Displaying all 14 publications

  1. Loo JM, Shi Y, Pu X
    J Gambl Stud, 2016 Jun;32(2):391-407.
    PMID: 26337063 DOI: 10.1007/s10899-015-9569-3
    The investigation of the interface between psychological constructs, compulsive consumption of alcohol and pathological gambling is an important avenue for development of future initiatives in social marketing or prevention programs. This cross-cultural study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of psychological variables such as gambling urge, gambling-related erroneous cognitions and comorbid alcohol consumption on pathological gambling behaviour and its impact on overall quality of life indicators. Participants consist of 445 Macao and Australian young adults (Mean age = 23 years). Results indicate that probable pathological gamblers as compared with non-gamblers reported significantly lower quality of life in all domains-physical health, psychological well-being, social relationships and environment. Adults who drank more alcohol and have stronger erroneous cognitions evidenced higher pathological gambling behavior. Our research model fits both cohorts and interestingly, erroneous gambling-related cognitions serve as a full mediator for the predictive relationship between gambling urge and pathological gambling in the Macao sample, but serve as a partial mediator in the Australian sample. Targeting erroneous cognitions in future social marketing or preventive campaigns should demonstrate to be an important strategy in reducing the effects of urge to gamble among at-risk individuals. Further implications for the industry, marketing and governmental strategies are discussed.
  2. Shi Y, Huang L, Soh AK, Weng GJ, Liu S, Redfern SAT
    Sci Rep, 2017 09 11;7(1):11111.
    PMID: 28894256 DOI: 10.1038/s41598-017-11633-y
    Electrocaloric (EC) materials show promise in eco-friendly solid-state refrigeration and integrable on-chip thermal management. While direct measurement of EC thin-films still remains challenging, a generic theoretical framework for quantifying the cooling properties of rich EC materials including normal-, relaxor-, organic- and anti-ferroelectrics is imperative for exploiting new flexible and room-temperature cooling alternatives. Here, we present a versatile theory that combines Master equation with Maxwell relations and analytically relates the macroscopic cooling responses in EC materials with the intrinsic diffuseness of phase transitions and correlation characteristics. Under increased electric fields, both EC entropy and adiabatic temperature changes increase quadratically initially, followed by further linear growth and eventual gradual saturation. The upper bound of entropy change (∆Smax) is limited by distinct correlation volumes (V cr ) and transition diffuseness. The linearity between V cr and the transition diffuseness is emphasized, while ∆Smax = 300 kJ/(K.m3) is obtained for Pb0.8Ba0.2ZrO3. The ∆Smax in antiferroelectric Pb0.95Zr0.05TiO3, Pb0.8Ba0.2ZrO3 and polymeric ferroelectrics scales proportionally with V cr-2.2, owing to the one-dimensional structural constraint on lattice-scale depolarization dynamics; whereas ∆Smax in relaxor and normal ferroelectrics scales as ∆Smax ~ V cr-0.37, which tallies with a dipolar interaction exponent of 2/3 in EC materials and the well-proven fractional dimensionality of 2.5 for ferroelectric domain walls.
  3. Wang SQ, Ying J, Zhang ML, Shi Y, Li Y, Xing ZJ, et al.
    Jpn J Nurs Sci, 2018 Oct;15(4):285-297.
    PMID: 29363255 DOI: 10.1111/jjns.12201
    AIM: With the rapid development of science and technology, the pace of life has accelerated. Health and life satisfaction issues of persons are gaining more attention. China, Japan, Malaysia, and Taiwan conducted international cooperative research on health of four regional populations. This research was a part of the study in mainland China, which aimed to explore health-related life satisfaction and its influencing factors on large samples in mainland China.

    METHODS: A random group of 1404 persons from universities, factories, companies, and elderly centers in Changchun completed a structured questionnaire. This study centered on life satisfaction indicators, which included the current whole life, income, family relationships, peer relationships, relationships with the neighbors, living environment, personal health, family health, spare time, and housework share. Other collected data included the Body Mass Index, blood pressure, self-rated health, Breslow's seven health practices, medical treatment within the past 6 months, physical examinations, General Health Questionnaire (GHQ)-12 Scale, social activities, networking relationships with persons around the community, social support, and sociodemographic variables. Associations between life satisfaction, demographics, and health-related variables were analyzed through a multiway ANOVA.

    RESULTS: The living environment and income of Chinese persons were related to their low life satisfaction. The multiway ANOVA showed that the independent relationship of self-rated health, regular physical examinations, GHQ-12 Scale, trust in the community, communication with the neighbors, education, and age related with life satisfaction accounting for 20.3% of the variance. Education and age showed interactive effects on life satisfaction.

    CONCLUSION: This study identified seven factors that influenced the life satisfaction of persons in mainland China. Life satisfaction can be enhanced through interventions to improve self-rated health, regular physical examinations, mental health, trust in the community, communication with the neighbors, education, and improvement in the health service.

  4. Johnson KR, Hindmarch CC, Salinas YD, Shi Y, Greenwood M, Hoe SZ, et al.
    PLoS ONE, 2015;10(4):e0124523.
    PMID: 25897513 DOI: 10.1371/journal.pone.0124523
    Magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system (HNS) are highly specialized to release large amounts of arginine vasopressin (Avp) or oxytocin (Oxt) into the blood stream and play critical roles in the regulation of body fluid homeostasis. The MCNs are osmosensory neurons and are excited by exposure to hypertonic solutions and inhibited by hypotonic solutions. The MCNs respond to systemic hypertonic and hypotonic stimulation with large changes in the expression of their Avp and Oxt genes, and microarray studies have shown that these osmotic perturbations also cause large changes in global gene expression in the HNS. In this paper, we examine gene expression in the rat supraoptic nucleus (SON) under normosmotic and chronic salt-loading SL) conditions by the first time using "new-generation", RNA sequencing (RNA-Seq) methods. We reliably detect 9,709 genes as present in the SON by RNA-Seq, and 552 of these genes were changed in expression as a result of chronic SL. These genes reflect diverse functions, and 42 of these are involved in either transcriptional or translational processes. In addition, we compare the SON transcriptomes resolved by RNA-Seq methods with the SON transcriptomes determined by Affymetrix microarray methods in rats under the same osmotic conditions, and find that there are 6,466 genes present in the SON that are represented in both data sets, although 1,040 of the expressed genes were found only in the microarray data, and 2,762 of the expressed genes are selectively found in the RNA-Seq data and not the microarray data. These data provide the research community a comprehensive view of the transcriptome in the SON under normosmotic conditions and the changes in specific gene expression evoked by salt loading.
  5. Chen X, Tan X, Li J, Jin Y, Gong L, Hong M, et al.
    PLoS ONE, 2013;8(12):e82861.
    PMID: 24340064 DOI: 10.1371/journal.pone.0082861
    Coxsackievirus A16 (CVA16) is responsible for nearly 50% of all the confirmed hand, foot, and mouth disease (HFMD) cases in mainland China, sometimes it could also cause severe complications, and even death. To clarify the genetic characteristics and the epidemic patterns of CVA16 in mainland China, comprehensive bioinfomatics analyses were performed by using 35 CVA16 whole genome sequences from 1998 to 2011, 593 complete CVA16 VP1 sequences from 1981 to 2011, and prototype strains of human enterovirus species A (EV-A). Analysis on complete VP1 sequences revealed that subgenotypes B1a and B1b were prevalent strains and have been co-circulating in many Asian countries since 2000, especially in mainland China for at least 13 years. While the prevalence of subgenotype B1c (totally 20 strains) was much limited, only found in Malaysia from 2005 to 2007 and in France in 2010. Genotype B2 only caused epidemic in Japan and Malaysia from 1981 to 2000. Both subgenotypes B1a and B1b were potential recombinant viruses containing sequences from other EV-A donors in the 5'-untranslated region and P2, P3 non-structural protein encoding regions.
  6. Cheung CMG, Ong PG, Neelam K, Tan PC, Shi Y, Mitchell P, et al.
    Ophthalmology, 2017 09;124(9):1305-1313.
    PMID: 28501376 DOI: 10.1016/j.ophtha.2017.03.056
    PURPOSE: To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians.

