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Computer Methods and Programs in Biomedicine

Elsevier BV

Preprints posted in the last 90 days, ranked by how well they match Computer Methods and Programs in Biomedicine's content profile, based on 27 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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MCA-UNet: A Multi-Scale Context and Attention U-Net for Colorectal Polyp Segmentation

Dong, Y.; Fang, G.; Du, R.; Hu, H.; Fang, Z.; Guo, C.; Lu, R.; Jia, Y.; Tian, Y.; Wang, Z.

2026-03-16 gastroenterology 10.64898/2026.03.11.26348049 medRxiv
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IntroductionTo propose an improved U-Net-based segmentation model for colorectal polyp segmentation, aiming to address the challenges of variable lesion morphology, ambiguous boundaries, complex background interference, and insufficient cross-level feature fusion in endoscopic images [5,12]. MethodsAn improved network termed MCA-UNet was developed based on U-Net [5]. The model incorporates a multi-scale context convolution block (MCCB) to enhance multi-scale feature extraction and an attention-guided feature fusion module (AGFF) to optimize skip-feature selection and fusion in the decoder. Experiments were conducted on publicly available colorectal polyp image datasets, including Kvasir-SEG and CVC-ClinicDB [13-15]. Four models, including U-Net, U-Net+MCCB, U-Net+AGFF, and MCA-UNet, were compared, and all models were trained for 100 epochs. Dice, intersection over union (IoU), and mean absolute error (MAE) were used as the main evaluation metrics [20]. ResultsOn the mixed validation set, the Dice scores of U-Net, U-Net+MCCB, U-Net+AGFF, and MCA-UNet were 0.742, 0.771, 0.754, and 0.783, respectively; the corresponding IoU values were 0.603, 0.635, 0.618, and 0.649; and the MAE values were 0.102, 0.090, 0.097, and 0.086. Compared with the baseline U-Net, MCA-UNet improved Dice and IoU by 5.53% and 7.63%, respectively, while reducing MAE by 15.69%. Comparisons on the Kvasir-SEG and CVC-ClinicDB validation subsets further demonstrated the more stable performance of the proposed model. ConclusionBy jointly integrating multi-scale contextual modeling and attention-guided feature fusion, MCA-UNet effectively improves the accuracy and robustness of colorectal polyp segmentation and may provide useful support for intelligent endoscopic image analysis [12,17,18].

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Study protocol Effects of Philips Visual Patient Avatar on vital sign deviations and audible alarm burden in perioperative care: a dual-centre, quasi-experimental pre-post big-data study protocol (NewYork-Presbyterian/Weill Cornell and University Hospital Zurich)

Jiang, S. Y.; Roche, T. R.; Cybulski, K.; Dugac, G.; Meier, L.; Tangel, V. E.; Ebensperger, M.; Maskos, A.; Tucci, M.; Noethiger, C. B.; Kalisch, M.; Turnbull, Z. A.; Tscholl, D. W.

2026-05-21 anesthesia 10.64898/2026.05.18.26353454 medRxiv
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Perioperative patient monitoring requires clinicians to integrate multiple physiological data streams under time pressure and frequent interruptions. Conventional monitors predominantly present vital signs as separate numerical values and waveforms, which must be sequentially interpreted and mentally integrated, imposing substantial cognitive demands. Audible alarms are intended to enhance safety but contribute to alarm fatigue and increased workload. Time spent outside predefined safe ranges for key physiological variables and excessive alarm burden are associated with adverse outcomes, motivating approaches that support earlier detection and improved situation awareness without increasing cognitive load. The Philips Visual Patient Avatar is an avatar-based visualisation technology displayed on the patient monitor that supports clinicians' situation awareness by integrating multiple vital signs and sensor states into a single animated virtual patient, while retaining conventional numerical displays. Although laboratory, simulation and qualitative studies suggest benefits of avatar-based monitoring, its impact on objective monitoring outcomes has not been systematically quantified.

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Hybrid Neural--Bayesian Belief Network Framework for Uncertainty-Aware Multimodal GBM Prediction

Jayme, A.; Heuveline, V.

