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Background: Assessment of growth-related or treatment-related changes in the maxilla requires a reliable method of superimposition. Such methods are well established for two-dimensional (2D) cephalometric images but not yet for three-dimensions (3D). The aims of this study were to identify natural reference structures (NRS) for the maxilla in growing patients in 3D, opportunistically using orthodontic mini-screws as reference; and to test the applicability of the proposed NRS for maxillary superimposition by assessing the concordance of this approach with Björk's 'stable reference structures' in lateral projection., Methods: The stability of the mini-screws was tested on longitudinal pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images by measuring the distance changes between screws. After verifying the stability of the mini-screws, rigid registration was performed for aligning the stable mini-screws. Then, non-rigid registration was used to establish the dense voxel-correspondence among CBCT images and calculate the displacement of each voxel belonging to the maxilla relative to the mini-screws. The displacement vectors were transformed to a standardized maxillary template to categorize the stability of the internal structures statistically. Those voxels that displaced less relative to the mini-screws were considered as the natural reference structures (NRS) for the maxilla. Test samples included another dataset of longitudinal CBCT scans. They were used to evaluate the applicability of the proposed NRS for maxillary superimposition. We assessed whether aligning the maxilla with proposed NRS is in concordance with the maxillary internal reference structures superimposition in the traditional 2D lateral view as suggested by Björk. This was quantitively assessed by comparing the mean sagittal and vertical tooth movements for both superimposition methods., Results: The stability of the mini-screws was tested on 10 pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images (T1: 12.9 ± 0.8 yrs, T2: 14.8 ± 0.7 yrs). Both the loaded and the unloaded mini-screws were shown to be stable during orthodontic treatment, which indicates that they can be used as reference points. By analyzing the deformation map of the maxilla, we confirmed that the infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than  1 cm distal to incisor foramen except the palatal suture) were stable during growth. Another dataset of longitudinal CBCT scans (T1: 12.2 ± 0.63 yrs, T2: 15.2 ± 0.96 yrs) was used to assess the concordance of this approach with Björk's 'stable reference structures'. The movement of the maxillary first molar and central incisor showed no statistically significant difference when superimposing the test images with the proposed NRS or with the classic Björk maxillary superimposition in the lateral view., Conclusions: The infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm posterior to incisal foramen except the palatal suture) were identified as stable regions in the maxilla. These stable structures can be used for maxillary superimposition in 3D and generate comparable results to Björk superimposition in the lateral view., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: FAT4 (FAT Atypical Cadherin 4) is a member of the cadherin-associated protein family, which has been shown to function as a tumor suppressor by inhibiting proliferation and metastasis. The Wnt/β-catenin pathway activation is highly associated with PD-L1-associated tumor immune escape. Here, we report the mechanism by which FAT4 overexpression regulates anti-tumor immunity in cervical cancer by inhibiting PD-L1 N-glycosylation and cell membrane localization in a β-catenin-dependent manner., Methods: FAT4 expression was first detected in cervical cancer tissues and cell lines. Cell proliferation, clone formation, and immunofluorescence were used to determine the tumor suppressive impact of FAT4 overexpression in vitro, and the findings were confirmed in immunodeficient and immunocomplete mice xenografts. Through functional and mechanistic experiments in vivo and in vitro, we investigated how FAT4 overexpression affects the antitumor immunity via the β-catenin/STT3/PD-L1 axis., Results: FAT4 is downregulated in cervical cancer tissues and cell lines. We determined that FAT4 binds to β-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of β-catenin by the degradation complexes (AXIN1, APC, GSK3β, CK1). FAT4 overexpression decreases programmed death-ligand 1 (PD-L1) mRNA expression at the transcriptional level, and causes aberrant glycosylation of PD-L1 via STT3A at the post-translational modifications (PTMs) level, leading to its endoplasmic reticulum (ER) accumulation and polyubiquitination-dependent degradation. We found that FAT4 overexpression promotes aberrant PD-L1 glycosylation and degradation in a β-catenin-dependent manner, thereby increasing cytotoxic T lymphocyte (CTL) activity in immunoreactive mouse models., Conclusions: These findings address the basis of Wnt/β-catenin pathway activation in cervical cancer and provide combination immunotherapy options for targeting the FAT4/β-catenin/STT3/PD-L1 axis. Schematic cartoons showing the antitumor immunity mechanism of FAT4. (left) when Wnts bind to their receptors, which are made up of Frizzled proteins and LRP5/6, the cytoplasmic protein DVL is activated, inducing the aggregation of degradation complexes (AXIN, GSK3β, CK1, APC) to the receptor. Subsequently, stable β-catenin translocates into the nucleus and binds to TCF/LEF and TCF7L2 transcription factors, leading to target genes transcription. The catalytically active subunit of oligosaccharyltransferase, STT3A, enhances PD-L1 glycosylation, and N-glycosylated PD-L1 translocates to the cell membrane via the ER-to-Golgi pathway, resulting in immune evasion. (Right) FAT4 exerts antitumor immunity mainly through following mechanisms: (i) FAT4 binds to β-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of β-catenin by the degradation complexes (AXIN1, APC, GSK3β, CK1); (ii) FAT4 inhibits PD-L1 and STT3A transcription in a β-catenin-dependent manner and induces aberrant PD-L1 glycosylation and ubiquitination-dependent degradation; (iii) Promotes activation of cytotoxic T lymphocytes (CTL) and infiltration into the tumor microenvironment., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Objective: The objective of the study was to explore and validate the consensus of orthodontic experts on the assessment of orthodontic treatment outcomes based on subjective and objective analysis., Materials and Methods: The research consisted of two parts: the exploration and verification of expert consensus. First, a sample of 108 cases randomly selected from six dental schools in China were evaluated by 69 orthodontic experts and measured by researchers based on post-treatment study casts and lateral cephalograms, respectively. Then, through statistical analysis, the objective indicators significantly correlated with experts' subjective evaluations were selected, their weights were determined, and the critical values of satisfactory, acceptable and unacceptable grades were screened. Subsequently, another sample of 72 cases were evaluated by another 36 orthodontic experts, and the subjective evaluation results were compared with the objective measurement results., Results: There were six model indicators and seven cephalometric indicators being significantly correlated with the experts' subjective evaluations, including occlusal contact, overjet, midline, interproximal contact, alignment, occlusal relationship, L1/NB, ANB, SN/OP, U1/SN, LL-EP, Cm-Sn-UL and Ns-Prn-Pos, with a cumulative R 2 of 0.704. In the verification part, the correlation coefficient between the 36 experts' subjective scores and objective regression scores was 0.716 (P < .001); the correlation coefficient between the 36 experts' subjective grades and objective grades was 0.757 (P < .001)., Conclusions: Orthodontic experts had good consistency in the subjective evaluation of the combined records of post-treatment study casts and lateral cephalograms. The objective indicators selected from subjective and objective analysis had good reliability and validity and could further improve the existing occlusal indices., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To apply geometric morphometrics and multivariate statistics to evaluate changes of the face for female Chinese patients who underwent orthodontic treatment with different type of anchorage control., Methods: Forty-six adult female patients were enrolled including 33 four first premolar extraction cases (17 patients with mini-implants for maximum anchorage control and 16 patients without mini-implants) and 13 non-extraction cases with minimum treatment duration of 15 months. Spatially dense correspondence was established among all the images The pre-and post-treatment average faces of the two extraction groups and the non-extraction group were generated. Partial least squares regression was used to test the statistical significance of the effects of treatment for different anchorage choice., Results: The upper and lower lips were retruded significantly after treatment in the extraction groups. In the maximum anchorage control group, the temple and cheek were depressed by approximately 1 mm, and the zygomatic regions were increased in the mid-face. However, these changes were not statistically significant. In comparison, no statistically significant facial changes occurred in the non-extraction group., Conclusions: The anchorage choice and the removal of four first premolar extraction influence lip shape as well as the perioral regions. However, extraction treatment does not impact the appearance of the cheeks and temples on a statistically level, as compared to orthodontic treatment without premolar extractions. Spatially dense geometric morphometric facilitates comprehensive treatment effect quantification and visualization on the full facial changes for improving orthodontic outcome evaluation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite advances in cervical cancer screening and human papilloma virus (HPV) vaccines, cervical cancer remains a global health burden. The standard treatment of cervical cancer includes surgery, radiation therapy, and chemotherapy. Radiotherapy (RT) is the primary treatment for advanced-stage disease. However, due to radioresistance, most patients in the advanced stage have an adverse outcome. Recent studies have shown that long noncoding RNAs (lncRNAs) participate in the regulation of cancer radiosensitivity by regulating DNA damage repair, apoptosis, cancer stem cells (CSCs), and epithelial-mesenchymal transition (EMT). In this review, we summarize the molecular mechanisms of long noncoding RNAs in cervical cancer and radiosensitivity, hoping to provide a theoretical basis and a new molecular target for the cervical cancer RT in the clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zhu, Wu, Wang, Duan and Xu.)

