Displaying publications 61 - 80 of 405 in total

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  1. Tee SH
    PMID: 30594412 DOI: 10.1016/j.shpsc.2018.12.001
    It is commonly held that in vivo biological experimental models are concrete and non-fictional. This belief is primarily supported by the fact that in vivo studies involve biological models which are alive, and what is alive cannot be fictional. However, I argue that this is not always the case. The design of an experimental model could still render an in vivo model fictional because fictional elements and processes can be built into these in vivo experimental models. These fictional elements are essential parts of a credentialed fiction because the designs of in vivo experimental models are constrained by imaginability, conceivability, and credit-worthiness. Therefore, despite its fictionality, it is credible for an in vivo experimental model to stand in for the phenomenon of interest.
    Matched MeSH terms: Models, Biological*
  2. Chew WX, Kaizu K, Watabe M, Muniandy SV, Takahashi K, Arjunan SNV
    Phys Rev E, 2019 Apr;99(4-1):042411.
    PMID: 31108654 DOI: 10.1103/PhysRevE.99.042411
    Microscopic models of reaction-diffusion processes on the cell membrane can link local spatiotemporal effects to macroscopic self-organized patterns often observed on the membrane. Simulation schemes based on the microscopic lattice method (MLM) can model these processes at the microscopic scale by tracking individual molecules, represented as hard spheres, on fine lattice voxels. Although MLM is simple to implement and is generally less computationally demanding than off-lattice approaches, its accuracy and consistency in modeling surface reactions have not been fully verified. Using the Spatiocyte scheme, we study the accuracy of MLM in diffusion-influenced surface reactions. We derive the lattice-based bimolecular association rates for two-dimensional (2D) surface-surface reaction and one-dimensional (1D) volume-surface adsorption according to the Smoluchowski-Collins-Kimball model and random walk theory. We match the time-dependent rates on lattice with off-lattice counterparts to obtain the correct expressions for MLM parameters in terms of physical constants. The expressions indicate that the voxel size needs to be at least 0.6% larger than the molecule to accurately simulate surface reactions on triangular lattice. On square lattice, the minimum voxel size should be even larger, at 5%. We also demonstrate the ability of MLM-based schemes such as Spatiocyte to simulate a reaction-diffusion model that involves all dimensions: three-dimensional (3D) diffusion in the cytoplasm, 2D diffusion on the cell membrane, and 1D cytoplasm-membrane adsorption. With the model, we examine the contribution of the 2D reaction pathway to the overall reaction rate at different reactant diffusivity, reactivity, and concentrations.
    Matched MeSH terms: Models, Biological*
  3. Ooi EH, Lee KW, Yap S, Khattab MA, Liao IY, Ooi ET, et al.
    Comput Biol Med, 2019 03;106:12-23.
    PMID: 30665137 DOI: 10.1016/j.compbiomed.2019.01.003
    Effects of different boundary conditions prescribed across the boundaries of radiofrequency ablation (RFA) models of liver cancer are investigated for the case where the tumour is at the liver boundary. Ground and Robin-type conditions (electrical field) and body temperature and thermal insulation (thermal field) conditions are examined. 3D models of the human liver based on publicly-available CT images of the liver are developed. An artificial tumour is placed inside the liver at the boundary. Simulations are carried out using the finite element method. The numerical results indicated that different electrical and thermal boundary conditions led to different predictions of the electrical potential, temperature and thermal coagulation distributions. Ground and body temperature conditions presented an unnatural physical conditions around the ablation site, which results in more intense Joule heating and excessive heat loss from the tissue. This led to thermal damage volumes that are smaller than the cases when the Robin type or the thermal insulation conditions are prescribed. The present study suggests that RFA simulations in the future must take into consideration the choice of the type of electrical and thermal boundary conditions to be prescribed in the case where the tumour is located near to the liver boundary.
    Matched MeSH terms: Models, Biological*
  4. Arellano G, Medina NG, Tan S, Mohamad M, Davies SJ
    New Phytol, 2019 01;221(1):169-179.
