Displaying publications 1 - 20 of 23 in total

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  1. Abdelrasoul M, El-Fattah AA, Kotry G, Ramadan O, Essawy M, Kamaldin J, et al.
    Oral Dis, 2023 Nov;29(8):3583-3598.
    PMID: 35839150 DOI: 10.1111/odi.14314
    BACKGROUND: Periodontal regenerative therapy using bone-substituting materials has gained favorable clinical significance in enhancing osseous regeneration. These materials should be biocompatible, osteogenic, malleable, and biodegradable. This study assessed the periodontal regenerative capacity of a novel biodegradable bioactive hydrogel template of organic-inorganic composite loaded with melatonin.

    MATERIALS AND METHODS: A melatonin-loaded alginate-chitosan/beta-tricalcium phosphate composite hydrogel was successfully prepared and characterized. Thirty-six critical-sized bilateral class II furcation defects were created in six Mongrel dogs, and were randomly divided and allocated to three cohorts; sham, unloaded composite, and melatonin-loaded. Periodontal regenerative capacity was evaluated via histologic and histomorphometric analysis.

    RESULTS: Melatonin-treated group showed accelerated bone formation and advanced maturity, with a significant twofold increase in newly formed inter-radicular bone compared with the unloaded composite. The short-term regenerative efficacy was evident 4 weeks postoperatively as a significant increase in cementum length concurrent with reduction of entrapped epithelium. After 8 weeks, the scaffold produced a quality of newly synthesized bone similar to normal compact bone, with potent periodontal ligament attachment.

    CONCLUSIONS: Melatonin-loaded hydrogel template accelerated formation and enhanced quality of newly formed bone, allowing complete periodontal regeneration. Furthermore, the scaffold prevented overgrowth and entrapment of epithelial cells in furcation defects.

  2. Abdullah Zubir AZ, Whawell SA, Wong TS, Khurram SA
    Oral Dis, 2020 Nov;26(8):1668-1676.
    PMID: 32562323 DOI: 10.1111/odi.13500
    BACKGROUND: The expression of XCR1 receptor and its metamorphic ligand lymphotactin (hLtn) has been shown in cancers but their precise role in tumorigenesis is poorly understood including the significance of the physiologically existing hLtn monomeric (CC3) and dimeric (W55D) confirmations where the latter thought to function as the receptor antagonist. The aim of this study was to explore the functional role of bioengineered hLtn variants and the role of fibroblasts in XCR1/hLtn expression regulation in oral cancer cells (OCCL).

    MATERIAL AND METHODS: qRT-PCR and flow cytometry were performed to evaluate mRNA and protein expression of XCR1 and hLtn. Recombinant hLtn variants (wild-type, CC3 and W55D mutant) were designed, expressed, purified and evaluated using proliferation, adhesion and chemotaxis assays. XCR1 and hLtn expression regulation by fibroblasts was determined using indirect co-culture. XCR1 and hLtn expression in primary and metastatic OSCC tissue was assessed using immunohistochemistry.

    RESULTS: hLtn caused a significant decrease in OCCL XCR1 surface protein expression. hLtn CC3 mutant was highly functional facilitating proliferation and migration. Conditioned media from primary cancer-associated and senescent fibroblasts significantly upregulated XCR1 and hLtn mRNA expression in OCCL. Immunohistochemistry revealed higher XCR1 and hLtn expression in metastatic tumour deposits and surrounding stroma compared to primary OSCC tissue.

    CONCLUSIONS: The development of hLtn biological mutants, regulation of XCR1 expression by its ligand hLtn and crosstalk with fibroblasts are novel findings suggesting an important role for the XCR1/hLtn axis within the OSCC tumour microenvironment. These discoveries build upon previous studies and suggest that the hLtn/XCR1 axis has a significant role in stromal crosstalk and OSCC progression.

  3. Bologna-Molina R, Schuch L, Magliocca K, van Heerden W, Robinson L, Bilodeau EA, et al.
    Oral Dis, 2024 May 01.
    PMID: 38693620 DOI: 10.1111/odi.14962
    Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.
  4. Ghani WMN, Razak IA, Doss JG, Yang YH, Rahman ZAA, Ismail SM, et al.
    Oral Dis, 2019 Mar;25(2):447-455.
    PMID: 30350902 DOI: 10.1111/odi.12995
    OBJECTIVE: To elucidate ethnic variations in the practice of oral cancer risk habits in a selected Malaysian population.

