Adaptable cascaded registration for personalized maxilla completion and cleft defect volume estimation.

BACKGROUND: Cone-beam computed tomography (CBCT) images provide high-resolution insights into the underlying craniofacial anomaly in patients with cleft lip and palate (CLP), requiring non-negligible annotation costs to measure the cleft defect for the guidance of the clinical secondary alveolar bone graft procedures. Considering the cumbersome volumetric image acquisition, there is a lack of paired CLP CBCTs and normal CBCTs for learning-based anatomical structure restoration models. Nowadays, the registration-based method relieves the annotation burden, though one-shot registration and the regular mask are limited to handling fine-grained shape variations and harmony between restored bony tissues and the defected maxilla. PURPOSE: This study aimed to design and evaluate a novel method for deformable partial registration of the CLP CBCTs and normal CBCTs, enabling personalized maxilla completion and cleft defect volume prediction from CLP CBCTs. METHODS: We proposed an adaptable deep registration framework for personalized maxilla completion and cleft defect volume prediction from CLP CBCTs. The key ingredient was a cascaded partial registration to exploit the maxillary morphology prior and attribute transfer. Cascaded registration with coarse-to-fine registration fields handled morphological variations of cleft defects and fine-grained maxillary restoration. We designed an adaptable cleft defect mask and volumetric Boolean operators for reliable voxel filling of the defected maxilla. A total of 36 clinically obtained CLP CBCTs were used to train and validate the proposed model, among which 22 CLP CBCTs were used to generate a training dataset with 440 synthetic CBCTs by B-spline deformation-based data augmentation and the remaining for testing. The proposed model was evaluated on maxilla completion and cleft defect volume prediction from clinically obtained unilateral and bilateral CLP CBCTs. RESULTS: Extensive experiments demonstrated the effectiveness of the adaptable cleft defect mask and the cascaded partial registration on maxilla completion and cleft defect volume prediction. The proposed method achieved state-of-the-art performances with the Dice similarity coefficient of 0.90 ± $\pm$ 0.02 on the restored maxilla and 0.84 ± $\pm$ 0.04 on the estimated cleft defect, respectively. The average Hausdorff distance between the estimated cleft defect and the manually annotated ground truth was 0.30 ± $\pm$ 0.08 mm. The relative volume error of the cleft defect was 0.09 ± $0.09\pm$ 0.08. The proposed model allowed for the prediction of cleft defect maps that were in line with the ground truth in the challenging unilateral and bilateral CLP CBCTs. CONCLUSIONS: The results suggest that the proposed adaptable deep registration model enables patient-specific maxilla completion and automatic annotation of cleft defects, relieving tedious voxel-wise annotation and image acquisition burdens.

Nanopore sequencing of infectious fluid is a promising supplement for gold-standard culture in real-world clinical scenario.

Introduction: Infectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples. Methods: In this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform-based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios. Results: Combined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. Discussion: Rapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

New insights about endometriosis-associated ovarian cancer: pathogenesis, risk factors, prediction and diagnosis and treatment.

Previous studies have shown that the risk of malignant transformation of endometriosis in premenopausal women is approximately 1%, significantly impacting the overall well-being and quality of life of affected women. Presently, the diagnostic gold standard for endometriosis-associated ovarian cancer (EAOC) continues to be invasive laparoscopy followed by histological examination. However, the application of this technique is limited due to its high cost, highlighting the importance of identifying a non-invasive diagnostic approach. Therefore, there is a critical need to explore non-invasive diagnostic methods to improve diagnostic precision and optimize clinical outcomes for patients. This review presents a comprehensive survey of the current progress in comprehending the pathogenesis of malignant transformation in endometriosis. Furthermore, it examines the most recent research discoveries concerning the diagnosis of EAOC and emphasizes potential targets for therapeutic intervention. The ultimate objective is to improve prevention, early detection, precise diagnosis, and treatment approaches, thereby optimizing the clinical outcomes for patients.

Effect of HPV Oncoprotein on Carbohydrate and Lipid Metabolism in Tumor Cells.

