Fully automated deep learning model for detecting proximity of mandibular third molar root to inferior alveolar canal using panoramic radiographs.

OBJECTIVE: This study endeavored to develop a novel, fully automated deep-learning model to determine the topographic relationship between mandibular third molar (MM3) roots and the inferior alveolar canal (IAC) using panoramic radiographs (PRs). STUDY DESIGN: A total of 1570 eligible subjects with MM3s who had paired PR and cone beam computed tomography (CBCT) from January 2019 to December 2020 were retrospectively collected and randomly grouped into training (80%), validation (10%), and testing (10%) cohorts. The spatial relationship of MM3/IAC was assessed by CBCT and set as the ground truth. MM3-IACnet, a modified deep learning network based on YOLOv5 (You only look once), was trained to detect MM3/IAC proximity using PR. Its diagnostic performance was further compared with dentists, AlexNet, GoogleNet, VGG-16, ResNet-50, and YOLOv5 in another independent cohort with 100 high-risk MM3 defined as root overlapping with IAC on PR. RESULTS: The MM3-IACnet performed best in predicting the MM3/IAC proximity, as evidenced by the highest accuracy (0.885), precision (0.899), area under the curve value (0.95), and minimal time-spending compared with other models. Moreover, our MM3-IACnet outperformed other models in MM3/IAC risk prediction in high-risk cases. CONCLUSION: MM3-IACnet model can assist clinicians in MM3s risk assessment and treatment planning by detecting MM3/IAC topographic relationship using PR.

Split AAV8 Mediated ABCA4 Expression for Gene Therapy of Mouse Stargardt Disease (STGD1).

Adeno-associated virus (AAV)-based gene therapy has been shown to be safe and effective in numerous animal models and clinical trials for various ophthalmic diseases. Stargardt disease (STGD1; MIM #248200) is the most common autosomal recessive macular dystrophy disease, and the most common form is caused by mutations in the ABCA4 gene, a gene with 6.8 kb coding sequence. Split intein approaches increase the capacity of dual AAV gene therapy, but at the cost of reduced protein expression, which may be insufficient to achieve a therapeutic effect. In this study, we designed various dual split intein ABCA4 vectors and showed that the efficiency of expression of full-length ABCA4 protein is dependent on combinations of types and split sites of the intein system. The most efficient vectors were identified through in vitro screening, and a novel dual AAV8-ABCA4 vector was constructed and subsequently proven to express full-length ABCA4 protein at a high level, reducing bisretinoid formation and correcting the visual function of ABCA4-knockout mice. Furthermore, we evaluated therapeutic effects of different dosages by subretinal injection in mice model. Both therapeutic effects and safety were guaranteed under the treatment of 1.00 × 109 GC/eye. These results support the optimized dual AAV8-ABCA4 approach in future clinical translation for treatment of Stargardt disease.

Characterizations of three-dimensional root morphology and topological location of mandibular third molars by cone-beam computed tomography.

PURPOSE: This study aimed to delineate three-dimensional (3D) root morphology and topological locations of mandibular third molars (MTMs) by cone-beam computed tomography (CBCT) in a Chinese adult dental population. METHODS: Adult patients with MTMs were retrospectively screened based on CBCT images at our institution between January 2018 and December 2019. Root morphology and spatial locations of these teeth were defined based on CBCT 3D images. Potential associations with epidemiological and clinical/radiological parameters were analyzed using Chi-square or Fisher exact test. Two-tailed P values less than 0.05 were considered statistically significant. RESULTS: A total number of 2680 eligible patients (male/female:0.74; 35 ± 10 years old) with 4180 MTMs were enrolled. The majority of MTMs had 2 roots 3064 (73.30%), followed by 800 (19.14%) 1 root, 302 (7.22%) 3 roots, and 14 (0.33%) 4 roots. More than half of one-rooted MTMs were convergent, followed by club-shaped and C-shaped. Among MTMs with 2 roots, 2860 (93.34%) were M-D (mesio-distal) types. Most MTMs with 3 roots were M-2D (one root in mesial, two roots in distal) types, followed by 2M-D (two roots in mesial, one root in distal) types, and B-2L (one root in buccal, two roots in lingual) types. The presence of root configurations was significantly associated with the angulation, depth, and width classification in two-rooted MTMs (P < 0.05). CONCLUSIONS: Although the morphology and spatial locations of MTMs vary greatly, our results from a large dental population reconfirm that most MTMs have two roots with mesial-distal type of spatial distribution.

Interleukin-13 peptide kinoid vaccination attenuates allergic inflammation in a mouse model of asthma.

Asthma is an atopic disorder with increasing frequency and severity in developed nations. Interleukin-13 (IL-13) is one of the most critical mediators of asthma pathology. In the present study, we developed a vaccine comprised of a keyhole limpet hemocyanin-mIL-13 heterocomplex immunogen to persistently neutralize excessive endogenous IL-13. Our results showed that the IL-13 peptide kinoid vaccine could induce sustained and high titer of IL-13-specific IgG when using aluminum hydroxide as an adjuvant, and could suppress the accumulation of eosinophils as well as IL-13 levels in bronchoalveolar lavage fluid (BALF). In addition, total IgE and ovalbumin (OVA)-specific IgE in serum were significantly inhibited. This study also showed that vaccination could prevent airway inflammation and epithelial cell proliferation with goblet cell hyperplasia in a mouse model of acute asthma. In summary, our findings suggest that the IL-13 peptide kinoid can serve as an innovative and effective vaccine against asthma.

Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment.

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Our previous studies have demonstrated that hepatitis B virus X protein (HBx) was able to inhibit the growth of HCC cells via inducing apoptosis and inhibiting tumor angiogenesis. Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. In this study, to further investigate the regulatory effect of IL-12 on HBx-mediated intervention of hepatoma microenvironment especially on intervention of neovessels and immune microenvironment, we constructed the recombinant adenovirus expressing HBx and mouse IL-12 named Ad-HBx-mIL-12. HBx-mIL-12 could effectively suppress tumor growth and induce apoptosis in vivo. Moreover, treatment with Ad-HBx-mIL-12 not only induced a massive accumulation of immune cells (CD8(+) T leukocytes, macrophages and dendritic cells) in tumors in situ, also apparently reduced the number of angiogenic blood vessels within tumor tissues. These results suggest that HBx-mIL-12 can not only induce cell cycle arrest and apoptosis in HCC cells, but also effectively shift the tumor microenvironment from pro-oncogenic to antitumor through recruitment of immune cells and inhibiting stromal cell growth, such as vascular endothelial cells.