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  1. Fulltext Giant Submandibular Calculus Eroding Oral Cavity Mucosa
    Lim EH, Nadarajah S, Mohamad I
    Oman Med J, 2017 Sep;32(5):432-435.
    PMID: 29026477 DOI: 10.5001/omj.2017.81
    Sialolithiasis is the formation of calculi or sialoliths in the salivary gland. It is the most common benign condition of the salivary gland. Sialolithiasis can occur in all salivary glands. The submandibular gland is most commonly affected followed by the parotid gland. Calculi commonly measure less than 10 mm. Calculi of more than 15 mm are termed giant salivary gland calculi and are infrequently reported in the literature. Here, we report a case of unusually large submandibular gland calculus of 5 cm in greatest dimension which caused erosion of the oral cavity.
  2. Fulltext Compact conformal tattoo-polymer antenna for on-body wireless power transfer
    Chang XL, Chee PS, Lim EH
    Sci Rep, 2023 Jun 15;13(1):9678.
    PMID: 37322083 DOI: 10.1038/s41598-023-36335-6
    This paper presents a 35.0 × 35.0 × 2.7 mm3 compact, low-profile, and lightweight wearable antenna for on-body wireless power transfer. The proposed antenna can be easily printed on a piece of flexible tattoo paper and transformed onto a PDMS substrate, making the entire antenna structure conform to the human body for achieving a better user experience. Here, a layer of frequency selective surface (FSS) is inserted in between the antenna and human tissue, which has successfully reduced the loading effects of the tissue, with 13.8 dB improvement on the antenna gain. Also, the operating frequency of the rectenna is not affected much by deformation. To maximize the RF-DC conversion efficiency, a matching loop, a matching stub, and two coupled lines are integrated with the antenna for tuning the rectenna so that a wide bandwidth (~ 24%) can be achieved without the use of any external matching networks. Measurement results show that the proposed rectenna can achieve a maximum conversion efficiency of 59.0% with an input power of 5.75 μW/cm2 and can even exceed 40% for a low input power of 1.0 μW/cm2 with a 20 kΩ resistive load, while many other reported rectennas can only achieve a high PCE at a high power density level, which is not always practical for a wearable antenna.
  3. Fulltext CT angiography versus Digital Subtraction angiography for intracranial vascular pathology in a clinical setting
    Cunli Y, Khoo LS, Lim PJ, Lim EH
    Med J Malaysia, 2013 Oct;68(5):415-23.
    PMID: 24632872
    No abstract available.
  4. Anatomical variations of anterior ethmoidal artery and their significance in endoscopic sinus surgery: a systematic review
    Abdullah B, Lim EH, Husain S, Snidvongs K, Wang Y
    Surg Radiol Anat, 2019 May;41(5):491-499.
    PMID: 30542930 DOI: 10.1007/s00276-018-2165-3
    PURPOSE: Anterior ethmoidal artery (AEA) is at risk of injury in endoscopic sinus surgery due to its location. The aim of this review was to assess the anatomical variations of AEA and their significance.

    METHODS: A literature search was performed on PUBMED, SCOPUS AND EMBASE. The following keywords were used: ethmoidal artery; anterior ethmoidal artery; anterior ethmoidal canal; ethmoid sinus; ethmoid roof; skull base. The search was conducted over a period of 6 months between October 2016 and April 2017.

    RESULTS: 105 articles were retrieved. 76 articles which were either case reports or unrelated topics were excluded. Out of the 29 full text articles retrieved, 16 articles were selected; 3 were cadaveric dissection, 5 combined cadaveric dissection and computed tomography (CT) and the rest were of CT studies. All studies were of level III evidence and a total of 1985 arteries were studied. Its position at the skull base was influenced by the presence of supraorbital ethmoid cell (SOEC) and length of the lateral lamella of cribriform plate (LLCP). Inter population morphological variations contribute to the anatomical variations.

    CONCLUSIONS: The average diameter of AEA was 0.80 mm and the intranasal length was 5.82 mm. 79.2% was found between the second and third lamellae, 12.0% in the third lamella, 6% posterior to third lamella and 1.2% in the second lamella. Extra precaution should be taken in the presence of a well-pneumatized SOEC and a long LLCP as AEA tends to run freely below skull base.

