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  1. Gu H, Huang X, Chen Q, Sun Y, Tan CP
    J Fluoresc, 2020 May;30(3):687-694.
    PMID: 32378115 DOI: 10.1007/s10895-020-02546-7
    The influences of metal atoms on optimized geometry structures, relative energies, frontline molecular orbitals, and binding energies of metalloporphyrin-based fluorescent array sensor were systematically investigated by density functional theory (DFT) at B3LYP/LAN2DZ level. DFT calculated results reveal that the selected metal atoms in the center of the metalloporphyrin plane provide difference performances of metalloporphyrin-based fluorescent array sensor for the rapid determination of trimethylamine. The calculated binding energies have displayed in the following order at the most stable states: zinc porphyrin (ZnP) 
  2. Lim PS, Loke CF, Ho YW, Tan HY
    J Appl Microbiol, 2020 Nov;129(5):1374-1388.
    PMID: 32356362 DOI: 10.1111/jam.14678
    AIMS: To determine the mechanism underlying the serum cholesterol reduction effect by probiotics isolated from local fermented tapioca (Tapai).

    METHODS AND RESULTS: Lactic acid bacteria strains were isolated and examined for acid tolerance, bile salt resistance and hypocholesterolemic properties. Among the isolates, Lactobacillus plantarum TAR4 showed the highest cholesterol reduction ability (48·01%). The focus in the in vivo trial was to elucidate the cholesterol balance from findings pertaining to serum cholesterol reduction in rat model fed with high fat diet via oral administration. Rats fed with high-cholesterol diet supplemented with Lact. plantarum TAR4 showed significant reduction in serum total cholesterol (29·55%), serum triglyceride (45·31%) and liver triglyceride (23·44%) as compared to high-cholesterol diet (HCD) group. There was a significant increment in faecal triglyceride (45·83%) and faecal total bile acid (384·95%) as compared to HCD group.

    CONCLUSIONS: The findings showed that probiotic Lact. plantarum TAR4 supplementation reduced the absorption of bile acids for enterohepatic recycling and increased the catabolism of cholesterol to bile acids and not by suppressing the rate of cholesterol synthesis.

    SIGNIFICANCE AND IMPACT OF STUDY: Probiotic supplements could provide a new nonpharmacological alternative to reduce cardiovascular risk factors.

  3. Abd Raman HS, Tan S, August JT, Khan AM
    PeerJ, 2020;7:e7954.
    PMID: 32518710 DOI: 10.7717/peerj.7954
    Background: Influenza A (H5N1) virus is a global concern with potential as a pandemic threat. High sequence variability of influenza A viruses is a major challenge for effective vaccine design. A continuing goal towards this is a greater understanding of influenza A (H5N1) proteome sequence diversity in the context of the immune system (antigenic diversity), the dynamics of mutation, and effective strategies to overcome the diversity for vaccine design.

    Methods: Herein, we report a comprehensive study of the dynamics of H5N1 mutations by analysis of the aligned overlapping nonamer positions (1-9, 2-10, etc.) of more than 13,000 protein sequences of avian and human influenza A (H5N1) viruses, reported over at least 50 years. Entropy calculations were performed on 9,408 overlapping nonamer position of the proteome to study the diversity in the context of immune system. The nonamers represent the predominant length of the binding cores for peptides recognized by the cellular immune system. To further dissect the sequence diversity, each overlapping nonamer position was quantitatively analyzed for four patterns of sequence diversity motifs: index, major, minor and unique.

    Results: Almost all of the aligned overlapping nonamer positions of each viral proteome exhibited variants (major, minor, and unique) to the predominant index sequence. Each variant motif displayed a characteristic pattern of incidence change in relation to increased total variants. The major variant exhibited a restrictive pyramidal incidence pattern, with peak incidence at 50% total variants. Post this peak incidence, the minor variants became the predominant motif for majority of the positions. Unique variants, each sequence observed only once, were present at nearly all of the nonamer positions. The diversity motifs (index and variants) demonstrated complex inter-relationships, with motif switching being a common phenomenon. Additionally, 25 highly conserved sequences were identified to be shared across viruses of both hosts, with half conserved to several other influenza A subtypes.

