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    Effects of Carbon–to–Nitrogen Ratio and Temperature on the Survival of Antibiotic-Resistant and Non-Resistant Escherichia coli During Chicken Manure Anaerobic Digestion

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    Anaerobic digestion (AD) is a suitable process to use manure for biogas production. During this process, antimicrobial resistant (AMR) bacteria are reduced. In this study, we investigated the reduction of extended-spectrum beta-lactamase (ESBL)-producing, fluoroquinolone-resistant, and total Escherichia (E.) coli concentrations in chicken manure during AD. AD was performed at 30 °C and 37 °C (mesophilic temperature range), with and without sawdust addition as a lignocellulosic biomass. The initial concentrations of total E. coli were 6.43 log10CFU/g to 7.84 log10CFU/g. The concentration of Fluoroquinolone-resistant E. coli was approx. 6.05 log10CFU/g (6.70%), and of ESBL-producing E. coli approx. 5.48 log10CFU/g (0.99%). During AD, we observed that temperature had the main influence on the bacterial reduction, as E. coli abundance was below the detection limit after day 7 at 37 °C and after day 14 at 30 °C. At 37 °C we observed higher amounts of free ammonia, which is an inhibitor of the AD process. The carbon-to-nitrogen (C/N) ratio has an important impact on the AD process because a higher C/N ratio decreases the amount of generated total ammonia nitrogen. However, we did not observe a significant difference in AMR and total E. coli reduction between chicken manure with a natural C/N ratio (10:1) and an increased C/N ratio (25:1)

    Physical activity and food intake during weight restoration of patients with anorexia nervosa

