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  1. Talal M, Zaidan AA, Zaidan BB, Albahri AS, Alamoodi AH, Albahri OS, et al.
    J Med Syst, 2019 Jan 15;43(3):42.
    PMID: 30648217 DOI: 10.1007/s10916-019-1158-z
    The Internet of Things (IoT) has been identified in various applications across different domains, such as in the healthcare sector. IoT has also been recognised for its revolution in reshaping modern healthcare with aspiring wide range prospects, including economical, technological and social. This study aims to establish IoT-based smart home security solutions for real-time health monitoring technologies in telemedicine architecture. A multilayer taxonomy is driven and conducted in this study. In the first layer, a comprehensive analysis on telemedicine, which focuses on the client and server sides, shows that other studies associated with IoT-based smart home applications have several limitations that remain unaddressed. Particularly, remote patient monitoring in healthcare applications presents various facilities and benefits by adopting IoT-based smart home technologies without compromising the security requirements and potentially large number of risks. An extensive search is conducted to identify articles that handle these issues, related applications are comprehensively reviewed and a coherent taxonomy for these articles is established. A total number of (n = 3064) are gathered between 2007 and 2017 for most reliable databases, such as ScienceDirect, Web of Science and Institute of Electrical and Electronic Engineer Xplore databases. Then, the articles based on IoT studies that are associated with telemedicine applications are filtered. Nine articles are selected and classified into two categories. The first category, which accounts for 22.22% (n = 2/9), includes surveys on telemedicine articles and their applications. The second category, which accounts for 77.78% (n = 7/9), includes articles on the client and server sides of telemedicine architecture. The collected studies reveal the essential requirement in constructing another taxonomy layer and review IoT-based smart home security studies. Therefore, IoT-based smart home security features are introduced and analysed in the second layer. The security of smart home design based on IoT applications is an aspect that represents a crucial matter for general occupants of smart homes, in which studies are required to provide a better solution with patient security, privacy protection and security of users' entities from being stolen or compromised. Innovative technologies have dispersed limitations related to this matter. The existing gaps and trends in this area should be investigated to provide valuable visions for technical environments and researchers. Thus, 67 articles are obtained in the second layer of our taxonomy and are classified into six categories. In the first category, 25.37% (n = 17/67) of the articles focus on architecture design. In the second category, 17.91% (n = 12/67) includes security analysis articles that investigate the research status in the security area of IoT-based smart home applications. In the third category, 10.44% (n = 7/67) includes articles about security schemes. In the fourth category, 17.91% (n = 12/67) comprises security examination. In the fifth category, 13.43% (n = 9/67) analyses security protocols. In the final category, 14.92% (n = 10/67) analyses the security framework. Then, the identified basic characteristics of this emerging field are presented and provided in the following aspects. Open challenges experienced on the development of IoT-based smart home security are addressed to be adopted fully in telemedicine applications. Then, the requirements are provided to increase researcher's interest in this study area. On this basis, a number of recommendations for different parties are described to provide insights on the next steps that should be considered to enhance the security of smart homes based on IoT. A map matching for both taxonomies is developed in this study to determine the novel risks and benefits of IoT-based smart home security for real-time remote health monitoring within client and server sides in telemedicine applications.
  2. Kwan MK, Chiu CK, Goh SH, Ng SJ, Tan PH, Chian XH, et al.
    Clin Spine Surg, 2019 Jul;32(6):256-262.
    PMID: 30640749 DOI: 10.1097/BSD.0000000000000769
    STUDY DESIGN: Retrospective study.

    OBJECTIVE: This study looked into whether crossbar can reliably measure Upper Instrumend Vertebra (UIV) tilt angle intraoperatively and accurately predict the UIV tilt angle postoperatively and at final follow-up.

    SUMMARY OF BACKGROUND DATA: Postoperative shoulder imbalance is a common cause of poor cosmetic appearance leading to patient dissatisfaction. There were no reports describing the technique or method in measuring the UIV tilt angle intraoperatively. Therefore, this study was designed to look into the reliability and accuracy of the usage of intraoperative crossbar in measuring the UIV tilt angle intraoperatively.

