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  • 1
    Online Resource
    Online Resource
    Adverse Prognostic Impact of the KIT D816V Transcriptional Activity in Advanced Systemic Mastocytosis
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 5 ( 2021-03-04), p. 2562-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 5 ( 2021-03-04), p. 2562-
    Abstract: In systemic mastocytosis (SM), qualitative and serial quantitative assessment of the KIT D816V mutation is of diagnostic and prognostic relevance. We investigated peripheral blood and bone marrow samples of 161 patients (indolent SM (ISM), n = 40; advanced SM, AdvSM, n = 121) at referral and during follow-up for the KIT D816V variant allele frequency (VAF) at the DNA-level and the KIT D816V expressed allele burden (EAB) at the RNA-level. A round robin test with four participating laboratories revealed an excellent correlation (r 〉 0.99, R2 〉 0.98) between three different DNA-assays. VAF and EAB strongly correlated in ISM (r = 0.91, coefficient of determination, R2 = 0.84) but only to a lesser extent in AdvSM (r = 0.71; R2 = 0.5). However, as compared to an EAB/VAF ratio ≤2 (cohort A, 77/121 patients, 64%) receiver operating characteristic (ROC) analysis identified an EAB/VAF ratio of 〉 2 (cohort B, 44/121 patients, 36%) as predictive for an advanced phenotype and a significantly inferior median survival (3.3 vs. 11.7 years; p = 0.005). In terms of overall survival, Cox-regression analysis was only significant for the EAB/VAF ratio 〉 2 (p = 0.006) but not for VAF or EAB individually. This study demonstrates for the first time that the transcriptional activity of KIT D816V may play an important role in the pathophysiology of SM.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22052562
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 6 ( 2023-06-12), p. 1357-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 6 ( 2023-06-12), p. 1357-
    Abstract: COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as well as ACE2 binding inhibition were measured. An ACE2 binding inhibition 〈 20% was defined as an inadequate neutralization capacity. Univariate and multivariable logistic regression analysis was used to detect the predictors of inadequate neutralization capacity. Ninety-one CCP donors (56 female; 61%) were analyzed. A robust correlation between all SARS-CoV-2 IgG antibodies and ACE2 binding inhibition, as well as a positive correlation between donor age, body mass index, and a negative correlation between time since symptom onset and antibody levels were found. We identified time since symptom onset, normal body mass index (BMI), and the absence of high fever as independent predictors of inadequate neutralization capacity. Gender, duration of symptoms, and number of symptoms were not associated with SARS-CoV-2 IgG antibody levels or neutralization. Neutralizing capacity was correlated with SARS-CoV-2 IgG antibodies and associated with time since symptom onset, BMI, and fever. These clinical parameters can be easily incorporated into the preselection of CCP donors.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15061357
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 3
    Online Resource
    Online Resource
    Humoral SARS-CoV-2 Immune Response in COVID-19 Recovered Vaccinated and Unvaccinated Individuals Related to Post-COVID-Syndrome
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 2 ( 2023-02-06), p. 454-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 2 ( 2023-02-06), p. 454-
    Abstract: Background: The duration of anti-SARS-CoV-2-antibody detectability up to 12 months was examined in individuals after either single convalescence or convalescence and vaccination. Moreover, variables that might influence an anti-RBD/S1 antibody decline and the existence of a post-COVID-syndrome (PCS) were addressed. Methods: Forty-nine SARS-CoV-2-qRT-PCR-confirmed participants completed a 12-month examination of anti-SARS-CoV-2-antibody levels and PCS-associated long-term sequelae. Overall, 324 samples were collected. Cell-free DNA (cfDNA) was isolated and quantified from EDTA-plasma. As cfDNA is released into the bloodstream from dying cells, it might provide information on organ damage in the late recovery of COIVD-19. Therefore, we evaluated cfDNA concentrations as a biomarker for a PCS. In the context of antibody dynamics, a random forest-based logistic regression with antibody decline as the target was performed and internally validated. Results: The mean percentage dynamic related to the maximum measured value was 96 (±38)% for anti-RBD/S1 antibodies and 30 (±26)% for anti-N antibodies. Anti-RBD/S1 antibodies decreased in 37%, whereas anti-SARS-CoV-2-anti-N antibodies decreased in 86% of the subjects. Clinical anti-RBD/S1 antibody decline prediction models, including vascular and other diseases, were cross-validated (highest AUC 0.74). Long-term follow-up revealed no significant reduction