bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Erikson Psychosocial Stage Inventory in Adolescent	Samples
Authors: Dimitrova Radosveta , Hatano Kai , Sugimura Kazumi , Ferrer-Wreder Laura 
Published: February 2018

Abstract. This study tested the factorial structure and equivalence of identity as measured by the Erikson Psychosocial Stage Inventory (EPSI; Rosenthal, Gurney, & Moore, 1981 ) in 2,666 adolescents ( Mage = 16.53, SD = 1.50, 55% girls) in the United States and Japan. The EPSI Identity Scale is a widely used measure of the Eriksonian conceptualization of personal identity (i.e., individual self-knowledge, synthesis, and consistency) and is measured with two factors: identity confusion and synthesis. A bi-factor model for the EPSI had a better fit than a single- and two-factor model. Moreover, the EPSI results showed configural and partial metric equivalence, but did not show scalar equivalence across samples. Future cross-national research with adolescents from the United States and Japan may investigate correlates between identity, as measured by the EPSI, with other measures of interest. However, group comparisons among these samples may be ill advised due to a lack of scalar equivalence.
Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling
Authors: Richter Melanie , Murtaza Nadeem , Scharrenberg Robin , White Sean H. , Johanns Ole , Walker Susan , Yuen Ryan K. C. , Schwanke Birgit , Bedürftig Bianca , Henis Melad , Scharf Sarah , Kraus Vanessa , Dörk Ronja , Hellmann Jakob , Lindenmaier Zsuzsa , Ellegood Jacob , Hartung Henrike , Kwan Vickie , Sedlacik Jan , Fiehler Jens , Schweizer Michaela , Lerch Jason P. , Hanganu-Opatz Ileana L. , Morellini Fabio , Scherer Stephen W. , Singh Karun K. , Calderon de Anda Froylan 
Published: February 2018

AbstractAtypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs). TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it contributes to NDDs is unknown. We performed behavioral analysis on Taok2 heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice also have dosage-dependent abnormalities in brain size and neural connectivity in multiple regions, deficits in cortical layering, dendrite and synapse formation, and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of ASD families identified three de novo mutations in TAOK2 and functional analysis in mice and human cells revealed that all the mutations impair protein stability, but they differentially impact kinase activity, dendrite growth, and spine/synapse development. Mechanistically, loss of Taok2 activity causes a reduction in RhoA activation, and pharmacological enhancement of RhoA activity rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator of TAOK2-dependent synaptic development.
Single-molecule theory of enzymatic inhibition
Authors: Robin Tal , Reuveni Shlomi , Urbakh Michael 
Published: February 2018

AbstractThe classical theory of enzymatic inhibition takes a deterministic, bulk based approach to quantitatively describe how inhibitors affect the progression of enzymatic reactions. Catalysis at the single-enzyme level is, however, inherently stochastic which could lead to strong deviations from classical predictions. To explore this, we take the single-enzyme perspective and rebuild the theory of enzymatic inhibition from the bottom up. We find that accounting for multi-conformational enzyme structure and intrinsic randomness should strongly change our view on the uncompetitive and mixed modes of inhibition. There, stochastic fluctuations at the single-enzyme level could make inhibitors act as activators; and we state—in terms of experimentally measurable quantities—a mathematical condition for the emergence of this surprising phenomenon. Our findings could explain why certain molecules that inhibit enzymatic activity when substrate concentrations are high, elicit a non-monotonic dose response when substrate concentrations are low.
Genetic contribution to ‘theory of mind’ in adolescence
Authors: Warrier Varun , Baron-Cohen Simon 
Published: February 2018

AbstractDifficulties in ‘theory of mind’ (the ability to attribute mental states to oneself or others, and to make predictions about another’s behaviour based on these attributions) have been observed in several psychiatric conditions. We investigate the genetic architecture of theory of mind in 4,577 13-year-olds who completed the Emotional Triangles Task (Triangles Task), a first-order test of theory of mind. We observe a small but significant female-advantage on the Triangles Task (Cohen’s d = 0.19, P < 0.01), in keeping with previous work using other tests of theory of mind. Genome-wide association analyses did not identify any significant loci, and SNP heritability was non-significant. Polygenic scores for six psychiatric conditions (ADHD, anorexia, autism, bipolar disorder, depression, and schizophrenia), and empathy were not associated with scores on the Triangles Task. However, polygenic scores of cognitive aptitude, and cognitive empathy, a term synonymous with theory of mind and measured using the “Reading the Mind in the Eyes” Test, were significantly associated with scores on the Triangles Task at multiple P-value thresholds, suggesting shared genetics between different measures of theory of mind and cognition.
The EphA2 receptor is activated through induction of distinct, ligand-dependent oligomeric structures
Authors: Singh Deo R. , Kanvinde Pranjali , King Christopher , Pasquale Elena B. , Hristova Kalina 
Published: February 2018

