Shilong Zhang, Tongyao Yu, Ge Zhang, Ming Chen, Dachuan Yin, Chenyan Zhang
{"title":"Systematic simulation of tumor cell invasion and migration in response to time-varying rotating magnetic field","authors":"Shilong Zhang, Tongyao Yu, Ge Zhang, Ming Chen, Dachuan Yin, Chenyan Zhang","doi":"10.1007/s10237-024-01858-y","DOIUrl":"10.1007/s10237-024-01858-y","url":null,"abstract":"<div><p>Cancer invasion and migration play a pivotal role in tumor malignancy, which is a major cause of most cancer deaths. Rotating magnetic field (RMF), one of the typical dynamic magnetic fields, can exert substantial mechanical influence on cells. However, studying the effects of RMF on cell is challenging due to its complex parameters, such as variation of magnetic field intensity and direction. Here, we developed a systematic simulation method to explore the influence of RMF on tumor invasion and migration, including a finite element method (FEM) model and a cell-based hybrid numerical model. Coupling with the data of magnetic field from FEM, the cell-based hybrid numerical model was established to simulate the tumor cell invasion and migration. This model employed partial differential equations (PDEs) and finite difference method to depict cellular activities and solve these equations in a discrete system. PDEs were used to depict cell activities, and finite difference method was used to solve the equations in discrete system. As a result, this study provides valuable insights into the potential applications of RMF in tumor treatment, and a series of in vitro experiments were performed to verify the simulation results, demonstrating the model's reliability and its capacity to predict experimental outcomes and identify pertinent factors. Furthermore, these findings shed new light on the mechanical and chemical interplay between cells and the ECM, offering new insights and providing a novel foundation for both experimental and theoretical advancements in tumor treatment by using RMF.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1617 - 1630"},"PeriodicalIF":3.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harriet G. Talbott, Richard A. Wilkins, Claire L. Brockett, Marlène Mengoni
{"title":"Incorporating pathological gait into patient-specific finite element models of the haemophilic ankle","authors":"Harriet G. Talbott, Richard A. Wilkins, Claire L. Brockett, Marlène Mengoni","doi":"10.1007/s10237-024-01857-z","DOIUrl":"10.1007/s10237-024-01857-z","url":null,"abstract":"<div><p>Haemarthrosis is an inherent clinical feature of haemophilia, a disease characterised by an absence or reduction in clotting proteins. Patients with severe haemophilia experience joint bleeding leading to blood-induced ankle arthropathy (haemarthropathy). Altered biomechanics of the ankle have been reported in people with haemophilia; however, the consequence of this on joint health is little understood. The aim of this study was to assess the changes in joint contact due to haemophilia disease-specific gait features using patient-specific modelling, to better understand the link between biomechanics and joint outcomes. Four, image-based, finite element models of haemophilic ankles were simulated through consecutive events in the stance phase of gait, using both patient-specific and healthy control group (n = 36) biomechanical inputs. One healthy control FE model was simulated through the healthy control stance phase of the gait cycle for a point of comparison. The method developed allowed cartilage contact mechanics to be assessed throughout the loading phase of the gait cycle. This showed areas of increased contact pressure in the medial and lateral regions of the talar dome, which may be linked to collapse in these regions. This method may allow the relationship between structure and function in the tibiotalar joint to be better understood.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1607 - 1616"},"PeriodicalIF":3.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel S. Fidalgo, Renato M. Natal Jorge, Marco P. L. Parente, Erin M. Louwagie, Ewelina Malanowska, Kristin M. Myers, Dulce A. Oliveira
