Displaying publications 1 - 20 of 81 in total

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  1. Zheng Y, Lamoureux EL, Chiang PP, Rahman Anuar A, Wong TY
    J Public Health (Oxf), 2014 Mar;36(1):104-10.
    PMID: 23658389 DOI: 10.1093/pubmed/fdt044
    To examine whether marital status is a significant determinant of visual impairment (VI) in urban multi-ethnic Asian population.
  2. Zheng Y, Lamoureux E, Finkelstein E, Wu R, Lavanya R, Chua D, et al.
    Invest Ophthalmol Vis Sci, 2011;52(12):8799-805.
    PMID: 21969296 DOI: 10.1167/iovs.11-7700
    It is known that a person's socioeconomic status (SES; individual-level SES) is closely correlated with his or her degree of visual impairment. Whether there is an independent relationship between area-level measures of SES (e.g., living in a lower SES environment) and visual impairment is unclear. This study describes the associations of area-level SES with visual impairment.
  3. Zheng Y, Fu J, Li S
    Mol Phylogenet Evol, 2009 Jul;52(1):70-83.
    PMID: 19348953 DOI: 10.1016/j.ympev.2009.03.026
    Several anuran groups of Laurasian origin are each co-distributed in four isolated regions of the Northern Hemisphere: central/southern Europe and adjacent areas, Korean Peninsula and adjacent areas, Indo-Malaya, and southern North America. Similar distribution patterns have been observed in diverse animal and plant groups. Savage [Savage, J.M., 1973. The geographic distribution of frogs: patterns and predictions. In: Vial, J.L. (Ed.), Evolutionary Biology of the Anurans. University of Missouri Press, Columbia, pp. 351-445] hypothesized that the Miocene global cooling and increasing aridities in interiors of Eurasia and North America caused a southward displacement and range contraction of Laurasian frogs (and other groups). We use the frog genus Bombina to test Savage's biogeographical hypothesis. A phylogeny of Bombina is reconstructed based on three mitochondrial and two nuclear gene fragments. The genus is divided into three major clades: an Indo-Malaya clade includes B. fortinuptialis, B. lichuanensis, B. maxima, and B. microdeladigitora; a European clade includes B. bombina, B. pachypus, and B. variegata; and a Korean clade contains B. orientalis. The European and Korean clades form sister-group relationship. Molecular dating of the phylogenetic tree using the penalized likelihood and Bayesian analyses suggests that the divergence between the Indo-Malaya clade and other Bombina species occurred 5.9-28.6 million years ago. The split time between the European clade and the Korean clade is estimated at 5.1-20.9 million years ago. The divergence times of these clades are not significantly later than the timing of Miocene cooling and drying, and therefore can not reject Savage's hypothesis. Some other aspects of biogeography of Bombina also are discussed. The Korean Peninsula and the Shandong Peninsula might have supplied distinct southern refugia for B. orientalis during the Pleistocene glacial maxima. In the Indo-Malaya clade, the uplift of the Tibetan Plateau might have promoted the split between B. maxima and the other species.
  4. Zheng Y, Wang Q, Zhuang W, Lu X, Miron A, Chai TT, et al.
    Molecules, 2016 Nov 02;21(11).
    PMID: 27827862
    Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water-soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.
  5. Zheng Y, Yuan C, Matsushita N, Lian C, Geng Q
    Ecol Evol, 2023 Sep;13(9):e10565.
    PMID: 37753310 DOI: 10.1002/ece3.10565
    Cenococcum geophilum (C. geophilum) is a widely distributed ectomycorrhizal fungus that plays a crucial role in forest ecosystems worldwide. However, the specific ecological factors influencing its global distribution and how climate change will affect its range are still relatively unknown. In this study, we used the MaxEnt model optimized with the kuenm package to simulate changes in the distribution pattern of C. geophilum from the Last Glacial Maximum to the future based on 164 global distribution records and 17 environmental variables and investigated the key environmental factors influencing its distribution. We employed the optimal parameter combination of RM = 4 and FC = QPH, resulting in a highly accurate predictive model. Our study clearly shows that the mean temperature of the coldest quarter and annual precipitation are the key environmental factors influencing the suitable habitats of C. geophilum. Currently, appropriate habitats of C. geophilum are mainly distributed in eastern Asia, west-central Europe, the western seaboard and eastern regions of North America, and southeastern Australia, covering a total area of approximately 36,578,300 km2 globally. During the Last Glacial Maximum and the mid-Holocene, C. geophilum had a much smaller distribution area, being mainly concentrated in the Qinling-Huaihe Line region of China and eastern Peninsular Malaysia. As global warming continues, the future suitable habitat for C. geophilum is projected to shift northward, leading to an expected expansion of the suitable area from 9.21% to 21.02%. This study provides a theoretical foundation for global conservation efforts and biogeographic understanding of C. geophilum, offering new insights into its distribution patterns and evolutionary trends.
