bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micro-environmental cross-talk in an organotypic human melanoma-in-skin model directs M2-like monocyte differentiation via IL-10
Authors: Michielon Elisabetta , López González Marta , Burm Judith L. A. , Waaijman Taco , Jordanova Ekaterina S. , de Gruijl Tanja D. , Gibbs Susan 
Published: June 2020

AbstractPreclinical assessment of novel therapies to fight cancer requires models that reflect the human physiology and immune response. Here, we established an in vitro three-dimensional (3D) reconstructed organotypic human melanoma-in-skin (Mel-RhS) model to investigate cellular and molecular features of tumor formation over a period of 6 weeks. Tumor nests developed over time at the epidermal–dermal junction and spread towards the dermis, in places disrupting the basement membrane. This coincided with secretion of matrix metalloproteinase 9 (MMP-9) by melanoma cells. These features resemble the initial stages of invasive melanoma. Interestingly, while the SK-MEL-28 cell line did not secrete detectable levels of interleukin-10 (IL-10) in traditional two-dimensional monolayers, it did express IL-10 in the 3D Mel-RhS, as did the surrounding keratinocytes and fibroblasts. This cellular cross-talk-induced secretion of IL-10 in the Mel-RhS indicated the generation of an immune suppressive microenvironment. Culture supernatants from Mel-RhS interfered with monocyte-to-dendritic-cell differentiation, leading to the development of M2-like macrophages, which was in part prevented by antibody-mediated IL-10 blockade. Indeed, high-dimensional single-cell analysis revealed a shift within the monocyte population away from a CD163+PD-L1+ M2-like phenotype upon IL-10 blockade. Thus, the 3D configuration of the Mel-RhS model revealed a role for IL-10 in immune escape through misdirected myeloid differentiation, which would have been missed in classical monolayer cultures.
Wechselseitige Effekte von Gruppenkohäsion und Symptomen
Authors: Dinger Ulrike , Zilcha-Mano Sigal , Schauenburg Henning 
Published: June 2020

ZusammenfassungKohäsion ist ein bedeutsamer Teil gruppentherapeutischer Beziehungen und stellt einen potenziell kurativen Faktor dar, der nachfolgende Symptomverbesserungen erklären kann. Trotz der häufig belegten Korrelation zwischen erlebter Kohäsion und der Symptomschwere fehlen longitudinale Studien, in denen sowohl die zeitliche Abfolge von Kohäsion und Symptomveränderungen angemessen berücksichtigt und zusätzlich zwischen dem mittleren Level der Kohäsion einzelner Gruppenteilnehmer („between-person effect“) und der individuellen Veränderung („within-person effect“) differenziert wird. Diese Studie untersucht das Kohäsionserleben zur Patientengruppe auf einer Psychotherapiestation mit integrierter Tagesklinik. Vierzig depressive Patienten wurden im Rahmen einer randomisierten kontrollierten Studie zum Vergleich tagesklinischer und stationärer Psychotherapie rekrutiert. Alle Patienten gaben wöchentlich Auskunft über die Therapiebeziehungen (einschließlich Kohäsion) und die aktuelle Symptombelastung; für die Auswertung der Multilevel Daten wurde ein autoregressives cross-lagged Modell verwendet. Die Ergebnisse deuten auf eine wechselseitige Beeinflussung hin. Ein individueller Anstieg der Kohäsion war ein signifikanter Prädiktor für verbesserte Symptome, auch wenn für die vorherige Symptombelastung kontrolliert wurde. Umgekehrt war auch eine Symptomverbesserung prädiktiv für ein höheres Kohäsionserleben im Verlauf. Damit zeigt die Studie die Bedeutung der Beziehungsqualität zur Gruppe der Mitpatienten und weist auf eine wechselseitige Beeinflussung von Kohäsion und Symptomen hin. Allerdings müssen die Ergebnisse aufgrund der kleinen Stichprobe mit Vorsicht interpretiert werden.
Validation of thoracic aortic dimensions on ECG-triggered SSFP as alternative to contrast-enhanced MRA
Authors: Snel G. J. H. , Hernandez L. M. , Slart R. H. J. A. , Nguyen C. T. , Sosnovik D. E. , van Deursen V. M. , Dierckx R. A. J. O. , Velthuis B. K. , Borra R. J. H. , Prakken N. H. J. 
Published: June 2020

