Journal of Theoretical Biology最新文献_第5页

Multiscale analysis of electrically stimulated vascularised tumours 电刺激血管肿瘤的多尺度分析。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-17 DOI: 10.1016/j.jtbi.2025.112307

Zita Borbála Fülöp, Raimondo Penta

Electroporation-based therapies such as electrochemotherapy (ECT) hold a great promise for improving cancer treatments. While highly effective for superficial tumours, its application for deep-seated malignancies is challenged by complex microstructural properties, and current models often lack a multiscale theoretical framework to capture those phenomena. Here we develop and solve a novel system of coupled partial differential equations of Darcy-Laplace type obtained by applying the asymptotic homogenisation technique. We study the tumour response stimulated by an electric field. We derive effective macroscale equations for the pressure, velocity, and electric potential, whilst incorporating both hydraulic and electric microscale tissue heterogeneities. Our coupled multiscale approach bridges the gap between the tumour microstructure and macroscale dynamics, offering a more comprehensive understanding of how tumour size, morphology, and hydraulic-electrical interactions influence interstitial flow. We present a parametric analysis of the hydraulic conductivity tensor and macroscale numerical simulation results for pressure and velocity fields, highlighting the role of the electric field in modulating fluid flow. Our findings provide meaningful insights towards advancing ECT protocols.

以电穿孔为基础的疗法，如电疗（ECT），对改善癌症治疗有很大的希望。虽然对浅表肿瘤非常有效，但其在深层恶性肿瘤中的应用受到复杂微观结构特性的挑战，目前的模型往往缺乏多尺度理论框架来捕捉这些现象。本文利用渐近均匀化技术，建立并求解了一类新的达西-拉普拉斯型耦合偏微分方程组。我们研究电场刺激下肿瘤的反应。我们推导了有效的宏观尺度的压力、速度和电势方程，同时结合了水力和电微观尺度的组织异质性。我们的耦合多尺度方法弥合了肿瘤微观结构和宏观尺度动力学之间的差距，提供了对肿瘤大小、形态和液压-电相互作用如何影响间隙流动的更全面的理解。我们给出了水力传导张量的参数化分析和压力场和速度场的宏观数值模拟结果，强调了电场在调节流体流动中的作用。我们的发现为推进电痉挛疗法提供了有意义的见解。

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引用次数: 0

Integrating community level transmission geographical networks into a dynamical system for better epidemic control 将社区层面的传播地理网络整合为动态系统，以更好地控制疫情。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-15 DOI: 10.1016/j.jtbi.2025.112319

Arni S.R. Srinivasa Rao , Steven G. Krantz , John P. Barile

Despite the widespread use of deterministic models in understanding and controlling epidemics, they are often criticized for their inability to provide timely practical solutions during rapid spread. Similarly, conventional stochastic and statistical models also have limitations in providing time-sensitive solutions. These models are useful for implementing policy measures when there is enough time to make changes. In this article, we propose a novel approach to address these limitations by introducing a graphical network model with time-sensitive data blending to enhance deterministic epidemic models like the SIR model. This innovative approach could be valuable for rapidly spreading epidemics, providing timely model-based solutions to control their spread. For the first time, this article introduces higher-dimensional transmission rate functions in the literature and methods to obtain such functions.

AMS MSC 2020 classifications: 92D30; 62P10; 65T60.

尽管确定性模型被广泛用于了解和控制流行病，但它们经常因无法在快速传播期间提供及时的实际解决方案而受到批评。同样，传统的随机和统计模型在提供时间敏感的解决方案方面也有局限性。当有足够的时间进行更改时，这些模型对于实施政策措施非常有用。在本文中，我们提出了一种新的方法来解决这些限制，通过引入具有时间敏感数据混合的图形网络模型来增强确定性流行病模型，如SIR模型。这种创新的方法对于迅速传播的流行病可能很有价值，可以提供及时的基于模型的解决方案来控制其传播。本文首次介绍了文献中已有的高维传输速率函数，以及高维传输速率函数的获取方法。AMS MSC 2020分类：92D30；62 p10;65诸如 T60。

