bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxyurea for nontransfusion-dependent β-thalassemia
Authors: Algiraigri Ali H. , Wright Nicola A.M. , Paolucci Elizabeth Oddone , Kassam Aliya 
Published: April 2017

Objective/background:
Nontransfusion-dependent β-thalassemia (NTDβT) syndromes consist of β-thalassemia intermedia and moderate hemoglobin E/β thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea (HU), an oral chemotherapeutic drug, is anticipated to decrease disease severity.

Methods:
We performed a meta-analysis to evaluate the clinical efficacy and safety of HU in NTDβT patients of any age. MEDLINE, EMBASE, Cochrane databases, and major conference proceedings for studies that assessed HU in NTDβT patients were searched. Qualities of eligible studies were assessed by National Institutes of Health tools.

Results:
Seventeen studies, collectively involving 709 patients, fulfilled the eligibility criteria. HU was associated with a significant decrease in transfusion need in severe NTDβT with complete and overall (≥50%) response rates of 42% and 79%, respectively. For mild NTDβT, HU was effective in raising hemoglobin by 1 g/L in 64% of patients.

Conclusion:
HU appears to be effective, well tolerated, and associated with mild and transient adverse events. NTDβT patients may benefit from a trial of HU, although large randomized clinical trials assessing its efficacy should be conducted to confirm the findings of this metaanalysis and to assess its long-term toxicity and response sustainability.
Volatility measures as predictors of extreme returns
Authors: Switzer Lorne N. , Tahaoglu Cagdas , Zhao Yun 
Published: April 2017

AbstractThis paper examines the relationship between volatility and the probability of occurrence of expected extreme returns in the Canadian market. Four measures of volatility are examined: implied volatility from firm option prices, conditional volatility calculated using an EGARCH model, idiosyncratic volatility, and expected shortfall. A significantly positive relationship is observed between a firm's idiosyncratic volatility and the probability of occurrence of an extreme return in the subsequent month for firms. A 10% increase in idiosyncratic volatility in a given month is associated with the probability of an extreme shock in the subsequent month (top or bottom 1.5% of the returns distribution) of 26.4%. Other firm characteristics, including firm age, price, volume and book‐to‐market ratio, are also shown to be significantly related to subsequent firm extreme returns. The effects of conditional and implied volatility are mixed. The E‐GARCH and expected shortfall measures of conditional volatility are consistent with mean reversion: high short term realizations of conditional volatility foreshadow a lower probability of extreme returns.
Posttraumatic stress disorder in the World Mental Health Surveys
Authors: Koenen K. C. , Ratanatharathorn A. , Ng L. , McLaughlin K. A. , Bromet E. J. , Stein D. J. , Karam E. G. , Meron Ruscio A. , Benjet C. , Scott K. , Atwoli L. , Petukhova M. , Lim C. C.W. , Aguilar-Gaxiola S. , Al-Hamzawi A. , Alonso J. , Bunting B. , Ciutan M. , de Girolamo G. , Degenhardt L. , Gureje O. , Haro J. M. , Huang Y. , Kawakami N. , Lee S. , Navarro-Mateu F. , Pennell B.-E. , Piazza M. , Sampson N. , ten Have M. , Torres Y. , Viana M. C. , Williams D. , Xavier M. , Kessler R. C. 
Published: April 2017

BackgroundTraumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.MethodsData were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.ResultsThe cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.ConclusionsPTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.
Seed germination in cleistogamous species: theoretical considerations and a literature survey of experimental results
Authors: Baskin Jerry M. , Baskin Carol C. 
Published: April 2017

AbstractA cleistogamous species consists of individuals that produce both chasmogamous (open, CH) and cleistogamous (permanently closed, CL) flowers, which facilitates a mixed-mating system. In contrast to what one might expect, CL (obligately selfed) seeds and the plants derived from them can be more fit than CH (potentially outcrossed) seeds and the plants they give rise to. Our aim was to review some theoretical aspects of mixed mating in relation to retention of both CH and CL in cleistogamous species and to determine if data on germination support the notion that CL is advantageous over that of CH. Based on germination (or seedling emergence) of CHvsCL seeds in 29 species in 21 genera and 11 families of monocots and eudicots, CL seeds germinated better in 107 and equally well as in 64 of 252 case studies as CH seeds (67.9%), and the (CH < CL):(CH > CL) ratio was 107/81 (1.32). We conclude that our study lends support to the notion that production of CL seeds by cleistogamous species is advantageous over that of CH seeds. Retention of CH by CL species may be due to the need to prevent complete selfing (s= 1.0) and thus total inbreeding depression (δ), which theory predicts would decrease reproductive success. Some caveats concerning the results of comparative studies on the germination biology of CHvsCL seeds of amphicarpicsensu strictoFabaceae species andCommelina benghalensisand the aerial cleistogamous grassDanthonia spicataare discussed.
Imatinib mesylate inhibits STAT5 phosphorylation in response to IL-7 and promotes T cell lymphopenia in chronic myelogenous leukemia patients
Authors: Thiant S , Moutuou M M , Laflamme P , Sidi Boumedine R , Leboeuf D M , Busque L , Roy J , Guimond M 
Published: April 2017

