Browse publications by year: 2021

  1. Low SC, Md Sari NA, Tan CY, Ahmad-Annuar A, Wong KT, Law WC, et al.
    Neuromuscul Disord, 2021 07;31(7):642-650.
    PMID: 34059423 DOI: 10.1016/j.nmd.2021.03.008
    We report the clinical and genetic characteristics of hereditary transthyretin amyloidosis in the multi-ethnic Malaysian population. Subjects with genetically confirmed transthyretin amyloidosis seen between 2001 till August 2020 were included. There were 30 patients and 14 asymptomatic carriers, of which 26 (59.1%) were men. The majority (86.7%) were ethnic Chinese while two (6.7%) each were Malay and Sri Lankan Tamil ethnicity respectively. Among patients, mean age of symptom-onset was 55.9 ± 9.8 years with mean duration from symptom-onset to diagnosis of 3.2 ± 2.5 years. Common presenting symptoms were sensory symptoms of upper limbs (43.3%), symmetric sensory symptoms of both lower limbs (16.7%) and autonomic symptoms (16.7%). Nerve conduction studies showed sensorimotor polyneuropathy in 25 (83.3%) patients (22, axonal). Abnormal echocardiograms were seen in 24 (80%) patients, although 15 were asymptomatic. Of six different TTR mutations found, Ala97Ser was the commonest, and found exclusively in 84.6% of Chinese patients. Other mutations among Chinese patients were Val30Met, Ala25Thr and Asp39Val. Our Malay and Tamil patients had Glu54Lys and Gly47Val mutations respectively. In conclusion, TTR Ala97Ser is the commonest mutation among ethnic Chinese Malaysians which presented with late-onset progressive sensorimotor polyneuropathy, autonomic dysfunction and subclinical cardiac involvement.
  2. Ohn MH, Ohn KM
    BMJ Case Rep, 2021 May 31;14(5).
    PMID: 34059541 DOI: 10.1136/bcr-2020-241408
    Poland's syndrome (PS) is a rare developmental anomaly that can manifest mild (pectoralis muscles involvement) to severe deformities (rib hypoplasia and hand deformities). We report a case of 69-year-old man who presented to the emergency department with a traumatic chest injury after a fall. It was initially thought to have a significant chest injury as the trauma survey revealed a palpable defect and tenderness in the right anterior chest wall. There was also a symbrachydactyly deformity in the right hand. CT of the chest showed lack of right pectoralis muscles, which were consistent with PS. This case highlights the importance of gathering detail history in adult trauma patients such as congenital disorder especially in the presence of bony deformity. With possibilities of several traumatic conditions in trauma patients eliminated, one can expand the non-traumatic differential, keeping in mind the possibility of a congenital disorder that can mimic traumatic chest injury.
    MeSH terms: Adult; Aged; Humans; Male; Syndactyly*; Thorax
  3. Ng DC, Chin L, Choo PPL, Paramasivam U
    BMJ Case Rep, 2021 May 31;14(5).
    PMID: 34059550 DOI: 10.1136/bcr-2021-243783