    METHODS: Lenke 1 and 2 Adolescent Idiopathic Scoliosis patients who underwent instrumented Posterior Spinal Fusion using pedicle screw constructs with minimum follow-up of 24 months were recruited for this study. After surgical correction, intraoperative UIV tilt angle was measured using a crossbar. Immediate postoperative and final follow up UIV tilt angle was measured on the standing anteroposterior radiographs.

    RESULTS: A total of 100 patients were included into this study. The reliability of the intraoperative crossbar to measure the optimal UIV tilt angle intraoperatively was determined by repeated measurements by assessors and measurement by different assessors. We found that the intra observer and inter observer reliability was very good with intraclass correlation coefficient values of >0.9. The accuracy of the intraoperative crossbar to measure the optimal UIV tilt angle intraoperatively was determined by comparing this measurement with the postoperative UIV tilt angle. We found that there was no significant difference (P>0.05) between intraoperative, immediate postoperative, and follow-up UIV tilt angle.

    CONCLUSIONS: The crossbar can be used to measure the intraoperative UIV tilt angle consistently and was able to predict the postoperative UIV tilt angle. It was a cheap, simple, reliable, and accurate instrument to measure the intraoperative UIV tilt angle.

  3. Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, et al.
    PLoS One, 2019;14(1):e0210869.
    PMID: 30677071 DOI: 10.1371/journal.pone.0210869
    Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC50 = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC50 of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.
  4. Fun WH, Sararaks S, Tan EH, Tang KF, Chong DWQ, Low LL, et al.
    BMC Health Serv Res, 2019 Apr 24;19(1):248.
    PMID: 31018843 DOI: 10.1186/s12913-019-4072-7
    BACKGROUND: Health Research Priority Setting (HRPS) in the Ministry of Health (MOH) Malaysia was initiated more than a decade ago to drive effort toward research for informed decision and policy-making. This study assessed the impact of funded prioritised research and identified research gaps to inform future priority setting initiatives for universal access and quality healthcare in Malaysia.

    METHODS: Research impact of universal access and quality healthcare projects funded by the National Institutes of Health Malaysia were assessed based on the modified Payback Framework, addressing categories of informing policy, knowledge production, and benefits to health and health sector. For the HRPS process, the Child Health and Nutrition Research Initiative methodology was adapted and adopted, with the incorporation of stakeholder values using weights and monetary allocation survey. Workshop discussions and interviews with stakeholders and research groups were conducted to identify research gaps, with the use of conceptual frameworks to guide the search.

    RESULTS: Seventeen ongoing and 50 completed projects were identified for research funding impact analysis. Overall, research fund allocation differed from stakeholders' expectation. For research impact, 48 out of 50 completed projects (96.0%) contributed to some form of policy-making efforts. Almost all completed projects resulted in outputs that contributed to knowledge production and were expected to lead to health and health sector benefits. The HRPS process led to the identification of research priority areas that stemmed from ongoing and new issues identified for universal access and quality healthcare.

    CONCLUSION: The concerted efforts of evaluation of research funding impact, prioritisation, dissemination and policy-maker involvement were valuable for optimal health research resource utilisation in a resource constrained developing country. Embedding impact evaluation into a priority setting process and funding research based on national needs could facilitate health research investment to reach its potential.

  5. Tan MP, Ho YY, Chin AV, Saedon N, Abidin IZ, Chee KH, et al.
    Clin Auton Res, 2020 04;30(2):121-128.
    PMID: 31079241 DOI: 10.1007/s10286-019-00610-2
    PURPOSE: To determine the lifetime cumulative incidence of syncope, potential ethnic differences and factors associated with syncope using the Malaysian elders longitudinal research (MELoR) study first wave dataset.

    METHODS: The MELoR study recruited community-dwelling adults aged 55 years and over, selected through stratified random sampling from three parliamentary constituencies. The baseline data collected during the first wave was obtained through face-to-face interviews in participants' homes using computer-assisted questionnaires. During their baseline assessments, participants were asked whether they had ever experienced a blackout in their lifetime and if they had experienced a blackout in the preceding 12 months.

