9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells

AbstractThere is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53

Visualization and unsupervised clustering of emphysema progression using t-SNE analysis of longitudinal CT images and SNPs

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death worldwide by 2030. A longitudinal study using CT scans of COPD is useful to assess the changes in structural abnormalities. In this study, we performed visualization and unsupervised clustering of emphysema progression using t-distributed stochastic neighbor embedding (t-SNE) analysis of longitudinal CT images, smoking history, and SNPs. The procedure of this analysis is as follows: (1) automatic segmentation of lung lobes using 3D U-Net, (2) quantitative image analysis of emphysema progression in lung lobes, and (3) visualization and unsupervised clustering of emphysema progression using t-SNE. Nine explanatory variables were used for the clustering: genotypes at two SNPs (rs13180 and rs3923564), smoking history (smoking years, number of cigarettes per day, pack-year), and LAV distribution (LAV size and density in upper lobes, LAV size, and density in lower lobes). The objective variable was emphysema progression which was defined as the annual change in low attenuation volume (LAV%/year) using linear regression. The nine-dimensional space was transformed to two-dimensional space by t-SNE, and divided into three clusters by Gaussian mixture model. This method was applied to 37 smokers with 68.2 pack-years and 97 past smokers with 51.1 pack-years. The results demonstrated that this method could be effective for quantitative assessment of emphysema progression by SNPs, smoking history, and imaging features

Association analysis of SNPs with CT image-based phenotype of emphysema progression in heavy smokers

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death worldwide by 2030. Smoking is a well-known risk factor in the development of COPD. Association between COPD genes and smoking have been studied. This paper presents an association analysis of single nucleotide polymorphisms (SNPs) with a CT image-based phenotype of emphysema progression in heavy smokers. The emphysema progression was quantitatively represented by the annual increment of low attenuation volume (LAV) on CT scans for five years. 10 candidate SNPs were selected from 316 SNPs in 125 papers of genetic studies of COPD and lung cancer. The genotypes were determined by real-time polymerase chain reaction (PCR) using deoxyribonucleic acid (DNA) extracted from saliva samples. The association analysis was performed by Fisher's exact test and logistic regression analysis. This method was applied to a dataset with 144 participants (71 smokers, 61 past smokers, and 12 non-smokers). The results showed that the genotypes of rs3923564 and rs13180 SNPs were candidate SNPs associated with the CT image based-emphysema progression

Automated Assessment of Aortic and Main Pulmonary Arterial Diameters using Model-Based Blood Vessel Segmentation for Predicting Chronic Thromboembolic Pulmonary Hypertension in Low-Dose CT Lung Screening

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of the pulmonary vasculature by residual organized thrombi. A morphological abnormality inside mediastinum of CTEPH patient is enlargement of pulmonary artery. This paper presents an automated assessment of aortic and main pulmonary arterial diameters for predicting CTEPH in low-dose CT lung screening. The distinctive feature of our method is to segment aorta and main pulmonary artery using both of prior probability and vascular direction which were estimated from mediastinal vascular region using principal curvatures of four-dimensional hyper surface. The method was applied to two datasets, 64 low-dose CT scans of lung cancer screening and 19 normal-dose CT scans of CTEPH patients through the training phase with 121 low-dose CT scans. This paper demonstrates effectiveness of our method for predicting CTEPH in low-dose CT screening

Segmentation of aorta and main pulmonary artery of non-contrast CT images using U-Net for chronic thromboembolic pulmonary hypertension : evaluation of robustness to contacts with blood vessels

