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- 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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| 3. |
- 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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| 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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| 6. |
- Beuther, H., et al.
(författare)
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JWST Observations of Young protoStars (JOYS): Outflows and accretion in the high-mass star-forming region IRAS 23385+6053
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
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Tidskriftsartikel (refereegranskat)abstract
- Context. Understanding the earliest stages of star formation, and setting it in the context of the general cycle of matter in the interstellar medium, is a central aspect of research with the James Webb Space Telescope (JWST). Aims. The JWST program JOYS (JWST Observations of Young protoStars) aims to characterize the physical and chemical properties of young high- and low-mass star-forming regions, in particular the unique mid-infrared diagnostics of the warmer gas and solid-state components. We present early results from the high-mass star formation region IRAS 23385+6053. Methods. The JOYS program uses the Mid-Infrared Instrument (MIRI) Medium Resolution Spectrometer (MRS) with its integral field unit (IFU) to investigate a sample of high- and low-mass star-forming protostellar systems. Results. The full 5-? 28 μm MIRI MRS spectrum of IRAS 23385+6053 shows a plethora of interesting features. While the general spectrum is typical for an embedded protostar, we see many atomic and molecular gas lines boosted by the higher spectral resolution and sensitivity compared to previous space missions. Furthermore, ice and dust absorption features are also present. Here, we focus on the continuum emission, outflow tracers such as the H2(0-? 0)S(7), [FeII](4F9/2-6D9/2), and [NeII](2P1/2-2P3/2) lines, and the potential accretion tracer Humphreys α H I(7-6). The short-wavelength MIRI data resolve two continuum sources, A and B; mid-infrared source A is associated with the main millimeter continuum peak. The combination of mid-infrared and millimeter data reveals a young cluster in the making. Combining the mid-infrared outflow tracers H2, [FeII], and [NeII] with millimeter SiO data reveals a complex interplay of at least three molecular outflows driven by protostars in the forming cluster. Furthermore, the Humphreys α line is detected at a 3-?4σ? level toward the mid-infrared sources A and B. One can roughly estimate both accretion luminosities and corresponding accretion rates to be between ∼2.6 × 10-6 and ∼0.9 × 10-4 Mo yr-1. This is discussed in the context of the observed outflow rates. Conclusions. The analysis of the MIRI MRS observations for this young high-mass star-forming region reveals connected outflow and accretion signatures, as well as the enormous potential of JWST to boost our understanding of the physical and chemical processes at play during star formation.
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