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  1. Wong YF, Saad B, Makahleh A
    J Chromatogr A, 2013 May 17;1290:82-90.
    PMID: 23578483 DOI: 10.1016/j.chroma.2013.03.014
    A capillary electrophoresis (CE)-capacitively coupled contactless conductivity detection (C(4)D) method for the simultaneous separation of eleven underivatized fatty acids (FAs), namely, lauric, myristic, tridecanoic (internal standard), pentadecanoic, palmitic, stearic, oleic, elaidic, linoleic, linolenic and arachidic acids is described. The separation was carried out in normal polarity mode at 20 °C, 30 kV and using hydrodynamic injection (50 mbar for 1 s). The separation was achieved in a bare fused-silica capillary (70 cm × 75 μm i.d.) using a background electrolyte of methyl-β-cyclodextrin (~6 mM) and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (~8 mM) dissolved in a mixture of Na2HPO4/KH2PO4 (5 mM, pH 7.4):ACN:MeOH:n-octanol (3:4:2.5:0.5, v/v/v/v). C(4)D parameters were set at fixed amplitude of 100 V and frequency of 1000 kHz. The developed method was validated. Calibration curves of the ten FAs were well correlated (r(2)>0.99) within the range of 5-250 μg mL(-1) for lauric acid, and 3-250 μg mL(-1) for the other FAs. The method was simple and sensitive with detection limits (S/N=3) of 0.9-1.9 μg mL(-1) and good relative standard deviations of intra- and inter-day for migration times and peak areas (≤9.7%) were achieved. The method was applied to the determination of FAs in margarine samples. The proposed method offers distinct advantages over the GC and HPLC methods, especially in terms of simplicity (without derivatization) and sensitivity.
  2. Wong YF, Makahleh A, Saad B, Ibrahim MN, Rahim AA, Brosse N
    Talanta, 2014 Dec;130:299-306.
    PMID: 25159413 DOI: 10.1016/j.talanta.2014.07.021
    A sensitive and rapid reversed-phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of tocopherols (α-, β-, γ-, δ-), tocotrienols (α-, β-, γ-, δ-), α-tocopherol acetate and α-tocopherol nicotinate is described. The separation was achieved using a Kinetex pentafluorophenyl (PFP) column (150 × 2.1mm, 2.6 µm) with both photodiode array (PDA) and fluorescence (FL) detectors that were connected in series. Column was thermostated at 42°C. Under a gradient system consisting of methanol and water at a constant flow rate of 0.38 mL min(-1), all the ten analytes were well separated in less than 9.5 min. The method was validated in terms of linearity, limits of detection and quantitation, precision and recoveries. Calibration curves of the ten compounds were well correlated (r(2)>0.999) within the range of 100 to 25,000 μg L(-1) for α-tocopherol acetate and α-tocopherol nicotinate, 10 to 25,000 μg L(-1) for α-tocotrienol and 5 to 25,000 μg L(-1) for the other components. The method is simple and sensitive with detection limits (S/N, 3) of 1.0 to 3.0 μg L(-1) (FL detection) and 30 to 74 μg L(-1) (PDA detection). Relative standard deviations for intra- and inter-day retention times (<1%) and peak areas (≤ 4%) were obtained. The method was successfully applied to the determination of vitamin E in vegetable oils (extra virgin olive, virgin olive, pomace olive, blended virgin and refined olive, sunflower, soybean, palm olein, carotino, crude palm, walnut, rice bran and grape seed), margarines and supplements.
  3. Wong YF, Yusof MM, Wan Ishak WZ, Alip A, Phua VC
    Asian Pac J Cancer Prev, 2015;16(7):2903-8.
    PMID: 25854381
    BACKGROUND: Head and neck cancer (HNC) is the eighth most common cancer as estimated from worldwide data. The incidence of HNC in Peninsular Malaysia was reported as 8.5 per 100,000 population. This study was aimed to determine the treatment outcomes for HNC patients treated in the Oncology Unit of University Malaya Medical Centre (UMMC).

    MATERIALS AND METHODS: All newly diagnosed patients with squamous cell carcinoma of head and neck (HNSCC) referred for treatment to the Oncology Unit at UMMC from 2003-2010 were retrospectively analyzed. Treatment outcomes were 5-year overall survival (OS), cause specific survival (CSS), loco-regional control (LRC) and radiotherapy (RT) related side effects. Kaplan-Meier and log rank analyses were used to determine survival outcomes, stratified according to American Joint Committee on Cancer (AJCC) stage.

