bluuebunny/crossref_metadata_2025_split huggingface dataset:
The orphan GPR50 receptor promotes constitutive TGFβ receptor signaling and protects against cancer development
Authors: Wojciech Stefanie , Ahmad Raise , Belaid-Choucair Zakia , Journé Anne-Sophie , Gallet Sarah , Dam Julie , Daulat Avais , Ndiaye-Lobry Delphine , Lahuna Olivier , Karamitri Angeliki , Guillaume Jean-Luc , Do Cruzeiro Marcio , Guillonneau François , Saade Anastasia , Clément Nathalie , Courivaud Thomas , Kaabi Nawel , Tadagaki Kenjiro , Delagrange Philippe , Prévot Vincent , Hermine Olivier , Prunier Céline , Jockers Ralf 
Published: March 2018

AbstractTransforming growth factor-β (TGFβ) signaling is initiated by the type I, II TGFβ receptor (TβRI/TβRII) complex. Here we report the formation of an alternative complex between TβRI and the orphan GPR50, belonging to the G protein-coupled receptor super-family. The interaction of GPR50 with TβRI induces spontaneous TβRI-dependent Smad and non-Smad signaling by stabilizing the active TβRI conformation and competing for the binding of the negative regulator FKBP12 to TβRI. GPR50 overexpression in MDA-MB-231 cells mimics the anti-proliferative effect of TβRI and decreases tumor growth in a xenograft mouse model. Inversely, targeted deletion of GPR50 in the MMTV/Neu spontaneous mammary cancer model shows decreased survival after tumor onset and increased tumor growth. Low GPR50 expression is associated with poor survival prognosis in human breast cancer irrespective of the breast cancer subtype. This describes a previously unappreciated spontaneous TGFβ-independent activation mode of TβRI and identifies GPR50 as a TβRI co-receptor with potential impact on cancer development.
Structure and evolution of the Fam20 kinases
Authors: Zhang Hui , Zhu Qinyu , Cui Jixin , Wang Yuxin , Chen Mark J. , Guo Xing , Tagliabracci Vincent S. , Dixon Jack E. , Xiao Junyu 
Published: March 2018

AbstractThe Fam20 proteins are novel kinases that phosphorylate secreted proteins and proteoglycans. Fam20C phosphorylates hundreds of secreted proteins and is activated by the pseudokinase Fam20A. Fam20B phosphorylates a xylose residue to regulate proteoglycan synthesis. Despite these wide-ranging and important functions, the molecular and structural basis for the regulation and substrate specificity of these kinases are unknown. Here we report molecular characterizations of all three Fam20 kinases, and show that Fam20C is activated by the formation of an evolutionarily conserved homodimer or heterodimer with Fam20A. Fam20B has a unique active site for recognizing Galβ1-4Xylβ1, the initiator disaccharide within the tetrasaccharide linker region of proteoglycans. We further show that in animals the monomeric Fam20B preceded the appearance of the dimeric Fam20C, and the dimerization trait of Fam20C emerged concomitantly with a change in substrate specificity. Our results provide comprehensive structural, biochemical, and evolutionary insights into the function of the Fam20 kinases.
Coupling of oceanic carbon and nitrogen facilitates spatially resolved quantitative reconstruction of nitrate inventories
Authors: Glock Nicolaas , Erdem Zeynep , Wallmann Klaus , Somes Christopher J. , Liebetrau Volker , Schönfeld Joachim , Gorb Stanislav , Eisenhauer Anton 
Published: March 2018

