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  1. Fulltext Performance Evaluation of Localization Accuracy for a Log-Normal Shadow Fading Wireless Sensor Network under Physical Barrier Attacks
    Hussein AA, Rahman TA, Leow CY
    Sensors (Basel), 2015;15(12):30545-70.
    PMID: 26690159 DOI: 10.3390/s151229817
    Localization is an apparent aspect of a wireless sensor network, which is the focus of much interesting research. One of the severe conditions that needs to be taken into consideration is localizing a mobile target through a dispersed sensor network in the presence of physical barrier attacks. These attacks confuse the localization process and cause location estimation errors. Range-based methods, like the received signal strength indication (RSSI), face the major influence of this kind of attack. This paper proposes a solution based on a combination of multi-frequency multi-power localization (C-MFMPL) and step function multi-frequency multi-power localization (SF-MFMPL), including the fingerprint matching technique and lateration, to provide a robust and accurate localization technique. In addition, this paper proposes a grid coloring algorithm to detect the signal hole map in the network, which refers to the attack-prone regions, in order to carry out corrective actions. The simulation results show the enhancement and robustness of RSS localization performance in the face of log normal shadow fading effects, besides the presence of physical barrier attacks, through detecting, filtering and eliminating the effect of these attacks.
  2. Fulltext Physical Layer Security Using Two-Path Successive Relaying
    Liau QY, Leow CY, Ding Z
    Sensors (Basel), 2016 Jun 09;16(6).
    PMID: 27294924 DOI: 10.3390/s16060846
    Relaying is one of the useful techniques to enhance wireless physical-layer security. Existing literature shows that employing full-duplex relay instead of conventional half-duplex relay improves secrecy capacity and secrecy outage probability, but this is at the price of sophisticated implementation. As an alternative, two-path successive relaying has been proposed to emulate operation of full-duplex relay by scheduling a pair of half-duplex relays to assist the source transmission alternately. However, the performance of two-path successive relaying in secrecy communication remains unexplored. This paper proposes a secrecy two-path successive relaying protocol for a scenario with one source, one destination and two half-duplex relays. The relays operate alternately in a time division mode to forward messages continuously from source to destination in the presence of an eavesdropper. Analytical results reveal that the use of two half-duplex relays in the proposed scheme contributes towards a quadratically lower probability of interception compared to full-duplex relaying. Numerical simulations show that the proposed protocol achieves the ergodic achievable secrecy rate of full-duplex relaying while delivering the lowest probability of interception and secrecy outage probability compared to the existing half duplex relaying, full duplex relaying and full duplex jamming schemes.
  3. Generation of soluble, disulfide-rich JEV NS1 protein recognizable by anti-NS1 antibodies through a simplified, in vitro refolding approach
    Chong HY, Leow CY, Leow CH
    Int J Biol Macromol, 2021 Aug 31;185:485-493.
    PMID: 34174313 DOI: 10.1016/j.ijbiomac.2021.06.146
    Co-existence of Japanese Encephalitis virus (JEV) with highly homologous antigenic epitopes results in antibody-based serodiagnosis being inaccurate at detecting and distinguishing JEV from other flaviviruses. This often causes misdiagnosis and inefficient treatments of flavivirus infection. Generation of JEV NS1 protein remains a challenge as it is notably expressed in the form of inactive aggregates known as inclusion bodies using bacterial expression systems. This study evaluated two trxB and gor E. coli strains in producing soluble JEV NS1 via a cold-shock expression system. High yield of JEV NS1 inclusion bodies was produced using cold-shocked expression system. Subsequently, a simplified yet successful approach in generating soluble, active JEV NS1 protein through solubilization, purification and in vitro refolding of JEV NS1 protein from inclusion bodies was developed. A step-wise dialysis refolding approach was used to facilitate JEV NS1 refolding. The authenticity of the refolded JEV NS1 was confirmed by specific antibody binding on indirect ELISA commercial anti-NS1 antibodies which showed that the refolded JEV NS1 was highly immunoreactive. This presented approach is cost-effective, and negates the need for mammalian or insect cell expression systems in order to synthesize this JEV NS1 protein of important diagnostic and therapeutic relevance in Japanese Encephalitis disease.