    RESULTS: A total of 130 cases were analysed. Most cases (81.5%) were at late stage (AJCC III-IVB) at presentation. The 5-year OS for the whole study population was 34.4% with a median follow up of 24 months. The 5-year OS according to AJCC stage was 100%, 48.2%, 41.4% and 22.0% for stage I, II, III and IVA-B, respectively. The 5-year overall CSS and LCR were 45.4% and 55.4%, respectively. Late effects of RT were documented in 41.4% of patients. The most common late effect was xerostomia.

    CONCLUSIONS: The treatment outcome of HNSCC at our centre is lagging behind those of developed nations. Efforts to increase the number of patients presenting in earlier stages, increase in the use of combined modality treatment, especially concurrent chemoradiotherapy and implementation of intensity modulated radiotherapy, may lead to better outcomes for our HNC patients.

  4. Tan SG, Barker JS, Selvaraj OS, Mukherjee TK, Wong YF
    Biochem Genet, 1993 Jun;31(5-6):223-30.
    PMID: 8259925
    We have developed the methodologies for typing and family studies to establish the modes of inheritance of water buffalo red cell acid phosphatase (Acp), protease inhibitor (Pi), and group-specific component (Gc) on isoelectric focusing and albumin (Alb), red cell alpha-esterase-3 (Est-3), and catalase (Cat) on polyacrylamide gel electrophoresis. Family studies showed that Pi, Gc, Alb, and Cat are coded by autosomal genes with two codominant alleles, while Est-3 is autosomal with two codominant alleles and a recessive null allele and Acp exhibits three codominant alleles.
  5. Yan D, Wong YF, Whittock SP, Koutoulis A, Shellie RA, Marriott PJ
    Anal Chem, 2018 04 17;90(8):5264-5271.
    PMID: 29575899 DOI: 10.1021/acs.analchem.8b00142
    A novel sequential three-dimensional gas chromatography-high-resolution time-of-flight mass spectrometry (3D GC-accTOFMS) approach for profiling secondary metabolites in complex plant extracts is described. This integrated system incorporates a nonpolar first-dimension (1Dnp) separation step, prior to a microfluidic heart-cut (H/C) of a targeted region(s) to a cryogenic trapping device, directly followed by the rapid reinjection of a trapped solute into a polar second-dimension (2DPEG) column for multidimensional separation (GCnp-GCPEG). For additional separation, the effluent from 2DPEG can then be modulated according to a comprehensive 2D GC process (GC×GC), using an ionic liquid phase as a third-dimension (3DIL) column, to produce a sequential GCnp-GCPEG×GCIL separation. Thus, the unresolved or poorly resolved components, or regions that require further separation, can be precisely selected and rapidly transferred for additional separation on 2D or 3D columns, based on the greater separation realized by these steps. The described integrated system can be used in a number of modes, but one useful approach is to target specific classes of compounds for improved resolution. This is demonstrated through the separation and detection of the oxygenated sesquiterpenes in hop ( Humulus lupulus L.) essential oil and agarwood ( Aquilaria malaccensis) oleoresin. Improved resolution and peak capacity were illustrated through the progressive comparison of the tentatively identified components for GCnp-GCPEG and GCnp-GCPEG×GCIL methods. Relative standard deviations of intraday retentions (1 tR, 2 tR,, and 3 tR) and peak areas of ≤0.01, 0.07, 0.71, and 7.5% were achieved. This analytical approach comprising three GC column selectivities, hyphenated with high-resolution TOFMS detection, should be a valuable adjunct for the improved characterization of complex plant samples, particularly in the area of plant metabolomics.
  6. Yan D, Wong YF, Shellie RA, Marriott PJ, Whittock SP, Koutoulis A
    Food Chem, 2019 Mar 01;275:15-23.
    PMID: 30724181 DOI: 10.1016/j.foodchem.2018.09.082
    This study investigated the volatile phytochemical diversity of 30 samples obtained from experimental hybrid and commercial H. lupulus L. plants. Essential oils distilled from these samples were analysed by high resolution gas chromatography coupled with accurate mass time-of-flight mass spectrometry (GC-accTOFMS). A total of 58 secondary metabolites, mainly comprising 18 esters, 6 monoterpene hydrocarbons, 2 oxygenated monoterpenes, 20 sesquiterpene hydrocarbons, 7 oxygenated sesquiterpenes, and 4 ketones, were positively or tentatively identified. A total of 24 metabolites were detected in all samples, but commercial cultivars (selected for brewing performance) had fewer compounds identified compared to experimental genotypes. Chemometrics analyses enabled distinct differentiation of experimental hybrids from commercial cultivars, discussed in terms of the different classes of compounds present in different genotypes. Differences among the mono- and sesquiterpenoids, appear to be related to either: i) the genetic origin of the plants; or ii) the processes of bioaccumulation of the identified secondary metabolites.
  7. Lavinya AA, Lee CS, Hashim OH, Azwa I, Rajasuriar R, Lim SK, et al.
    Clin Biochem, 2019 Nov;73:90-97.
    PMID: 31401122 DOI: 10.1016/j.clinbiochem.2019.08.006
    BACKGROUND: Patients treated for human immunodeficiency virus (HIV) infection are prone to developing chronic kidney disease (CKD). Current methods used in assessing kidney function suffer inaccuracy in HIV-infected patients. This study aims to identify biomarkers that could complement existing methods of kidney assessment among HIV-infected subjects.

