Research-Data Management Planning in the German Mathematical Community

In this paper we discuss the notion of research data for the field of mathematics and report on the status quo of research-data management and planning. A number of decentralized approaches are presented and compared to needs and challenges faced in three use cases from different mathematical subdisciplines. We highlight the importance of tailoring research-data management plans to mathematicians' research processes and discuss their usage all along the data life cycle

Is the Hyporheic Zone Relevant beyond the Scientific Community?

Rivers are important ecosystems under continuous anthropogenic stresses. The hyporheic zone is a ubiquitous, reactive interface between the main channel and its surrounding sediments along the river network. We elaborate on the main physical, biological, and biogeochemical drivers and processes within the hyporheic zone that have been studied by multiple scientific disciplines for almost half a century. These previous efforts have shown that the hyporheic zone is a modulator for most metabolic stream processes and serves as a refuge and habitat for a diverse range of aquatic organisms. It also exerts a major control on river water quality by increasing the contact time with reactive environments, which in turn results in retention and transformation of nutrients, trace organic compounds, fine suspended particles, and microplastics, among others. The paper showcases the critical importance of hyporheic zones, both from a scientific and an applied perspective, and their role in ecosystem services to answer the question of the manuscript title. It identifies major research gaps in our understanding of hyporheic processes. In conclusion, we highlight the potential of hyporheic restoration to efficiently manage and reactivate ecosystem functions and services in river corridors

Determinants of severe QTc prolongation in a real-world gerontopsychiatric setting.

INTRODUCTION QTc prolongation carries the risk of ventricular tachyarrhythmia (Torsades de Pointes) and sudden cardiac death. Psychotropic drugs can affect ventricular repolarization and thus prolong the QTc interval. The present study sought to investigate the risk factors (pharmacological and non-pharmacological) of severe QTc prolongation in gerontopsychiatric patients. METHODS Electrocardiograms of patients on a gerontopsychiatric ward were screened for QTc prolongation. Medication lists were examined utilizing the AzCERT classification. Potential drug interactions were identified with the electronic drug interaction program mediQ. RESULTS The overall prevalence of QTc prolongation was 13.6%, with 1.9% displaying severe QTc prolongation (≥ 500 ms). No statistically significant differences between patients with moderate and severe QTc prolongation were identified; however, patients with severe QTc prolongation tended to take more drugs (p = 0.063). 92.7% of patients with QTc prolongation took at least one AzCERT-listed drug, most frequently risperidone and pantoprazole. Risperidone and pantoprazole, along with pipamperone, were also most frequently involved in potential drug interactions. All patients displayed additional risk factors for QTc prolongation, particularly cardiac diseases. CONCLUSION In addition to the use of potentially QTc-prolonging drugs, other risk factors, especially cardiac diseases, appear to be relevant for the development of QTc prolongation in gerontopsychiatric patients. Pantoprazole was frequently involved in potential drug interactions and should generally not be used for more than 8 weeks in geriatric populations. As clinical consequences of QTc prolongation were rare, potentially QTc-prolonging drugs should not be used overcautiously; their therapeutic benefit should be considered as well. It is paramount to perform diligent benefit-risk analyses prior to the initiation of potentially QTc-prolonging drugs and to closely monitor their clinical (side) effects

