| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. 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.
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| 4. |
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| 5. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)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.
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| 7. |
- Hidaka, R., et al.
(författare)
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Impact of the Comprehensive Awareness Modification of Mouth, Chewing and Meal (CAMCAM) Program on the Attitude and Behavior Towards Oral Health and Eating Habits as Well as the Condition of Oral Frailty : A Pilot Study
- 2023
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer-Verlag Italia s.r.l.. - 1279-7707 .- 1760-4788. ; 27:5, s. 340-
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Preserving sufficient oral function and maintaining adequate nutrition are essential for preventing physical frailty and the following long-term care. We recently developed the 6-month Comprehensive Awareness Modification of Mouth, Chewing And Meal (CAMCAM) program, in which participants gather monthly to learn about oral health and nutrition while eating a textured lunch together. This study examined whether the CAMCAM program could improve attitude and behavior towards oral health, mastication, and diet as well as ameliorate oral frailty in community-dwelling older adults. Design: Single-arm pre-post comparison study. Setting and Participants: A total of 271 community-dwelling adults (72.3 ± 5.7 years of age; 159 women [58.7%]) in 4 Japanese municipalities were recruited, of which 249 participants (92%) were assessed at the final evaluation. Intervention: Participants gathered once a month at community centers to learn about oral health and nutrition while eating a “munchy” textured lunch containing proper nutrition. Measurements: Oral frailty, frailty, and eating behavior were evaluated with the Oral Frailty Index-8 (OFI-8), Kihon checklist (KCL), and CAMCAM checklist, respectively. Participants were divided into Oral frailty (OF) and Robust groups according to OFI-8 scores. The differences in KCL and CAMCAM checklist results between the OF and Robust groups were statistically tested along with changes in scores after the program. Results: KCL and CAMCAM checklist scores were significantly lower in the OF group at the initial assessment. OFI-8 and KCL findings were significantly improved in the OF group after completing the program (all P <0.05). Regarding the CAMCAM checklist, awareness of chewing improved significantly in the Robust group (P=0.009), with a similar tendency in the OF group (P=0.080). Conclusion: The findings of this pilot study suggest that the CAMCAM program may improve both oral and systemic frailty in addition to attitudes towards chewing, oral health, and meals, especially in individuals with oral frailty. The CAMCAM program merits expansion as a community-based frailty prevention program.
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