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Computers in Biology and Medicine

○ Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match Computers in Biology and Medicine's content profile, based on 128 papers previously published here. The average preprint has a 0.16% match score for this journal, so anything above that is already an above-average fit.

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Joint Vector Flow Mapping and Segmentation: Ill-Posedness,Differentiable Bayesian Inference, and Synthetic Vortex-FlowBenchmarks

del Alamo, J. C.; Nguyen, C. M.; Guerrero-Hurtado, M.; Kandasamy, A.; Maidu, B.; Kahn, A. M.; Bermejo, J.; Martinez-Legazpi, P.

2026-09-28 bioengineering 10.64898/2026.09.24.754220 medRxiv
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Vector flow mapping (VFM) reconstructs left-ventricular (LV) blood velocity from color-Doppler echocardiography by combining the measured beamwise component with physical and regularizing constraints. Analysis of the discrete VFM formulation shows that the inverse problem is intrinsically ill posed: the occurrence of singular modes can be predicted from the geometry of the segmented blood-pool domain, the imposed boundary conditions, and the degree of smoothing. These modes can propagate uncertainty along entire transverse bands of the reconstructed velocity field, yet conventional VFM neither quantifies this uncertainty nor allows for correcting the blood-pool segmentation. We introduce Bayesian VFM (B--VFM), a hierarchical framework that jointly infers radial and transverse velocities, a probabilistic blood-pool mask, their spatially resolved uncertainties, and hyperparameters weighting Doppler and segmentation fidelity, mass conservation, boundary conditions, and smoothness. The discretized posterior admits a closed-form gradient and exact Hessian, enabling computationally efficient, gradient-based MAP estimation, sampling, and direct analysis of ill-posed modes. Posterior inference combines Gibbs sampling of conjugate Gamma-distributed hyperparameters with conditional maximum-a-posteriori estimation and a Laplace approximation for the high-dimensional velocity and mask fields. To accommodate systematic departures from planar mass conservation, B-VFM can learn the covariance of the planar divergence residual from an ensemble of flows and incorporate it as a structured model-discrepancy prior. Independent chains converged reproducibly, while covariance priors learned from flow ensembles illustrated how model discrepancies can be incorporated into the inference. B--VFM was evaluated using Lamb-Chaplygin dipoles under ideal conditions and with Doppler corruption, Doppler voids, and segmentation defects, and using the Hicks-Moffatt family of spherical vortices to assess violations of planar mass conservation. The method produced smooth reconstructions, localized uncertainty near unreliable measurements and regions of model inconsistency, and used flow information to correct segmentation errors. Within the tested vortex family, the data-informed planar divergence prior reduced velocity bias and mask distortion. B--VFM thus provides an uncertainty-aware reconstruction method and a flexible foundation for future VFM formulations incorporating additional priors, observations, and physical models. Future work will evaluate the method using clinical data and more complex three-dimensional benchmark flows.

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Removing Redundant Anatomical Inputs Improves Deep Learning-Based Forensic Dental Age and Sex Estimation

Wu, Z.; Shan, W.; Zhang, W.; Kang, Z.; Yang, B.; Liao, Z.; Huang, Z.; Zhang, Y.; Yue, X.

2026-10-08 forensic medicine 10.64898/2026.10.05.26364771 medRxiv
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Age and sex estimation from dental radiographs supports forensic identification and age-dependent legal assessment. Multi-input models may combine global and regional representations, but when these inputs are derived from the same radiograph, they may repeat anatomical information rather than provide complementary signals. We developed HMA-Net, a hierarchical multi-stream anatomical network, together with a task-specific input audit that evaluates whether each candidate representation improves at least one prediction task without materially degrading the other. The model was developed using a retrospective single-centre cohort of 4,293 panoramic radiographs from individuals aged 3-18 years and combined a panoramic-image stream with graph-linked tooth representations. On the held-out test set, the final panoramic-plus-permanent-tooth model achieved a mean absolute age error of 0.51 years and a sex-classification accuracy of 85.2%; 99.4% of age estimates were within 2 years of chronological age. Across three independent training runs, removing the jaw-region stream reduced mean absolute age error from 0.68 +/- 0.01 to 0.52 +/- 0.01 years and increased sex accuracy from 81.3+/- 1.7% to 85.8 +/- 0.8%. Adding 20 deciduous-tooth classes provided no age benefit and reduced sex accuracy by 7.9% relative to the permanent-only representation. The mandibular first molars received the greatest tooth-level attention, and their occlusion impaired both prediction tasks. These findings show that anatomically plausible inputs do not necessarily provide incremental predictive value. Task-specific input auditing can improve joint model performance, reduce input redundancy and preserve anatomically traceable predictions. More broadly, this framework provides a testable approach for selecting correlated inputs in medical-imaging systems in which regional views re-present anatomy already contained in the whole image. Keywords: Forensic odontology; Dental age estimation; Sex classification; Panoramic radiography; Multi-input learning; Anatomical input auditing

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Fibrosis burden and spatial pattern affect left atrial appendage stasis in multi-beat multi-physics simulations

Stöcker, Y.; Augustin, C. M.; Guerrero-Hurtado, M.; Flores, O.; Gonzalo, A.; Telle, A.; Boyle, P.; Akoum, N.; del Alamo, J. C.; Garcia-Villalba, M.

