bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study
Authors: de Groot Bas , Ansems Annemieke , Gerling Daan H , Rijpsma Douwe , van Amstel Paul , Linzel Durk , Kostense Piet J , Jonker Marianne , de Jonge Evert 
Published: April 2015

Abstract
Introduction
In early sepsis stages, optimal treatment could contribute to prevention of progression to severe sepsis. Therefore, we investigated if there was an association between time to antibiotics and relevant clinical outcomes in hospitalized emergency department (ED) patients with mild to severe sepsis stages.

Methods
This is a prospective multicenter study in three Dutch EDs. Patients were stratified into three categories of illness severity, as assessed by the predisposition, infection, response, and organ failure (PIRO) score: PIRO score 1 to 7, 8 to 14 and >14 points, reflected low, intermediate, and high illness severity, respectively. Consecutive hospitalized ED patients with a suspected infection who were treated with intravenous antibiotics were eligible to participate in the study. The primary outcome measure was the number of surviving days outside the hospital at day 28 which was used as an inverse measure of hospital length of stay (LOS). The secondary outcome measure was 28-day mortality, taking into account the time to mortality.
Multivariable Cox regression analysis was used to estimate the association between time to antibiotics and the primary and secondary outcome measures corrected for confounders, including appropriateness of antibiotics and initial ED resuscitation, in three categories of illness severity.

Results
Of the 1,168 included patients, 112 died (10%), while 85% and 95% received antibiotics within three and six hours, respectively. No association between time to antibiotics and surviving days outside the hospital or mortality was found. Only in PIRO group 1 to 7 was delayed administration of antibiotics (>3 hours) associated with an increase in surviving days outside the hospital at day 28 (hazard ratio: 1.46, 95% confidence interval: 1.05 to 2.02 after correction for potential confounders).

Conclusions
In ED patients with mild to severe sepsis who received antibiotics within six hours after ED presentation, a reduction in time to antibiotics was not found to be associated with an improvement in relevant clinical outcomes.
Sagittal and vertical effects of transverse sagittal maxillary expander (TSME) in three different malocclusion groups
Authors: Maspero Cinzia , Galbiati Guido , Giannini Lucia , Farronato Giampietro 
Published: April 2015

Abstract

Background
The aim of this retrospective study was to cephalometrically evaluate the skeletal and dental effects of the transverse sagittal maxillary expander (TSME), for the correction of sagittal and transverse maxillary deficiency in class I, II, and III malocclusions.

Methods
The sample for this retrospective study included 45 patients (mean age, 8.4 years; 26 females, 19 males; 15 skeletal class I subjects, 15 skeletal class II subjects, and 15 skeletal class III subjects) with maxillary bilateral cross-bite.
For each patient, a lateral cephalogram was obtained before treatment and at the end of the retention period. Changes in the groups during the observation period were calculated, compared, and statistically analyzed with a t-test.

Results
The cephalometric values before T0 and T1 showed significant changes.

Conclusions
The TSME can produce skeletal changes due to the transverse force and sagittal effects on the maxillary alveolar process. These modifications have benefic effects in classes I, II, and III. The data obtained in this study permit us to underline the fact that TSME can be used in all of the skeletal classes, with good vertical and sagittal results.
Enhancement of neutrophil autophagy by an IVIG preparation against multidrug-resistant bacteria as well as drug-sensitive strains
Authors: Itoh Hiroshi , Matsuo Hidemasa , Kitamura Naoko , Yamamoto Sho , Higuchi Takeshi , Takematsu Hiromu , Kamikubo Yasuhiko , Kondo Tadakazu , Yamashita Kouhei , Sasada Masataka , Takaori-Kondo Akifumi , Adachi Souichi 
Published: April 2015