  6. Zheng Y, Ooi MCG, Juneng L, Wee HB, Latif MT, Nadzir MSM, et al.
    Sci Total Environ, 2023 Nov 25;901:166430.
    PMID: 37607626 DOI: 10.1016/j.scitotenv.2023.166430
    Climate change is thought to influence the composition of atmospheric air, but little is known about the direct relationship between these variables, especially in a hot tropical climate like that of Malaysia. This work summarizes and analyzes the climate state and air quality of Peninsular Malaysia based on selected ground-based observations of the temperature, precipitation, relative humidity, wind speed, wind direction and concentrations of PM10, O3, CO, NO2, and SO2 over the last 20 years (2000-2019). The relationship between the climate state and air quality is analyzed using the Pearson correlation and canonical correlation analysis (CCA) methods is employed to predict the degree of change in the future air quality under different warming scenarios. It is found that the Peninsular Malaysia mainly experienced strong precipitation in the central and mountainous regions, while air pollutants are primarily concentrated in densely populated areas. Throughout the period of study (interannual, monthly, and diurnal time series analyses), Peninsular Malaysia became warmer and drier, with a significant increase in temperature (+4.2 %), decrease in the relative humidity (-4.5 %), and greater fluctuation in precipitation amount. The pollution conditions have worsened; there has been an increase in the PM10 (+16.4 %), O3 (+39.5 %), and NO2 (+2.1 %) concentration over the last 20 years. However, the amount of SO2 (-53.6 %) and CO (-20.6 %) decreased significantly. The analysis of the monthly variation shows a strong bimodality of the PM10 and O3 concentrations that corresponds to the monsoon transition. Intensive diurnal fluctuations and correlations are observed for all the variables in this study. According to the CCA, the air quality factors are strongly correlated with meteorological factors; in particular, the CO, O3, and PM10 concentrations interact strongly with the air temperature. These findings show that the future air quality in Peninsular Malaysia has high possibility to deteriorate under warming condition.
  7. Zheng Y, Qin H, Ma X
    Sci Rep, 2024 Mar 19;14(1):6562.
    PMID: 38503822 DOI: 10.1038/s41598-024-56922-5
    Interval-valued q-rung orthopair fuzzy set (IVq-ROFS) is a powerful tool for dealing with uncertainty. In this paper, we first propose a new method for aggregating multiple IVq-ROFSs, which is easier to understand and implement in the multi-attribute group decision making process compared to current aggregation operators. Secondly, this paper introduces a new fuzzy entropy with parameters based on IVq-ROFS, which is highly flexible due to its adjustable parameters. Based on this, the IVq-ROFS-based attribute weight calculation method is proposed to obtain the objective weights of the attributes, which is more reasonable and objective than the existing methods. Then, for the dimensional differences between the three compromise scores in the original Combined Compromise Solution (CoCoSo) method, the enhanced compromise scores are proposed. These scores are obtained by normalizing the three dependent compromise scores, ensuring that they fall within the same range. Finally, a novel CoCoSo mothed on IVq-ROFS using the proposed fuzzy entropy and enhanced compromise scores is presented. The proposed method is highly adaptable and scalable, not limited to IVq-ROFS. The excellent performance and robustness of the proposed method are verified in sepsis diagnosis applications.
  8. Zhang X, Zheng Y, Zhou C, Cao J, Zhang Y, Wu Z, et al.
    Ultrason Sonochem, 2024 Mar 25;105:106857.
    PMID: 38552299 DOI: 10.1016/j.ultsonch.2024.106857
    This work investigated the effects of the combined use of thermosonication-preconditioned lactic acid bacteria (LAB) with the addition of ultrasound-assisted pineapple peel extracts (UU group) on the post-acidification potential, physicochemical and functional qualities of yogurt products, aimed at achieving prolonged preservation and enhancing functional attributes. Accordingly, the physical-chemical features, adhesion properties, and sensory profiles, acidification kinetics, the contents of major organic acids, and antioxidant activities of the differentially processed yogurts during refrigeration were characterized. Following a 14-day chilled storage process, UU group exhibited acidity levels of 0.5-2 oT lower than the control group and a higher lactose content of 0.07 mg/ml as well as unmodified adhesion potential, indicating