Radiotherapy quality assurance review in a multi-center randomized trial of limited-disease small cell lung cancer: the Japan Clinical Oncology Group (JCOG) trial 0202

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to analyze the radiotherapy (RT) quality assurance (QA) assessment in Japan Clinical Oncology Group (JCOG) 0202, which was the first trial that required on-going RT QA review in the JCOG.</p> <p>Methods</p> <p>JCOG 0202 was a multi-center phase III trial comparing two types of consolidation chemotherapy after concurrent chemoradiotherapy for limited-disease small cell lung cancer. RT requirements included a total dose of 45 Gy/30 fx (bis in die, BID/twice a day) without heterogeneity correction; elective nodal irradiation (ENI) of 30 Gy; at least 1 cm margin around the clinical target volume (CTV); and interfraction interval of 6 hours or longer. Dose constraints were defined in regards to the spinal cord and the lung. The QA assessment was classed as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable (I/NE).</p> <p>Results</p> <p>A total of 283 cases were accrued, of which 204 were fully evaluable, excluding 79 I/NE cases. There were 18 VU in gross tumor volume (GTV) coverage (8% of 238 evaluated); 4 VU and 23 DA in elective nodal irradiation (ENI) (2% and 9% of 243 evaluated, respectively). Some VU were observed in organs at risk (1 VU in the lung and 5 VU in the spinal cord). Overall RT compliance (PP + DA) was 92% (187 of 204 fully evaluable). Comparison between the former and latter halves of the accrued cases revealed that the number of VU and DA had decreased.</p> <p>Conclusion</p> <p>The results of the RT QA assessment in JCOG 0202 seemed to be acceptable, providing reliable results.</p

A Study to Establish an Online Database for Bronze Inscriptions

本稿の目的は，同時代史料としての青銅器の拓本や器影といった金文に関するアナログデータ史料をデジタルアーカイブ化してデータベースを作成する際に求められる方法や手順などを考察することである．甲骨文や金文の研究を発展させるためには，様々な拓本や通釈を整理しデータベース化することが必要であり，拓本や画像等をデジタルアーカイブ化することで，史料の収集や検索などに費やす時間や手間を削減できるだろう．departmental bulletin pape

Recent Internet Usage and Communication

本稿の目的は，インターネットを利用したコミュニケーションの状況や特徴を，総務省の「令和4 年通信利用動向調査」を題材に整理し，Web2.0 以降のインターネット接続の構造に焦点を当てることで，現代のインターネットコミュニケーションの複雑化の背景を明らかにすることである．同時に，情報教育の観点から，インターネットコミュニケーションを実践する上での注意点やマナー等についても述べる．departmental bulletin pape

Upper limb coordination differs among ages and between dominant and non-dominant hands utilizing digital trace test

Evaluation of motor coordination is carried out in the rehabilitation scene at the clinical site. However, most of the conventional evaluation methods are too subjective, or rather most are insufficiently elaborate to trace the target of diachronic change. Thus, we attempted evaluation of upper extremity motor coordination utilizing an originally developed ‘Digital trace method' on 65 persons of physically unimpaired status, ages 8 to 90. In this experiment, four types of measurement were tried for both the dominant and non-dominant hand for the large and small circle, and factors of age, sex and handedness were analyzed. As a result, the trace error of the dominant hand decreased significantly compared with that of the non-dominant hand. A change in the error value of the small circle was hardly observed in the dominant hand. However, it was admitted that the error value of the large circle was significantly smaller in the non-dominant hand. Observing this when separated by age, it was found that the error at trace testing indicated a drastic decrease from childhood period to adult age. In constant, it indicated a gradual increase from the thirties. From these observations, it was found that variations in motor coordination depend on age and thus have a bearing on the use status of the dominant hand and the non-dominant hand. Operability of the dominant hand and the supplement role of the non-dominant hand are considered to be affected by such conditions