Abstract
Autophagy occurs in human neutrophils after the phagocytosis of multidrug-resistant bacteria and drug-sensitive strains, including Escherichia coli and Pseudomonas aeruginosa. The present study detected autophagy by immunoblot analysis of LC3B conversion, by confocal scanning microscopic examination of LC3B aggregate formation and by transmission electron microscopic examination of bacteria-containing autophagosomes. Patients with severe bacterial infections are often treated with IVIG alongside antimicrobial agents. Here, we showed that IVIG induced neutrophil-mediated phagocytosis of multidrug-resistant strains. Compared with untreated neutrophils, neutrophils exposed to IVIG showed increased levels of bacterial cell killing, phagocytosis, O2− release, MPO release, and NET formation. IVIG also increased autophagy in these cells. Inhibiting the late phase of autophagy (fusion of lysosomes with autophagosomes) with bafilomycin A1-reduced, neutrophil-mediated bactericidal activity. These findings indicate that autophagy plays a critical role in the bactericidal activity mediated by human neutrophils. Furthermore, the autophagosomes within the neutrophils contained bacteria only and their organelles only, or both bacteria and their organelles, a previously undocumented observation. Taken together, these results suggest that the contents of neutrophil autophagosomes may be derived from specific autophagic systems, which provide the neutrophil with an advantage. Thus, IVIG promotes the neutrophil-mediated killing of multidrug-resistant bacteria as well as drug-sensitive strains.
A general psychopathology factor in early adolescence
Authors: Patalay Praveetha , Fonagy Peter , Deighton Jessica , Belsky Jay , Vostanis Panos , Wolpert Miranda 
Published: April 2015

BackgroundRecently, a general psychopathology dimension reflecting common aspects among disorders has been identified in adults. This has not yet been considered in children and adolescents, where the focus has been on externalising and internalising dimensions.AimsTo examine the existence, correlates and predictive value of a general psychopathology dimension in young people.MethodAlternative factor models were estimated using self-reports of symptoms in a large community-based sample aged 11–13.5 years (N= 23 477), and resulting dimensions were assessed in terms of associations with external correlates and future functioning.ResultsBoth a traditional two-factor model and a bi-factor model with a general psychopathology bi-factor fitted the data well. The general psychopathology bi-factor best predicted future psychopathology and academic attainment. Associations with correlates and factor loadings are discussed.ConclusionsA general psychopathology factor, which is equal across genders, can be identified in young people. Its associations with correlates and future functioning indicate that investigating this factor can increase our understanding of the aetiology, risk and correlates of psychopathology.
PML induces compaction, TRF2 depletion and DNA damage signaling at telomeres and promotes their alternative lengthening
Authors: Osterwald Sarah , Deeg Katharina I. , Chung Inn , Parisotto Daniel , Wörz Stefan , Rohr Karl , Erfle Holger , Rippe Karsten 
Published: April 2015

ABSTRACT
The alternative lengthening of telomeres (ALT) mechanism allows cancer cells to escape senescence and apoptosis in the absence of active telomerase. A characteristic feature of this pathway is the assembly of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) at telomeres. Here, we dissected the role of APBs in a human ALT cell line by performing an RNA interference screen using an automated 3D fluorescence microscopy platform and advanced 3D image analysis. We identified 29 proteins that affected APB formation, which included proteins involved in telomere and chromatin organization, protein sumoylation and DNA repair. By integrating and extending these findings, we found that APB formation induced clustering of telomere repeats, telomere compaction and concomitant depletion of the shelterin protein TRF2 (also known as TERF2). These APB-dependent changes correlated with the induction of a DNA damage response at telomeres in APBs as evident by a strong enrichment of the phosphorylated form of the ataxia telangiectasia mutated (ATM) kinase. Accordingly, we propose that APBs promote telomere maintenance by inducing a DNA damage response in ALT-positive tumor cells through changing the telomeric chromatin state to trigger ATM phosphorylation.
HGF-induced serine 897 phosphorylation of EphA2 regulates epithelial morphogenesis of MDCK cells in 3D culture
Authors: Harada Kohei , Negishi Manabu , Katoh Hironori 
Published: April 2015

ABSTRACT
Expression of EphA2 is upregulated in various cancers that are derived from epithelial cells and correlates with the ability of a cancer cell to undergo migration and invasion. Here we have investigated the role of EphA2 in the epithelial morphogenesis of Madin-Darby canine kidney (MDCK) cells in three-dimensional culture. We show that EphA2 is phosphorylated on serine residue 897 through hepatocyte growth factor (HGF) stimulation using a phosphatidylinositol 3-kinase (PI3K)–Akt-dependent mechanism and that this phosphorylation is required for the formation of extensions, the first step of tubulogenesis, in MDCK cysts. By contrast, stimulation using the ligand ephrinA1 dephosphorylates EphA2 on serine residue 897 and suppresses the HGF-induced morphological change. Furthermore, activation of the small GTPase RhoG is involved in the HGF-induced formation of extensions downstream of EphA2. These observations suggest that a ligand-independent activity of EphA2 contributes to epithelial morphogenesis.
Localization of cofilin mRNA to the leading edge of migrating cells promotes directed cell migration
Authors: Maizels Yael , Oberman Froma , Miloslavski Rachel , Ginzach Nava , Berman Malka , Yisraeli Joel K. 
Published: April 2015