that the proposed combination method efficiently inhibited post-acidification and delayed lactose metabolism without leading to significant impairment of the probiotic properties. The results of physicochemical analysis showed no significant changes in viscosity, hardness, and color of yogurt. Furthermore, the total phenolic content of UU-treated samples was 98 μg/mL, 1.78 times higher than that of the control, corresponding with the significantly lower IC50 values of DPPH and ABTS radical scavenging activities of the UU group than those of the control group. Observations by fluorescence inverted microscopy demonstrated the obvious adhesion phenomenon with no significant difference found among differentially prepared yogurts. The results of targeted metabolomics indicated the proposed combination strategy significantly modified the microbial metabolism, leading to the delayed utilization of lactose and the inhibited conversion into glucose during post-fermentation, as well as the decreased lactic acid production and a notable shift towards the formation of relatively weak acids such as succinic acid and citric acid. This study confirmed the feasibility of thermosonication-preconditioned LAB inocula, in combination with the use of natural active components from fruit processing byproducts, to alleviate post-acidification in yogurt and to enhance its antioxidant activities as well as simultaneously maintaining sensory features.
  9. Zhang J, Zhao J, Zuo X, You W, Ru X, Xu F, et al.
    Food Chem, 2024 Jun 15;443:138545.
    PMID: 38306904 DOI: 10.1016/j.foodchem.2024.138545
    The effects of exogenous glutamate treatment on the quality attributes, γ-aminobutyric acid (GABA) shunt, phenylpropanoid pathway, and antioxidant capacity of fresh-cut carrots were investigated. Results showed that glutamate treatment suppressed the increases in lightness and whiteness values, inhibited the degradation of total carotenoids and maintained better flavor and taste in fresh-cut carrots. Moreover, glutamate treatment rapidly promoted the activities of glutamate decarboxylase and GABA transaminase, thus improving the GABA content. It also significantly enhanced the activities of phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate coenzyme A ligase and promoted the accumulation of total phenolics as well as the main individual phenolic compounds, including chlorogenic and caffeic acid. In addition, glutamate application activated the reactive oxygen system-related enzyme including peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase activities to maintain higher antioxidant capacity in fresh-cut carrots. These results demonstrated that exogenous glutamate treatment maintained better nutritional quality and alleviated color deterioration by accelerating the accumulation of GABA and phenolics and enhancing the antioxidant capacity in fresh-cut carrots.
  10. Yu H, Zheng Y, Zhou C, Liu L, Wang L, Cao J, et al.
    Carbohydr Polym, 2024 Feb 01;325:121583.
    PMID: 38008470 DOI: 10.1016/j.carbpol.2023.121583
    The potential of ultrasonication-driven molecular self-assembly of whey protein isolate (WPI) with chitosan (CS)/chitooligosaccharide (COS) to stabilize Pickering emulsions was examined, based on CS/COS ligands-induced partial unfolding in remodeling the Pickering particles features. Multi-spectral analysis suggested obvious changes in conformational structures of WPI due to interaction with CS/COS, with significantly higher unfolding degrees of WPI induced by COS. Non-covalent interactions were identified as the major forces for WPI-CS/COS conjugates. Ultrasonication enhanced electrostatic interaction between CS's -NH3 groups and WPI's -COO- groups which improved emulsification activity and storability of WPI-COS stabilized Pickering emulsion. This was attributed to increased surface hydrophobicity and decreased particle size compared to WPI-CS associated with differential unfolding degrees induced by different saccharide ligands. CLSM and SEM consistently observed smaller emulsion droplets in WPI-COS complexes than WPI-CS/COS particles tightly adsorbed at the oil-water interface. The electrostatic self-assembly of WPI with CS/COS greatly enhanced the encapsulation efficiency of quercetin than those stabilized by WPI alone and ultrasound further improved encapsulation efficiency. This corresponded well with the quantitative affinity parameters between quercetin and WPI-CS/COS complexes. This investigation revealed the great potential of glycan ligands-induced conformational transitions of extrinsic physical disruption in tuning Pickering particle features.
  11. You W, Zhang J, Ru X, Xu F, Wu Z, Jin P, et al.
    Plant Physiol Biochem, 2024 Jan;206:108217.
    PMID: 38039581 DOI: 10.1016/j.plaphy.2023.108217