    PMID: 30067290 DOI: 10.1111/nph.15381
    What causes individual tree death in tropical forests remains a major gap in our understanding of the biology of tropical trees and leads to significant uncertainty in predicting global carbon cycle dynamics. We measured individual characteristics (diameter at breast height, wood density, growth rate, crown illumination and crown form) and environmental conditions (soil fertility and habitat suitability) for 26 425 trees ≥ 10 cm diameter at breast height belonging to 416 species in a 52-ha plot in Lambir Hills National Park, Malaysia. We used structural equation models to investigate the relationships among the different factors and tree mortality. Crown form (a proxy for mechanical damage and other stresses) and prior growth were the two most important factors related to mortality. The effect of all variables on mortality (except habitat suitability) was substantially greater than expected by chance. Tree death is the result of interactions between factors, including direct and indirect effects. Crown form/damage and prior growth mediated most of the effect of tree size, wood density, fertility and habitat suitability on mortality. Large-scale assessment of crown form or status may result in improved prediction of individual tree death at the landscape scale.
    Matched MeSH terms: Models, Biological
  5. Mincham G, Baldock KL, Rozilawati H, Williams CR
    Epidemiol Infect, 2019 01;147:e125.
    PMID: 30869038 DOI: 10.1017/S095026881900030X
    Dengue infection in China has increased dramatically in recent years. Guangdong province (main city Guangzhou) accounted for more than 94% of all dengue cases in the 2014 outbreak. Currently, there is no existing effective vaccine and most efforts of control are focused on the vector itself. This study aimed to evaluate different dengue management strategies in a region where this disease is emerging. This work was done by establishing a dengue simulation model for Guangzhou to enable the testing of control strategies aimed at vector control and vaccination. For that purpose, the computer-based dengue simulation model (DENSiM) together with the Container-Inhabiting Mosquito Simulation Model (CIMSiM) has been used to create a working dengue simulation model for the city of Guangzhou. In order to achieve the best model fit against historical surveillance data, virus introduction scenarios were run and then matched against the actual dengue surveillance data. The simulation model was able to predict retrospective outbreaks with a sensitivity of 0.18 and a specificity of 0.98. This new parameterisation can now be used to evaluate the potential impact of different control strategies on dengue transmission in Guangzhou. The knowledge generated from this research would provide useful information for authorities regarding the historic patterns of dengue outbreaks, as well as the effectiveness of different disease management strategies.
    Matched MeSH terms: Models, Biological*
  6. Liang Y, Ahmad Mohiddin MN, Bahauddin R, Hidayatul FO, Nazni WA, Lee HL, et al.
    Comput Math Methods Med, 2019;2019:1923479.
    PMID: 31481976 DOI: 10.1155/2019/1923479
    In this paper, we will start off by introducing the classical Ross-Macdonald model for vector-borne diseases which we use to describe the transmission of dengue between humans and Aedes mosquitoes in Shah Alam, which is a city and the state capital of Selangor, Malaysia. We will focus on analysing the effect of using the Mosquito Home System (MHS), which is an example of an autodissemination trap, in reducing the number of dengue cases by changing the Ross-Macdonald model. By using the national dengue data from Malaysia, we are able to estimate λ, which represents the initial growth rate of the dengue epidemic, and this allows us to estimate the number of mosquitoes in Malaysia. A mathematical expression is also constructed which allows us to estimate the potential number of breeding sites of Aedes mosquitoes. By using the data available from the MHS trial carried out in Section 15 of Shah Alam, we included the potential effect of the MHS into the dengue model and thus modelled the impact MHS has on the spread of dengue within the trial area. We then extended our results to analyse the effect of the MHSs on reducing the number of dengue cases in the whole of Malaysia. A new model was constructed with a basic reproduction number, R0,MalaMHS, which allows us to identify the required MHSs coverage needed to achieve extinction in Malaysia. Numerical simulations and tables of results were also produced to illustrate our results.
    Matched MeSH terms: Models, Biological
  7. Chong SY, Tiňo P, He J, Yao X
    Evol Comput, 2019;27(2):195-228.
