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  1. Shao M, Li S, Tan CP, Kraithong S, Gao Q, Fu X, et al.
    Int J Biol Macromol, 2021 Mar 15;173:118-127.
    PMID: 33444656 DOI: 10.1016/j.ijbiomac.2021.01.043
    In this study, caffeine (CA) was encapsulated into food-grade starch matrices, including swelled starch (SS), porous starch (PS), and V-type starch (VS). The bitterness of the microcapsules and suppression mechanisms were investigated using an electronic tongue, molecular dynamics (MD) simulation and the in vitro release kinetics of CA. All the CA-loaded microcapsules showed a lower bitterness intensity than the control. The MD results proved that the weak interactions between starch and CA resulted in a moderate CA release rate for SS-CA microcapsules. The PS-CA microcapsule presented the longest CA release, up to 40 min, whereas the VS-CA microcapsule completely released CA in 9 min. The CA release rate was found to be related to the microcapsule structure and rehydration properties. A low CA bitterness intensity could be attributed to a delay in the CA release rate and resistance to erosion of the microcapsules. The results of this work are valuable for improving starch-based microcapsules (oral-targeted drug-delivery systems) by suppressing the bitterness of alkaloid compounds.
  2. Lim L, Ng TP, Ong AP, Tan MP, Cenina AR, Gao Q, et al.
    Alzheimers Res Ther, 2018 01 22;10(1):6.
    PMID: 29370825 DOI: 10.1186/s13195-017-0333-z
    BACKGROUND: Cognitive screeners are imperative for early diagnosis of dementia. The Visual Cognitive Assessment Test (VCAT) is a language-neutral, visual-based test which has proven useful for a multilingual population in a single-center study. However, its performance utility is unknown in a wider and more diverse Southeast Asian cohort.

    METHODS: We recruited 164 healthy controls (HC) and 120 cognitively impaired (CI) subjects- 47 mild cognitive impairment (MCI) and 73 mild Alzheimer's disease (AD) dementia participants, from four countries between January 2015 and August 2016 to determine the usefulness of a single version of the VCAT, without translation or adaptation, in a multinational, multilingual population. The VCAT was administered along with established cognitive evaluation.

    RESULTS: The VCAT, without local translation or adaptation, was effective in discriminating between HC and CI subjects (MCI and mild AD dementia). Mean (SD) VCAT scores for HC and CI subjects were 22.48 (3.50) and 14.17 (5.05) respectively. Areas under the curve for Montreal Cognitive Assessment (0.916, 95% CI 0.884-0.948) and the VCAT (0.905, 95% CI 0.870-0.940) in discriminating between HCs and CIs were comparable. The multiple languages used to administer VCAT in four countries did not significantly influence test scores.

    CONCLUSIONS: The VCAT without the need for language translation or cultural adaptation showed satisfactory discriminative ability and was effective in a multinational, multilingual Southeast Asian population.

  3. Sun Q, Guo F, Liu Y, Zhang Y, Zhang K, Wang Y, et al.
    J Org Chem, 2024 Mar 01;89(5):3304-3308.
    PMID: 38356371 DOI: 10.1021/acs.joc.3c02754
    A protocol for the construction of an angular tricyclic benzofuran skeleton based on the C-H activation strategy has been established. Different phthalide lactones on this skeleton can be easily assembled with various side chains by using C-H activation with aldehydes and subsequent reduction. This skeleton provides a versatile and crucial motif for the total synthesis of naturally occurring angular tricyclic benzofurans and their derivatives. Based on this protocol, the improved total syntheses of daldinin A and annullatin D were achieved in yields of 17.3 and 7.6%, respectively.
  4. Ang LW, Gao Q, Cui L, Farwin A, Toh MPHS, Boudville IC, et al.
    BMC Infect Dis, 2022 Jan 25;22(1):88.
    PMID: 35078426 DOI: 10.1186/s12879-022-07066-2
    BACKGROUND: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore.

    METHODS: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT).

    RESULTS: A total of 2234 migrant workers aged 20-49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2-91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965-1989 than those born in 1990-1999 (95.3% vs. 86.6%, p 

  5. Ang LW, Gao Q, Cui L, Farwin A, Toh MPHS, Boudville IC, et al.
    BMC Public Health, 2022 Jan 16;22(1):111.
    PMID: 35033034 DOI: 10.1186/s12889-022-12528-y
    BACKGROUND: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore.

    METHODS: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure.

    RESULTS: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20-43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 - 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 - 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 - 15.4%) in Chinese workers to 23.0% (95% CI 17.1 - 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989.