    RESULTS: Information on blackouts and ethnicity were available for 1530 participants. The weight-adjusted lifetime cumulative incidence of syncope for the overall population aged 55 years and above was 27.7%. The estimated lifetime cumulative incidence according to ethnic groups was 34.6% for Malays, 27.8% for Indians and 23.7% for Chinese. The estimated 12-month incidence of syncope was 6.1% overall, equating to 11.7% for Malays, 8.7 % for Indians and 2.3% for Chinese. Both Malay [odds ratio (OR) 1.46; 95% confidence interval (CI) 1.10-1.95 and OR 3.62, 95% CI 1.96-6.68] and Indian (OR 1.34; 95% CI 1.01-1.80 and OR 3.31, 1.78-6.15) ethnicities were independently associated with lifetime and 12-month cumulative incidence of syncope, respectively, together with falls, dizziness and myocardial infarction.

    CONCLUSION: Ethnic differences exist for lifetime cumulative incidence of syncope in community-dwelling individuals aged 55 years and over in an urban area in Southeast Asia. Future studies should now seek to determine potential genetic, cultural and lifestyle differences which may predispose to syncope.

  6. Berry C, Michelson D, Othman E, Tan JC, Gee B, Hodgekins J, et al.
    Early intervention in psychiatry, 2020 02;14(1):115-123.
    PMID: 31111672 DOI: 10.1111/eip.12832
    AIM: Mental health problems are prevalent among young people in Malaysia yet access to specialist mental health care is extremely limited. More context-specific research is needed to understand the factors affecting help-seeking in youth, when mental health problems typically have first onset. We aimed to explore the attitudes of vulnerable young Malaysians regarding mental health problems including unusual psychological experiences, help-seeking and mental health treatment.

    METHODS: In the present study, nine young people (aged 16-23 years) from low-income backgrounds participated in a semi-structured interview about their perspectives on mental health problems, unusual psychological experiences and help-seeking.

    RESULTS: Four themes were developed using thematic analysis. "Is it that they [have] family problems?" reflected participants' explanatory models of mental health problems. "Maybe in Malaysia" was concerned with perceptions of Malaysian culture as both encouraging of open sharing of problems and experiences, but also potentially stigmatizing. "You have to ask for help" emphasized the importance of mental health help-seeking despite potential stigma. "It depends on the person" addressed the challenges of engaging with psychological therapy.

    CONCLUSIONS: We conclude that young people in Malaysia may hold compassionate, non-stigmatizing views towards people experiencing mental health problems and a desire to increase their knowledge and understandings. Yet societal stigma is a perceived reputational risk that may affect mental health problem disclosure and help-seeking. We suggest that efforts to improve mental health literacy would be valued by young Malaysians and could support reduced stigma and earlier help-seeking.

  7. Kemp Z, Turnbull A, Yost S, Seal S, Mahamdallie S, Poyastro-Pearson E, et al.
    JAMA Netw Open, 2019 05 03;2(5):e194428.
    PMID: 31125106 DOI: 10.1001/jamanetworkopen.2019.4428
    Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers.

    Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer.

    Design, Setting, and Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017.

    Main Outcomes and Measures: Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes.

    Results: Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion-breast cancer plus a parent, sibling, or child with any of the other criteria-can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process.

    Conclusions and Relevance: This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing.

  8. Radzi Ah M, S Tan S, Mohamed R, Jaya F, K S, C Aun A, et al.
    Euroasian J Hepatogastroenterol, 2019 02 01;8(2):101-107.
    PMID: 30828549 DOI: 10.5005/jp-journals-10018-1273
    Background: Two major challenges in implementing budget-constrained Hepatitis screening and treatment campaign in Malaysia are the availability of low-cost point of care tests (POCT) and nucleic acid tests (NAT) for hepatitis C virus ribonucleic acid (HCV RNA) and hepatitis B virus dioxyribo nucleic acid (HBV DNA). We evaluated the performance of these tests in this study.

    Methods: We conducted a cross-sectional study to evaluate the diagnostic performance of four POCT brands at 12 sites in Malaysia. We assessed the sensitivity and specificity of the POCTs for the detection of HBsAg and anti-HCV in a finger-stick capillary or venepuncture whole-blood samples compared with test results from lab-based enzyme immunoassay (EIA) or chemi-luminescence immunoassay (CLIA) assay as the reference standard. We also conducted a cross-sectional study on 30 to 139 serum specimen panel to evaluate the diagnostic performance of a low-cost in-house Applied Biosystem®TaqMan real-time polymerase chain reaction (PCR) assay (ABS) for the detection of HCV RNA and HBV DNA, compare with Roche Cobas® Ampliprep/TaqMan assay (COBAS).

