bluuebunny/crossref_metadata_2025_split huggingface dataset:
The serum protein levels of the tPA–BDNF pathway are implicated in depression and antidepressant treatment
Authors: Jiang H , Chen S , Li C , Lu N , Yue Y , Yin Y , Zhang Y , Zhi X , Zhang D , Yuan Y 
Published: April 2017

AbstractEvidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA–BDNF pathway in MDD. We examined serum protein concentrations in the tPA–BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA–BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.
Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations
Authors: Hornig M , Gottschalk C G , Eddy M L , Che X , Ukaigwe J E , Peterson D L , Lipkin W I 
Published: April 2017

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and debilitating disorder marked by cognitive and sensory dysfunction and unexplained physical fatigue. Classically, cases present after a prodrome consistent with infection; however, some cases are atypical and have a different presentation and comorbidities that pose challenges for differential diagnosis. We analyzed cerebrospinal fluid (CSF) from 32 cases with classical ME/CFS and 27 cases with atypical ME/CFS using a 51-plex cytokine assay. Atypical subjects differed in cytokine profiles from classical subjects. In logistic regression models incorporating immune molecules that were identified as potential predictor variables through feature selection, we found strong associations between the atypical ME/CFS phenotype and lower CSF levels of the inflammatory mediators, interleukin 17A and CXCL9. Network analysis revealed an absence of inverse inter-cytokine relationships in CSF from atypical patients, and more sparse positive intercorrelations, than classical subjects. Interleukin 1 receptor antagonist appeared to be a negative regulator in classical ME/CFS, with patterns suggestive of disturbances in interleukin 1 signaling and autoimmunity-type patterns of immune activation. Immune signatures in the central nervous system of ME/CFS patients with atypical features may be distinct from those with more typical clinical presentations.
Permanent magnet working point ripple in synchronous generators
Authors: Sjökvist Stefan , Rossander Morgan , Eriksson Sandra 
Published: April 2017

Permanent magnets (PMs) are today widely used in electrical machines of all sorts. With their increase in popularity, the amount of research has increased as well. In this study, the magnetic flux density ripple of the working point of the PMs in a 100 kW PM synchronous generator has been investigated for three different load cases: no load, AC load, and DC load. The PMs will be subjected to a shift in working point as a consequence of the characteristics of the electrical loading. This study is based on finite element method simulations where the ripple of the magnetic flux density in the PMs was recorded at three positions within a PM. The slot harmonic of 7.5 times the electrical frequency was present in the results for all load cases, but mainly at the surface of the PM, as expected. Results showed an unexpected harmonic of , assumed to be an undertone of the slot harmonics. The harmonic for the DC load case was significantly higher than for the AC load case and is caused by the current fluctuation during passive rectification. For the studied machine, the added harmonics in the magnetic field due to passive rectification are less than the slot‐related harmonics.
European Census on Pediatric Surgery
Authors: Czauderna Piotr , Rolle Udo , Zachariou Zacharias , Parigi Gian 
Published: April 2017

Background Detailed data on the distribution of pediatric surgical institutions in Europe are sparse. Therefore, the Section and Board of Pediatric Surgery of the Union of European Medical Specialists (UEMS) and the European Pediatric Surgeons' Association (EUPSA) jointly organized the first official census of the European centers of pediatric surgery (PS).
Materials and Methods After obtaining a list of pediatric surgical centers in Europe, a specialized questionnaire was created and made available on the Internet. General, workload, staff, and ancillary data were collected for the centers.
Results Total 215 out of 431 centers answered. PS center density is 1 in every 177,000 children or 1 in every 1,142,000 inhabitants. Approximately 77% of the centers (167 out of 215) are training centers in PS. Every center has an average inpatients procedures/year equal to 1,588, and 92.6 neonatal procedures/year. There are 3.9 surgeons/100,000 children, and 1,662 neonates for every surgeon. In average every EU surgeon performs 202 procedures/year, of which 11 procedures are on neonates. Trainees represent the 38% of the total workforce, and there are 2.3 trainees for every staff aged > 60 years.
Conclusion The paper aims to offer a more grounded basis on which the future of PS in our Continent should be planned. Presented data will provide an invaluable help to all our colleagues, as well as national policy makers, to press for and to make better informed and well-grounded sound political choices in the field of PS.
New Perspectives in Autism Spectrum Disorder associated with Tuberous Sclerosis
Authors: Benvenuto Arianna , Graziola Federica , Moavero Romina , Mazzone Luigi , Gialloreti Leonardo , Curatolo Paolo , Siracusano Martina 
Published: April 2017

