Optimization by Smoothed Bandpass Calibration in Radio Spectroscopy

We have developed the Smoothed Bandpass Calibration (SBC) method and the best suitable scan pattern to optimize radio spectroscopic observations. Adequate spectral smoothing is applied to the spectrum toward OFF-source blank sky adjacent to a target source direction for the purpose of bandpass correction. Because the smoothing process reduces noise, the integration time for OFF-source scans can be reduced keeping the signal-to-noise ratio. Since the smoothing is not applied to ON-source scans, the spectral resolution for line features is kept. An optimal smoothing window is determined by bandpass flatness evaluated by Spectral Allan Variance (SAV). An efficient scan pattern is designed to the OFF-source scans within the bandpass stability timescale estimated by Time-based Allan Variance (TAV). We have tested the SBC using the digital spectrometer, VESPA, on the VERA Iriki station. For the targeted noise level of 5e-4 as a ratio to the system noise, the optimal smoothing window was 32 - 60 ch in the whole bandwidth of 1024 ch, and the optimal scan pattern was designed as a sequence of 70-s ON + 10-s OFF scan pairs. The noise level with the SBC was reduced by a factor of 1.74 compared with the conventional method. The total telescope time to achieve the goal with the SBC was 400 s, which was 1/3 of 1200 s required by the conventional way. Improvement in telescope time efficiency with the SBC was calculated as 3x, 2x and 1.3x for single-beam, dual-beam, and on-the-fly (OTF) scans, respectively. The SBC works to optimize scan patterns for observations from now, and also works to improve signal-to-noise ratios of archival data if ON- and OFF-source spectra are individually recorded, though the efficiency depends on the spectral stability of the receiving system.Comment: 12 pages, 11 figures, to appear in the Publications of Astronomical Society of Japan, Vol.64, No.

Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma

We sought to identify a secreted biomarker for β-catenin activation commonly seen in hepatocellular carcinoma (HCC). By examination of our previously published genearray of hepatocyte-specific β-catenin knockout (KO) livers, we identified secreted factors whose expression may be β-catenin-dependent. We verified expression and secretion of the leading factor in HCC cells transfected with mutated (Hep3BS33Y)-β- catenin. Serum levels of biomarker were next investigated in a mouse model of HCC with β-catenin gene (Ctnnb1) mutations and eventually in HCC patients. Leukocyte cell-derived chemotaxin-2 (LECT2) expression was decreased in KO livers. Hep3BS33Y expressed and secreted more LECT2 in media as compared to Hep3BWT. Mice developing HCC with Ctnnb1 mutations showed significantly higher serum LECT2 levels. However patients with CTNNB1 mutations showed LECT2 levels of 54.28±22.32 ng/mL (Mean ± SD; n = 8) that were insignificantly different from patients with non-neoplastic chronic liver disease (32.8±21.1 ng/mL; n = 15) or healthy volunteers (33.2±7.2 ng/mL; n = 11). Intriguingly, patients without β-catenin mutations showed significantly higher serum LECT2 levels (54.26 ± 22.25 ng/mL; n = 46). While β-catenin activation was evident in a subset of non-mutant β-catenin HCC group with high LECT2 expression, serum LECT2 was unequivocally similar between β-catenin-active and -normal group. Further analysis showed that LECT2 levels greater than 50 ng/ml diagnosed HCC in patients irrespective of β-catenin mutations with specificity of 96.1% and positive predictive value of 97.0%. Thus, LECT2 is regulated by β-catenin in HCC in both mice and men, but serum LECT2 reflects β-catenin activity only in mice. Serum LECT2 could be a potential biomarker of HCC in patients. © 2014 Okabe et al

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

Management of future liver remnant: strategies to promote hepatic hypertrophy

The resectability of hepatocellular carcinoma (HCC) has been assessed based on the liver functional test, the liver volume of the future liver remnant (FLR), and, more recently, the functional liver volume of FLR. Liver volume is estimated via multi-detector computed tomography and three-dimensional image visualization technologies, and functional liver volume is investigated via 99mTc-galactosyl human serum albumin scintigraphy, 99mTc-mebrofenin hepatobiliary scintigraphy, and gadoxetic acid-enhanced magnetic resonance imaging. Several special techniques have been developed to promote FLR hypertrophy, thus allowing for safe hepatectomy. As an interventional technique, portal vein embolization (PVE) is essential, and, along with transarterial chemoembolization or hepatic vein embolization, this is beneficial in promoting a much larger FLR. Dual embolization is recommended for patients with very small FLR or with PVE failure. Radioembolization by Yttrium-90 microspheres (i.e., radiation lobectomy) can help in achieving FLR hypertrophy and has an anticancer effect on HCC. Transarterial chemoembolization on PVE has a similar anticancer effect. Surgical procedures, such as two-stage hepatectomy as well as associated liver partition and portal vein ligation for staged hepatectomy, are somewhat invasive. Therefore, they should be applied as a salvage procedure for patients with HCC who had inadequate response to the interventional approach. However, the best approach should be selected mainly based on the functional volume of FLR and the patients’ condition; in addition, the resources of each facility should be considered