AbstractImatinib mesylate (IM) therapy has been shown to induce lower T cell counts in chronic myelogenous leukemia (CML) patients and an interference of IM with T cell receptor (TCR) signaling has been invoked to explain this observation. However, IL-7 and TCR signaling are both essential for lymphocyte survival. This study was undertaken to determine whether IM interferes with IL-7 or TCR signaling to explain lower T cell counts in patients. At diagnosis, CML patients have typically lower CD4+ counts in their blood, yet CD8+ counts are normal or even increased in some. Following the initiation of IM treatment, CD4+ counts were further diminished and CD8+ T lymphocytes were dramatically decreased. In vitro studies confirmed IM interference with TCR signaling through the inhibition of ERK phosphorylation and we showed a similar effect on IL-7 signaling and STAT5 phosphorylation (STAT5-p). Importantly however, using an in vivo mouse model, we demonstrated that IM impaired T cell survival through the inhibition of IL-7 and STAT5-p but not TCR signaling which remained unaffected during IM therapy. Thus, off-target inhibitory effects of IM on IL-7 and STAT5-p explain how T cell lymphopenia occurs in patients treated with IM.
Spiral volumetric optoacoustic tomography visualizes multi-scale dynamics in mice
Authors: Deán-Ben X Luís , Fehm Thomas F , Ford Steven J , Gottschalk Sven , Razansky Daniel 
Published: April 2017

AbstractImaging dynamics at different temporal and spatial scales is essential for understanding the biological complexity of living organisms, disease state and progression. Optoacoustic imaging has been shown to offer exclusive applicability across multiple scales with excellent optical contrast and high resolution in deep-tissue observations. Yet, efficient visualization of multi-scale dynamics remained difficult with state-of-the-art systems due to inefficient trade-offs between image acquisition time and effective field of view. Herein, we introduce the spiral volumetric optoacoustic tomography technique that provides spectrally enriched high-resolution contrast across multiple spatiotemporal scales. In vivo experiments in mice demonstrate a wide range of dynamic imaging capabilities, from three-dimensional high-frame-rate visualization of moving organs and contrast agent kinetics in selected areas to whole-body longitudinal studies with unprecedented image quality. The newly introduced paradigm shift in imaging of multi-scale dynamics adds to the multifarious advantages provided by the optoacoustic technology for structural, functional and molecular imaging.
Chemical labelling for visualizing native AMPA receptors in live neurons
Authors: Wakayama Sho , Kiyonaka Shigeki , Arai Itaru , Kakegawa Wataru , Matsuda Shinji , Ibata Keiji , Nemoto Yuri L. , Kusumi Akihiro , Yuzaki Michisuke , Hamachi Itaru 
Published: April 2017

AbstractThe location and number of neurotransmitter receptors are dynamically regulated at postsynaptic sites. However, currently available methods for visualizing receptor trafficking require the introduction of genetically engineered receptors into neurons, which can disrupt the normal functioning and processing of the original receptor. Here we report a powerful method for visualizing native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) which are essential for cognitive functions without any genetic manipulation. This is based on a covalent chemical labelling strategy driven by selective ligand-protein recognition to tether small fluorophores to AMPARs using chemical AMPAR modification (CAM) reagents. The high penetrability of CAM reagents enables visualization of native AMPARs deep in brain tissues without affecting receptor function. Moreover, CAM reagents are used to characterize the diffusion dynamics of endogenous AMPARs in both cultured neurons and hippocampal slices. This method will help clarify the involvement of AMPAR trafficking in various neuropsychiatric and neurodevelopmental disorders.
Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting
Authors: Chen Fuqiang , Ding Xiao , Feng Yongmei , Seebeck Timothy , Jiang Yanfang , Davis Gregory D. 
Published: April 2017

AbstractBacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.
Multi-scale chromatin state annotation using a hierarchical hidden Markov model
Authors: Marco Eugenio , Meuleman Wouter , Huang Jialiang , Glass Kimberly , Pinello Luca , Wang Jianrong , Kellis Manolis , Yuan Guo-Cheng 
Published: April 2017

AbstractChromatin-state analysis is widely applied in the studies of development and diseases. However, existing methods operate at a single length scale, and therefore cannot distinguish large domains from isolated elements of the same type. To overcome this limitation, we present a hierarchical hidden Markov model, diHMM, to systematically annotate chromatin states at multiple length scales. We apply diHMM to analyse a public ChIP-seq data set. diHMM not only accurately captures nucleosome-level information, but identifies domain-level states that vary in nucleosome-level state composition, spatial distribution and functionality. The domain-level states recapitulate known patterns such as super-enhancers, bivalent promoters and Polycomb repressed regions, and identify additional patterns whose biological functions are not yet characterized. By integrating chromatin-state information with gene expression and Hi-C data, we identify context-dependent functions of nucleosome-level states. Thus, diHMM provides a powerful tool for investigating the role of higher-order chromatin structure in gene regulation.
Multi-component quantitative magnetic resonance imaging by phasor representation
Authors: Vergeldt Frank J. , Prusova Alena , Fereidouni Farzad , Amerongen Herbert van , Van As Henk , Scheenen Tom W. J. , Bader Arjen N. 
Published: April 2017

AbstractQuantitative magnetic resonance imaging (qMRI) is a versatile, non-destructive and non-invasive tool in life, material, and medical sciences. When multiple components contribute to the signal in a single pixel, however, it is difficult to quantify their individual contributions and characteristic parameters. Here we introduce the concept of phasor representation to qMRI to disentangle the signals from multiple components in imaging data. Plotting the phasors allowed for decomposition, unmixing, segmentation and quantification of our in vivo data from a plant stem, a human and mouse brain and a human prostate. In human brain images, we could identify 3 main T
2
components and 3 apparent diffusion coefficients; in human prostate 5 main contributing spectral shapes were distinguished. The presented phasor analysis is model-free, fast and accurate. Moreover, we also show that it works for undersampled data.
Temporal dynamics of saccades explained by a self-paced process
Authors: Amit Roy , Abeles Dekel , Bar-Gad Izhar , Yuval-Greenberg Shlomit 
Published: April 2017

AbstractSensory organs are thought to sample the environment rhythmically thereby providing periodic perceptual input. Whisking and sniffing are governed by oscillators which impose rhythms on the motor-control of sensory acquisition and consequently on sensory input. Saccadic eye movements are the main visual sampling mechanism in primates, and were suggested to constitute part of such a rhythmic exploration system. In this study we characterized saccadic rhythmicity, and examined whether it is consistent with autonomous oscillatory generator or with self-paced generation. Eye movements were tracked while observers were either free-viewing a movie or fixating a static stimulus. We inspected the temporal dynamics of exploratory and fixational saccades and quantified their first-order and high-order dependencies. Data were analyzed using methods derived from spike-train analysis, and tested against mathematical models and simulations. The findings show that saccade timings are explained by first-order dependencies, specifically by their refractory period. Saccade-timings are inconsistent with an autonomous pace-maker but are consistent with a “self-paced” generator, where each saccade is a link in a chain of neural processes that depend on the outcome of the saccade itself. We propose a mathematical model parsimoniously capturing various facets of saccade-timings, and suggest a possible neural mechanism producing the observed dynamics.
A combined experimental and first-principle study on the oxidation mechanism of super austenitic stainless steel S32654 at 900 °C
Authors: Dong Nan , Zhang Caili , Li Huabing , Zhang Binbin , Han Peide 
Published: April 2017

AbstractA combined experimental and first-principle study on the oxidation mechanism of super austenitic stainless steel S32654 at 900 °C for a short time period (1, 3, and 5 h) in air is presented. The samples exhibit excellent oxidation resistance because of the initial and gradual formation of the denser Fe- and Cr-rich layer with increasing oxidation time. Meanwhile, the Mo-rich layer gradually forms because of the Mo diffusion, which results in the formation of the oxide layer with two distinct regions: an inner Fe- and Cr-rich layer and an outer Mo-rich layer. Density functional theory is applied to investigate the diffusion behaviour of Mo atom in the Fe-Cr-Ni/Cr2O3interface and the effects of alloying elements (Fe, Ni, and Mn) on the Mo diffusion. The Mo originating from the alloy matrix tends to diffuse into the Cr2O3part, thereby resulting in the formation of the continuous Mo-rich layer, which is consistent with the experimental behaviour. Moreover, the introduction of Ni to the Cr2O3part can promote the Mo diffusion and the formation of the Mo-rich oxide layer, whereas Fe and Mn can hinder the Mo diffusion. The calculated results provide a microcosmic explanation of the experimental results.
North Andean origin and diversification of the largest ithomiine butterfly genus
Authors: Lisa De-Silva Donna , Mota Luísa L. , Chazot Nicolas , Mallarino Ricardo , Silva-Brandão Karina L. , Piñerez Luz Miryam Gómez , Freitas André V.L. , Lamas Gerardo , Joron Mathieu , Mallet James , Giraldo Carlos E. , Uribe Sandra , Särkinen Tiina , Knapp Sandra , Jiggins Chris D. , Willmott Keith R. , Elias Marianne 
Published: April 2017

