bluuebunny/crossref_metadata_2025 huggingface dataset:
Imported dengue in Spain: a nationwide analysis with predictive time series analyses
Authors: Redondo-Bravo Lidia , Ruiz-Huerta Claudia , Gomez-Barroso Diana , Sierra-Moros María José , Benito Agustín , Herrador Zaida
Published: October 2019

Background

Of febrile illnesses in Europe, dengue is second only to malaria as a cause of travellers being hospitalized. Local transmission has been reported in several European countries, including Spain. This study assesses the evolution of dengue-related admissions in Spain in terms of time, geographical distribution and individuals’ common characteristics; it also creates a predictive model to evaluate the risk of local transmission.

Methods

This is a retrospective study using the Hospital Discharge Records Database from 1997 to 2016. We calculated hospitalization rates and described clinical characteristics. Spatial distribution and temporal behaviour were also assessed, and a predictive time series model was created to estimate expected cases in the near future. Figures for resident foreign population, Spanish residents’ trips to endemic regions and the expansion of Aedes albopictus were also evaluated.

Results

A total of 588 dengue-related admissions were recorded: 49.6% were women, and the mean age was 34.3 years. One person died (0.2%), 82% presented with mild-to-moderate dengue and 7–8% with severe dengue. We observed a trend of steady and consistent increase in incidence (P < 0.05), in parallel with the increase in trips to dengue-endemic regions. Most admissions occurred during the summer, showing significant seasonality with 3-year peaks. We also found important regional differences. According to the predictive time series analysis, a continuing increase in imported dengue incidence can be expected in the near future, which, in the worst case scenario (upper 95% confidence interval), would mean an increase of 65% by 2025.

Conclusion

We present a nationwide study based on hospital, immigration, travel and entomological data. The constant increase in dengue-related hospitalizations, in combination with wider vector distribution, could imply a higher risk of autochthonous dengue transmission in the years to come. Strengthening the human and vector surveillance systems is a necessity, as are improvements in control measures, in the education of the general public and in fostering their collaboration in order to reduce the impact of imported dengue and to prevent the occurrence of autochthonous cases.
Pharmacokinetics of voriconazole after a single intramuscular injection in large falcons (Falco spp.)
Authors: Azmanis P , Pappalardo L , Sara Ziad A J , Silvanose C , Naidoo V
Published: October 2019

Voriconazole is one of the main azoles used to treat invasive aspergillosis in falconry raptors and birds. Despite the fact that there are studies for oral and intravenous use of voriconazole in birds, there are none for its effect after intramuscular use. Empirical use of intramuscular voriconazole in falcons, indicated quicker therapy response than the oral one. Aim of this study is to evaluate the in vivo pharmacokinetic disposition of injectable voriconazole after a single intramuscular injection in large falcons (i.e., Gyrfalcons, Saker falcons, Peregrine falcons). No clinical side effects were observed in the falcons. Absorption of voriconazole was rapid (0.5–2 hours) and reached a plasma level (>1 μg/ml) which is above the minimal inhibitory concentration (MIC) for all known Aspergillus strains. This level was maintained for 16 to 20 hours, thus indicating that a single injection of 12.5 mg/kg is not enough if T > MIC is taken into consideration. On a newer aspect, according to the AUC24 unbound: MIC parameter would be indicated that this dose would be rather sufficient for most Aspergillus strains.
Molecules in the Cep E-mm jet: evidence for shock-driven photochemistry?
Authors: Ospina-Zamudio J , Lefloch B , Favre C , López-Sepulcre A , Bianchi E , Ceccarelli C , De Simone M , Bouvier M , Kahane C
Published: October 2019

The chemical composition of protostellar jets and its origin are still badly understood. More observational constraints are needed to make progress. With that objective, we have carried out a systematic search for molecular species in the jet of Cep E-mm, a template for intermediate-mass Class 0 protostars, associated with a luminous, high-velocity outflow. We made use of an unbiased spectral line survey in the range 72–350 GHz obtained with the IRAM 30-m telescope, complementary observations of the CO J = 3–2 transition with the JCMT, and observations at 1 arcsec angular resolution of the CO J = 2–1 transition with the IRAM Plateau de Bure Interferometer. In addition to CO, we have detected rotational transitions from SiO, SO, H2CO, CS, HCO+, and HCN. A strong chemical differentiation is observed in the southern and northern lobes of the jet. Radiative transfer analysis in the large velocity gradient approximation yields typical molecular abundances of the order of 10−8 for all molecular species other than CO. Overall, the jets exhibit an unusual chemical composition, as CS, SO, and H2CO are found to be the most abundant species, with a typical abundance of (3–4)× 10−8. The transverse size of the CO jet emission estimated from interferometric observations is about 1000 au, suggesting that we are detecting emission from a turbulent layer of gas entrained by the jet in its propagation and not the jet itself. We propose that some molecular species could be the signatures of the specific photochemistry driven by the UV radiation field generated in the turbulent envelope.
Herschel spectroscopy of massive young stellar objects in the Magellanic Clouds
Authors: Oliveira J M , van Loon J Th , Sewiło M , Lee M-Y , Lebouteiller V , Chen C-H R , Cormier D , Filipović M D , Carlson L R , Indebetouw R , Madden S , Meixner M , Sargent B , Fukui Y
Published: October 2019