    DESIGN: Prospective, population cohort study.

    PARTICIPANTS: The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006-2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.

    METHODS: Fundus photographs were graded using the Wisconsin AMD grading system.

    MAIN OUTCOME MEASURES: Incidence of early and late AMD.

    RESULTS: Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81-7.16) and 0.76% (95% CI, 0.42-1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43-7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49-1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52-9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54-4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%).

    CONCLUSIONS: This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians.

  7. Blair GW, Appleton JP, Flaherty K, Doubal F, Sprigg N, Dooley R, et al.
    EClinicalMedicine, 2019 04 24;11:34-43.
    PMID: 31317131 DOI: 10.1016/j.eclinm.2019.04.001
    Background: Lacunar stroke, a frequent clinical manifestation of small vessel disease (SVD), differs pathologically from other ischaemic stroke subtypes and has no specific long-term secondary prevention. Licenced drugs, isosorbide mononitrate (ISMN) and cilostazol, have relevant actions to prevent SVD progression.

    Methods: We recruited independent patients with clinically confirmed lacunar ischaemic stroke without cognitive impairment to a prospective randomised clinical trial, LACunar Intervention-1 (LACI-1). We randomised patients using a central web-based system, 1:1:1:1 with minimisation, to masked ISMN 25 mg bd, cilostazol 100 mg bd, both ISMN and cilostazol started immediately, or both with start delayed. We escalated doses to target over two weeks, sustained for eight weeks. Primary outcome was the proportion achieving target dose. Secondary outcomes included symptoms, safety (haemorrhage, recurrent vascular events), cognition, haematology, vascular function, and neuroimaging. LACI-1 was powered (80%, alpha 0.05) to detect 35% (90% versus 55%) difference between the proportion reaching target dose on one versus both drugs at 55 patients. Registration ISRCTN12580546.

    Findings: LACI-1 enrolled 57 participants between March 2016 and August 2017: 18 (32%) females, mean age 66 (SD 11, range 40-85) years, onset-randomisation 203 (range 6-920) days. Most achieved full (64%) or over half (87%) dose, with no difference between cilostazol vs ISMN, single vs dual drugs. Headache and palpitations increased initially then declined similarly with dual versus single drugs. There was no between-group difference in BP, pulse-wave velocity, haemoglobin or platelet function, but pulse rate was higher (mean difference, MD, 6.4, 95%CI 1.2-11.7, p = 0.02), platelet count higher (MD 35.7, 95%CI 2.8, 68.7, p = 0.03) and white matter hyperintensities reduced more (Chi-square p = 0.007) with cilostazol versus no cilostazol.

    Interpretation: Cilostazol and ISMN are well tolerated when the dose is escalated, without safety concerns, in patients with lacunar stroke. Larger trials with longer term follow-up are justified.

    Funding: Alzheimer's Society (AS-PG-14-033).