2026-09-28 bioengineering 10.64898/2026.09.26.754330 medRxiv
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Purpose: Atrial fibrosis is associated with thromboembolic risk in atrial fibrillation, but how fibrosis-related contractile impairment alters blood transport in the left atrium (LA) and left atrial appendage (LAA) remains unclear. Prior multi-physics simulations coupled electromechanical (EM) and computational fluid dynamics (CFD) models to show that fibrosis impairs LA function and flow, but were limited to booster-only contraction and could not separate the effects of fibrosis burden from its spatial distribution. Here we examined how fibrosis burden and spatial pattern independently relate to long-term LA and LAA hemodynamics in full-cycle, multi-beat simulations on a common LA anatomy. Methods: Three fibrosis patterns derived from late gadolinium enhancement MRI were considered: one from the patient providing the common anatomy and two from additional patients, with the latter mapped onto the common anatomy via universal atrial coordinates. All three patterns were applied globally at matched burdens of 15.6% and 31.2%, yielding six global-fibrosis cases and a non-fibrotic reference. Two patterns were also confined to the LAA at three local burdens (10%, 25%, and 50%), yielding six LAA-fibrosis cases. A 3D EM model for the LA anatomy was coupled to a 0D circulatory model, so that the simulations resolved the reservoir, conduit, and booster phases. Full-cycle EM-derived wall motion drove subsequent multi-beat CFD simulations. Region-specific emptying fraction (EF), non-dimensional kinetic energy (KE), and the 90th percentile of blood residence time (TR) were evaluated for the LA and LAA. Results: Left ventricular stroke volume remained nearly constant across cases, while increasing global fibrosis burden progressively reduced LA and LAA EF (LA: 36% to 30-31%; LAA: 44% to 28-38%) and monotonically increased LA TR across all patterns. Non-dimensional LA KE showed an approximately quadratic association with LA EF across patterns, whereas LAA KE was more scattered but still increased with LAA EF. In contrast, the relationship between the 90th percentile of LAA TR and LAA EF showed pattern-specific, non-monotonic trends. Conclusions: Fibrosis burden and spatial distribution jointly shape LA and LAA hemodynamics, but through different mechanisms. LAA EF is a robust functional descriptor of chamber-averaged kinetic energy regardless of fibrosis pattern, whereas LAA blood stasis depends additionally on the spatial distribution of fibrosis beyond what bulk emptying fraction predicts. These findings support incorporating imaging-derived fibrosis pattern, and not only burden, alongside functional metrics when assessing thrombogenic risk in the LAA.

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Sensitivity of Pulmonary 4D Flow MRI Biomarkers to Controlled Spatial and Temporal Degradation in a CFD Benchmark

Zubillaga-Unsain, A.; Caballero-Gaudes, C.; Ruiz-Cabello, J.

2026-10-02 bioengineering 10.64898/2026.09.30.755784 medRxiv
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Purpose: To quantify, in a computational fluid dynamics (CFD) benchmark, how spatial degradation, temporal acquisition and noise change the error of plane-based pulmonary-artery flow endpoints. Methods: Twenty-two historical, non-converged CFD simulations (11 geometry families) were voxelised at 2 mm with 80 frames per cycle. Simulations with numerical divergence were excluded, leaving 13 (7 families). Fields were degraded to 4 and 8 mm and with noise, plane waveforms were sampled at 20 phases with one-interval averaging, and errors were computed against the noise-free reference waveform on 66 geometric planes. Family-mean paired differences are reported with t-based 95% confidence intervals under an analysis plan fixed in advance. Results: Spatial degradation from 2 to 4 mm increased full-waveform nRMSE by 0.0032 [0.0021, 0.0043], in 7 of 7 families; cycle-mean flow bias accounted for 23% of the squared error, against 60% at 8 mm. With SNR scaled to voxel volume, the increase was not resolved (0.0002 [-0.0012, 0.0015]). Twenty-phase acquisition increased PI error (0.0223 [0.0214, 0.0233]) and diastolic-trough timing error (0.63 [0.52, 0.74] frames) more than spatial degradation, and its point estimates for these endpoints were larger with every recovery method; the nRMSE ordering and peak timing depended on the recovery method. The implementation of the downsampling operator mattered: an alternative, corner-aligned implementation of the same 4 mm degradation gave a larger spatial effect (nRMSE difference 0.0010 [0.0002, 0.0017]). Conclusion: In this benchmark, a 2 to 4 mm degradation produced a small, consistent, mostly shape-related nRMSE increase that depended on the noise model, whereas 20-phase acquisition changed PI error and trough timing more. The results describe benchmark behaviour, not clinical acquisition requirements.

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Impact of Driving Dynamic Fluctuations of 6DOF-SVC Model Predictions Across Five Real-World Driving Studies

Buchheit, B.; Robin, Y.; Schneider, E. N.; Alayan, M.; Strauss, D. J.

