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Minimal cellular automaton model with heterogeneous cell sizes predicts epithelial colony growth 具有异质细胞大小的最小细胞自动机模型可预测上皮细胞集落的生长
Pub Date : 2024-03-12 DOI: arxiv-2403.07612
Steffen Lange, Jannik Schmied, Paul Willam, Anja Voss-Böhme
Regulation of cell proliferation is a crucial aspect of tissue developmentand homeostasis and plays a major role in morphogenesis, wound healing, andtumor invasion. A phenomenon of such regulation is contact inhibition, whichdescribes the dramatic slowing of proliferation, cell migration and individualcell growth when multiple cells are in contact with each other. While manyphysiological, molecular and genetic factors are known, the mechanism ofcontact inhibition is still not fully understood. In particular, the relevanceof cellular signaling due to interfacial contact for contact inhibition isstill debated. Cellular automata (CA) have been employed in the past asnumerically efficient mathematical models to study the dynamics of cellensembles, but they are not suitable to explore the origins of contactinhibition as such agent-based models assume fixed cell sizes. We develop aminimal, data-driven model to simulate the dynamics of planar cell cultures byextending a probabilistic CA to incorporate size changes of individual cellsduring growth and cell division. We successfully apply this model to previousin-vitro experiments on contact inhibition in epithelial tissue: After asystematic calibration of the model parameters to measurements of single-celldynamics, our CA model quantitatively reproduces independent measurements ofemergent, culture-wide features, like colony size, cell density and collectivecell migration. In particular, the dynamics of the CA model also exhibit thetransition from a low-density confluent regime to a stationary postconfluentregime with a rapid decrease in cell size and motion. This implies that thevolume exclusion principle, a mechanical constraint which is the onlyinter-cellular interaction incorporated in the model, paired with asize-dependent proliferation rate is sufficient to generate the observedcontact inhibition.
细胞增殖调控是组织发育和稳态的一个重要方面,在形态发生、伤口愈合和肿瘤侵袭中发挥着重要作用。这种调控的一种现象是接触抑制,它描述了当多个细胞相互接触时,细胞增殖、细胞迁移和单个细胞生长的速度急剧减慢。虽然许多生理、分子和遗传因素已经为人所知,但接触抑制的机制仍未完全明了。尤其是界面接触导致的细胞信号传导与接触抑制的相关性仍存在争议。细胞自动机(CA)过去曾被用作研究细胞团动态的高效数学模型,但它们并不适合探索接触抑制的起源,因为这种基于代理的模型假定细胞大小是固定的。我们通过扩展概率 CA,将单个细胞在生长和细胞分裂过程中的大小变化纳入其中,开发了一个最小的、数据驱动的模型来模拟平面细胞培养的动态。我们成功地将这一模型应用于之前的上皮组织接触抑制体外实验:在根据单细胞动力学测量结果对模型参数进行系统校准后,我们的 CA 模型定量地再现了对菌落大小、细胞密度和细胞集体迁移等整个培养物特征的独立测量结果。特别是,CA 模型的动力学还表现出从低密度汇合状态到静止的后汇合状态的过渡,细胞体积和运动迅速减小。这意味着体积排斥原理--模型中唯一包含的细胞间相互作用的机械约束--与依赖于细胞大小的增殖率配对,足以产生观察到的接触抑制。
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引用次数: 0
Study of the mechanism of electroacupuncture regulating ferroptosis, inhibiting bladder neck fibrosis, and improving bladder urination function after suprasacral spinal cord injury using proteomics 利用蛋白质组学研究电针调节铁蛋白沉积、抑制膀胱颈纤维化、改善骶骨上脊髓损伤后膀胱排尿功能的机制
Pub Date : 2024-03-11 DOI: arxiv-2403.06792
Jin-Can Liu, Li-Ya Tang, Xiao-Ying Sun, Qi-Rui Qu, Qiong Liu, Lu Zhou, Hong Zhang, Bruce Song, Ming Xu, Kun Ai
Purpose The aim of this study was to explore whether electroacupunctureregulates phenotypic transformation of smooth muscle cells by inhibitingferroptosis and inhibiting fibrosis, thereby improving bladder urinationfunction after suprasacral spinal cord injury (SSCI). Methods The experimentwas divided into sham, model, and electroacupuncture group. After 10 days ofelectroacupuncture intervention, urodynamic examination was performed, andbladder neck was taken for HE staining, tandem mass tag (TMT)-basedquantitative proteomics analysis, Western blot(WB) detection, ferrous ionconcentration detection and Masson staining. Conclusion Electroacupuncture mayprevent the phenotype of bladder neck smooth muscle cells from transformingfrom contraction type to synthesis type by inhibiting ferroptosis, inhibitbladder neck fibrosis, improve bladder neck compliance, and thus improvebladder urination function after SSCI.
