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Background/Objectives: To systematically review and summarize the existing scientific evidence on the diagnostic performance of artificial intelligence (AI) in assessing cervical vertebral maturation (CVM). This review aimed to evaluate the accuracy and reliability of AI algorithms in comparison to those of experienced clinicians. Methods: Comprehensive searches were conducted across multiple databases, including PubMed, Scopus, Web of Science, and Embase, using a combination of Boolean operators and MeSH terms. The inclusion criteria were cross-sectional studies with neural network research, reporting diagnostic accuracy, and involving human subjects. Data extraction and quality assessment were performed independently by two reviewers, with a third reviewer resolving any disagreements. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool was used for bias assessment. Results: Eighteen studies met the inclusion criteria, predominantly employing supervised learning techniques, especially convolutional neural networks (CNNs). The diagnostic accuracy of AI models for CVM assessment varied widely, ranging from 57% to 95%. The factors influencing accuracy included the type of AI model, training data, and study methods. Geographic concentration and variability in the experience of radiograph readers also impacted the results. Conclusions: AI has considerable potential for enhancing the accuracy and reliability of CVM assessments in orthodontics. However, the variability in AI performance and the limited number of high-quality studies suggest the need for further research.

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Computed tomography (CT) has been recognized as a robust and dependable technique for delineating osseous alterations and anomalies within hard tissues. The necessity for accurate diagnosis and management of patients with temporomandibular disorders in dental practices has increasingly come to the forefront. There is ongoing scholarly debate regarding the equivalence of diagnostic outcomes yielded by cone beam computed tomography (CBCT), which offers greater accessibility in dental settings than traditional CT, in identifying bony changes within the temporomandibular joint (TMJ). Our principal aim was to conduct a systematic review of studies that compare the efficacy of CT and CBCT in the detailed assessment of bone conditions affecting the TMJ. An electronic search was conducted across databases: PubMed, Medline, Web of Science, Cochrane and Scopus. Two independent reviewers screened titles and abstracts against predefined inclusion criteria. The included articles underwent rigorous critical appraisal, during which relevant data were extracted and systematically presented in a tabular format. This systematic review incorporates 5 studies published between 2006 and 2015. In 3 studies, CBCT demonstrated comparable outcomes to CT, while 2 investigations revealed significantly enhanced accuracy for CBCT compared to CT, with reported accuracies of 0.95 ± 0.04, 0.77 ± 0.17, and 89-91% for CBCT. The aggregated evidence from the included studies indicates that CBCT offers comparable or superior accuracy in detecting osseous changes within TMJ structures. Owing to its lower radiation exposure and increased accessibility, CBCT emerges as the preferred choice over conventional CT for evaluating bony structures of the TMJ.

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Background: Cephalometric analysis (CA) is an indispensable diagnostic tool in orthodontics for treatment planning and outcome assessment. Manual CA is time-consuming and prone to variability. Methods: This study aims to compare the accuracy and repeatability of CA results among three commercial AI-driven programs: CephX, WebCeph, and AudaxCeph. This study involved a retrospective analysis of lateral cephalograms from a single orthodontic center. Automated CA was performed using the AI programs, focusing on common parameters defined by Downs, Ricketts, and Steiner. Repeatability was tested through 50 randomly reanalyzed cases by each software. Statistical analyses included intraclass correlation coefficients (ICC3) for agreement and the Friedman test for concordance. Results: One hundred twenty-four cephalograms were analyzed. High agreement between the AI systems was noted for most parameters (ICC3 > 0.9). Notable differences were found in the measurements of angle convexity and the occlusal plane, where discrepancies suggested different methodologies among the programs. Some analyses presented high variability in the results, indicating errors. Repeatability analysis revealed perfect agreement within each program. Conclusions: AI-driven cephalometric analysis tools demonstrate a high potential for reliable and efficient orthodontic assessments, with substantial agreement in repeated analyses. Despite this, the observed discrepancies and high variability in part of analyses underscore the need for standardization across AI platforms and the critical evaluation of automated results by clinicians, particularly in parameters with significant treatment implications.

