Mapping an intelligent algorithm for predicting female adolescents' cervical vertebrae maturation stage with high recall and accuracy.

BACKGROUNDS AND OBJECTIVES: The present study was designed to define a novel algorithm capable of predicting female adolescents' cervical vertebrae maturation stage with high recall and accuracy. METHODS: A total of 560 female cephalograms were collected, and cephalograms with unclear vertebral shapes and deformed scales were removed. 480 films from female adolescents (mean age: 11.5 years; age range: 6-19 years) were used for the model development phase, and 80 subjects were randomly and stratified allocated to the validation cohort to further assess the model's performance. Derived significant predictive parameters from 15 anatomic points and 25 quantitative parameters of the second to fourth cervical vertebrae (C2-C4) to establish the ordinary logistic regression model. Evaluation metrics including precision, recall, and F1 score are employed to assess the efficacy of the models in each identified cervical vertebrae maturation stage (iCS). In cases of confusion and mispredictions, the model underwent modification to improve consistency. RESULTS: Four significant parameters, including chronological age, the ratio of D3 to AH3 (D3:AH3), anterosuperior angle of C4 (@4), and distance between C3lp and C4up (C3lp-C4up) were administered into the ordinary regression model. The primary predicting model that implements the novel algorithm was built and the performance evaluation with all stages of 93.96% for accuracy, 93.98% for precision, 93.98% for recall, and 93.95% for F1-score were obtained. Despite the hybrid logistic-based model achieving high accuracy, the unsatisfactory performance of stage estimation was noticed for iCS3 in the primary cohort (89.17%) and validation cohort (85.00%). Through bivariate logistic regression analysis, the posterior height of C4 (PH4) was further selected in the iCS3 to establish a corrected model, thus the evaluation metrics were upgraded to 95.83% and 90.00%, respectively. CONCLUSIONS: An unbiased and objective assessment of the cervical vertebrae maturation (CVM) method can function as a decision-support tool, assisting in the evaluation of the optimal timing for treatment in growing adults. Our novel proposed logistic model yielded individual formulas for each specific CVM stage and attained exceptional performance, indicating the capability to function as a benchmark for maturity evaluation in clinical craniofacial orthopedics for Chinese female adolescents.

PRMT1-mediated arginine methylation promotes postnatal calvaria bone formation through BMP-Smad signaling.

PRMT1 deficiency leads to severely compromised craniofacial development in neural crest cells and profound abnormalities of the craniofacial tissues. Here, we show PRMT1 controls several key processes in calvarial development, including frontal and parietal bone growth rate and the boundary between sutural and osteogenic cells. Pharmacologic PRMT1 inhibition suppresses MC3T3-E1 cell viability and proliferation and impairs osteogenic differentiation. In this text, we investigate the cellular events behind the morphological changes and uncover an essential role of PRMT1 in simulating postnatal bone formation. Inhibition of PRMT1 alleviated BMP signaling through Smads phosphorylation and reduced the deposition of the H4R3me2a mark. Our study demonstrates a regulatory mechanism whereby PRMT1 regulates BMP signaling and the overall properties of the calvaria bone through Smads methylation, which may facilitate the development of an effective therapeutic strategy for craniosynostosis.

Is automatic cephalometric software using artificial intelligence better than orthodontist experts in landmark identification?

BACKGROUND: To evaluate the techniques used for the automatic digitization of cephalograms using artificial intelligence algorithms, highlighting the strengths and weaknesses of each one and reviewing the percentage of success in localizing each cephalometric point. METHODS: Lateral cephalograms were digitized and traced by three calibrated senior orthodontic residents with or without artificial intelligence (AI) assistance. The same radiographs of 43 patients were uploaded to AI-based machine learning programs MyOrthoX, Angelalign, and Digident. Image J was used to extract x- and y-coordinates for 32 cephalometric points: 11 soft tissue landmarks and 21 hard tissue landmarks. The mean radical errors (MRE) were assessed radical to the threshold of 1.0 mm,1.5 mm, and 2 mm to compare the successful detection rate (SDR). One-way ANOVA analysis at a significance level of P < .05 was used to compare MRE and SDR. The SPSS (IBM-vs. 27.0) and PRISM (GraphPad-vs.8.0.2) software were used for the data analysis. RESULTS: Experimental results showed that three methods were able to achieve detection rates greater than 85% using the 2 mm precision threshold, which is the acceptable range in clinical practice. The Angelalign group even achieved a detection rate greater than 78.08% using the 1.0 mm threshold. A marked difference in time was found between the AI-assisted group and the manual group due to heterogeneity in the performance of techniques to detect the same landmark. CONCLUSIONS: AI assistance may increase efficiency without compromising accuracy with cephalometric tracings in routine clinical practice and research settings.