目的 探讨电针是否能通过抑制膀胱平滑肌细胞变性和纤维化来改善骶骨上脊髓损伤(SSCI)后的膀胱排尿功能。方法 实验分为假组、模型组和电针组。电针干预10天后,进行尿动力学检查,取膀胱颈部进行HE染色、基于串联质量标记(TMT)的蛋白质组学定量分析、Western blot(WB)检测、亚铁离子浓度检测和Masson染色。结论 电针可通过抑制铁变态反应防止膀胱颈平滑肌细胞表型由收缩型向合成型转变,抑制膀胱颈纤维化,改善膀胱颈顺应性,从而改善膀胱损伤后的排尿功能。
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引用次数: 0
Visualizing, Analyzing and Constructing L-System from Arborized 3D Model Using a Web Application 使用网络应用程序,从 Arborized 3D 模型可视化、分析和构建 L 系统
Pub Date : 2024-03-11 DOI: arxiv-2403.06638
Nick van Nielen, Fons Verbeek, Lu Cao
In biology, arborized structures are well represented and typically complexfor visualization and analysis. In order to have a profound understanding ofthe topology of arborized 3D biological model, higher level abstraction isneeded. We aim at constructing an abstraction of arborized 3D biological modelto an L-system that provides a generalized formalization in a grammar torepresent complex structures. The focus of this paper is to combine 3Dvisualization, analysis and L-system abstraction into a single web application.We designed a front-end user interface and a back-end. In the front-end, weused A-Frame and defined algorithms to generate and visualize L-systems. In theback-end, we utilized the Vascular Modelling Toolkit's (VMTK) centerlineanalysis methods to extract important features from the arborized 3D models,which can be applied to L-system generation. In addition, two 3D biologicalmodels: lactiferous duct and artery are used as two case studies to verify thefunctionality of this web application. In conclusion, our web application isable to visualize, analyse and create L-system abstractions of arborized 3Dmodels. This in turn provides workflow-improving benefits, easy accessibilityand extensibility.
在生物学中,树枝状结构有很好的表现形式,通常可用于可视化和分析。为了深刻理解树枝状三维生物模型的拓扑结构,需要更高层次的抽象。我们的目标是将树枝化三维生物模型抽象为一个 L 系统,用语法提供一个通用的形式化来表示复杂的结构。本文的重点是将三维可视化、分析和 L 系统抽象结合到一个单一的网络应用程序中。在前端,我们使用了 A-Frame,并定义了生成和可视化 L 系统的算法。在后端,我们利用血管建模工具包(VMTK)的中心线分析方法从树枝化三维模型中提取重要特征,并将其应用于 L 系统的生成。此外,我们还使用了两个三维生物模型:乳腺导管和动脉作为案例研究,以验证该网络应用程序的功能。总之,我们的网络应用程序能够可视化、分析和创建树枝化三维模型的 L 系统抽象。这反过来又提供了改进工作流程的好处、易访问性和可扩展性。
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引用次数: 0
Complementing cell taxonomies with a multicellular functional analysis of tissues 用组织的多细胞功能分析补充细胞分类法
Pub Date : 2024-03-11 DOI: arxiv-2403.06753
Ricardo Omar Ramirez Flores, Philipp Sven Lars Schäfer, Leonie Küchenhoff, Julio Saez-Rodriguez
The application of single-cell molecular profiling coupled with spatialtechnologies has enabled charting cellular heterogeneity in reference tissuesand in disease. This new wave of molecular data has highlighted the expecteddiversity of single-cell dynamics upon shared external queues and spatialorganizations. However, little is known about the relationship between singlecell heterogeneity and the emergence and maintenance of robust multicellularprocesses in developed tissues and its role in (patho)physiology. Here, wepresent emerging computational modeling strategies that use increasinglyavailable large-scale cross-condition single cell and spatial datasets, tostudy multicellular organization in tissues and complement cell taxonomies.This perspective should enable us to better understand how cells within tissuescollectively process information and adapt synchronized responses in diseasecontexts and to bridge the gap between structural changes and functions intissues.
