Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2′-modified-4′-thionucleosides

AbstractGene suppression via U1 small nuclear RNA interference (U1i) is considered to be one of the most attractive approaches, and takes the place of general antisense, RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a ‘target domain’ and a ‘U1 domain’, we prepared adaptor ONs using 2′-modified-4′-thionucleosides developed by our group, and evaluated their U1i activity. As a result, the desired gene suppression via U1i was observed in ONs prepared as a combination of 2′-fluoro-4′-thionucleoside and 2′-fluoronucleoside units as well as only 2′-fluoronucleoside units, while those prepared as combination of 2′-OMe nucleoside/2′-OMe-4′-thionucleoside and 2′-fluoronucleoside units did not show significant activity. Measurement of Tm values indicated that a higher hybridization ability of adaptor ONs with complementary RNA is one of the important factors to show potent U1i activity

Three-dimensional iodine mapping quantified by dual-energy CT for predicting programmed death-ligand 1 expression in invasive pulmonary adenocarcinoma

Yamagata K., Yanagawa M., Hata A., et al. Three-dimensional iodine mapping quantified by dual-energy CT for predicting programmed death-ligand 1 expression in invasive pulmonary adenocarcinoma. Scientific Reports 14, 18310 (2024); https://doi.org/10.1038/s41598-024-69470-9.We examined the association between texture features using three-dimensional (3D) io-dine density histogram on delayed phase of dual-energy CT (DECT) and expression of programmed death-ligand 1 (PD-L1) using immunostaining methods in non-small cell lung cancer. Consecutive 37 patients were scanned by DECT. Unenhanced and enhanced (3 min delay) images were obtained. 3D texture analysis was performed for each nodule to obtain 7 features (max, min, median, mean, standard deviation, skewness, and kurtosis) from iodine density mapping and extracellular volume (ECV). A pathologist evaluated a tumor proportion score (TPS, %) using PD-L1 immunostaining: PD-L1 high (TPS ≥ 50%) and low or negative expression (TPS < 50%). Associations between PD-L1 expression and each 8 parameter were evaluated using logistic regression analysis. The multivariate logistic regression analysis revealed that skewness and ECV were independent indicators associated with high PD-L1 expression (skewness: odds ratio [OR] 7.1 [95% CI 1.1, 45.6], p = 0.039; ECV: OR 6.6 [95% CI 1.1, 38.4], p = 0.037). In the receiver-operating characteristic analysis, the area under the curve of the combination of skewness and ECV was 0.83 (95% CI 0.67, 0.93) with sensitivity of 64% and specificity of 96%. Skewness from 3D iodine density histogram and ECV on dual energy CT were significant factors for predicting PD-L1 expression

Inter-rater reliability of streetscape audits using online observations: Microscale Audit of Pedestrian Streetscapes (MAPS) global in Japan

This study aimed to evaluate the inter-rater reliability of streetscape audits among online observations using the Microscale Audit of Pedestrian Streetscapes-Global version (MAPS-Global) in Japan. MAPS-Global observations were conducted on routes with distances ranging from 400 to 725 m from a residence toward a non-residential destination. Google Street View audits were independently conducted by two trained raters on each route. A tiered scoring system was applied to summarize the items at multiple levels of aggregation. Positive and negative valence scores were created based on the expected association with physical activity. Inter-rater reliability analyses were performed using kappa statistics or intraclass correlation coefficients (ICC). Of the 32 older adults participating in an intervention study in the community-wide physical activity promotion project in Fujisawa City, 19 addresses were used, excluding those with nearby addresses. Results demonstrated “excellent” agreement for most of the summary scores analyzed (kappa or ICC values of 0.75 or higher [80.4 %]), while 6.5 % of items exhibited “good” agreement (ICC = 0.60–0.74). By contrast, only 13.0 % of the scales had ICC values lower than 0.60 (“fair” or “poor” reliability). The results illustrated high reliability for the grand summary scores and composite subscale measures. However, caution should be exercised when interpreting subscale scores for less frequently observed negative attributes and aesthetic/social characteristics. The results presented in this study support the application of online observations using MAPS-Global in urban areas of Japan, which could be implemented to inform decisions related not only to physical activity but also to traffic safety

Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2'-modified-4'-thionucleosides

Gene suppression via U1 small nuclear RNA interference (U1i) is considered to be one of the most attractive approaches, and takes the place of general antisense, RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a ‘target domain’ and a ‘U1 domain’, we prepared adaptor ONs using 2'-modified-4'-thionucleosides developed by our group, and evaluated their U1i activity. As a result, the desired gene suppression via U1i was observed in ONs prepared as a combination of 2'-fluoro-4'-thionucleoside and 2'-fluoronucleoside units as well as only 2'-fluoronucleoside units, while those prepared as combination of 2'-OMe nucleoside/2'-OMe-4'-thionucleoside and 2'-fluoronucleoside units did not show significant activity. Measurement of Tm values indicated that a higher hybridization ability of adaptor ONs with complementary RNA is one of the important factors to show potent U1i activity

Association between interstitial lung abnormality and mortality in patients with esophageal cancer

The version of record of this article, first published in Japanese Journal of Radiology, is available online at Publisher’s website: https://doi.org/10.1007/s11604-024-01563-x.Purpose: To investigate the relationship between interstitial lung abnormalities (ILAs) and mortality in patients with esophageal cancer and the cause of mortality. Materials and methods: This retrospective study investigated patients with esophageal cancer from January 2011 to December 2015. ILAs were visually scored on baseline CT using a 3-point scale (0 = non-ILA, 1 = indeterminate for ILA, and 2 = ILA). ILAs were classified into subcategories of non-subpleural, subpleural non-fibrotic, and subpleural fibrotic. Five-year overall survival (OS) was compared between patients with and without ILAs using the multivariable Cox proportional hazards model. Subgroup analyses were performed based on cancer stage and ILA subcategories. The prevalences of treatment complications and death due to esophageal cancer and pneumonia/respiratory failure were analyzed using Fisher’s exact test. Results: A total of 478 patients with esophageal cancer (age, 66.8 years ± 8.6 [standard deviation]; 64 women) were evaluated in this study. Among them, 267 patients showed no ILAs, 125 patients were indeterminate for ILAs, and 86 patients showed ILAs. ILAs were a significant factor for shorter OS (hazard ratio [HR] = 1.68, 95% confidence interval [CI] 1.10–2.55, P = 0.016) in the multivariable Cox proportional hazards model adjusting for age, sex, smoking history, clinical stage, and histology. On subgroup analysis using patients with clinical stage IVB, the presence of ILAs was a significant factor (HR = 3.78, 95% CI 1.67–8.54, P = 0.001). Subpleural fibrotic ILAs were significantly associated with shorter OS (HR = 2.22, 95% CI 1.25–3.93, P = 0.006). There was no significant difference in treatment complications. Patients with ILAs showed a higher prevalence of death due to pneumonia/respiratory failure than those without ILAs (non-ILA, 2/95 [2%]; ILA, 5/39 [13%]; P = 0.022). The prevalence of death due to esophageal cancer was similar in patients with and without ILA (non-ILA, 82/95 [86%]; ILA 32/39 [82%]; P = 0.596). Conclusion: ILAs were significantly associated with shorter survival in patients with esophageal cancer