Evaluation of the mass forming intrahepatic cholangiocarcinoma with viral hepatitis

Aim: The correlation between the mass-forming type of intrahepatic cholangiocarcinoma (ICC) and the infection of the hepatitis B virus and hepatitis C virus are poorly understood. In this study, the clinical features of 34 patients with the mass-forming type ICC were reviewed to evaluate prognostic determinants. Methodology: Between January 1997, and December 2007, 34 patients underwent surgical resection for the mass-forming type of ICC in Kumamoto University Hospital. The significance of 14 clinicopathological factors consisting of age, gender, CA19-9 levels, CEA levels, size, intrahepatic metastases, portal vein invasion, bile duct invasion,histological differentiation, lymph node involvement, type B or C hepatitis, lymph node dissection, Sirius Red score of the tumor and platelet count in peripheral blood were analyzed, with regard to prognostic aspect. Results: Univariate analysis showed that significant risk factors for poor survival included age ≧65 years, CEA levels ≧1.6ng/ml and pathological lymph node involvement. Multivariate analysis revealed that age, CEA levels and lymph node involvement were independent and significant poor prognostic factors.Conclusions: It was concluded that age, CEA levels and lymph node involvement were significantly poor prognostic factors. However, the infection with type B or C hepatitis was not a prognostic factor of the mass forming type ICC

Varied application of intercostal trans-diaphragmatic ports for laparoscopic hepatectomy.

BackgroundThe ribcage and diaphragm are mechanical barriers for laparoscopic access during hepatectomy. Here, we introduce the varied application of intercostal trans-diaphragmatic ports during laparoscopic hepatectomy, and describe the management of intercostal ports with key technical points.MethodsFrom January 2013 to December 2017, 180 patients underwent laparoscopic hepatectomy. In 32 of these patients (17.8%), intercostal ports (31 right and one left) were applied, and we analyzed the feasibility and safety of intercostal ports during laparoscopic hepatectomy.ResultsThe main tumor location was segment VII and VIII (78%). The major type of laparoscopic hepatectomy was partial hepatectomy (91%). In the majority of cases (66%) the number and size of intercostal trocars was a single 5-mm port. The median operative time and blood loss were 232 min and 50 mL, respectively. A chest drain was placed via the hole of the intercostal port on the chest wall in two cases (6.3%). The median duration of the post-operative hospital stay was 6 days. There was no conversion, and a pure laparoscopic hepatectomy was achieved in all cases. There was no mortality. As for complications due to the application of intercostal ports, an asymptomatic pneumothorax was detected in only one case, and it was cured by conservative treatment.ConclusionsThe ribcage and diaphragm could be overcome as barriers to laparoscopic access by the placement of intercostal ports with minimal access during laparoscopic hepatectomy. The use of an intercostal port and proper management allows for a feasible approach and safe resection during laparoscopic hepatectomy

Inducible factors for cancer-associated fibroblasts in liver cancer versus myofibroblasts in inflammatory liver disease

The importance of cancer-associated fibroblasts (CAFs) in liver cancer, cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC), has been appreciated in the past 5 years. We focused on how they get activated in the tumor microenvironment in this review. Not only hepatic stellate cells (HSCs) but also portal fibroblasts (PFs) have been appreciated to be key players in liver fibrogenesis, and their different roles have just started to be recognized. Since the role of cholangiocyte in biliary fibrogenic disease might have some similarities to that of CC, we focused on the role of cholangiocytes activating stromal fibroblasts, which would presumably be helpful for better understanding the mechanism of tumor-CAFs interaction. In addition, the activation of CAFs should be different from that of CAFs in HCC, which we consider to be potentially similar to MFs in hepatocyte injury-dependent liver fibrogesis. Herein, we describe the activation of CAFs in CC in comparison to MFs seen in other liver diseases such as 1) MFs in liver fibrosis caused by hepatocyte injury such as alcoholic hepatitis, viral hepatitis, and nonalcoholic steatosis, 2) MFs in liver fibrosis caused by cholestatic disease, and 3) CAFs in hepatocellular carcinoma (HCC). This review on the activation of fibroblasts either in liver cancer or in chronic liver disease would contribute to CAF-targeted therapy in liver cancer

Epithelial-mesenchymal transition in gastroenterological cancer

Epithelial-mesenchymal transition (EMT) was first reported as an essential process in embryonic cells and later showed that cancer cells, regardless of the context, exhibit a similar phenomenonthat is crucial for tumor progression. Epithelial cells lose their adhesive characteristic capacity which is necessary for their functions but gain a mesenchymal phenotype. This change from epithelial to mesenchymal phenotype of cancer cells makes it difficult tounderstand the mechanism underlying cancer biology and tumor progression. A number of transcription factors involved in tumor cell EMT and miRNA-regulated EMT have been reported. This review discussed recent findings and new players in EMT in gastrointestinal cancers. Since the molecular mechanisms of tumor progression are sometimes context dependent, the recent findings of EMT have been reviewed in the context-dependent manner