单细胞分子剖析技术与空间技术的结合应用,使得绘制参考组织和疾病中的细胞异质性图成为可能。这一新的分子数据浪潮凸显了单细胞动态在共享外部队列和空间组织时的预期多样性。然而,人们对单细胞异质性与发达组织中稳健多细胞过程的出现和维持之间的关系及其在(病理)生理学中的作用知之甚少。在这里,我们将介绍新兴的计算建模策略,这些策略利用越来越多的大规模跨条件单细胞和空间数据集来研究组织中的多细胞组织,并补充细胞分类学。这种视角应能让我们更好地理解组织内的细胞如何在疾病背景下集体处理信息和适应同步反应,并弥合组织内结构变化与功能之间的差距。
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引用次数: 0
General surgery vision transformer: A video pre-trained foundation model for general surgery 普外科视觉转换器:用于普外科手术的视频预训练基础模型
Pub Date : 2024-03-09 DOI: arxiv-2403.05949
Samuel Schmidgall, Ji Woong Kim, Jeffery Jopling, Axel Krieger
The absence of openly accessible data and specialized foundation models is amajor barrier for computational research in surgery. Toward this, (i) weopen-source the largest dataset of general surgery videos to-date, consistingof 680 hours of surgical videos, including data from robotic and laparoscopictechniques across 28 procedures; (ii) we propose a technique for videopre-training a general surgery vision transformer (GSViT) on surgical videosbased on forward video prediction that can run in real-time for surgicalapplications, toward which we open-source the code and weights of GSViT; (iii)we also release code and weights for procedure-specific fine-tuned versions ofGSViT across 10 procedures; (iv) we demonstrate the performance of GSViT on theCholec80 phase annotation task, displaying improved performance overstate-of-the-art single frame predictors.
缺乏可公开访问的数据和专业基础模型是外科计算研究的一大障碍。为此,(i) 我们开源了迄今为止最大的普外科手术视频数据集,该数据集由 680 小时的手术视频组成,包括来自机器人和腹腔镜技术的 28 种手术数据;(ii) 我们提出了一种基于前向视频预测的普外科手术视觉转换器(GSViT)视频预训练技术,该技术可实时运行于手术应用中,为此我们开源了 GSViT 的代码和权重;(iv) 我们展示了 GSViT 在 Cholec80 阶段标注任务中的性能,其性能超过了最先进的单帧预测器。
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引用次数: 0
An in-silico approach to meniscus tissue regeneration: Modeling, numerical simulation, and experimental analysis 半月板组织再生的模拟方法:建模、数值模拟和实验分析
Pub Date : 2024-03-09 DOI: arxiv-2403.05909
Elise Grosjean, Alex Keilmann, Henry Jäger, Shimi Mohanan, Claudia Redenbach, Bernd Simeon, Christina Surulescu, Luisa de Roy, Andreas Seitz, Graciosa Teixeira, Martin Dauner, Carsten Linti, Günter Schmidt
We develop a model the dynamics of human mesenchymal stem cells (hMSCs) andchondrocytes evolving in a nonwoven polyethylene terephtalate (PET) scaffoldimpregnated with hyaluron and supplied with a differentiation medium. Thescaffold and the cells are assumed to be contained in a bioreactor with fluidperfusion. The differentiation of hMSCs into chondrocytes favors the productionof extracellular matrix (ECM) and is influenced by fluid stress. The modeltakes deformations of ECM and PET scaffold into account. The scaffold structureis explicitly included by statistical assessment of the fibre distribution fromCT images. The effective macroscopic equations are obtained by appropriateupscaling from dynamics on lower (microscopic and mesoscopic) scales andfeature in the motility terms an explicit cell diffusion tensor encoding theassessed anisotropic scaffold structure. Numerical simulations show itsinfluence on the overall cell and tissue dynamics.
我们建立了一个人类间充质干细胞(hMSCs)和软骨细胞在用透明质酸浸渍并提供分化培养基的无纺布聚对苯二甲酸乙二醇酯(PET)支架中进化的动力学模型。假定支架和细胞都包含在有液体灌注的生物反应器中。hMSCs 向软骨细胞的分化有利于细胞外基质(ECM)的生成,并受到流体应力的影响。该模型考虑了 ECM 和 PET 支架的变形。通过对 CT 图像中纤维分布的统计评估,支架结构被明确包括在内。通过对较低(微观和中观)尺度的动力学进行适当的放大,得到了有效的宏观方程,并在运动项中加入了一个明确的细胞扩散张量,该张量对评估的各向异性支架结构进行了编码。数值模拟显示了它对整个细胞和组织动力学的影响。
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引用次数: 0
Synthetic Privileged Information Enhances Medical Image Representation Learning 合成特权信息加强医学图像表征学习
Pub Date : 2024-03-08 DOI: arxiv-2403.05220
Lucas Farndale, Chris Walsh, Robert Insall, Ke Yuan
Multimodal self-supervised representation learning has consistently proven tobe a highly effective method in medical image analysis, offering strong taskperformance and producing biologically informed insights. However, thesemethods heavily rely on large, paired datasets, which is prohibitive for theiruse in scenarios where paired data does not exist, or there is only a smallamount available. In contrast, image generation methods can work well on verysmall datasets, and can find mappings between unpaired datasets, meaning aneffectively unlimited amount of paired synthetic data can be generated. In thiswork, we demonstrate that representation learning can be significantly improvedby synthetically generating paired information, both compared to training oneither single-modality (up to 4.4x error reduction) or authentic multi-modalpaired datasets (up to 5.6x error reduction).