AbstractThe Neotropics harbour the most diverse flora and fauna on Earth. The Andes are a major centre of diversification and source of diversity for adjacent areas in plants and vertebrates, but studies on insects remain scarce, even though they constitute the largest fraction of terrestrial biodiversity. Here, we combine molecular and morphological characters to generate a dated phylogeny of the butterfly genus Pteronymia (Nymphalidae: Danainae), which we use to infer spatial, elevational and temporal diversification patterns. We first propose six taxonomic changes that raise the generic species total to 53, making Pteronymia the most diverse genus of the tribe Ithomiini. Our biogeographic reconstruction shows that Pteronymia originated in the Northern Andes, where it diversified extensively. Some lineages colonized lowlands and adjacent montane areas, but diversification in those areas remained scarce. The recent colonization of lowland areas was reflected by an increase in the rate of evolution of species’ elevational ranges towards present. By contrast, speciation rate decelerated with time, with no extinction. The geological history of the Andes and adjacent regions have likely contributed to Pteronymia diversification by providing compartmentalized habitats and an array of biotic and abiotic conditions, and by limiting dispersal between some areas while promoting interchange across others.
Design and application of a lactulose biosensor
Authors: Wu Jieyuan , Jiang Peixia , Chen Wei , Xiong Dandan , Huang Linglan , Jia Junying , Chen Yuanyuan , Jin Jian-Ming , Tang Shuang-Yan 
Published: April 2017

AbstractIn this study the repressor of Escherichia coli lac operon, LacI, has been engineered for altered effector specificity. A LacI saturation mutagenesis library was subjected to Fluorescence Activated Cell Sorting (FACS) dual screening. Mutant LacI-L5 was selected and it is specifically induced by lactulose but not by other disaccharides tested (lactose, epilactose, maltose, sucrose, cellobiose and melibiose). LacI-L5 has been successfully used to construct a whole-cell lactulose biosensor which was then applied in directed evolution of cellobiose 2-epimerase (C2E) for elevated lactulose production. The mutant C2E enzyme with ~32-fold enhanced expression level was selected, demonstrating the high efficiency of the lactulose biosensor. LacI-L5 can also be used as a novel regulatory tool. This work explores the potential of engineering LacI for customized molecular biosensors which can be applied in practice.
Central nervous system and muscular bundles preserved in a 240 million year old giant bristletail (Archaeognatha: Machilidae)
Authors: Montagna Matteo , Haug Joachim T. , Strada Laura , Haug Carolin , Felber Markus , Tintori Andrea 
Published: April 2017

AbstractAmong the incomparably diverse group of insects no cases of central nervous system (CNS) preservation have been so far described in compression fossils. A third of the fossil insects collected from a 240–239 million year old (Ma) level at Monte San Giorgio UNESCO World Heritage (Switzerland-Italy) underwent phosphatization, resulting in the extraordinary preservation of soft tissues. Here we describeGigamachilis triassicusgen. et sp. nov. (Archaeognatha: Machiloidea: Machilidae) that, with an estimated total length of ~80 millimeters, represents the largest apterygote insect ever recorded. The holotype preserves: (i) components of the CNS represented by four abdominal ganglia, optic lobes with neuropils and compound retina; (ii) muscular bundles. Moreover,G. triassicus, possessing morphological features that prompt its assignment to the extant archaeognathan ingroup Machilidae, places the origin of modern lineages to Middle Triassic. Interestingly, at Monte San Giorgio, in the same stratigraphic unit the modern morphology ofG. triassicusco-occurs with the ancient one represented byDasyleptus triassicus(Archaeognatha: †Monura). Comparing these two types of body organization we provide a new reconstruction of the possible character evolution leading towards modern archaeognathan forms, suggesting the acquisition of novel features in a lineage of apterygote insects during the Permian or the Lower Triassic.
Reproducing the hierarchy of disorder for Morpho-inspired, broad-angle color reflection
Authors: Song Bokwang , Johansen Villads Egede , Sigmund Ole , Shin Jung H. 
Published: April 2017

AbstractThe scales of Morpho butterflies are covered with intricate, hierarchical ridge structures that produce a bright, blue reflection that remains stable across wide viewing angles. This effect has been researched extensively, and much understanding has been achieved using modeling that has focused on the positional disorder among the identical, multilayered ridges as the critical factor for producing angular independent color. Realizing such positional disorder of identical nanostructures is difficult, which in turn has limited experimental verification of different physical mechanisms that have been proposed. In this paper, we suggest an alternative model of inter-structural disorder that can achieve the same broad-angle color reflection, and is applicable to wafer-scale fabrication using conventional thin film technologies. Fabrication of a thin film that produces pure, stable blue across a viewing angle of more than 120 ° is demonstrated, together with a robust, conformal color coating.