AbstractThe EphA2 receptor tyrosine kinase is capable of activating multiple diverse signaling pathways with roles in processes such as tissue homeostasis and cancer. EphA2 is known to form activated oligomers in the presence of ephrin-A ligands. Here, we characterize the lateral interactions between full-length EphA2 molecules in the plasma membrane in the presence of three types of ligands (dimeric ephrinA1-Fc, monomeric ephrinA1, and an engineered peptide ligand) as well as in the absence of ligand, using a quantitative FRET technique. The data show that EphA2 forms higher-order oligomers and two different types of dimers that all lead to increased EphA2 tyrosine phosphorylation, which is indicative of increased kinase-dependent signaling. We find that different ligands stabilize conformationally distinct oligomers that are assembled through two different interfaces. Our results suggest that these different oligomeric assemblies could have distinct signaling properties, contributing to the diverse activities of the EphA2 receptor.
Diffuse interstellar bands λ5780 and λ5797 in the Antennae Galaxy as seen by MUSE
Authors: Monreal-Ibero A. , Weilbacher P. M. , Wendt M. 
Published: February 2018

Context. Diffuse interstellar bands (DIBs) are faint spectral absorption features of unknown origin. Research on DIBs beyond the Local Group is very limited and will surely blossom in the era of the Extremely Large Telescopes. However, we can already start paving the way. One possibility that needs to be explored is the use of high-sensitivity integral field spectrographs.
Aims. Our goals are twofold. First, we aim to derive reliable mapping of at least one DIB in a galaxy outside the Local Group. Second, we want to explore the relation between DIBs and other properties of the interstellar medium (ISM) in the galaxy.
Methods. We use Multi Unit Spectroscopic Explorer (MUSE) data for the Antennae Galaxy, the closest major galaxy merger. High signal-to-noise spectra were created by co-adding the signal of many spatial elements with the Voronoi binning technique. The emission of the underlying stellar population was modelled and substracted with the STARLIGHT spectral synthesis code. Flux and equivalent width of the features of interest were measured by means of fitting to Gaussian functions.
Results. To our knowledge, we have derived the first maps for the DIBs at λ5780 and λ5797 in galaxies outside the Local Group. The strongest of the two DIBs (at λ5780) was detected in an area of ~0.6□′, corresponding to a linear scale of ~25 kpc2. This region was sampled using >200 out of ~1200 independent lines of sight. The DIB λ5797 was detected in >100 independent lines of sight. Both DIBs are associated with a region of high emission in the H I 21 cm line, implying a connection between atomic gas and DIBs, as the correlations in the Milky Way also suggest. Conversely, there is mild spatial association between the two DIBs and the molecular gas, in agreement with results for our Galaxy that indicate a lack of correlation between DIBs and molecular gas. The overall structures for the DIB strength distribution and extinction are comparable. Within the system, the λ5780 DIB clearly correlates with the extinction, and both DIBs follow the relationship between equivalent width and reddening when data for several galaxies are considered. This relationship is tighter when comparing only with galaxies with metallicities close to solar. Unidentified infrared emission bands (UIBs, likely caused by polycyclic aromatic hydrocarbons PAHs) and the λ5780 and λ5797 DIBs show similar but not identical spatial distributions. We attribute the differences to extinction effects without necessarily implying a radically different nature of the respective carriers.
Conclusions. The results illustrate the enormous potential of integral field spectrographs for extragalactic DIB research.
Spinalkanalstenose – eine Diagnose für unterschiedliche Krankheitsbilder
Authors: Beyerlein Jörg 
Published: February 2018

ZusammenfassungEine Diagnose und sehr verschiedene Therapieoptionen – so präsentiert sich die lumbale Spinalkanalstenose. Auf
den ersten Blick simpel, entpuppt sie sich als komplexe Pathologie, die gründlich analysiert werden sollte, um
die richtige Therapieentscheidung zu treffen.
Manuelle Therapie nach Mulligan zur Verbesserung der Knieflexion bei Patienten nach
Knietotalendoprothese
Authors: Halil Deniz 
Published: February 2018

