Ultra–sensitive droplet digital PCR for detecting a low–prevalence somatic GNAQ mutation in Sturge–Weber syndrome

学位記番号：医博甲1691

Study Abroad and the Transnational Experience of Japanese Women from 1860s–1920s: Four Stages of Female Study Abroad, Sumi Miyakawa and Tano Jōdai

This article aims to analyse the study abroad and transnational experiences of Japanese women between the 1860s and the 1920s. First, this article analyses the tendencies, periods, agents (both government-funded and privately-funded), aims and subjects studied in female study abroad in the four stages during this period from school history materials of individual institutions which supported female study abroad. In its later stages, female study abroad tended to strengthen the function of raising leaders of girls’ and women’s education, while in its early stages it tended to introduce a variety of Western culture and academic knowledge. Second, the article focuses on the forms of government- and privately-funded study abroad for women by tracing the study-abroad experience of two women educators in the early 20th century. Within government-funded study abroad, academic disciplines studied and students’ experiences were controlled by the government and focused on building a national female educational system. However, privately-funded study abroad possessed wider aims. It allowed female students to study various academic disciplines and introduced new international trends for promoting women’s social participation. Most female students who experienced study abroad became pioneers of female education and/or social activities in Japan as a result of their transnational experiences

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Study abroad and the transnational experience of Japanese women from 1860s–1920s: fours stages of female study abroad, Sumi Miyakawa and Tano Jōdai

This article aims to analyse the study abroad and transnational experiences of Japanese women between the 1860s and the 1920s. First, this article analyses the tendencies, periods, agents (both government-funded and privately-funded), aims and subjects studied in female study abroad in the four stages during this period from school history materials of individual institutions which supported female study abroad. In its later stages, female study abroad tended to strengthen the function of raising leaders of girls’ and women’s education, while in its early stages it tended to introduce a variety of Western culture and academic knowledge. Second, the article focuses on the forms of government- and privately-funded study abroad for women by tracing the study-abroad experience of two women educators in the early 20th century. Within government-funded study abroad, academic disciplines studied and students’ experiences were controlled by the government and focused on building a national female educational system. However, privately-funded study abroad possessed wider aims. It allowed female students to study various academic disciplines and introduced new international trends for promoting women’s social participation. Most female students who experienced study abroad became pioneers of female education and/or social activities in Japan as a result of their transnational experiences

Case Report Tracheal Intubation through the I-gel for Emergency Cesarean Section in a Patient with Multidrug Hypersensitivity: A New Technique

31-year-old female with hypersensitivity to local anesthetics and neuromuscular blocking agents presented for emergency Cesarean section. We successfully performed I-gel-assisted tracheal intubation without using neuromuscular blockers. We believe this method would be helpful in selected situations

Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants

Background Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size. Methods We first constructed a model estimating the rates of de novo CNVs per gene from several factors such as gene length and number of exons. Second, we compiled a comprehensive list of de novo single-nucleotide variants (SNVs) in 41,165 individuals and de novo CNVs in 3675 individuals with NDDs by aggregating our own and publicly available datasets, including denovo-db and the Deciphering Developmental Disorders study data. Third, summing up the de novo CNV rates that we estimated and SNV rates previously established, gene-based enrichment of de novo deleterious SNVs and CNVs were assessed in the 41,165 cases. Significantly enriched genes were further prioritized according to their similarity to known NDD genes using a deep learning model that considers functional characteristics (e.g., gene ontology and expression patterns). Results We identified a total of 380 genes achieving statistical significance (5% false discovery rate), including 31 genes affected by de novo CNVs. Of the 380 genes, 52 have not previously been reported as NDD genes, and the data of de novo CNVs contributed to the significance of three genes (GLTSCR1, MARK2, and UBR3). Among the 52 genes, we reasonably excluded 18 genes [a number almost identical to the theoretically expected false positives (i.e., 380 x 0.05 = 19)] given their constraints against deleterious variants and extracted 34 plausible candidate genes. Their validity as NDD genes was consistently supported by their similarity in function and gene expression patterns to known NDD genes. Quantifying the overall similarity using deep learning, we identified 11 high-confidence (> 90% true-positive probabilities) candidate genes: HDAC2, SUPT16H, HECTD4, CHD5, XPO1, GSK3B, NLGN2, ADGRB1, CTR9, BRD3, and MARK2. Conclusions We identified dozens of new candidates for NDD genes. Both the methods and the resources developed here will contribute to the further identification of novel NDD-associated genes.This work was supported by AMED under grant numbers JP21ek0109486, JP21ek0109549, and JP21ek0109493 (N. Matsumoto); JP19dm0107133, JP19ek0109381, 19dm0307028, and 19km0405214 (A. Takata); JSPS KAKENHI grant numbers JP20H03641 (H. Saitsu); JP19H03621 (N. Miyake), JP20H05777, JP21H02855, and JP16H06254 (A. Takata); JP15K10367 (M. Nakashima); JP20K07907 (S. Miyatake); JP20K08164 (T. Mizuguchi); JP20K17936 (A. Fujita); and JP20K16932 (K. Hamanaka); the Takeda Science Foundation (T. Mizuguchi, N. Miyake, H. Saitsu, N. Matsumoto); The Ichiro Kanehara Foundation for the Promotion of Medical Science ; Medical Care (S. Miyatake); and an intramural grant of YCU (K. Hamanaka). The funding source had no role in the conduct of the study.AMED [JP21ek0109486, JP21ek0109549, JP21ek0109493, JP19dm0107133, JP19ek0109381, 19dm0307028, 19km0405214]; JSPS KAKENHI [JP20H03641, JP19H03621, JP20H05777, JP21H02855, JP16H06254, JP15K10367, JP20K07907, JP20K08164, JP20K17936, JP20K16932]; Takeda Science Foundation; Ichiro Kanehara Foundation for the Promotion of Medical Science Medical Care; YC

A quantitative experimental phantom study on MRI image uniformity

Objectives: Our goal was to assess MR image uniformity by investigating aspects influencing said uniformity via a method laid out by the National Electrical Manufacturers Association (NEMA). Methods: Six metallic materials embedded in a glass phantom were scanned (i.e. Au, Ag, Al, Au-Ag-Pd alloy, Ti and Co-Cr alloy) as well as a reference image. Sequences included spin echo (SE) and gradient echo (GRE) scanned in three planes (i.e. axial, coronal, and sagittal). Moreover, three surface coil types (i.e. head and neck, Brain, and temporomandibular joint coils) and two image correction methods (i.e. surface coil intensity correction or SCIC, phased array uniformity enhancement or PURE) were employed to evaluate their effectiveness on image uniformity. Image uniformity was assessed using the National Electrical Manufacturers Association peak-deviation non-uniformity method. Results: Results showed that temporomandibular joint coils elicited the least uniform image and brain coils outperformed head and neck coils when metallic materials were present. Additionally, when metallic materials were present, spin echo outperformed gradient echo especially for Co-Cr (particularly in the axial plane). Furthermore, both SCIC and PURE improved image uniformity compared to uncorrected images, and SCIC slightly surpassed PURE when metallic metals were present. Lastly, Co-Cr elicited the least uniform image while other metallic materials generally showed similar patterns (i.e. no significant deviation from images without metallic metals). Conclusions: Overall, a quantitative understanding of the factors influencing MR image uniformity (e.g. coil type, imaging method, metal susceptibility, and post-hoc correction method) is advantageous to optimize image quality, assists clinical interpretation, and may result in improved medical and dental care