bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux
Authors: Darlow John M. , Darlay Rebecca , Dobson Mark G. , Stewart Aisling , Charoen Pimphen , Southgate Jennifer , Baker Simon C. , Xu Yaobo , Hunziker Manuela , Lambert Heather J. , Green Andrew J. , Santibanez-Koref Mauro , Sayer John A. , Goodship Timothy H. J. , Puri Prem , Woolf Adrian S. , Kenda Rajko B. , Barton David E. , Cordell Heather J. 
Published: October 2017

AbstractVesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions – congenital dysplasia, acquired scarring or both – are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene butFOXI2,FANK1andGLRX3remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations.
A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro
Authors: Maggi Maristella , Mittelman Steven D. , Parmentier Jean Hugues , Colombo Giorgio , Meli Massimiliano , Whitmire Jeannette Marie , Merrell D. Scott , Whitelegge Julian , Scotti Claudia 
Published: October 2017

AbstractL-Asparaginases (ASNases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than 40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi (ErAII) type II ASNases currently used in the clinics are characterized by high in vivo instability, short half-life and the requirement of several administrations to obtain a pharmacologically active concentration. Moreover, they are sensitive to proteases (cathepsin B and asparagine endopeptidase) that are over-expressed by resistant leukaemia lymphoblasts, thereby impairing drug activity and pharmacokinetics. Herein, we present the biochemical, structural and in vitro antiproliferative characterization of a new EcAII variant, N24S. The mutant shows completely preserved asparaginase and glutaminase activities, long-term storage stability, improved thermal parameters, and outstanding resistance to proteases derived from leukaemia cells. Structural analysis demonstrates a modification in the hydrogen bond network related to residue 24, while Normal Mode-based geometric Simulation and Molecular Dynamics predict a general rigidification of the monomer as compared to wild-type. These improved features render N24S a potential alternative treatment to reduce the number of drug administrations in vivo and to successfully address one of the major current challenges of ALL treatment: spontaneous, protease-dependent and immunological inactivation of ASNase.
Shotgun Glycomics Identifies Tumor-Associated Glycan Ligands Bound by an Ovarian Carcinoma-Specific Monoclonal Antibody
Authors: Liau B. , Tan B. , Teo G. , Zhang P. , Choo A. , Rudd P. M. 
Published: October 2017

AbstractCancers display distinctive carbohydrate molecules (glycans) on their surface proteins and lipids. mAb A4, an in-house generated monoclonal IgM antibody, is capable of distinguishing malignant ovarian carcinoma cells from benign ovarian epithelia by binding specifically to cancer cell-associated glycans. However, the structural details of the glycan targets of mAb A4 have been elusive. Here we developed a novel approach of isolating and fractionating glycan molecules released from glycoproteins in cancer cell lysates using HILIC-UPLC, and used them as probes on a microarray for affinity-based identification of the binding targets, allowing full-size, difficult to synthesize, cancer-associated glycans to be directly studied. As a result of this “shotgun” glycomics approach, we corroborate the previously assigned specificity of mAb A4 by showing that mAb A4 binds primarily to large (>15 glucose units), sialylated N-glycans containing the H-type 1 antigen (Fuc-α1,2-Gal-β1,3-GlcNAc). Although mAb A4 was also capable of directly binding to type 1 N-acetyl-lactosamine, this epitope was mostly shielded by sialylation and thus relatively inaccessible to binding. Knowledge of the structure of mAb A4 antigen will facilitate its clinical development as well as its use as a diagnostic biomarker.
L290P/V mutations increase ERK3’s cytoplasmic localization and migration/invasion-promoting capability in cancer cells
Authors: Alsaran Hadel , Elkhadragy Lobna , Shakya Astha , Long Weiwen 
Published: October 2017