We present Herschel Space Observatory Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver Fourier Transform Spectrometer (SPIRE FTS) spectroscopy of a sample of 20 massive Young Stellar Objects (YSOs) in the Large and Small Magellanic Clouds (LMC and SMC). We analyse the brightest far-infrared (far-IR) emission lines, that diagnose the conditions of the heated gas in the YSO envelope and pinpoint their physical origin. We compare the properties of massive Magellanic and Galactic YSOs. We find that [O i] and [C ii] emission, that originates from the photo-dissociation region associated with the YSOs, is enhanced with respect to the dust continuum in the Magellanic sample. Furthermore the photoelectric heating efficiency is systematically higher for Magellanic YSOs, consistent with reduced grain charge in low metallicity environments. The observed CO emission is likely due to multiple shock components. The gas temperatures, derived from the analysis of CO rotational diagrams, are similar to Galactic estimates. This suggests a common origin to the observed CO excitation, from low-luminosity to massive YSOs, both in the Galaxy and the Magellanic Clouds. Bright far-IR line emission provides a mechanism to cool the YSO environment. We find that, even though [O i], CO, and [C ii] are the main line coolants, there is an indication that CO becomes less important at low metallicity, especially for the SMC sources. This is consistent with a reduction in CO abundance in environments where the dust is warmer due to reduced ultraviolet-shielding. Weak H2O and OH emission is detected, consistent with a modest role in the energy balance of wider massive YSO environments.
Predicting the LISA white dwarf binary population in the Milky Way with cosmological simulations
Authors: Lamberts Astrid , Blunt Sarah , Littenberg Tyson B , Garrison-Kimmel Shea , Kupfer Thomas , Sanderson Robyn E
Published: October 2019

White dwarf binaries with orbital periods below 1 h will be the most numerous sources for the space-based gravitational wave detector Laser Interferometer Space Antenna (LISA). Based on thousands of individually resolved systems, we will be able to constrain binary evolution and provide a new map of the Milky Way and its close surroundings. In this paper we predict the main properties of populations of different types of detached white dwarf binaries detected by LISA over time. For the first time, we combine a high-resolution cosmological simulation of a Milky Way-mass galaxy (taken from the FIRE project) with a binary population synthesis model for low- and intermediate-mass stars. Our Galaxy model therefore provides a cosmologically realistic star formation and metallicity history for the Galaxy and naturally produces its different components such as the thin and thick disc, the bulge, the stellar halo, and satellite galaxies and streams. Thanks to the simulation, we show how different Galactic components contribute differently to the gravitational wave signal, mostly due to their typical age and distance distributions. We find that the dominant LISA sources will be He–He double white dwarfs (DWDs) and He–CO DWDs with important contributions from the thick disc and bulge. The resulting sky map of the sources is different from previous models, with important consequences for the searches for electromagnetic counterparts and data analysis. We also emphasize that much of the science-enabling information regarding white dwarf binaries, such as the chirp mass and the sky localization, becomes increasingly rich with long observations, including an extended mission up to 8 yr.
Crust of accreting neutron stars within simplified reaction network
Authors: Shchechilin N N , Chugunov A I
Published: October 2019

Transiently accreting neutron stars in low-mass X-ray binaries are generally believed to be heated up by nuclear reactions in accreted matter during hydrostatic compression. Detailed modelling of these reactions is required for the correct interpretation of observations. In this paper, we construct a simplified reaction network, which can be easily implemented and depends mainly on atomic mass tables as nuclear physics input. We show that it reproduces results of the detailed network by Lau et al. very well, if one applies the same mass model. However, the composition and the heating power are shown to be sensitive to the mass table used and treatment of mass tables boundary, if one applies several of them in one simulation. In particular, the impurity parameter Qimp at density ρ = 2 × 1012 g cm−3 can differ for a factor of few, and even increase with density increase. The profile of integrated heat release shown to be well confined between results by Fantina et al. and Lau et al.
Mutual approximations between the five main moons of Uranus
Authors: Santos-Filho S , Assafin M , Morgado B E , Vieira-Martins R , Camargo J I B , Gomes-Júnior A R , Benedetti-Rossi G
Published: October 2019