This study proposes a method that integrates maxillary dental cast and cephalograms and evaluates its accuracy compared with cone-beam computed tomography (CBCT) scans. The study sample comprised 20 adult patients with records of dental casts, cephalograms, and craniofacial CBCT scans. The maxillary dental cast was integrated with lateral and frontal cephalograms based on best-fit registration of palatal and dental outline curves from dental cast with cephalogram tracings. Linear measurement was conducted to assess the intra- and inter-examiner reproducibility of the proposed integration method using intraclass correlation coefficients; linear and angular measurements were conducted to assess its accuracy with CBCT scans as a standard reference. Paired t test, one sample t test, and mean ± standard deviation of the absolute value of difference were used to compare the integrated images and CBCT. The integration method showed good intra- and inter-examiner reproducibility (intraclass correlation coefficients > 0.98). The differences in linear and angular measurements between the integrated images and CBCT were not statistically significant but with a large deviation. When absolute value of difference was computed, the linear distance error was 0.51 ± 0.34 mm, the tooth point coordinate errors in X, Y and Z axes were 0.22 ± 0.22, 0.38 ± 0.32 and 0.21 ± 0.21 mm, respectively; the angular error in pitch, roll and yaw of the dental cast was 0.82 ± 0.51, 0.92 ± 0.59 and 0.80 ± 0.41 degree, respectively. The proposed method for integration of dental cast and cephalograms showed good reproducibility and acceptable accuracy compared with CBCT. It could be helpful for researchers to study three-dimensional tooth growth changes using the existing craniofacial growth data especially cephalograms., (© 2022. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Segmentation of the masseter muscle (MM) on cone-beam computed tomography (CBCT) is challenging due to the lack of sufficient soft-tissue contrast. Moreover, manual segmentation is laborious and time-consuming. The purpose of this study was to propose a deep learning-based automatic approach to accurately segment the MM from CBCT under the refinement of high-quality paired computed tomography (CT). Fifty independent CBCT and 42 clinically hard-to-obtain paired CBCT and CT were manually annotated by two observers. A 3D U-shape network was carefully designed to segment the MM effectively. Manual annotations on CT were set as the ground truth. Additionally, an extra five CT and five CBCT auto-segmentation results were revised by one oral and maxillofacial anatomy expert to evaluate their clinical suitability. CBCT auto-segmentation results were comparable to the CT counterparts and significantly improved the similarity with the ground truth compared with manual annotations on CBCT. The automatic approach was more than 332 times shorter than that of a human operation. Only 0.52% of the manual revision fraction was required. This automatic model could simultaneously and accurately segment the MM structures on CBCT and CT, which can improve clinical efficiency and efficacy, and provide critical information for personalized treatment and long-term follow-up.

Introduction: To objectively quantify nasal characteristics of patients with asymmetric mandibular prognathism and to evaluate the association between nasal asymmetry and dentofacial abnormalities., Methods: Ninety adult patients with asymmetric mandibular prognathism were included. Images were captured during pretreatment using 3-dimensional stereophotogrammetry. A total of 7160 uniformly sampled quasi-landmarks were automatically identified on each facial image to establish correspondence using a template mapping technique. Fifteen commonly used anatomic landmarks were automatically located on each image through barycentric to Cartesian coordinate conversion. Nasal characteristics and asymmetry were quantified by anthropometric linear distances, angular measurements, and surface-based analysis. The degree of the nasal, chin, and periorbital asymmetry in a patient was scored using a root-mean-squared error between the left and right sides. The correlations among these regional asymmetries were evaluated., Results: The nasal tip was significantly shifted to the deviated side of the chin, and the nostrils were asymmetrical. The location and degree of nasal asymmetry varied among patients with asymmetric mandibular prognathism. The level of nasal asymmetry was significantly and positively correlated with chin and periorbital asymmetry., Conclusions: Nasal asymmetry is present in asymmetric mandibular prognathism patients. Furthermore, it is positively associated with periorbital deviation and chin deviation. Individualized nasal asymmetry evaluation should be performed, and clinicians should inform patients about preexisting nasal asymmetry., (Copyright © 2022 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due to the improved biopharmaceutical and pharmacokinetic properties and targeted and controlled drug release, nano-based drug delivery systems have emerged as a promising strategy for the treatment of periodontal defects, allowing for increased efficacy and safety in controlling local inflammation, establishing a regenerative microenvironment, and regaining bone and attachments. This review provides an overview of nano-based drug delivery systems and illustrates their practical applications, future prospects, and limitations in the field of periodontal tissue regeneration.

The deep neural network has achieved great success in 3D volumetric correspondence. These methods infer the dense displacement or velocity fields directly from the extracted volumetric features without addressing the intrinsic structure correspondence, being prone to shape and pose variations. On the other hand, the spectral maps address the intrinsic structure matching in the low dimensional embedding space, remain less involved in volumetric image correspondence. This paper presents an unsupervised deep volumetric descriptor learning neural network via the low dimensional spectral maps to address the dense volumetric correspondence. The neural network is optimized by a novel criterion on descriptor alignments in the spectral domain regarding the supervoxel graph. Aside from the deep convolved multi-scale features, we explicitly address the supervoxel-wise spatial and cross-channel dependencies to enrich deep descriptors. The dense volumetric correspondence is formulated as the low-dimensional spectral mapping. The proposed approach has been applied to both synthetic and clinically obtained cone-beam computed tomography images to establish dense supervoxel-wise and up-scaled voxel-wise correspondences. Extensive series of experimental results demonstrate the contribution of the proposed approach in volumetric descriptor extraction and consistent correspondence, facilitating attribute transfer for segmentation and landmark location. The proposed approach performs favorably against the state-of-the-art volumetric descriptors and the deep registration models, being resilient to pose or shape variations and independent of the prior transformations.

Background: Few studies have investigated the impacts of metabolic syndrome (MS) on coronavirus disease 2019 (COVID-19). We described the clinical features and prognosis of confirmed COVID-19 patients with MS during hospitalization and after discharge., Methods: Two hundred and thirty-three COVID-19 patients from the hospitals in 8 cities of Jiangsu, China were retrospectively included. Clinical characteristics of COVID-19 patients were described and risk factors of severe illness were analyzed by logistic regression analysis., Results: Forty-five (19.3%) of 233 COVID-19 patients had MS. The median age of COVID-19 patients with MS was significantly higher than non-MS patients (53.0 years vs. 46.0 years, P  = 0.004). There were no significant differences of clinical symptoms, abnormal chest CT images, and treatment drugs between two groups. More patients with MS had severe illness (33.3% vs. 6.4%, P  < 0.001) and critical illness (4.4% vs. 0.5%, P  = 0.037) than non-MS patients. The proportions of respiratory failure and acute respiratory distress syndrome in MS patients were also higher than non-MS patients during hospitalization. Multivariate analysis showed that concurrent MS (odds ratio [OR] 7.668, 95% confidence interval [CI] 3.062-19.201, P  < 0.001) and lymphopenia (OR 3.315, 95% CI 1.306-8.411, P  = 0.012) were independent risk factors of severe illness of COVID-19. At a median follow-up of 28 days after discharge, bilateral pneumonia was found in 95.2% of MS patients, while only 54.7% of non-MS patients presented bilateral pneumonia., Conclusions: 19.3% of COVID-19 patients had MS in our study. COVID-19 patients with MS are more likely to develop severe complications and have worse prognosis. More attention should be paid to COVID-19 patients with MS., (© 2021 Elsevier España, S.L.U. All rights reserved.)