多模态自监督表征学习一直被证明是医学图像分析中非常有效的方法,它能提供强大的任务性能,并产生生物学意义上的见解。然而,这些方法在很大程度上依赖于大型配对数据集,在不存在配对数据或只有少量可用数据的情况下,使用这些方法是非常困难的。相比之下,图像生成方法可以在非常小的数据集上很好地工作,并且可以找到未配对数据集之间的映射,这意味着实际上可以生成无限量的配对合成数据。在这项工作中,我们证明了通过合成生成配对信息可以显著改善表征学习,无论是与单模态训练相比(误差减少高达 4.4 倍),还是与真实的多模态配对数据集相比(误差减少高达 5.6 倍),都是如此。
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引用次数: 0
Correction and standardisation of lung oscillometry techniques using parameter inference: A study group report 利用参数推理对肺振荡测量技术进行校正和标准化:研究小组报告
Pub Date : 2024-03-07 DOI: arxiv-2403.04621
Bindi S. Brook, Graeham R. Douglas, Oliver E. Jensen, Sonal Mistry, Sujit Kumar Nath, Matthew J. Russell, Sina Saffaran, James Shemilt, Liam Weaver, Carl A. Whitfield
This report relates to a study group hosted by the EPSRC funded network,Integrating data-driven BIOphysical models into REspiratory MEdicine (BIOREME),and supported by The Insigneo Institute and The Knowledge Transfer Network. TheBIOREME network hosts events, including this study group, to bring togethermulti-disciplinary researchers, clinicians, companies and charities to catalyseresearch in the applications of mathematical modelling for respiratorymedicine. The goal of this study group was to provide an interface betweencompanies, clinicians, and mathematicians to develop mathematical tools to theproblems presented. The study group was held at The University of Sheffield onthe 17 - 20 April 2023 and was attended by 24 researchers from 13 differentinstitutions. This report relates to a challenge presented by Arete Medical Technologiesrelating to impulse oscillometry (IOS), whereby a short pressure oscillation isimposed at a person's mouth during normal breathing, usually by a loudspeaker.The resulting pressure and flow rate changes can be used to the impedance ofthe airways, which in turn can provide proxy measurements for(patho)physiological changes in the small airways. Disentangling the signal sothat airway mechanics can be measured accurately (and deviceproperties/environmental effects can be accounted for) remains an openchallenge that has the potential to significantly improve the device and itstranslation to clinic. In this report, several approaches to this problem, andthe wider problem of interpreting oscillometry resuts are explored.
本报告涉及一个研究小组,该小组由英国工程与科学研究中心(EPSRC)资助的网络 "将数据驱动的生物物理模型融入呼吸医学(BIOREME)"主办,并得到了英西尼奥研究所(Insigneo Institute)和知识转移网络(Knowledge Transfer Network)的支持。BIOREME 网络举办包括本研究小组在内的各种活动,将多学科研究人员、临床医生、公司和慈善机构聚集在一起,促进呼吸医学数学建模应用方面的研究。该研究小组的目标是在公司、临床医生和数学家之间提供一个接口,以开发数学工具来解决所提出的问题。研究小组于 2023 年 4 月 17-20 日在谢菲尔德大学举行,来自 13 个不同机构的 24 名研究人员参加了会议。本报告涉及 Arete 医疗技术公司提出的与脉冲振荡测量(IOS)有关的挑战,即在正常呼吸过程中,通常通过扬声器在人的口腔处施加一个短时压力振荡,由此产生的压力和流速变化可用于测量气道阻抗,进而提供小气道(病理)生理变化的替代测量值。分解信号以便准确测量气道力学(并考虑设备特性/环境影响)仍然是一个有待解决的难题,它有可能极大地改进设备并将其应用于临床。本报告探讨了解决这一问题的几种方法,以及解释示波测量结果这一更广泛的问题。
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引用次数: 0
Hitchhiker's guide to cancer-associated lymphoid aggregates in histology images: manual and deep learning-based quantification approaches 组织学图像中癌症相关淋巴聚集体的 "搭便车指南":手动和基于深度学习的量化方法
Pub Date : 2024-03-06 DOI: arxiv-2403.04142
Karina Silina, Francesco Ciompi
Quantification of lymphoid aggregates including tertiary lymphoid structureswith germinal centers in histology images of cancer is a promising approach fordeveloping prognostic and predictive tissue biomarkers. In this article, weprovide recommendations for identifying lymphoid aggregates in tissue sectionsfrom routine pathology workflows such as hematoxylin and eosin staining. Toovercome the intrinsic variability associated with manual image analysis (suchas subjective decision making, attention span), we recently developed a deeplearning-based algorithm called HookNet-TLS to detect lymphoid aggregates andgerminal centers in various tissues. Here, we additionally provide a guidelinefor using manually annotated images for training and implementing HookNet-TLSfor automated and objective quantification of lymphoid aggregates in variouscancer types.
