Computer Methods and Programs in Biomedicine

The present study presents a systematic approach for generating data-driven synthetic cerebral aneurysm geometries and evaluating their hemodynamics through computational fluid dynamics. Seven patient-specific aneurysm geometries from the right internal carotid artery were reconstructed from time-of-flight magnetic resonance angiography images and standardized through orientation alignment, followed by non-rigid registration onto a common spherical point cloud as a template. Principal component analysis (PCA) was then applied to the aligned point-cloud data to quantify morphological variability and parameterize shape deformation. The first four principal components captured over 90% of the total variance; however, higher-order components were required to capture the detailed geometrical features of the original geometries. Computational fluid dynamic simulations were performed on the PCA-based synthetic geometries under pulsatile flow conditions to investigate the influence of shape variations on intra-aneurysmal flow patterns, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI). The first principal component score (PCS1), which was associated with changes in aneurysm height and dome width, had the strongest effects on TAWSS and OSI levels. Lower PCS1 values, which corresponded to taller and more oblique domes, produced slower adjacent flow and elevated OSI, whereas higher PCS1 values increased TAWSS. The second principal component score primarily modulated lateral geometric asymmetry and further influenced OSI distribution for the lower PCS1 values. Collectively, these findings indicate that PCA-based shape parameterization provides a practical approach for generating synthetic aneurysm datasets and systematically assessing how specific morphological features govern hemodynamic behavior. The proposed approach is expected to contribute to the future development of surrogate modeling and data-driven hemodynamic prediction.

Computational growth and remodeling (G&R) models have been extentively used to investigate abdominal aortic aneurysm (AAA) progression and to support clinical decision-making. However, the development of robust predictive models is often limited by the scarcity of large-scale longitudinal imaging datasets. In this study, we propose a physics-based G&R framework to simulate AAA shape evolution and generate a virtual cohort of aneurysms, thereby addressing data limitations and enabling integration with data-driven machine learning approaches for growth prediction. The proposed arterial G&R model incorporates key mechanisms influencing aneurysm progression, including elastin degradation and stress-mediated collagen production. A modified elastin degradation formulation was introduced to generate realistic aneurysm geometries exhibiting clinically relevant features such as asymmetry and tortuosity. By systematically varying parameters governing elastin damage and collagen production, 200 distinct G&R simulations were performed to produce a diverse set of AAA geometries. The dataset was further expanded using kriging-based spatial interpolation to construct a large in silico cohort. The synthetic dataset, combined with longitudinal imaging data from 25 patients, was used to train and validate four machine learning models: Deep Belief Network (DBN), Recurrent Neural Network (RNN), Long Short-Term Memory (LSTM), and Gated Recurrent Unit (GRU). A two-step training strategy was adopted to predict maximum aneurysm diameter and growth rate based on prior geometric characteristics. The LSTM model achieved the highest performance for maximum diameter prediction (R{superscript 2} = 0.92), while the RNN demonstrated strong overall performance (R{superscript 2} = 0.90 for maximum diameter and 0.89 for growth rate). The DBN and GRU models also showed competitive predictive capability. Overall, this study demonstrates that integrating physics-based G&R simulations with machine learning enables accurate prediction of AAA growth and maximum diameter. The proposed framework provides a scalable strategy for augmenting limited clinical datasets and offers a promising tool to support personalized risk assessment and treatment planning.

I.AO_SCPLOWBSTRACTC_SCPLOWCoronary Artery Disease (CAD) is a leading cause of cardiovascular-related mortality and affects 20.5 million people in the United States and approximately 315 million people worldwide in 2022. The asymptomatic and progressive nature of CAD presents challenges for early diagnosis and timely intervention. Traditional diagnostic methods such angiography and stress tests are known to be resource-intensive and prone to human error. This calls for a need for automated and time-effective detection methods. In this paper, this paper introduces a novel approach to the diagnosis of CAD based on a Convolutional Neural Network (CNN) with a temporal attention mechanism. The model will be developed on an architecture that will automatically extract and emphasize critical features from sequential medical imaging data from coronary angiograms, allowing subtle signs of CAD to be easily spotted, which could not have been detected by convention. The temporal attention mechanism strengthens the ability of a model to focus on relevant temporal patterns, thus improving sensitivity and robustness in detecting CAD for various stages of the disease. Experimental validation on a large and diverse dataset demonstrates the efficacy of the proposed method, with significant improvements in both detection accuracy and processing time compared to traditional CNN architectures. The results of this study propose a scalable solution system for the diagnosis of CAD. This proposed system can be integrated into clinical workflows to assist healthcare professionals. Ultimately, this research contributes to the field of AI-driven healthcare solutions and has the potential to reduce the global burden of CAD through early automated detection.