AbstractRecent advances in molecular genetics and preclinical studies of tuberous sclerosis complex (TSC) have helped to better understand the pathophysiology of TSC-related autism spectrum disorder (ASD). Furthermore, developmental studies have shown that infants with TSC begin to diverge from the neurotypical trajectories at the age of 6 months. Early abnormalities are often characterized by a delay in nonverbal cognitive skills, such as fine motor and visual reception domains followed by qualitative impairment of social communication. The expanding possibilities of an early diagnosis of TSC should increasingly allow the prompt identification of a population of infants at high risk for developing ASD. A presymptomatic diagnosis of TSC could facilitate not only the prospective investigation of developmental trajectories and early markers of ASD but also the evaluation of the efficacy of early interventions. Early identification of infants at high-risk for ASD, such as TSC infants, can allow designing individualized treatment strategies to address deficits in specific developmental domains associated with autism. The involvement of mammalian target of rapamycin (mTOR) in determining the behavioral phenotypes associated with TSC led to the hypothesis that mTOR inhibitors could also have a benefit on ASD symptoms. After the promising results from preclinical studies administrating rapamycin, clinical trials studying mTOR inhibitors are now undergoing.
Effects of shRNA Targeting Maspin on the Invasion of Extravillous Trophoblast Cell
Authors: Shi Xinwei , Liu Qing , Liu Hao , Deng Dongrui , Qiao Fuyuan , Wu Yuanyuan 
Published: April 2017

Objective Hypomethylation of the maspin gene results in increased expression of maspin in preeclamptic placentas. However, maspin gene function and the molecular aspects in placentation remain largely unclear. The study was designed to investigate the effects of maspin on the invasion of extravillous trophoblast cell line (TEV-1) and the molecular mechanism.
Study Design We cloned short hairpin RNA (shRNA) targeting maspin gene into plasmid pGenesil-1.1 eukaryotic expression vector and then transfected it using adenovirus. The methylation rates in the maspin gene were detected by bisulfite sequencing polymerase chain reaction; the invasive ability of trophoblast cells was examined by Transwell chamber assay; the mRNA and protein expression of maspin and some invasive related gene was detected by reverse transcription-polymerase chain reaction and Western blot analysis.
Results After the maspin expression was successfully knocked down, the methylation rates in the maspin gene were significantly increased, and the number of cells invading through Matrigel (Corning Life Sciences and BD Biosciences) was obviously increased. The mRNA levels of vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor-C (VEGF-C), and matrix metalloproteinase-2 (MMP2) were increased significantly.
Conclusion Using shRNA technology, this study further verified that maspin gene methylation could decrease maspin expression and inhibit the invasion of TEV-1 cells through VEGF-A, VEGF-C, and MMP2.
Update on cholangiocarcinoma: potential impact of genomic studies on clinical management
Authors: Walter Dirk , Hartmann Sylvia , Waidmann Oliver 
Published: April 2017

AbstractThe term cholangiocarcinoma (CCA) comprises neoplasms of the intrahepatic, perihilar, and distal bile duct. Five-year survival rates of patients with CCA are below 20 %, and no targeted therapy could prove a benefit in comparison to the standard treatment of cisplatinum and gemcitabine. In recent years, next generation sequencing studies revealed a profound genomic heterogeneity of CCA subtypes potentially affecting the design of future therapy trials. This review provides a concise update on current clinical management of CCA including data of recent genomic studies and differences between CCA subtypes.
Suprachoroidale Hydrogelplombe – eine neue minimalinvasive Technik zur Behandlung der rhegmatogenen Netzhautablösung
Authors: Boden K. , Januschowski K. , Szurman P. 
Published: April 2017

