bluuebunny/crossref_metadata_2025_split huggingface dataset:
Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study
Authors: Gustafsson Nina , Poulsen Peter Bo , Stallknecht Sandra Elkjær , Dybro Lars , Paaske Johnsen Søren 
Published: July 2019

Abstract

Aims
Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark.

Methods and results
Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the ‘difference-in-actual-cost’ method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year.

Conclusion
The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.
Detection of weak seismic sequences based on arrival time coherence and empiric network detectability: an application at a near fault observatory
Authors: Adinolfi G M , Cesca S , Picozzi M , Heimann S , Zollo A 
Published: July 2019

SUMMARYMicroseismic monitoring is a primary tool for understanding and tracking the progress of mechanical processes occurring in active rock fracture systems. In geothermal or hydrocarbon fields or along seismogenic fault systems, the detection and location of microseismicity facilitates resolution of the fracture system geometry and the investigation of the interaction between fluids and rocks, in response of stress field perturbations. Seismic monitoring aims to detect locate and characterize seismic sources. The detection of weak signals is often achieved at the cost of increasing the number of false detections, related to transient signals generated by a range of noise sources, or related to instrumental problems, ambient conditions or human activity that often affect seismic records. A variety of fast and automated methods has been recently proposed to detect and locate microseismicity based on the coherent detection of signal anomalies, such as increase in amplitude or coherent polarization, at dense seismic networks. While these methods proved to be very powerful to detect weak events and to reduce the magnitude of completeness, a major problem remains to discriminate among weak seismic signals produced by microseismicity and false detections. In this work, the microseimic data recorded along the Irpinia fault zone (Southern Apennines, Italy) are analysed to detect weak, natural earthquakes using one of such automated, migration-based, method. We propose a new method for the automatic discrimination of real vs false detections, which is based on empirical data and information about the detectability (i.e. detection capability) of the seismic network. Our approach allows obtaining high performances in detecting earthquakes without requiring a visual inspection of the seismic signals and minimizing analyst intervention. The proposed methodology is automated, self-updating and can be tuned at different success rates.
Bayesian joint muographic and gravimetric inversion applied to volcanoes
Authors: Barnoud Anne , Cayol Valérie , Niess Valentin , Cârloganu Cristina , Lelièvre Peter , Labazuy Philippe , Le Ménédeu Eve 
Published: July 2019

SUMMARY
Gravimetry is a technique widely used to image the structure of the Earth. However, inversions are ill-posed and the imaging power of the technique rapidly decreases with depth. To overcome this limitation, muography, a new imaging technique relying on high energy atmospheric muons, has recently been developed. Because muography only provides integrated densities above the detector from a limited number of observation points, inversions are also ill-posed. Previous studies have shown that joint muographic and gravimetric inversions better reconstruct the 3-D density structure of volcanic edifices than independent density inversions. These studies address the ill-posedness of the joint problem by regularizing the solution with respect to a prior density model. However, the obtained solutions depend on some hyperparameters, which are either determined relative to a single test case or rely on ad-hoc parameters. This can lead to inaccurate retrieved models, sometimes associated with artefacts linked to the muon data acquisition. In this study, we use a synthetic example based on the Puy de Dôme volcano to determine a robust method to obtain the resulting model closest to the synthetic model and devoid of acquisition artefacts. We choose a Bayesian approach to include an a priori density model and a smoothing by a Gaussian spatial correlation function relying on two hyperparameters: an a priori density standard deviation and an isotropic spatial correlation length. This approach has the advantage to provide a posteriori standard deviations on the resulting densities. Using our synthetic volcano, we investigate the most reliable criterion to determine the hyperparameters. Our results suggest that k-fold Cross-Validation Sum of Squares and the Leave One Out methods are more robust criteria than the classically used L-curves. The determined hyperparameters allow to overcome the artefacts linked to the data acquisition geometry, even when only a limited number of muon telescopes is available. We also illustrate the behaviour of the inversion in case of offsets in the a priori density or in the data and show that they lead to recognizable structures that help identify them.
Gene therapy for primary immunodeficiency
Authors: Booth Claire , Romano Rosa , Roncarolo Maria Grazia , Thrasher Adrian J 
Published: July 2019