    Discussion: The presence of distinct sequences (nonatypes) at nearly all nonamer positions represents a large repertoire of reported viral variants in the proteome, which influence the variability dynamics of the viral population. This work elucidated and provided important insights on the components that make up the viral diversity, delineating inherent patterns in the organization of sequence changes that function in the viral fitness-selection. Additionally, it provides a catalogue of all the mutational changes involved in the dynamics of H5N1 viral diversity for both avian and human host populations. This work provides data relevant for the design of prophylactics and therapeutics that overcome the diversity of the virus, and can aid in the surveillance of existing and future strains of influenza viruses.

  4. Abdul Aziz AF, Tan CE, Ali MF, Aljunid SM
    Health Qual Life Outcomes, 2020 Jun 20;18(1):193.
    PMID: 32563246 DOI: 10.1186/s12955-020-01450-9
    BACKGROUND: Satisfaction with post stroke services would assist stakeholders in addressing gaps in service delivery. Tools used to evaluate satisfaction with stroke care services need to be validated to match healthcare services provided in each country. Studies on satisfaction with post discharge stroke care delivery in low- and middle-income countries (LMIC) are scarce, despite knowledge that post stroke care delivery is fragmented and poorly coordinated. This study aims to modify and validate the HomeSat subscale of the Dutch Satisfaction with Stroke Care-19 (SASC-19) questionnaire for use in Malaysia and in countries with similar public healthcare services in the region.

    METHODS: The HomeSat subscale of the Dutch SASC-19 questionnaire (11 items) underwent back-to-back translation to produce a Malay language version. Content validation was done by Family Medicine Specialists involved in community post-stroke care. Community social support services in the original questionnaire were substituted with equivalent local services to ensure contextual relevance. Internal consistency reliability was determined using Cronbach alpha. Exploratory factor analysis was done to validate the factor structure of the Malay version of the questionnaire (SASC10-My™). The SASC10-My™ was then tested on 175 post-stroke patients who were recruited at ten public primary care healthcentres across Peninsular Malaysia, in a trial-within a trial study.

    RESULTS: One item from the original Dutch SASC19 (HomeSat) was dropped. Internal consistency for remaining 10 items was high (Cronbach alpha 0.830). Exploratory factor analysis showed the SASC10-My™ had 2 factors: discharge transition and social support services after discharge. The mean total score for SASC10-My™ was 10.74 (SD 7.33). Overall, only 18.2% were satisfied with outpatient stroke care services (SASC10-My™ score ≥ 20). Detailed analysis revealed only 10.9% of respondents were satisfied with discharge transition services, while only 40.9% were satisfied with support services after discharge.

    CONCLUSIONS: The SASC10-My™ questionnaire is a reliable and valid tool to measure caregiver or patient satisfaction with outpatient stroke care services in the Malaysian healthcare setting. Studies linking discharge protocol patterns and satisfaction with outpatient stroke care services should be conducted to improve care delivery and longer-term outcomes.

    TRIAL REGISTRATION: No.: ACTRN12616001322426 (Registration Date: 21st September 2016.

