International Journal for Numerical Methods in Biomedical Engineering最新文献

{"title":"Optimisation of Intervertebral Disc Mechanical Properties and the Impact of Vertebral Alignment in Subject-Specific Finite Element Models","authors":"Emily S. Kelly,&nbsp;Akbar A. Javadi,&nbsp;Timothy P. Holsgrove,&nbsp;Michael Ward,&nbsp;David Williams,&nbsp;Jenny Williams,&nbsp;Cathy Holt,&nbsp;Judith R. Meakin","doi":"10.1002/cnm.70052","DOIUrl":"https://doi.org/10.1002/cnm.70052","url":null,"abstract":"<p>Subject-specific finite element models could improve understanding of how spinal loading varies between people, based on differences in morphology and tissue properties. However, determining accurate subject-specific intervertebral disc (IVD) properties can be difficult due to the spine's complex behaviour, in six degrees of freedom. Previous studies optimising IVD properties have utilised axial compression alone or range of motion data in three axes. This study aimed to optimise IVD properties using 6-axis force-moment data, and compare the resultant model's accuracy against a model optimised using IVD pressure data. Additionally, model vertebral alignment was assessed to determine if differences between imaged specimen alignment and in vitro 6-axis test alignment affected the optimisation process. A finite element model of a porcine lumbar motion segment was developed, with generic IVD properties. The model loading and boundary conditions replicated in vitro 6-axis stiffness matrix testing of the same specimen. The model was then optimised twice, once using experimental IVD pressures and once using forces and moments. A second model with geometry based on the specimen's vertebral alignment from the 6-axis testing was also developed and optimised. The 6-axis force-moment optimised model had more accurate overall 6-axis load-displacement behaviour, but less accurate IVD pressures than the pressure optimised model. Neither optimised model fully captured spinal behaviours, due to model and optimisation process limitations. The 6-axis vertebral alignment model had lower error and different optimised IVD properties than the imaged vertebral alignment model. Thus, vertebral alignment affected segment stiffness, so should be considered when developing spine models.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translation of Animal Study to Human: In Silico Based Development of Implantable Pulmonary Artery Pressure Sensor","authors":"Leonid Goubergrits,&nbsp;Pavlo Yevtushenko,&nbsp;Adriano Schlief,&nbsp;Jan Romberg,&nbsp;Titus Kuehne,&nbsp;Andreas Arndt,&nbsp;Jan Bruening","doi":"10.1002/cnm.70050","DOIUrl":"https://doi.org/10.1002/cnm.70050","url":null,"abstract":"<p>Implantable pulmonary artery pressure sensors (PAPS) might impose a flow-induced risk of thrombus formation in the pulmonary artery (PA). To assess this risk, an in silico study-enhanced animal study with 20 sensors implanted in 10 pigs had previously been conducted. In the in silico study, PAPS were virtually implanted mimicking real implantations, based upon data acquired by CT. This animal in silico study investigated changes in hemodynamics caused by PAPS using image-based computational fluid dynamics (CFD). However, porcine and human PA differ significantly in geometry and hemodynamics. To investigate the transferability of animal in silico study findings toward human conditions, we propose a parallel in silico human study. Based on a similarity analysis (L1 norm for 8 geometric features) human PA geometries with the least difference to 10 porcine PA were selected. PAPS were virtually implanted in human PA as close as possible, mimicking the implantation configuration of the animal study. Finally, a numerical flow analysis of the hemodynamic changes due to PAPS implantation was done. Comparing human and porcine PA, we found significantly larger left and right PA diameters in humans, whereas no differences were found for main PA diameters and bifurcation angle. Comparing hemodynamic boundary conditions, we found a significantly smaller heart rate and a significantly higher peak systolic main PA flow rate in humans, whereas no significant differences for cardiac output were found. The human in silico PAPS study found no relevant changes in hemodynamics increasing the risk of thrombus formation after sensor implantation. This is also valid for PAPS that were non-optimally implanted. Thus, despite differences between species, findings of the in silico animal study were confirmed by the human in silico study.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Machine Learning for the Sensitivity Analysis of a Model of the Cellular Uptake of Nanoparticles for the Treatment of Cancer”","authors":"","doi":"10.1002/cnm.70046","DOIUrl":"https://doi.org/10.1002/cnm.70046","url":null,"abstract":"&lt;p&gt;S. Iaquinta, S. Khazaie, S. Albanna, et al., “Machine Learning for the Sensitivity Analysis of a Model of the Cellular Uptake of Nanoparticles for the Treatment of Cancer,” &lt;i&gt;International Journal for Numerical Methods in Biomedical Engineering&lt;/i&gt; (2024): e3878.&lt;/p&gt;&lt;p&gt;The “PREPRINT” mention was removed from the title of the article.