Quantification of the tug-back by measuring the pulling force and micro computed tomographic evaluation

Objectives The aims of this study were to quantify tug-back by measuring the pulling force and investigate the correlation of clinical tug-back pulling force with in vitro gutta-percha (GP) cone adaptation score using micro-computed tomography (µCT). Materials and Methods Twenty-eight roots from human single-rooted teeth were divided into 2 groups. In the ProTaper Next (PTN) group, root canals were prepared with PTN, and in the ProFile (PF) group, root canals were prepared using PF (n = 14). The degree of tug-back was scored after selecting taper-matched GP cones. A novel method using a spring balance was designed to quantify the tug-back by measuring the pulling force. The correlation between tug-back scores, pulling force, and percentage of the gutta-percha occupied area (pGPOA) within apical 3 mm was investigated using µCT. The data were analyzed using Pearson's correlation analysis, one-way analysis of variance (ANOVA) and Tukey's test. Results Specimens with a strong tug-back had a mean pulling force of 1.24 N (range, 0.15–1.70 N). This study showed a positive correlation between tug-back score, pulling force, and pGPOA. However, there was no significant difference in these factors between the PTN and PF groups. Regardless of the groups, pGPOA and pulling force were significantly higher in the specimens with a higher tug-back score (p < 0.05). Conclusions The degree of subjective tug-back was a definitive determinant for master cone adaptation in the root canal. The use of the tug-back scoring system and pulling force allows the interpretation of subjective tug-back in a more objective and quantitative manner

Analysis of gene expression during odontogenic differentiation of cultured human dental pulp cells

Objectives We analyzed gene-expression profiles after 14 day odontogenic induction of human dental pulp cells (DPCs) using a DNA microarray and sought candidate genes possibly associated with mineralization. Materials and Methods Induced human dental pulp cells were obtained by culturing DPCs in odontogenic induction medium (OM) for 14 day. Cells exposed to normal culture medium were used as controls. Total RNA was extracted from cells and analyzed by microarray analysis and the key results were confirmed selectively by reverse-transcriptase polymerase chain reaction (RT-PCR). We also performed a gene set enrichment analysis (GSEA) of the microarray data. Results Six hundred and five genes among the 47,320 probes on the BeadChip differed by a factor of more than two-fold in the induced cells. Of these, 217 genes were upregulated, and 388 were down-regulated. GSEA revealed that in the induced cells, genes implicated in Apoptosis and Signaling by wingless MMTV integration (Wnt) were significantly upregulated. Conclusions Genes implicated in Apoptosis and Signaling by Wnt are highly connected to the differentiation of dental pulp cells into odontoblast

Differential diagnosis of cemento-osseous dysplasia and periapical cyst using texture analysis of CBCT

Abstract Background Radiolucencies found at the root apex in patients with cemento-osseous dysplasia (COD) may be mistaken for periapical cysts (PC) of endodontic origin. The purpose of this study was to examine the utility of quantitative texture analysis using cone-beam computed tomography (CBCT) to differentiate between COD and PC. Methods Patients who underwent CBCT at Wonkwang University Daejeon Dental Hospital between January 2019 and December 2022 and were diagnosed with COD and PC by clinical, radiologic, and, if necessary, histopathologic examination were included. Twenty-five patients each were retrospectively enrolled in the COD and PC group. All lesions observed on axial CBCT images were manually segmented using the open-access software MaZda version 4.6 to establish the regions of interest, which were then subjected to texture analysis. Among the 279 texture features obtained, 10 texture features with the highest Fisher coefficients were selected. Statistical analysis was performed using the Mann-Whitney U-test, Welch’s t-test, or Student’s t-test. Texture features that showed significant differences were subjected to receiver operating characteristics (ROC) curve analysis to evaluate the differential diagnostic ability of COD and PC. Results The COD group consisted of 22 men and 3 women, while the PC group consisted of 14 men and 11 women, showing a significant difference between the two groups in terms of sex (p=0.003). The 10 selected texture features belonged to the gray level co-occurrence matrix and included the sum of average, sum of entropy, entropy, and difference of entropy. All 10 selected texture features showed statistically significant differences (p<0.05) when comparing patients with COD (n=25) versus those with PC (n=25), osteolytic-stage COD (n=11) versus PC (n=25), and osteolytic-stage COD (n=11) versus cementoblastic-stage COD (n=14). ROC curve analysis to determine the ability to differentiate between COD and PC showed a high area under the curve ranging from 0.96 to 0.98. Conclusion Texture analysis of CBCT images has shown good diagnostic value in the differential diagnosis of COD and PC, which can help prevent unnecessary endodontic treatment, invasive biopsy, or surgical intervention associated with increased risk of infection