    METHODS: This retrospective case-control study involves 790 cases of cancers of the oral cavity and 450 controls presenting with non-malignant oral diseases, recruited from seven hospital-based centres nationwide. Data on risk habits (smoking, drinking, chewing) were obtained using a structured questionnaire via face-to-face interviews. Multiple logistic regression was used to determine association between risk habits and oral cancer risk; chi-square test was used to assess association between risk habits and ethnicity. Population attributable risks were calculated for all habits.

    RESULTS: Except for alcohol consumption, increased risk was observed for all habits; the highest risk was for smoking + chewing + drinking (aOR 22.37 95% CI 5.06, 98.95). Significant ethnic differences were observed in the practice of habits. The most common habit among Malays was smoking (24.2%); smoking + drinking were most common among Chinese (16.8%), whereas chewing was the most prevalent among Indians (45.2%) and Indigenous people (24.8%). Cessation of chewing, smoking and drinking is estimated to reduce cancer incidence by 22.6%, 8.5% and 6.9%, respectively.

    CONCLUSION: Ethnic variations in the practice of oral cancer risk habits are evident. Betel quid chewing is the biggest attributable factor for this population.

  5. Haron N, Rajendran S, Kallarakkal TG, Zain RB, Ramanathan A, Abraham MT, et al.
    Oral Dis, 2023 Mar;29(2):380-389.
    PMID: 33914993 DOI: 10.1111/odi.13892
    OBJECTIVE: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral.

    SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions.

    RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®.

    CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.

  6. Jnanendrappa N, Arora S, Yerebairapura Math S
    Oral Dis, 2019 10;25(7):1831.
    PMID: 31206951 DOI: 10.1111/odi.13146
  7. Junxian L, Mehrabanian M, Mivehchi H, Banakar M, Etajuri EA
    Oral Dis, 2023 Oct;29(7):2552-2564.
    PMID: 36004490 DOI: 10.1111/odi.14360
    OBJECTIVES: Periodontitis (PD) is one of the most common dental disorders. This chronic oral inflammation is caused by complicated interrelations between bacterial infections, dysregulated immune reactions, and environmental risk factors. A dysregulated immune response can lead to inflammatory bone resorption by allowing the recruitment of pro-inflammatory immune cells to the periodontal tissues.

    SUBJECTS: The recruitment of innate and adaptive immune cells in PD initiates the acute and following chronic inflammatory processes. The inflamed tissues, on the other hand, can be restored if the anti-inflammatory lineages are predominantly established in the periodontal tissues. Therefore, we aimed to review the published literature to provide an overview of the existing knowledge about the role of immune cells in PD, as well as their possible therapeutic applications.

    RESULTS: Experimental studies showed that drugs/systems that negatively regulate inflammatory cells in the body, as well as interventions aimed at increasing the number of anti-inflammatory cells such as Tregs and Bregs, can both help in the healing process of PD.

    CONCLUSION: Targeting immune cells or their positive/negative manipulations has been demonstrated to be an effective therapeutic method. However, to use this sort of immunotherapy in humans, further pre-clinical investigations, as well as randomized clinical trials, are required.

  8. Koay CL, Lim JA, Siar CH
    Oral Dis, 2011 Mar;17(2):210-6.
    PMID: 20796228 DOI: 10.1111/j.1601-0825.2010.01724.x
    OBJECTIVES: To determine the prevalence of tongue lesions in Malaysian dental outpatients from the Klang Valley area.
    SUBJECTS AND METHODS: A cross sectional study was conducted on 600 Malaysian outpatients (257 men, 343 women, mean age, 37.7 years) attending the Primary Dental Care Unit at the Faculty of Dentistry, University of Malaya. Demographic and medical data were recorded for all respondents.
    RESULTS: One hundred eighty-one patients (30.2%) (81 men, 100 women, mean age 42.0 years) were diagnosed with at least one tongue lesion (n = 207) at the time of examination. Of these, 24 patients (4%) had two or more tongue lesions present synchronously. Seven different lesions were diagnosed: fissured tongue (13.8%), crenated tongue (7.8%), pigmented tongue (6.2%), geographic tongue (2.2%), ankyloglossia (1.7%), hairy tongue (1.0%) and median rhomboid glossitis (0.2%). Their racial prevalences were Malays (n = 65, 10.8%), Indians (n = 62, 10.3%), Chinese (n = 53, 8.8%) and other race (n = 1, 0.2%). A significant relationship was observed between crenated tongue and race; between four types of tongue lesions (fissured tongue, geographic tongue, crenated tongue and pigmented tongue) and age; and between fissured tongue and gender (P 
  9. Pentenero M, Bowers L, Jayasinghe R, Cheong SC, Farah CS, Kerr AR, et al.
    Oral Dis, 2019 Jun;25 Suppl 1:79-87.
    PMID: 31140691 DOI: 10.1111/odi.13051
    Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.
  10. Pentenero M, Bowers LM, Jayasinghe R, Yap T, Cheong SC, Kerr AR, et al.
    Oral Dis, 2019 Jun;25 Suppl 1(Suppl 1):88-101.
    PMID: 31140697 DOI: 10.1111/odi.13076
    BACKGROUND: Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis.