  4. Fulltext Robust multiple frequency multiple power localization schemes in the presence of multiple jamming attacks
    Hussein AA, Leow CY, Rahman TA
    PLoS One, 2017;12(5):e0177326.
    PMID: 28493977 DOI: 10.1371/journal.pone.0177326
    Localization of the wireless sensor network is a vital area acquiring an impressive research concern and called upon to expand more with the rising of its applications. As localization is gaining prominence in wireless sensor network, it is vulnerable to jamming attacks. Jamming attacks disrupt communication opportunity among the sender and receiver and deeply impact the localization process, leading to a huge error of the estimated sensor node position. Therefore, detection and elimination of jamming influence are absolutely indispensable. Range-based techniques especially Received Signal Strength (RSS) is facing severe impact of these attacks. This paper proposes algorithms based on Combination Multiple Frequency Multiple Power Localization (C-MFMPL) and Step Function Multiple Frequency Multiple Power Localization (SF-MFMPL). The algorithms have been tested in the presence of multiple types of jamming attacks including capture and replay, random and constant jammers over a log normal shadow fading propagation model. In order to overcome the impact of random and constant jammers, the proposed method uses two sets of frequencies shared by the implemented anchor nodes to obtain the averaged RSS readings all over the transmitted frequencies successfully. In addition, three stages of filters have been used to cope with the replayed beacons caused by the capture and replay jammers. In this paper the localization performance of the proposed algorithms for the ideal case which is defined by without the existence of the jamming attack are compared with the case of jamming attacks. The main contribution of this paper is to achieve robust localization performance in the presence of multiple jamming attacks under log normal shadow fading environment with a different simulation conditions and scenarios.
  5. Flavivirus infection-A review of immunopathogenesis, immunological response, and immunodiagnosis
    Chong HY, Leow CY, Abdul Majeed AB, Leow CH
    Virus Res, 2019 12;274:197770.
    PMID: 31626874 DOI: 10.1016/j.virusres.2019.197770
    Flaviviruses are group of single stranded RNA viruses that cause severe endemic infection and epidemics on a global scale. It presents a significant health impact worldwide and the viruses have the potential to emerge and outbreak in a non-endemic geographical region. Effective vaccines for prophylaxis are only available for several flaviviruses such as Yellow Fever virus, Tick-borne Encephalitis Virus, Dengue Virus and Japanese Encephalitis Virus and there is no antiflaviviral agent being marketed. This review discusses the flavivirus genome, replication cycle, epidemiology, clinical presentation and pathogenesis upon infection. Effective humoral response is critical to confer protective immunity against flaviviruses. Hence, we have also highlighted the immune responses elicited upon infection, various diagnostic facilities available for flaviviral disease and monoclonal antibodies available to date against flavivirus infection.
  6. Molecular characterization of Schistosoma mansoni tegument annexins and comparative analysis of antibody responses following parasite infection
    Leow CY, Willis C, Leow CH, Hofmann A, Jones M
    Mol Biochem Parasitol, 2019 12;234:111231.
