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  • Springer Science and Business Media LLC  (19)
  • 1
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    DOCK2 is involved in the host genetics and biology of severe COVID-19
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 609, No. 7928 ( 2022-09-22), p. 754-760
    Abstract: Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1–5 . 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.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-05163-5
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 2
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    The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-08-22)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-08-22)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-32276-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 3
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    Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
    Springer Science and Business Media LLC ; 2023
    In:  Nature Genetics Vol. 55, No. 5 ( 2023-05), p. 753-767
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 55, No. 5 ( 2023-05), p. 753-767
    Abstract: Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of 〉 895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-023-01375-1
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 4
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    Characteristics of hospitalized patients with COVID-19 during the first to fifth waves of infection: a report from the Japan COVID-19 Task Force
    Springer Science and Business Media LLC ; 2022
    In:  BMC Infectious Diseases Vol. 22, No. 1 ( 2022-12-12)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12-12)
    Abstract: We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. Methods We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. Results Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9] ) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p  〈  0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p  〈  0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. Conclusions We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-022-07927-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041550-3
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  • 5
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    Annual dialysis data report 2020, JSDT renal data registry
    Springer Science and Business Media LLC ; 2024
    In:  Renal Replacement Therapy Vol. 10, No. 1 ( 2024-03-11)
    Details
    In: Renal Replacement Therapy, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2024-03-11)
    Abstract: The 2020 Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) annual survey was sent to 4493 dialysis facilities in Japan. Methods Questionnaires were sent to all facilities that provide patients with dialysis therapy in Japan. Data were collected and compiled to form cross-sectional results of renal replacement therapy from various aspects. Results In total, 4437 facilities (98.8%) responded to the facility questionnaire and 4271 (95.1%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year, reaching 347,671 at the end of 2020 and giving a prevalence rate of 2754 patients per million population. The mean age was 69.40 years. Diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.5%), followed by chronic glomerulonephritis (25.3%) and nephrosclerosis (12.1%). There were 40,744 incident dialysis patients during 2020, representing a decrease of 141 from 2019. The average age of patients on dialysis was 70.88 years, with diabetic nephropathy being the most common underlying disease (40.7%) second most common was nephrosclerosis (17.5%), which was unchanged from the previous year and surpassed chronic glomerulonephritis (15.0%). There were 34,414 patient deaths in 2020; the crude mortality rate was 9.9%. The main causes of death were heart failure (22.4%), infection (21.5%), and malignancy (9.0%), which were almost the same as the percentages for the previous year. Since 2012, the number of patients treated by hemodiafiltration has increased rapidly; in 2020, the number of patients on this modality was 163,825, accounting for 47.1% of all patients on maintenance dialysis. The number of patients on peritoneal dialysis has been on the rise since 2017, reaching 10,338 in 2020; 20.8% of whom received combined therapy with hemodialysis or hemodiafiltration, showing no change from the previous year. A total of 751 patients were on home hemodialysis at the end of 2020, representing a decrease of 9 from the end of 2018. In 2020, coronavirus disease 2019 (COVID-19) infection and malignancy were added as new items in the survey. Continuing on from the 2019 survey, history of kidney donation for a living-donor transplant was investigated. Conclusions Present issues and challenges in renal replacement therapy were identified in the responses to the new questionnaire items included in this survey. A more detailed evaluation with adjustment for patient background factors should clarify the characteristics of the underlying diseases and conditions in dialysis patients. Trial registration The JRDR was approved by the Japanese Society for Dialysis Therapy ethics committee. It was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry on 10 September 2020 and in the UMIN clinical trials registration system (UMIN000018641).