ZusammenfassungPatienten nach Implantation einer Knietotalendoprothese (TEP) benötigen zur Bewältigung ihres Alltags zügig
eine ausreichende Gelenkbeweglichkeit. Evidenz für manualtherapeutische Techniken zur Förderung der
Beweglichkeit in der Rehabilitationsphase nach Knie-TEP wurde bisher nicht veröffentlicht. Das primäre Ziel
dieser monozentrischen randomisierten kontrollierten Pilotstudie war zu untersuchen, wie sich die Anwendung
der manualtherapeutischen Technik „Mobilisation with Movement“ (MWM) nach dem Mulligan-Konzept 1
2 auf die Funktion der Knieflexion nach primärer Knie-TEP auswirkt. Primärer
Zielparameter war die Mittelwertdifferenz der aktiven Flexion, sekundärer Zielparameter die
Mittelwertdifferenz der aktiven Extension, Schmerzreduktion und Funktionsstatus.Beim primären Zielparameter bestand ein statistisch signifikanter Unterschied zwischen der Interventions- und
der Kontrollgruppe. Der sekundären Zielparameter Schmerzlinderung zeigte ebenfalls einen signifikanten
Unterschied zugunsten der Interventionsgruppe. Bei den weiteren sekundären Zielparametern fanden sich keine
signifikanten Unterschiede.Ein statistisch und klinisch signifikanter Effekt zugunsten der MWM-Technik gegenüber rotatorischen
Mobilisationstechniken konnte nachgewiesen werden. Zur Bestätigung der Effekte sind weitere Studien mit
höheren Fallzahlen und Follow-ups nötig.
Chronischer Schmerz: Verhalten der Patienten und die kommunikativen Fähigkeiten der
Therapeuten
Authors: Haantjes Wijnand 
Published: February 2018

ZusammenfassungWenn sich chronische Schmerzen einfach behandeln ließen, wären sie nicht chronisch. Bei dieser
Patientenkategorie spielen die psychosozialen Faktoren eine erhebliche Rolle. Diese sind mit gewissen
Grundkenntnissen der menschlichen Psychologie leicht zu erkennen. Manualtherapeuten können so zu ihren
Patienten mit chronischen Schmerzen eine vertrauensvollere Beziehung aufbauen und die Chancen auf einen
Behandlungserfolg verbessern.
Personalisierte Ophthalmologie – induzierte pluripotente Stammzellen als In-vitro-Modellsysteme für degenerative Netzhauterkrankungen
Authors: Brandl Caroline , Weber Bernhard 
Published: February 2018

ZusammenfassungDie Suche nach kausalen Therapieoptionen für degenerative Netzhauterkrankungen kann mit einem detaillierten Verständnis pathologischer Vorgänge gezielt vorangetrieben werden. Alternativ kann sie sich auch auf einen eher ungerichteten Suchansatz für therapeutische Wirkstoffe verlassen. Für beide Forschungsansätze werden In-vitro- und, falls möglich, auch In-vivo-Krankheitsmodelle benötigt, die eine möglichst genaue Abbildung des primären Ortes der Schädigung reflektieren. Tiermodelle unterliegen Einschränkungen und können oft nur dezidierte Aspekte eines komplexen Krankheitsprozesses abbilden. Primärkulturen von Zelltypen des hinteren Augenpols sind lediglich invasiv bzw. post mortem zugänglich und aufgrund ihrer raschen Seneszenz nur ungenügend geeignet für zeitlich anspruchsvolle Analysen oder pharmakologische Suchansätze. Immortalisierte retinale Zelllinien wiederum unterscheiden sich in einigen Aspekten zu sehr von den nativen Zelltypen. Eine vielversprechende Alternative bieten induzierte pluripotente Stammzellen (iPSCs). Sie sind wenig invasiv zugänglich, patientenspezifisch generierbar, uneingeschränkt vermehrbar und können aufgrund ihrer Pluripotenz bereits jetzt in einige retinale Zelltypen gezielt ausdifferenziert werden. Diese iPSC-abgeleiteten retinalen Zellen gleichen nativen Zellen in vielen charakteristischen Schlüsseleigenschaften. In diesem Übersichtsartikel werden bereits etablierte In-vivo-und In-vitro-Krankheitsmodelle degenerativer Netzhauterkrankungen vorgestellt und das Potenzial von iPSCs für eine personalisierte In-vitro-Modellierung ausgeleuchtet. Darüber hinaus werden bisher etablierte iPSC-abgeleitete Zelltypen des hinteren Augenpols – insbesondere Zellen des retinalen Pigmentepithels – detaillierter betrachtet und ein Ausblick für das Potenzial dieser Zellen in der allgemeinen ophthalmologischen Forschung gegeben.
Co-culture of human bone marrow mesenchymal stem cells and macrophages attenuates lipopolysaccharide-induced inflammation in human corneal epithelial cells
Authors: Jeong Won-Yong , Kim Ji-Hye , Kim Chan-Wha 
Published: February 2018