Negative feedback by IRE1β optimizes mucin production in goblet cells

In mammals, the prototypical endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1 (IRE1) has diverged into two paralogs. IRE1α is broadly expressed and mediates the unconventional splicing of X-box binding protein 1 (XBP1) mRNA during ER stress. By contrast, IRE1β is expressed selectively in the digestive tract, and its function remains unclear. Here, we report that IRE1β plays a distinctive role in mucin-secreting goblet cells. In IRE1β-/- mice, aberrant mucin 2 (MUC2) accumulated in the ER of goblet cells, accompanied by ER distension and elevated ER stress signaling such as increased XBP1 mRNA splicing. In contrast, conditional IRE1α-/- mice showed no such ER distension but a marked decrease in spliced XBP1 mRNA. mRNA stability assay revealed that MUC2 mRNA was greatly stabilized in IRE1β-/- mice. These findings suggest that in goblet cells, IRE1β, but not IRE1α, promotes efficient protein folding and secretion in the ER by optimizing the level of mRNA encoding their major secretory product, MUC2

Reduction of thermal fluctuations in a cryogenic laser interferometric gravitational wave detector

The thermal fluctuation of mirror surfaces is the fundamental limitation for interferometric gravitational wave (GW) detectors. Here, we experimentally demonstrate for the first time a reduction in a mirror's thermal fluctuation in a GW detector with sapphire mirrors from the Cryogenic Laser Interferometer Observatory at 17\,K and 18\,K. The detector sensitivity, which was limited by the mirror's thermal fluctuation at room temperature, was improved in the frequency range of 90\,Hz to 240\,Hz by cooling the mirrors. The improved sensitivity reached a maximum of $2.2 \times 10^{-19}\,\textrm{m}/\sqrt{\textrm{Hz}}$ at 165\,Hz.Comment: Accepted for publication in Physical Review Letters, 5 pages, 2 figure

Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography

<p>Abstract</p> <p>Background</p> <p>Although oxidative stress by accumulation of reactive oxygen species (ROS) in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D).</p> <p>Methods</p> <p>An index for coronary-arteriosclerosis, coronary artery calcium score (CACS) was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, <it>Glutathione peroxidase-1 (GPx-1)</it>, <it>Catalase, Mn-SOD</it>, <it>Cu/Zn-SOD</it>, as well as SNPs of <it>NADPH oxidase </it>as ROS-promoting elements, genes related to onset of T2D (<it>CAPN10, ADRB3, PPAR gamma, FATP4</it>). Age, blood pressure, BMI, HbA_1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis.</p> <p>Results</p> <p>CACS with Pro/Leu genotype of the <it>GPx-1 </it>gene was significantly higher than in those with Pro/Pro (744 ± 1,291 vs. 245 ± 399, respectively, <it>p </it>= 0.006). In addition, genotype frequency of Pro/Leu in those with CACS ≥ 1000 was significantly higher than in those with CACS < 1000 (45.5% vs. 18.8%; <it>OR </it>= 3.61, <it>CI </it>= 0.97–13.42; <it>p </it>= 0.045) when tested for deviation from Hardy-Weinberg's equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with <it>GPx-1 </it>genotypes and age.</p> <p>Conclusion</p> <p>The presence of Pro197Leu substitution of the <it>GPx-1 </it>gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant <it>GPx-1</it>.</p

Low immunogenicity of LNP allows repeated administrations of CRISPR-Cas9 mRNA into skeletal muscle in mice

筋ジストロフィーのゲノム編集治療を目指したLNP-mRNA輸送システムの開発. 京都大学プレスリリース. 2021-12-08.Nanotechnology for genome editing in multiple muscles simultaneously. 京都大学プレスリリース. 2021-12-08.Genome editing therapy for Duchenne muscular dystrophy (DMD) holds great promise, however, one major obstacle is delivery of the CRISPR-Cas9/sgRNA system to skeletal muscle tissues. In general, AAV vectors are used for in vivo delivery, but AAV injections cannot be repeated because of neutralization antibodies. Here we report a chemically defined lipid nanoparticle (LNP) system which is able to deliver Cas9 mRNA and sgRNA into skeletal muscle by repeated intramuscular injections. Although the expressions of Cas9 protein and sgRNA were transient, our LNP system could induce stable genomic exon skipping and restore dystrophin protein in a DMD mouse model that harbors a humanized exon sequence. Furthermore, administration of our LNP via limb perfusion method enables to target multiple muscle groups. The repeated administration and low immunogenicity of our LNP system are promising features for a delivery vehicle of CRISPR-Cas9 to treat skeletal muscle disorders