AbstractObjectivesAssessment of thoracic aortic dimensions with non-ECG-triggered contrast-enhanced magnetic resonance angiography (CE-MRA) is accompanied with motion artefacts and requires gadolinium. To avoid both motion artefacts and gadolinium administration, we evaluated the similarity and reproducibility of dimensions measured on ECG-triggered, balanced steady-state free precession (SSFP) MRA as alternative to CE-MRA.MethodsAll patients, with varying medical conditions, referred for thoracic aortic examination between September 2016 and March 2018, who underwent non-ECG-triggered CE-MRA and SSFP-MRA (1.5 T) were retrospectively included (n= 30). Aortic dimensions were measured after double-oblique multiplanar reconstruction by two observers at nine landmarks predefined by literature guidelines. Image quality was scored at the sinus of Valsalva, mid-ascending aorta and mid-descending aorta by semi-automatically assessing the vessel sharpness.ResultsAortic dimensions showed high agreement between non-ECG-triggered CE-MRA and SSFP-MRA (r= 0.99,p< 0.05) without overestimation or underestimation of aortic dimensions in SSFP-MRA (mean difference, 0.1 mm; limits of agreement, − 1.9 mm and 1.9 mm). Intra- and inter-observer variabilities were significantly smaller with SSFP-MRA for the sinus of Valsalva and sinotubular junction. Image quality of the sinus of Valsalva was significantly better with SSFP-MRA, as fewer images were of impaired quality (3/30) than in CE-MRA (21/30). Reproducibility of dimensions was significantly better in images scored as good quality compared to impaired quality in both sequences.ConclusionsThoracic aortic dimensions measured on SSFP-MRA and non-ECG-triggered CE-MRA were similar. As expected, SSFP-MRA showed better reproducibility close to the aortic root because of lesser motion artefacts, making it a feasible non-contrast imaging alternative.Key Points•SSFP-MRA provides similar dimensions as non-ECG-triggered CE-MRA.•Intra- and inter-observer reproducibilities improve for the sinus of Valsalva and sinotubular junction with SSFP-MRA.•ECG-triggered SSFP-MRA shows better image quality for landmarks close to the aortic root in the absence of cardiac motion.
Hemangioblastoma and von Hippel-Lindau disease: genetic background, spectrum of disease, and neurosurgical treatment
Authors: Klingler Jan-Helge , Gläsker Sven , Bausch Birke , Urbach Horst , Krauss Tobias , Jilg Cordula A. , Steiert Christine , Puzik Alexander , Neumann-Haefelin Elke , Kotsis Fruzsina , Agostini Hansjürgen , Neumann Hartmut P.H. , Beck Jürgen 
Published: June 2020

Abstract
Introduction
Hemangioblastomas are rare, histologically benign, highly vascularized tumors of the brain, the spinal cord, and the retina, occurring sporadically or associated with the autosomal dominant inherited von Hippel-Lindau (VHL) disease. Children or adults with VHL disease have one of > 300 known germline mutations of the VHL gene located on chromosome 3. They are prone to develop hemangioblastomas, extremely rarely starting at age 6, rarely at age 12–18, and, typically and almost all, as adults. There is a plethora of VHL-associated tumors and cysts, mainly in the kidney, pancreas, adrenals, reproductive organs, and central nervous system. Due to a lack of causal treatment, alleviation of symptoms and prevention of permanent neurological deficits as well as malignant transformation are the main task. Paucity of data and the nonlinear course of tumor progression make management of pediatric VHL patients with hemangioblastomas challenging.

Methods
The Freiburg surveillance protocol was developed by combining data from the literature and our experience of examinations of > 300 VHL patients per year at our university VHL center.

