| 1. |
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| 2. |
- Barbe, Jeremy, et al.
(författare)
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Silicon nanocrystals on amorphous silicon carbide alloy thin films : Control of film properties and nanocrystals growth
- 2012
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Ingår i: Thin Solid Films. - : Elsevier. - 0040-6090 .- 1879-2731. ; 522, s. 136-144
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Tidskriftsartikel (refereegranskat)abstract
- The present study demonstrates the growth of silicon nanocrystals on amorphous silicon carbide alloy thin films. Amorphous silicon carbide films [a-Si1 − xCx:H (with x < 0.3)] were obtained by plasma enhanced chemical vapor deposition from a mixture of silane and methane diluted in hydrogen. The effect of varying the precursor gas-flow ratio on the film properties was investigated. In particular, a wide optical band gap (2.3 eV) was reached by using a high methane-to-silane flow ratio during the deposition of the a-Si1 − xCx:H layer. The effect of short-time annealing at 700 °C on the composition and properties of the layer was studied by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. It was observed that the silicon-to-carbon ratio in the layer remains unchanged after short-time annealing, but the reorganization of the film due to a large dehydrogenation leads to a higher density of SiC bonds. Moreover, the film remains amorphous after the performed short-time annealing. In a second part, it was shown that a high density (1 × 1012 cm− 2) of silicon nanocrystals can be grown by low pressure chemical vapor deposition on a-Si0.8C0.2 surfaces at 700 °C, from silane diluted in hydrogen. The influence of growth time and silane partial pressure on nanocrystals size and density was studied. It was also found that amorphous silicon carbide surfaces enhance silicon nanocrystal nucleation with respect to SiO2, due to the differences in surface chemical properties.
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| 3. |
- Brunet-Ratnasingham, Elsa, et al.
(författare)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized COVID-19 patients. Integrated analysis using k-means reveal four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors are delineated by high and low antibody responses. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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| 4. |
- Brunet-Ratnasingham, Elsa, et al.
(författare)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1, s. 4177-
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Tidskriftsartikel (refereegranskat)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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| 5. |
- de Glanville, William A., et al.
(författare)
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Poor performance of the rapid test for human brucellosis in health facilities in Kenya
- 2017
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Human brucellosis is considered to be an important but typically under-diagnosed cause of febrile illness in many low and middle-income countries. In Kenya, and throughout East Africa, laboratory diagnosis for the disease is based primarily on the febrile antigen Brucella agglutination test (FBAT), yet few studies of the diagnostic accuracy of this test exist. Assessment of the performance of the FBAT is essential for its appropriate clinical use, as well as for evaluating surveillance data reported by public health systems. To assess FBAT performance, we collected sera from people with symptoms compatible with brucellosis attending two health facilities in Busia County, Kenya. Sera were tested using the FBAT and results compared with those from the Rose Bengal Test (RBT), an assay with well-known performance characteristics. Positives on either test were confirmed using the classical serum agglutination test (SAT)-Coombs test combination and a rapid IgM/IgG lateral flow immunochromatography assay (LFA). A questionnaire focussing on known risk factors for exposure to Brucella spp. was also conducted, and relationships with FBAT positivity examined using logistic regression. Out of 825 recruited individuals, 162 (19.6%) were classified as positive using the FBAT. In contrast, only eight (1.0%) were positive using the RBT. Of the 162 FBAT positives, one (0.62%) had an atypical agglutination in SAT and three (1.9%) showed low Coombs titres. Out of 148 FBAT positive individuals tested using the LFA, five (3.4%) were IgM positive and none were IgG positive. Poor or no correlation was observed between FBAT results and most established risk factors for Brucella infection. We observed substantial disagreement between the FBAT and a number of well-known serological tests, with the majority of reactive FBAT results appearing to be false positives. Poor FBAT specificity, combined with a lack of confirmatory testing, strongly suggests overdiagnosis of brucellosis is common in this low prevalence setting. This is expected to have important economic impacts on affected patients subjected to the long and likely unnecessary courses of multiple antibiotics required for treatment of the disease.
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| 6. |
- Knox, Sara H., et al.
