The complex interplay of a pathogen with its virulence and fitness factors, the host's immune response, and the endogenous microbiome determine the course and outcome of gastrointestinal infection. The expansion of a pathogen within the gastrointestinal tract implies an increased risk of developing severe systemic infections, especially in dysbiotic or immunocompromised individuals. We developed a mechanistic computational model that calculates and simulates such scenarios, based on an ordinary differential equation system, to explain the bacterial population dynamics during gastrointestinal infection. For implementing the model and estimating its parameters, oral mouse infection experiments with the enteropathogen, (Ye), were carried out. Our model accounts for specific pathogen characteristics and is intended to reflect scenarios where colonization resistance, mediated by the endogenous microbiome, is lacking, or where the immune response is partially impaired. Fitting our data from experimental mouse infections, we can justify our model setup and deduce cues for further model improvement. The model is freely available, in SBML format, from the BioModels Database under the accession number MODEL2002070001.
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http://dx.doi.org/10.3390/biology11020297 | DOI Listing |
Med Phys
January 2025
Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Background: A cylindrical free-air chamber, the Attix FAC, is used for absolute air-kerma measurements of low-energy photon beams at the University of Wisconsin Medical Radiation Research Center. Correction factors for air-kerma measurements of specific beams were determined in the 1990s. In order to measure air-kerma rates of beams in development, new correction factors must be computed.
View Article and Find Full Text PDFStat Med
February 2025
Department of Mathematical Sciences, University of Texas at Dallas, Richardson, Texas, USA.
Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.
View Article and Find Full Text PDFProtein Sci
February 2025
Department of Physics, University of Washington, Seattle, Washington, USA.
Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.
View Article and Find Full Text PDFOphthalmic Physiol Opt
January 2025
Robert O Curle Ophthalmology Suite, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.
Purpose: To determine whether imaging features derived from fundus photographs contain 3D eye shape information beyond that available from spherical equivalent refraction (SER).
Methods: We analysed 99 eyes of 68 normal adults in the UK Biobank. An ellipsoid was fitted to the entire volume of each posterior eye (vitreous chamber without the lens)-segmented from magnetic resonance imaging of the brain.
Stat Med
February 2025
Biostatistics, Innovatio Statistics Inc., Bridgewater, New Jersey, USA.
Sample size re-estimation (SSR) is perhaps the most used adaptive procedure in both frequentist and Bayesian adaptive designs for clinical trials. The primary focus of all current frequentist and Bayesian SSR procedures is type I error control. We propose a hybrid frequentist-Bayesian SSR approach that focuses on optimizing operating characteristics (OC), which uses simulations to investigate the associated OC and adjusts accordingly.
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