{"title":"Caries Is the Hub of a Complex Network of Chronic Diseases across the Life Decades","authors":"S. Alves-Costa, F.A. Rodrigues, A.A. Ferraro, G.G. Nascimento, F.R.M. Leite, B.F. Souza, C.C.C. Ribeiro","doi":"10.1177/00220345251317487","DOIUrl":"https://doi.org/10.1177/00220345251317487","url":null,"abstract":"Caries precedes periodontitis; both may predict fatal noncommunicable diseases (NCDs) decades in advance. However, the complex network of relationships between these and other NCDs remains unclear. Understanding the intricate nonlinear connections among NCDs from the early life stages holds profound significance for public health management strategies to prevent NCDs. Accordingly, we modeled the connections among NCDs and identified the underlying patterns in the US population from childhood to elderhood. Indicators of metabolic risks, diabetes, and cancer, as well as cardiovascular, autoimmune, mental, respiratory, and oral diseases, were collected from National Health and Nutrition Examination Survey data (2011–2012 and 2013–2014 cycles), encompassing 4 age groups of Americans aged 1 to ≥60 y. Diseases were represented as nodes in the complex network analysis, and edges indicated their co-occurrences. To characterize the networks, we computed degree, betweenness, eigenvector, local transitivity, assortative mixing, Shannon entropy, and cluster coefficients. Caries was the central hub in all models. Caries and obesity were linked since the first years of life, and with age, new diseases became connected, increasing network complexity with Shannon entropy from −2.79 to −4.07. Depression plays an essential role in adult life; however, episodes of forgetting and mental confusion surpass depression’s significance in elderhood. The centrality of diabetes, cardiovascular disease, and cancer increases with age, peaking at ≥60 y, with diabetes being the most prominent. All groups had coefficients indicating that NCDs were highly connected, with cluster coefficients of 0.85 to 0.98 and assortativity mixing of −0.23 to −0.06. Caries was the central element over the decades, with the other diseases orbiting around it. It was mainly linked to overweight/obesity from early childhood. Integrated strategies targeting shared risk factors for caries and obesity can boost childhood health and potentially affect the development of other NCDs later.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"8 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Rao, K.E.N. Watt, L. Maili, M. Lamb, E. Farrow, H. Hassan, K. Weaver, B. Miller, S. Dash, L.L. Cox, L. Gallacher, S.G. Kant, M. Gibson, T. Pastinen, D. Li, E.J.K. Bhoj, H. Zhu, J. Zhang, Y.-B. Zhang, T.Y. Tan, P.A. Trainor, T.C. Cox
{"title":"Splicing Defects and Cell Death Cause SF3B2 -Linked Craniofacial Microsomia","authors":"S. Rao, K.E.N. Watt, L. Maili, M. Lamb, E. Farrow, H. Hassan, K. Weaver, B. Miller, S. Dash, L.L. Cox, L. Gallacher, S.G. Kant, M. Gibson, T. Pastinen, D. Li, E.J.K. Bhoj, H. Zhu, J. Zhang, Y.-B. Zhang, T.Y. Tan, P.A. Trainor, T.C. Cox","doi":"10.1177/00220345251325818","DOIUrl":"https://doi.org/10.1177/00220345251325818","url":null,"abstract":"Craniofacial microsomia (CFM) is a genetically and phenotypically heterogeneous disorder characterized by hypoplasia of facial tissue that is often asymmetric. Affected tissues typically include the ears (external and internal), mandible, and maxilla, but various extracranial anomalies have also been reported. Loss-of-function variants in the <jats:italic>SF3B2</jats:italic> gene have recently been reported in 8 cases of CFM, representing one of the more common genetic causes identified to date. To better define the full phenotypic spectrum associated with variants in <jats:italic>SF3B2</jats:italic> , we report novel loss-of-function variants in <jats:italic>SF3B2</jats:italic> in 5 new families with CFM. Furthermore, to determine the mechanism by which <jats:italic>SF3B2</jats:italic> loss-of-function perturbs craniofacial development, we established <jats:italic>sf3b2</jats:italic> -null mutant zebrafish, which exhibited severe deficiencies in craniofacial cartilage and bone progenitors due to elevated apoptosis and reduced proliferation of cranial neural crest cells. In addition, we generated a heterozygous truncating variant of <jats:italic>SF3B2</jats:italic> in human induced