α-Smooth muscle actin expression in cancerassociated fibroblasts in canine epithelial tumors

Tumor tissues contain not only cancer cells but also other cell types including, fibroblasts, immune cells, and endothelial cells, which interact with cancer cells. In human medicine, cancer-associated fibroblasts (CAFs) have been reported to promote tumor growth. CAFs are known to express α-smooth muscle actin (α-SMA), and this expression is correlated with poor prognosis in humans with cancer. However, the role of CAFs in canines and α-SMA expression in canine CAFs remains unknown. This study evaluated whether CAFs are present within the stroma of various types of canine epithelial tumors, for example, mammary gland tumors, squamous cell carcinoma, and anal sac adenocarcinoma, and assessed α-SMA expression in CAFs isolated from canine epithelial tumors. α-SMA analysis of tumor tissues revealed a cytoplasmic localization with variable levels of expression. α-SMA was detected in 60.9% (14/23) of epithelial tumor tissues and in 80% (8/10) of anal sac adenocarcinoma tissues. CAFs and normal fibroblasts (NFs) were isolated from tumor and skin tissues. The size of CAFs was variable, and most CAFs had large cell volume, in contrast to NFs. Most CAFs expressed α-SMA stress fibers and had higher α-SMA protein levels than NFs. Taken together, our findings provide evidence that canine CAFs express α-SMA in various canine epithelial tumors. Further studies are required to investigate the correlation between canine CAFs and clinical parameters and to elucidate the mechanisms underlying the effects of CAFs on cancer progression

Natural Language Generation for Advertising: A Survey

Natural language generation methods have emerged as effective tools to help advertisers increase the number of online advertisements they produce. This survey entails a review of the research trends on this topic over the past decade, from template-based to extractive and abstractive approaches using neural networks. Additionally, key challenges and directions revealed through the survey, including metric optimization, faithfulness, diversity, multimodality, and the development of benchmark datasets, are discussed

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Future Changes in Tropical and Extratropical Cyclones Affecting Hokkaido and Their Related Precipitation Based on Large-Ensemble Climate Simulations

This study investigates the impact of future climate warming on tropical cyclones (TC) and extratropical cy-clones (ETC) using the database for Policy Decision-Making for Future Climate Change (d4PDF) large ensemble simula-tions. Cyclone tracking was performed using the neighbor enclosed area tracking algorithm (NEAT), and TC and ETCs were identified over the western North Pacific Ocean (WNP). For cyclone frequency, it was revealed that, although a slight underestimation of the total number of TCs and ETCs in both the WNP and near Hokkaido, Japan, exists, the d4PDF re-produced the spatial distribution of both TC and ETC tracks well when compared with observations/reanalysis. The 4-K warming scenarios derived from six different sea surface temperature warming patterns showed robust decreases in TC fre-quency in the tropical WNP and a slight reduction in ETCs near Japan. Next, precipitation characteristics for TCs or ETCs in the vicinity of Hokkaido were examined using 5-km-mesh regional climate ensemble simulations. Four representative cyclone locations near Hokkaido are identified using K-means clustering and revealed distinct precipitation characteristics between clusters, with higher TC-associated precipitation than ETC-associated precipitation and the heaviest precipitation in the southern portion of the prefecture. The 4-K warming scenarios revealed increased precipitation for all cyclone place-ments for both TCs and ETCs. Last, average cyclone intensity, translation speed, and size were examined. It was shown that TCs in future climates are more intense, propagate more slowly, and are smaller in terms of enclosed vorticity area as they approach Hokkaido. For ETCs, mean intensity does not change much; they travel slightly faster, and become smaller

Simultaneous post-transcriptional gene silencing of two different chalcone synthase genes resulting in pure white flowers in the octoploid dahlia.

Garden dahlias (Dahlia variabilis) are autoallooctoploids with redundant genes producing wide color variations in flowers. There are no pure white dahlia cultivars, despite its long breeding history. However, the white areas of bicolor flower petals appear to be pure white. The objective of this experiment was to elucidate the mechanism by which the pure white color is expressed in the petals of some bicolor cultivars. A pigment analysis showed that no flavonoid derivatives were detected in the white areas of petals in a star-type cultivar 'Yuino' and the two seedling cultivars 'OriW1' and 'OriW2' borne from a red-white bicolor cultivar, 'Orihime', indicating that their white areas are pure white. Semi-quantitative RT-PCR showed that in the pure white areas, transcripts of two chalcone synthases (CHS), DvCHS1 and DvCHS2 which share 69% nucleotide similarity with each other, were barely detected. Premature mRNA of DvCHS1 and DvCHS2 were detected, indicating that these two CHS genes are silenced post-transcriptionally. RNA gel blot analysis revealed that small interfering RNAs (siRNAs) derived from CHSs were produced in these pure white areas. By high-throughput sequence analysis of small RNAs in the pure white areas with no mismatch acceptance, small RNAs were mapped to two alleles of DvCHS1 and two alleles of DvCHS2 expressed in 'Yuino' petals. Therefore, we concluded that simultaneous siRNA-mediated post-transcriptional gene silencing of redundant CHS genes results in the appearance of pure white color in dahlias

Climate Change Impacts on Heavy Snowfall in Sapporo Using 5-km Mesh Large Ensemble Simulations

Synoptic circulation patterns associated with heavy snowfall events in Sapporo are examined using large ensemble simulation with 60-km global climate experiments. For snowfall, a 5-km dynamically downscaled model from the 20-km regional simulation is utilized. To identify synoptic circulation patterns, self-organizing maps (SOMs) are applied, and their response to a warming climate is examined. The authors find that heavy snow events predominantly occur due to low pressure anomalies to the north/east of Hokkaido or over central Japan, and by high pressure anomalies over the Siberian continent. The 4 K warming climate shows robust decreases in heavy snowfall amounts associated with low pressure anomalies over central Japan and increases in heavy snowfall amounts under patterns with high pressure anomalies over Siberia. This is attributed to surface air temperature characteristics in future climates, as precipitation in the former with surface winds transporting warm, moist air from the south and east, develops predominantly above 0 degrees C in the +4 K climate, while the latter, often resulting in intense snow band events, continues to be dominated by temperatures near or below zero