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- Goubet, AG, et al.
(författare)
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Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
- 2021
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 28:12, s. 3297-3315
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
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| 2. |
- Brönnimann, D., et al.
(författare)
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The lay of land: Strontium isotope variability in the dietary catchment of the Late Iron Age proto-urban settlement of Basel-Gasfabrik, Switzerland
- 2018
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Ingår i: Journal of Archaeological Science: Reports. - : Elsevier BV. - 2352-409X. ; 17, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- Basel-Gasfabrik (Switzerland) comprises an extensive La Tène (chiefly Lt D, 150–80 BCE) settlement and two associated cemeteries at which strontium (87Sr/86Sr) isotope analysis of human and animal teeth investigated regional and supra-regional contacts. The interpretation of the analytic data, however, requires information on the isotopic baseline values around the site. Using 102 modern vegetation and 9 water samples from 51 localities, this study characterizes the isotopic ratios of the biologically available strontium of geological units and watercourses around Basel and compares these to 28 human infant, 6 pig, and 5 dog teeth from the site. Furthermore, pedological criteria evaluate the suitability of landforms for crop and pasturelands. The 87Sr/86Sr ratios of the environmental samples from geological units in up to 50 km distance varied between 0.70776 and 0.71794. Human infant teeth exhibited much more homogeneous 87Sr/86Sr ratios (0.70847–0.70950), which coincided largely with those of potential arable soils around Basel and indicate targeted exploitation of landscapes for agriculture. The more variable values of the faunal teeth suggest more widely ranging habitats or imports from the site's hinterlands. Two local isotope ranges were defined based on archaeological enamel samples and modern vegetation data from a confined radius around Basel. The study documents the complexity of distinguishing local and non-local individuals in a geologically heterogeneous region as well as the potential of isotope analyses to explore prehistoric land-use patterns.
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| 4. |
- Fournier, Laure, et al.
(författare)
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Incorporating radiomics into clinical trials : expert consensus endorsed by the European Society of Radiology on considerations for data-driven compared to biologically driven quantitative biomarkers
- 2021
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Ingår i: European Radiology. - : SPRINGER. - 0938-7994 .- 1432-1084. ; 31:8, s. 6001-6012
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Tidskriftsartikel (refereegranskat)abstract
- Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials.
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