Clear aligner vs fixed self-ligating appliances: Orthodontic emergency during the 2020 coronavirus disease 2019 pandemic.

INTRODUCTION: The aim was to investigate the type, incidence, and degree of orthodontic-related emergencies in orthodontic patients during the 2020 coronavirus disease 2019 pandemic and compare the different effects of clear aligner (CA) and fixed self-ligating appliances on the orthodontic emergency. METHODS: The questionnaire was based on emergencies in orthodontics. The responses of 428 patients between the ages of 12 and 38 years (20.4 ± 7.03) in orthodontic treatment during 2020 were examined. RESULTS: The gender, age, and the type of orthodontic appliance affect the incidence of orthodontic-related emergencies. Female or adolescent patients treated by self-ligating appliances showed a higher incidence of emergencies. The patients treated by CA exhibited a much lower incidence of emergency. Appliance detachment and mucosa injury were very common in respondents, whereas accidental ingestion and other rare emergencies were less common. The most common reason leading to appliance detachment was chewing hard food. Interestingly, the fixed self-ligating appliances group was also affected by the accidental detachment of appliances to a large extent. The CA and self-ligating groups showed an almost equal incidence of accidental ingestion. The most common foreign body was elastics in both groups. However, the self-ligating group could accidentally ingest dangerous foreign bodies, such as archwires, miniscrews, and welded attachments. CONCLUSIONS: Orthodontic-related emergencies were very common in patients. The CA could effectively reduce orthodontic-related emergencies. Dentists should raise patients' awareness of proper appliance care. A proper and standard protocol should be developed.

Arginine methylation of R81 in Smad6 confines BMP-induced Smad1 signaling.

Bone morphogenetic proteins (BMPs) secreted by a variety of cell types are known to play essential roles in cell differentiation and matrix formation in the bone, cartilage, muscle, blood vessel, and neuronal tissue. BMPs activate intracellular effectors via C-terminal phosphorylation of Smad1, Smad5, and Smad9, which relay the signaling by forming a complex with Smad4 and translocate to the nucleus for transcriptional activation. Smad6 inhibits BMP signaling through diverse mechanisms operative at the membrane, cytosolic, and nuclear levels. However, the mechanistic underpinnings of Smad6 functional diversity remain unclear. Here, using a biochemical approach and cell differentiation systems, we report a cytosolic mechanism of action for Smad6 that requires arginine methylation at arginine 81 (R81) and functions through association with Smad1 and interference with the formation of Smad1-Smad4 complexes. By mutating the methylated arginine residue, R81, and by silencing the expression of protein arginine methyltransferase 1, we show that protein arginine methyltransferase 1 catalyzes R81 methylation of Smad6 upon BMP treatment, R81 methylation subsequently facilitates Smad6 interaction with the phosphorylated active Smad1, and R81 methylation facilitates Smad6-mediated interruption of Smad1-Smad4 complex formation and nuclear translocation. Furthermore, Smad6 WT but not the methylation-deficient R81A mutant inhibited BMP-responsive transcription, attenuated BMP-mediated osteogenic differentiation, and antagonized BMP-mediated inhibition of cell invasion. Taken together, our results suggest that R81 methylation plays an essential role in Smad6-mediated inhibition of BMP responses.

PRMT1-p53 Pathway Controls Epicardial EMT and Invasion.

Epicardial cells are cardiac progenitors that give rise to the majority of cardiac fibroblasts, coronary smooth muscle cells, and pericytes during development. An integral phase of epicardial fate transition is epithelial-to-mesenchymal transition (EMT) that confers motility. We uncover an essential role for the protein arginine methyltransferase 1 (PRMT1) in epicardial invasion and differentiation. Using scRNA-seq, we show that epicardial-specific deletion of Prmt1 reduced matrix and ribosomal gene expression in epicardial-derived cell lineages. PRMT1 regulates splicing of Mdm4, which is a key controller of p53 stability. Loss of PRMT1 leads to accumulation of p53 that enhances Slug degradation and blocks EMT. During heart development, the PRMT1-p53 pathway is required for epicardial invasion and formation of epicardial-derived lineages: cardiac fibroblasts, coronary smooth muscle cells, and pericytes. Consequently, this pathway modulates ventricular morphogenesis and coronary vessel formation. Altogether, our study reveals molecular mechanisms involving the PRMT1-p53 pathway and establish its roles in heart development.