引用次数: 0

Reducing size bias in epidemic network modelling 减少流行病网络模型中的大小偏差。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-15 DOI: 10.1016/j.jtbi.2025.112314

Neha Bansal, Katerina Kaouri, Thomas E. Woolley

Epidemiological models can inform policymaking on disease control strategies, and these models often rely on sampled contact networks. The Random Walk (RW) sampling algorithm, commonly used for network sampling, produces size-biased samples that over-represent highly connected individuals, leading to biased estimates of disease spread. The Metropolis-Hastings Random Walk (MHRW) addresses this by providing samples representative of the underlying network’s connectivity distribution. We compare MHRW and RW in reducing size bias across four network types: Erdös-Rényi (ER), Small-world (SW), Negative-binomial (NB), and Scale-free (SF). We simulate disease spread using a stochastic Susceptible-Infected-Recovered (SIR) framework. RW tends to overestimate infections (by 25 % in ER, SW, NB) and secondary infections (by 25 % in ER, SW and 80 % in NB), and underestimate time-to-infection in NB networks. MHRW reduces the size bias, except on SF networks, where both algorithms provide non-representative samples and highly variable estimates. We find that RW is appropriate for fast-spreading, high-mortality epidemics in homogeneous or moderately random networks (ER, SW). In contrast, MHRW is better suited for slower and low-severity epidemics and can be effective in both homogeneous and heterogeneous networks (ER, SW, NB). However, MHRW is computationally expensive and less accurate when duplicate nodes are removed. We also analyse real-world data from cattle movement and human contact networks; MHRW generates disease spread estimates closer to the underlying network than RW. Our findings guide the selection of sampling algorithms based on network structure and epidemic characteristics, enhancing the reliability of disease modelling for policymaking.

流行病学模型可以为疾病控制战略的决策提供信息，而这些模型往往依赖于抽样接触网络。随机漫步（RW）抽样算法通常用于网络抽样，它产生的样本有大小偏差，过度代表高度联系的个体，导致对疾病传播的估计有偏差。Metropolis-Hastings Random Walk （MHRW）通过提供代表底层网络连接分布的样本来解决这个问题。我们比较了MHRW和RW在四种网络类型（Erdös-Rényi （ER）、小世界（SW）、负二项（NB）和无标度（SF））中减少尺寸偏差的效果。我们使用随机易感-感染-恢复（SIR）框架模拟疾病传播。RW倾向于高估感染（在ER、SW、NB中为25%）和继发性感染（在ER、SW中为25%，在NB中为80%），并低估NB网络中的感染时间。除了SF网络，MHRW减少了大小偏差，其中两种算法都提供了非代表性样本和高度可变的估计。我们发现RW适用于同质或中等随机网络中快速传播、高死亡率的流行病（ER， SW）。相比之下，MHRW更适合于较慢和低严重程度的流行病，并且可以在同质和异质网络中有效（ER、SW、NB）。然而，MHRW的计算成本很高，并且在删除重复节点时准确性较低。我们还分析了来自牛的运动和人类接触网络的真实数据；MHRW产生的疾病传播估计值比RW更接近基础网络。我们的研究结果指导了基于网络结构和流行病特征的抽样算法的选择，提高了疾病建模为政策制定提供的可靠性。

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引用次数: 0

Drug mode of action and resource constraints modulate antimicrobial resistance evolution 药物作用模式和资源限制调节抗菌素耐药性的演变。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-14 DOI: 10.1016/j.jtbi.2025.112316

Oscar Delaney, Christopher~R.~P. Brown, Andrew~D. Letten, Jan Engelstäder

An increasingly important goal in the design of antimicrobial treatment regimens is to minimise the probability of resistance evolving, without harming individual patients’ outcomes. A key characteristic to consider when choosing an antibiotic for treatment is its mode of action: bacteriostatic (growth-inhibiting) or bactericidal (mortality-inducing). We present a theoretical model comparing the efficacy of bacteriostatic, bactericidal, and intermediate drugs at preventing the evolutionary rescue of an initially susceptible bacterial population. We find that, all else equal, in resource-abundant environments, bacteriostatic drugs are best, as they constrain cell divisions and thus allow fewer resistance mutations to occur. This contrasts with the prevailing assumption that bactericidal drugs are best as they actively kill cells. When multiple drugs are employed, using one bacteriostatic and one bactericidal drug is usually optimal, because the cell division rate cannot fall below zero, so there are diminishing returns to bacteriostatic activity from two drugs. Severe resource constraints mean that growth rates are already low, and thus there is less benefit to bacteriostatic drugs further limiting growth, so bactericidal drugs are favoured. If these findings are empirically verified in the laboratory and in vivo, they could significantly guide clinical practice.

