Clinical and laboratory predictors for plaque erosion in patients with acute coronary syndromes

Background-—Plaque erosion is responsible for 25% to 40% of patients with acute coronary syndromes (ACS). Recent studies suggest that anti-thrombotic therapy without stenting may be an option for this subset of patients. Currently, however, an invasive procedure is required to make a diagnosis of plaque erosion. The aim of this study was to identify clinical or laboratory predictors of plaque erosion in patients with ACS to enable a diagnosis of erosion without additional invasive procedures. Methods and Results-—Patients with ACS who underwent optical coherence tomography imaging were selected from 11 institutions in 6 countries. The patients were classified into plaque rupture, plaque erosion, or calcified plaque, and predictors were identified using multivariable logistic modeling. Among 1241 patients with ACS, 477 (38.4%) patients were found to have plaque erosion. Plaque erosion was more frequent in non–ST-segment elevation-ACS than in ST-segment–elevation myocardial infarction (47.9% versus 29.8%, P=0.0002). Multivariable logistic regression models showed 5 independent parameters associated with plaque erosion: age 15.0 g/dL, and normal renal function. When all 5 parameters are present in a patient with non–ST-segment elevation-ACS, the probability of plaque erosion increased to 73.1%. Conclusions-—Clinical and laboratory parameters associatedwith plaque erosion are explored in this retrospective registry study. These parametersmay be useful to identify the subset ofACS patients with plaque erosion and guide themto conservativemanagement without invasive procedures. The results of this exploratory analysis need to be confirmed in large scale prospective clinical studiesDr. Jang has received an educational grant from Abbott Vascular and Medicure. Dr. Adriaenssens has received grants and consulting fees from Abbott Vascula

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

An attempt to reduce the effects of black material from the spectral reflectance of meteorites or asteroids

An attempt to reduce the effects of black materials from the spectral reflectances of meteorites or asteroids was made by using the Kubelka-Munk function with minor modifications. Our reduction method has for its object to make clear the spectral contrast which is suppressed by the effects of the black materials. For this purpose, spectral reflectances (0.25-2.5μm) were measured on samples of the Yamato-75258 meteorite (LL6 chondrite) which contain various amounts of black materials (carbon black or magnetite), and their changes with the effects of black materials were examined. Only a few weight percents of the black materials lower the reflectivity and weaken the absorption band strength. On the basis of these reflectance measurements, we tried to construct the spectral reflectance curve by reducing the effects of the black material from that of the Murchison meteorite and to compare the constructed curve with the spectral reflectance of Ceres. The results imply that the material which contains less carbon than the Murchison meteorite, is a better candidate for the surface material of Ceres. Our method will be a useful one for making the spectral contrast clear, although some problems remain to be solved

Spectral reflectace (0.25-2.5μm) of olivine and pyroxene from an ordinary chondrite

We measured the diffuse reflectance spectra (0.25-2.5μm) of olivine and pyroxene from the ALH-769 ordinary chondrite (L6). We examined the systematic variations of the spectral reflectances of olivine-pyroxene mixtures. We also measured the spectral reflectances for olivine and pyroxene from the olivine sand in Hanauma Bay, Hawaii for comparison. The absolute calibration of the relationship between pyroxene chemistry and absorption band position determined by ADAMS (J. Geophys. Res., 79,4829,1974) is not accurate. The spectral feature of the pyroxene around 1.25μm is sensitive to the existence of the small amount of olivine. This observation does not, however, hold true of the results for the Hawaii clinopyroxene-olivine mixtures. The apparent peak near 0.6μm of the olivine is depressed by the existence of the Hawaii clinopyroxene. The absorption band depth around 2μm is sensitive to the amount of pyroxene. With quantities of pyroxene less than 30%, the wavelength position of the olivine absorption band near 1.05μm shifts drastically. This shift seems to be available for detecting the existence of the small amount of pyroxene in conjunction with the spectral feature around 2μm. It is hoped to examine the systematic variations of the spectral reflectances of two-component mixtures by using the coexisting pair of the minerals which are separated from meteorites (or rocks)

Spectral reflectance (0.25-2.5μm) of powdered olivines and meteorites, and their bearing on surface materials of asteroids

Spectral reflectance changes with the particle size, the thickness of the sample, the species of the background materials, and effects of carbon black were examined on powdered samples of sized olivines and some meteorites in the 0.25-2.5μm wavelength region. The effects of the pulverization on the spectral changes are dependent mainly on very fine-grained materials (e.g.<46μm) in the sample. These spectral changes of meteorites are as follows : 1) The albedo increases; 2) The spectra \u27redden\u27 in the range of about 1.6-2.5μm; 3) The absorption band strengths in the region of about 0.5-1.5μm become weak and broad; 4) The reflectance near 0.4μm is raised; 5) The sharp drop-off less than 0.35μm is found. The thickness of the sample has little effect on the reflectance spectra when the sample is more than 0.2mm thick, while a very thin sample (<0.1mm) reduces spectral contrast. When the background material has low reflectivity such as some meteorites, the spectral reflectance depends almost entirely on a very thin layer of the materials on the surface. A very small amount (1-2wt%) of carbon black lowers the reflectance and depresses the details of the absorption features. Taking into consideration these results and the brecciation processes by impacts on the asteroid surface, the finer-grained C1 or C2 meteorite seems to be a better candidate for the surface material of Ceres (or Pallas) than a coarse-grained sample of this meteorite