    Type of Medium: Online Resource
    ISSN: 2059-1381
    URL: Article
    DOI: 10.1186/s41100-024-00531-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2866852-2
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  • 6
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    Annual dialysis data report for 2018, JSDT Renal Data Registry: survey methods, facility data, incidence, prevalence, and mortality
    Springer Science and Business Media LLC ; 2020
    In:  Renal Replacement Therapy Vol. 6, No. 1 ( 2020-12)
    Details
    In: Renal Replacement Therapy, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2020-12)
    Abstract: The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was sent to 4458 dialysis facilities at the end of 2018; among these facilities, 4402 facilities (98.7%) responded to the facility questionnaire, and 4222 (94.7%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year; as of the end of 2018, it had reached 339,841 patients, representing 2688 patients per million population. Among the prevalent dialysis patients, the mean age was 68.75 years, and diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (26.8%) and nephrosclerosis (10.8%). The number of incident dialysis patients was 40,468, and a reduction by 491 from 2017. The mean age of the incident dialysis patients was 69.99 years old. Diabetic nephropathy was also the most common primary disease (42.3%), representing a 0.2 percent point reduction from 2017. The distribution of diabetic nephropathy appears to have reached a plateau. The number of deceased patients during 2018 was 33,863, and the crude annual death rate was 10.0%. Heart failure was the most common cause of death (23.5%), followed by infection (21.3%) and malignant tumor (8.4%); these causes were similar to those for 2017. The number of patients receiving hemodiafiltration has been increasing since 2012, reaching 125,793 or 37.0% of all dialysis patients at the end of 2018. The number of patients receiving peritoneal dialysis has been gradually increasing since 2017, reaching 9445, and 19.7% of these patients were treated using a combination of peritoneal dialysis and hemodialysis or hemodiafiltration. The proportion of patients receiving combination therapy has remained at around 20% of all peritoneal dialysis patients. The number of patients undergoing home hemodialysis was 720, representing an increase of 36 patients from 2017. The 2018 JRDR survey included several topics such as the present status of the patient kinetics of chronic dialysis patients at the end of 2018, water treatment and hemodiafiltration, peritoneal dialysis, treatments for diabetes, mental and physical conditions, and the present status of viral hepatitis. In this paper, we describe the patient and facility kinetics. Trial registration The JRDR was approved by the ethics committee of the JSDT (approval number 1-3) and was registered in the “University hospital Medical Information Network (UMIN) Clinical Trials Registry” under the clinical trial ID of UMIN000018641 on August 8, 2015: (Accessed June 2, 2020)
    Type of Medium: Online Resource
    ISSN: 2059-1381
    URL: Article
    DOI: 10.1186/s41100-020-00286-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2866852-2
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  • 7
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    Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study
    Springer Science and Business Media LLC ; 2024
    In:  Journal of Gastroenterology
    Details
    In: Journal of Gastroenterology, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 0944-1174 , 1435-5922
    URL: Article
    DOI: 10.1007/s00535-023-02071-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 1473159-9
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  • 8
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    Annual dialysis data report of the 2018 JSDT Renal Data Registry: dementia, performance status, and exercise habits
    Springer Science and Business Media LLC ; 2021
    In:  Renal Replacement Therapy Vol. 7, No. 1 ( 2021-12)
    Details
    In: Renal Replacement Therapy, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-12)
    Abstract: According to the annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) conducted at the end of 2018, there were a total of 339,841 patients receiving dialysis (hereinafter, dialysis patients) in Japan. The survey included questions regarding the presence/absence of dementia, the performance status (PS), and the exercise habits of individual patients. The survey revealed that 10.8% of all dialysis patients had dementia (1.8% in the age group of less than 65 years, 6.8% in the age group of 65–74 years, and 22.7% in the age group of 75 years or older). These prevalences of dementia were approximately equal to those estimated from the survey conducted in 2010. Regarding PS, the percentage of patients with lower activity levels tended to be relatively high among patients who were less than 15 years old and those who were 60 years old or older. Concerning the exercise habits of dialysis patients, the percentage of patients who were classified as “not at all or hardly” in response to the question about exercise habit was the highest (60–80%) of all the exercise habit classifications in each of the age groups analyzed.
    Type of Medium: Online Resource
    ISSN: 2059-1381
    URL: Article
    DOI: 10.1186/s41100-021-00357-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2866852-2
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  • 9
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    Mapping the human genetic architecture of COVID-19
    Springer Science and Business Media LLC ; 2021
    In:  Nature Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-021-03767-x
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 10
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    Substitution for copper in a high-Tc superconductor YBa2Cu3O7–δ
    Springer Science and Business Media LLC ; 1987
    In:  Nature Vol. 328, No. 6130 ( 1987-8), p. 512-514
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 328, No. 6130 ( 1987-8), p. 512-514
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/328512a0
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1987
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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