bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems assessment of intercalated combination of chemotherapy and EGFR TKIs versus chemotherapy or EGFR TKIs alone in advanced NSCLC patients
Authors: Yan Han , Li Qin , Wang Wei , Zhen Hongchao , Cao Bangwei 
Published: October 2015

AbstractBoth chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied for the treatment of non-small cell lung cancer (NSCLC), but the efficacy of these two treatments in combination is not yet clear. Thus, we sought to evaluate the efficacy of the intercalated combination of these two treatments in NSCLC. The PubMed database, EMBASE, Cochrane Controlled Trials Register and Chinese Biomedical Database were systematically searched by two researchers for randomized clinical trials (RCTs) that examined the intercalated combination of chemotherapy and EGFR TKIs in NSCLC. Ten studies involving 1,660 patients were included in this systematic review. The statistical results showed that the intercalated combination of chemotherapy and EGFR TKIs significantly improved overall survival (OS) (hazard ratio (HR) = 0.83, 95% confidence interval (CI): 0.70–0.98), progression-free survival (PFS) (HR = 0.65, 95% CI: 0.51–0.84) and the objective response rate (ORR) (risk ratio (RR) = 1.90, 95% CI: 1.22–2.98) compared to chemotherapy alone. Similarly, compared to EGFR TKIs monotherapy, the intercalated combination of chemotherapy and EGFR TKIs seemed superior to EGFR TKIs alone in terms of PFS, ORR and DCR (PFS: HR = 0.75, 95% CI: 0.62–0.91, ORR: RR = 1.49, 95% CI: 1.12–2.00 and DCR: RR = 1.33, 95% CI: 1.15–1.54) in advanced NSCLC therapy.
Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration
Authors: Liao Ru-jia , Jiang Lei , Wang Rong-rong , Zhao Hua-wei , Chen Ying , Li Ya , Wang Lu , Jie Li-Yong , Zhou Yu-dong , Zhang Xiang-nan , Chen Zhong , Hu Wei-wei 
Published: October 2015

AbstractThe formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn’t been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable long-term neuroprotection with decreased infarct volume and improved neurological function. Notably, this treatment regimen also robustly reduced the glial scar area and facilitated the astrocyte migration towards the infarct core. In wound-healing assay and transwell test, histamine significantly promoted astrocyte migration. H2 receptor antagonists reversed the promotion of astrocyte migration and the neuroprotection provided by histidine. Moreover, histamine upregulated the GTP-bound small GTPase Rac1, while a Rac1 inhibitor, NSC23766, abrogated the neuroprotection of histidine and its promotion of astrocyte migration. Our data indicated that a dose/stage-dependent histidine treatment, mediated by H2 receptor, promoted astrocyte migration towards the infarct core, which benefited long-term post-cerebral ischemia neurological recovery. Therefore, targeting histaminergic system may be an effective therapeutic strategy for long-term cerebral ischemia injury through its actions on astrocytes.
Coupling and electrical control of structural, orbital and magnetic orders in perovskites
Authors: Varignon Julien , Bristowe Nicholas C. , Bousquet Eric , Ghosez Philippe 
Published: October 2015

AbstractPerovskite oxides are already widely used in industry and have huge potential for novel device applications thanks to the rich physical behaviour displayed in these materials. The key to the functional electronic properties exhibited by perovskites is often the so-called Jahn-Teller distortion. For applications, an electrical control of the Jahn-Teller distortions, which is so far out of reach, would therefore be highly desirable. Based on universal symmetry arguments, we determine new lattice mode couplings that can provide exactly this paradigm and exemplify the effect from first-principles calculations. The proposed mechanism is completely general, however for illustrative purposes, we demonstrate the concept on vanadium based perovskites where we reveal an unprecedented orbital ordering and Jahn-Teller induced ferroelectricity. Thanks to the intimate coupling between Jahn-Teller distortions and electronic degrees of freedom, the electric field control of Jahn-Teller distortions is of general relevance and may find broad interest in various functional devices.
Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison
Authors: De Meyer Tim , Bady Pierre , Trooskens Geert , Kurscheid Sebastian , Bloch Jocelyne , Kros Johan M. , Hainfellner Johannes A. , Stupp Roger , Delorenzi Mauro , Hegi Monika E. , Van Criekinge Wim 
Published: October 2015

