看護教育におけるCancer Survivorの「病と共に生きる」体験談からの学生の学び

看護教育において看護の対象者についての理解を促進する教育方法として、当事者参加型授業がある。成人看護学「がん看護」においてCancer Survivorによる授業を行い、その授業から学生が何を学んだのかを明らかにし、教育効果を検討した。学生は対象の理解、看護の理解、がんを取りまく社会のあり方、自分自身のあり方、の4領域に関する学びをしていた。がんと共に生きているCancer Survivorの体験談を直接聞くことは、より深くCancer Survivorの内面に接近することにつながり、対象の理解と必要とされる看護を考え、自己のあり方にまで思考を及ばせる教育効果があった。今後は、これらの学びを活かし、発展させていくことが必要である

PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation

Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

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

Fatigue Evaluation Under Continuous Strain Rate Changing Condition of Carbon Steel in BWR Environment

Fatigue evaluation methods have been proposed based on environmental fatigue test results regarding parameters selected for simulating Boiling Water Reactor (BWR) and Pressurized Water Reactor (PWR) conditions. The effects of strain wave form have been discussed by comparing experimental fatigue life with predicted fatigue life evaluated by modified rate approach (MRA) method. The applicability of the MRA method has been verified extensively by the environmental fatigue tests with strain rate changing conditions consisting of combined constant strain rates. However, different results have been obtained for a sine strain wave in simulated BWR and PWR conditions. More study for evaluating the applicability of MRA method was required by evaluating with continuous strain rate conditions such as a sine wave. For the purpose of verification, two approaches were applied. One is performing the environmental fatigue tests with the sine strain wave in simulated BWR condition. The other is to evaluate the low cycle thermal fatigue test performed in simulated BWR condition because the wave form of this test contains continuous strain rate changing condition. MRA method was indicated to be applicable to predict fatigue lives under these kinds of continuous strain rate changing conditions. All of the studies including this study verifying the applicability of the MRA method were performed with small specimens having the well polished surfaces in the gage length. These results indicate that the evaluation by the MRA method includes the synergistic effect between the water environment and the transient. However, the synergistic effects with the surface roughness and the component size are not known. Design margin derived by the multiplication of the sub-factors of environment, surface roughness and component size may be conservative. The evaluation of the conservatism is considered to be beneficial

Evaluation of an Education Program on Community Orientation among Community Health Nurses in Fiji

Abstract Aim The study objective was to evaluate the effectiveness of an education program to improve community orientation among community health nurses in Fiji. A 1.5‐day education program was developed that enabled participants to learn a concept through discussion, as they reviewed their experiences. Design This study used mixed methods research. Methods The education program involving 78 community health nurses and supervisors was conducted. The 30‐item Community Orientation among Community Health Nurses scale, six‐item program evaluation questionnaire, and participant reflection sheets were analyzed using both quantitative and qualitative methods. Results Program evaluations demonstrated high satisfaction among participants. The content analysis of participant views on community orientation revealed three categories; utilizing community intelligence in community activities, relationships with community members as a community health nurses, and human resource development tool. Our findings suggest that this education program should be held regularly, in conjunction with on‐the‐job and off‐site training