ZusammenfassungDie suprachoroidale Hydrogelplombe ist ein neues, einfaches und sicheres Verfahren zur Behandlung der Netzhautablösung. Die technischen Vorteile der modernen Vitrektomie und der klassischen Buckelchirurgie sollen in diesem operativen Ansatz vereint werden. Die Technik kann additiv in Kombination mit der Vitrektomie oder als „stand-alone procedure“ angewendet werden. Als geeignetes Tamponadematerial hat sich das quervernetzte Hydrogel mit einer Resorptionsdauer von bis zu 8 Wochen herausgestellt. Es werden noch weitere Untersuchungen mit Langzeiterfahrungen empfohlen, die zu einer weiteren Verbreitung der suprachoroidalen Hydrogelplombe als operatives Verfahren zur Behandlung der Netzhautablösung führen sollten.
Uveale Melanomzellen unter oxidativem Stress – Einfluss von VEGF und VEGF-Inhibitoren
Authors: Dithmer M. , Kirsch A. , Gräfenstein L. , Wang F. , Schmidt H. , Coupland S. , Fuchs S. , Roider J. , Klettner A. 
Published: April 2017

Zusammenfassung
Hintergrund Die Rolle des oxidativen Stresses bei Krebserkrankungen ist komplex. Während die durch ihn ausgelösten pathologischen Veränderungen an der Krebsentstehung beteiligt sind, kann er in späteren Stadien das Absterben von Tumorzellen fördern und sogar Metastasierungen eindämmen. Krebszellen zeigen durch ihren veränderten Metabolismus häufig eine verstärkte Bildung von radikalen Sauerstoffspezies, was sie anfällig für zusätzlichen oxidativen Stress macht. Dies ist ein wichtiger Wirkmechanismus von verschiedenen Chemotherapeutika und von therapeutisch eingesetzter ionisierender Strahlung. Das uveale Melanom ist der häufigste primäre Tumor im adulten Auge. Für die bei etwa 50 % der Patienten auftretenden Metastasen sind zurzeit leider keine wirksamen Behandlungsoptionen verfügbar. Der Primärtumor kann aber mit gutem Erfolg mit ionisierender Strahlung behandelt werden. Eine wichtige Nebenwirkung ist hierbei die Strahlenretinopathie, die wiederum mit VEGF-Antagonisten (VEGF: Vascular endothelial Growth Factor) behandelt wird. Eine Therapie des Primärtumors mit Anti-VEGF-Substanzen wird ebenfalls in der Literatur diskutiert. Über eine solche Anwendung liegen bisher nur wenige Daten vor, es ist aber eine paradoxe Verschlechterung der Situation bei einem uvealen Melanommodell in der Maus unter Anti-VEGF-Therapie berichtet worden.
Methoden In einer Studie haben wir den Einfluss von VEGF und dem VEGF-Antagonisten Bevacizumab auf das Überleben von 5 unterschiedlichen uvealen Melanomzelllinien, die mit oxidativem Stress (Wasserstoffperoxid) behandelt worden sind, untersucht. Im Weiteren haben wir uns die Expression relevanter Proteine sowie den Einfluss von Bevacizumab auf das Proliferationsverhalten der Zellen und auf das Angiogeneseverhalten von Endothelzellen in einer Kokultur mit uvealen Melanomzellen angesehen.
Ergebnisse Wir konnten in dieser Studie zeigen, dass nicht nur VEGF, sondern paradoxerweise auch der VEGF-Antagonist Bevacizumab uveale Melanomzellen vor einem Zelltod durch oxidativen Stress schützen kann. Bevacizumab zeigt darüber hinaus keinen Einfluss auf die Proliferation der Zellen und ist nur bedingt in der Lage, angiogene Strukturen in diesem System zu verhindern.
Schlussfolgerungen Die Protektion der uvealen Melanomzellen vor oxidativem Stress durch Bevacizumab ist, gerade in Anbetracht des Wirkprinzips der ionisierenden Strahlung, durch oxidativen Stress in den Tumorzellen einen Zelltod auszulösen, ein besorgniserregender Befund, der gegen eine Verwendung von Anti-VEGF bei uvealem Melanom spricht.
Nutzerinteresse an mobilen digitalen Assistenzsystemen zur Förderung körperlicher Aktivität bei Studierenden und Mitarbeitern einer Universität
Authors: Salzwedel Annett , Rabe Sophie , Zahn Thomas , Neuwirth Julia , Eichler Sarah , Haubold Kathrin , Wachholz Anne , Reibis Rona , Völler Heinz 
Published: April 2017

