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Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.
Am J Physiol Gastrointest Liver Physiol
January 2025
Department of Molecular Biomedical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, NC, USA.
Intestinal ischemic injury damages the epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined.
View Article and Find Full Text PDFExploration of linear and interpretable models for quantification of cell parameters via contactless short-wave infrared hyperspectral sensing.
Sci Rep
January 2025
Fischell Department of Bioengineering, University of Maryland, College Park, USA.
The development of optical sensors for label-free quantification of cell parameters has numerous uses in the biomedical arena. However, using current optical probes requires the laborious collection of sufficiently large datasets that can be used to calibrate optical probe signals to true metabolite concentrations. Further, most practitioners find it difficult to confidently adapt black box chemometric models that are difficult to troubleshoot in high-stakes applications such as biopharmaceutical manufacturing.
View Article and Find Full Text PDFCD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.
iScience
January 2025
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.
View Article and Find Full Text PDFManagement of Perianal Fistulizing Crohn's Disease According to Principles of Wound Repair.
Aliment Pharmacol Ther
February 2025
Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
Background: Perianal fistulizing Crohn's disease (PFCD) is a challenging and debilitating phenotype of Crohn's disease that can negatively affect quality of life. Studies have begun to uncover the physiologic mechanisms involved in wound repair as it relates to PFCD and how aberrations in these mechanisms may contribute to fistula persistence.
Aims: To review the physiologic and pathophysiologic mechanisms of wound repair in PFCD and how specific therapeutic strategies may impact their outcomes.
A simulation study of the impact of drug-I binding mechanisms on biomarkers of proarrhythmic risk reveals a crucial role in reverse use-dependence of action potential duration and a marked influence on the vulnerable window.
Comput Methods Programs Biomed
December 2024
Centro de Investigación e Innovación en Bioingeniería (Ci2B), Universitat Politècnica de València, Valencia, Spain. Electronic address:
Background And Objective: In silico human models are being used more and more to predict the potential proarrhythmic risk of compounds. It has been shown that incorporation of the dynamics of drug-hERG channel interactions can have an important impact on the action potential duration (APD) at normal heart rates. Our aim is to investigate the relevance of drug dynamics on other important biomarkers of proarrhythmic risk.
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