BioMedInformatics

Background: Quantum machine learning (QML) holds significant promise for advancing medical image classification. However, its practical application to large-scale, high-resolution datasets is constrained by the limited number of qubits and the inherent noise in current quantum hardware. Methods: In this study, we propose the Fused Quantum Dual-Backbone Network (FQDN), a novel hybrid architecture that integrates classical convolutional neural networks (CNNs) with quantum circuits. This design is optimized for the noisy intermediate-scale quantum (NISQ), enabling efficient computation despite hardware limitations. We evaluate FQDN on the task of gastrointestinal (GI) disease classification using wireless capsule endoscopy (WCE) images. Results: The proposed model achieves a substantial reduction in parameter complexity, with a 29.04% decrease in total parameters and a 94.44% reduction in trainable parameters, while outperforming its classical counterpart. FQDN achieves an accuracy of 95.80% on the validation set and 95.42% on the test set. Conclusions: These results demonstrate the potential of QML to enhance diagnostic accuracy in medical imaging. Full article

Background: Virtual coaching can help people adopt new healthful behaviors by encouraging them to set specific goals and helping them review their progress. One challenge in creating such systems is analyzing clients’ statements about their activities. Limiting people to selecting among predefined answers detracts from the naturalness of conversations and user engagement. Large Language Models (LLMs) offer the promise of covering a wide range of expressions. However, using an LLM for simple entity extraction would not necessarily perform better than functions coded in a programming language, while creating higher long-term costs. Methods: This study uses a real data set of annotated human coaching dialogs to develop LLM-based models for two training scenarios: one that generates pattern-matching functions and the other which does direct extraction. We use models of different sizes and complexity, including Meta-Llama, Gemma, and ChatGPT, and calculate their speed and accuracy. Results: LLM-generated pattern-matching functions took an average of 10 milliseconds (ms) per item as compared to 900 ms. (ChatGPT 3.5 Turbo) to 5 s (Llama 2 70B). The accuracy for pattern matching was 99% on real data, while LLM accuracy ranged from 90% (Llama 2 70B) to 100% (ChatGPT 3.5 Turbo), on both real and synthetically generated examples created for fine-tuning. Conclusions: These findings suggest promising directions for future research that combines both methods (reserving the LLM for cases that cannot be matched directly) or that use LLMs to generate synthetic training data with more expressive variety which can be used to improve the coverage of either generated codes or fine-tuned models. Full article

Background/Objectives: Dementia is a leading cause of cognitive decline, with significant challenges for early detection and timely intervention. The lack of effective, user-centred technologies further limits clinical response, particularly in underserved areas. This study aimed to develop and describe a co-design process for creating a Diagnostic and Statistical Manual of Mental Disorders (DSM-5)-compliant, AI-powered Smart Assistant (SmartApp) to monitor neurocognitive decline, while ensuring accessibility, clinical relevance, and responsible AI integration. Methods: A co-design framework was applied using a novel combination of Agile principles and the Double Diamond Model (DDM). More than twenty iterative Scrum sprints were conducted, involving key stakeholders such as clinicians (psychiatrist, psychologist, physician), designers, students, and academic researchers. Prototype testing and design workshops were organised to gather structured feedback. Feedback was systematically incorporated into subsequent iterations to refine functionality, usability, and clinical applicability. Results: The iterative process resulted in a SmartApp that integrates a DSM-5-based screening tool with 24 items across key cognitive domains. Key features include longitudinal tracking of cognitive performance, comparative visual graphs, predictive analytics using a regression-based machine learning module, and adaptive user interfaces. Workshop participants reported high satisfaction with features such as simplified navigation, notification reminders, and clinician-focused reporting modules. Conclusions: The findings suggest that combining co-design methods with Agile/DDM frameworks provides an effective pathway for developing AI-powered clinical tools as per responsible AI standards. The SmartApp offers a clinically relevant, user-friendly platform for dementia screening and monitoring, with potential to support vulnerable populations through scalable, responsible digital health solutions. Full article

