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Liver transplantation in the Asia Pacific region--trials and tribulations

Fan ST

Med J Malaysia, 2005 Jul;60 Suppl B:1-4.
PMID: 16108164
Fulltext Prevalence of melanocortin receptor 4 (MC4R) V103I gene variant and its association with obesity among the Kampar Health Clinic cohort, Perak, Malaysia

Chua HN, Fan SH, Say YH

Med J Malaysia, 2012 Apr;67(2):234-5.
PMID: 22822657 MyJurnal

This study investigated the prevalence of the Melanocortin receptor 4 (MC4R) V1031 gene variant and its association with obesity among a cohort of 254 patients (101 males; 118 obese) attending the Kampar Health Clinic. Genotyping revealed the mutated I allele frequency of 0.02, no homozygous mutated (II), and similar distribution of V and I alleles across BMI groups, genders and ethnic groups. No significant difference was found for the means of anthropometric measurements between alleles. Prevalence of this gene variant among the Malaysian cohort was similar with previous populations (2-4% of mutated allele carrier), but was not associated with obesity.
Fulltext No association of peptide tyrosine-tyrosine (PYY) gene R72T variant with obesity in the Kampar Health Clinic cohort, Malaysia

Chan PM, Fan SH, Say YH

Malays J Nutr, 2011 Aug;17(2):201-12.
PMID: 22303574 MyJurnal

Peptide Tyrosine-Tyrosine (PYY) is a 36-amino acid peptide hormone released post-prandially from the endocrine cells in the intestinal tract to suppress pancreatic secretions and eventually reduce appetite. The R72T variant in the PYY gene (rs1058046) has been associated with increased susceptibility to obesity. Therefore, the objective of this study was to investigate the association of this variant with obesity and its related anthropometric measurements among the Kampar Health Clinic cohort, Malaysia.
Fulltext Plasma total antioxidant capacity (TAC) in obese Malaysian subjects

Lim SH, Fan SH, Say YH

Malays J Nutr, 2012 Dec;18(3):345-54.
PMID: 24568075 MyJurnal

INTRODUCTION: There is a pressing need to better understand the complex biochemical pathways that lead to the pathogenesis of obesity. Increased oxidative stress and decreased antioxidant capacity have been identified to be associated with obesity. Therefore, the objectives of this study were to determine the plasma total antioxidant capacity (TAC) levels of Malaysian subjects and to evaluate its potential association with obesity and related anthropometric measurements.
METHODS: Plasma TAC of 362 multi-ethnic Malaysian subjects from the Kampar Health Clinic (138 males, 224 females; 124 ethnic Malays, 152 Chinese, 86 Indians; 192 non-obese, 170 obese) was measured using Trolox equivalent antioxidant capacity (TEAC) 96-well plate assay.
RESULTS: Plasma TAC was significantly lower in obese subjects (M +/- SE = 292 +/- 10.4 micromol/L) compared to non-obese subjects (397 +/- 8.58 micromol/L), whereas it was significantly higher in males and those in the 21-30 age group. Those with salty food preference and practising a strict vegetarian diet also had significantly higher plasma TAC. However, no association was found for other dietary habits (coffee intake) and lifestyle factors (physical activity, smoking). Plasma TAC was also significantly negatively correlated with diastolic blood pressure, waist and hip circumferences, weight, body mass index, total body fat, % subcutaneous fat, visceral fat level, resting metabolism and % skeletal muscle.
CONCLUSION: Plasma TAC was found to be associated with obesity, strict vegetarian practice, salty food preference and all obesity anthropometric indicators, except systolic blood pressure and pulse rate. Obese people have decreased plasma TAC indicating a compromised systemic antioxidant defence and increased oxidative stress.
Fulltext Exploring Regional Advanced Manufacturing and Its Driving Factors: A Case Study of the Guangdong-Hong Kong-Macao Greater Bay Area

Dou Z, Sun Y, Wang T, Wan H, Fan S

Int J Environ Res Public Health, 2021 05 28;18(11).
PMID: 34071373 DOI: 10.3390/ijerph18115800