High-risk HPV infection accounts for 99.7% of cervical cancer, over 90% of anal cancer, 50% of head and neck cancers, 40% of vulvar cancer, and some cases of vaginal and penile cancer, contributing to approximately 5% of cancers worldwide. The development of cancer is a complex, multi-step process characterized by dysregulation of signaling pathways and alterations in metabolic pathways. Extensive research has demonstrated that metabolic reprogramming plays a key role in the progression of various cancers, such as cervical, head and neck, bladder, and prostate cancers, providing the material and energy foundation for rapid proliferation and migration of cancer cells. Metabolic reprogramming of tumor cells allows for the rapid generation of ATP, aiding in meeting the high energy demands of HPV-related cancer cell proliferation. The interaction between Human Papillomavirus (HPV) and its associated cancers has become a recent focus of investigation. The impact of HPV on cellular metabolism has emerged as an emerging research topic. A significant body of research has shown that HPV influences relevant metabolic signaling pathways, leading to cellular metabolic alterations. Exploring the underlying mechanisms may facilitate the discovery of biomarkers for diagnosis and treatment of HPV-associated diseases. In this review, we introduced the molecular structure of HPV and its replication process, discussed the diseases associated with HPV infection, described the energy metabolism of normal cells, highlighted the metabolic features of tumor cells, and provided an overview of recent advances in potential therapeutic targets that act on cellular metabolism. We discussed the potential mechanisms underlying these changes. This article aims to elucidate the role of Human Papillomavirus (HPV) in reshaping cellular metabolism and the application of metabolic changes in the research of related diseases. Targeting cancer metabolism may serve as an effective strategy to support traditional cancer treatments, as metabolic reprogramming is crucial for malignant transformation in cancer.

Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral.

BACKGROUND: Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. MATERIAL AND METHODS: Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (µCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1ß, IL-4). RESULTS: Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1ß levels, and less active MMP-9 in cell culture. CONCLUSION: This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

Hepatitis E virus and Klebsiella pneumoniae co-infection detected by metagenomics next-generation sequencing in a patient with central nervous system and bloodstream Infection: a case report.

BACKGROUND: Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide with major prevalence in the developing countries and can cause extrahepatic disease including the nervous system. Central nervous system infections caused by HEV are rare and caused by HEV together with other bacteria are even rarer. CASE PRESENTATION: A 68-year-old man was admitted to the hospital due to a headache lasting for 6 days and a fever for 3 days. Lab tests showed significantly raised indicators of inflammation, cloudy cerebrospinal fluid, and liver dysfunction. Hepatitis E virus and Klebsiella pneumoniae were identified in the blood and cerebrospinal fluid using metagenomic next-generation sequencing. The patient received meropenem injection to treat K. pneumoniae infection, isoglycoside magnesium oxalate injection and polyene phosphatidylcholine injection for liver protection. After ten days of treatment, the patient improved and was discharged from the hospital. CONCLUSION: Metagenomic next-generation sequencing, which can detect various types of microorganisms, is powerful for identifying complicated infections.

Alveolar bone morphology in patients with palatally-displaced maxillary lateral incisors before and after orthodontic treatment: A cone-beam computed tomography study.

INTRODUCTION: Palatal displacement of maxillary anterior teeth is common in clinical practice. Previous studies have reported that the labial bone around palatally-displaced incisors is thinner than that around normally-placed teeth. Therefore, it is necessary to elucidate alveolar bone changes after alignment to guide orthodontic treatment. In this study, we investigated the alveolar bone changes around palatally-displaced maxillary lateral incisors before and after treatment, and the effects of extraction and age using cone-beam computed tomography. METHODS: In this retrospective study, 55 patients with unilateral palatally-displaced maxillary lateral incisors were included. Three-dimensional alveolar bone changes were measured at three levels (25%, 50% and 75% of the root length) using cone-beam computed tomography. Group comparisons were made between displaced and control teeth, extraction and non-extraction groups, and adult and minor groups. RESULTS: After orthodontic treatment, labiopalatal and palatal alveolar bone widths decreased at all measured levels. Labial alveolar bone width increased significantly at P25, but decreased at P75. Concavity decreased, while tooth-axis angle, tooth length, B-CEJ and P-CEJ increased. Changes in LB and LP at P75, B-CEJ and P-CEJ were statistically significant. After treatment, the tooth-axis angle on the PD side increased by 9.46°. The change in tooth-axis angle on the PD side was significantly smaller, and LB and LP decreased more at P75, in the extraction group. CONCLUSIONS: Compared to the control teeth, alveolar bone thickness and height for the displaced teeth decreased more significantly after treatment. Tooth extraction and age also influenced alveolar bone changes.