AbstractTwo cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina’s Infinium HumanMethylation450 BeadChips (HM450). Objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples, i.e. 65 glioblastoma and 5 non-tumoral tissues. As MethylCap-seq coverages were limited, we focused on the inherent capacity of the methodology to detect methylated loci rather than a quantitative analysis. MethylCap-seq and HM450 data were dichotomized and performances were compared using a gold standard free Bayesian modelling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. In addition, genome-wide characteristics were compared, revealing that HM450 probes identified substantially fewer regions compared to MethylCap-seq. Although results indicated that the latter method can detect more potentially relevant DNA-methylation, this did not translate into the discovery of more differentially methylated loci between tumours and controls compared to HM450. Our results therefore indicate that both methodologies are complementary, with a higher sensitivity for HM450 and a far larger genome-wide coverage for MethylCap-seq, but also that a more comprehensive character does not automatically imply more significant results in biomarker studies.
Cavity enhanced atomic magnetometry
Authors: Crepaz Herbert , Ley Li Yuan , Dumke Rainer 
Published: October 2015

AbstractAtom sensing based on Faraday rotation is an indispensable method for precision measurements, universally suitable for both hot and cold atomic systems. Here we demonstrate an all-optical magnetometer where the optical cell for Faraday rotation spectroscopy is augmented with a low finesse cavity. Unlike in previous experiments, where specifically designed multipass cells had been employed, our scheme allows to use conventional, spherical vapour cells. Spherical shaped cells have the advantage that they can be effectively coated inside with a spin relaxation suppressing layer providing long spin coherence times without addition of a buffer gas. Cavity enhancement shows in an increase in optical polarization rotation and sensitivity compared to single-pass configurations.
Effects of random rewiring on the degree correlation of scale-free networks
Authors: Qu Jing , Wang Sheng-Jun , Jusup Marko , Wang Zhen 
Published: October 2015

AbstractRandom rewiring is used to generate null networks for the purpose of analyzing the topological properties of scale-free networks, yet the effects of random rewiring on the degree correlation are subject to contradicting interpretations in the literature. We comprehensively analyze the degree correlation of randomly rewired scale-free networks and show that random rewiring increases disassortativity by reducing the average degree of the nearest neighbors of high-degree nodes. The effect can be captured by the measures of the degree correlation that consider all links in the network, but not by analogous measures that consider only links between degree peers, hence the potential for contradicting interpretations. We furthermore find that random and directional rewiring affect the topology of a scale-free network differently, even if the degree correlation of the rewired networks is the same. Consequently, the network dynamics is changed, which is proven here by means of the biased random walk.
Constitutional de novo deletion of the FBXW7 gene in a patient with focal segmental glomerulosclerosis and multiple primitive tumors
Authors: Roversi Gaia , Picinelli Chiara , Bestetti Ilaria , Crippa Milena , Perotti Daniela , Ciceri Sara , Saccheri Fabiana , Collini Paola , Poliani Pietro L. , Catania Serena , Peissel Bernard , Pagni Fabio , Russo Silvia , Peterlongo Paolo , Manoukian Siranoush , Finelli Palma 
Published: October 2015

AbstractMultiple primary malignant neoplasms are rare entities in the clinical setting, but represent an important issue in the clinical management of patients since they could be expression of a genetic predisposition to malignancy. A high resolution genome wide array CGH led us to identify the first case of a de novo constitutional deletion confined to the FBXW7 gene, a well known tumor suppressor, in a patient with a syndromic phenotype characterized by focal segmental glomerulosclerosis and multiple primary early/atypical onset tumors, including Hodgkin’s lymphoma, Wilms tumor and breast cancer. Other genetic defects may be associated with patient’s phenotype. In this light, constitutional mutations at BRCA1, BRCA2, TP53, PALB2 and WT1 genes were excluded by performing sequencing and MLPA analysis; similarly, we ruled out constitutional abnormalities at the imprinted 11p15 region by methylation specific -MLPA assay. Our observations sustain the role of FBXW7 as cancer predisposition gene and expand the spectrum of its possible associated diseases.
Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics
Authors: Ragonnet Romain , Trauer James M. , Denholm Justin T. , Geard Nicholas L. , Hellard Margaret , McBryde Emma S. 
Published: October 2015

AbstractVaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.
Highly photosensitive graphene field-effect transistor with optical memory function
Authors: Ishida Shohei , Anno Yuki , Takeuchi Masato , Matsuoka Masaya , Takei Kuniharu , Arie Takayuki , Akita Seiji 
Published: October 2015

