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  1. Ng WL, Rahmat K, Fadzli F, Rozalli FI, Mohd-Shah MN, Chandran PA, et al.
    Medicine (Baltimore), 2016 Mar;95(12):e3146.
    PMID: 27015196 DOI: 10.1097/MD.0000000000003146
    The purpose of this study was to investigate the diagnostic efficacy of shearwave elastography (SWE) in differentiating between benign and malignant breast lesions.One hundred and fifty-nine lesions were assessed using B-mode ultrasound (US) and SWE parameters were recorded (Emax, Emean, Emin, Eratio, SD). SWE measurements were then correlated with histopathological diagnosis.The final sample contained 85 benign and 74 malignant lesions. The maximum stiffness (Emax) with a cutoff point of ≥ 56.0 kPa (based on ROC curves) provided sensitivity of 100.0%, specificity of 97.6%, positive predictive value (PPV) of 97.4%, and negative predictive value (NPV) of 100% in detecting malignant lesions. A cutoff of ≥80 kPa managed to downgrade 95.5% of the Breast Imaging-Reporting and Data System (BI-RADS) 4a lesions to BI-RADS 3, negating the need for biopsy. Using a combination of BI-RADS and SWE, the authors managed to improve the PPV from 2.3% to 50% in BI-RADS 4a lesions.SWE of the breast provides highly specific and sensitive quantitative values that are beneficial in the characterization of breast lesions. Our results showed that Emax is the most accurate value for differentiating benign from malignant lesions.
  2. Ng WL, Abdullah N
    Singapore Med J, 2020 Feb;61(2):81-85.
    PMID: 32152640 DOI: 10.11622/smedj.2020016
    INTRODUCTION: Medical emergencies occur at a rate of one in 604‒753 flights. Doctors travelling on commercial flights may encounter an in-flight medical emergency requiring their assistance. There is a paucity of studies on how confident primary care doctors are in managing in-flight medical emergencies. This study aimed to determine the knowledge, confidence and attitude of primary care doctors in managing in-flight medical emergencies.

    METHODS: A cross-sectional study was conducted on all primary care doctors working in government health clinics in Kuala Lumpur, Malaysia, from October 2016 to November 2016. A self-reported questionnaire was used, which included questions on demographic information, knowledge of in-flight medicine, and the attitude and confidence of primary care doctors in managing in-flight medical emergencies.

    RESULTS: 182 doctors completed the questionnaire (92.9% response rate). The mean knowledge score was 8.9 out of a maximum score of 20. Only 11.5% of doctors felt confident managing in-flight medical emergencies. The majority (69.2%) would assist in an in-flight medical emergency, but the readiness to assist was reduced if someone else was already helping or if they were not familiar with the emergency. Total knowledge score was positively associated with confidence in managing in-flight medical emergencies (p = 0.03).

    CONCLUSION: Only one in ten primary care doctors in this study felt confident managing in-flight medical emergencies. A higher total knowledge score of in-flight medical emergencies was positively associated with greater confidence in managing them. Educational programmes to address this gap in knowledge may be useful to improve doctors' confidence in managing in-flight medical emergencies.