Objectives: Machine learning is increasingly being used in the medical field. Based on machine learning models, the present study aims to improve the prediction performance of craniodentofacial morphological harmony judgment after orthodontic treatment and to determine the most significant factors. Methods: A dataset of 180 subjects was randomly selected from a large sample of 3,706 finished orthodontic cases from six top orthodontic treatment centers around China. Thirteen algorithms were used to predict the value of the cephalometric morphological harmony score of each subject and to search for the optimal model. Based on the feature importance ranking and by removing features, the regression models of machine learning (including the Adaboost, ExtraTree, XGBoost, and linear regression models) were used to predict and compare the score of harmony for each subject from the dataset with cross validations. By analyzing the prediction values, the most optimal model and the most significant cephalometric characteristics were determined. Results: When nine features were included, the performance of the XGBoost regression model was MAE = 0.267, RMSE = 0.341, and Pearson correlation coefficient = 0.683, which indicated that the XGBoost regression model exhibited the best fitting and predicting performance for craniodentofacial morphological harmony judgment. Nine cephalometric features including L1/NB (inclination of the lower central incisors), ANB (sagittal position between the maxilla and mandible), LL-EP (distance from the point of the prominence of the lower lip to the aesthetic plane), SN/OP (inclination of the occlusal plane), SNB (sagittal position of the mandible in relation to the cranial base), U1/SN (inclination of the upper incisors to the cranial base), L1-NB (protrusion of the lower central incisors), Ns-Prn-Pos (nasal protrusion), and U1/L1 (relationship between the protrusions of the upper and lower central incisors) were revealed to significantly influence the judgment. Conclusion: The application of the XGBoost regression model enhanced the predictive ability regarding the craniodentofacial morphological harmony evaluation by experts after orthodontic treatment. Teeth position, teeth alignment, jaw position, and soft tissue morphology would be the most significant factors influencing the judgment. The methodology also provided guidance for the application of machine learning models to resolve medical problems characterized by limited sample size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Song, Niu and Xu.)

Introduction: This study aimed to develop an automatic pipeline for analyzing mandibular shape asymmetry in 3-dimensions., Methods: Forty patients with skeletal Class I pattern and 80 patients with skeletal Class III pattern were used. The mandible was automatically segmented from the cone-beam computed tomography images using a U-net deep learning network. A total of 17,415 uniformly sampled quasi-landmarks were automatically identified on the mandibular surface via a template mapping technique. After alignment with the robust Procrustes superimposition, the pointwise surface-to-surface distance between original and reflected mandibles was visualized in a color-coded map, indicating the location of asymmetry. The degree of overall mandibular asymmetry and the asymmetry of subskeletal units were scored using the root-mean-squared-error between the left and right sides. These asymmetry parameters were compared between the skeletal Class I and skeletal Class III groups., Results: The mandible shape was significantly more asymmetrical in patients with skeletal Class III pattern with positional asymmetry. The condyles were identified as the most asymmetric region in all groups, followed by the coronoid process and the ramus., Conclusions: This automated approach to quantify mandibular shape asymmetry will facilitate high-throughput image processing for big data analysis. The spatially-dense landmarks allow for evaluating mandibular asymmetry over the entire surface, which overcomes the information loss inherent in conventional linear distance or angular measurements. Precise quantification of the asymmetry can provide important information for individualized diagnosis and treatment planning in orthodontics and orthognathic surgery., (Copyright © 2022. Published by Elsevier Inc.)

Background: To evaluate the validity and reliability of cone-beam computed tomography (CBCT) masseter muscle segmentation by comparing with the magnetic resonance imaging (MRI) masseter muscle segmentation of the same patients., Methods: Seventeen volunteers were included in this study. CBCT and MRI scans of the volunteers were taken, respectively, within one month. The masseter muscles in the CBCT scans were segmented by a generative adversarial network (GAN)-based framework combined with manual check. The masseter muscles in the MRI scans were segmented manually. The segmentations were repeated by the first examiner and a second examiner. For cross-sectional area (CSA), paired t-test, intraclass correlation coefficient (ICC) and standard error of measurement (SEM) were calculated to evaluate the validity and reliability of the segmentations. The validity and reliability were also calculated by Dice similarity coefficient (DSC) and average Hausdorff distance (aHD) between different segmentations. Seventeen volunteers were included in this study. CBCT and MRI scans of the volunteers were taken, respectively, within one month. The masseter muscles in the CBCT scans were segmented by a generative adversarial network (GAN)-based framework combined with manual check. The masseter muscles in the MRI scans were segmented manually. The segmentations were repeated by the first examiner and a second examiner. For cross-sectional area (CSA), paired t-test, intraclass correlation coefficient (ICC) and standard error of measurement (SEM) were calculated to evaluate the validity and reliability of the segmentations. The validity and reliability were also calculated by Dice similarity coefficient (DSC) and average Hausdorff distance (aHD) between different segmentations., Results: Paired t-test showed that there was no significant difference in CSA between CBCT and MRI masseter segmentations. The ICCs were all larger than 0.95 and the SEM was less than 4.85 mm 2 for CSA. The DSC was all larger than 0.95 showing over 95% of similarity between CBCT and MRI masseter segmentations. The aHD was all smaller than 0.09 mm showing great consistency of the contour of CBCT and MRI segmentations., Conclusion: Masseter muscle segmentation from CBCT scans was not significantly different from the segmentation from MRI scans. CBCT muscle segmentation showed great validity compared with MRI scans, and great reliability in retests., (© 2021. CARS.)

Objective: Quantification and visualization of the location and magnitude of facial asymmetry is important for diagnosis and treatment planning. The objective of this study was to analyze the asymmetric features of the face for skeletal Class III patients using spatially-dense geometric morphometrics., Methods: Three-dimensional facial images were obtained for 86 skeletal Class III patients. About 7160 uniformly sampled quasi-landmarks were automatically identified on each face using template mapping technique. The pointwise surface-to-surface distance between original and mirror face was measured and visualized for the whole face after robust Procrustes superimposition. The degree of overall asymmetry in an individual was scored using a root-mean-squared-error. Automatic partitioning of the face was obtained, and the severity of the asymmetry compared among seven facial regions., Results: Facial asymmetry was mainly located on, but not limited to, the lower two-thirds of the face in skeletal Class III patients. The lower cheek and nose asymmetry were detected to have more extensive and of a greater magnitude of asymmetry than other facial anatomical regions but with various individual variations. The overall facial asymmetry index and the regional facial asymmetry indices were higher in males and patients with chin deviation., Conclusions: Soft tissue asymmetry is predominately presented in the lower-third of the face in skeletal Class III patients and with various variations on other facial anatomical regions. Morphometric techniques and computer intensive analysis have allowed sophisticated quantification and visualization of the pointwise asymmetry on the full face., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.