    We report a case of COVID-19 in a 29-week preterm infant. This child is the youngest reported case of SARS-CoV-2 infection in Malaysia, and to the best of our knowledge, one of the youngest documented cases of established vertical transmission of SARS-CoV-2 reported in literature. Our report highlights the clinical course, timelines of viral shedding by real-time reverse transcription-PCR and antibody seroconversion in a premature infant infected with SARS-CoV-2. In addition, we discuss the challenges faced in managing a preterm infant infected with SARS-CoV-2 and the knowledge gaps that need to be explored.
    MeSH terms: Child; Humans; Infant, Newborn; Infant, Premature; Malaysia; Real-Time Polymerase Chain Reaction
  4. Tan TL, Kang CW, Ooi KS, Tan ST, Ahmad NS, Nasuruddin DN, et al.
    Sci Rep, 2021 05 31;11(1):11369.
    PMID: 34059757 DOI: 10.1038/s41598-021-90894-0
    Early bacterial infection (BI) identification in resource-limiting Emergency Departments (ED) is challenging, especially in low- and middle-income counties (LMIC). Misdiagnosis predisposes to antibiotic overuse and propagates antimicrobial resistance. This study evaluates new emerging biomarkers, secretory phospholipase A2 group IIA (sPLA2-IIA) and compares with other biomarkers on their performance characteristic of BI detection in Malaysia, an LMIC. A prospective cohort study was conducted involving 151 consecutive patients admitted to the ED. A single measurement was taken upon patient arrival in ED and was analysed for serum levels of sPLA2-IIA, high-sensitive C-reactive protein (CRP), procalcitonin (PCT), neutrophil percentage (N%), and lactate. All biomarkers' performance was compared for the outcomes using area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. The performance of sPLA2-IIA (AUROC 0.93 [95% CI: 0.89-0.97]; Sn 80% [95% CI: 72-87]; Sp 94% [95% CI: 81-89]) was the highest among all. It was comparable with high-sensitive CRP (AUROC 0.93 [95% CI: 0.88-0.97]; Sn 75% [95% CI: 66-83]; Sp 91 [95% CI: 77-98]) but had a higher Sn and Sp. The sPLA2-IIA was also found superior to N%, PCT, and lactate. This finding suggested sPLA2-IIA was recommended biomarkers for BI detection in LMIC.
    MeSH terms: Adult; Aged; Bacterial Infections/blood; Bacterial Infections/diagnosis*; C-Reactive Protein/metabolism*; Female; Humans; Male; Middle Aged; Neutrophils/cytology*; Biomarkers/metabolism; Phospholipases A2, Secretory/metabolism*
  5. Boo WH
    Aust J Gen Pract, 2021 06;50(6):381-382.
    PMID: 34059840 DOI: 10.31128/AJGP-06-20-5499
    MeSH terms: Aged; Color*; Humans; Male; Syndrome
  6. Arifin A, Thambiah SC, Abdullah H, Samsudin IN
    Clin Chem, 2021 06 01;67(6):823-826.
    PMID: 34059896 DOI: 10.1093/clinchem/hvab031
    MeSH terms: Chromosomes, Human, Pair 22; DiGeorge Syndrome*; Humans; Infant, Newborn
  7. Al-Shabi M, Shak K, Tan M
    Int J Comput Assist Radiol Surg, 2021 Aug;16(8):1319-1324.
    PMID: 34060010 DOI: 10.1007/s11548-021-02415-z
    PURPOSE: In recent years, Non-Local-based methods have been successfully applied to lung nodule classification. However, these methods offer 2D attention or limited 3D attention to low-resolution feature maps. Moreover, they still depend on a convenient local filter such as convolution as full 3D attention is expensive to compute and requires a big dataset, which might not be available.