AbstractProtein kinases are frequently mutated in human cancers, which leads to altered signaling pathways and contributes to tumor growth and progression. ERK3 is an atypical mitogen-activated protein kinase (MAPK) containing an S-E-G activation motif rather than the conserved T-X-Y motif in conventional MAPKs such as ERK1/2. Recent studies have revealed important roles for ERK3 in cancers. ERK3 promotes cancer cell migration/invasion and tumor metastasis, and its expression is upregulated in multiple cancers. Little is known, however, regarding ERK3 mutations in cancers. In the present study, we functionally and mechanistically characterized ERK3 L290P/V mutations, which are located within ERK3’s kinase domain, and are shown to exist in several cancers including lung cancer and colon cancer. We found that in comparison with wild type ERK3, both L290P and L290V mutants have greatly increased activity in promoting cancer cell migration and invasion, but have little impact on ERK3’s role in cell proliferation. Mechanistically, while they have no clear effect on kinase activity, L290P/V mutations enhance ERK3’s cytoplasmic localization by increasing the interaction with the nuclear export factor CRM1. Our findings suggest that L290P/V mutations of ERK3 may confer increased invasiveness to cancers.
Dynamic coupling between slow waves and sleep spindles during slow wave sleep in humans is modulated by functional pre-sleep activation
Authors: Yordanova Juliana , Kirov Roumen , Verleger Rolf , Kolev Vasil 
Published: October 2017

AbstractCo-existent sleep spindles and slow waves have been viewed as a mechanism for offline information processing. Here we explored if the temporal synchronization between slow waves and spindle activity during slow wave sleep (SWS) in humans was modulated by preceding functional activations during pre-sleep learning. We activated differentially the left and right hemisphere before sleep by using a lateralized variant of serial response time task (SRTT) and verified these inter-hemispheric differences by analysing alpha and beta electroencephalographic (EEG) activities during learning. The stability and timing of coupling between positive and negative phases of slow waves and sleep spindle activity during SWS were quantified. Spindle activity was temporally synchronized with both positive (up-state) and negative (down-state) slow half waves. Synchronization of only the fast spindle activity was laterally asymmetric after learning, corresponding to hemisphere-specific activations before sleep. However, the down state was associated with decoupling, whereas the up-state was associated with increased coupling of fast spindle activity over the pre-activated hemisphere. These observations provide original evidence that (1) the temporal grouping of fast spindles by slow waves is a dynamic property of human SWS modulated by functional pre-sleep activation patterns, and (2) fast spindles synchronized by slow waves are functionally distinct.
A deep ensemble model to predict miRNA-disease association
Authors: Fu Laiyi , Peng Qinke 
Published: October 2017

AbstractCumulative evidence from biological experiments has confirmed that microRNAs (miRNAs) are related to many types of human diseases through different biological processes. It is anticipated that precise miRNA-disease association prediction could not only help infer potential disease-related miRNA but also boost human diagnosis and disease prevention. Considering the limitations of previous computational models, a more effective computational model needs to be implemented to predict miRNA-disease associations. In this work, we first constructed a human miRNA-miRNA similarity network utilizing miRNA-miRNA functional similarity data and heterogeneous miRNA Gaussian interaction profile kernel similarities based on the assumption that similar miRNAs with similar functions tend to be associated with similar diseases, and vice versa. Then, we constructed disease-disease similarity using disease semantic information and heterogeneous disease-related interaction data. We proposed a deep ensemble model called DeepMDA that extracts high-level features from similarity information using stacked autoencoders and then predicts miRNA-disease associations by adopting a 3-layer neural network. In addition to five-fold cross-validation, we also proposed another cross-validation method to evaluate the performance of the model. The results show that the proposed model is superior to previous methods with high robustness.
Monitoring microbial responses to ocean deoxygenation in a model oxygen minimum zone
Authors: Hallam Steven J. , Torres-Beltrán Mónica , Hawley Alyse K. 
Published: October 2017

AbstractToday in Scientific Data, two compendia of geochemical and multi-omic sequence information (DNA, RNA, protein) generated over almost a decade of time series monitoring in a seasonally anoxic coastal marine setting are presented to the scientific community. These data descriptors introduce a model ecosystem for the study of microbial responses to ocean deoxygenation, a phenotype that is currently expanding due to climate change. Public access to this time series information is intended to promote scientific collaborations and the generation of new hypotheses relevant to microbial ecology, biogeochemistry and global change issues.
Morphological Associations between the Distal Radioulnar Joint and the Lunate
Authors: Beaulieu Jean-Yves , Mauler Flavien 
Published: October 2017