2026-05-13 health informatics 10.64898/2026.05.10.26352710 medRxiv
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Background and ObjectiveGlioblastoma outcome prediction remains difficult because clinically relevant signals are distributed across heterogeneous imaging and genomic modalities, cohorts are small, and conventional neural predictors do not quantify their own uncertainty. This study evaluates a hybrid neural-Bayesian belief network framework for uncertainty-aware multimodal glioblastoma prediction and examines how modality selection, model family, and structure-aware regularization affect predictive performance and confidence quality. MethodsThe framework was evaluated on the TCGA-GBM radiogenomic cohort using four input modalities (T1Gd, FLAIR, mRNA, and CNA), five model families, five structural-weight settings, and 15 view subsets. A secondary benchmark on the UCI Human Activity Recognition dataset was included to assess whether observed limitations were specific to the glioblastoma setting. ResultsCNA features consistently reduced performance in most multimodal settings, and selective fusion excluding CNA outperformed both the full four-view baseline and imaging-only alternatives. Model families showed clear differences in uncertainty behaviour: non-Bayesian families achieved the strongest predictive accuracy, whereas the Bayesian family achieved the lowest calibration error over a narrower confidence range. Bayesian belief network regularization produced consistent directional improvements without supporting reliable structure-discovery claims, as learned graph structures were not reproducible across folds. On the secondary bench-mark, the same framework achieved much higher predictive performance, indicating that the glioblastoma performance ceiling primarily reflects data limitations rather than an architectural constraint. ConclusionsIn small-sample radiogenomic prediction, modality choice is at least as important as model choice, and uncertainty quality differs substantially across uncertainty-aware model families. The proposed framework provides a practical basis for comparing accuracy, calibration, modality selection, and structure-aware regularization in multimodal biomedical prediction.

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Assessing the Reliability of a Controllable Sound Source Driven Bowel Sound Monitoring Device in Physiological Tissue Acoustic Environments

Zhao, J.; Zhao, Z.; Huang, X.; Li, Y.; Wu, J.; Peng, S.; Wang, S.; Sun, G.; Luan, Z.

2026-06-04 gastroenterology 10.64898/2026.06.03.26354788 medRxiv
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Objective To verify the reliability of a self developed bowel sound monitoring device under real biological tissue acoustic propagation conditions using a controllable sound source, and to establish quantitative evidence for its translational applicability. Methods Freshly euthanized six month old Bama miniature pigs were used as an experimental model. A high fidelity Bluetooth audio playback device was implanted into the abdominal cavity to deliver manually annotated bowel sound recordings as controllable acoustic stimuli. A self developed bowel sound monitoring device was fixed on the abdominal surface for continuous signal acquisition. Playback timestamps were defined as the ground truth, and event level matching was performed within a predefined temporal tolerance window. Four performance indicators were evaluated: (1) bowel sound acquisition and energy amplification, (2) event matching accuracy, (3) acoustic feature consistency, and (4) subjective agreement assessed by blinded auscultation from gastroenterologists with different levels of clinical experience. Results The monitoring device exhibited stable detection capability and effectively covered the full spectral range of the original signals. It significantly enhanced bowel sound energy while preserving temporal and spectral characteristics, demonstrating high consistency in time and frequency domain features. Blinded clinician assessments showed a subjective agreement rate of 88.9% between original and surface recorded bowel sound events. Conclusions Under real tissue acoustic propagation conditions, the self-developed bowel sound monitoring device reliably captures bowel sound events with high temporal accuracy, acoustic fidelity, and clinical perceptual consistency. This controllable sound source based validation provides robust technical evidence for subsequent in vivo studies and clinical translation, supporting the development of objective and continuous gastrointestinal function monitoring.

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From CCTA to Surgical Strategy: An Integrated AI Framework for Patient-Specific Coronary artery bypass grafting Planning

Rezaeitaleshmahalleh, M.; Masoumi, S.; Debalme, E.; Sundt, T. M.; Aranki, S. F.; Shin, B.; Nezami, F. R.

2026-06-01 cardiovascular medicine 10.64898/2026.05.28.26354400 medRxiv
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Background: Coronary artery bypass grafting (CABG) remains the standard of care for complex multivessel and left main coronary artery disease. However, current preoperative planning remains largely subjective, relying on qualitative interpretation of coronary CT angiography (CCTA), operator-dependent stenosis grading, and fragmented multi-software workflows. Invasive fractional flow reserve (FFR), the reference standard for physiologic lesion assessment, is infrequently acquired preoperatively, leaving distal anastomosis planning without an objective hemodynamic basis. Methods: We developed a fully automated, AI-powered platform that converts routine CCTA into a patient-specific CABG planning workflow through five integrated modules: nnU-Net based segmentation of coronary lumen and calcification; quantitative morphological and topological characterization generating more than thirty descriptors; automated stenosis detection using a local reference-radius formulation; a nine-point composite scoring framework for distal anastomosis site selection incorporating luminal caliber, landing-zone length, calcification burden, distal perfusion reserve, and bifurcation proximity; and interactive virtual graft construction coupled to a distributed reduced-order solver for pre- and post-bypass FFR estimation. Results: Lumen segmentation achieved a mean Dice similarity coefficient of 0.96 {+/-} 0.01, whereas calcium segmentation achieved 0.73 {+/-} 0.15 on the held-out cohort. Platform-derived FFR demonstrated strong agreement with invasively measured FFR (r=0.96, mean absolute relative difference 1.73 {+/-}1.42%) across the evaluated lesions, supporting the physiologic validity of the reduced-order hemodynamic solver. End-to-end analysis from raw CCTA to hemodynamic assessment and virtual graft planning was completed in approximately seven minutes per case on a standard workstation, representing a substantial reduction in processing time compared with conventional multi-tool and CFD-based workflows. Conclusions: The proposed platform demonstrates the feasibility of rapid, reproducible, and physiology-informed CABG planning using routine CCTA. By integrating anatomical characterization, automated target-site analysis, virtual graft construction, and reduced-order hemodynamic assessment into a single workflow, the framework provides objective, quantitative surgical decision support compatible with routine clinical workflows. Keywords: Coronary artery bypass grafting (CABG); Fractional flow reserve (FFR); Coronary CT angiography (CCTA); Surgical planning