    The effect of calcium chloride (CaCl2) treatment on γ-aminobutyric acid (GABA) accumulation in fresh-cut cantaloupe and the involved mechanisms were investigated. The result showed that 1% (w/v) CaCl2 treatment increased GABA content and activities of glutamate decarboxylase (GAD) and succinate semialdehyde dehydrogenase (SSADH), while decreased glutamate (Glu) content and GABA transaminase (GABA-T) activities in fresh-cut cantaloupe. CmCML11 and CmCAMTA5 expressions of CaCl2-treated fruit increased by 187.4% and 165.6% than control fruit in the initial 6 h. Besides, expressions of GABA shunt genes, including CmGAD1, CmGAD2, CmGABA-T and CmSSADH were also up-regulated by CaCl2 treatment during early storage. Moreover, acting as a transcriptional activator, CmCAMTA5 could bind to the CG-box in promoters of CmGAD1, CmGABA-T and CmSSADH and activate their transcription. Furthermore, the interaction between CmCML11 and CmCAMTA5 could enhance the transcriptional activation on GABA shunt genes which were regulated by CmCAMTA5. Collectively, our findings revealed that CaCl2 treatment promoted GABA accumulation in fresh-cut cantaloupe via the combined effect of CmCML11 and CmCAMTA5 in the regulation of expressions of CmGAD1, CmGABA-T, and CmSSADH in GABA shunt.
  12. You W, Wang C, Zhang J, Ru X, Xu F, Wu Z, et al.
    Food Chem, 2024 Jul 15;446:138866.
    PMID: 38430769 DOI: 10.1016/j.foodchem.2024.138866
    Fresh-cut potatoes are prone to surface browning and physiological degradation. Chlorogenic acid (CGA), a natural phenolic antioxidant, has demonstrated preservative properties in various postharvest products. However, the underlying mechanisms of its application on maintaining quality remain unclear. Therefore, the effect of exogenous CGA treatment on quality deterioration of potato slices and the mechanisms involved were investigated. Results revealed CGA treatment retarded the browning coloration, suppressed microbial growth and inhibited the declines in starch, and ascorbic acid contents in potato slices. Meanwhile, the treatment activated the phenylpropanoid pathway but decreased the activities of phenolic decomposition-related enzymes such as polyphenol oxidase (PPO) and tyrosinase and downregulated StPPO expression. Moreover, the treated slices exhibited reduced accumulation of reactive oxygen species and increased activity of antioxidant enzymes. Additionally, they displayed enhanced 2,2-diphenyl-1-picrylhydrazyl radicals scavenging capacity and higher ATP levels. Therefore, these findings indicated that CGA treatment was effective for quality maintenance and antioxidant capacity enhancement in fresh-cut potatoes, thereby providing potential strategies for the preservation and processing of fresh-cut produce.
  13. Yip CH, Cazap E, Anderson BO, Bright KL, Caleffi M, Cardoso F, et al.
    Breast, 2011 Apr;20 Suppl 2:S12-9.
    PMID: 21388811 DOI: 10.1016/j.breast.2011.02.015
    In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer.
  14. Yan L, Chen W, Wang C, Liu S, Liu C, Yu L, et al.
    Chemosphere, 2022 Feb;288(Pt 2):132510.
    PMID: 34627823 DOI: 10.1016/j.chemosphere.2021.132510
    Tetracycline is a potentially hazardous residual antibiotic detected in various sewages. High concentration (mg/L) of tetracycline is found in pharmaceutical/hospital wastewater and wastewater derived from livestock and poultry. So far, only antibiotics in μg/L level have been reported in granulation of aerobic sludge during wastewater treatment, but its effects in high concentration are rarely reported. In this study, the influence of tetracycline in high concentration (∼2 mg/L) on the formation of granular sludge, structure, and metabolic function of the microbial community during the granulation of aerobic sludge was investigated to improve the understanding of the aerobic granular sludge formation under high-level of tetracycline. The role of extracellular polymers substances (EPSs) derived from granular sludge in the granulation and tetracycline removal process was also investigated, showing that tetracycline improved the relative hydrophobicity, flocculability and protein/polysaccharide ratio of EPSs, accelerating the granulation of sludge. Succession of microbial communities occurred during the domestication of functional bacteria present in the sludge and was accompanied with regulation of metabolic function. The addition of tetracycline lead to an increase of tetracycline-degrading bacteria or antibiotic resistance genus. Those findings provide new perspectives of the influence of tetracycline on aerobic sludge granulation and the removal mechanism of tetracycline.
  15. Wu J, Wang HL, Liu X, Ding C, Zhou Y, Fu X, et al.
    Liver Int, 2020 02;40(2):298-307.
    PMID: 31674705 DOI: 10.1111/liv.14289
    BACKGROUND & AIMS: Trends in long-term mortality rates for viral hepatitis in East and Southeast Asia have been rarely reported. The aim of our study was to explore the long-term trends in viral hepatitis mortality rates in East and Southeast Asian countries between 1987 and 2015 and provide predictions of mortality to 2030.