Background Variations in morphology of the carpal bones have been described. Their implication in wrist disease and specific kinematic features has been recognized, and a better knowledge of these variations is essential.
Questions/Purpose To radiographically determine any association between the morphological variations of the distal radioulnar joint (DRUJ) and the lunate bone.
Materials and Methods Radiographs of 100 wrists of patients presenting to the emergency department with wrist pain and referred to our outpatient clinic were retrospectively reviewed for DRUJ inclination, ulnar variance, and radiocarpal and midcarpal morphology of the lunate.
Results There were 51 females and 49 males, mean age 51.2 years (range: 21–94). There was a statistically significant association between the DRUJ inclination and the morphology of the radiocarpal side of the lunate (p < 0.001). The mean values of ulnar variance changed according to DRUJ inclination and the radiocarpal side of the lunate (p < 0.001) but not according to the midcarpal side of the lunate. There was no significant association between the morphology of the DRUJ and the midcarpal side of the lunate or between the midcarpal and the radiocarpal morphology of the lunate.
Conclusion This study demonstrated a statistically significant association at the radiocarpal level between the DRUJ inclination, ulnar variance, and the morphology of the lunate. No association was found with the morphology of the midcarpal side of the lunate. Accordingly, a classification of these carpal associations is proposed, highlighting seven main wrist configurations.
Clinical Relevance These associations can guide future studies of wrist kinematics.
Radial Nerve Palsy following Endovascular Embolization of an Arteriovenous Malformation
Authors: Alluri Ram , Mahajan Anuj , Ghiassi Alidad , Vakhshori Venus 
Published: October 2017

Background Arteriovenous malformations (AVMs) are commonly treated using endovascular techniques. Previous nerve palsies after embolization have been reported as isolated case reports, none of which affected the forearm.
Case Description A case of acute, transient neuropathy of the radial nerve following embolization of a forearm AVM is described. The patient, an otherwise healthy 27-year-old man, began having symptoms of superficial radial nerve (SRN) and posterior interosseous nerve (PIN) palsies immediately following endovascular embolization. He underwent decompression of the radial nerve within 5 days and was found to have direct compression of the PIN and SRN. The patient recovered completely at the time of his 7-month follow-up.
Literature Review Few cases of nerve palsy after endovascular embolization have been reported in the literature. Many are intracranial, but rare instances of peripheral nerve palsy have been reported, including two sciatic nerve and four digital nerve palsies after endovascular embolization. No cases of peripheral nerve palsy in the forearm have been reported.
Clinical Relevance We recommend careful consideration of surrounding neural elements at risk for palsy prior to endovascular embolization and detailed discussion with the patient during the informed consent process.
Subjektive und objektive Langzeitanalyse nach Mammareduktionsplastik in 159 Fällen: Patientinnen urteilen anders als
Plastische Chirurgen
Authors: Osinga Rik , Babst Doris , Bodmer Elvira , Link Bjoern , Fritsche Elmar , Hug Urs 
Published: October 2017

Zusammenfassung
Hintergrund Hauptziel der vorliegenden Arbeit war einerseits die Erhebung subjektiver und objektiver postoperativer Parameter nach
Mammareduktionsplastik und andererseits der Vergleich derselben zwischen Patientinnen und Plastischen Chirurgen.
Patientinnen und Methode Es konnten 259 Patientinnen in die retrospektive Fallserie eingeschlossen und 159 Patientinnen (61 %) nach
einem durchschnittlichen Beobachtungszeitraum von 6.7 ± 2.7 (2 – 13) Jahren nachkontrolliert werden. Das mittlere Alter zum Zeitpunkt der
Operation betrug 37 ± 14 (15 – 74) Jahre. Die postoperative Anatomie der Brust sowie weitere anthropometrische Parameter wurden bei
stehender Patientin in cm gemessen und die visuellen Analogskala-Werte für Symmetrie, Grösse, Form, Narbenverlauf und Gesamtzufriedenheit
zwischen Patientinnen und vier Plastischen Chirurgen verglichen.
Ergebnisse Die subjektiven Beurteilungen durch die Patientinnen waren stets besser als diejenigen der Chirurgen. Gute subjektive
Bewertungen der Patientinnen für Form, Symmetrie und Sensibilität korrelierten mit einer guten Bewertung der Gesamtzufriedenheit. Dabei
hatte die Form den stärksten Einfluss auf die Gesamtzufriedenheit (Regressionskoeffizient 0.357; p < 0.001) gefolgt von Symmetrie
(Regressionskoeffizient 0.239; p < 0.001) und Sensibilität (Regressionskoeffizient 0.109; p = 0.040). Gute subjektive Bewertungen der
Patientinnen für Symmetrie waren mit abnehmender Seitendifferenz des Jugulum-Mamillenabstandes (Regressionskoeffizient –0.773; p = 0.002)
und abnehmender Seitendifferenz des Mammaunterrand – Bodenabstandes (Regressionskoeffizient –0.465; p = 0.035) korreliert. Es fand sich
keine signifikante Korrelation von Alter, Gewicht, Grösse, BMI, Resektionsgewicht, postoperativer Brustgrösse oder Narbenverlauf mit
Gesamtzufriedenheit.
Schlussfolgerung Patientinnen beurteilten das Langzeitresultat nach Mammareduktionsplastik signifikant besser als plastische
Chirurgen. Gute subjektive Bewertungen der Patientinnen für Form, Symmetrie und Sensibilität der Brust korrelierten mit einer guten
Bewertung der Gesamtzufriedenheit. Dabei hatte die Form den stärksten Einfluss, gefolgt von Symmetrie und Sensibilität. Die postoperative
Brustgrösse, das Resektionsgewicht, der Narbenverlauf, das Alter und der BMI der Patientin hingegen zeigten keinen signifikanten Einfluss.
Symmetrie war der einzige gemessene subjektive Parameter dieser Studie, welcher durch postoperative Messungen objektiviert werden
konnte.
Zerebrale und spinale Bildgebung der Multiplen Sklerose: ein Update
Authors: Wattjes Mike , Raab Peter 
Published: October 2017

