bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time‐Dependent Binding of Molecules and Nanoparticles at Receptor‐Modified Supported Lipid Bilayer Gradients in a Microfluidic Device
Authors: Overeem Nico J. , Hamming Pieter H. (Erik) , Huskens Jurriaan 
Published: August 2020

AbstractMicrofluidic devices are widely used for the sensing of small quantities of analytes. In these applications, the measurement can be easily perturbed by loss of analyte due to binding of the analyte outside the sensing area. We studied the binding of small molecules and nanoparticles up to 400 nm in a state‐of‐the‐art sensing platform – receptor gradients on supported lipid bilayers (SLBs) – in a microfluidic device over time. Biotin‐streptavidin was used as the model interaction motif for specific binding and a biotin‐modified dye, which can bind to the streptavidin on the SLB, as a small‐molecule model analyte. We used finite element simulations to show that the time‐dependent binding of analytes in the sensing area depends strongly on the extent of the nonspecific binding of the vesicles, used in a preceding step to make the SLB platform, outside of the sensing area (e. g., in the tubing). At sufficiently high flow rates, proteins and nanoparticles were only partially depleted by nonspecifically adsorbed lipids, and no delayed onset of binding was observed, because of their lower diffusion coefficients. As a practical solution, a flow cell with two inlets was used to avoid the presence of nonspecifically adsorbed receptors in the sample inlet, which allowed us to decouple the formation of the sensor layer on the surface from the subsequent sensing event. We found that in the absence of lipids adsorbed to the tubing, the nonspecific binding of dye molecules was negligible.
Synthesis of Calcite Superstructures Using Water Reducer as Adjuster
Authors: Liu Yuxi , Xu Huanhuan , Wu Gang 
Published: August 2020

AbstractThe precipitation of calcium carbonate from solutions was synthesized at different temperature using CaCl2 and Na2CO3 as raw materials and with poly(acrylic acid‐allyl glycol ether) water reducer as adjuster. The resulted solids were further characterized by X‐ray diffraction (XRD), Fourier transform infrared (FT‐IR) spectroscopy and scanning electron microscopy(SEM) to investigate the structural property and morphology without and in the presence of adding the poly(acrylic acid‐allyl glycol ether). The results exhibited that when poly(acrylic acid‐allyl glycol ether) was in the presence of reaction system, the calcite CaCO3 microcrystals could be generated with different morphology and size at different temperature. And the concentration of the water reducer used for crystallization could significantly control the morphology and dimensions of the precipitated crystals. As a consequence, the water reducer poly(acrylic acid‐allyl glycol ether) can facilitate and stabilize the formation of calcite.
Diastereoselective Synthesis of Coumarin‐Based Fused Heterocycles via Intramolecular Diels‐Alder and 1,3‐Dipolar Cycloaddition Reactions
Authors: Alizadeh Abdolali , Farajpour Behnaz , Amir Ashjaee Asalemi Kaveh , Taghipour Sajad 
Published: August 2020

AbstractIn this work, a two‐steps strategy for the synthesis of novel coumarin‐based fused heterocycles is presented. The strategy involved i) initial nucleophilic substitution / intramolecular Diels‐Alder reaction of furfurylamine with 4‐chloro‐3‐vinylcoumarins followed by ii) base‐mediated 1,3‐dipolar cycloaddition reaction of resultant coumarin‐based bicyclic products with dibromoformaldoxime. The methodology provides a straightforward access to compounds containing the coumarin, isoquinoline, and isoxazole motifs in a single molecular entity in satisfactory yields. The reaction proceeded with remarkable diastereoselectivity that leads to the formation of five new bonds and six new stereogenic centres. Furthermore, the observed diastereoselectivity was analysed with the help of DFT calculations to substantiate the thermodynamic stability of the obtained products.
Enteric Coating Systems for the Oral Administration of Bioactive Calcium Phosphate Nanoparticles Carrying Nucleic Acids into the Colon
Authors: Hosseini Shabnam , Wey Karolin , Epple Matthias 
Published: August 2020