    Results: Between March and December 2017, we enroll 295 participants for the evaluation of POCT for HBsAg and another 307 participants for POCT anti-HCV evaluation. Three of the four POCT brands dropped out of evaluation early on account of sub-optimal sensitivity. The sensitivity of the remaining POCT for HBsAg was 95.2%and specificity 100%, while the POCT for anti-HCV has a sensitivity of 98.1% and specificity 100%.Hepatitis B virus dioxyribo nucleic acid and HCV RNA concentrations detected by the ABS were systematically higher than those measured by COBAS (mean bias +0.10 and +0.17 log10 IU/mL respectively). The 95% limits of agreement between the two assays are -1.28 to 1.47 log10 IU/mL for HBV DNA and -0.41 to 0.75 log10 IU/mL for HCV RNA.

    Conclusion: We found adequate evidence for the diagnostic validity of a low-cost POCT for anti-HCV and HBsAg, as well as for an in-house nucleic acid tests (NAT), to provide support for their broader use in our Hepatitis screening and treatment campaign.

    Abbreviations: ABS: Applied Biosystem®TaqMan real-time PCR assay, CI: Confidence interval, CLD: Chronic liver disease, CLIA: Chemi-luminescence immunoassay, COBAS: Roche Cobas® Ampliprep/ TaqMan assay, DAA: Direct Acting Anti-Viral drugs, EIA: Enzyme immunoassay, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HFPM: Hepatitis Free Pahang Malaysia, LOA: Limits of agreement, LOD: Limit of detection, MOH: Ministry of Health, Malaysia, NAT: Nucleic Acid Tests, POCT: Point of Care Tests, SD: Standard deviation, WHO: World Health OrganizationHow to cite this article: Radzi AHM, Tan SS, Mohamed R, Jaya F, Senamjit K, Aun AC, Kutty GA, Wong HS, Abdullah R, Seman MR, Mahtab MA, Morad Z, Lim TO. Hepatitis Screening and Treatment Campaign in Malaysia-Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C. Euroasian J Hepatogastroenterol, 2018;8(2):101-107.

  9. Tan CW, Huan Hor CH, Kwek SS, Tee HK, Sam IC, Goh ELK, et al.
    Emerg Microbes Infect, 2019;8(1):426-437.
    PMID: 30898036 DOI: 10.1080/22221751.2019.1590130
    The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis.
  10. Gan CP, Sam KK, Yee PS, Zainal NS, Lee BKB, Abdul Rahman ZA, et al.
    Cell Oncol (Dordr), 2019 Aug;42(4):477-490.
    PMID: 30949979 DOI: 10.1007/s13402-019-00437-z
    PURPOSE: Oral squamous cell carcinoma (OSCC) is a challenging disease to treat. Up to 50% of OSCC patients with advanced disease develop recurrences. Elucidation of key molecular mechanisms underlying OSCC development may provide opportunities to target specific genes and, thus, to improve patient survival. In this study, we examined the expression and functional role of interferon transmembrane protein 3 (IFITM3) in OSCC development.

    METHODS: The expression of IFITM3 in OSCC and normal oral mucosal tissues was assessed by qRT-PCR and immunohistochemistry. The role of IFITM3 in driving OSCC cell proliferation and survival was examined using siRNA-mediated gene knockdown, and the role of IFITM3 in driving cell cycle regulators was examined using Western blotting.

    RESULTS: We found that IFITM3 is overexpressed in more than 79% of primary OSCCs. We also found that IFITM3 knockdown led to impaired OSCC cell growth through inhibition of cell proliferation, induction of cell cycle arrest, senescence and apoptosis. In addition, we found that IFITM3 knockdown led to reduced expressions of CCND1 and CDK4 and reduced RB phosphorylation, leading to inhibition of OSCC cell growth. This information may be instrumental for the design of novel targeted therapeutic strategies.

    CONCLUSIONS: From our data we conclude that IFITM3 is overexpressed in OSCC and may regulate the CCND1-CDK4/6-pRB axis to mediate OSCC cell growth.

