Utilising an in silico model to predict outcomes in senescence-driven acute liver injury.

Currently liver transplantation is the only treatment option for liver disease, but organ availability cannot meet patient demand. Alternative regenerative therapies, including cell transplantation, aim to modulate the injured microenvironment from inflammation and scarring towards regeneration. The complexity of the liver injury response makes it challenging to identify suitable therapeutic targets when relying on experimental approaches alone.

Enhancing nanoscale viscoelasticity characterization in bimodal atomic force microscopy.

Polymeric, soft, and biological materials exhibit viscoelasticity, which is a time dependent mechanical response to deformation. Material viscoelasticity emerges from the movement of a material's constituent molecules at the nano- and microscale in response to applied deformation. Therefore, viscoelastic properties depend on the speed at which a material is deformed.

Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside.

Cell therapies are emerging as promising treatments for a range of liver diseases but translational bottlenecks still remain including: securing and assessing the safe and effective delivery of cells to the disease site; ensuring successful cell engraftment and function; and preventing immunogenic responses. Here we highlight three therapies, each utilising a different cell type, at different stages in their clinical translation journey: transplantation of multipotent mesenchymal stromal/signalling cells, hepatocytes and macrophages. To overcome bottlenecks impeding clinical progression, we advocate for wider use of mechanistic in silico modelling approaches.

An automated method for tendon image segmentation on ultrasound using grey-level co-occurrence matrix features and hidden Gaussian Markov random fields.

Background: Despite knowledge of qualitative changes that occur on ultrasound in tendinopathy, there is currently no objective and reliable means to quantify the severity or prognosis of tendinopathy on ultrasound.

Objective: The primary objective of this study is to produce a quantitative and automated means of inferring potential structural changes in tendinopathy by developing and implementing an algorithm which performs a texture based segmentation of tendon ultrasound (US) images.

Method: A model-based segmentation approach is used which combines Gaussian mixture models, Markov random field theory and grey-level co-occurrence (GLCM) features.

Debiased ambient vibrations optical coherence elastography to profile cell, organoid and tissue mechanical properties.

The role of the mechanical environment in defining tissue function, development and growth has been shown to be fundamental. Assessment of the changes in stiffness of tissue matrices at multiple scales has relied mostly on invasive and often specialist equipment such as AFM or mechanical testing devices poorly suited to the cell culture workflow.In this paper, we have developed a unbiased passive optical coherence elastography method, exploiting ambient vibrations in the sample that enables real-time noninvasive quantitative profiling of cells and tissues.

Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales.

Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed.

A model-informed approach to assess the risk of immune checkpoint inhibitor-induced autoimmune myocarditis.

Immune checkpoint inhibitors (ICIs), as a novel immunotherapy, are designed to modulate the immune system to attack malignancies. Despite their promising benefits, immune-related adverse events (IRAEs) may occur, and incidences are bound to increase with surging demand of this class of drugs in treating cancer. Myocarditis, although rare compared to other IRAEs, has a significantly higher fatal frequency.

Assess and address: Screening and management of depression in patients with chronic heart failure.

Background: About one in three patients with heart failure (HF) have depression. Comorbid HF and depression are associated with poor outcomes and increased health care burden. Clinical guidelines recommend routine depression screening in patients with HF.

Evaluation of a scalable online videogame-based biofeedback program to improve emotion regulation: A descriptive study assessing parent perspectives.

Individuals and families increasingly turn to e-mental health apps for education, diagnosis, and treatment of mental health disorders and to promote mental wellness. These apps provide significant increases in convenience from existing services, since they can augment or replace services with on-demand access within the home. This raises important questions about self-selection of interventions.

Mathematical modelling of autoimmune myocarditis and the effects of immune checkpoint inhibitors.

Autoimmune myocarditis is a rare, but frequently fatal, side effect of immune checkpoint inhibitors (ICIs), a class of cancer therapies. Despite extensive experimental work on the causes, development and progression of this disease, much still remains unknown about the importance of the different immunological pathways involved. We present a mathematical model of autoimmune myocarditis and the effects of ICIs on its development and progression to either resolution or chronic inflammation.

Fluid mechanical modeling of the upper urinary tract.

The upper urinary tract (UUT) consists of kidneys and ureters, and is an integral part of the human urogenital system. Yet malfunctioning and complications of the UUT can happen at all stages of life, attributed to reasons such as congenital anomalies, urinary tract infections, urolithiasis and urothelial cancers, all of which require urological interventions and significantly compromise patients' quality of life. Therefore, many models have been developed to address the relevant scientific and clinical challenges of the UUT.

Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. The pattern of lower motor neuron loss along the spinal cord follows the pattern of deposition of phosphorylated TDP-43 aggregates. The blood-spinal cord barrier (BSCB) restricts entry into the spinal cord parenchyma of blood components that can promote motor neuron degeneration, but in ALS there is evidence for barrier breakdown.

A Systematically Reduced Mathematical Model for Organoid Expansion.