2026-09-22 bioengineering 10.64898/2026.09.18.752352 medRxiv
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Despite the use of technological countermeasures, studies show that the sensory conflict, and thus symptoms of motion sickness such as nausea, cannot be completely prevented while traveling as a car passenger. Accordingly, reliable prediction of motion sickness will represent a possible solution for intelligent vehicles to avoid the abortion of the drive, e.g., through adapted driving strategies or route planning. In previous works, the authors were able to demonstrate an application-oriented parameter set for the popular 6DOF-SVC model to estimate motion sickness incidence (MSI) in passengers with a lowered gaze on a non-driving-related task. In the current study, these parameters were validated and further optimized using five previous conducted motion sickness driving experiments. For the first time, it is also shown that the expected natural MSI fluctuations based on the driving dynamic profile, due to route characteristics or driving style, as well as the variation in experimental determined MSI is approximately 10%. Moreover, findings indicate that the participants appear to have an individual MSI threshold that correlates with their susceptibility to motion sickness, however, this threshold fluctuates too strongly across experiments to be suitable for practical application. As a result, the model can successfully estimate motion sickness risk across the test tracks, however, inaccuracies in the predicted MSI trajectories remain.

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An explainable multimodal framework for exploring depression-associated speech representations in Alzheimer's disease

Hassan, H.; Patel, D.; Aagela, H.; Johnson, A.

2026-10-01 health informatics 10.64898/2026.09.29.26364278 medRxiv
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Depression in Alzheimer's disease (AD) is clinically challenging to characterise because affective and cognitive manifestations frequently overlap with the underlying neurodegenerative condition. This study investigates depression-related speech patterns in AD using an explainable multimodal framework that integrates linguistic and acoustic features from elicited picture-description speech. To address the absence of directly observed depression labels in the target AD cohort, we employ a source-informed cross-dataset transfer strategy. Unsupervised clustering identified two distinct speech sub-phenotypes within the AD cohort. By comparing these unsupervised representations to a depression-labelled source corpus, one cluster demonstrated mathematical proximity (measured via cosine similarity in a shared latent space) to the source depression centroid. We explicitly acknowledge that this proximity reflects geometric similarity in a shared latent space, which may encapsulate overlapping domain characteristics alongside affective variance. To validate the structural integrity and separability of these discovered clusters, a proxy supervised classification task was employed. The retained multimodal artificial neural network (ANN) integrated information from both modalities and achieved 92.73\% cluster separability accuracy. This demonstrates that the representation-derived two-cluster partition was highly learnable on the independent internal hold-out test set; it does not establish clinical validity, longitudinal stability, or diagnostic validity of the identified sub-phenotypes. For interpretability, Shapley Additive exPlanations (SHAP) analysis was utilised to extract feature attributions and organise influential acoustic and linguistic features into a multimodal taxonomy. Furthermore, a Multimodal SHAP Attribution Magnitude (MSAM) score was derived as an exploratory model-based attribution score rather than a clinically validated severity measure. Ultimately, this study provides an interpretable computational baseline for characterising depression-related speech variance in AD, establishing a structural foundation for future prospective validation using independently labelled clinical cohorts.

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Blood Pressure and Heart Rate Stationarity in Predicting TEVAR Response

Alakhdar, A.; Washburn, N.; Pocivavsek, L.; Bohr, N. L.

2026-10-13 cardiovascular medicine 10.64898/2026.10.12.26365335 medRxiv
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Background: Hypertension is a major risk factor for type B aortic dissections and rupture, with guidelines recommending systolic blood pressure (SBP) control below 130 mmHg to improve outcomes. While post-TEVAR blood pressure is often managed with a focus on mean SBP, little is known about temporal hemodynamic patterns and their association with surgical success. This study investigates blood pressure and heart rate (HR) time-series metrics within 24 hours post-TEVAR and their predictive potential for outcomes. Methods: Blood pressure (n = 560) and HR (n = 680) time-series data from 31 patients were analyzed alongside preoperative aortic geometry metrics. Exploratory data analysis identified correlations between BP variability and outcomes. Stationarity tests were performed on time-series data to assess statistical properties. Logistic regression models incorporating hemodynamic metrics, along with CT-derived features, were used to predict TEVAR outcomes. Results: Successful outcomes correlated with greater diastolic blood pressure variability and strictly stationary SBP. Logistic regression models combining these metrics along with heart rate standard deviation and preoperative aortic geometry achieved 96.67% 5-fold cross-validation accuracy in predicting outcomes. Conclusion: Post-TEVAR behaviors of hemodynamic variables are critical predictors of TEVAR success, with higher DBP standard deviation and strict stationarity of SBP significantly associated with favorable outcomes. These findings highlight the importance of hemodynamic variability and stationarity in optimizing post-TEVAR patient care.

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A Multi-Domain EEG Framework Integrating Spectral, Functional Connectivity, and Topological Features for Subject-Level ADHD Classification

Rohani, F.; Mostafavi, S.; Ebrahimifakhar, P.; Zomorrodi, R.; Mueller, A.