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A clinicoradiological model for preoperative prediction of lateral lymph node metastasis in rectal cancer

Shen, Q.; Wang, G.; Fu, M.; Yao, K.; Yang, Y.; Zeng, Q.; Guo, Y.

2026-04-15 gastroenterology 10.64898/2026.04.13.26350816 medRxiv
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BackgroundLateral lymph node metastasis (LLNM) is associated with poor prognosis in patients with rectal cancer and may influence the indication for lateral lymph node dissection. Accurate preoperative identification of LLNM remains challenging. This study aimed to develop and internally validate a clinicoradiological model for preoperative prediction of LLNM in rectal cancer. MethodsA retrospective cohort of 64 patients undergoing lateral lymph node dissection (LLND) for rectal cancer was analysed; 21 (32.8%) had pathological lateral lymph node metastasis (LLNM). A prespecified preoperative clinicoradiological model was fitted using penalised logistic regression with L2 regularisation (ridge), incorporating MRI-measured lateral lymph node short-axis diameter (LLN-SAD), dichotomised clinical T stage (T3-4 vs T1-2), dichotomised clinical N stage (N+ vs N0), and log(CA19-9+1). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration analysis, and bootstrap internal validation. ResultsThe model showed good discrimination (AUC 0.914), with an optimism-corrected AUC of 0.887 on bootstrap validation. Calibration remained acceptable after optimism correction (calibration intercept -0.127; slope 1.045). Decision curve analysis suggested net benefit across clinically relevant threshold probabilities, particularly between 0.10 and 0.30. The model was implemented as a web-based calculator to facilitate clinical use. ConclusionThis clinicoradiological model showed good discrimination, acceptable calibration, and potential clinical utility for preoperative assessment of LLNM risk in rectal cancer. It may assist individualized risk stratification and treatment planning, although external validation is required before routine clinical implementation.

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QRS Detection by Combinatorial Optimization With MLP Assisted Peak Scoring

Hopenfeld, B.

2026-04-22 bioengineering 10.64898/2026.04.19.719501 medRxiv
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A multiple channel QRS detector is described. The detector partitions raw signal segments into peak domains, extracts parameters associated with the peak domains, and scores peaks based on these parameters. A multi-layer perceptron (MLP) with 11 inputs generates provisional peak scores, which are refined through application of rules involving 20-30 parameters. An optimal sequence of supra threshold peaks is determined. Separately, combinatorial optimization determines an optimal structured heart rhythm sequence. Adjudication between the general supra threshold sequence and the structured sequence depends on noise level, peak quality, and rhythm structure quality. For multiple channel fusion, peak scores are determined as a noise weighted function of channel peak scores. The MLP was trained on approximately 70% of channel 1 of the MIT-BIH Arrhythmia Database. The supplementary rules were heuristically chosen over all channel 1 records. Sensitivity (SE) and positive predictive value (PPV) of the detector applied to channel 2 were a function of the noise threshold used to discard segments. At a noise level that would exclude 2.2% of channel 1 data, the SE and PPV were 99.67% and 99.75% respectively. Importantly, even in high noise, the detector was able to track large scale features of heart rhythm. Fused channel 1 and channel 2 SE and PPV were 99.96% and 99.98% respectively. The present algorithm points the way toward maximal extraction of heart rhythm information from noisy signals, and the potential to reduce false alarms generated by automated rhythm analysis software.

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MOE-ECG: Multi-Objective Ensemble Fusion for Robust Atrial Fibrillation Detection Using Electrocardiograms

Peimankar, A.; Hossein Motlagh, N.; K. Khare, S.; Spicher, N.; Dominguez, H.; Abolghasemi, V.; Fujiwara, K.; Teichmann, D.; Rahmani, R.; Puthusserypady, S.