  11. Song DSS, Leong SW, Ng KW, Abas F, Shaari K, Leong CO, et al.
    SLAS Discov, 2019 06;24(5):548-562.
    PMID: 30897027 DOI: 10.1177/2472555219831405
    DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.
  12. Mohan A, Munusamy C, Tan YC, Muthuvelu S, Hashim R, Chien SL, et al.
    BMC Infect Dis, 2019 Apr 18;19(1):330.
    PMID: 30999894 DOI: 10.1186/s12879-019-3963-x
    BACKGROUND: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited.

    METHODS: A retrospective study identifying all children aged

  13. Tan KH, Chen YW, Van CN, Wang H, Chen JW, Lim FS, et al.
    ACS Appl Mater Interfaces, 2019 Jan 09;11(1):1655-1664.
    PMID: 30561192 DOI: 10.1021/acsami.8b17758
    The ability of band offsets at multiferroic/metal and multiferroic/electrolyte interfaces in controlling charge transfer and thus altering the photoactivity performance has sparked significant attention in solar energy conversion applications. Here, we demonstrate that the band offsets of the two interfaces play the key role in determining charge transport direction in a downward self-polarized BFO film. Electrons tend to move to BFO/electrolyte interface for water reduction. Our experimental and first-principle calculations reveal that the presence of neodymium (Nd) dopants in BFO enhances the photoelectrochemical performance by reduction of the local electron-hole pair recombination sites and modulation of the band gap to improve the visible light absorption. This opens a promising route to the heterostructure design by modulating the band gap to promote efficient charge transfer.
  14. Rajendra Acharya U, Meiburger KM, Wei Koh JE, Vicnesh J, Ciaccio EJ, Shu Lih O, et al.
    Artif Intell Med, 2019 09;100:101724.
    PMID: 31607348 DOI: 10.1016/j.artmed.2019.101724
    Cardiovascular diseases are the primary cause of death globally. These are often associated with atherosclerosis. This inflammation process triggers important variations in the coronary arteries (CA) and can lead to coronary artery disease (CAD). The presence of CA calcification (CAC) has recently been shown to be a strong predictor of CAD. In this clinical setting, computed tomography angiography (CTA) has begun to play a crucial role as a non-intrusive imaging method to characterize and study CA plaques. Herein, we describe an automated algorithm to classify plaque as either normal, calcified, or non-calcified using 2646 CTA images acquired from 73 patients. The automated technique is based on various features that are extracted from the Gabor transform of the acquired CTA images. Specifically, seven features are extracted from the Gabor coefficients : energy, and Kapur, Max, Rényi, Shannon, Vajda, and Yager entropies. The features were then ordered based on the F-value and input to numerous classification methods to achieve the best classification accuracy with the least number of features. Moreover, two well-known feature reduction techniques were employed, and the features acquired were also ranked according to F-value and input to several classifiers. The best classification results were obtained using all computed features without the employment of feature reduction, using a probabilistic neural network. An accuracy, positive predictive value, sensitivity, and specificity of 89.09%, 91.70%, 91.83% and 83.70% was obtained, respectively. Based on these results, it is evident that the technique can be helpful in the automated classification of plaques present in CTA images, and may become an important tool to reduce procedural costs and patient radiation dose. This could also aid clinicians in plaque diagnostics.
  15. Too CL, Tan LK, Heselynn H, Nor-Shuhaila S, Eashwary M, Wahinuddin S, et al.
    Hum Immunol, 2019 Nov;80(11):906-907.
    PMID: 31558331 DOI: 10.1016/j.humimm.2019.09.005
    A total of 194 Southeast Asia Chinese from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, the HLA-B, HLA-DRB1 and HLA-DQB1 were in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from HWEP in HLA-A (p 
  16. Hamzah N, Narayanan V, Ramli N, Mustapha NA, Mohammad Tahir NA, Tan LK, et al.
    BMJ Open, 2019 09 18;9(9):e028711.
    PMID: 31537559 DOI: 10.1136/bmjopen-2018-028711
    OBJECTIVES: To measure the clinical, structural and functional changes of an individualised structured cognitive rehabilitation in mild traumatic brain injury (mTBI) population.

    SETTING: A single centre study, Malaysia.