AbstractAnthropogenic impacts are perturbing the global nitrogen cycle via warming effects and pollutant sources such as chemical fertilizers and burning of fossil fuels. Understanding controls on past nitrogen inventories might improve predictions for future global biogeochemical cycling. Here we show the quantitative reconstruction of deglacial bottom water nitrate concentrations from intermediate depths of the Peruvian upwelling region, using foraminiferal pore density. Deglacial nitrate concentrations correlate strongly with downcore δ13C, consistent with modern water column observations in the intermediate Pacific, facilitating the use of δ13C records as a paleo-nitrate-proxy at intermediate depths and suggesting that the carbon and nitrogen cycles were closely coupled throughout the last deglaciation in the Peruvian upwelling region. Combining the pore density and intermediate Pacific δ13C records shows an elevated nitrate inventory of >10% during the Last Glacial Maximum relative to the Holocene, consistent with a δ13C-based and δ15N-based 3D ocean biogeochemical model and previous box modeling studies.
Speech-Language Pathologist Interventions for Communication in Moderate–Severe Dementia: A Systematic Review
Authors: Swan Katina , Hopper Marie , Wenke Rachel , Jackson Claire , Till Tracy , Conway Erin 
Published: March 2018

Purpose
The purpose of this study is to evaluate the evidence for direct and indirect interventions for communication in people with moderate–severe dementia.

Method
A systematic search of the literature was conducted, as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysed guidelines, across 8 electronic databases. Studies were included if they included direct or indirect interventions, which could be administered by a speech-language pathologist to people with moderate–severe dementia (defined as having Mini-Mental State Examination of ≤ 15; Folstein, Folstein, & McHugh, 1975). Studies also were required to include outcome measures, which reported on communication function or participation and/or well-being related to communication. Included studies were evaluated for methodological quality using the McMaster critical appraisal tool (Law et al., 1998).

Results

Eleven studies met the inclusion criteria. Ten of these studies related to direct interventions and included cognitive stimulation approaches using group (
n
= 5) or individual therapy (
n
= 1); cognitive training, including naming therapy (
n
= 1) and spaced retrieval training (
n
= 1); and cognitive rehabilitation approaches using augmentative and alternative communication (
n
= 2). One study reported an indirect intervention: conversation partner training. Due to the heterogeneity of studies, a meta-analysis was unable to be conducted. A descriptive synthesis of results indicated that interventions generally resulted in positive changes to communication and related quality-of-life outcomes compared with baseline or control groups.

Conclusions
Preliminary evidence was found to support communication interventions for people with moderate–severe dementia. The use of cognitive stimulation approaches, which use a group treatment model and conversation, as a therapy medium show promise as direct intervention options. Implications for clinical practice for speech-language pathologists and future research are discussed.

Supplemental Material

https://doi.org/10.23641/asha.5985241
Comparison of Percentage of Syllables Stuttered With Parent-Reported Severity Ratings as a Primary Outcome Measure in Clinical Trials of Early Stuttering Treatment
Authors: Onslow Mark , Jones Mark , O'Brian Sue , Packman Ann , Menzies Ross , Lowe Robyn , Arnott Simone , Bridgman Kate , de Sonneville Caroline , Franken Marie-Christine 
Published: March 2018

PurposeThis report investigates whether parent-reported stuttering severity ratings (SRs) provide similar estimates of effect size as percentage of syllables stuttered (%SS) for randomized trials of early stuttering treatment with preschool children.MethodData sets from 3 randomized controlled trials of an early stuttering intervention were selected for analyses. Analyses included median changes and 95% confidence intervals per treatment group, Bland–Altman plots, analysis of covariance, and Spearman rho correlations.ResultsBoth SRs and %SS showed large effect sizes from pretreatment to follow-up, although correlations between the 2 measures were moderate at best. Absolute agreement between the 2 measures improved as percentage reduction of stuttering frequency and severity increased, probably due to innate measurement limitations for participants with low baseline severity. Analysis of covariance for the 3 trials showed consistent results.ConclusionThere is no statistical reason to favor %SS over parent-reported stuttering SRs as primary outcomes for clinical trials of early stuttering treatment. However, there are logistical reasons to favor parent-reported stuttering SRs. We conclude that parent-reported rating of the child's typical stuttering severity for the week or month prior to each assessment is a justifiable alternative to %SS as a primary outcome measure in clinical trials of early stuttering treatment.
The XXL Survey
Authors: Smolčić Vernesa , Intema Huib , Šlaus Bruno , Raychaudhury Somak , Novak Mladen , Horellou Cathy , Chiappetti Lucio , Delhaize Jacinta , Birkinshaw Mark , Bondi Marco , Bremer Malcolm , Ciliegi Paolo , Ferrari Chiara , Kolokythas Konstantinos , Lidman Chris , McGee Sean L. , Norris Ray , Pierre Marguerite , Röttgering Huub , Tasse Cyril , Williams Wendy 
Published: March 2018