  5. Fulltext Compact organic liquid dielectric resonator antenna for air pressure sensing using soft material
    Low JH, Chee PS, Lim EH, Lee KY
    Sci Rep, 2020 Sep 10;10(1):14907.
    PMID: 32913321 DOI: 10.1038/s41598-020-72021-7
    For the first time, a flexible and deformable liquid dielectric resonator antenna (LDRA) is proposed for air pressure sensing. The proposed LDRA can be made very compact as it has employed liquidized organic dielectric with high dielectric constant (~ 33) with low loss tangent (~ 0.05). Here, a soft elastomer container has been fabricated using soft-lithography method for holding the liquid, and an air cavity is tactfully embedded into the central part of a cylindrical DRA to form an annular structure that can be used for sensing air pressure. It will be shown that the inclusion of the air cavity is essential for making the antenna structure sensitive to pressure changes. Simulations and experiments have been conducted to verify the functionalities of the proposed organic LDRA as microwave radiator and as air pressure sensor. It has been proven to have higher antenna gain than the water LDRA in the frequency range of 1.8-2.8 GHz, while achieving a good air pressure sensitivity of 270 MHz/bar.
  6. Fulltext Artificial Intelligence-Assisted Throat Sensor Using Ionic Polymer-Metal Composite (IPMC) Material
    Lee JH, Chee PS, Lim EH, Tan CH
    Polymers (Basel), 2021 Sep 09;13(18).
    PMID: 34577942 DOI: 10.3390/polym13183041
    Throat sensing has received increasing demands in recent years, especially for oropharyngeal treatment applications. The conventional videofluoroscopy (VFS) approach is limited by either exposing the patient to radiation or incurring expensive costs on sophisticated equipment as well as well-trained speech-language pathologists. Here, we propose a smart and non-invasive throat sensor that can be fabricated using an ionic polymer-metal composite (IPMC) material. Through the cation's movement inside the IPMC material, the sensor can detect muscle movement at the throat using a self-generated signal. We have further improved the output responses of the sensor by coating it with a corrosive-resistant gold material. A support vector machine algorithm is used to train the sensor in recognizing the pattern of the throat movements, with a high accuracy of 95%. Our proposed throat sensor has revealed its potential to be used as a promising solution for smart healthcare devices, which can benefit many practical applications such as human-machine interactions, sports training, and rehabilitation.
  7. Anatomical variations of anterior ethmoidal artery at the ethmoidal roof and anterior skull base in Asians
    Abdullah B, Lim EH, Mohamad H, Husain S, Aziz ME, Snidvongs K, et al.
    Surg Radiol Anat, 2019 May;41(5):543-550.
    PMID: 30542929 DOI: 10.1007/s00276-018-2157-3
    PURPOSE: The variations of the anterior ethmoidal artery (AEA) in different populations should be recognized by surgeons to prevent unwarranted complications during surgery. The aim of this study was to assess the anatomical variations of AEA in Asian population.

    METHODS: A cross-sectional study of 252 AEA identified by computed tomography (CT) of the paranasal sinuses. The multiplanar CT images were acquired from SOMATOM® Definition AS+ and reconstructed to axial, coronal and sagittal view at 1 mm slice thickness.

    RESULTS: 42.5% of AEA was within skull base (grade I), 20.2% at skull base (grade II) and 37.3% coursed freely below skull base (grade III). The prevalence of supraorbital ethmoid cell (SOEC) and suprabullar cell (SBC) was 29.8% and 48.0%. The position of AEA at skull base has significant association with SOEC (p 