Results
Key recommendations are to start screening of patients at risk by funduscopy with dilated pupils for retinal tumors with admission to school and with MRI of the brain and spinal cord at age 14, then continue biannually until age 18, with emergency MRI in case of neurological symptoms. Indication for surgery remains personalized and should be approved by an experienced VHL board, but we regard neurological symptoms, rapid tumor growth, or critically large tumor/cyst sizes as the key indications to remove hemangioblastomas. Since repeated surgery on hemangioblastomas in VHL patients is not rare, modern neurosurgical techniques should encompass microsurgery, neuronavigation, intraoperative neuromonitoring, fluorescein dye-based intraoperative angiography, intraoperative ultrasound, and minimally invasive approaches, preceded in selected cases by endovascular embolization. Highly specialized neurosurgeons are able to achieve a very low risk of permanent morbidity for the removal of hemangioblastomas from the cerebellum and spinal cord. Small retinal tumors of the peripheral retina can be treated by laser coagulation, larger tumors by cryocoagulation or brachytherapy.

Conclusion
We consider management at experienced VHL centers mandatory and careful surveillance and monitoring of asymptomatic lesions are required to prevent unnecessary operations and minimize morbidity.
Tetraspanins in the regulation of mast cell function
Authors: Orinska Zane , Hagemann Philipp M. , Halova Ivana , Draber Petr 
Published: June 2020

AbstractMast cells (MCs) are long-living immune cells highly specialized in the storage and release of different biologically active compounds and are involved in the regulation of innate and adaptive immunity. MC degranulation and replacement of MC granules are accompanied by active membrane remodelling. Tetraspanins represent an evolutionary conserved family of transmembrane proteins. By interacting with lipids and other membrane and intracellular proteins, they are involved in organisation of membrane protein complexes and act as “molecular facilitators” connecting extracellular and cytoplasmic signaling elements. MCs express different tetraspanins and MC degranulation is accompanied by changes in membrane organisation. Therefore, tetraspanins are very likely involved in the regulation of MC exocytosis and membrane reorganisation after degranulation. Antiviral response and production of exosomes are further aspects of MC function characterized by dynamic changes of membrane organization. In this review, we pay a particular attention to tetraspanin gene expression in different human and murine MC populations, discuss tetraspanin involvement in regulation of key MC signaling complexes, and analyze the potential contribution of tetraspanins to MC antiviral response and exosome production. In-depth knowledge of tetraspanin-mediated molecular mechanisms involved in different aspects of the regulation of MC response will be beneficial for patients with allergies, characterized by overwhelming MC reactions.
Emergence delirium is associated with increased postoperative delirium in elderly: a prospective observational study
Authors: Zhang Yan , He Shu-Ting , Nie Bin , Li Xue-Ying , Wang Dong-Xin 
Published: June 2020

AbstractBackgroundThe clinical significance of emergence delirium remains unclear. The purpose of this study was to investigate the association between emergence delirium and postoperative delirium in elderly after general anesthesia and surgery.MethodsThis prospective observational study was done in a tertiary hospital in Beijing, China. Elderly patients (65–90 years) who underwent major noncardiac surgery under general anesthesia and admitted to the postanesthesia care unit (PACU) after surgery were enrolled. Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay. Postoperative delirium was assessed with the Confusion Assessment Method during the first 5 postoperative days. The association between emergence delirium and postoperative delirium was analyzed with a multivariable logistic regression model.ResultsA total of 942 patients were enrolled and 915 completed the study. Emergence delirium developed in 37.0% (339/915) of patients during PACU stay; and postoperative delirium developed in 11.4% (104/915) of patients within the first 5 postoperative days. After adjusted confounding factors, the occurrence of emergence delirium is independently associated with an increased risk of postoperative delirium (OR 1.717, 95% CI 1.078–2.735,P = 0.023). Patients with emergence delirium stayed longer in PACU and hospital after surgery, and developed more non-delirium complications within 30 days.ConclusionsEmergence delirium in elderly admitted to the PACU after general anesthesia and major surgery is independently associated with an increased risk of postoperative delirium. Patients with emergence delirium had worse perioperative outcomes.Chinese Clinical Trial Registry (chictr.org.cn)ChiCTR-OOC-17012734
Voltammetry coupled with impedance spectroscopy
Authors: Pajkossy Tamás 
Published: June 2020