We present the 25 square-degree GMRT-XXL-N 610 MHz radio continuum survey, conducted at 50 cm wavelength with the Giant Metrewave Radio Telescope (GMRT) towards the XXL Northern field (XXL-N). We combined previously published observations of the XMM-Large Scale Structure (XMM-LSS) field, located in the central part of XXL-N, with newly conducted observations towards the remaining XXL-N area, and imaged the combined data-set using the Source Peeling and Atmospheric Modeling (SPAM) pipeline. The final mosaic encompasses a total area of 30.4 square degrees, with rms <150 μJy beam−1 over 60% of the area. The rms achieved in the inner 9.6 square degree area, enclosing the XMM-LSS field, is about 200 μJy beam−1, while that over the outer 12.66 square degree area (which excludes the noisy edges) is about 45 μJy beam−1. The resolution of the final mosaic is 6.5 arcsec. We present a catalogue of 5434 sources detected at ≥7 ×rms. We verify, and correct the reliability of, the catalog in terms of astrometry, flux, and false detection rate. Making use of the (to date) deepest radio continuum survey over a relatively large (2 square degree) field, complete at the flux levels probed by the GMRT-XXL-N survey, we also assess the survey’s incompleteness as a function of flux density. The radio continuum sensitivity reached over a large field with a wealth of multi-wavelength data available makes the GMRT-XXL-N 610 MHz survey an important asset for studying the physical properties, environments and cosmic evolution of radio sources, in particular radio-selected active galactic nuclei (AGN).
TheGaia-ESO Survey: a kinematical and dynamical study of four young open clusters
Authors: Bravi L. , Zari E. , Sacco G. G. , Randich S. , Jeffries R. D. , Jackson R. J. , Franciosini E. , Moraux E. , López-Santiago J. , Pancino E. , Spina L. , Wright N. J. , Jiménez-Esteban F. M. , Klutsch A. , Roccatagliata V. , Gilmore G. , Bragaglia A. , Flaccomio E. , Francois P. , Koposov S. E. , Bayo A. , Carraro G. , Costado M. T. , Damiani F. , Frasca A. , Hourihane A. , Jofré P. , Lardo C. , Lewis J. , Magrini L. , Morbidelli L. , Prisinzano L. , Sousa S. G. , Worley C. C. , Zaggia S. 
Published: March 2018

Context.The origin and dynamical evolution of star clusters is an important topic in stellar astrophysics. Several models have been proposed in order to understand the formation of bound and unbound clusters and their evolution, and they can be tested by examining the kinematical and dynamical properties of clusters over a wide range of ages and masses.Aims.We use theGaia-ESO Survey products to study four open clusters (IC 2602, IC 2391, IC 4665, and NGC 2547) that lie in the age range between 20 and 50 Myr.Methods.We employ the gravity indexγand the equivalent width of the lithium line at 6708 Å together with effective temperatureTeffand the metallicity of the stars in order to discard observed contaminant stars. Then we derive the cluster radial velocity dispersionsσc, the total cluster massMtot, and the half mass radiusrhm. Using theGaia-DR1 TGAS catalogue, we independently derive the intrinsic velocity dispersion of the clusters from the astrometric parameters of cluster members.Results.The intrinsic radial velocity dispersions derived by the spectroscopic data are higher than those derived from the TGAS data, possibly due to the different masses of the considered stars. UsingMtotandrhmwe derive the virial velocity dispersionσvirand we find that three out of four clusters are supervirial. This result is in agreement with the hypothesis that these clusters are dispersing, as predicted by the “residual gas expulsion” scenario. However, recent simulations show that the virial ratio of young star clustersmay be overestimated if it is determined using the global velocity dispersion, since the clusters are not fully relaxed.
Clozapine-Induced DRESS Syndrome: A Case Series From the AMSP Multicenter Drug Safety Surveillance Project
Authors: Sanader Bruna , Grohmann Renate , Grötsch Philipp , Schumann Thomas , Toto Sermin , Fernando Piyumi , Stübner Susanne 
Published: March 2018

