Background: The prevailing paradigm posits orthodontic tooth movement (OTM) as primarily a localized inflammatory process. In this study, we endeavor to elucidate the potential ramifications of mechanical force on systemic immunity, employing a time-dependent approach.
Materials and methods: A previously described mouse orthodontic model was used. Ni-Ti. springs were set to move the upper 1st-molar in C57BL/6 mice and the amount of OTM was. measured by µCT. Mice were allocated randomly into four experimental groups, each. corresponding to clinical phases of OTM, relative to force application. Terminal blood. samples were collected and a comprehensive blood count test for 7 cell types as well as. proteome profiling of 111 pivotal cytokines and chemokines were conducted. Two controls. groups were included: one comprised non-treated mice and the other mice with inactivated springs.
Results: Serum immuno-profiling unveiled alterations in cellular immunity, manifesting as. changes in percentages of leukocytes, monocytes, macrophages, neutrophils, and. lymphocytes, alongside key signaling factors in comparison to both control groups. The systemic cellular and molecular alterations triggered by OTM mirrored the dynamics previously described in the local immune response.
Conclusions: Although the exact interplay between local and systemic immune responses to orthodontic forces require further elucidation, our findings demonstrate a tangible link between the two. Future investigations should aim to correlate these results with human subjects, and strive to delve deeper into the specific mechanisms by which mechanical force modulates the systemic immune response.
{"title":"Breaking a dogma: orthodontic tooth movement alters systemic immunity.","authors":"Yehuda Klein, Eilon David, Noy Pinto, Yasmin Khoury, Yechezkel Barenholz, Stella Chaushu","doi":"10.1186/s40510-024-00537-z","DOIUrl":"10.1186/s40510-024-00537-z","url":null,"abstract":"<p><strong>Background: </strong>The prevailing paradigm posits orthodontic tooth movement (OTM) as primarily a localized inflammatory process. In this study, we endeavor to elucidate the potential ramifications of mechanical force on systemic immunity, employing a time-dependent approach.</p><p><strong>Materials and methods: </strong>A previously described mouse orthodontic model was used. Ni-Ti. springs were set to move the upper 1st-molar in C57BL/6 mice and the amount of OTM was. measured by µCT. Mice were allocated randomly into four experimental groups, each. corresponding to clinical phases of OTM, relative to force application. Terminal blood. samples were collected and a comprehensive blood count test for 7 cell types as well as. proteome profiling of 111 pivotal cytokines and chemokines were conducted. Two controls. groups were included: one comprised non-treated mice and the other mice with inactivated springs.</p><p><strong>Results: </strong>Serum immuno-profiling unveiled alterations in cellular immunity, manifesting as. changes in percentages of leukocytes, monocytes, macrophages, neutrophils, and. lymphocytes, alongside key signaling factors in comparison to both control groups. The systemic cellular and molecular alterations triggered by OTM mirrored the dynamics previously described in the local immune response.</p><p><strong>Conclusions: </strong>Although the exact interplay between local and systemic immune responses to orthodontic forces require further elucidation, our findings demonstrate a tangible link between the two. Future investigations should aim to correlate these results with human subjects, and strive to delve deeper into the specific mechanisms by which mechanical force modulates the systemic immune response.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"38"},"PeriodicalIF":4.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1186/s40510-024-00536-0
Yao Chen, Li Mei, Yuran Qian, Xinlianyi Zhou, Zhihe Zhao, Wei Zheng, Yu Li
Background: The biological mechanisms driving orthodontic tooth movement (OTM) remain incompletely understood. Gingival crevicular fluid (GCF) is an important indicator of the periodontal bioprocess, providing valuable cues for probing the molecular mechanisms of OTM.
Methods: A rigorous review of the clinical studies over the past decade was conducted after registering the protocol with PROSPERO and adhering to inclusion criteria comprising human subjects, specified force magnitudes and force application modes. The thorough screening investigated differentially expressed proteins (DEPs) in GCF associated with OTM. Protein-protein interaction (PPI) analysis was carried out using the STRING database, followed by further refinement through Cytoscape to isolate top hub proteins.
