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Publikation Microstructures, phase and mechanical characterisation of Al2O3-ZrO2-TiO2 coating produced by atmospheric plasma spraying(Elsevier, 20.12.2024) Chang, Cynthia Sin Ting; Wyss, Marcus; Andrzejewski, Michal; Darut, Geoffrey; Graf, Lukas; Novak, Vladimir; Olbinado, Margie; Erpel, Susanne; Vogel, Alexander; Bode, Simon; de Wild, Michael; Salito, ArmandoThe microstructure, crystallographic phases, and mechanical properties of a newly developed Al2O3 – TiO2 – ZrO2 ternary ceramic coating were characterized. The coatings were produced by atmospheric plasma spraying as a preblended powder on Ti-6Al-4 V substrates using the new generation of the Debye-Larmor cascaded plasma torch. The 400 μm thick as-sprayed ternary ceramic coating is compact and neither delamination nor inter-/trans-granular cracks were found. The coating consists of single phase α-Al2O3, monoclinic m-ZrO2, and a nanocrystalline dual phase structure of α-Al2O3 and m-ZrO2. Ti is either present as ZrTiO4 or as solute in the dual phase. Cracking from the tip of the indent is rare and delamination was not observed after the progressive scratch test. The coating has potential in high wear applications for example in medical devices.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Electrochemical reconfiguration of NiFe layered double hydroxide on BiVO4 induced by black phosphorus quantum dots for promoting photoelectrochemical water splitting(Elsevier, 12/2024) Sun, Yunshuyu; Chen, Hao; Hou, Zhiang; Wang, Jinnan; Li, Aimin; Corvini, PhilippeIn this work, black phosphorus quantum dots (BPQDs) and NiFe layered double hydroxide (NiFe-LDHs) were loaded on BiVO4 photoanode for promoting photoelectrochemical (PEC) water splitting. As a narrow bandgap p-type semiconductor with high work function, BPQDs could not only form p-n junction with BiVO4 to enhance light harvest but also construct Schottky junction for charge carriers separation. More importantly, introduction of BPQDs facilitates the transformation of Ni(OH)2 into NiOOH so as to improve the water oxidation capacity at low bias voltage. Density functional theory (DFT) calculation demonstrates that introduction of BPQDs accelerates the α/γ phase transition dynamically and thermodynamically, thus BiVO4/BPQDs/NiFe-LDHs photoanode achieves photocurrent density of 5.28 mA cm−2 at 1.23 VRHE, AM 1.5 G and maintains good stability. In summary, this work provides new ideas for constructing efficient hole extraction layers on photoelectrode, well expanding the application of BPQDs in PEC water splitting.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Bi atom sharing Co-Bi₂O₂CO₃/BiOI S-scheme induced singlet oxygen-dominated photocatalytic oxidation system(Elsevier, 12/2024) Hou, Zhiang; Yue, Jinzhu; Chen, Hao; Wang, Jinnan; Li, Aimin; Corvini, PhilippeEndocrine disrupting chemicals (EDCs) interfere with the normal secretion, transport and metabolism of human hormones, thus affecting neurological, reproductive and immune functions. Photocatalysis is regarded as a facile organic degradation technique. The construction of heterojunctions can modulate the reactive oxygen species and enhance the photocatalytic performance of semiconductors. However, poor contact interfaces still severely limit carrier separation and transfer. Herein, we have doped Co to modulate the band structure of Bi₂O₂CO₃ while facilitating the in situ growth of BiOI on its surface via shared Bi atoms. This approach led to the development of a 2D/2D Co-Bi₂O₂CO₃/BiOI (Co-BOC/BiOI) S-scheme heterojunction characterized by atomically close contact interfaces. Furthermore, the photo-electrochemical characterization results indicate that the light adsorption capacity, carrier separation and transport efficiency of the optimized Co-BOC/BiOI-3 are greatly improved. This system demonstrates almost 100% removal rate for three typical EDCs within 60 min. The degradation kinetic constants show an improvement by an order of magnitude compared to single BiOI and Bi₂O₂CO₃. More importantly, O₂•﹣, which is produced from O₂ reduction on high negative conduction band, can be subsequently oxidized into 1O2 by photogenerated hole. Electron paramagnetic resonance and quenching experiments indicate that the organics degradation process is dominated by 1O2. This work offers new insights into the construction of high-quality S-scheme heterojunction interfaces for modulation of reactive oxygen species.