AbstractA system to deliver bioactive calcium phosphate nanoparticles (about 60 nm, loaded with nucleic acids) across the stomach into the colon was developed by freeze‐drying the nanoparticles in the presence of the cryoprotectant trehalose, incorporation into gelatin capsules, and coating the capsules with an enteric polymer. These capsules were stable at pH 1 (stomach conditions) and dissolved at pH 7.1 (colon conditions). The nanoparticles were released after about 60–120 min at pH 7.1. Cell culture experiments with HeLa and Caco‐2 cells showed an uptake of the nanoparticles, a transfection with EGFP‐encoding plasmid DNA, and a gene‐silencing with anti‐EGFP siRNA. From a variety of enteric coating polymers, the systems cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose‐Eudragit L100, and hydroxypropylmethylcellulose‐polyvinylalcohol‐Eudragit L100 were the most suitable to accomplish the desired biological effect. The presented method is applicable for colon therapy, e. g. for an oral administration of bioactive nanoparticles which are sensitive to acidic conditions.
Emerging Advances of Cell‐Free Systems toward Artificial Cells
Authors: Zhu Yi , Guo Xiaocui , Liu Jinqiao , Li Feng , Yang Dayong 
Published: August 2020

AbstractArtificial cells that mimic the architectural and functional characteristics of living cells not only shed light on the physical principle of life but also facilitate development in the areas such as cell engineering and biomedicine. Cell‐free systems carry out the central dogma that refers to the transcription and translation in the absence of living cells, offering a simplified and controllable platform to study cellular biological processes and design principle. Many efforts have been devoted to construct artificial cells by using cell‐free systems with mimicking cellular structures and characteristics, such as molecular crowding, compartments, gene noise, network, dynamic behavior, and cell communication. Here, the recent emerging advances of cell‐free system toward artificial cells are summarized and discussed. It is notable that this area involves multidisciplinary fields such as material chemistry, nanotechnology, and molecular biology. Although there are still much difficulties and challenges for bottom‐up designing systems with desirable properties for cells, it is firmly believed that with the development of synthetic biology, artificial cells based on the cell‐free systems will provide more possibilities to mimic the complex structures and behaviors of cells.
Motivationale Faktoren im Wirkungskontext von Forschendem Lernen
Authors: Wulf Carmen , Thiem Janina , Gess Christopher 
Published: August 2020

Zusammenfassung
In der Diskussion um Forschendes Lernen wird davon ausgegangen, dass es einerseits ein besonders geeignetes Format zur Förderung unterschiedlicher (Forschungs- und Schlüssel-)Kompetenzen darstellt, andererseits dieses Format aber in enger Verbindung zur Ausprägung der Lern- und Forschungsmotivation Studierender steht. Im Beitrag wird der Förderung von kognitiven und affektiv-motivationalen Forschungskompetenzen sowie der allgemeinen autonomen (Lern-)Motivation durch ein Format Forschendes Lernens in einem Prä-Post-Kontrollgruppendesign nachgegangen und Zusammenhänge zwischen Kompetenzveränderung und Motivation geprüft.
Forschendes Lernen in der ersten Phase der Lehrkräftebildung
Authors: Spies Anke , Knapp Katja 
Published: August 2020

Zusammenfassung
Diese qualitativ-explorative Studie evaluiert, wie Erfahrungen aus dem Forschenden Lernen im Lehramtsstudium nach Berufseintritt unter anderem im Hinblick auf berufspraktische Relevanz rekonstruiert werden. Es zeigt sich, dass die mit Forschendem Lernen verbundenen Erwartungen im Kontrast zum professionellen Selbstverständnis nach der Berufseinmündung stehen und die für eine aktive forschend-evaluative Mitwirkung an Schulentwicklungsprozessen nötigen strukturellen Voraussetzungen in der Praxis nicht gegeben sind.
Forschendes Lernen im Lehramt
Authors: Saunders Constanze , Gess Christopher , Lehmann Malte 
Published: August 2020

