{"title":"Mathematical modelling of ageing acceleration of the human follicle due to oxidative stress and other factors","authors":"A M Portillo;C Peláez","doi":"10.1093/imammb/dqab004","DOIUrl":"10.1093/imammb/dqab004","url":null,"abstract":"There is a gradual telomere shortening due to the inability of the replication machinery to copy the very ends of chromosomes. Additionally, other factors such as high levels of oxidation (free radicals or reactive oxygen species (ROS)), e.g. due to cumulated stress, inflammation or tobacco smoke, accelerate telomere shortening. In humans, the average telomere length is about 10–15 kb at birth and telomeres shorten at a pace of 70 bp per year. However, when cells are exposed to ROS, telomere attrition happens at a faster pace, generating a wide variety of telomere size distribution in different length percentiles, which are different to what is expected just by age. In this work, the generational age of a cell is associated with its telomere length (TL), from certain maximum to the minimal TL that allows replication. In order to study the accumulation of aged granulosa cells in human follicles, from preantral to preovulatory size, a mathematical model is proposed, regarding different degrees of accelerated telomere shortening, which reflect the action of ROS in addition to the telomere shortening that happens after cell division. In cases of cells with TL shorter than cells with average TL, with low telomerase activity and accelerated telomere shortening, the mathematical model predicts an aged outcome in preovulatory follicles. The model provides a plausible explanation for what has been observed in oocytes from older women, which have been exposed to ROS for a longer period of time and have bad outcomes after in vitro fertilization.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"273-291"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqab004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25532334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A mathematical framework for modelling 3D cell motility: applications to glioblastoma cell migration","authors":"M Scott;K Żychaluk;R N Bearon","doi":"10.1093/imammb/dqab009","DOIUrl":"10.1093/imammb/dqab009","url":null,"abstract":"The collection of 3D cell tracking data from live images of micro-tissues is a recent innovation made possible due to advances in imaging techniques. As such there is increased interest in studying cell motility in 3D in vitro model systems but a lack of rigorous methodology for analysing the resulting data sets. One such instance of the use of these in vitro models is in the study of cancerous tumours. Growing multicellular tumour spheroids in vitro allows for modelling of the tumour microenvironment and the study of tumour cell behaviours, such as migration, which improves understanding of these cells and in turn could potentially improve cancer treatments. In this paper, we present a workflow for the rigorous analysis of 3D cell tracking data, based on the persistent random walk model, but adaptable to other biologically informed mathematical models. We use statistical measures to assess the fit of the model to the motility data and to estimate model parameters and provide confidence intervals for those parameters, to allow for parametrization of the model taking correlation in the data into account. We use in silico simulations to validate the workflow in 3D before testing our method on cell tracking data taken from in vitro experiments on glioblastoma tumour cells, a brain cancer with a very poor prognosis. The presented approach is intended to be accessible to both modellers and experimentalists alike in that it provides tools for uncovering features of the data set that may suggest amendments to future experiments or modelling attempts.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"333-354"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39143759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter Mortensen;Hao Gao;Godfrey Smith;Radostin D Simitev
{"title":"Addendum: Action potential propagation and block in a model of atrial tissue with myocyte–fibroblast coupling","authors":"Peter Mortensen;Hao Gao;Godfrey Smith;Radostin D Simitev","doi":"10.1093/imammb/dqab005","DOIUrl":"10.1093/imammb/dqab005","url":null,"abstract":"The analytical theory of our earlier study (Mortensen et al., 2021, Math. Med. Biol., 38, 106–131) is extended to address the outstanding cases of fibroblast barrier distribution and myocyte strait distribution. In particular, closed-form approximations to the resting membrane potential and to the critical parameter values for propagation are derived for these two non-uniform fibroblast distributions and are in good agreement with numerical estimates.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"292-298"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/iel7/8016811/9579095/09579097.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38958678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel M Anderson;Maria Corsaro;Jonathan Horton;Tim Reid;Padmanabhan Seshaiyer