在设计抗微生物治疗方案时，一个日益重要的目标是在不损害个别患者预后的情况下，尽量减少耐药性演变的可能性。选择用于治疗的抗生素时要考虑的一个关键特征是其作用方式：抑菌（抑制生长）还是杀菌（诱导死亡）。我们提出了一个理论模型，比较抑菌、杀菌和中间药物在防止最初易感细菌种群的进化拯救方面的功效。我们发现，在其他条件相同的情况下，在资源丰富的环境中，抑菌药物是最好的，因为它们限制细胞分裂，从而允许更少的耐药突变发生。这与流行的假设相反，即杀菌药物是最好的，因为它们能主动杀死细胞。当使用多种药物时，使用一种抑菌药和一种杀菌药通常是最佳的，因为细胞分裂率不能低于零，所以两种药物的抑菌活性回报递减。严重的资源限制意味着生长速度已经很低，因此进一步限制生长的抑菌药物的益处较小，因此更倾向于使用杀菌药物。如果这些发现在实验室和体内得到实证验证，将对临床实践具有重要指导意义。

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引用次数: 0

Stiffness-sensitive gene regulation in human mesenchymal stem cells: Modelling mechanotransduction to predict mineralization and bone protein expression 人间充质干细胞的刚度敏感基因调控：模拟机械转导以预测矿化和骨蛋白表达。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-13 DOI: 10.1016/j.jtbi.2025.112284

Jean-Philippe Berteau , Abdennasser Chekroun , Laurent Pujo-Menjouet , Kevin Yueh-Hsun Yang

The goal of our study was to establish how a specific part of the bone Gene Regulatory Network (GRN) controls mineralization in response to stiffness. We hypothesized that a system of differential equations model stiffness-sensitive gene regulation in human mesenchymal stem cells through the epistatic genetic interactions between stiffness (e.g. WNT-β catenin pathway) and five of the main transcription factors and bone proteins (e.g. RUNX2, BSP, OSX, OC, and OPN). To test this hypothesis, we (i) performed in-vitro experiments culturing bone cells on different stiffness, (i) adapted our previously published model from being continuously time-dependent to continuously stiffness-sensitive, and (iii) simulated protein production in function of stiffness and other protein production from the best estimate of parameters coming from the experimental work. Our experimental findings reveal a non-parametric relationship between stiffness and RUNX2 production, with no discernible linear trends for other proteins. Modeling results demonstrate that continuous variations in stiffness enable simulation of bone GRN gene expression, fitting our novel experimental dataset. Specifically, our computational results indicate that OPN production peaks at low stiffness (8 kPa), while RUNX2, OSX, and OC achieve maximum production at higher stiffness levels (64 kPa). This alignment underscores the model’s capacity to replicate experimental data accurately. Additionally, our approach predicts that WNT-β-catenin activation serves as an enhancer for OPN and BSP production. The model also highlights a negative feedback-like interaction between OC and BSP production. Stiffness variations were shown to have a significant impact on OC and BSP production and a moderate effect on OPN production. By employing a stiffness-sensitive gene regulation model, we provide insights into one of the mineralization patterns through the prediction of bone protein expression dynamics.