(författare)
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FLUXNET-CH4 Synthesis Activity : Objectives, Observations, and Future Directions
- 2019
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 100:12, s. 2607-2632
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the formation of, and initial results for, a new FLUXNET coordination network for ecosystem-scale methane (CH4) measurements at 60 sites globally, organized by the Global Carbon Project in partnership with other initiatives and regional flux tower networks. The objectives of the effort are presented along with an overview of the coverage of eddy covariance (EC) CH4 flux measurements globally, initial results comparing CH4 fluxes across the sites, and future research directions and needs. Annual estimates of net CH4 fluxes across sites ranged from -0.2 +/- 0.02 g C m(-2) yr(-1) for an upland forest site to 114.9 +/- 13.4 g C m(-2) yr(-1) for an estuarine freshwater marsh, with fluxes exceeding 40 g C m(-2) yr(-1) at multiple sites. Average annual soil and air temperatures were found to be the strongest predictor of annual CH4 flux across wetland sites globally. Water table position was positively correlated with annual CH4 emissions, although only for wetland sites that were not consistently inundated throughout the year. The ratio of annual CH4 fluxes to ecosystem respiration increased significantly with mean site temperature. Uncertainties in annual CH4 estimates due to gap-filling and random errors were on average +/- 1.6 g C m(-2) yr(-1) at 95% confidence, with the relative error decreasing exponentially with increasing flux magnitude across sites. Through the analysis and synthesis of a growing EC CH4 flux database, the controls on ecosystem CH4 fluxes can be better understood, used to inform and validate Earth system models, and reconcile differences between land surface model- and atmospheric-based estimates of CH4 emissions.
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| 7. |
- Koch, Sina, et al.
(författare)
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NRP1 Presented in trans to the Endothelium Arrests VEGFR2 Endocytosis, Preventing Angiogenic Signaling and Tumor Initiation
- 2014
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Ingår i: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 28:6, s. 633-646
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Tidskriftsartikel (refereegranskat)abstract
- Neuropilin 1 (NRP1) modulates angiogenesis by binding vascular endothelial growth factor (VEGF) and its receptor, VEGFR2. We examined the consequences when VEGFR2 and NRP1 were expressed on the same cell (cis) or on different cells (trans). In cis, VEGF induced rapid VEGFR2/NRP1 complex formation and internalization. In trans, complex formation was delayed and phosphorylation of phospholipase C gamma (PLC gamma) and extracellular regulated kinase 2 (ERK2) was prolonged, whereas ERK1 phosphorylation was reduced. Trans complex formation suppressed initiation and vascularization of NRP1-expressing mouse fibrosarcoma and melanoma. Suppression in trans required high-affinity, steady-state binding of VEGF to NRP1, which was dependent on the NRP1 C-terminal domain. Compatible with a trans effect of NRP1, quiescent vasculature in the developing retina showed continuous high NRP1 expression, whereas angiogenic sprouting occurred where NRP1 levels fluctuated between adjacent endothelial cells. Therefore, through communication in trans, NRP1 can modulate VEGFR2 signaling and suppress angiogenesis.
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| 8. |
- Marconi, A., et al.
(författare)
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ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
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Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Konferensbidrag (refereegranskat)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
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| 9. |
- Morin, Dominique, et al.
(författare)
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BioMinE : integrated project for the development of biotechnology for metal-bearing materials in Europe
- 2006
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Ingår i: Hydrometallurgy. - : Elsevier. - 0304-386X .- 1879-1158. ; 83:1-4, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- Biohydrometallurgy is the offspring of the unexpected union of biotechnology and metallurgy. From specific properties of some extreme biotopes, active principles of interactions between microbial metabolisms and minerals have been extracted to be used as efficient metallurgical processes.Many profitable industrial operations based on these bioprocesses have been running to recover copper, gold, uranium or cobalt for instance and many other applications have been designed.Europe was quite active in this area in the past, but currently the leadership is in South Africa, America and Australia.BioMinE (Biotechnology for Metal-bearing material In Europe) is a large integrated project launched with the support of the European Commission. It is aimed at stimulating synergies between the most relevant universities, research and industrial organisations to develop new concepts in this technical field that allow a better exploitation of the mineral resources in the future.The main technical subject is the investigation of the opportunities to apply bioleach processes to primary and secondary resources of metal-bearing materials. The second technical area of the project in terms of effort is the study of the recovery of metals from pregnant bioleach solution using biological reagents. All along the project duration, these investigations are focussed on the relevant resources in Europe screened according to an iterative process. The integration of the innovative pathways of processing will be evaluated up to the pilot scale whenever it is appropriate.The Consortium of BioMinE comprises 35 partners from industry (12 including 5 SMEs) research organisations (9) universities (14) and government (2). The participants are from 12 EU member states, from 1 candidate country (Romania), and from South Africa (INCO Country).The overall budget of the project is 17.9 million Euros, with a contribution from the European Commission of 11.6 million Euros. Started on November 1, 2004, the project will last 4 years.An overview of BioMinE in the general context of the biohydrometallurgy development is the subject of this presentation.
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| 10. |
- Morin, Dominique, et al.