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    Anorexia nervosa (AN) entsteht zumeist im Kindes- und Jugendalter und die Langzeit-Outcomes für Menschen mit AN sind derzeit bestenfalls als moderat zu bezeichnen. Aktuelle Behandlungsleitlinien in Deutschland, den USA und England stellen die Gewichtsrehabilitation als zentrales Therapieziel in den Vordergrund. Eine schnelle, frühe Gewichtszunahme gilt dabei als positiver Prädiktor für das längerfristige Outcome. Die ausreichende Nahrungszufuhr ist für eine angemessene Gewichtszunahme entscheidend, dennoch wird aus Furcht vor dem Refeeding-Syndrom initial oft niedrigkalorisch (z.B. < 1400 kcal/d) ernährt. In Tiermodellen wird das sogenannte Activity-Based Anorexia (ABA)-Modell untersucht: niedrige Leptinspiegel durch eine niedrige Fettmasse im Hungerzustand führen zu erhöhter, körperlicher Aktivität, welche möglicherweise die Futtersuche und das Überleben sichern könnten. Die gesteigerte, körperliche Aktivität gilt bei Patient:innen mit AN als krankheitsaufrechterhaltend. Inwiefern sich jedoch das ABA-Modell auf an AN erkrankte Personen übertragen lässt, ist ungewiss. Um die Behandlungsoutcomes für Menschen mit AN zu verbessern, ist ein tieferes Verständnis derjenigen Faktoren erforderlich, welche die Gewichtszunahme bei Patient:innen mit AN limitieren bzw. fördern. Diese Habilitationsschrift basiert auf 5 Originalarbeiten, die an 3 unterschiedlichen Patient:innen-Kohorten während der stationären Behandlung und in 2 Arbeiten im Vergleich mit altersgleichen, gesunden Kontrollproband:innen durchgeführt wurden: 2 im Kindes- und Jugendalter und eine im Erwachsenenalter. Vier Publikationen basieren auf prospektivem Studiendesign, eine auf retrospektiven Aktenanalysen. Im Fokus der Arbeit stehen mit der körperlichen Aktivität, der Körperfettmasse und der Nahrungsaufnahme ernährungsphysiologische Parameter. Zur Erfassung der körperlichen Aktivität wurde die Akzelerometrie eingesetzt, um spezifische Bewegungsmuster objektiv zu charakterisieren. Die Körperfettmasse wurde mit der Bioelektrischen Impedanzanalyse gemessen. Es konnte gezeigt werden, dass bei Patientinnen mit AN im Vergleich zu gesunden Personen vor allem die körperliche Aktivität im niedrigschwelligen Bereich erhöht ist, dass jedoch dieses Bewegungsmuster nicht auf alle Patient:innen mit AN zutrifft. Dennoch wurde ein Zusammenhang zwischen der erhöhten, körperlichen Aktivität und der niedrigeren Gewichtszunahme während der Hospitalisierung sichtbar. Zudem zeigte sich ein Zusammenhang zwischen der Nahrungszusammensetzung und der körperlichen Aktivität bei Patient:innen mit AN. Diese Zusammenhänge sind jedoch in den vorliegenden Artikeln nicht im Sinne einer Kausalität belegt. Ein klarer Effekt der Hypoleptinämie auf eine erhöhte Schrittzahl war nicht ersichtlich. Um die gemäß S3-Leitlinien geforderte, wöchentliche Gewichtszunahme von 0.5-1.0 kg/Woche im stationären Setting zu erreichen, war eine initiale Energiezufuhr von 2000 kcal erforderlich. Diese Energiezufuhr war bei engem, medizinischem Monitoring und Korrektur der Phosphat- und Thiaminspiegel durch Supplemente bei Bedarf, nicht mit dem Auftreten eines Refeeding-Syndroms, sondern mit einer Normalisierung der zu Beginn pathologischen Blutwerte verbunden. Eine Studie, die im ambulanten Setting kausale Beziehungen zwischen niedrigem Fettverzehr, niedrigem Leptinspiegel, gesteigerter PA und daraus resultierend mangelnder Gewichtszunahme untersucht, stellt den nächsten, wichtigen Schritt dar - auch um daraus neue, therapeutische Ansätze zu entwickeln. Um weiteren Bezug zur klinischen Relevanz der untersuchten Fragestellungen aufzuzeigen, werden im Ausblick drei neue Therapieansätze vorgestellt: eine manualisierte Intervention zur Reduktion des zwanghaften Bewegungsverhaltens, die Gabe von Metreleptin sowie die ambulante, familienbasierte Therapie für Kinder und Jugendliche mit Essstörungen (FBT). Die FBT ist ein ambulanter, intensiver und störungsspezifischer Therapieansatz, der auf eine rasche Gewichtsnormalisierung, eine Regulation des gestörten Ess- und Bewegungsverhalten sowie damit auf die Reduktion der Anorexie-spezifischen Psychopathologie abzielt. Diese Therapieansätze könnten das Potenzial aufweisen, die Outcomes für einen signifikanten Teil der Betroffenen zu verbessern

    Employing Advanced In Vitro Models and Patient Data to Uncover Mucin Expression Patterns and Barrier Function in the Human Intestine

