Learning coefficients for hierarchical learning models in Bayesian Estimation

Recently, singular learning theory has been analyzed using algebraic geometry as its basis. It is essential to determine the normal crossing divisors of learning machine singularities through a blowing-up process to observe the behaviors of state probability functions in learning theory. In this paper, we investigate learning coefficients for multi-layered neural networks with linear units, especially when dealing with a large number of layers in Bayesian estimation. We make use of the valuable results obtained by Aoyagi(2023), which provide the main terms for Bayesian generalization error and the average stochastic complexity (free energy). These terms are widely employed in numerical experiments, such as in information criteria

The relationship between childhood aerobic fitness and brain functional connectivity

AbstractSeveral studies have indicated that higher levels of childhood aerobic fitness is associated with superior cognitive function, and this association is disproportionately observed in tasks requiring greater top-down control. We designed the current study to clarify the relationship between childhood fitness and top-down control in terms of functional connectivity among brain regions, by evaluating phase-locking values (PLVs), which is a measure of frequency-specific phase synchrony between electroencephalographic signals during a visual search task. Lower-fit and higher-fit children performed a visual search task that included feature search and conjunction search conditions. The conjunction search condition required greater top-down control to reduce interference from task-irrelevant distractors that shared a basic feature with the target. Results indicated that higher-fit children exhibited higher response accuracy relative to lower-fit children across search conditions. The results of PLVs showed that higher-fit children had greater functional connectivity for the conjunction relative to the feature search condition, whereas lower-fit children showed no difference in functional connectivity between search conditions. Furthermore, PLVs showed different time courses between groups; that is, higher-fit children sustained upregulation of top-down control throughout the task period, whereas lower-fit children transiently upregulated top-down control after stimulus onset and could not sustain the upregulation. These findings suggest that higher levels of childhood aerobic fitness is related to brain functional connectivity involved in the sustained upregulation of top-down control

Implementation and Evaluation of Teacher Training on Food Allergy Education in Kindergarten ― Aiming to Foster Children Leading Healthy Lives, Regardless of the Presence of Food Allergies ―

　本研究の目的は，幼稚園において食物アレルギーと共に生活する子供を育む方策を検討することである。本研究では，食物アレルギー教育に関する教員研修を行い，研修中の教員の反応と研修前後のアンケート調査の結果を基に，その効果を評価した。 　研修後には,食物アレルギーやその対応によって生じる子供達の心境へも目を向ける必要性の理解が深まった。また事例検討を通して，幼稚園においても幼児なりに食物アレルギーを理解して対応できるように伝える必要性があると明らかになり，実際に指導できそうな具体的な場面も挙げられた。さらに研修中，脈々と受け継がれてきた“教育観”と，現在の多様化した時代背景や子供達の実態，社会的なつながりを踏まえて更新される“教育観”の中で揺れ動く教員の姿が見られ，その揺らぎや葛藤自体が，個別のニーズを適切に受け入れ，多様性を尊重する教師の観念を磨くことにつながっていると考えられた。This study aims to explore strategies for nurturing kindergarten children with food allergies. Teacher training on food allergy education was conducted, and its effectiveness was evaluated based on teacher reactions and pre- and post-training surveys. The training deepened the understanding of the importance of addressing the emotional needs of children with food allergies. Case studies revealed the necessity of conveying this understanding to preschoolers and equipping them to respond appropriately. The study also observed teachers navigating between traditional and evolving educational perspectives, with observed fluctuations and conflicts contributing to refining teachers' beliefs tow ard embracing individual needs and diversity

NGS utility for diagnosis of MCA/ID

Background : In clinical practice, a large proportion of patients with multiple congenital anomalies and/or intellectual disabilities (MCA/ID) lacks a specific diagnosis. Recently, next-generation sequencing (NGS) has become an efficient strategy for genetic diagnosis of patients with MCA/ID. Objective : To review the utility of NGS for the diagnosis of patients with MCA/ID. Method : Patients with MCA/ID were recruited between 2013 and 2017. Molecular diagnosis was performed using NGS-based targeted panel sequencing for 4,813 genes. Promising causative variants underwent confirmation by Sanger sequencing or chromosomal microarray. Results : Eighteen patients with MCA/ID were enrolled in this study. Of them, 8 cases (44%) were diagnosed by targeted panel sequencing. Most of diagnosed patients were able to receive better counseling and more appropriate medical management. Conclusion : NGS-based targeted panel sequencing seems to be an effective testing strategy for diagnosis of patients with MCA/ID

Three Severe Cases of Viral Infections with Post-Kidney Transplantation Successfully Confirmed by Polymerase Chain Reaction and Flow Cytometry

Viral infections in patients with post-kidney transplantation are often difficult to diagnose as well as treat. We herein report three cases with severe viral infections after kidney transplantation. All their causative pathogens could be detected promptly by polymerase chain reaction and flow cytometry during the early stages of infection. These examinations would also be of great use to monitor therapeutic responses and disease activity. It is indeed true that no specific treatment is available for most of the viral infections, but we should be aware that some infections, such as Epstein-Barr virus infection, can be treatable with prompt and specific treatment, such as rituximab

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed

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