Virtual-reality exposure therapy (VRET) is an emerging treatment for psychiatric disorders that enables immersive and controlled exposure to anxiety-provoking stimuli. Recent developments integrate real-time physiological monitoring, including heart rate (HR), electrodermal activity (EDA), and electroencephalography (EEG), to dynamically tailor therapeutic interventions. This systematic review examines studies that combine VRET with physiological data to adapt virtual environments in real time. A comprehensive search of major databases identified fifteen studies meeting the inclusion criteria: all employed physiological monitoring and adaptive features, with ten using biofeedback to modulate exposure based on single or multimodal physiological measures. The remaining studies leveraged physiological signals to inform scenario selection or threat modulation using dynamic categorization algorithms and machine learning. Although findings currently show an overrepresentation of anxiety disorders, recent studies are increasingly involving more diverse clinical populations. Results suggest that adaptive VRET is technically feasible and offers promising personalization benefits; however, the limited number of studies, methodological variability, and small sample sizes constrain broader conclusions. Future research should prioritize rigorous experimental designs, standardized outcome measures, and greater diversity in clinical populations. Adaptive VRET represents a frontier in precision psychiatry, where real-time biosensing and immersive technologies converge to enhance individualized mental health care. Full article

Background: Human Metapneumovirus (HMPV) is a respiratory virus in the Pneumoviridae family. HMPV is an enveloped, negative-sense RNA virus encoding three surface proteins: SH, G, and F. The highly immunogenic fusion (F) protein is essential for viral entry and a key target for vaccine development. The F protein exists in two conformations: prefusion and postfusion. The prefusion form is highly immunogenic and considered a potent vaccine antigen. However, this conformation needs to be stabilized to improve its immunogenicity for effective vaccine development. Specific mutations are necessary to maintain the prefusion state and prevent it from changing to the postfusion form. Methods: In silico mutagenesis was performed on the C-terminal domain of the pre-F protein, focusing on five amino acids at positions 469 to 473 (LVDQS), using the established pre-F structure (PDB: 8W3Q) as the reference. The amino acid sequence was sequentially mutated based on hydrophobicity, resulting in mutants M1 (IIFLL), M2 (LLIVL), M3 (WWVLL), and M4 (YMWLL). Increasing hydrophobicity was found to enhance protein stability and structural rigidity. Results: Epitope mapping revealed that all mutants displayed significant B and T cell epitopes similar to the reference protein. The structure and stability of all mutants were analyzed using molecular dynamics simulations, free energy calculations, and secondary structure analysis. Based on the lowest RMSD, clash score, MolProbity value, stable radius of gyration, and low RMSF, the M1 mutant demonstrated superior structural stability. Conclusions: Our findings indicate that the M1 mutant of the pre-F protein could be the most stable and structurally accurate candidate for vaccine development against HMPV. Full article

Breast cancer remains a critical global health challenge, with over 2.1 million new cases annually. This review systematically evaluates recent advancements (2022–2024) in machine and deep learning approaches for breast cancer detection and risk management. Our analysis demonstrates that deep learning models achieve 90–99% accuracy across imaging modalities, with convolutional neural networks showing particular promise in mammography (99.96% accuracy) and ultrasound (100% accuracy) applications. Tabular data models using XGBoost achieve comparable performance (99.12% accuracy) for risk prediction. The study confirms that lifestyle modifications (dietary changes, BMI management, and alcohol reduction) significantly mitigate breast cancer risk. Key findings include the following: (1) hybrid models combining imaging and clinical data enhance early detection, (2) thermal imaging achieves high diagnostic accuracy (97–100% in optimized models) while offering a cost-effective, less hazardous screening option, (3) challenges persist in data variability and model interpretability. These results highlight the need for integrated diagnostic systems combining technological innovations with preventive strategies. The review underscores AI’s transformative potential in breast cancer diagnosis while emphasizing the continued importance of risk factor management. Future research should prioritize multi-modal data integration and clinically interpretable models. Full article

