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International Dental Journal[JOURNAL]

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METTL3 Regulates the Senescence of Stem Cells From the Apical Papilla by Mediating the mA Modification of E2F3.

Sun C, Fang Y, Li Z … +1 more , Li W

Int Dent J · 2026 May · PMID 42150342 · Full text

INTRODUCTION AND AIMS: We aimed to investigate whether N6-methyladenosine (m⁶A) methylation modification mediated by METTL3 regulates the senescence of SCAPs, and to elucidate the underlying molecular mechanisms. METHODS... INTRODUCTION AND AIMS: We aimed to investigate whether N6-methyladenosine (m⁶A) methylation modification mediated by METTL3 regulates the senescence of SCAPs, and to elucidate the underlying molecular mechanisms. METHODS: Gain- and loss-of-function assays were performed using METTL3 overexpression and knockdown models to evaluate their effects on SCAP senescence and proliferation. To identify downstream targets of METTL3, Me-RIP (methylated RNA immunoprecipitation) high-throughput sequencing was conducted. The functional role of the METTL3-m⁶A-E2F3 axis in SCAP cell cycle progression was further validated via rescue experiments. RESULTS: SCAP senescence was accompanied by reduced m⁶A modification levels and downregulated METTL3 expression. Functional assays demonstrated that METTL3 overexpression attenuated SCAP senescence and enhanced proliferation, whereas METTL3 knockdown exerted the opposite effects. Me-RIP sequencing identified E2F3 as a potential downstream target gene of METTL3 in regulating SCAP senescence and proliferation. Rescue experiments confirmed that the METTL3-m⁶A-E2F3 axis modulated SCAP cell cycle progression, establishing a mechanistic link between METTL3-mediated m⁶A modification and SCAP fate. CONCLUSION: The METTL3-E2F3 axis serves as a critical anti-senescence mechanism in SCAPs under in vitro culture conditions. CLINICAL RELEVANCE: These findings lay the groundwork for the development of novel epigenetic therapies aimed at improving the therapeutic efficacy of SCAPs in regenerative endodontics.

Oral Health in Early and Advanced Stages (1-4) of Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Niederau C, Ali AA, Chahboun S … +8 more , Kalim S, Portillo MR, Kramann R, Schulze-Späte U, Wolfart S, Jankowski J, Wolf M, Craveiro RB

Int Dent J · 2026 May · PMID 42150341 · Full text

It is essential to identify oral health changes in the early stages of chronic kidney disease (CKD) to prevent oral degeneration. The effects of early-stage CKD on the periodontium and the manifestation of associated ora... It is essential to identify oral health changes in the early stages of chronic kidney disease (CKD) to prevent oral degeneration. The effects of early-stage CKD on the periodontium and the manifestation of associated oral symptoms remain poorly understood. Periodontitis is well documented in late-stage CKD. These changes represent a considerable burden for patients, leading to consequences like tooth loss and stomatognathic disorders. This study evaluates oral health parameters in patients with early- and advanced-stage CKD (stages 1-4), to identify potential changes in oral health and provide important insights into CKD-specific dental treatment. We performed a comprehensive literature search of the databases 'Pubmed', 'Web of Science', 'ClinicalTrials.gov', and 'Cochrane' up to June 2025. Of 1,584 search results, 24 studies met the inclusion criteria. The meta-analysis revealed that patients with early- and advanced-stage CKD exhibited significantly higher levels of plaque and calculus accumulation compared to healthy patients. These patients experienced pronounced gingival inflammation, elevated gingival index scores, and increased 'bleeding on probing' levels. They demonstrated significantly higher salivary pH levels and reduced salivary flow rates. There is a strong relationship between early and advanced-stage CKD and increased oral inflammation, plaque accumulation, and reduced saliva flow rate. To prevent the dental health of these patients from deteriorating, it is crucial to refer them to a dentist rapidly during the progression of the disease. Based on their understanding of the impact of CKD on oral health, the dentist will then determine a patient-specific recall interval.

Titanium Dioxide Particle Size Influences Macrophage Signal Switch Towards Osteogenesis In Vitro.

Aghila Rani KG, Rizvi Z, Suresh S … +3 more , Samsudin AR, AlKawas S, Kheder W

Int Dent J · 2026 May · PMID 42150340 · Full text

OBJECTIVE: The aim of this study was to investigate the impact of titanium dioxide microparticles (TiO MPs) and titanium dioxide nanoparticles (TiO NPs) on macrophage internalisation and their downstream influence on reg... OBJECTIVE: The aim of this study was to investigate the impact of titanium dioxide microparticles (TiO MPs) and titanium dioxide nanoparticles (TiO NPs) on macrophage internalisation and their downstream influence on regulating osteogenesis in vitro. DESIGN: The viability of THP-1-derived macrophages exposed to TiO MPs and TiO NPs was evaluated using XTT assays. Conditioned medium (CM) from macrophages treated with TiO MPs and NPs was collected and applied to human osteoblast (HOB) cells, with their functionality analysed at gene and protein expression levels, receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANKL/OPG) ratio, and matrix mineralisation. RESULTS: Both TiO MPs and NPs were nontoxic even at 100 µg/mL. Exposure of HOB to MP and NP CM induced significant proinflammatory responses, including increased IL-1β and IL-8 expression, alongside elevated TNF-α cytokine and MMP8 release. The TiO MP CM group elicited stronger inflammatory responses, whereas the TiO NP CM group demonstrated enhanced osteogenic activity, evidenced by upregulation of RUNX2, increased alkaline phosphatase activity, collagen type I secretion, and extracellular matrix mineralisation, generating a lower RANKL/OPG ratio in HOB cells. Western blotting revealed elevated osteocalcin and BMP-7 levels in NP CM-treated cells. CONCLUSION: Titanium dioxide particle sizes are able to "switch" macrophage signalling toward either bone formation (nano) or bone resorption (micro) and may play a crucial role in osteo-immunomodulation.