  8. Blair GW, Appleton JP, Law ZK, Doubal F, Flaherty K, Dooley R, et al.
    Int J Stroke, 2018 07;13(5):530-538.
    PMID: 28906205 DOI: 10.1177/1747493017731947
    Rationale The pathophysiology of most lacunar stroke, a form of small vessel disease, is thought to differ from large artery atherothrombo- or cardio-embolic stroke. Licensed drugs, isosorbide mononitrate and cilostazol, have promising mechanisms of action to support their testing to prevent stroke recurrence, cognitive impairment, or radiological progression after lacunar stroke. Aim LACI-1 will assess the tolerability, safety, and efficacy, by dose, of isosorbide mononitrate and cilostazol, alone and in combination, in patients with ischemic lacunar stroke. Sample size A sample of 60 provides 80+% power (significance 0.05) to detect a difference of 35% (90% versus 55%) between those reaching target dose on one versus both drugs. Methods and design LACI-1 is a phase IIa partial factorial, dose-escalation, prospective, randomized, open label, blinded endpoint trial. Participants are randomized to isosorbide mononitrate and/or cilostazol for 11 weeks with dose escalation to target as tolerated in two centers (Edinburgh, Nottingham). At three visits, tolerability, safety, blood pressure, pulse wave velocity, and platelet function are assessed, plus magnetic resonance imaging to assess cerebrovascular reactivity in a subgroup. Study outcomes Primary: proportion of patients completing study achieving target maximum dose. Secondary symptoms whilst taking medications; safety (hemorrhage, recurrent vascular events, falls); blood pressure, platelet function, arterial stiffness, and cerebrovascular reactivity. Discussion This study will inform the design of a larger phase III trial of isosorbide mononitrate and cilostazol in lacunar stroke, whilst providing data on the drugs' effects on vascular and platelet function. Trial registration ISRCTN (ISRCTN12580546) and EudraCT (2015-001953-33).
  9. Liu C, Kanazawa T, Tian Y, Mohamed Saini S, Mancuso S, Mostaid MS, et al.
    Transl Psychiatry, 2019 08 27;9(1):205.
    PMID: 31455759 DOI: 10.1038/s41398-019-0532-4
    Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.
  10. van Panhuis WG, Choisy M, Xiong X, Chok NS, Akarasewi P, Iamsirithaworn S, et al.
    Proc. Natl. Acad. Sci. U.S.A., 2015 Oct 20;112(42):13069-74.
    PMID: 26438851 DOI: 10.1073/pnas.1501375112
    Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual epidemics are commonly observed, but there is substantial spatiotemporal heterogeneity in intensity. A better understanding of this heterogeneity in dengue transmission could lead to improved epidemic prediction and disease control. Time series decomposition methods enable the isolation and study of temporal epidemic dynamics with a specific periodicity (e.g., annual cycles related to climatic drivers and multiannual cycles caused by dynamics in population immunity). We collected and analyzed up to 18 y of monthly dengue surveillance reports on a total of 3.5 million reported dengue cases from 273 provinces in eight countries in Southeast Asia, covering ∼ 10(7) km(2). We detected strong patterns of synchronous dengue transmission across the entire region, most markedly during a period of high incidence in 1997-1998, which was followed by a period of extremely low incidence in 2001-2002. This synchrony in dengue incidence coincided with elevated temperatures throughout the region in 1997-1998 and the strongest El Niño episode of the century. Multiannual dengue cycles (2-5 y) were highly coherent with the Oceanic Niño Index, and synchrony of these cycles increased with temperature. We also detected localized traveling waves of multiannual dengue epidemic cycles in Thailand, Laos, and the Philippines that were dependent on temperature. This study reveals forcing mechanisms that drive synchronization of dengue epidemics on a continental scale across Southeast Asia.
  11. Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, et al.
    JAMA, 2014 Aug 6;312(5):525-34.
    PMID: 25096692 DOI: 10.1001/jama.2014.7859
    The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown.
  12. Lin GW, Xu C, Chen K, Huang HQ, Chen J, Song B, et al.
    Lancet Oncol., 2019 Dec 23.
    PMID: 31879220 DOI: 10.1016/S1470-2045(19)30799-5
    BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL.

    METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.

    FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.

    INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.

    FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.

  13. Lawrenson K, Song F, Hazelett DJ, Kar SP, Tyrer J, Phelan CM, et al.
    Gynecol. Oncol., 2019 05;153(2):343-355.
    PMID: 30898391 DOI: 10.1016/j.ygyno.2019.02.023
    OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women.

    METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations.

    RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7).

    CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.

  14. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
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