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Outputs (8)

Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics (2023)
Journal Article
Shuttleworth, J. G., Lei, C. L., Whittaker, D. G., Windley, M. J., Hill, A. P., Preston, S. P., & Mirams, G. R. (2024). Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics. Bulletin of Mathematical Biology, 86(1), Article 2. https://doi.org/10.1007/s11538-023-01224-6

When using mathematical models to make quantitative predictions for clinical or industrial use, it is important that predictions come with a reliable estimate of their accuracy (uncertainty quantification). Because models of complex biological system... Read More about Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics.

The impact of uncertainty in hERG binding mechanism on in silico predictions of drug-induced proarrhythmic risk (2023)
Journal Article
Lei, C. L., Whittaker, D. G., & Mirams, G. R. (2024). The impact of uncertainty in hERG binding mechanism on in silico predictions of drug-induced proarrhythmic risk. British Journal of Pharmacology, 181(7), 987-1004. https://doi.org/10.1111/bph.16250

Background and Purpose
Drug-induced reduction of the rapid delayed rectifier potassium current carried by the human Ether-à-go-go-Related Gene (hERG) channel is associated with increased risk of arrhythmias. Recent updates to drug safety regulatory... Read More about The impact of uncertainty in hERG binding mechanism on in silico predictions of drug-induced proarrhythmic risk.

Systematic Review: Sarcopenia in paediatric inflammatory bowel disease (2023)
Journal Article
Aljilani, B., Tsintzas, K., Jacques, M., Radford, S., & Moran, G. W. (2023). Systematic Review: Sarcopenia in paediatric inflammatory bowel disease. Clinical Nutrition ESPEN, 57, 647-654. https://doi.org/10.1016/j.clnesp.2023.08.009

Background: Low skeletal muscle mass (MM) and deteriorated function (sarcopenia) can be a frequent complication in paediatric inflammatory bowel disease (IBD). Aim: To conduct a systematic review of the paediatric IBD literature on skeletal muscle fu... Read More about Systematic Review: Sarcopenia in paediatric inflammatory bowel disease.

Computational Cardiac Safety Testing (2023)
Book Chapter
Mirams, G. R. (2023). Computational Cardiac Safety Testing. In F. J. Hock, M. R. Gralinski, & M. K. Pugsley (Eds.), Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays (1-33). Springer. https://doi.org/10.1007/978-3-030-73317-9_137-1

In recent years, computational cardiac electrophysiology simulations using mathematical models have begun to be used in industrial and regulatory assessment of the proarrhythmic risk of candidate drug compounds. The aim of this chapter is to equip th... Read More about Computational Cardiac Safety Testing.

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men (2022)
Journal Article
Abbara, A., Koysombat, K., Phylactou, M., Chia Eng, P., Clarke, S., Comninos, A. N., Yang, L., Izzi-Engbeaya, C., Hanassab, S., Smith, N., Jayasena, C. N., Xu, C., Quinton, R., Pitteloud, N., Binder, G., Anand-Ivell, R., Ivell, R., & Dhillo, W. S. (2022). Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men. Frontiers in Endocrinology, 13, Article 1076984. https://doi.org/10.3389/fendo.2022.1076984

Background: Delayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” fea... Read More about Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men.

SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells (2020)
Journal Article
Kim, J. Y., Bai, Y., Jayne, L. A., Abdulkader, F., Gandhi, M., Perreau, T., Parikh, S. V., Gardner, D. S., Davidson, A. J., Sander, V., Song, M. A., Bajwa, A., & Pabla, N. S. (2020). SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells. Journal of Biological Chemistry, 295(48), 16328-16341. https://doi.org/10.1074/jbc.RA120.015110

© 2020 Kim et al. Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, and cardiovascular disorders, the underlying disease or... Read More about SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells.

A Population-based PBPK Model for the Prediction of Time-Variant Bile Salt Disposition within GI Luminal Fluids (2020)
Journal Article
Stamatopoulos, K., Pathak, S., Marciani, L., & Turner, D. (2020). A Population-based PBPK Model for the Prediction of Time-Variant Bile Salt Disposition within GI Luminal Fluids. Molecular Pharmaceutics, 17(4), 1310-1323. https://doi.org/10.1021/acs.molpharmaceut.0c00019

In vivo studies have shown cyclic bile salt (BS) outputs during fasting whereas higher amounts have been observed in fed states. This leads to fluctuations of intestinal BS concentrations ([BS]) that can affect the rate and extent of absorption of li... Read More about A Population-based PBPK Model for the Prediction of Time-Variant Bile Salt Disposition within GI Luminal Fluids.

Simvastatin inhibits L-type Ca 2+ -channel activity through impairment of mitochondrial function (2019)
Journal Article
Curry, L., Almukhtar, H., Alahmed, J., Roberts, R., & Smith, P. A. (2019). Simvastatin inhibits L-type Ca 2+ -channel activity through impairment of mitochondrial function. Toxicological Sciences, 169(2), 543–552. https://doi.org/10.1093/toxsci/kfz068

Plasma membrane ion channels and mitochondrial electron transport complexes (mETC) are recognised “off-targets” for certain drugs. Simvastatin is one such drug, a lipophilic statin used to treat hypercholesterolaemia, but which is also associated wit... Read More about Simvastatin inhibits L-type Ca 2+ -channel activity through impairment of mitochondrial function.