Mathematical Biosciences最新文献

{"title":"Unraveling autonomic cardiovascular control complexity during orthostatic stress: Insights from a mathematical model","authors":"Martin Miranda Hurtado ,&nbsp;Rafael Kaempfer ,&nbsp;Justen R. Geddes ,&nbsp;Mette S. Olufsen ,&nbsp;Maria Rodriguez-Fernandez","doi":"10.1016/j.mbs.2024.109306","DOIUrl":"10.1016/j.mbs.2024.109306","url":null,"abstract":"<div><div>Understanding cardiovascular control mediated by the autonomic system remains challenging due to its inherent complexity. Consequently, syndromes such as orthostatic intolerance continue to evoke debates regarding the underlying pathophysiological mechanisms. This study develops a comprehensive mathematical model simulating the control of the sympathetic branch of the cardiovascular system in individuals with normal and abnormal responses to the head-up-tilt test. We recruited four young women: one control, one with vasovagal syncope, one with orthostatic hypertension, and one with orthostatic hypotension, exposing them to an orthostatic head-up tilt test (HUTT) employing non-invasive methods to measure electrocardiography and continuous blood pressure.</div><div>Our work encompasses a compartmental model formulated using a system of ordinary differential equations. Using heart rate as input, we predict blood pressure, flow, and volume in compartments representing the veins, arteries, heart, and the sympathetic branch of the baroreflex control system. The latter is modulated by high- and low-pressure baroreceptor afferents activated by changes in blood pressure induced by the HUTT. Sensitivity analysis, parameter subset selection, and optimization are employed to estimate patient-specific parameters associated with autonomic performance. The model has seven sensitive and identifiable parameters with significant physiological relevance that can serve as biomarkers for patient classification.</div><div>Results show that the model can reproduce a spectrum of blood pressure responses successfully, fitting the trajectory displayed by the experimental data. The controller exhibits behavior that emulates the operation of the sympathetic system. These encouraging findings underscore the potential of computational methods in evaluating pathologies associated with autonomic nervous system control, warranting further exploration and novel approaches.</div></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109306"},"PeriodicalIF":1.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecoepidemic modeling and dynamics of alveolar echinococcosis transmission","authors":"Xinmiao Rong ,&nbsp;Meng Fan","doi":"10.1016/j.mbs.2024.109304","DOIUrl":"10.1016/j.mbs.2024.109304","url":null,"abstract":"<div><div>Alveolar echinococcosis, transmitted between definitive hosts and intermediate hosts via predation, threatens the health of humans and causes great economic losses in western China. In order to explore the transmission mechanism of this disease, an eco-epidemiological lifecycle model is formulated to illustrate interactions between two hosts. The basic and demographic reproduction numbers are developed to characterize the stability of the disease-free and endemic equilibria as well as bifurcation dynamics. The existence of forward bifurcation and Hopf bifurcation are confirmed and are used to explain the threshold transmission dynamics. Numerical simulations and bifurcation diagrams are also presented to depict rich dynamics of the model. Numerical analysis suggests that improving the control rate of voles will reduce the risk of transmission, while the high predation rate of foxes may also lead to a lower transmission risk, which is different from the predictions of previous studies. The evaluation of three control measures on voles implies that, when the fox’s predation rate is low (high), the chemical (integrated) control will be more effective.</div></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109304"},"PeriodicalIF":1.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in-silico approach to the dynamics of proliferation potential in stem cells and the study of different therapies in cases of ovarian dysfunction","authors":"A.M. Portillo ,&nbsp;J.A. García-Velasco ,&nbsp;E. Varela","doi":"10.1016/j.mbs.2024.109305","DOIUrl":"10.1016/j.mbs.2024.109305","url":null,"abstract":"<div><div>A discrete mathematical model based on ordinary differential equations and the associated continuous model formed by a partial differential equation, which simulate the generational and temporal evolution of a stem cell population, are proposed. The model parameters are the maximum proliferation potential and the rates of mitosis, death events and telomerase activity. The mean proliferation potential at each point in time is suggested as an indicator of population aging. The