Vertical changes in the hard tissues after space closure by miniscrew sliding mechanics: a three-dimensional modality analysis.

OBJECTIVES: This study aimed to investigate vertical changes in the maxillary central incisor and the maxillary first molar, along with alterations in the mandibular plane angle during space closure using miniscrew sliding mechanics. METHODS: Twenty adult patients treated at Peking University Hospital of Stomatology between 2008 and 2013 were included. Digital dental models and craniofacial cone-beam computed tomography (CBCT) scans were obtained at the start of treatment (T0) and immediately after space closure (T1). Stable miniscrews were used for superimposing maxillary digital dental models (T0 and T1), and vertical changes in the maxillary first molar and the maxillary central incisor were measured. Three-dimensional changes in the mandibular plane were assessed through CBCT superimposition. RESULTS: The maxillary central incisor exhibited an average extrusion of 2.56 ± 0.18 mm, while the maxillary first molar showed an average intrusion of 1.25 ± 1.11 mm with a distal movement of 0.97 ± 0.99 mm. Additionally, the mandibular plane angle decreased by an average of 0.83 ± 1.65°. All three indices exhibited statistically significant differences. CONCLUSION: During space closure using the miniscrew sliding technique, significant changes occurred in both the sagittal and vertical dimensions of the upper dentition. This included extrusion of the maxillary central incisors, intrusion of the maxillary first molars, and a slight counterclockwise rotation of the mandibular plane.

The recent advancements of ferroptosis in the diagnosis, treatment and prognosis of ovarian cancer.

Ovarian cancer affects the female reproductive system and is the primary cause of cancer related mortality globally. The imprecise and non-specific nature of ovarian cancer symptoms often results in patients being diagnosed at an advanced stage, with metastatic lesions extending beyond the ovary. This presents a significant clinical challenge and imposes a substantial economic burden on both patients and society. Despite advancements in surgery, chemotherapy, and immunotherapy, the prognosis for most patients with ovarian cancer remains unsatisfactory. Therefore, the development of novel treatment strategies is imperative. Ferroptosis, a distinct form of regulated cell death, characterized by iron-dependent lipid peroxidation, differs from autophagy, apoptosis, and necrosis, and may hold promise as a novel cell death. Numerous studies have demonstrated the involvement of ferroptosis in various conventional signaling pathways and biological processes. Recent investigations have revealed the significant contribution of ferroptosis in the initiation, progression, and metastasis of diverse malignant tumors, including ovarian cancer. Moreover, ferroptosis exhibits a synergistic effect with chemotherapy, radiotherapy, and immunotherapy in restraining the proliferation of ovarian cancer cells. The aforementioned implies that ferroptosis holds considerable importance in the management of ovarian cancer and has the potential to serve as a novel therapeutic target. The present review provides a comprehensive overview of the salient features of ferroptosis, encompassing its underlying mechanisms and functional role in ovarian cancer, along with the associated signaling pathways and genes. Furthermore, the review highlights the prospective utility of ferroptosis in the treatment of ovarian cancer.

Pyogenic liver abscess caused by extended-spectrum ß-lactamase-producing hypervirulent Klebsiella pneumoniae diagnosed by third-generation sequencing: a case report and literature review.