ZusammenfassungDie Magnetresonanztomografie spielt in der Diagnostik der Multiplen Sklerose (MS) eine entscheidende Rolle und wurde deshalb innerhalb der MS-Diagnosekriterien verankert. Insbesondere für den Ausschluss wichtiger Differenzialdiagnosen werden immer neue MRT-Marker etabliert, wie beispielsweise das sogenannte „central vein sign“. Neben der Diagnostik hat die MRT in der MS-Verlaufsbeobachtung, und hierbei insbesondere bei der Pharmakovigilanz, eine zunehmende klinische Relevanz erlangt. Dies beinhaltet nicht nur die Erfassung der Behandlungseffektivität, sondern auch die Prädiktion des Behandlungserfolges und das Sicherheitsmonitoring. Quantitative MRT-Methoden sowie der Einsatz der (Ultra-)Hochfeld-MRT bieten uns in zunehmendem Maße die Möglichkeit, die MS-Pathologie insbesondere in auf dem konventionellen MRT-Bild normal erscheinendem Gewebe zu erfassen und zu quantifizieren. Dennoch wird die Standardisierung dieser Techniken für die MS-Diagnostik und Verlaufsbeobachtung zu den großen Herausforderungen in der Zukunft zählen, um damit diese vielversprechenden Methoden in die klinische Routine zu implementieren und zu etablieren.
Prävention von postoperativen Wundinfektionen – mit Fokus auf die Gefäßchirurgie
Authors: Bischoff Peter , Gastmeier Petra 
Published: October 2017