  5. Dong AN, Tan BH, Pan Y, Ong CE
    J Pharm Pharm Sci, 2021;24:94-112.
    PMID: 33626316 DOI: 10.18433/jpps31305
    Since the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike most other CYP isoforms that carry nine exons. CYP2R1 crystal structure displays a fold pattern typical of a CYP protein, with 12 a-helices as its structural core, and b-sheets mostly arranged on one side, and the heme buried in the interior part of the protein. Overall, CYP2R1 structure adopts a closed conformation with the B' helix serving as a gate covering the substrate access channel, with the substrate vitamin D3 occupying a position with the side chain pointing toward the heme group. In liver, CYP2R1 25-hydroxylates vitamin D and serves as an important determinant of 25(OH)D level in the tissue and in circulation. While substrate profile has been well studied, inhibitor specificity for CYP2R1 requires further investigation. Both exonic and non-exonic single nucleotide polymorphisms (SNPs) have been reported in CYP2R1, including the CYP2R1*2 carrying Leu99Pro exchange, and a number of non-exonic SNPs with variable functional consequences in gene regulation. A non-exonic SNP, rs10741657, has its causal relationship with diseases established, including that of rickets, ovarian cancer, and multiple sclerosis. The role of other CYP2R1 SNPs in vitamin D deficiency and their causal link to other traits however remain uncertain currently and more studies are warranted to help identify possible physiological mechanisms underlying those complex traits.
  6. Karlson CKS, Mohd-Noor SN, Nolte N, Tan BC
    Plants (Basel), 2021 Sep 29;10(10).
    PMID: 34685863 DOI: 10.3390/plants10102055
    RNA-guided genomic transcriptional regulation tools, namely clustered regularly interspaced short palindromic repeats interference (CRISPRi) and CRISPR-mediated gene activation (CRISPRa), are a powerful technology for gene functional studies. Deriving from the CRISPR/Cas9 system, both systems consist of a catalytically dead Cas9 (dCas9), a transcriptional effector and a single guide RNA (sgRNA). This type of dCas9 is incapable to cleave DNA but retains its ability to specifically bind to DNA. The binding of the dCas9/sgRNA complex to a target gene results in transcriptional interference. The CRISPR/dCas9 system has been explored as a tool for transcriptional modulation and genome imaging. Despite its potential applications and benefits, the challenges and limitations faced by the CRISPR/dCas9 system include the off-target effects, protospacer adjacent motif (PAM) sequence requirements, efficient delivery methods and the CRISPR/dCas9-interfered crops being labeled as genetically modified organisms in several countries. This review highlights the progression of CRISPR/dCas9 technology as well as its applications and potential challenges in crop improvement.
  7. Ponnusamy A, Ajis AH, Tan YS, Chai LC
    J Appl Microbiol, 2021 Oct 12.
    PMID: 34637602 DOI: 10.1111/jam.15327
    AIMS: Green-mould contamination is identified as one of the challenges faced by mushroom cultivation industry globally which believed to be caused by Trichoderma spp.

    METHODS AND RESULTS: To explore the dynamics of microbial population in mushroom substrate during commercial mushroom cultivation and how microbiota might play a role in green-mould contamination, we applied both culturing and targeted metagenomics approaches to identify microbiota in noncomposted sawdust substrates at different cultivation stages. The microbiological analysis showed that the green-mould contaminated substrates harboured higher total mesophilic bacteria count. The green-moulds isolated from the contaminated mushroom substrates were identified as Trichoderma pleurotum (n = 15; 93.8%) and Graphium penicillioides (n = 1; 6.3%). To our surprise, the targeted metagenomic analysis revealed that Graphium comprised 56.3% while Trichoderma consisted of only 36.1% of the total fungi population, suggesting that green-mould contamination might not be caused by Trichoderma alone, but also Graphium that grows very slowly in the laboratory.

    CONCLUSION: It is worthwhile to note that G. penicillioides was also isolated in the early stages of mushroom cultivation, but not T. pleurotum. The results indicated that the structure and composition of the bacterial population in the mushroom substrate varied and the bacterial population shifted along the cultivation process.

    SIGNIFICANCE AND IMPACT OF STUDY: This study revealed a possibility of G. penicillioides as an overlooked fungi causing green-mould contamination.