    PMID: 29155606 DOI: 10.1162/evco_a_00218
    Studying coevolutionary systems in the context of simplified models (i.e., games with pairwise interactions between coevolving solutions modeled as self plays) remains an open challenge since the rich underlying structures associated with pairwise-comparison-based fitness measures are often not taken fully into account. Although cyclic dynamics have been demonstrated in several contexts (such as intransitivity in coevolutionary problems), there is no complete characterization of cycle structures and their effects on coevolutionary search. We develop a new framework to address this issue. At the core of our approach is the directed graph (digraph) representation of coevolutionary problems that fully captures structures in the relations between candidate solutions. Coevolutionary processes are modeled as a specific type of Markov chains-random walks on digraphs. Using this framework, we show that coevolutionary problems admit a qualitative characterization: a coevolutionary problem is either solvable (there is a subset of solutions that dominates the remaining candidate solutions) or not. This has an implication on coevolutionary search. We further develop our framework that provides the means to construct quantitative tools for analysis of coevolutionary processes and demonstrate their applications through case studies. We show that coevolution of solvable problems corresponds to an absorbing Markov chain for which we can compute the expected hitting time of the absorbing class. Otherwise, coevolution will cycle indefinitely and the quantity of interest will be the limiting invariant distribution of the Markov chain. We also provide an index for characterizing complexity in coevolutionary problems and show how they can be generated in a controlled manner.
    Matched MeSH terms: Models, Biological*
  8. Thakur N, Bailey D
    Microbes Infect, 2019;21(7):278-286.
    PMID: 30817995 DOI: 10.1016/j.micinf.2019.02.002
    Nipah virus is an emerging zoonotic paramyxovirus that causes severe and often fatal respiratory and neurological disease in humans. The virus was first discovered after an outbreak of encephalitis in pig farmers in Malaysia and Singapore with subsequent outbreaks in Bangladesh or India occurring almost annually. Due to the highly pathogenic nature of NiV, its pandemic potential, and the lack of licensed vaccines or therapeutics, there is a requirement for research and development into highly sensitive and specific diagnostic tools as well as antivirals and vaccines to help prevent and control future outbreak situations.
    Matched MeSH terms: Models, Biological
  9. Teh AHT, Lee SM, Dykes GA
    PLoS One, 2019;14(4):e0215275.
    PMID: 30970009 DOI: 10.1371/journal.pone.0215275
    Campylobacter jejuni is a microaerophilic bacterial species which is a major food-borne pathogen worldwide. Attachment and biofilm formation have been suggested to contribute to the survival of this fastidious bacteria in the environment. In this study the attachment of three C. jejuni strains (C. jejuni strains 2868 and 2871 isolated from poultry and ATCC 33291) to different abiotic surfaces (stainless steel, glass and polystyrene) alone or with Pseudomonas aeruginosa biofilms on them, in air at 25°C and under static or flow conditions, were investigated using a modified Robbins Device. Bacteria were enumerated and scanning electron microscopy was carried out. The results indicated that both C. jejuni strains isolated from poultry attached better to Pseudomonas aeruginosa biofilms on abiotic surfaces than to the surfaces alone under the different conditions tested. This suggests that biofilms of other bacterial species may passively protect C. jejuni against shear forces and potentially oxygen stress which then contribute to their persistence in environments which are detrimental to them. By contrast the C. jejuni ATCC 33291 strain did not attach differentially to P. aeruginosa biofilms, suggesting that different C. jejuni strains may have alternative strategies for persistence in the environment. This study supports the hypothesis that C. jejuni do not form biofilms per se under conditions they encounter in the environment but simply attach to surfaces or biofilms of other species.
    Matched MeSH terms: Models, Biological
  10. Li K, Anderson G, Viallon V, Arveux P, Kvaskoff M, Fournier A, et al.
    Breast Cancer Res, 2018 12 03;20(1):147.
    PMID: 30509329 DOI: 10.1186/s13058-018-1073-0
    BACKGROUND: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction.

    METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention.

    RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+ and 3.0 × 10- 6 for ModelGail.

    CONCLUSIONS: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.

    Matched MeSH terms: Models, Biological*
  11. Ooi EH, J Y Chia N, Ooi ET, Foo JJ, Liao IY, R Nair S, et al.
    Int J Hyperthermia, 2018 12;34(8):1142-1156.
