低インスリン血症は、非糖尿病急性非代償性心不全患者において、全死亡、心血管死の独立した予後予測因子である

Background Insulin beneficially affects myocardial functions during myocardial ischemia. It increases glucose-derived ATP production, decreases oxygen consumption, suppresses apoptosis of cardiomyocytes, and promotes the survival of cardiomyocytes. Patients with chronic heart failure generally have high insulin resistance, which is correlated with poor outcomes. The role of insulin in acute decompensated heart failure (ADHF) remains unclear. This study aimed to investigate the prognostic value of serum insulin level at the time of admission for long-term outcomes in patients with ADHF. Methods and Results We enrolled 1074 consecutive patients who were admitted to our department for ADHF. Of these 1074 patients, we studied the impact of insulin on the prognosis of ADHF in 241 patients without diabetes mellitus. The patients were divided into groups according to low, intermediate, and high tertiles of serum insulin levels. Primary end points were all-cause death and cardiovascular death. During a mean follow-up of 21.8 months, 71 all-cause deaths and 38 cardiovascular deaths occurred. Kaplan-Meier analysis showed that all-cause and cardiovascular mortality was significantly higher in the low-insulin group than those in the intermediate- and high-insulin groups (log-rank P=0.0046 and P=0.038, respectively). Moreover, according to the multivariable analysis, low serum insulin was an independent predictor of all-cause and cardiovascular mortality (hazard ratio, 2.37 [95% CI, 1.24-4.65; P=0.009] and 2.94 [95% CI, 1.12-8.19; P=0.028], respectively). Conclusions Low serum insulin levels were associated with increased risk of all-cause and cardiovascular death in ADHF patients without diabetes mellitus.博士（医学）・甲第808号・令和4年3月15日© 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes

日本における非代償性急性心不全患者の30日および90日以内の心不全再入院の発生率と臨床的意義 : NARA-HF研究より

Background: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.Methods and Results:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. Conclusions: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.博士（医学）・甲第735号・令和2年3月16日日本循環器学会の許諾を得て登録（2020年9月2日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

急性心不全における退院時の尿素窒素分画排泄率の予後判定への有用性

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group (P<0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P=0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m2, interaction P=0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.博士（医学）・甲第814号・令和4年3月15日Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made

僧帽弁閉鎖不全症を伴うまたは伴わない非代償性急性心不全患者の予後に心房細動が与える影響

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) are frequently combined in patients with heart failure (HF). However, the effect of AF on the prognosis of patients with HF and MR remains unknown. Methods and Results: We studied 867 patients (mean age 73 years; 42.7% female) with acute decompensated HF (ADHF) in the NARA-HF registry. Patients were divided into 4 groups based on the presence or absence of AF and MR at discharge. Patients with severe MR were excluded. The primary endpoint was the composite of cardiovascular (CV) death and HF-related readmission. During the median follow-up of 621 days, 398 patients (45.9%) reached the primary endpoint. In patients with MR, AF was associated with a higher incidence of the primary endpoint regardless of left ventricular function; however, in patients without MR, AF was not associated with CV events. Cox multivariate analyses showed that the incidence of CV events was significantly higher in patients with AF and MR than in patients with MR but without AF (hazard ratio 1.381, P=0.036). Similar findings were obtained in subgroup analysis of patients with AF and only mild MR. Conclusions: The present study demonstrated that AF is associated with poor prognosis in patients with ADHF with mild to moderate MR, but not in those without MR.博士（医学）・甲第799号・令和3年9月29日© 2021, THE JAPANESE CIRCULATION SOCIETY This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0

Effect on Blood Pressure of Daily Lemon Ingestion and Walking

Background. Recent studies suggest that the daily intake of lemon (Citrus limon) has a good effect on health, but this has not been confirmed in humans. In our previous studies, it was observed that people who are conscious of their health performed more lemon intake and exercise. An analysis that took this into account was required. Methodology. For 101 middle-aged women in an island area in Hiroshima, Japan, a record of lemon ingestion efforts and the number of steps walked was carried out for five months. The change rates (Δ%) of the physical measurements, blood test, blood pressure, and pulse wave measured value during the observation period were calculated, and correlations with lemon intake and the number of steps walked were considered. As a result, it was suggested that daily lemon intake and walking are effective for high blood pressure because both showed significant negative correlation to systolic blood pressure Δ%. Conclusions. As a result of multiple linear regression analysis, it was possible that lemon ingestion is involved more greatly with the blood citric acid concentration Δ% and the number of steps with blood pressure Δ%, and it was surmised that the number of steps and lemon ingestion are related to blood pressure improvement by different action mechanisms

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

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss