Displaying publications 1 - 20 of 268 in total

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  1. Ahmad S, Zamry AA, Tan HT, Wong KK, Lim J, Mohamud R
    Mol Immunol, 2017 11;91:123-133.
    PMID: 28898717 DOI: 10.1016/j.molimm.2017.09.001
    Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity. In this review, we describe the synthesis and physiochemical properties of gold NPs as well as the importance of gold NPs in immunotherapies through their actions on human DCs.
  2. Ahmad S, Azid NA, Boer JC, Lim J, Chen X, Plebanski M, et al.
    Front Immunol, 2018;9:2572.
    PMID: 30473698 DOI: 10.3389/fimmu.2018.02572
    Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine, which is thought to play a major role in the pathogenesis of inflammatory diseases, including allergy. TNF is produced at the early stage of allergen sensitization, and then continues to promote the inflammation cascade in the effector phase of allergic reactions. Consequently, anti-TNF treatment has been proposed as a potential therapeutic option. However, recent studies reveal anti-intuitive effects of TNF in the activation and proliferative expansion of immunosuppressive Tregs, tolerogenic DCs and MDSCs. This immunosuppressive effect of TNF is mediated by TNFR2, which is preferentially expressed by immunosuppressive cells. These findings redefine the role of TNF in allergic reaction, and suggest that targeting TNF-TNFR2 interaction itself may represent a novel strategy in the treatment of allergy.
  3. Ahn J, Lim J, Jusoh N, Lee J, Park TE, Kim Y, et al.
    PMID: 31380359 DOI: 10.3389/fbioe.2019.00168
    Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
  4. Al-Hatamleh MAI, Ahmad S, Boer JC, Lim J, Chen X, Plebanski M, et al.
    J Oncol, 2019;2019:6313242.
    PMID: 31239840 DOI: 10.1155/2019/6313242
    In the past decade, nanomedicine research has provided us with highly useful agents (nanoparticles) delivering therapeutic drugs to target cancer cells. The present review highlights nanomedicine applications for breast cancer immunotherapy. Recent studies have suggested that tumour necrosis factor (TNF) and its receptor 2 (TNFR2) expressed on breast cancer cells have important functional consequences. This cytokine/receptor interaction is also critical for promoting highly immune-suppressive phenotypes by regulatory T cells (Tregs). This review generally provides a background for nanoparticles as potential drug delivery agents for immunomodulators and further discusses in depth the potential of TNF antagonists delivery to modulate TNF-TNFR2 interactions and inhibit breast cancer progression.
  5. Anbarasen L, Lim J, Rajandram R, Mun KS, Sia SF
    PeerJ, 2019;7:e7058.
    PMID: 31275742 DOI: 10.7717/peerj.7058
    Background: Matrix metalloproteinase (MMP)-2 and -9 are Osteopontin (OPN) dependent molecules implicated in the destabilization of blood vessels. OPN and MMPs have been studied in brain arteriovenous malformation (BAVM) patients' tissues and blood samples before intervention. In this study, we compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease.

    Methodology: Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry.

    Result: MMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues.

    Conclusion: Findings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers' potential applications as primary medical therapy targets for BAVM patients.