  3. Barua PD, Muhammad Gowdh NF, Rahmat K, Ramli N, Ng WL, Chan WY, et al.
    PMID: 34360343 DOI: 10.3390/ijerph18158052
    COVID-19 and pneumonia detection using medical images is a topic of immense interest in medical and healthcare research. Various advanced medical imaging and machine learning techniques have been presented to detect these respiratory disorders accurately. In this work, we have proposed a novel COVID-19 detection system using an exemplar and hybrid fused deep feature generator with X-ray images. The proposed Exemplar COVID-19FclNet9 comprises three basic steps: exemplar deep feature generation, iterative feature selection and classification. The novelty of this work is the feature extraction using three pre-trained convolutional neural networks (CNNs) in the presented feature extraction phase. The common aspects of these pre-trained CNNs are that they have three fully connected layers, and these networks are AlexNet, VGG16 and VGG19. The fully connected layer of these networks is used to generate deep features using an exemplar structure, and a nine-feature generation method is obtained. The loss values of these feature extractors are computed, and the best three extractors are selected. The features of the top three fully connected features are merged. An iterative selector is used to select the most informative features. The chosen features are classified using a support vector machine (SVM) classifier. The proposed COVID-19FclNet9 applied nine deep feature extraction methods by using three deep networks together. The most appropriate deep feature generation model selection and iterative feature selection have been employed to utilise their advantages together. By using these techniques, the image classification ability of the used three deep networks has been improved. The presented model is developed using four X-ray image corpora (DB1, DB2, DB3 and DB4) with two, three and four classes. The proposed Exemplar COVID-19FclNet9 achieved a classification accuracy of 97.60%, 89.96%, 98.84% and 99.64% using the SVM classifier with 10-fold cross-validation for four datasets, respectively. Our developed Exemplar COVID-19FclNet9 model has achieved high classification accuracy for all four databases and may be deployed for clinical application.
  4. Lim QL, Tan YL, Ng WL, Yong CSY, Ismail A, Rovie-Ryan JJ, et al.
    Sci Rep, 2020 03 04;10(1):3973.
    PMID: 32132572 DOI: 10.1038/s41598-020-60552-y
    A molecular sexing method by polymerase chain reaction (PCR) amplification of a portion of the sex-determining region Y (SRY) and the zinc finger (ZF) gene, as well as six equine Y-chromosome-specific microsatellite markers, were tested in the Malayan tapir (Tapirus indicus). While the microsatellite markers did not yield any male-specific amplicons for sex-typing, the SRY/ZF marker system produced reliable molecular sexing results by accurately sex-typing 31 reference Malayan tapirs, using whole blood, dried blood spot (DBS), or tissue samples as materials for DNA extraction. The marker system was also tested on 16 faecal samples, and the results were in general consistent with the pre-determined sexes of the animals, despite some amplification failures. A preliminary estimation of wild Malayan tapir population sex ratio was estimated from the Wildlife Genomic Resource Bank (WGRB) database of the Malaysian Department of Wildlife and National Parks (PERHILITAN), zoos, and the Sungai Dusun Wildlife Conservation Centre (WCC), as well as from the results of molecular sexing 12 samples of unknown sex. The overall sex ratio favoured females, but the deviation from parity was statistically not significant when tested using the binomial test (p > 0.05), which may be due to reduced statistical power caused by small sample sizes.
  5. Ng WL, Hussein N, Ng CJ, Qureshi N, Lee YK, Kwan Z, et al.
    PLoS One, 2024;19(1):e0296498.
    PMID: 38206925 DOI: 10.1371/journal.pone.0296498
    INTRODUCTION: Allopurinol, the first-line treatment for chronic gout, is a common causative drug for severe cutaneous adverse reactions (SCAR). HLA-B*58:01 allele was strongly associated with allopurinol-induced SCAR in Asian countries such as Taiwan, Japan, Thailand and Malaysia. HLA-B*58:01 screening before allopurinol initiation is conditionally recommended in the Southeast-Asian population, but the uptake of this screening is slow in primary care settings, including Malaysia. This study aimed to explore the views and experiences of primary care doctors and patients with gout on implementing HLA-B*58:01 testing in Malaysia as part of a more extensive study exploring the feasibility of implementing it routinely.

    METHODS: This qualitative study used in-depth interviews and focus group discussions to obtain information from patients with gout under follow-up in primary care and doctors who cared for them. Patients and doctors shared their gout management experiences and views on implementing HLA-B*58:01 screening in primary care. Data were coded and analysed using thematic analysis.

    RESULTS: 18 patients and 18 doctors from three different healthcare settings (university hospital, public health clinics, private general practitioner clinics) participated. The acceptability to HLA-B*58:01 screening was good among the doctors and patients. We discovered inadequate disclosure of severe side effects of allopurinol by doctors due to concerns about medication refusal by patients, which could potentially be improved by introducing HLA-B*58:01 testing. Barriers to implementation included out-of-pocket costs for patients, the cost-effectiveness of this implementation, lack of established alternative treatment pathway besides allopurinol, counselling burden and concern about genetic data security. Our participants preferred targeted screening for high-risk populations instead of universal screening.