AbstractDynamic EIS (dEIS) is the joint use of cyclic voltammetry and electrochemical impedance spectroscopy. A method is planned for data evaluation which involves transformations yielding potential program invariant forms of certain characteristic functions. This way of calculation is illustrated by the analysis of two archetypes of electrochemical kinetics. A future task is to develop the related theories and to perform demonstration experiments aimed at establishing dEIS as a robust, general-purpose technique for characterizing electrochemical systems.
Tidal response to sea level rise and bathymetric changes in the German Wadden Sea
Authors: Wachler Benno , Seiffert Rita , Rasquin Caroline , Kösters Frank 
Published: June 2020

AbstractTidally dominated coasts are directly affected not only by projected rise in mean sea level, but also by changes in tidal dynamics due to sea level rise and bathymetric changes. By use of a hydrodynamic model, which covers the entire German Bight (South-Eastern North Sea), we analyse the effects of sea level rise and potential bathymetric changes in the Wadden Sea on tidal current velocities. The model results indicate that tidal current velocities in the tidal inlets and channels of the Wadden Sea are increased in response to sea level rise. This is explained by the increased ratio of tidal prism to tidal inlet cross-sectional area, which is due to the characteristic hypsometry of tidal basins in the Wadden Sea including wide and shallow tidal flats and relatively narrow tidal channels. The results further indicate that sea level rise decreases ebb dominance and increases flood dominance in tidal channels. This is, amongst others, related to a decreased intertidal area again demonstrating the strong interaction between tidal wave and tidal basin hypsometry in the Wadden Sea. The bathymetry scenario defined in this study includes elevated tidal flats and deepened tidal channels, which is considered a potential future situation under accelerated sea level rise. Application of these bathymetric changes to the model mostly compensates the effects of sea level rise. Furthermore, changes in current velocity due to the altered bathymetry are in the same order of magnitude as changes due to mean sea level rise. This highlights the significance of considering potential bathymetric changes in the Wadden Sea for regional projections of the tidal response to sea level rise.
Decades of Tight Fiscal Policy Have Left the Health Care System in Italy Ill-Prepared to Fight the COVID-19 Outbreak
Authors: Prante Franz J. , Bramucci Alessandro , Truger Achim 
Published: June 2020

AbstractAlthough austerity was particularly strong in the aftermath of the economic crisis of 2008 and its consequences in the euro area, Italian fiscal policies have been characterised by tough consolidation periods ever since the 1990s.
Why Current EU Proposals for Corona-Related Financial Aid Cannot Replace Coronabonds
Authors: Dullien Sebastian , Theobald Thomas , Tober Silke , Watt Andrew 
Published: June 2020

AbstractWith public debt-to-GDP levels now set to surpass post-war records and Italy’s ratio approaching levels reached in Greece on the eve of the country’s debt restructuring in early 2012, fears of a return of the sovereign debt crisis have emerged.
A European Mechanism for the Issuance and Initial Distribution of Debt Securities
Authors: Pavlidis Georgios 
Published: June 2020

AbstractAlthough the European Union (EU) has implemented initiatives and common rules regarding securities settlements, no similar integration initiatives have been proposed for the issuance and initial distribution of debt securities. The EU does not function as a single market given that issuers of euro debt instruments still have to use multiple and non-harmonised channels and procedures. A harmonised European framework for the issuance and initial distribution of debt securities or the establishment of a new European market infrastructure service is widely considered a way to create a deep and liquid single market for debt instruments. While such a paradigm shift promises significant improvements compared with the existing debt issuance and distribution landscape, a hasty and poorly designed public intervention would risk distorting the market, thereby increasing complexity and bringing more fragmentation.
Cytochrome P450-mediated N-demethylation of noscapine by whole-cell biotransformation: process limitations and strategies for optimisation
Authors: Richards Luke , Jarrold Ailsa , Bowser Tim , Stevens Geoffrey W , Gras Sally L 
Published: June 2020