AbstractGraphene is a promising material for use in photodetectors for the ultrawide wavelength region: from ultraviolet to terahertz. Nevertheless, only the 2.3% light absorption of monolayer graphene and fast recombination time of photo-excited charge restrict its sensitivity. To enhance the photosensitivity, hybridization of photosensitive material and graphene has been widely studied, where the accumulated photo-excited charge adjacent to the graphene channel modifies the Fermi level of graphene. However, the charge accumulation process slows the response to around a few tens of seconds to minutes. In contrast, a charge accumulation at the contact would induce the efficient light-induced modification of the contact resistance, which would enhance its photosensitivity. Herein, we demonstrate a highly photosensitive graphene field-effect transistor with noise-equivalent power of ~3 × 10−15 W/Hz1/2 and with response time within milliseconds at room temperature, where the Au oxide on Au electrodes modulates the contact resistance because of the light-assisted relaxation of the trapped charge at the contact. Additionally, this light-induced relaxation imparts an optical memory function with retention time of ~5 s. These findings are expected to open avenues to realization of graphene photodetectors with high sensitivity toward single photon detection with optical memory function.
InSAR analysis of surface deformation over permafrost to estimate active layer thickness based on one-dimensional heat transfer model of soils
Authors: Li Zhiwei , Zhao Rong , Hu Jun , Wen Lianxing , Feng Guangcai , Zhang Zeyu , Wang Qijie 
Published: October 2015

AbstractThis paper presents a novel method to estimate active layer thickness (ALT) over permafrost based on InSAR (Interferometric Synthetic Aperture Radar) observation and the heat transfer model of soils. The time lags between the periodic feature of InSAR-observed surface deformation over permafrost and the meteorologically recorded temperatures are assumed to be the time intervals that the temperature maximum to diffuse from the ground surface downward to the bottom of the active layer. By exploiting the time lags and the one-dimensional heat transfer model of soils, we estimate the ALTs. Using the frozen soil region in southern Qinghai-Tibet Plateau (QTP) as examples, we provided a conceptual demonstration of the estimation of the InSAR pixel-wise ALTs. In the case study, the ALTs are ranging from 1.02 to 3.14 m and with an average of 1.95 m. The results are compatible with those sparse ALT observations/estimations by traditional methods, while with extraordinary high spatial resolution at pixel level (~40 meter). The presented method is simple and can potentially be used for deriving high-resolution ALTs in other remote areas similar to QTP, where only sparse observations are available now.
Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection
Authors: Hou Panpan , Chen Shuliang , Wang Shilei , Yu Xiao , Chen Yu , Jiang Meng , Zhuang Ke , Ho Wenzhe , Hou Wei , Huang Jian , Guo Deyin 
Published: October 2015

AbstractGenome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4+ cells by binding to envelope protein, gp120. Here, we show that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to HIV-1 resistance of human primary CD4+ T cells. We also show that the Cas9-mediated ablation of CXCR4 demonstrated high specificity and negligible off-target effects without affecting cell division and propagation. The precise and efficient genome editing of CXCR4 will provide a new strategy for therapeutic application against HIV-1 infection.
Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients
Authors: Topol A , English J A , Flaherty E , Rajarajan P , Hartley B J , Gupta S , Desland F , Zhu S , Goff T , Friedman L , Rapoport J , Felsenfeld D , Cagney G , Mackay-Sim A , Savas J N , Aronow B , Fang G , Zhang B , Cotter D , Brennand K J 
Published: October 2015

AbstractThe genetic and epigenetic factors contributing to risk for schizophrenia (SZ) remain unresolved. Here we demonstrate, for the first time, perturbed global protein translation in human-induced pluripotent stem cell (hiPSC)-derived forebrain neural progenitor cells (NPCs) from four SZ patients relative to six unaffected controls. We report increased total protein levels and protein synthesis, together with two independent sets of quantitative mass spectrometry evidence indicating markedly increased levels of ribosomal and translation initiation and elongation factor proteins, in SZ hiPSC NPCs. We posit that perturbed levels of global protein synthesis in SZ hiPSC NPCs represent a novel post-transcriptional mechanism that might contribute to disease progression.
Reduced protein synthesis in schizophrenia patient-derived olfactory cells
Authors: English J A , Fan Y , Föcking M , Lopez L M , Hryniewiecka M , Wynne K , Dicker P , Matigian N , Cagney G , Mackay-Sim A , Cotter D R 
Published: October 2015