AbstractDrug reaction with eosinophilia and systemic symptoms (DRESS) is an infrequent, but severe, adverse drug-induced reaction which occurs due to massive T-cell stimulation resulting in cytotoxicity and eosinophil activation and recruitment. The incidence is 0.4 cases per 100, 0000 in the general population; the mortality rate is up to 10%. Therefore, we believe that recognizing this syndrome is of particular importance. The problem we notice is that DRESS is often seen and described in patients receiving rheumatologic or anticonvulsant drugs, but very rarely in psychiatric hospitals, where Clozapine is frequently used, and that is the importance of this paper. DRESS Syndrome must be recognized promptly, and causative drugs withdrawn. Indeed, it has been reported that the earlier the drug withdrawal, the better the prognosis. In this paper, we present three cases of Clozapine-induced DRESS. All cases were recorded in the Multicenter Drug Safety Surveillance Project (AMSP).
Discovery of Bioactive Natural Products for the Treatment of Acute Respiratory Infections – An Integrated Approach
Authors: Grienke Ulrike , Mair Christina , Kirchmair Johannes , Schmidtke Michaela , Rollinger Judith 
Published: March 2018

AbstractIn this work, an integrated approach for the identification of new antiviral agents from natural sources for the treatment of acute respiratory infections is presented. The approach comprises (i) the selection of starting material based on traditional knowledge, (ii) phenotypic screening of extracts for antiviral activity, and (iii) the implementation of in silico predictions to identify antiviral compounds and derive the molecular mechanism underlying their biological activity. A variety of starting materials from plants and fungi was selected for the production of 162 extracts. These extracts were tested in cytopathic effect inhibition assays against influenza virus A/Hong Kong/68 (HK/68), rhinovirus A2 (RV-A2), and coxsackie virus B3 (CV-B3). All extracts were also evaluated regarding their cytotoxicity. At an IC50 threshold of 50 µg/mL, 20, 11, and 14% of all tested extracts showed antiviral activity against HK/68, CV-B3, and RV-A2, respectively. Among all active extracts (n = 47), 68% showed antiviral activity against one of the investigated viruses, whereas 31% inhibited at least two viruses. Herein, we present a comprehensive dataset of probed extracts along with their antiviral activities and cytotoxicity. Application examples presented in this work illustrate the phytochemical workflow for the identification of antiviral natural compounds. We also discuss the challenges, pitfalls, and advantages of the integrated approach.
Regioselective C–H Activation of Substituted Pyridines and other Azines using Mg- and Zn-TMP-Bases
Authors: Balkenhohl Moritz , Knochel Paul 
Published: March 2018

The metalation of substituted pyridines, diazines and related N-heterocycles using TMPMgCl·LiCl, TMP2Mg·2LiCl, TMPZnCl·LiCl or TMP2Zn·2LiCl2·2MgCl2 (TMP = 2,2,6,6-tetramethylpiperidyl) in the presence or absence of a Lewis acid is reviewed.
Contents
1	Introduction2	Magnesiation of Pyridines and Related Azines2.1	Magnesiations using TMPMgCl·LiCl2.2	Magnesiations using TMP2Mg·2LiCl and Related Bases2.3	BF3·OEt2 Promoted Metalations of Pyridines3	Zincation of Pyridines and Related Azines using TMPZnCl·LiCl and	TMP2Zn·2LiCl·2MgCl2
4	Metalation of Pyridines using other TMP-Bases5	Magnesiation and Zincation of Diazines6	Conclusion
Successful Outcomes at Midterm Follow-up of Periacetabular Osteotomy Done for Mild Hip Dysplasia
Authors: Potter G. , Novais Eduardo , Trousdale Robert , Sierra Rafael 
Published: March 2018

