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The purpose of the presented Artificial Intelligence (AI)-tool was to automatically segment the mandibular molars on panoramic radiographs and extract the molar orientations in order to predict the third molars' eruption potential. In total, 838 panoramic radiographs were used for training (n = 588) and validation (n = 250) of the network. A fully convolutional neural network with ResNet-101 backbone jointly predicted the molar segmentation maps and an estimate of the orientation lines, which was then iteratively refined by regression on the mesial and distal sides of the segmentation contours. Accuracy was quantified as the fraction of correct angulations (with predefined error intervals) compared to human reference measurements. Performance differences between the network and reference measurements were visually assessed using Bland-Altman plots. The quantitative analysis for automatic molar segmentation resulted in mean IoUs approximating 90%. Mean Hausdorff distances were lowest for first and second molars. The network angulation measurements reached accuracies of 79.7% [-2.5°; 2.5°] and 98.1% [-5°; 5°], combined with a clinically significant reduction in user-time of >53%. In conclusion, this study validated a new and unique AI-driven tool for fast, accurate, and consistent automated measurement of molar angulations on panoramic radiographs. Complementing the dental practitioner with accurate AI-tools will facilitate and optimize dental care and synergistically lead to ever-increasing diagnostic accuracies.

The purpose of this study was to evaluate the change in periodontal status of the adjacent second molar of the impacted mandibular third molar after surgical extraction and its association with the third molar condition in the presurgical stages, including position, eruption level, and local complications.

Do developmental systems preferentially produce certain types of variation that orient phenotypic evolution along preferred directions? At different scales, from the intra-population to the interspecific, the murine first upper molar shows repeated anterior elongation. Using a novel quantitative approach to compare the development of two mouse strains with short or long molars, we identified temporal, spatial and functional differences in tooth signaling center activity, that arise from differential tuning of the activation-inhibition mechanisms underlying tooth patterning. By tracing their fate, we could explain why only the upper first molar reacts via elongation of its anterior part. Despite a lack of genetic variation, individuals of the elongated strain varied in tooth length and the temporal dynamics of their signaling centers, highlighting the intrinsic instability of the upper molar developmental system. Collectively, these results reveal the variational properties of murine molar development that drive morphological evolution along a line of least resistance.

Analyze defects in the state of maturation of the enamel result in an adequate volume of enamel, but in an insufficient mineralization, which can affect both deciduous teeth and permanent teeth. Among the most common defects, we recognize Deciduous Molar Hypominerlization (DMH), Hypomineralized Second Primary Molar (HSPM), and Molar Incisor Hypomineralization (MIH). These, in fact, affect the first deciduous molars, the second deciduous molars and molars, and permanent incisors, respectively, but their etiology remains unclear. The objective of the paper is to review studies that focus on investigating possible associations between genetic factors or prenatal, perinatal, and postnatal causes and these enamel defects.

A 15-year-old female presented to the emergency department with complaints of vaginal bleeding. She was pale, anxious, cool and clammy with tachycardic, thready peripheral pulses and hemoglobin of 2.4g/dL. Her abdomen was gravid appearing, approximately early to mid-second trimester in size. Pelvic examination revealed 2 cm open cervical os with spontaneous discharge of blood, clots and a copious amount of champagne-colored grapelike spongy material. After 2L boluses of normal saline and two units of crossmatched blood, patient was transported to the operating room. Surgical pathology confirmed a complete hydatidiform mole.

Uterine natural killer (uNK) cells have been hypothesized to serve a role in controlling trophoblast invasion and proliferation. The aim of the present study was to identify the distribution and number of uNK cells in normal pregnancy (NP), partial mole (PM), complete mole (CM) and invasive mole (IM). uNK cells were detected using dolichos biflorus agglutinin lectin immunohistochemistry in decidual and villous tissues from early NP (n=15), late NP (n=15), PM (n=22), CM (n=20) and IM (n=10). A scaled eye piece was used for cell counting to obtain semi-quantitative results. It was revealed that uNK cells were mainly located in the uterine deciduas of early NP. As pregnancy progressed, the number of decidual uNK cells significantly decreased. Decidual uNK cells of PM, CM and IM were located near blood vessel endothelial cells. No significant differences were detected with respect to the numbers of decidual uNK between early NP and PM. However, the number of decidual uNK cells was significantly reduced in CM and IM compared with early NP. The populations of decidual uNK cells were not significantly different between CM and IM. No uNK cells were detected in the villi of PM, CM or IM. The decrease of decidual uNK cells in late NP, CP and IM, compared with early NP, suggested that uNK cells served an important role in controlling trophoblast invasion and proliferation.

