution) with Physics-Informed Neural Networks (PINNs), a specialized architecture designed to embed physical constraints directly into the learning process. By "teaching" the AI the underlying biological laws of cancer growth, our hybrid approach can accurately estimate a patients unique disease parameters even when raw data is limited. We validated this method using a "virtual patient" system derived from real-world clinical trials. Our results show that this hybrid approach provides a more robust and reliable way to personalize cancer models, offering a powerful new tool for doctors to simulate and optimize individual treatment plans before they are even administered.

Accessible screening for type 2 diabetes (T2D) is critical, with millions of cases remaining undiagnosed globally. Here, we present the largest known real-world validation study for a speech-based T2D prediction model, trained on speech data from over 21,000 individuals, that works on features extracted from 20-second speech recordings. The model was evaluated in two stages: 1) Against self-reported diagnoses in 7,319 English-speaking participants using AUC, and 2) Against HbA1c blood tests in a subset of 801 participants drawn from the full cohort. Performance was also compared against QDiabetes and in the presence of key confounding variables. The model demonstrated clinically useful predictive capacity on self-reported data (AUC = 0.80 {+/-} 0.03), approaching QDiabetes (AUC = 0.86 {+/-} 0.03). It was robust to most demographic confounds (e.g., age and sex) and medication use, with reduced performance in the presence of comorbidities (e.g., cardiovascular disease and hypertension). At diabetes threshold of HbA1c [&ge;]48 mmol/mol, the model achieved an AUC of 0.75 ({+/-}0.07). This biomarker-validated speech-based tool demonstrates potential to complement existing methods through accessible, scalable screening requiring only a 20-second speech sample.

Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent hepatic condition caused by the buildup of fat in the liver. It is frequently associated with metabolic comorbidities such as hypertension, cardiovascular disease (CVD), and prediabetes. However, early detection remains challenging due to the asymptomatic progression, and existing primary diagnostic methods, such as imaging or liver biopsy, are often expensive and inaccessible in rural areas. This study proposes a two-stage, interpretable machine learning pipeline for the non-invasive and cost-effective prediction of NAFLD and its key comorbidities using routine clinical parameters. The NAFLD prediction model was developed using the XGBoost algorithm, trained on a hybrid dataset that combines real patient data with rule-based synthetic data generated by simulating clinically plausible cases. Upon NAFLD-positive prediction, three separate XGB models, trained on data labelled based on thresholds, assess individual risks for hypertension, cardiovascular disease, and prediabetes. Explainability is obtained using SHAP (SHapley Additive exPlanations), which provides insight into feature relevance, while biomarker radar plots help in the visual interpretation of comorbidities. A user-friendly Streamlit interface enables real-time interaction with the tool for potential clinical application. The NAFLD model demonstrated robust performance, while the models used for predicting comorbidities achieved perfect performance, which may be a reflection of the limited dataset size used in the second stage. This work underscores the potential of AI-driven tools in NAFLD diagnosis, particularly when combined with explainable AI methods.

ObjectiveThis study investigates whether incorporating physiological coupling concepts into neural network design can support stable and interpretable feature learning for histopathological image classification under limited data conditions. MethodsA physiologically inspired architecture, termed CardioPulmoNet, is introduced to model interacting feature streams analogous to pulmonary ventilation and cardiac perfusion. Local and global tissue features are integrated through bidirectional multi-head attention, while a homeostatic regularization term encourages balanced information exchange between streams. The model was evaluated on three histopathological datasets involving oral squamous cell carcinoma, oral submucous fibrosis, and heart failure. In addition to end-to-end training, learned representations were assessed using linear support vector machines to examine feature separability. ResultsCardioPulmoNet achieved performance comparable to several pretrained convolutional neural networks across the evaluated datasets. When combined with a linear classifier, improved classification performance and higher area under the receiver operating characteristic curve were observed, suggesting that the learned feature embeddings are well structured for downstream discrimination. ConclusionThese results indicate that physiologically motivated architectural constraints may contribute to stable and discriminative representation learning in computational pathology, particularly when training data are limited. The proposed framework provides a step toward integrating physiological modeling principles into medical image analysis and may support future development of transferable and interpretable learning systems for histopathological diagnosis.