{"title":"Pregnancy state before the onset of labor: a holistic mechanical perspective","authors":"Daniel S. Fidalgo, Renato M. Natal Jorge, Marco P. L. Parente, Erin M. Louwagie, Ewelina Malanowska, Kristin M. Myers, Dulce A. Oliveira","doi":"10.1007/s10237-024-01853-3","DOIUrl":"10.1007/s10237-024-01853-3","url":null,"abstract":"<div><p>Successful pregnancy highly depends on the complex interaction between the uterine body, cervix, and fetal membrane. This interaction is synchronized, usually following a specific sequence in normal vaginal deliveries: (1) cervical ripening, (2) uterine contractions, and (3) rupture of fetal membrane. The complex interaction between the cervix, fetal membrane, and uterine contractions before the onset of labor is investigated using a complete third-trimester gravid model of the uterus, cervix, fetal membrane, and abdomen. Through a series of numerical simulations, we investigate the mechanical impact of (i) initial cervical shape, (ii) cervical stiffness, (iii) cervical contractions, and (iv) intrauterine pressure. The findings of this work reveal several key observations: (i) maximum principal stress values in the cervix decrease in more dilated, shorter, and softer cervices; (ii) reduced cervical stiffness produces increased cervical dilation, larger cervical opening, and decreased cervical length; (iii) the initial cervical shape impacts final cervical dimensions; (iv) cervical contractions increase the maximum principal stress values and change the stress distributions; (v) cervical contractions potentiate cervical shortening and dilation; (vi) larger intrauterine pressure (IUP) causes considerably larger stress values and cervical opening, larger dilation, and smaller cervical length; and (vii) the biaxial strength of the fetal membrane is only surpassed in the cases of the (1) shortest and most dilated initial cervical geometry and (2) larger IUP.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1531 - 1550"},"PeriodicalIF":3.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caterina Balzotti, Pierfrancesco Siena, Michele Girfoglio, Giovanni Stabile, Jorge Dueñas-Pamplona, José Sierra-Pallares, Ignacio Amat-Santos, Gianluigi Rozza
{"title":"A reduced order model formulation for left atrium flow: an atrial fibrillation case","authors":"Caterina Balzotti, Pierfrancesco Siena, Michele Girfoglio, Giovanni Stabile, Jorge Dueñas-Pamplona, José Sierra-Pallares, Ignacio Amat-Santos, Gianluigi Rozza","doi":"10.1007/s10237-024-01847-1","DOIUrl":"10.1007/s10237-024-01847-1","url":null,"abstract":"<div><p>A data-driven reduced order model (ROM) based on a proper orthogonal decomposition-radial basis function (POD-RBF) approach is adopted in this paper for the analysis of blood flow dynamics in a patient-specific case of atrial fibrillation (AF). The full order model (FOM) is represented by incompressible Navier–Stokes equations, discretized with a finite volume (FV) approach. Both the Newtonian and the Casson’s constitutive laws are employed. The aim is to build a computational tool able to efficiently and accurately reconstruct the patterns of relevant hemodynamics indices related to the stasis of the blood in a physical parametrization framework including the cardiac output in the Newtonian case and also the plasma viscosity and the hematocrit in the non-Newtonian one. Many FOM-ROM comparisons are shown to analyze the performance of our approach as regards errors and computational speed-up.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 4","pages":"1411 - 1429"},"PeriodicalIF":3.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A computationally efficient gradient-enhanced healing model for soft biological tissues","authors":"Di Zuo, Mingji Zhu, Daye Chen, Qiwen Xue","doi":"10.1007/s10237-024-01851-5","DOIUrl":"10.1007/s10237-024-01851-5","url":null,"abstract":"<div><p>Soft biological tissues, such as arterial tissue, have the ability to grow and remodel in response to damage. Computational method plays a critical role in understanding the underlying mechanisms of tissue damage and healing. However, the existing healing model often requires huge computation time and it is inconvenient to implement finite element simulation. In this paper, we propose a computationally efficient gradient-enhanced healing model that combines the advantages of the gradient-enhanced damage model, the homeostatic-driven turnover remodeling model, and the damage-induced growth model. In the proposed model, the evolution of healing-related parameters can be solved explicitly. Additionally, an adaptive time increment method is used to further reduce computation time. The proposed model can be easily implemented in Abaqus, requiring only a user subroutine UMAT. The effectiveness of proposed model is verified through a semi-analytical example, and the influence of the variables in the proposed model is investigated using uniaxial tension and open-hole plate tests. Finally, the long-term development of aneurysms is simulated to demonstrate the potential applications of the proposed model in real biomechanical problems.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1491 - 1509"},"PeriodicalIF":3.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gregory M. Boiczyk, Noah Pearson, Vivek Bhaskar Kote, Aravind Sundaramurthy, Dhananjay Radhakrishnan Subramaniam, Jose E. Rubio, Ginu Unnikrishnan, Jaques Reifman, Kenneth L. Monson