ABSTRACT
mRNA trafficking, which enables the localization of mRNAs to particular intracellular targets, occurs in a wide variety of cells. The importance of the resulting RNA distribution for cellular functions, however, has been difficult to assess. We have found that cofilin-1 mRNA is rapidly localized to the leading edge of human lung carcinoma cells and that VICKZ family RNA-binding proteins help mediate this localization through specific interactions with the 3′UTR of cofilin mRNA. Using a phagokinetic assay for cell motility, we have been able to quantify the effect of mRNA localization on the rescue of lung carcinoma cells in which cofilin was knocked down by using short hairpin RNA (shRNA). Although restoring cofilin protein to normal endogenous levels rescues general lamellipodia formation around the periphery of the cell, only when the rescuing cofilin mRNA can localize to the leading edge is it capable of also fully rescuing directed cell movement. These results demonstrate that localization of an mRNA can provide an additional level of regulation for the function of its protein product.
Regulation of Cdc42 polarization by the Rsr1 GTPase and Rga1, a Cdc42 GTPase-activating protein, in budding yeast
Authors: Lee Mid Eum , Lo Wing-Cheong , Miller Kristi E. , Chou Ching-Shan , Park Hay-Oak 
Published: April 2015

ABSTRACT
Cdc42 plays a central role in establishing polarity in yeast and animals, yet how polarization of Cdc42 is achieved in response to spatial cues is poorly understood. Using live-cell imaging, we found distinct dynamics of Cdc42 polarization in haploid budding yeast in correlation with two temporal steps of the G1 phase. The position at which the Cdc42–GTP cluster develops changes rapidly around the division site during the first step but becomes stabilized in the second step, suggesting that an axis of polarized growth is determined in mid G1. Cdc42 polarization in the first step and its proper positioning depend on Rsr1 and its GTPase-activating protein (GAP) Bud2. Interestingly, Rga1, a Cdc42 GAP, exhibits transient localization to a site near the bud neck and to the division site during cytokinesis and G1, and this temporal change of Rga1 distribution is necessary for determination of a proper growth site. Mathematical modeling suggests that a proper axis of Cdc42 polarization in haploid cells might be established through a biphasic mechanism involving sequential positive feedback and transient negative feedback.
ENTH and ANTH domain proteins participate in AP2-independent clathrin-mediated endocytosis
Authors: Manna Paul T. , Gadelha Catarina , Puttick Amy E. , Field Mark C. 
Published: April 2015

ABSTRACT
Clathrin-mediated endocytosis (CME) is a major route of entry into eukaryotic cells. A core of evolutionarily ancient genes encodes many components of this system but much of our mechanistic understanding of CME is derived from a phylogenetically narrow sampling of a few model organisms. In the parasite Trypanosoma brucei, which is distantly related to the better characterised animals and fungi, exceptionally fast endocytic turnover aids its evasion of the host immune system. Although clathrin is absolutely essential for this process, the adaptor protein complex 2 (AP2) has been secondarily lost, suggesting mechanistic divergence. Here, we characterise two phosphoinositide-binding monomeric clathrin adaptors, T. brucei (Tb)EpsinR and TbCALM, which in trypanosomes are represented by single genes, unlike the expansions present in animals and fungi. Depletion of these gene products reveals essential, but partially redundant, activities in CME. Ultrastructural analysis of TbCALM and TbEpsinR double-knockdown cells demonstrated severe defects to clathrin-coated pit formation and morphology associated with a dramatic inhibition of endocytosis. Depletion of TbCALM alone, however, produced a distinct lysosomal segregation phenotype, indicating an additional non-redundant role for this protein. Therefore, TbEpsinR and TbCALM represent ancient phosphoinositide-binding proteins with distinct and vital roles in AP2-independent endocytosis.
Essential role of flotillin-1 palmitoylation in the intracellular localization and signaling function of IGF-1 receptor
Authors: Jang Donghwan , Kwon Hayeong , Jeong Kyuho , Lee Jaewoong , Pak Yunbae 
Published: April 2015