    PMID: 31628972 DOI: 10.1016/j.molbiopara.2019.111231
    Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis to produce long-term protection in endemic regions. Surface-associated proteins, and in particular, those expressed in the body wall, or tegument, have been proposed as potential vaccine targets. Of these, annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the structural and immunobiochemical characterization of four homologous annexins namely annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni. Bioinformatics analysis showed that there was no signal peptide predicted for any annexin in this study. Further analysis showed that each of all four annexin protein possesses a primary structure consisting of a short but variable N-terminal region and a long C-terminal core containing four homologous annexin repeats (I-IV), which contain five alpha-helices. The life cycle expression profile of each annexin was assessed using quantitative PCR. The results showed that the overall transcript levels of the each of four homologous annexins were relatively low in the egg stage, but increased gradually after the transition of cercariae (the invasive schistosome larvae) to schistosomula (the post-invasive larvae). Circular dichroism (CD) demonstrated that rAnnexin B30, rAnnexin B5a and rAnnexin 7a were folded, showing a secondary structure content rich in alpha-helices. The membrane binding affinity was enhanced when rAnnexin B30, rAnnexin B5a and rAnnexin 7a was incubated in the presence of Ca2+. All annexin members evaluated in this study were immunolocalized to the tegument, with immunoreactivity also occurring in cells and in muscle of adult parasites. All four recombinant annexins were immunoreactive and they were recognized by the sera of mice infected with S. mansoni. In conclusion, the overall results present the molecular characterization of annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni in host-parasite interactions and strongly suggest that the molecules could be useful candidates for vaccine or diagnostic development.
  7. Fulltext Sidelobe reduction and capacity improvement of open-loop collaborative beamforming in wireless sensor networks
    Jayaprakasam S, Abdul Rahim SK, Leow CY, Ting TO
    PLoS One, 2017;12(5):e0175510.
    PMID: 28464000 DOI: 10.1371/journal.pone.0175510
    Collaborative beamforming (CBF) with a finite number of collaborating nodes (CNs) produces sidelobes that are highly dependent on the collaborating nodes' locations. The sidelobes cause interference and affect the communication rate of unintended receivers located within the transmission range. Nulling is not possible in an open-loop CBF since the collaborating nodes are unable to receive feedback from the receivers. Hence, the overall sidelobe reduction is required to avoid interference in the directions of the unintended receivers. However, the impact of sidelobe reduction on the capacity improvement at the unintended receiver has never been reported in previous works. In this paper, the effect of peak sidelobe (PSL) reduction in CBF on the capacity of an unintended receiver is analyzed. Three meta-heuristic optimization methods are applied to perform PSL minimization, namely genetic algorithm (GA), particle swarm algorithm (PSO) and a simplified version of the PSO called the weightless swarm algorithm (WSA). An average reduction of 20 dB in PSL alongside 162% capacity improvement is achieved in the worst case scenario with the WSA optimization. It is discovered that the PSL minimization in the CBF provides capacity improvement at an unintended receiver only if the CBF cluster is small and dense.
  8. Immunogenicity, antibody responses and vaccine efficacy of recombinant annexin B30 against Schistosoma mansoni
    Leow CY, Willis C, Chuah C, Leow CH, Jones M
    Parasite Immunol., 2020 03;42(3):e12693.
    PMID: 31880816 DOI: 10.1111/pim.12693
    AIMS: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of individuals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model.

    METHODS AND RESULTS: Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected.

    CONCLUSION: Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.

  9. Fulltext Diagnostic and therapeutic potential of shark variable new antigen receptor (VNAR) single domain antibody
    Cheong WS, Leow CY, Abdul Majeed AB, Leow CH
    Int J Biol Macromol, 2020 Mar 15;147:369-375.
    PMID: 31926922 DOI: 10.1016/j.ijbiomac.2020.01.039
    Conventional monoclonal antibodies (mAbs) have been widely used in research and diagnostic applications due to their high affinity and specificity. However, multiple limitations, such as large size, complex structure and sensitivity to extreme ambient temperature potentially weaken the performance of mAbs in certain applications. To address this problem, the exploration of new antigen binders is extensively required in relation to improve the quality of current diagnostic platforms. In recent years, a new immunoglobulin-based protein, namely variable domain of new antigen receptor (VNAR) was discovered in sharks. Unlike conventional mAbs, several advantages of VNARs, include small size, better thermostability and peculiar paratope structure have attracted interest of researchers to further explore on it. This article aims to first present an overview of the shark VNARs and outline the characteristics as an outstanding new reagent for diagnostic and therapeutic applications.