Prmt1 regulates craniofacial bone formation upstream of Msx1.

Protein arginine methylation has been recently identified as an important form of post-translational modification (PTM). It is carried out by the protein arginine methyltransferase (PRMT) family of enzymes, which in mammals consists of nine members. Among them, PRMT1 is the major arginine methyltransferase and participates in transcription, signal transduction, development and cancer. The function of PRMT1 in craniofacial development remains unclear. We generated Wnt1-Cre;Prmt1fl/fl mice with cranial neural crest (CNC)-specific deletion of Prmt1 and compared CNC-derived craniofacial bones from newborn control and Wnt1-Cre;Prmt1fl/fl mice. The size, surface area and volume of the premaxilla, maxilla, palatine bone, frontal bone, and mandible were analyzed using three-dimensional (3D) micro-computed tomography (microCT). We found that Prmt1 deficiency led to alterations in craniofacial bones including the premaxilla, maxilla, palatine bone, frontal bone, and mandible, as well as defects in the incisor and alveolar bone, recapitulating changes seen in Msx1-deficient mice. We further determined that Prmt1 depletion resulted in significant downregulation of Msx1 in calvaria-derived preosteoblast and primordium of frontal bone and mandible. Our study reveals critical roles of PRMT1 in the formation of CNC-derived craniofacial bones and suggests that Prmt1 is an upstream regulator of Msx1 in craniofacial bone development.

Transcription Factors in Craniofacial Development: From Receptor Signaling to Transcriptional and Epigenetic Regulation.

Craniofacial morphogenesis is driven by spatial-temporal terrains of gene expression, which give rise to stereotypical pattern formation. Transcription factors are key cellular components that control these gene expressions. They are information hubs that integrate inputs from extracellular factors and environmental cues, direct epigenetic modifications, and define transcriptional status. These activities allow transcription factors to confer specificity and potency to transcription regulation during development.

The endothelial-mesenchymal transition (EndMT) and tissue regeneration.

Recent studies have brought endothelial-mesenchymal transition (EndMT) as a special perspective of epithelial- mesenchymal transition (EMT) into eyes. Traditionally, EndMT is considered as a source for fibroblasts and myofibroblasts, and it is extensively investigated in physiologic cardiac development as well as in pathologic tumor and fibrosis. Recently, new studies have found that EndMT-transformed cells had 'stemness', which means they could differentiate into chondroblasts, osteoblasts, and adipoblasts in differential culture, respectively. This gives EndMT a bright application future in tissue engineering and regeneration, especially for the formation of cartilage and bone.

The immune factors involved in the pathogenesis, diagnosis, and treatment of Sjogren's syndrome.

Sjogren's syndrome (SS) is a systemic, autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Even though the mechanism of its pathology and progression has been researched ever since its discovery, the roles of different parts of immune system remain inconclusive. There is no straightforward and simple theory for the pathogenesis and diagnosis of Sjogren's syndrome because of the multiple kinds and functions of autoantibodies, changing proportion of different T-lymphocyte subsets with the progression of disease, unsuspected abilities of B lymphocytes discovered recently, crosstalk between cytokines connecting the factors mentioned previously, and genetic predisposition that contributes to the initiation of this disease. On the other hand, the number of significant reports and open-label studies of B-cell depletion therapy showing clinical efficacy in sjogren's syndrome has continued to accumulate, which provides a promising future for the patients. In a word, further elucidation of the role of different components of the immune system will open avenues for better diagnosis and treatment of SS, whose current management is still mainly supportive.

Visualization studies on evidence-based medicine domain knowledge (series 1): mapping of evidence-based medicine research subjects.

OBJECTIVE: To use visualization methods to illustrate and compare major subjects, domains, and developments in evidence-based medicine (EBM) in recent years. METHOD: We analyzed MeSH terms and keywords in EBM articles in the MEDLINE and CNKI databases, and developed subject charts, research field relationship charts, and strategy coordination charts using word co-occurrence, PFNET algorithms, and visualization methods. RESULT: Rapid developments and growth are taking place in EBM in China and around the world. Studies on humans comprised 94.4% of the EBM studies that we identified, while animal studies accounted for 2.6% (three quarters of these animal studies were on primates). The six countries with the largest number of EBM articles and the eight host nations for the 108 journals with the most EBM publications were from high-income countries. In China, 31 provinces, municipalities, and autonomous regions have published EBM articles, although most of these publications come from the more highly-developed areas of the country. The investigation of word co-occurrence showed that EBM articles outside of China involve seven main fields: "Therapy", "Methods", "Standards", "Research", "Education", "Nursing" and "Organization and Administration". Five of these fields ("Therapy", "Nursing", "Research", "Education" and "Management") were common to China but the top seven fields for this country included "Traditional Chinese Medicine (TCM)" and "Information resources"; and did not include "Methods" and "Standards". Furthermore, studies on "Nursing" and "Research" were not as advanced in China as in other countries. CONCLUSION: There are similarities between China and the rest of the world in several areas in the EBM literature but also some important differences. Throughout the world, the most resource-rich regions o organizations tend to have the most well-developed EBM. These regions and organizations are pdocuing more evidence and conducting more methodology research than the less resourced regions and organizations. There is an urgent need for these regions and organizations to strengthen their use of evidence, to learn more about the philosophy that underpins EBM, and to improve accessibility to, and use of, evidence in choices about health care.