    METHODS: Plasma protein profiling was performed for HIV patients with CKD presented with negative/trace proteinuria (non-proteinuric) (n = 8) and their matched non-CKD controls, using two-dimensional gel electrophoresis (2DE); selected protein candidates were identified using mass spectrometry. Subsequently, altered plasma abundance of protein candidates were verified using Western blotting in HIV-infected subjects with non-proteinuric CKD (n = 8), proteinuric CKD (n = 5), and their matched non-CKD controls, as well as in HIV-uninfected subjects with impaired kidney function (n = 3) and their matched controls.

    RESULTS: Analysis of 2DE found significantly altered abundance of five protein candidates between HIV-infected patients with non-proteinuric CKD and without CKD: alpha-1-microglobulin (A1M), serum albumin (ALB), zinc-alpha-2-glycoprotein (AZGP1), haptoglobin (HP), and retinol binding protein (RBP4). Western blotting showed an increased abundance of A1M and HP in HIV-infected patients with non-proteinuric CKD compared to their non-CKD controls, whereas A1M, AZGP1, and RBP4 were significantly increased in HIV-infected patients with proteinuric CKD compared to their non-CKD controls. Such pattern was not found in HIV-uninfected subjects with impaired kidney function.

    CONCLUSION: The data suggests four proteins that may be used as biomarkers of CKD in HIV-infected patients. Further validation in a larger cohort of HIV-infected patients is necessary for assessing the clinical use of these proposed biomarkers for CKD.

  8. Wong YF, Ng HT, Leung KY, Chan KY, Chan SY, Loy CC
    J Biomed Inform, 2017 Oct;74:130-136.
    PMID: 28923366 DOI: 10.1016/j.jbi.2017.09.005
    OBJECTIVE: Oral pills, including tablets and capsules, are one of the most popular pharmaceutical dosage forms available. Compared to other dosage forms, such as liquid and injections, oral pills are very stable and are easy to be administered. However, it is not uncommon for pills to be misidentified, be it within the healthcare institutes or after the pills were dispensed to the patients. Our objective is to develop groundwork for automatic pill identification and verification using Deep Convolutional Network (DCN) that surpasses the existing methods.

    MATERIALS AND METHODS: A DCN model was developed using pill images captured with mobile phones under unconstraint environments. The performance of the DCN model was compared to two baseline methods of hand-crafted features.

    RESULTS: The DCN model outperforms the baseline methods. The mean accuracy rate of DCN at Top-1 return was 95.35%, whereas the mean accuracy rates of the two baseline methods were 89.00% and 70.65%, respectively. The mean accuracy rates of DCN for Top-5 and Top-10 returns, i.e., 98.75% and 99.55%, were also consistently higher than those of the baseline methods.

    DISCUSSION: The images used in this study were captured at various angles and under different level of illumination. DCN model achieved high accuracy despite the suboptimal image quality.

    CONCLUSION: The superior performance of DCN underscores the potential of Deep Learning model in the application of pill identification and verification.