{"title":"Tear film dynamics with blinking and contact lens motion","authors":"Daniel M Anderson;Maria Corsaro;Jonathan Horton;Tim Reid;Padmanabhan Seshaiyer","doi":"10.1093/imammb/dqab010","DOIUrl":"10.1093/imammb/dqab010","url":null,"abstract":"We develop a lubrication theory-based mathematical model that describes the dynamics of a tear film during blinking and contact lens (CL) wear. The model extends previous work on pre-corneal tear film dynamics during blinking by coupling the partial differential equation for tear film thickness to a dynamic model for CL motion. We explore different models for eyelid motion and also account for possible voluntary and involuntary globe (eyeball) rotation that may accompany blinking. Boundary conditions for mass flux at the eyelids are also adapted to account for the presence and motion of the CL. Our predictions for CL motion compare reasonably with existing data. Away from the eyelids the pre-lens tear film (PrLTF) is shifted, relative to its pre-corneal counterpart, in the direction of CL motion. Near the eyelids, the inflow/outflow of fluid under the eyelids also influences the PrLTF profile. We also compare our PrLTF dynamics to existing in vivo tear film thickness measurements.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"355-395"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39204057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Data assimilation of synthetic data as a novel strategy for predicting disease progression in alopecia areata","authors":"NG Cogan;Feng Bao;Ralf Paus;Atanaska Dobreva","doi":"10.1093/imammb/dqab008","DOIUrl":"10.1093/imammb/dqab008","url":null,"abstract":"The goal of patient-specific treatment of diseases requires a connection between clinical observations with models that are able to accurately predict the disease progression. Even when realistic models are available, it is very difficult to parameterize them and often parameter estimates that are made using early time course data prove to be highly inaccurate. Inaccuracies can cause different predictions, especially when the progression depends sensitively on the parameters. In this study, we apply a Bayesian data assimilation method, where the data are incorporated sequentially, to a model of the autoimmune disease alopecia areata that is characterized by distinct spatial patterns of hair loss. Using synthetic data as simulated clinical observations, we show that our method is relatively robust with respect to variations in parameter estimates. Moreover, we compare convergence rates for parameters with different sensitivities, varying observational times and varying levels of noise. We find that this method works better for sparse observations, sensitive parameters and noisy observations. Taken together, we find that our data assimilation, in conjunction with our biologically inspired model, provides directions for individualized diagnosis and treatments.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"314-332"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39078946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A James;M J Plank;R N Binny;A Lustig;K Hannah;S C Hendy;N Steyn
{"title":"A structured model for COVID-19 spread: modelling age and healthcare inequities","authors":"A James;M J Plank;R N Binny;A Lustig;K Hannah;S C Hendy;N Steyn","doi":"10.1093/imammb/dqab006","DOIUrl":"10.1093/imammb/dqab006","url":null,"abstract":"We use a stochastic branching process model, structured by age and level of healthcare access, to look at the heterogeneous spread of COVID-19 within a population. We examine the effect of control scenarios targeted at particular groups, such as school closures or social distancing by older people. Although we currently lack detailed empirical data about contact and infection rates between age groups and groups with different levels of healthcare access within New Zealand, these scenarios illustrate how such evidence could be used to inform specific interventions. We find that an increase in the transmission rates among children from reopening schools is unlikely to significantly increase the number of cases, unless this is accompanied by a change in adult behaviour. We also find that there is a risk of undetected outbreaks occurring in communities that have low access to healthcare and that are socially isolated from more privileged communities. The greater the degree of inequity and extent of social segregation, the longer it will take before any outbreaks are detected. A well-established evidence for health inequities, particularly in accessing primary healthcare and testing, indicates that Māori and Pacific peoples are at a higher risk of undetected outbreaks in Aotearoa New Zealand. This highlights the importance of ensuring that community needs for access to healthcare, including early proactive testing, rapid contact tracing and the ability to isolate, are being met equitably. Finally, these scenarios illustrate how information concerning contact and infection rates across different demographic groups may be useful in informing specific policy interventions.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 3","pages":"299-313"},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqab006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39004967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A mathematical model for bleb regulation in zebrafish primordial germ cells","authors":"Carolin Dirks;Paul Striewski;Benedikt Wirth;Anne Aalto;Adan Olguin-Olguin","doi":"10.1093/imammb/dqab002","DOIUrl":"10.1093/imammb/dqab002","url":null,"abstract":"Blebs are cell protrusions generated by local membrane–cortex detachments followed by expansion of the plasma membrane. Blebs are formed by some migrating cells, e.g. primordial germ cells of the zebrafish. While blebs occur randomly at each part of the membrane in unpolarized cells, a polarization process guarantees the occurrence of blebs at a preferential site and thereby facilitates migration toward a specified direction. Little is known about the factors involved in the controlled and directed bleb generation, yet recent studies revealed the influence of an intracellular flow and the stabilizing role of the membrane–cortex linker molecule Ezrin. Based on this information, we develop and analyse a coupled bulk-surface model describing a potential cellular mechanism by which a bleb could be induced at a controlled site. The model rests upon intracellular Darcy flow and a diffusion–advection–reaction system, describing the temporal evolution from a homogeneous to a strongly anisotropic Ezrin distribution. We prove the well-posedness of the mathematical model and show that simulations qualitatively correspond to experimental observations, suggesting that indeed the interaction of an intracellular flow with membrane proteins can be the cause of the Ezrin redistribution accompanying bleb formation.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 2","pages":"218-254"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqab002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9303904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles Puelz;Zach Danial;Jay S Raval;Jonathan L Marinaro;Boyce E Griffith;Charles S Peskin
