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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., …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.

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization (2022)
Journal Article
Shur, N. F., Simpson, E. J., Crossland, H., Chivaka, P. K., Constantin, D., Cordon, S. M., …Greenhaff, P. L. (2022). Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 2999-3013. https://doi.org/10.1002/jcsm.13075

Background: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers... Read More about Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

Ion channel model reduction using manifold boundaries (2022)
Journal Article
Whittaker, D. G., Wang, J., Shuttleworth, J., Venkateshappa, R., Kemp, J. M., Claydon, T. W., & Mirams, G. R. (2022). Ion channel model reduction using manifold boundaries. Journal of the Royal Society, Interface, 19(193), Article 20220193. https://doi.org/10.1098/rsif.2022.0193

Mathematical models of voltage-gated ion channels are used in basic research, industrial and clinical settings. These models range in complexity, but typically contain numerous variables representing the proportion of channels in a given state, and p... Read More about Ion channel model reduction using manifold boundaries.

Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants (2020)
Journal Article
Heissam, K., Abrehart, N., Hoad, C. L., Wright, J., Menys, A., Murray, K., …Marciani, L. (2020). Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants. PLoS ONE, 15(11), e0241441. https://doi.org/10.1371/journal.pone.0241441

Objective The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo dat... Read More about Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants.

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., …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.

The Differential Expression of ERAP1/ERAP2 and Immune Cell Activation in Pre-eclampsia (2020)
Journal Article
Stratikos, E., Warthan, M., Strauss, J. F., Kurlak, L. O., Seamon, K., Lee, E. D., & Mistry, H. D. (2020). The Differential Expression of ERAP1/ERAP2 and Immune Cell Activation in Pre-eclampsia. Frontiers in Immunology, 11, Article 396. https://doi.org/10.3389/fimmu.2020.00396

Pre-eclampsia (PE) is a disorder of pregnancy, often leading to serious and fatal complications. Endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1/ERAP2) are present in the placenta. They are involved in processes regulating blood pressure, angioge... Read More about The Differential Expression of ERAP1/ERAP2 and Immune Cell Activation in Pre-eclampsia.

Glycemic, Gastrointestinal, Hormonal and Appetitive Responses to Pearl Millet or Oats Porridge Breakfasts: a Randomized, Crossover Trial in Healthy Humans (2019)
Journal Article
Alyami, J., Whitehouse, E., Yakubov, G. E., Pritchard, S. E., Hoad, C. L., Blackshaw, E., …Marciani, L. (2019). Glycemic, Gastrointestinal, Hormonal and Appetitive Responses to Pearl Millet or Oats Porridge Breakfasts: a Randomized, Crossover Trial in Healthy Humans. British Journal of Nutrition, https://doi.org/10.1017/S0007114519001880

Whole grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known... Read More about Glycemic, Gastrointestinal, Hormonal and Appetitive Responses to Pearl Millet or Oats Porridge Breakfasts: a Randomized, Crossover Trial in Healthy Humans.

Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans (2019)
Journal Article
Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., …Higashitani, A. (2019). Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans. FASEB Journal, 33(8), 9540-9550. https://doi.org/10.1096/fj.201802298r

Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)–based proteolysis and, consequentially, musc... Read More about Mitochondrial dysfunction causes Ca2+ overload and ECM degradation–mediated muscle damage in C. elegans.

The acute transcriptional response to resistance exercise: impact of age and contraction mode (2019)
Journal Article
Deane, C. S., Ames, R. M., Phillips, B. E., Weedon, M. N., Willis, C. R., Boereboom, C., …Etheridge, T. (2019). The acute transcriptional response to resistance exercise: impact of age and contraction mode. Aging, 11(7), 2111-2126. https://doi.org/10.18632/aging.101904

Optimization of resistance exercise (RE) remains a hotbed of research for muscle building and maintenance. However, the interactions between the contractile components of RE (i.e. concentric (CON) and eccentric (ECC)) and age, are poorly defined. We... Read More about The acute transcriptional response to resistance exercise: impact of age and contraction mode.

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.