AbstractYoung hip surgeons are often faced with the decision to either perform arthroscopic surgery or a periacetabular osteotomy (PAO) in patients with symptomatic mild hip dysplasia (MHD). There is, however, a paucity of data on the results of PAO in this group. The aim of this paper is to report the results of PAOs in patients with MHD and compare those to hips with more severe forms of hip dysplasia (SHD). This data can then be used to compare emerging data reporting the results of hip arthroscopy for MHD. From January, 1996 to May, 2009, 299 hips in 268 patients were identified that underwent PAO at one institution. After removing those with <2 years of follow-up, 182 hips were followed up. The average age of the cohort was 31 years, and 85% were female. Nineteen hips with lateral center edge (LCE) angle from 18 to 25° and a Tönnis angle (TA) between 10 and 15° were considered to have MHD. This group was compared with the rest of the cohort (SHD). The mean clinical follow-up for the MHD group was 121 months. There was no significant difference in demographic variables between the groups. There were no complications in the MHD cohort. Surgical correction resulted in significant improvements in all radiographic measurements consistent with hip dysplasia in both groups. The Harris Hip Score (HHS) improved significantly in both groups ([MHD: 52–92] [SHD: 66–89]). Two hips (10.5%) in the MHD group and 15 hips (9.2%) in the SHD group underwent future THA (p = 0.69). The survivorship free from THA was 100%, 100%, and 86% at 3, 5, and 10 years, respectively, in the MHD group. The corresponding rates for hips in the control group at 3, 5, and 10 years, respectively, were 99%, 95%, and 81%. PAO in patients with MHD provides predictable improvements in pain, function, and results that are durable and comparable to hips with SHD. This data should be used to compare the early and midterm results of arthroscopic surgery performed in mildly dysplastic hips.
Toward Flow Cytometry Based Platelet Function Diagnostics
Authors: van Asten Ivar , Schutgens Roger , Urbanus Rolf 
Published: March 2018

AbstractThe laboratory diagnostics of (inherited) platelet function disorders mainly comprises aggregation and secretion assays, which may be suitable for diagnosing some specific severe platelet function disorders, but are not reliable enough for diagnosing mild platelet function disorders or disorders associated with low platelet count. Flow cytometric assessment of platelet reactivity will expectedly provide additional value during the diagnostic work-up of platelet function disorders because it only requires a small volume of whole blood and allows the measurement of platelet function in thrombocytopenic samples. Flow cytometry has frequently been used to evaluate platelet function in the research setting, and therefore, these assays will require clinical validation before they can be used as routine diagnostic tools. The main challenge in the validation of innovative platelet function diagnostic tests is the lack of a gold standard test for mild platelet function disorders. This review aims to address the many applications of flow cytometry in the current diagnostic work-up of platelet function testing and to discuss the challenges in introducing new tools for diagnosing platelet function disorders.
Human Dendritic Cells Synergistically Activated by FVIII Plus LPS Induce Activation of Autologous CD4+ T Cells
Authors: Miller Lilija , Ringler Eva , Kistner Klaus , Waibler Zoe ,   on behalf of the ABIRISK Consortium
Published: March 2018