    CONCLUSION: Implementing HLA-B*58:01 testing in primary care is potentially feasible if a cost-effective, targeted screening policy on high-risk groups can be developed. A clear treatment pathway for patients who test positive should be made available.

  6. Lim HM, Teo CH, Ng CJ, Chiew TK, Ng WL, Abdullah A, et al.
    JMIR Med Inform, 2021 Feb 26;9(2):e23427.
    PMID: 33600345 DOI: 10.2196/23427
    BACKGROUND: During the COVID-19 pandemic, there was an urgent need to develop an automated COVID-19 symptom monitoring system to reduce the burden on the health care system and to provide better self-monitoring at home.

    OBJECTIVE: This paper aimed to describe the development process of the COVID-19 Symptom Monitoring System (CoSMoS), which consists of a self-monitoring, algorithm-based Telegram bot and a teleconsultation system. We describe all the essential steps from the clinical perspective and our technical approach in designing, developing, and integrating the system into clinical practice during the COVID-19 pandemic as well as lessons learned from this development process.

    METHODS: CoSMoS was developed in three phases: (1) requirement formation to identify clinical problems and to draft the clinical algorithm, (2) development testing iteration using the agile software development method, and (3) integration into clinical practice to design an effective clinical workflow using repeated simulations and role-playing.

    RESULTS: We completed the development of CoSMoS in 19 days. In Phase 1 (ie, requirement formation), we identified three main functions: a daily automated reminder system for patients to self-check their symptoms, a safe patient risk assessment to guide patients in clinical decision making, and an active telemonitoring system with real-time phone consultations. The system architecture of CoSMoS involved five components: Telegram instant messaging, a clinician dashboard, system administration (ie, back end), a database, and development and operations infrastructure. The integration of CoSMoS into clinical practice involved the consideration of COVID-19 infectivity and patient safety.

    CONCLUSIONS: This study demonstrated that developing a COVID-19 symptom monitoring system within a short time during a pandemic is feasible using the agile development method. Time factors and communication between the technical and clinical teams were the main challenges in the development process. The development process and lessons learned from this study can guide the future development of digital monitoring systems during the next pandemic, especially in developing countries.

  7. Pang T, Wong JHD, Ng WL, Chan CS
    Comput Methods Programs Biomed, 2021 May;203:106018.
    PMID: 33714900 DOI: 10.1016/j.cmpb.2021.106018
    BACKGROUND AND OBJECTIVE: The capability of deep learning radiomics (DLR) to extract high-level medical imaging features has promoted the use of computer-aided diagnosis of breast mass detected on ultrasound. Recently, generative adversarial network (GAN) has aided in tackling a general issue in DLR, i.e., obtaining a sufficient number of medical images. However, GAN methods require a pair of input and labeled images, which require an exhaustive human annotation process that is very time-consuming. The aim of this paper is to develop a radiomics model based on a semi-supervised GAN method to perform data augmentation in breast ultrasound images.

    METHODS: A total of 1447 ultrasound images, including 767 benign masses and 680 malignant masses were acquired from a tertiary hospital. A semi-supervised GAN model was developed to augment the breast ultrasound images. The synthesized images were subsequently used to classify breast masses using a convolutional neural network (CNN). The model was validated using a 5-fold cross-validation method.

    RESULTS: The proposed GAN architecture generated high-quality breast ultrasound images, verified by two experienced radiologists. The improved performance of semi-supervised learning increased the quality of the synthetic data produced in comparison to the baseline method. We achieved more accurate breast mass classification results (accuracy 90.41%, sensitivity 87.94%, specificity 85.86%) with our synthetic data augmentation compared to other state-of-the-art methods.

    CONCLUSION: The proposed radiomics model has demonstrated a promising potential to synthesize and classify breast masses on ultrasound in a semi-supervised manner.