2026-10-11 health informatics 10.64898/2026.10.08.26365043 medRxiv
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Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity, and impulsivity that significantly affect cognitive, academic, and social functioning. Although electroencephalography (EEG) has emerged as a promising non-invasive tool for identifying objective neurophysiological biomarkers of ADHD because of its high temporal resolution and cost-effectiveness, many existing machine learning studies rely on single-domain EEG features, which may not adequately capture the complex functional organization of the brain. Methods: This study proposes a subject-level EEG classification framework that integrates three complementary feature domains: spectral characteristics, weighted Phase Lag Index (wPLI)-based functional connectivity, and topological descriptors derived from persistent homology. EEG recordings from 121 subjects were preprocessed and segmented into overlapping windows for feature extraction. Window-level features were aggregated to generate subject-level representations. Recursive Feature Elimination (RFE) was employed to select the 110 most informative features from an initial set of 1,043 descriptors. Five machine learning classifiers, including Support Vector Machine (SVM), Random Forest, XGBoost, CatBoost, and Multi-Layer Perceptron (MLP), were evaluated using stratified five-fold cross-validation. An ablation study was further conducted to assess the contribution of each feature domain. Model interpretability was investigated using SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME), two widely adopted Explainable Artificial Intelligence techniques for interpreting machine learning models. Results: Among the evaluated classifiers, the SVM achieved the highest classification performance, yielding an accuracy of 80.17%, an F1-score of 80.95%, a balanced accuracy of 80.14%, a receiver operating characteristic area under the curve (ROC-AUC) of 86.72%, and a precision recall area under the curve (PR-AUC) of 87.34%. The ablation study demonstrated that combining spectral, functional connectivity, and topological features consistently outperformed individual feature domains, highlighting the complementary nature of these representations. Explainable AI analyses further identified functional connectivity features as the primary contributors to classification performance while confirming the additional value of spectral and topological descriptors. Conclusions: The proposed framework demonstrates that integrating spectral analysis, functional connectivity, and topological data analysis provides an effective and interpretable approach for subject-level ADHD classification from EEG recordings. The combination of recursive feature selection, multi-domain feature fusion, ablation analysis, and Explainable Artificial Intelligence establishes a transparent and reproducible pipeline that may facilitate the development of reliable EEG-based clinical decision-support systems for ADHD.

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Clinically Translatable Uncertainty Aware Machine Learning for Cardiovascular Disease Risk Analysis

Roy, S.; Imran, R.; Haque, M. R.; Mostafa, F.

2026-09-23 health informatics 10.64898/2026.09.18.26363375 medRxiv
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ImportanceCardiovascular disease remains the leading cause of mortality worldwide. Although machine learning models have demonstrated strong predictive performance, limited attention has been given to uncertainty quantification and gender-specific risk factor identification, which are essential for clinically trustworthy artificial intelligence. ObjectiveTo develop and evaluate an interpretable and uncertainty-aware machine learning framework for cardiovascular disease prediction that integrates an association study on biomarkers, explainable artificial intelligence, and gender-stratified risk assessment. Design, Setting, and ParticipantsThis retrospective observational study utilized the UCI Heart Disease dataset comprising 918 participants, including 725 males and 193 females. Demographic, clinical, laboratory, and exercise-related variables were analyzed. Missing values were addressed using a hybrid imputation strategy combining MICE and supervised Random Forest imputation. MethodsAn ensemble machine learning imputation strategy was developed to address missingness. Then advanced machine learning models were developed and evaluated using stratified training/testing partitions and 5-fold cross-validation. Predictive performance was assessed using several evaluation metrics. Uncertainty was quantified through bootstrap resampling, predictive entropy, and mutual information. Linear Double machine learning and Causal Forest double machine learning were applied to estimate gender-specific averages and association studies for risk factors. ResultsRandom Forest achieved the strongest and most stable predictive performance across male and female cohorts, with ROC-AUC values exceeding 0.90 and robust cross-validation performance. Hybrid imputation improved classification performance, increasing the F1-score from 0.87 to 0.89 and ROC-AUC from 0.90 to 0.92. The causal association study analyzes identified the number of major vessels, ST-segment slope, thalassemia, and exercise-induced angina as the strongest determinants of heart disease, with notable differences observed between male and female subgroups. Conclusions and RelevanceIntegrating predictive modeling, uncertainty quantification, and association study machine learning provides a robust and clinically interpretable framework for cardiovascular disease risk assessment. The proposed approach improves prediction reliability while identifying gender-specific causally important risk factors, supporting precision cardiovascular medicine and trustworthy clinical artificial intelligence.

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Left Ventricular Diastolic Intraventricular Pressure Differences and Propagation Velocity with 4D-Flow MRI in Patients with Hypertrophic Cardiomyopathy

Stipechi, L. V.; Craiem, D.; Gencer, U.; Casciaro, M. E.; Hulot, J.-S.; Hagege, A.; Soulat, G.; Mousseaux, E.