  8. Nisha M, Aiman M, Asyhira N, Syafiq H, Atiqah N, Kumarasamy V, et al.
    Trop Biomed, 2020 Jun 01;37(2):379-388.
    PMID: 33612807
    Soil-transmitted helminth (STH) could possibly cause mild to severe health effects such as diarrhea, weakness, intestinal blood loss, and impaired cognitive development and growth. In Malaysia, previous studies depicted a high prevalence rate of STH was due to poor hygiene practice and low efficacies of anthelminthic drugs. This study was conducted to investigate hand hygiene practice and WASH criteria's (Water, sanitation and hygiene) related to STH infection among two indigenous tribes in Peninsular Malaysia. A cross-sectional study was carried out to study the relationship among STH infection compared to water quality, sanitation, and hygiene conditions. A total of 190 individuals from two indigenous villages participated in the study, with ages ranging from 5 to 60 years old. In addition, Pearson's Chisquare (X2) test was utilized to test the relationship among STH with demographic socioeconomic and behavioral factors. The confidence interval (CI) of 95% is used to estimate the precision of the odds ratio (OR). Multivariate logistic regression models were also used to identify the risk factors associated with STH infections. The overall findings indicated a prevalence rate of 72% for STH, and distributed mainly among children aged < 12 years. Furthermore, multivariate analyses using logistic regression revealed chronic health problems, incorrect hand washing, and walking bare footed were associated with STH infection. Overall results indicated high prevalence of STH among the indigenous villagers, which aligns with the published literature and proves to be a problem need to be addressed as neglected disease. Interestingly, there was a significant relationship between the presences of chronic diseases and STH infection, which prompted other questions the awareness needs to be educated and the simple and low-cost intervention on the proper way of hand washing may help to reduce STH infection in these indigenous communities.
  9. Tan PC, Aziz AZ, Ismail IS, Omar SZ
    Clin Biochem, 2012 Oct;45(15):1192-6.
    PMID: 22659058 DOI: 10.1016/j.clinbiochem.2012.05.025
    OBJECTIVES: To evaluate gamma-glutamyltransferase (GGT), alanine transaminases (ALT) and aspartate transaminases (AST) levels and prevalent gestational diabetes mellitus (GDM).
    DESIGN AND METHODS: Random plasma glucose, GGT, ALT and AST and the 50-g glucose challenge test were done on antenatal women followed by diagnostic 3-point 75-g oral glucose tolerance test within two weeks. GDM was diagnosed by ADA (2011) criteria.
    RESULTS: The GDM rate was 12.2% (319/2610). Mean GGT level was higher in GDM women, 18 ± 12 vs. 16 ± 11 IU/L; P=0.03. The risk for GDM was higher for women in the highest GGT quartile band compared to the lowest: RR 1.35 95%CI 1.0-1.8; P=0.04. However, after adjustment for confounders, GGT was no longer associated with GDM. There was no correlation between ALT and AST levels and GDM.
    CONCLUSIONS: Liver transaminases do not predict GDM in contrast to type 2 diabetes.
  10. Tan ACC, Kumar HK, Lokeman Hazli FL, Chin L
    Med J Malaysia, 2021 09;76(5):624-629.
    PMID: 34508366
    INTRODUCTION: The use of intramuscular (IM) dexamethasone injections before an elective caesarean delivery at term has been shown in multiple randomized controlled trials to reduce the rates of transient tachypnoea of the newborn, and admission to neonatal care. Recent studies have suggested that a complete course of IM steroids can be associated with long term harmful consequences to the infants born, and there have been studies suggesting that a lower dose of IM corticosteroids can be beneficial. Therefore, we aim to establish if halving the dose of dexamethasone to 12mg can demonstrate any benefit for term elective caesarean section deliveries whilst minimizing foetal exposure.

    METHODS: An observational controlled study comparing neonatal respiratory morbidities before and after the single dose 12mg dexamethasone was implemented in our obstetrics and gynaecology centre for term elective caesarean section deliveries. We included singleton pregnancies from 37+0 to 38+6 weeks undergoing elective caesarean section into our study. A total of 674 patients fulfilled the inclusion criteria and were recruited. We compared the rates and duration of admission to neonatal intensive care unit, the need for mechanical ventilation and the rate of transient tachypnoea of the newborn in the first half of 2019 without IM dexamethasone injections against the second half of the year when a single dose IM dexamethasone was given.