Doing high-precision astrometry on Uranus’ moons is currently quite challenging. No probes will orbit the system before 2040. New high-precision mutual phenomena measurements will only occur in 2050. Besides, Uranus is slowly passing through a sky region without many stars, which makes it difficult to map field of view (FOV) distortions below 50 mas. In this context, the new astrometric technique of mutual approximations comes in handy. It measures central instants at the closest approach between two moving satellites in the sky plane. Measurements are made on small portions of the FOV, benefiting from the so-called precision premium. Approximations and mutual phenomena share geometric principles and parameters, with similar precision in the central instant as indicated by first applications to the Jovian moons. However, mutual phenomena can only be observed at the planet’s equinoxes, while approximations always occur. Central instants do not depend on reference stars and are useful in orbit and ephemeris fittings. Here, we present results for 23 mutual approximations between the five main Uranus satellites observed in Brazil during 2015–2018 with a 1.6 m aperture telescope. Digital coronagraphy mitigated Uranus’ scattered light, improving measurements for Miranda, Ariel and Umbriel. We measured the impact parameter and relative velocity in milliarcseconds for the first time by using a variant of the method. Relative position errors, including Miranda, were 45 mas per coordinate, twice as good as in classical CCD astrometry for this satellite, and comparable to mutual phenomena. This shows the potential of mutual approximations for improving the current orbits and ephemerides of Uranus’ moons.
PathBank: a comprehensive pathway database for model organisms
Authors: Wishart David S , Li Carin , Marcu Ana , Badran Hasan , Pon Allison , Budinski Zachary , Patron Jonas , Lipton Debra , Cao Xuan , Oler Eponine , Li Krissa , Paccoud Maïlys , Hong Chelsea , Guo An C , Chan Christopher , Wei William , Ramirez-Gaona Miguel
Published: October 2019

PathBank (www.pathbank.org) is a new, comprehensive, visually rich pathway database containing more than 110 000 machine-readable pathways found in 10 model organisms (Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, Escherichia coli and Pseudomonas aeruginosa). PathBank aims to provide a pathway for every protein and a map for every metabolite. This resource is designed specifically to support pathway elucidation and pathway discovery in transcriptomics, proteomics, metabolomics and systems biology. It provides detailed, fully searchable, hyperlinked diagrams of metabolic, metabolite signaling, protein signaling, disease, drug and physiological pathways. All PathBank pathways include information on the relevant organs, organelles, subcellular compartments, cofactors, molecular locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to the rich data contained in public chemical databases such as HMDB or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All PathBank pathways are accompanied with references and detailed descriptions which provide an overview of the pathway, condition or processes depicted in each diagram. Every PathBank pathway is downloadable in several machine-readable and image formats including BioPAX, SBML, PWML, SBGN, RXN, PNG and SVG. PathBank also supports community annotations and submissions through the web-based PathWhiz pathway illustrator. The vast majority of PathBank's pathways (>95%) are not found in any other public pathway database.
The regulation of sequence specific NF-κB DNA binding and transcription by IKKβ phosphorylation of NF-κB p50 at serine 80
Authors: Smith Emma L , Somma Domenico , Kerrigan David , McIntyre Zoe , Cole John J , Liang Kai Ling , Kiely Patrick A , Keeshan Karen , Carmody Ruaidhrí J
Published: October 2019

Phosphorylation of the NF-κB transcription factor is an important regulatory mechanism for the control of transcription. Here we identify serine 80 (S80) as a phosphorylation site on the p50 subunit of NF-κB, and IKKβ as a p50 kinase. Transcriptomic analysis of cells expressing a p50 S80A mutant reveals a critical role for S80 in selectively regulating the TNFα inducible expression of a subset of NF-κB target genes including pro-inflammatory cytokines and chemokines. S80 phosphorylation regulates the binding of p50 to NF-κB binding (κB) sites in a sequence specific manner. Specifically, phosphorylation of S80 reduces the binding of p50 at κB sites with an adenine at the −1 position. Our analyses demonstrate that p50 S80 phosphorylation predominantly regulates transcription through the p50:p65 heterodimer, where S80 phosphorylation acts in trans to limit the NF-κB mediated transcription of pro-inflammatory genes. The regulation of a functional class of pro-inflammatory genes by the interaction of S80 phosphorylated p50 with a specific κB sequence describes a novel mechanism for the control of cytokine-induced transcriptional responses.
Star-PAP controlled alternative polyadenylation coupled poly(A) tail length regulates protein expression in hypertrophic heart
Authors: Sudheesh A P , Mohan Nimmy , Francis Nimmy , Laishram Rakesh S , Anderson Richard A
Published: October 2019

Alternative polyadenylation (APA)-mediated 3′-untranslated region (UTR) shortening is known to increase protein expression due to the loss of miRNA regulatory sites. Yet, mRNAs with longer 3′-UTR also show enhanced protein expression. Here, we identify a mechanism by which longer transcripts generated by the distal-most APA site leads to increased protein expression compared to the shorter transcripts and the longer transcripts are positioned to regulate heart failure (HF). A Star-PAP target gene, NQO1 has three poly(A) sites (PA-sites) at the terminal exon on the pre-mRNA. Star-PAP selects the distal-most site that results in the expression of the longest isoform. We show that the NQO1 distal-specific mRNA isoform accounts for the majority of cellular NQO1 protein. Star-PAP control of the distal-specific isoform is stimulated by oxidative stress and the toxin dioxin. The longest NQO1 transcript has increased poly(A) tail (PA-tail) length that accounts for the difference in translation potentials of the three NQO1 isoforms. This mechanism is involved in the regulation of cardiac hypertrophy (CH), an antecedent condition to HF where NQO1 downregulation stems from the loss of the distal-specific transcript. The loss of NQO1 during hypertrophy was rescued by ectopic expression of the distal- but not the proximal- or middle-specific NQO1 mRNA isoforms in the presence of Star-PAP expression, and reverses molecular events of hypertrophy in cardiomyocytes.
KnockTF: a comprehensive human gene expression profile database with knockdown/knockout of transcription factors
Authors: Feng Chenchen , Song Chao , Liu Yuejuan , Qian Fengcui , Gao Yu , Ning Ziyu , Wang Qiuyu , Jiang Yong , Li Yanyu , Li Meng , Chen Jiaxin , Zhang Jian , Li Chunquan
Published: October 2019