AbstractHuman olfactory neurosphere-derived (ONS) cells have the potential to provide novel insights into the cellular pathology of schizophrenia. We used discovery-based proteomics and targeted functional analyses to reveal reductions in 17 ribosomal proteins, with an 18% decrease in the total ribosomal signal intensity in schizophrenia-patient-derived ONS cells. We quantified the rates of global protein synthesis in vitro and found a significant reduction in the rate of protein synthesis in schizophrenia patient-derived ONS cells compared with control-derived cells. Protein synthesis rates in fibroblast cell lines from the same patients did not differ, suggesting cell type-specific effects. Pathway analysis of dysregulated proteomic and transcriptomic data sets from these ONS cells converged to highlight perturbation of the eIF2α, eIF4 and mammalian target of rapamycin (mTOR) translational control pathways, and these pathways were also implicated in an independent induced pluripotent stem cell-derived neural stem model, and cohort, of schizophrenia patients. Analysis in schizophrenia genome-wide association data from the Psychiatric Genetics Consortium specifically implicated eIF2α regulatory kinase EIF2AK2, and confirmed the importance of the eIF2α, eIF4 and mTOR translational control pathways at the level of the genome. Thus, we integrated data from proteomic, transcriptomic, and functional assays from schizophrenia patient-derived ONS cells with genomics data to implicate dysregulated protein synthesis for the first time in schizophrenia.
Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus
Authors: Brugman Martijn H. , Wiekmeijer Anna-Sophia , van Eggermond Marja , Wolvers-Tettero Ingrid , Langerak Anton W. , de Haas Edwin F. E. , Bystrykh Leonid V. , van Rood Jon J. , de Haan Gerald , Fibbe Willem E. , Staal Frank J. T. 
Published: October 2015

SignificanceThe number of hematopoietic stem cell clones contributing to T-cell development is restricted at entry of and during further development inside the thymus. However, despite this severe restriction, a fully diverse T-cell receptor repertoire can be generated, indicating that hematological and immunological clonality are independently regulated.
DIDA: A curated and annotated digenic diseases database
Authors: Gazzo Andrea M. , Daneels Dorien , Cilia Elisa , Bonduelle Maryse , Abramowicz Marc , Van Dooren Sonia , Smits Guillaume , Lenaerts Tom 
Published: October 2015

Abstract
DIDA (DIgenic diseases DAtabase) is a novel database that provides for the first time detailed information on genes and associated genetic variants involved in digenic diseases, the simplest form of oligogenic inheritance. The database is accessible via http://dida.ibsquare.be and currently includes 213 digenic combinations involved in 44 different digenic diseases. These combinations are composed of 364 distinct variants, which are distributed over 136 distinct genes. The web interface provides browsing and search functionalities, as well as documentation and help pages, general database statistics and references to the original publications from which the data have been collected. The possibility to submit novel digenic data to DIDA is also provided. Creating this new repository was essential as current databases do not allow one to retrieve detailed records regarding digenic combinations. Genes, variants, diseases and digenic combinations in DIDA are annotated with manually curated information and information mined from other online resources. Next to providing a unique resource for the development of new analysis methods, DIDA gives clinical and molecular geneticists a tool to find the most comprehensive information on the digenic nature of their diseases of interest.
Introduction
Authors: Féry Caroline , Ishihara Shinichiro 
Published: October 2015

AbstractThis chapter is an introduction to the Oxford Handbook of Information Structure. After introducing the goals of the handbook and a brief history of information structure studies, this introductory chapter provides the definitions of the key notions of information structure (focus, givenness, and topic) in Krifka (2008), which were used as the baseline for all the chapters of the handbook. The Handbook is organized in four parts: an overview of various linguistic theories of information structure in semantics, pragmatics, morpho-syntax and phonology (Part I); case studies of various information structure-related topics (Part II); the state of the art in the study of information structure from experimental perspectives (Part III); and chapters discussing information structure in selected languages or language families (Part IV). The introduction contains short summaries of each of the chapters in the Handbook.
Understanding the Distribution of Crime Victimization Using “British Crime Survey” Data
Authors: Hope Tim 
Published: October 2015

Abstract
This chapter focuses upon understanding the data-generating process that gives rise to the frequency distribution of crime victimization count data sampled from the British Crime Survey (BCS). Having described the form of this data, it introduces the problem of explaining the overdispersion of the distribution. It discusses and compares various models of the data that make assumptions about the data-generation process, including risk-heterogeneity, state-dependency, conditional probability, the double hurdle model, and the spells model. Its principal conclusion is that the crime victimization frequency distribution found in BCS data is the heterogeneous product of the mixing of two probability distributions: one concerns victim-prevalence, where zero-inflation predominates; the other concerns victimization-frequency, expressing the long-tail of high-frequencies. This conceptualization sheds new light on some persistent difficulties that might point the way towards future progress in understanding and remedying the distribution of crime victimization among citizens.
Affect and Emotion in Greek Literature
Authors: Konstan David 
Published: October 2015

Abstract
This article examines the way the ancient Greeks conceived of the emotions. Special attention is paid to the differences between classical Greek and modern English conceptions, in line with the view that culture plays a significant role in shaping the way emotions are experienced. The analysis draws on ancient Greek literature, from Homer’s Iliad to tragedy, comedy, and lyric poetry, as well as on historical and philosophical works by Aristotle and Xenophon. Also considered are changes in the way the emotions are understood in early Christian and later texts, with occasional reference to Latin adaptations. In particular, the emotions of pity, anger, fear, love, and jealousy are examined in detail.