Background: To establish the digital diagnostic templates by cluster analysis based on a set of cephalometric films and evaluate the outcome of the different treatment methods in the patients affiliated to the same cephalometric morphology template (CMT). These templates could be used for the automatic diagnosis of dentofacial deformities and prediction of treatment outcomes in the future., Methods: In this study, we assessed the coordinates of 60 different landmarks on the cephalograms of 2249 patients (14.35 ± 4.99 years, range from 7 to 62) with dentofacial deformities. The cephalometric data were subjected to dentist for clustering without a priori pattern definitions to generate biologically informative CMTs. Three templates were selected to evaluate the treatment outcome of patients affiliated to the same CMT., Results: The cluster analysis yielded 21 distinct groups. The total discriminant accuracy was 89.1%, while the cross-validation accuracy was 85.0%, showing that the clusters were robust. All CMTs were automatically created and drawn using a computer, based on the average coordinates of each cluster. Individuals affiliated to the same CMT showed similar dentofacial features. We also evaluated differences in the outcomes of patients affiliated to the same CMT., Conclusions: Our results demonstrated the utility of clustering methods for grouping dentofacial deformities with similar dentofacial features. Clustering methods can be used to evaluate the differences in the outcomes of patients affiliated to the same CMT, which has good clinical application value., (© 2022. The Author(s).)

Background: Since December 2019, there has been a global outbreak of COVID-19. As of the end of July 2020, more than 600,000 deaths had been reported globally. The purpose of this paper is to further explore the application of non-invasive ventilation in severe COVID-19 patients., Methods: A retrospective study was conducted to included 57 confirmed COVID-19 patients, among which 36 cases were severe. According to different oxygen inhalation methods, they were divided into non-invasive ventilator assisted ventilation group with 21 cases (group A) and 15 cases of nasal catheter oxygen inhalation group (group B). The data of respiration (RR), heart rate (HR), partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygenation index (OI) before the treatment of noninvasive ventilator assisted ventilation or nasal catheter oxygen treatment at 24, 48, and 72 hours of treatment of the 2 groups were collected and analyzed to determine whether the above indicators were statistically different in each time period., Results: After 24 hours of treatment with noninvasive ventilator assisted ventilation in group A, RR gradually decreased, PaO2 and OI were significantly higher than before treatment, while after 24 hours of treatment, PaO2, RR, HR and other indexes in group B showed no significant improvement, and OI increased gradually after 48 hours of treatment, with statistically significant difference compared with that before treatment., Conclusions: Early adoption of non-invasive ventilation can effectively improve the hypoxic state of patients with severe COVID-19. The combination of underlying diseases will not prolong the use of non-invasive ventilation.

This paper presents an unsupervised clustering random-forest-based metric for affinity estimation in large and high-dimensional data. The criterion used for node splitting during forest construction can handle rank-deficiency when measuring cluster compactness. The binary forest-based metric is extended to continuous metrics by exploiting both the common traversal path and the smallest shared parent node. The proposed forest-based metric efficiently estimates affinity by passing down data pairs in the forest using a limited number of decision trees. A pseudo-leaf-splitting (PLS) algorithm is introduced to account for spatial relationships, which regularizes affinity measures and overcomes inconsistent leaf assign-ments. The random-forest-based metric with PLS facilitates the establishment of consistent and point-wise correspondences. The proposed method has been applied to automatic phrase recognition using color and depth videos and point-wise correspondence. Extensive experiments demonstrate the effectiveness of the proposed method in affinity estimation in a comparison with the state-of-the-art., (© The Author(s) 2021.)

Objectives: To develop and evaluate a geometric deep-learning network to automatically place seven palatal landmarks on digitized maxillary dental casts., Settings and Sample Population: The sample comprised individuals with permanent dentition of various ethnicities. The network was trained from manual landmark annotations on 732 dental casts and evaluated on 104 dental casts., Materials and Methods: A geometric deep-learning network was developed to hierarchically learn features from point-clouds representing the 3D surface of each cast. These features predict the locations of seven palatal landmarks., Results: Repeat-measurement reliability was <0.3 mm for all landmarks on all casts. Accuracy is promising. The proportion of test subjects with errors less than 2 mm was between 0.93 and 0.68, depending on the landmark. Unusually shaped and large palates generate the highest errors. There was no evidence for a difference in mean palatal shape estimated from manual compared to the automatic landmarking. The automatic landmarking reduces sample variation around the mean and reduces measurements of palatal size., Conclusions: The automatic landmarking method shows excellent repeatability and promising accuracy, which can streamline patient assessment and research studies. However, landmark indications should be subject to visual quality control., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Palatal shape contains a lot of information that is of clinical interest. Moreover, palatal shape analysis can be used to guide or evaluate orthodontic treatments. A statistical shape model (SSM) is a tool that, by means of dimensionality reduction, aims at compactly modeling the variance of complex shapes for efficient analysis. In this report, we evaluate several competing approaches to constructing SSMs for the human palate., Setting and Sample Population: This study used a sample comprising digitized 3D maxillary dental casts from 1,324 individuals., Materials and Methods: Principal component analysis (PCA) and autoencoders (AE) are popular approaches to construct SSMs. PCA is a dimension reduction technique that provides a compact description of shapes by uncorrelated variables. AEs are situated in the field of deep learning and provide a non-linear framework for dimension reduction. This work introduces the singular autoencoder (SAE), a hybrid approach that combines the most important properties of PCA and AEs. We assess the performance of the SAE using standard evaluation tools for SSMs, including accuracy, generalization, and specificity., Results: We found that the SAE obtains equivalent results to PCA and AEs for all evaluation metrics. SAE scores were found to be uncorrelated and provided an optimally compact representation of the shapes., Conclusion: We conclude that the SAE is a promising tool for 3D palatal shape analysis, which effectively combines the power of PCA with the flexibility of deep learning. This opens future AI driven applications of shape analysis in orthodontics and other related clinical disciplines., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: This study aimed to design and evaluate a novel method for the registration of 2D lateral cephalograms and 3D craniofacial cone-beam computed tomography (CBCT) images, providing patient-specific 3D structures from a 2D lateral cephalogram without additional radiation exposure., Methods: We developed a cross-modal deformable registration model based on a deep convolutional neural network. Our approach took advantage of a low-dimensional deformation field encoding and an iterative feedback scheme to infer coarse-to-fine volumetric deformations. In particular, we constructed a statistical subspace of deformation fields and parameterized the nonlinear mapping function from an image pair, consisting of the target 2D lateral cephalogram and the reference volumetric CBCT, to a latent encoding of the deformation field. Instead of the one-shot registration by the learned mapping function, a feedback scheme was introduced to progressively update the reference volumetric image and to infer coarse-to-fine deformations fields, accounting for the shape variations of anatomical structures. A total of 220 clinically obtained CBCTs were used to train and validate the proposed model, among which 120 CBCTs were used to generate a training dataset with 24k paired synthetic lateral cephalograms and CBCTs. The proposed approach was evaluated on the deformable 2D-3D registration of clinically obtained lateral cephalograms and CBCTs from growing and adult orthodontic patients., Results: Strong structural consistencies were observed between the deformed CBCT and the target lateral cephalogram in all criteria. The proposed method achieved state-of-the-art performances with the mean contour deviation of 0.41 ± 0.12 mm on the anterior cranial base, 0.48 ± 0.17 mm on the mandible, and 0.35 ± 0.08 mm on the maxilla, respectively. The mean surface mesh ranged from 0.78 to 0.97 mm on various craniofacial structures, and the LREs ranged from 0.83 to 1.24 mm on the growing datasets regarding 14 landmarks. The proposed iterative feedback scheme handled the structural details and improved the registration. The resultant deformed volumetric image was consistent with the target lateral cephalogram in both 2D projective planes and 3D volumetric space regarding the multicategory craniofacial structures., Conclusions: The results suggest that the deep learning-based 2D-3D registration model enables the deformable alignment of 2D lateral cephalograms and CBCTs and estimates patient-specific 3D craniofacial structures., (© 2021 American Association of Physicists in Medicine.)