We report a case of a woman with diabetes mellitus and choledocholithiasis who had a low fever with chills and severe weakness for 7 days. The patient's abdominal tenderness was positive. Computed tomography and magnetic resonance imaging showed a giant abscess in the liver. The production of extended-spectrum ß-lactamases by hypervirulent Klebsiella pneumoniae was found in the purulent fluid of the liver by nanopore-based metagenomic third-generation sequencing combined with an antibiotic susceptibility test. The patient recovered after intravenous antibiotic therapy and percutaneous drainage. Patients with a history of diabetes mellitus and choledocholithiasis should be aware of the possibility of pyogenic liver abscesses caused by hypervirulent Klebsiella pneumoniae. To rapidly control the development of this disease, nanopore-based metagenomic third-generation sequencing plays an important role not only in rapidly identifying pathogens, but also in guiding the use of antibiotics.

Natural reference structures for three-dimensional maxillary regional superimposition in growing patients.

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.

A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization.

To assess resolving-like activity by a novel chemically-modified curcumin (CMC2.24) in a "two-hit" model of diabetes-associated periodontitis. Macrophages from rats were cultured in the presence/absence of either Lipopolysaccharide (LPS, 1st hit); or advanced-glycation-end products (AGE, 2nd hit); or both combined. CMC2.24 was added as treatment. The conditioned media were analyzed for MMP-9, cytokines (IL-1ß, IL-6, TNF-α), resolvins (RvD1, RvE1, lipoxin A4), and soluble receptor for AGE (sRAGE). The phenotypes of M1/M2 macrophage were analyzed by flow cytometry. Both LPS/AGE-alone, and two-combined, dramatically increased the secretion of MMP-9 by macrophages. CMC2.24 "normalized" the elevated levels of MMP-9 under all conditions. Moreover, CMC2.24 significantly reduced the secretion of IL-1ß and IL-6 with a fewer effects on TNF-α. Importantly, CMC2.24 increased RvD1 and sRAGE secretion by macrophages exposed to LPS/AGE; and both treatment groups exhibited increased M2 relative to M1 populations. Furthermore, scatter-diagram showed the macrophages gradually shifted from M1 towards M2 with CMC2.24-treated, whereas LPS/AGE-alone groups remained unchanged. CMC2.24 "normalized" cytokines and MMP-9, but also enhanced RvD1 and sRAGE in macrophages. Crucially, CMC2.24 appears to be a potent inhibitor of the pro-inflammatory M1 phenotype; and a promotor of the pro-resolving M2 phenotype, thus acting like a crucial "switch" to reduce inflammation.

FAT4 overexpression promotes antitumor immunity by regulating the ß-catenin/STT3/PD-L1 axis in cervical cancer.

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/ß-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 ß-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 ß-catenin/STT3/PD-L1 axis. RESULTS: FAT4 is downregulated in cervical cancer tissues and cell lines. We determined that FAT4 binds to ß-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of ß-catenin by the degradation complexes (AXIN1, APC, GSK3ß, 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 ß-catenin-dependent manner, thereby increasing cytotoxic T lymphocyte (CTL) activity in immunoreactive mouse models. CONCLUSIONS: These findings address the basis of Wnt/ß-catenin pathway activation in cervical cancer and provide combination immunotherapy options for targeting the FAT4/ß-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, GSK3ß, CK1, APC) to the receptor. Subsequently, stable ß-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 ß-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of ß-catenin by the degradation complexes (AXIN1, APC, GSK3ß, CK1); (ii) FAT4 inhibits PD-L1 and STT3A transcription in a ß-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.

Bi-Graph Reasoning for Masticatory Muscle Segmentation From Cone-Beam Computed Tomography.

Automated segmentation of masticatory muscles is a challenging task considering ambiguous soft tissue attachments and image artifacts of low-radiation cone-beam computed tomography (CBCT) images. In this paper, we propose a bi-graph reasoning model (BGR) for the simultaneous detection and segmentation of multi-category masticatory muscles from CBCTs. The BGR exploits the local and long-range interdependencies of regions of interest and category-specific prior knowledge of masticatory muscles by reasoning on the category graph and the region graph. The category graph of the learnable muscle prior knowledge handles high-level dependencies of muscle categories, enhancing the feature representation with noise-agnostic category knowledge. The region graph models both local and global dependencies of the candidate muscle regions of interest. The proposed BGR accommodates the high-level dependencies and enhances the region features in the presence of entangled soft tissue and image artifacts. We evaluated the proposed approach by segmenting masticatory muscles on clinically acquired CBCTs. Extensive experimental results show that the BGR effectively segments masticatory muscles with state-of-the-art accuracy.

