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A physiologically-based flow network model for hepatic drug elimination III: 2D/3D DLA lobule models

Overview of attention for article published in Theoretical Biology and Medical Modelling, March 2016
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1 tweeter

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25 Mendeley
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Title
A physiologically-based flow network model for hepatic drug elimination III: 2D/3D DLA lobule models
Published in
Theoretical Biology and Medical Modelling, March 2016
DOI 10.1186/s12976-016-0034-5
Pubmed ID
Authors

Vahid Rezania, Dennis Coombe, Jack A. Tuszynski

Abstract

One of the major issues in current pharmaceutical development is potential hepatotoxicity and drug-induced liver damage. This is due to the unique metabolic processes performed in the liver to prevent accumulation of a wide range of chemicals in the blood. Recently, we developed a physiologically-based lattice model to address the transport and metabolism of drugs in the liver lobule (liver functional unit). In this paper, we extend our idealized model to consider structural and spatial variability in two and three dimensions. We introduce a hexagonal-based model with one input (portal vein) and six outputs (hepatic veins) to represent a typical liver lobule. To capture even more realistic structures, we implement a novel sequential diffusion-limited aggregation (DLA) method to construct a morphological sinusoid network in the lobule. A 3D model constructed with stacks of multiple 2D sinusoid realizations is explored to study the effects of 3D structural variations. The role of liver zonation on drug metabolism in the lobule is also addressed, based on flow-based predicted steady-state O2 profiles used as a zonation indicator. With this model, we analyze predicted drug concentration levels observed exiting the lobule with their detailed distribution inside the lobule, and compare with our earlier idealized models. In 2D, due to randomness of the sinusoidal structure, individual hepatic veins respond differently (i.e. at different times) to injected drug. In 3D, however, the variation of response to the injected drug is observed to be less extreme. Also, the production curves show more diffusive behavior in 3D than in 2D. Although, the individual producing ports respond differently, the average lobule production summed over all hepatic veins is more diffuse. Thus the net effect of all these variations makes the overall response smoother. We also show that, in 3D, the effect of zonation on drug production characteristics appears quite small. Our new biophysical structural analysis of a physiologically-based 3D lobule can therefore form the basis for a quantitative assessment of liver function and performance both in health and disease.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 24%
Researcher 6 24%
Student > Master 3 12%
Student > Doctoral Student 2 8%
Professor > Associate Professor 2 8%
Other 2 8%
Unknown 4 16%
Readers by discipline Count As %
Engineering 5 20%
Pharmacology, Toxicology and Pharmaceutical Science 5 20%
Medicine and Dentistry 3 12%
Biochemistry, Genetics and Molecular Biology 2 8%
Nursing and Health Professions 1 4%
Other 4 16%
Unknown 5 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 January 2018.
All research outputs
#7,750,575
of 12,352,887 outputs
Outputs from Theoretical Biology and Medical Modelling
#119
of 224 outputs
Outputs of similar age
#199,247
of 354,810 outputs
Outputs of similar age from Theoretical Biology and Medical Modelling
#2
of 5 outputs
Altmetric has tracked 12,352,887 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 224 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 354,810 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.