  10. Exploring shark VNAR antibody against infectious diseases using phage display technology
    Lim HT, Kok BH, Leow CY, Leow CH
    Fish Shellfish Immunol, 2023 Sep;140:108986.
    PMID: 37541634 DOI: 10.1016/j.fsi.2023.108986
    Antibody with high affinity and specificity to antigen has widely used as a tool to combat various diseases. The variable domain of immunoglobulin new antigen receptor (VNAR) naturally found in shark contains autonomous function as single-domain antibody. Due to its excellent characteristics, the small, non-complex, and highly stable have made shark VNAR can acquires the antigen-binding capability that might not be reached by conventional antibody. Phage display technology enables shark VNAR to be presented on the surface of phage, allowing the exploration of shark VNAR as an alternative antibody format to target antigens from various infectious diseases. The application of phage-displayed shark VNAR in antibody library and biopanning eventually leads to the discovery and isolation of antigen-specific VNARs with diagnostic and therapeutic potential towards infectious diseases. This review provides an overview of the shark VNAR antibody, the types of phage display technology with comparison to the other types of display system, as well as the application and case studies of phage-displayed shark VNAR antibodies against infectious diseases.
  11. Fulltext Structure-function analysis of apical membrane-associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control
    Leow CY, Willis C, Hofmann A, Jones MK
    Br J Pharmacol, 2015 Apr;172(7):1653-63.
    PMID: 25176442 DOI: 10.1111/bph.12898
    Neglected tropical diseases are a group of some 17 diseases that afflict poor and predominantly rural people in developing nations. One significant disease that contributes to substantial morbidity in endemic areas is schistosomiasis, caused by infection with one of five species of blood fluke belonging to the trematode genus Schistosoma. Although there is one drug available for treatment of affected individuals in clinics, or for mass administration in endemic regions, there is a need for new therapies. A prominent target organ of schistosomes, either for drug or vaccine development, is the peculiar epithelial syncytium that forms the body wall (tegument) of this parasite. This dynamic layer is maintained and organized by concerted activity of a range of proteins, among which are the abundant tegumentary annexins. In this review, we will outline advances in structure-function analyses of these annexins, as a means to understanding tegument cell biology in host-parasite interaction and their potential exploitation as targets for anti-schistosomiasis therapies.
  12. Fulltext Two-Stage Design Method for Enhanced Inductive Energy Transmission with Q-Constrained Planar Square Loops
    Eteng AA, Abdul Rahim SK, Leow CY, Chew BW, Vandenbosch GA
    PLoS One, 2016;11(2):e0148808.
    PMID: 26890878 DOI: 10.1371/journal.pone.0148808
    Q-factor constraints are usually imposed on conductor loops employed as proximity range High Frequency Radio Frequency Identification (HF-RFID) reader antennas to ensure adequate data bandwidth. However, pairing such low Q-factor loops in inductive energy transmission links restricts the link transmission performance. The contribution of this paper is to assess the improvement that is reached with a two-stage design method, concerning the transmission performance of a planar square loop relative to an initial design, without compromise to a Q-factor constraint. The first stage of the synthesis flow is analytical in approach, and determines the number and spacing of turns by which coupling between similar paired square loops can be enhanced with low deviation from the Q-factor limit presented by an initial design. The second stage applies full-wave electromagnetic simulations to determine more appropriate turn spacing and widths to match the Q-factor constraint, and achieve improved coupling relative to the initial design. Evaluating the design method in a test scenario yielded a more than 5% increase in link transmission efficiency, as well as an improvement in the link fractional bandwidth by more than 3%, without violating the loop Q-factor limit. These transmission performance enhancements are indicative of a potential for modifying proximity HF-RFID reader antennas for efficient inductive energy transfer and data telemetry links.