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This retrospective study aims to investigate the impact of cone-beam computed tomography (CBCT) viewing parameters such as contrast, slice thickness, and sharpness on the identification of the inferior alveolar nerve (IAC). A total of 25 CBCT scans, resulting in 50 IACs, were assessed by two investigators using a three-score system (good, average, and poor) on cross-sectional images. Slice thicknesses of 0.25 mm, 0.5 mm, and 1 mm were tested, along with varying sharpness (0, 6, 8, and 10) and contrast (0, 400, 800, and 1200) settings. The results were statistically analyzed to determine the optimal slice thickness for improved visibility of IAC, followed by evaluating the influence of sharpness and contrast using the optimal thickness. The identified parameters were then validated by performing semi-automated segmentation of the IACs and structure overlapping to evaluate the mean distance. Inter-rater and intra-rater reliability were assessed using Kappa statistics, and inferential statistics used Pearson's Chi-square test. Inter-rater and intra-rater reliability for all parameters were significant, ranging from 69% to 83%. A slice thickness of 0.25 mm showed consistently "good" visibility (80%). Sharpness values of zero and contrast values of 1200 also demonstrated high frequencies of "good" visibility. Overlap analysis resulted in an average mean distance of 0.295 mm and a standard deviation of 0.307 mm across all patients' sides. The study revealed that a slice thickness of 0.25 mm, zero sharpness value, and higher contrast value of 1200 improved the visibility and accuracy of IAC segmentation in CBCT scans. The individual patient's characteristics, such as anatomical variations, decreased bone density, and absence of canal walls cortication, should be considered when using these parameters.

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Small extracellular vesicles (sEVs) are a type of membranous vesicles that can be released by cells into the extracellular space. The relationship between sEVs and non-coding RNAs (ncRNAs) is highly intricate and interdependent. This symbiotic relationship plays a pivotal role in facilitating intercellular communication and holds profound implications for a myriad of biological processes. The concept of sEVs and their ncRNA cargo as a "Trojan Horse" highlights their remarkable capacity to traverse biological barriers and surreptitiously deliver their cargo to target cells, evading detection by the host-immune system. Accumulating evidence suggests that sEVs may be harnessed as carriers to ferry therapeutic ncRNAs capable of selectively silencing disease-driving genes, particularly in conditions such as cancer. This approach presents several advantages over conventional drug delivery methods, opening up new possibilities for targeted therapy and improved treatment outcomes. However, the utilization of sEVs and ncRNAs as therapeutic agents raises valid concerns regarding the possibility of unforeseen consequences and unintended impacts that may emerge from their application. It is important to consider the fundamental attributes of sEVs and ncRNAs, including by an in-depth analysis of the practical and clinical potentials of exosomes, serving as a representative model for sEVs encapsulating ncRNAs.

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This study aims to evaluate the diagnostic accuracy of artificial intelligence in detecting apical pathosis on periapical radiographs. A total of twenty anonymized periapical radiographs were retrieved from the database of Poznan University of Medical Sciences. These radiographs displayed a sequence of 60 visible teeth. The evaluation of the radiographs was conducted using two methods (manual and automatic), and the results obtained from each technique were afterward compared. For the ground-truth method, one oral and maxillofacial radiology expert with more than ten years of experience and one trainee in oral and maxillofacial radiology evaluated the radiographs by classifying teeth as healthy and unhealthy. A tooth was considered unhealthy when periapical periodontitis related to this tooth had been detected on the radiograph. At the same time, a tooth was classified as healthy when no periapical radiolucency was detected on the periapical radiographs. Then, the same radiographs were evaluated by artificial intelligence, Diagnocat (Diagnocat Ltd., San Francisco, CA, USA). Diagnocat (Diagnocat Ltd., San Francisco, CA, USA) correctly identified periapical lesions on periapical radiographs with a sensitivity of 92.30% and identified healthy teeth with a specificity of 97.87%. The recorded accuracy and F1 score were 96.66% and 0.92, respectively. The artificial intelligence algorithm misdiagnosed one unhealthy tooth (false negative) and over-diagnosed one healthy tooth (false positive) compared to the ground-truth results. Diagnocat (Diagnocat Ltd., San Francisco, CA, USA) showed an optimum accuracy for detecting periapical periodontitis on periapical radiographs. However, more research is needed to assess the diagnostic accuracy of artificial intelligence-based algorithms in dentistry.

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Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40-160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies.

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This systematic scoping review aims to map and identify the available artificial-intelligence-based techniques for imaging analysis, the characterization of stem cell differentiation, and trans-differentiation pathways. On the ninth of March 2022, data were collected from five electronic databases (PubMed, Medline, Web of Science, Cochrane, and Scopus) and manual citation searching; all data were gathered in Zotero 5.0. A total of 4422 articles were collected after deduplication; only twenty-seven studies were included in this systematic scoping review after a two-phase screening against inclusion criteria by two independent reviewers. The amount of research in this field is significantly increasing over the years. While the current state of artificial intelligence (AI) can tackle a multitude of medical problems, the consensus amongst researchers remains that AI still falls short in multiple ways that investigators should examine, ranging from the quality of images used in training sets and appropriate sample size, as well as the unexpected events that may occur which the algorithm cannot predict.

