胃がんリスク評価におけるABC分類とX線所見の関連性について

PURPOSE:To investigate the correlation between ABC risk assessment and radiological findings of gastric mucosa and to propose an improved method for gastric cancer screening. MATERIALS AND METHODS:We evaluated 318 participants with Helicobacter pylori (Hp) antibody titers, serum pepsinogen (PG) and upper GI radiography and then classified them into three groups: A, double-negative; B, Hp-positive, PG-negative; C, PG-positive. Group A was subclassified as: A-1, Hp antibody titer <3.0 U/ml; A-2, Hp antibody titer ≥3.0 U/ml. Results for group A and non-A (B or C) participants and radiological findings of gastric mucosa (fold and area gastricae) were analyzed retrospectively. RESULTS:Radiological findings differed significantly between the 207 A-1 and 98 non-A group. Odds ratios were 17.72 for fold distribution, 10.63 for fold thickness, 6.10 for fold characteristics, and 10.62 for area gastricae. Presence of ≥2 risk factors offered 90.3 % sensitivity, 94.7 % specificity, and 93.3 % accuracy. Nine (69.2 %) of the 13 A-2 group participants and 11 (5.3 %) A-1 group participants had a risk for gastric cancer according to radiological findings. CONCLUSION:A good correlation exists between ABC classifications and radiological findings for gastric cancer risk, but some discrepant cases exist. We recommend both methods as screening for gastric cancer.博士（医学）・乙第1370号・平成27年11月27日© Japan Radiological Society 2015© Springer-Verlag Berlin Heidelberg 2015The final publication is available at Springer via http://dx.doi.org/10.1007/s11604-015-0469-

MODELLING INGREDIENT OF JAMU TO PREDICT ITS EFFICACY

Jamu is an Indonesian herbal medicine made from a mixture of several plants.  Nowadays, many jamu are  produced commercially by many industries in Indonesia.  Each producer may have their own jamu formula. However, one is certain; the efficacy of jamu is determined by the composition of the plants used.  Thus, it is interesting to model the ingredient of jamu which consist of plants and use it to predict efficacy of jamu.  In this analysis, Partial Least Squares Discriminant Analysis (PLSDA) is used in modeling jamu ingredients to predict  the  efficacy.  It  is  obtained  that  utilizing the prediction of  y ij obtained  from  PLSDA  directly  rather  than  use  it  to calculate probability of jamu i belong to efficacy j and then use the probability to predict efficacy produces lower False Positive Rate (FPR) in predicting efficacy group.  Keywords: Jamu, PLSD

乳房ソナゾイド造影超音波における背景乳腺の造影効果についての検討

Purpose: The objective of this study was to retrospectively evaluate the association between background parenchymal enhancement (BPE) on contrast-enhanced ultrasound (CEUS) with Sonazoid® and patient characteristics. Additionally, background parenchymal tissues with the high-contrast effect were pathologically observed compared to those showing the low-contrast effect. Methods: A total of 65 patients who underwent breast CEUS with Sonazoid® between January 2010 and November 2013 were enrolled. Regions of interest (ROIs) were put on the tumor and on the background parenchymal tissue. The dB values during the nonenhanced time and at peak contrast enhancement were measured based on the time intensity curve (TIC) drawn by the ROI. The differences in the dB values of pre- and post-enhanced time were obtained separately for ROIs on the tumor and ROIs on the parenchymal tissue. The patient characteristics studied were age, menstrual status, mammographic density, BPE on magnetic resonance imaging (MRI), and pathological diagnoses of breast tumors. Results: There was a weak negative correlation between BPE on CEUS and age. As for the contrast effect of parenchymal tissue, there was a significant difference between the menstruating and menopausal groups. There was no significant difference among the levels of mammographic density, and among the degrees of contrast effect on MRI. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status. The parenchymal tissue with the low-contrast effect showed pathological atrophy. Conclusion: The degree of BPE on CEUS appeared related to age, menstruating or menopausal, and atrophy of breast tissue. BPE on CEUS was the same between those with a malignant tumor and those with a benign tumor in each menstrual status.博士（医学）・乙第1508号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020.© The Japan Society of Ultrasonics in Medicine 2020.This is a post-peer-review, pre-copyedit version of an article published in Journal of medical ultrasonics. The final authenticated version is available online at: https://doi.org/10.1007/s10396-020-01052-4