The present study evaluates the real-world clinical predictive performance of FDA-authorized artificial intelligence (AI) devices used in radiology, focusing on the false positive paradox (FPP) and its implications for clinical practice. To do this, we analyzed publicly available FDA data on AI radiology devices from 2024 and 2025 from 510(k) summaries, demonstrating how diagnostic accuracy metrics like sensitivity and specificity do not necessarily translate into high positive predictive value (PPV) due to the influence of target disease prevalence. We show the importance of disclosing the false discovery (FDR) and false omission rates (FOR) and argue that this transparency enables clinicians to select AI systems that balance false positive and false negative costs in a clinically, ethically, and financially appropriate manner. Finally, we provide recommendations for what data should be provided to best serve practices and radiologists.

Thyroid carcinoma is one of the most prevalent endocrine malignancies worldwide, and accurate preoperative differentiation between benign and malignant thyroid nodules remains clinically challenging. Diagnostic methods that medical practitioners use at present depend on their personal judgment to evaluate both imaging results and separate clinical tests, which creates inconsistency that leads to incorrect medical evaluations. The combination of radiological imaging with clinical information systems enables healthcare providers to enhance their capacity to make reliable predictions about patient outcomes while improving their decision-making abilities. The study introduces a deep learning framework that utilizes multiple data sources by combining magnetic resonance imaging (MRI) data with clinical text to predict thyroid cancer. The system uses a Vision Transformer (ViT) to obtain advanced MRI scan features, while a domain-adapted language model processes clinical documents that contain patient medical history and symptoms and laboratory results. The cross-modal attention system enables the system to merge imaging data with textual information from different sources, which helps to identify how the two types of data are interconnected. The system uses a classification layer to classify the fused features, which allows it to determine the probability of cancerous tumors. The experimental results show that the proposed multimodal system achieves better results than the unimodal base systems because it has higher accuracy, sensitivity, specificity, and AUC values, which help medical personnel to make better preoperative decisions.

PurposeDeep learning models are increasingly being used in medical diagnostics, but their vulnerability to adversarial perturbations raises concerns about their reliability in clinical applications. Capsule networks (CapsNets) are a promising architecture for medical imaging tasks, given their ability to model spatial relationships and train with smaller amounts of data. Although previous studies have focused on adversarial training approaches to improve robustness, exploring alternative architectures is an underexplored direction for combating poor adversarial stability. Prior work has suggested that CapsNets may exhibit improved robustness to adversarial perturbations compared to convolutional neural networks (CNNs), but performance on adversarial images has not been studied systematically in clinical environments. We evaluated the robustness of CapsNets compared to CNNs and vision transformers (ViTs) across multiple medical image classification tasks. MethodsWe trained two CNNs (ResNet-18 and ResNet-50), one ViT (MedViT), and two CapsNets (DR-CapsNet and BP-CapsNet) on four distinct medical imaging datasets (PneumoniaMNIST, BreastMNIST, NoduleMNIST3D, and BloodMNIST) and one natural image dataset (MNIST). Models were evaluated on adversarial examples generated by projected gradient descent and fast gradient sign method across a range of perturbation bounds. Interpretability experiments, including latent space and Gradient-weighted Class Activation Mapping (Grad-CAM) analyses, were conducted to better understand model stability on adversarial inputs. ResultsCapsNets demonstrated superior robustness under adversarial perturbations compared to CNNs and ViTs across all medical imaging datasets and the natural image dataset. Latent space and Grad-CAM visualizations revealed that CapsNets maintained more consistent embedding representations and attention maps after adversarial perturbations compared to CNNs and ViTs, suggesting that advantages in CapsNet robustness are supported, at least in part, by more stable feature encodings. Bayes-Pearson routing further improved robustness over standard dynamic routing in CapsNets without compromising baseline performance, suggesting a potential architectural improvement. ConclusionCapsNets exhibit intrinsic advantages in adversarial robustness over CNN- and ViT-based models on medical imaging tasks, suggesting they are a reliable alternative for medical image classification. These findings support the use of CapsNets in clinical applications where model reliability is critical.

Abstract Objectives: To develop and evaluate a deployable deep learning system with Gradient-weighted Class Activation Mapping (Grad-CAM) for tuberculosis screening from chest radiographs and to assess its classification performance and explainability across desktop and mobile deployment platforms. Materials and methods: This study used publicly available chest X-ray datasets containing Normal and Tuberculosis images. A DenseNet121-based transfer learning model was trained using stratified training, validation, and test splits with data augmentation and class weighting. Model performance was evaluated using accuracy, precision, recall, F1 score, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC). Grad-CAM was used to visualize regions influencing model predictions. The trained model was converted to TensorFlow Lite and deployed in both a Windows desktop application and a Flutter-based mobile application for offline inference and visualization. Results: The model demonstrated strong classification performance on the independent test dataset, with high accuracy and AUC values indicating effective discrimination between Normal and Tuberculosis cases. Grad-CAM visualizations showed that the model focused primarily on anatomically relevant lung regions, particularly the upper and mid-lung fields in Tuberculosis cases. Deployment testing confirmed consistent prediction outputs and Grad-CAM visualizations across both Windows and mobile platforms. Conclusion: The proposed deployable deep learning system with Grad-CAM provides accurate and interpretable tuberculosis screening from chest radiographs and demonstrates feasibility for offline mobile and desktop deployment. This approach has potential as an artificial intelligence-assisted screening and decision support tool in radiology, particularly in resource-limited and remote healthcare settings.

Effective public health planning and intervention strategies necessitate an understanding of the temporal and geographic distribution of disease incidences. This requires robust frameworks for disease incidence forecasting. However, due to variations in cases and temporal dynamics, grasping the distinct patterns of climate-sensitive diseases poses significant challenges, including identifying hotspots, trends, and seasonal variations in disease incidence. Furthermore, although most studies focus on directly predicting future incidence using historical patterns and covariates, a significant gap remains between methodological proliferation marked by diverse architectures, where models are trained and validated on benchmark datasets that are standardized and statistically stable, and epidemiological reality, which is often characterized by irregular, sparse, and highly skewed data, as well as rare but high-magnitude or bimodally distributed incidences. Hence, traditional end-to-end approaches that directly map climate and disease data often fail in these data-scarce settings due to overfitting and poor generalization. To understand disease epidemiology and mitigate the impact of incidence, we analyzed a decade of retrospective datasets in Ethiopia to examine how climate and weather conditions influence the incidence or spread of climate-sensitive diseases, including malaria and dysentery. In this study, we proposed a two-stage hybrid framework, a climate-informed disease prediction model, to forecast the likelihood of disease incidences using decades of climate and weather data. First, deep learning was applied to capture latent weather dynamics. Then, a hurdle model using Extreme Gradient Boosting (XGB) was designed for zero-inflated incidence data, combining XGBClassifier to predict incidence and XGBRegressor to estimate its size, based on weather dynamics to forecast disease incidence. Our proposed multivariate climate-driven disease incidence model incorporates both spatial (elevation, coordinates) and temporal (year, month) factors, along with key weather parameters (precipitation, sunlight, wind, relative humidity, temperature) to predict the likelihood of multiple diseases occurring in each area, serving as a foundation for future disease incidence predictions in the region. Out of 72 evaluated experiments across four categories and six targets, we found that the Transformer model showed highest number of statistically significant wins (n=18, 25.0%) comparison with Long Short-Term Memory (LSTM) (n=9, 12.5%) and the Temporal Convolutional Neural Network (TCN) (n=5, 6.9%) at climate variable forecasting using Pairwise Model Comparison Diebold-Mariano Test. The hurdle model that combines XGBClassifier and XGBRegressor outperformed the baseline in both Malaria and Dysentery forecasting. Error stratification revealed that the hurdle model provided the greatest benefit during incidence periods, as indicated by a substantially lower Mean Average Error (MAE) in both incidence and non-incidence periods than the baseline. Our proposed modular pipeline first forecasts climate variables, then predicts disease incidence, thereby enhancing interpretability and generalization in data-sparse settings. Overall, this approach provides a scalable, climate-aware forecasting tool for public health planning, particularly in regions where these diseases are endemic or where climate change may affect their prevalence, as well as in data-scarce settings.

This research presents multimodal deep learning for structural heart disease prediction. We evaluated multiple deep learning architectures, including TCN, Simple CNN, ResNet1d18, Light transformer and Hybrid model. The models were examined across the three seeds to ensure robustness, and bootstrap confidence interval is used to measure performance differences. TCN consistently outperforms other competing architectures, achieving statistically significant improvements with stable performance across runs. Similarly in predictive analysis, TCN has efficient computation and stable training compared to all competing architectures. Our results show that TCN emphasizes fairness evaluation when developing deep learning models for healthcare applications.

Deep learning model classification on large datasets is often limited in countries with restricted computational resources. While transfer learning can offset these limitations, standard architectures often maintain a high memory footprint. This study introduces HybridNet-XR, a memory-efficient and computationally lightweight hybrid convolutional neural network (CNN) designed to bridge the domain gap in medical radiography using autonomous self-supervised learning protocols. The HybridNet-XR architecture integrates depthwise separable convolutions for parameter reduction, residual connections for gradient stability, and aggressive early downsampling to minimize the video RAM (VRAM) footprint. We evaluated several training paradigms, including teacher-free self-supervised learning (SSL-SimCLR), teacher-led knowledge distillation (KD), and domain-gap (DG) adaptation. Each variant was pre-trained on ImageNet-1k subsets and fine-tuned on the ChestX6 multi-class dataset. Model interpretability was validated through gradient-weighted class activation mapping (Grad-CAM). The performance frontier analysis identified the HybridNet-XR-150-PW (Pre-warmed) as the optimal configuration, achieving a 93.38% average accuracy and 99% AUC while utilizing only 814.80 MB of VRAM. Regarding class-wise accuracy, this variant significantly outperformed standard MobileNetV2 and teacher-led models in critical diagnostic categories, notably Covid-19 (97.98%) and Emphysema (96.80%). Grad-CAM visualizations confirmed that the teacher-free pre-warming phase allows the model to develop sharper, anatomically grounded focus on pathological landmarks compared to distilled models. Specialized pre-warming schedules offer a viable, computationally autonomous alternative to knowledge distillation for medical imaging. By eliminating the requirement for high-performance teacher models, HybridNet-XR provides a robust and trustworthy diagnostic foundation suitable for clinical deployment in resource-constrained environments. Author summaryTraditional deep learning models for medical imaging are often too large for the low-power computers available in many global health settings. We developed a new model to bridge this computational gap. We designed HybridNet-XR, a highly efficient AI architecture, and trained it using a "teacher-free" method that doesnt require a massive supercomputer. We found a specific version (H-XR150-PW) that provides high accuracy while using very little memory. Our results show that high-performance diagnostic AI can be deployed on standard, low-cost hardware. Furthermore, using visual heatmaps (Grad-CAM), we proved that the AI correctly identifies medical landmarks like lung opacities, ensuring it is safe and reliable for real-world clinical use.

Access to positron emission tomography (PET) remains limited in rural and low-resource healthcare settings due to high infrastructure cost and radiotracer logistics. This restricts early oncologic screening in underserved populations. The study proposes a rural-optimized conditional diffusion framework for synthetic PET generation directly from widely available CT scans. The architecture employs a two-stage residual design consisting of a lightweight coarse predictor followed by computationally efficient diffusion refinement with reduced timesteps and deterministic sampling. A multi-objective SUV-aware loss ensures metabolic consistency. To emulate rural deployment conditions, this study simulates low-dose noise, Hounsfield unit miscalibration, and resolution degradation. Clinical validation demonstrates strong structural fidelity (SSIM 0.81) and stable SUVmean preservation. Domain-matched training achieves SUVmax error as low as 0.61. Cross-dataset analysis highlights the importance of SUV harmonization for robust rural deployment. This work presents a resource-sensitive AI frame-work supporting equitable oncology screening in rural healthcare systems. HighlightsO_LITwo-stage residual conditional diffusion for CT-to-PET translation. C_LIO_LISUV-aware multi-objective optimization preserves metabolic biomarkers. C_LIO_LIFew-shot adaptation improves cross-dataset SUV calibration. C_LI

