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

Long-term storage under pressure in deep sea improved the microbiological safety and physical properties of whale meat

This study aimed to clarify the effects of deep-sea pressure storage on the quality of whale meat, especially microbiological safety and physical properties, to examine the effectiveness of deep-sea storage for long-term aging of whale meat. Microbiological safety, physical properties, color and appearance, water content, water activity, and pH of whale meat were examined after storage in the deep sea at depths of 2200–6000 m (22–60 MPa) for 4 months. During storage under high pressure at a depth of >4000 m (40 MPa), the growth of aerobic bacteria was inhibited in whale meat. The toughness of whale meat stored in deep sea at a depth of >4000 m became significantly tender than that before deep-sea storage. Long-term storage of whale meat under high pressure and low-temperature conditions in the deep sea at a depth of >4000 m was clarified to improve the microbiological safety and tenderness of whale meat

Postoperative Bleeding Risk after Gastric Endoscopic Submucosal Dissection in Patients Receiving a P2Y12 Receptor Antagonist

Background/Aims: The safety of gastric endoscopic submucosal dissection (ESD) in users of a P2Y12 receptor antagonist (P2Y12RA) under current guidelines has not been verified. Methods: Patients treated by gastric ESD at Okayama University Hospital between January 2013 and December 2020 were registered. The postoperative bleeding rates of patients (group A) who did not receive any antithrombotic drugs; patients (group B) receiving aspirin or cilostazol monotherapy; and P2Y12RA users (group C) those on including monotherapy or dual antiplatelet therapy were compared. The risk factors for post-ESD bleeding were examined in a multivariate analysis of patient background, tumor factors, and antithrombotic drug management. Results: Ultimately, 1,036 lesions (847 patients) were enrolled. The bleeding rates of group B and C were significantly higher than that of group A (p=0.012 and p Conclusions: P2Y12RA use is a risk factor for postoperative bleeding in patients who undergo ESD even if receiving drug management according to guidelines. Dual antiplatelet therapy carries a higher risk of bleeding than monotherapy

Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS

¹³C NMR Spectroscopic Studies of Intra- and Intermolecular Interactions of Amino Acid Derivatives and Peptide Derivatives in Solutions

13C NMR spectroscopic investigations were conducted for various amino acid derivatives and peptides. It was observed that 13C NMR chemical shifts of the carbonyl carbons are correlated with the solvent polarities, but the extent depends on the structures. The size of the functional groups and inter- and intra-molecular hydrogen bonding appear to be the major contributors for this tendency

Congenital basal meningoceles with different outcomes: a case series

Abstract Background Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis. Case presentation We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring. Conclusions These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications

Methods of Cleaning Taps to Prevent Hospital-Associated Infections: An Environmental Survey-Based Study

In hospitals, outbreaks can occur due to pathogens accumulating in the areas around the wards’ washbasins. Carbapenem-resistant Enterobacterales (CRE) was detected in an environmental survey in the high-care unit of a university hospital in Isehara, Japan, and effective cleaning methods were investigated. This study investigated methods of cleaning taps using commonly used detergents and disinfectants, and it assessed their effectiveness in removing hard scale and pathogens, including CRE. The taps were cleaned using various methods and cleaning agents, including environmentally neutral detergent, citric acid, baking soda, cleanser, 80% ethanol, 0.1% sodium hypochlorite, and a phosphoric acid-based environmental detergent (Space Shot). The cleaning effect was assessed based on the agent’s effectiveness at removing hard scale from taps. Biofilms and scale were identified on taps, and several bacterial species were cultured. Only phosphoric acid-based detergent was effective at removing hard scale. After cleaning with the phosphoric acid-based detergent, the bacterial count decreased, and no CRE or other pathogens were detected. These results provide a reference for other facilities considering introducing this cleaning method

Evaluation of the basic assay performance of the GeneSoc® rapid PCR testing system for detection of severe acute respiratory syndrome coronavirus 2.

In the ongoing coronavirus disease 2019 (COVID-19) pandemic, PCR has been widely used for screening patients displaying relevant symptoms. The rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enables prompt diagnosis and the implementation of proper precautionary and isolation measures for the patient. In the present study, we aimed to evaluate the basic assay performance of an innovative PCR system, GeneSoC® (Kyorin Pharmaceutical Co. Ltd., Tokyo, Japan). A total of 1,445 clinical samples were submitted to the clinical laboratory, including confirmed or suspected cases of COVID-19, from February 13 to August 31. Specimen types included nasopharyngeal swabs. The sampling was performed several times for each patient every 2-7 days. Using this system, sequences specific for SARS-CoV-2 RNA could be detected in a sample within 10-15 min using the microfluidic thermal cycling technology. Analytical sensitivity studies showed that GeneSoC® could detect the target sequence of the viral envelope and RNA-dependent RNA-polymerase (RdRp) genes at 5 and 10 copies/μL, respectively. The precision of the GeneSoC® measurements using clinical isolates of the virus at a concentration of 103 copies/μL was favorable for both the genes; within-run repeatability and between-run reproducibility coefficient of variation values were less than 3% and 2%, respectively; and the reproducibility of inter-detection units was less than 5%. Method comparison by LightCycler® 480 showed the positive and negative agreement to be 100% [(174/174) and (1271/1271), respectively]. GeneSoC® proved to be a rapid and reliable detection system for the prompt diagnosis of symptomatic COVID-19 patients and could help reduce the spread of infections and facilitate more rapid treatment of infected patients