Background: The amount of data produced from biological experiments has increased geometrically, posing a challenge for the development of new methodologies that could enable their interpretation. We propose a novel approach for the analysis of transcriptomic data derived from acute lymphoblastic leukemia (ALL) and rhabdomyosarcoma (RMS) cell lines, using bioinformatics, systems biology and geometrical approaches. Methods: The expression profile of each cell line was investigated using microarrays, and identified genes were used to create a systems pathway model, which was then simulated using differential equations. The transcriptomic profile used involved genes with similar expression levels. The simulated results were further analyzed using geometrical approaches to identify common expressional dynamics. Results: We simulated and analyzed the system network using time series, regression analysis and helical functions, detecting predictable structures after iterating the modelled biological network, focusing on TIE1, STAT1, MAPK14 and ADAM17. Our results show that such common attributes in gene expression patterns can lead to more effective treatment options and help in the discovery of universal tumor biomarkers. Discussion: Our approach was able to identify complex structures in gene expression patterns, indicating that such approaches could prove useful towards the understanding of the complex tumor dynamics. Full article

Accurate segmentation of kidney microstructures in whole slide images (WSIs) is essential for the diagnosis and monitoring of renal diseases. In this study, an end-to-end instance segmentation pipeline was developed for the detection of glomeruli and blood vessels in hematoxylin and eosin (H&E) stained kidney tissue. A tiling-based strategy was employed using Slicing Aided Hyper Inference (SAHI) to manage the resolution and scale of WSIs and the performance of two segmentation models, YOLOv11 and YOLOv12, was comparatively evaluated. The influence of tile overlap ratios on segmentation quality and inference efficiency was assessed, with configurations identified that balance object continuity and computational cost. To address object fragmentation at tile boundaries, an Enhanced Syncretic Mask Merging algorithm was introduced, incorporating morphological and spatial constraints. The algorithm’s hyperparameters were optimized using Particle Swarm Optimization (PSO), with vessel and glomerulus-specific performance targets. The optimization process revealed key parameters affecting segmentation quality, particularly for vessel structures with fine, elongated morphology. When compared with a baseline without postprocessing, improvements in segmentation precision were observed, notably a 48% average increase for glomeruli and up to 17% for blood vessels. The proposed framework demonstrates a balance between accuracy and efficiency, supporting scalable histopathology analysis and contributing to the Vasculature Common Coordinate Framework (VCCF) and Human Reference Atlas (HRA). Full article

Skin cancer is the most common cancer worldwide, for which early detection is crucial to improve survival rates. Visual inspection and biopsies have limitations, including being error-prone, costly, and time-consuming. Although several deep learning models have been developed, they demonstrate significant limitations. An interpretable and improved transfer learning model for binary skin cancer classification is proposed in this research, which uses the last convolutional block of VGG16 as the feature extractor. The methodology focuses on addressing the existing limitations in skin cancer classification, to support dermatologists and potentially saving lives through advanced, reliable, and accessible AI-driven diagnostic tools. Explainable AI is incorporated for the visualization and explanation of classifications. Multiple optimization techniques are applied to avoid overfitting, ensure stable training, and enhance the classification accuracy of dermoscopic images into benign and malignant classes. The proposed model shows 90.91% classification accuracy, which is better than state-of-the-art models and established approaches in skin cancer classification. An interactive desktop application integrating the model is developed, enabling real-time preliminary screening with offline access. Full article

Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding when to switch from androgen deprivation therapy (ADT) to more aggressive treatments like abiraterone or enzalutamide. Methods: We analyzed 5037 nmCRPC patients and employed a Weibull Time to Event Recurrent Neural Network to identify patients who would benefit from switching from ADT to abiraterone/enzalutamide. We evaluated this model using differential treatment benefits measured by the Kaplan–Meier estimation and milestone probabilities. Results: The model achieved an area under the curve of 0.738 (standard deviation (SD): 0.057) for patients treated with abiraterone/enzalutamide and 0.693 (SD: 0.02) for patients exclusively treated with ADT at the 2-year milestone. The model recommended 14% of ADT patients switch to abiraterone/enzalutamide. Analysis showed a statistically significant absolute improvement using model-recommended treatments in progression-free survival (PFS) of 0.24 (95% confidence interval (CI): 0.23–0.24) at the 2-year milestone (PFS rate increasing from 0.50 to 0.74) with a hazard ratio of 0.44 (95% CI: 0.39–0.50). Conclusions: Our model successfully identified nmCRPC patients who would benefit from switching to abiraterone/enzalutamide, demonstrating potential outcome improvements. Full article