Enlargement of the pulmonary artery is a morphological abnormality of pulmonary hypertension patients. Diameters of the aorta and main pulmonary artery (MPA) are useful for predicting the presence of pulmonary hypertension. A major problem in the automatic segmentation of the aorta and MPA from non-contrast CT images is the invisible boundary caused by contact with blood vessels. In this study, we applied U-Net to the segmentation of the aorta and MPA from non-contrast CT images for normal and chronic thromboembolic pulmonary hypertension (CTEPH) cases and evaluated the robustness to the contacts between blood vessels. Our approach of the segmentation consists of three steps: (1) detection of trachea branch point, (2) cropping region of interest centered to the trachea branch point, and (3) segmentation of the aorta and MPA using U-Net. The segmentation performances were compared in seven methods: 2D U-Net, 2D U-Net with pre-trained VGG-16 encoder, 2D U-Net with pre-trained VGG-19 encoder, 2D Attention U-Net, 3D U-Net, an ensemble method of them, and our conventional method. The aorta and MPA segmentation methods using these U-Net achieved higher performance than a conventional method. Although the contact boundaries of blood vessels caused lower performance compared with the non-contact boundaries, the mean boundary distances were below about one pixel

The association between farm-level antimicrobial usage and resistance of Staphylococcus spp., as the major genus isolated from aerosol samples, in Japanese piggeries

Bacteria are the dominant particulate matter in livestock houses and can threaten animal and public health. Antimicrobial resistance (AMR) is a crucial concern worldwide, and nationwide measures established based on the One Health approach are being implemented in many countries. This requires multidisciplinary perspectives and collaboration among the human, animal, and environmental sectors. However, information on the AMR risk in livestock house aerosol is limited, especially its association with antimicrobial usage (AMU). Therefore, this study was conducted to reveal the AMR profile of Staphylococcus, the major bacterial genus in the aerosol of the piggeries of Japanese farms, and the association between farm-level AMU and AMR. The investigation at 10 farrow-to-finish pig farms revealed that regardless of the sampling season and the piggery group, the resistance rate of isolated staphylococci for oxacillin, erythromycin, and lincomycin was more than 40% of the median and tended to be higher than that for other antimicrobials. The AMU adjusted by the defined daily dose (DDD-adjusted AMU) in the fattening piggery group was significantly higher than that in the sow piggery group (p < 0.05). Finally, for the fattening piggery group, the generalized linear mixed model revealed that the AMR rate for oxacillin, erythromycin, tetracycline, and chloramphenicol was positively associated with the corresponding class-based DDD-adjusted AMU of penicillins (odds ratio (OR) = 2.63, p = 0.03), macrolides (OR = 6.89, p = 0.0001), tetracyclines (OR = 2.48, p = 0.04), and amphenicols (OR = 3.22, p = 0.03), respectively. These significant positive associations observed in this study imply that the resistance rate for these antimicrobials may decrease by reducing the corresponding antimicrobials’ use. In addition, the resistance rates for erythromycin and chloramphenicol also displayed a positive association with the AMU of antimicrobial classes other than macrolides and amphenicols, respectively. The mechanism underlying these phenomena is unclear; therefore, further evaluation will be needed. As limited studies have reported staphylococci in piggery aerosol and its AMR with quantitative AMU, these results based on on-farm investigations are expected to aid in establishing countermeasures for AMR of aerosol bacteria in pig farms

Automated detection method of thoracic aorta calcification from non-contrast CT images using mediastinal anatomical label map

Progression of thoracic aortic calcification (TAC) has been shown to be associated with hard cardiovascular events including stroke and all-cause mortality as well as coronary events. In this study, we propose an automated detection method of TACs of non-contrast CT images using mediastinal anatomical label map. This method consists of two steps: (1) the construction of a mediastinal anatomical label map, and (2) the detection of TACs using the intensity and the mediastinal anatomical label map. The proposed method was applied to two non-contrast CT image datasets: 24 cases of chronic thromboembolic pulmonary hypertension (CTEPH) and 100 non-CTEPH cases of low-dose CT screening. The method was compared with two-dimensional U-Nets and the Swin UNETR. The results showed that the method achieved significantly higher F1 score of 0.937 than other methods for the non-CTEPH case dataset (p-value < 0.05, pairwise Wilcoxon signed rank test with Bonferroni correction)

Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study

Background The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. Methods We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). Results The average age was older in the Hp group than in the uninfected group (68.1 +/- 8.1 vs. 63.4 +/- 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). Conclusions The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection