Corrigendum: Retrospective cohort study to determine the effect of preinjury antiplatelet or anticoagulant therapy on mortality in patients with major trauma

OBJECTIVE: This study aimed to compare outcomes among patients who sustained major trauma from injury with and without receiving antiplatelet therapy (APT) or anticoagulant therapy (ACT) to test the hypothesis that APT does not increase the risk of mortality. However, ACT increases the mortality risk in the acute phase of trauma. METHODS: Patients registered in the Japanese Observational body for Coagulation and Thrombolysis in Early Trauma 2 between April 2017 and March 2018 who had sustained a severe injury in any anatomic region of the body, as determined using an injury severity score (ISS) ≥ 16 were included in this retrospective cohort study. We analyzed the mortality within 24 h from the arrival using a multivariable linear regression analysis adjusted for several confounding variables. RESULTS: We identified 1,186 eligible participants who met the inclusion criteria for this study: 105 in the APT (cases), 1,081 in the non-antiplatelet therapy (nAPT) group (controls), 65 in the ACT (cases), and 1,121 in the non-anticoagulant therapy (nACT) group (controls). The mortality within 24 h in the ACT group was significantly higher than in the nACT group (odds ratio 4.5; 95%CI: 1.2–16.79; p = 0.025); however, there was no significant difference between the two groups with or without the antiplatelet drug (odds ratio 0.32; 95%CI: 0.04–2.79; p = 0.3) administration. Other outcomes, like the 28-day mortality, mortality at discharge, and surgery for hemostasis, were not significantly different between regular users and non-users of either antiplatelet or anticoagulant drugs. CONCLUSION: Regular antiplatelet medications did not increase mortality within 24 h, 28 days, or at discharge in patients with major trauma, suggesting that standard treatment, including surgery, is sufficient

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients

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

<Original>Studies on the Improvement of the Pinning Method for Marking Xylem Growth I. : Minute Examination of Pin Marks in Taeda Pine and other Species

この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました。In order to make an accurate estimation of the location of cambium at the time of pin insertion, pin marks left in the xylem tissue were minutely examined. The size and shape of the abnormal tissue induced by pin insertion depended on the size of needle, growth rate of trees, and the tree species. Since the abnormal tissue changed its shape and size as the cross section receded from the center, it was concluded to be necessary to use the cross section obtained from the center of pinning for correct application of the pinning method. The site relation between cambial initials at the time of pinning and the abnormal tissue was investigated following the modified Wolter's procedure. As a result, the site of cambial initials at the time of pinning was assumed to be at the cambial-side margin of the spindle-like abnormal tissue

Spin trapping of 13C-labeled p-benzynes generated by Masamune–Bergman cyclization of bicyclic nine-membered enediynes

Our understanding of the chemistry and biology of the enediyne class of antitumor antibiotics is still developing and faces further challenges. The cleavage of double-stranded DNA through hydrogen abstraction by enediyne-derived radicals is a generally well-accepted mechanism. However, the mechanisms of several unexpected and complex cytotoxic effects of enediynes,such as RNA and protein damage or the generation of p-quinone species, have yet to be fully elucidated. Despite several carefully crafted experimental and theoretical studies on simplified systems,the behavior of the major chemical perpetrators of such cytotoxicity, namely the biradical intermediates formed by natural enediynes, remains more a matter of conjecture than a point of fact

Direct observation of ESR spectra of bicyclic nine-membered enediynes at ambient temperature

The ESR spectra for synthetic bicyclo[7.3.0]epoxydodecadienediynes in solution at room temperature are steady. These spectra originate from the Masamune-Bergman cyclization of bicyclo[7.3.0]epoxydodecadienediynes to p-benzyne biradicals and the equilibrium between the two forms. Comparison of the ESR spectra of the unlabeled and 13C-labeled nine-membered enediynes indicated that the spectra are not directly due to the p-benzyne biradicals but rather to more stable secondary radical intermediates