(författare)
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Progress after three years of BioMinE-Research and Technological Development project for a global assessment of biohydrometallurgical processes applied to European non-ferrous metal resources
- 2008
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Ingår i: Hydrometallurgy. - : Elsevier. - 0304-386X .- 1879-1158. ; 94:1-4, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- BioMinE is an integrated project under the sixth framework programme of research supported by the European Commission, which started in November 2004 and will last until October 2008 (Ref. NMP2-CT-2005-500329). It is dedicated to the evaluation of biohydrometallurgy to improve the exploitation of the European non-ferrous metal resources in a sustainable way. At the end of 2007, the Consortium of BioMinE comprised 37 partners from industry (13 including 6 Small or Medium Enterprises), research organisations (8), universities (15), and government (1). The participants are from 13 EU member states and from Serbia and South Africa (INCO Countries). For more details see http://biomine.brgm.fr.The three main kinds of resources considered for bioleaching studies are:- Copper polymetallics (concentrates and tailings),- Zinc polymetallics (zinc and zinc polymetallic concentrates)- Secondary wastes (tailings, rock and metallurgical wastes, etc.)For each of these resources, amenability studies of application of bioleaching technologies by various approaches have been undertaken or still ongoing. Further processing assessment will be conducted up to the demonstration scale. Technological improvements have been made to apply bioleaching in the context of the European resources in terms of complexity and sustainability requirements. The relevant fundamental studies covering bio-prospecting, molecular ecology, biochemistry, and genetics areas aimed at improving the understanding and the control of the selected technologies have given original results.Much progress has also been obtained in the use of the microbial sulfate-reducing process to polish effluents and to recover metals from leachates containing low concentrations of metals. The finding of micro-organisms thriving at low and high temperature, respectively 8 and 65 °C, leads to an extension of the application range of the process. It has been also observed that this process could be pushed down to pH 4.5 and 4 creating opportunities of selective metal recovery as metal sulphides. It has also been demonstrated that sulphate can be removed at high concentrations, as well as arsenic or selenium. The next step in this work is pilot testing. This will allow to determine scale-up criteria and to assess the residual metal concentration under actual conditions.The pilot-scale demonstration operations, as well as the techno-economic and comparative sustainability assessments will be achieved during 2008, the last year of the project.The prototypes of the learning objects for training about biohydrometallurgy accessible by internet have been elaborated. A public output of this work is accessible at http://wiki.biomine.skelleftea.se/wiki. The basic knowledge thus delivered is aimed at disseminating the understanding of the origins and use of biohydrometallurgy.Contacts with mining operators in Europe have been taken and collaboration schemes have been established in various ways according to the respective contexts. When a high potential of technical involvement could be foreseen, a direct participation of the mining operators in the project was favoured, this led to integrate KGHM (Pol), Boliden (Sw) and Copper Institute of Bor (Serbia) into the consortium of partners.When no direct technical commitment was conceivable at the first stage, collaboration was established with companies with the most urgent requirement to have access to the relevant resource.
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| 11. |
- Morin, Eric
(författare)
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Neuropilin-1 regulation of tumor vascularization and growth
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiogenesis, the formation of new blood vessels from existing ones, is dysregulated during tumor progression as a result of chronic hypoxia and inflammation. Such alterations lead to a lack of vessel hierarchy, and the formation of poorly perfused, leaky and blunt-ended vessels, contributing to disease progression. This thesis explores the impact of neuropilin-1 (NRP1) presentation of vascular endothelial growth factor-A (VEGF-A) to its cognate receptor, VEGFR2. NRP1 presentation of VEGF-A occurs in cis (when NRP1 and VEGFR2 are present on the same cell) or in trans (when molecules are present on adjacent cells). As shown in this thesis, the different modes of NRP1 presentation influence endothelial cell signaling and tumor angiogenesis. The overall aim with the studies has been to identify new biomarkers for cancer survival and potential therapeutic targets.In paper I, we explored if signaling downstream of VEGFR2 was affected by NRP1 presentation in cis compared to trans. Complex formation in trans was readily identified, however, the kinetics were delayed and prolonged, inhibiting VEGFR2 internalization and downstream signaling. Additionally, in vivo tumor studies in mice demonstrated that trans presentation of NRP1 led to early inhibition of angiogenesis and suppressed tumor initiation.In paper II, the presence and clinical impact of trans VEGFR2/NRP1 complexes in human cancer was investigated. We first identified gastric and pancreatic adenocarcinomas (PDAC) as candidates for further investigation. VEGFR2/NRP1 complexes were identified in both tumor types but were more prevalent in PDAC. Trans presentation of NRP1 in PDAC correlated with a reduction in several vessel parameters and tumor cell proliferation. Importantly, this study identified the presence of trans complexes as an independent marker of longer overall survival for PDAC patients.In paper III, we explored the impact of NRP1 presentation modes on renal cell carcinoma (RCC) patient survival. We performed in situ proximity ligation assay (PLA) and immunofluorescence staining on a RCC cohort. Tumor cell NRP1, either trans-complexed with endothelial cell-expressed VEGFR2 as detected by in situ PLA, or alternatively, detected by immunofluorescent staining, was identified as an independent predictor of increased overall survival. These data reinforce the importance of the cell type-specific expression of cancer biomarkers.