    PMID: 29490513 DOI: 10.1080/02656736.2018.1437282
    A recent study by Ooi and Ooi (EH Ooi, ET Ooi, Mass transport in biological tissues: Comparisons between single- and dual-porosity models in the context of saline-infused radiofrequency ablation, Applied Mathematical Modelling, 2017, 41, 271-284) has shown that single-porosity (SP) models for describing fluid transport in biological tissues significantly underestimate the fluid penetration depth when compared to dual-porosity (DP) models. This has raised some concerns on whether the SP model, when coupled with models of radiofrequency ablation (RFA) to simulate saline-infused RFA, could lead to an underestimation of the coagulation size. This paper compares the coagulation volumes obtained following saline-infused RFA predicted based on the SP and DP models for fluid transport. Results showed that the SP model predicted coagulation zones that are consistently 0.5 to 0.9 times smaller than that of DP model. This may be explained by the low permeability value of the tissue interstitial space, which causes the majority of the saline to flow through the vasculature. The absence of fluid flow tracking in the vasculature in the SP model meant that any flow of saline into the vasculature is treated as losses and do not contribute to the saline penetration depth of the tissue. Comparisons with experimental results from the literature revealed that the DP models predicted coagulation zone sizes that are closer to the experimental values than the SP models. This supports the hypothesis that the SP model is a poor choice for simulating the outcome of saline-infused RFA.
    Matched MeSH terms: Models, Biological*
  12. Jeevaratnam K, Salvage SC, Li M, Huang CL
    Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
    PMID: 29846007 DOI: 10.1111/nyas.13861
    Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.
    Matched MeSH terms: Models, Biological
  13. Venkataraman VV, Yegian AK, Wallace IJ, Holowka NB, Tacey I, Gurven M, et al.
    Proc Biol Sci, 2018 11 07;285(1890).
    PMID: 30404871 DOI: 10.1098/rspb.2018.1492
    The convergent evolution of the human pygmy phenotype in tropical rainforests is widely assumed to reflect adaptation in response to the distinct ecological challenges of this habitat (e.g. high levels of heat and humidity, high pathogen load, low food availability, and dense forest structure), yet few precise adaptive benefits of this phenotype have been proposed. Here, we describe and test a biomechanical model of how the rainforest environment can alter gait kinematics such that short stature is advantageous in dense habitats. We hypothesized that environmental constraints on step length in rainforests alter walking mechanics such that taller individuals are expected to walk more slowly due to their inability to achieve preferred step lengths in the rainforest. We tested predictions from this model with experimental field data from two short-statured populations that regularly forage in the rainforest: the Batek of Peninsular Malaysia and the Tsimane of the Bolivian Amazon. In accordance with model expectations, we found stature-dependent constraints on step length in the rainforest and concomitant reductions in walking speed that are expected to compromise foraging efficiency. These results provide the first evidence that the human pygmy phenotype is beneficial in terms of locomotor performance and highlight the value of applying laboratory-derived biomechanical models to field settings for testing evolutionary hypotheses.
    Matched MeSH terms: Models, Biological
  14. Kiyasudeen K, Ibrahim MH, Muhammad SA, Ismail SA, Gonawan FN, Zuknik MH
    Environ Sci Pollut Res Int, 2018 Nov;25(31):31062-31070.
    PMID: 30187407 DOI: 10.1007/s11356-018-3074-z
    Earthworms are commonly referred as environmental engineers and their guts are often compared with chemical reactors. However, modeling experiments to substantiate it are lacking. The aim of this study was to use established reactor models, particularly PFR, on the gut of the vermicomposting earthworm Eudrilus eugeniae to understand more on its digestion. To achieve the objective, a mathematical model based on first-order kinetics was framed and used to determine the pattern of digestion rates of nutrient indicators, namely total carbon (%), total nitrogen (%), C/N ratio, 13C (‰), and 15N (‰) at five intersections (pre-intestine, foregut, midgut A, midgut B, and hindgut) along the gut of E. eugeniae. The experimental results revealed that the concentrations of TC, TN, 13C, and 15N decreased during gut transit, whereas C/N ratio increased. The first-order model demonstrated that all the nutrients exhibit a linear pattern of digestion during gut transit, which supports the PFR model. On this basis, the present study concludes that the gut of E. eugeniae functions as PFR.