AbstractDry eye syndrome (DES) is considered as an ocular surface inflammatory disease. Previous studies have shown inflammation plays an important role in the progression and onset of DES. Co-culture of human bone marrow mesenchymal stem cells (HBMSCs) and macrophages showed immunomodulatory effects via regulation of cytokine regulation. Thus, the aim of this study was to investigate the effect of the interaction of these cells on in vitro DES model. The conditioned media (CM) from macrophages, HBMSCs, and HBMSCs + macrophages were treated to human corneal epithelial cells, which showed significant reduction in IL-1α and IL-1β expression levels in HBMSCs + macrophages group. Moreover, the IL-1 Receptor Antagonist (IL-1RA) was highly expressed in the CM from the HBMSCs + macrophages group. Wounded eyes of mice were treated with IL-1RA at 0–100 ng/mL for 16 h, the wound size was reduced. The results of this study might lead to the identification of new therapeutic targets for DES.
Multiobjective multifactor dimensionality reduction to detect SNP–SNP interactions
Authors: Yang Cheng-Hong , Chuang Li-Yeh , Lin Yu-Da 
Published: February 2018

Abstract

Motivation
Single-nucleotide polymorphism (SNP)–SNP interactions (SSIs) are popular markers for understanding disease susceptibility. Multifactor dimensionality reduction (MDR) can successfully detect considerable SSIs. Currently, MDR-based methods mainly adopt a single-objective function (a single measure based on contingency tables) to detect SSIs. However, generally, a single-measure function might not yield favorable results due to potential model preferences and disease complexities.

Approach
This study proposes a multiobjective MDR (MOMDR) method that is based on a contingency table of MDR as an objective function. MOMDR considers the incorporated measures, including correct classification and likelihood rates, to detect SSIs and adopts set theory to predict the most favorable SSIs with cross-validation consistency. MOMDR enables simultaneously using multiple measures to determine potential SSIs.

Results
Three simulation studies were conducted to compare the detection success rates of MOMDR and single-objective MDR (SOMDR), revealing that MOMDR had higher detection success rates than SOMDR. Furthermore, the Wellcome Trust Case Control Consortium dataset was analyzed by MOMDR to detect SSIs associated with coronary artery disease.
Availability and implementation: MOMDR is freely available at https://goo.gl/M8dpDg

Supplementary information
Supplementary data are available at Bioinformatics online.
Cost function network-based design of protein–protein interactions: predicting changes in binding affinity
Authors: Viricel Clément , de Givry Simon , Schiex Thomas , Barbe Sophie 
Published: February 2018

Abstract

Motivation
Accurate and economic methods to predict change in protein binding free energy upon mutation are imperative to accelerate the design of proteins for a wide range of applications. Free energy is defined by enthalpic and entropic contributions. Following the recent progresses of Artificial Intelligence-based algorithms for guaranteed NP-hard energy optimization and partition function computation, it becomes possible to quickly compute minimum energy conformations and to reliably estimate the entropic contribution of side-chains in the change of free energy of large protein interfaces.

Results
Using guaranteed Cost Function Network algorithms, Rosetta energy functions and Dunbrack’s rotamer library, we developed and assessed EasyE and JayZ, two methods for binding affinity estimation that ignore or include conformational entropic contributions on a large benchmark of binding affinity experimental measures. If both approaches outperform most established tools, we observe that side-chain conformational entropy brings little or no improvement on most systems but becomes crucial in some rare cases.

Availability and implementation
as open-source Python/C++ code at sourcesup.renater.fr/projects/easy-jayz.