  13. Fulltext Compact circularly polarized truncated square ring slot antenna with suppressed higher resonances
    Sabran MI, Abdul Rahim SK, Leow CY, Soh PJ, Chew BW, Vandenbosch GA
    PLoS One, 2017;12(2):e0172162.
    PMID: 28192504 DOI: 10.1371/journal.pone.0172162
    This paper presents a compact circularly polarized (CP) antenna with an integrated higher order harmonic rejection filter. The proposed design operates within the ISM band of 2.32 GHz- 2.63 GHz and is suitable for example for wireless power transfer applications. Asymmetrical truncated edges on a square ring create a defected ground structure to excite the CP property, simultaneously realizing compactness. It offers a 50.5% reduced patch area compared to a conventional design. Novel stubs and slot shapes are integrated in the transmission line to reduce higher (up to the third) order harmonics. The proposed prototype yields a -10 dB reflection coefficient (S11) impedance bandwidth of 12.53%, a 3 dB axial ratio bandwidth of 3.27%, and a gain of 5.64 dBi. Measurements also show good agreement with simulations.
  14. Isolation and characterization of a novel anti-salbutamol chicken scFv for human doping urinalysis
    Lee W, Syed A A, Leow CY, Tan SC, Leow CH
    Anal Biochem, 2018 08 15;555:81-93.
    PMID: 29775561 DOI: 10.1016/j.ab.2018.05.009
    Anti-salbutamol antibodies remain as important tools for the detection of salbutamol abuse in athletic doping. This study evaluated the feasibility and efficiency of the chicken (Gallus gallus domesticus) as an immunization host to generate anti-salbutamol scFv antibodies by phage display. A phage display antibody library was constructed from a single chicken immunized against salbutamol-KLH conjugate. After a stringent biopanning strategy, a novel scFv clone which was inhibited by free salbutamol recorded the highest affinity. This scFv was expressed as soluble and functional protein in Escherichia coli T7 SHuffle Express B (DE3) strain. Cross-reactivity studies of the scFv towards other relevant β2-agonists revealed that the scFv cross-reacted significantly towards clenbuterol. The determined IC50 of the scFv towards the two β2-agonists were; IC50 salbutamol = ∼0.310 μg/ml, IC50 clenbuterol = ∼0.076 μg/ml. The generated scFv demonstrated poor stability based on accelerated stability studies. The scFv was used to develop an competitive indirect ELISA (LOD = 0.125 μg/ml) for detection of parent salbutamol in spiked human urine (n = 18) with ∼83.4% reliability at the cut-off of 1 μg/ml currently implemented by WADA and may be of potential use in human doping urinalysis.
  15. Schistosomiasis in Malaysia: A review
    Chuah C, Gobert GN, Latif B, Heo CC, Leow CY
    Acta Trop, 2019 Feb;190:137-143.
    PMID: 30448471 DOI: 10.1016/j.actatropica.2018.11.012
    Schistosomiasis, a neglected tropical parasitic disease caused by the trematode flatworms of the genus Schistosoma, affects approximately 207 million people worldwide. Among the five main species infecting humans, Schistosoma mansoni and S. japonicum are responsible for the majority of hepatointestinal schistosomiasis. Human settlements near fresh water sites that lack proper sanitary systems often contribute to the transmission of disease. This risk particularly impacts on travellers or immigrants who come into contact with larvae-contaminated water. This review discusses the central features of schistosomiasis; including clinical manifestations, diagnosis, treatments, and the preventive measures available for the control of this disease. The description of the Malaysian schistosome species Schistosoma malayensis and the current status of schistosomiasis in Malaysia including the compilation of cases diagnosed from 1904 to 2015 are also discussed in this paper.
  16. Differential expression of cytokine genes in THP-1-derived macrophages infected with mild and virulence strains of Shigella flexneri 2a
    Shabani NRM, Mokhtar M, Leow CH, Lean QY, Chuah C, Singh KKB, et al.