model is applied on hematopoietic stem cells (HSCs), with different telomerase activity rates, in a range of variation of maximum proliferation potential in healthy individuals, to study the temporal evolution of aging. HSCs express telomerase, however not at levels that are sufficient for maintaining constant telomere length with aging <span><span>[1]</span></span>, <span><span>[2]</span></span>. Women with primary ovarian insufficiency (POI) are known to have low telomerase activity in granulosa cells and peripheral blood mononuclear cells <span><span>[3]</span></span>. Extrapolating this to hematopoietic stem cells, the mathematical model shows the differences in proliferation potential of the cell populations when telomerase expression is activated using sexual steroids, though the endogenous promoter or with gene therapy using exogenous, stronger promoters within the adeno-associated virus. In the first case, proliferation potential of cells from POI condition increases, but when adeno-associated viruses are used, the proliferation potential reaches the levels of healthy cell populations.</div></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109305"},"PeriodicalIF":1.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A joint-threshold Filippov model describing the effect of intermittent androgen-deprivation therapy in controlling prostate cancer","authors":"Aili Wang ,&nbsp;Rong Yan ,&nbsp;Haixia Li ,&nbsp;Xiaodan Sun ,&nbsp;Weike Zhou ,&nbsp;Stacey R. Smith?","doi":"10.1016/j.mbs.2024.109301","DOIUrl":"10.1016/j.mbs.2024.109301","url":null,"abstract":"<div><div>Intermittent androgen-deprivation therapy (IADT) can be beneficial to delay the occurrence of treatment resistance and cancer relapse compared to the standard continuous therapy. To study the effect of IADT in controlling prostate cancer, we developed a Filippov prostate cancer model with a joint threshold function: therapy is implemented once the total population of androgen-dependent cells (AC-Ds) and androgen-independent cells (AC-Is) is greater than the threshold value <span><math><mrow><mi>E</mi><mi>T</mi></mrow></math></span>, and it is suspended once the population is less than <span><math><mrow><mi>E</mi><mi>T</mi></mrow></math></span>. As the parameters vary, our model undergoes a series of sliding bifurcations, including boundary node, focus, saddle, saddle-node and tangency bifurcations. We also obtained the coexistence of one, two or three real equilibria and the bistability of two equilibria. Our results demonstrate that the population of AC-Is can be contained at a predetermined level if the initial population of AC-Is is less than this level, and we choose a suitable threshold value.</div></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109301"},"PeriodicalIF":1.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent vaping behaviours: Exploring the dynamics of a social contagion model","authors":"Sarah I. Machado-Marques,&nbsp;Iain R. Moyles","doi":"10.1016/j.mbs.2024.109303","DOIUrl":"10.1016/j.mbs.2024.109303","url":null,"abstract":"<div><p>Vaping, or the use of electronic cigarettes (e-cigarettes), is an ongoing issue for public health. The rapid increase in e-cigarette usage, particularly among adolescents, has often been referred to as an epidemic. Drawing upon this epidemiological analogy between vaping and infectious diseases as a theoretical framework, we present a deterministic compartmental model of adolescent e-cigarette smoking which accounts for social influences on initiation, relapse, and cessation behaviours. We use results from a sensitivity analysis of the model’s parameters on various response variables to identify key influences on system dynamics and simplify the model into one that can be analysed more thoroughly. We identify a single feasible endemic equilibrium for the proportion of smokers that decreases as social influence on cessation increases. Through steady state and stability analyses, as well as simulations of the model, we conclude that social influences from and on temporary quitters are not important in overall model dynamics, and that social influences from permanent quitters can have a significant impact on long-term system dynamics. In particular, we show that social influence on cessation can induce persistent recurrent smoking outbreaks.</p></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109303"},"PeriodicalIF":1.