  8. Lim HM, Abdullah A, Ng CJ, Teo CH, Valliyappan IG, Abdul Hadi H, et al.
    Int J Med Inform, 2021 Nov;155:104567.
    PMID: 34536808 DOI: 10.1016/j.ijmedinf.2021.104567
    BACKGROUND: COVID-19 telemonitoring applications have been developed and used in primary care to monitor patients quarantined at home. There is a lack of evidence on the utility and usability of telemonitoring applications from end-users' perspective.

    OBJECTIVES: This study aimed to evaluate the feasibility of a COVID-19 symptom monitoring system (CoSMoS) by exploring its utility and usability with end-users.

    METHODS: This was a qualitative study using in-depth interviews. Patients with suspected COVID-19 infection who used CoSMoS Telegram bot to monitor their COVID-19 symptoms and doctors who conducted the telemonitoring via CoSMoS dashboard were recruited. Universal sampling was used in this study. We stopped the recruitment when data saturation was reached. Patients and doctors shared their experiences using CoSMoS, its utility and usability for COVID-19 symptoms monitoring. Data were coded and analysed using thematic analysis.

    RESULTS: A total of 11 patients and 4 doctors were recruited into this study. For utility, CoSMoS was useful in providing close monitoring and continuity of care, supporting patients' decision making, ensuring adherence to reporting, and reducing healthcare workers' burden during the pandemic. In terms of usability, patients expressed that CoSMoS was convenient and easy to use. The use of the existing social media application for symptom monitoring was acceptable for the patients. The content in the Telegram bot was easy to understand, although revision was needed to keep the content updated. Doctors preferred to integrate CoSMoS into the electronic medical record.

    CONCLUSION: CoSMoS is feasible and useful to patients and doctors in providing remote monitoring and teleconsultation during the COVID-19 pandemic. The utility and usability evaluation enables the refinement of CoSMoS to be a patient-centred monitoring system.

  9. Khor LA, A Wahid UNI, Ling LL, Liansim SMS, Oon J, Balakrishnan MN, et al.
    PLoS One, 2023;18(3):e0282733.
    PMID: 36877714 DOI: 10.1371/journal.pone.0282733
    INTRODUCTION: Tuberculosis remains a major health problem globally and in Malaysia, particularly in the state of Sabah. Delayed sputum conversion is associated with treatment failure, drug-resistant tuberculosis and mortality. We aimed to determine the prevalence of delayed sputum conversion among smear positive pulmonary tuberculosis (PTB) patients and its associated factors in Sabah, Malaysia.

    METHODS: A retrospective follow up study on all patients newly diagnosed with smear positive pulmonary tuberculosis from 2017 to 2019 was conducted at three government health clinics in Sabah, utilizing data from a national electronic tuberculosis database and medical records. Descriptive statistics and binary logistic regression were applied for data analysis. The outcome of the study was the sputum conversion status at the end of the two-month intensive treatment phase with either successful conversion to smear negative or non-conversion.

    RESULTS: 374 patients were included in the analysis. Our patients were generally younger than 60 years old with no medical illness and varying proportions of tuberculosis severity as judged by radiographic appearance and sputum bacillary load upon diagnosis. Foreigners constituted 27.8% of our sample. 8.8% (confidence interval: 6.2-12.2) did not convert to smear negative at the end of the intensive phase. Binary logistic regression showed that older patients ≥60 years old (adjusted odds ratio, AOR = 4.303), foreigners (AOR = 3.184) and patients with higher sputum bacillary load at diagnosis [2+ (AOR = 5.061) and 3+ (AOR = 4.992)] were more likely to have delayed sputum smear conversion.

    CONCLUSION: The prevalence of delayed sputum conversion in our study was considerably low at 8.8% with age ≥60 years old, foreigners and higher pre-treatment sputum bacillary load associated with delayed conversion. Healthcare providers should take note of these factors and ensure the patients receive proper follow up treatment.