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Insecticide exposure alters flight-dependent gene-expression in honey bees, Apis mellifera(Elsevier, 12/2024) Christen, Verena; Jeker, Lukas; Lim, Ka S.; Menz, Myles H.M.; Straub, LarsThe increased reports of wild bee declines and annual losses of managed bees pose a significant threat to biodiversity and agricultural productivity. While these losses and declines are likely driven by various factors, the exposure of bees to agrochemicals has raised significant concern due to their ubiquitous use and potential adverse effects. Despite numerous studies suggesting neonicotinoids can negatively affect bees at the behavioral and molecular level, data linking these two factors remains sparse. Here we provide data on the impact of an acute dose of the neonicotinoid thiamethoxam on the flight performance and molecular transcription profiles of foraging honey bees (Apis mellifera). Using a controlled experimental design with tethered flight mills, we measured flight distance, duration, and speed, alongside the expression of genes involved in energy metabolism, hormone regulation, and biosynthesis. Acute thiamethoxam exposure resulted in hyperactive flight behavior but led to significant dysregulation of genes associated with oxidative phosphorylation, indicating potential disruptions in cellular energy production. These molecular changes were particularly evident when bees engaged in flight activities, suggesting that the combined stress of pesticide exposure and physical exertion exacerbates negative outcomes. Our study provides new insights into the molecular mechanisms underlying neonicotinoid-induced impairments in bee physiology that can help understand the potential long-term consequences of xenobiotic exposure on the foraging abilities of bees and ultimately fitness.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Modulating the electronic structure of Mn promotes singlet oxygen generation from electrochemical oxidation of H₂O via O-O coupling(Elsevier, 12/2024) Chen, Hao; Hou, Zhiang; Yue, Jinzhu; Wang, Jinnan; Wang, Yi; Li, Aimin; Corvini, PhilippeSelectively catalytic conversion H₂O into singlet oxygen (¹O₂) without additional oxidants is considered as an economic-efficient method for organic pollutants degradation. However, H₂O are more consistent with the spin state of ¹O₂ than common oxygen (O₂), retarding the kinetics of spin transition-induced reaction between O₂ and ¹O₂. Herein, we report an unprecedented ¹O₂ mediated electrocatalytic oxidation process, which allows O–O coupling for ¹O₂ evolution from H₂O over CrMn@C anode. The electron occupancy (eg) of CrMn@C (0.89) is very close to the optimal eg (0.95) of manganese-based materials reported in the literature, which facilitates the activation of H₂O on surface. Mn(Mn0.193Cr1.808)O₄-Mn in CrMn@C electrode significantly promotes the activation of H₂O to produce *O, followed by coupling of *O at adjacent sites to produce *OO, which further spontaneously forms ¹O₂. And H₂¹⁸O isotope experiments provide direct evidence for the production of ¹O₂ directly from H₂O. Consequently, the production of ¹O₂ is enhanced with the yield of 785.6 μmol·L⁻¹. Such ¹O₂-dominated electrocatalytic oxidation system can achieve efficient removal of electron-rich pollutant (bisphenol A) and improve the biodegradability of pharmaceutical wastewater (from 0.17 to 0.39).01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Exploring the potential of various cyclodextrin‐based derivatives in enzyme supramolecular engineering(Wiley, 28.11.2024) Foroutan Kalourazi, Ali; Nazemi, Amir; Unniram, Ajmal; Ferrer, Manuel; Shahangian, S. Shirin; Shahgaldian, PatrickEnzyme stability and activity are pivotal factors for their implementation in different industrial applications. Enzyme supramolecular engineering relies on the fabrication of a tailor-made enzyme nano-environment to ensure enzyme stability without impairing activity. Cyclodextrins (CDs), cyclic oligomers of glucose, act as protein chaperones and stabilize, upon interaction with hydrophobic amino acid residues exposed at the protein surface, its three-dimensional structure. When used to build an organosilica layer shielding an enzyme, they enhance the protective effect of this layer. In the present study, we systematically assessed the protective effects of three organosilane derivatives based on ɑ-, β- and γ-CDs. A model lipase enzyme was immobilized at the surface of silica nanoparticles and shielded in an organosilica layer containing these organosilanes. Besides layer thickness optimization, the effect of different stressors (i. e., temperature, SDS, urea) was tested. Our results showed that organosilica layers produced with CDs improve enzyme thermal stability. They also support enzyme refolding after denaturation under chaotic conditions. Additionally, we demonstrated that the protective effect of the smallest CD derivative tested, namely ɑ-CD, surpassed the other macrocycles studied for conferring the immobilized enzyme with higher resistance to stress conditions. This protection strategy was also applied to a thermostable β-galactosidase enzyme.