A virtual audit system for intensity-modulated radiation therapy credentialing in Japan Clinical Oncology Group clinical trials: A pilot study

PURPOSE The Medical Physics Working Group of the Radiation Therapy Study Group at the Japan Clinical Oncology Group is currently developing a virtual audit system for intensity-modulated radiation therapy dosimetry credentialing. The target dosimeters include films and array detectors, such as ArcCHECK (Sun Nuclear Corporation, Melbourne, Florida, USA) and Delta4 (ScandiDos, Uppsala, Sweden). This pilot study investigated the feasibility of our virtual audit system using previously acquired data. METHODS We analyzed 46 films (32 and 14 in the axial and coronal planes, respectively) from 29 institutions. Global gamma analysis between measured and planned dose distributions used the following settings: 3%/3 mm criteria (the dose denominator was 2 Gy), 30% threshold dose, no scaling of the datasets, and 90% tolerance level. In addition, 21 datasets from nine institutions were obtained for array evaluation. Five institutions used ArcCHECK, while the others used Delta4. Global gamma analysis was performed with 3%/2 mm criteria (the dose denominator was the maximum calculated dose), 10% threshold dose, and 95% tolerance level. The film calibration and gamma analysis were conducted with in-house software developed using Python (version 3.9.2). RESULTS The means ± standard deviations of the gamma passing rates were 99.4 ± 1.5% (range, 92.8%-100%) and 99.2 ± 1.0% (range, 97.0%-100%) in the film and array evaluations, respectively. CONCLUSION This pilot study demonstrated the feasibility of virtual audits. The proposed virtual audit system will contribute to more efficient, cheaper, and more rapid trial credentialing than on-site and postal audits; however, the limitations should be considered when operating our virtual audit system

Pretreatment glasgow prognostic score predicts survival among patients administered first-line atezolizumab plus carboplatin and etoposide for small cell lung cancer

BackgroundThere are no established predictive biomarkers for the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with small-cell lung cancer (SCLC). Therefore, the current study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC.MethodsWe reviewed data from 84 patients who received first-line atezolizumab plus carboplatin and etoposide therapy for SCLC at nine Japanese institutions between August 2019 and May 2021. Further, we evaluated the prognostic value of the GPS, NLR, and BMI. The Kaplan–Meier and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). Moreover, the GPS, NLR, and BMI consisted of C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively.ResultsThe response rate was 72.6% (95% confidence interval: 63.0–82.1%). The median PFS and OS from the initiation of treatment were 5.4 (95% CI: 4.9–5.9) months and 15.4 (95% CI: 11.4–16.8) months, respectively. The GPS independently predicted the effectiveness of first-line atezolizumab plus carboplatin and etoposide treatment, as a favorable GPS (GPS 0–1) was correlated with significantly better PFS and OS rates compared to a poor GPS (GPS 2) (PFS: 5.8 vs. 3.8 months, p = 0.0005; OS: 16.5 vs. 8.4 months, p<0.0001).ConclusionsThis is the first analysis to evaluate the association between the GPS, NLR, and BMI and the treatment effectiveness of survival among patients receiving first-line atezolizumab plus carboplatin and etoposide therapy for SCLC. Among patients receiving this treatment for SCLC, GPS was significantly associated with the PFS and OS rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients

工具回転機能を有したダイヤモンドチップバニシング加工の基礎的検討

金沢大学理工研究域機械工学系立方体形状の工作物の表面仕上げ法として，表面の平滑化，加工硬化ならびに圧縮残留応力の付与を目指したバニシング加工法について検討する．本加工法はフライス加工の要領で，先端に半球形状を有するダイヤモンドチップを高速で回転させながら，対象面上を定力下で摺動させる．本報では，高硬度材の平坦面に本加工法を適用した場合の基礎的な加工特性について，仕上げ面形状の観点から評価した結果を報告する．The effectiveness of a diamond burnishing method with rotating tool, which is proposed by the authors, is investigated. A proposed hybrid-type parallel mechanism with spherical 5-degree-of-freedom range and force control was used as a burnishing machine. A diamond tipped tool, which is rotated by the high-speeed-motor spindle, was used as a burnishing tool. A hardened die steel surface were targeted. The fundamental characteristics of the proposed method were evaluated by the surface profile and appearance of the burnishing mark and metallographic structure of the burnished surface layer, and the advantages of the proposed method were clarified by comparing with the conventional method, which is without the tool rotation.出版者照会後に全文公

