Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases

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    Associations of blood-based biomarkers of neurodegenerative diseases with mortality, cardio- and cerebrovascular events in persons with chronic coronary syndrome

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    [Artikel-Nr. 112684] Background: In light of growing evidence highlighting interactions between cardiac and brain health, we investigated associations of biomarkers of neurodegenerative diseases with adverse outcomes (all-cause and cardiovascular mortality, major cardiovascular events, and stroke) in persons with chronic coronary syndrome (CCS). Methods: We used data from a cohort of persons with CCS for whom major adverse events were recorded over a follow-up of 20 years. We measured biomarkers of neurodegenerative diseases in baseline blood samples, using the Single-Molecule Array Technology on a HD-1 Analyzer. These include biomarkers of neuronal (neurofilament light chain (NfL) (n = 379)) and glial neurodegeneration (glial fibrillary acidic protein (GFAP) (n = 379)), and Alzheimer's disease pathology (phosphorylated tau181 (n = 379), total tau (n = 377), and amyloid β (Aβ40, Aβ42, Aβ42/Aβ40) (n = 377)). We applied Cox-proportional hazards models to evaluate associations of these biomarkers with adverse outcomes, adjusting for covariates and exploring interactions with apolipoprotein E (ApoE) ε4 genotype. Results: Participants with higher NfL levels had increased rates of all-cause and cardiovascular mortality (Hazard ratio per increase by one standard deviation (95 % confidence interval): all-cause mortality: 1.36 (1.10–1.68); cardiovascular mortality: 1.42 (1.05–1.93)). The Aβ40/Aβ42-ratio was linked to incident stroke (0.72 (0.52–1.00)). Associations of GFAP with all-cause mortality and incident stroke were depending on ApoE ε4 genotype. The other biomarkers were not significantly associated with the studied outcomes. Conclusions: In persons with CSS, NfL and the Aβ40/Aβ42-ratio were related to mortality and incident stroke, respectively, whereas associations of GFAP with adverse outcomes varied by ApoE genotype. These biomarkers might play a role in linking aging, cardiovascular and neurodegenerative disease

    The Effects of Remoteness and Forest Cover on Bird Knowledge in Two Language Communities of Myanmar

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    The link between language loss and traditional ecological knowledge (TEK) loss in small language communities is well documented, but the causal mechanisms are difficult to tease apart. We investigate the transmission of bird knowledge in two ethnic minority communities of Myanmar, Lainong and Danu, which differ greatly in their degree of remoteness and the level of local forest cover. Older and younger native speakers from numerous villages were asked to name local birds from audio-visual stimuli, and their responses were analyzed quantitatively to detect any disruptions in TEK transmission to younger generations. Remoteness has a protective effect on TEK transmission in two Lainong villages, and higher levels of forest cover may be associated with a larger ethno-ornithological vocabulary at the regional level, but not at the village level. Cultural and religious practices may also play an important role in determining knowledge maintenance or loss. By documenting bird names in two understudied languages, this study makes an important contribution to both documentary linguistics as well as conservation science

    Non-canonical quantification in Old Persian: The adverb vasai̯

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    Vim3 and Mxi‐2 as Promising New Molecular Biomarkers for the Diagnosis of Sperm Disorders

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    Introduction: Male infertility remains a significant clinical challenge that requires the exploration of new diagnostics strategies. Truncated proteins, such as Vim3, a truncated variant of vimentin, show promise as a new class of biomarkers for diagnosing fertility disorders. Our objective was to assess the potential utility of Vim3 and Mxi‐2, a shortened iteration of mitogen‐activated protein kinase (MAPK) p38, as noninvasive biomarkers for diagnosing sperm disorders. Methods: Semen samples of 19 fertile males (control group) and 82 infertile males with semen abnormalities and no female factor ( n = 28 OAT [oligo–astheno–teratozoospermia] syndrome, n = 8 azoospermia, n = 29 teratozoospermia, n = 11 astheno–teratozoospermia, and n = 6 oligozoospermia) were analyzed using ELISA (enzyme‐linked immunosorbent assay) and flow cytometry. Furthermore, we conducted a lateral flow assay (LFA) specific to Vim3. Results: Our analysis revealed that Vim3 and endothelin‐1 (ET‐1) expression levels were significantly downregulated in non‐normozoospermic patients (e.g., OAT syndrome), while Mxi‐2 was overexpressed in these patients compared to the control group ( p < 0.01). Additionally, we introduced a novel LFA that provides a user‐friendly and effective method for examining Vim3 as a biomarker in clinical settings. Conclusion: Our results suggest that Vim3 and Mxi‐2 have potential as noninvasive semen biomarkers for diagnosing sperm disorders

