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PCA loading plot visualizing the correlation between the biomarkers tested and clusters of samples, grouped based on their similarity. The red-colored arrows show the four biomarkers (ordered from top to bottom): IL-4, IL-13, IL-2-RA, and eotaxin/CCL11. The S. mutans arrow is colored in green, in close proximity to IL-4.

PCA loading plot visualizing the correlation between the biomarkers tested and clusters of samples, grouped based on their similarity. The red-colored arrows show the four biomarkers (ordered from top to bottom): IL-4, IL-13, IL-2-RA, and eotaxin/CCL11. The S. mutans arrow is colored in green, in close proximity to IL-4.

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This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), or patients with deep caries lesions (n = 38) were collected and anal...

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... loading plots were generated to visualize potential correlations between the tested biomarkers and clusters of samples. The directions and angles of the plots showed a positive correlation between IL-2-RA and IL-13, followed by IL-4 ( Figure 6). Another interesting observation is that periodontitis and caries-associated bacteria are not likely to be correlated, although, as expected, bacterial protease activity appeared to correlate better with the periodontitis-associated strains. ...
Context 2
... loading plots were generated to visualize potential correlations between the tested biomarkers and clusters of samples. The directions and angles of the plots showed a positive correlation between IL-2-RA and IL-13, followed by IL-4 ( Figure 6). Another interesting observation is that periodontitis and caries-associated bacteria are not likely to be correlated, although, as expected, bacterial protease activity appeared to correlate better with the periodontitis-associated strains. ...