2026-03-30 health informatics 10.64898/2026.03.28.26349522 medRxiv
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Background: Atrial fibrillation (AFib) is the most common sustained arrhythmia in the world, imposing a heavy clinical and economic burden on global healthcare systems. Early detection of AFib can reduce mortality and morbidity, while helping to alleviate the growing economic burden of cardiovascular diseases. With the increasing availability of digital health technologies, computational solutions have great potential to support the timely diagnosis of cardiac abnormalities. Objectives: With the increasing availability of electrocardiogram (ECG) data from clinical and wearable devices, manual interpretation has become impractical due to its time-consuming and subjective nature. Existing automated approaches often rely on single classifiers or fixed ensembles that primarily optimize predictive accuracy while neglecting model diversity, which leads to limited robustness and generalization across heterogeneous datasets. Therefore, this study aims to develop a robust and diversity-aware framework for automatic AFib detection that simultaneously improves classification performance and model generalizability. To this end, we propose MOE-ECG, a multi-objective ensemble selection and fusion framework that explicitly optimizes both predictive performance and inter-model diversity for reliable AFib detection from ECG recordings. Methods: The proposed multi-objective ensemble (MOE) framework uses ensemble selection as a bi-objective optimization problem and employs multi-objective particle swarm optimization to identify complementary classifiers from a heterogeneous model pool. Unlike conventional ensembles, it explicitly optimizes both predictive performance and diversity and integrates Dempster-Shafer theory for uncertainty-aware decision fusion. After filtering the ECG signals to remove baseline wander and noise, they were segmented into windows of 20, 60, and 120 heartbeats with 50% overlap. The proposed approach was evaluated over five independent runs to assess its stability and generalization. Fifteen statistical and nonlinear features were obtained from the RR-intervals of the pre-processed ECG signals, of which eight features were selected with correlation analysis to capture subtle information from the ECG data. We trained and evaluated the performance of the proposed model in three open source databases, namely, the MIT-BIH Atrial Fibrillation Database, Saitama Heart Database Atrial Fibrillation, and Long-Term AF Database. Results: The proposed approach achieved the best overall performance on 60-beat segments, with an average accuracy of 89.85%, precision of 91.14%, recall of 94.19%, an F1-score of 92.64%, and area under the curve (AUC) of around 0.95. Statistical analysis using Holm-adjusted Wilcoxon tests confirmed significant improvements (p<0.05) compared to both the best individual classifier and the unoptimized average ensemble of all classifiers. These findings show that the proposed selection and evaluation methodology, rather than group aggregation alone, is the key driver of performance improvements. Conclusion: The results obtained demonstrate that the MOE-ECG model offers a robust, accurate, and reliable solution for the detection of AFib from short ECG segments. The empirical findings, in general, confirm that multi-objective ensemble fusion enhances diagnostic performance and offers robust predictions that will open up possibilities for real-time AFib detection in clinical and tele-health settings.

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Enhanced precision of tensor electrocardiography through increased cumulative distribution function resolution: Validation in healthy individuals

TSUKADA, Y. T.; Hirayama, H.; Yodogawa, K.; Murata, H.; Iwasaki, Y.-k.; Fujino, T.; Shiozawa, A.; Tsukada, S.

2026-06-02 cardiovascular medicine 10.64898/2026.05.31.26354561 medRxiv
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Deep-learning ECG analysis is advancing rapidly but lacks stable, physiologically interpretable indicators to anchor explainable artificial intelligence (AI). Tensor cardiography (TCG) models electrocardiographic (ECG) waveforms as differences between pairs of cumulative distribution functions (CDFs), representing collective myocardial action potential transitions. However, the original 4-CDF model has limitations in fitting P waves and complex QRST patterns. This study aimed to evaluate whether increasing the number of CDFs from 4 to 10 improves TCG fitting accuracy and to characterize normative distributions of 10-CDF parameters in healthy individuals. Participants were recruited through occupational health screening at Tobu Railway Co., Ltd. (n = 415) and from the Nippon Medical School Hospital ECG database (n = 29). Standard 12-lead ECGs from 444 healthy participants, including 345 men and 99 women with a mean age of 46.9 years, were analyzed using TCG software. Reconstruction accuracy was assessed using RMSE, paired t-tests, and Cohens d. The 10-CDF model achieved significantly lower RMSE values across all leads than the 4-CDF model, with all p values < 0.0001 and very large effect sizes. In representative leads, RMSEs for the 4-CDF versus 10-CDF models were 0.0256 versus 0.0061 in lead II, 0.0230 versus 0.0063 in lead V1, and 0.0265 versus 0.0062 in lead V5. The coefficient of determination improved from a median of 0.952 with the 4-CDF model to 0.997 with the 10-CDF model in lead II. Parameter dispersion was reduced, suggesting improved estimation stability. Two new parameters, T_mean_diff and RT_mean_duration, were derivable from the expanded model; RT_mean_duration showed significant correlations with age and body surface area. In conclusion, increasing the CDF resolution from 4 to 10 significantly enhanced ECG waveform reconstruction accuracy and parameter stability. These findings provide normative distributions of 10-CDF TCG parameters and may support future explainable AI-based ECG analysis.

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AI and Hierarchical clustering techniques for accurate patient stratification

Diaz Ochoa, J. G.; Puskaric, M.; Layer, N.; Jensch, A.; Knott, M.; Krohn, A.