    RESULTS: IM dexamethasone injection did not show any significant benefit with regards to reducing the admission to neonatal care (OR 0.97, p- value 0.69), admission to neonatal intensive care unit (OR 0.91, p- value 0.80), the need for mechanical ventilation (OR 0.98, p- value 0.95), and the incidence of transient tachypnoea of the newborn (OR1.01, p- value 0.96). There was also no significant difference for the duration of admission in the neonatal intensive care unit for both groups (p- value 0.17).

    CONCLUSIONS: This study showed that there was no significant benefit gained from the lower dose antenatal corticosteroids for term elective caesarean section deliveries and considering that there have been long term harmful consequences demonstrated from the higher dose of antenatal corticosteroids at term, this practice should therefore be discontinued until a larger study is done to refute these findings. The use of such dexamethasone should only be a viable option in a research setting.

  11. Tan SF, Kirby BP, Stanslas J, Basri HB
    J Pharm Pharmacol, 2017 Nov;69(11):1447-1457.
    PMID: 28809443 DOI: 10.1111/jphp.12800
    OBJECTIVE: This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA).

    METHODS: Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain.

    KEY FINDINGS: Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80.

    CONCLUSIONS: Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.

  12. Tan JM, Bullo S, Fakurazi S, Hussein MZ
    Sci Rep, 2020 10 09;10(1):16941.
    PMID: 33037287 DOI: 10.1038/s41598-020-73963-8
    This research work represents the first major step towards constructing an effective therapeutic silibinin (SB) in cancer treatment using oxidised multi-walled carbon nanotubes (MWCNT-COOH) functionalised with biocompatible polymers as the potential drug carrier. In an attempt to increase the solubility and dispersibility of SB-loaded nanotubes (MWSB), four water-soluble polymers were adopted in the preparation process, namely polysorbate 20 (T20), polysorbate 80 (T80), polyethylene glycol (PEG) and chitosan (CHI). From the geometry point of view, the hydrophobic regions of the nanotubes were loaded with water-insoluble SB while the hydrophilic polymers functionalised on the outer surfaces of the nanotubes serve as a protective shell to the external environment. The chemical interaction between MWSB nanocomposites and polymer molecules was confirmed by Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. Besides, high-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA) and UV-visible spectrophotometry were also employed to characterise the synthesised nanocomposites. The morphological study indicated that the polymers were deposited on the external surfaces of MWSB and the nanocomposites were seen to preserve their tubular structures even after the coating process was applied. The TGA results revealed that the incorporation of biopolymers practically improved the overall thermal stability of the coated MWSB nanocomposites. Evaluation of the in vitro effect on drug release rate by the nanocomposites was found to follow a biphasic release manner, showing a fast release at an initial stage and then a sustained-release over 2500 min. Besides, the drug release mechanisms of the nanocomposites demonstrated that the amount of SB released in the simulated environment was governed by pseudo-second order in which, the rate-limiting step mainly depends on diffusion of drug through chemisorption reaction. Finally, MTT assay showed that the coated MWSB nanocomposites on 3T3 cells were very much biocompatible at a concentration up to 100 g/mL, which is an evidence of MWSB reduced cytotoxicity.
  13. Norazlina MR, Tan YS, Hasmadi M, Jahurul MHA
    Heliyon, 2021 Sep;7(9):e08073.
    PMID: 34622074 DOI: 10.1016/j.heliyon.2021.e08073
    In this work, the effect of solvent pre-treatment (hexane, petroleum ether and ethanol) on the physicochemical, thermal and morphology behavior of Mangifera pajang seed fat (MPSF) were investigated. Fat extraction was performed using Soxhlet method, and results showed that the yield, physicochemical, and crystalline structures of the MPSF were significantly (p < 0.05) influenced by the extraction solvents. Hexane gave the highest fat yield (7.67 %) with low unsaturation value (52.13 g iodine/g) compared with petroleum ether and ethanol. Hexane MPSF also had low oxidation rate (peroxide value of 1.1 mEq/g). Both non-stabilized and stabilized hexane MPSF showed a single melting endothermic peak at high temperature with onset, maximum peak and offset temperature of 16.23 ˚C-18.21 °C, 28.22 ˚C-31.25 °C and 34.85 ˚C-39.58 °C, respectively. Hexane MPSF crystallized rapidly at high temperature with single maximum peak starting at 16.51 ˚C-16.68 °C and ending at 0.23 ˚C-1.13 °C. In comparison with ethanol extract, hexane MPSF demonstrated a compact crystalline structure with a large densely packed center. Therefore, MPSF obtained from hexane presented better overall quality than those obtained from other extraction solvents. MPSF exhibited similar melting and morphological behavior to mango kernel fat and commercial cocoa butter. These results suggested that hexane was the best solvent for the extraction of MPSF. This fat also has the potential to be applied as a cocoa butter alternative fat or functional fat.
  14. Mardiana O, Nor Afiah MZ, Ahmad N, Tan KA, Murallitharan M
    Med J Malaysia, 2021 07;76(4):480-487.
    PMID: 34305108
    BACKGROUND: Previous research has documented the benefits of physical activity (PA) for cancer survivors which include improved quality of life, physical, physiological, emotional and social functioning, reduced relapse of cancer and the mitigation of cancer mortality. This study aims to evaluate the effects of an independent PA programme based on PA level, quality of life, self-efficacy, outcome expectations, reinforcement, behavioural capability and observational learning amongst registered National Cancer Society Malaysia's (NCSM) cancer survivors.