Organoids are three-dimensional multicellular tissue constructs. When cultured , they recapitulate the structure, heterogeneity, and function of their counterparts. As awareness of the multiple uses of organoids has grown, .

The Interplay Between Beta-Amyloid 1-42 (Aβ)-Induced Hippocampal Inflammatory Response, p-tau, Vascular Pathology, and Their Synergistic Contributions to Neuronal Death and Behavioral Deficits.

Alzheimer's disease (AD), the most common chronic neurodegenerative disorder, has complex neuropathology. The principal neuropathological hallmarks of the disease are the deposition of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) comprised of hyperphosphorylated tau (p-tau) protein. These changes occur with neuroinflammation, a compromised blood-brain barrier (BBB) integrity, and neuronal synaptic dysfunction, all of which ultimately lead to neuronal cell loss and cognitive deficits in AD.

Combining multiple spatial statistics enhances the description of immune cell localisation within tumours.

Digital pathology enables computational analysis algorithms to be applied at scale to histological images. An example is the identification of immune cells within solid tumours. Image analysis algorithms can extract precise cell locations from immunohistochemistry slides, but the resulting spatial coordinates, or point patterns, can be difficult to interpret.

Mathematical modelling reveals cellular dynamics within tumour spheroids.

Tumour spheroids are widely used as an in vitro assay for characterising the dynamics and response to treatment of different cancer cell lines. Their popularity is largely due to the reproducible manner in which spheroids grow: the diffusion of nutrients and oxygen from the surrounding culture medium, and their consumption by tumour cells, causes proliferation to be localised at the spheroid boundary. As the spheroid grows, cells at the spheroid centre may become hypoxic and die, forming a necrotic core.

Predicting Bone Formation in Mesenchymal Stromal Cell-Seeded Hydrogels Using Experiment-Based Mathematical Modeling.

bone formation by mesenchymal stromal cells encapsulated in type-1 collagen hydrogels is demonstrated after a 28-day culture period. Analysis of the hydrogels is carried out by X-ray microcomputed tomography, histology, and immunohistochemistry, which collectively demonstrates that bone formation in the hydrogels was quantifiably proportional to the initial collagen concentration, and subsequently the population density of seeded cells. This was established by varying the initial collagen concentration at a constant cell seeding density (3 × 10 cells/0.

Identifying chondrogenesis strategies for tissue engineering of articular cartilage.

A key step in the tissue engineering of articular cartilage is the chondrogenic differentiation of mesenchymal stem cells (MSCs) into chondrocytes (native cartilage cells). Chondrogenesis is regulated by transforming growth factor- (TGF-), a short-lived cytokine whose effect is prolonged by storage in the extracellular matrix. Tissue engineering applications aim to maximise the yield of differentiated MSCs.

The Fluid Mechanics of Ureteroscope Irrigation.

Purpose: To develop a physical understanding of ureterorenoscopy irrigation, we derive mathematical models from basic physical principles and compare these predictions with the results of benchtop experiments. Mathematical modeling can be used to understand the role of inlet pressure, tip deflection, the presence of working tools, geometric properties of the instruments used, and material properties of the irrigation fluid on resulting flow rate.

Materials And Methods: We develop theoretical models to describe irrigation flow in an idealized setup and compare with benchtop experiments for flow through a straight scope, a scope with a deflected tip, and a scope with a working tool inserted.

Lattice and continuum modelling of a bioactive porous tissue scaffold.

A contemporary procedure to grow artificial tissue is to seed cells onto a porous biomaterial scaffold and culture it within a perfusion bioreactor to facilitate the transport of nutrients to growing cells. Typical models of cell growth for tissue engineering applications make use of spatially homogeneous or spatially continuous equations to model cell growth, flow of culture medium, nutrient transport and their interactions. The network structure of the physical porous scaffold is often incorporated through parameters in these models, either phenomenologically or through techniques like mathematical homogenization.

Allostatic load but not medical burden predicts memory performance in late-life bipolar disorder.

Objective: Older patients with bipolar disorder (BD) present with variable degrees of cognitive impairment. Over time, stress, mood episodes, and comorbidities increase the body's allostatic load. We assessed the extent to which allostatic load vs more traditional measures of medical burden account for the heterogeneity in cognition in this population.

Inducing chondrogenesis in MSC/chondrocyte co-cultures using exogenous TGF-β: a mathematical model.

The differentiation of mesenchymal stem cells (MSCs) into chondrocytes (native cartilage cells), or chondrogenesis, is a key step in the tissue engineering of articular cartilage, where the motility and high proliferation rate of MSCs used as seed cells are exploited. Chondrogenesis is regulated by transforming growth factor-beta (TGF-β), a short-lived cytokine whose effect is prolonged by storage in the extracellular matrix. Tissue engineering applications require the complete differentiation of an initial population of MSCs, and two common strategies used to achieve this in vitro are (1) co-culture the MSCs with chondrocytes, which constitutively produce TGF-β; or (2) add exogenous TGF-β.