Melittin's non-specific cytotoxicity and hemolytic activity restrict its clinical use, but polypeptide modification is thoμght to be highly selective and well-tolerated. Here, we synthesized a novel antineoplastic peptide UM-6 based on melittin and explored the mechanism related to its anti-proliferation and metastasis on cervical cancer (CC). In the present study, we demonstrated that UM-6 inhibits viability of CC cell lines Caski and Hela in vitro by inducing apoptosis and autophagy with low toxicity to normal epithelial cells. UM-6 also triggers the Hippo signaling pathway, promoting cytoplasmic retention and phosphorylation-dependent degradation of YAP, as well as inhibiting YAP-TEAD binding and reducing transcriptional activity, suppressing downstream target gene expression. Injection of UM-6 in mice can significantly inhibit the growth of xenograft tumors, and greatly reduce the number, volume, and burden of abdominal tumors in the metastasis models without significant toxicity. These current results suggest that UM-6 has the potential to serve as a new anticancer drug candidate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), an RNA-binding protein that can regulate the translation of specific mRNAs. In this study, we developed an FXS human forebrain organoid model and observed that the loss of FMRP led to dysregulated neurogenesis, neuronal maturation and neuronal excitability. Bulk and single-cell gene expression analyses of FXS forebrain organoids revealed that the loss of FMRP altered gene expression in a cell-type-specific manner. The developmental deficits in FXS forebrain organoids could be rescued by inhibiting the phosphoinositide 3-kinase pathway but not the metabotropic glutamate pathway disrupted in the FXS mouse model. We identified a large number of human-specific mRNAs bound by FMRP. One of these human-specific FMRP targets, CHD2, contributed to the altered gene expression in FXS organoids. Collectively, our study revealed molecular, cellular and electrophysiological abnormalities associated with the loss of FMRP during human brain development., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated., Methods: A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed., Results: The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0-21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454-0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050-1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased., Conclusions: Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2., (© 2021. The Author(s).)

Introduction: Determination of improvement in orthodontic treatment may depend on the measurement method used and the purpose., Methods: Improvement after orthodontic treatment (from T1 to T2 [beginning to end of treatment]) was assessed 3 ways from a set of 98 patient records: (1) calculated by subtracting judges' assessments at T2 from T1 for records presented in random order, (2) judged as a holistic impression viewing T1 and T2 records side by side, and (3) determined from proxies (American Board of Orthodontics Discrepancy Index, the American Board of Orthodontics Objective Grading System, and the Peer Assessment Rating index)., Results: High levels of intramethod consistency were observed, with intraclass correlation coefficient clustering around an intraclass correlation coefficient of 0.900, and distributions were normal. Calculated and judged improvements correlated at r = 0.606. Calculated or judged improvements were correlated at a lower level with proxies. Calculated improvement was significantly associated with "challenge" (T1) scores and judged improvement associated with "results" (T2) scores. Common method bias was observed, with higher correlations among similar indexes than among indexes at the same time that used various methods. Relative to differences in Peer Assessment Rating scores, calculated improvement overestimated low scores and underestimated high ones. The same effect, but statistically greater, was observed using direct judgment of improvement., Conclusions: These findings are consistent with decision science and measurement theory. In some circumstances, such as third-party reimbursement and research, operationally defined measures of occlusion are appropriate. In practice, the determination of occlusion and improvement are best performed by judgment that naturally corrects for biases in proxies and incorporates background information., (Copyright © 2021. Published by Elsevier Inc.)

The molecular mechanisms underlying the development of thyroid cancer (TC) have been examined through extensive experiments. A large number of studies have shown that the incidences of thyroid cancer in women is much higher than that in men, so estrogen plays a key role in the development of thyroid cancer. Estrogen plays its growth-promoting role through classical genomic and non-genomic pathways mediated by membrane-bound estrogen receptors. It also can affect tumor progression by regulating the tumor microenvironment. We summarize the understanding of molecular mechanisms of estrogen signaling pathways in thyroid cancer. Furthermore, it will provide a new target for the treatment of thyroid carcinoma by blocking estrogen and its related action pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Xu, Ma and Chang.)

Circular RNAs (circRNAs) are non-coding RNA molecules, and these are differentially expressed in various diseases, including cancer, suggesting that circRNAs can regulate certain diseases. CircRNAs can act as miRNAs sponges, RNA-binding protein (RBP) sponges, and translation regulators, and they can become an important part of the regulation of gene expression. Furthermore, because of their biomedical features in body fluids, such as high abundance, conservation, and stability, circRNAs are seen as potential biomarkers for various cancers. Cervical cancer (CC) is one of the main causes of cancer-related death in women, and there have been a large number of studies that analyze circRNAs as a new object to be evaluated in CC. Therefore, this review, by understanding the role of circRNAs in CC, may create innovative strategies in the future clinical diagnosis, treatment, and prognosis of CC and promote the development of personalized and highly accurate cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Zhu, Fu and Xu.)

Cancer has been a daunting challenge for human beings because of its clonal heterogeneity and compositional complexity. Tumors are composed of cancer cells and a variety of non-cancer cells, which together with the extracellular matrix form the tumor microenvironment. These cancer-related cells and components and immune mechanisms can affect the development and progression of cancer and are associated with patient diagnosis, treatment and prognosis. As the first choice for the study of complex biological systems, single-cell transcriptional sequencing (scRNA-seq) has been widely used in cancer research. ScRNA-seq has made breakthrough discoveries in tumor heterogeneity, tumor evolution, metastasis and spread, development of chemoresistance, and the relationship between the tumor microenvironment and the immune system. These results will guide clinical cancer treatment and promote personalized and highly accurate cancer treatment. In this paper, we summarize the latest research progress of scRNA-seq and its guiding significance for clinical treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Xu, Jin, Huang and Zhang.)

Recent studies have shown that the innate immune cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway may play an important role in antitumor immunity. Additionally, the cGAS-STING pathway promotes the senescence of cancer cells, induces apoptosis of cancer cells, and increases the protective effect of cytotoxic T cells and natural killer cell-mediated cytotoxicity. We believe that the combination of the cGAS-STING signaling pathway with other therapeutic methods provides a new perspective from which to overcome obstacles in the application of this review. Further, we highlight the antitumor mechanism of the cGAS-STING signaling pathway and the latest advances in monotherapy and combination therapy with related agonists., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The female lower genital tract melanomas mainly include vulvar, vaginal and cervical melanoma. There is little clinical data on the melanomas thus making them highly lethal with their prognosis being worse than for cutaneous melanoma and other gynecological malignancies. Surgery is still the primary treatment for gynecological melanomas with wide local resection (WLE) of tumors with adequate margins being preferred for early-stage vulvar melanoma while complete resection of the primary tumor is the standard treatment for early-stage cervical and vaginal melanoma. Sentinel lymph node biopsy seems to avoid unnecessary complete regional lymphadenectomy. However, it should be chosen cautiously. Recently discovered molecular changes have provided new hopes for effective systemic treatment of female genital tract melanomas. In this review, we summarize the pathogenesis and clinicopathological characteristics of these rare melanomas with particular emphasis on new therapies and clinical management methods that may affect prognosis. The review aims to provide a viable direction for clinicians to diagnose and treat female lower genital tract melanomas., Competing Interests: None., (AJCR Copyright © 2020.)

Objective : To characterize ethnic differences between Chinese and White-Americans between 8.5 and 17.5 years of age, with respect to transverse cephalometric characteristics and to establish transverse craniofacial normative values for Chinese adolescents. Methods : Two-hundred fifty-seven and 547 posteroanterior cephalograms were selected from 35 White-Americans and 157 Chinese with individual normal occlusions. Transverse measurements were obtained and compared between ethnicities to guide determination of normative values for Chinese adolescents. Student's t -test or one-way analysis of variance was used, as appropriate. Results : Chinese girls demonstrated significantly larger measurements than White-American girls at all ages, with the exception of nasal width. Chinese boys exhibited larger measurements than White-American boys at different ages. Chinese boys had larger measurements than girls for most measurements. These data established normative values for Chinese adolescents. Discussion : Ethnic differences existed between Chinese and White-American adolescents with respect to transverse craniofacial measurements. Transverse normative values were established for Chinese adolescents.