Visualization studies on evidence-based medicine domain knowledge (series 2): structural diagrams of author networks.

OBJECTIVE: To investigate the output of evidence-based medicine (EBM) researchers in China and elsewhere by examining the EBM domains they work within and the networks that exist among them; using visualization methods to analyze these relationships. This maps the current situation and helps with the identification of areas for future growth. METHODS: We used co-citation matrixes with Pathfinder networks and hierarchical clustering algorithms, and constructed a co-author matrix which were analyzed with a whole network approach. The analyzed matrixes were visualized with the UCINET program. RESULTS: Much of the development of EBM has been centered around three authors, David Sackett, Gordon Guyatt and L Manchikanti, within three different clusters. The main authors of EBM articles in China were divided into nine academic domains. The relations among core authors of articles indexed by the Science Citation Index (SCI) was loose. There was a stronger co-authorship network among core authors in the Chinese literature, with three groups and 21 cliques. Nine distinct academic communities appeared to have formed around Li Youping, Liu Ming and Zhang Mingming. CONCLUSION: The EBM literature contains several key clusters, with universities in high-income countries being the source of the majority of articles. Outside China, McMaster University in Canada, the original home of EBM, is the dominant producer of EBM publications. In China, Sichuan University is the main source of EBM publications. The EBM cooperation network in China is comprised of three major groups, the largest and most productive in this sample is led by Li Youping with Liu Ming, Zhang Mingming, Li Jing, Wang Li, Wu Taixiang, and Liu Guanjian as central members.

Visualization studies on evidence-based medicine domain knowledge (series 3): visualization for dissemination of evidence based medicine information.

PURPOSE: To identify patterns in information sharing between a series of Chinese evidence based medicine (EBM) journals and the Cochrane Database of Systematic Reviews, to determine key evidence dissemination areas for EBM and to provide a scientific basis for improving the dissemination of EBM research. METHOD: Data were collected on citing and cited from the Chinese Journal of Evidence-Based Medicine (CJEBM), Journal of Evidence-Based Medicine (JEBMc), Chinese Journal of Evidence Based Pediatrics (CJEBP), and the Cochrane Database of Systematic Reviews (CDSR). Relationships between citations were visualized. High-frequency key words from these sources were identified, to build a word co-occurrence matrix and to map research subjects. RESULT: CDSR contains a large collection of information of relevance to EBM and its contents are widely cited across many journals, suggesting a well-developed citation environment. The content and citation of the Chinese journals have been increasing in recent years. However, their citation environments are much less developed, and there is a wide variation in the breadth and strength of their knowledge communication, with the ranking from highest to lowest being CJEBM, JEBMc and CJEBP. The content of CDSR is almost exclusively Cochrane intervention reviews examining the effects of healthcare interventions, so it's contribution to EBM is mostly in disease control and treatment. On the other hand, the Chinese journals on evidence-based medicine and practice focused more on areas such as education and research, design and quality of clinical trials, evidence based policymaking, evidence based clinical practice, tumor treatment, and pediatrics. CONCLUSION: Knowledge and findings of EBM are widely communicated and disseminated. However, citation environments and range of knowledge communication differ greatly between the journals examined in this study. This finds that Chinese EBM has focused mainly on clinical medicine, Traditional Chinese Medicine, pediatrics, tumor treatment, nursing, health economic and management, and medical education. Internationally, EBM research topics have begun to shift, from drug treatment to surgery or other non-pharmacological treatments; from therapy to diagnosis, rehabilitation, and prevention; from evidence based clinical practice to evidence based management and policymaking. The philosophy and method of EBM, evidence production and translation are also shifting from well resourced settings to low- and middle-income countries, especially those in which English is not a major language.