2026-10-21 cardiovascular medicine 10.64898/2026.10.15.26365692 medRxiv
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Background: Transthoracic echocardiography (TTE) remains the gold standard for assessing left ventricular (LV) diastolic dysfunction (DD), but noninvasive alternatives are needed to overcome geometric and acoustic limitations. 4D-Flow MRI enables comprehensive assessment of intraventricular pressure differences (IVPDs) and flow propagation velocity (VP). We aimed to evaluate 4D-Flow-derived IVPDs and VP in patients with hypertrophic cardiomyopathy (HCM). Methods: Thirty-eight HCM patients and 38 age- and sex-matched healthy controls underwent TTE and 4D-Flow MRI. Spatiotemporal maps of velocity and IVPDs, decomposed into inertial and convective components, were derived along the main inflow streamline from the mitral valve to the apex. Peak early filling rate (PEFR) was used to normalize IVPDs and VP. Results: While absolute peak flow rates were comparable, HCM patients exhibited significantly faster VP (100.4 vs. 60.2 cm/s, p < 0.01) and higher positive early E IVPD (1.40 vs. 0.92 mmHg, p < 0.01) compared to controls. Normalizing IVPDs by PEFR amplified group differences, revealing a markedly increased flow-normalized E-IVPD (5.13 vs. 2.94 x 103 mmHg.ml1.s, p < 0.001) and deeper reverse ER IVPD (-6.06 vs. -4.61 x 103 mmHg.ml1.s, p < 0.01) in HCM. These differences were primarily driven by the inertial components. Multivariable analysis demonstrated that ER IVPD is independently determined by PEFR and the TTE E/E' ratio (r = 0.65, p < 0.001). Conclusions: 4D-Flow MRI-derived, flow-normalized IVPDs and propagation velocity provide robust, noninvasive markers of altered LV chamber stiffness and impaired diastolic filling in HCM, offering deeper 3D hemodynamic insights into diastolic dysfunction.

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PhysioFusion: A Multi-Modal Ensemble using Static Preoperative Variables and Time Series Intraoperative Data to Predict Adverse Events Following Cardiothoracic Surgery

Korutla, R.; Hicks, A.; Milosevic, M.; Kulkarni, D.; Mazhude, F.; Kelting, T.; Rabb, J. B.; Jin, Q.; Kramer, R.; Sawyer, D.; Winslow, R. L.; Amal, S.

2026-09-28 health informatics 10.64898/2026.09.24.26363920 medRxiv
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Accurate prediction of adverse events in the intensive care unit (ICU) following cardiothoracic surgery is crucial for timely interventions, improving patient outcomes and optimizing value in healthcare. By leveraging advanced machine learning techniques, this study demonstrates the transformative potential of predictive analytics to enhance postoperative care using a dataset from the Society of Thoracic Surgeons' (STS) database and time-series intraoperative data. We developed a multi-modal late fusion approach integrating static patient variables with intraoperative time-series data, utilizing an ensemble of models including residual neural networks for static features, CNN and Bidirectional GRU for time-series processing, XGBoost, logistic regression, SVM and Gradient Boosting. Through five-fold cross-validation, our ensemble model with balanced threshold selection achieved an AUC of 0.87, sensitivity of 0.76, specificity of 0.83, PPV of 0.40, and NPV of 0.96. Preoperative heart failure, IABP insertion, cardiopulmonary bypass (CPB) duration and white blood cell (WBC) count emerged as key predictors. Training the same pipeline on each modality separately showed that the static registry variables alone reached the same AUC of 0.87, and that the intraoperative signals alone reached 0.83, so on this cohort the two modalities act as substitutes rather than complements and fusion changed the sensitivity and precision trade-off rather than the amount of separable signal. A per-signal ablation found that no individual monitoring channel was load bearing, with mean arterial pressure and central venous pressure the least substitutable. This balanced approach optimizes the trade-off between sensitivity and specificity, providing a screening tool with high negative predictive value for monitoring high-risk patients, and the modality comparison indicates that comparable performance is attainable at sites holding registry data alone.

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A Semi-Automated Interactive Annotation Framework for Intraoperative Neurosurgical Ultrasound: A Proof-of-Concept Study

Bertani, R.; Bahadir, S.; Ferreira, M. Y.; Campos Cardoso, L. J.; Thomas, G.; Ben-Shalom, N.

2026-10-05 radiology and imaging 10.64898/2026.10.03.26364663 medRxiv
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Objectives: Intraoperative ultrasound (IOUS) is an increasingly valuable real-time imaging modality in neurosurgery, enabling visualization of brain parenchyma, tumor margins, ventricular anatomy, and vascular structures during cranial procedures. Despite its clinical relevance, the development of artificial intelligence (AI)-assisted interpretation tools for neurosurgical IOUS has been limited by the scarcity of large, annotated datasets. Manual pixel-level annotation of ultrasound video frames is labor-intensive, requires specialized neuroanatomical expertise, and scales poorly. To address this bottleneck, we developed a proof-of-concept interactive semi-automated annotation pipeline designed to explore the feasibility of scalable, expert-guided labeling for intraoperative neurosurgical IOUS. Methods: We implemented the system as a napari-based graphical interface coupled with a scikit-learn Random Forest (RF) pixel classifier. Real intraoperative neurosurgical ultrasound videos from five craniotomy cases were used as training material. A neurosurgical expert annotated a minimal set of representative frames using brush-based labeling to define anatomical classes of interest. For each labeled pixel, a feature vector was computed comprising raw intensity, multi-scale Gaussian filtering ({sigma} = 1, 2, 3), Laplacian of Gaussian, and Sobel edge magnitude. The RF classifier was trained on accumulated annotations using class-balanced weighting and out-of-bag (OOB) validation, then applied across full video sequences. An incremental accumulator module enabled multi-case training. Segmentation outputs were exported as TIFF overlays for expert quality review. Results: Across five intraoperative cases, sparse expert annotation of a small number of representative frames per case was sufficient to train case-specific Random Forest classifiers that propagated labels across the full video sequences. Out-of-bag estimation served as an internal coherence check during training, and the classifier additionally produced per-class probability maps that exposed regions of uncertainty at acoustic boundaries. On expert qualitative review, the auto-segmented frames were anatomically coherent, with the classifier reliably distinguishing anechoic fluid compartments from echogenic tissue interfaces; residual misclassification was concentrated in low-contrast boundary regions. Conclusions: This proof-of-concept study demonstrates that semi-automated, expert-guided annotation of intraoperative neurosurgical ultrasound is technically feasible using classical machine learning. By combining neurosurgical domain expertise with an interactive, incremental annotation workflow applied to real intraoperative acquisitions, this framework represents a foundational step toward scalable generation of labeled datasets for neurosurgical IOUS. Future directions include formal multi-rater validation, expanded multi-class anatomical labeling, and eventual migration to deep learning architectures as annotated datasets grow.