Purpose: The aim of this study was to investigate the clinical characteristics and management of malignant ovarian tumors during pregnancy, as well as the feto-maternal outcomes and analyze the influential factors on the pregnancy outcomes., Patients and Methods: Eighty-five patients with ovarian malignancies during pregnancy treated at 12 tertiary hospitals between 2009 and 2019 were analyzed in this study. The clinical features, histopathological characteristics, clinical management, and maternal and perinatal outcomes were retrospectively analyzed. The clinical features and managements were compared between abortion group and live birth group., Results: The following diagnoses were made: 41 (48.24%) patients with borderline ovarian tumors, 18 (21.18%) patients with epithelial ovarian cancers, 17 (20.00%) patients with non-epithelial ovarian malignancies and 9 (10.59%) patients with metastatic ovarian tumors. Thirty-six (42.45%) patients underwent conservative surgical treatment. Thirty-four (40.00%) patients opted for fertility-sparing surgery, and fifteen (17.56%) patients received radical surgery. Chemotherapy was administered to 32.94% of the patients. The proportion of ovarian malignancies diagnosed in the first trimester in the abortion group was higher than that in the live birth group ( P <0.05). However, tumor diameter, reproductive history, stage and surgical indications showed no significant differences between groups. A total of 67 live babies were recorded in this study, including 19 premature babies and 1 full-term newborn who died of respiratory distress. All of the BOTs were diagnosed with stage I, among whom 38 (92.68%) patients exhibited disease-free survival. Twenty-eight ovarian cancers were in stage I-II and 26 of them had disease-free survival with the longest follow-up time of 10 years. Five of the sixteen patients in advanced stage (stage III-IV) died, four of whom had metastatic tumors., Conclusion: Pregnant women with early-stage malignant ovarian tumors appear to have favorable outcomes. Conservative surgery is acceptable for early-stage borderline ovarian tumors during pregnancy. The gestational age of ovarian malignancy detection is key for pregnancy outcomes., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Wang et al.)

Autophagy is a dynamic circulatory system that occurs in all eukaryotic cells. Cytoplasmic material is transported to lysosomes for degradation and recovery through autophagy. This provides energy and macromolecular precursors for cell renewal and homeostasis. The Hippo-YAP pathway has significant biological properties in controlling organ size, tissue homeostasis, and regeneration. Recently, the Hippo-YAP axis has been extensively referred to as the pathophysiological processes regulating autophagy. Understanding the cellular and molecular basis of these processes is crucial for identifying disease pathogenesis and novel therapeutic targets. Here we review recent findings from Drosophila models to organisms. We particularly emphasize the regulation between Hippo core components and autophagy, which is involved in normal cellular regulation and the pathogenesis of human diseases, and its application to disease treatment.

Background: Facial esthetics is a major concern of orthodontic patients. This study aims to evaluate orthodontic treatment-related thickness changes of the masseter muscles and surrounding soft tissues and the potential factors that would influence these changes during orthodontic treatment in female adults., Methods: Forty-two female adult patients were included in this retrospective study and were divided into extraction (n = 22) and nonextraction (n = 20) groups. Pretreatment and posttreatment cone-beam computed tomography (CBCT) images were superimposed and reconstructed. The thickness changes of the masseter area of facial soft tissue (MAS), masseter muscles (MM) and surrounding fat tissue (FT) were measured. Pretreatment age, treatment duration, sagittal relationship (ANB), and vertical relationship (Frankfort-mandibular plane angle, FMA)-related MAS, MM and FT changes were compared between extraction and nonextraction groups. Spearman's correlation coefficient was calculated between the above variables. Regression analysis was conducted to confirm the causal relations of the variables., Results: The thickness of MAS and MM significantly decreased in both groups, with larger decreases (> 1 mm) in the extraction group. There were strong correlations (r > 0.7) between the thickness decrease in MAS and MM in both groups and moderate correlations (r > 0.4) between MAS and FT in the nonextraction group. A significantly greater decrease of MAS and MM were found to be moderately correlated with a smaller FMA (r > 0.4) in the extraction group. Scatter plots and regression analysis confirmed these correlations., Conclusions: Masseter muscles and the surrounding soft tissue exhibited a significant decrease in thickness during orthodontic treatment in female adults. Low-angle patients experienced a greater decrease in soft tissue thickness in the masseter area in the extraction case. But the thickness changes were clinically very small in most patients.

Background: With the aid of implants, Björk identified two-dimensional mandibular stable structures in cephalograms during facial growth. However, we do not know what the three-dimensional stable structures are with certainty. The purpose of this study was to identify the most stable mandibular landmarks in growing patients using three-dimensional images., Methods: The sample was comprised of two cone-beam computed tomography (CBCT) scans taken about 4.6 years apart in 20 growing patients between the ages of 12.5 (T1) and 17.1 years (T2). After head orientation, landmarks were located on the chin (Pog), internal symphysis (Points C, D and E), and mandibular canals, which included the mental foramina (MF and MFA) and mandibular foramina (MdF). The linear distance change between Point C and these landmarks was measured on each CBCT to test stability through time. The reliability of the suggested stable landmarks was also evaluated., Results: The total distance changes between Point C and points D, E, Pog, MF, and MFA were all less than 1.0 mm from T1 to T2. The reliability measures of these landmarks, which were measured by the Cronbach alpha, were above 0.94 in all three dimensions for each landmark. From T1 to T2, the distance changes from Point C to the right and left mandibular foramina were 3.39 ± 3.29 mm and 3.03 ± 2.83 mm, respectively., Conclusions: During a growth period that averaged 4.6 years, ranging from 11.2 to 19.8 years old, the structures that appeared relatively stable and could be used in mandibular regional superimpositions included Pog, landmarks on the inferior part of the internal symphysis, and the mental foramen. The centers of the mandibular foramina and the starting points of the mandibular canal underwent significant changes in the transverse and sagittal dimensions.

5-Methylcytosine (5mC) is considered as a common epigenetic modification that plays an important role in the regulation of gene expression. At the same time, 5-hydroxymethylcytosine (5hmC) has been found as an emerging modification of cytosine bases of recent years. Unlike 5mC, global 5hmC levels vary from tissues that have differential distribution both in mammalian tissues and in the genome. DNA hydroxymethylation is the process that 5mC oxidates into 5hmC with the catalysis of TET (ten-eleven translocation) enzymes. It is an essential option of DNA demethylation, which modulates gene expression by adjusting the DNA methylation level. Various factors can regulate the demethylation of DNA, such as environmental toxins and mental stress. In this review, we summarize the progress in the formation of 5hmC, and obtaining 5hmC in a cell-free DNA sample presents multiple advantages and challenges for the subject. Furthermore, the clinical potential for 5hmC modification in dealing with cancer early diagnosis, prognostic evaluation, and prediction of therapeutic effect is also mentioned.

