Evaluierung von Saflor- und Leindotter-Genotypen zur Nutzung als Ölpflanze im Ökologischen Landbau

Im Ökologischen Landbau fehlt bislang eine geeignete Ölpflanzenart, deren Samen als Rohstoff für die Speiseölerzeugung dienen können. Raps und Sonnenblumen bieten aufgrund der Schädlingsproblematik, des hohen N-Bedarfes bzw. durch die geringe ökologische Adaptation keine günstigen Voraussetzungen für den Anbau. 2002 wurden in einer zweiortigen Prüfung auf Mikroparzellen unter insgesamt nahezu 1000 Genotypen (Genbank-Akzessionen, Sorten, Zuchtstämme) von Saflor und Leindotter als alternative Arten geeignete Formen für den Anbau gesucht. Die Ergebnisse zeigen, dass beide Arten hinsichtlich ihrer Anfälligkeit für verschiedene Krankheiten und anderer agronomisch relevanter Merkmale hohe genotypische Variation aufweisen, welche direkt im Anbau oder aber als Ausgangsmaterial in der Entwicklung neuer Sorten nutzbar ist

Evaluierung von Saflor-Akzessionen für den Ökologischen Landbau

In Deutschland werden im Ökologischen Landbau trotz vorhandener Nachfrage nach Speiseöl nur sehr wenige Ölpflanzen angebaut. Saflor oder Färberdistel ist dabei als eine sinnvolle Alternative zu Raps bzw. Sonnenblumen anzusehen, es liegen jedoch bislang nur wenige Untersuchungen zur Anbauwürdigkeit vor. 741 Saflorherkünfte wurden 2002 auf ihre Anbaueignung unter hiesigen Klimabedingungen zweiortig geprüft. 2003 wurden 65 daraus ausgelesene, überlegene Herkünfte in einer dreiortigen Leistungsprüfung getestet. Es zeigte sich neben einer sehr großen Variabilität des verwendeten Materials, dass sich vorrangig europäische Formen durch eine gute Kornausbildung und höhere Samenerträge auszeichneten. Zwischen beiden Jahren bestand keine Beziehung in den Samenerträgen der 65 Herkünfte

Plasma medical oncology: Immunological interpretation in head and neck squamous cell carcinoma

Over the past several years, various important articles focusing on cancer therapy approaches in head and neck squamous cell carcinomas (HNSCCs) using cold atmospheric plasma (CAP) have been published (SEMMLER et al. 2020 [53], METELMANN et al. 2018 [44], KEIDAR et al. 2011 [33]). This doctoral thesis presents selected results from a prospective observational clinical study in CAP therapy of palliative HNSCC patients, carried out at the Department of Oral and Maxillofacial Surgery/Plastic Surgery of the Greifswald University Medicine. For oral and maxillofacial surgeons, ulcerated surfaces of locally advanced head and neck squamous cell carcinomas (UICC IV) offer a challenging treatment assignment with microbial contamination and tumour progression. The clinical attempt appears to eradicate microbial contamination and to initiate tumour regression. This doctoral thesis will describe the processes of human tumour biology and tumour immunology in HNSCCs and the extent of present knowledge concerning plasma medical oncology as an anticancer modality. In the introduction of the doctoral thesis clinical results of plasma therapy in locally advanced HNSCCs (UICC IV) are set out. This mainly includes the investigation of a therapeutic concept, the treatment phases, the tumour size development and the morphological changes of the infected tumour surface following cold atmospheric plasma therapy. In the main part, a detailed immunological interpretation is proposed on the basis of present preclinical and clinical immunological knowledge. Finally, unexplored questions in plasma medical oncology are highlighted. This is highly significant for future plasma research and clinical anticancer therapy

The role of soluble mediators in the clinical course of EBV infection and B cell homeostasis after kidney transplantation

Epstein-Barr virus (EBV) reactivation can lead to serious complications in kidney transplant patients, including post-transplant lymphoproliferative disorder (PTLD). Here, we have assessed the impact of EBV on B cell homeostasis at cellular and humoral level. In a multicenter study monitoring 540 kidney transplant patients during the first post-transplant year, EBV reactivation was detected in 109 patients. Thirteen soluble factors and B cell counts were analyzed in an $EBV^{+}$ sub-cohort (N = 54) before, at peak and after EBV clearance and compared to a control group (N = 50). The B cell activating factor (BAFF) was significantly elevated among $EBV^{+}$ patients. No additional soluble factors were associated with EBV. Importantly, in vitro experiments confirmed the proliferative effect of BAFF on EBV-infected B cells, simultaneously promoting EBV production. In contrast, elevated levels of BAFF in $EBV^{+}$ patients did not lead to B cell expansion in vivo. Moreover, diminished positive inter-correlations of soluble factors and alterations of the bi-directional interplay between B cell and soluble factors were observed in $EBV^{+}$ patients at peak and after clearance. Our data suggest that such alterations may counteract the proliferative effect of BAFF, preventing B cell expansion. The role of these alterations in lymphoma development should be analyzed in future studies

Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019

It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC)

$\bf Background$ A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. $\bf Methods$ In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. $\bf Results$ The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4$^{+}$ and CD8$^{+}$ T cells among the PASC study group, characterized by TNF$\alpha$ and IFN$\gamma$ production and low functional avidity. CRP levels are positively correlated with IFN$\gamma$ producing reactive CD8$^{+}$ T cells. $\bf Conclusions$ Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies

Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC

Plasma proteomics enable differentiation of lung adenocarcinoma from chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a major risk factor for the development of lung adenocarcinoma (AC). AC often develops on underlying COPD; thus, the differentiation of both entities by biomarker is challenging. Although survival of AC patients strongly depends on early diagnosis, a biomarker panel for AC detection and differentiation from COPD is still missing. Plasma samples from 176 patients with AC with or without underlying COPD, COPD patients, and hospital controls were analyzed using mass-spectrometry-based proteomics. We performed univariate statistics and additionally evaluated machine learning algorithms regarding the differentiation of AC vs. COPD and AC with COPD vs. COPD. Univariate statistics revealed significantly regulated proteins that were significantly regulated between the patient groups. Furthermore, random forest classification yielded the best performance for differentiation of AC vs. COPD (area under the curve (AUC) 0.935) and AC with COPD vs. COPD (AUC 0.916). The most influential proteins were identified by permutation feature importance and compared to those identified by univariate testing. We demonstrate the great potential of machine learning for differentiation of highly similar disease entities and present a panel of biomarker candidates that should be considered for the development of a future biomarker panel