我们研究的目的是确定骨基因调控网络（GRN）的特定部分如何控制矿化以响应刚度。我们假设一个微分方程系统通过刚度（如WNT-β catenin通路）与五种主要转录因子和骨蛋白（如RUNX2、BSP、OSX、OC和OPN）之间的上位性遗传相互作用来模拟人间充质干细胞中刚度敏感基因的调控。为了验证这一假设，我们(i)进行了体外实验，培养不同刚度的骨细胞，(i)调整了我们之前发表的模型，从连续的时间依赖到连续的刚度敏感，（iii）模拟了刚度和其他蛋白质产量的函数，从实验工作中得到的参数的最佳估计。我们的实验结果揭示了刚度和RUNX2产量之间的非参数关系，对其他蛋白质没有明显的线性趋势。建模结果表明，刚度的连续变化可以模拟骨GRN基因表达，符合我们新的实验数据集。具体来说，我们的计算结果表明，OPN产量在低刚度（8 kPa）时达到峰值，而RUNX2、OSX和OC在较高刚度水平（64 kPa）时达到最大产量。这种一致性强调了模型精确复制实验数据的能力。此外，我们的方法预测WNT-β-catenin的激活可以促进OPN和BSP的产生。该模型还强调了OC和BSP产量之间的负反馈式相互作用。刚度变化对OC和BSP产量有显著影响，对OPN产量影响不大。通过采用刚度敏感基因调控模型，我们通过预测骨蛋白表达动态来深入了解矿化模式之一。

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引用次数: 0

Mathematical modeling of tuberculosis with two strains, seasonality, and age heterogeneity 两株结核的数学模型、季节性和年龄异质性。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-13 DOI: 10.1016/j.jtbi.2025.112313

Yang Deng , Yi Zhao

Tuberculosis (TB) remains a significant global health threat, particularly in the regions with diverse age-specific transmission patterns and increasing drug resistance. To address these challenges, this study establishes a dual-strain model that incorporates both drug-resistant and drug-sensitive strains to investigate how these strains contribute to the dynamics of TB transmission. By integrating age heterogeneity, social interactions, and seasonal variations, the model offers a detailed depiction of TB transmission process, highlighting its inherent complexity across various population groups. We derive the basic reproduction number of the model as the maximum of the two reproduction numbers: one for the drug-resistant strain (

R_{0}^{r}

) and one for the drug-sensitive strain (

R_{0}^{s}

). It is found that the disease-free periodic equilibrium of the system is globally asymptotically stable when

R_{0} = \max (R_{0}^{r}, R_{0}^{s}) < 1

, in the absence of reinfection. We further explore the competitive dynamics of drug-resistant and drug-sensitive strains under

R_{0}^{r} > 1 > R_{0}^{s}

and

R_{0}^{s} > 1 > R_{0}^{r}

. Using a Markov Chain Monte Carlo (MCMC) algorithm, the model is calibrated with monthly TB infection data from mainland China, enabling the reconstruction of TB transmission dynamics across eight age-specific groups. The study reveals that drug-sensitive tuberculosis strains exhibit more prominent transmission characteristics compared to drug-resistant strains. Moreover, increased vaccination coverage significantly reduces TB prevalence, particularly in younger populations, while reducing contact intensity effectively suppresses TB across all age groups. These findings highlight the role of combining age-structured modeling, strain dynamics, and behavioral interventions, offering implications for the targeted TB control strategies.

结核病仍然是一个重大的全球健康威胁，特别是在具有不同年龄传播模式和耐药性日益增加的区域。为了应对这些挑战，本研究建立了一个包含耐药菌株和药敏菌株的双菌株模型，以调查这些菌株如何促进结核病传播的动态。通过整合年龄异质性、社会互动和季节变化，该模型提供了结核病传播过程的详细描述，突出了其在不同人群中的固有复杂性。我们推导出模型的基本复制数为耐药菌株（R0r）和药敏菌株（R0s）两个复制数的最大值。发现当R0=max(R0r,R0s)0r >> R0s和R0s >> R0r时，系统的无病周期平衡点是全局渐近稳定的。使用马尔可夫链蒙特卡罗（MCMC）算法，该模型使用来自中国大陆的每月结核病感染数据进行校准，从而能够重建8个特定年龄群体的结核病传播动态。该研究表明，与耐药菌株相比，药敏结核菌株表现出更突出的传播特征。此外，增加疫苗接种覆盖率可显著降低结核病患病率，特别是在年轻人群中，同时降低接触强度可有效抑制所有年龄组的结核病。这些发现突出了结合年龄结构建模、应变动力学和行为干预的作用，为有针对性的结核病控制策略提供了启示。