Results: A comprehensive summarization of the OTM-related GCF studies was conducted, followed by an in-depth exploration of biomarkers within the GCF. We identified 13 DEPs, including ALP, IL-1β, IL-6, Leptin, MMP-1, MMP-3, MMP-8, MMP-9, PGE2, TGF-β1, TNF-α, OPG, RANKL. Bioinformatic analysis spotlighted the top 10 hub proteins and their interactions involved in OTM. Based on these findings, we have proposed a hypothetic diagram for the time-course bioprocess in OTM, which involves three phases containing sequential cellular and molecular components and their interplay network.
Conclusions: This work has further improved our understanding to the bioprocess of OTM, suggesting biomarkers as potential modulating targets to enhance OTM, mitigate adverse effects and support real-time monitoring and personalized orthodontic cycles.
{"title":"Integrated bioinformatic analysis of protein landscape in gingival crevicular fluid unveils sequential bioprocess in orthodontic tooth movement.","authors":"Yao Chen, Li Mei, Yuran Qian, Xinlianyi Zhou, Zhihe Zhao, Wei Zheng, Yu Li","doi":"10.1186/s40510-024-00536-0","DOIUrl":"10.1186/s40510-024-00536-0","url":null,"abstract":"<p><strong>Background: </strong>The biological mechanisms driving orthodontic tooth movement (OTM) remain incompletely understood. Gingival crevicular fluid (GCF) is an important indicator of the periodontal bioprocess, providing valuable cues for probing the molecular mechanisms of OTM.</p><p><strong>Methods: </strong>A rigorous review of the clinical studies over the past decade was conducted after registering the protocol with PROSPERO and adhering to inclusion criteria comprising human subjects, specified force magnitudes and force application modes. The thorough screening investigated differentially expressed proteins (DEPs) in GCF associated with OTM. Protein-protein interaction (PPI) analysis was carried out using the STRING database, followed by further refinement through Cytoscape to isolate top hub proteins.</p><p><strong>Results: </strong>A comprehensive summarization of the OTM-related GCF studies was conducted, followed by an in-depth exploration of biomarkers within the GCF. We identified 13 DEPs, including ALP, IL-1β, IL-6, Leptin, MMP-1, MMP-3, MMP-8, MMP-9, PGE<sub>2</sub>, TGF-β1, TNF-α, OPG, RANKL. Bioinformatic analysis spotlighted the top 10 hub proteins and their interactions involved in OTM. Based on these findings, we have proposed a hypothetic diagram for the time-course bioprocess in OTM, which involves three phases containing sequential cellular and molecular components and their interplay network.</p><p><strong>Conclusions: </strong>This work has further improved our understanding to the bioprocess of OTM, suggesting biomarkers as potential modulating targets to enhance OTM, mitigate adverse effects and support real-time monitoring and personalized orthodontic cycles.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"37"},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to assess the accuracy of machine learning (ML) models with feature selection technique in classifying cervical vertebral maturation stages (CVMS). Consensus-based datasets were used for models training and evaluation for their model generalization capabilities on unseen datasets. Three clinicians independently rated CVMS on 1380 lateral cephalograms, resulting in the creation of five datasets: two consensus-based datasets (Complete Agreement and Majority Voting), and three datasets based on a single rater’s evaluations. Additionally, landmarks annotation of the second to fourth cervical vertebrae and patients’ information underwent a feature selection process. These datasets were used to train various ML models and identify the top-performing model for each dataset. These models were subsequently tested on their generalization capabilities. Features that considered significant in the consensus-based datasets were consistent with a CVMS guideline. The Support Vector Machine model on the Complete Agreement dataset achieved the highest accuracy (77.4%), followed by the Multi-Layer Perceptron model on the Majority Voting dataset (69.6%). Models from individual ratings showed lower accuracies (60.4–67.9%). The consensus-based training models also exhibited lower coefficient of variation (CV), indicating superior generalization capability compared to models from single raters. ML models trained on consensus-based datasets for CVMS classification exhibited the highest accuracy, with significant features consistent with the original CVMS guidelines. These models also showed robust generalization capabilities, underscoring the importance of dataset quality.