Supplementary information
Supplementary data are available at Bioinformatics online.
Infliximab for Crohn’s Disease: More Than 13 Years of Real-world Experience
Authors: Lichtenstein Gary R , Feagan Brian G , Cohen Russell D , Salzberg Bruce A , Safdi Michael , Popp John W , Langholff Wayne , Sandborn William J 
Published: February 2018

Abstract

Background
The purpose of this study was to compare the long-term safety of infliximab and nonbiologic agents as Crohn’s disease (CD) therapy.

Methods
Patients with CD were prospectively evaluated in this large, observational registry.

Results
Patients (n = 6273) participated in this observational registry from July 1999 through March 2012; 3440 (54.8%) received infliximab (20,971 patient-years), and 2833 (45.2%) received other treatments only (14,806 patient-years). Overall, 59,875 infliximab infusions were administered (80%, 5 mg/kg); 3006 (89.9%) patients received ≥2 infusions. Adverse events (AEs), most commonly those related to CD (eg, abdominal pain, diarrhea), and serious AEs occurred at a higher rate among infliximab-treated patients. Mortality (0.57/100 patient-years, 0.67/100 patient-years) and malignancy rates (0.69/100 patient-years, 0.71/100 patient-years) for infliximab-treated and other-treatments-only patients, respectively, were generally similar. Serious infection rates were higher for infliximab-treated (2.15/100 patient-years) than other-treatments-only patients (0.86/100 patient-years). Infliximab dose was not associated with mortality or serious infection. An increased risk of serious infection was observed with age (&gt;52 years vs ≤30 years) when examined in infliximab-treated patients. Nonserious cerebrovascular accidents (13 events, 0.06/100 patient-years; 5 events, 0.03/100 patient-years) and pulmonary embolisms (11 events, 0.05/100 patient-years; 4 events 0.03/100 patient-years) also occurred at higher rates among infliximab-treated patients than other-treatments-only patients.

Conclusions
Through more than 13 years of registry experience and an overall median duration of patient follow-up &gt;6 years, mortality was similar between the infliximab-treated and other-treatments-only groups. These final cumulative results are representative of real-world experience among infliximab-treated patients with CD and are consistent with the known risks of disease activity and tumor necrosis factor antagonist therapy.
Changes Over Time in Nasopharyngeal Colonization in Children Under 2 Years of Age at the Time of Diagnosis of Acute Otitis Media (1999–2014)
Authors: Martin Judith M , Hoberman Alejandro , Shaikh Nader , Shope Timothy , onika Bhatnagar S , Block Stan L , Haralam Mary Ann , Kurs-Lasky Marcia , Green Michael 
Published: February 2018

AbstractBackgroundIn children with acute otitis media (AOM), a decrease in nasopharyngeal (NP) colonization with vaccine serotypes of Streptococcus pneumoniae has been noted since the introduction of pneumococcal conjugate vaccines (PCVs). The purpose of this study is to describe corresponding changes in colonization with Haemophilus influenzae.MethodsIn 4 separate studies, we obtained NP cultures from children aged 6–23 months presenting with AOM. Cohort 1 was recruited before routine use of PCV7 (1999–2000); 93% of children in cohort 2 (2003–2005) and 100% in cohort 3 (2006–2009) received ≥2 doses of PCV7. All children in cohort 4 (2012–2014) received ≥2 doses of PCV13. Isolates of H. influenzae were tested for ß-lactamase production; ß-lactamase negative isolates from cohorts 3 and 4 underwent susceptibility testing.ResultsA total of 899 children were evaluated. NP colonization with H. influenzae was found in 26% of children in cohort 1 (n = 175), 41% in cohort 2 (n = 87), 33% in cohort 3 (n = 282), and 29% in cohort 4 (n = 355). Colonization with H. influenzae increased initially from cohort 1 to cohort 2 (P = .01), then decreased across cohorts 2, 3, and 4 (P = .03, test for trend). The prevalence rates of ß-lactamase production were 27%, 42%, 33%, and 30% in each of the 4 cohorts, respectively (P = .50).ConclusionsAlthough an initial increase in H. influenzae colonization was observed, suggesting an impact of PCVs, the most recent prevalence rates of NP colonization with H. influenzae and ß-lactamase production were like those observed before universal administration of PCV7. This knowledge is critical to guide appropriate treatment recommendations for children with AOM.