  6. Arumugam K, Lim JM
    Br J Obstet Gynaecol, 1997 Aug;104(8):948-50.
    PMID: 9255089
    This case-controlled study investigates whether the presence of menstrual characteristics, which may increase the exposure of the peritoneal cavity to retrograde menstruation, increases the risk of developing endometriosis. The menstrual characteristics considered were 1. age at menarche of less than 12 years, 2. duration of menstrual flow greater than five days and 3. menstrual cycle lengths of < 28 days. The frequency with which these menstrual characteristics occurred in 305 women with proven endometriosis was compared with their frequency in 305 age-matched women without endometriosis. Adjusting for the confounding factors of parity, age at first childbirth and social class, the only menstrual characteristic that was significantly associated with endometriosis was menstrual cycle lengths of less than 28 days (odds ratio 1.83; 95% confidence intervals 1.60-2.55). There was insufficient evidence to conclude that the presence of menstrual characteristics which may increase the exposure of the peritoneal cavity to retrograde menstruation, increase a women's risk of developing endometriosis. The association of short menstrual cycle lengths with endometriosis may have been consequential rather than causal.
  7. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(7):629.
    PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z
    Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.
  8. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, et al.
    Eur Phys J C Part Fields, 2021;81(6):488.
    PMID: 34727143 DOI: 10.1140/epjc/s10052-021-09200-x
    Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.
  9. CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.
    Eur Phys J C Part Fields, 2020;80(3):189.
    PMID: 32226948 DOI: 10.1140/epjc/s10052-020-7739-7
    A search is presented for τ slepton pairs produced in proton-proton collisions at a center-of-mass energy of 13 TeV . The search is carried out in events containing two τ leptons in the final state, on the assumption that each τ slepton decays primarily to a τ lepton and a neutralino. Events are considered in which each τ lepton decays to one or more hadrons and a neutrino, or in which one of the τ leptons decays instead to an electron or a muon and two neutrinos. The data, collected with the CMS detector in 2016 and 2017, correspond to an integrated luminosity of 77.2 fb - 1 . The observed data are consistent with the standard model background expectation. The results are used to set 95% confidence level upper limits on the cross section for τ slepton pair production in various models for τ slepton masses between 90 and 200 GeV and neutralino masses of 1, 10, and 20 GeV . In the case of purely left-handed τ slepton production and decay to a τ lepton and a neutralino with a mass of 1 GeV , the strongest limit is obtained for a τ slepton mass of 125 GeV at a factor of 1.14 larger than the theoretical cross section.
  10. Che HX, Yeap SP, Osman MS, Ahmad AL, Lim J
    ACS Appl Mater Interfaces, 2014 Oct 8;6(19):16508-18.
    PMID: 25198872 DOI: 10.1021/am5050949
    The synthesis of nanocomposite with controlled surface morphology plays a key role for pollutant removal from aqueous environments. The influence of the molecular size of the polyelectrolyte in synthesizing silica-iron oxide core-shell nanocomposite with open shell structure was investigated by using dynamic light scattering, atomic force microscopy, and quartz crystal microbalance with dissipation (QCM-D). Here, poly(diallydimethylammonium chloride) (PDDA) was used to promote the attachment of iron oxide nanoparticles (IONPs) onto the silica surface to assemble a nanocomposite with magnetic and catalytic bifunctionality. High molecular weight PDDA tended to adsorb on silica colloid, forming a more extended conformation layer than low molecular weight PDDA. Subsequent attachment of IONPs onto this extended PDDA layer was more randomly distributed, forming isolated islands with open space between them. By taking amoxicillin, an antibiotic commonly found in pharmaceutical waste, as the model system, better removal was observed for silica-iron oxide nanocomposite with a more extended open shell structure.
  11. Chen RYT, Lim JKH, Chuo AML
    Med J Malaysia, 2003 Aug;58(3):330-6.
    PMID: 14750371
    Medical audit is vital to ensure continuous quality assurance and quality improvements. We did a retrospective study to ascertain the adequacy of clinical documentation and the factors hindering early discharge after an acute stroke in a restructured hospital. The medical records of all patients with acute stroke who died or were discharged from a restructured hospital in Singapore in January and February 1999 were reviewed retrospectively. Demographic data and the presence or absence of clinical documentation were noted. Factors hindering the discharge of patients at Day 5, Day 10 of stroke and at final discharge were noted and classified into: stroke-related, complications of stroke, medical-related and social factors. There were 101 patients in the study cohort, 55 males (54.5%) and 46 females (45.5%). The mean age was 67.9 years (SD 12.3). Documentation in Barthel scores (0%), presence of depression (0%), mental scores (1.0%), visual problems (10.0%), bladder continence (39.6%), admission functional status (37.6%) and dysphagia (52.5%) were deficient. The mean length of stay (LOS) was 13.0 (SD 14.2) days. The main factor hindering discharge at Day 5 (90.4%), Day 10 (95.2%) and at final discharge (82.1%) was stroke-related problems. Poor function (60.3%) and dysphagia (15.8%) were the 2 most common stroke-related problems hindering final discharge. Complications of stroke, medical-related problems and social reasons hindered final discharge in 10.8%, 17.8% and 2.9% of patients respectively. This audit revealed inadequacy in clinical documentation in patients with acute stroke. The main hindrance to final discharge of patients was stroke-related problems. The 2 most important stroke-related problems were poor function and dysphagia.
  12. Chhablani J, Wong K, Tan GS, Sudhalkar A, Laude A, Cheung CMG, et al.
    Asia Pac J Ophthalmol (Phila), 2020;9(5):426-434.
    PMID: 32956188 DOI: 10.1097/APO.0000000000000312
    PURPOSE: The aim of this consensus article was to provide comprehensive recommendations in the management of diabetic macular edema (DME) by reviewing recent clinical evidence.