本研究旨在评估采用特征选择技术的机器学习(ML)模型在对颈椎成熟阶段(CVMS)进行分类时的准确性。研究使用基于共识的数据集进行模型训练,并评估模型在未见数据集上的泛化能力。三位临床医生对 1380 张侧位头颅影像进行了独立的 CVMS 评级,最终创建了五个数据集:两个基于共识的数据集(完全一致和多数表决),以及三个基于单个评定者评估的数据集。此外,第二至第四颈椎的地标标注和患者信息也经过了特征选择过程。这些数据集被用来训练各种 ML 模型,并为每个数据集找出性能最好的模型。随后对这些模型的泛化能力进行了测试。在基于共识的数据集中被认为重要的特征与 CVMS 准则一致。支持向量机模型在完全一致数据集上的准确率最高(77.4%),其次是多层感知器模型在多数票数据集上的准确率(69.6%)。单个评分模型的准确率较低(60.4%-67.9%)。基于共识的训练模型还表现出较低的变异系数(CV),这表明与来自单个评分者的模型相比,基于共识的训练模型具有更强的泛化能力。在基于共识的数据集上训练的用于 CVMS 分类的 ML 模型表现出最高的准确性,其重要特征与最初的 CVMS 指南一致。这些模型还显示出强大的泛化能力,强调了数据集质量的重要性。
{"title":"Classification of cervical vertebral maturation stages with machine learning models: leveraging datasets with high inter- and intra-observer agreement","authors":"Potjanee Kanchanapiboon, Pitipat Tunksook, Prinya Tunksook, Panrasee Ritthipravat, Supatchai Boonpratham, Yodhathai Satravaha, Chaiyapol Chaweewannakorn, Supakit Peanchitlertkajorn","doi":"10.1186/s40510-024-00535-1","DOIUrl":"https://doi.org/10.1186/s40510-024-00535-1","url":null,"abstract":"This study aimed to assess the accuracy of machine learning (ML) models with feature selection technique in classifying cervical vertebral maturation stages (CVMS). Consensus-based datasets were used for models training and evaluation for their model generalization capabilities on unseen datasets. Three clinicians independently rated CVMS on 1380 lateral cephalograms, resulting in the creation of five datasets: two consensus-based datasets (Complete Agreement and Majority Voting), and three datasets based on a single rater’s evaluations. Additionally, landmarks annotation of the second to fourth cervical vertebrae and patients’ information underwent a feature selection process. These datasets were used to train various ML models and identify the top-performing model for each dataset. These models were subsequently tested on their generalization capabilities. Features that considered significant in the consensus-based datasets were consistent with a CVMS guideline. The Support Vector Machine model on the Complete Agreement dataset achieved the highest accuracy (77.4%), followed by the Multi-Layer Perceptron model on the Majority Voting dataset (69.6%). Models from individual ratings showed lower accuracies (60.4–67.9%). The consensus-based training models also exhibited lower coefficient of variation (CV), indicating superior generalization capability compared to models from single raters. ML models trained on consensus-based datasets for CVMS classification exhibited the highest accuracy, with significant features consistent with the original CVMS guidelines. These models also showed robust generalization capabilities, underscoring the importance of dataset quality.","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"57 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1186/s40510-024-00534-2
David Togninalli, Gregory S Antonarakis, Alexandra K Papadopoulou
Background: The anatomic characteristics of the masticatory muscles differ across craniofacial skeletal patterns.
Objective: To identify differences in the anatomic characteristics of masticatory muscles across different sagittal and vertical craniofacial skeletal patterns.
Eligibility criteria: Studies measuring the thickness, width, cross-sectional area (CSA), volume and orientation of masticatory muscles in healthy patients of different sagittal (Class I, Class II, and Class III) and/or vertical (normodivergent, hypodivergent, and hyperdivergent) patterns.
Information sources: Unrestricted literature searches in 8 electronic databases/registers until December 2023.
Risk of bias and synthesis of results: Study selection, data extraction, and risk of bias assessment with a customised tool were performed independently in duplicate. Random-effects meta-analysis and assessment of the certainty of clinical recommendations with the GRADE approach were conducted.
Results: 34 studies (37 publications) were selected with a total of 2047 participants and data from 16 studies were pulled in the meta-analysis. Masseter muscle thickness in relaxation was significantly greater by 1.14 mm (95% CI 0.74-1.53 mm) in hypodivergent compared to normodivergent patients while it was significantly decreased in hyperdivergent patients by - 1.14 mm (95% CI - 1.56 to - 0.73 mm) and - 2.28 mm (95% CI - 2.71 to - 1.85 mm) compared to normodivergent and hypodivergent patients respectively. Similar significant differences were seen between these groups in masseter muscle thickness during contraction as well as masseter muscle CSA and volume. Meta-analyses could not be performed for sagittal categorizations due to insufficient number of studies.