Accuracy of Large Language Models in Answering Dental Examination Questions: A Systematic Review and Meta-Analysis.

Dashti M, Khosraviani F, Meyari A … +7 more , Amirzade-Iranaq MH, Chaurasia A, Hefzi D, Ghadimi N, Tichy A, Khurshid Z, Schwendicke F

Int Dent J · 2026 May · PMID 42150339 · Full text

INTRODUCTION: Large language models (LLMs), including OpenAI's GPT family accessed via interfaces such as ChatGPT and Microsoft Copilot, as well as non-GPT systems such as Google Gemini, are increasingly applied in healt... INTRODUCTION: Large language models (LLMs), including OpenAI's GPT family accessed via interfaces such as ChatGPT and Microsoft Copilot, as well as non-GPT systems such as Google Gemini, are increasingly applied in healthcare and dental education. However, the accuracy of these systems in specialized tasks such as answering dental examination questions remains unclear. METHODS: This systematic review and meta-analysis evaluated LLM performance in answering dental questions. Databases searched were PubMed, Embase, Scopus, and Web of Science. Data on question type and number, LLM versions, and accuracy rates were extracted. Pooled accuracy was estimated using a random-effects model; heterogeneity and publication bias were assessed. RESULTS: A total of 39 studies were included, with ChatGPT-4 being the most frequently evaluated model. The pooled accuracy for LLMs was 63.7% (95% CI: 60.3%-67.1%), with high heterogeneity (I² = 91.5%). Subgroup analysis revealed ChatGPT-4 and Copilot (a GPT-based interface) achieved the highest pooled accuracies (∼73% and ∼75%, respectively). Direct comparisons confirmed ChatGPT-4 significantly outperformed earlier versions and some competitor models. Sensitivity analyses supported the robustness of findings. CONCLUSION: LLMs demonstrate moderate accuracy in answering dental examination questions and are currently insufficient for autonomous clinical decision-making. When their limitations are explicitly recognized, however, these systems may serve as valuable adjuncts in dental education and examination preparation. Methodological strategies such as structured prompting and retrieval-augmented approaches warrant further investigation but were not the primary focus of the present analysis.

When Does Synthetic Realism Become Clinical Utility? Reflections on Generative Orthopantomogram Datasets.

Ardila CM, Pineda-Vélez E, Díaz-Laclaustra AI

Int Dent J · 2026 May · PMID 42142408 · Full text

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Cost-Effectiveness of Population-Level Fluoride Policies: A Systematic Review of Health and Economic Outcomes.

Almutairi D, Al Humaidi M, Alshahrani SM … +1 more , Albalawi A

Int Dent J · 2026 May · PMID 42142407 · Full text

National Health Policies have adopted fluoridation-based programmes for the prevention of dental caries in many communities. Assessing their economic value across different settings is important for informing health poli... National Health Policies have adopted fluoridation-based programmes for the prevention of dental caries in many communities. Assessing their economic value across different settings is important for informing health policy and optimising resource allocation. To synthesise evidence of the economic efficiency of population-level public health interventions that use fluoride to prevent dental caries, compared with no fluoride policy or with alternative dental preventive interventions. Five electronic databases (PubMed/Medline, Cochrane Library, Embase, Global Health and EconLit) were searched for English-published studies on economic evaluations conducted in any country or population, without time restrictions. Eligible studies compared fluoridated water with no fluoridation, fluoridation cessation or alternative fluoride delivery strategies. Data were extracted on study design, perspective, time horizon, cost components, outcome measures and economic results. Given heterogeneity in settings, methods and outcomes, qualitative synthesis was conducted without pooling of the estimates. The review included 15 economic evaluations from high- and middle-income settings. Most studies reported that fluoridation was cost-effective or cost-saving compared with no fluoridation. More favourable economic results were generally observed in larger populations, those with a higher baseline caries risk and in studies focused on children. The evidence suggests cost-effectiveness and favourable budget impact of public fluoridation programmes compared with no fluoridation across diverse settings. However, the magnitude of economic benefit likely varies by population characteristics, study design and analytic assumptions. Therefore, careful interpretation is warranted when applying these findings to policy decisions. These findings provide clinicians and policymakers with robust economic evidence to support the continuation or implementation of fluoridation programmes as a primary preventive measure against dental caries.

Demineralization of Camel Dentin for Dental Tissue Engineering.

Khurshid Z, Cooper PR, Khan AS … +4 more , Dias G, Mazher J, Moin SF, Ratnayake J

Int Dent J · 2026 May · PMID 42139789 · Full text

BACKGROUND: Demineralisation of dentin effectively removes the crystalline hydroxyapatite phase while preserving the collagen matrix and associated bioactive proteins. This process results in an osteoinductive scaffold w... BACKGROUND: Demineralisation of dentin effectively removes the crystalline hydroxyapatite phase while preserving the collagen matrix and associated bioactive proteins. This process results in an osteoinductive scaffold with favourable biological properties, making demineralised dentin a promising naturally derived biomaterial for dentoalveolar bone and orthopaedic bone tissue regeneration. OBJECTIVE: This study aimed to evaluate the structural and elemental characteristics of camel dentin matrix after demineralisation using ethylenediaminetetraacetic acid (EDTA) and citric acid (CA) at various concentrations at 24 hours, with the goal of assessing its suitability as a biomaterial for bone grafting. METHODS: Camel dentin granules were extracted after removal of enamel and cementum and treated with EDTA and citric acid for 24 hours. Post-treatment, samples were analysed using scanning electron microscopy to assess morphological changes, energy-dispersive X-ray spectroscopy for elemental composition, Fourier-transform infrared spectroscopy and Raman spectroscopy for molecular characterisation. The degree of demineralisation was compared across groups. RESULTS: Scanning electron microscopy analysis revealed increased porosity and surface roughness following acid treatment, indicating demineralisation. Energy-dispersive X-ray spectroscopy analysis demonstrated a significant reduction in calcium and phosphorus levels, confirming mineral loss. Fourier-transform infrared spectra confirmed efficient demineralisation, evidenced by reduced phosphate and carbonate bands and enhanced Amide I to III peaks, indicating increased exposure of the collagen framework. Raman spectra showed diminished intensity of phosphate and carbonate peaks in treated samples, further supporting successful demineralisation. EDTA treatment for 24 hours yielded the most pronounced structural and chemical alterations. CONCLUSION: Demineralisation of camel dentin using EDTA and citric acid effectively alters its morphology and elemental composition. The optimised demineralisation protocol provides a promising approach for developing future demineralised dentin-derived graft materials from animal sources with potential osteoinductive properties.

FAM30A Induces Inflammation and Oxidative Damage in PDLSCs by Targeting miR-424-5p.

Zhi W, Huang L, Kang J … +2 more , Chu Z, Tu M

Int Dent J · 2026 May · PMID 42134194 · Full text

OBJECTIVE: To investigate the diagnostic value and regulatory role of FAM30A in patients with chronic periodontitis (CP). METHODS: The study included 104 CP patients. Saliva and periodontal ligament tissue samples were s... OBJECTIVE: To investigate the diagnostic value and regulatory role of FAM30A in patients with chronic periodontitis (CP). METHODS: The study included 104 CP patients. Saliva and periodontal ligament tissue samples were stored at -80°C. Logistic regression predicted risk factors for CP. Periodontal ligament stem cells (PDLSCs) were stimulated with 100 ng/mL LPS to establish an in vitro model. RT-qPCR assessed gene expression. CCK-8 and flow cytometry evaluated cell proliferation and apoptosis. ELISA measured inflammatory cytokine expression, while kits quantified oxidative stress products. Dual luciferase reporter assays and RNA immunoprecipitation examined gene-target relationships. RESULTS: FAM30A was upregulated in saliva and periodontal ligament tissue from CP patients. FAM30A demonstrated diagnostic value in both sample types and was identified as a risk factor for CP. LPS stimulation increased FAM30A expression in cells. si-FAM30A promoted cell proliferation, reduced apoptosis, and suppressed inflammatory and oxidative stress levels. miR-424-5p was downregulated in CP patients. Furthermore, FAM30A competitively binds miR-424-5p to modulate PDLSCs' function. Transfection with miR inhibitor counteracts si- FAM30A-induced cellular dysfunction and inflammatory responses. CONCLUSION: FAM30A induces CP by targeting miR-424-5p to inhibit PDLSCs proliferation, promote apoptosis, and increase inflammatory and oxidative stress levels.

MMP1 Modulates Head and Neck Squamous Cell Carcinoma Progression and Therapeutic Response Via Tumour Microenvironment.

Mao C, Chen D, Lai Y … +2 more , Lu M, Wang C

Int Dent J · 2026 May · PMID 42134193 · Full text

AIM: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive malignancy driven by complex molecular interactions within the tumour microenvironment (TME). This study aimed to investigate the critical role of M... AIM: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive malignancy driven by complex molecular interactions within the tumour microenvironment (TME). This study aimed to investigate the critical role of MMP1 in HNSCC progression, particularly its interplay with the microbiome and immune remodelling, to uncover potential therapeutic targets. METHODS: We conducted transcriptomic analysis of HNSCC tissues and performed functional experiments in Cal-27 cells using a zebrafish tumour model, including MMP1 knockdown. The effects of TPF chemotherapy, Bifidobacterium longum, and their combination were evaluated in vitro. Additionally, we assessed macrophage recruitment, proinflammatory cytokine expression (IL-6, IL-1B, TNF-A), angiogenesis-related genes (VEGFA), zebrafish transcriptomic profiles, and gut microbiota diversity. RESULTS: Transcriptomic profiling revealed significant gene expression differences between cancer and healthy tissues, with enrichment in metabolic, neurodegenerative, and cardiovascular pathways. MMP1 was markedly up-regulated in tumours and strongly correlated with invasion and metastasis. Functional studies demonstrated that MMP1 knockdown reduced the efficacy of TPF, B. longum, and their combination, impairing tumour growth suppression, macrophage recruitment, and proinflammatory cytokine expression. However, B. longum partially counteracted MMP1-mediated immune activation, suggesting microbial-immune crosstalk. MMP1 knockdown also retained partial inhibition of angiogenesis-related genes (eg, VEGFA), indicating a selective role in vascular remodelling. Furthermore, MMP1 knockdown attenuated the Cal-27 cell-induced reduction in zebrafish gut microbiome diversity and alterations in transcriptomic expression patterns. CONCLUSION: Our findings establish MMP1 as a key regulator of HNSCC progression and therapeutic response, influencing microbiome-mediated immune remodelling, inflammation, and angiogenesis. These insights suggest that targeting MMP1 and modulating the microbiome could enhance therapeutic strategies for HNSCC by reshaping the TME. This study provides a foundation for further exploration of TME-targeted interventions in HNSCC treatment.

In Vivo Complete Arch Implant Impressions: Comparison of the Linear Precision of Digital and Conventional Techniques.

Martínez-Marugán A, Santamaria-Laorden A, Ortiz-Collado I … +3 more , Freire Y, Andreu-Vázquez C, Orejas-Pérez J

Int Dent J · 2026 May · PMID 42134192 · Full text

BACKGROUND: The aims of this in vivo study were to determine which implant impression technique has the best in-mouth precision and to analyse whether the maxillary or mandibular position of the implants and the increase... BACKGROUND: The aims of this in vivo study were to determine which implant impression technique has the best in-mouth precision and to analyse whether the maxillary or mandibular position of the implants and the increase in the interimplant distance affect the precision. METHODS: A fully edentulous patient rehabilitated with 8 implants in each arch was included in this in vivo study. Five impressions per technique and arch were obtained using 6 impression techniques: closed tray (IT), unsplinted direct technique (UDT), acrylic resin-splinted direct technique (ASDT), metal-splinted direct technique (MSDT), stereophotogrammetry (PIC system), and intraoral scanning (Trios). Precision was evaluated by comparing 28 Euclidean interabutment distances per impression. A threshold of 75 μm was used as a reference value based on previously published implant misfit studies. RESULTS: Within the limitations of this study, the PIC system showed the highest precision among the evaluated techniques with 95% of the values <75 μm for the mandibular arch and 99% for the maxillary arch. The IT technique did not result in differences in the precision between the maxillary and the mandibular arches (P = .663); the other techniques showed statistically significant differences between the maxillary and the mandibular positions of the implants (P < .001). CONCLUSIONS: Significant differences were observed when comparing the precision of the 6 techniques, with the PIC system tending to show the highest precision within the limitations of this study. Statistically significant differences were also obtained between the maxillary arch and the mandibular arch within each technique and the precision decreased as the interimplant distance increased, particularly for the T technique.

Oral Health-related Quality of Life Among 2SLGBTQIAPN+: A Systematic Review.

Phyo WM, Ma A, Detsomboonrat P … +3 more , Sáenz JRV, Duangthip D, Hong G

Int Dent J · 2026 May · PMID 42134191 · Full text

Emerging evidence indicates that 2-spirit, lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, pansexual, nonbinary and other sexual and gender minorities (2SLGBTQIAPN+) individuals experience disp... Emerging evidence indicates that 2-spirit, lesbian, gay, bisexual, transgender, queer/questioning, intersex, asexual, pansexual, nonbinary and other sexual and gender minorities (2SLGBTQIAPN+) individuals experience disproportionately higher oral disease burdens, which may negatively affect their oral health-related quality of life (OHRQoL). These inequities are associated with financial barriers, lower income, limited affordability of dental care and discrimination, such as misgendering in health care settings. Reviewing OHRQoL in this population is essential to understand the broader impacts of oral health disparities and to guide inclusive, culturally sensitive oral health policies and interventions. A systematic search was conducted on 1 March 2026 across EBSCOhost, PubMed, Scopus and Web of Science, without restrictions on publication year. After removing duplicates, 3 researchers independently performed the selection process, with disagreements resolved through discussion. Google Scholar, reference list screening and citation tracking of included studies were also used to identify additional relevant literature. The inclusion criteria encompassed observational studies that examined OHRQoL among 2SLGBTQIAPN+ individuals using at least 1 validated OHRQoL tool. Six studies met the inclusion criteria. Three were conducted in Brazil and 1 each in India, Malaysia and Australia, with publication dates between 2018 and 2025. Half of the included studies (50%, 3/6) used the Oral Health Impact Profile-14 to measure OHRQoL, with psychological discomfort frequently reported as the most negatively affected domain. Poorer OHRQoL was associated with indicators of dental disease and psychosocial and structural factors, including gender identity, sexual orientation, suicidal ideation, challenges in accessing dental care and discrimination. Current evidence, though limited, suggests notable OHRQoL disparities among 2SLGBTQIAPN+ individuals. These findings highlight the need for more rigorous research and the development of inclusive oral health policies addressing the unique needs of 2SLGBTQIAPN+ populations.

Injection of Adipose-Derived Mesenchymal Stem Cell-Enriched Adipose Extract for Temporomandibular Joint Osteoarthritis: A Randomised Controlled Trial.