Zusammenfassung
Forschendes Lernen wird derzeit in der Ausbildung von Lehramtsstudierenden häufig hinsichtlich seiner Begründungen und Umsetzungspraktiken diskutiert, allerdings weist das Thema in Bezug auf Wirkungen noch Forschungsbedarf auf. Im Beitrag wird daher ein Instrument vorgestellt, mit dem studentische Meinungen zu den Rollen bildungswissenschaftlicher Theorien, eigener Forschung und der Reflexion für die eigene Lehrpraxis erfasst und so Haltungsveränderungen im Rahmen forschungsorientierter Hochschullehre im Lehramt erforscht werden können.
Forschendes Lernen als Studiengangsprofil – was meint dies konkret?
Authors: Kaufmann Margrit E. , Koch Henning 
Published: August 2020

ZusammenfassungDieser Beitrag zeigt beispielhaft auf, wie an der Universität Bremen das Forschende Lernen als Studiengangsprofil implementiert wird. Dabei wird Bezug genommen auf eine Begleitforschung zum studentischen Erleben des Forschenden Lernens, sowohl im Einzelmodul als auch im Verlauf des Curriculums. Auch wird nachgezeichnet, wie sich – basierend auf den Ergebnissen der Begleitforschung – im Lehrteam an der curricularen Profilbildung zum Forschenden Lernen arbeiten lässt.
Forschendes Lehren und Lernen – ein mehrdimensionales Modell für die Lehrpraxis aus Perspektive der empirischen Wissenschaften
Authors: Selje-Aßmann Natascha 
Published: August 2020

Zusammenfassung
Ausgangspunkt des Beitrags ist die Analyse von Definitionen des Forschenden Lernens im Hinblick auf Herausforderungen bei der praktischen Umsetzung in empirischen Wissenschaften. Die vorliegenden Konzepte werden um die Perspektive eines mehrdimensionalen Modells ergänzt, das unterschiedliche Phasen und Grade des Forschungsprozesses integriert. Das Modell lässt sich zur Reflexion von Formaten Forschenden Lernens bei der Planung einzelner Lehrveranstaltungen oder zur Integration von Forschendem Lernen entlang eines Curriculums einsetzen.
Humangenetische Beratung in Deutschland: Entwicklung der Inanspruchnahme
Authors: Schmidtke Jörg , Epplen Jörg T. , Glaubitz Ralf , Grimm Tiemo , Nippert R. Peter , Tönnies Holger , Zerres Klaus , Nippert Irmgard 
Published: August 2020

Zusammenfassung
Hintergrund
Mit dem Gendiagnostikgesetz (GenDG) hat der deutsche Gesetzgeber tief greifende Vorschriften für die humangenetische Leistungserbringung einschließlich der genetischen Beratung erlassen. In dieser Arbeit werden Daten zur Inanspruchnahme der humangenetischen Beratung in den Jahren vor und nach dem Inkrafttreten des GenDG vorgelegt. Diese Daten sollen einer informierten Abschätzung möglicher Auswirkungen des Gesetzes dienen.

Material und Methoden
Die in den Jahren 2005 bis 2017 im Rahmen der gesetzlichen Krankenversicherung erbrachten und nach Einheitlichem Bewertungsmaßstab (EBM) über die kassenärztlichen Vereinigungen (KVen) abrechenbaren humangenetischen Beratungsleistungen wurden über eine Datenbankabfrage beim Zentralinstitut der Kassenärztlichen Bundesvereinigung (ZI-KBV) sowie bei einzelnen KVen Deutschlands erfasst. Für die Diskussion der beobachtbaren Entwicklung der Inanspruchnahme genetischer Beratung und der möglichen zukünftigen Entwicklung werden zusätzlich Daten zum Überweisungsverhalten, den Wartezeiten und Beratungsanlässen aus der GenBIn(Studie „Genetische Beratung in Deutschland“)-Datenbank herangezogen.