Conclusions: Considerable differences in masseter muscle thickness, CSA and volume were found across vertical skeletal configurations being significantly reduced in hyperdivergent patients; however, results should be interpreted with caution due to the high risk of bias of the included studies. These variations in the anatomic characteristics of masticatory muscles among different craniofacial patterns could be part of the orthodontic diagnosis and treatment planning process.
{"title":"Relationship between craniofacial skeletal patterns and anatomic characteristics of masticatory muscles: a systematic review and meta-analysis.","authors":"David Togninalli, Gregory S Antonarakis, Alexandra K Papadopoulou","doi":"10.1186/s40510-024-00534-2","DOIUrl":"10.1186/s40510-024-00534-2","url":null,"abstract":"<p><strong>Background: </strong>The anatomic characteristics of the masticatory muscles differ across craniofacial skeletal patterns.</p><p><strong>Objective: </strong>To identify differences in the anatomic characteristics of masticatory muscles across different sagittal and vertical craniofacial skeletal patterns.</p><p><strong>Eligibility criteria: </strong>Studies measuring the thickness, width, cross-sectional area (CSA), volume and orientation of masticatory muscles in healthy patients of different sagittal (Class I, Class II, and Class III) and/or vertical (normodivergent, hypodivergent, and hyperdivergent) patterns.</p><p><strong>Information sources: </strong>Unrestricted literature searches in 8 electronic databases/registers until December 2023.</p><p><strong>Risk of bias and synthesis of results: </strong>Study selection, data extraction, and risk of bias assessment with a customised tool were performed independently in duplicate. Random-effects meta-analysis and assessment of the certainty of clinical recommendations with the GRADE approach were conducted.</p><p><strong>Results: </strong>34 studies (37 publications) were selected with a total of 2047 participants and data from 16 studies were pulled in the meta-analysis. Masseter muscle thickness in relaxation was significantly greater by 1.14 mm (95% CI 0.74-1.53 mm) in hypodivergent compared to normodivergent patients while it was significantly decreased in hyperdivergent patients by - 1.14 mm (95% CI - 1.56 to - 0.73 mm) and - 2.28 mm (95% CI - 2.71 to - 1.85 mm) compared to normodivergent and hypodivergent patients respectively. Similar significant differences were seen between these groups in masseter muscle thickness during contraction as well as masseter muscle CSA and volume. Meta-analyses could not be performed for sagittal categorizations due to insufficient number of studies.</p><p><strong>Conclusions: </strong>Considerable differences in masseter muscle thickness, CSA and volume were found across vertical skeletal configurations being significantly reduced in hyperdivergent patients; however, results should be interpreted with caution due to the high risk of bias of the included studies. These variations in the anatomic characteristics of masticatory muscles among different craniofacial patterns could be part of the orthodontic diagnosis and treatment planning process.</p><p><strong>Registration: </strong>PROSPERO CRD42022371187 .</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"36"},"PeriodicalIF":5.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s40510-024-00533-3
Ishita Z Taneja, Guihua Zhai, Neal D Kravitz, Bill Dischinger, Mark Johnston, Chung-How Kau, Ejvis Lamani
Background: Mandibular second premolar agenesis is a common problem in orthodontics and is often treated in conjunction with maxillary counterbalancing extractions. However, in cases without maxillary crowding or dental protrusion, space closure may pose challenges leading to compromised occlusal results or patient profile. Multiple techniques have been described to treat these patients; nevertheless, there is a paucity of data comparing effectiveness of space closure utilizing various anchorage techniques. The goal of this study is to assess the effectiveness of the Herbst device during mandibular molar protraction and compare it to the use of temporary anchorage device (TADs) in patients with mandibular second premolar agenesis.
Materials and methods: This retrospective study included 33 patients with mandibular premolar agenesis treated without maxillary extractions. Of these patients, 21 were treated with protraction Herbst devices and 12 with TADs. Changes in molar and incisor positions, skeletal base positions and occlusal plane angulations were assessed on pretreatment (T0) and post-treatment (T1) lateral cephalograms. Scans/photographs at T0 and T1 were used to evaluate canine relationship changes representing anchorage control. Space closure and breakage/failure rates were also compared. Data was analyzed with paired and unpaired t-tests at the significance level of 0.05.