    METHODS: A two-armed, parallel, double-blinded, randomized, controlled trial, intervention and wait-list control groups will be conducted amongst 106 NCSM's cancer survivors. The programme is developed based on a Social Cognitive Theory that combines both psychoeducation and social media approaches to behavioural intervention. The duration of intervention will be 2 months, in which data will be collected at baseline, 2- month (immediately post-intervention) and 4-month. The primary outcome of the study is to determine the PA level of the participant which will be measured as METminutes/ week of PA using the International Physical Activity Questionnaire (IPAQ). There are four measurements of PA that are measured which are moderate and vigorous PA (MVPA) MET-minutes/week, light PA MET-minutes/week, moderate PA MET-minutes/week and vigorous PA METminutes/ week. A Generalised Estimating Equation (GEE) analysis will be used to evaluate the effectiveness of the intervention, adjusted for baseline covariates on both continuous and categorical outcomes. This study will utilize a significance level of 0.05 with a confidence interval of 95% for means estimation in rejecting null hypothesis. The trial registered to the Australian New Zealand Clinical Trials (ANZCTR) with the Registration Number, ACTRN12620000039987.

    CONCLUSION: The programme will be useful as a supplementary prescription to assist policy makers to strengthen non-pharmacological cancer management options and to empower cancer survivors to be self-reliant and self-sufficient to include PA as part of their recovery process.