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... One of the diseases caused by S. mutans is dental caries. There are several factors that cause dental caries to get worse including sugar, saliva, and also putrefactive bacteria [25][26][27]. In addition, the growth of bacteria in the mouth and forming biofilms is caused by several factors, namely saliva which plays a role in modulating the plaque layer on the teeth, the temperature in the environment around the mouth in the range of 35-36°C, and pH 6.75-7.25 [28,29]. ...
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Based on data from The Global Burden of Disease Study in 2016, dental and oral health problems, especially dental caries, are a disease experienced by almost half of the world’s population (3.58 billion people). One of the main causes of dental caries is the pathogenesis of Streptococcus mutans. Prevention can be achieved by controlling S. mutans using an antibacterial agent. The most commonly used antibacterial for the treatment of dental caries is chlorhexidine. However, long-term use of chlorhexidine has been reported to cause resistance and some side effects. Therefore, the discovery of a natural antibacterial agent is an urgent need. A natural antibacterial agent that can be used are herbal medicines derived from medicinal plants. Piper crocatum Ruiz and Pav has the potential to be used as a natural antibacterial agent for treating dental and oral health problems. Several studies reported that the leaves of P. crocatum Ruiz and Pav contain secondary metabolites such as essential oils, flavonoids, alkaloids, terpenoids, tannins, and phenolic compounds that are active against S. mutans. This review summarizes some information about P. crocatum Ruiz and Pav, various isolation methods, bioactivity, S. mutans bacteria that cause dental caries, biofilm formation mechanism, antibacterial properties, and the antibacterial mechanism of secondary metabolites in P. crocatum Ruiz and Pav.
... It is the dynamic changes over time of bacteria among the oral microbiota, rather than their mere presence/absence, that drives the dysbiotic changes that lead to oral disease [72]. The fact that the OralDisk has demonstrated its capacity to analyze oral bacteria provides a basis upon which the platform can be implemented in time-course studies associated with patient monitoring, similar to the rationale reported by Paqué et al. [73]. In such future studies, we will have the opportunity to proceed to the quantification of bacteria, using OralDisk-derived calibration curves to convert Cq values into numeric bacterial loads. ...
... This will increase the interoperability between immunological and microbiological diagnostic outputs using this platform [76]. Subsequently, by using combined computational technologies and the OralDisk device, new diagnostic predictive models of disease development and progression may be generated [73]. Such developments will enable evidence-based pre-and post-treatment monitoring of a range of oral (OralDisk) and non-oral (application-specific LabDisk) diseases. ...
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Periodontitis and dental caries are two major bacterially induced, non-communicable diseases that cause the deterioration of oral health, with implications in patients' general health. Early, precise diagnosis and personalized monitoring are essential for the efficient prevention and management of these diseases. Here, we present a disk-shaped microfluidic platform (OralDisk) compatible with chair-side use that enables analysis of non-invasively collected whole saliva samples and molecular-based detection of ten bacteria: seven periodontitis-associated (Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and three caries-associated (oral Lactobacilli, Streptococcus mutans, Streptococcus sobrinus). Each OralDisk test required 400 µL of homogenized whole saliva. The automated workflow included bacterial DNA extraction, purification and hydrolysis probe real-time PCR detection of the target pathogens. All reagents were pre-stored within the disk and sample-to-answer processing took < 3 h using a compact, customized processing device. A technical feasibility study (25 OralDisks) was conducted using samples from healthy, periodontitis and caries patients. The comparison of the OralDisk with a lab-based reference method revealed a ~90% agreement amongst targets detected as positive and negative. This shows the OralDisk's potential and suitability for inclusion in larger prospective implementation studies in dental care settings.
... Paqué et al. [15] investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals with caries. Saliva samples from caries and gingivitis-free individuals (n = 18), patients with deep caries lesions (n = 38) was collected and analysed for 44 candidate biomarkers namely: selected oral bacteria, growth factors, chemokines and proteolytic enzymes among others. ...
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Dental Caries are one of the most prevalent chronic diseases around the globe. Detecting carious lesions is a challenging task. Conventional computer aided diagnosis and detection methods in the past have heavily relied on the visual inspection of teeth. These methods are only effective on large and clearly visible caries on affected teeth. Conventional methods have been limited in performance due to the complex visual characteristics of dental caries images, which consist of hidden or inaccessible lesions. The early detection of dental caries is an important determinant for treatment and benefits much from the introduction of new tools, such as dental radiography. In this paper, we propose a deep learning-based technique for dental caries detection namely: blob detection. The proposed technique automatically detects hidden and inaccessible dental caries lesions in bitewing radio-graphs. The approach employs data augmentation to increase the number of images in the data set to have a total of 11,114 dental images. Image pre-processing on the data set was through the use of Gaussian blur filters. Image segmentation was handled through thresholding, erosion and dilation morphology, while image boundary detection was achieved through active contours method. Furthermore, the deep learning based network through the sequential model in Keras extracts features from the images through blob detection. Finally, a convexity threshold value of 0.9 is introduced to aid in the classification of caries as either present or not present. The process of detection and classifying dental caries achieved the results of 97% and 96% for the precision and recall values, respectively.
... This article is protected by copyright. All rights reserved Paqué et al. 2021), or qualitative detection of antibiotic resistance genes (Belibasakis et al. 2020). Saliva sampling may also conveniently replace the uncomfortable nasal or oropharyngeal sampling for select applications, such as SARS-CoV-2 RNA detection, with high specificity and sensitivity (Atieh et al. 2021). ...
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The authors of this narrative review aimed to address various experimental methods and make recommendations for how research should move forward in the context of studying biomarkers in clinical Endodontic research. The approach adopted is exemplified using two prominent clinical problems, namely a) the "reversible" versus "irreversible" pulpitis conundrum and b) persistent idiopathic dentoalveolar pain (PIDAP). Pulpitis under deep caries or dentinal cracks is understood from a histological perspective, but clinical assessment tools to indicate irreversibly inflamed aspects of the dental pulp are elusive. PIDAP, on the other hand, is a diagnosis of exclusion; its pathophysiology is complex and not understood sufficiently to avoid unnecessary dental treatments. This review addresses how diagnostic biomarkers could further our understanding of those and other clinical problems, and how issues can be tackled from a methodological point of view. Hence, different methodological approaches to identify suitable diagnostic biomarker(s) or use known biomarkers are presented. The importance of asking a relevant research question, collecting the most suitable fluid, and using the ideal collection vehicle for the research question under investigation is discussed based on the defined clinical problems.
... The prevalence and damage generated by these bacteria are influenced by host protective factors, such as immune competence, the production and buffering capacity of saliva, and hygiene and dietary habits [5]. Mechanisms have been sought to diagnose the risk of caries based on these factors using software such as Cariogram [6] or through the identification of biomarkers [7,8,9]. However, a significant amount of new studies are required to evaluate the validity of caries biomarkers, among other things because tooth decay is a multi-factorial disease with genetic, environmental and microbial effects playing a role, and because of a large inter-individual variability that renders the task of finding universal caries markers [10]. ...
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Background: Electrolytes, proteins, and other salivary molecules play an important role in tooth integrity and can serve as biomarkers associated with caries. Objective: To determine the concentration of potential biomarkers in children without caries (CF) and children with caries (CA). Methods: Unstimulated saliva was collected, and the biomarkers quantified in duplicate, using commercial Enzyme Linked Immunosorbent Assay (ELISA) kits to determine IgA, fibronectin, cathelicidin LL-37, and statherin levels, as well as colorimetric tests to detect formate and phosphate. Results: Significantly higher concentrations of statherin was detected in the CF group (Median: 94,734.6; IQR: 92,934.6–95,113.7) compared to the CA2 group (90,875.0; IQR: 83,580.2–94,633.4) (p = 0.03). Slightly higher median IgA (48,250.0; IQR: 31,461.9–67,418.8) and LL-37 levels (56.1; IQR 43.6–116.2) and a lower concentration of formate were detected in the CF group (0.02; IQR 0.0034–0.15) compared to the group with caries (IgA: 37,776.42; IQR: 33,383.9–44,128.5; LL-37: 46.3; IQR: 40.1011–67.7; formate: 0.10; IQR: 0.01–0.18), but these differences were not statistically significant. Conclusion: The fact that these compounds have been identified as good markers for caries among European adults highlights the difficulty of identifying universal biomarkers that are applicable to all ages or to different populations.