{"title":"Mathematical modeling of tuberculosis with two strains, seasonality, and age heterogeneity","authors":"Yang Deng , Yi Zhao","doi":"10.1016/j.jtbi.2025.112313","DOIUrl":"10.1016/j.jtbi.2025.112313","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a significant global health threat, particularly in the regions with diverse age-specific transmission patterns and increasing drug resistance. To address these challenges, this study establishes a dual-strain model that incorporates both drug-resistant and drug-sensitive strains to investigate how these strains contribute to the dynamics of TB transmission. By integrating age heterogeneity, social interactions, and seasonal variations, the model offers a detailed depiction of TB transmission process, highlighting its inherent complexity across various population groups. We derive the basic reproduction number of the model as the maximum of the two reproduction numbers: one for the drug-resistant strain (<span><math><msubsup><mi>R</mi><mn>0</mn><mi>r</mi></msubsup></math></span>) and one for the drug-sensitive strain (<span><math><msubsup><mi>R</mi><mn>0</mn><mi>s</mi></msubsup></math></span>). It is found that the disease-free periodic equilibrium of the system is globally asymptotically stable when <span><math><mrow><msub><mi>R</mi><mn>0</mn></msub><mo>=</mo><mi>max</mi><mrow><mo>(</mo><msubsup><mi>R</mi><mrow><mn>0</mn></mrow><mi>r</mi></msubsup><mo>,</mo><msubsup><mi>R</mi><mrow><mn>0</mn></mrow><mi>s</mi></msubsup><mo>)</mo></mrow><mo><</mo><mn>1</mn></mrow></math></span>, in the absence of reinfection. We further explore the competitive dynamics of drug-resistant and drug-sensitive strains under <span><math><mrow><msubsup><mi>R</mi><mn>0</mn><mi>r</mi></msubsup><mo>></mo><mn>1</mn><mo>></mo><msubsup><mi>R</mi><mn>0</mn><mi>s</mi></msubsup></mrow></math></span> and <span><math><mrow><msubsup><mi>R</mi><mn>0</mn><mi>s</mi></msubsup><mo>></mo><mn>1</mn><mo>></mo><msubsup><mi>R</mi><mn>0</mn><mi>r</mi></msubsup></mrow></math></span>. Using a Markov Chain Monte Carlo (MCMC) algorithm, the model is calibrated with monthly TB infection data from mainland China, enabling the reconstruction of TB transmission dynamics across eight age-specific groups. The study reveals that drug-sensitive tuberculosis strains exhibit more prominent transmission characteristics compared to drug-resistant strains. Moreover, increased vaccination coverage significantly reduces TB prevalence, particularly in younger populations, while reducing contact intensity effectively suppresses TB across all age groups. These findings highlight the role of combining age-structured modeling, strain dynamics, and behavioral interventions, offering implications for the targeted TB control strategies.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"619 ","pages":"Article 112313"},"PeriodicalIF":2.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531003","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}

引用次数: 0

Emergence of longitudinal queue behavior based on topological interaction and asynchronous dynamics 基于拓扑交互和异步动态的纵向队列行为的出现。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-12 DOI: 10.1016/j.jtbi.2025.112318

Decheng Kong, Kai Xue, Ping Wang, Zeyu Xu, Zhiqin Huang

Coordinated longitudinal queue behavior in biological groups, such as migratory bird flocks, remains underexplored in classical collective motion models that focus on metric-based interactions and synchronous dynamics. This study utilizes a modified self-propelled particle model incorporating topological interactions, gliding asynchrony, and limited view angle to investigate the mechanisms driving longitudinal queue formation. Simulations reveal that interacting with only two topological neighbors is critical for stable queue emergence, with an optimal view angle range of [200°, 270°] balancing frontward tracking and lateral collision avoidance. Gliding asynchrony enhances queue formation efficiency by reducing neighbor interaction frequency, leading to higher success rates and lower interaction complexity compared to synchronous or random update mechanisms. Topological interaction networks exhibit high connectivity and stability, fundamentally supporting queue maintenance, while metric-based or Voronoi interactions fail to produce linear order. The study highlights the interplay of limited sensory perception, low neighbor connectivity, and asynchronous dynamics in self-organized migration queues, providing a theoretical guidance for understanding animal collective behavior and guiding robotic swarm design.