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    The intestinal epithelium plays a crucial role in regulating the immune response and maintaining homeostasis. It serves as a barrier that restricts the passage of water and macromolecules, and this barrier function is integral to its role. The barrier function is provided by a single layer of diverse epithelial cells, connected by cell junctions, supported by the extracellular matrix, and covered by a mucus layer. The study of epithelium has been limited for a long time to standard cell lines and synthetic substrates under conditions that do not mimic the physiological state. Thankfully, the next generation of intestinal models was developed with the advancement of organoids, small intestinal submucosa substrates, and microfluidic systems. In our study, we utilized these newly developed approaches in cell culture to investigate the barrier function in a better in vivo-mimicking state. Firstly, given the key role of mucus in the barrier function, we aimed to gain insights into mucin expression in human intestines, both in health and inflammatory bowel disease, by leveraging large-scale omic datasets generated from RNA-sequenced samples from ileum and colon tissues. In this thesis, we analyzed the mucin expression profiles within the dataset and provided an atlas of mucin expression for Crohn’s disease, ulcerative colitis, and the healthy state. We also identified a subgroup of Crohn's patients who exhibited de novo expression of secreted mucins and explored this further. Additionally, we implemented a new method for cell culture, in which we seeded intestinal stem cell-derived monolayers generated from human organoids onto hydrogels developed from porcine small intestinal submucosa enriched with native extracellular matrix proteins. We compared the cellular behavior of cells cultured on hydrogels to that of cells cultured on tissue culture plastic coated with Matrigel at early and late time points, and we employed bulk RNA sequencing to obtain a comprehensive overview of gene expression under these conditions. We found that the hydrogels supported the long-term survival of culture and resulted in the consistent upregulation of key survival, proliferation, and differentiation pathways. In contrast, these pathways were downregulated when the cells were cultured on tissue culture plastic, resulting in a short-lived culture. Furthermore, we utilized a custom-designed dynamic chamber within a millifluidic system to expose cells cultured on the hydrogels to physiological shear stress. Similarly, we applied bulk RNA sequencing at early and late time points. Our findings demonstrated that shear stress induced the differentiation of intestinal stem cells without the need for exogenous differentiation factors and increased the metabolic activity of these cells. Shear stress also induced the upregulation of pathways involved in the innate immune response, as well as an early downregulation of mechanotransduction pathways that had been previously upregulated on hydrogels. Interestingly, we observed an upregulation of stem cell markers at early exposure to shear stress, suggesting a potential role for short-term shear stress in stimulating cell stemness. In summary, our study represents a significant step forward in developing advanced in vitro models that yield more transferable results, thereby enhancing our understanding of intestinal barrier function and facilitating their application in disease research and drug discovery

    With an introduction by Olli O. Silvennoinen

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    Synopsis: Otto Jespersen's landmark study of negation provides a wide-ranging analysis of how languages express negative meaning. Drawing on an impressive array of historical texts and comparative examples, primarily from Germanic and Romance languages, Jespersen examines the forms, functions, and historical development of negative expressions. The work traces the evolution of negative markers, analyzes how negative prefixes modify word meanings, and reveals coherent patterns in how languages structure negative expressions. Through meticulous analysis of authentic examples, Jespersen documents both common patterns and language-specific variations in negative expressions. His treatment of topics such as double negation, the distinction between special and nexal negation, and the various forms of negative particles provides a methodical account of negation's complexity. The work's enduring importance stems not only from its analysis of the cyclical renewal of negative markers (later termed “Jespersen's Cycle”) but from its comprehensive scope and detailed examination of negative expressions across multiple languages and historical periods. This new critical edition makes this classic work accessible to modern readers while preserving its scholarly depth. The text has been completely re-typeset, with examples presented in contemporary numbered format and non-English examples given Leipzig-style glosses. A new introduction contextualizes Jespersen's achievement and demonstrates its continued significance for current linguistic research

    Zur Behandlung local-eitriger Prozesse des Pferdes mit Antifermentserum (Leukofermantin-Merck)

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    Digitalisat der Ausgabe von 1912, erschienen 202

    Consumer Acceptance of Alternative Proteins: Exploring Determinants of the Consumer Willingness to Buy in Germany

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    In Western countries, a shift to a diet rich in proteins from diverse sources could aid the transition to more sustainable patterns of protein consumption and production, contributing to meet the future demand for protein from the growing population. The successful integration of alternative proteins into diets hinges, however, on consumer acceptance. Despite a plethora of acceptance studies on alternative proteins, comparative insights remain limited. To improve the fragmented understanding of the drivers and barriers of alternative protein acceptance, this study examines consumer willingness in Germany to buy food products containing proteins from three sources—algae, crickets and jellyfish—using the same methodological approach. The findings indicate that environmental consciousness strengthens the willingness to buy products based on all three protein sources while neophobia weakens it. In contrast, past meat consumption habits contribute positively to the acceptance of animal-origin alternative proteins, like crickets and jellyfish, but negatively to the acceptance of algae. The acceptance is also influenced by demographic factors. It is argued that strategies targeting these factors can enhance the acceptance of alternative protein sources such as algae, crickets and jellyfish. However, it is important to tailor the strategies to the determinants that influence the willingness to buy products from a particular protein source

    Impact of the Channel Length in Nanoporous Electric Double-Layer Capacitors on the Charge Transport Explored by Metal–Organic Framework Films