The opioid crisis has severely impacted Ohio, with overdose death rates surpassing national averages and disproportionately affecting rural and Appalachian regions. Accurately predicting county-level opioid overdose deaths (OD) is critical for timely intervention but remains challenging due to the wide differences in opioid OD between large and small counties. We propose a Spatial-Temporal Graph Neural Network (ST-GNN) framework that integrates graph neural networks (GNNs) to capture spatial relationships between counties and Long Short-Term Memory (LSTM) networks to model temporal dynamics. Using quarterly OD data from Q1 2017 to Q2 2023 for 88 Ohio counties, we incorporate a nine-dimensional dynamic feature set, including naloxone administration events and high-risk opioid prescribing, along with a static Social Determinants of Health (SDoH) index. Compared to traditional statistical models and temporal deep learning baselines, our ST-GNN demonstrates superior performance, particularly in larger counties, while classification-based strategy improve predictions for small counties, leading to more stable and reliable results. Our findings emphasize the need for spatial-temporal modeling and customized training to enhance public health decision-making in addressing the opioid crisis.

Targeted drug therapies offer a promising approach for treating complex diseases, with combinational drug therapies often employed to enhance therapeutic efficacy. However, unintended drug-drug interactions may undermine treatment outcomes or cause adverse side effects. In this work, we propose a novel joint learning framework for the simultaneous prediction of effective drug combinations and drug-drug interactions, based on coupled tensor-tensor factorization. Specifically, we model drug combination therapies and DDI by representing drug-drug-disease associations and drug-drug interaction profiles as coupled three-way tensors. To address the challenges of data incompleteness and sparsity, the proposed model integrates auxiliary drug similarity information, such as chemical structure similarities, drug-specific side effects, drug target profiles, and drug inhibition data on cancer cell lines, within a multi-view learning frame-work. For optimization, we adopt a modified Alternating Direction Method of Multipliers (ADMM) algorithm that ensures convergence while enforcing non-negativity constraints. In addition to standard tensor completion tasks, we further evaluate the proposed method under a more realistic new-drug prediction setting, where all interactions involving a previously unseen drug are withheld. This scenario closely aligns with real-world applications, in which reliable predictions for emerging or under-studied compounds are essential. We evaluate the proposed method on a comprehensive dataset compiled from multiple sources, including DrugBank, CDCDB, SIDER, and PubChem. Our experiments show that SI-ADMM maintains robust performance and achieves the best results comparing to other tensor factorization approaches, with or without auxiliary information, particularly in the new-drug prediction setting. The implementation of our method is publicly available at: https://github.com/Xiaoge-Zhang/SI-ADMM.

The practices of identifying biomarkers and developing prognostic models using genomic data has become increasingly prevalent. Such data often features characteristics that make these practices difficult, namely high dimensionality, correlations between predictors, and sparsity. Many modern methods have been developed to address these problematic characteristics while performing feature selection and prognostic modeling, but a large-scale comparison of their performances in these tasks on diverse right-censored time to event data (aka survival time data) is much needed. We have compiled many existing methods, including some machine learning methods, several which have performed well in previous benchmarks, primarily for comparison in regards to variable selection capability, and secondarily for survival time prediction on many synthetic datasets with varying levels of sparsity, correlation between predictors, and signal strength of informative predictors. For illustration, we have also performed multiple analyses on a publicly available and widely used cancer cohort from The Cancer Genome Atlas using these methods. We evaluated the methods through extensive simulation studies in terms of the false discovery rate, F1-score, concordance index, Brier score, root mean square error, and computation time. Of the methods compared, CoxBoost and the Adaptive LASSO performed well in all metrics, and the LASSO and elastic net excelled when evaluating concordance index and F1-score. The Benjamini-Hoschberg and q-value procedures showed volatile performances in controlling the false discovery rate. Some methods performances were greatly affected by differences in the data characteristics. With our extensive numerical study, we have identified the best performing methods for a plethora of data characteristics using informative metrics. This will help cancer researchers in choosing the best approach for their needs when working with genomic data.