Objectives: To compare the clinical characteristics and the dynamics of viral load between imported and non-imported patients with COVID-19., Design and Methods: Data from 51 laboratory-confirmed patients were retrospectively analyzed., Results: The incubation period in the tertiary group was longer than that in the imported and secondary groups (both p < 0.05). Fever was the most common symptom at the onset of illness (73.33%, 58.82%, and 68.42%, respectively), and half of the patients had a low-grade temperature (<38.0 °C) with a short duration of fever (<7 days). CT scans showed that most patients in the three groups had bilateral pneumonia (80.00%, 76.47%, and 73.68%, respectively). Ct values detected in the tertiary patients were similar to those for the imported and secondary groups at the time of admission (both p > 0.05). For the tertiary group, the viral load was undetectable in half of the patients (52.63%) on day 7, and in all patients on day 14. For one third of the patients in the imported and secondary groups, the viral load remained positive on day 14 after the admission., Conclusions: COVID-19 can present as pneumonia with a low onset of symptoms, and the infectivity of SARS-CoV2 may gradually decrease in tertiary patients., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A functional appliance is commonly used to optimize the development of the facial skeleton in the treatment of Class II malocclusion. Recent three-dimensional(3D) image-based analysis offers numerous advantages in quantitative measurement and visualization in orthodontics. The aim of this study was to localize in 3D the skeletal effect produced by the Herbst appliance on the mandible using the geometric morphometric technique., Methods: Twenty patients treated with a Herbst appliance and subsequent fixed appliances were included. Cone-beam computed tomography (CBCT) images were taken before treatment (T1), 8 weeks after Herbst appliance removal (T2), and after subsequent fixed appliance treatment (T3). Spatially dense morphometric techniques were used to establish the corresponding points of the mandible. The mandibular morphological changes from T1-T2, T2-T3, and T1-T3 were calculated for each patient by superimposing two mandibular models at two time points with robust Procrustes superimposition. These changes were then compared to the morphological changes estimated from normative mandibular growth curves over the same period. The proportion of cases exceeding the growth expression for controls was compared to a normal population using a one tailed binomial test., Results: Approximately 1.5-2 mm greater condylar changes and 0.5 mm greater changes in the chin occurred from Tl to T2. This effect lasted until the completion of treatment (T1-T3), but there was no obvious skeletal effect during the orthodontic phase (T2-T3). Approximately 40-50% of the patient sample exceeded condylar growth by > 1.5 mm compared to untreated controls (p < .05). However, changes at the chin were not statistically significant., Conclusions: The principal skeletal effect of Herbst appliance treatment was additional increase in condylar length for about half of the sample. This inconsistency may relate to the degree of mandibular growth suppression associated with a specific malocclusion.

Background: The aim of this study was to establish a computer-aided automated method for cephalometric superimposition and to evaluate the accuracy of this method based on free-hand tracing., Methods: Twenty-eight pairs of pre-treatment (T 1 ) and post-treatment (T 2 ) cephalograms were selected. Structural superimpositions of the anterior cranial base, maxilla and mandible were independently completed by three operators performing traditional hand tracing methods and by computerized automation using the feature matching algorithm. To quantitatively evaluate the differences between the two methods, the hand superimposed patterns were digitized. After automated and hand superimposition of T 2 cephalograms to T 1 cephalometric templates, landmark distances between paired automated and hand T 2 cephalometric landmarks were measured. Differences in hand superimposition among the operators were also calculated., Results: The T 2 landmark differences in hand tracing between the operators ranged from 0.61 mm to 1.65 mm for the three types of superimposition. There were no significant differences in accuracy between hand and automated superimposition (p > 0.05)., Conclusions: Computer-aided cephalometric superimposition provides comparably accurate results to those of traditional hand tracing and will provide a powerful tool for academic research.

Grainyhead-like 2 (GRHL2), one of the three homologs of Drosophila grainyhead, contributes to epithelial morphogenesis and differentiation. Dysregulation of GRHL2 has been shown to be involved in hearing loss and neural tube defects during embryogenesis. Moreover, it is well-recognized that GRHL2 suppresses epithelial-to-mesenchymal transition (EMT) that is required for migration and invasion of carcinoma, implicating, GRHL2 in carcinogenesis. Diverse mechanisms, as well as the varied roles of GRHL2 in different tumor tissues, have been elucidated. However, the functions of GRHL2 appear to be more complicated than initially thought. GRHL2, acting as either a tumor enhancer or a tumor inhibitor, depends on the type of cancer. In this review, we summarize research progress about normal physiological functions of GRHL2 including epithelial morphogenesis, neural tube closure, and hearing loss. Moreover, the mechanisms of GRHL2 in tumorigenesis, containing EMT suppression, forming a negative feedback loop with ZEB1 and miR200 family, interactions with estrogen receptor (ER)-dependent signaling pathway, regulation of telomerase reverse transcriptase and relationships with TGF-beta signaling pathway are discussed in this review in an effort to better understand the roles of GRHL2 in a variety of cancers toward the goal of GRHL2-targeted treatment in the near future., Competing Interests: None., (AJTR Copyright © 2020.)

The Hippo pathway has been initially discovered by screening genes that regulate organ size in Drosophila . Recent studies have highlighted the role of the Hippo pathway in controlling organ size, tissue homeostasis and regeneration, and signaling dysregulation, especially the overactivation of the transcriptional coactivator YAP/TAZ, which leads to uncontrolled cell growth and malignant transformation. The core components of the Hippo pathway may initiate tumorigenesis by inducing tumor stem cells and proliferation, ultimately leading to metastasis and drug resistance, which occurs extensively in gynecological malignancies, including cervical cancer, ovarian cancer, and endometrial cancer. In this review, we attempt to systematically summarize recent progress in our understanding of the mechanism of Hippo pathway regulation in tumorigenesis and the mechanisms that underlie alterations during gynecological malignancies, as well as new therapeutic strategies., Competing Interests: None., (AJCR Copyright © 2020.)

Background: Ovarian cancer during pregnancy is relatively rare and treatment strategies are inexperienced in surgery and chemotherapy. Multidisciplinary management of advanced epithelial ovarian cancer in pregnant patients with strong desire of fertility including sufficient mental and medical understanding, perioperative consideration, intraoperative decision, chemotherapy sensitivity and follow-up after treatment can gain successful outcomes for both maternal disease and fetus's development., Case Presentation: A 34-year-old primigravidae was diagnosed with advanced epithelial ovarian tumor and then first cytoreductive surgery to resect macroscopical lesions and protect the uterus for fetus was performed following with four chemotherapy courses (docetaxel and carboplatin) before delivery and four other chemotherapy courses after delivery. Chemotherapy drugs were decided by sensitivity test and the patient's anaphylaxis. Second surgery involved cesarean section with a healthy offspring and secondary cytoreductive surgery. Operative strategies were considered to gain a balance of disease and risk for fetus. Psychosocial support was provided during the course of diagnosis and treatment for a healthy coping situation. This patient relapsed 19 months after the last chemotherapy course and was treated by additional adjuvant therapy to a clinical remission. The 33-month baby boy has no evidence with disease until now. The follow-up of both mother and baby is still continuing., Conclusions: Ovarian cancer during pregnancy has low incidence which must increase in future as women delay reproduction age. Ovarian cancer cytoreductive surgery and chemotherapy have limitation to handle conditions under a desire of fetus protection. Multidisciplinary treatment model is a therapeutic solution and a challenge for gynecological surgeons, medical oncologists, pathologists, obstetricians, neonatologists, pharmacists, anesthetist, and psychologists.

Background: Orthodontic treatment can result in root resorption (RR). Traditional two-dimensional (2D) data exhibit magnification, deformation and positioning problems. Cone beam computed tomography (CBCT) contains more accurate three-dimensional (3D) information. This study identified and qualified the extent and location of root resorption using cone beam computed tomography (CBCT) after comprehensive orthodontic treatment., Methods: Studies comparing the RR before and after comprehensive orthodontic treatment using CBCT were identified using electronic searches of databases, including Cochrane, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Web of Science, and manual searches in relevant journals and the reference lists of the included studies until Oct 25, 2017. The extraction of data and the risk of bias evaluation were conducted by two investigators independently. The methodological quality of the included studies was assessed using the methodological index for non-randomized studies (MINORS). Studies that reported the length and volume of teeth were used for quantitative analyses., Results: Twelve studies were included in the meta-analysis. The length of all teeth after intervention was significantly shorter than that before treatment (MD = 0.80, 95% CI 0.56, 1.03, P < 0.00001). The sequence of RR from heaviest to lightest was maxillary lateral incisors, maxillary central incisors, mandibular anterior teeth, and maxillary canines. Studies were divided into two subgroups based on the use of tooth extraction. Root shortening after treatment was observed in both groups, and extraction caused more root resorption than was observed in the non-extraction group., Conclusions: There were different degrees of root resorption after orthodontics, but it was clinically acceptable. Root resorption established in CBCT research was less serious and more accurate than that observed in the two-dimensional research. Current evidence suggests that root length and volume were reduced after orthodontic treatment. The order of the amount of RR was maxillary lateral incisors, maxillary central incisors and mandibular anterior teeth. Most of the articles were complicated by different confounding factors. Therefore, more high-quality clinical trials are needed to determine the risk factors of root resorption and optimal protocols for treatment and to draw more reliable conclusions.