Inklusive Familienbildung. Konzepte des Teams „Inklusive Bildungswerkstatt“

Angesichts zunehmender Heterogenität von Familienleben stellt sich die Frage, wie alle Familien an Angeboten der Familienhilfe und Familienbildung teilhaben können. Im Wintersemester 2020 wurden deshalb im Rahmen eines Seminars im Masterstudiengang Erziehungswissenschaft der Universität Hildesheim Konzepte einer „inklusiven Familienbildung“ entwickelt und gemeinsam mit Vertreter:innen aus der Praxis der Familienbildung Ideen für die Weiterentwicklung von Angebo-ten erarbeitet. Der Fokus der Konzepte liegt auf Familien mit besonderen Belastungen (Armut, Behinderung, psychosoziale Belastungen). Den meisten Familien geht es wirt¬schaftlich gut, jedes fünfte Kind wächst aber in einer Familie auf, deren Einkom¬men unter der Armutsgefährdungsgrenze liegt oder die staatliche Grundsiche¬rungsleistung bezieht. 2019 waren in Niedersachsen 21,7 % aller Minderjährigen armutsgefährdet, insbesondere Alleinerziehenden-Haushalte sind betroffen. 3 – 5% aller Kinder und Jugend¬lichen leben mit einer Behinderung (Schwerbehinderung über 50%), 99% aller pflegebedürftigen Kinder und Jugendlichen wachsen in ihrer Familie auf. Schät¬zungsweise 390.000 Kinder unter 14 Jahren wachsen mit einem Elternteil mit Behinderung auf. Hinzukommen 3 bis 4 Millionen Kinder psychisch erkrankter Eltern, davon 2,6 Millionen suchtbelastete Eltern und Kinder und Jugendliche als pflegende Angehörige. Im Seminar wurden Bildungs- und Beratungseinrichtungen über Erfahrungen in der Arbeit mit belasteten Familien befragt. Aus den Ergebnissen der Befra¬gung wurden Ideen für die Bildungsarbeit mit belasteten Familien entwickelt und in zwei Workshops mit Vertreter:innen der Bildungspraxis diskutiert. Die Workshop-Diskussionen wurden ausgewertet und anschließend ausgewählte Konzepte schriftlich ausgearbeitet. Die vorliegende Publikation dokumentiert diese Konzepte

Effectiveness, barriers and facilitating factors of strategies for active delabelling of patients with penicillin allergy labels: a systematic review protocol

Introduction Up to 15% of adult patients in the clinical setting report to be allergic to penicillin. However, in most cases, penicillin allergy is not confirmed. Due to the negative aspects associated with erroneous penicillin allergy, the implementation of active delabelling processes for penicillin allergy is an important part of antibiotic stewardship programmes. Depending on the clinical setting, different factors need to be considered during implementation. This review examines the effectiveness of different delabelling interventions and summarises components and structures that facilitate, support or constrain structured penicillin allergy delabelling.Methods and analysis This review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases MEDLINE (via PubMed), EMBASE and Cochrane Library were searched for studies reporting on any intervention to identify, assess or rule out uncertain penicillin allergy. To improve completeness, two further databases are also searched for grey literature. Study design, intervention type, professional groups involved, effectiveness, limitations, barriers, facilitating factors, clinical setting and associated regulatory factors will be extracted and analysed. In addition, exclusion criteria for participation in the delabelling intervention and criteria for not delabelling penicillin allergy will be summarised. In case of failed protocols, these are highlighted and quantitatively analysed if possible. Two independent reviewers will perform the screening process and data extraction. Discordant decisions will be resolved through review by a third reviewer. Bias assessment of the individual studies will be performed using the Newcastle Ottawa Scale.Ethics and dissemination Because individual patient-related data are not analysed, an ethical approval is not required. The review will be published in a peer-reviewed scientific journal