    METHODS: We propose to use 3D Axial-Attention, which requires a fraction of the computing power of a regular Non-Local network (i.e., self-attention). Unlike a regular Non-Local network, the 3D Axial-Attention network applies the attention operation to each axis separately. Additionally, we solve the invariant position problem of the Non-Local network by proposing to add 3D positional encoding to shared embeddings.

    RESULTS: We validated the proposed method on 442 benign nodules and 406 malignant nodules, extracted from the public LIDC-IDRI dataset by following a rigorous experimental setup using only nodules annotated by at least three radiologists. Our results show that the 3D Axial-Attention model achieves state-of-the-art performance on all evaluation metrics, including AUC and Accuracy.

    CONCLUSIONS: The proposed model provides full 3D attention, whereby every element (i.e., pixel) in the 3D volume space attends to every other element in the nodule effectively. Thus, the 3D Axial-Attention network can be used in all layers without the need for local filters. The experimental results show the importance of full 3D attention for classifying lung nodules.

  8. Fatiha Muhammad E, Kumar A, Wahab HA, Zhang KYJ
    Mol Inform, 2021 08;40(8):e2100020.
    PMID: 34060234 DOI: 10.1002/minf.202100020
    Acetylcholinesterase (AChE) inhibitors are the most effective drugs for Alzheimer's disease treatment. However, considering the potential and failure rates of AChE inhibitors, chemical scaffolds targeting cholinesterase specifically are still very limited. Herein, we report a new class of AChE inhibitors identified by employing a virtual screening approach that combines shape similarity with molecular docking calculations. Virtual screening followed by the evaluation of AChE inhibitory activity allowed us to identify 1,2,4-triazolylthioethanones as a novel class of AChE inhibitors. Thirteen compounds with 1,2,4-triazolylthiothanone core and IC50 values in the range of 0.15±0.07 to 3.32±0.92 μM have been reported here. Our findings shed light into a class of AChE inhibitors that could be useful starting point for the development of novel therapeutics to tackle Alzheimer's disease.
  9. Ripen AM, Chear CT, Baharin MF, Nallusamy R, Chan KC, Kassim A, et al.
    Clin Exp Immunol, 2021 Nov;206(2):119-128.
    PMID: 34060650 DOI: 10.1111/cei.13626
    Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.
  10. Yong TSM, Perialathan K, Ahmad M, Juatan N, Abdul Majid L, Johari MZ
    JMIR Pediatr Parent, 2021 Jun 01;4(2):e24156.
    PMID: 34061039 DOI: 10.2196/24156
    BACKGROUND: Home is a vulnerable place for accidental child injuries. Unintentional injuries are a leading cause of death, hospitalization, and disabilities. These injuries are considered preventable and if not tackled, they will continue to be a persisting problem. Smartphones have become increasingly important in our everyday life and is an important tool not only for communication but also for other purposes-they have apps that can be used for various purposes. Therefore, an app-based intervention (ChildSafe) was developed to assess and reduce child injury at home.

    OBJECTIVE: This study aimed to evaluate the acceptance of the ChildSafe smartphone app intervention by parents/guardians.

    METHODS: This study was conducted using a qualitative exploratory approach on selected participants of the ChildSafe intervention app study. A total of 27 semistructured in-depth interviews were carried out among parents or guardians who have at least one child between the age of 0 and 59 months in the area of Sungai Buloh, Selangor, between November 2017 and March 2018. Interview questions were developed from the consolidated framework for implementation research (CFIR). Interviews were recorded, transcribed verbatim, and data were thematically analyzed guided by CFIR.

    RESULTS: The study revealed users' perception on usability, feasibility, and acceptability toward the ChildSafe app. Three CFIR domains were identified: intervention characteristics, inner setting, and characteristics of individuals. A total of 5 constructs were revealed under intervention characteristics: evidence strength and quality, relative advantage, adaptability, trialability, and design quality and packaging; 2 under inner setting: implementation climate and readiness for implementation; and 4 under characteristics of individuals: knowledge and beliefs about the intervention, self-efficacy, individual stage of change, and other personal attributes. In general, participants felt the app is extremely useful and effective, easy to use, and purposeful in achieving home safety assessment via reminders. The app replaces the need for participants to search for information on home safety and dangers, as the app itself was designed as a tool to assess for this specific purpose. Even at the nascent stage and despite its limitations, the app has prompted users to consider and make changes around their own home. However, future versions of the app should be expanded to make it more attractive to users as it lacks interactive feedback and additional features.

    CONCLUSIONS: Parents/guardians are accepting the use of the ChildSafe app to prevent child injury at home. However, further expansion and improvements are needed to increase the acceptability of this app by parents/guardians.