    METHODS: We obtained viral hepatitis mortality data from the WHO Mortality Database for six East and Southeast Asian countries between 1987 and 2015. We produced choropleth maps of viral hepatitis mortality rates in 1987 and 2015 in East and Southeast Asia to illustrate geographic variations. We made predictions of mortality rates for each included country until the year 2030 using a series of joinpoint models.

    RESULTS: Viral hepatitis mortality rates declined in China (the average annual percent change (AAPC) = -5.1%, 95% CI: -7.5, -2.6), Singapore (AAPC = -5.4%, 95% CI: -7.5, -3.2), and the Philippines (AAPC = -3.4%, 95% CI: -4.9, -1.8). In contrast, Japan, the Republic of Korea, and Malaysia have experienced increasing trends in mortality rates, followed by decreasing trends. Our predictions indicate that all countries will experience slight to moderate downward trends until 2030.

    CONCLUSION: Favourable decreasing trends have been noted in East and Southeast Asian countries, which may not only inform the control and management of viral hepatitis in this region but also guide the prevention of viral hepatitis deaths in another region with a similar viral hepatitis epidemic.

  16. Wen W, Shu XO, Guo X, Cai Q, Long J, Bolla MK, et al.
    Breast Cancer Res, 2016 12 08;18(1):124.
    PMID: 27931260
    BACKGROUND: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry.

    METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.