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This systematic review aims to identify the available semi-automatic and fully automatic algorithms for inferior alveolar canal localization as well as to present their diagnostic accuracy. Articles related to inferior alveolar nerve/canal localization using methods based on artificial intelligence (semi-automated and fully automated) were collected electronically from five different databases (PubMed, Medline, Web of Science, Cochrane, and Scopus). Two independent reviewers screened the titles and abstracts of the collected data, stored in EndnoteX7, against the inclusion criteria. Afterward, the included articles have been critically appraised to assess the quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Seven studies were included following the deduplication and screening against exclusion criteria of the 990 initially collected articles. In total, 1288 human cone-beam computed tomography (CBCT) scans were investigated for inferior alveolar canal localization using different algorithms and compared to the results obtained from manual tracing executed by experts in the field. The reported values for diagnostic accuracy of the used algorithms were extracted. A wide range of testing measures was implemented in the analyzed studies, while some of the expected indexes were still missing in the results. Future studies should consider the new artificial intelligence guidelines to ensure proper methodology, reporting, results, and validation.

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The COVID-19 pandemic is a global challenge, demanding researchers address different approaches in relation to prevention, diagnostics and therapeutics. Amongst the many tactics of tackling these therapeutic challenges, small extracellular vesicles (sEVs) or exosomes are emerging as a new frontier in the field of ameliorating viral infections. Exosomes are part of extracellular vesicles (EVs)-spherical biological structures with a lipid bilayer of a diameter of up to 5000 nm, which are released into the intercellular space by most types of eukaryotic cells, both in physiological and pathological states. EVs share structural similarities to viruses, such as small size, common mechanisms of biogenesis and mechanisms for cell entry. The role of EVs in promoting the viral spread by evading the immune response of the host, which is exhibited by retroviruses, indicates the potential for further investigation and possible manipulation of these processes when tackling the spread and treatment of COVID-19. The following paper introduces the topic of the use of exosomes in the treatment of viral infections, and presents the future prospects for the use of these EVs.

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Photobiomodulation (PBM), also called low-level laser treatment (LLLT), has been considered a promising tool in periodontal treatment due to its anti-inflammatory and wound healing properties. However, photobiomodulation's effectiveness depends on a combination of parameters, such as energy density, the duration and frequency of the irradiation sessions, and wavelength, which has been shown to play a key role in laser-tissue interaction. The objective of the study was to compare the in vitro effects of two different wavelengths-635 nm and 808 nm-on the human primary gingival fibroblasts in terms of viability, oxidative stress, inflammation markers, and specific gene expression during the four treatment sessions at power and energy density widely used in dental practice (100 mW, 4 J/cm2). PBM with both 635 and 808 nm at 4 J/cm2 increased the cell number, modulated extracellular oxidative stress and inflammation markers and decreased the susceptibility of human primary gingival fibroblasts to apoptosis through the downregulation of apoptotic-related genes (P53, CASP9, BAX). Moreover, modulation of mesenchymal markers expression (CD90, CD105) can reflect the possible changes in the differentiation status of irradiated fibroblasts. The most pronounced results were observed following the third irradiation session. They should be considered for the possible optimization of existing low-level laser irradiation protocols used in periodontal therapies.

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The methylated resveratrol analogue 3'-hydroxy-3,4,5,4'-tetramethoxystilbene (DMU-214) has been revealed to exert the anti-cancer activity by a block of the cell cycle at the G2/M phase, apoptosis induction, and metastasis inhibition. These biological events may be involved in crosstalk with the epidermal growth factor receptor (EGFR), which belongs to the ErbB family of receptor tyrosine kinases. Several cancer therapeutic approaches employ small molecules capable of inhibiting tyrosine kinases (e.g., gefitinib). According to more recent reports, combining gefitinib with chemotherapeutics, such as cisplatin, seems to be more effective than monotherapy. The present study aimed to assess the molecular mechanism of the potential anti-proliferative activity of individual and combined treatments with DMU-214 and gefitinib in SCC-25 and CAL-27 human tongue cancer cell lines. We showed for the first time the anti-cancer effects of DMU-214, gefitinib, and their combination in tongue cancer cells triggered via cell cycle arrest, apoptosis induction, and inhibition of the EGFR signaling pathway. The anti-proliferative effects of DMU-214 and gefitinib are also suggested to be related to the EGFR and EGFRP (phosphorylated epidermal growth factor receptor) expression status since we found significantly weaker cytotoxic activity of the compounds tested in SCC-25 cells, which overexpressed EGFR and EGFRP proteins.