生物群体（如候鸟群）的协调纵向队列行为，在经典的基于度量的相互作用和同步动力学的集体运动模型中仍未得到充分研究。本研究利用一个改进的自推进粒子模型，结合拓扑相互作用、滑行异步和有限视角来研究驱动纵向队列形成的机制。仿真结果表明，仅与两个拓扑邻居相互作用对于稳定的队列涌现至关重要，最佳视角范围为[200°，270°]，以平衡前向跟踪和侧避碰撞。与同步或随机更新机制相比，滑动异步通过降低邻居交互频率来提高队列形成效率，从而获得更高的成功率和更低的交互复杂性。拓扑交互网络表现出高度的连通性和稳定性，从根本上支持队列维护，而基于度量或Voronoi的交互不能产生线性秩序。该研究突出了自组织迁移队列中有限感官知觉、低邻居连通性和异步动力学的相互作用，为理解动物集体行为和指导机器人群体设计提供了理论指导。

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引用次数: 0

Fast approximate Bayesian inference of HIV indicators using PCA adaptive Gauss-Hermite quadrature 基于PCA自适应高斯-埃尔米特正交的HIV指标快速近似贝叶斯推断。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-11 DOI: 10.1016/j.jtbi.2025.112290

Adam Howes , Alex Stringer , Seth R. Flaxman , Jeffrey W. Imai–Eaton

Naomi is a spatial evidence synthesis model used to produce district-level HIV epidemic indicators in sub-Saharan Africa. Multiple outcomes of policy interest, including HIV prevalence, HIV incidence, and antiretroviral therapy treatment coverage are jointly modelled using both household survey data and routinely reported health system data. The model is provided as a tool for countries to input their data to and generate estimates with during a yearly process supported by UNAIDS. Previously, inference has been conducted using empirical Bayes and a Gaussian approximation, implemented via the TMB R package. We propose a new inference method based on an extension of adaptive Gauss-Hermite quadrature to deal with more than 20 hyperparameters. Using data from Malawi, our method improves the accuracy of inferences for model parameters, while being substantially faster to run than Hamiltonian Monte Carlo with the No-U-Turn sampler. Our implementation leverages the existing TMB C++ template for the model’s log-posterior, and is compatible with any model with such a template.

Naomi是一个空间证据综合模型，用于编制撒哈拉以南非洲地区一级的艾滋病毒流行指标。使用住户调查数据和常规报告的卫生系统数据，对包括艾滋病毒流行率、艾滋病毒发病率和抗逆转录病毒治疗覆盖在内的多种政策结果进行了联合建模。该模型是作为一种工具提供的，供各国在艾滋病规划署支助的年度进程中输入其数据并产生估计数。以前，推理是使用经验贝叶斯和高斯近似进行的，通过TMBR包实现。提出了一种基于自适应高斯-埃尔米特正交扩展的超参数推理方法。使用来自马拉维的数据，我们的方法提高了模型参数推断的准确性，同时比使用无u型转弯采样器的哈密顿蒙特卡罗运行速度快得多。我们的实现利用现有的TMBC++模板进行模型的对数后验，并且与具有这种模板的任何模型兼容。

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引用次数: 0

Treatment of methanol toxicity through ethanol and folinic acid: A mathematical study 乙醇和亚叶酸处理甲醇毒性的数学研究。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-10 DOI: 10.1016/j.jtbi.2025.112304

Sanju Sardar , Priti Kumar Roy , Sk Mosaraf Ahammed , Tushar Ghosh , David Greenhalgh