  11. Low ZY, Yip AJW, Sharma A, Lal SK
    Virus Genes, 2021 Aug;57(4):307-317.
    PMID: 34061288 DOI: 10.1007/s11262-021-01846-9
    The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.
    MeSH terms: Animals; Disease Outbreaks; Humans; Coronavirus Infections/epidemiology*; Coronavirus Infections/virology; SARS Virus/genetics; Middle East Respiratory Syndrome Coronavirus/genetics
  12. Tan KL, Chia WC, How CW, Tor YS, Show PL, Looi QHD, et al.
    Mol Biotechnol, 2021 Sep;63(9):780-791.
    PMID: 34061307 DOI: 10.1007/s12033-021-00339-2
    The objective of this study is to develop a simple protocol to isolate and characterise small extracellular vesicles (sEVs) from human umbilical cord-derived MSCs (hUC-MSCs). hUC-MSCs were characterised through analysis of morphology, immunophenotyping and multidifferentiation ability. SEVs were successfully isolated by ultrafiltration from the conditioned medium of hUC-MSCs. The sEVs' size distribution, intensity within a specific surface marker population were measured with zetasizer or nanoparticle tracking analysis. The expression of surface and internal markers of sEVs was also assessed by western blotting. Morphology of hUC-MSCs displayed as spindle-shaped, fibroblast-like adherent cells. Phenotypic analysis by flow cytometry revealed that hUC-MSCs expressed MSC surface marker, including CD90, CD73, CD105, CD44 and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. Populations of sEVs with CD9, CD63 and CD81 positive were detected with size distribution in the diameter of 63.2 to 162.5 nm. Typical sEVs biomarkers such as CD9, CD63, CD81, HSP70 and TSG101 were also detected with western blotting. Our study showed that sEVs from hUC-MSCs conditioned medium were successfully isolated and characterised. Downstream application of hUC-MSCs-sEVs will be further explored.
    MeSH terms: Extracellular Vesicles/metabolism*; Extracellular Vesicles/chemistry; Cell Adhesion; Cell Differentiation; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Fetal Blood/cytology; Fetal Blood/metabolism; Chemical Fractionation/methods*; Humans; Osteoblasts/cytology*; Osteoblasts/metabolism; Particle Size; Transcription Factors/genetics; Transcription Factors/metabolism; Biomarkers/metabolism; Antigens, CD/genetics; Antigens, CD/metabolism; Gene Expression; Culture Media, Conditioned/chemistry; Adipocytes/cytology*; Adipocytes/metabolism; HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/metabolism; Chondrocytes/cytology*; Chondrocytes/metabolism; Endosomal Sorting Complexes Required for Transport/genetics; Endosomal Sorting Complexes Required for Transport/metabolism; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/metabolism
  13. Hassan HJ, Hashim S, Mohd Sanusi MS, Jamal MH, Hassan SA, Bradley DA, et al.
    PLoS One, 2021;16(6):e0250528.
    PMID: 34061865 DOI: 10.1371/journal.pone.0250528
    Forming part of a study of radiological risk arising from use of radioactive consumer products, investigation is made of pendants containing naturally occurring radioactive material. Based on use of gamma-ray spectrometry and Monte Carlo (MC) simulations, the study investigates commercially available 'scalar energy pendants'. The doses from these have been simulated using MIRD5 mathematical phantoms, evaluation being made of dose conversion factors (DCFs) and organ dose. Metallic pendants code MP15 were found to contain the greatest activity, at 7043 ± 471 Bq from 232Th, while glass pendants code GP11 were presented the greatest 238U and 40K activity, at 1001 ± 172 and 687 ± 130 Bq respectively. MP15 pendants offered the greatest percentage concentrations of Th, Ce, U and Zr, with means of 25.6 ± 0.06, 5.6 ± 0.005, 1.03 ± 0.04 and 28.5 ± 0.08 respectively, giving rise to an effective dose of 2.8 mSv for a nominal wearing period of 2000 h. Accordingly, these products can give rise to annual doses in excess of the public limit of 1 mSv.
    MeSH terms: Humans; Monte Carlo Method*; Radiation Dosage; Radioactivity; Spectrometry, Gamma; Thorium/analysis; Uranium/analysis; Phantoms, Imaging
  14. Ishak SNH, Kamarudin NHA, Ali MSM, Leow ATC, Shariff FM, Rahman RNZRA
    PLoS One, 2021;16(6):e0251751.
    PMID: 34061877 DOI: 10.1371/journal.pone.0251751