Ergebnisse und Diskussion
Die Inanspruchnahme der genetischen Beratung wächst seit 2009 mit einer durchschnittlichen Rate von ca. 6 % pro Jahr. Die gestiegene Nachfrage wird begleitet von veränderten relativen Anteilen der Zuweiser und steigenden Selbstüberweisungen und hat zu längeren Wartezeiten geführt. Unsere Daten legen die Vermutung nahe, dass der beobachtbare ständige Anstieg genetischer Beratungsleistungen multifaktoriell bedingt ist und nicht allein auf das GenDG zurückzuführen ist. Da die Zahl der hier wesentlichen Leistungserbringer, der vertragsärztlichen Fachärzte für Humangenetik, nahezu konstant bleibt, ist absehbar, dass bei weiter steigender Inanspruchnahme Kapazitätsgrenzen erreicht werden.
Predictive Factors for Postoperative Pancreatic Fistula—A Swedish Nationwide Register‐Based Study
Authors: Williamsson C. , Stenvall K. , Wennerblom J. , Andersson R. , Andersson B. , Tingstedt B. 
Published: August 2020

AbstractBackgroundA serious complication after pancreatoduodenectomy (PD) is postoperative pancreatic fistula (POPF). The aim of this study was to analyse the incidence and predictive factors for POPF by using a large nationwide cohort.MethodsData from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients undergoing a PD from 2010 until 30th June 2018 were collected. The material was analysed in two groups, no POPF and clinically relevant (grade B and C) POPF.ResultsA total of 2503 patients underwent PD, of which 245 (10%) developed POPF. Patients with POPF had significantly more overall complications (Clavien Dindo ≥3a, 75% vs. 21%, p < 0.001) and longer hospital stay (median 23 [16–35] vs. 11 [8–15], p < 0.001) than patients without POPF. The risk of POPF was higher with increased BMI (OR 1.08, p < 0.001). Preoperative presence of diabetes (OR 0.52, p = 0.012) and preoperative biliary drainage (OR 0.34, p < 0.001) reduced the risk of POPF. Reconstruction with pancreaticojejunostomy caused a more than two folded increase in POPF compared with pancreaticogastrostomy (OR 2.41, p < 0.001). Weight gain ≥2 kg on postoperative day 1 was also a risk factor (OR 1.76, p < 0.001).ConclusionA high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective.
Clozapine-induced agranulocytosis
Authors: Mijovic Aleksandar , MacCabe James H. 
Published: August 2020

AbstractWider use of clozapine, one of the most effective antipshychotic drugs, is precluded by its propensity to cause agranulocytosis. Currently, clozapine is used for treatment-resistant schizophrenia, with mandatory blood count monitoring for the duration of treatment. Agranulocytosis occurs in up to 0.8% of patients and presents a significant medical challenge, despite decreasing mortality rates. In this paper, we review the epidemiology of clozapine-induced agranulocytosis (CLIA), advances in identifying genetic risk factors, and the preventive measures to reduce the risk of CLIA. We discuss the pathogenesis of CLIA, which, despite receiving considerable scientific attention, has not been fully elucidated. Finally, we address the clinical management and suggest the approach to clozapine re-challenge in patients with a previous episode of neutropenia. With a significant proportion of clozapine recipients in Western hemisphere being Black, we comment on the importance of recognizing benign ethnic neutropenia as a potential impediment to clozapine administration. This review aims to aid haematologists and psychiatrists to jointly manage neutropenia and agranulocytosis caused by clozapine.
Familiäre Transmission der Borderline-Persönlichkeitsstörung
Authors: Zitzmann Jana , Rombold Larissa , Renneberg Babette 
Published: August 2020

Zusammenfassung
Hintergrund
Forschungsergebnisse weisen übereinstimmend darauf hin, dass Kinder von Müttern mit einer Borderline-Persönlichkeitsstörung (BPS) ein erhöhtes Risiko aufweisen, emotionale und verhaltensbezogene Auffälligkeiten zu entwickeln und/oder im Jugendalter selbst BPS-spezifische Symptomausprägungen zu zeigen.