Jing B, Zhang Z, Lv Y … +5 more , Zhou S, Liu F, Chen M, Gong Z, Li Y

Int Dent J · 2026 May · PMID 42134190 · Full text

AIMS: This study aims to compare the efficacy of adipose-derived mesenchymal stem cells-enriched adipose extract (ARDE) with hyaluronic acid (HA) intra-articular injection in the treatment of temporomandibular joint oste... AIMS: This study aims to compare the efficacy of adipose-derived mesenchymal stem cells-enriched adipose extract (ARDE) with hyaluronic acid (HA) intra-articular injection in the treatment of temporomandibular joint osteoarthritis. METHODS: The randomised controlled trial included patients who did not respond to conservative treatment, were diagnosed with anterior disc displacement without reduction according to the diagnostic criteria for Temporomandibular Disorders, and had a Visual Analogue Scale (VAS) score >4. After joint lavage, the control group received HA injections, while the study group received ARDE injections. The primary outcome included VAS scores for pain, while secondary outcome measures included maximum mouth opening (MMO) and magnetic resonance imaging results. Evaluations were performed at baseline, 1 month, and 6 months postoperatively. RESULTS: A total of 50 patients were enrolled (25 per group), with comparable baseline characteristics between groups (P > .05). Analysis of covariance showed that the least-squares (LS) mean change in VAS score from baseline to month 6 in the ARDE vs HA groups was -4.9 vs -4.3 cm, respectively (LS mean difference, -0.7; 95% CI, -1.1 to -0.2; P = .009). For the MMO, the LS mean change was 1.7 vs 1.4 cm, respectively (LS mean difference, 0.3; 95% CI, 0 to 0.5; P = .022). Linear mixed-effects models verified significant group and time main effects for VAS score (both P < .001) and significant group main effect for MMO (P = .009), but no significant group-by-time interaction was found for either indicator (both P > .05). Magnetic resonance imaging indicated more significant resolution of preoperative joint effusion in ARDE group (18/22 vs 6/20, P < .01). CONCLUSION: ARDE injections demonstrate promising potential in relieving pain and improving joint function in patients with temporomandibular joint osteoarthritis, as compared with HA injections.

Non-Invasive Screening of AI-Assisted DNA Aneuploidy Cytology by Image Cytometry for the Early Diagnosis of Malignant Transformation of OPMDs.

Tan YQ, Wang F, Chen XY … +9 more , Huang XX, Wei XY, Lu R, Chen XJ, Du GF, Wang F, He MJ, Zhang J, Zhou G

Int Dent J · 2026 May · PMID 42134189 · Full text

INTRODUCTION AND AIMS: Oral exfoliative DNA aneuploidy cytology by image cytometry (DNA-ICM) has been introduced for the early diagnosis of malignant transformation. This study aimed to investigate the optimal cut-off va... INTRODUCTION AND AIMS: Oral exfoliative DNA aneuploidy cytology by image cytometry (DNA-ICM) has been introduced for the early diagnosis of malignant transformation. This study aimed to investigate the optimal cut-off values of DNA content and assess the diagnostic accuracy of artificial intelligence (AI)-assisted DNA-ICM for detecting the risk of malignant transformation in oral potentially malignant disorders (OPMDs). METHODS: A total of 6,874 consecutive patients with clinical lesions of OPMDs were subjected to AI-assisted DNA-ICM analysis. In this study, both oral exfoliative cytobrushing and surgical biopsy samples were obtained from 415 patients with OPMDs and then allocated by AI-assisted DNA-ICM and histopathological examination, respectively. The diagnostic efficiency and accuracy of AI-assisted DNA-ICM analysis were evaluated in this OPMDs cohort. Fisher's exact test was applied to evaluate differences in qualitative variables. Logistic regression analysis was used to estimate the odds ratio (OR) and the associations among confounding variables. RESULTS: For the optimal cut-off values of at least 1 aneuploid cell with DNA content ≥4.86c, the area under the curve (AUC) was 0.840 (sensitivity, 76.19%; specificity, 74.40%) for the discrimination of dysplasia from OPMDs. For the DNA content ≥6.2c, the AUC was 0.766 (sensitivity, 80.52%; specificity, 64.38%) for detecting carcinoma from OPMDs. Notably, OR analysis by logistic regression suggested that ages ≥60 years and the areca nut chewing habit were significantly associated with dysplasia or worse in OPMDs. In addition, DNA aneuploidy criteria and their diagnostic accuracy vary among different subtypes of OPMDs. CONCLUSION: This diagnostic study optimised the criteria of DNA aneuploidy cytology for detecting malignant transformation of OPMDs. AI-assisted DNA-ICM may be an efficient noninvasive diagnostic tool for screening different high-risk OPMDs and early-stage oral cancers. CLINICAL RELEVANCE: This clinicopathological diagnostic study establishes a methodological foundation for future broader screening applications of oral exfoliative AI-assisted DNA-ICM.

Multimodal Prediction of Periodontitis Using Root Exposure in Intraoral Images and Age.