Zusammenfassung
Hintergrund Einem Großteil der Bevölkerung gelingt es trotz ausreichenden Wissens um die protektiven Effekte nicht, ausreichende körperliche Aktivität in den Alltag zu integrieren. Digitale Assistenzsysteme könnten hierbei unterstützend eingesetzt werden. Dies setzt jedoch das Interesse potentieller Nutzer voraus.
Methode In einer Online-Befragung wurden im Juni/Juli 2015 Mitarbeiter und Studierende der Universität Potsdam zum individuellen Ausmaß der sportlichen Aktivität, dem Interesse an elektronischer Trainingsunterstützung und weiteren Parametern befragt.
Ergebnis 1217 Studierende und 485 Mitarbeiter (67,3 bzw. 67,5% Frauen, 26±4,9 bzw. 42,7±11,7 Jahre) nahmen an der Studie teil. Die empfohlene sportliche Aktivität (≥3 Tage bzw. 150 min/Woche) wurde von 70,1% der Mitarbeiter und 52,7% der Studierenden nicht erreicht. Innerhalb dieser Gruppen zeigten 53,2% (Studierende) bzw. 44,2% (Mitarbeiter), unabhängig von Alter, Geschlecht, BMI bzw. Bildungsniveau, Interesse an einer elektronischen Trainingsunterstützung.
Schlussfolgerung Auch in jüngeren Bevölkerungsgruppen mit hohem Bildungsniveau ist die Mehrzahl der Personen unzureichend körperlich aktiv. Ein Interesse an Trainingsunterstützung besteht in etwa der Hälfte dieser sportlich inaktiven Gruppe. Dies legt den Schluss nahe, dass der personalisierte Einsatz mobiler Assistenzsysteme für die positive Beeinflussung des Lebensstils zunehmend an Bedeutung gewinnen könnte.
Titling indigenous communities protects forests in the Peruvian Amazon
Authors: Blackman Allen , Corral Leonardo , Lima Eirivelthon Santos , Asner Gregory P. 
Published: April 2017

SignificanceDeveloping countries are increasingly granting local communities legal title to forests. Almost a third of forests in the global south are now managed by local communities, more than twice the share currently found in protected areas. However, we know little about the effects of titling on forest clearing and disturbance, which remain urgent problems. We use community-level longitudinal data derived from high-resolution satellite images, along with statistical techniques that control for confounding factors, to measure the effect of titling indigenous communities in the Peruvian Amazon. Results indicate that titling significantly reduces both clearing and disturbance, at least in the short term. The implication is that awarding formal land titles to local communities can protect forests.
Accelerated body size evolution during cold climatic periods in the Cenozoic
Authors: Clavel Julien , Morlon Hélène 
Published: April 2017

SignificanceWe do not have a clear understanding of the impact of past climatic changes on evolution. This question has been investigated for a few lineages in the fossil record, but a global vision is still lacking. Here, we present a phylogenetic comparative framework for examining the effects of past climate changes on morphological evolution with data from almost all existing birds and mammals. We show that global temperatures fluctuations through the Cenozoic impacted body size evolution. The evolution of body size was faster during periods of global cooling in most of the groups, challenging the hypothesis that evolution is faster under warm climates. These results have important implications for our understanding of how ongoing climate changes may affect future evolution.
Posterior parietal cortex contains a command apparatus for hand movements
Authors: Rathelot Jean-Alban , Dum Richard P. , Strick Peter L. 
Published: April 2017

Significance
The primate hand has evolved into a specialized sensorimotor device that can grasp, explore, and manipulate objects with extraordinary skill. The frontal lobe is generally thought to be the exclusive source of descending commands to the spinal cord to control hand movements. Here, we identify a region within the parietal lobe that could also contribute commands to control hand movements directly at spinal levels. Intracortical stimulation in a lateral region in area 5 of posterior parietal cortex reliably evokes hand movements. Corticospinal neurons in this region make disynaptic connections with hand motoneurons. These observations suggest that a region within lateral area 5 contains a unique command apparatus that could assist in generating dexterous finger movements required during haptic behavior.
Reach and speed of judgment propagation in the laboratory
Authors: Moussaïd Mehdi , Herzog Stefan M. , Kämmer Juliane E. , Hertwig Ralph 
Published: April 2017