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    For enhancing the performance of electric double-layer capacitors, the porous electrodes must be further optimized. While many studies on electrolyte and electrode structures enable detailed insights, the length of the pore channels of the electrode has been overlooked. Here, we use films of two-dimensional conductive metal–organic frameworks, where the film thickness (and thus the pore channel length) is rationally tuned over a wide range. Cyclic voltammetry experiments with two different electrolytes were conducted, revealing the charge transport kinetics in the porous electrodes. For the highly mobile electrolyte, the kinetics is not limited by ion transport (i.e., diffusion) even for thick films, exhibiting mainly surface-controlled kinetic behavior. In contrast, for the less mobile electrolyte, the kinetics is primarily limited by ion diffusion, and the pore channel length has a severe impact, where long channels result in strongly decreased capacitances, highlighting the importance of adjusting the channel length

    Discrete JT gravity as an Ising model

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    Inspired by the program of discrete holography, we show that Jackiw-Teitelboim (JT) gravity on a hyperbolic tiling of Euclidean AdS2 gives rise to an Ising model on the dual lattice, subject to a topological constraint. The Ising model involves an asymptotic boundary condition with spins pointing opposite to the magnetic field. The topological constraint enforces a single domain wall between the spins of opposite direction, with the topology of a circle. The resolvent of JT gravity is related to the free energy of this Ising model, and the classical limit of JT gravity corresponds to the Ising low-temperature limit. We study this Ising model through a Monte Carlo approach and a mean-field approximation. For finite truncations of the infinite hyperbolic lattice, the map between both theories is only valid in a regime in which the domain wall has a finite size. For the extremal cases of large positive or negative coupling, the domain wall either shrinks to zero or touches the boundary of the lattice. This behavior is confirmed by the mean-field analysis. We expect that our results may be used as a starting point for establishing a holographic matrix model duality for discretized gravity

    Uranium(VI) retention by calcium (alumino)silicate hydrates – Impact of temperature and ionic strength

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    Calcium aluminosilicate hydrates (C-A-S-H) are the main hydration products of cement formulations with Al-rich additives such as blast furnace slags, fly ashes or calcined clays. We studied systematically the effect of Al substitution on both the structure of C-A-S-H phases and their U(VI) retention properties in comparison to C-S-H phases. To represent the different stages of cement degradation, three series of samples were synthesized, which included samples with Ca/Si molar ratios of 0.8, 1.2 and 1.6 and different Al/Si molar ratios of 0, 0.06 and 0.18 for each series. Furthermore, the impact of synthesis temperature (room temperature, 100 °C, 200 °C) on the C-(A-)S-H structure was studied. The U(VI) retention, studied either by sorption experiments or by direct synthesis of U(VI)-containing C-(A-)S-H phases, was found to be strong with log Rd between 4.9 and 5.6. Structural characteristics of the cementitious phases were obtained from powder X-ray diffraction (XRD) as well as 29Si and 27Al solid-state magic angle spinning nuclear magnetic resonance (SS MAS NMR) spectroscopy. AlO4 tetrahedra were identified to occupy bridging positions of the silicate chains, thereby increasing the mean chain length and providing additional sorption sites for U(VI) at room temperature. Elevated temperatures during solid phase formation, however, lead to a stronger cross-linking of the silicate chains with the appearance of neoformed crystalline phases. Luminescence spectroscopy was applied to characterize the U(VI) binding. Various U(VI) species (interlayer or surface sorbed) are formed in different proportions, depending on the composition and structure of the C-(A-)S-H phases, which are partly affected by elevated temperatures. To simulate salinity changes of the pore water, the effect of enhanced ionic strengths and the presence of carbonate on the stability of the U(VI) retention by the C-(A-)S-H phases was studied by sorption and leaching experiments over extended timescales of up to 6 months. For C-(A-)S-H phases previously exposed to temperatures of up to 100 °C, the effect of medium ionic strengths (up to 2.6 M) on U(VI) retention was insignificant