    5M mutant lipase was derived through cumulative mutagenesis of amino acid residues (D43E/T118N/E226D/E250L/N304E) of T1 lipase from Geobacillus zalihae. A previous study revealed that cumulative mutations in 5M mutant lipase resulted in decreased thermostability compared to wild-type T1 lipase. Multiple amino acids substitution might cause structural destabilization due to negative cooperation. Hence, the three-dimensional structure of 5M mutant lipase was elucidated to determine the evolution in structural elements caused by amino acids substitution. A suitable crystal for X-ray diffraction was obtained from an optimized formulation containing 0.5 M sodium cacodylate trihydrate, 0.4 M sodium citrate tribasic pH 6.4 and 0.2 M sodium chloride with 2.5 mg/mL protein concentration. The three-dimensional structure of 5M mutant lipase was solved at 2.64 Å with two molecules per asymmetric unit. The detailed analysis of the structure revealed that there was a decrease in the number of molecular interactions, including hydrogen bonds and ion interactions, which are important in maintaining the stability of lipase. This study facilitates understanding of and highlights the importance of hydrogen bonds and ion interactions towards protein stability. Substrate specificity and docking analysis on the open structure of 5M mutant lipase revealed changes in substrate preference. The molecular dynamics simulation of 5M-substrates complexes validated the substrate preference of 5M lipase towards long-chain p-nitrophenyl-esters.
    MeSH terms: Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Bacterial Proteins/chemistry; Enzyme Stability; Hydrogen Bonding; Mutation; Protein Conformation; Crystallography, X-Ray; Amino Acid Substitution; Molecular Docking Simulation*
  15. Ahmad MFB, Das S
    Am J Obstet Gynecol, 2021 09;225(3):353-354.
    PMID: 34062121 DOI: 10.1016/j.ajog.2021.05.040
    MeSH terms: Female; Humans; Labor, Obstetric*; Placenta; Pregnancy
  16. Sanusi MSM, Hassan WMSW, Hashim S, Ramli AT
    Appl Radiat Isot, 2021 Aug;174:109791.
    PMID: 34062400 DOI: 10.1016/j.apradiso.2021.109791
    Terrestrial radioactivity monitoring of 238U and 232Th series, and 40K in soil is an essential practice for radioactivity and radiation measurement of a place. In conventional practice, only basic data can be in-situ measured using a survey instrument, for example radioactivity concentration in soil and ambient dose equivalent rate. For other physical quantities, for example organ absorbed dose and organ equivalent dose, the measurement is impossible to be performed and can only be computed using Monte Carlo radiation transport simulations. In the past, most of the works only focused on calculating air-kerma-to-effective dose conversion factors. However, the information on organ dose conversion factors is scarcely documented and reported. This study was conducted to calculate organ absorbed and tissue-weighted equivalent dose conversion factors as a result of exposure from terrestrial gamma radiation. Series of organ dose conversion factors is produced based on computations from Monte Carlo MCNP5 simulations using modelled gamma irradiation geometry and established adult MIRD phantom. The study found out that most of the radiation exposed organs absorb energy at comparable rates, except for dense and superficial tissues i.e., skeleton and skin, which indicated slightly higher values. The good agreement between this work and previous studies demonstrated that our gamma irradiation geometry and modelling of gamma radiation sources are adequate. Therefore, the proposed organ dose conversion factors from this study are reasonably acceptable for dose estimation in environmental radioactivity monitoring practices.
    MeSH terms: Gamma Rays; Humans; Monte Carlo Method; Organ Specificity*; Radiation Monitoring/methods*; Soil Pollutants, Radioactive/pharmacokinetics*; Photons; Phantoms, Imaging
  17. Lutfi SNN, Abd Razak NA, Ali S, Gholizadeh H
    Biomed Tech (Berl), 2021 Jun 25;66(3):317-322.
    PMID: 34062632 DOI: 10.1515/bmt-2019-0110
    Materials with low-strength and low-impedance properties, such as elastomers and polymeric foams are major contributors to prosthetic liner design. Polyethylene-Light (Pelite™) is a foam liner that is the most frequently used in prosthetics but it does not cater to all amputees' limb and skin conditions. The study aims to investigate the newly modified Foam Liner, a combination of two different types of foams (EVA + PU + EVA) as the newly modified Foam Liner in terms of compressive and tensile properties in comparison to Pelite™, polyurethane (PU) foam, and ethylene-vinyl acetate (EVA) foam. Universal testing machine (AGS-X, Shimadzu, Kyoto, Japan) has been used to measure the tensile and compressive stress. Pelite™ had the highest compressive stress at 566.63 kPa and tensile stress at 1145 kPa. Foam Liner fell between EVA and Pelite™ with 551.83 kPa at compression and 715.40 kPa at tension. PU foam had the lowest compressive stress at 2.80 kPa and tensile stress at 33.93 kPa. Foam Liner has intermediate compressive elasticity but has high tensile elasticity compared to EVA and Pelite™. Pelite™ remains the highest in compressive and tensile stiffness. Although it is good for amputees with bony prominence, constant pressure might result in skin breakdown or ulcer. Foam Liner would be the best for amputees with soft tissues on the residual limbs to accommodate movement.
    MeSH terms: Amputees; Artificial Limbs; Elasticity; Humans; Materials Testing*; Polyurethanes*; Stress, Mechanical; Vinyl Compounds/chemistry*
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