  15. Liew A, Lee CC, Lan BL, Tan M
    Comput Biol Med, 2021 09;136:104690.
    PMID: 34352452 DOI: 10.1016/j.compbiomed.2021.104690
    Convolutional neural networks (CNNs) have been used quite successfully for semantic segmentation of brain tumors. However, current CNNs and attention mechanisms are stochastic in nature and neglect the morphological indicators used by radiologists to manually annotate regions of interest. In this paper, we introduce a channel and spatial wise asymmetric attention (CASPIAN) by leveraging the inherent structure of tumors to detect regions of saliency. To demonstrate the efficacy of our proposed layer, we integrate this into a well-established convolutional neural network (CNN) architecture to achieve higher Dice scores, with less GPU resources. Also, we investigate the inclusion of auxiliary multiscale and multiplanar attention branches to increase the spatial context crucial in semantic segmentation tasks. The resulting architecture is the new CASPIANET++, which achieves Dice Scores of 91.19%, 87.6% and 81.03% for whole tumor, tumor core and enhancing tumor respectively. Furthermore, driven by the scarcity of brain tumor data, we investigate the Noisy Student method for segmentation tasks. Our new Noisy Student Curriculum Learning paradigm, which infuses noise incrementally to increase the complexity of the training images exposed to the network, further boosts the enhancing tumor region to 81.53%. Additional validation performed on the BraTS2020 data shows that the Noisy Student Curriculum Learning method works well without any additional training or finetuning.
  16. Lee JX, Chieng WK, Lau SCD, Tan CE
    Front Med (Lausanne), 2021;8:757510.
    PMID: 34722593 DOI: 10.3389/fmed.2021.757510
    This systematic review aimed to provide an overview of the clinical profile and outcome of COVID-19 infection in patients with hemoglobinopathy. The rate of COVID-19 mortality and its predictors were also identified. A systematic search was conducted in accordance with PRISMA guidelines in five electronic databases (PubMed, Scopus, Web of Science, Embase, WHO COVID-19 database) for articles published between 1st December 2019 to 31st October 2020. All articles with laboratory-confirmed COVID-19 cases with underlying hemoglobinopathy were included. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Thirty-one articles with data on 246 patients with hemoglobinopathy were included in this review. In general, clinical manifestations of COVID-19 infection among patients with hemoglobinopathy were similar to the general population. Vaso-occlusive crisis occurred in 55.6% of sickle cell disease patients with COVID-19 infection. Mortality from COVID-19 infection among patients with hemoglobinopathy was 6.9%. After adjusting for age, gender, types of hemoglobinopathy and oxygen supplementation, respiratory (adj OR = 89.63, 95% CI 2.514-3195.537, p = 0.014) and cardiovascular (adj OR = 35.20, 95% CI 1.291-959.526, p = 0.035) comorbidities were significant predictors of mortality. Patients with hemoglobinopathy had a higher mortality rate from COVID-19 infection compared to the general population. Those with coexisting cardiovascular or respiratory comorbidities require closer monitoring during the course of illness. More data are needed to allow a better understanding on the clinical impact of COVID-19 infections among patients with hemoglobinopathy. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020218200.
  17. Heaw YC, Singh DKA, Tan MP, Kumar S
    Australas J Ageing, 2021 Nov 01.
    PMID: 34724301 DOI: 10.1111/ajag.13008
    OBJECTIVE: We aimed to examine the bidirectional associations between specific executive function (EF) and physical function (PF) subdomains among older adults.

    METHODS: A systematic literature search (MEDLINE, EMBASE, PsycINFO, EBSCOHOST, Scopus and EmCare) was undertaken from February 2018 to May 2020. Observational studies measuring associations between EF and PF subdomains among older adults were included.

    RESULTS: Twenty-nine studies met the inclusion criteria. Twenty-seven studies reported associations between EF and PF. There were bidirectional associations between slower processing speed and slower gait speed; slower processing speed and lower muscle strength; and lower verbal fluency and slower gait speed. Lower muscle strength was unilaterally associated with lower working memory.

    CONCLUSIONS: We found consistent bidirectional associations between processing speed with gait speed and muscle strength, and verbal fluency and gait speed. There was a unidirectional association between muscle strength and working memory. Common causal mechanisms for EF and PF require further studies.

