Multicellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53.

Neuroblastoma is the most common extra-cranial solid tumour in children. Over half of all high-risk cases are expected to succumb to the disease even after chemotherapy, surgery, and immunotherapy. Although the importance of MYCN amplification in this disease is indisputable, the mechanistic details remain enigmatic.

Sensitivity analysis of closed-loop one-chamber and four-chamber models with baroreflex.

The baroreflex is one of the most important control mechanisms in the human cardiovascular system. This work utilises a closed-loop in silico model of baroreflex regulation, coupled to pulsatile mechanical models with (i) one heart chamber and 36-parameters and (ii) four chambers and 51 parameters. We perform the first global sensitivity analysis of these closed-loop systems which considers both cardiovascular and baroreflex parameters, and compare the models with their respective unregulated equivalents.

Individual Variability in the Structural Connectivity Architecture of the Human Brain.

The human brain exhibits high degree of individual variability in both its structure and function, which underlies inter-subject differences in cognition and behavior. It was previously shown that functional connectivity is more variable in the hetero-modal association cortex but less variable in the unimodal cortices. Structural connectivity is the anatomical substrate of functional connectivity, but the spatial and temporal patterns of individual variability in structural connectivity (IVSC) remain largely unknown.

Pickering polymerized high internal phase emulsions: Fundamentals to advanced applications.

Pickering-polymerized high internal phase emulsions have attracted attention since their successful first preparation 15 years ago, primarily due to their large pores and potential for functionalization during production. This review elucidates the fundamental principles of Pickering emulsions, Pickering HIPEs, and Pickering PolyHIPEs while comparing them to conventional surfactant-stabilized counterparts. The morphology of Pickering PolyHIPEs, with particular emphasis on methods for achieving interconnected structures, is explored and critically assessed.

openBF: an open-source finite volume 1D blood flow solver.

Computational simulations are widely adopted in cardiovascular biomechanics because of their capability of producing physiological data otherwise impossible to measure with non-invasive modalities.This study presents openBF, a computational library for simulating the blood dynamics in the cardiovascular system.openBF adopts a one-dimensional viscoelastic representation of the arterial system, and is coupled with zero-dimensional windkessel models at the outlets.

Computational fluid dynamics and shape analysis enhance aneurysm rupture risk stratification.

Purpose: Accurately quantifying the rupture risk of unruptured intracranial aneurysms (UIAs) is crucial for guiding treatment decisions and remains an unmet clinical challenge. Computational Flow Dynamics and morphological measurements have been shown to differ between ruptured and unruptured aneurysms. It is not clear if these provide any additional information above routinely available clinical observations or not.

A novel framework for elucidating the effect of mechanical loading on the geometry of ovariectomized mouse tibiae using principal component analysis.

Introduction: Murine models are used to test the effect of anti-osteoporosis treatments as they replicate some of the bone phenotypes observed in osteoporotic (OP) patients. The effect of disease and treatment is typically described as changes in bone geometry and microstructure over time. Conventional assessment of geometric changes relies on morphometric scalar parameters.

Sympathetic reinnervation in cardiac transplant recipients: Prevalence, time course, and association with long-term survival.

Background: Partial cardiac sympathetic reinnervation after cardiac transplant has been extensively investigated and evidenced. However, there have been no large-scale, long-term studies evaluating the prevalence, time-course, and association with long-term survival of sympathetic reinnervation of the heart.

Methods: Cardiac transplant recipients (n = 232) were recruited from outpatient clinic at a single transplant center in the United Kingdom.

Do Hemodynamic Definitions of Chronic Thromboembolic Pulmonary Hypertension Distinguish Between Distinct Phenotypes of Chronic Thromboembolic Pulmonary Disease?

Background: Chronic thromboembolic pulmonary disease (CTEPD) is defined by chronic organized thrombi in the pulmonary circulation without or with pulmonary hypertension (CTEPH). The current definition of CTEPH has adopted lower mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) thresholds. Our aim was to identify its impact on the characterization of patients with CTEPD.

The effects of APOEe4 allele on cerebral structure, function, and related interactions with cognition in young adults.

In the last decade, extensive research has emerged into understanding the impact of risk factors for Alzheimer's Disease (AD) on brain in pre-symptomatic stages. We investigated the neuroimaging correlates of the APOEe4 genetic risk factor for AD in young adulthood, its relationship with cognition, and potential effects of other variables on the findings. While conventional volumetric analyses revealed no consistent differences, more sophisticated analyses identified subtle structural differences between APOEe4 carriers and non-carriers.

Evidence of time dependent degradation of polypropylene surgical mesh explanted from the abdomen and vagina of sheep.