对癌症组织学图像中的淋巴聚集体(包括带有生殖中心的三级淋巴结构)进行定量是开发预后和预测性组织生物标记物的一种很有前景的方法。在本文中,我们将为从苏木精和伊红染色等常规病理工作流程中识别组织切片中的淋巴聚集提供建议。为了克服人工图像分析的内在可变性(如主观决策、注意力等),我们最近开发了一种基于深度学习的算法,称为 HookNet-TLS,用于检测各种组织中的淋巴聚集体和生殖中心。在此,我们还提供了使用人工标注图像进行训练和实施 HookNet-TLS 的指南,以便自动、客观地量化各种癌症类型中的淋巴聚集。
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引用次数: 0
NIR ICG-Enhanced Fluorescence: A Quantitative Evaluation of Bowel Microperfusion and Its Relation to Central Perfusion in Colorectal Surgery 近红外 ICG 增强荧光:定量评估结肠直肠手术中的肠道微灌注及其与中心灌注的关系
Pub Date : 2024-03-04 DOI: arxiv-2403.01844
N. Depalma, S. D Ugo, F. Manoochehri, A. Libia, W. Sergi, T. R. L. Marchese, S. Forciniti, L. L. del Mercato, P. Piscitelli, S. Garritano, F. Castellana, R. Zupo, M. G. Spampinato
Background: To date, no standardized protocols nor a quantitative assessmentof the near-infrared fluorescence angiography with indocyanine green (NIR-ICG)are available. The aim of this study was to evaluate the timing of fluorescenceas a reproducible parameter and its efficacy in predicting anastomotic leakage(AL) in colorectal surgery. Methods: A consecutive cohort of 108 patientsundergoing minimally invasive elective procedures for colorectal cancer wasprospectively enrolled. The difference between macro and microperfusion DeltaTwas obtained by calculating the timing of fluorescence at the level of iliacartery division and colonic wall, respectively. Results: Subjects with a DeltaThigher 15.5 s had a higher tendency to develop an AL (p lower 0.01). TheDeltaT/heart rate interaction was found to predict AL with an odds ratio of1.02 (p lower 0.01); a cut-off threshold of 832 was identified (sensitivity0.86, specificity 0.77). Perfusion parameters were also associated with afaster bowel motility resumption and a reduced length of hospital stay.Conclusions: The analysis of the timing of fluorescence provides aquantitative, easy evaluation of tissue perfusion. A DeltaT/HR interactionhigher 832 may be used as a real-time parameter to guide surgical decisionmaking in colorectal surgery.
背景:迄今为止,吲哚菁绿近红外荧光血管造影术(NIR-ICG)尚无标准化方案或定量评估。本研究旨在评估荧光时间这一可重复性参数及其在预测结直肠手术吻合口漏(AL)方面的有效性。方法:连续观察108例接受微创择期结直肠癌手术的患者。通过计算髂动脉分叉处和结肠壁荧光的时间,分别得出宏观和微观灌注 DeltaT 的差异。结果显示DeltaT 高于 15.5 秒的受试者更容易发生 AL(p 低于 0.01)。发现 DeltaT 与心率的交互作用可预测 AL,几率比为 1.02(p 低于 0.01);确定了 832 的临界值(敏感性 0.86,特异性 0.77)。灌注参数还与肠蠕动恢复速度加快和住院时间缩短有关:对荧光时间的分析可对组织灌注进行定量、简便的评估。DeltaT/HR 相互作用高于 832 时,可用作结直肠手术中指导手术决策的实时参数。
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引用次数: 0
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arXiv - QuanBio - Tissues and Organs
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