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| 114. |
- Hoffmann, Markus, et al.
(författare)
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Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. Methods: We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, respectively, by Camostat mesylate and its metabolite GBPA. Findings: We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. Interpretation: Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA. Funding: NIH, Damon Runyon Foundation, ACS, NYCT, DFG, EU, Berlin Mathematics center MATH+, BMBF, Lower Saxony, Lundbeck Foundation, Novo Nordisk Foundation.
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| 115. |
- Im, Annie, et al.
(författare)
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Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
- 2020
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
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Tidskriftsartikel (refereegranskat)abstract
- Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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| 116. |
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| 117. |
- Keller, Mark W., et al.
(författare)
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Near-unity spin Hall ratio in NixCu1-x alloys
- 2019
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Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 99:21
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Tidskriftsartikel (refereegranskat)abstract
- We report a large spin Hall effect in the 3d transition metal alloy NixCu1-x for x is an element of {0.3, 0.75}, detected via the ferromagnetic resonance of a permalloy (Py = Ni80Fe20) film deposited in a bilayer with the alloy. A thickness series at x = 0.6, for which the alloy is paramagnetic at room temperature, allows us to determine the spin Hall ratio theta(SH) approximate to 1, spin diffusion length lambda(s), spin mixing conductance G(up arrow down arrow) and damping due to spin memory loss alpha(SML). We compare our results with similar experiments on Py/Pt bilayers measured using the same method. Ab initio band structure calculations with disorder and spin-orbit coupling suggest an intrinsic spin Hall effect in NixCu1-x alloys, although the experiments here cannot distinguish between extrinsic and intrinsic mechanisms.
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| 118. |
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| 119. |
- Kompani, K., et al.
(författare)
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Who Said What : A Multi-Country Content Analysis of European Health Organisations' COVID-19 Social Media Communication
- 2022
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Ingår i: International Journal of Public Health. - : Frontiers Media SA. - 1661-8556 .- 1661-8564. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: As a risk communication tool, social media was mobilised at an unprecedented level during the COVID-19 pandemic. This study examined health authorities' risk communication on social media in response to the pandemic in 2020. Methods: We analysed 1,633 COVID-19-related posts from 15 social media accounts managed by official health authorities in Germany, Norway, Sweden, Switzerland, and the United Kingdom. Results: The rate at which the authorities posted about COVID-19 on social media fluctuated throughout 2020. Each account's posting frequency peaked between March and May 2020, before dropping considerably during the summer. The messages that the organisations focused on also varied throughout the year but covered most risk communication guidelines. Yet, our analysis highlighted themes that were communicated infrequently, such as long COVID or exercising during the pandemic. Conclusion: With more individuals now following health authorities on social media, platforms such as Instagram hold great potential for future risk communication campaigns and strategies.
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| 120. |
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