Kang S, Go H, Kwon YE … +3 more , Choi YH, Park EY, Kim EK

Int Dent J · 2026 May · PMID 42119243 · Full text

INTRODUCTION AND AIMS: Despite advances in AI-based periodontitis screening, quantifiable and interpretable biomarkers from intraoral photographs remain underexplored. Therefore, this study aimed to develop a deep learni... INTRODUCTION AND AIMS: Despite advances in AI-based periodontitis screening, quantifiable and interpretable biomarkers from intraoral photographs remain underexplored. Therefore, this study aimed to develop a deep learning pipeline for exposed root area quantification from photographs and to evaluate its predictive value for periodontitis risk within a multimodal framework integrating age. METHODS: Intraoral photographs of the mandibular anterior sextant and covariate questionnaires were obtained from 269 participants. A fine-tuned YOLOv11 segmentation model quantified tooth and exposed root surface areas, from which the exposed root ratio (ERR) was derived. ERR was combined with age and self-reported data to train four machine learning models (logistic regression, SVM, random forest, gradient boosting) for periodontitis prediction. Performance was assessed using AUROC and permutation feature importance across different feature sets. RESULTS: The YOLOv11 segmentation model achieved an overall mAP@0.5 of 0.901, with mean Dice coefficients of 0.928 and 0.844 for tooth and exposed root, respectively. In the ≥35 age group, ERR-only models outperformed age-only models across all four machine learning algorithms, with statistically significant differences in 13 of 24 comparisons (mean ΔAUROC: 0.031-0.094, p < .05). Integration of ERR with age further improved predictive performance, yielding significant gains in 19 of 24 comparisons (mean ΔAUROC: 0.029-0.131, p < .05). Permutation feature importance analysis revealed ERR as the dominant predictor in the ≥45 age group, with importance scores of 0.391 and 0.366 for ERR compared to 0.151 and 0.273 for age in Gradient Boosting and Random Forest, respectively. CONCLUSION: AI-derived ERR from mandibular anterior images is a reproducible, interpretable biomarker that outperforms age and enhances periodontitis prediction when combined with conventional risk factors. CLINICAL RELEVANCE: AI-driven quantification of ERR from intraoral photographs offers a practical, non-invasive, and cost-effective screening tool for periodontitis risk assessment in primary care and community settings, particularly among middle-aged and older populations.

Panoramic Soft Tissue Calcifications as Vascular Risk Markers in Diabetes: A Pilot Case-Control Study in Hungarians.

Lipták L, Lipták K, Hermann P … +7 more , Rózsa NK, Végh Á, Bányai D, Kolarovszki B, Marada G, Végh D, Mühl A

Int Dent J · 2026 May · PMID 42107456 · Full text

INTRODUCTION: Soft tissue calcifications on dental panoramic radiographs (PR) may reflect systemic vascular disease. Given the increased cardiovascular and cerebrovascular risk in diabetes, this study compared their prev... INTRODUCTION: Soft tissue calcifications on dental panoramic radiographs (PR) may reflect systemic vascular disease. Given the increased cardiovascular and cerebrovascular risk in diabetes, this study compared their prevalence in patients with diabetes and baseline-comparable nondiabetic controls and explored associations in the combined sample. METHODS: This retrospective case-control study included 56 adults with diabetes and 56 nondiabetic controls, frequency-matched by age (±5 years) and sex. Four calibrated examiners independently evaluated PRs with consensus adjudication. Outcomes were soft tissue calcification, carotid-region calcification, and stylohyoid ligament complex calcification/ossification. Crude prevalence was calculated for each group and the total sample, and multivariable logistic regression adjusted for age, sex, diabetes status, smoking, alcohol use, renal disease, and rheumatic disease. RESULTS: A total of 112 participants were analysed (56 with diabetes mellitus and 56 controls), with comparable baseline characteristics between groups. In the total sample, the crude prevalence of any soft tissue calcification was 42.0%, carotid-region calcification 27.7%, and stylohyoid ligament complex calcification/ossification 35.7%. In adjusted models across the combined sample, age was independently associated with higher odds of any soft tissue calcification (per 10-year increase: aOR 1.68, 95% CI 1.23-2.29; P = 0.001) and carotid-region calcification (aOR 1.52, 95% CI 1.08-2.14; P = .016). Male sex was associated with lower odds of any soft tissue calcification (aOR 0.40, 95% CI 0.16-0.99; P = .047). Diabetes status was not independently associated with the outcomes in the fully adjusted models. CONCLUSION: Panoramic soft tissue calcifications were common. Although diabetes was not an independent predictor, frequent detection of suspected carotid-region calcifications supports structured reporting and opportunistic vascular risk assessment on routine PR, especially in older patients. CLINICAL RELEVANCE: Opportunistic identification of carotid-region calcifications on routine PR may support early cardiovascular risk assessment, particularly in patients with diabetes and older adults.

Macrophage-MSCs Interplay in Orthodontic Bone Remodelling: Mechanics-Immunity-Stem Cell Axis.

Chen M, Li Y, Hu J

Int Dent J · 2026 May · PMID 42105727 · Full text

During orthodontic treatment, the balance of bone remodelling is dynamically regulated by macrophages and site-specific mesenchymal stem cells (MSCs) through the mechanics-immunity-stem cell axis. Polarization of macroph... During orthodontic treatment, the balance of bone remodelling is dynamically regulated by macrophages and site-specific mesenchymal stem cells (MSCs) through the mechanics-immunity-stem cell axis. Polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is driven by mechanical forces via mechanosensors such as the Piezo1 channel. Macrophage polarization is induced by MSCs through exosomes and cytokine feedback, establishing a positive feedback loop of 'inflammation resolution-bone regeneration'. Moreover, other immune cells such as neutrophils and T lymphocytes participate in modulating the microenvironment. The dynamic balance of bone remodelling is collectively maintained by crosstalk among key signalling pathways: Wnt/β-catenin for osteogenesis, RANKL/RANK for bone resorption, and PI3K-Akt for macrophage polarization. These insights offer actionable targets for developing adjunctive therapies to accelerate orthodontic bone remodelling and improve treatment efficiency. Therefore, understanding the crosstalk mechanism between macrophages and MSCs under mechanical force is of significant clinical importance for targeting this interaction axis to optimize orthodontic treatment and accelerate bone remodelling.