{"title":"Region specific anisotropy and rate dependence of Göttingen minipig brain tissue","authors":"Gregory M. Boiczyk, Noah Pearson, Vivek Bhaskar Kote, Aravind Sundaramurthy, Dhananjay Radhakrishnan Subramaniam, Jose E. Rubio, Ginu Unnikrishnan, Jaques Reifman, Kenneth L. Monson","doi":"10.1007/s10237-024-01852-4","DOIUrl":"10.1007/s10237-024-01852-4","url":null,"abstract":"<div><p>Traumatic brain injury is a major cause of morbidity in civilian as well as military populations. Computational simulations of injurious events are an important tool to understanding the biomechanics of brain injury and evaluating injury criteria and safety measures. However, these computational models are highly dependent on the material parameters used to represent the brain tissue. Reported material properties of tissue from the cerebrum and cerebellum remain poorly defined at high rates and with respect to anisotropy. In this work, brain tissue from the cerebrum and cerebellum of male Göttingen minipigs was tested in one of three directions relative to axon fibers in oscillatory simple shear over a large range of strain rates from 0.025 to 250 s<sup>−1</sup>. Brain tissue showed significant direction dependence in both regions, each with a single preferred loading direction. The tissue also showed strong rate dependence over the full range of rates considered. Transversely isotropic hyper-viscoelastic constitutive models were fit to experimental data using dynamic inverse finite element models to account for wave propagation observed at high strain rates. The fit constitutive models predicted the response in all directions well at rates below 100 s<sup>−1</sup>, after which they adequately predicted the initial two loading cycles, with the exception of the 250 s<sup>−1</sup> rate, where models performed poorly. These constitutive models can be readily implemented in finite element packages and are suitable for simulation of both conventional and blast injury in porcine, especially Göttingen minipig, models.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1511 - 1529"},"PeriodicalIF":3.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rocío Ruiz-Lozano, José Luis Calvo-Gallego, Peter Pivonka, Michelle M. McDonald, Javier Martínez-Reina
{"title":"An in silico approach to elucidate the pathways leading to primary osteoporosis: age-related vs. postmenopausal","authors":"Rocío Ruiz-Lozano, José Luis Calvo-Gallego, Peter Pivonka, Michelle M. McDonald, Javier Martínez-Reina","doi":"10.1007/s10237-024-01846-2","DOIUrl":"10.1007/s10237-024-01846-2","url":null,"abstract":"<div><p>Numerical models of bone remodelling have traditionally been used to perform in silico tests of bone loss in postmenopausal women and also to simulate the response to different drug treatments. These models simulate the menopausal oestrogen decline by altering certain signalling pathways. However, they do not consider the simultaneous effect that ageing can have on cell function and bone remodelling, and thus on bone loss. Considering ageing and oestrogen decline together is important for designing osteoporosis treatments that can selectively counteract one or the other disease mechanism. A previously developed bone cell population model was adapted to consider the effect of ageing through: (1) the decrease of TGF-<span>(upbeta)</span> contained in the bone matrix and (2) an increased production of sclerostin by non-skeletal cells. Oestrogen deficiency is simulated in three different ways: (a) an increase in RANKL expression, (b) a decrease in OPG production, and (c) an increase in the responsiveness of osteoclasts to RANKL. The effect of ageing was validated using the cross-sectional study of (Riggs et al. in J Bone Miner Res 19: 1945-1954, 2004) on BMD of trabecular bone of the vertebral body of men. The joint effect of ageing and oestrogen deficiency was validated using these same clinical results but in women. In ageing, the effect of the increasing production of sclerostin is more important than the decrease of TGF-<span>(upbeta)</span>, while the three mechanisms used to simulate the effect of oestrogen deficiency produce almost identical responses. The results show that an early menopause leads to a lower average density in the fifth decade, but after the sixth decade the average density is independent of the age at menopause. Treatment of osteoporosis with denosumab was also simulated to conclude that the drug is not very effective if started before 10 years after menopause or before age 60.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 4","pages":"1393 - 1409"},"PeriodicalIF":3.