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0025556424001639/pdfft?md5=a3403f8b7858cb1615546af170478764&pid=1-s2.0-S0025556424001639-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling virus-stimulated proliferation of CD4+ T-cell, cell-to-cell transmission and viral loss in HIV infection dynamics","authors":"Jiawei Deng ,&nbsp;Hongying Shu ,&nbsp;Lin Wang ,&nbsp;Xingfu Zou","doi":"10.1016/j.mbs.2024.109302","DOIUrl":"10.1016/j.mbs.2024.109302","url":null,"abstract":"<div><p>Human immunodeficiency virus (HIV) can persist in infected individuals despite prolonged antiretroviral therapy and it may spread through two modes: virus-to-cell and cell-to-cell transmissions. Understanding viral infection dynamics is pivotal for elucidating HIV pathogenesis. In this study, we incorporate the loss term of virions, and both virus-to-cell and cell-to-cell infection modes into a within-host HIV model, which also takes into consideration the proliferation of healthy target cells stimulated by free viruses. By constructing suitable Lyapunov function and applying geometric methods, we establish global stability results of the infection free equilibrium and the infection persistent equilibrium, respectively. Our findings highlight the crucial role of the basic reproduction number in the threshold dynamics. Moreover, we use the loss rate of virions as the bifurcation parameter to investigate stability switches of the positive equilibrium, local Hopf bifurcation, and its global continuation. Numerical simulations validate our theoretical results, revealing rich viral dynamics including backward bifurcation, saddle–node bifurcation, and bistability phenomenon in the sense that the infection free equilibrium and a limit cycle are both locally asymptotically stable. These insights contribute to a deeper understanding of HIV dynamics and inform the development of effective therapeutic strategies.</p></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109302"},"PeriodicalIF":1.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of the Sterile Insect Technique in the presence of inaccessible areas: A study using two-patch models","authors":"P.A. Bliman ,&nbsp;N. Nguyen ,&nbsp;N. Vauchelet","doi":"10.1016/j.mbs.2024.109290","DOIUrl":"10.1016/j.mbs.2024.109290","url":null,"abstract":"<div><p>The Sterile Insect Technique (SIT) is one of the sustainable strategies for the control of disease vectors, which consists of releasing sterilized males that will mate with the wild females, resulting in a reduction and, eventually a local elimination, of the wild population. The implementation of the SIT in the field can become problematic when there are inaccessible areas where the release of sterile insects cannot be carried out directly, and the migration of wild insects from these areas to the treated zone may influence the efficacy of this technique. However, we can also take advantage of the movement of sterile individuals to control the wild population in these unreachable places. In this paper, we derive a two-patch model for <em>Aedes</em> mosquitoes where we consider the discrete diffusion between the treated area and the inaccessible zone. We investigate two different release strategies (constant and impulsive periodic releases), and by using the monotonicity of the model, we show that if the number of released sterile males exceeds some threshold, the technique succeeds in driving the whole population in both areas to extinction. This threshold depends on not only the biological parameters of the population but also the diffusion between the two patches.</p></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109290"},"PeriodicalIF":1.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0025556424001500/pdfft?md5=041fb684ce157fa53ac9c228a4080586&pid=1-s2.0-S0025556424001500-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of virulence factors shapes ecology and treatment outcomes in polymicrobial infections","authors":"C. Herzberg ,&nbsp;E.N. van Meegen ,&nbsp;J.G.C. van Hasselt","doi":"10.1016/j.mbs.2024.109293","DOIUrl":"10.1016/j.mbs.2024.109293","url":null,"abstract":"<div><p>Polymicrobial infections, caused by a community of multiple micro-organisms, are often associated with increased infection severity and poorer patient outcomes. The design of improved antimicrobial treatment strategies for PMIs can be supported by an understanding of their ecological and evolutionary dynamics. Bacterial species present in polymicrobial infections can produce virulence factors to inhibit host immune responses, such as neutrophil recruitment and phagocytosis. The presence of virulence factors can indirectly affect other bacterial species acting as a type of host-mediated interspecies interaction. The aim of this study was to assess how bacterial virulence factors targeting neutrophil function influence ecology and treatment outcomes of PMIs. An agent-based model was constructed which describes a dual-species bacterial population in the presence of neutrophils and a bacteriostatic drug. Our analysis has revealed unforeseen dynamics of the interplay of multiple virulence factors acting as interspecies interaction. We found that the distribution of two phagocytosis-inhibiting virulence factors amongst species can impact whether they have a mutually protective effect for both species. The addition of a virulence factor inhibiting neutrophil recruitment was found to reduce the protective effect of phagocytosis-inhibiting virulence factors. Furthermore we demonstrate the importance of virulence strength of a species relative to other virulent species to determine the fate of a species. We conclude that virulence factors are an important driver of population dynamics in polymicrobial infections, and may be a relevant therapeutic target for treatment of polymicrobial infections.