Advances in molecular mechanism of HPV16 E5 oncoprotein carcinogenesis.

For a considerable duration, cervical cancer has posed a significant risk to the well-being and survival of women. The emergence and progression of cervical cancer have garnered extensive attention, with prolonged chronic infection of HPV serving as a crucial etiological factor. Consequently, investigating the molecular mechanism underlying HPV-induced cervical cancer has become a prominent research area. The HPV molecule is composed of a long control region (LCR), an early coding region and a late coding region.The early coding region encompasses E1, E2, E4, E5, E6, E7, while the late coding region comprises L1 and L2 ORF.The investigation into the molecular structure and function of HPV has garnered significant attention, with the aim of elucidating the carcinogenic mechanism of HPV and identifying potential targets for the treatment of cervical cancer. Research has demonstrated that the HPV gene and its encoded protein play a crucial role in the invasion and malignant transformation of host cells. Consequently, understanding the function of HPV oncoprotein is of paramount importance in comprehending the pathogenesis of cervical cancer. E6 and E7, the primary HPV oncogenic proteins, have been the subject of extensive study. Moreover, a number of contemporary investigations have demonstrated the significant involvement of HPV16 E5 oncoprotein in the malignant conversion of healthy cells through its regulation of cell proliferation, differentiation, and apoptosis via diverse pathways, albeit the precise molecular mechanism remains unclear. This manuscript aims to provide a comprehensive account of the molecular structure and life cycle of HPV.The HPV E5 oncoprotein mechanism modulates cellular processes such as proliferation, differentiation, apoptosis, and energy metabolism through its interaction with cell growth factor receptors and other cellular proteins. This mechanism is crucial for the survival, adhesion, migration, and invasion of tumor cells in the early stages of carcinogenesis. Recent studies have identified the HPV E5 oncoprotein as a promising therapeutic target for early-stage cervical cancer, thus offering a novel approach for treatment.

Early and 1-year postsurgical stability and its factors in patients with complicated skeletal Class â ¢ malocclusion treated by conventional and surgery-first approach: A prospective cohort study.

INTRODUCTION: This study aimed to compare postsurgical stability between conventional (CSA) and surgery-first (SFA) approaches and investigate its prognostic factors in patients with a skeletal Class Ⅲ extraction. METHODS: Twenty and 19 patients treated with LeFort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) with premolar extraction were enrolled in SFA and CSA groups, respectively. Serial cone-beam computed tomography images obtained before surgery, immediately after surgery (T1), 3 months after surgery, and 12 months after surgery were used for 3-dimensional quantitative analysis. The condyle was segmented for analyzing volumetric changes. Repeated measures analysis of variance, independent t test, and chi-square test were used to compare time-course and intergroup differences. Pearson and Kendall correlation and multivariate linear regression analyses were used to explore prognostic factors affecting skeletal stability. RESULTS: In both CSA and SFA, postsurgical relapse mainly occurred in the mandible sagittal and vertical dimensions and during the first 3 months after surgery. Stability in SFA was significantly less than that in CSA. Intraoperatively, inferolateral condylar displacement with proximal segment inwards, clockwise rotation, and return movements after surgery were observed regardless of the treatment approach. The condylar volume remained stable over time. Multivariate regression analysis showed that posterior vertical dimension (VD) at T1 (-1.63 mm), surgical amount of mandibular setback (-10.33 mm), surgical condylar downwards displacement (-1.28 mm), and anterior overjet at T1 (6.43 mm) were the most important predictors of early mandibular relapse (r2 = 0.593). CONCLUSIONS: The risk of early relapse could be reduced by controlling the anterior, middle, and posterior constraints provided by the prediction model.

CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy.

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

Accuracy of integration of dental cast and cephalograms compared with cone-beam computed tomography: a comparative study.

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.

Quantification and visualization of the tooth extraction effects on face with spatially dense geometric morphometrics.

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.