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HMVA-DDI: A Hierarchical Multi-View Attention Network for Drug-Drug Interaction and Severity Prediction

Hati, B.; Bhat, R.; Kudari, Z. D.; Kaira, V. S.; P, S. S.; Gnana Sekaran, J.

2026-10-01 bioinformatics 10.64898/2026.09.25.754374 medRxiv
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Background and Objective: Prescribing multiple drugs simultaneously, known as polypharmacy, is increasingly common in managing chronic diseases such as diabetes and cardiovascular conditions. Studies show that roughly 40% of elderly patients are on five or more medications, putting them at significant risk of adverse drug-drug interactions (DDIs) [1]. While computational methods based on Graph Neural Networks (GNNs) have shown strong potential for predicting these interactions from a drugs molecular structure, most existing models are limited in two important ways: they rely on attention mechanisms that cannot adapt to the unique context of each atom in a molecule, and they only predict whether an interaction exists rather than how dangerous it might be. Methods: We propose HMVA-DDI, a two-stage deep learning framework that addresses both shortcomings. In the first stage, our model predicts whether two drugs will interact. If it detects an interaction, the second stage classifies it into one of three clinical severity levels: minor, moderate, or major. To better capture molecular structure, we replace the standard attention mechanism with a more powerful version called Graph Attention Network v2 (GATv2), which considers each atoms specific context when learning its representation. We also introduce a technique to prevent information loss in deeper network layers, and we tailor the input features separately for each prediction task. Results: Evaluated on two standard benchmarks, DrugBank 5.0.3 [2] and DDInter [3], HMVA-DDI achieves an AUROC of 0.9819 and AUPRC of 0.9759 on binary interaction detection, a marked improvement over the baseline. For severity classification, our best model variant (qcSvr4) reaches an overall AUROC of 0.9444, with a particularly large improvement in detecting low-severity (Minor) interactions, a historically difficult class. Conclusion: HMVA-DDI bridges the gap between computational drug research and clinical usefulness by not only predicting interactions accurately but also indicating interaction severity. This two-level system can help healthcare professionals prioritize warnings, reducing the alert fatigue problem where doctors are overwhelmed by too many non-critical notifications.

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Neuropathological Features of Fatal Electrocution: A Histopathological Study for Cause-of-Death determination

Rastogi, A. K.; Kumar, A.; Nangelil, D. D.; Paikra, s. K.; Dhokne, M. D.; Reddy, Y. M.; Wankhade, T. D.; Kumar, R.

2026-09-28 forensic medicine 10.64898/2026.09.21.26363180 medRxiv
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Background: Determining the cause of death in electrocution is often challenging at autopsy, particularly when characteristic external electrical marks are absent. Reliable internal markers are scarce, and the neuropathological changes associated with electrocution remain underexplored. Objective: To identify and characterize histopathological alterations in the brain in cases of fatal electrocution and evaluate their diagnostic utility. Methods: A prospective observational study was conducted on 12 autopsy cases, including 7 confirmed electrocution deaths and 5 non-electrocution deaths (control). Brain tissue samples from multiple regions were processed using H&E and Golgi Cox staining. Histopathological parameters, including neuronal morphology, vascular changes, haemorrhage, and dendritic architecture, were evaluated. Results: Electrocution cases demonstrated neuronal destruction, axonal ballooning, focal hemorrhages, and dendritic disruption. Cerebellar involvement with Purkinje cell damage. Conclusion: Comprehensive neurohistological technique may helpful in evaluation neuronal damage in electrocution death. Neuropathological findings, particularly neuronal and dendritic injury, may serve as supportive evidence in determining cause of death when external signs are absent. Keywords: Electrocution, Neuropathology, Golgi Cox stain, Forensic histopathology, death.

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Unifying Vision and Language: Benchmarking End to End Transformer Model Against the ClipCap Framework

Anand, S.; M S, D.; Dekker, A.; Wee, L. Y.