    OBJECTIVES: To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.

    METHODS: PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.

    RESULTS: Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.

    CONCLUSIONS: Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.

  11. Pilana Vithanage Kalani Shihanika H, Nadisha P, Bogahawatte Samarakoon Mudiyanselage Samadarani S, Ruwan Duminda J, Sriyani P, Tilakaratne WM
    Oral Dis, 2023 Nov;29(8):3049-3060.
    PMID: 35801381 DOI: 10.1111/odi.14306
    INTRODUCTION: Verruco papillary lesions (VPL) in the oral cavity encompass a spectrum of lesions starting from benign, potentially malignant to entirely malignant tumors. Much of the controversies in these entities occur due to lack of consensus on the disease characteristics and the management. This systematic review was conducted to identify and describe different lesions categorized as VPL in the oral cavity and their association with malignancy.

    METHODS: An electronic literature search was conducted in MEDLINE (via PubMed), Scopus, LILAC, IMSEAR, and CENTRAL databases, which retrieved a total of 1020 abstracts. These abstracts were managed through Rayyan and Mendeley software, and only 28 studies with high quality were included in the systematic review.

    RESULTS: Studies were published from 1992 to 2021. From the extracted data, nine different entities under the umbrella term VPL were identified associated with malignancy. We describe the clinical and histopathological characteristics of these and propose a uniform framework for nomenclature.

    CONCLUSIONS: Lack of well-planned research with adequate follow-up duration and inadequate quality standards are major barriers for the lack of evidence. The use of uniform nomenclature, as proposed in this study, and research at the molecular level will greatly reduce the controversies in understanding oral VPL associated with malignancy.

  12. Pimolbutr K, Lim WT, Leeson R, Hopper C, Kalavrezos N, Liew C, et al.
    Oral Dis, 2024 Mar;30(2):504-517.
    PMID: 36648368 DOI: 10.1111/odi.14503
    OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED).

    METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed.

    RESULTS: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non-cancer-prone sites (p = 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality.

    CONCLUSIONS: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.

  13. R H, Ramani P, Tilakaratne WM, Sukumaran G, Ramasubramanian A, Krishnan RP
    Oral Dis, 2021 Jun 21.
    PMID: 34152662 DOI: 10.1111/odi.13937
    Pemphigus vulgaris is an autoimmune blistering disease with an increased potential for mortality. The epithelium is key in understanding the pathobiology as it is specialized to perform functions like mechanical protection, immunological defense, and proprioception. In order to perform these array of functions, epithelial integrity is important. This integrity is maintained by a host of molecules which orchestrate the ability of the keratinocytes to function as a single unit. Desmoglein 3 antibodies formed in genetically susceptible individuals are known to cause the disruption of the intact oral mucosa leading to the formation of blisters in pemphigus vulgaris patients. However, there are underlying complex triggering pathways leading to the clinical disease. The aim of the review is to congregate and critically appraise the various triggering pathways which contribute toward the pathobiology of pemphigus vulgaris. Articles relevant to the pathobiology of pemphigus vulgaris were identified from various search databases till the year 2020. The pathogenesis of pemphigus vulgaris is complex, and it involves an in-depth understanding of the various predisposing factors, provoking factors, and progression mechanisms. Congregation of the various triggering pathways will open our minds to understand pemphigus vulgaris better and in turn develop a reliable treatment in the near future.
  14. 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.

  15. Ramanathan A, Zaini ZM, Ghani WMN, Wong GR, Zainuddin NI, Yang YH, et al.
    Oral Dis, 2024 Mar 15.
    PMID: 38488212 DOI: 10.1111/odi.14927
    OBJECTIVE: This study evaluated the effectiveness of face-to-face (F2F) and online OralDETECT training programme in enhancing early detection skills for oral cancer.