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Machine learning for precision diagnostics of autoimmunity(Nature, 13.11.2024) Kruta, Jan; Carapito, Raphael; Trendelenburg, Marten; Martin, Thierry; Rizzi, Marta; Voll, Reinhard E.; Cavalli, Andrea; Natali, Eriberto; Meier, Patrick; Stawiski, Marc; Mosbacher, Johannes; Mollet, Annette; Santoro, Aurelia; Capri, Miriam; Giampieri, Enrico; Schkommodau, Erik; Miho, EnkelejdaEarly and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Towards quantitative microplastic analysis using pyrolysis-gas chromatography coupled with mass spectrometry(Elsevier, 11/2024) Grafinger, Katharina Elisabeth; Ochiai, Celandin; Zhou, Huan-Xiao; Hettich, Timm; Büttler, Andre; Álvarez Troncoso, Romina; Zenker, Armin; Gaugler, StefanMicroplastic pollution from everyday plastic items has increased tremendously worldwide. Pyrolysis gas chromatography coupled to mass spectrometry (Py-GC/MS) has been widely investigated for the qualitative and quantitative analysis of microplastics in environmental samples. However, there are several pitfalls to consider when developing an appropriate protocol for their analysis. This study aimed at the development of an in-house database of primary (single) polymers, binary (two) polymers and tertiary (three) polymer mixtures. In this context the potential occurrence of gas phase reactions during pyrolysis of binary and tertiary polymers were investigated. Further, different diluters were tested for the accurate preparation of calibration standards for quantification purposes. Seven different polymers were included in this study, which were chosen due to their prevalence in daily plastic appliances. For each single polymer specific peaks could be identified and recommendation for quantifier analytes given. The analysis of binary polymer mixtures revealed gas phase reactions for PET with PVC, PVC with MDI-PU and PE with PVC. For these binary polymers, several different novel pyrolysis products, specific for the according binary polymer mixture, could be identified. These results confirmed that especially PVC exhibits strong interactions during co-pyrolysis with ester- and ether-based polymers. Similar results were obtained for tertiary polymers. For accurate preparation of calibration standards different diluters (silica, deactivated silica, calcium carbonate, THF and HFIP) were tested. It was observed that deactivated silica had only an influence on the pyrolysis of PET. Whereas, dilution with silica affected PA-6/66, PE, PET and MDI-PU. Only PVC was not influenced by dilution with silica. In conclusion, our results highlight the necessity of an international standard of reference material as well as a standardized analytical protocol for the analysis and quantification of polymers in environmental samples. It is crucial to use diluters suitable for the specific polymer, to exclude potential interactions of diluters with the polymer. The present work has to be seen as a foundation, but future work is needed to adequately address the quantification of polymers in environmental samples.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Computational support to explore ternary solid dispersions of challenging drugs using coformer and hydroxypropyl cellulose(American Chemical Society, 10.10.2024) Niederquell, Andreas; Herzig, Susanne; Schönenberger, Monica; Stoyanov, Edmont; Kuentz, MartinA majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e., hydroxypropyl cellulose) and a coformer as stabilizing excipients. The aim was to introduce a computational approach by preselecting additives using solubility parameter intervals (i.e., overlap range of solubility parameter, ORSP) followed by more advanced COSMO-RS theory modeling. Thus, a mapping of calculated mixing enthalpy and melting points is proposed for in silico evaluation prior to hot melt extrusion. Following experimental testing of process feasibility, the selected formulations were tested for their physical stability using conventional bulk analytics and by confocal laser scanning and atomic force microscopy imaging. In line with the in silico screening, dl-malic and l-tartaric acid (20%, w/w) in HPC formulations showed no signs of early drug crystallization after 3 months. However, l-tartaric acid formulations displayed few crystals on the surface, which was likely a humidity-induced surface phenomenon. Although more research is needed, the conclusion is that the proposed computational small-scale extrusion approach of ternary solid dispersion has great potential in the formulation development of challenging drugs.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements(Nature, 09.10.2024) Raimondi, Federica; Siow, Kah Mun; Wrona, Dominik; Fuster-García, Carla; Pastukhov, Oleksandr; Schmitz, Michael; Bargsten, Katja; Kissling, Lucas; Swarts, Daan C.; Andrieux, Geoffroy; Cathomen, Toni; Modlich, Ute; Jinek, Martin; Siler, Ulrich; Reichenbach, JanineCRISPR-based genome editing of pseudogene-associated disorders, such as p47phox-deficient chronic granulomatous disease (p47 CGD), is challenged by chromosomal rearrangements due to presence of multiple targets. We report that interactions between highly homologous sequences that are localized on the same chromosome contribute substantially to post-editing chromosomal rearrangements. We successfully employed editing approaches at the NCF1 gene and its pseudogenes, NCF1B and NCF1C, in a human cell line model of p47 CGD and in patient-derived human hematopoietic stem and progenitor cells. Upon genetic engineering, a droplet digital PCR-based method identified cells with altered copy numbers, spanning megabases from the edited loci. We attributed the high aberration frequency to the interaction between repetitive sequences and their predisposition to recombination events. Our findings emphasize the need for careful evaluation of the target-specific genomic context, such as the presence of homologous regions, whose instability can constitute a risk factor for chromosomal rearrangements upon genome editing.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Intracoronary ECG ST-segment shift remission time during reactive myocardial hyperemia. A new method to assess hemodynamic coronary stenosis severity(American Physiological Society, 01.10.2024) Bigler, Marius Reto; Kieninger-Gräfitsch, Andrea; Rohla, Miklos; Corpateaux, Noé; Waldmann, Frédéric; Wildhaber, Reto; Häner, Jonas; Seiler, ChristianFractional flow reserve (FFR) measurements are recommended for assessing hemodynamic coronary stenosis severity. Intracoronary ECG (icECG) is easily obtainable and highly sensitive in detecting myocardial ischemia due to its close vicinity to the myocardium. We hypothesized that the remission time of myocardial ischemia on icECG after a controlled coronary occlusion accurately detects hemodynamically relevant coronary stenosis. This retrospective, observational study included patients with chronic coronary syndrome undergoing hemodynamic coronary stenosis assessment immediately following a strictly 1-min proximal coronary artery balloon occlusion with simultaneous icECG recording. icECG was used for a beat-to-beat analysis of the ST-segment shift during reactive hyperemia immediately following balloon deflation. The time from coronary balloon deflation until the ST-segment shift reached 37% of its maximum level, i.e., icECG ST-segment shift remission time (τ-icECG in seconds), was obtained by an automatic algorithm. τ-icECG was tested against the simultaneously obtained reactive hyperemia FFR at a threshold of 0.80 as a reference parameter. From 120 patients, 139 icECGs (age, 68 ± 10 yr old) were analyzed. Receiver operating characteristic (ROC) analysis of τ-icECG for the detection of hemodynamically relevant coronary stenosis at an FFR of ≤0.80 was performed. The area under the ROC curve was equal to 0.621 (P = 0.0363) at an optimal τ-icECG threshold of 8 s (sensitivity, 61%; specificity, 67%). τ-icECG correlated inversely and linearly with FFR (P = 0.0327). This first proof-of-concept study demonstrates that τ-icECG, a measure of icECG ST segment-shift remission after a 1-min coronary artery balloon occlusion accurately detects hemodynamically relevant coronary artery stenosis according to FFR at a threshold of ≥8 s.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Phosphorization of α-Fe₂O₃ boosts active hydrogen mediated electrochemical nitrate reduction to ammonia(Wiley, 25.09.2024) Hou, Zhiang; Zhang, Yixuan; Chen, Hao; Wang, Jinnan; Li, Aimin; Corvini, PhilippeInexpensive iron-based materials are considered promising electrocatalysts for nitrate (NO₃−) reduction, but their catalytic activity and spontaneous corrosion remain challenges. Here, the α-Fe₂O₃ active surface is reconstructed by gradient phosphorization to obtain FePₓ with higher electrochemical activity. FeP₂.₀ optimizes the adsorption energy of NO₃- and its reduction intermediates, meanwhile promote the generation of active hydrogen (*H) but inhibit its generation of H₂. More importantly, Fe and P can serve as binding sites for NO₃- and *H, respectively, which improves the electron utilization of NO₃- deoxygenation and the efficiency of the subsequent hydrogenation for the selective synthesis of NH₃. 91.7% NO₃- conversion rate is achieved for the reduction of 100 mL 200 mg L-¹ NO₃−−N, 99.3% ammonia (NH₃ selectivity (yield of 1.79 mg h−¹ cm−2), and 91.4% Faraday efficiency in 3 h. The high-purity solid NH₄Cl is finally extracted by gas extraction and vacuum distillation (81.4% recovery). This study provides new insights and strategies for the conversion of NO₃− to NH₃ products over iron-based electrocatalysts.