    RESULTS: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P 

  17. Wang X, Lamoureux E, Zheng Y, Ang M, Wong TY, Luo N
    Ophthalmology, 2014 Sep;121(9):1837-42.
    PMID: 24768238 DOI: 10.1016/j.ophtha.2014.03.017
    To assess the impact of visual impairment (VI) on health-related quality of life and to compare the health burden of VI and other health conditions in Singapore.
  18. Wang C, Zhang Y, Lim LG, Cao W, Zhang W, Wan X, et al.
    Sci Rep, 2023 Jul 10;13(1):11141.
    PMID: 37429942 DOI: 10.1038/s41598-023-38057-1
    Living in high expressed emotion (EE) environments tends to increase the relapse rate in schizophrenia (SZ). At present, the neural substrates responsible for high EE in SZ remain poorly understood. Functional near-infrared spectroscopy (fNIRS) may be of great use to quantitatively assess cortical hemodynamics and elucidate the pathophysiology of psychiatric disorders. In this study, we designed novel low- (positivity and warmth) and high-EE (criticism, negative emotion, and hostility) stimulations, in the form of audio, to investigate cortical hemodynamics. We used fNIRS to measure hemodynamic signals while participants listened to the recorded audio. Healthy controls (HCs, [Formula: see text]) showed increased hemodynamic activation in the major language centers across EE stimulations, with stronger activation in Wernicke's area during the processing of negative emotional language. Compared to HCs, people with SZ ([Formula: see text]) exhibited smaller hemodynamic activation in the major language centers across EE stimulations. In addition, people with SZ showed weaker or insignificant hemodynamic deactivation in the medial prefrontal cortex. Notably, hemodynamic activation in SZ was found to be negatively correlated with the negative syndrome scale score at high EE. Our findings suggest that the neural mechanisms in SZ are altered and disrupted, especially during negative emotional language processing. This supports the feasibility of using the designed EE stimulations to assess people who are vulnerable to high-EE environments, such as SZ. Furthermore, our findings provide preliminary evidence for future research on functional neuroimaging biomarkers for people with psychiatric disorders.
  19. Vithana EN, Aung T, Khor CC, Cornes BK, Tay WT, Sim X, et al.
    Hum Mol Genet, 2011 Feb 15;20(4):649-58.
    PMID: 21098505 DOI: 10.1093/hmg/ddq511
    Central corneal thickness (CCT) is a risk factor of glaucoma, the most common cause of irreversible blindness worldwide. The identification of genetic determinants affecting CCT in the normal population will provide insights into the mechanisms underlying the association between CCT and glaucoma, as well as the pathogenesis of glaucoma itself. We conducted two genome-wide association studies for CCT in 5080 individuals drawn from two ethnic populations in Singapore (2538 Indian and 2542 Malays) and identified novel genetic loci significantly associated with CCT (COL8A2 rs96067, p(meta) = 5.40 × 10⁻¹³, interval of RXRA-COL5A1 rs1536478, p(meta) = 3.05 × 10⁻⁹). We confirmed the involvement of a previously reported gene for CCT and brittle cornea syndrome (ZNF469) [rs9938149 (p(meta) = 1.63 × 10⁻¹⁶) and rs12447690 (p(meta) = 1.92 × 10⁻¹⁴)]. Evidence of association exceeding the formal threshold for genome-wide significance was observed at rs7044529, an SNP located within COL5A1 when data from this study (n = 5080, P = 0.0012) were considered together with all published data (reflecting an additional 7349 individuals, p(Fisher) = 1.5 × 10⁻⁹). These findings implicate the involvement of collagen genes influencing CCT and thus, possibly the pathogenesis of glaucoma.
  20. Tang BH, Guan Z, Allegaert K, Wu YE, Manolis E, Leroux S, et al.
    Clin Pharmacokinet, 2021 11;60(11):1435-1448.
    PMID: 34041714 DOI: 10.1007/s40262-021-01033-x
    BACKGROUND: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data.

    OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates.

    METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods.

    RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods.

    CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.

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