    METHODS: A total of 328 final-year dental students were trained across six cohorts. Three cohorts (175 students) received F2F training from the academic years 2016/2017 to 2018/2019, and the remaining three (153 students) underwent online training during the Covid-19 pandemic from 2019/2020 to 2021/2022. Participant scores were analysed using the Wilcoxon signed rank test, the Mann-Whitney test, Cohen's d effect size, and multiple linear regression.

    RESULTS: Both F2F and online training showed increases in mean scores from pre-test to post-test 3: from 67.66 ± 11.81 to 92.06 ± 5.27 and 75.89 ± 11.03 to 90.95 ± 5.22, respectively. Comparison between F2F and online methods revealed significant differences in mean scores with large effect sizes at the pre-test stage (p 

  16. Shen Loo Y, Yee Wong T, Veettil SK, Se Wong P, Gopinath D, Mooi Ching S, et al.
    Oral Dis, 2021 Oct;27(7):1631-1643.
    PMID: 32762108 DOI: 10.1111/odi.13588
    OBJECTIVE: This review examined the comparative efficacy and safety of antifungal agents in preventing oral candidiasis among patients on cancer treatment.

    METHODS: We performed a systematic review and network meta-analysis based on randomised controlled trials that compared antifungal agents to placebo or other antifungal agents used in patients undergoing cancer treatment. Relative ranking of antifungal agents was evaluated with surface under the cumulative ranking (SUCRA) probability score. A total of 20 randomised controlled trials (3,215 participants) comparing 11 interventions were included.

    RESULTS: Compared with placebo, clotrimazole was ranked the best agent for preventing the incidence of oral candidiasis (risk ratio (RR), 0.21 [95% CI 0.08 to 0.55]; SUCRA = 0.89). Fluconazole was ranked the safest among other antifungal agents (SUCRA = 0.80), whereas clotrimazole (SUCRA = 0.36) and amphotericin B (SUCRA = 0.18) were ranked low for safety. Amphotericin B was associated with highest risk of adverse events (RR, 3.52 [95% CI 1.27 to 9.75]).

    CONCLUSION: Clotrimazole is the most effective in preventing oral candidiasis, whereas fluconazole has the most favourable risk-benefit profile in patients undergoing cancer treatment. However, we are unable to recommend clotrimazole as the best choice to prevent oral candidiasis due to unavailability of studies comparing clotrimazole with other antifungal agents.

  17. Siow MY, Ng LP, Vincent-Chong VK, Jamaludin M, Abraham MT, Abdul Rahman ZA, et al.
    Oral Dis, 2014 May;20(4):345-51.
    PMID: 23651447 DOI: 10.1111/odi.12118
    To identify differentially expressed miRNA between oral squamous cell carcinoma (OSCC) and non-cancer (NC) and to associate these with clinico-pathological parameters.
  18. Sosroseno W, Bird PS, Gemmell E, Seymour GJ
    Oral Dis, 2006 Jul;12(4):387-94.
    PMID: 16792724
    To determine whether oral tolerance with the oral bacterium Actinomyces viscosus was inducible in mice.
  19. Syed Mohd Sobri SNS, Kanapathy J, Liew CS, Cheong SC
    Oral Dis, 2020 Jul;26(5):1094-1097.
    PMID: 32145142 DOI: 10.1111/odi.13320
    The majority of oral cancer cases occur in Asia and the incidence is expected to continue to rise. Oral cancer is amenable to early detection through visual oral examination yet in many Asian countries, the disease presents at a late stage. The barriers to early detection are similar across the Asia-Pacific countries therefore, strategies to address these could be more effective if there were concerted efforts and joint resources amongst the countries. To facilitate better engagement and collaboration between stakeholders in oral cancer detection and management, the Asia-Pacific Oral Cancer Network (APOCNET) was established and the inaugural meeting was held in Kuala Lumpur on the 13th to 15th of September 2019. In this meeting, we identified the challenges faced in the early detection and management of oral cancer amongst the stakeholder countries, showcased the successful oral cancer programs in the region and identified strategic areas for collaboration. For this, notable international speakers and those from local universities and the Ministry of Health Malaysia were invited to share their experiences. The lessons learned from our neighbouring countries could lead to the implementation of similar programs that could help reduce the oral cancer burden in the region.
  20. Vaithilingam RD, Safii SH, Baharuddin NA, Karen-Ng LP, Saub R, Ariffin F, et al.
    Oral Dis, 2015 Jan;21(1):e62-9.
    PMID: 24930489 DOI: 10.1111/odi.12267
    Periodontal bio-repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad-based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.
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