This study aims to analyze the development trend of the manufacturing industry of the Guangdong-Hong Kong-Macao Greater Bay Area (from 2008 to 2018) by constructing an evaluation system. On the basis of push-pull-mooring theory, we analyze these factors by using an entropy and cluster model. The results show the following: (1) Technological development had an obvious spatial distribution pattern of core regional radiation, while others did not. (2) Economic development was based on the city's existing industrial development system, while environmental development depended on governmental policies. (3) Compared with the environmental factor, the development trends of the economic and technological factors were more similar. Lastly, we provide four strategies for the development of the manufacturing industry in different cities.
Microalgal-bacterial granular sludge process for non-aerated aquaculture wastewater treatment

Fan S, Ji B, Abu Hasan H, Fan J, Guo S, Wang J, et al.

Bioprocess Biosyst Eng, 2021 Aug;44(8):1733-1739.
PMID: 33772637 DOI: 10.1007/s00449-021-02556-0

Microalgal-bacterial granular sludge (MBGS) process has become a focal point in treating municipal wastewater. However, it remains elusive whether the emerging process can be applied for the treatment of aquaculture wastewater, which contains considerable concentrations of nitrate and nitrite. This study evaluated the feasibility of MBGS process for aquaculture wastewater treatment. Result showed that the MBGS process was competent to remove respective 64.8%, 84.9%, 70.8%, 50.0% and 84.2% of chemical oxygen demand, ammonia-nitrogen, nitrate-nitrogen, nitrite-nitrogen and phosphate-phosphorus under non-aerated conditions within 8 h. The dominant microalgae and bacteria were identified to be Coelastrella and Rhodobacteraceae, respectively. Further metagenomics analysis implied that microbial assimilation was the main contributor in organics, nitrogen and phosphorus removal. Specifically, considerable nitrate and nitrite removals were also obtained with the synergy between microalgae and bacteria. Consequently, this work demonstrated that the MBGS process showed a prospect of becoming an environmentally friendly and efficient alternative in aquaculture wastewater treatment.
Multiple roles of food-derived bioactive peptides in the management of T2DM and commercial solutions: A review

Fan S, Liu Q, Du Q, Zeng X, Wu Z, Pan D, et al.

Int J Biol Macromol, 2024 Aug 23;279(Pt 1):134993.
PMID: 39181375 DOI: 10.1016/j.ijbiomac.2024.134993

Type 2 diabetes mellitus (T2DM), a disease that threatens public health worldwide and can cause a series of irreversible complications, has been a major concern. Although the treatment based on hypoglycemic drugs is effective, its side effects should not be ignored, which has led to an urgent need for developing new hypoglycemic drugs. Bioactive peptides with antidiabetic effects obtained from food proteins have become a research hotspot as they are safer and with higher specificity than traditional hypoglycemic drugs. Here, we reviewed antidiabetic peptides that have the ability to inhibit key enzymes (α-glucosidase, α-amylase, and DPP-IV) in T2DM, the hypoglycemic mechanisms and structure-activity relationships were summarized, some antidiabetic peptides that improve insulin resistance and reverse gut microbiota and their metabolites were overviewed, the bitterness of antidiabetic peptides was predicted in silico, proposed solutions to the current challenges encountered in the development of antidiabetic peptide drugs, and provided an outlook on the future focus of commercial production. It provides a reference for the application of food-derived antidiabetic peptides.
Comparison of Patient Health Questionnaire-9, Edinburgh Postnatal Depression Scale and Hospital Anxiety and Depression - Depression subscale scores by administration mode: An individual participant data differential item functioning meta-analysis

Harel D, Wu Y, Levis B, Fan S, Sun Y, Xu M, et al.