This paper proposes a hybrid method for skin lesion classification combining deep learning features with conventional descriptors such as HOG, Gabor, SIFT, and LBP. Feature extraction was performed by extracting features of interest within the tumor area using suggested fusion methods. We tested and compared features obtained from different deep learning models coupled to HOG-based features. Dimensionality reduction and performance improvement were achieved by Principal Component Analysis, after which SVM was used for classification. The compared methods were tested on the reference database skin cancer-malignant-vs-benign. The results show a significant improvement in terms of accuracy due to complementarity between the conventional and deep learning-based methods. Specifically, the addition of HOG descriptors led to an accuracy increase of 5% for EfficientNetB0, 7% for ResNet50, 5% for ResNet101, 1% for NASNetMobile, 1% for DenseNet201, and 1% for MobileNetV2. These findings confirm that feature fusion significantly enhances performance compared to the individual application of each method. Full article

Background: Social media represents a unique opportunity to investigate the perspectives of people with eating disorders at scale. One forum alone, r/EatingDisorders, now has 113,000 members worldwide. In less than a day, where a manual analysis might sample a few dozen items, automatic classification using large language models (LLMs) can analyze thousands of posts. Methods: Here, we compare multiple strategies for invoking an LLM, including ones that include examples (few-shot) and annotation guidelines, to classify eating disorder content across 14 predefined themes using Llama3.1:8b on 6850 social media posts. In addition to standard metrics, we calculate four novel dimensions of classification quality: a Category Divergence Index, confidence scores (overall model certainty), focus scores (a measure of decisiveness for selected subsets of themes), and dominance scores (primary theme identification strength). Results: By every measure, invoking an LLM without extensive guidance and examples (zero-shot) is insufficient. Zero-shot had worse mean category divergence (7.17 versus 3.17). Whereas, few-shot yielded higher mean confidence, 0.42 versus 0.27, and higher mean dominance, 0.81 versus 0.46. Overall, a few-shot approach improved quality measures across nearly 90% of predictions. Conclusions: These findings suggest that LLMs, if invoked with expert instructions and helpful examples, can provide instantaneous high-quality annotation, enabling automated mental health content moderation systems or future clinical research. Full article

Lung-cancer incidence is projected to rise by 50% by 2035, underscoring the need for accurate yet accessible risk-stratification tools. We trained a Bayesian neural network on 300 annotated chest-CT scans from the public LIDC–IDRI cohort, integrating clinical metadata. Hamiltonian Monte-Carlo sampling (10 000 posterior draws) captured parameter uncertainty; performance was assessed with stratified five-fold cross-validation and on three independent multi-centre cohorts. On the locked internal test set, the model achieved 99.0% accuracy, AUC = 0.990 and macro-F1 = 0.987. External validation across 824 scans yielded a mean AUC of 0.933 and an expected calibration error $<0.034$, while eliminating false positives for benign nodules and providing voxel-level uncertainty maps. Uncertainty-aware Bayesian deep learning delivers state-of-the-art, well-calibrated lung-cancer risk predictions from a single CT scan, supporting personalised screening intervals and safe deployment in clinical workflows. Full article

Technological advancements and AI-based research have significantly influenced our daily lives. Human activity recognition (HAR) is a key area at the intersection of various AI technologies and application domains. In this study, we present our novel time series classification approach for monitoring the physical behaviors of the elderly and patients. This approach, which integrates supervised and unsupervised methods with generative models, has been validated for HAR, showing promising results. Our method was specifically adapted for healthcare and surveillance applications, enhancing the classification of physical behaviors in the elderly. The hybrid approach proved its effectiveness on the HAR70+ dataset, surpassing traditional recurrent convolutional network-based approaches. We further evaluated the surveillance system for the elderly (Surv-Sys-Elderly) model on the HARTH and HAR70+ datasets, achieving an accuracy of 94,3% on the HAR70+ dataset for recognizing elderly behaviors, highlighting its robustness and suitability for both clinical and domestic environments. Full article

