Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan

金沢大学医薬保健研究域医学系Backgrounds: Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. Methods: A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using 99mTc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 ± 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. Results: Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 ± 17% and 55 ± 18%, p < 0.0001 for non-gated; 64 ± 16% and 51 ± 17% for ES percent uptake, p < 0.0001). The area under the curve of receiver operating characteristics curve for non-gated percent uptake, ES percent uptake, end-diastolic percent uptake and visual perfusion defect score was 0.70, 0.71, 0.61, and 0.56, respectively. Sensitivity and specificity of percent uptake were 68% and 64% for non-gated map and 80% and 52% for ES percent uptake map. An optimal threshold for predicting segmental improvement was 63% for non-gated and 52% for ES percent uptake values. Conclusion: Segmental 99mTc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study. © 2008 Springer-Verlag

A Human-Computer Duet System for Music Performance

Virtual musicians have become a remarkable phenomenon in the contemporary multimedia arts. However, most of the virtual musicians nowadays have not been endowed with abilities to create their own behaviors, or to perform music with human musicians. In this paper, we firstly create a virtual violinist, who can collaborate with a human pianist to perform chamber music automatically without any intervention. The system incorporates the techniques from various fields, including real-time music tracking, pose estimation, and body movement generation. In our system, the virtual musician's behavior is generated based on the given music audio alone, and such a system results in a low-cost, efficient and scalable way to produce human and virtual musicians' co-performance. The proposed system has been validated in public concerts. Objective quality assessment approaches and possible ways to systematically improve the system are also discussed

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

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

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

New Bioinformatics program for the extraction of biological intelligence

When we want to evaluate the radiation risks realistically, it is importantto study the low-dose-rate irradiation as well as the high-dose-rateirradiation. Since the radiation effects by low-dose-rate irradiation weredifficult to detect comparing to the high-dose-rate irradiation, we have notbeen able to understand the mechanism of the specific biological reaction ofthe low-dose-rate irradiation. To understand the low-dose-rate specificbiological response, C57BL/6J mice were continuously irradiated withgamma-rays for 485 days at the dose rates in the range of 32 - 13,000nGy/min whose levels were as low as about 15 times to 65,000 times over thenatural background. Gene expression profiles in the kidneys from irradiatedand unirradiated mice were analyzed and differentially expressed genes wereidentified after quality control of the data. In order to get moreinformation of the specific pathway, we used the Boomerang program whichadopted the algorithm (1) of SHAFT (2) and showed the possibility of theparticipation of p53 transcription factor. The results suggested that it islikely to be able to obtain more information by using the specializingmethod of dealing with the inclusive data even if it might be a very smallresponse as it was not detectable.CBI学会2008年大

Gene expression profiles in mouse liver after long-term low-dose-rate irradiation with gamma rays.

Changes in gene expression profiles in mouse liver induced by long-term low-dose-rate gamma irradiation were examined by microarray analysis. Three groups of male C57BL/6J mice were exposed to whole-body radiation at dose rates of 17&#8211;20 mGy/day, 0.86&#8211;1.0 mGy/day or 0.042&#8211;0.050 mGy/day for 401&#8211;485 days with cumulative doses of approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively. The gene expression levels in the livers of six animals from each exposure group were compared individually with that of pooled sham-irradiated animals. Some genes revealed a large variation in expression levels among individuals within each group, and the number of genes showing common changes in individuals from each group was limited: 20 and 11 genes showed more than 1.5-fold modulation with 17&#8211;20 mGy/day and 0.86&#8211;1.0 mGy/day, respectively. Three genes showed more than 1.5-fold modulation even at the lowest dose-rate of 0.04&#8211;0.05 mGy/day. Most of these genes were down-regulated. RT-PCR analysis confirmed the expression profiles of the majority of these genes. The results indicate that a few genes are modulated in response to very low-dose-rate irradiation. The functional analysis suggests that these genes may influence many processes, including obesity and tumorigenesis