2026-03-15 health informatics 10.64898/2026.03.13.26348331 medRxiv
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Graph-based methods for data representation and analysis are well suited for encoding both data points and their interrelationships. This approach integrates data and topology, enabling the representation of interrelated information. In this study, we represent patient cohorts as cohort graphs and discuss their application for real-world patient data. We particularly focus on developing methods to cluster patients with similar symptoms and examine how bias parameters (such as sex and age group) influence interlinking within CGs, thereby improving results for accurate patient stratification and personalized decision-making in a clinical context. In particular we illustrate how by considering sex and age groups we can improve the symptom-clustering of a patient population with lung and gastro-intestinal cancer. Finally, we discuss the essential role of high-performance computing (HPC) in upscaling analytical methods for CGs.

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PRAM: Post-hoc Retrieval Augmentation for Parameter-Free Domain Adaptation of ICU Clinical Prediction Models

Jeong, I.; Lee, T.; Kim, B.; Park, J.-H.; Kim, Y.; Lee, H.

2026-04-05 health systems and quality improvement 10.64898/2026.04.03.26350132 medRxiv
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Background Clinical prediction models degrade when deployed across hospitals, yet retraining requires technical expertise, labeled data, and regulatory re-approval. We investigated whether post-hoc retrieval augmentation of a frozen model's output, analogous to retrieval-augmented methods in natural language processing, can mitigate this degradation without any parameter modification. Methods We developed the Post-hoc Retrieval Augmentation Module (PRAM), which combines predictions from a frozen base model with outcome information retrieved from similar patients in a local patient bank. Five base models (logistic regression through CatBoost) and three retrieval strategies were evaluated on 116,010 ICU patients across three databases (MIMIC-IV, MIMIC-III, eICU-CRD) for acute kidney injury (AKI) and mortality prediction. A bank size deployment simulation modeled performance from zero to full local data accumulation, complemented by source bank cold start, stress tests, and calibration experiments. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Results Retrieval benefit was inversely associated with base model complexity ({rho} = -0.90 for AKI, -1.00 for mortality): simpler models benefited more, consistent with retrieval capturing residual signal unexploited by the base model. PRAM showed a statistically significant monotone dose-response between bank size and prediction performance across all six outcome-target combinations (Kendall {tau} trend test, q = 0.031 for all). At the pre-specified primary comparison (bank = 5,000), the improvement was confirmed for the two largest-shift settings (eICU-CRD AKI: {Delta}AUROC = +0.012, q < 0.001; eICU-CRD mortality: {Delta}AUROC = +0.026, q < 0.001). Pre-loading a source bank bridged the cold-start gap, providing an immediate performance gain equivalent to approximately 2,000 to 5,000 local patients. Conclusions PRAM provides a parameter-free adaptation mechanism that requires no model retraining, gradient computation, or regulatory re-evaluation at the deployment site. Effect sizes were modest and did not reach cross-model superiority, but the consistent dose-response pattern and the absence of retraining requirements establish retrieval-based adaptation as a viable approach for clinical model transportability. The retrieval mechanism additionally opens a pathway toward case-based interpretability, where predictions are accompanied by identifiable similar patients from the deploying institution.

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HybridNet-XR: Efficient Teacher-Free Self-Supervised Learning for Autonomous Medical Diagnostic Systems in Resource-Constrained Environments.

Mayala, S.; Mzurikwao, D.; Suluba, E.

2026-03-19 health informatics 10.64898/2026.03.16.26348570 medRxiv
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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.

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Explainable machine learning for revisiting reported Irritable Bowel Syndrome correlates in a student cohort

Ramirez-Lopez, L.; Kang, P.

2026-04-15 gastroenterology 10.64898/2026.04.13.26350820 medRxiv
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Irritable Bowel Syndrome (IBS) affects a substantial proportion of university students, yet its factors remain incompletely characterised in South Asian populations. We reanalysed a publicly available dataset of 550 Bangladeshi students from Hasan et al. [1], conducting a data audit that identified implausible records, including males reporting menstrual symptoms, and reduced the analytic sample to 506 observations. Using Explainable Boosting Machines (EBMs), which capture non-linear effects and pairwise interactions without sacrificing interpretability, we found that psychological distress, elevated BMI and academic dissatisfaction were the strongest predictors of IBS (mean AUC = 0.852 across 100 stratified train-test splits). Critically, several findings diverged from the original logistic regression analysis. Physical activity showed a non-linear risk pattern only at high intensity, the association with gender was substantially weaker when we accounted for metabolic and psychological factors as well and malnourishment does not have a strong an impact as in the original study. These divergences likely arise because the machine-learning model captures non-linear effects and interactions that were not represented in the original regression specification. Our findings underscore the value of reanalysing existing datasets with methods suited to capturing complexity and highlight data quality verification as a necessary step in the secondary analysis. Author summaryWe reanalysed a dataset on Irritable Bowel Syndrome (IBS) among university students in Dhaka, Bangladesh. Before modelling, we audited the dataset, removed implausible records, and reconstructed the IBS classification from the Rome III questionnaire. We then applied an interpretable machine-learning model capable of modelling non-linear effects and interactions between variables. Psychological distress (particularly anxiety and stress), body mass index, and dissatisfaction with academic major showed the strongest associations with IBS. The model also identified several interaction effects involving BMI. Our results differ in several respects from the original regression analysis, suggesting that modelling assumptions and data validation can influence the interpretation of IBS correlates. This study shows how explainable machine-learning models can complement conventional statistical analyses and how data validation can affect results in secondary analyses.

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Synthetic Data Generation and Nonparametric Techniques for Assessing Multivariate Similarity to Address Small-Sample Size Challenges

Heine, J.; Fowler, E.; Eschrich, S. A.; Schell, M.

2026-05-07 bioinformatics 10.64898/2026.05.04.722226 medRxiv
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Data modeling in biomedical research often operates in the small-sample regime, where the number of observations is small relative to the data dimensionality; the detrimental effects of limited sample sizes are well documented in cancer studies. Synthetic data offers a potential solution to data shortfalls provided that the data generated is an adequate facsimile of the underlying distribution; the adequacy of such synthetic data remains an open-ended problem. In this work, we evaluate a synthetic generator proposed previously. The generator applies a series of transformations to the observed data to accommodate the small-sample size resulting in an uncoupled representation, where uncorrelated marginal distributions are modeled with optimized univariate kernel density estimation. In this report, (1) we develop a nonparametric method for assessing multivariate similarity based on the Cramer-Wold theorem and random projection testing, (2) investigate when the absence of bivariate correlation approximates independence in a non-normal setting, and (3) evaluate artifacts induced by data compression. The presentation is primarily methodological; low-dimensional data were used so each stage of the generation process could be analyzed explicitly. A formal testing framework was developed by comparing random projection level outcomes with a two-sample test, modeling these outcomes as Bernoulli trials, aggregating replicate outcomes within each projection direction, and pooling outcomes across many directions, yielding a scalable standardized normal test-statistic. The key innovation was decoupling the two-sample test significance level from that governing finalized normal inference. We showed the same projection framework also evaluates the full multivariate covariance structure. The generator produced high-fidelity multivariate synthetic data when the bivariate correlation approximates independence in the non-normal setting; in highly compressed data, residual modes were best modeled as normally distributed regardless of their intrinsic distributional form. Ongoing work includes applying these methods to higher-dimensional, diverse data.

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Performance Assessment of ECG Delineators on Single-Lead Wearable Ambulatory Data

Chuma, A. T.; Youssef, A. S.; Asmare, M. H.; Wang, C.; Kassie, D. M.; Voigt, J.-U.; Vanrumste, B.

2026-03-26 cardiovascular medicine 10.64898/2026.03.24.26349185 medRxiv
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Reliable interpretation of electrocardiograms (ECGs) requires precise identification of P, QRS, and T (PQRST) wave boundaries. However, it remains challenging due to noise, signal quality variability, and inherent morphological diversity particularly in recordings from children. This study systematically compares the performance of leading deep neural networks (DNN) and heuristic-based delineation algorithms on ambulatory single-lead ECG signals focusing on temporal accuracy. Experiments were conducted using the publicly available LUDB dataset and a private validation dataset comprising 21,759 annotated single-lead wave segments from 611 children recorded using KardiaMobile ECG sensor. DNN were first trained on the LUDB dataset and subsequently tested on the validation dataset. The delineation performance was assessed using Sensitivity (Se) and positive-predictive-value (P+) metrics. The best-performing heuristic based and DNN models reached Se and P+ of (98.9% vs 97.9%) for P, (99.8% vs 99.2%) for QRS, and (98.7% vs 95.9%) for T wave fiducials, respectively. The lowest standard-deviation (in ms) of wave onset/offset delineation was achieved by attention based 1DU-Net model; {+/-}16.6/{+/-}16.3 for P-wave, {+/-}14.0/{+/-}16.3 for QRS, and {+/-}26.3/{+/-}18.8 for T-wave, respectively. The findings indicate that optimized heuristic models can perform comparably to complex DNN, highlighting their efficiency and suitability for real-time ECG delineation in digital health monitoring applications.

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Development and Validation of a Two-Stage NLP-LLM System for Automated Extraction of Deprescribing Recommendations from Discharge Summaries

Fujita, K.; Matheson, M.; Valecha, B.; Hilmer, S. N.