ABSTRACT
Here, we explored flotillin-1-mediated regulation of insulin-like growth factor-1 (IGF-1) signaling. Flotillin-1-deficient cells exhibited a reduction in the activation of IGF-1 receptor (IGF-1R), ERK1/2 and Akt pathways, and the transcriptional activation of Elk-1 and the proliferation in response to IGF-1 were reduced in these cells. We found that IGF-1-independent flotillin-1 palmitoylation at Cys34 in the endoplasmic reticulum (ER) was required for the ER exit and the plasma membrane localization of flotillin-1 and IGF-1R. IGF-1-dependent depalmitoylation and repalmitoylation of flotillin-1 sustained tyrosine kinase activation of the plasma-membrane-targeted IGF-1R. Dysfunction and blocking the turnover of flotillin-1 palmitoylation abrogated cancer cell proliferation after IGF-1R signaling activation. Our data show that flotillin-1 palmitoylation is a new mechanism by which the intracellular localization and activation of IGF-1R are controlled.
Amorphous Ca2+ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells
Authors: Müller Werner E. G. , Tolba Emad , Feng Qingling , Schröder Heinz C. , Markl Julia S. , Kokkinopoulou Maria , Wang Xiaohong 
Published: April 2015

ABSTRACT
Polyphosphate (polyP) is a physiologically occurring polyanion that is synthesized especially in bone-forming osteoblast cells and blood platelets. We used amorphous polyP nanoparticles, complexed with Ca2+, that have a globular size of ∼100 nm. Because polyP comprises inorganic orthophosphate units that are linked together through high-energy phosphoanhydride bonds, we questioned whether the observed morphogenetic effect, elicited by polyP, is correlated with the energy-generating machinery within the cells. We show that exposure of SaOS-2 osteoblast-like cells to polyP results in a strong accumulation of mitochondria and a parallel translocation of the polyP-degrading enzyme alkaline phosphatase to the cell surface. If SaOS-2 cells are activated by the mineralization activation cocktail (comprising β-glycerophosphate, ascorbic acid and dexamethasone) and additionally incubated with polyP, a tenfold intracellular increase of the ATP level occurs. Even more, in those cells, an intensified release of ATP into the extracellular space is also seen. We propose and conclude that polyP acts as metabolic fuel after the hydrolytic cleavage of the phosphoanhydride linkages, which contributes to hydroxyapatite formation on the plasma membranes of osteoblasts.
Energy-dissipative Self-assembly Driven in Microflow: A Time-programmed Self-organization and Decomposition of Metastable Nanofibers
Authors: Numata Munenori , Sato Akiko , Nogami Rie 
Published: April 2015

Abstract
Energy-dissipative self-assembly in microflow enables us to approach an energetically unstable self-assembled structure, which undergoes morphological transition in a cascade manner from fibers, sheets, and finally “running down” to thermodynamically stable dots, with switching intermolecular interactions.
Influences of Non-axial Process Loads on the Transducer and the Associated Mounting in Ultrasonic Machining
Authors: Bruns Peter , Twiefel Jens 
Published: April 2015

Abstract
An analysis method allowing investigations of load influences on ultrasonic transducer oscillations is developed and presented. The focus here is on transducers utilized in ultrasonic-assisted machining due to the high process loads occurring. These loads can affect the operational vibration by exciting bending or torsion modes. However, the explicit impact on the process has yet to be determined. Hereby, conclusions about each oscillation mode effecting the operational vibration separately would be desirable. To achieve this, the eigenmodes being excited in dependence of the load have to be determined. Though the question remains of how big the respective influence on the operational vibration is. In the contribution at hand both questions will be answered by means of a modal transformation-based analysis that is illustrated by an explicit example. It is shown that a defined modal force permits determining the excited modes and the explicit share of the applied load coupling into the particular mode, respectively. In addition, the qualitative impact of each eigenmode on the resulting vibration can be evaluated by means of the magnitude of the modal equation’s particular solution. The developed analysis is applied on process and mounting loads. Therefore, different load setups are investigated in dependence of the force direction and the application point, thus leading to the conclusion that the presented analysis method is versatile usable, trustable and efficient.
Marauders, Daredevils, and Noble Savages: Perceptions of Arab Nomads in Late Antique Hagiography
Authors: Klein Konstantin M. 
Published: April 2015