    Matched MeSH terms: Models, Biological*
  15. Shanmugam R, Jian CYCCS, Haseeb A, Aik S
    J Orthop Surg (Hong Kong), 2018 10 3;26(3):2309499018802511.
    PMID: 30270746 DOI: 10.1177/2309499018802511
    PURPOSE: Metacarpal bone fractures constitute 10% of all fractures. Unstable metacarpal fractures require surgical intervention, which poses danger to flexor tendon either due to bicortical drilling or construct of the implant. Unicortical locking plate fixation may be the solution to preventing flexor tendon injury. Studies have compared locking and compression plates. However, in these studies, the biomechanical properties were tested using the static loading method. This study looks into cyclical loading that is more representative of in vivo conditions, particularly for early rehabilitation. We compared the biomechanical strength of the unicortical locking plate and bicortical compression plate system in a transverse metacarpal fracture, tested with cyclical loading and torsion.

    METHOD: Twenty pieces of fourth-generation, biomechanical testing grade, left third metacarpal composite bones were used. Resin was used to create the holding block at both ends of the bone. An oscillating saw with 0.8 mm thick saw blade was used to osteotomize the metacarpal sawbones to create a midshaft transverse metacarpal fracture model. Ten pieces were fixed with a 2.0 mm titanium locking plate via unicortical screw purchase and 10 were fixed with a 2.0 mm, four holes, titanium dynamic compression plate, bicortical purchase of screws. They were subjected to cyclic load to failure testing three-point bending and torsion.

    RESULTS: There were no significant difference in stiffness and cyclic three-point bending to failure between the unicortical locking plate group and the bicortical compression plate group. The bicortical compression plate group is stiffer and has a higher cyclic bending load to failure as compared to the unicortical locking plate group.

    CONCLUSION: Unicortical locking plate fixation of metacarpal fracture can be reliably applied clinically to produce a strong and stable construct that allows early mobilization of the joints. This will not only reduce the complication rate of metacarpal plating, but also improve the functional outcome of the hand.

    Matched MeSH terms: Models, Biological
  16. Tee SH
    PMID: 30318277 DOI: 10.1016/j.shpsc.2018.10.003
    Mechanism diagrams exhibit visually the organized parts and operations of a biological mechanism. A mechanism diagram can facilitate mechanistic research by providing a mechanistic explanation of the phenomenon of interest. Much research has been focusing on the mechanistic explanation and the explanatory mechanistic models. As a specific type of scientific diagram, a simple mechanism diagram can be explanatory by drawing on the rich explanatory resources of non-depicted background knowledge. The relationship between the visually depicted and the background knowledge is underexplored. It is unclear how the non-depicted background knowledge of a mechanism diagram contributes to providing a better-informed explanation of the phenomenon of interest in biological sciences. With the aim to explore this relationship, I articulate that a mechanism diagram provides a mechanistic explanation by a process called abstraction-by-aggregation. Through visual cues, the unified relevant background knowledge provides an epistemic access to a better-informed explanation.
    Matched MeSH terms: Models, Biological
  17. Badhan R, Zakaria Z, Olafuyi O
    J Pharm Sci, 2018 08;107(8):2236-2250.
    PMID: 29626533 DOI: 10.1016/j.xphs.2018.03.026
    Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance, attention has turned toward ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiology-based pharmacokinetic model in healthy adults (20-50 years), pediatric (3-5 years/15-25 kg) subjects, and a representative adult malaria population group (Thailand). Dosing optimization demonstrating a twice-daily dose for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and pediatric subjects. Furthermore, to address the occurrence of CYP450 induction that is often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1-mg/kg once-daily dose for 5 days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 h in adults and 141.2 h in pediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.
    Matched MeSH terms: Models, Biological
  18. Cheng WK, Oon CE
    Biomed Pharmacother, 2018 Jul;103:1246-1252.