Zusammenfassung
Einleitung Postoperative Wundinfektionen rangieren, je nach epidemiologischer Auswertung, zwischen den weltweit am häufigsten bzw. zweithäufigsten vorkommenden nosokomialen Infektionen. Erleidet ein Patient eine postoperative Wundinfektion, stellt dies für ihn, je nach Schwere, ein ernstzunehmendes Morbiditäts- und Mortalitätsrisiko dar. Die negativen Auswirkungen beschränken sich nicht nur auf den einzelnen Patienten, auch für die Angehörigen, das Krankenhaus und für das gesamte Gesundheitssystem bedeutet dies eine enorme Belastung. In der Gefäßchirurgie machen grampositive Hautkeime fast die Hälfte aller Infektionen aus, bei denen ein Erreger nachgewiesen werden konnte. Staphylococcus aureus allein ist mit einem Drittel dieser Infektionen assoziiert.
Präventionsmaßnahmen Neben generellen Maßnahmen zur Prävention von postoperativen Wundinfektionen lassen sich weitere, besonders für die Gefäßchirurgie relevante Interventionen ins Feld führen. Die im November 2016 veröffentlichte WHO Guideline zur Prävention von postoperativen Wundinfektionen ist die erste international gültige Leitlinie auf diesem Gebiet. Den Empfehlungen liegen ein systematischer Review und eine transparente und rigorose Beurteilung der Studienlage zugrunde. Dieser Beitrag beleuchtet den Stellenwert der Leitlinie und stellt prä-, intra-, und postoperative Maßnahmen mit einem speziellen Fokus auf die Studienlage in der Gefäßchirurgie vor.
Schlussfolgerung Es stehen eine Reihe von evidenzbasierten Maßnahmen zur Verfügung, die das Risiko für den chirurgischen Patienten, eine operationsassoziierte Wundinfektion zu erleiden, nachweislich senken können. Auf dem Gebiet der Gefäßchirurgie sollte ein besonderes Augenmerk auf jene Maßnahmen gelegt werden, die auf die Reduzierung der patienteneigenen Haut- und Schleimhautflora (Nase/Rachen) abzielen. Dazu gehören das präoperative Duschen/Waschen mit Seife, die Dekolonisation von nasalen Staphylococcus-aureus-Trägern mit Mupirocin und die chirurgische Hautantiseptik mit einem alkoholischen Kombinationspräparat. Chirurgen sollten in enger Zusammenarbeit mit Kollegen anderer Disziplinen sowie der Krankenhaushygiene und dem Krankenhausmanagement entsprechende Maßnahmen unter Berücksichtigung der lokalen Bedürfnisse und Besonderheiten Schritt für Schritt in die Praxis integrieren.
Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission
Authors: Yarwood Rebecca E. , Imlach Wendy L. , Lieu TinaMarie , Veldhuis Nicholas A. , Jensen Dane D. , Klein Herenbrink Carmen , Aurelio Luigi , Cai Zhijian , Christie MacDonald J. , Poole Daniel P. , Porter Christopher J. H. , McLean Peter , Hicks Gareth A. , Geppetti Pierangelo , Halls Michelle L. , Canals Meritxell , Bunnett Nigel W. 
Published: October 2017

Significance
G protein-coupled receptors (GPCRs) have long been considered to function primarily at the plasma membrane. Consequently, most drugs are designed to target GPCRs at the cell surface. Ligand-bound GPCRs undergo clathrin- and dynamin-dependent endocytosis. It is uncertain whether GPCRs in endosomes control complex pathophysiological processes in vivo and are a viable therapeutic target. We report that the CGRP receptor signals from endosomes to regulate activity of pain-transmitting neurons in the spinal cord. Lipid-conjugated CGRP receptor antagonists accumulate in endosomes, selectively inhibit endosomal signals, and block sustained excitation of spinal neurons and persistent nociception. The results suggest that GPCRs in endosomes, in addition to those at the cell surface, control ongoing pathophysiological processes in vivo and identify GPCRs in endosomes as a new target for therapy.
White blood cell population dynamics for risk stratification of acute coronary syndrome
Authors: Chaudhury Anwesha , Noiret Lorette , Higgins John M. 
Published: October 2017

SignificanceMedical doctors use blood counts to help diagnose and monitor almost all diseases. In the process of counting blood cells, most hematology analyzers actually measure features of thousands of individual blood cells, but this single-cell information is rarely utilized, and only the derived total cell counts are used to guide clinical care. This single-cell information helps further characterize each patient’s inflammatory or immunologic state. Using a mathematical model, we show how this routinely available single-cell information can help distinguish healthy and sick patients in general and those with acute coronary syndrome in particular. More broadly, our study shows how mathematical modeling of existing routine clinical laboratory data can help realize the vision of precision medicine today.
Large domain movements upon UvrD dimerization and helicase activation
Authors: Nguyen Binh , Ordabayev Yerdos , Sokoloski Joshua E. , Weiland Elizabeth , Lohman Timothy M. 
Published: October 2017

Significance
UvrD helicase plays essential roles in multiple DNA metabolic processes. Although UvrD monomers can translocate along single-stranded DNA, processive DNA unwinding in vitro requires self-assembly to form at least a UvrD dimer. However, the mechanism of activation by dimerization is not known. Using single-molecule fluorescence approaches, we show that the 2B subdomain of UvrD can freely rotate among at least four substates. Binding of a DNA substrate to a UvrD monomer induces an open conformation that does not activate its helicase activity. UvrD dimerization on DNA is accompanied by closing of the 2B subdomain conformation and helicase activation. The results emphasize the important role of the 2B subdomain in regulating helicase activity.