2026-09-27 radiology and imaging 10.64898/2026.09.24.26363914 medRxiv
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Background and purpose: Accurate identification of cardiac MRI volume orientations is essential for reliable image interpretation and for enabling downstream automated analysis pipelines. However, orientation labels and commonly assigned manually, making the process time-consuming and prone to variability. Recent advances in vision-language models offers new opportunities for automated label generation by jointly modeling visual and semantic information. Methods: In this study, we systematically compare a conventional end-to-end transformer-based captioning model with a CLIPCap architecture for automated cardiac MRI view labelling. Both models were evaluated on a dataset of 1184 de-identified cardiac MR images spanning across six clinically relevant orientations: short axis, two-, three-, four-chamber views, left and right ventricular outflow tract views. The caption transformer was trained from scratch, whereas CLIPCap leveraged pretrained CLIP image embeddings combined with lightweight mapping network and a frozen language model. Results: Experimental results demonstrate a substantial performance advantage from CLIPCap, which achieved an overall accuracy of 98% compared to 68% for the caption transformer. CLIPCap consistently delivered high precision and recall across all orientation classes, including those of high clinical importance, while the end to end transformer exhibited unstable performance and complete failure in certain views. Conclusion: These findings highlight the benefits of leveraging large scale multimodal pretrained model for medical image labeling tasks, particularly in data limited settings. The study suggests that CLIPCap provides a more robust and clinically reliable solution for automated cardiac MRI orientation labeling, supporting its integration into efficient and scalable clinical workflows.

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Biomarker-Aware Super-Resolution for 4D Flow MRI in a Synthetic Pulmonary-Artery Benchmark

Zubillaga-Unsain, A.; Lluveras-Sires, A.; Caballero-Gaudes, C.; Ruiz-Cabello, J.

2026-09-28 bioengineering 10.64898/2026.09.25.754495 medRxiv
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Purpose: To evaluate, within a synthetic pulmonary-artery benchmark, whether biomarker-aware super-resolution improves hemodynamic endpoint fidelity in 4D flow MRI. Methods: A 3D residual channel attention network (RCAN) was trained on 22 CFD simulations from 11 pulmonary-artery geometries with 2x spatial degradation. The original primary comparison evaluated full biomarker-aware training against a combined divergence-temporal-regularization control across 14 matched seeds on a fixed six-case test set. Additional matched analyses subsequently separated divergence and adjacent-frame temporal-difference regularization and evaluated biomarker supervision in a controlled 2x2 design with a common reconstruction schedule. Results: In the original primary comparison, biomarker-aware training reduced PI error relative to the matched combined-regularization control (12.76 +/- 2.34% vs. 17.12 +/- 1.23%; paired difference -4.35 percentage points [95% CI -5.58, -3.09]; p = 0.0015). In the matched factorial analysis, biomarker supervision reduced PI error without (-2.235 percentage points [95% CI -3.514, -0.849]) and with (-4.125 percentage points [95% CI -5.392, -2.732]) combined regularization. PI improvement was not mirrored by uniformly improved reconstruction metrics: PSNR changed by -0.058 (p = 0.50) and +0.144 dB (p = 0.28), while SSIM decreased by 0.009 (p = 0.004) and 0.007 (p = 0.009), respectively. Divergence alone changed PI by +0.034 percentage points [95% CI -0.705, 0.809] while reducing DivRMS by 1.869 percentage points; temporal-difference regularization increased PI error by 1.562 percentage points [95% CI 0.594, 2.439]. Conclusion: Within this synthetic, fixed-case RCAN benchmark, biomarker supervision improved PI under both regularization conditions. PI improvement was not mirrored by uniformly improved reconstruction metrics. Temporal-difference - not divergence - regularization was the only isolated component associated with reproducible PI deterioration. These findings are configuration-specific and require geometry-independent and in vivo validation.

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Modeling aroma release during in vivo food oral processing using digimouth

Peltier, C.; Mourabit, O.; Andriot, I.; Coulibaly, K.; Trelea, I. C.

2026-10-07 systems biology 10.64898/2026.10.01.755679 medRxiv
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The perception of flavor during food consumption is a complex process governed by the dynamic release of aroma compounds, which is influenced by the interaction between the food matrix and human physiology. While mechanistic models have been developed to simulate these phenomena, their practical application has often been limited by the lack of flexible software tools capable of integrating diverse food structures and real-time physiological data. This study addresses this gap by incorporating in vivo mechanistic models for both liquid foods and melting solid matrices in a modular Python-based framework: digimouth. The modeling approach treats the oral, pharyngeal, and nasal cavities as a series of interconnected reactors with mass transfer governed by ordinary differential equations (ODEs). These models explicitly integrate key physiological parameters, including salivary flow, bidirectional respiratory airflow, and discrete events such as mastication and swallowing. For solid foods, the framework incorporates additional mechanisms for matrix dissolution, temperature-dependent melting, and dynamic surface area change. The models were validated using experimental data from 30 subjects who consumed aroma solutions and flavored gelatin gummy discs while monitored by PTR-MS (Proton Transfer Reaction - Mass Spectrometry). The simulations successfully reproduced the main kinetic features and release profiles observed experimentally for both types of matrices. Despite some limitations related to the self-reporting of physiological events and the non-inclusion of initial orthonasal mass transfer in the models, the developed software package proved to be a robust and evolutive tool. It offers a foundation for exploring inter-individual variability and the impact of complex food structures on sensory perception.

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Cardiac MRI at 3.0T in the presence of implantable cardioverter defibrillators (ICDs)

Reiter, T.; Weber, O. M.; Weiss, i.; Kraus, N.; Kress, S.; Bauer, W. R.

