Formulae Based on Biomathematics to Estimate the Standard Value of Fetal Growth of Japanese

We devised biomathematics-based formulae to estimate the standard values of fetal growth of Japanese after 22 weeks' gestation. The growth rates of bi-parietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal body weight (EFBW) at the time of gestation were assumed to be proportional to the product of the value at the time and the rest value of an unknown maximum value, respectively. The EFBW was also assumed to follow a multiple logistic function of BPD, AC and FL to fit the standard values of Japanese fetuses published by the Japan Society of Ultrasonics in Medicine. The Mann-Whitney test was used for statistical analysis. The values as a function of gestational day, t, were as follows: BPD(t)=99.6/(1+exp (2.725−0.01837＊t)) (mm); AC(t)=39.7/(1+exp (2.454−0.01379＊t)) (cm); FL(t)=79.6/(1+exp (2.851−0.01710＊t)) (mm); EFBW(t)=8045.1/(1+exp (6.028−0.06582＊BPD(t)−0.1469＊AC(t)+ 0.07377＊FL(t))) (g). EFBW as a function of BPD, AC and FL was as follows: EFBW=8045.1/(1+exp (4.747+ 0.02584＊BPD+0.1010＊AC−0.1416＊FL)) (g). When the BPD, AC and FL were at −2 standard deviation (SD), −1SD, mean and + 2SD, the EFBW values calculated by the formula were statistically closer to the standard values than conventional formulas with p-values of 4.871×10−7, 4.228×10−7, 9.777×10−7 and 0.028, respectively. The formulae based on biomathematics might be useful to estimate the fetal growth standard values

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

Difference Is Not Indifference: Cicero and Modern Japan

As Warsaw celebrated the 30th anniversary of its liberation from the totalitarian regime by reinvoking the Ciceronian tradition of republican ideal government, Japan found itself in a celebratory mood for the succession of imperial dynasty. Emperor Hirohito (d.1989)’s son was to be replaced by his grandson and thus Japan’s modern invention of an old tradition was to be consolidated. If European modernity has its origins in Renaissance and Reformation (i.e., critical renovation of the past both Classical and Christian) against the backdrop of the benighted Middle Ages, Japan’s modernity, ultimately a result of the emergency measure it took against the great wave of colonization by the west, cannot but be a composite of disparate ingredients. Whereas quick Westernization was prerequisite, equally indispensable was the spiritual consolidation of national identity. And herein comes the idea of renovating the ancient emperorship in a modern mold of absolute monarchy by singling out Shintoism for a kind of national religion: under such circumstances, the doom of Cicero’s reception needs no explanation. But this does not entirely exclude the possibility that an intellectual perspective characteristic of Japanese modernity can contribute to a better understanding of Cicero: where Cicero has been alienated, as indeed he still is, in the main stream of philosophy, the so-called European tradition of metaphysics, Japanese modernity with its inveterate polytheistic background of non-metaphysics has a chance to intervene for hermeneutic negotiations.Alors que Varsovie célébrait le 30e anniversaire de sa libération du régime totalitaire en réinvoquant la tradition cicéronienne de l’idéal républicain, le Japon se trouvait dans une situation de célébration de la succession de la dynastie impériale, dans laquelle le fils de l’empereur Hirohito (décédé en 1989) devait être remplacé par son petit-fils et consolider ainsi son invention moderne d’une vieille tradition. Si la modernité européenne trouve ses origines dans la Renaissance et la Réforme (c’est-à-dire la rénovation critique du passé, tant classique que chrétien) sur fond de l’arriéré Moyen-Âge, la modernité du Japon, qui résulte en fin de compte de la mesure d’urgence qu’il prend contre la grande vague de colonisation par l’Occident, ne peut être qu’un composite d’ingrédients disparates. Si une occidentalisation rapide était indispensable, la consolidation spirituelle de l’identité nationale l’était tout autant. Et c’est là qu’intervient l’idée de rénover l’ancien empereur dans un moule moderne de monarchie absolue en faisant du shintoïsme une sorte de religion nationale. Dans de telles circonstances, le sort de la réception de Cicéron n’a pas besoin d’être expliqué. Mais cela n’exclut pas entièrement la possibilité qu’une perspective intellectuelle caractéristique de la modernité japonaise puisse contribuer à une meilleure compréhension de Cicéron : là où Cicéron a été aliéné, comme il l’est d’ailleurs toujours, dans le courant principal de la philosophie, c’est-à-dire la tradition dite européenne de la métaphysique, la modernité japonaise avec son fond polythéiste invétéré de non-métaphysique a une chance d’intervenir pour des négociations herméneutiques.Mentre Varsavia celebrava il trentesimo anniversario della sua liberazione dal regime totalitario, facendo nuovamente appello all’ideale repubblicano tramandato da Cicerone, il Giappone era immerso in un’atmosfera celebrativa per la successione imperiale, nella quale al figlio dell’imperatore Hirohito (deceduto nel 1989) doveva subentrare suo nipote consolidando la recente invenzione di un’antica tradizione. Se l’Europa moderna trova le sue origini nel Rinascimento e nella Riforma (vale a dire il rinnovamento critico del passato sia classico che cristiano) in contrasto con lo scenario di arretratezza del Medioevo, il Giappone moderno, fondamentalmente un risultato della misura d’emergenza presa in reazione all’impetuosa ondata di colonizzazione ad opera dell’Occidente, non può che essere una miscela di ingredienti disparati. Premesso che una rapida occidentalizzazione costituiva un prerequisito, altrettanto fondamentale era il consolidamento spirituale dell’identità nazionale. A questo punto sorge l’idea di rinnovare l’antica istituzione imperiale in una forma moderna di monarchia assoluta, individuando nello Shintoismo una sorta di religione nazionale. In tali circostanze, la sorte della ricezione dell’Arpinate non necessita di spiegazioni. Eppure ciò non esclude completamente la possibilità che una prospettiva intellettuale peculiare del Giappone moderno possa contribuire a una migliore comprensione di Cicerone: se Cicerone è stato marginalizzato, come certamente è tuttora, nella visione tradizionale della filosofia, vale a dire nella cosiddetta tradizione europea della metafisica, la modernità giapponese, con il suo radicato retroterra di politeismo non metafisico, si trova nelle condizioni di intervenire per una negoziazione ermeneutica