Abdominal aortic aneurysms (AAA) affect more than 1% of adults over 50 and carry significant mortality risk. Current surveillance relies on intermittent imaging (ultrasound or MRI) at 6-24 month intervals, which may miss rapid growth acceleration between visits. We investigate the feasibility of continuous aneurysm diameter tracking using photoplethysmography (PPG) signals. Using a one-dimensional hemodynamic model that simulates pulse wave propagation from the heart to the digital artery, we demonstrate that while single-observation diameter estimation is fundamentally limited by noise and confounding variables, aggregating thousands of observations over one or more days may achieve sub-millimeter precision. Specifically, the lower bound error analysis shows diameter uncertainty decreases to 0.7 mm with 1,600 measurements under baseline noise conditions. We validate this approach through 12- month tracking simulations of eight virtual patients with constant and accelerating growth rates, achieving root-mean-square tracking errors of [~]0.3 mm. Furthermore, we demonstrate that patient-specific model calibration from clinical measurements, despite yielding imperfect parameter estimates, still enables accurate diameter tracking (median RMSE = 0.49 mm across 50 virtual patients). These results suggest that wearable PPG monitoring could complement traditional imaging for aneurysm surveillance, potentially enabling earlier detection of growth acceleration and more timely clinical intervention. Data and Code AvailabilityAll data produced in the present study and code for generating said data are available upon reasonable request to the authors. Institutional Review Board (IRB)This research does not require IRB approval since it is not "human subjects research" as it does not include activities that involve interaction with individuals or access to identifiable private information.

Background and ObjectiveThe dysbiosis of human gut microbiome has been increasingly seen to have a relation in the development of autoimmune diseases, with specific microbial signatures having causative association with specific conditions. Inflammatory bowel disease (IBD) is one such autoimmune ailment. This paper proposes a predictive tool that can identify the IBD status of an individual based on the composition of the gut microbiome using machine learning and AI agents driven techniques. The technology can strengthen the suspicion of a potential IBD diagnosis a patient may have based on their gut microbiome profile. MethodsThe tool processes patient gut metagenome using integrated Kneaddata and MetaPhlAn to generate taxonomic profiles. These are fed into an XGBoost classifier to predict IBD or healthy status. Dysbiotic taxa are identified via Z-score and fold change. CrewAI delivers personalized probiotic recommendations based on diagnosis and dysbiosis. ResultsThe tuned XGBoost model achieved 86.6% accuracy. On validation using single ulcerative colitis sample, the tool correctly predicted IBD status but misclassified it as Crohns disease(possibly due to overlapping microbial signatures), identifying Faecalibacterium and Flavonifractor as dysbiotic taxa.The probiotic recommended was Faecalibacterium prausnitzii, backed with reasoning basedon scientific literature. ConclusionsDespite limited validation sample size, the high accuracy, correct IBD detection, dysbiosis analysis and elaborate probiotic recommendation suggest promising potential; further validation needed

Handheld ultrasound devices have revolutionized point-of-care diagnostics, but their effectiveness remains limited by operator dependency and the need for specialized training. This paper presents an intelligent guidance and diagnostic assistance system for the handheld wireless ultrasound device, enabling automated carotid artery and thyroid examinations through handheld operation. Drawing inspiration from the Actor-Critic framework, we implement a simulation-based reinforcement learning approach for real-time probe navigation toward standard anatomical views. The system integrates YOLOv8n-based detection networks for carotid plaque and thyroid nodule identification, achieving real-time inference at 30 frames per second. Furthermore, we propose a hybrid measurement approach combining UNet segmentation with the Snake algorithm for precise biometric quantification, including carotid intima-media thickness (IMT), lumen diameter, and lesion dimensions. Experimental validation on clinical datasets demonstrates that the proposed system achieves 91.2% accuracy in standard plane acquisition, 87.5% mean average precision (mAP) for plaque detection, and 89.3% mAP for nodule identification. Measurement results show excellent agreement with expert sonographers, with IMT measurements exhibiting a mean absolute difference of 0.08 mm. These findings demonstrate the feasibility of intelligent handheld ultrasound examination, significantly reducing operator dependency while maintaining diagnostic accuracy comparable to experienced clinicians.

