| 1. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Namkoong, H, et al.
(author)
-
DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Journal article (peer-reviewed)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.
|
|
| 4. |
|
|
| 5. |
- Wang, QBS, et al.
(author)
-
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
Journal article (peer-reviewed)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.
|
|
| 6. |
|
|
| 7. |
- Chuter, V., et al.
(author)
-
Effectiveness of revascularisation for the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review
- 2024
-
In: Diabetes-Metabolism Research and Reviews. - 1520-7552. ; 40:3
-
Journal article (peer-reviewed)abstract
- Introduction: Peripheral artery disease (PAD) is associated with an increased likelihood of delayed or non-healing of a diabetes-related foot ulcer, gangrene, and amputation. The selection of the most effective surgical technique for revascularisation of the lower limb in this population is challenging and there is a lack of conclusive evidence to support the choice of intervention. This systematic review aimed to determine, in people with diabetes and tissue loss, if direct revascularisation is superior to indirect revascularisation and if endovascular revascularisation is superior to open revascularisation for the outcomes of wound healing, minor or major amputation, and adverse events including mortality. Methods: Title and abstract searches of Medline, Embase, PubMed, and EBSCO were conducted from 1980 to 30th November 2022. Cohort and case-control studies and randomised controlled trials reporting comparative outcomes of direct (angiosome) revascularisation (DR) and indirect revascularisation (IR) or the comparative outcomes of endovascular revascularisation and open or hybrid revascularisation for the outcomes of healing, minor amputation, and major amputation in people with diabetes, PAD and tissue loss (including foot ulcer and/or gangrene) were eligible. Methodological quality was assessed using the Cochrane risk-of-bias tool for randomised trials, the ROBINS-I tool for non-randomised studies, and Newcastle-Ottawa Scale for observational and cohort studies where details regarding the allocation to intervention groups were not provided. Results: From a total 7086 abstracts retrieved, 26 studies met the inclusion criteria for the comparison of direct angiosome revascularisation (DR) and indirect revascularisation (IR), and 11 studies met the inclusion criteria for the comparison of endovascular and open revascularisation. One study was included in both comparisons. Of the included studies, 35 were observational (31 retrospective and 4 prospective cohorts) and 1 was a randomised controlled trial. Cohort study quality was variable and generally low, with common sources of bias related to heterogeneous participant populations and interventions and lack of reporting of or adjusting for confounding factors. The randomised controlled trial had a low risk of bias. For studies of DR and IR, results were variable, and it is uncertain if one technique is superior to the other for healing, prevention of minor or major amputation, or mortality. However, the majority of studies reported that a greater proportion of participants receiving DR healed compared with IR, and that IR with collaterals may have similar outcomes to DR for wound healing. For patients with diabetes, infrainguinal PAD, and an adequate great saphenous vein available for use as a bypass conduit who were deemed suitable for either surgical procedure, an open revascularisation first approach was superior to endovascular therapy to prevent a major adverse limb event or death (Hazard Ratio: 0.72; 95% CI 0.61-0.86). For other studies of open and endovascular approaches, there was generally no difference in outcomes between the interventions. Conclusions: The majority of available evidence for the effectiveness of DR and IR and open and endovascular revascularisation for wound healing and prevention of minor and major amputation and adverse events including mortality in people with diabetes, PAD and tissue loss is inconclusive, and the certainty of evidence is very low. Data from one high quality randomised controlled trial supports the use of open over endovascular revascularisation to prevent a major limb event and death in people with diabetes, infrainguinal disease and tissue loss who have an adequate great saphenous vein available and who are deemed suitable for either approach.
|
|
| 8. |
- Erhardt, Tobias, et al.
(author)
-
High-resolution aerosol concentration data from the Greenland NorthGRIP and NEEM deep ice cores
- 2022
-
In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:3, s. 1215-1231
-
Journal article (peer-reviewed)abstract
- Records of chemical impurities from ice cores enable us to reconstruct the past deposition of aerosols onto polar ice sheets and alpine glaciers. Through this they allow us to gain insight into changes of the source, transport and deposition processes that ultimately determine the deposition flux at the coring location. However, the low concentrations of the aerosol species in the ice and the resulting high risk of contamination pose a formidable analytical challenge, especially if long, continuous and highly resolved records are needed. Continuous flow analysis, CFA, the continuous melting, decontamination and analysis of ice-core samples has mostly overcome this issue and has quickly become the de facto standard to obtain high-resolution aerosol records from ice cores after its inception at the University of Bern in the mid-1990s.Here, we present continuous records of calcium (Ca2+), sodium (Na+), ammonium (NH+4), nitrate (NO-3) and electrolytic conductivity at 1 mm depth resolution from the NGRIP (North Greenland Ice Core Project) and NEEM (North Greenland Eemian Ice Drilling) ice cores produced by the Bern Continuous Flow Analysis group in the years 2000 to 2011 (Erhardt et al., 2021). Both of the records were previously used in a number of studies but were never published in full 1 mm resolution. Alongside the 1 mm datasets we provide decadal averages, a detailed description of the methods, relevant references, an assessment of the quality of the data and its usable resolution. Along the way we will also give some historical context on the development of the Bern CFA system.
|
|
| 9. |
- Mizumaki, H, et al.
(author)
-
A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia
- 2021
-
In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:6, s. 1581-1590
-
Journal article (peer-reviewed)abstract
- Leukocytes that lack HLA allelic expression are frequently detected in patients with acquired aplastic anemia (AA) who respond to immunosuppressive therapy (IST), although the exact mechanisms underlying the HLA loss and HLA allele repertoire likely to acquire loss-of-function mutations are unknown. We identified a common nonsense mutation at position 19 (c.19C>T, p.R7X) in exon 1 (Exon1mut) of different HLA-A and -B alleles in HLA-lacking granulocytes from AA patients. A droplet digital PCR (ddPCR) assay capable of detecting as few as 0.07% Exon1mut HLA alleles in total DNA revealed the mutation was present in 29% (101/353) of AA patients, with a median allele frequency of 0.42% (range, 0.071% to 21.3%). Exon1mut occurred in only 12 different HLA-A (n=4) and HLA-B (n=8) alleles, including B*40:02 (n=31) and A*02:06 (n=15), which correspond to 4 HLA supertypes (A02, A03, B07, and B44). The percentages of patients who possessed at least one of these 12 HLA alleles were significantly higher in the 353 AA patients (92%, P
|
|
| 10. |
- Püttner, R., et al.
(author)
-
Argon KLL Auger spectrum: Initial states, core-hole lifetimes, shake, and knock-down processes
- 2020
-
In: Physical Review A. - : AMER PHYSICAL SOC. - 2469-9926 .- 2469-9934. ; 102:5
-
Journal article (peer-reviewed)abstract
- State-of-the-art argon KLL Auger spectra measured using photon energies of hν=3216 and 3400 eV are presented along with an Ar [1s] photoelectron spectrum (square brackets indicate holes in the respective orbital). The two different photon energies used for measuring the Auger spectra allow distinguishing between the shake transitions during the Auger decay and the Auger transitions of the photoelectron satellites. A complete assignment of satellite transitions is provided, partially based on configuration-interaction calculations. In addition, Ar [1s3(s,p)]n′l′→[2p2(1D2)] transitions are observed, which can be explained by knock-down transitions leading to a direct exchange of angular momentum between the excited electron and the Auger electron. The lifetime broadenings of the Ar [2s] single-core-hole state and the [2s2] and [2s2p] double-core-hole states are also determined, confirming previously observed trends for double-core-hole states. © 2020 American Physical Society.
|
|