&lt;/p&gt;&lt;p&gt;A new first section, &lt;b&gt;Introduction&lt;/b&gt;, has been added, which provides the following clarifications. This addition thus changes the numbering of the subsequent sections.&lt;/p&gt;&lt;p&gt;The cellular uptake of nanoparticles (NPs) is investigated for the purpose of drug delivery. The latter are attached to NPs and are delivered to the cell. These drugs aim, depending on the treatment, at killing or altering the functioning of the cell. Such therapy is currently used and knows an exponential growth for cancer treatment [1]. Hence, it is crucial to properly calibrate the NPs for them to efficiently target the cells and avoid damaging healthy cells. The way of targeting cancer cells can be biochemical or even mechanical. In the second case, the NP is designed to take advantage of significant discrepancies that are observed between the mechanical properties of healthy and cancer cells [2–4]. For instance, comparison between M10 and MCF7 breast cells show that mammalian cancer cells are softer than their healthy counterparts [3, 5–7]. In order to properly understand the phenomena and the parameters that drive mechanically controlled drug delivery, experimental and numerical investigations have been conducted. In our previous works, focused on drug delivery via endocytosis cellular uptake, we proposed a method, based on an existing model of the cellular uptake of NPs [8], for the quantification of the influence of the NP's aspect ratio, NP-cell adhesion and cell membrane tension on the NP's uptake [9]. Then, we presented an enhanced model that accounts for the mechanical response of the cell membrane during the wrapping of the NP by the membrane and we demonstrated that the predictions of the model were altered when considering this mechanical response [10]. Still, the influence of the initial parameters of the system could not be compared to those that represent the mechanical response of the membrane because of the complexity and the computational cost of the approach. As such, the objective of this article is to build a surrogate model in order to evaluate the sensitivity indices (Sobol indices) that describe the influence of the input parameters of the model on its predictions. The outline of this article is the following. Section 2 introduces the model, whose complete description is provided in [9, 10]. Then, the strategies for building a surrogate model, using Kriging, Polynomial Chaos Expansion (PCE), and deep learning approaches, are presented in Section 3. The sensitivity analysis is subsequently conducted in Section 4.&lt;/p&gt;&lt;p&gt;In line 4 of the section &lt;b&gt;Presentation of the model&lt;/b&gt;, after the phrase ending with “","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Hemodynamic Effects of the Closure Procedure of Carotid Artery Endarterectomy","authors":"Laurel Morgan Miller Marsh,&nbsp;Rainald Löhner,&nbsp;Tatiana Abou-Mrad,&nbsp;Laura Stone McGuire,&nbsp;Fady T. Charbel,&nbsp;Juan Raul Cebral","doi":"10.1002/cnm.70048","DOIUrl":"https://doi.org/10.1002/cnm.70048","url":null,"abstract":"<p>Currently, it is unclear why some patients experience restenosis after carotid endarterectomy (CEA) and whether the closing procedure is linked to greater rates of restenosis. Here, the morphology and hemodynamics are compared for the carotid bulb of two patients post-CEA. One carotid bulb was closed with a patch which later suffered a restenosis, while the other patient's bulb was treated using primary closure and did not. Contrast-enhanced magnetic resonance angiography (CE-MRA) was segmented to provide the domain for computational fluid dynamics (CFD). Flowrate waveforms measured with phase-contrast MR were provided for the common carotid artery (CCA) and internal carotid artery (ICA), while only the mean flow rate was provided for the external carotid artery (ECA), requiring the ECA waveform to be calculated. A Womersley profile was applied to the CCA inlet and ECA outlet, with a traction-free boundary condition applied to the ICA outlet. The patch patient who restenosed exhibited a nonphysiological hemodynamic environment that differed from the flow environment observed in the healthy, contralateral bulb. In contrast, the hemodynamics of the primary closure patient who underwent a successful CEA showed more favorable levels and trends of WSS as well as healthy mixing from vortices that were both present in the healthy, contralateral bulb. Changing model parameters such as flow rate, wall compliance, and flow waveforms did not alter these conclusions. Therefore, the geometry of the carotid bulb, as opposed to flow characteristics, seems responsible for the observed differences between these two cases in hemodynamic environments and subsequent outcomes.