    Infect Genet Evol, 2020 11;85:104532.
    PMID: 32911076 DOI: 10.1016/j.meegid.2020.104532
    Shigella is an intracellular bacterial pathogen that causes bacterial dysentery called shigellosis. The assessment of pro- and anti-inflammatory mediators produced by immune cells against this bacteria are vital in identifying the effectiveness of the immune reaction in protecting the host. In Malaysia, Shigella is ranked as the third most common bacteria causing diarrheal disease among children below 5 years old. In the present study, we aim to examine the differential cytokine gene expressions of macrophages in response to two types of clinical strains of Shigella flexneri 2a (S. flexneri 2a) isolated from patients admitted in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. THP-1-derived macrophages, as the model of human macrophages, were infected separately with S. flexneri 2a mild (SH062) and virulence (SH057) strains for 6, 12, and 24 h, respectively. The gene expression level of inflammatory mediators was identified using real-time quantitative polymerase chain reaction (RT-qPCR). The production of nitric oxide (NO) by the macrophages was measured by using a commercialized NO assay kit. The ability of macrophages to kill the intracellular bacteria was assessed by intracellular killing assay. Induction of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, IL-12, inducible NO synthase (iNOS), and NO, confirmed the pro-inflammatory reaction of the THP-1-derived macrophages in response to S. flexneri 2a, especially against the SH507 strain. The SH057 also induced a marked increase in the expression levels of the anti-inflammatory cytokine mRNAs at 12 h and 24 h post-infection. In the intracellular killing assay, both strains showed less viable, indicating the generation of pro-inflammatory cytokines in the presence of iNOS and NO was crucial in the stimulation of macrophages for the host defense against shigellosis. Transcription analysis of THP-1-derived macrophages in this study identifies differentially expressed cytokine genes that correlated with the virulence factor of S. flexneri 2a.
  17. Application of Reverse Vaccinology and Immunoinformatic Strategies for the Identification of Vaccine Candidates Against Shigella flexneri
    Leow CY, Chuah C, Abdul Majeed AB, Mohd Nor N, Leow CH
    Methods Mol Biol, 2022;2414:17-35.
    PMID: 34784029 DOI: 10.1007/978-1-0716-1900-1_2
    Reverse vaccinology (RV) was first introduced by Rappuoli for the development of an effective vaccine against serogroup B Neisseria meningitidis (MenB). With the advances in next generation sequencing technologies, the amount of genomic data has risen exponentially. Since then, the RV approach has widely been used to discover potential vaccine protein targets by screening whole genome sequences of pathogens using a combination of sophisticated computational algorithms and bioinformatic tools. In contrast to conventional vaccine development strategies, RV offers a novel method to facilitate rapid vaccine design and reduces reliance on the traditional, relatively tedious, and labor-intensive approach based on Pasteur"s principles of isolating, inactivating, and injecting the causative agent of an infectious disease. Advances in biocomputational techniques have remarkably increased the significance for the rapid identification of the proteins that are secreted or expressed on the surface of pathogens. Immunogenic proteins which are able to induce the immune response in the hosts can be predicted based on the immune epitopes present within the protein sequence. To date, RV has successfully been applied to develop vaccines against a variety of infectious pathogens. In this chapter, we apply a pipeline of bioinformatic programs for identification of Shigella flexneri potential vaccine candidates as an illustration immunoinformatic tools available for RV.
  18. Fulltext Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design
    Kazi A, Chuah C, Majeed ABA, Leow CH, Lim BH, Leow CY
    Pathog Glob Health, 2018 05;112(3):123-131.
    PMID: 29528265 DOI: 10.1080/20477724.2018.1446773
    Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.
  19. Fulltext Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants
    Campos DMO, Silva MKD, Barbosa ED, Leow CY, Fulco UL, Oliveira JIN
    Comput Biol Chem, 2022 Dec;101:107754.