Current clinical risk stratification for thoracic aortic aneurysms (TAA) relies primarily on maximum diameter, which is a poor predictor of rupture. Recent fluid-structure interaction studies have identified a dimensionless "flutter instability parameter" (N{omega} ) that accurately classifies abnormal aortic growth. However, this parameter currently serves as a static diagnostic snapshot. In this work, we propose a proof-of-concept computational framework that links flutter instability to microstructural tissue damage via a coupled system of ordinary differential equations (ODEs). We model a feedback loop where flutter-induced energy dissipation drives elastin degradation and collagen remodeling, which in turn reduces wall stiffness and amplifies the instability. To address the challenge of unobservable tissue properties, we implement a Bayesian inference engine to infer model parameters. We demonstrate feasibility on a synthetic patient cohort calibrated to published clinical growth rates and diameters. Our results show that this approach can infer hidden damage parameters and capture the qualitative bifurcation between stabilizing remodeling and runaway aneurysm expansion. While validation on real patient data remains essential, this work establishes the mathematical foundation for transforming a static physiomarker into a personalized prognostic trajectory.

Sodium (23Na) magnetic resonance imaging (MRI) provides valuable metabolic information, but it is limited by a low signal-to-noise ratio (SNR) and long acquisition times. To overcome these challenges, we present a Deep Image Prior (DIP)-based framework that combines anatomically guided proton (1H) MRI and metabolically guided 23Na MRI denoising via a fused proton-sodium prior within a directional total variation (dTV) regularization scheme. The DIP-Fusion approach minimizes a variational loss function combining data fidelity, fused dTV regularization, gradient consistency, and bias-field correction to reconstruct sodium images. MRI data were acquired from healthy volunteers and breast cancer patients. Healthy datasets were retrospectively undersampled at multiple factors, and fully sampled scans served as the ground truth. Patient datasets acquired for clinical purposes were reconstructed using the baseline DIP and the proposed DIP-Fusion methods. Sodium images were reconstructed using sum-of-squares (SoS) and adaptive combined (ADC) coil combination methods. We evaluated reconstruction performance using quantitative image quality metrics, including peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), mean squared error (MSE), learned perceptual image patch similarity (LPIPS), feature similarity index (FSIM), and Laplacian focus. In healthy volunteers, DIP-Fusion outperformed state-of-the-art reconstruction techniques across all undersampling factors. In patient datasets, DIP-Fusion demonstrated superior performance compared with baseline DIP, achieving improved structural fidelity and sodium-specific signal preservation. These results demonstrate the potential for robust, highquality sodium MRI reconstruction under accelerated acquisition, which could lead to reduced scan times and enhanced clinical feasibility.

Background: Pressure volume (PV) loop analysis remains the gold standard for assessing the intrinsic global diastolic properties of the left ventricle (LV). Traditional fitting techniques rely on local, phase-constrained fittings and are limited due to their sensitivity to noise, landmark selection, violation of assumptions, and non-convergence. Objective: To develop and validate DIAPINN, a physics-informed neural network (PINN) framework capable of calculating intrinsic diastolic properties of the LV from measured instantaneous PV data, combining mechanistic interpretability with machine learning flexibility. Methods: Instantaneous LV diastolic pressure was modeled as the sum of 1) time-dependent relaxation-related pressure and 2) volume-dependent recoil and stiffness-related pressures. DIAPINN was trained using time, LV pressure and volume as inputs, enforcing data fidelity, model consistency, and physiological plausibility within the loss function. Performance was evaluated in 4,000 Monte Carlo simulations of LV PVloops, and in clinical data from 59 patients who underwent catheterization (39 with heart failure and normal ejection fraction and 20 controls). DIAPINN derived indices were compared to those obtained from a previously validated global optimization method (GOM). Results: On the simulation data, DIA-PINN accurately recovered all constitutive indices (intraclass correlation coefficients near unity) and improved GOM performance. On the clinical data, diastolic indices derived using DIA-PINN strongly correlated with GOM estimates (R>0.90, p<0.001) but were insensitive to initialization. DIAPINN performed best under vena cava occlusion, as varying preload improved parameter identifiability. Conclusions: When applied to instantaneous pressure volume data, a generalizable PINN framework, DIAPINN, provides an improved method for assessing global intrinsic diastolic properties of cardiac chambers.