Introduction: The purpose of this study was to investigate the eruptive and posteruptive tooth displacements of untreated growing subjects longitudinally and the potential connections between posteruptive displacement of the maxillary and mandibular first molars and skeletal facial growth., Methods: The sample comprised 11 series of right 45° oblique cephalograms and lateral cephalograms of untreated children with metallic implants of the Björk type obtained from the archives of a growth study. Cephalograms generated at approximately 2-year intervals between the ages of 8.5 and 16 years were selected and traced. Superimpositions of serial tracings of oblique cephalograms on stable intraosseous implants were made to determine the displacements of buccal segment teeth in both arches, and superimpositions of serial tracings of lateral cephalograms were used to evaluate growth of the jaws., Results: Continuous mesial tipping of the maxillary molars was observed from 8.5 to 16 years of age, averaging 8.2° ± 5.5° for the first molars and 18.3°± 8.5° for the second molars. Compared with the maxillary molars, the mandibular first molars showed less change in angulation except in the later mixed dentition when more than half of the subjects had accelerated forward tipping of the first molar in the late mixed dentition associated with migration into the leeway space. Average amounts of cumulative eruption from 8.5 to 16 years of age were 12.1 ± 2.1 mm downward and 3.8 ± 1.7 mm forward for the maxillary first molar. The mandibular first molar showed 8.6 ± 2.3 mm of eruption and 4.4 ± 1.9 mm of mesial migration. Peak velocity of vertical eruption of the maxillary and mandibular first molars corresponded to the skeletal vertical growth spurt. The maxillary canines and first premolars showed remarkable and continuous uprighting migration during eruption, averaging 9.5° ± 5.0° and 10.5° ± 6.7°, respectively. However, when they erupted into the occlusion, their changes in angulation reverted to forward tipping. The same tendency was also found in the mandibular canines and first premolars., Conclusions: Remarkable eruption and migration occur to the teeth of both arches during childhood and adolescence. Rates of first molar eruption during adolescence follow the general pattern of somatic growth. We infer that maintaining the original distal crown angulation of the maxillary molars may be an effective protocol for preservation of anchorage., (Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objective: Determine optimal weightings of Peer Assessment Rating (PAR) index and Discrepancy Index (DI) for malocclusion severity assessment in Chinese orthodontic patients., Methods: Sixty-nine Chinese orthodontists assessed a full set of pre-treatment records from a stratified random sample of 120 subjects gathered from six university orthodontic centres. Using professional judgment as the outcome variable, multiple regression analyses were performed to derive customized weighting systems for the PAR index and DI, for all subjects and each Angle classification subgroup., Results: Professional judgment was consistent, with an Intraclass Correlation Coefficient (ICC) of 0.995. The PAR index or DI can be reliably measured, with ICC = 0.959 and 0.990, respectively. The predictive accuracy of PAR index was greatly improved by the Chinese weighting process (from r = 0.431 to r = 0.788) with almost equal distribution in each Angle classification subgroup. The Chinese-weighted DI showed a higher predictive accuracy, at P = 0.01, compared with the PAR index (r = 0.851 versus r = 0.788). A better performance was found in the Class II group (r = 0.890) when compared to Class I (r = 0.736) and III (r = 0.785) groups., Conclusions: The Chinese-weighted PAR index and DI were capable of predicting 62 per cent and 73 per cent of total variance in the professional judgment of malocclusion severity in Chinese patients. Differential prediction across Angle classifications merits attention since different weighting formulas were found.

MicroRNA-215 (miR-215) has been showed to play crucial roles in tumorigenesis and tumor progression in many types of cancer. However, its biological function and underlying mechanism in epithelial ovarian cancer (EOC) remains greatly unknown. The aims of this study were to investigate biological role and underlying mechanism of miR-215 in EOC. Here, we found that miR-215 expression was significantly decreased in EOC tissues or cell lines compared with adjacent normal tissues or normal ovarian cell line. Decreased miR-215 expression was significantly associated with International Federation of Gynaecology and Obstetrics (FIGO) stage and lymph node metastasis. Function analysis revealed that overexpression of miR-215 using miR-215 mimic significantly inhibit EOC cell proliferation, colony formation, migration and invasion in vitro. as well as suppress tumor growth in vivo. Moreover, we identified ribosome assembly factor NIN/RPN12 binding protein (NOB1) as a direct targets for miR-215 binding, resulting in suppression it expression, which in turn activated the MAPK signaling pathway. In clinical EOC specimens, NOB1 expression was upregulated, and inversely correlated with miR-215 expression (r = -0.675, P<0.001). Overexpression of NOB1 effectively rescued inhibition effect on EOC cells by induced miR-215 overexpression. Taken together, our findings suggested that miR-215 suppressed EOC growth and invasion by targeting NOB1.

Cervical minimal deviation adenocarcinoma (MDA) is a rare variant of cervical adenocarcinoma that is difficult to diagnose due to the deep location, endogenous growth pattern, deceptively benign appearance of tumor cells, and lack of connection to human papillomavirus (HPV). Cytological evaluation and biopsies offer suboptimal detection and transvaginal sonography or Magnetic Resonance Imaging (MRI) only reveal multiple lesions that mimic multiple benign nabothian cysts. Besides, standard screening, diagnostic tools, and treatments are not established. Thus, MDA tends to be misdiagnosed with other gynecological diseases. In this study, we examine three cases with extensive abdominal metastasis and adhesions, which are not initially associated clinically with HPV and cervical malignancies. All cases were misdiagnosed as nabothian cysts, endometrial adenocarcinoma or ovarian cancer, though finally diagnosed as MDA by postoperative pathology. Delay in diagnosis and treatment can result in irreversible outcomes. Misdiagnoses are analyzed and suggestions for improving early detection are discussed with a brief review of the literature., (© 2016 by the Association of Clinical Scientists, Inc.)

Melittin is well known to possess cytolytic activity with wide-spectrum lytic properties and its potential use as an agent to treat several types of cancer has been tested. Due to the non-specific toxicity, melittin can impair not only cancer cells but also normal tissue. Thus, tumor-targeted toxins may be helpful for developing novel anticancer therapeutics. The urokinase-type plasminogen activator (uPA) plays a central role in tissue remodelling events occurring in normal physiology and in pathophysiology, including cancer invasion and metastasis. Heartening findings showed that uPA receptor is predominantly expressed on many types of cancer. Therefore, the amino-terminal fragment (ATF) of uPA which was able to identify and bond with cancer cells was used as the cell-targeting domain to make up tumor-targeted toxin in this study. In the present study, pPICZαC-ATF-melittin eukaryotic expression vector was successfully constructed. After transformed into P. pastoris and induced by methanol, rATF-mellitin was detected by SDS-PAGE and western blot analysis. After induction with methanol, the expression level of rATF-mellitin was 312 mg/l in 80-l fermentor. rATF‑mellitin was purified to >95% purity using SP Sepharose ion exchange chromatography and source™ 30 RPC with 67.2% recovery. Cell proliferation assay showed that rATF-melittin inhibited growth of SKOV3 cells and had no cytotoxicity effect on normal cells. For the first time, we established a stable and effective rATF-mellitin P. pastoris expression system to obtain a high level of expression of secreted rATF-mellitin which was purified by a highly efficient purification procedure.