SCOPE OF REVIEW: This review paper concisely collates and reviews the information reported in the simulation research in terms of MC simulation of radiosensitization and dose enhancement effects caused by the inclusion of Au NPs in tumor cells, simulation mechanisms, benefits and limitations.
MAJOR CONCLUSIONS: In this review, we first explore the recent advances in MC simulation on Au NPs radiosensitization. The MC methods, physical dose enhancement and enhanced chemical and biological effects is discussed, followed by some results regarding the prediction of dose enhancement. We then review Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation. Moreover, we explain and look at Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation.
GENERAL SIGNIFICANCE: Using advanced chemical module-implemented MC simulations, there is a need to assess the radiation-induced chemical radicals that contribute to the dose-enhancing and biological effects of multiple Au NPs.
METHODS: In silico target prediction was first employed to predict the probability of the bromophenols interacting with key protein targets based on a model trained on known bioactivity data and chemical similarity considerations. Next, we tested the functional effect of natural bromophenols from Symphyocladia latiuscula on the CCK2 receptor followed by a molecular docking simulation to predict interactions between a compound and the binding site of the target protein.
RESULTS: Results of cell-based functional G-protein coupled receptor (GPCR) assays demonstrate that bromophenols 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (3) are full CCK2 antagonists. Molecular docking simulation of 1‒3 with CCK2 demonstrated strong binding by means of interaction with prime interacting residues: Arg356, Asn353, Val349, His376, Phe227, and Pro210. Simulation results predicted good binding scores and interactions with prime residues, such as the reference antagonist YM022.
CONCLUSIONS: The results of this study suggest bromophenols 1-3 are CCK2R antagonists that could be novel therapeutic agents for CCK2R-related diseases, especially anxiety and depression.
METHODS: This study proposed a deterministic, compartmental model with contact tracing and vaccination components. We defined contact tracing effectiveness as the proportion of contacts of a positive case that was successfully traced and the vaccination rate as the proportion of daily doses administered per population in Malaysia. Sensitivity analyses on the untraced and infectious populations were conducted.
RESULTS: At a vaccination rate of 1.4%, contact tracing with an effectiveness of 70% could delay the peak of untraced asymptomatic cases by 17 d and reduce it by 70% compared with 30% contact tracing effectiveness. A similar trend was observed for symptomatic cases when a similar experiment setting was used. We also performed sensitivity analyses by using different combinations of contact tracing effectiveness and vaccination rates. In all scenarios, the effect of contact tracing on COVID-19 incidence persisted for both asymptomatic and symptomatic cases.
CONCLUSIONS: While vaccines are progressively rolled out, efficient contact tracing must be rapidly implemented concurrently to reach, find, test, isolate and support the affected populations to bring COVID-19 under control.
METHOD: Compartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness-of-fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re-estimated as the initial estimates were perturbed 100 times and resultant changes evaluated.
RESULTS: The absorption kinetics of metformin depend significantly on food status. Under the fasted state, the first-order absorption into the central compartment was preceded by zero-order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first-order absorption from depot into the central compartment. The means of relative mean estimation error (rMEE) ( ME E SAEM ME E FOCEi ) and rRMSE ( RMS E SAEM RMS E FOCEi ) were 0.48 and 0.35, respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased. When initial estimates were perturbed, FOCEi estimates were more biased and imprecise.
DISCUSSION: nlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations.
OBJECTIVE: The aim of this study is to analyze the multiphase pulsatile blood flow in the left coronary artery tree with stenosis.
METHODS: The 3D left coronary artery model was reconstructed using 2D computerized tomography (CT) scan images. The Red Blood Cell (RBC) and varying hemodynamic parameters for single and multiphase blood flow conditions were analyzed.
RESULTS: Results asserted that the multiphase blood flow modeling has a maximum velocity of 1.017 m/s and1.339 m/s at the stenosed region during the systolic and diastolic phases respectively. The increase in Wall Shear Stress (WSS) observed at the stenosed region during the diastole phase as compared during the systolic phase. It was also observed that the highest Oscillatory Shear Index (OSI) regions are found in the downstream area of stenosis and across the bifurcations. The increase in RBCs velocity from 0.45 m/s to 0.6 m/s across the stenosis was also noticed.
CONCLUSION: The computational multiphase blood flow analysis improves the understanding and accuracy of the complex flow conditions of blood elements (RBC and Plasma) and provides the progression of the disease development in the coronary arteries. This study helps to enhance the diagnosis of the blocked (stenosed) arteries more precisely compared to the single-phase blood flow modeling.