Knowledge and Awareness of Performance Metrics in Dental Image Analysis With Artificial Intelligence: A Cross-Sectional Survey of Researchers and Clinicians.

Ramani R, Jones B, Chaurasia A … +5 more , Khazaei Y, Schwärzler J, Uribe SE, Schwendicke F, Tichy A

Int Dent J · 2026 May · PMID 42096837 · Full text

INTRODUCTION AND AIM: Appropriate performance metrics are essential for evaluating machine learning (ML) algorithm performance in dental image analysis. A broad variety of performance metrics are used in dental artificia... INTRODUCTION AND AIM: Appropriate performance metrics are essential for evaluating machine learning (ML) algorithm performance in dental image analysis. A broad variety of performance metrics are used in dental artificial intelligence (AI) research which could cause confusion regarding model performance. This study aimed to assess the knowledge, awareness, and self-reported confidence of oral health researchers and clinicians regarding AI performance metrics. METHODS: This cross-sectional, questionnaire-based survey initially recruited participants (n = 100) from the ITU/WHO/WIPO Global Initiative on AI for Health Topic Group - Oral Health and affiliated professional global networks. An online self-administered questionnaire evaluated theoretical knowledge and applied knowledge. Participants also reported basic demographics and their confidence in using different metrics. RESULTS: Overall performance was poor with participants achieving a mean score of 17.1% (SD: 15.2%, median: 16.7%, IQR: 16.7%) for fully correct responses. Responses to theoretical questions were rarely fully correct (range: 1%-15%; median: 5.5%). Applied scenario performance ranged from 17% to 37% correct responses (median: 29%). Participants demonstrated greater knowledge of common metrics (accuracy, specificity) but struggled with advanced measures (Intersection over Union & Dice Similarity Coefficient). Common errors included terminology confusion, familiarity bias towards accuracy, and task-metric misalignment. CONCLUSION: Substantial gaps exist in knowledge and awareness of both theory and practical applications of AI performance metrics amongst dental professionals and researchers. Frequent misapplication of commonly known metrics suggests overgeneralisation without consideration of task-specific requirements. CLINICAL RELEVANCE: Inadequate knowledge or awareness of metric selection and interpretation may lead to the deployment of suboptimal algorithms, which can compromise diagnostic accuracy and patient outcomes. Enhanced understanding of performance metrics is critical for ensuring reliable, fair, safe, and effective AI systems in clinical dentistry.

Anatomical Predictors of Second Molar External Root Resorption: A Cone-Beam Computed Tomography Study of Impacted Third Molars.

Wang M, Wang J, U I … +4 more , Wu Y, Zhang S, Liu Z, Wu Z

Int Dent J · 2026 May · PMID 42096836 · Full text

OBJECTIVES: This study aimed to identify anatomical and radiographic risk factors associated with second molar (M2) external root resorption (ERR) induced by impacted third molars (M3) using cone-beam computed tomography... OBJECTIVES: This study aimed to identify anatomical and radiographic risk factors associated with second molar (M2) external root resorption (ERR) induced by impacted third molars (M3) using cone-beam computed tomography, providing a strategic framework for clinical decision-making regarding prophylactic extraction. METHODS: A retrospective analysis was conducted on cone-beam computed tomography scans of 513 impacted M3s. Anatomical parameters, including M3 angulation, impaction depth (Pell and Gregory classification), and skeletal constraints (M3 to the posterior border of the maxilla, distance from the M3 root to the posterior border of the mandible, etc.) were quantified. The severity and anatomical location of M2 ERR were evaluated using stratified statistical methods to identify key predictors of resorption. RESULTS: In the univariate analysis, M2 ERR severity was significantly associated with M3 impaction depth and skeletal space constraints rather than angulation alone (P < .05). Class C impaction with apical-third involvement represented the highest risk profile; notably, 100% of severe maxillary ERR cases were localized to the M2 apical third. In the multivariate model, an increased distance from the M3 to the posterior border of the maxilla (OR = 1.26) and a reduced cervical width of the M2 were key predictors of severity. Furthermore, a distinct sexual dimorphism was observed, with female patients exhibiting a significantly higher prevalence of severe maxillary ERR, likely due to more restricted skeletal space. CONCLUSIONS: The severity of M2 ERR is primarily driven by impaction depth and anatomical constraints, particularly the limited space in the maxillary tuberosity and mandibular retromolar area. Class C impaction targeting the M2 apical third is the most critical risk factor for severe resorption. CLINICAL RELEVANCE: Clinicians should consider a proactive management strategy, prioritizing preventive M3 extraction in high-risk cases - specifically Class C impactions in female patients - to avoid irreversible pulp involvement and potential M2 loss. These findings support shifting from passive observation to early intervention based on specific anatomical risk profiles.