Sequence-specific error profile of Illumina sequencers

We identified the sequence-specific starting positions of consecutive miscalls in the mapping of reads obtained from the Illumina Genome Analyser (GA). Detailed analysis of the miscall pattern indicated that the underlying mechanism involves sequence-specific interference of the base elongation process during sequencing. The two major sequence patterns that trigger this sequence-specific error (SSE) are: (i) inverted repeats and (ii) GGC sequences. We speculate that these sequences favor dephasing by inhibiting single-base elongation, by: (i) folding single-stranded DNA and (ii) altering enzyme preference. This phenomenon is a major cause of sequence coverage variability and of the unfavorable bias observed for population-targeted methods such as RNA-seq and ChIP-seq. Moreover, SSE is a potential cause of false single-nucleotide polymorphism (SNP) calls and also significantly hinders de novo assembly. This article highlights the importance of recognizing SSE and its underlying mechanisms in the hope of enhancing the potential usefulness of the Illumina sequencers

Effects of APETALA2 on embryo, endosperm, and seed coat development determine seed size in Arabidopsis

Arabidopsis APETALA2 (AP2) controls seed mass maternally, with ap2 mutants producing larger seeds than wild type. Here, we show that AP2 influences development of the three major seed compartments: embryo, endosperm, and seed coat. AP2 appears to have a significant effect on endosperm development. ap2 mutant seeds undergo an extended period of rapid endosperm growth early in development relative to wild type. This early expanded growth period in ap2 seeds is associated with delayed endosperm cellularization and overgrowth of the endosperm central vacuole. The subsequent period of moderate endosperm growth is also extended in ap2 seeds largely due to persistent cell divisions at the endosperm periphery. The effect of AP2 on endosperm development is mediated by different mechanisms than parent-of-origin effects on seed size observed in interploidy crosses. Seed coat development is affected; integument cells of ap2 mutants are more elongated than wild type. We conclude that endosperm overgrowth and/or integument cell elongation create a larger postfertilization embryo sac into which the ap2 embryo can grow. Morphological development of the embryo is initially delayed in ap2 compared with wild-type seeds, but ap2 embryos become larger than wild type after the bent-cotyledon stage of development. ap2 embryos are able to fill the enlarged postfertilization embryo sac, because they undergo extended periods of cell proliferation and seed filling. We discuss potential mechanisms by which maternally acting AP2 influences development of the zygotic embryo and endosperm to repress seed size

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

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

Two cases of orbital adenocarcinoma treated with heavy charged carbon particle irradiation

Background: Orbital adenocarcinoma is a relatively rare, primary orbital malignant epithelial tumor, and shares the poor prognosis of orbital adenoid cystic carcinoma.We report the cases of two patients with orbital adenocarcinoma who were treated with heavy charged carbon particle irradiation and followed up for more 6 years. Method: Two patients with orbital adenocarcinoma, 62 and 74 years old, received 57.6 GyE of heavy charged particle irradiation therapy. Results: In both cases, the size of the tumor gradually decreased after carbon ion irradiation therapy. No recurrences or metastasis of the tumor were found for more than 6 years. Conclusion: Orbital adenocarcinoma has a poor prognosis in general. Two patients with orbital adenocarcinoma were treated with heavy charged carbon particle irradiation therapy and had a relatively good outcome and good prognosis. We believe that heavy charged carbon particle irradiation therapy is a promising therapy for orbital adenoud cystic carcinoma and adenocarcinoma

Iron Oxide Arrays Prepared from Ferrocene- and Silsesquioxane-Containing Block Copolymers

Arrays of iron oxides as precursors of iron clusters were prepared by oxygen plasma treatment of block copolymer microphase-separated nanostructures in thin films. Block copolymers composed of ferrocene-containing and silsesquioxane-containing polymethacrylate (PMAPOSS-b-PMAHFC) were successfully prepared, with different molecular weights and compositions and narrow molecular weight distributions, by living anionic polymerization. The formed microphase-separated nanostructures in the bulk were characterized by wide- and small-angle X-ray scattering (WAXS and SAXS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Thin films were prepared from a solution of PMAPOSS-b-PMAHFC in tetrahydrofuran by spin coating onto silicon wafers. Fingerprint-type line nanostructures were formed in the PMAPOSS-b-PMAHFCs thin films after solvent annealing with carbon disulfide. Oxygen plasma treatment provided the final line arrays of iron oxides based on the formed nanostructural patterns