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  1. Woon KL, Chong ZX, Ariffin A, Chan CS
    J Mol Graph Model, 2021 06;105:107891.
    PMID: 33765526 DOI: 10.1016/j.jmgm.2021.107891
    Fused tricyclic organic compounds are an important class of organic electronic materials. In designing molecules for organic electronics, knowing what chemical structure that be used to tune the molecular property is one of the keys that can help to improve the material performance. In this research, we applied machine learning and data analytic approaches in addressing this problem. The energy states (Lowest Unoccupied Molecular Orbital (HOMO), Highest Occupied Molecular Orbitals (LUMO), singlet (Es) and triplet (ET) energy) of more than 10 thousand fused tricyclics are calculated. Corresponding descriptors are also generated. We find that the Coulomb matrix is a poorer descriptor than high-level descriptors in a multilayer perceptron neural network. Correlations as high as 0.95 is obtained using a multilayer perceptron neural network with Mean Absolute Error as low as 0.08 eV. The descriptors that are important in tuning the energy levels are revealed using the Random Forest algorithm. Correlations of such descriptors are also plotted. We found that the higher the number of tertiary amines, the deeper are the HOMO and LUMO levels. The presence of NN in the aromatic rings can be used to tune the ES. However, there is no single dominant descriptor that can be correlated with the ET. A collection of descriptors is found to give a far better correlation with ET. This research demonstrated that machine learning and data analytics in guiding how certain chemical substructures correlate with the molecule energy states.
  2. 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.