AbstractThis contribution investigates perceptions of Arab nomads in the hagiography of the Late Antique East. Over the past decades, these texts, mostly saints’ lives and episodes from church histories, have often been used to provide social and cultural historians with information on the ethnography, geography, customs and manners of those labelled “Saracens” or “Ishmaelites” in the texts. However, the historicity of the narratives is difficult to assess, and a closer inspection reveals that most of the motifs used in Late Antiquity revert to older models from Classical Antiquity. The article therefore focuses on specific aspects, such as how the writers depicted the Arabs’ manners and customs as contrasting with their own societies and constructed a dichotomy between the civilisation and the animal-like ferocity of the former. It becomes clear that Christian authors used the depiction of the Arabs’ seemingly deviant lifestyle in order to both reassure their readership and excite its curiosity. The display of God’s omnipotence in a large number of the texts discussed here offered a chance to demonstrate that Christian saints could eventually convert such people, or, when conversion was not possible, could still hope for very potent miracles.
Fieldwork and Preconceptions: The Role of the Bedouin as Informants in Mediaeval Muslim Scholarly Culture (Second-Third/Eighth-Ninth Centuries)
Authors: Zoltan Szombathy 
Published: April 2015

AbstractThis article examines the methods of urban Muslim scholars of the early Abbasid period in their endeavour to collect information from Bedouin informants. Analogies with the problems of modern anthropological fieldwork are investigated, and the impact of the preconceptions and assumptions that the scholars brought to the field is highlighted. It is shown that mediaeval Muslim scholars’ fieldwork might involve varying activities taking place in different settings, and the term ‘Bedouin informants’ masks quite a variety of individuals claiming some expertise in ‘Bedouin’ culture. The idealised image of a scholar heading for the Arabian deserts to visit genuine nomads and make lengthy inquiries among them might be less typical than is often implicitly thought to have been. On the basis of concrete cases of data-collection, three fundamental assumptions heavily influencing the scholars’ thinking regarding Bedouin culture are identified.
Town and Steppe in Ottoman Syria: Hostility, Exploitation and Cooperation in the Late Seventeenth and Eighteenth Centuries
Authors: Reilly James A. 
Published: April 2015

AbstractLate-seventeenth- and eighteenth-century sources from the Homs and Hama region in Ottoman Syria present contrasting portrayals of Bedouins. Taken together, these sources offer conflicting perspectives with respect to relationships between peoples of the towns and the steppe. On the one hand, literary sources typically portray Bedouins as antitheses of urban life, as savage wanderers who lived outside the norms of propriety and who collectively posed a threat to the wellbeing and property of settled people and of travelers. But on the other hand, legal sources portray Bedouins variously as targets of exploitation or taxation by urban-based governments; or as partners with urban people in contractual undertakings; or as imperial subjects who, like any others, would seek justice in the urban Sharīʿa courts. The article explores these differing characterizations, and seeks to explain the multifarious realities that different sources convey. It concludes by suggesting that relationships between town and steppe were on their way to becoming more institutionalized in the last years of the eighteenth century. This development foreshadowed documented nineteenth-century trends in which urban civil norms and institutions became noticeable in the lives of Bedouins who lived in proximity to towns and urban centers.
1147: The Battle of Qara-Tegin and the Rise of Azarbayjan
Authors: Durand-Guédy David 
Published: April 2015

AbstractThis article aims to show the limits of a dynastic approach to dealing with Iranian history during the sixth/twelfth century, when the Saljuq sultan in the West was only one of the actors on the chessboard, and not even the most powerful. It focuses on the events leading up to the great battle of Qara-Tegin near Hamadan in 542–1/1147. Various struggles passed over in the sources are highlighted through a macro-regional approach. The showdown at Qara-Tegin can be interpreted as the last confrontation between Azarbayjan and Fārs for control of the resources of the central Saljuq space. It ushered in the long-lasting pre-eminence of Azarbayjan, the withdrawal of Fārs and the eventual marginalization of the province of Jibāl/ʿIrāq al-ajamī.