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10237-024-01846-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fingertip dynamic response simulated across excitation points and frequencies","authors":"Gokhan Serhat, Katherine J. Kuchenbecker","doi":"10.1007/s10237-024-01844-4","DOIUrl":"10.1007/s10237-024-01844-4","url":null,"abstract":"<div><p>Predicting how the fingertip will mechanically respond to different stimuli can help explain human haptic perception and enable improvements to actuation approaches such as ultrasonic mid-air haptics. This study addresses this goal using high-fidelity 3D finite element analyses. We compute the deformation profiles and amplitudes caused by harmonic forces applied in the normal direction at four locations: the center of the finger pad, the side of the finger, the tip of the finger, and the oblique midpoint of these three sites. The excitation frequency is swept from 2.5 to 260 Hz. The simulated frequency response functions (FRFs) obtained for displacement demonstrate that the relative magnitudes of the deformations elicited by stimulating at each of these four locations greatly depend on whether only the excitation point or the entire finger is considered. The point force that induces the smallest local deformation can even cause the largest overall deformation at certain frequency intervals. Above 225 Hz, oblique excitation produces larger mean displacement amplitudes than the other three forces due to excitation of multiple modes involving diagonal deformation. These simulation results give novel insights into the combined influence of excitation location and frequency on the fingertip dynamic response, potentially facilitating the design of future vibration feedback devices.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 4","pages":"1369 - 1376"},"PeriodicalIF":3.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Green, Wei Xuan Chan, Andreas Tulzer, Gerald Tulzer, Choon Hwai Yap
{"title":"Myocardial biomechanical effects of fetal aortic valvuloplasty","authors":"Laura Green, Wei Xuan Chan, Andreas Tulzer, Gerald Tulzer, Choon Hwai Yap","doi":"10.1007/s10237-024-01848-0","DOIUrl":"10.1007/s10237-024-01848-0","url":null,"abstract":"<div><p>Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1433 - 1448"},"PeriodicalIF":3.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10237-024-01848-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RuiChun Dong, Shuai Zhu, Xiang Cheng, Xiang Gao, ZhongLong Wang, Yi Wang
{"title":"Study on the biodynamic characteristics and internal vibration behaviors of a seated human body under biomechanical characteristics","authors":"RuiChun Dong, Shuai Zhu, Xiang Cheng, Xiang Gao, ZhongLong Wang, Yi Wang","doi":"10.1007/s10237-024-01849-z","DOIUrl":"10.1007/s10237-024-01849-z","url":null,"abstract":"<div><p>To provide reference and theoretical guidance for establishing human body dynamics models and studying biomechanical vibration behavior, this study aimed to develop and verify a computational model of a three-dimensional seated human body with detailed anatomical structure under complex biomechanical characteristics to investigate dynamic characteristics and internal vibration behaviors of the human body. Fifty modes of a seated human body were extracted by modal method. The intervertebral disc and head motions under uniaxial white noise excitation (between 0 and 20 Hz at 1.0, 0.5 and 0.5 m/s<sup>2</sup> r.m.s. for vertical, fore-aft and lateral direction, respectively) were computed by random response analysis method. It was found that there were many modes of the seated human body in the low-frequency range, and the modes that had a great impact on seated human vibration were mainly distributed below 13 Hz. The responses of different positions of the spine varied greatly under the fore-aft and lateral excitation, but the maximum stress was distributed in the lumbar under different excitations, which could explain why drivers were prone to lower back pain after prolonged driving. Moreover, there was a large vibration coupling between the vertical and fore-aft direction of an upright seated human body, while the vibration couplings between the lateral and other directions were very small. Overall, the study could provide new insights into not only the overall dynamic characteristics of the human body, but also the internal local motion and biomechanical characteristics under different excitations.</p></div>","PeriodicalId":489,"journal":{"name":"Biomechanics and Modeling in Mechanobiology","volume":"23 5","pages":"1449 - 1468"},"PeriodicalIF":3.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140801949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}