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| 12. |
- Morin, Eric, et al.
(författare)
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Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 250:4, s. 387-396
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10–15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium.
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| 13. |
- Morin, Eric, et al.
(författare)
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VEGF receptor-2/neuropilin 1 trans-complex formation between endothelial and tumor cells is an independent predictor of pancreatic cancer survival
- 2018
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 246:3, s. 311-322
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Tidskriftsartikel (refereegranskat)abstract
- Unstable and dysfunctional tumor vasculature promotes cancer progression and spread. Signal transduction by the pro-angiogenic vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) is modulated by VEGFA-dependent complex formation with neuropilin 1 (NRP1). NRP1 expressed on tumor cells can form VEGFR2/NRP1 trans-complexes between tumor cells and endothelial cells which arrests VEGFR2 on the endothelial surface, thus interfering with productive VEGFR2 signaling. In mouse fibrosarcoma, VEGFR2/NRP1 trans-complexes correlated with reduced tumor vessel branching and reduced tumor cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) strongly expressed NRP1 on both tumor cells and endothelial cells, in contrast to other common cancer forms. Using proximity ligation assay, VEGFR2/NRP1 trans-complexes were identified in human PDAC tumor tissue, and its presence was associated with reduced tumor vessel branching, reduced tumor cell proliferation, and improved patient survival after adjusting for other known survival predictors. We conclude that VEGFR2/NRP1 trans-complex formation is an independent predictor of PDAC patient survival.
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| 14. |
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| 15. |
- Mortensen, Anja, et al.
(författare)
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Enhancing the therapeutic effects of in vitro targeted radionuclide therapy of 3D multicellular tumor spheroids using the novel stapled MDM2/X-p53 antagonist PM2
- 2020
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Ingår i: EJNMMI Research. - : SPRINGER. - 2191-219X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Precision therapeutics continuously make advances in cancer therapy, and a field of growing interest is the combination of targeted radionuclide therapy (TRNT) with potential radiosensitizing agents. This study evaluated whether the effects of in vitro TRNT, using the Lu-177-labeled anti-CD44v6 antibody AbN44v6, were potentiated by the novel stapled MDM2/X-p53 antagonist PM2.Materials and methods: Two wt p53 cell lines, HCT116 (colorectal carcinoma) and UM-SCC-74B (head and neck squamous cell carcinoma), expressing different levels of the target antigen, CD44v6, were used. Antigen-specific binding of Lu-177-AbN44v6 was initially verified in a 2D cell assay, after which the potential effects of unlabeled AbN44v6 on downstream phosphorylation of Erk1/2 were evaluated by western blotting. Further, the therapeutic effects of unlabeled AbN44v6, Lu-177-AbN44v6, PM2, or a combination (labeled/unlabeled AbN44v6 +/- PM2) were assessed in 3D multicellular tumor spheroid assays.Results: Radiolabeled antibody bound specifically to CD44v6 on both cell lines. Unlabeled AbN44v6 binding did not induce downstream phosphorylation of Erk1/2 at any of the concentrations tested, and repeated treatments with the unlabeled antibody did not result in any spheroid growth inhibition. Lu-177-AbN44v6 impaired spheroid growth in a dose-dependent and antigen-dependent manner. A single modality treatment with 20 mu M of PM2 significantly impaired spheroid growth in both spheroid models. Furthermore, the combination of TRNT and PM2-based therapy proved significantly more potent than either monotherapy. In HCT116 spheroids, this resulted in a two- and threefold spheroid growth rate decrease for the combination of PM2 and 100 kBq Lu-177-AbN44v6 compared to monotherapies 14-day post treatment. In UM-SCC-74B spheroids, the combination therapy resulted in a reduction in spheroid size compared to the initial spheroid size 10-day post treatment.Conclusion: TRNT using Lu-177-AbN44v6 proved efficient in stalling spheroid growth in a dose-dependent and antigen-dependent manner, and PM2 treatment demonstrated a growth inhibitory effect as a monotherapy. Moreover, by combining TRNT with PM2-based therapy, therapeutic effects of TRNT were potentiated in a 3D multicellular tumor spheroid model. This proof-of-concept study exemplifies the strength and possibility of combining TRNT targeting CD44v6 with PM2-based therapy.
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| 16. |
- Scutelnic, Adrian, et al.
(författare)
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Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
- 2022
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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| 17. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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