    PMID: 36037724 DOI: 10.1016/j.compbiolchem.2022.107754
    The current COVID-19 pandemic, an infectious disease caused by the novel coronavirus (SARS-CoV-2), poses a threat to global health because of its high rate of spread and death. Currently, vaccination is the most effective method to prevent the spread of this disease. In the present study, we developed a novel multiepitope vaccine against SARS-CoV-2 containing Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (BA.1) variants. To this end, we performed a robust immunoinformatics approach based on multiple epitopes of the four structural proteins of SARS-CoV-2 (S, M, N, and E) from 475 SARS-CoV-2 genomes sequenced from the regions with the highest number of registered cases, namely the United States, India, Brazil, France, Germany, and the United Kingdom. To investigate the best immunogenic epitopes for linear B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL), we evaluated antigenicity, allergenicity, conservation, immunogenicity, toxicity, human population coverage, IFN-inducing, post-translational modifications, and physicochemical properties. The tertiary structure of a vaccine prototype was predicted, refined, and validated. Through docking experiments, we evaluated its molecular coupling to the key immune receptor Toll-Like Receptor 3 (TLR3). To improve the quality of docking calculations, quantum mechanics/molecular mechanics calculations (QM/MM) were used, with the QM part of the simulations performed using the density functional theory formalism (DFT). Cloning and codon optimization were performed for the successful expression of the vaccine in E. coli. Finally, we investigated the immunogenic properties and immune response of our SARS-CoV-2 multiepitope vaccine. The results of the simulations show that administering our prototype three times significantly increases the antibody response and decreases the amount of antigens. The proposed vaccine candidate should therefore be tested in clinical trials for its efficacy in neutralizing SARS-CoV-2.
  20. Advances in research on schistosomiasis and toxoplasmosis in China: A bibliometric analysis of Chinese academic journals published from 1980 to 2021
    Tao Y, Shen C, Zhang Y, Zhao X, Leow CY, Wu J, et al.
    Acta Trop, 2023 Feb;238:106783.
    PMID: 36455636 DOI: 10.1016/j.actatropica.2022.106783
    BACKGROUND: The scale-up of zoonoses prevention control and eradication in China, coupled with numerous academic articles in Chinese journals has led to the development of new tools and strategies aimed at further consolidating parasite control goals. As a result, there is a growing need for an up-to-date understanding of the research progress and prevention and control experience of parasitic diseases in China.

    METHODS: To understand the research status of schistosomiasis and toxoplasmosis in China, academic articles published in Chinese journals from 1980 to 2021 were retrieved from China National Knowledge Infrastructure (CNKI) and Wanfang databases. The Bibliographic Items Co-occurrence Matrix Builder (BICOMB) software was used to extract and analyze the keyword frequencies. The 'K/A ratio' as the frequency of a keyword that occurred in all the articles within a certain time stage was calculated to compare the popularity of the same keyword in different time stages. Keyword co-occurrence network maps were constructed by VOSviewer software.

    RESULTS: A total of 18,508 articles in the research field of Schistosoma and 13,289 articles in the field of Toxoplasma gondii were included. Results in both fields showed some similarities: the annual number of articles presented an increasing trend before entering the 21st century and decreased rapidly in recent years. Two opposite changing trends of keyword frequency could be observed in the K/A ratio analysis: the K/A ratios of 'Surveillance' and 'Infection' continuously increased over time, while those of 'Schistosoma mansoni' and 'Mesenteric lymph nodes' decreased. The diversification of keyword co-occurrence networks could be observed in the co-occurrence network maps.

    CONCLUSIONS: This bibliometric analysis reveals trends in research themes in the fields of Schistosoma and Toxoplasma gondii from 1980 to 2021, presenting China's experience such as a high degree of government involvement and multidisciplinary participation in schistosomiasis and toxoplasmosis control and elimination.

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