Let’s Talk about Love! Das Liebesbriefarchiv in der forschungsnahen Lehre

Dieses Working Paper ist das Ergebnis eines Experiments: Im Rahmen des Seminars Let’s talk about love! Linguistische und kulturhistorische Forschungen zu Liebesbriefen, das im Sommersemester 2021 an der Technischen Universität Darmstadt angeboten wurde, haben Studierende Transkriptionen und Basiserschließungen mit Briefmetadaten und Annotationen zahlreicher Liebesbriefe aus dem Bestand des Liebesbriefarchivs, das in der UB Koblenz aufbewahrt wird, erstellt. Alle Beteiligten hatten dabei mehrere Herausforderungen zu meistern: Zum einen galt es mit dem Umstand des pandemiebedingten digitalen Semesters zurechtzukommen. Zum anderen kamen im Seminar Studierende aus mehreren unterschiedlichen Studiengängen zusammen, was eine Vielfalt an unterschiedlichen Vorerfahrungen bezüglich der Transkription und Annotation von Textzeugen sowie an unterschiedlichen Leistungsvoraussetzungen der einzelnen Studierenden mit sich brachte. Anstelle der üblichen Hausarbeiten wurden daher als Seminarleistung von einzelnen Studierenden Aufsätze über seminarbezogene Themen erstellt, die wir nun neben einem Überblick über das Koblenzer Liebesbriefarchiv, das aktuelle Citizen-Science-Projekt Gruß & Kuss sowie über das durchgeführte Seminar in diesem Working Paper präsentieren

Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids

To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and proton irradiation and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and tumorigenicity was investigated in NMRI Foxn1nu/nu mice. We found a mutational pattern containing common mutations associated with PDAC within the PDOs. Although we could unravel potential complications of the viability assay for PDOs in radiobiology, distinct synergistic effects of gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translational proton radiation research

Validation of CD98hc as a Therapeutic Target for a Combination of Radiation and Immunotherapies in Head and Neck Squamous Cell Carcinoma

Most patients with head and neck squamous cell carcinomas (HNSCC) are diagnosed at a locally advanced stage and show heterogeneous treatment responses. Low SLC3A2 (solute carrier family 3 member 2) mRNA and protein (CD98hc) expression levels are associated with higher locoregional control in HNSCC patients treated with primary radiochemotherapy or postoperative radiochemotherapy, suggesting that CD98hc could be a target for HNSCC radiosensitization. One of the targeted strategies for tumor radiosensitization is precision immunotherapy, e.g., the use of chimeric antigen receptor (CAR) T cells. This study aimed to define the potential clinical value of new treatment approaches combining conventional radiotherapy with CD98hc-targeted immunotherapy. To address this question, we analyzed the antitumor activity of the combination of fractionated irradiation and switchable universal CAR (UniCAR) system against radioresistant HNSCC cells in 3D culture. CD98hc-redirected UniCAR T cells showed the ability to destroy radioresistant HNSCC spheroids. Also, the infiltration rate of the UniCAR T cells was enhanced in the presence of the CD98hc target module. Furthermore, sequential treatment with fractionated irradiation followed by CD98hc-redirected UniCAR T treatment showed a synergistic effect. Taken together, our obtained data underline the improved antitumor effect of the combination of radiotherapy with CD98hc-targeted immunotherapy. Such a combination presents an attractive approach for the treatment of high-risk HNSCC patients

Sensitization of Patient-Derived Colorectal Cancer Organoids to Photon and Proton Radiation by Targeting DNA Damage Response Mechanisms

Pathological complete response (pCR) has been correlated with overall survival in several cancer entities including colorectal cancer. Novel total neoadjuvant treatment (TNT) in rectal cancer has achieved pathological complete response in one-third of the patients. To define better treatment options for nonresponding patients, we used patient-derived organoids (PDOs) as avatars of the patient’s tumor to apply both photon- and proton-based irradiation as well as single and combined chemo(radio)therapeutic treatments. While response to photon and proton therapy was similar, PDOs revealed heterogeneous responses to irradiation and different chemotherapeutic drugs. Radiotherapeutic response of the PDOs was significantly correlated with their ability to repair irradiation-induced DNA damage. The classical combination of 5-FU and irradiation could not sensitize radioresistant tumor cells. Ataxia-telangiectasia mutated (ATM) kinase was activated upon radiation, and by inhibition of this central sensor of DNA damage, radioresistant PDOs were resensitized. The study underlined the capability of PDOs to define nonresponders to irradiation and could delineate therapeutic approaches for radioresistant patients