Results: Within the Herbst group, changes in mandibular central incisor uprighting and mandibular molar crown angulations were statistically significant. However, no significant differences were noted between the Herbst and TAD groups. Protraction rates as well as overall treatment times were comparable (0.77 mm/month vs. 0.55 mm/month and 3.02 years vs. 2.67 years, respectively). Canine relationships were maintained or improved toward a class I in 82.85% of the Herbst sample, compared to in 66.7% of the TAD sample. Emergency visits occurred in 80.1% of the Herbst group, with cementation failures or appliance breakages as the most common reasons.
Conclusion: The Herbst device could be a viable modality in cases with missing mandibular premolars where maximum anterior anchorage is desired, or if patients/parents are resistant to TADs. Furthermore, they could be beneficial in skeletal class II patients with mandibular deficiency who also need molar protraction. However, the increased incidence of emergency visits must be considered when treatment is planned.
背景:下颌第二前磨牙缺失是正畸学中的一个常见问题,通常与上颌平衡拔牙一起治疗。然而,在没有上颌拥挤或牙齿前突的情况下,空间闭合可能会带来挑战,导致咬合效果或患者形象受损。目前已经有多种技术用于治疗这类患者,但利用各种锚固技术比较间隙封闭效果的数据却很少。本研究的目的是评估 Herbst 装置在下颌磨牙牵引过程中的有效性,并将其与下颌第二前磨牙缺失患者使用的临时锚定装置(TADs)进行比较:这项回顾性研究包括33名下颌第二前磨牙缺失患者,他们均未进行上颌拔牙治疗。在这些患者中,21 人接受了赫氏牵引装置治疗,12 人接受了 TADs 治疗。通过治疗前(T0)和治疗后(T1)的侧位头颅影像评估臼齿和门齿位置、骨骼基底位置和咬合面角度的变化。T0和T1的扫描/照片用于评估代表锚定控制的犬齿关系变化。同时还比较了空间闭合率和断裂/失败率。数据采用配对和非配对 t 检验进行分析,显著性水平为 0.05:在 Herbst 组中,下颌中切牙直立和下颌磨牙牙冠角度的变化具有统计学意义。但是,赫氏组和 TAD 组之间没有明显差异。拔牙率和总体治疗时间相当(分别为 0.77 毫米/月对 0.55 毫米/月和 3.02 年对 2.67 年)。82.85%的Herbst样本与66.7%的TAD样本相比,犬关系得到了维持或改善,达到了I级。80.1%的赫氏装置使用者出现了急诊,最常见的原因是固位失败或矫治器破损:结论:对于下颌前磨牙缺失的病例,如果需要最大程度的前牙固定,或者患者/家长对TAD有抵触情绪,那么Herbst装置可能是一种可行的方式。此外,对于下颌缺失且同时需要臼齿牵引的骨骼等级为 II 的患者来说,这种装置也是有益的。但是,在计划治疗时必须考虑到急诊就诊率的增加。
{"title":"Evaluating the efficiency of mandibular molar protraction using Herbst appliances versus temporary anchorage devices: a retrospective case-controlled study.","authors":"Ishita Z Taneja, Guihua Zhai, Neal D Kravitz, Bill Dischinger, Mark Johnston, Chung-How Kau, Ejvis Lamani","doi":"10.1186/s40510-024-00533-3","DOIUrl":"10.1186/s40510-024-00533-3","url":null,"abstract":"<p><strong>Background: </strong>Mandibular second premolar agenesis is a common problem in orthodontics and is often treated in conjunction with maxillary counterbalancing extractions. However, in cases without maxillary crowding or dental protrusion, space closure may pose challenges leading to compromised occlusal results or patient profile. Multiple techniques have been described to treat these patients; nevertheless, there is a paucity of data comparing effectiveness of space closure utilizing various anchorage techniques. The goal of this study is to assess the effectiveness of the Herbst device during mandibular molar protraction and compare it to the use of temporary anchorage device (TADs) in patients with mandibular second premolar agenesis.</p><p><strong>Materials and methods: </strong>This retrospective study included 33 patients with mandibular premolar agenesis treated without maxillary extractions. Of these patients, 21 were treated with protraction Herbst devices and 12 with TADs. Changes in molar and incisor positions, skeletal base positions and occlusal plane angulations were assessed on pretreatment (T0) and post-treatment (T1) lateral cephalograms. Scans/photographs at T0 and T1 were used to evaluate canine relationship changes representing anchorage control. Space closure and breakage/failure rates were also compared. Data was analyzed with paired and unpaired t-tests at the significance level of 0.05.