| 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. |
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| 8. |
- Raposeiras-Roubin, Sergio, et al.
(författare)
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Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome : The BleeMACS score
- 2018
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 254, s. 10-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome(ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients.Methods: The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI.Results: Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts.Conclusions: The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding.
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| 9. |
- Shen, B., et al.
(författare)
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Enhanced boiling heat transfer on surfaces patterned with mixed wettability
- 2018
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Ingår i: International Heat Transfer Conference. - : Begell House Inc.. ; , s. 1379-1386
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Konferensbidrag (refereegranskat)abstract
- Amongst an extensive collection of surface characteristics that could affect boiling performance, surface wettability (as measured by the contact angle with water) proves to play a unique role in potentially manipulating bubble behavior to the advantage of higher heat transfer rates. In this study, we show experimentally that controlled bubble behavior be realized under the surface design incorporating these two characteristics (namely, by coating an array of hydrophobic spots on a hydrophilic substrate), which leads to a great enhancement in boiling heat transfer under various conditions. In reduced-pressure pool boiling, the strong pinning of the bubble contact line at the border between the hydrophilic and hydrophobic regions manages to prevent total deactivation of nucleation sites. As a result, the deleterious transition to intermittent boiling is effectively delayed, whereby no heat transfer deterioration occurs until a very low pressure of about 8 kPa is reached. Moreover, in subcooled boiling, bubble growth on a patterned surface is found to be facilitated by a pronounced presence of dissolved gas in defiance of exhaustive degassing efforts through continuous boiling, thanks to an unusually strong retention of gas contents by the hydrophobic surface. As experimental and numerical evidence show, only bubbles with sufficiently high concentrations of gas components (i.e., causing weakened condensation) are able to grow large enough on the hydrophobic surface such that periodic pinch-offs might take place, which is responsible for most of the initial heat transfer enhancement before large-scale bubble nucleation starts on the hydrophilic surface as well.
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| 10. |
- Wang, G., et al.
(författare)
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Enhanced High Thermal Conductivity Cellulose Filaments via Hydrodynamic Focusing
- 2022
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 22:21, s. 8406-8412
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Tidskriftsartikel (refereegranskat)abstract
- Nanocellulose is regarded as a green and renewable nanomaterial that has attracted increased attention. In this study, we demonstrate that nanocellulose materials can exhibit high thermal conductivity when their nanofibrils are highly aligned and bonded in the form of filaments. The thermal conductivity of individual filaments, consisting of highly aligned cellulose nanofibrils, fabricated by the flow-focusing method is measured in dried condition using a T-type measurement technique. The maximum thermal conductivity of the nanocellulose filaments obtained is 14.5 W/m-K, which is approximately five times higher than those of cellulose nanopaper and cellulose nanocrystals. Structural investigations suggest that the crystallinity of the filament remarkably influence their thermal conductivity. Smaller diameter filaments with higher crystallinity, that is, more internanofibril hydrogen bonds and less intrananofibril disorder, tend to have higher thermal conductivity. Temperature-dependence measurements also reveal that the filaments exhibit phonon transport at effective dimension between 2D and 3D.
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