    PARTICIPANTS: Adults aged between 18 and 60 years with mTBI as a result of road traffic accident, with no previous history of head trauma, minimum of 9 years education and abnormal cognition at 3 months will be included. The exclusion criteria include pre-existing chronic illness or neurological/psychiatric condition, long-term medication that affects cognitive/psychological status, clinical evidence of substance intoxication at the time of injury and major polytrauma. Based on multiple estimated calculations, the minimum intended sample size is 50 participants (Cohen's d effect size=0.35; alpha level of 0.05; 85% power to detect statistical significance; 40% attrition rate).

    INTERVENTIONS: Intervention group will receive individualised structured cognitive rehabilitation. Control group will receive the best patient-centred care for attention disorders. Therapy frequency for both groups will be 1 hour per week for 12 weeks.

    OUTCOME MEASURES: Primary: Neuropsychological Assessment Battery-Screening Module (S-NAB) scores. Secondary: Diffusion Tensor Imaging (DTI) parameters and Goal Attainment Scaling score (GAS).

    RESULTS: Results will include descriptive statistics of population demographics, CogniPlus cognitive program and metacognitive strategies. The effect of intervention will be the effect size of S-NAB scores and mean GAS T scores. DTI parameters will be compared between groups via repeated measure analysis. Correlation analysis of outcome measures will be calculated using Pearson's correlation coefficient.

    CONCLUSION: This is a complex clinical intervention with multiple outcome measures to provide a comprehensive evidence-based treatment model.

    ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Ethics Committee UMMC (MREC ID NO: 2016928-4293). The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.

    TRIAL REGISTRATION NUMBER: NCT03237676.

  17. Mohamed Amin Z, Che Ani MA, Tan SW, Yeap SK, Alitheen NB, Syed Najmuddin SUF, et al.
    Sci Rep, 2019 Sep 30;9(1):13999.
    PMID: 31570732 DOI: 10.1038/s41598-019-50222-z
    The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 29. Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine.
  18. Chiu CK, Chan CYW, Tan PH, Goh SH, Ng SJ, Chian XH, et al.
    Spine (Phila Pa 1976), 2020 Mar 15;45(6):E319-E328.
    PMID: 31593064 DOI: 10.1097/BRS.0000000000003275
    STUDY DESIGN: Retrospective study.

    OBJECTIVE: The primary objective of this study was to assess the conformity of the radiological neck and shoulder balance parameters throughout a follow-up period of more than 2 years.

    SUMMARY OF BACKGROUND DATA: Postoperative shoulder and neck imbalance are undesirable features among Adolescent Idiopathic Scoliosis patients who underwent Posterior Spinal Fusion. There are many clinical and radiological parameters used to assess this clinical outcome. However, we do not know whether these radiological parameters conform throughout the entire follow-up period.

    METHODS: This was a retrospective study done in a single academic institution. Inclusion criteria were patients with scoliosis who underwent posterior instrumented spinal fusion with pedicle screw fixation and attended all scheduled follow-ups for at least 24 months postoperatively. Radiological shoulder parameters were measured from both preoperative antero-posterior and postoperative antero-posterior radiographs. Lateral shoulder parameters were: Radiographic Shoulder Height, Clavicle Angle (Cla-A), Clavicle-Rib Intersection Difference, and Coracoid Height Difference. Medial shoulder and neck parameters were: T1 Tilt and Cervical Axis (CA).

    RESULTS: The radiographs of 50 patients who had surgery done from November 2013 to November 2015 were analyzed. Mean age of this cohort was 16.3 ± 7.0 years. There were 38 (76%) female patients and 12 (24%) male patients. Mean final follow-up was 38.6 ± 5.8 months. When conformity assessment of the radiological parameter using the interclass coefficient correlation was done, we found that all parameters had significant correlation (P 