pluripotent stem cells using CRISPR/Cas9 gene editing. Differentiation of these cells into neural crest cells was accompanied by increased cell death and reduced proliferation. RNA sequencing of <jats:italic>sf3b2</jats:italic> mutant zebrafish revealed widespread disruption of mRNA splicing, including <jats:italic>mdm2</jats:italic> , a key regulator of Tp53-mediated apoptosis. Genetic inhibition of <jats:italic>tp53</jats:italic> in <jats:italic>sf3b2</jats:italic> mutants demonstrated that <jats:italic>tp53</jats:italic> inhibition reduces early cell death but does not improve proliferation or craniofacial cartilage development. Therefore, our functional studies indicate that widespread mRNA splicing disruption, in addition to Tp53-dependent cell death, contributes to the craniofacial features observed in <jats:italic>SF3B2</jats:italic> -related CFM.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"53 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
X Xu,L Xi,J Zhu,C Feng,P Zhou,K Liu,Z Shang,Z Shao
{"title":"Intelligent Diagnosis of Cervical Lymph Node Metastasis Using a CNN Model.","authors":"X Xu,L Xi,J Zhu,C Feng,P Zhou,K Liu,Z Shang,Z Shao","doi":"10.1177/00220345251322508","DOIUrl":"https://doi.org/10.1177/00220345251322508","url":null,"abstract":"Lymph node (LN) metastasis is a prevalent cause of recurrence in oral squamous cell carcinoma (OSCC). However, accurately identifying metastatic LNs (LNs+) remains challenging. This prospective clinical study aims to test the effectiveness of our convolutional neural network (CNN) model for identifying OSCC cervical LN+ in contrast-enhanced computed tomography (CECT) in clinical practice. A CNN model was developed and trained using a dataset of 8,380 CECT images from previous OSCC patients. It was then prospectively validated on 17,777 preoperative CECT images from 354 OSCC patients between October 17, 2023, and August 31, 2024. The model's predicted LN results were provided to the surgical team without influencing surgical or treatment plans. During surgery, the predicted LN+ were identified and sent for separate pathological examination. The accuracy of the model's predictions was compared with those of human experts and verified against pathology reports. The capacity of the model to assist radiologists in LN+ diagnosis was also assessed. The CNN model was trained over 40 epochs and successfully validated after each. Compared with human experts (2 radiologists, 2 surgeons, and 2 students), the CNN model achieved higher sensitivity (81.89% vs. 81.48%, 46.91%, 50.62%), specificity (99.31% vs. 99.15%, 98.36%, 96.27%), LN+ accuracy (76.19% vs. 75.43%, P = 0.854; 40.64%, P < 0.001; 37.44%, P < 0.001), and clinical accuracy (86.16% vs. 83%, 61%, 56%). With the model's assistance, the radiologists surpassed both the previous predictive results without the model's support and the model's performance alone. The CNN model demonstrated an accuracy comparable to that of radiologists in identifying, locating, and predicting cervical LN+ in OSCC patients. Furthermore, the model has the potential to assist radiologists in making more accurate diagnoses.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":"220345251322508"},"PeriodicalIF":7.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to the Letter to the Editor: \"A Deep Learning System to Predict Epithelial Dysplasia in Oral Leukoplakia\".","authors":"J Adeoye,Y-X Su","doi":"10.1177/00220345251329356","DOIUrl":"https://doi.org/10.1177/00220345251329356","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"56 1","pages":"220345251329356"},"PeriodicalIF":7.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O Duverger,S K Wang,Q N Liu,Y Wang,D Martin,,V Baena,Z A Syed,F Mendoza,T T Nguyen,P A Frischmeyer-Guerrerio,P H Jani,J S Lee