in PCS prevalence but an increase in cognitive impairment, with no indication for cfDNA as a marker for a PCS. Conclusion: Long-term anti-RBD/S1-antibody positivity was confirmed, and clinical parameters associated with declining titers were presented. A fulminant decrease in anti-SARS-CoV-2-anti-N antibodies was observed (mean change to maximum value 30 (±26)%). Anti-RBD/S1 antibody titers of SARS-CoV-2 recovered subjects boosted with a vaccine exceeded the maximum values measured after single infection by 235 ± 382-fold, with no influence on preexisting PCS. PCS long-term prevalence was 38.6%, with an increase in cognitive impairment compromising the quality of life. Quantified cfDNA measured in the early post-COVID-19 phase might not be an effective marker for PCS identification.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15020454
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 4
    Online Resource
    Online Resource
    Biomarkers of Vascular Injury and Type 2 Diabetes: A Prospective Study, Systematic Review and Meta-Analysis
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 12 ( 2019-11-27), p. 2075-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 12 ( 2019-11-27), p. 2075-
    Abstract: Data on biomarkers of vascular injury and type 2 diabetes (T2D) risk from prospective studies are lacking. We evaluated seven biomarkers of vascular injury in relation to T2D. Additionally, a meta-analysis was performed. From the EPIC–Heidelberg cohort, 2224 participants were followed-up from baseline for 16 (median) years. E-Selectin, P-Selectin, intercellular adhesion molecule 3 (ICAM3), thrombomodulin, thrombopoietin, glycoprotein IIb/IIIa and fibrinogen levels were measured in baseline blood samples. The systematic review and meta-analysis included prospective studies identified through MEDLINE and Web of Science that investigated the association between mentioned biomarkers and T2D. The study population included 55% women, median age was 50 years, and 163 developed T2D. ICAM3 was associated with lower T2D risk (fully adjusted HRhighest vs. lowest tertile 0.62 (95% CI: 0.43, 0.91)), but no other studies on ICAM3 were identified. Overall, fifteen studies were included in the systematic review and meta-analysis (6,171 cases). E-Selectin was associated with higher T2D risk HRper SD: 1.34 (95% CI: 1.16, 1.54; I2 = 63%, n = 9 studies), while thrombomodulin was associated with lower risk HRper SD: 0.82 (95% CI: 0.71, 0.95; I2 = 0%, n = 2 studies). In the EPIC–Heidelberg, ICAM3 was associated with lower T2D risk. The meta-analysis showed a consistent positive association between E-Selectin and T2D. It was also suggestive of an inverse association between thrombomodulin and T2D, although further studies are needed to corroborate this finding.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8122075
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 5
    Online Resource
    Online Resource
    Thrombomodulin and Thrombopoietin, Two Biomarkers of Hemostasis, Are Positively Associated with Adherence to the World Cancer Research Fund/American Institute for Cancer Research Recommendations for Cancer Prevention in a Population-Based Cross-Sectional Study
    MDPI AG ; 2019
    In:  Nutrients Vol. 11, No. 9 ( 2019-09-03), p. 2067-
    Details
    In: Nutrients, MDPI AG, Vol. 11, No. 9 ( 2019-09-03), p. 2067-
    Abstract: A pro-coagulative state is related to increased risk of cardiovascular diseases but also certain cancers. Since experimental and smaller human studies suggest that diet, physical activity, and body weight may all affect coagulation, we evaluated associations between these lifestyle factors and hemostatic biomarkers in a population-based study. Cross-sectional baseline data from 2267 randomly selected participants of EPIC-Heidelberg (age range 35–65 years) was used. Fibrinogen, glycoprotein IIb/IIIa, P-selectin, thrombomodulin (TM), and thrombopoietin (TPO) were measured in baseline plasma samples. A score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention was created. Associations between the WCRF/AICR score as well as its individual components and hemostatic biomarkers were analyzed by linear regression models. Multivariable-adjusted geometric means (95% confidence intervals) of TM and TPO were higher with greater adherence to the WCRF/AICR recommendations (TM, lowest vs. highest score category: 2.90 (2.7,3.1) vs. 3.10 (2.9,3.3) ng/mL, plinear trend = 0.0001; TPO: 328 (302,356) vs. 348 (321,378) pg/mL, plinear trend = 0.0007). These associations were driven by lower alcohol and meat consumption among persons with higher WCRF/AICR scores. Our results indicate that lifestyle factors favorably affect TM and TPO, two hemostatic factors implicated in chronic disease development.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu11092067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2518386-2
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