Diagnostic Performance of Ultrasound Computer-Aided Diagnosis Software Compared with That of Radiologists with Different Levels of Expertise for Thyroid Malignancy: A Multicenter Prospective Study.

The aim of the work described here was to evaluate the diagnostic performance of ultrasound thyroid computer-aided diagnosis (CAD) software. This multicenter prospective study included 494 patients (565 thyroid nodules) who underwent surgery or biopsy after ultrasonography at four hospitals from January 2019 to September 2019. The diagnostic performance metrics of different readers were calculated and compared with the pathologic results. The sensitivity of CAD was outstanding and was equivalent to that of a senior radiologist (90.51% vs. 88.47%, p > 0.05). The area under the curve of CAD was equivalent to that of a junior radiologist (0.748 vs. 0.739, p > 0.05). However, the specificity was only 49.63%, which was lower than those of the three radiologists (75.56%, 85.93% and 90.37% for the junior, intermediate and senior radiologists, respectively). The diagnostic performance of the junior radiologist was significantly improved with the aid of CAD (junior + CAD). The sensitivity and area under the curve of junior + CAD were improved from 72.20% to 89.93% and from 0.739 to 0.816, respectively (both p values <0.05), and the positive predictive value, negative predictive value and κ coefficient improved from 76.3% to 78.6%, 82.0% to 86.8% and 0.394 to 0.511, respectively. Though specificity slightly decreased from 75.56% to 73.33%, the difference was not statistically significant (p > 0.05). In general, the clinical application value of CAD is promising, and its instrumental value for junior radiologists is significant.

Methylome and transcriptome analyses reveal insights into the epigenetic basis for the good survival of hypomethylated ER-positive breast cancer subtype.

BACKGROUND: Breast cancer (BRCA) is a heterogeneous disease, characterized by different histopathological and clinical features and responses to various therapeutic measures. Despite the research progress of DNA methylation in classification and diagnosis of BRCA and the close relationship between DNA methylation and hormone receptor status, especially estrogen receptor (ER), the epigenetic mechanisms in various BRCA subtypes and the biomarkers associated with diagnostic characteristics of patients under specific hormone receptor status remain elusive. RESULTS: In this study, we collected and analyzed methylation data from 785 invasive BRCA and 98 normal breast tissue samples from The Cancer Genome Atlas (TCGA) database. Consensus classification analysis revealed that ER-positive BRCA samples were constitutive of two distinct methylation subgroups; with the hypomethylated subgroup showing good survival probability. This finding was further supported by another cohort of ER-positive BRCA containing 30 subjects. Additionally, we identified 977 hypomethylated CpG loci showing significant associations with good survival probability in ER-positive BRCA. Genes with these loci were enriched in cancer-related pathways (e.g., Wnt signaling pathway). Among them, the upregulated 47 genes were also in line with good survival probability of ER-positive BRCA, while they showed significantly negative correlations between their expression and methylation level of certain hypomethylated loci. Functional assay in numerous literatures provided further evidences supporting that some of the loci have close links with the modulation of tumor-suppressive mechanisms via regulation gene transcription (e.g., SFRP1 and WIF1). CONCLUSIONS: Our study identified a hypomethylated ER-positive BRCA subtype. Notably, this subgroup presented the best survival probability compared with the hypermethylated ER-positive and hypomethylated ER-negative BRCA subtypes. Specifically, we found that certain upregulated genes (e.g., SFRP1 and WIF1) have great potential to suppress the progression of ER-positive BRCA, concurrently exist negative correlations between their expression and methylation of corresponding hypomethylated CpG loci. Therefore, our study indicates that different epigenetic mechanisms likely exist in ER-positive BRCA and provides novel clinical biomarkers specific to ER-positive BRCA diagnosis and therapy.

Transcriptome responses to elevated CO2 level and Wolbachia-infection stress in Hylyphantes graminicola (Araneae: Linyphiidae).

Hylyphantes graminicola is a resident spider species found in maize and cotton fields and is an important biological control agent of various pests. Previous studies have demonstrated that stress from elevated CO2 and Wolbachia infection can strongly affect spider species. Thus, based on CO2 levels (400 ppm, current atmospheric CO2 concentration and 800 ppm, high CO2 concentration) and Wolbachia status (Wolbachia-infected, W+ and Wolbachia-uninfected, W- ), we divided H. graminicola individuals into four treatment groups: W- 400 ppm, W- 800 ppm, W+ 400 ppm, and W+ 800 ppm. To investigate the effects of elevated CO2 levels (W- 400 vs W- 800), Wolbachia infection (W- 400 vs W+ 400), and the interactions between these two factors (W- 400 vs W+ 800), high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and identify stress-related differentially expressed genes (DEGs). De novo assembly of complementary DNA sequences generated 86 688 unigenes, 23 938 of which were annotated in public databases. A total of 84, 21, and 157 DEGs were found among W- 400 vs W- 800, W- 400 vs W+ 400, and W- 400 vs W+ 800, respectively. Functional enrichment analysis revealed that metabolic processes, signaling, and catalytic activity were significantly affected by elevated CO2 levels and Wolbachia infection. Our findings suggest that the impact of elevated CO2 levels and Wolbachia infection on the H. graminicola transcriptome was, to a large extent, on genes involved in metabolic processes. This study is the first description of transcriptome changes in response to elevated CO2 levels and Wolbachia infection in spiders.

Relationship between survivin expression and recurrence, and prognosis in hepatocellular carcinoma.

AIM: To study the expression of the inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC), and its correlation with clinicopathological factors, cell proliferation, recurrence and prognosis after hepatectomy. METHODS: Immunohistochemical staining of survivin and Ki-67 was performed by the standard streptavidin-peroxidase technique on paraffin sections of 55 cases of HCC. RESULTS: The positive rate of survivin in HCC was 52.7% (29/55). Significant correlation was found between survivin expression with portal vein thrombi and intrahepatic matastasistic nodes (P < 0.05). The recurrent rate in survivin-positive HCC was significantly higher than that in survivin-negative HCC after hepatectomy, the 1- and 3-year survival rate in patients with survivin-positive tumors was significantly lower than that in patients with survivin-negative tumors (58.62 and 10.34% vs 76.92 and 30.77%, P < 0.05, log-rank test). The proliferation index (Ki-67) in survivin-positive HCC (33.83% +/- 18.90%) was significantly higher than that in survivin-negative HCC (19.60% +/- 19.35%) (P < 0.05). CONCLUSION: Survivin may play an important role in progression of HCC by promoting cell proliferation, and may be positively correlated with high risk of disease recurrence and poor prognosis in HCC. Its expression may serve as a prognostic factor for patients with HCC after hepatectomy.