Transcription factors (TFs) and their target genes have important functions in human diseases and biological processes. Gene expression profile analysis before and after knockdown or knockout is one of the most important strategies for obtaining target genes of TFs and exploring TF functions. Human gene expression profile datasets with TF knockdown and knockout are accumulating rapidly. Based on the urgent need to comprehensively and effectively collect and process these data, we developed KnockTF (http://www.licpathway.net/KnockTF/index.html), a comprehensive human gene expression profile database of TF knockdown and knockout. KnockTF provides a number of resources for human gene expression profile datasets associated with TF knockdown and knockout and annotates TFs and their target genes in a tissue/cell type-specific manner. The current version of KnockTF has 570 manually curated RNA-seq and microarray datasets associated with 308 TFs disrupted by different knockdown and knockout techniques and across multiple tissue/cell types. KnockTF collects upstream pathway information of TFs and functional annotation results of downstream target genes. It provides details about TFs binding to promoters, super-enhancers and typical enhancers of target genes. KnockTF constructs a TF-differentially expressed gene network and performs network analyses for genes of interest. KnockTF will help elucidate TF-related functions and potential biological effects.
MicroScope: an integrated platform for the annotation and exploration of microbial gene functions through genomic, pangenomic and metabolic comparative analysis
Authors: Vallenet David , Calteau Alexandra , Dubois Mathieu , Amours Paul , Bazin Adelme , Beuvin Mylène , Burlot Laura , Bussell Xavier , Fouteau Stéphanie , Gautreau Guillaume , Lajus Aurélie , Langlois Jordan , Planel Rémi , Roche David , Rollin Johan , Rouy Zoe , Sabatet Valentin , Médigue Claudine
Published: October 2019

Large-scale genome sequencing and the increasingly massive use of high-throughput approaches produce a vast amount of new information that completely transforms our understanding of thousands of microbial species. However, despite the development of powerful bioinformatics approaches, full interpretation of the content of these genomes remains a difficult task. Launched in 2005, the MicroScope platform (https://www.genoscope.cns.fr/agc/microscope) has been under continuous development and provides analysis for prokaryotic genome projects together with metabolic network reconstruction and post-genomic experiments allowing users to improve the understanding of gene functions. Here we present new improvements of the MicroScope user interface for genome selection, navigation and expert gene annotation. Automatic functional annotation procedures of the platform have also been updated and we added several new tools for the functional annotation of genes and genomic regions. We finally focus on new tools and pipeline developed to perform comparative analyses on hundreds of genomes based on pangenome graphs. To date, MicroScope contains data for >11 800 microbial genomes, part of which are manually curated and maintained by microbiologists (>4500 personal accounts in September 2019). The platform enables collaborative work in a rich comparative genomic context and improves community-based curation efforts.
Large-scale multiferroic complex oxide epitaxy with magnetically switched polarization enabled by solution processing
Authors: Liu Cong , An Feng , Gharavi Paria S M , Lu Qinwen , Zha Junkun , Chen Chao , Wang Liming , Zhan Xiaozhi , Xu Zedong , Zhang Yuan , Qu Ke , Yao Junxiang , Ou Yun , Zhao Zhiming , Zhong Xiangli , Zhang Dongwen , Valanoor Nagarajan , Chen Lang , Zhu Tao , Chen Deyang , Zhai Xiaofang , Gao Peng , Jia Tingting , Xie Shuhong , Zhong Gaokuo , Li Jiangyu
Published: October 2019

Complex oxides with tunable structures have many fascinating properties, though high-quality complex oxide epitaxy with precisely controlled composition is still out of reach. Here we have successfully developed solution-based single-crystalline epitaxy for multiferroic (1-x)BiTi(1-y)/2FeyMg(1-y)/2O3–(x)CaTiO3 (BTFM–CTO) solid solution in large area, confirming its ferroelectricity at the atomic scale with strong spontaneous polarization. Careful compositional tuning leads to a bulk magnetization of 0.07 ± 0.035 μB/Fe at room temperature, enabling magnetically induced polarization switching exhibiting a large magnetoelectric coefficient of 2.7–3.0 × 10−7 s/m. This work demonstrates the great potential of solution processing in large-scale complex oxide epitaxy and establishes novel room-temperature magnetoelectric coupling in epitaxial BTFM–CTO film, making it possible to explore a much wider space of composition, phase, and structure that can be easily scaled up for industrial applications.
Orbital element distribution of invariant manifolds associated with Lyapunov family of periodic orbits around L1 and L2
Authors: Saito Masaya M
Published: October 2019