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Modeling of Cardiovascular-Induced Chest Vibrations: A Review and Practical Guide for Seismocardiography Simulation","authors":"Mohammadali Monfared,&nbsp;Peshala T. Gamage,&nbsp;Ali Loghmani,&nbsp;Amirtahà Taebi","doi":"10.1002/cnm.70047","DOIUrl":"https://doi.org/10.1002/cnm.70047","url":null,"abstract":"<p>This paper presents a comprehensive examination of finite element modeling (FEM) approaches for seismocardiography (SCG), a non-invasive method for assessing cardiac function through chest surface vibrations. The paper provides a comparative analysis of existing FEM approaches, exploring the strengths and challenges of various modeling choices in the literature. Additionally, we introduce a sample framework for developing FEM models of SCG, detailing key methodologies from governing equations and meshing techniques to boundary conditions and material property selection. This framework serves as a guide for researchers aiming to create accurate models of SCG signal propagation and offers insights into capturing complex cardiac mechanics and their transmission to the chest surface. By consolidating the current methodologies, this paper aims to establish a reference point for advancing FEM-based SCG modeling, ultimately improving our understanding of SCG waveforms and enhancing their reliability and applicability in cardiovascular health assessment.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparison of Generic and Subject-Specific Finite Element Models of Distal Femur Fractures Treated With Locking Plates","authors":"Gareth Buhl,&nbsp;Pankaj Pankaj","doi":"10.1002/cnm.70043","DOIUrl":"https://doi.org/10.1002/cnm.70043","url":null,"abstract":"<p>While the need for employing subject-specific computational biomechanics models for treatment planning in orthopaedics is being increasingly voiced, it has not been clear when such specificity is essential and for which questions simpler models might be adequate. This study uses a novel modelling approach to generate finite element models to examine the influence of subject-specificity in the treatment of distal femur fractures. Three subject-specific finite element models are created from clinical CT scans, and the proposed approach is employed to impose identical fractures and locking plate treatments upon them. Additionally, the performance of the generic two-material model based on a Sawbones fourth generation femur is also evaluated. Interfragmentary motions, plate stresses, and strains at the screw-bone interface are examined due to a physiological loading at different stages of healing. The study finds that subject-specificity has a major effect on strains in the bone at the screw-bone interface. However, interfragmentary motions at the far cortex and plate stresses show minimal sensitivity to subject-specific factors, while near-cortical and shear interfragmentary motions are influenced by them. The influence of subject-specificity decreases as healing progresses. These results indicate that while generic approaches may be sufficient to calculate global assembly responses, material heterogeneity and subject-specific bone stock variations have a large impact on the interaction between the screws and bone. The study also shows that the proposed method, which enables manipulating bone geometry while retaining subject-specific properties, can be used to evaluate the influence of subject-specificity for other orthopaedic simulations.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Uncertainty-Aware Hemolysis Modeling: A Universal Approach to Address Experimental Variance","authors":"Christopher Blum,&nbsp;Ulrich Steinseifer,&nbsp;Michael Neidlin","doi":"10.1002/cnm.70040","DOIUrl":"https://doi.org/10.1002/cnm.70040","url":null,"abstract":"<p>The purpose of this study is to address the lack of uncertainty quantification in numerical hemolysis models, which are critical for medical device evaluations. Specifically, we aim to develop a probabilistic hemolysis model, which incorporates experimental variability using the Markov Chain Monte Carlo (MCMC) method to enhance predictive accuracy and robustness. Initially, we examined the objective function landscape for fitting a Power Law hemolysis model, whose parameters are derived from inherently uncertain experimental data, by employing a grid search approach. Building on this, we applied MCMC to derive detailed stochastic distributions for the hemolysis Power Law model parameters <i>C</i>, <i>α</i>, and <i>β</i>. These distributions were then propagated through a reduced order model of the FDA benchmark pump to quantify the experimental uncertainty in hemolysis measurements with respect to the predicted pump hemolysis. Our analysis revealed a global flat minimum in the objective function landscape of the multi-parameter power law model, a phenomenon attributable to fundamental mathematical limitations in the fitting process. The probabilistic hemolysis model converged to a constant optimal <i>C</i> = 3.515 × 10⁻⁵ and log normal distributions of <i>α</i> and <i>β</i> with means of 0.614 and 1.795, respectively. This probabilistic approach successfully captured both the mean and variance observed in the experimental FDA benchmark pump data. In comparison, conventional deterministic models are not able to describe experimental variation. Incorporating uncertainty quantification through MCMC enhances the robustness and predictive accuracy of hemolysis models. This method allows for better comparison of simulated hemolysis outcomes with in vitro experiments and can integrate additional datasets, potentially setting a new standard in hemolysis modeling.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Numerical Simulation of Blood Flow in Nutcracker Syndrome: Acquisition of Hemodynamic Parameters and Clinical Application","authors":"Lei Chen,&nbsp;Guoqiu Liu,&nbsp;Lei Xian,&nbsp;Bo Zhang,&nbsp;Wen-Quan Tao","doi":"10.1002/cnm.70031","DOIUrl":"https://doi.org/10.1002/cnm.