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation In situ minimally invasive 3D printing for bone and cartilage regeneration - a scoping review(De Gruyter, 14.09.2024) Maintz, Michaela; Tomooka, Yukiko; Eugster, Manuela; Gerig, Nicolas; Sharma, Neha; Thieringer, Florian M.; Rauter, GeorgAdvancements in personalized medicine, three-dimensional (3D) printing, miniaturization, and robot-assistedsurgery are driving innovation in tissue engineering. A novelapproach, known asin situprinting, focuses on the direct depo-sition of materials at the surgical site. Using thein situprintingapproach, bone and/or cartilage defects can be addressed withhigh precision. Furthermore, highly customized 3D printed tis-sue constructs or implants can be deposited directly insidethe body. Currently, most applications ofin situprinting arelimited to areas near the skin or open surgeries. Even thougha minimally invasive approach would bring clinical benefits,only a few research groups have focused on this field. In thisscoping review, we provide an overview of the current stateofin situminimally invasive 3D printing technology for boneand cartilage regeneration and discuss its advantages and cur-rent challenges.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Optimizing neuroscience data management by combining REDCap, BIDS and SQLite. A case study in Deep Brain Stimulation(Frontiers Research Foundation, 05.09.2024) Stawiski, Marc; Bucciarelli, Vittoria; Vogel, Dorian; Hemm-Ode, SimoneNeuroscience studies entail the generation of massive collections of heterogeneous data (e.g. demographics, clinical records, medical images). Integration and analysis of such data in research centers is pivotal for elucidating disease mechanisms and improving clinical outcomes. However, data collection in clinics often relies on non-standardized methods, such as paper-based documentation. Moreover, diverse data types are collected in different departments hindering efficient data organization, secure sharing and compliance to the FAIR (Findable, Accessible, Interoperable, Reusable) principles. Henceforth, in this manuscript we present a specialized data management system designed to enhance research workflows in Deep Brain Stimulation (DBS), a state-of-the-art neurosurgical procedure employed to treat symptoms of movement and psychiatric disorders. The system leverages REDCap to promote accurate data capture in hospital settings and secure sharing with research institutes, Brain Imaging Data Structure (BIDS) as image storing standard and a DBS-specific SQLite database as comprehensive data store and unified interface to all data types. A self-developed Python tool automates the data flow between these three components, ensuring their full interoperability. The proposed framework has already been successfully employed for capturing and analyzing data of 107 patients from 2 medical institutions. It effectively addresses the challenges of managing, sharing and retrieving diverse data types, fostering advancements in data quality, organization, analysis, and collaboration among medical and research institutions.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Amorphous metal-organic frameworks loaded on BiVO4 photoanodes with unique internal metal-like structure for promoting photoelectrochemical water splitting(Elsevier, 09/2024) Bai, Weihao; Li, Hao; Peng, Gang; Wang, Jinnan; Li, Aimin; Corvini, PhilippeAlthough ferrocene (Fc) based Metal-Organic Frameworks (MOFs) can act as oxygen evolution co-catalysts (OECs) for improvement of catalytic reactivity, the poor conductivity and lack of highly active metal sites limit its further application in photoelectrochemical (PEC) water splitting. Herein, the amorphous NiFc-MOF was grafted on BiVO4 photoanode (BiVO4@aNiFc-MOFs) for efficient PEC water splitting. This novel BiVO4@aNiFc-MOFs exhibits high current density of 4.34 mA cm−2 at 1.23 VRHE and relative low onset potential of 0.223 VRHE. The subsequent characterizations demonstrate that Ni species with metal-like state in bulk of aNiFc-MOFs form strong metal-support interaction with BiVO4, thereby promoting the interfacial charge transfer. Moreover, the surface of aNiFc-MOFs is short-range ordered with abundant coordinatively unsaturated Ni sites, creating a more favorable pathway for oxygen evolution reaction from thermodynamics. This work provides a simple method to design photoanodes with efficient OECs of amorphous MOFs for feasible PEC water splitting application.