  3. Belduz AO, Canakci S, Chan KG, Kahar UM, Chan CS, Yaakop AS, et al.
    Stand Genomic Sci, 2015;10:70.
    PMID: 26413199 DOI: 10.1186/s40793-015-0065-2
    Species of Anoxybacillus are thermophiles and, therefore, their enzymes are suitable for many biotechnological applications. Anoxybacillus ayderensis AB04(T) (= NCIMB 13972(T) = NCCB 100050(T)) was isolated from the Ayder hot spring in Rize, Turkey, and is one of the earliest described Anoxybacillus type strains. The present work reports the cellular features of A. ayderensis AB04(T), together with a high-quality draft genome sequence and its annotation. The genome is 2,832,347 bp long (74 contigs) and contains 2,895 protein-coding sequences and 103 RNA genes including 14 rRNAs, 88 tRNAs, and 1 tmRNA. Based on the genome annotation of strain AB04(T), we identified genes encoding various glycoside hydrolases that are important for carbohydrate-related industries, which we compared with those of other, sequenced Anoxybacillus spp. Insights into under-explored industrially applicable enzymes and the possible applications of strain AB04(T) were also described.
  4. Wan Hassan WN, Abu Kassim NL, Jhawar A, Shurkri NM, Kamarul Baharin NA, Chan CS
    Am J Orthod Dentofacial Orthop, 2016 Apr;149(4):567-78.
    PMID: 27021461 DOI: 10.1016/j.ajodo.2015.10.018
    In this article, we present an evaluation of user acceptance of our innovative hand-gesture-based touchless sterile system for interaction with and control of a set of 3-dimensional digitized orthodontic study models using the Kinect motion-capture sensor (Microsoft, Redmond, Wash).
  5. Poli A, Nicolaus B, Chan KG, Kahar UM, Chan CS, Goh KM
    Genome Announc, 2015;3(3).
    PMID: 25999577 DOI: 10.1128/genomeA.00490-15
    Anoxybacillus thermarum AF/04(T) was isolated from the Euganean hot springs in Abano Terme, Italy. The present work reports a high-quality draft genome sequence of strain AF/04(T). This work also provides useful insights into glycoside hydrolases, glycoside transferases, and sugar transporters that may be involved in cellular carbohydrate metabolism.
  6. Goh KM, Chan KG, Yaakop AS, Chan CS, Ee R, Tan WS, et al.
    Genome Announc, 2015;3(3).
    PMID: 25999554 DOI: 10.1128/genomeA.00512-15
    Jeotgalibacillus soli, a bacterium capable of degrading N-acyl homoserine lactone, was isolated from a soil sample in Portugal. J. soli constitutes the only Jeotgalibacillus species isolated from a non-marine source. Here, the draft genome, several interesting glycosyl hydrolases, and its putative N-acyl homoserine lactonases are presented.
  7. Yaakop AS, Chan CS, Kahar UM, Ee R, Chan KG, Goh KM
    Genome Announc, 2015;3(3).
    PMID: 25977433 DOI: 10.1128/genomeA.00457-15
    Erythrobacter vulgaris strain O1, a moderate halophile, was isolated from a beach in Johor, Malaysia. Here, we present the draft genome and suggest potential applications of this bacterium.
  8. Chan CS, Chan KG, Tay YL, Chua YH, Goh KM
    Front Microbiol, 2015;6:177.
    PMID: 25798135 DOI: 10.3389/fmicb.2015.00177
    The Sungai Klah (SK) hot spring is the second hottest geothermal spring in Malaysia. This hot spring is a shallow, 150-m-long, fast-flowing stream, with temperatures varying from 50 to 110°C and a pH range of 7.0-9.0. Hidden within a wooded area, the SK hot spring is continually fed by plant litter, resulting in a relatively high degree of total organic content (TOC). In this study, a sample taken from the middle of the stream was analyzed at the 16S rRNA V3-V4 region by amplicon metagenome sequencing. Over 35 phyla were detected by analyzing the 16S rRNA data. Firmicutes and Proteobacteria represented approximately 57% of the microbiome. Approximately 70% of the detected thermophiles were strict anaerobes; however, Hydrogenobacter spp., obligate chemolithotrophic thermophiles, represented one of the major taxa. Several thermophilic photosynthetic microorganisms and acidothermophiles were also detected. Most of the phyla identified by 16S rRNA were also found using the shotgun metagenome approaches. The carbon, sulfur, and nitrogen metabolism within the SK hot spring community were evaluated by shotgun metagenome sequencing, and the data revealed diversity in terms of metabolic activity and dynamics. This hot spring has a rich diversified phylogenetic community partly due to its natural environment (plant litter, high TOC, and a shallow stream) and geochemical parameters (broad temperature and pH range). It is speculated that symbiotic relationships occur between the members of the community.
  9. Lee LS, Goh KM, Chan CS, Annie Tan GY, Yin WF, Chong CS, et al.
    Microbiologyopen, 2018 12;7(6):e00615.
    PMID: 29602271 DOI: 10.1002/mbo3.615
    The ability of thermophilic microorganisms and their enzymes to decompose biomass have attracted attention due to their quick reaction time, thermostability, and decreased risk of contamination. Exploitation of efficient thermostable glycoside hydrolases (GHs) could accelerate the industrialization of biofuels and biochemicals. However, the full spectrum of thermophiles and their enzymes that are important for biomass degradation at high temperatures have not yet been thoroughly studied. We examined a Malaysian Y-shaped Sungai Klah hot spring located within a wooded area. The fallen foliage that formed a thick layer of biomass bed under the heated water of the Y-shaped Sungai Klah hot spring was an ideal environment for the discovery and analysis of microbial biomass decay communities. We sequenced the hypervariable regions of bacterial and archaeal 16S rRNA genes using total community DNA extracted from the hot spring. Data suggested that 25 phyla, 58 classes, 110 orders, 171 families, and 328 genera inhabited this hot spring. Among the detected genera, members of Acidimicrobium, Aeropyrum, Caldilinea, Caldisphaera, Chloracidobacterium, Chloroflexus, Desulfurobacterium, Fervidobacterium, Geobacillus, Meiothermus, Melioribacter, Methanothermococcus, Methanotorris, Roseiflexus, Thermoanaerobacter, Thermoanaerobacterium, Thermoanaerobaculum, and Thermosipho were the main thermophiles containing various GHs that play an important role in cellulose and hemicellulose breakdown. Collectively, the results suggest that the microbial community in this hot spring represents a good source for isolating efficient biomass degrading thermophiles and thermozymes.
  10. Wan Hassan WN, Othman SA, Chan CS, Ahmad R, Ali SN, Abd Rohim A
    Am J Orthod Dentofacial Orthop, 2016 Nov;150(5):886-895.
    PMID: 27871715 DOI: 10.1016/j.ajodo.2016.04.021
    INTRODUCTION: In this study we aimed to compare measurements on plaster models using a digital caliper, and on 3-dimensional (3D) digital models, produced using a structured-light scanner, using 3D software.

    METHODS: Fifty digital models were scanned from the same plaster models. Arch and tooth size measurements were made by 2 operators, twice. Calibration was done on 10 sets of models and checked using the Pearson correlation coefficient. Data were analyzed by error variances, repeatability coefficient, repeated-measures analysis of variance, and Bland-Altman plots.