Methanol poisoning is an infrequent but immensely dangerous intoxication, causing severe metabolic disturbances, neurological dysfunction, and even death, if not treated timely and properly. In this article, we formulate a mathematical model based on the chemical kinetics reaction, to analyse the effect of co-administration of the antidote ethanol and folinic acid for the treatment of methanol toxicity. The maximum concentration level of formic acid has been identified, and through a one-dimensional impulsive system, we determined the maximum dosing interval of folinic acid. Under appropriate assumptions we have demonstrated the existence and stability of the equilibrium-like periodic orbit of our system with impulsive administration of folinic acid and ethanol. The dynamical changes of toxic metabolites are illustrated numerically for different doses and dosing intervals. We performed a sensitivity analysis to identify the key parameters affecting formic acid concentration during treatment. Model results were validated by comparing them with clinical and experimental data on methanol half-life during ethanol therapy and formic acid clearance under folinic acid treatment. Based on our detailed analytical and numerical analysis, we recommend an effective dosing regimen of folinic acid and ethanol to detoxify the human body and clearly identify the conditions beyond which hemodialysis becomes essential. We verified all of our analytical outcomes through numerical simulation.

甲醇中毒是一种不常见但非常危险的中毒，如果治疗不及时和适当，会引起严重的代谢紊乱、神经功能障碍，甚至死亡。本文建立了基于化学动力学反应的数学模型，分析了解毒剂乙醇与亚叶酸共给药治疗甲醇中毒的效果。确定了甲酸的最大浓度水平，并通过一维脉冲系统确定了亚叶酸的最大给药间隔。在适当的假设下，我们证明了该系统的类平衡周期轨道的存在性和稳定性。数值说明了不同剂量和给药间隔下毒性代谢物的动态变化。我们进行了敏感性分析，以确定治疗期间影响甲酸浓度的关键参数。通过将模型结果与乙醇治疗时甲醇半衰期和亚叶酸治疗时甲酸清除率的临床和实验数据进行比较，验证了模型结果。基于我们详细的分析和数值分析，我们推荐了一种有效的叶酸和乙醇的剂量方案来解毒人体，并清楚地确定了超过血液透析必须的条件。我们通过数值模拟验证了所有的分析结果。

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引用次数: 0

Rapid cell turnover to model adipocyte size distribution 快速细胞更新以模拟脂肪细胞大小分布。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-10 DOI: 10.1016/j.jtbi.2025.112311

Louis Fostier , Aloïs Dauger , Romain Yvinec , Magali Ribot , Chloe Audebert , Hedi Soula

White adipose tissue, composed of adipocyte cells, primarily stores energy as lipid droplets. The size of adipocytes varies significantly within the tissue according to the amount of stored lipids. A striking observation is that the adipocyte size distribution is bimodal, and thus, this tissue is lacking a characteristic size.

We propose a novel dynamical model, based on a partial differential equation, to represent the adipocyte size distribution. The model assumes continuous adipocyte growth, with a velocity dependent on cell radius and extracellular lipid availability, together with constant rates of cell recruitment and death.

We prove the existence and local stability of a unique stationary solution for a broad range of growth velocity functions. Choosing a parcimonious formulation, we show that only three parameters are enough to describe adipocyte size distributions measurements in rats. These parameters are robustly estimated through approximate Bayesian computation, and the model demonstrates excellent agreement with experimental data. This mechanistic, three-parameter framework offers a new and interpretable approach to characterizing adipocyte size distributions.

白色脂肪组织由脂肪细胞组成，主要以脂滴的形式储存能量。脂肪细胞的大小在组织内根据储存的脂质量有显著变化。一个引人注目的观察是，脂肪细胞的大小分布是双峰的，因此，该组织缺乏特征大小。我们提出了一个新的动态模型，基于偏微分方程，以表示脂肪细胞的大小分布。该模型假设脂肪细胞持续生长，其速度取决于细胞半径和细胞外脂质可用性，同时细胞招募和死亡的速率恒定。证明了一类大范围生长速度函数的唯一平稳解的存在性和局部稳定性。选择一个和谐的公式，我们表明只有三个参数足以描述脂肪细胞的大小分布测量在大鼠。通过近似贝叶斯计算对这些参数进行了稳健估计，模型与实验数据吻合良好。这种机制，三参数框架提供了一个新的和可解释的方法来表征脂肪细胞的大小分布。

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引用次数: 0