    Anwendung von “machine learning“ Algorithmen für die Vorhersage der funktionellen Erholung nach subarachnoidaler Blutung - eine monozentrische retrospektive Studie

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    Background: There is a controversy about the superiority of the performance of prognostic tools based on advanced machine learning (ML) algorithms for patients with aneurysmal subarachnoid hemorrhage (aSAH). Unfortunately, evaluation of the performance of current ML-based tools is not comprehensive enough, often using a single model and exclusively the area under the receiver operating characteristic curve (AUROC) to quantify the performance. Therefore, it remains unclear whether these would be reliable and benefit patients. My goal was to develop and evaluate ML models for predicting unfavorable functional outcome in aSAH patients and identify the model with the best performance. Methods: A retrospective dataset comprising 955 patients with aSAH was randomly split into training and internal test sets, with 670 (70%) and 285 (30%) patients respectively. Clinical scores, along with clinical and radiological features at admission, as well as secondary complications from the training set were used to construct models based on five machine learning (ML) algorithms (logistic regression [LR], K-nearest neighbor [KNN], extreme gradient boosting [XGB], random forest [RF] and artificial neural network [ANN]). For comparison and evaluation among models, AUROC, the area under the precision-recall curve (AUPR), calibration curve, and decision curve analysis (DCA) were utilized on the internal test set. Results: Composite models (based on LR, XGB, RF and ANN algorithms) had significantly higher AUROC than simple models in predicting unfavorable functional outcomes. Compared to other composite models (RF and XGB algorithms) with good calibration, LR had the highest value of AUPR and showed the greatest benefit in DCA. Conclusion: A prediction model employing LR algorithm has shown superior performance in identifying patients with aSAH who are at high risk for adverse functional outcomes. Thus, this model could be a useful tool to assisting healthcare professionals in their decision-making processes.Hintergrund: Die Bewertung von prognostischen Instrumenten auf der Basis von „advanced machine learning“-Algorithmen für Patienten mit subarachnoidalen Blutungen bei Aneurysmen (aSAH) ist bisher kaum möglich. Der Grund dafür ist eine noch unzureichende Datenlage. Das Ziel der Studie ist die Entwicklung und der Vergleich verschiedener Verfahren des „machine learning“ für die Prognose ungünstigen klinischen Verlaufs bei aSAH-Patienten. Methoden: Ein retrospektiv erhobener Datensatz von 955 Patienten mit aSAH wurde nach dem Zufallsprinzip in einen Trainingsdatensatz mit 670 (70%) Patienten sowie in einen internen Testdatensatz mit 285 (30%) geteilt. Die Modellgestaltung erfolgte unter Verwendung des klinischen Scores bei Aufnahme des Patienten, weiterer klinischer und radiologischer Merkmale sowie unter Beachtung sekundärer Komplikationen. Folgende fünf “machine learning” Algorithmen wurden einbezogen: “logistic regression” [LR], “K-nearest neighbor” [KNN], “extreme gradient boosting” [XGB], “random forest” [RF] und “artificial neural network“ [ANN]. Die Modellbewertung am Testdatensatz erfolgte mit Hilfe der Fläche unter der „receiver operating characteristic curve“ (AUROC), der „precision-recall curve“ (AUPR), der „calibration curve“, und der „decision curve analysis“ (DCA). Ergebnisse: Komplexere Modelle basierend auf LR, XGB, RF und ANN Algorithmen zeigten höhere AUROCs als die einfachen Modelle und sie waren prädiktiver hinsichtlich eines ungünstigen funktionellen Verlaufes der Patienten. Im Vergleich mit anderen komplexen Modellen (RF und XGB), die eine gute „calibration curve“ zeigten, hatte LR die größte AUPR und war bei DCA überlegen. Schlussfolgerungen: Das Vorhersagemodell auf Basis des LR-Algorithmus zeigte die beste Ergebnisse bei der Erkennung von aSAH-Patienten mit einer ungünstigen klinischen Entwicklung. Es kann ein sinnvolles Hilfsmittel zur Unterstützung ärztlichen Handeln bei der klinischen Betreuung von aSAH-Patienten sein

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