2026-04-30 geriatric medicine 10.64898/2026.04.29.26352010 medRxiv
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IntroductionPolypharmacy in older adults is associated with increased risks of adverse drug events and functional decline. Discharge summaries often contain deprescribing recommendations, but these are frequently overlooked due to documentation complexity. ObjectiveTo develop and validate a two-stage hybrid system combining rule-based natural language processing (NLP) and large language model (LLM) for automated extraction of deprescribing recommendations from discharge summaries. MethodsThis retrospective cohort study included 850 discharge summaries from patients aged [&ge;]65 years with hospitalisation [&ge;]48 hours across six public hospitals in New South Wales, Australia. Model 1 (rule-based NLP) extracted discharge medications and candidate sentences containing pre-defined deprescribing keywords. Model 2 (open-source LLM) classified candidate sentences into five categories. Data were split into training (80%) and test (20%) sets. Gold standard classifications were established by independent reviews, followed by adjudication of discrepancies. ResultsModel 1 extracted 9,631 discharge medications (median 11 per patient) and 1,061 candidate sentences from 850 patients (median age 82.8 years). Model 2 achieved an F1 score of 0.91 and accuracy of 0.90 on the test set. Inter-rater reliability showed substantial agreement (Cohens kappa = 0.70). The most frequently identified medications recommended for deprescribing were antibiotics and opioids. The most common misclassification was incorrectly identifying actions completed during hospitalisation as post-discharge recommendations. The combined processing time averaged 12.6 seconds per discharge summary. ConclusionsA two-stage hybrid approach combining rule-based NLP and open-source LLM can accurately extract deprescribing recommendations from discharge summaries, enabling cost-efficient, privacy-compliant local deployment. Key Points- A two-stage system combining rule-based NLP and open-source LLM extracted and classified deprescribing recommendations from 850 discharge summaries, achieving an F1 score of 0.91 and accuracy of 0.90. - The use of an open-source LLM (Llama 3.3) enables cost-efficient, privacy-compliant local deployment in healthcare institutions. - Antibiotics and opioids were the most frequently identified medications recommended for deprescribing in discharge summaries.

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A direct forcing immersed boundary method for biofluid simulations using a non-linear rotation free shell model on unstructured grids

Kim, T.; Malipeddi, A. R.; Capecelatro, J.; Figueroa, A.

2026-05-19 bioengineering 10.64898/2026.05.16.725689 medRxiv
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Thin structures such as heart valves and aortic dissection flaps interact dynamically with blood flow in human vessels. Their flexibility and capacity for large deformations generate complex, highly transient hemodynamic patterns over the cardiac cycle. Accurately resolving these interactions remains challenging for conventional boundary-fitted fluid-structure interaction approaches. We present an immersed boundary method for simulating thin structures in incompressible flow on unstructured grids. The method couples a stabilized finite element fluid solver with a nonlinear, rotation-free shell formulation through a direct forcing immersed boundary approach. The framework supports both weak (explicit) and strong (implicit) time-coupling strategies, enabling stable simulations over a wide range of solid-to-fluid density ratios. Hydrodynamic forces acting on thin structures are computed from fluid solutions sampled on both sides of the structure, allowing accurate force reconstruction for zero-thickness shells. To our knowledge, this is the first immersed boundary formulation that couples an unstructured finite element fluid solver with a two-dimensional, rotation-free shell model to simulate interactions between thin structures and incompressible flow. Fluid-structure coupling is achieved using predefined finite element shape functions, which provide consistent projection between Eulerian and Lagrangian fields without additional interpolation procedures. The framework is validated using three-dimensional benchmark problems involving thin structures. Then, valve-like model is used to compare strong and weak coupling strategies. Finally, the method is applied to an idealized type-B aortic dissection model. The proposed approach is implemented within the open-source software CRIMSON, a finite element platform for cardiovascular simulation.

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Explainable Advanced Electrocardiography Heart Age Shows Good Reproducibility in Healthy Young Adults

Warrington, C. R.; Al-Falahi, Z.; Premawardhana, U.; Ugander, M.; Green, S.

2026-03-25 cardiovascular medicine 10.64898/2026.03.24.26349147 medRxiv
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Aims: Explainable advanced electrocardiography (A-ECG) can be used to estimate heart age from the standard 12-lead ECG. A-ECG heart age gap (HAG) represents the difference between A-ECG heart age and chronological age. Increased A-ECG HAG is associated with cardiovascular outcomes and can be used to communicate risk. The aim was to investigate whether A-ECG heart age demonstrates acceptable within- and between-session reproducibility. Methods: Healthy adults (n=42, age 23+/-4 years, 52% male) attended up to two sessions ~14 days apart, with 36 participants completing both sessions. During each session, five standard resting 12-lead ECGs were obtained while lying in the supine position with unchanged electrode positions. A-ECG heart age was extracted using dedicated software. Within-session reproducibility was assessed using all five recorded ECGs with coefficient of variation (CV) and a two-way random effects intraclass correlation coefficient (ICC). Between-session reproducibility was assessed using the first recorded ECG of each session with a paired t-test, CV and ICC. A further analysis assessed the reproducibility of the parameters used in the A-ECG heart age regression model. Results: A-ECG heart age showed excellent within-session reproducibility in session one and two (both CV 5.8%, ICC 0.99). A-ECG heart age was slightly lower in session one than two (24.0+/-7.5 vs. 25.5+/-7.8 years, p=0.04) and showed good between-session reproducibility (CV 8.3%, ICC 0.84). All but one parameter used to estimate A-ECG heart age showed acceptable within- and between-session reproducibility (CV<10%). Conclusion: A-ECG heart age demonstrates excellent within-session reproducibility and good between-session reproducibility in healthy young adults.