    Vergleich der operativen Zugangswege und des Resektionsausmaßes zwischen Patienten mit erster Remission und Patienten mit Rezidiv eines abdominellen Hochrisiko-Neuroblastoms

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    In dieser Dissertation wurde erstmalig untersucht, ob für Patienten mit einem metastasierten abdominalen Neuroblastom, die in der Neuroblastom (NB) 97 Studie eine Hochdosis-Chemotherapie erhalten hatten, ein Zusammenhang zwischen operativen Zugangswegenb, Resektionsausmaß und anhaltender 1. Remission bestand

    Accuracy of Self-Evaluation in Biology Education: Investigating Potential Effects of Skill Practice, Prompting, and Physical Exercise

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    Enabling students to become life-long learners is an overarching educational goal. Self evaluations are an integral part of self-regulated learning, a key concept used to support life-long learning. The accuracy of self-evaluation plays a major role in learning processes, as it can influence subsequent learning behaviour. Yet, inaccurate self-evaluations are frequently observed across disciplines and contexts, including biology education. Deliberate, theory and evidence-based approaches are needed to enhance the accuracy of self-evaluation. This dissertation comprises two published studies and one unpublished manuscript that examine three interdisciplinary approaches potentially affecting the accuracy of self evaluation. Study I examined the potential effects of skill practice on the accuracy of self evaluation. In this controlled, quasi-experimental intervention study, 167 eighth-grade students took part in a concept map construction, concept map study, or control training. They evaluated their concept mapping skills in a subsequent cross-over learning phase. The accuracy of self evaluation was measured using correlations. The study findings revealed a slightly increased alignment of self-evaluation and “objective” concept mapping skills after concept map construction training compared to concept map study training. Study II examined the potential effects of prompting on the accuracy of self evaluation. In this controlled and randomised online study, 162 pre-service teachers were prompted to use resource-oriented and deficit-oriented comprehension questions while reading a biology text. They evaluated their text comprehension before taking a short comprehension test. The accuracy of self evaluation was determined by calculating the difference between subjective self-evaluation and “objective” performance. The results showed no evidence for an effect of prompting with resource-oriented or deficit-oriented self questions. Study III examined the potential acute effects of physical exercise on the accuracy of self evaluation. In this controlled, within subjects laboratory study, 24 children with Attention Deficit Hyperactivity Disorder (ADHD) took part in strength-based, flexibility-based, and control training. They evaluated their task accuracy and reaction time in a subsequent Eriksen Flanker Task, which measured attentional performance. The accuracy of self evaluation of task accuracy was measured by calculating the difference between subjective self-evaluation and “objective” task accuracy. The accuracy of self-evaluation of reaction time was determined using a categorisation of correct and incorrect self-evaluations. The findings of Study III showed no evidence for altered attentional performance or positive effect on the accuracy of self evaluation. The results of the studies included in this dissertation support previous findings indicating an increase in the accuracy of self-evaluation after practicing the skill to be evaluated. To contextualise the results, the methodological approaches are critically discussed, and the role of non-significant research findings is addressed. This dissertation provides interdisciplinary insights into the complexity of self-evaluation and self-regulated learning by applying approaches from cognitive and educational psychology to biology education

    Die Bedeutung zellfreier DNA als prognostischer Marker bei kardiochirurgischen Risikopatienten für die späte akute Nierenschädigung