This study explores the initial configurations that lead to an eventual approach to a given planet, particularly Jupiter, using the invariant manifold of Lyapunov orbits around Lagrangian points L1 or L2. Reachability to the vicinity of planets would provide information on developing a process for capturing irregular satellites, which are small bodies orbiting around a giant planet with a high eccentricity that are considered to have been captured by the mother planet, rather than formed in situ. A region several times the Hill radius is often used for determining reachability, combined with checking the velocity of the planetesimal with respect to the mother planet. This kind of direct computation is inapplicable when the Hill sphere is widely open and its boundary cannot be clearly recognized. Here, we thus employ Lyapunov periodic orbits (LOs) as a formal definition of the vicinity of Jupiter and numerically track the orbital distribution of the invariant manifold of an LO while varying the Jacobi constant, CJ. Numerical tracking of the manifold is carried out directly via repeated Poincaré mapping of points initially allocated densely on a fragment of the manifold near the fixed points, with the assistance of multi-precision arithmetic using the Multiple Precision Floating-Point Reliable Library. The numerical computations show that the distribution of the semi-major axis of points on the manifolds is quite heavily tailed and that its median spans roughly 1–2 times the Jovian orbital radius. The invariant manifold provides a distribution profile of a that is similar to that obtained using a direct method.
The Desert at the End of Empire: An Environmental History of the Armenian Genocide*
Authors: Dolbee Samuel
Published: October 2019

In the contentious historiography of the Armenian genocide, the desert has been acknowledged by almost everyone as the endpoint of the deportations of hundreds of thousands of Ottoman Armenian citizens in 1915 and the years that followed. Those who use the term ‘genocide’ suggest that this action was tantamount to a death sentence, while those who oppose the term claim that the desert exculpates the Ottoman state. This article unpacks the meaning of the Jazira region — one of the arid regions to which Armenians were sent — and suggests how Ottoman officials used the desert to kill and Armenians used it to survive, mostly as part of nomadic groups among whom they were somewhere between slaves and family members. The desert even came to shape the humanitarian rescue campaign in the wake of the genocide and World War I, as organizations worked to remove Armenian children from the desert and, subsequently, to transform the desert itself by establishing Armenian agricultural colonies. Yet some Armenians stayed, and remain to this day in the Jazira calling themselves Armenian Muslims in honor of their heritage. The desert not only shaped Armenian suffering and survival. The marginal environment also incubated a population of imperial survivors, whose existence did not fit comfortably with post-Ottoman national divisions, or the historiographies influenced by them.
A lattice implementation of the η-invariant and effective action for chiral fermions on the lattice
Authors: Tatsumi Aoyama , Kikukawa Yoshio
Published: October 2019

We consider a lattice implementation of the $\eta$-invariant, using the complex phase of the determinant of the simplified domain-wall fermion, which couples to an interpolating 5D gauge field. We clarify the relation to the effective action for chiral Ginsparg–Wilson fermions. The integrability, which holds true for anomaly-free theories in the classical continuum limit, is not assured on a lattice with finite spacing. A lattice expression for the 5D Chern–Simons term is obtained.
Langland and the Reinvention of Array in Late-Medieval England
Authors: Galloway Andrew
Published: October 2019

Tradecraft lurks throughout the allegories of cloth-making in William Langland’s Piers Plowman, more fully and sympathetically expressed than scholars have realized. But in spite of the depth of lore there, the poem continually examines the problem of supervising such craft production and producers. Assessing this double perspective adds a distinctive chapter to understandings of how Piers Plowman invokes and requires wide economic and social contexts, specifically those focused on cloth production, a topic more amenable to ‘thing theory’ than the ‘costume rhetoric’ often applied to the presentations of array in Chaucer and other poets. All writers in the period were confronted with major changes in how clothing was made, sold, and worn, but Piers Plowman’s concerns differ significantly from contemporary writings both in how intricately the poem invokes the cloth industry yet how frequently it indicates the need for its punctilious governance (and that of craft and labour in general). Langland’s presentations of array offer not only an original and highly informed contribution to a central instance of late-medieval social and allegorical signification but also a contradictory response to its changing social, industrial, and institutional dimensions. Langland uses array and its making and remaking to affirm craft, process, and aesthetics in general while imagining new forms of governance, religious and political, that might contain its social and ethical disruptions.
International Financial Integration and Crisis Contagion
Authors: Devereux Michael B , Yu Changhua
Published: October 2019

International financial integration helps to diversify risk but also may spread crises across countries. We provide a quantitative analysis of this trade-off in a two-country general equilibrium model with collateral-constrained borrowing using a global solution method. Borrowing constraints bind occasionally, depending upon the state of the economy and levels of inherited debt. We examine different degrees of international financial integration, moving from financial autarky, to bond and equity market integration. Financial integration leads to a significant increase in global leverage, substantially escalates the probability of crises for any one country, and dramatically increases the degree of “contagion” across countries. Outside of crises, the impact of financial integration on macroeconomic aggregates is relatively small. But the impact of a crisis with integrated international financial markets is much less severe than that under financial market autarky. Thus, a trade-off emerges between the probability of crises and the severity of crises. Using a large cross-country database of financial crises in developing and developed economies over a forty-year period, we find evidence in support of the model.
Dissecting Characteristics Nonparametrically
Authors: Freyberger Joachim , Neuhierl Andreas , Weber Michael
Published: October 2019