{"title":"Distinctive Amelogenesis Imperfecta in Loeys-Dietz Syndrome Type II.","authors":"O Duverger,S K Wang,Q N Liu,Y Wang,D Martin,,V Baena,Z A Syed,F Mendoza,T T Nguyen,P A Frischmeyer-Guerrerio,P H Jani,J S Lee","doi":"10.1177/00220345251326094","DOIUrl":"https://doi.org/10.1177/00220345251326094","url":null,"abstract":"Loeys-Dietz syndrome (LDS1-6) is caused by mutations along the transforming growth factor-β (TGF-β) signaling pathway and features aortic aneurysms and craniofacial dysmorphology. Mutations that cause LDS can be found in the genes encoding transforming growth factor-β (TGF-β) ligands (TGFB2 and TGFB3), receptors (TGFBR1 and TGFBR2), and signal transducers (SMAD2 and SMAD3). Variable enamel anomalies are seen in patients with LDS, but the most severe enamel defects with advanced attrition have been observed specifically in some patients with mutation in the TGFBR2 gene (LDS2). We used human specimens as well as a mouse model to further characterize enamel defects in LDS2 and to investigate the mechanism that leads to this phenotype. Deciduous teeth from patients with LDS2 exhibited normal enamel thickness, normal or localized reduction in enamel mineral density, impaired enamel ultrastructure, and impaired biomechanical properties, with some changes likely associated with environmental and systemic effects. Mice with mutation in the Tgfbr2 gene exhibited no significant changes in the amount of enamel produced or degree of mineralization. However, they presented with unique disruption of enamel rod decussation (crisscross pattern), resulting in impaired biomechanical properties. This phenotype is caused by impaired coordinated movement of ameloblasts (enamel-producing cells) during matrix deposition. Molecular analyses revealed that mutation in Tgfbr2 in ameloblasts does not significantly affect pSMAD2/3 levels in vivo and has a minimal effect on gene expression in the enamel organ when compared with the aorta, in which hundreds of genes were differentially expressed and consistent with aortic aneurysm. However, we identified changes in the distribution and activation of the metastasis suppressor NDRG1, Rac1/Cdc42, and Myosin II that appear consistent with the disruption of ameloblast coordinated movement, although the exact mechanism through which mutation in Tgfbr2 causes this unique enamel phenotype remains to be elucidated.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"24 1","pages":"220345251326094"},"PeriodicalIF":7.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the Editor: \"Oral Health Research in the WHO African Region: A Scoping Review\".","authors":"M O Foláyan,A Bhayat,M El Tantawi","doi":"10.1177/00220345251323875","DOIUrl":"https://doi.org/10.1177/00220345251323875","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"50 1","pages":"220345251323875"},"PeriodicalIF":7.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oral Health as a Marker of Social Progress.","authors":"S Listl,T Bärnighausen","doi":"10.1177/00220345251324120","DOIUrl":"https://doi.org/10.1177/00220345251324120","url":null,"abstract":"Society strives to improve the quality of life and well-being of its members. While a broad range of social, economic, political, health, and environmental dimensions have been considered to contribute to human development, the perception of what constitutes social progress has been evolving over time. This article provides an overview of widely used social progress indices and their previous lack of oral health metrics. The article further discusses how information on oral health can portray dimensions of social progress over and above conventional markers of social progress. The article identifies unique characteristics of oral health, which qualify it as a relevant marker of social progress. To optimize people's life and well-being, we argue that concise oral health metrics (tentative items: number of natural teeth; global oral health rating; unmet oral health needs) can put oral health forward as a pertinent and practical marker of social progress. The World Health Organization's global strategy and action plan on oral health 2023-2030 offers a unique window of opportunity to enhance the uptake of oral health as a routine and central marker of social progress. The feasibility of implementing oral health as a marker of social progress has recently been exemplified by the European Commission's inclusion of an oral health-specific indicator in the 2024 edition of the EU regional Social Progress Index. Future research is encouraged to demonstrate the worldwide viability of concise and easy-to-use oral health metrics for inclusion in indices to measure social progress. Oral health is critical to ensure social progress and human development.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"74 1","pages":"220345251324120"},"PeriodicalIF":7.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}