</p><p><strong>Results: </strong>Within the Herbst group, changes in mandibular central incisor uprighting and mandibular molar crown angulations were statistically significant. However, no significant differences were noted between the Herbst and TAD groups. Protraction rates as well as overall treatment times were comparable (0.77 mm/month vs. 0.55 mm/month and 3.02 years vs. 2.67 years, respectively). Canine relationships were maintained or improved toward a class I in 82.85% of the Herbst sample, compared to in 66.7% of the TAD sample. Emergency visits occurred in 80.1% of the Herbst group, with cementation failures or appliance breakages as the most common reasons.</p><p><strong>Conclusion: </strong>The Herbst device could be a viable modality in cases with missing mandibular premolars where maximum anterior anchorage is desired, or if patients/parents are resistant to TADs. Furthermore, they could be beneficial in skeletal class II patients with mandibular deficiency who also need molar protraction. However, the increased incidence of emergency visits must be considered when treatment is planned.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"32"},"PeriodicalIF":5.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1186/s40510-024-00532-4
Nora Alhazmi, Ali Alaqla, Bader Almuzzaini, Mohammed Aldrees, Ghaida Alnaqa, Farah Almasoud, Omar Aldibasi, Hala Alshamlan
Background: Hypodontia is the most prevalent dental anomaly in humans, and is primarily attributed to genetic factors. Although genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNP) associated with hypodontia, genetic risk assessment remains challenging due to population-specific SNP variants. Therefore, we aimed to conducted a genetic analysis and developed a machine-learning-based predictive model to examine the association between previously reported SNPs and hypodontia in the Saudi Arabian population. Our case-control study included 106 participants (aged 8-50 years; 64 females and 42 males), comprising 54 hypodontia cases and 52 controls. We utilized TaqManTM Real-Time Polymerase Chain Reaction and allelic genotyping to analyze three selected SNPs (AXIN2: rs2240308, PAX9: rs61754301, and MSX1: rs12532) in unstimulated whole saliva samples. The chi-square test, multinomial logistic regression, and machine-learning techniques were used to assess genetic risk by using odds ratios (ORs) for multiple target variables.
Results: Multivariate logistic regression indicated a significant association between homozygous AXIN2 rs2240308 and the hypodontia phenotype (ORs [95% confidence interval] 2.893 [1.28-6.53]). Machine-learning algorithms revealed that the AXIN2 homozygous (A/A) genotype is a genetic risk factor for hypodontia of teeth #12, #22, and #35, whereas the AXIN2 homozygous (G/G) genotype increases the risk for hypodontia of teeth #22, #35, and #45. The PAX9 homozygous (C/C) genotype is associated with an increased risk for hypodontia of teeth #22 and #35.
Conclusions: Our study confirms a link between AXIN2 and hypodontia in Saudi orthodontic patients and suggests that combining machine-learning models with SNP analysis of saliva samples can effectively identify individuals with non-syndromic hypodontia.