We propose a nonparametric method to study which characteristics provide incremental information for the cross-section of expected returns. We use the adaptive group LASSO to select characteristics and to estimate how selected characteristics affect expected returns nonparametrically. Our method can handle a large number of characteristics and allows for a flexible functional form. Our implementation is insensitive to outliers. Many of the previously identified return predictors don’t provide incremental information for expected returns, and nonlinearities are important. We study our method’s properties in simulations and find large improvements in both model selection and prediction compared to alternative selection methods.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Fli1 deficiency induces endothelial adipsin expression, contributing to the onset of pulmonary arterial hypertension in systemic sclerosis
Authors: Miyagawa Takuya , Taniguchi Takashi , Saigusa Ryosuke , Fukayama Maiko , Takahashi Takehiro , Yamashita Takashi , Hirabayashi Megumi , Miura Shunsuke , Nakamura Kouki , Yoshizaki Ayumi , Sato Shinichi , Asano Yoshihide
Published: October 2019

Objectives

Adipsin, or complement factor D, is a serine proteinase catalysing complement factor C3 breakdown, leading to the production of opsonin (C3b), membrane attack complex (C5b–C9) and anaphylatoxins (C3a and C5a). Since adipsin is potentially associated with pulmonary arterial hypertension in SSc, we investigated adipsin expression in dermal small vessels of SSc-involved skin, the mechanism regulating adipsin expression in endothelial cells, and the correlation of serum adipsin levels with SSc clinical symptoms.

Methods

Adipsin expression was assessed by immunohistochemistry with skin sections of SSc and healthy subjects. mRNA levels of target genes and transcription factor binding to the ADIPSIN promoter were evaluated by quantitative reverse transcription PCR and chromatin immunoprecipitation, respectively. Serum adipsin levels were determined by enzyme-linked immunosorbent assay.

Results

Adipsin expression was remarkably increased in dermal small vessels of SSc-involved skin as compared with those of healthy control skin. Consistent with the notion that Fli1 deficiency induces SSc-like phenotypes in various types of cells, FLI1 siRNA enhanced adipsin expression at protein and mRNA levels and Fli1 bound to the ADIPSIN promoter in human dermal microvascular endothelial cells. Serum adipsin levels were significantly lower in diffuse cutaneous SSc patients than in limited cutaneous SSc patients and healthy controls, and were associated positively with elevated right ventricular systolic pressure and inversely with interstitial lung disease by multivariate regression analysis.

Conclusion

Adipsin is up-regulated at least partially by Fli1 deficiency in endothelial cells, potentially contributing to the development of pulmonary vascular involvement in SSc.
Amygdala activity to angry and fearful faces relates to bullying and victimization in adolescents
Authors: Swartz Johnna R , Carranza Angelica F , Knodt Annchen R
Published: October 2019

Relational bullying and victimization are common social experiences during adolescence, but relatively little functional magnetic resonance imaging (fMRI) research has examined the neural correlates of bullying and victimization in adolescents. The aim of the present study was to address this gap by examining the association between amygdala activity to angry and fearful faces and peer relational bullying and victimization in a community-based sample of adolescents. Participants included 49 adolescents, 12–15 years old, who underwent fMRI scanning while completing an emotional face matching task. Results indicated that interactions between amygdala activity to angry and fearful faces predicted self-reported relational bullying and victimization. Specifically, a combination of higher amygdala activity to angry faces and lower amygdala activity to fearful faces predicted more bullying behavior, whereas a combination of lower amygdala activity to angry faces and lower amygdala activity to fearful faces predicted less relational victimization. Exploratory whole-brain analyses also suggested that increased rostral anterior cingulate cortex activity to fearful faces was associated with less bullying. These results suggest that relational bullying and victimization are related to different patterns of neural activity to angry and fearful faces, which may help in understanding how patterns of social information processing predict these experiences.
Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study
Authors: Rössler Julian , Rössler Wulf , Seifritz Erich , Unterrassner Lui , Wyss Thomas , Haker Helene , Wotruba Diana
Published: October 2019

Dopamine is involved in the pathophysiology of schizophrenia. Disrupted salience processing by the salience network (SN) may be a central link between dysregulated dopamine function and psychotic symptoms. However, dopaminergic influence on the SN and its presumed influence on psychotic and subpsychotic symptoms or psychotic-like experiences in healthy individuals remain unclear. Therefore, we investigated dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central SN hub, and their association with psychotic-like experiences. We enrolled 54 healthy, right-handed male subjects in a randomized, double-blind, cross-sectional placebo-controlled experiment. Psychotic-like experiences were assessed using the revised Exceptional Experiences Questionnaire (PAGE-R). They then received either placebo (n = 32) or 200 mg L-DOPA (n = 33), a dopamine precursor, orally and underwent resting-state functional magnetic resonance imaging. In a seed-to-voxel approach, we analyzed dopamine-induced changes in functional connectivity of the rAI and assessed the relationship between functional connectivity changes and PAGE-R score. L-DOPA reduced functional connectivity between the rAI and the left auditory cortex planum polare. In the placebo group, we found a strong negative correlation between PAGE-R score and rAI to planum polare functional connectivity; in the L-DOPA group, there was a strong positive correlation between PAGE-R score and functional connectivity between rAI and planum polare. The PAGE-R score explained about 30% of the functional connectivity variation between rAI and planum polare in the two groups. Our findings suggest that psychotic-like experiences are associated with dopamine-induced disruption of auditory input to the SN, which may lead to aberrant attribution of salience.
Biphasic feature of placebo response in primary insomnia: pooled analysis of data from randomized controlled clinical trials of orexin receptor antagonists
Authors: He Dongmei , Jiang Binghu , Guo Zhiwei , Mu Qiwen , Mcclure Morgan A
Published: October 2019

Objectives

The placebo response to orexin receptor antagonists in primary insomnia is little-known. Our aim was, therefore, to conduct a systematic review of placebo-controlled randomized clinical trials to characterize placebo response.