  8. WiFi-Powered Sensor Integrated into a Smart Glove with a Fully Fabric Antenna for the Human-Machine Interface
    Lee KT, Lim EH, Tan CH, Low JH, Wong KL, Guan C, et al.
    ACS Appl Mater Interfaces, 2024 Nov 13;16(45):62914-62924.
    PMID: 39497522 DOI: 10.1021/acsami.4c12371
    The integration of flexible sensors into human-machine interfaces (HMIs) is in increasing demand for intuitive and effective manipulation. Traditional glove-based HMIs, constrained by nonconformal rigid structures or the need for bulky batteries, face limitations in continuous operation. Addressing this, we introduce yarn-based bend sensors in our smart glove, which are wirelessly powered and harvest energy from a fully textile 5.8 GHz WiFi-band antenna receiver. These sensors exhibit a gauge factor (GF) of 5.60 for strains ranging from 0 to 10%. They show a consistent performance regardless of the straining frequency when being stretched and released at frequencies between 0.1 and 0.7 Hz. This reliability ensures that the sensor output is solely dependent on the yarn's elongation. Accurately detecting finger-bending movements from 0° to 90° in a virtual environment, the sensors enable enhanced degrees of freedom for human finger interaction. When integrated with advanced machine-learning techniques, the system achieves a classification accuracy of 98.75% for object recognition, demonstrating its potential for precise and accurate HMI. Unlike conventional near-field energy transfer methods that rely on magnetic flux and are limited by power loss over distance, our fully textile design effectively harvests microwave energy, showing no voltage deterioration up to 1 m away. This minimalist microwave-powered smart glove represents a significant advancement, offering a viable and practical solution for developing intuitive and reliable HMIs.
  9. Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study
    Yeoh AEJ, Lu Y, Chin WHN, Chiew EKH, Lim EH, Li Z, et al.
    J Clin Oncol, 2018 09 10;36(26):2726-2735.
    PMID: 30044693 DOI: 10.1200/JCO.2018.78.3050
    Purpose Although IKZF1 deletion ( IKZF1del) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10-7), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1-negative disease, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.
  10. Identifying IGH disease clones for MRD monitoring in childhood B-cell acute lymphoblastic leukemia using RNA-Seq
    Li Z, Jiang N, Lim EH, Chin WHN, Lu Y, Chiew KH, et al.
    Leukemia, 2020 09;34(9):2418-2429.
    PMID: 32099036 DOI: 10.1038/s41375-020-0774-4
    Identifying patient-specific clonal IGH/TCR junctional sequences is critical for minimal residual disease (MRD) monitoring. Conventionally these junctional sequences are identified using laborious Sanger sequencing of excised heteroduplex bands. We found that the IGH is highly expressed in our diagnostic B-cell acute lymphoblastic leukemia (B-ALL) samples using RNA-Seq. Therefore, we used RNA-Seq to identify IGH disease clone sequences in 258 childhood B-ALL samples for MRD monitoring. The amount of background IGH rearrangements uncovered by RNA-Seq followed the Zipf's law with IGH disease clones easily identified as outliers. Four hundred and ninety-seven IGH disease clones (median 2, range 0-7 clones/patient) are identified in 90.3% of patients. High hyperdiploid patients have the most IGH disease clones (median 3) while DUX4 subtype has the least (median 1) due to the rearrangements involving the IGH locus. In all, 90.8% of IGH disease clones found by Sanger sequencing are also identified by RNA-Seq. In addition, RNA-Seq identified 43% more IGH disease clones. In 69 patients lacking sensitive IGH targets, targeted NGS IGH MRD showed high correlation (R = 0.93; P = 1.3 × 10-14), better relapse prediction than conventional RQ-PCR MRD using non-IGH targets. In conclusion, RNA-Seq can identify patient-specific clonal IGH junctional sequences for MRD monitoring, adding to its usefulness for molecular diagnosis in childhood B-ALL.
  11. Fulltext Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia
    Li Z, Lee SHR, Chin WHN, Lu Y, Jiang N, Lim EH, et al.
    Blood Adv, 2021 12 14;5(23):5226-5238.
    PMID: 34547766 DOI: 10.1182/bloodadvances.2021004895
    Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
  12. Practical Considerations for Using RNA Sequencing in Management of B-Lymphoblastic Leukemia: Malaysia-Singapore Acute Lymphoblastic Leukemia 2020 Implementation Strategy
    Ni Chin WH, Li Z, Jiang N, Lim EH, Suang Lim JY, Lu Y, et al.
    J Mol Diagn, 2021 10;23(10):1359-1372.
    PMID: 34365011 DOI: 10.1016/j.jmoldx.2021.07.013
    Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients.
  13. Anthracycline-Free Protocol for Favorable-Risk Childhood ALL: A Noninferiority Comparison Between Malaysia-Singapore ALL 2003 and ALL 2010 Studies
    Ariffin H, Chiew EKH, Oh BLZ, Lee SHR, Lim EH, Kham SKY, et al.
    J Clin Oncol, 2023 Jul 10;41(20):3642-3651.
    PMID: 37276496 DOI: 10.1200/JCO.22.02347
    PURPOSE: To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m2 of anthracyclines.

    PATIENTS AND METHODS: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts.

    RESULTS: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004).

    CONCLUSION: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.

  14. Fulltext Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
    Im SA, Gennari A, Park YH, Kim JH, Jiang ZF, Gupta S, et al.
    ESMO Open, 2023 Jun;8(3):101541.
    PMID: 37178669 DOI: 10.1016/j.esmoop.2023.101541
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.
  15. Fulltext Germline breast cancer susceptibility genes, tumor characteristics, and survival
    Ho PJ, Khng AJ, Loh HW, Ho WK, Yip CH, Mohd-Taib NA, et al.
    Genome Med, 2021 Dec 02;13(1):185.
    PMID: 34857041 DOI: 10.1186/s13073-021-00978-9
    BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.

    METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease.

    RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]).

    CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

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