AbstractThe most severe side effect in haemophilia A (HA) treatment is the development of anti-factor VIII antibodies, also called inhibitors. Why inhibitors develop in a proportion of treated HA patients and how this can be prevented remains largely unanswered. Among numerous theories, the presence of immunological danger signals, associated with events such as surgery or infection, has been proposed to play a role. In this study, we demonstrate that human dendritic cells (DC) synergistically activated by a combination of factor VIII (FVIII) concentrate plus the bacterial danger signal lipopolysaccharide (LPS) induce a significantly stronger activation of autologous CD4+ T cells than DC pretreated with FVIII or LPS alone. The observed T cell activation is dependent on antigen processing, presentation on MHC class II molecules and costimulation via CD86. Of note, FVIII plus LPS pretreated DC predominantly induce the activation of memory T cells and a minor proportion of naive T cells. Collectively, our data support a model in which immunological danger signals plus FVIII concentrates synergistically increase human CD4+ T cell responses to FVIII protein.
Ungewöhnlicher Fall eines schweren Polytraumas beim Kleinkind – Happy End trotz Fallstricken
Authors: Klinger Andreas , Sperling Patrick , Jansen Hendrik , Wirbelauer Johannes , Vergho Daniel , Seitz Florian , Roewer Norbert , Meyer Thomas , Muellenbach Ralf 
Published: March 2018

ZusammenfassungEin 16 Monate alter Junge erleidet bei einem Verkehrsunfall ein schwerstes Polytrauma (dislozierte offene Beckenfraktur, pelvines Décollement und hämorrhagischer Schock). Die dabei auftretenden Besonderheiten und Fallstricke in der präklinischen und frühen klinischen Versorgung dieses schweren und seltenen Traumas bei pädiatrischen Patienten werden herausgearbeitet, wobei besonders auf die damit einhergehenden medizinisch-einsatztaktischen Schwierigkeiten eingegangen wird.
Atemwegsmanagement – der schwierige Atemweg beim thoraxchirurgischen Patienten
Authors: Müller Sarah-Hélène , Defosse Jérôme , Gerbershagen Mark , Loop Torsten 
Published: March 2018

ZusammenfassungDas Management des schwierigen Atemwegs bei thoraxchirurgischen Patienten ist in den gültigen Leitlinien kaum abgebildet und stellt insbesondere in der Thoraxanästhesie mit der notwendigen Seitentrennung der Atemwege durch einen Doppellumentubus oder Bronchusblocker eine Herausforderung dar. Die Definition des schwierigen Atemwegs mit erschwerter Maskenbeatmung, Laryngoskopie oder endotrachealer Intubation wird überwiegend durch Veränderungen der Anatomie der oberen Atemwege (schwieriger oberer Atemweg) charakterisiert. Pathologische Veränderungen in der tracheobronchialen Anatomie, die die Platzierung des Doppellumentubus oder anderer Atemwegshilfen erschweren (schwieriger unterer Atemweg; schwierige Seitentrennung), sind in die Definition miteinzubeziehen. Der vorliegende Artikel beschreibt die Identifikation von Risikopatienten, Techniken, Empfehlungen und Algorithmen für das Management bei erwartet und unerwartet schwierigem Atemweg. Darüber hinaus gibt er einen Überblick über die Auswahl verschiedener Verfahren und Hilfsmittel zur Seitentrennung der Lungen zur Etablierung einer Ein-Lungen-Ventilation.
Futter für die Willenskraft – Guten
Appetit!
Authors: Jürgens Ute 
Published: March 2018

ZusammenfassungNicht selten bleiben bei der Umsetzung von allerlei Vorhaben manche auf der
Strecke! Den Betrieb besser zu organisieren, das in der Fortbildung Gelernte zu
wiederholen, aufzuräumen – die Willenskraft ist oft genug zu klein. Vergrößern
Sie sie!
Hyponatriämie in der Neurologie
Authors: Reich Maja 
Published: March 2018

ZusammenfassungDie häufigste Störung des Wasserhaushaltes ist die Hyponatriämie; sie
ist damit auch die häufigste Elektrolytstörung. Die auftretenden Symptome der
Hyponatriämie sind vielfältig und oft nicht leicht zu erkennen. Die
Hyponatriämie ist mit erhöhter Morbidität und Mortalität assoziiert 1, 2.