</p></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109293"},"PeriodicalIF":1.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0025556424001536/pdfft?md5=970ee5fd8e1c951f77badf57edaadad7&pid=1-s2.0-S0025556424001536-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mathematical model of melatonin synthesis and interactions with the circadian clock","authors":"Janet Best ,&nbsp;Ruby Kim ,&nbsp;Michael Reed ,&nbsp;H. Frederik Nijhout","doi":"10.1016/j.mbs.2024.109280","DOIUrl":"10.1016/j.mbs.2024.109280","url":null,"abstract":"<div><p>A new mathematical model of melatonin synthesis in pineal cells is created and connected to a slightly modified previously created model of the circadian clock in the suprachiasmatic nucleus (SCN). The SCN influences the production of melatonin by upregulating two key enzymes in the pineal. The melatonin produced enters the blood and the cerebrospinal fluid and thus the SCN, influencing the circadian clock. We show that the model of melatonin synthesis corresponds well with extant experimental data and responds similarly to clinical experiments on bright light in the middle of the night. Melatonin is widely used to treat jet lag and sleep disorders. We show how the feedback from the pineal to the SCN causes phase resetting of the circadian clock. Melatonin doses early in the evening advance the clock and doses late at night delay the clock with a dead zone in between where the phase of the clock does not change.</p></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109280"},"PeriodicalIF":1.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling the continuum of macrophage phenotypes and their role in inflammation","authors":"Suliman Almansour ,&nbsp;Joanne L. Dunster ,&nbsp;Jonathan J. Crofts ,&nbsp;Martin R. Nelson","doi":"10.1016/j.mbs.2024.109289","DOIUrl":"10.1016/j.mbs.2024.109289","url":null,"abstract":"<div><p>Macrophages are a type of white blood cell that play a significant role in determining the inflammatory response associated with a wide range of medical conditions. They are highly plastic, having the capacity to adopt numerous polarisation states or ‘phenotypes’ with disparate pro- or anti-inflammatory roles. Many previous studies divide macrophages into two categorisations: M1 macrophages are largely pro-inflammatory in nature, while M2 macrophages are largely restorative. However, there is a growing body of evidence that the M1 and M2 classifications represent the extremes of a much broader spectrum of phenotypes, and that intermediate phenotypes can play important roles in the progression or treatment of many medical conditions. In this article, we present a model of macrophage dynamics that includes a continuous description of phenotype, and hence incorporates intermediate phenotype configurations. We describe macrophage phenotype switching via nonlinear convective flux terms that scale with background levels of generic pro- and anti-inflammatory mediators. Through numerical simulation and bifurcation analysis, we unravel the model’s resulting dynamics, paying close attention to the system’s multistability and the extent to which key macrophage–mediator interactions provide bifurcations that act as switches between chronic states and restoration of health. We show that interactions that promote M1-like phenotypes generally result in a greater array of stable chronic states, while interactions that promote M2-like phenotypes can promote restoration of health. Additionally, our model admits oscillatory solutions reminiscent of relapsing–remitting conditions, with macrophages being largely polarised toward anti-inflammatory activity during remission, but with intermediate phenotypes playing a role in inflammatory flare-ups. We conclude by reflecting on our observations in the context of the ongoing pursuance of novel therapeutic interventions.</p></div>","PeriodicalId":51119,"journal":{"name":"Mathematical Biosciences","volume":"377 ","pages":"Article 109289"},"PeriodicalIF":1.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0025556424001494/pdfft?md5=7b3f9fd16861e65bf2cee220684dd62a&pid=1-s2.0-S0025556424001494-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}