Significance
Individual judgments, feelings, and behaviors can spread from person to person in social networks, similarly to the propagation of infectious diseases. Despite major implications for many social phenomena, the underlying social-contagion processes are poorly understood. We examined how participants’ perceptual judgments spread from one person to another and across diffusion chains. We gauged the speed, reach, and scale of social contagion. Judgment propagation tended to slow down with increasing social distance from the source. Crucially, it vanished beyond a social horizon of three to four people. These results advance the understanding of some of the mechanisms underlying social-contagion phenomena as well as their scope across domains as diverse as political mobilization, health practices, and emotions.
Parietal neurons encode expected gains in instrumental information
Authors: Foley Nicholas C. , Kelly Simon P. , Mhatre Himanshu , Lopes Manuel , Gottlieb Jacqueline 
Published: April 2017

Significance
We examine how the brain guides active sensing in awake, behaving primates using a paradigm in which information sampling is dissociated from reinforcement variables, such as cumulative future reward or reward prediction errors. We show that target selective cells in lateral intraparietal cortex encode decision variables based on expected gains in instrumental information—the extent to which a visual cue, when discriminated, is expected to reduce the uncertainty of a subsequent action.
Uplift-driven diversification in the Hengduan Mountains, a temperate biodiversity hotspot
Authors: Xing Yaowu , Ree Richard H. 
Published: April 2017

Significance
Why do so many species occur in mountains? A popular but little-tested hypothesis is that tectonic uplift creates environmental conditions (new habitats, dispersal barriers, etc.) that increase the rate at which resident species divide and evolve to form new ones. In China’s Hengduan Mountains region, a biodiversity hotspot uplifted over the last 8 million years, this rate does in fact show a significant increase during that time, relative to the rate for adjacent older mountains, and to the rate of species immigration. The Hengduan Mountains flora is thus made up disproportionately of species that evolved within the region during its uplift, supporting the original hypothesis and helping to explain the prevalence of mountains as global biodiversity hotspots.
Membrane fission by protein crowding
Authors: Snead Wilton T. , Hayden Carl C. , Gadok Avinash K. , Zhao Chi , Lafer Eileen M. , Rangamani Padmini , Stachowiak Jeanne C. 
Published: April 2017

Significance
The division of membrane-bound compartments into smaller, separate volumes is essential to cells. The process of membrane fission is required for the separation of two membrane compartments. The prevailing view has been that to drive fission, proteins must contain specific structural features such as curved scaffolds and wedge-like membrane insertions. In contrast, this work demonstrates a more general mechanism, in which crowding among membrane-bound proteins drives fission. Like a compressed gas, collisions among crowded proteins generate pressure that can stretch, bend, and ultimately disrupt membrane surfaces, leading to fission. The discovery of this mechanism broadens our perspective on membrane fission by demonstrating how any protein, independent of its structure, can assist in this essential cellular process.
Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity
Authors: Nagata Masahiro , Izumi Yoshihiro , Ishikawa Eri , Kiyotake Ryoko , Doi Rieko , Iwai Satoru , Omahdi Zakaria , Yamaji Toshiyuki , Miyamoto Tomofumi , Bamba Takeshi , Yamasaki Sho 
Published: April 2017

Significance
Sensing tissue damage is a crucial function of pattern recognition receptors (PRRs). However, endogenous ligand recognition by PRRs is not well documented. Macrophage inducible C-type lectin (Mincle) is a PRR that recognizes both pathogens and damaged cells. In this study, we isolated endogenous glycolipids derived from damaged cells and identified a ubiquitous intracellular metabolite, β-glucosylceramide (GlcCer), as a Mincle ligand. β-GlcCer induced inflammatory and acquired immune responses via Mincle on myeloid cells. Accumulation of β-GlcCer leads to Gaucher disease, a disorder characterized mainly by systemic inflammation. In a Gaucher model in which mice are deficient in the β-GlcCer–degrading enzyme, further deletion of the Mincle gene attenuated inflammatory responses. These results suggest that β-GlcCer is an endogenous Mincle ligand and acts as an immunostimulatory factor upon cell damage.