  19. Abdul Manap AS, Wei Tan AC, Leong WH, Yin Chia AY, Vijayabalan S, Arya A, et al.
    Front Aging Neurosci, 2019;11:206.
    PMID: 31507403 DOI: 10.3389/fnagi.2019.00206
    Hallmarks of Alzheimer's disease (AD) pathology include acetylcholine (ACh) deficiency and plaque deposition. Emerging studies suggest that acetylcholinesterase (AChE) may interact with amyloid β (Aβ) to promote aggregation of insoluble Aβ plaques in brains of patients. Current therapeutic options available for AD patients, such as AChE inhibitors, provide only symptomatic relief. In this study, we screened four natural compounds believed to harbor cognitive benefits-curcumin, piperine, bacoside A, and chebulinic acid. In the first section, preliminary screening through computational molecular docking simulations gauged the suitability of the compounds as novel AChE inhibitors. From here, only compounds that met the in silico selection criteria were selected for the second section through in vitro investigations, including AChE enzyme inhibition assay, 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTT) assay, Thioflavin T (ThT) assay, and biochemical analysis via a neuronal cell line model. Of the four compounds screened, only curcumin (-9.6 kcal/mol) and piperine (-10.5 kcal/mol) showed favorable binding affinities and interactions towards AChE and were hence selected. In vitro AChE inhibition demonstrated that combination of curcumin and piperine showed greater AChE inhibition with an IC50 of 62.81 ± 0.01 μg/ml as compared to individual compounds, i.e., IC50 of curcumin at 134.5 ± 0.06 μg/ml and IC50 of piperine at 76.6 ± 0.08 μg/ml. In the SH-SY5Y cell model, this combination preserved cell viability up to 85%, indicating that the compounds protect against Aβ-induced neuronal damage (p < 0.01). Interestingly, our results also showed that curcumin and piperine achieved a synergistic effect at 35 μM with an synergism quotient (SQ) value of 1.824. Synergistic behavior indicates that the combination of these two compounds at lower concentrations may provide a better outcome than singularly used for Aβ proteins. Combined curcumin and piperine managed to inhibit aggregation (reduced ThT intensity at 0.432 a.u.; p < 0.01) as well as disaggregation (reduced ThT intensity at 0.532 a.u.; p < 0.01) of fibrillar Aβ42. Furthermore, combined curcumin and piperine reversed the Aβ-induced up-regulation of neuronal oxidative stress (p < 0.01). In conclusion, curcumin and piperine demonstrated promising neuroprotective effects, whereas bacoside A and chebulinic acid may not be suitable lead compounds. These results are hoped to advance the field of natural products research as potentially therapeutic and curative AD agents.
  20. Woon FC, Chin YS, Ismail IH, Batterham M, Abdul Latiff AH, Gan WY, et al.
    PLoS One, 2019;14(6):e0216439.
    PMID: 31233513 DOI: 10.1371/journal.pone.0216439
    BACKGROUND: Despite perennial sunshine, vitamin D deficiency is prevalent among Malaysians especially pregnant women. This study determines the vitamin D status and its associated factors among third trimester pregnant women attending government health clinics in Selangor and Kuala Lumpur, Malaysia.

    METHODS: Information on socio-demographic characteristics, obstetrical history, and sun exposure were obtained through face-to-face interviews. Vitamin D intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). Serum 25-hydroxyvitamin D concentration was measured and classified as deficient (< 30 nmol/L), insufficient (30-50 nmol/L), and sufficient (≥ 50 nmol/L).

    RESULTS: Of the 535 pregnant women recruited, 42.6% were vitamin D deficient. They consumed an average of 8.7 ± 6.7 μg of vitamin D daily. A total of 80.4% of the vitamin D were obtained from the food sources, while 19.6% were from dietary supplements. Fish and fish products showed the highest contribution to vitamin D intake (35.8%). The multivariable generalized linear mixed models, with clinic as a random effect, indicates that higher intake of vitamin D is associated with lower odds of vitamin D deficiency among pregnant women (OR = 0.96; 95% CI = 0.93-0.99). The odds of having vitamin D deficiency was reduced by 87% in non-Malays (OR = 0.14; 95% CI = 0.05-0.41) compared to Malays. No associations were found between age, educational level, monthly household income, work status, gravidity, parity, pre-pregnancy body mass index, total hours of sun exposure, total percentage of body surface area, and sun exposure index per day with vitamin D deficiency.

    CONCLUSION: Vitamin D deficiency is prevalent among Malaysian pregnant women. Considering the possible adverse obstetric and fetal outcomes of vitamin D deficiency during pregnancy, future nutrition education should emphasise on vitamin D-fortified foods consumption among pregnant women by taking into consideration ethnic differences.
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