  10. Wong CK, Ng KS, Choo SQR, Lee CJ, Teo YP, Liew SM, et al.
    J Infect Dev Ctries, 2023 Aug 31;17(8):1138-1145.
    PMID: 37699097 DOI: 10.3855/jidc.16967
    INTRODUCTION: The all-cause mortality for tuberculosis is 1 in every 10 patients in Malaysia. The currently available national surveillance database does not record patients' variables such as socio-economic factors, existing co-morbidities, and risk behavior for investigation. An electronic medical record system can capture this missing information and use it to determine all-cause mortality factors more accurately. Our study aims to determine the factors associated with all-cause mortality in a cohort of tuberculosis patients in a Malaysian tertiary hospital which is equipped with an electronic medical record system.

    METHODOLOGY: Records of patients diagnosed with tuberculosis from 1st January 2018 to 30th September 2019 were retrieved. Sociodemographic and clinical data were extracted. Treatment outcomes and all-cause mortality were recorded at 1 year after diagnosis. Univariate, multivariate, and stepwise regression were used to determine the factors associated with all-cause mortality.

    RESULTS: Four-hundred and seventy-one patients were reviewed. The mean age was 46.6 ± 19.7 years. The all-cause mortality rate at one year of diagnosis was 15.3%. Factors identified were age [aOR 1.026 (95% CI: 1.004-1.049)], chronic kidney disease [aOR 3.269 (1.508-7.088)], HIV positive status [aOR 4.743 (1.505-14.953)], active cancer [aOR 5.758 (1.605-20.652)], liver disease [aOR 6.220 (1.028-37.621)], and moderate to advanced chest X-ray findings [aOR 3.851 (1.033-14.354)].

    CONCLUSIONS: On average, one in seven patients diagnosed with TB died within a year in a Malaysian tertiary hospital. Identification of this vulnerable group using the associated factors found in this study may help to reduce the risk of mortality through early intervention strategies.