The failure of polypropylene mesh is marked by significant side effects and debilitation, arising from a complex interplay of factors. One key contributor is the pronounced physico-mechanical mismatch between the polypropylene (PP) fibres and surrounding tissues, resulting in substantial physical damage, inflammation, and persistent pain. However, the primary cause of sustained inflammation due to polypropylene itself remains incompletely understood.

Air Pollution and Osteoporosis.

Purpose Of Review: The purpose of this review is to provide a background of osteoporosis and air pollution, discussing increasing incidence of the disease with exposure to pollutants and the role that inflammation may play in this process.

Recent Findings: Osteoporosis-related fractures are one of the most pressing challenges for the ageing global population, with significant increases in mortality known to occur after major osteoporotic fractures in the elderly population. Recent studies have established a firm correlative link between areas of high air pollution and increased risk of osteoporosis, particularly alarming given the increasingly urban global population.

Remotely actuated programmable self-folding origami strings using magnetic induction heating.

Transforming planar structures into volumetric objects typically requires manual folding processes, akin to origami. However, manual intervention at sub-centimeter scales is impractical. Instead, folding is achieved using volume-changing smart materials that respond to physical or chemical stimuli, be it with direct contact such as hydration, pH, or remotely e.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant.

Analytical and computational studies predict negligible risk of cell death from eddy generation off flat surfaces in cell culture flow systems.

Cell-based therapies represent the current frontier of biomedical innovations, with the technologies required underpinning treatments as broad as CAR-T cell therapies, stem cell treatments, genetic therapies and mRNA manufacture. A key bottleneck in the manufacturing process for each of these lies in the expansion of cells within a bioreactor vessel, requiring by far the greatest share of time for what are often time-critical therapies. While various designs, culture feeding and mixing methods are employed in these bioreactors, a common concern among manufacturers and researchers lies in whether shear stresses generated by culture media flow will damage cells and inhibit expansion.

3D Melt-Extrusion Printing of Medium Chain Length Polyhydroxyalkanoates and Their Application as Antibiotic-Free Antibacterial Scaffolds for Bone Regeneration.

In this work, we investigated, for the first time, the possibility of developing scaffolds for bone tissue engineering through three-dimensional (3D) melt-extrusion printing of medium chain length polyhydroxyalkanoate (mcl-PHA) (i.e., poly(3-hydroxyoctanoate--hydroxydecanoate--hydroxydodecanoate), P(3HO--3HD--3HDD)).

Multimodal soft valve enables physical responsiveness for preemptive resilience of soft robots.

Resilience is crucial for the self-preservation of biological systems: Humans recover from wounds thanks to an immune system that autonomously enacts a multistage response to promote healing. Similar passive mechanisms can enable pneumatic soft robots to overcome common faults such as bursts originating from punctures or overpressurization. Recent technological advancements, ranging from fault-tolerant controllers for robot reconfigurability to self-healing materials, have paved the way for robot resilience.

Convergence, sampling and total order estimator effects on parameter orthogonality in global sensitivity analysis.

Dynamical system models typically involve numerous input parameters whose "effects" and orthogonality need to be quantified through sensitivity analysis, to identify inputs contributing the greatest uncertainty. Whilst prior art has compared total-order estimators' role in recovering "true" effects, assessing their ability to recover robust parameter orthogonality for use in identifiability metrics has not been investigated. In this paper, we perform: (i) an assessment using a different class of numerical models representing the cardiovascular system, (ii) a wider evaluation of sampling methodologies and their interactions with estimators, (iii) an investigation of the consequences of permuting estimators and sampling methodologies on input parameter orthogonality, (iv) a study of sample convergence through resampling, and (v) an assessment of whether positive outcomes are sustained when model input dimensionality increases.

Texture perception at the foot sole: comparison between walking, sitting, and to the hand.

We frequently interact with textured surfaces with both our feet and hands. Like texture's importance for grasping, texture perception via the foot sole might provide important signals about the stability of a surface, aiding in maintaining balance. However, how textures are perceived by the foot, and especially under the high forces experienced during walking, is unknown.

Re-entry in models of cardiac ventricular tissue with scar represented as a Gaussian random field.

Fibrotic scar in the heart is known to act as a substrate for arrhythmias. Regions of fibrotic scar are associated with slowed or blocked conduction of the action potential, but the detailed mechanisms of arrhythmia formation are not well characterised and this can limit the effective diagnosis and treatment of scar in patients. The aim of this computational study was to evaluate different representations of fibrotic scar in models of 2D 10 10 cm ventricular tissue, where the region of scar was defined by sampling a Gaussian random field with an adjustable length scale of between 1.