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    Diese Studie befasst sich mit der prognostischen Bedeutung zellfreier DNA nach Bypassoperationen am Herzen unter Einsatz der Herzlungenmaschine im Zusammenhang mit akuter Nierenschädigung (AKI). Durch den Einsatz einer Herzlungenmaschine werden sowohl physiologische Mechanismen beeinflusst als auch das Immunsystem aktiviert, was zu einer systemischen Inflammation mit Aktivierung von unter anderem neutrophilen Granulozyten führt. Neutrophile Granulozyten können durch Freisetzung extrazellulärer Neutrophilenfallen (neutrophil extracellular traps - NETs) zusätzliche Gewebeschäden bewirken. Durch die Induktion von Apoptose und Zellnekrosen im Rahmen der Inflammation wird ebenfalls nukleäre DNA freigesetzt, was zu einem Anstieg der zirkulierenden zellfreien DNA (cfDNA) führt. In dieser prospektiven Studie wurden 58 Patienten eingeschlossen, welche alle unter Einsatz der Herzlungenmaschine eine Bypassoperation erhielten. 21 Patienten entwickelten eine AKI (drei davon dialysepflichtig) und 37 Patienten wiesen eine normale Nierenfunktion innerhalb des Beobachtungszeitraums auf. Fünf Patienten der AKI-Gruppe verstarben im postoperativen Verlauf. In allen Patienten wurden sowohl präoperativ, als auch unmittelbar postoperativ, sowie am ersten, zweiten, dritten und fünften postoperativen Tag die Biomarker Kreatinin, Neutrophilen-Gelatinase-assoziiertem Lipocalin (NGAL) und cfDNA/NETs im Blutplasma quantifiziert. Die Bewertung des Prognosewertes der Biomarker bezüglich eines AKI erfolgte anhand von ROCKurven (receiver operating characteristic curve). Erfasst wurden außerdem perioperative Voraussetzungen wie Vorerkrankungen, Medikation, BMI und Geschlecht der Patienten, sowie die Dauer und Art des Eingriffes bzw. der Zeitraum unter Einsatz der Herzlungenmaschine. Miteinbezogen wurde auch die Verweildauer auf Intensivstation und die Ein-Jahres Mortalität. Die Analyse der Plasmaspiegel zeigte, dass die cfDNA- und NGAL-Spiegel bei AKI-Patienten stark anstiegen, im Gegensatz zur Nicht-AKI-Gruppe. Diese Unterschiede konnten auch bis Tag 3 bzw. Tag 5 nach der Operation beobachtet werden. Im Vergleich zur Gruppe mit früher AKI waren die cfDNA-Spiegel bei Patienten, die eine späte AKI (>24 Stunden postoperativ) entwickelten, signifikant erhöht. Bei der Entwicklung einer frühen AKI (innerhalb der ersten 24 Stunden postoperativ) hingegen zeigten die Biomarker NGAL und Kreatinin im Vergleich zur cfDNA eine höhere Signifikanz. NGAL konnte somit in den ersten 24 Stunden nach Operation als ein valider Vorhersageparameter für die frühe AKI verwendet werden. Als präziser Prädiktor für die späte AKI konnte am dritten postoperativen Tag die cfDNA mit einem Schwellenwert von 260,53 ng/ml (AUC = 0,804) ermittelt werden; im Vergleich dazu zeigten NGAL (AUC = 0,699) und Kreatinin (AUC =0,688) eine geringere AUC. Es deutete sich ein Zusammenhang zwischen erhöhter Mortalität und dem Anstieg von NGAL an. Dieser konnte in Bezug auf cfDNA nicht beobachtet werden. Die Ergebnisse dieser Arbeit deuten insgesamt darauf hin, dass die Bestimmung der cfDNASpiegel ab dem ersten postoperativen Tag ein wertvolles Instrument zur Vorhersage von später AKI nach Herzoperationen mit Herzlungenmaschineneinsatz sein könnte

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