  18. Tan YH, Lim CS, Wong KH, Sabaratnam V
    Int J Med Mushrooms, 2021;23(6):1-11.
    PMID: 34369729 DOI: 10.1615/IntJMedMushrooms.2021038578
    Neuritin is important in neuritogenesis, neurite arborization, and neurite extension. Lignosus rhinocerotis sclerotia extracts and nerve growth factor (NGF) have been well documented to possess positive neurite stimulatory effects. However, the correlation of neuritin expression with neurite outgrowth of L. rhinocerotis and NGF cotreatment of PC12 cells remains unknown. Thus, the present study investigated neuritin expression in PC12 cells treated with 5 ng/mL of NGF and L. rhinocerotis extracts (20-1280 μg/mL) concurrently for 48 h. The neurite outgrowth score was quantitated, and total protein was harvested for enzyme-linked immunosorbent assay. There was a significant difference (P = 0.051) in neuritin protein abundance in 640 μg/mL of L. rhinocerotis aqueous cotreatment with 5 ng/mL of NGF-treated cells (5 ± 0.39 ng/mL) and 50 ng/mL of NGF-treated PC12 cells (5 ± 0.48 ng/mL) compared to untreated cells (1.9 ± 0.65 ng/ mL), with an average neurite length of 98 ± 3.66, 106 ± 3.00, and 73 ± 4.79 μm, respectively. Expression of microtubule element β3 tubulin was increased in PC12 cells treated with 50 ng/mL of NGF (3.5 ± 0.21-fold) and also cells cotreated with 640 μg/mL of extract and 5 ng/mL of NGF (4.9 ± 0.29-fold) compared to untreated cells. Upregulation of β3 tubulin expression in this study confirmed the elongation of PC12 cell processes. Correlation analysis showed that neuritin protein abundance is positively proportional to the average neurite length in PC12 cells cotreated with L. rhinocerotis extract and 5 ng/mL of NGF. This study highlights that neuritin modulation is involved in neurite outgrowth induced by L. rhinocerotis treatment. To our knowledge, this is the first report to show that tiger milk mushroom extracts induce neuritin expression.
  19. Tan CY, Razali SNO, Goh KJ, Shahrizaila N
    J Med Ultrasound, 2021 04 03;29(3):181-186.
    PMID: 34729327 DOI: 10.4103/JMU.JMU_105_20
    Background: High-resolution nerve ultrasound provides morphological information of peripheral nerves. We aimed to determine the normal ultrasonographic reference values of nerve cross-sectional area (CSA) in multiethnic Malaysian healthy participants.

    Methods: Nerve ultrasound of the median, ulnar, radial, tibial, fibular, and sural nerves was performed in 84 healthy participants at anatomical-defined locations. The CSA at each scanned site was measured by tracing circumferentially inside the hyperechoic rim of each nerve. Comparisons were made between genders and ethnic groups. Correlations with age, ethnicity, gender, height, weight, and body mass index (BMI) were evaluated.

    Results: CSA values and reference ranges in healthy participants were generated. Nerve CSA was significantly different in different gender (P = 0.002-0.032) and ethnic groups (P = 0.006-0.038). Men had larger nerve CSA than women, and Malay participants had larger nerve CSA compared to other ethnic groups. Nerve CSA had significant correlations to age, height, weight, and BMI (r = 0.220-0.349, P = 0.001-0.045).

    Conclusion: This study provides normative values for CSA of peripheral nerves in a multiethnic Malaysian population, which serves as reference values in the evaluation of peripheral nerve disorders. The ethnic differences in nerve CSA values should be considered during nerve ultrasound.

  20. Cheng C, Shen C, Lai OM, Tan CP, Cheong LZ
    Anal Methods, 2021 Nov 04;13(42):4974-4984.
    PMID: 34661208 DOI: 10.1039/d1ay01307f
    Protox inhibiting herbicides such as nitrofen have detrimental effects on the environment and human health. The current work aims to fabricate a Candida rugosa lipase (CRL)-based electrochemical sensor for rapid and sensitive detection of protox inhibiting herbicides (nitrofen). We proposed the use of poly(vinylpyrrolidone) (PVP) and amino-acids to promote accumulation of Zn2+ ions at the surfaces of Candida rugosa lipase (CRL) and subsequently induce self-assembly of a CRL-zeolitic imidazolate framework (ZIF) structure. This process can be easily and rapidly achieved via a one-pot facile self-assembly method. Steady-state fluorescence spectroscopy indicated that CRL has undergone a conformational change following encapsulation within the ZIF structure. This conformational change is beneficial as the prepared PVP/Glu/CRL@ZIF-8 exhibited enhanced catalytic activity (207% of native CRL), and higher substrate affinity (lower Km than native CRL) and showed high stability under harsh denaturing conditions. PVP/Glu/CRL@ZIF-8 was finally used for electrochemical biosensing of nitrofen. The fabricated biosensor has a wide linear detection range (0-100 μM), a lower limit of detection and a good recovery rate.
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