| 1. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 2. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 4. |
- Schiller, D, et al.
(författare)
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The Human Affectome
- 2024
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Ingår i: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Tidskriftsartikel (refereegranskat)
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| 5. |
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| 6. |
- Smid, Marcel, et al.
(författare)
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Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.
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| 8. |
- Rocha, W. R.M., et al.
(författare)
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JWST Observations of Young protoStars (JOYS+): Detecting icy complex organic molecules and ions: I. CH4, SO2, HCOO, OCN, H2CO, HCOOH, CH3CH2OH, CH3CHO, CH3OCHO, and CH3COOH
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Complex organic molecules (COMs) are ubiquitously detected in the gas phase and thought to be mostly formed on icy grains. Nevertheless, there have not been any unambiguous detections of COMs larger than CH3OH in ices reported thus far. Exploring this matter in greater detail has now become possible with the unprecedented possibilities offered by the James Webb Space Telescope (JWST) within the infrared (IR) spectral range with its very high sensitivity and spectral resolution in the critical 5 10 μm range, the fingerprint region of oxygen-bearing COMs. Aims. In the JWST Observations of Young protoStars (JOYS+) program, more than 30 protostars are undergoing observation with the Medium Resolution Spectrograph (MRS) of the Mid-IR Instrument (MIRI). The goal of this study is to comprehensively explore the COMs ice signatures in one low- and one high-mass protostar: NGC 1333 IRAS 2A and IRAS 23385+6053, respectively. Methods. We performed global continuum and silicate subtractions of the MIRI-MRS spectra, followed by a local continuum subtraction in optical depth scale in the range around 6.8 and 8.6 μm, the ice COM fingerprint region. We explored different choices for the local continuum and silicate subtraction. Next, we fit the observational data with a large sample of available IR laboratory ice spectra. We used the ENIIGMA fitting tool, a genetic algorithm-based code that not only finds the best fit between the lab data and the observations, but also performs a statistical analysis of the solutions, such as deriving the confidence intervals and quantifying fit degeneracy. Results. We report the best fits for the spectral ranges between 6.8 and 8.6 μm in NGC 1333 IRAS 2A and IRAS 23385+6053, originating from simple molecules and COMs, as well as negative ions. Overall, we find that ten chemical species are needed to reproduce the astronomical data. The strongest feature in this range (7.7 μm) is dominated by CH4, with contributions from SO2 and OCN. Our results indicate that the 7.2 and 7.4 μm bands are mostly dominated by HCOO. We also find statistically robust detections of COMs based on multiple bands, most notably, CH3CHO, CH3CH2OH, and CH3OCHO. We also report a likely detection of CH3COOH. Based on the ice column density ratios between CH3CH2OH and CH3CHO of NGC 1333 IRAS 2A and IRAS 23385+6053, we find compelling evidence that these COMs are formed on icy grains. Finally, the derived ice abundances for NGC 1333 IRAS 2A correlate well with those in comet 67P/GC within a factor of 5. Conclusions. Based on the high-quality JWST (MIRI-MRS) spectra, we conclude that COMs are present in interstellar ices, thus providing additional proof for the solid-state origin of these species in star-forming regions. In addition, the good correlation between the ice abundances in comet 67P and NGC 1333 IRAS 2A is fully in line with the idea that cometary COMs may be inherited from the early protostellar phases to a significant extent.
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