    RESULTS: Error variances ranged between 0.001 and 0.044 mm for the digital caliper method, and between 0.002 and 0.054 mm for the 3D software method. Repeated-measures analysis of variance showed small but statistically significant differences (P <0.05) between the repeated measurements in the arch and buccolingual planes (0.011 and 0.008 mm, respectively). There were no statistically significant differences between methods and between operators. Bland-Altman plots showed that the mean biases were close to zero, and the 95% limits of agreement were within ±0.50 mm. Repeatability coefficients for all measurements were similar.

    CONCLUSIONS: Measurements made on models scanned by the 3D structured-light scanner were in good agreement with those made on conventional plaster models and were, therefore, clinically acceptable.

  11. Massello FL, Chan CS, Chan KG, Goh KM, Donati E, Urbieta MS
    Microorganisms, 2020 Jun 16;8(6).
    PMID: 32560103 DOI: 10.3390/microorganisms8060906
    The study of microbial communities from extreme environments is a fascinating topic. With every study, biologists and ecologists reveal interesting facts and questions that dispel the old belief that these are inhospitable environments. In this work, we assess the microbial diversity of three hot springs from Neuquén, Argentina, using high-throughput amplicon sequencing. We predicted a distinct metabolic profile in the acidic and the circumneutral samples, with the first ones being dominated by chemolithotrophs and the second ones by chemoheterotrophs. Then, we collected data of the microbial communities of hot springs around the world in an effort to comprehend the roles of pH and temperature as shaping factors. Interestingly, there was a covariation between both parameters and the phylogenetic distance between communities; however, neither of them could explain much of the microbial profile in an ordination model. Moreover, there was no correlation between alpha diversity and these parameters. Therefore, the microbial communities' profile seemed to have complex shaping factors beyond pH and temperature. Lastly, we looked for taxa associated with different environmental conditions. Several such taxa were found. For example, Hydrogenobaculum was frequently present in acidic springs, as was the Sulfolobaceae family; on the other hand, Candidatus Hydrothermae phylum was strongly associated with circumneutral conditions. Interestingly, some singularities related to sites featuring certain taxa were also observed.
  12. Chan CS, Sin LL, Chan KG, Shamsir MS, Manan FA, Sani RK, et al.
    Biotechnol Biofuels, 2016;9(1):174.
    PMID: 27555880 DOI: 10.1186/s13068-016-0587-x
    In general, biofuel production involves biomass pretreatment and enzymatic saccharification, followed by the subsequent sugar conversion to biofuel via fermentation. The crucial step in the production of biofuel from biomass is the enzymatic saccharification. Many of the commercial cellulase enzyme cocktails, such as Spezyme(®) CP (Genencor), Acellerase™ 1000 (Genencor), and Celluclast(®) 1.5L (Novozymes), are ineffectively to release free glucose from the pretreated biomass without additional β-glucosidase.
  13. Pang T, Wong JHD, Ng WL, Chan CS, Wang C, Zhou X, et al.
    Phys Med Biol, 2024 Feb 19.
    PMID: 38373345 DOI: 10.1088/1361-6560/ad2a95
    OBJECTIVE: Generally, due to a lack of explainability, radiomics based on deep learning has been perceived as a black-box solution for radiologists. Automatic generation of diagnostic reports is a semantic approach to enhance the explanation of deep learning radiomics (DLR).

    APPROACH: In this paper, we propose a novel model called radiomics-reporting network (Radioport), which incorporates text attention. This model aims to improve the interpretability of deep learning radiomics in mammographic calcification diagnosis. Firstly, it employs convolutional neural networks (CNN) to extract visual features as radiomics for multi-category classification based on Breast Imaging Reporting and Data System (BI-RADS). Then, it builds a mapping between these visual features and textual features to generate diagnostic reports, incorporating an attention module for improved clarity.

    MAIN RESULTS: To demonstrate the effectiveness of our proposed model, we conducted experiments on a breast calcification dataset comprising mammograms and diagnostic reports. The results demonstrate that our model can: (i) semantically enhance the interpretability of deep learning radiomics; and, (ii) improve the readability of generated medical reports.

    SIGNIFICANCE: Our interpretable textual model can explicitly simulate the mammographic calcification diagnosis process.

  14. 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.