    PMID: 29864905 DOI: 10.1016/j.biopha.2018.04.119
    Glycosylation is an enzymatic process in which a carbohydrate is attached to a functional group from another molecule. Glycosylation is a crucial post translational process in protein modification. The tumor microenvironment produces altered glycans that contribute to cancer progression and aggressiveness. Abnormal glycosylation is widely observed in tumor angiogenesis. Despite many attempts to decipher the role of glycosylation in different aspects of cancer, little is known regarding the roles of glycans in angiogenesis. The blood vessels in tumors are often used to transport oxygen and nutrients for tumor progression and metastasis. The crosstalk within the tumor microenvironment can induce angiogenesis by manipulating these glycans to hijack the normal angiogenesis process, thus promoting tumor growth. Abnormal glycosylation has been shown to promote tumor angiogenesis by degrading the extracellular matrix to activate the angiogenic signaling pathways. This review highlights the latest update on how glycosylation can contribute to tumor angiogenesis that may affect treatment outcomes.
    Matched MeSH terms: Models, Biological
  19. Zakaria Z, Badhan RKS
    Eur J Pharm Sci, 2018 Jul 01;119:90-101.
    PMID: 29635009 DOI: 10.1016/j.ejps.2018.04.012
    Lumefantrine is a widely used antimalarial in children in sub-Saharan Africa and is predominantly metabolised by CYP3A4. The concomitant use of lumefantrine with the antiretroviral efavirenz, which is metabolised by CYP2B6 and is an inducer of CYP3A4, increases the risk of lumefantrine failure and can result in an increased recrudescence rate in HIV-infected children. This is further confounded by CYP2B6 being highly polymorphic resulting in a 2-3 fold higher efavirenz plasma concentration in polymorphic subjects, which enhances the potential for an efavirenz-lumefantrine drug-drug interaction (DDI). This study developed a population-based PBPK model capable of predicting the impact of efavirenz-mediated DDIs on lumefantrine pharmacokinetics in African paediatric population groups, which also considered the polymorphic nature of CYP2B6. The validated model demonstrated a significant difference in lumefantrine target day 7 concentrations (Cd7) in the presence and absence of efavirenz and confirmed the capability of efavirenz to initiate this DDI. This was more apparent in the *6/*6 compared to *1/*1 population group and resulted in a significantly lower (P 
    Matched MeSH terms: Models, Biological
  20. Oyehan TA, Alade IO, Bagudu A, Sulaiman KO, Olatunji SO, Saleh TA
    Comput Biol Med, 2018 07 01;98:85-92.
    PMID: 29777986 DOI: 10.1016/j.compbiomed.2018.04.024
    The optical properties of blood play crucial roles in medical diagnostics and treatment, and in the design of new medical devices. Haemoglobin is a vital constituent of the blood whose optical properties affect all of the optical properties of human blood. The refractive index of haemoglobin has been reported to strongly depend on its concentration which is a function of the physiology of biological cells. This makes the refractive index of haemoglobin an essential non-invasive bio-marker of diseases. Unfortunately, the complexity of blood tissue makes it challenging to experimentally measure the refractive index of haemoglobin. While a few studies have reported on the refractive index of haemoglobin, there is no solid consensus with the data obtained due to different measuring instruments and the conditions of the experiments. Moreover, obtaining the refractive index via an experimental approach is quite laborious. In this work, an accurate, fast and relatively convenient strategy to estimate the refractive index of haemoglobin is reported. Thus, the GA-SVR model is presented for the prediction of the refractive index of haemoglobin using wavelength, temperature, and the concentration of haemoglobin as descriptors. The model developed is characterised by an excellent accuracy and very low error estimates. The correlation coefficients obtained in these studies are 99.94% and 99.91% for the training and testing results, respectively. In addition, the result shows an almost perfect match with the experimental data and also demonstrates significant improvement over a recent mathematical model available in the literature. The GA-SVR model predictions also give insights into the influence of concentration, wavelength, and temperature on the RI measurement values. The model outcome can be used not only to accurately estimate the refractive index of haemoglobin but also could provide a reliable common ground to benchmark the experimental refractive index results.
    Matched MeSH terms: Models, Biological
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