Accurate polyp segmentation from colonoscopy images is critical for colorectal cancer prevention, yet the generalization of deep learning models under domain shift remains insufficiently explored. We propose Boundary-Explicit Guided Attention U-Net (BEGA-UNet), a boundary-aware segmentation architecture that introduces explicit edge modeling as a structural inductive bias to enhance both segmentation accuracy and cross-domain robustness. The framework integrates three components: an Edge-Guided Module (EGM) with learnable Sobel-initialized operators to capture boundary cues, a Dual-Path Attention (DPA) module that processes channel and spatial attention in parallel, and a Multi-Scale Feature Aggregation (MSFA) module to encode contextual information across multiple receptive fields. Evaluated on the combined Kvasir-SEG and CVC-ClinicDB benchmarks, BEGA-UNet achieves 88.53% Dice and 82.51% IoU, outperforming representative convolutional and transformer-based baselines. More importantly, cross-dataset evaluation demonstrates strong robustness under domain shift, with BEGA-UNet retaining 83.2% of its in-distribution performance-substantially higher than U-Net (64.5%), Attention U-Net (47.5%), and TransUNet (53.1%). In a zero-shot setting on an entirely unseen dataset, the model further maintains 72.6% performance retention. Comprehensive ablation studies indicate that explicit boundary modeling plays a central role in improving generalization, while multi-scale context aggregation further stabilizes performance across domains. Feature distribution analyses support this observation by showing that edge-oriented representations exhibit markedly reduced cross-domain variability compared to appearance-driven features. Overall, BEGA-UNet provides an effective and interpretable solution for robust polyp segmentation, demonstrating that explicit boundary modeling serves as a critical inductive bias for ensuring reliability under clinical domain shifts.

Gait variability is a critical functional indicator of dynamic balance and neurocognitive decline in health. Its translation into clinical practice is, however, challenged by a lack of age-related normative trajectories and reference values under real-world ecological settings. Furthermore, the conventional metrics used to estimate gait variability (Coefficient of Variation, CV; Standard Deviation, SD) have a fundamental methodological flaw: the inherent sensitivity of conventional metrics to the statistical outliers and environmental noise in real-world walking. In this study, we mitigate this factor by applying a robust statistical framework to quantify gait variability. Analysing a large-scale cohort of community-dwelling older adults (n=2,193), we first demonstrate that free-living gait data follows a heavy-tailed distribution, necessitating the use of robust estimators like the Robust Coefficient of Variation (RCV-MAD) and Median Absolute Deviation (MAD). Leveraging these metrics, we established the normative trajectory and reference values of real-world gait variability across the ageing lifespan, revealing a distinct, age-dependent increase in spatio-temporal fluctuations, indicating a decline in rhythmicity and steadiness with age. We further demonstrated the clinical utility of these robust metrics: RCV-MAD consistently yielded larger effect sizes than conventional CV in discriminating between fallers and non-fallers across all gait parameters. Furthermore, we illustrate the potential of long-term unsupervised monitoring to capture intrinsic variability during real-world walking. Validated for consistency and reliability, this robust framework provides the necessary ecological validity to transform gait variability into a standardised, rapid clinical metric for assessing functional decline at an early timepoint.

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

AimsWe aimed to develop and evaluate fully automated artificial intelligence (AI) system. for detection of mitral valve prolapse (MVP) and mitral regurgitation (MR) from echocardiographic studies. Methods and ResultsWe used a dataset of 24,869 echocardiographic studies from the University of California San Francisco (UCSF) to train a multi-view deep neural network (DNN) to detect MVP using apical 4-chamber, 2-chamber, and parasternal long-axis views. A separate dataset of 27,906 studies from UCSF was used to train a second multi-view DNN model to detect moderate-to-severe or severe MR using color Doppler in the same views. External validation was performed on echocardiographic MVP videos from Houston Methodist Hospital. The DNN model for MVP detection achieved an AUC of 0.917 (95% CI: 0.899-0.934), with stronger performance in those with mitral annular disjunction or bileaflet MVP. External validation for MVP detection in a geographically and demographically distinct population yielded an AUC of 0.835 (95% CI: 0.803-0.869). The DNN for detection of moderate-to-severe or severe MR in patients with concurrent MVP achieved an AUC of 0.877 (95% CI: (0.805-0.939). ConclusionsAI algorithms can perform automatic detection of MVP and clinically significant MR from echocardiogram studies with high performance. The MVP DNN performed particularly well for more severe MVP phenotypes such as mitral annular disjunction or bileaflet MVP. These algorithms could provide a novel approach for automated, accurate, and rapid diagnosis of MVP and its common clinical sequelae across institutions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/26347229v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1d78db8org.highwire.dtl.DTLVardef@995b29org.highwire.dtl.DTLVardef@301b86org.highwire.dtl.DTLVardef@5f1427_HPS_FORMAT_FIGEXP M_FIG C_FIG

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

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

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

Chemical shift-encoded magnetic resonance imaging using high-resolved 3D Dixon techniques enables the non-invasive and radiation-free assessment of whole-body adipose tissue and ectopic fat distribution. Automatic deep learning-based segmentation of metabolically relevant adipose tissue compartments and ectopic fat deposits in parenchymal tissue is the most important image processing step for the quantification of adipose tissue volumes and ectopic fat percentages from whole-body imaging. This work presents a segmentation model dedicated to the segmentation of 19 metabolically relevant adipose tissue compartments and ectopic fat deposits from whole-body Dixon MRI. The trained segmentation model is available upon request. Related post-processing routines to compute volumes and fat percentages are publicly available: https://github.com/tobihaui/WholeBodyATQuantification.