J Affect Disord, 2024 Sep 15;361:674-683.
PMID: 38908554 DOI: 10.1016/j.jad.2024.06.033

Administration mode of patient-reported outcome measures (PROMs) may influence responses. We assessed if Patient Health Questionnaire-9 (PHQ-9), Edinburgh Postnatal Depression Scale (EPDS) and Hospital Anxiety and Depression Scale - Depression subscale (HADS-D) item responses and scores were associated with administration mode. We compared (1) self-administration versus interview-administration; within self-administration (2) research or medical setting versus private; and (3) pen-and-paper versus electronic; and within interview-administration (4) in-person versus phone. We analysed individual participant data meta-analysis datasets with item-level data for the PHQ-9 (N = 34,529), EPDS (N = 16,813), and HADS-D (N = 16,768). We used multiple indicator multiple cause models to assess differential item functioning (DIF) by administration mode. We found statistically significant DIF for most items on all measures due to large samples, but influence on total scores was negligible. In 10 comparisons conducted across the PHQ-9, EPDS, and HADS-D, Pearson's correlations and intraclass correlation coefficients between latent depression symptom scores from models that did or did not account for DIF were between 0.995 and 1.000. Total PHQ-9, EPDS, and HADS-D scores did not differ materially across administration modes. Researcher and clinicians who evaluate depression symptoms with these questionnaires can select administration methods based on patient preferences, feasibility, or cost.
Fulltext ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma

Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al.

PLoS Genet, 2014 Mar;10(3):e1004089.
PMID: 24603532 DOI: 10.1371/journal.pgen.1004089

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
Fulltext Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma

Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al.

Nat Genet, 2012 Oct;44(10):1142-1146.
PMID: 22922875 DOI: 10.1038/ng.2390

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
Comparison of the accuracy of the 7-item HADS Depression subscale and 14-item total HADS for screening for major depression: A systematic review and individual participant data meta-analysis

Wu Y, Levis B, Daray FM, Ioannidis JPA, Patten SB, Cuijpers P, et al.

Psychol Assess, 2023 Feb;35(2):95-114.
PMID: 36689386 DOI: 10.1037/pas0001181

The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool

Levis B, Bhandari PM, Neupane D, Fan S, Sun Y, He C, et al.

JAMA Netw Open, 2024 Nov 04;7(11):e2429630.
PMID: 39576645 DOI: 10.1001/jamanetworkopen.2024.29630

IMPORTANCE: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.
OBJECTIVE: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.
DESIGN, SETTING, AND PARTICIPANTS: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 scores with a major depression classification. From the IPDMA population, 1000 studies of 100, 200, 500, and 1000 participants each were resampled.
MAIN OUTCOMES AND MEASURES: For the full IPDMA population and each simulated study, an optimal cutoff score was selected by maximizing the Youden index. Accuracy estimates for optimal cutoff scores in simulated studies were compared with accuracy in the full population.
RESULTS: The IPDMA database included 100 primary studies with 44 503 participants (4541 [10%] cases of major depression). The population-level optimal cutoff score was 8 or higher. Optimal cutoff scores in simulated studies ranged from 2 or higher to 21 or higher in samples of 100 participants and 5 or higher to 11 or higher in samples of 1000 participants. The percentage of simulated studies that identified the true optimal cutoff score of 8 or higher was 17% for samples of 100 participants and 33% for samples of 1000 participants. Compared with estimates for a cutoff score of 8 or higher in the population, sensitivity was overestimated by 6.4 (95% CI, 5.7-7.1) percentage points in samples of 100 participants, 4.9 (95% CI, 4.3-5.5) percentage points in samples of 200 participants, 2.2 (95% CI, 1.8-2.6) percentage points in samples of 500 participants, and 1.8 (95% CI, 1.5-2.1) percentage points in samples of 1000 participants. Specificity was within 1 percentage point across sample sizes.
CONCLUSIONS AND RELEVANCE: This study of cross-sectional data found that optimal cutoff scores and accuracy estimates differed substantially from population values when data-driven methods were used to simultaneously identify an optimal cutoff score and estimate accuracy. Users of diagnostic accuracy evidence should evaluate studies of accuracy with caution and ensure that cutoff score recommendations are based on adequately powered research or well-conducted meta-analyses.
Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma

Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.

Nat Genet, 2016 May;48(5):556-62.
PMID: 27064256 DOI: 10.1038/ng.3540

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

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