  11. Chia YC, Devaraj NK, Chook JB, Chew MT, Ooi PB, Mohamed M, et al.
    Eur Heart J Suppl, 2021 May;23(Suppl B):B98-B100.
    PMID: 34054370 DOI: 10.1093/eurheartj/suab058
    Despite hypertension remaining the leading cause of death worldwide, awareness of hypertension and its control rate is still suboptimal in Malaysia. This study aims to determine the proportion of both diagnosed and undiagnosed hypertension, awareness and its control rate during the yearly May Measurement Month (MMM) campaign that has been coordinated by the International Society of Hypertension. Participants aged ≥18 years were recruited at various screening sites namely universities, health facilities, shopping malls, and other sites. Participant's socio-demographic, environmental, and lifestyle data were captured using a questionnaire. Three blood pressure (BP) readings as well as anthropometric measurements were obtained from all participants. The mean of the second and third BP readings was used in analyses. Hypertension was defined as a systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or taking antihypertensive medication. A total of 3062 participants were recruited. The proportion with hypertension in our study was 18.7% (n = 572). The proportion who were aware of their BP status was 63.2%. More than half (57.2%) of the hypertensives were on antihypertensive medication and 70.3% of those treated were controlled. In conclusion, in this BP screening campaign, one in five were hypertensive with almost two thirds aware of their hypertensive status. BP control among those who are taking medications was high at 70% but under 60% of hypertensives were on treatment. Hypertension screening programmes are important to promote awareness and control of hypertension as well as to reduce the devastating complications associated with this disorder.
  12. Tang ASO, Loh WH, Wong QY, Yeo ST, Ng WL, Teoh PI, et al.
    Am J Case Rep, 2021 Mar 13;22:e928659.
    PMID: 33712551 DOI: 10.12659/AJCR.928659
    BACKGROUND Good syndrome (thymoma with immunodeficiency) is a frequently missed and forgotten entity. It is a rare cause of combined B and T cell immunodeficiency in adults. To date, fewer than 200 patients with Good syndrome have been reported in the literature. CASE REPORT We report a case of type AB Masaoka-Koga stage I thymoma which predated the evidence of immune dysregulation by 5 years, manifesting as bilateral cytomegalovirus retinitis, multiple bouts of pneumonia, and bronchiectasis in a HIV-seronegative 55-year-old man. Intravitreal ganciclovir was administered in addition to intravenous systemic ganciclovir, which resulted in severe neutropenic sepsis. A thorough immunodeficiency workup confirmed the presence of hypogammaglobulinemia with complete absence of B cells and reduced CD4/CD8 ratio. The patient responded well to monthly intravenous immunoglobulin replacement therapy, with no further episodes of infection since then. The immunoglobulin level doubled after 1 year of treatment. However, as the patient refused further intravitreal and CMV-targeted treatment, his vision did not recover. CONCLUSIONS Clinicians should be aware that thymoma can precede the onset of immunodeficiency. Clinical suspicion should be heightened in at-risk patients who present with multiple bouts of infection, particularly in thymoma cases with adult-onset immune dysfunction. It is of paramount importance to follow up those patients with annual clinical reviews and immunodeficiency screening.
  13. Tan WM, Ng WL, Ganggayah MD, Hoe VCW, Rahmat K, Zaini HS, et al.
    Health Informatics J, 2023;29(3):14604582231203763.
    PMID: 37740904 DOI: 10.1177/14604582231203763
    Radiology reporting is narrative, and its content depends on the clinician's ability to interpret the images accurately. A tertiary hospital, such as anonymous institute, focuses on writing reports narratively as part of training for medical personnel. Nevertheless, free-text reports make it inconvenient to extract information for clinical audits and data mining. Therefore, we aim to convert unstructured breast radiology reports into structured formats using natural language processing (NLP) algorithm. This study used 327 de-identified breast radiology reports from the anonymous institute. The radiologist identified the significant data elements to be extracted. Our NLP algorithm achieved 97% and 94.9% accuracy in training and testing data, respectively. Henceforth, the structured information was used to build the predictive model for predicting the value of the BIRADS category. The model based on random forest generated the highest accuracy of 92%. Our study not only fulfilled the demands of clinicians by enhancing communication between medical personnel, but it also demonstrated the usefulness of mineable structured data in yielding significant insights.
  14. Wong WY, Loh SW, Ng WL, Tan MC, Yeo KS, Looi CY, et al.
    Sci Rep, 2015;5:8672.
    PMID: 25728279 DOI: 10.1038/srep08672
    Emerging of drug resistant influenza A virus (IAV) has been a big challenge for anti-IAV therapy. In this study, we describe a relatively easy and safe cell-based screening system for anti-IAV replication inhibitors using a non-replicative strain of IAV. A nickel (II) complex of polyhydroxybenzaldehyde N4-thiosemicarbazone (NiPT5) was recently found to exhibit anti-inflammatory activity in vivo and in vitro. NiPT5 impedes the signaling cascades that lead to the activation of NF-κB in response to different stimuli, such as LPS and TNFα. Using our cell-based screening system, we report that pretreating cells with NiPT5 protects cells from influenza A virus (IAV) and vesicular stomatitis virus (VSV) infection. Furthermore, NiPT5 inhibits replication of IAV by inhibiting transcription and translation of vRNAs of IAV. Additionally, NiPT5 reduces IAV-induced type I interferon response and cytokines production. Moreover, NiPT5 prevents activation of NF-κB, and IRF3 in response to IAV infection. These results demonstrate that NiPT5 is a potent antiviral agent that inhibits the early phase of IAV replication.
  15. Loh SW, Ng WL, Yeo KS, Lim YY, Ea CK
    PLoS One, 2014;9(7):e103915.
    PMID: 25079219 DOI: 10.1371/journal.pone.0103915
    H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.
  16. Ng WL, Marinov GK, Liau ES, Lam YL, Lim YY, Ea CK
    RNA Biol, 2016 09;13(9):861-71.
    PMID: 27362560 DOI: 10.1080/15476286.2016.1207036
    Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, we identify an LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. We show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, we demonstrate that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses and protecting cells against microbial infection.
  17. Ng WL, Marinov GK, Chin YM, Lim YY, Ea CK
    Sci Rep, 2017 09 25;7(1):12227.
    PMID: 28947785 DOI: 10.1038/s41598-017-12550-w
    Circular RNAs (circRNAs) have recently emerged as a large class of novel non-coding RNA species. However, the detailed functional significance of the vast majority of them remains to be elucidated. Most functional characterization studies targeting circRNAs have been limited to resting cells, leaving their role in dynamic cellular responses to stimuli largely unexplored. In this study, we focus on the LPS-induced cytoplasmic circRNA, mcircRasGEF1B, and combine targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis to gain insight into its function during the cellular response to LPS stimulation. We show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis revealed an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways, and macrophage activation. These findings expand the set of functionally characterized circRNAs and support the regulatory role of mcircRasGEF1B in immune response during macrophage activation and protection against microbial infections.
  18. Tan MC, Wong WY, Ng WL, Yeo KS, Mohidin TB, Lim YY, et al.
    PLoS One, 2017;12(1):e0170352.
    PMID: 28114392 DOI: 10.1371/journal.pone.0170352
    Influenza virus is estimated to cause 3-5 million severe complications and about 250-500 thousand deaths per year. Different kinds of anti-influenza virus drugs have been developed. However, the emergence of drug resistant strains has presented a big challenge for efficient antiviral therapy. Indole derivatives have been shown to exhibit both antiviral and anti-inflammatory activities. In this study, we adopted a cell-based system to screen for potential anti-IAV agents. Four indole derivatives (named 525A, 526A, 527A and 528A) were subjected to the antiviral screening, of which 526A was selected for further investigation. We reported that pre-treating cells with 526A protects cells from IAV infection. Furthermore, 526A inhibits IAV replication by inhibiting the expression of IAV genes. Interestingly, 526A suppresses the activation of IRF3 and STAT1 in host cells and thus represses the production of type I interferon response and cytokines in IAV-infected cells. Importantly, 526A also partially blocks the activation of RIG-I pathway. Taken together, these results suggest that 526A may be a potential anti-influenza A virus agent.
  19. Adeeb F, Ng WL, Khan MU, Devlin J, Stack AG, Fraser AD
    Eur J Rheumatol, 2017 Dec;4(4):254-259.
    PMID: 29308279 DOI: 10.5152/eurjrheum.2017.17046
    Objective: The aim of this study was to evaluate prescription practices, treatment responses, and serious adverse events of anti-tumor necrosis factor (anti-TNF) therapies in Behçet's disease (BD).