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Registered Report: Artifact Index for Capacitive Electrocardiography Acquired with an Armchair

Warnecke, J. M.; Baumgärtel, D.; Bollmann, J.; Deserno, T. M.

2026-06-09 health informatics 10.64898/2026.06.03.26353526 medRxiv
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Background Continuous health monitoring enables early detection of diseases and improves therapeutic outcomes. Non-intrusive biosignal sensors, such as capacitive ECG (cECG), offer a practical solution for daily monitoring in private environments, such as smart homes and vehicles. However, artifacts reduce signal quality and compromise reliability. Methods Following a registered report protocol (Warnecke JM et al. Plos One. 2021; 16(7):e0254780), we record data of 44 subjects and develop an artifact index for cECG. We use three signal quality indices (SQIs): the correlation of QRS complexes (corSQI), the R-peak detection consistency (bSQI) and the absolute amplitude ratio (aSQI). Our index classifies overlapping 10s segments with a step-width of 2s into clean or artifact segments. We label a 2s interval as artifacts if all five overlapping segments indicate artifacts. We record cECGs using an armchair with integrated electrodes in a single-arm study involving 44 subjects performing two activities -- reading and watching television (TV); for 11 minutes each. We record a time-synchronized reference ECG with skin electrodes on the chest. To evaluate the artifact index, we compare it with manually generated ground truth. Moreover, we evaluate the clothing materials cotton, linen, jeans, and polyester in 5 subjects. Results Watching TV results in longer, continuously clean signal durations than reading. On average, 88.3% of the signal has a minimum continuous clean duration of 10s, versus 79.8% during reading. All clothing configurations achieve a clean signal duration exceeding 10s. Among the SQI metrics, bSQI performs best, achieving an accuracy of 90.7% and an F1 score of 79.9%. Combining the three SQI metrics in a voting approach improves accuracy to 92.0% and F1 score to 82.1%. Discussion Our artifact index automatically distinguishes clean from artifact cECG segments, promoting health monitoring in unsupervised real-world settings, earlier disease detection, and preventive health management. A limitation is the investigation of only two scenarios (reading and watching TV).

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AutoClip: AI-Guided TEE Semantic Segmentation for TEER A Proof-of-Concept Study

Chen, M.; Li, X.; Yang, K.; Taramasso, M.

2026-06-06 cardiovascular medicine 10.64898/2026.05.29.26354195 medRxiv
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**Abstract** **Background:** Transcatheter edge-to-edge repair (TEER) is an established treatment for mitral regurgitation but remains highly dependent on operator experience and complex transesophageal echocardiography (TEE)-guided intraprocedural imaging. Artificial intelligence (AI)-based semantic segmentation may improve procedural reproducibility and intraprocedural guidance; however, no TEER-specific segmentation framework has been reported. **Objectives:** To develop and evaluate AutoClip, a clinician-driven AI-guided TEE semantic segmentation model designed for simultaneous delineation of mitral valve anatomy and in-vivo TEER device components. **Methods:** A retrospective proof-of-concept study was conducted using 987 intraprocedural TEE frames derived from 10 video clips in 3 patients undergoing MitraClip G4 implantation. Seven semantic labels, including mitral leaflets and device components, were manually annotated using ITK-SNAP. Following standardized preprocessing and region-of-interest extraction, an Attention U-Net architecture was trained frame-wise on bicommissural and corresponding X-plane TEE views. Model performance was assessed using mean intersection-over-union (IoU) and Dice coefficient on an independent test set. **Results:** The Attention U-Net demonstrated improved sensitivity to small device structures compared with conventional U-Net architectures. Preliminary training performance achieved a mean IoU of approximately 0.93, while independent test performance reached a mean IoU of 0.46 across foreground classes. Qualitative assessment demonstrated feasible simultaneous segmentation of mitral leaflets, clip arms, grippers, and delivery shaft during TEER procedures. **Conclusions:** AutoClip represents a proof-of-concept TEER-specific TEE semantic segmentation framework initiated through a clinician-oriented workflow without formal computer science expertise. Although preliminary accuracy remains modest due to limited sample size, this study establishes a reproducible pathway for future AI-assisted intraprocedural guidance systems and larger multicenter development efforts in structural heart interventions.