{"title":"What could be the role of genetic tests and machine learning of AXIN2 variant dominance in non-syndromic hypodontia? A case-control study in orthodontically treated patients.","authors":"Nora Alhazmi, Ali Alaqla, Bader Almuzzaini, Mohammed Aldrees, Ghaida Alnaqa, Farah Almasoud, Omar Aldibasi, Hala Alshamlan","doi":"10.1186/s40510-024-00532-4","DOIUrl":"10.1186/s40510-024-00532-4","url":null,"abstract":"<p><strong>Background: </strong>Hypodontia is the most prevalent dental anomaly in humans, and is primarily attributed to genetic factors. Although genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNP) associated with hypodontia, genetic risk assessment remains challenging due to population-specific SNP variants. Therefore, we aimed to conducted a genetic analysis and developed a machine-learning-based predictive model to examine the association between previously reported SNPs and hypodontia in the Saudi Arabian population. Our case-control study included 106 participants (aged 8-50 years; 64 females and 42 males), comprising 54 hypodontia cases and 52 controls. We utilized TaqMan<sup>TM</sup> Real-Time Polymerase Chain Reaction and allelic genotyping to analyze three selected SNPs (AXIN2: rs2240308, PAX9: rs61754301, and MSX1: rs12532) in unstimulated whole saliva samples. The chi-square test, multinomial logistic regression, and machine-learning techniques were used to assess genetic risk by using odds ratios (ORs) for multiple target variables.</p><p><strong>Results: </strong>Multivariate logistic regression indicated a significant association between homozygous AXIN2 rs2240308 and the hypodontia phenotype (ORs [95% confidence interval] 2.893 [1.28-6.53]). Machine-learning algorithms revealed that the AXIN2 homozygous (A/A) genotype is a genetic risk factor for hypodontia of teeth #12, #22, and #35, whereas the AXIN2 homozygous (G/G) genotype increases the risk for hypodontia of teeth #22, #35, and #45. The PAX9 homozygous (C/C) genotype is associated with an increased risk for hypodontia of teeth #22 and #35.</p><p><strong>Conclusions: </strong>Our study confirms a link between AXIN2 and hypodontia in Saudi orthodontic patients and suggests that combining machine-learning models with SNP analysis of saliva samples can effectively identify individuals with non-syndromic hypodontia.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"31"},"PeriodicalIF":4.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1186/s40510-024-00531-5
Michael Nemec, Giacomo Garzarolli-Thurnlackh, Stefan Lettner, Hemma Nemec-Neuner, André Gahleitner, Andreas Stavropoulos, Kristina Bertl, Erwin Jonke
Background: Large variation in the prevalence of ankylosis and replacement resorption (ARR) is reported in the literature and most studies have relatively small patient numbers. The present retrospective study aimed to provide an overview on prevalence, location of, and associated risk factors with ARR based on a large sample of computed tomography (CT) / cone beam computed tomography (CBCT) scans of impacted teeth. The results should allow clinicians to better estimate the risk of ARR at impacted teeth.
Methods: The CT/CBCT scans of 5764 patients of a single center in Central Europe were screened with predefined eligibility criteria. The following parameters were recorded for the finally included population: gender, age, tooth type/position, number of impacted teeth per patient, and presence/absence of ARR. For teeth with ARR the tooth location in reference to the dental arch, tooth angulation, and part of the tooth affected by ARR were additionally registered.
Results: Altogether, 4142 patients with 7170 impacted teeth were included. ARR was diagnosed at 187 impacted teeth (2.6%) of 157 patients (3.7%); 58% of these patients were female and the number of teeth with ARR per patient ranged from 1 to 10. Depending on the tooth type the prevalence ranged from 0 (upper first premolars, lower central and lateral incisors) to 41.2% (upper first molars). ARR was detected at the crown (57.2%), root (32.1%), or at both (10.7%). After correcting for confounders, the odds for ARR significantly increased with higher age; further, incisors and first/second molars had the highest odds for ARR, while wisdom teeth had the lowest. More specifically, for 20-year-old patients the risk for ARR at impacted incisors and first/second molars ranged from 7.7 to 10.8%, but it approximately tripled to 27.3-35.5% for 40-year-old patients. In addition, female patients had significantly less often ARR at the root, while with increasing age the root was significantly more often affected by ARR than the crown.
Conclusion: ARR at impacted teeth is indeed a rare event, i.e., only 2.6% of 7170 impacted teeth were ankylosed with signs of replacement resorption. On the patient level, higher age significantly increased the odds for ARR and on the tooth level, incisors and first/second molars had the highest odds for ARR, while wisdom teeth had the lowest.