Methods

We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of orexin receptor antagonists addressing primary insomnia. To pool effect size estimates (Cohen’s d) of placebo and orexin receptor antagonists across trials for outcome measures, a meta-analysis was done according to the Cochrane guideline.

Results

The placebo response was significant and robust to improve the symptoms of insomnia in terms of objective and subjective measures, and the effects (0.70 ± 0.51) in subjective measures were smaller than that (1.10 ± 1.14) in objective measures (p = 0.027). The biphasic feature of placebo response showed an initial short-term increase of placebo effect and subsequent changeless long-term effect.

Conclusion

The biphasic feature of placebo response is clinically useful, and neuroimaging is essential to clarify the long-term mechanism in the future.
Acute 4,4′-Methylene Diphenyl Diisocyanate Exposure-Mediated Downregulation of miR-206-3p and miR-381-3p Activates Inducible Nitric Oxide Synthase Transcription by Targeting Calcineurin/NFAT Signaling in Macrophages
Authors: Lin Chen-Chung , Law Brandon F , Hettick Justin M
Published: October 2019

Exposure to 4,4′-methylene diphenyl diisocyanate (MDI) in the occupational setting may lead to development of occupational asthma (OA), and the underlying molecular mechanisms of MDI-induced disease pathogenesis remain an active area of research. Using a nose-only mouse inhalation model, we find that circulating microRNA (miR)-206-3p and miR-381-3p are downregulated after MDI exposure; however, cellular miR-206-3p and miR-381-3p responses after MDI aerosol exposure and their pathophysiological roles in MDI-OA are unknown. We hypothesize that miR-206-3p and miR-381-3p-regulated mechanisms cause increased expression of the inducible nitric oxide synthase (iNOS) after MDI aerosol exposure. We examined cellular miR-206-3p and miR-381-3p, calcineurins, nuclear factors of activated T cells (NFATs), and iNOS levels from both nose-only exposed murine bronchoalveolar lavage cells (BALCs) and differentiated THP-1 macrophages treated with MDI-glutathione (GSH) conjugates. Both in vivo murine MDI aerosol exposure and in vitro MDI-GSH exposures in THP-1 macrophages result in downregulation of endogenous miR-206-3p and miR-381-3p and upregulation of PPP3CA and iNOS expression. Transfection of THP-1 macrophages with miR-inhibitor-206-3p and miR-inhibitor-381-3p resulted in the upregulation of PPP3CA and iNOS. Using RNA-induced silencing complex immunoprecipitation and translational reporter assays, we verified that PPP3CA, but not iNOS, is directly targeted by both miR-206-3p and miR-381-3p. Downregulation of miR-206-3p and miR-381-3p following by MDI exposure induces calcineurin/NFAT signaling-mediated iNOS transcription in macrophages and BALCs.
Exogenous miR‐26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease
Authors: Zhang Aiqing , Wang Haidong , Wang Bin , Yuan Yanggang , Klein Janet D. , Wang Xiaonan H.
Published: October 2019

Kidney fibrosis occurs in almost every type of chronic kidney disease. We found that microRNA (miR)‐26a was decreased in the kidney, muscle, and exosomes of unilateral ureteral obstruction (UUO) mice. We hypothesized that exogenous miR‐26 could suppresses renal fibrosis and muscle wasting in obstructive kidney disease. For this purpose, we generated exosomes that encapsulated miR‐26, then injected these into skeletal muscle of UUO mice. The expression of miR‐26a was elevated in serum exosomes from UUO mice following exosome‐miR‐26a injection. In these mice, muscle wasting has been ameliorated as evidenced by increased muscle weights. In addition, a muscle atrophy marker, myostatin, is increased in UUO muscle; provision of miR‐26a abolished this increase. We detected a remote effect of exosomes containing miR‐26a in UUO‐induced renal fibrosis. The intervention of miR‐26a attenuated UUO‐induced renal fibrosis as determined by immunohistological assessment of a‐smooth muscle actin and Masson's trichrome staining. Furthermore, exogenous miR‐26a decreased the protein levels of 2 profibrosis proteins, connective tissue growth factor (CTGF) and TGF‐β1, in UUO kidney. Our data showed that exosomes containing miR‐26a prevented muscle atrophy by inhibiting the transcription factor forkhead box O1. Likewise, the exosome‐carried miR‐26a limited renal fibrosis by directly suppressing CTGF. Our findings provide an experimental basis for exosome‐mediated therapy of muscle atrophy and renal fibrosis.—Zhang, A., Wang, H., Wang, B., Yuan, Y., Klein, J. D., Wang, X. H. Exogenous miR‐26a suppresses muscle wasting and renal fibrosis in obstructive kidney disease. FASEB J. 33, 13590‐13601 (2019). www.fasebj.org
Demonstrating advanced practice provider value
Authors: Brooks Paula B. , Fulton Megan E.
Published: October 2019

Background:

Rapid changes in healthcare are driving the adjustment of work flow by which providers serve patients in team-based care. Specifically, there is a need to develop more effective and efficient utilization with accurate attribution of advanced practice providers' (APPs) productivity.