Fragestellung
Welche Faktoren sind bei der familiären Transmission der BPS involviert, und welche Implikationen für die Praxis können darauf aufbauend abgeleitet werden?

Material und Methode
Auf der Basis einer umfassenden Literaturrecherche wurden aktuelle Forschungsbefunde zur familiären Transmission der BPS von Müttern zu ihren Kindern zusammengetragen und Kernbefunde in einem Transmissionsmodell integriert.

Ergebnisse
Das hier postulierte Transmissionsmodell bildet ein komplexes Zusammenspiel verschiedener Einflussfaktoren und Übertragungsmechanismen ab. Neben Faktoren aufseiten der Mutter und des Kindes werden externe Faktoren in das Modell integriert. Darüber hinaus werden (epi-)genetische und pränatale Einflüsse, die Bedeutung der Mutter-Kind-Interaktion und familiäre sowie soziale bzw. gesellschaftliche Einflüsse als Übertragungsmechanismen betont. Zudem wird eine potenziell präventive Wirkung der Hilfesysteme angenommen.

Schlussfolgerung
Aus dem Modell werden Ansatzpunkte abgeleitet, die dazu beitragen könnten, die Vulnerabilität sowie Belastungsfaktoren zu reduzieren und somit eine gesunde kindliche Entwicklung in dieser Risikogruppe zu fördern.
Cisplatin and carboplatin pharmacokinetics in a pediatric patient with hepatoblastoma receiving peritoneal dialysis
Authors: Nijstad A. Laura , van Eijkelenburg Natasha K. A. , Kraal Kathelijne C. J. M. , Meijs Marieke J. M. , de Kanter Clara T. M. M. , Lilien Marc R. , Huitema Alwin D. R. 
Published: August 2020

Abstract
Purpose
Cisplatin and carboplatin are frequently used drugs in the treatment of pediatric hepatoblastoma. Dosing guidelines for these drugs in children requiring peritoneal dialysis are lacking. Here, we describe the case of a 3-year-old boy with pre-existing end-stage renal disease on peritoneal dialysis, requiring treatment with cisplatin and carboplatin for hepatoblastoma.

Methods
Pharmacokinetic data were generated to support clinical dosing decisions, with the aim of adequate exposure and minimal toxicity. In the first chemotherapy cycle, 25% of the standard cisplatin dose and 75% of the carboplatin dose, calculated using the pediatric Calvert formula, were administered. Free platinum concentrations were determined in plasma ultrafiltrate and dialysate samples drawn after administration of cis- and carboplatin.

Results
Cisplatin was well tolerated and the observed AUC of cisplatin were 15.3 and 14.3 mg/L h in cycles 1 and 3, respectively. The calculated AUC of carboplatin in cycle 1 (9.8 mg/mL min) exceeded target AUC of 6.5 mg/mL min and toxicity was observed; therefore, the dose was reduced in cycles 2 and 3. The observed AUC in cycles 2 and 3 was 5.4 and 5.7 mg/mL min respectively. Platinum concentrations in the dialysate showed that 3–4% of the total dose of cisplatin and 10–12% of the total dose of carboplatin were excreted via peritoneal dialysis. Chemotherapy enabled extended hemihepatectomy and complete remission was achieved.

Conclusion
This report shows that it is feasible to measure AUCs for both drugs and to individualize the dose of these drugs according to the PK results and clinical parameters. Our advice for future cases would be to calculate the starting dose of carboplatin using the (pediatric) Calvert formula, assuming a dialytic clearance of zero, and to adjust the dose if required, based on therapeutic drug monitoring.
Microbial insights from Antarctic and Mediterranean shallow-water bone-eating worms
Authors: Hewitt Olivia H. , Díez-Vives Cristina , Taboada Sergi 
Published: August 2020