  9. Kulsing C, Nolvachai Y, Wong YF, Glouzman MI, Marriott PJ
    J Chromatogr A, 2018 Apr 20;1546:97-105.
    PMID: 29548566 DOI: 10.1016/j.chroma.2018.02.035
    Real-time interconversion processes produce unconventional peak broadening in gas chromatography (GC), and can be used to generate kinetic and thermodynamic data. In this study, an unusual separation situation in comprehensive two dimensional GC where two dimensional interconversion (i.e. a raised plateau in both first and second dimension, 1D and 2D) was observed in analysis of oxime isomers. This resulted in a characteristic and unusual rectangular peak shape in the two dimensional result. A related theoretical approach was introduced to explain the peak shape supported by simulation results which can be varied depending on concentration profiles and kinetics of the process. The simulated results were supported by experimental results obtained by a comprehensive heart-cut multidimensional GC (H/C MDGC) approach which was developed to clearly investigate isomerisation of E/Z oxime molecules in both 1D and 2D separations under different isothermal conditions. The carrier gas flow and oven temperature were selected according to initial results for 1D interconversion on a poly(ethyleneglycol) stationary phase, which was further used in both 1D and 2D separations to result in broad zones of oxime interconversion in both dimensions. The method involved repetitive injections of oxime sample, then sampling contiguous fractions of sample into a long 2D column which is intended to promote considerable interconversion. Comprehensiveness arises from the fact that the whole sample is sampled from the 1D to the 2D column, with the long 2D column replacing the short 2D column used in classical comprehensive two-dimensional gas chromatography, where the latter will not promote sufficient interconversion. Data processing and presentation permits a 'rectangular' distribution corresponding to the separated compounds, characteristic of this experiment.
  10. Lim RJ, Nik Nabil WN, Chan SY, Wong YF, Han LX, Gong JY, et al.
    Support Care Cancer, 2019 Sep;27(9):3491-3498.
    PMID: 30675667 DOI: 10.1007/s00520-019-4646-2
    PURPOSE: More than 80% head and neck cancer patients endured radiotherapy-induced xerostomia which impacts their quality of life (QoL). This observational study evaluated the effect of herbal treatment on head and neck cancer patients' xerostomia and QoL.

    METHODS: Head and neck cancer patients were recruited from July 2016 till March 2017 at National Cancer Institute, Ministry of Health, Malaysia. All study participants continued their standard oncology surveillance. Treatment group participants additionally received Chinese herbal treatment. The assessments included unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and QoL questionnaire.

    RESULTS: Of 42 recruited participants, 28 were in the treatment group and 14 were in the control group. Participants were mainly Chinese (71.4%), stage III cancer (40.5%), and had nasopharynx cancer (76.2%). The commonly used single herbs were Wu Mei, San Qi, and Tian Hua Fen. Sha Shen Mai Dong Tang, Liu Wei Di Huang Wan, and Gan Lu Yin were the frequently prescribed herbal formulas. The baseline characteristics, USFR, SSFR, and QoL between control and treatment groups were comparable (p > 0.05). USFR between control and treatment groups were similar throughout the 6-month study period. SSFR for the treatment group significantly improved from 0.15 ± 0.28 ml/min (baseline) to 0.32 ± 0.22 ml/min (p = 0.04; at the 3rd month) and subsequently achieved 0.46 ± 0.23 ml/min (p = 0.001; at the 6th month). The treatment group had better QoL in terms of speech (p = 0.005), eating (p = 0.02), and head and neck pain (p = 0.04) at the 6th month.

    CONCLUSION: Herbal treatment may improve xerostomia and QoL in post-radiotherapy head and cancer patients.

  11. Nies YH, Islahudin F, Chong WW, Abdullah N, Ismail F, Ahmad Bustamam RS, et al.
    Patient Prefer Adherence, 2017;11:1767-1777.
    PMID: 29081652 DOI: 10.2147/PPA.S143611
    PURPOSE: This study investigated breast cancer patients' involvement level in the treatment decision-making process and the concordance between patients' and physician's perspectives in decision-making.

    PARTICIPANTS AND METHODS: A cross-sectional study was conducted involving physicians and newly diagnosed breast cancer patients from three public/teaching hospitals in Malaysia. The Control Preference Scale (CPS) was administered to patients and physicians, and the Krantz Health Opinion Survey (KHOS) was completed by the patients alone. Binary logistic regression was used to determine the association between sociodemographic characteristics, the patients' involvement in treatment decision-making, and patients' preference for behavioral involvement and information related to their disease.

    RESULTS: The majority of patients preferred to share decision-making with their physicians (47.5%), while the second largest group preferred being passive (42.6%) and a small number preferred being active (9.8%). However, the physicians perceived that the majority of patients preferred active decision-making (56.9%), followed by those who desired shared decision-making (32.8%), and those who preferred passive decision-making (10.3%). The overall concordance was 26.5% (54 of 204 patient-physician dyads). The median of preference for information score and behavioral involvement score was 4 (interquartile range [IQR] =3-5) and 2 (IQR =2-3), respectively. In univariate analysis, the ethnicity and educational qualification of patients were significantly associated with the patients' preferred role in the process of treatment decision-making and the patients' preference for information seeking (p>0.05). However, only educational qualification (p=0.004) was significantly associated with patients' preference for information seeking in multivariate analysis.