{"title":"Models for plasma kinetics during simultaneous therapeutic plasma exchange and extracorporeal membrane oxygenation","authors":"Charles Puelz;Zach Danial;Jay S Raval;Jonathan L Marinaro;Boyce E Griffith;Charles S Peskin","doi":"10.1093/imammb/dqab003","DOIUrl":"10.1093/imammb/dqab003","url":null,"abstract":"This paper focuses on the derivation and simulation of mathematical models describing new plasma fraction in blood for patients undergoing simultaneous extracorporeal membrane oxygenation and therapeutic plasma exchange. Models for plasma exchange with either veno-arterial or veno-venous extracorporeal membrane oxygenation are considered. Two classes of models are derived for each case, one in the form of an algebraic delay equation and another in the form of a system of delay differential equations. In special cases, our models reduce to single compartment ones for plasma exchange that have been validated with experimental data (Randerson et al., 1982, Artif. Organs, 6, 43–49). We also show that the algebraic differential equations are forward Euler discretizations of the delay differential equations, with timesteps equal to transit times through model compartments. Numerical simulations are performed to compare different model types, to investigate the impact of plasma device port switching on the efficiency of the exchange process, and to study the sensitivity of the models to their parameters.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 2","pages":"255-271"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqab003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25401293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Partial differential model of lactate neuro-energetics: analytic results and numerical simulations","authors":"Angélique Perrillat-Mercerot;Alain Miranville;Abramo Agosti;Elisabetta Rocca;Pasquale Ciarletta;Rémy Guillevin","doi":"10.1093/imammb/dqaa016","DOIUrl":"10.1093/imammb/dqaa016","url":null,"abstract":"Interfaces play a key role on diseases development because they dictate the energy inflow of nutrients from the surrounding tissues. What is underestimated by existing mathematical models is the biological fact that cells are able to use different resources through nonlinear mechanisms. Among all nutrients, lactate appears to be a sensitive metabolic when talking about brain tumours or neurodegenerative diseases. Here we present a partial differential model to investigate the lactate exchanges between cells and the vascular network in the brain. By extending an existing kinetic model for lactate neuro-energetics, we first provide analytical proofs of the uniqueness and the derivation of precise bounds on the solutions of the problem including diffusion of lactate in a representative volume element comprising the interface between a capillary and cells. We further perform finite element simulations of the model in two test cases, discussing the relevant physical parameters governing the lactate dynamics.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 2","pages":"178-201"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/imammb/dqaa016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38851438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyun Mo Yang;Luis Pedro Lombardi Junior;Ariana Campos Yang
{"title":"Modeling the transmission of the new coronavirus in São Paulo State, Brazil—assessing the epidemiological impacts of isolating young and elder persons","authors":"Hyun Mo Yang;Luis Pedro Lombardi Junior;Ariana Campos Yang","doi":"10.1093/imammb/dqaa015","DOIUrl":"10.1093/imammb/dqaa015","url":null,"abstract":"We developed a mathematical model to describe the new coronavirus transmission in São Paulo State, Brazil. The model divided a community into subpopulations composed of young and elder persons considering a higher risk of fatality among elder persons with severe CoViD-19. From the data collected in São Paulo State, we estimated the transmission and additional mortality rates. Based on the estimated model parameters, we calculated the basic reproduction number \u0000<tex>$R_{0}$</tex>\u0000, and we retrieved the number of deaths due to CoViD-19, which was three times lower than those found in the literature. Considering isolation as a control mechanism, we varied the isolation rates in the young and elder subpopulations to assess the epidemiological impacts. The epidemiological scenarios focused mainly on evaluating the reduction in the number of severe CoViD-19 cases and deaths due to this disease when isolation is introduced in a population.","PeriodicalId":94130,"journal":{"name":"Mathematical medicine and biology : a journal of the IMA","volume":"38 2","pages":"137-177"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928895/pdf/dqaa015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38810900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}