    DESIGN: A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide.

    METHODS: An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation.

    RESULTS: The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed.

    CONCLUSIONS: This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.

  13. Chia PL, Earnest A, Lee R, Lim J, Wong CP, Chia YW, et al.
    Ann Acad Med Singap, 2013 Sep;42(9):432-6.
    PMID: 24162317
    INTRODUCTION: In Singapore, the age-standardised event rates of myocardial infarction (MI) are 2- and 3-fold higher for Malays and Indians respectively compared to the Chinese. The objectives of this study were to determine the prevalence and quantity of coronary artery calcification (CAC) and non-calcified plaques across these 3 ethnic groups.

    MATERIALS AND METHODS: This was a retrospective descriptive study. We identified 1041 patients (810 Chinese, 139 Malays, 92 Indians) without previous history of cardiovascular disease who underwent cardiac computed tomography for atypical chest pain evaluation. A cardiologist, who was blinded to the patients' clinical demographics, reviewed all scans. We retrospectively analysed all their case records.

    RESULTS: Overall, Malays were most likely to be active smokers (P = 0.02), Indians had the highest prevalence of diabetes mellitus (P = 0.01) and Chinese had the highest mean age (P <0.0001). The overall prevalence of patients with non-calcified plaques as the only manifestation of sub-clinical coronary artery disease was 2.1%. There was no significant difference in the prevalence of CAC, mean CAC score or prevalence of non-calcified plaques among the 3 ethnic groups. Active smoking, age and hypertension were independent predictors of CAC. Non-calcified plaques were positively associated with male gender, age, dyslipidaemia and diabetes mellitus.

    CONCLUSION: The higher MI rates in Malays and Indians in Singapore cannot be explained by any difference in CAC or non-calcified plaque. More research with prospective follow-up of larger patient populations is necessary to establish if ethnic-specific calibration of CAC measures is needed to adjust for differences among ethnic groups.