    CONCLUSION: Physicians failed to understand patients' perspectives and preferences in treatment decision-making. The concordance between physicians' perception and patients' perception was quite low as the physicians perceived that more than half of the patients were active in treatment decision-making. In actuality, more than half of patients perceived that they shared decision-making with their physicians.

  12. Othman HIA, Alkatib HH, Zaid A, Sasidharan S, Rahiman SSF, Lee TP, et al.
    Plants (Basel), 2022 Dec 27;12(1).
    PMID: 36616263 DOI: 10.3390/plants12010134
    The essential oil derived from Citrus plants has long been used for medicinal purposes, due to its broad spectrum of therapeutic characteristics. To date, approximately 162 Citrus species have been identified, and many investigational studies have been conducted to explore the pharmacological potential of Citrus spp. oils. This study investigated the volatile constituents of essential oil distilled from the leaves of C. hystrix, C. limon, C. pyriformis, and C. microcarpa, using gas chromatography-quadrupole mass spectrometry. A total of 80 secondary compounds were tentatively identified, representing 84.88-97.99% of the total ion count and mainly comprising monoterpene (5.20-76.15%) and sesquiterpene (1.36-27.14%) hydrocarbons, oxygenated monoterpenes (3.91-89.52%) and sesquiterpenes (0.21-38.87%), and other minor chemical classes (0.10-0.52%). In particular, 27 compounds (1.19-39.06%) were detected across all Citrus species. Principal component analysis of the identified phytoconstituents and their relative quantities enabled differentiation of the Citrus leaf oils according to their species, with the loading variables contributing to these metabolic differences being identified. The Citrus leaf oils were tested for their antioxidant and antiproliferative activities using 2,2-diphenyl-1-picryl-hydrazylhydrate (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The results indicated that C. limon displayed the highest DPPH radical scavenging ability (IC50 value of 29.14 ± 1.97 mg/mL), while C. hystrix exhibited the lowest activity (IC50 value of 279.03 ± 10.37 mg/mL). On the other hand, all the Citrus oils exhibit potent antiproliferative activities against the HeLa cervical cancer cell line, with IC50 values of 11.66 μg/mL (C. limon), 20.41 μg/mL (C. microcarpa), 25.91 μg/mL (C. hystrix), and 87.17 μg/mL (C. pyriformis).
  13. Wong YF, Cacciola F, Fermas S, Riga S, James D, Manzin V, et al.
    Electrophoresis, 2018 Feb 07.
    PMID: 29412471 DOI: 10.1002/elps.201700469
    Metabolic profiling of Glycyrrhiza glabra using comprehensive two-dimensional liquid chromatography (LC × LC) coupled with photodiode array (PDA) and mass spectrometry (MS) detection is described. The separation was conducted under reversed-phase conditions, using a combination of first dimension (1 D) 150 mm microbore cyano column utilising 2.7 μm diameter (dp ) particles, and second dimension (2 D) 50 mm superficially porous octadecylsilica column with 2.7 μm dp particles. A multi-segmented shift gradient (MSG) for the 2 D separation was developed, and the orthogonality achieved was compared with other modes of gradients, such as full in-fraction, and shift gradient systems. Results demonstrated a significant expansion of metabolic coverage using MSG in 2 D, providing the highest measure of orthogonality compared to other gradient modes. Compound identifications were performed by employing complementary data from PDA and MS detection, with reference to structural group-type distribution in 2D space. A total of ca. 120 compounds were detected, and among them 37 were tentatively identified, distributed over the chemical families of glycosylated flavanones, triterpene saponins, and others. In comparison with one-dimensional LC, the total number of compounds detected was ca. 2-fold greater when LC × LC was employed. To the best of our knowledge, this is the first demonstration of the MSG mode in LC × LC, representing a powerful strategy to expand the metabolic coverage for analysis of plant-derived extracts, containing a multitude of different phytochemical classes.
  14. Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.
    BMC Cancer, 2021 Sep 14;21(1):1021.
    PMID: 34521387 DOI: 10.1186/s12885-021-08738-z
    BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.

    METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).

    RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving  10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).

    CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

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