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>Adopting noninvasive techniques to provide more precise parameters related to the clinical diagnosis and treatment of nutcracker syndrome is currently the focus of research on nutcracker syndrome. However, due to individual differences in patients and limitations in monitoring techniques, there is an urgent need for a new method to obtain more accurate parameters. This work is based on imaging data from two patients with nutcracker syndrome and numerically simulates the blood flow process in the left renal vein, revealing different clinical symptoms caused by changes in flow velocity, pressure, and wall shear stress. Besides, this work also compares the dynamic changes of blood flow parameters under two different degrees of compression. The study indicates that an increase in pressure at the entrance of the left renal vein increases the risk of venous congestion. The flow separation reduces the blood flow rate by 50%–60%, causing a series of flow obstacles. The wall shear stress near the compressed area increased by 15–20 times, exacerbating the damage of blood flow to the left renal vein. The increase in the degree of compression exacerbates flow barriers and the impact of blood flow on the vascular wall. This study introduces a method of obtaining hemodynamic parameters through computational fluid dynamics and summarizes the clinical symptoms caused by abnormal changes in different blood flow parameters. This method provides a more reliable approach for the clinical diagnosis of nutcracker syndrome and the optimization design of extracorporeal stent structures since it is not limited by monitoring techniques.</p>\u0000 </div>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Computational Model-Based Study on Trans-Stenotic Pressure Ratio of Carotid Artery Stenosis and Its Predictive Value for Cerebral Ischemia","authors":"Yingjie Xia,&nbsp;Changpeng Wang,&nbsp;Yan Wang,&nbsp;Fuyou Liang","doi":"10.1002/cnm.70044","DOIUrl":"https://doi.org/10.1002/cnm.70044","url":null,"abstract":"<div>\u0000 \u0000 <p>Trans-stenotic pressure ratio (herein denoted by dpPR) has been proposed as a complementary index to stenosis rate (SR) for assessing the functional severity of carotid artery stenosis (CAS); however, it remains unclear how well dpPR can indicate cerebral ischemia. In this study, a physiology-based computational model of the cerebral circulation was developed to yield a tool for generating large-scale in silico data to characterize the changes of the dpPR of the left internal CAS in response to variations in SR and various anatomical/pathophysiological factors that represent inter-patient differences. In addition, a cerebral ischemia index (CII) was defined to evaluate the predictive value of dpPR for cerebral ischemia. Results showed that dpPR was affected by many factors unrelated to the severity of stenosis, such as the anatomical structure and geometrical size of cerebral arteries, mean systemic arterial blood pressure (MAP), flow autoregulation function of cerebral microcirculation (quantified by CFAI), and coexisting contralateral CAS. In comparison with SR, dpPR exhibited a stronger correlation with CII. In particular, the relationship between dpPR and CII was found to be describable by a mathematical function if MAP and CFAI were fixed. The findings not only deepen our understanding of the physiological implications of dpPR but also provide valuable theoretical insights to guide the application of dpPR in clinical practice.</p>\u0000 </div>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Criterion for Assessing Accumulated Neurotoxicity of Alpha-Synuclein Oligomers in Parkinson's Disease","authors":"Andrey V. Kuznetsov","doi":"10.1002/cnm.70027","DOIUrl":"https://doi.org/10.1002/cnm.70027","url":null,"abstract":"<p>The paper introduces a parameter called “accumulated neurotoxicity” of α-syn oligomers, which measures the cumulative damage these toxic species inflict on neurons over time, given the years it typically takes for such damage to manifest. A threshold value for accumulated neurotoxicity is estimated, beyond which neuron death is likely. Numerical results suggest that rapid deposition of α-syn oligomers into fibrils minimizes neurotoxicity, indicating that the formation of Lewy bodies might play a neuroprotective role. Strategies such as reducing α-syn monomer production or enhancing degradation can decrease accumulated neurotoxicity. In contrast, slower degradation (reflected by longer half-lives of monomers and free aggregates) increases neurotoxicity, supporting the idea that impaired protein degradation may contribute to Parkinson's disease progression. Accumulated neurotoxicity is highly sensitive to the half-deposition time of free α-syn aggregates into fibrils, exhibiting a sharp increase as it transitions from negligible to elevated levels, indicative of neural damage.</p>","PeriodicalId":50349,"journal":{"name":"International Journal for Numerical Methods in Biomedical Engineering","volume":"41 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}