  14. Chong SE, Mohd Nikman A, Saedah A, Wan Mohd Nazaruddin WH, Kueh YC, Lim JA, et al.
    Br J Anaesth, 2017 05 01;118(5):799-801.
    PMID: 28510752 DOI: 10.1093/bja/aex108
  15. Chong WH, Leong SS, Lim J
    Electrophoresis, 2021 11;42(21-22):2303-2328.
    PMID: 34213767 DOI: 10.1002/elps.202100081
    Combining both device and particle designs are the essential concepts to be considered in magnetophoretic system development. Researcher efforts are often dedicated to only one of these design aspects and neglecting the interplay between them. Herein, to bring out importance of the idea of integration between device and particle, we reviewed the working principle of magnetophoretic system (includes both device and particle design concepts). Since, the magnetophoretic force is influenced by both field gradient and magnetization volume, hence, accurate prediction of the magnetophoretic force is relying on the availability of information on both parameters. In device design, we focus on the different strategies used to create localized high-field gradient. For particle design, we emphasize on the scaling between hydrodynamic size and magnetization volume. Moreover, we also briefly discussed the importance of magnetoshape anisotropy related to particle design aspect of magnetophoretic systems. Next, we illustrated the need for integration between device and particle design using microscale applications of magnetophoretic systems, include magnetic tweezers and microfluidic systems, as our working example. On the basis of our discussion, we highlighted several promising examples of microscale magnetophoretic systems which greatly utilized the interplay between device and particle design. Further, we concluded the review with several factors that possibly resulted in the lack of research efforts related to device and particle design integration.
  16. Chong WH, Chan DJC, Liu CZ, Lim J
    Electrophoresis, 2024 Mar;45(5-6):357-368.
    PMID: 38044267 DOI: 10.1002/elps.202300042
    The spatiotemporal accuracy of microscale magnetophoresis has improved significantly over the course of several decades of development. However, most of the studies so far were using magnetic microbead composed of nanosphere particle for magnetophoretic actuation purpose. Here, we developed an in-house method for magnetic sample analysis called quadrupole magnetic steering control (QMSC). QMSC was used to study the magnetophoretic behavior of polystyrene microbeads decorated with iron oxide nanospheres-coated polystyrene microbeads (IONSs-PS) and iron oxide nanorods-coated polystyrene microbeads (IONRs-PS) under the influence of a quadrupole low field gradient. During a 4-s QMSC experiment, the IONSs-PS and IONRs-PS were navigated to perform 180° flip and 90° turn formations, and their kinematic results (2 s before and 2 s after the flip/turn) were measured and compared. The results showed that the IONRs-PS suffered from significant kinematic disproportion, translating a highly uneven amount of kinetic energy from the same magnitude of magnetic control. Combining the kinematic analysis, transmission electron microscopy micrographs, and vibrating sample magnetometry measurements, it was found that the IONRs-PS experienced higher fluid drag force and had lower consistency than the IONSs-PS due to its extensive open fractal nanorod structure on the bead surface and uneven magnetization, which was attributed to its ferrimagnetic nature.
  17. Chye JK, Lim CT, Ng KB, Lim JM, George R, Lam SK
    Clin Infect Dis, 1997 Dec;25(6):1374-7.
    PMID: 9431381
    Dengue, an important mosquito-borne flavivirus infection, is endemic in Southeast Asia. We describe two mothers who had acute dengue 4 and 8 days before the births of their infants. One mother had worsening of her proteinuric pregnancy-induced hypertension, liver dysfunction, and coagulopathy and required multiple transfusions of whole blood, platelets, and fresh frozen plasma. Her male infant was ill at birth, developed respiratory distress and a large uncontrollable left intracerebral hemorrhage, and died of multiorgan failure on day 6 of life. Dengue virus type 2 was isolated from the infant's blood, and IgM antibody specific to dengue virus was detected in the mother's blood. The second mother had a milder clinical course; she gave birth to a female infant who was thrombocytopenic at birth and had an uneventful hospitalization. Dengue virus type 2 was recovered from the mother's blood, and IgM antibody specific to dengue virus was detected in the infant's blood. This report highlights not only the apparently rare occurrence of vertical transmission of dengue virus in humans but also the potential risk of death for infected neonates.
  18. Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, et al.
    Nat Genet, 2021 Jan;53(1):65-75.
    PMID: 33398198 DOI: 10.1038/s41588-020-00748-0
    Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
  19. Corduff N, Chao YY, Lam SC, Lim J, Lim TS, Lohia K, et al.
    J Clin Aesthet Dermatol, 2020 Apr;13(4):23-34.
    PMID: 33144908
    OBJECTIVE: A group of established aesthetic physicians sought to develop treatment guidelines for assessing Asian face morphologies that reflect accurate and current beauty standards across Asia. DESIGN: Physicians completed surveys, debated, and voted on their clinical strategies and developed an alternative simplified visual tool of assessment (SVAT) that discerns between country variations in genetic and ideal morphotypes. SETTING: Electronic and paper surveys were followed by consensus debates and voting. PARTICIPANTS: Established aesthetic physicians practicing regularly on Asian patients. MEAUSUREMENTS: A clinically applicable SVAT was developed, which considered facial index, mid-face projection, upper and lower face shape, submalar contour, nose length and dorsal height, eye shape and brow shape, proportion of lips-to-lower face and ratio of upper-to-lower lip, and chin shape. RESULTS: For facial shape change, physicians always assessed the horizontal thirds, facial symmetry, and lip-chin complex profile, and also analyzed overall face shapes and Ogee curves. Criteria for creating oval-shaped faces was also defined and included treating indications, such as loss of angularity and bilateral masseter muscle hypertrophy, narrow jawlines, and longer and wider foreheads. Critical differences and similarities in country-specific aesthetic preferences, treatment requests, and considerations or strategies were uncovered, including the inadequacy of assessing overall peripheral facial shapes. CONCLUSION: This consensus establishes the assessment and treatment criteria for achieving ideal shapes for Asian patients. Specific descriptors are affected by variations; therefore, we present the visual criteria for Asian facial morphotypes. We hope that physicians new to treating Asian patients can use this clinical information to improve their practice.
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