Generative artificial intelligence (AI) is rapidly transforming healthcare systems since the advent of OpenAI in 2022. It encompasses a class of machine learning techniques designed to create new content and is classified into large language models (LLMs) for text generation and image-generating models for creating or enhancing visual data. These generative AI models have shown widespread applications in clinical practice and research. Such applications range from medical documentation and diagnostics to patient communication and drug discovery. These models are capable of generating text messages, answering clinical questions, interpreting CT scan and MRI images, assisting in rare diagnoses, discovering new molecules, and providing medical education and training. Early studies have indicated that generative AI models can improve efficiency, reduce administrative burdens, and enhance patient engagement, although most findings are preliminary and require rigorous validation. However, the technology also raises serious concerns around accuracy, bias, privacy, ethical use, and clinical safety. Regulatory bodies, including the FDA and EMA, are beginning to define governance frameworks, while academic institutions and healthcare organizations emphasize the need for transparency, supervision, and evidence-based implementation. Generative AI is not a replacement for medical professionals but a potential partner—augmenting decision-making, streamlining communication, and supporting personalized care. Its responsible integration into healthcare could mark a paradigm shift toward more proactive, precise, and patient-centered systems. Full article

Food pattern recognition plays a crucial role in modern healthcare by enabling automated dietary monitoring and personalised nutritional interventions, particularly for vulnerable populations with complex dietary needs. Current food recognition systems struggle to balance high accuracy with interpretability and computational efficiency when analysing complex meal compositions in real-world settings. We developed a novel self-explaining neural architecture that integrates specialised attention mechanisms with temporal modules within a streamlined framework. Our methodology employs hierarchical feature extraction through successive convolution operations, multi-head attention mechanisms for pattern classification, and bidirectional LSTM networks for temporal analysis. Architecture incorporates self-explaining components utilising attention-based mechanisms and interpretable concept encoders to maintain transparency. We evaluated our model on the FOOD101 dataset using 5-fold cross-validation, ablation studies, and comprehensive computational efficiency assessments. Training employed multi-objective optimisation with adaptive learning rates and specialised loss functions designed for dietary pattern recognition. Experiments demonstrate our model’s superior performance, achieving 94.1% accuracy with only 29.3 ms inference latency and 3.8 GB memory usage, representing a 63.3% parameter reduction compared to baseline transformers. The system maintains detection rates above 84% in complex multi-item recognition scenarios, whilst feature attribution analysis achieved scores of 0.89 for primary components. Cross-validation confirmed consistent performance with accuracy ranging from 92.8% to 93.5% across all folds. This research advances automated dietary analysis by providing an efficient, interpretable solution for food recognition with direct applications in nutritional monitoring and personalised healthcare, particularly benefiting vulnerable populations who require transparent and trustworthy dietary guidance. Full article

Background: Anemia, a common health disorder affecting populations globally, demands timely and accurate diagnosis for treatment to be effective. The aim of this paper is to detect and classify four types of anemia: hgb, iron-deficiency, folate-deficiency, and B12-deficiency anemia. Methods: This paper proposes an ontology-enhanced machine learning (ML) framework to classify types of anemia from CBC data obtained from Kaggle, which contains 15,300 patient records. It evaluates the effects of classical versus deep classifiers on imbalanced and oversampled training samples. Tests include KNN, SVM, DT, RF, CNN, CNN+SVM, CNN+RF, and XGBoost. Another interesting contribution is the use of ontological reasoning via SPARQL queries to semantically enrich clinical features with categories like “Low Hemoglobin” or “Macrocytic MCV”. These semantic features were then used in both classical (SVM) and deep hybrid models (CNN+SVM). Results: Ontology-enhanced and CNN hybrid models perform competitively when paired with ROS or ADASYN, but their performance degrades significantly on the original dataset. There were tremendous performance gains with ontology-enhanced models in that Onto-CNN+SVM achieved an F1-score (1.00) for all the four types of anemia under ROS sampling, while Onto-SVM exhibited more than 20% improvement in F1-scores for minority categories like folate and B12 when compared to baseline models, except XGBoost. Conclusions: Ontology-driven knowledge coalescence has been shown to improve classification results; however, XGBoost consistently outperformed all other classifiers across all data conditions, making it the most robust and reliable model for clinically relevant decision-support systems in anemia diagnosis. Full article