A major challenge in evolutionary developmental biology is to understand how genetic mutations underlie phenotypic changes. In principle, selective pressures on the phenotype screen the gene pool of the population. Teeth are an excellent model for understanding evolutionary changes in the genotype-phenotype relationship since they exist throughout vertebrates. Genetically modified mice (mutants) with abnormalities in teeth have been used to explore tooth development. The relationship between signaling pathways and molar shape, however, remains elusive due to the high intrinsic complexity of tooth crowns. This hampers our understanding of the extent to which developmental factors explored in mutants explain developmental and phenotypic variation in natural species that represent the consequence of natural selection. Here we combine a novel morphometric method with two kinds of data mining techniques to extract data sets from the three-dimensional surface models of lower first molars: i) machine learning to maximize classification accuracy of 22 mutants, and ii) phylogenetic signal for 31 Murinae species. Major shape variation among mutants is explained by the number of cusps and cusp distribution on a tooth crown. The distribution of mutant mice in morphospace suggests a nonlinear relationship between the signaling pathways and molar shape variation. Comparative analysis of mutants and wild murines reveals that mutant variation overlaps naturally occurring diversity, including more ancestral and derived morphologies. However, taxa with transverse lophs are not fully covered by mutant variation, suggesting experimentally unexplored developmental factors in the evolutionary radiation of Murines.

The relationship between the impacted mandibular third molar (IMTM) and the external root resorption (ERR) of the mandibular second molar (MSM) was analysed with cone-beam computed tomography (CBCT). The risk factors affecting the ERR of the MSM were examined to provide a reference.

Tooth development requires proliferation, differentiation, and specific migration of dental epithelial cells, through well-organized signaling interactions with mesenchymal cells. Recently, it has been reported that leucine-rich repeat-containing G protein coupled receptor 4 (LGR4), the receptor of R-spondins, is expressed in many epithelial cells in various organs and tissues and is essential for organ development and stem cell maintenance. Here, we report that LGR4 contributes to the sequential development of molars in mice. LGR4 expression in dental epithelium was detected in SOX2+ cells in the posterior end of the second molar (M2) and the early tooth germ of the third molar (M3). In keratinocyte-specific Lgr4-deficient mice (Lgr4K5 KO ), the developmental defect became obvious by postnatal day 14 (P14) in M3. Lgr4K5 KO adult mice showed complete absence or the dwarfed form of M3. In M3 development in Lgr4K5 KO mice, at Wnt/β-catenin signal activity was down-regulated in the dental epithelium at P3, as indicated by lymphoid enhancer-binding factor-1 (LEF1) expression. We also confirmed the decrease, in dental epithelium of Lgr4K5 KO mice, of the number of SOX2+ cells and the arrest of cell proliferation at P7, and observed abnormal differentiation at P14. Our data demonstrated that LGR4 controls the sequential development of molars by maintaining SOX2+ cells in the dental epithelium, which have the ability to form normal molars.

Tooth germs undergo a series of dynamic morphologic changes through bud, cap, and bell stages, in which odontogenic epithelium continuously extends into the underlying mesenchyme. During the transition from the bud stage to the cap stage, the base of the bud flattens and then bends into a cap shape whose edges are referred to as "cervical loops." Although genetic mechanisms for cap formation have been well described, little is understood about the morphogenetic mechanisms. Computer modeling and cell trajectory tracking have suggested that the epithelial bending is driven purely by differential cell proliferation and adhesion in different parts of the tooth germ. Here, we show that, unexpectedly, inhibition of cell proliferation did not prevent bud-to-cap morphogenesis. We quantified cell shapes and actin and myosin distributions in different parts of the tooth epithelium at the critical stages and found that these are consistent with basal relaxation in the forming cervical loops and basal constriction around enamel knot at the center of the cap. Inhibition of focal adhesion kinase, which is required for basal constriction in other systems, arrested the molar explant morphogenesis at the bud stage. Together, these results show that the bud-to-cap transition is largely proliferation independent, and we propose that it is driven by classic actomyosin-driven cell shape-dependent mechanisms. We discuss how these results can be reconciled with the previous models and data.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.