研究公正に関する自己記述式尺度における質問文の検討 : 尺度作成における議論を通して

京都府立医科大学大学院医学研究科医学生命倫理学人文・社会科学教室京都府立医科大学大学院医学研究科生物統計学教室京都府立医科大学大学院保健看護学研究科東京医科歯科大学臨床医学教育学開発分野新潟大学創生学部日本医科大学医療管理学京都府立医科大学大学院医学研究科生命基礎数理学教室京都府立医科大学大学院医学研究科医療フロンティア展開学九州大学病院ARO次世代医療センター群馬パース大学教養部AMED研究公正高度化モデル開発支援事業「学際的アプローチによる研究倫理教育のモデル評価プログラムの開発と検証」（瀬戸山班）では、研究活動に関する倫理的意思決定を測定する尺度を開発している。本論文では、この開発中の尺度の質問文に着目し、自己記述式尺度が抱える問題点を克服するため、質問文の作成において検討した内容や、この質問文のオリジナリティ、課題について述べる

研究活動における「隠れたカリキュラム」の可視化の試み : 重回帰分析による分析と考察

京都府立医科大学大学院医学研究科医学生命倫理学人文・社会科学教室京都府立医科大学大学院医学研究科生命基礎数理学教室京都府立医科大学大学院医学研究科生物統計学教室京都府立医科大学大学院保健看護学研究科東京医科歯科大学臨床医学教育学開発分野新潟大学創生学部日本医科大学医療管理学京都府立医科大学大学院医学研究科医療フロンティア展開学九州大学病院ARO次世代医療センター群馬パース大学教養部本稿では，医学教育分野で注目されている「隠れたカリキュラム（hidden curriculum）」を，医学研究の倫理分野において倫理的意思決定やそれに影響を与える組織の環境に応用し，研究倫理に関する規範意識・行動様式を問う情意領域問題の測定尺度を作成したものを用いて，「あなたならばどう行動するか」と「あなたの周りの人ならばどう行動すると考えるか」についてそれぞれ質問を行い，その得点差を見ることで隠れたカリキュラムの影響を可視化することを試みた。その結果，全体及びすべてのカテゴリーにおいて「あなたならばどう行動するか」の得点が高いこと，属性との関連について調べたところ，一部のカテゴリーと性別，人に関わる研究の有無で有意な得点差がみられた

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

A Patient with Non-alcoholic Steatohepatitis Complicated by Multiple Myeloma

A 68-year-old woman with liver dysfunction was diagnosed with nonalcoholic steatohepatitis (NASH) stage 1. Three years later, she showed massive ascites and jaundice. A trans-jugular liver biopsy confirmed advanced cirrhosis, suggesting that her liver fibrosis had progressed rapidly. At the same time, she was diagnosed with multiple myeloma (MM). In this case, the plasma levels of osteopontin (OPN), a proinflammatory cytokine that promotes liver fibrosis progression through the hedgehog pathway and is increased in patients with MM, were increased. This increased OPN expression was accompanied by the upregulation of the hedgehog pathway in this patient, suggesting that the MM-associated increase in OPN had promoted the progression of liver fibrosis through the hedgehog pathway. The progression of liver fibrosis should be monitored in patients with NASH if other diseases, such as MM, are present

Developing a behaviour rubric for the practical model of ethical behaviour for clinical nursing

Abstract Aim The present study aimed to develop an ethical behaviour rubric for nurses and evaluate its reliability and validity. Method This study was to designed to construct a rubric and evaluate the reliability and validity. The ethical behaviour rubric was distributed to 241 nurses and 154 were completed and returned. The intra‐rater and inter‐rater reliability were evaluated by intraclass correlation coefficient (ICC) for all 10 items on the ethical behaviour rubric, and the internal consistency reliability was evaluated using Cronbach's α. Construct validity was tested with explanatory factor analysis, and criterion validity was tested using the known‐groups method. Results Intra‐rater reliability had a high interrater agreement (ICC = 0.9), and inter‐rater reliability had a high interrater agreement (ICC = 0.84). The Cronbach's α coefficient was 0.96. There was a linear correlation between the number of years of nursing experience and rubric scores p < 0.001. Exploratory factor analysis revealed 10 items loading on four factors. The result of factor analysis is that Cronbach's α was 0.93 for the first factor, 0.83 for the second factor, 0.91 for the third factor, and 0.77 for the fourth factor. Conclusions Our rubric was found to be a valid and reliable tool for the assessment of ethical behaviour among nurses in Japan