AbstractBone-eating worms of the genusOsedax(Annelida, Siboglinidae) form unique holobionts (functional entity comprising host and associated microbiota), highly adapted to inhabit bone tissue of marine vertebrates. These gutless worms have developed nutritional symbioses housing intracellular, horizontally acquired, heterotrophic bacteria hypothesised to harness nutrients from organic compounds, sequestered within the bone. Despite previous efforts, critical mechanisms mediating activity and acquisition of diverse bacterial assemblages remain unclear. Using 16S rRNA amplicon sequencing, we performed detailed taxonomic and predicted functional analyses shedding light on the microbial communities of two shallow-waterOsedaxspecies (Osedax deceptionensisandOsedax‘mediterranea’) from contrasting habitats (Antarctic and Mediterranean Sea), in two tissue types (roots and palps). Comparative assessments between host species revealed distinct microbial assemblages whilst, within host species and body tissue, relative symbiont frequencies retained high variability. We reported relatively high abundances of microbes previously classified as primary endosymbionts, Ribotype 1 (order Oceanospirillales), and diverse likely secondary epibionts warranting further exploration as recurrentOsedaxassociates. Surprisingly,O.‘mediterranea’ exhibited relatively low abundance of Oceanospirillales, but increased abundance of other potentially hydrocarbon degrading bacteria from the family Alteromonadaceae. We hypothesise the presence of functionally similar, non-Oceanospirillales primary endosymbionts withinO.‘mediterranea’. Functional metagenomic profiling (using 16S rRNA sequences) predicted broad metabolic capabilities, encompassing relatively large abundances of genes associated with amino acid metabolism. Comparative analyses between host body tissue communities highlighted several genes potentially providing critical functions to theOsedaxhost or that confer adaptations for intracellular life, housed within bone embedded host root tissues.
Interplay of the leading-edge vortex and the tip vortex of a low-aspect-ratio thin wing
Authors: Dong Lei , Choi Kwing-So , Mao Xuerui 
Published: August 2020

Abstract
Three-dimensional vortical structures and their interaction over a low-aspect-ratio thin wing have been studied via particle image velocimetry at the chord Reynolds number of $$10^5$$

10
5

. The maximum lift of this thin wing is found at an angle of attack of $$42^\circ$$

42
∘

. The flow separates at the leading-edge and reattaches to the wing surface, forming a strong leading-edge vortex which plays an important role on the total lift. The results show that the induced velocity of the tip vortex increases with the angle of attack, which helps reattach the separated flow and maintains the leading-edge vortex. Turbulent mixing indicated by the high Reynolds stress can be observed near the leading-edge due to an intense interaction between the leading-edge vortex and the tip vortex; however, the reattachment point of the leading-edge vortex moves upstream closer to the wing tip.

Graphic abstract
Prognostic impact of additional HPV diagnostics in 102 patients with p16-stratified advanced oropharyngeal squamous cell carcinoma
Authors: Weiss Bernhard G. , Anczykowski Mahalia Zoe , Küffer Stefan , Spiegel Jennifer L. , Bertlich Mattis , Canis Martin , Ihler Friedrich , Kitz Julia , Jakob Mark 
Published: August 2020

Abstract
Purpose
p16 overexpression was considered as surrogate marker to identify human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCCs).

Methods
102 patients with advanced stage OPSCCs treated primarily by transoral lasermicrosurgery were included. Prognostic associations of p16- and HPV-status were analyzed separately and combined.

Results
In contrast to p16, the HPV-status resulted in no significant survival discrepancies (5-year overall survival (OS) HPV-positive 64.9%, HPV-negative 78.7%). Combining both markers, p16-positive (p16-positive/HPV-positive, p16-positive/HPV-negative) and p16-negative/HPV-negative groups demonstrated comparable high survival (OS 78.1% vs. 85.6% vs. 73.6%). Lowest survival was observed for patients with p16-negative/HPV-positive OPSCCs (OS 40.8%).
Never smoking patients with p16-positive OPSCCs demonstrated the highest survival, whereas within former/current smokers with p16-positive and p16-negative disease it was comparable low (OS 90.0% vs. 63.0% vs. 57.4%).

Conclusions
p16- and HPV-status should not be considered as equivalent markers for a better prognosis. Furthermore, they should not generally predominate patient associated factors like smoking.