    Material and Methods: Patients with BD satisfying the International Study Group for Behçet's Disease or the International Criteria for Behçet's Disease criteria were recruited from a regional rheumatology program. The choice of anti-TNF, treatment response, and adverse events were specified. Response to treatment was evaluated by the detection of new, worsening, or improving clinical features, and management was benchmarked against current The European League against Rheumatism recommendations published in 2008.

    Results: Out of the total of 22 patients, 18 (81.9%) received anti-TNF therapies, resulting in 14 (77.8%) complete and 4 (22.2%) partial remissions. Eleven (61.1%) patients switched to a second anti-TNF, seven patients (38.9%) required three different anti-TNFs, and one required a fourth anti-TNF to achieve remission. Two patients required retrials before their disease was controlled. Anti-TNF therapy included infliximab (IFX): n=15, 83.3%; adalimumab (ADA): n=9, 50%; golimumab: n=6, 33.3%; etanercept: n=5, 27.8%; and certolizumab pegol: n=2, 11.1%. Secondary failure was observed with IFX (4/15; 26.7%) and ADA (2/9; 22.2%), and these (100%) were manifested after at least 2 years of treatment. Five patients with potentially life-threatening laryngeal involvement received anti-TNFs successfully halting disease progression. Five allergic reactions were encountered, and five serious infections were documented involving three patients aged ≥ 50 years, all with the use of IFX.

    Conclusion: Anti-TNF therapy induced a clinical response in 100% patients and achieved complete remission in 78% patients. It provides an effective alternative option for first-line therapy in severe BD where many conventional immunosuppressive therapies fail. Patients with BD who do not respond to one or more anti-TNFs because of intolerance, ineffectiveness, or secondary failure might benefit from switching to another drug from this group or even a retrial of a previously administered anti-TNF because unsatisfactory results with one biologic is not predictive of response to another anti-TNF. For those with potentially life-threatening destructive laryngeal manifestation, anti-TNF as a first choice may be considered.

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