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Formulation and dermal delivery of a new active pharmaceutical ingredient in an in vitro wound model for the treatment of chronic ulcers(Elsevier, 09/2024) Thormann, Ursula; Marti, Selina; Lensmith, Elizabeth; Lanz, Michael; Herzig, Susanne; Naef, Reto; Imanidis, GeorgiosThe aim of this study was to investigate dermal delivery of the new active pharmaceutical ingredient (API) TOP-N53 into diabetic foot ulcer using an in vitro wound model consisting of pig ear dermis and elucidate the impact of drug formulation and wound dressing taking into consideration clinical relevance in the home care setting and possible bacterial infection. Different formulation approaches for the poorly water-soluble API including colloidal solubilization, drug micro-suspension and cosolvent addition were investigated; moreover, the effect of (micro-)viscosity of hydrogels used as primary wound dressing on delivery was assessed. Addition of Transcutol® P as cosolvent to water improved solubility and was significantly superior to all other approaches providing a sustained three-day delivery that reached therapeutic drug levels in the tissue. Solubilization in micelles or liposomes, on the contrary, did not boost delivery while micro-suspensions exhibited sedimentation on the tissue surface. Microbial contamination was responsible for considerable metabolism of the drug leading to tissue penetration of metabolites which may be relevant for therapeutic effect. Use of hydrogels under semi-occlusive conditions significantly reduced drug delivery in a viscosity-dependent fashion. Micro-rheologic analysis of the gels using diffusive wave spectroscopy confirmed the restricted diffusion of drug particles in the gel lattice which correlated with the obtained tissue delivery results. Hence, the advantages of hydrogel dressings from the applicatory characteristic point of view must be weighed against their adverse effect on drug delivery. The employed in vitro wound model was useful for the assessment of drug delivery and the development of a drug therapy concept for chronic diabetic foot ulcer. Mechanistic insights about formulation and dressing performance may be applied to drug delivery in other skin conditions such as digital ulcer.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation No relationship between outputs of simple humus balance calculators (VDLUFA and STAND) and soil organic carbon trends(Wiley, 09/2024) Rainford, Shauna‐kay; Leifeld, Jens; Siegl, Sonja; Hagenbucher, Steffen; Riedel, Judith; Gross, Thomas; Niggli, Urs; Keel, Sonja G.Simple humus balance calculators were developed for farmers and consultants to determine the best crop rotation and amount of organic fertilizer required to improve soil quality and prevent nutrient leaching in croplands. Although the potential of these tools to infer the impact of different agricultural practices on soil organic carbon (SOC) dynamics in croplands is not well studied, they have been integrated in several farm-level climate or environmental impact assessment calculators. Here we examine the correlation between humus balance values estimated with two different tools developed in Germany/Central Europe and observed changes in SOC content at 14 long-term sites in Switzerland. The first tool was developed by the Association of German Agricultural Investigation and Research Institutes and is referred to as the VDLUFA. The humus balance calculator STAND is a descendent of the VDLUFA that accounts for pedoclimatic factors in Central Europe. Crop rotations were distinguished based on cultivation practice, whereby those with mixed fertilization were supplied with mineral fertilizer alone and in combination with organic materials, while those with organic fertilization include unfertilized and organic fertilizer treatments. An analysis of 133 short-term observations (i.e. individual crop rotations of five and 6-year duration) and 26 long-term observations (i.e. several crop rotations with a total duration of ≥10 years) showed that humus balance values (kg C ha−1 year−1) of short-term crop rotations were not or only poorly correlated with the observed change in SOC content (%) (R2 = 0.06 in STAND and R2 = 0.05 in VDLUFA for crop rotations with organic fertilization, and R2 < 0.01 for crop rotations with mixed fertilization). The correlation did not improve when the humus balance values of long-term observations with mixed fertilization were compared with decadal SOC development (R2 = 0.04 for STAND and R2 = 0.06 for the VDLUFA). Stronger correlations were found only for long-term observations with organic fertilization (R2 = 0.68 for STAND and R2 = 0.64 for the VDLUFA). These findings underline that while the studied humus balance calculators are able to distinguish the effect of different fertilizers (organic vs. mineral) on a farm's humus supply on the longer term, neither are suited for predicting SOC trends over single crop rotations. Although this study was carried out in Switzerland, the results should apply to any region with temperate climate and similar soil properties.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Predictions of biorelevant solubility change during dispersion and digestion of lipid-based formulations(Elsevier, 09/2024) Ejskjær, Lotte; Holm, René; Kuentz, Martin; Box, Karl J.; Griffin, Brendan T.; O'Dwyer, Patrick J.Computational approaches are increasingly explored in development of drug products, including the development of lipid-based formulations (LBFs), to assess their feasibility for achieving adequate oral absorption at an early stage. This study investigated the use of computational pharmaceutics approaches to predict solubility changes of poorly soluble drugs during dispersion and digestion in biorelevant media. Concentrations of 30 poorly water-soluble drugs were determined pre- and post-digestion with in-line UV probes using the MicroDISS Profiler™. Generally, cationic drugs displayed higher drug concentrations post-digestion, whereas for non-ionized drugs there was no discernible trend between drug concentration in dispersed and digested phase. In the case of anionic drugs there tended to be a decrease or no change in the drug concentration post-digestion. Partial least squares modelling was used to identify the molecular descriptors and drug properties which predict changes in solubility ratio in long-chain LBF pre-digestion (R2 of calibration = 0.80, Q2 of validation = 0.64) and post-digestion (R2 of calibration = 0.76, Q2 of validation = 0.72). Furthermore, multiple linear regression equations were developed to facilitate prediction of the solubility ratio pre- and post-digestion. Applying three molecular descriptors (melting point, LogD, and number of aromatic rings) these equations showed good predictivity (pre-digestion R2 = 0.70, and post-digestion R2 = 0.68). The model developed will support a computationally guided LBF strategy for emerging poorly water-soluble drugs by predicting biorelevant solubility changes during dispersion and digestion. This facilitates a more data-informed developability decision making and subsequently facilitates a more efficient use of formulation screening resources.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Case report. One-stage craniectomy and cranioplasty digital workflow for three-dimensional printed polyetheretherketone implant for an extensive skull multilobular osteochondosarcoma in a dog(Frontiers Research Foundation, 29.08.2024) Hobert, Marc; Sharma, Neha; Benzimra, Caroline; Hinden, Sandro; Oevermann, Anna; Maintz, Michaela; Beyer, Michel; Thieringer, Florian; Guevar, JulienObjective: To report a digital workflow for use and long-term outcome of cranioplasty with a 3D-printed patient-specific Polyetheretherketone (PEEK) implant in a 12-y-old German Shepherd dog after surgical removal of an extensive occipital bone multilobular osteochondrosarcoma (MLO). Study design: Retrospective case report. Animal: A 12-year-old neutered female German Shepherd dog was presented with facial deformity, blindness, tetraparesis, and ataxia. Magnetic resonance imaging (MRI) and computed tomography (CT) identified a large skull-based mass extending extra-and intracranially with severe compression of the cerebellum and occipital lobes of the cerebrum. Methods: One-stage decompressive craniectomy using virtual surgical planned 3D-printed craniotomy cutting guides and the Misonix BoneScalpel® and reconstruction with a patient-specific 3D-printed PEEK cranial implant. Results: 3D-printed craniectomy cutting guides allowed an adequate fit of the cranial implant to the original skull. Misonix BoneScalpel® allowed performing a safe and extensive craniectomy. Postoperative CT (8 weeks after surgery) confirmed the PEEK cranial implant to be in place and without implant rejection. Clinically, the neurological examination identified only a right-hind limb delay in proprioception 8 weeks postoperatively, which remained unchanged at 18 months after surgery. Adjunctive treatment included metronomic chemotherapy. Eighteen months after surgery the dog passed away for reasons unrelated to the MLO, no implant-related complications were reported. Conclusion: 3D-printed craniectomy cutting guides, patient-specific PEEK cranial implant, and metronomic chemotherapy can lead to a successful long-term outcome in dogs with extensive skull MLO. Clinical significance: PEEK is an alternative biomaterial that can be used successfully for skull reconstruction.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Hydrophobic deep eutectic solvent (HDES) as oil phase in lipid-based drug formulations(Elsevier, 15.08.2024) Panbachi, Shaida; Beranek, Josef; Kuentz, MartinThere is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.01A - Beitrag in wissenschaftlicher Zeitschrift