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

BackgroundVarious measurements around the aortic valve are typically made on computed tomography angiograms (CTAs) before transcathether aortic valve replacement (TAVR) for aortic stenosis (AS), but their collective prognostic inference on periprocedural conduction disturbances (CDs) is not known. Here, we aimed to use unsupervised machine learning (UML) to analyze a multitude of pre-TAVR CTA features and uncover patient subphenotypes with differential risks of CDs. MethodsTwelve nonredundant features involving the aortic valve, aortic root, and ascending aorta were extracted from the CTAs of 660 AS patients. UML of these features using agglomerative hierarchical clustering was performed on separate male and female datasets, with the optimal number of clusters determined by 30 cluster indices. Multivariable logistic regression was conducted to assess the dependence of CDs on cluster type and the latters incremental prognostic value over conventional risk factors. ResultsThree male clusters were optimally identified (M1-M3): M1 was associated with small valve leaflet calcification loads and aortic root dimensions; both M2 and M3 were associated with large valve leaflet calcification loads and a wide aortic root, but the aortic root was shorter in M2 than M3. Two female clusters were optimally determined (F1-F2): F2 was associated with larger valve leaflet calcification loads and aortic root dimensions. By logistic regression analysis, compared to M1 (reference), M2, but not M3, was more associated with CDs (ORM2/M1=2.15, P=0.032; ORM3/M1=2.12, P=0.085), with no difference between M3 and M2 (ORM3/M2=0.986, P=0.974) or between F1 and F2 (ORF2/F1=1.294, P=0.581). Including cluster type as a predictor in a regression model of CDs containing conventional risk factors as covariates improved the goodness-of-fit (P=0.020). ConclusionsUML of pre-TAVR CTAs can reveal subgroups of male patients with differential risks for CDs and improve prognostication over conventional risk factors. UML-augmented pre-TAVR CTAs may help better guide personalized strategies to minimize CDs.

Background Older adults' walking has so far been evaluated using standardised assessments of walking capacity within a clinical setting. By taking the evaluation out of the laboratory into the real world, this study provides first evidence of the ability of Digital Mobility Outcomes (DMOs) to detect changes over time and the Minimal Important Difference (MID) in patients after proximal femoral fracture (PFF). This will guide the implementation of DMOs in research and clinical care. Methods For this multicenter prospective cohort study, 381 community-dwelling older adults were included within one year after sustaining a PFF and assessed at two time points, separated by six months. Walking activity and gait DMOs were measured using a single wearable device worn on the lower back for up to seven days. A global impression of change question and three mobility-related outcome measures (Late-Life Function and Disability Instrument; Short Physical Performance Battery; 4m gait speed) were used as anchor variables. To assess each DMOs ability to detect changes, we calculated the standardized mean change as effect size. For estimating MIDs, both distribution-based and anchor-based methods were applied, followed by triangulation by experts if at least three anchor-based estimates were available per DMO, resulting in single-point estimates. Results All three anchor variables demonstrated substantial changes. Overall, 10 out of 24 available DMOs showed large and 7 DMOs moderate positive effects in the expected direction of the respective anchors. Seven DMOs showed no or only small effects. For 12 DMOs, at least three anchor-based estimates were available, enabling MID triangulation. MIDs for walking activity DMOs per day were: a walking duration of 10 minutes, a step count of 1,000 steps, 50 walking bouts (WB), and 15 WBs in WBs over 10 seconds. For gait DMOs, depending on the walking bout length, MIDs for walking speed were between 0.04 m/s and 0.08 m/s, and MIDs for cadence between 4 and 6 steps/minute. Almost all DMOs showed a strong ability to detect improvement in mobility, but rarely in detecting decline. Conclusions For the first time, MIDs are presented for real-world DMOs in PFF patients. These MIDs inform sample size requirements and interpretation of intervention effects for clinical trials, thereby providing guidance and reassurance for clinicians and regulatory bodies.