Background: Gliomas represent the most prevalent and aggressive primary brain tumors, requiring precise classification to guide treatment strategies and improve patient outcomes. Purpose: This study aimed to develop and evaluate a machine learning-driven approach for glioma classification by identifying the most relevant genetic and clinical biomarkers while demonstrating clinical utility. Methods: A dataset from The Cancer Genome Atlas (TCGA) containing 23 features was analyzed using an integrative approach combining Boruta, Least Absolute Shrinkage and Selection Operator (LASSO), and SHapley Additive exPlanations (SHAP) for feature selection. The refined feature set was used to train four machine learning models: Random Forest, Support Vector Machine, XGBoost, and Logistic Regression. Comprehensive evaluation included class distribution analysis, calibration assessment, and decision curve analysis. Results: The feature selection approach identified 13 key predictors, including IDH1, TP53, ATRX, PTEN, NF1, EGFR, NOTCH1, PIK3R1, MUC16, CIC mutations, along with Age at Diagnosis and race. XGBoost achieved the highest AUC (0.93), while Logistic Regression recorded the highest testing accuracy (88.09%). Class distribution analysis revealed excellent GBM detection (Average Precision 0.840–0.880) with minimal false negatives (5–7 cases). Calibration analysis demonstrated reliable probability estimates (Brier scores 0.103–0.124), and decision curve analysis confirmed substantial clinical utility with net benefit values of 0.36–0.39 across clinically relevant thresholds. Conclusions: The integration of feature selection techniques with machine learning models enhances diagnostic precision, interpretability, and clinical utility in glioma classification, providing a clinically ready framework that bridges computational predictions with evidence-based medical decision-making. Full article

Background: Chronic diseases significantly burden healthcare systems due to the need for long-term treatment. Early diagnosis is critical for effective management and minimizing risk. The current traditional diagnostic approaches face various challenges regarding efficiency and cost. Digitized healthcare demonstrates several opportunities for reducing human errors, increasing clinical outcomes, tracing data, etc. Artificial Intelligence (AI) has emerged as a transformative tool in healthcare. Subsequently, the evolution of Generative AI represents a new wave. Large Language Models (LLMs), such as ChatGPT, are promising tools for enhancing diagnostic processes, but their potential in this domain remains underexplored. Methods: This study represents the first systematic evaluation of ChatGPT’s performance in chronic disease prediction, specifically targeting heart disease and diabetes. This study compares the effectiveness of zero-shot, few-shot, and CoT reasoning with feature selection techniques and prompt formulations in disease prediction tasks. The two latest versions of GPT4 (GPT-4o and GPT-4o-mini) are tested. Then, the results are evaluated against the best models from the literature. Results: The results indicate that GPT-4o significantly beat GPT-4o-mini in all scenarios regarding accuracy, precision, and F1-score. Moreover, a 5-shot learning strategy demonstrates superior performance to zero-shot, few-shot (3-shot and 10-shot), and various CoT reasoning strategies. The 5-shot learning strategy with GPT-4o achieved an accuracy of 77.07% in diabetes prediction using the Pima Indian Diabetes Dataset, 75.85% using the Frankfurt Hospital Diabetes Dataset, and 83.65% in heart disease prediction. Subsequently, refining prompt formulations resulted in notable improvements, particularly for the heart dataset (5% performance increase using GPT-4o), emphasizing the importance of prompt engineering. Conclusions: Even though ChatGPT does not outperform traditional machine learning and deep learning models, the findings highlight its potential as a complementary tool in disease prediction. Additionally, this work provides value by setting a clear performance baseline for future work on these tasks Full article