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Resorbable synthetic and natural polymer-based membranes have been extensively studied for guided tissue regeneration. Alloplastic biomaterials are often used for tissue regeneration due to their lower immunoreactivity when compared with allogeneic and xenogeneic materials. Plenum® Guide is a synthetic membrane material based on polydioxanone (PDO), whose surface morphology closely mimics the extracellular matrix. In this study, Plenum® Guide was compared with collagen membranes as a barrier material for bone-tissue regeneration in terms of acute and subchronic systemic toxicity. Moreover, characterizations such as morphology, thermal analysis (Tm = 107.35 °C and crystallinity degree = 52.86 ± 2.97 %, final product), swelling (thickness: 0.25 mm ≅ 436% and 0.5 mm ≅ 425% within 24 h), and mechanical tests (E = 30.1 ± 6.25 MPa; σ = 3.92 ± 0.28 MPa; ε = 287.96 ± 34.68%, final product) were performed. The in vivo results revealed that the PDO membranes induced a slightly higher quantity of newly formed bone tissue than the control group (score: treated group = 15, control group = 13) without detectable systemic toxicity (clinical signs and evaluation of the membranes after necropsy did not result in differences between groups, i.e., non-reaction -> tissue-reaction index = 1.3), showing that these synthetic membranes have the essential characteristics for an effective tissue regeneration. Human adipose-derived stem cells (hASCs) were seeded on PDO membranes; results demonstrated efficient cell migration, adhesion, spread, and proliferation, such that there was a slightly better hASC osteogenic differentiation on PDO than on collagen membranes. Hence, Plenum® Guide membranes are a safe and efficient alternative for resorbable membranes for tissue regeneration.

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Transcriptional analysis and live-cell imaging are a powerful tool to investigate the dynamics of complex biological systems. In vitro expanded porcine oral mucosal cells, consisting of populations of epithelial and connective lineages, are interesting and complex systems for study via microarray transcriptomic assays to analyze gene expression profile. The transcriptomic analysis included 56 ontological groups with particular focus on 7 gene ontology groups that are related to the processes of differentiation and development. Most analyzed genes were upregulated after 7 days and downregulated after 15 and 30 days of in vitro culture. The performed transcriptomic analysis was then extended to include automated analysis of differential interference contrast microscopy (DIC) images obtained during in vitro culture. The analysis of DIC imaging allowed to identify the different populations of keratinocytes and fibroblasts during seven days of in vitro culture, and it was possible to evaluate the proportion of these two populations of cells. Porcine mucosa may be a suitable model for reference research on human tissues. In addition, it can provide a reference point for research on the use of cells, scaffolds, or tissues derived from transgenic animals for applications in human tissues reconstruction.

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Background: One of the procedures enhancing implants stability can be photobiomodulation. Objective: To assess the effect of a 635 nm wavelength on orthodontic microscrews stability, survival rate, and an individual patient's pain score. Materials and methods: The study was done with 15 subjects, 30 orthodontic microscrews with a length of 10 mm and diameter 1.4 mm. Implants inserted on the right and left side of the maxilla. The implants in the test group (G1) were irradiated with the laser at palatal and buccal part of peri-implant area (two points). The diode laser (SmartM PRO; Lasotronix, Warsaw, Poland) was used with the following settings: power: 100 mW, spot size: 0.5 cm2, mean power density (irradiance): 200 mW/cm2, in continuous wave (CW) mode, energy per point: 4 J, radiant exposure: 8 J/cm2, time per point: 40 sec, the total energy dose (radiant energy) per session: 8 J in contact mode, handpiece diameter: 8 mm. Laser sessions: day of surgery and 3, 6, 9, 12, 15, 30 days later. Cumulative radiant energy was 59 J. Periotest appliance was used to assess the microscrews stability at day of surgery and 3, 6, 9, 12, 15, 30, 60 days later. Each patient received a survey for individual pain assessment (NRS-11) promptly after the implantation. Results: The analysis after 60 days revealed significantly higher secondary stability for the laser-irradiated microscrews group in comparison with control implants (G2 group) (p = 0.0037). We observed significantly higher stability in the experimental group compared with the control after 30 days (p = 0.0218). Moreover, we noted significantly higher microimplants stability for the control group in comparison with the test group, 9 days after implantation (p = 0.0374). Laser application had no effect on pain reduction noted in the first day in comparison with the control sites (p = 0.6690). No microscrews were lost in the study. Conclusions: Application of a 635 nm laser on peri-implant soft tissue increased the microscrews stability after 30 and 60 days.