2026-10-21 cardiovascular medicine 10.64898/2026.10.16.26364740 medRxiv
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Patients with implantable cardioverter-defibrillators (ICDs) often are excluded from receiving CMR scans at 3.0T due to ICD-induced image artifacts. This work aims to transfer sequence protocols established for CMR imaging in the presence of ICDs at 1.5T to a first human application at 3.0T. All measurements were performed on a clinical 3T MRI scanner. Phantom measurements were used to establish and optimize wideband PSIR LGE imaging at 3.0T. Volunteer measurements with externally placed ICDs were used for optimization of CINE imaging and wideband PSIR imaging. Thirdly, patients with implanted ICD were examined with the optimized protocols. Human measurements showed that SA stacks obtained with spoiled GRE after contrast agent showed a markedly lower artifact burden than the conventional approach. For scar imaging, a wideband PSIR with a bandwidth of 3kHz and a frequency offset of +750Hz allowed a sufficient suppression of relevant artifacts in the majority of scans. No strong correlation between the image quality and the distance between the cardiac silhouette and the device was detected. The presented work shows the feasibility of clinical cardiac MRI at 3.0T including GRE-CINE and wideband PSIR-LGE for patients with ICDs.

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Self-supervised pretraining for dermoscopic lesion segmentation with limited labels: A controlled comparison of initialisation strategies

Hamda, H. K. H.; Mustafa, S.; Khalili Moghaddam, G.

2026-10-15 dermatology 10.64898/2026.10.14.26365443 medRxiv
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Background: Self-supervised learning may improve segmentation when labelled data are limited, but its benefit may depend on model and initialisation strategy. This study evaluated in-domain masked-reconstruction pretraining across limited annotation budgets. Methods: The International Skin Imaging Collaboration (ISIC) 2016 development set was partitioned into 765 images for self-supervised pretraining, 94 for fine-tuning and 41 for validation. Five nested annotation budgets (12-94 images) and five seeds were evaluated on the 379-image test set. A custom U-Net compared random and in-domain self-supervised initialisation; a ResNet-34 U-Net compared random, ImageNet, in-domain self-supervised and sequential ImageNet-to-self-supervised initialisation. Models trained with 94 labelled images were evaluated without adaptation on ISIC 2017. A separate experiment examined restoration-based pretraining. Results: In the custom U-Net, self-supervised pretraining achieved higher mean Dice than random initialisation at all five budgets, including 0.664 versus 0.615 with 12 labels and 0.811 versus 0.768 with 94 labels. Seed-level 95% confidence intervals for paired differences excluded zero at 47 and 94 labels but not at the other budgets. With 47 labels, the self-supervised model achieved mean Dice of 0.789, compared with 0.768 for random initialisation with 94 labels. In ResNet-34, ImageNet initialisation achieved higher mean Dice than in-domain self-supervised pretraining at all five budgets, and adding self-supervised pretraining after ImageNet reduced mean Dice at four of five budgets. All six 94-label configurations achieved lower mean Dice on ISIC 2017 than ISIC 2016. In the restoration experiment, mean Dice was 0.686 with random initialisation and 0.638-0.642 following pretraining. Conclusions: In-domain masked-reconstruction pretraining improved mean Dice relative to random initialisation in the custom U-Net, but not consistently in the ResNet-34 U-Net, where ImageNet initialisation performed better at every budget. Adding self-supervised pretraining after ImageNet provided no consistent gain. These findings are specific to the dermoscopic lesion-segmentation experiments and do not establish melanoma-specific diagnostic or clinical performance.

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Right Versus Left Ventricular Myofiber Orientation in Various Congenital Heart Diseases Analyzed with X-Ray Phase-Contrast Tomography

Matsushima, S.; Hoshino, M.; Shinohara, G.; Shiraishi, S.; Hirata, Y.; Tsukube, T.; Oshima, Y.; Matsuhisa, H.

2026-10-06 cardiovascular medicine 10.64898/2026.10.01.26364061 medRxiv
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BACKGROUND: While the systemic right and left ventricles have different functional prognoses, only a limited number of reports have addressed their myocardial architecture. This study analyzed myofiber orientation of human specimens with various congenital heart diseases using X-ray phase-contrast tomography. METHODS: Three specimens of each normal heart, ventricular septal defect, right atrial isomerism, left atrial isomerism, and ventricular inversion were examined. In reconstructed images of both ventricles, the center of the free wall was resliced parallel to the myocardial surface. A myofiber helical angle was identified in each slice and plotted from epicardium to endocardium. The plotted curves were compared between both ventricles. RESULTS: In all ventricles, the helical angle was changed from left-handed on epicardial slices to right-handed on endocardial slices. Whereas the right ventricle?s helical angle curves showed a plateau with or without a rapid rise on the endocardial side, the left ventricle?s curves had sustained increase with or without a plateau in the middle. The median wall-thickness?scaled helical angle change rates were 53{degrees} and 102{degrees} in the right and left ventricle, respectively, and their distribution of each specimen was higher in the left ventricle than in the right ventricle. CONCLUSIONS: Ventricular myofiber orientation has a consistent transmural helical transition independently of cardiac morphology and looping. Their transitions can have a plateau and rapid changes permitting the identification of layers within the ventricular wall. The left ventricle has more helical fibers and the right ventricle has more circumferential fibers, which may explain their difference of ventricular performance.