  15. Willis Poratti G, Yaakop AS, Chan CS, Urbieta MS, Chan KG, Ee R, et al.
    Genome Announc, 2016;4(4).
    PMID: 27540078 DOI: 10.1128/genomeA.00870-16
    Desulfotomaculum copahuensis strain CINDEFI1 is a novel spore-forming sulfate-reducing bacterium isolated from the Copahue volcano area, Argentina. Here, we present its draft genome in which we found genes related with the anaerobic respiration of sulfur compounds similar to those present in the Copahue environment.
  16. Chan CS, Chan KG, Ee R, Hong KW, Urbieta MS, Donati ER, et al.
    Front Microbiol, 2017;8:1252.
    PMID: 28729863 DOI: 10.3389/fmicb.2017.01252
    Malaysia has a great number of hot springs, especially along the flank of the Banjaran Titiwangsa mountain range. Biological studies of the Malaysian hot springs are rare because of the lack of comprehensive information on their microbial communities. In this study, we report a cultivation-independent census to describe microbial communities in six hot springs. The Ulu Slim (US), Sungai Klah (SK), Dusun Tua (DT), Sungai Serai (SS), Semenyih (SE), and Ayer Hangat (AH) hot springs exhibit circumneutral pH with temperatures ranging from 43°C to 90°C. Genomic DNA was extracted from environmental samples and the V3-V4 hypervariable regions of 16S rRNA genes were amplified, sequenced, and analyzed. High-throughput sequencing analysis showed that microbial richness was high in all samples as indicated by the detection of 6,334-26,244 operational taxonomy units. In total, 59, 61, 72, 73, 65, and 52 bacterial phyla were identified in the US, SK, DT, SS, SE, and AH hot springs, respectively. Generally, Firmicutes and Proteobacteria dominated the bacterial communities in all hot springs. Archaeal communities mainly consisted of Crenarchaeota, Euryarchaeota, and Parvarchaeota. In beta diversity analysis, the hot spring microbial memberships were clustered primarily on the basis of temperature and salinity. Canonical correlation analysis to assess the relationship between the microbial communities and physicochemical variables revealed that diversity patterns were best explained by a combination of physicochemical variables, rather than by individual abiotic variables such as temperature and salinity.
  17. 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.

  18. Rajendran S, Lim JH, Yogalingam K, Kallarakkal TG, Zain RB, Jayasinghe RD, et al.
    Oral Dis, 2023 Jul;29(5):2230-2238.
    PMID: 35398971 DOI: 10.1111/odi.14206
    OBJECTIVE: To describe the development of a platform for image collection and annotation that resulted in a multi-sourced international image dataset of oral lesions to facilitate the development of automated lesion classification algorithms.

    MATERIALS AND METHODS: We developed a web-interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web-interface for systematic annotation of images to build a rich clinically labelled dataset. We evaluated the sensitivities comparing referral decisions through the annotation process with the clinical diagnosis of the lesions.

    RESULTS: The image repository hosts 2474 images of oral lesions consisting of oral cancer, oral potentially malignant disorders and other oral lesions that were collected through MeMoSA® UPLOAD. Eight-hundred images were annotated by seven oral medicine specialists on MeMoSA® ANNOTATE, to mark the lesion and to collect clinical labels. The sensitivity in referral decision for all lesions that required a referral for cancer management/surveillance was moderate to high depending on the type of lesion (64.3%-100%).

    CONCLUSION: This is the first description of a database with clinically labelled oral lesions. This database could accelerate the improvement of AI algorithms that can promote the early detection of high-risk oral lesions.

  19. Ariffin H, Hainaut P, Puzio-Kuter A, Choong SS, Chan AS, Tolkunov D, et al.
    Proc Natl Acad Sci U S A, 2014 Oct 28;111(43):15497-501.
    PMID: 25313051 DOI: 10.1073/pnas.1417322111
    The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations. To address the genetic basis of phenotypic disparities of LFS/LFL, we performed whole-genome sequencing (WGS) of 13 subjects from two generations of an LFS kindred. Neither de novo CNV nor significant difference in total CNV was detected in relation with successive generations or with age at cancer onset. These observations were consistent with an experimental mouse model system showing that trp53 deficiency in the germ line of father or mother did not increase CNV occurrence in the offspring. On the other hand, individual records on 1,771 TP53 mutation carriers from 294 pedigrees were compiled to assess genetic anticipation patterns (International Agency for Research on Cancer TP53 database). No strictly defined anticipation pattern was observed. Rather, in multigeneration families, cancer onset was delayed in older compared with recent generations. These observations support an alternative model for apparent anticipation in which rare variants from noncarrier parents may attenuate constitutive resistance to tumorigenesis in the offspring of TP53 mutation carriers with late cancer onset.
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