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- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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- Castro Dopico, Xaquin, et al.
(författare)
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Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates
- 2022
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Ingår i: Clinical & Translational Immunology (CTI). - : John Wiley & Sons. - 2050-0068. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50–99% likelihood, and 4.0% (n = 203) to have a 10–49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
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- Edvardsson, H., et al.
(författare)
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Nationwide Rereview of Normal Cervical Cytologies before High-Grade Cervical Lesions or before Invasive Cervical Cancer
- 2021
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Ingår i: Acta Cytologica. - : S. Karger AG. - 0001-5547 .- 1938-2650. ; 65:5, s. 377-384
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Tidskriftsartikel (refereegranskat)abstract
- Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001-2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer. © 2021 The Author(s). Published by S. Karger AG, Basel.
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- Merino Martinez, R, et al.
(författare)
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Human exposome assessment platform
- 2021
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Ingår i: Environmental epidemiology (Philadelphia, Pa.). - 2474-7882. ; 5:6, s. e182-
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Tidskriftsartikel (refereegranskat)
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- Moro, CF, et al.
(författare)
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Drug-induced tumor-specific cytotoxicity in a whole tissue ex vivo model of human pancreatic ductal adenocarcinoma
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 965182-
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. PDAC has a dismal prognosis and an inherent resistance to cytostatic drugs. The lack of reliable experimental models is a severe limitation for drug development targeting PDAC. We have employed a whole tissue ex vivo culture model to explore the effect of redox-modulation by sodium selenite on the viability and growth of PDAC. Drug-resistant tumors are more vulnerable to redox-active selenium compounds because of high metabolic activity and redox imbalance. Sodium selenite efficiently and specifically reduced PDAC cell viability (p <0.02) (n=8) and decreased viable de novo tumor cell outgrowth (p<0.05) while preserving non-neoplastic tissues. Major cellular responses (damaged tumor cells > 90%, tumor regression grades III-IV according to Evans) were observed for sodium selenite concentrations between 15-30 µM. Moreover, selenium levels used in this study were significantly below the previously reported maximum tolerated dose for humans. Transcriptome data analysis revealed decreased expression of genes known to drive PDAC growth and metastatic potential (CEMIP, DDR2, PLOD2, P4HA1) while the cell death-inducing genes (ATF3, ACHE) were significantly upregulated (p<0.0001). In conclusion, we report that sodium selenite has an extraordinary efficacy and specificity against drug-resistant pancreatic cancer in an organotypic slice culture model. Our ex vivo organotypic tissue slice culture model can be used to test a variety of drug candidates for swift and reliable drug responses to individual PDAC cases.
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- Wang, J. R., et al.
(författare)
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Increase of cervical cancer incidence in Sweden in relation to screening history: population cohort study
- 2020
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:8, s. 988-993
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cervical cancer incidence in Sweden decreased from 24/100,000 in 1965 to 8/100,000 in 2011, but has from 2014 increased to 11/100,000. The increase appears to correlate to screening history. We perform a study of the cancer risk change in relation to screening history over two screening rounds to verify the correlation. Material and methods: We studied the cohorts of all 3,047,850 individual women living in Sweden in each year from 2002-2015. Registry linkages between the Total Population Register, the Swedish National Cervical Screening Registry, the Swedish Cervical Cancer Audit database and the National Quality Register for Gynecological Cancer, defined the incidence rates of invasive cervical cancer comparing time periods 2002-2013 to 2014-2015, in women whose screening history in 2 screening intervals prior to each year were either (i) adequately screened with normal results (almost exclusively cytology, 52% of the population) or (ii) unscreened (13% of the population). We also investigated the incidence increase by time since a normal smear performed in 2002-2012. Results: Among women adequately screened with normal results there was a strong incidence increase in 2014-2015 compared to previous years (Incidence rate ratio (IRR) = 1.59, 95%CI = 1.36-1.85), but no significant increase among unscreened women (IRR = 1.09, 95%CI = 0.94-1.27). There was no increase in incidence 0-2.5 years after a normal smear over the study period (IRR = 1.04, 95% CI = 0.88-1.24), but a strong increase 3-4 years after a normal smear since year 2009 (IRR = 1.52, 95% CI = 1.25-1.84). Conclusion: The results suggest that the overall increase is associated with an increased cancer risk in women adequately screened with normal cytological results. Possibly, precursor lesions missed in one screening round might result in detection of early stage invasive cancer in the subsequent screening.
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