社会的ワーキングメモリ：人物情報保持の認知的基盤

付記する学位プログラム名: デザイン学大学院連携プログラム京都大学0048新制・課程博士博士(教育学)甲第22712号教博第254号新制||教||197(附属図書館)京都大学大学院教育学研究科教育科学専攻(主査)教授 齊藤 智, 教授 Emmanuel MANALO, 准教授 野村 理朗, 教授 田中 利幸学位規則第4条第1項該当Doctor of Philosophy (Education)Kyoto UniversityDGA

The detrimental effect of semantic similarity in short-term memory tasks: A meta-regression approach

The literature suggests that semantic similarity has a weak or null effect for immediate serial reconstruction and a facilitative effect for immediate serial recall. These observed semantic similarity effects are inconsistent with the assumptions of short-term memory (STM) models on the detrimental effect of similarity (e.g., confusion) and with observations of a robust detrimental effect of phonological similarity. Our review indicates that the experimental results are likely dependent on the manipulation strength for semantic similarity and that manipulations used in previous studies might have affected semantic assvociation as well as semantic similarity. To address these possible issues, two indices are proposed: (a) strength of manipulation on semantic similarity, gained by quantifying semantic similarity based on Osgood and associates’ dimensional view of semantics, and (b) inter-item associative strength, a possible confounding factor. Our review and the results of a meta-regression analysis using these two indices suggest that semantic similarity has a detrimental effect on both serial reconstruction and serial recall, while semantic association, which is correlated with semantic similarity, contributes to an apparent facilitative effect. An effect that is not attributable to similarity or association was also implied. Review on item and order memory further suggests the facilitative effect of semantic association on item memory and the detrimental effect of the semantic similarity on order memory. Based on our findings, we propose a unified explanation of observations of semantic similarity effects for both serial reconstruction and serial recall that is in good accord with STM models

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

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Person-based organisation in working memory

Working memory (WM) helps maintain information during a variety of cognitive activities in scholastic and social situations. This study focused on a social aspect of WM, specifically, how it maintains information related to people. We investigated person-based organisation of information across four experiments using the reading span task (RST). Person information (i.e., an occupational title) was provided with sentences manipulated across conditions. In Experiment 1, consistent with the assumption that person-based organisation exists in WM, participants performed better when they could easily organise target items in a person-based manner (person-based organisation) than when they were prevented from using such information. Experiments 2 and 3 investigated the process of person-based organisation using alphabetical letters as targets (unlike words in Experiment 1), which prevented possible semantic associations between person information and target items. Experiment 2 replicated Experiment 1, suggesting that contextual retrieval is critical in person-based organisation. Experiment 3 showed the person-based organisation effect even after controlling for the difficulty of the process component in the RST. The results of Experiments 2 and 3 suggest that person information could serve as contextual retrieval cues in WM. Experiment 4, which did not show the organisation effect based on information about an object (i.e., a fruit name), suggests along with Experiments 1 to 3 that the observed organisation effect in Experiments 1 to 3 was specific to person information. In addition to showing the enhanced WM performance by person-based organisation, we have suggested contextual cue-dependent retrieval as the underlying cognitive process

SOCIAL DIMENSIONS IN SIMILARITY JUDGMENT OF FACES

We spontaneously infer the social traits of people from their appearance. In the current study, the 3 possibility that the perceived similarity of faces is based on perceived social traits, more 4 specifically, evaluations on valence and power dimensions, was tested. Pilot studies provided the 5 dissimilarity data of Japanese female faces with the similarity judgment task and validated them 6 with a memory task. The current study demonstrated that two axes provided by multidimensional 7 scaling analysis to the dissimilarity data could be interpreted in terms of valence and power 8 dimensions. As participants were not explicitly asked to focus on social dimensions when rating 9 the similarities of faces, the results suggested that participants automatically used social 10 dimensions in the similarity judgment task. The present study suggests that the similarity of faces 11 across social dimensions affects the perceived similarity of faces