{"title":"Prevalence and characteristics of and risk factors for impacted teeth with ankylosis and replacement resorption - a retrospective, 3D-radiographic assessment.","authors":"Michael Nemec, Giacomo Garzarolli-Thurnlackh, Stefan Lettner, Hemma Nemec-Neuner, André Gahleitner, Andreas Stavropoulos, Kristina Bertl, Erwin Jonke","doi":"10.1186/s40510-024-00531-5","DOIUrl":"10.1186/s40510-024-00531-5","url":null,"abstract":"<p><strong>Background: </strong>Large variation in the prevalence of ankylosis and replacement resorption (ARR) is reported in the literature and most studies have relatively small patient numbers. The present retrospective study aimed to provide an overview on prevalence, location of, and associated risk factors with ARR based on a large sample of computed tomography (CT) / cone beam computed tomography (CBCT) scans of impacted teeth. The results should allow clinicians to better estimate the risk of ARR at impacted teeth.</p><p><strong>Methods: </strong>The CT/CBCT scans of 5764 patients of a single center in Central Europe were screened with predefined eligibility criteria. The following parameters were recorded for the finally included population: gender, age, tooth type/position, number of impacted teeth per patient, and presence/absence of ARR. For teeth with ARR the tooth location in reference to the dental arch, tooth angulation, and part of the tooth affected by ARR were additionally registered.</p><p><strong>Results: </strong>Altogether, 4142 patients with 7170 impacted teeth were included. ARR was diagnosed at 187 impacted teeth (2.6%) of 157 patients (3.7%); 58% of these patients were female and the number of teeth with ARR per patient ranged from 1 to 10. Depending on the tooth type the prevalence ranged from 0 (upper first premolars, lower central and lateral incisors) to 41.2% (upper first molars). ARR was detected at the crown (57.2%), root (32.1%), or at both (10.7%). After correcting for confounders, the odds for ARR significantly increased with higher age; further, incisors and first/second molars had the highest odds for ARR, while wisdom teeth had the lowest. More specifically, for 20-year-old patients the risk for ARR at impacted incisors and first/second molars ranged from 7.7 to 10.8%, but it approximately tripled to 27.3-35.5% for 40-year-old patients. In addition, female patients had significantly less often ARR at the root, while with increasing age the root was significantly more often affected by ARR than the crown.</p><p><strong>Conclusion: </strong>ARR at impacted teeth is indeed a rare event, i.e., only 2.6% of 7170 impacted teeth were ankylosed with signs of replacement resorption. On the patient level, higher age significantly increased the odds for ARR and on the tooth level, incisors and first/second molars had the highest odds for ARR, while wisdom teeth had the lowest.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"34"},"PeriodicalIF":4.8,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1186/s40510-024-00530-6
Kuang Tan, Jiayi Wang, Xinyu Su, Yunfei Zheng, Weiran Li
Background: Orthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear.
Results: In this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force.
Conclusion: Our study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM.
{"title":"KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement.","authors":"Kuang Tan, Jiayi Wang, Xinyu Su, Yunfei Zheng, Weiran Li","doi":"10.1186/s40510-024-00530-6","DOIUrl":"10.1186/s40510-024-00530-6","url":null,"abstract":"<p><strong>Background: </strong>Orthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear.</p><p><strong>Results: </strong>In this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force.</p><p><strong>Conclusion: </strong>Our study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"29"},"PeriodicalIF":4.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling.
Methods: Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro.
Results: The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio.
Conclusions: Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization.
{"title":"Mechanically induced M2 macrophages are involved in bone remodeling of the midpalatal suture during palatal expansion.","authors":"Lan Li, Mingrui Zhai, Chen Cheng, Shuyue Cui, Jixiao Wang, Zijie Zhang, Jiani Liu, Fulan Wei","doi":"10.1186/s40510-024-00529-z","DOIUrl":"10.1186/s40510-024-00529-z","url":null,"abstract":"<p><strong>Background: </strong>Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling.</p><p><strong>Methods: </strong>Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro.</p><p><strong>Results: </strong>The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio.</p><p><strong>Conclusions: </strong>Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"30"},"PeriodicalIF":4.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1186/s40510-024-00518-2
Wenyuanfeng Chen, Yuan Qu, Yining Liu, Guorui Zhang, Hasan M Sharhan, Xinzhu Zhang, Kunwu Zhang, Baocheng Cao
Background: Orthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators.
Results: In the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1β and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-β was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF.
Conclusion: This study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.
{"title":"Effects of fasudil on glial cell activation induced by tooth movement.","authors":"Wenyuanfeng Chen, Yuan Qu, Yining Liu, Guorui Zhang, Hasan M Sharhan, Xinzhu Zhang, Kunwu Zhang, Baocheng Cao","doi":"10.1186/s40510-024-00518-2","DOIUrl":"10.1186/s40510-024-00518-2","url":null,"abstract":"<p><strong>Background: </strong>Orthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators.</p><p><strong>Results: </strong>In the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1β and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-β was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF.</p><p><strong>Conclusion: </strong>This study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.</p>","PeriodicalId":56071,"journal":{"name":"Progress in Orthodontics","volume":"25 1","pages":"33"},"PeriodicalIF":4.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}