The Effect of Er:YAG Laser Therapy as an Adjunct to Surgical Treatment Compared to Latter Alone in Managing Medication-Related Osteonecrosis of the Jaw: A Randomised Controlled Clinical Trial.

Michalak F, Dominiak M, Kiryk J … +2 more , Abd-Ul-Salam H, Grzech-Leśniak K

Int Dent J · 2026 May · PMID 42090951 · Full text

OBJECTIVE: The aim of this double-blind randomised controlled clinical trial was to assess the effectiveness of the Er:YAG laser as an adjunct to conventional surgical treatment compared to surgical treatment alone in ma... OBJECTIVE: The aim of this double-blind randomised controlled clinical trial was to assess the effectiveness of the Er:YAG laser as an adjunct to conventional surgical treatment compared to surgical treatment alone in managing medication-related osteonecrosis of the jaw (MRONJ). METHODS: Sixty-five patients diagnosed with stage II or III MRONJ were randomly allocated into 2 groups: a control group (n = 30) treated using conventional surgery alone and a test group (n = 35) treated using conventional surgery with adjunctive Er:YAG laser. All patients received 3-day preoperative and 14-day postoperative antibiotics. Follow-up assessments were scheduled at 1, 2, 4, 12, and 24 weeks postoperatively. Postoperative outcomes, including complications, disease progression, pain, and soft tissue healing, were assessed. Descriptive and inferential statistical analyses were utilised. RESULTS: Compared to conventional surgery alone, adjunctive Er:YAG laser therapy resulted in significantly reduced postoperative complication rates (17.1% vs 60%, P < .001), improved mucosal healing (85.7% vs 26.7%, P < .001), and reduced pain. The laser-assisted procedure, however, was significantly longer (70.03 vs 57.90 minutes, P < .001). CONCLUSIONS: Incorporating Er:YAG laser therapy as an adjunct to conventional surgical treatment for MRONJ (stages II and III) positively influenced clinical outcomes by enhancing soft tissue healing and reducing postoperative complications.

In Vitro Single-Cell Transcriptomic Profiling of Cultured Stem Cells From Apical Papilla and Dental Pulp Stem Cells: Unveiling Cellular Heterogeneity.

Shah MS, Sayegh MA, Khalil MM … +7 more , Sundarabupathi M, AlKhnbashi O, Samaranayake L, Khyriem C, Sultana M, Egusa H, Jamal M

Int Dent J · 2026 May · PMID 42090950 · Full text

INTRODUCTION: Dental-derived mesenchymal stem cells show considerable variability in their differentiation potential due to the use of nonspecific surface markers and technical limitations in isolation protocols. This st... INTRODUCTION: Dental-derived mesenchymal stem cells show considerable variability in their differentiation potential due to the use of nonspecific surface markers and technical limitations in isolation protocols. This study aimed to employ single-cell RNA sequencing to compare the cellular composition of cultured stem cells from apical papilla (SCAPs) and dental pulp (DPSCs), with the goal of detecting subpopulations underlying their divergent regenerative behaviour and identifying markers that can facilitate future isolation and functional targeting. METHOD: SCAP and DPSC tissues were obtained from 3 human donors and cultured to passage 2. Single-cell suspensions were sequenced to generate gene expression profiles. Dimensionality reduction and clustering were performed using the Seurat package and visualised using uniform manifold approximation and projection. Cluster-specific differential gene expression was computed as log2 fold change, followed by gene set enrichment analysis. Pseudotime trajectory analysis was used to map lineage progression based on transcriptional gene expression. RESULTS: Transcriptomic analysis identified 12 distinct clusters shared across DPSC and SCAP cultures. While both cell types contributed comparably to overall biological processes, key differences emerged within specific clusters. Clusters 3, 4, 5, 6, and 9 expressed high levels of proliferative markers (MKI67, TOP2A, and TYMS), suggesting active proliferating populations. Cluster 9 was notable for the coexpression of pericyte-associated markers (NOTCH3, PDGFRB) alongside canonical mesenchymal stromal cell markers (MCAM, THY1, DCN), identifying a previously uncharacterised progenitor-like subset. NOTCH3 and PDGFRB were also present in a more mature fibroblast-enriched population in cluster 7, dominated by collagen-related genes. IGFBP3 and IGFBP5 were selectively enriched in SCAP-derived clusters 7 and 9, whereas IGFBP4, 6, and 7 were expressed across both DPSC and SCAP populations. Clusters 10 and 11, primarily derived from DPSCs, were enriched in stress-response, heat shock, and apoptotic genes, which may reflect culture-induced adaptations. Pseudotime trajectory inference positioned cluster 9 at a putative progenitor-like node; however, this represents a hypothesis-generating model based on transcriptional similarity in cultured cells rather than validated lineage relationships. CONCLUSION: This study provides a high-resolution single-cell transcriptomic comparison of cultured SCAPs and DPSCs, revealing distinct transcriptional profiles and cellular heterogeneity. SCAPs may harbour a broader spectrum of proliferative progenitors under these culture conditions, particularly in clusters 7 and 9, enriched in IGF-, PDGFRB-, and NOTCH-associated genes. These findings generate testable hypotheses regarding subpopulation-specific regenerative roles. Future studies using prospective isolation based on NOTCH3/PDGFRB and functional in vitro and in vivo validation are needed to establish their regenerative potential and translational relevance.
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