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The mechanisms of wound healing and vascularization are crucial steps of the complex morphological process of tissue reconstruction. In addition to epithelial cells, fibroblasts play an important role in this process. They are characterized by dynamic proliferation and they form the stroma for epithelial cells. In this study, we have used primary cultures of oral fibroblasts, obtained from porcine buccal mucosa. Cells were maintained long-term in in vitro conditions, in order to investigate the expression profile of the molecular markers involved in wound healing and vascularization. Based on the Affymetrix assays, we have observed three ontological groups of markers as wound healing group, response to wounding group and vascularization group, represented by different genes characterized by their expression profile during long-term primary in vitro culture (IVC) of porcine oral fibroblasts. Following the analysis of gene expression in three previously identified groups of genes, we have identified that transforming growth factor beta 1 (TGFB1), ITGB3, PDPN, and ETS1 are involved in all three processes, suggesting that these genes could be recognized as markers of repair specific for oral fibroblasts within the porcine mucosal tissue.

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Even though chemotherapy and immunotherapy emerged to limit continual and unregulated proliferation of cancer cells, currently available therapeutic agents are associated with high toxicity levels and low success rates. Additionally, ongoing multi-targeted therapies are limited only for few carcinogenesis pathways, due to continually emerging and evolving mutations of proto-oncogenes and tumor-suppressive genes. CRISPR/Cas9, as a specific gene-editing tool, is used to correct causative mutations with minimal toxicity, but is also employed as an adjuvant to immunotherapy to achieve a more robust immunological response. Some of the most critical limitations of the CRISPR/Cas9 technology include off-target mutations, resulting in nonspecific restrictions of DNA upstream of the Protospacer Adjacent Motifs (PAM), ethical agreements, and the lack of a scientific consensus aiming at risk evaluation. Currently, CRISPR/Cas9 is tested on animal models to enhance genome editing specificity and induce a stronger anti-tumor response. Moreover, ongoing clinical trials use the CRISPR/Cas9 system in immune cells to modify genomes in a target-specific manner. Recently, error-free in vitro systems have been engineered to overcome limitations of this gene-editing system. The aim of the article is to present the knowledge concerning the use of CRISPR Cas9 technique in targeting treatment-resistant cancers. Additionally, the use of CRISPR/Cas9 is aided as an emerging supplementation of immunotherapy, currently used in experimental oncology. Demonstrating further, applications and advances of the CRISPR/Cas9 technique are presented in animal models and human clinical trials. Concluding, an overview of the limitations of the gene-editing tool is proffered.

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Gingivae, as the part of periodontium, are involved in tooth support and possess the ability to heal rapidly, without scar formation. Recently, dental tissues have been identified as a potential source of mesenchymal stem cells (MSCs) and several populations of MSCs were isolated from the orofacial region, including gingival mesenchymal stem cells (GMSCs). GMSCs exhibit robust immunomodulatory and differentiation potential and are easily obtainable, which make them promising candidates for cellular therapies. Apart from being tested for application in immunologic- and inflammatory-related disorders and various tissue regeneration, GMSCs promise to be a valuable tool in cancer treatment, especially in tongue squamous cell carcinoma (TSCC) with the use of targeted therapy, since GMSCs are able to selectively migrate towards the cancerous cells both in vitro and in vivo. In addition to their ability to uptake and release anti-neoplastic drugs, GMSCs may be transduced with apoptosis-inducing factors and used for cancer growth inhibition. Moreover, GMSCs, as most mammalian cells, secrete exosomes, which are a subset of extracellular vesicles with a diameter of 40-160 nm, containing DNA, RNA, lipids, metabolites, and proteins. Such GMSCs-derived exosomes may be useful therapeutic tool in cell-free therapy, as well as their culture medium. GMSCs exhibit molecular and stem-cell properties that make them well suited in preclinical and clinical studies.

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Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

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The purpose of this study is to explore the possibilities for the application of laser therapy in medicine and dentistry by analyzing lasers' underlying mechanism of action on different cells, with a special focus on stem cells and mechanisms of repair. The interest in the application of laser therapy in medicine and dentistry has remarkably increased in the last decade. There are different types of lasers available and their usage is well defined by different parameters, such as: wavelength, energy density, power output, and duration of radiation. Laser irradiation can induce a photobiomodulatory (PBM) effect on cells and tissues, contributing to a directed modulation of cell behaviors, enhancing the processes of tissue repair. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), can induce cell proliferation and enhance stem cell differentiation. Laser therapy is a non-invasive method that contributes to pain relief and reduces inflammation, parallel to the enhanced healing and tissue repair processes. The application of these properties was employed and observed in the treatment of various diseases and conditions, such as diabetes, brain injury, spinal cord damage, dermatological conditions, oral irritation, and in different areas of dentistry.