Abstract
Cytochrome P450 enzymes catalyse reactions of significant industrial interest but are underutilised in large-scale bioprocesses due to enzyme stability, cofactor requirements and the poor aqueous solubility and microbial toxicity of typical substrates and products. In this work, we investigate the potential for preparative-scale N-demethylation of the opium poppy alkaloid noscapine by a P450BM3 (CYP102A1) mutant enzyme in a whole-cell biotransformation system. We identify and address several common limitations of whole-cell P450 biotransformations using this model N-demethylation process. Mass transfer into Escherichia coli cells was found to be a major limitation of biotransformation rate and an alternative Gram-positive expression host Bacillus megaterium provided a 25-fold improvement in specific initial rate. Two methods were investigated to address poor substrate solubility. First, a biphasic biotransformation system was developed by systematic selection of potentially biocompatible solvents and in silico solubility modelling using Hansen solubility parameters. The best-performing biphasic system gave a 2.3-fold improvement in final product titre compared to a single-phase system but had slower initial rates of biotransformation due to low substrate concentration in the aqueous phase. The second strategy aimed to improve aqueous substrate solubility using cyclodextrin and hydrophilic polymers. This approach provided a fivefold improvement in initial biotransformation rate and allowed a sixfold increase in final product concentration. Enzyme stability and cell viability were identified as the next parameters requiring optimisation to improve productivity. The approaches used are also applicable to the development of other pharmaceutical P450-mediated biotransformations.
Climatic factors controlling stem growth of alien tree species at a mesic forest site: a multispecies approach
Authors: Hoffmann Nils , Heinrichs Steffi , Schall Peter , Vor Torsten 
Published: June 2020

AbstractThe introduction of non-native species with various ecological and functional traits to European forests may be a potential tool for mitigating climate risks. We analyzed the growth sensitivity to climate of seven alien (Acer rubrum,Betula maximowicziana,Castanea sativa,Cryptomeria japonica,Metasequoia glyptostroboides,Thuja plicataandTsuga heterophylla) and two native (Fagus sylvaticaandPicea abies) tree species on a productive forest site in western Germany in order to assess their potential suitability in light of climate change. Retrospective basal area increment at breast height (BAI) and total stem volume increment (VI) were statistically related to a total of 11 multiscale climatic variables showing minor discrepancies between BAI and VI in climatic sensitivity. Across the tree species, the strongest climate signals were found for the standardized precipitation evapotranspiration index (spei), vapor pressure deficit (vpd) and the number of frost days (nfr) representing water availability, heat and coldness, respectively. Growth of most species was positively affected by mild winters and growing season spei. Importance of the investigated variables differed among tree species with, e.g.,C. sativaandT. plicatabeing mainly driven by winter vpd andA. rubrum,C. japonicaandP. abiesby water availability in the growing seasons. We conclude that particularly more anisohydric species (e.g.,C. sativa) may profit from their low sensitivity to drier conditions. Highly sensitive and isohydric species (e.g.,A. rubrum)will undergo significant growth reductions when climate becomes more variable.
Biological Energy and the Experiencing Subject
Authors: Gamper Johan 
Published: June 2020

AbstractAs physical things have mathematical properties we in this paper let mental things have biological properties. The work is based on recent metaphysical findings that shows that there could be interfaces between separate ontological domains. According to this view there could be mathematical objects, physical objects, and also mental objects. The aim of this study is to establish a view of the biological object that allows it to possibly generate the experiencing subject. Based on the notion that energy per se is related to the ability of a system to do some work, biological energy is defined as a biological object’s ability to recover from the load it is exposed to. Introducing the concept of the experiencing subject, the experiencing subject would be the agent experiencing the biological object’s need of recovery from the load it is exposed to. Once established, the experiencing subject may develop non-biological needs. On this basis experiencing subjects have biological properties without being biological in exactly the same manner as physical things have mathematical properties without being mathematical (would that be the case).
Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?
Authors: Gires Olivier , Pan Min , Schinke Henrik , Canis Martin , Baeuerle Patrick A. 
Published: June 2020

AbstractEpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.