The aim of the study is to compare the frequency and the distribution of molar incisor hypomineralization (MIH) in children with intellectual disabilities.

Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

This study aimed to compare the survival of mandibular first molars (MnM1s) adjacent to implants placed in mandibular second molar sites (ImM2s) with MnM1s adjacent to mandibular second molars (MnM2s) and to investigate risk indicators affecting the survival of MnM1s adjacent to ImM2s. A total of 144 patients who had MnM1s adjacent to ImM2s and MnM1s adjacent to MnM2s on the contralateral side were included in this study. Clinical variables and radiographic bone levels were evaluated. The survival of MnM1s adjacent to ImM2s or MnM2s was evaluated using a Kaplan-Meier analysis and Cox proportional hazards model. The 5-year cumulative survival rates of MnM1s adjacent to ImM2s and MnM2s were 85% and 95%, respectively. MnM1s adjacent to ImM2s of the internal implant-abutment connection type had higher multivariate hazard ratios (HR) for loss. MnM1s that had antagonists with implant-supported prostheses also had higher HR for loss. The multivariate HR for the loss of MnM1s adjacent to ImM2s with peri-implant mucositis was 3.74 times higher than MnM1s adjacent to healthy ImM2s. This study demonstrated several risk indicators affecting the survival of MnM1s adjacent to ImM2s. It is suggested that supportive periodontal and peri-implant therapy combined with meticulous occlusal adjustment can prolong the survival of MnM1s and ImM2s.

Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal. Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated. Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day. Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03169127.

Objective: An insufficient mineralization (hypomineralization) in the teeth during the maturation stage of amelogenesis cause defects in 3-44% of children. Here, we describe for the first time the microbiota associated with these defects and compared it to healthy teeth within the same subjects. Methods: Supragingival dental plaque was sampled from healthy and affected teeth from 25 children with molar-incisor hypomineralization (MIH). Total DNA was extracted and the 16S rRNA gene was sequenced by Illumina sequencing in order to describe the bacterial composition. Results: We detected a higher bacterial diversity in MIH samples, suggesting better bacterial adhesion or higher number of niches in those surfaces. We found the genera Catonella, Fusobacterium, Campylobacter, Tannerella, Centipeda, Streptobacillus, Alloprevotella and Selenomonas associated with hypomineralized teeth, whereas Rothia and Lautropia were associated with healthy sites. Conclusion: The higher protein content of MIH-affected teeth could favour colonization by proteolytic microorganisms. The over-representation of bacteria associated with endodontic infections and periodontal pathologies suggests that, in addition to promote caries development, MIH could increase the risk of other oral diseases.

The periodontal healing distal to the mandibular second molar (M2M) after coronectomy of the M3M has shown controversial results. We aimed to combine a digital method with cone-beam computed tomography (CBCT) and estimate periodontal healing of M2M after M3M coronectomy. An accurate and stable indicator in three dimensions was also explored tentatively.

The aim of this study was to investigate the mandibular ramus features that could contribute to the etiology of mandibular third molar impaction.

Development of mammalian teeth and surrounding tissues includes time-space changes in the extracellular matrix composition and organization. This requires complex control mechanisms to regulate its synthesis and remodeling. Fibril-associated collagens with interrupted triple helices (FACITs) and a group of small leucine-rich proteoglycans (SLRPs) are involved in the regulation of collagen fibrillogenesis. Recently, collagen type XII and collagen type XIV, members of the FACITs family, were found in the peridental mesenchyme contributing to alveolar bone formation. This study was designed to follow temporospatial expression of collagen types XIIa and XIVa in mouse first molar and adjacent tissues from embryonic day 13, when the alveolar bone becomes morphologically apparent around the molar tooth bud, until postnatal day 22, as the posteruption stage. The patterns of decorin, biglycan, and fibromodulin, all members of the SLRPs family and interacting with collagens XIIa and XIVa, were investigated simultaneously. The situation in the tooth was related to what happens in the alveolar bone, and both were compared to the periodontal ligament. The investigation provided a complex localization of the five antigens in soft tissues, the dental pulp, and periodontal ligaments; in the mineralized tissues, predentin/dentin and alveolar bone; and junction between soft and hard tissues. The results illustrated developmentally regulated and tissue-specific changes in the balance of the two FACITs and three SLRPs.