Artificial intelligence in diagnosing dens evaginatus on periapical radiography with limited data availability

Abstract This study aimed to develop an artificial intelligence (AI) model using deep learning techniques to diagnose dens evaginatus (DE) on periapical radiography (PA) and compare its performance with endodontist evaluations. In total, 402 PA images (138 DE and 264 normal cases) were used. A pre-trained ResNet model, which had the highest AUC of 0.878, was selected due to the small number of data. The PA images were handled in both the full (F model) and cropped (C model) models. There were no significant statistical differences between the C and F model in AI, while there were in endodontists (p = 0.753 and 0.04 in AUC, respectively). The AI model exhibited superior AUC in both the F and C models compared to endodontists. Cohen’s kappa demonstrated a substantial level of agreement for the AI model (0.774 in the F model and 0.684 in C) and fair agreement for specialists. The AI’s judgment was also based on the coronal pulp area on full PA, as shown by the class activation map. Therefore, these findings suggest that the AI model can improve diagnostic accuracy and support clinicians in diagnosing DE on PA, improving the long-term prognosis of the tooth

Circulating Exosomal miR-1290 for Diagnosis of Epithelial Ovarian Cancer

The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change &ge; 2, p &lt; 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC

HER2 Heterogeneity Affects Trastuzumab Responses and Survival in Patients With HER2-Positive Metastatic Breast Cancer

Objectives: Heterogeneity ofHER2 gene amplification is found in a subset of breast cancers. We investigated the impact ofHER2 heterogeneity on trastuzumab responses and clinical outcomes in 112 patients with HER2-positive metastatic breast cancer. Methods: Regional and genetic heterogeneity of HER2 gene amplification was determined in three different areas of each tumor by immunohistochemistry and silver in situ hybridization. We also assessed the overall levels ofHER2 amplification and the proportion of tumor cells with a HER2/CEP17 ratio of more than 2.2 or strong and complete membranous (3+) expression of HER2 protein. Results: HER2 regional and genetic heterogeneity based on the HER2/CEP17 ratio was confirmed in 8.7% and 2.7% of cases, respectively. Poor response to trastuzumab was associated with overall low-level or equivocal amplification, HER2 regional heterogeneity by the HER2/CEP17 ratio, the HER2/CEP17 ratio of more than 2.2 in less than 80% of tumor cells, and HER2 immunohistochemical expression of 3+ in less than 75% of tumor cells. In survival analyses, low-level or equivocal HER2 amplification, HER2 regional heterogeneity based on the HER2/CEP17 ratio, and the HER2/CEP17 ratio of more than 2.2 in less than 80% of tumor cells were associated with shorter time to progression and lower overall survival in univariate and multivariate analyses. Conclusions: These results suggest that accurate assessment of HER2 status, including HER2 heterogeneity, is important in predicting trastuzumab responses and outcomes in patients with HER2-positive metastatic breast cancer

Expression of breast cancer stem cell markers as predictors of prognosis and response to trastuzumab in HER2-positive breast cancer

Background: Breast cancer stem cells (BCSCs) have been suggested to have clinical implications for cancer therapeutics because of their proposed role in chemoresistance. The aim of this study was to investigate the impact of BCSC marker expression on clinical outcome and trastuzumab response in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: We analysed the expression of BCSC markers, CD44+/CD24- and aldehyde dehydrogenase 1 (ALDH1), and clinical outcomes in three sets of breast cancer cases: Set 1, 242 HER2-positive primary breast cancers treated by various modalities; Set 2, 447 HER2-positive primary breast cancers treated with surgery and chemotherapy plus adjuvant trastuzumab; Set 3, 112 metastatic HER2-positive breast cancers treated with trastuzumab. Results: Expression of CD44+/CD24- and ALDH1 was detected in 30.7% and 10.0%, respectively, of the Set 1 cases, and was associated with hormone receptor negativity. In survival analyses, expression of CD44+/CD24-, but not ALDH1, was found to be an independent prognostic factor for poor disease-free and overall survival in whole patients and also in the subgroup not receiving adjuvant trastuzumab. In Set 2 cases treated with adjuvant trastuzumab, CD44+/CD24- expression was an independent prognostic factor for poor disease-free survival, but not for overall survival; expression of ALDH1 had no impact on disease-free or overall survival. In metastatic disease treated with trastuzumab (Set 3 cases), CD44+/CD24- and ALDH1 expression had no effect on trastuzumab response or survival. Conclusions: These results suggest that the CD44+/CD24- phenotype can be used as a prognostic factor for clinical outcome and a predictive factor of trastuzumab response in patients with HER2-positive primary breast cancer