    CONCLUSIONS: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks.

  6. Zhao H, Zhao S, International Network for Bamboo and Rattan, Fei B, Liu H, Yang H, et al.
    Gigascience, 2017 07 01;6(7):1-7.
    PMID: 28637269 DOI: 10.1093/gigascience/gix046
    Bamboo and rattan are widely grown for manufacturing, horticulture, and agroforestry. Bamboo and rattan production might help reduce poverty, boost economic growth, mitigate climate change, and protect the natural environment. Despite progress in research, sufficient molecular and genomic resources to study these species are lacking. We launched the Genome Atlas of Bamboo and Rattan (GABR) project, a comprehensive, coordinated international effort to accelerate understanding of bamboo and rattan genetics through genome analysis. GABR includes 2 core subprojects: Bamboo-T1K (Transcriptomes of 1000 Bamboos) and Rattan-G5 (Genomes of 5 Rattans), and several other subprojects. Here we describe the organization, directions, and status of GABR.
  7. Park JH, Kim MH, Sutanto E, Na SW, Kim MJ, Yeom JS, et al.
    PLoS Negl Trop Dis, 2022 Jun;16(6):e0010492.
    PMID: 35737709 DOI: 10.1371/journal.pntd.0010492
    Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152-625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157-560 aa.) and PvRBP1a-C (606-962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels.
  8. Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, et al.
    Clin Cancer Res, 2022 Jun 01;28(11):2278-2285.
    PMID: 35131903 DOI: 10.1158/1078-0432.CCR-21-3023
    PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer.

    PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

    RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.

    CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

  9. Li Z, Lin Z, Liu S, Yagi H, Zhang X, Yocum L, et al.
    Adv Sci (Weinh), 2022 Jul;9(21):e2105909.
    PMID: 35436042 DOI: 10.1002/advs.202105909
    Diseases of the knee joint such as osteoarthritis (OA) affect all joint elements. An in vitro human cell-derived microphysiological system capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies/pathogenesis of joint diseases and testing potential therapeutics. Herein, a human mesenchymal stem cell-derived miniature joint system (miniJoint) is generated, in which engineered osteochondral complex, synovial-like fibrous tissue, and adipose tissue are integrated into a microfluidics-enabled bioreactor. This novel design facilitates different tissues communicating while still maintaining their respective phenotypes. The miniJoint exhibits physiologically relevant changes when exposed to interleukin-1β mediated inflammation, which are similar to observations in joint diseases in humans. The potential of the miniJoint in predicting in vivo efficacy of drug treatment is confirmed by testing the "therapeutic effect" of the nonsteroidal anti-inflammatory drug, naproxen, as well as four other potential disease-modifying OA drugs. The data demonstrate that the miniJoint recapitulates complex tissue interactions, thus providing a robust organ chip model for the study of joint pathology and the development of novel therapeutic interventions.
  10. Wu W, Ding D, Zhao Q, Xiao Z, Luo J, Ganguli M, et al.
    Alzheimers Dement, 2023 Jan;19(1):107-122.
    PMID: 35290713 DOI: 10.1002/alz.12628
    INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear.

    METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.

    RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).

    DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

  11. Pearson RD, Amato R, Auburn S, Miotto O, Almagro-Garcia J, Amaratunga C, et al.
    Nat Genet, 2016 Aug;48(8):959-964.
    PMID: 27348299 DOI: 10.1038/ng.3599
    The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.
  12. Makkar SR, Lipnicki DM, Crawford JD, Kochan NA, Castro-Costa E, Lima-Costa MF, et al.
    J Gerontol A Biol Sci Med Sci, 2020 09 25;75(10):1863-1873.
    PMID: 32396611 DOI: 10.1093/gerona/glaa116
    We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.
  13. Röhr S, Pabst A, Riedel-Heller SG, Jessen F, Turana Y, Handajani YS, et al.
    Alzheimers Res Ther, 2020 12 18;12(1):167.
    PMID: 33339532 DOI: 10.1186/s13195-020-00734-y
    BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.

    METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.

    RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.

    CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

  14. MalariaGEN, Adam I, Alam MS, Alemu S, Amaratunga C, Amato R, et al.
    Wellcome Open Res, 2022;7:136.
    PMID: 35651694 DOI: 10.12688/wellcomeopenres.17795.1
    This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.
  15. Trimarsanto H, Amato R, Pearson RD, Sutanto E, Noviyanti R, Trianty L, et al.
    Commun Biol, 2022 Dec 23;5(1):1411.
    PMID: 36564617 DOI: 10.1038/s42003-022-04352-2
    Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs.
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