Local problem:

The directors of the APP-Best Practice Center conducted assessments of each clinical area at the Medical University of South Carolina (MUSC) Health, a large academic medical center. A knowledge gap was identified, not only regarding billing practices of the APPs (NPs and physician assistants) but also in the use of APPs to practice to the fullest extent of their license, education, and experience.

Methods:

By substantiating APPs' contribution margin through the process of implementing a new standardized APP billing algorithm, a change in practice was accepted by senior leadership and a new APP billing algorithm was built that follows updated practice laws, compliance/legal standards, and hospital bylaws and regulations.

Interventions:

A new billing algorithm was implemented on July 1, 2017, and outcomes were evaluated 12 months after implementation.

Results:

This project uncovered the work already performed by APPs while increasing relative value units, collections, and overall patient encounters by the APP/physician team. Findings suggest improved utilization and appropriate attribution of productivity.

Conclusions:

With the APP workforce growing, the implementation of electronic medical record systems, and today's healthcare financial constraints, healthcare systems must standardize their billing practices. The APP billing algorithm is a critical tool that will help to meet this demand.
Cervical spine clearance in adult trauma patients
Authors: Yorkgitis Brian K. , McCauley D. Michelle
Published: October 2019

Up to 4% of adults with blunt trauma suffer cervical spine injury. Clinicians who evaluate trauma patients can use validated clinical decision tools to assess whether patients are at risk for these injuries. Beyond these tools, imaging (most often CT) remains the mainstay of evaluation. Further challenges exist when patients have persistent pain or cannot be evaluated clinically. This article reviews the evidence available to assist clinicians in evaluating adults for significant cervical spine injury after blunt trauma.
Primary care provider type
Authors: Everett Christine M. , Morgan Perri , Smith Valerie A. , Woolson Sandra , Edelman David , Hendrix Cristina C. , Berkowitz Theodore , White Brandolyn , Jackson George L.
Published: October 2019

Growing demand for services is leading primary care organizations to explore new delivery models. One approach incorporates multiple primary care providers on a team. Effective incorporation of multiple clinicians into teams requires well-defined roles, including the usual provider (who provides the majority of primary care) and supplemental providers (who provide a minority of primary care visits). Using data from the Veterans Health Administration, we examined whether differences in diabetes outcomes exist among patients with different types of primary and supplemental providers (physicians, physician assistants (PAs), and NPs). No clinically meaningful differences were observed based on the profession of the usual provider or supplemental provider, or whether physicians provided supplemental care to patients with PAs or NPs as usual providers. These results suggest that physicians, PAs, and NPs can perform a variety of roles depending on the needs of the organization and patient population.
Physician assistant burnout, job satisfaction, and career flexibility in Minnesota
Authors: Osborn Molly , Satrom Jessica , Schlenker Alyssa , Hazel Megan , Mason Meghan , Hartwig Kari
Published: October 2019

Objectives:

This study explores associations between job satisfaction, career flexibility, and burnout among physician assistants (PAs) in Minnesota.

Methods:

A survey comprising the Maslach Burnout Inventory (a validated burnout tool) and original questions was emailed to PAs practicing in Minnesota. Spearman rank correlation coefficients were used to assess associations between variables and burnout.

Results:

PAs (response rate = 31.4%, N = 312) reported moderate levels of burnout. Working in primary care and being female were independently associated with higher rates of burnout. Satisfaction with one's career and one's current position were both high (95.9% and 87.8%, respectively) and independently associated with lower rates of burnout.

Conclusions:

Despite high levels of career and job satisfaction, PAs in Minnesota report moderate levels of burnout, particularly women in primary care. Further research should examine a broader population and the effect of burnout on patient care.
Recognition, diagnosis, and treatment of hidradenitis suppurativa
Authors: Duran Caitlyn , Baumeister Angela
Published: October 2019

Hidradenitis suppurativa is a chronic skin condition characterized by recurrent painful abscesses usually limited to the intertriginous areas. Global prevalence has been estimated at up to 4% of the population. The exact pathogenesis of hidradenitis suppurativa is yet to be elucidated; however, recent research has shown that the disease occurs under the influence of multiple genetic, environmental, and lifestyle factors. Repeated insults result in sinus tract formation and disfigurement, which can have a significant psychosocial effect on patients. A wide range of treatments are available but none are curative. A combination antibiotic regimen is considered first line, and research into the use of biologics has been promising. Early recognition and treatment is paramount to achieving a better prognosis and improving patient quality of life.