AbstractGene therapy is now being trialled as a therapeutic option for an expanding number of conditions, based primarily on the successful treatment over the past two decades of patients with specific primary immunodeficiencies (PIDs) including severe combined immunodeficiency and Wiskott–Aldrich syndrome and metabolic conditions such as leukodystrophy. The field has evolved from the use of gammaretroviral vectors to more sophisticated lentiviral platforms that offer an improved biosafety profile alongside greater efficiency for hematopoietic stem cells gene transfer. Here we review more recent developments including licensing of gene therapies, use of gene corrected autologous T cells as an alternative strategy for some PIDs and the potential of targeted gene correction using various gene editing platforms. Given the promising results of recent clinical trials, it is likely that autologous gene therapies will become standard of care for a number of devastating diseases in the coming decade.
Voros coefficients for the hypergeometric differential equations and Eynard–Orantin’s topological recursion: Part II: For confluent family of hypergeometric equations
Authors: Iwaki Kohei , Koike Tatsuya , Takei Yumiko 
Published: July 2019

Abstract
We show that each member of the confluent family of the Gauss hypergeometric equations is realized as quantum curves for appropriate spectral curves. As an application, relations between the Voros coefficients of those equations and the free energy of their classical limit computed by the topological recursion are established. We will also find explicit expressions of the free energy and the Voros coefficients in terms of the Bernoulli numbers and Bernoulli polynomials.
Communicated by: Youjin Zhang
Mechanisms and phenotypic consequences of acquisition of tigecycline resistance by Stenotrophomonas maltophilia
Authors: Blanco Paula , Corona Fernando , Martinez José Luis 
Published: July 2019

Abstract

Objectives
To elucidate the potential mutation-driven mechanisms involved in the acquisition of tigecycline resistance by the opportunistic pathogen Stenotrophomonas maltophilia. The mutational trajectories and their effects on bacterial fitness, as well as cross-resistance and/or collateral susceptibility to other antibiotics, were also addressed.

Methods
S. maltophilia populations were submitted to experimental evolution in the presence of increasing concentrations of tigecycline for 30 days. The genetic mechanisms involved in the acquisition of tigecycline resistance were determined by WGS. Resistance was evaluated by performing MIC assays. Fitness of the evolved populations and individual clones was assessed by measurement of the maximum growth rates.

Results
All the tigecycline-evolved populations attained high-level resistance to tigecycline following different mutational trajectories, yet with some common elements. Among the mechanisms involved in low susceptibility to tigecycline, mutations in the SmeDEF efflux pump negative regulator smeT, changes in proteins involved in the biogenesis of the ribosome and modifications in the LPS biosynthesis pathway seem to play a major role. Besides tigecycline resistance, the evolved populations presented cross-resistance to other antibiotics, such as aztreonam and quinolones, and they were hypersusceptible to fosfomycin, suggesting a possible combination treatment. Further, we found that the selected resistance mechanisms impose a relevant fitness cost when bacteria grow in the absence of antibiotic.

Conclusions
Mutational resistance to tigecycline was easily selected during exposure to this antibiotic. However, the fitness cost may compromise the maintenance of S. maltophilia tigecycline-resistant populations in the absence of antibiotic.
VprBP mitigates TGF-β and Activin signaling by promoting Smurf1-mediated type I receptor degradation
Authors: Li Yihao , Cui Chao , Xie Feng , Kiełbasa Szymon , Mei Hailiang , van Dinther Maarten , van Dam Hans , Bauer Andreas , Zhang Long , ten Dijke Peter 
Published: July 2019

Abstract
The transforming growth factor-β (TGF-β) family controls embryogenesis, stem cell differentiation, and tissue homeostasis. However, how post-translation modifications contribute to fine-tuning of TGF-β family signaling responses is not well understood. Inhibitory (I)-Smads can antagonize TGF-β/Smad signaling by recruiting Smurf E3 ubiquitin ligases to target the active TGF-β receptor for proteasomal degradation. A proteomic interaction screen identified Vpr binding protein (VprBP) as novel binding partner of Smad7. Mis-expression studies revealed that VprBP negatively controls Smad2 phosphorylation, Smad2–Smad4 interaction, as well as TGF-β target gene expression. VprBP was found to promote Smad7–Smurf1–TβRI complex formation and induce proteasomal degradation of TGF-β type I receptor (TβRI). Moreover, VprBP appears to stabilize Smurf1 by suppressing Smurf1 poly-ubiquitination. In multiple adult and mouse embryonic stem cells, depletion of VprBP promotes TGF-β or Activin-induced responses. In the mouse embryo VprBP expression negatively correlates with mesoderm marker expression, and VprBP attenuated mesoderm induction during zebrafish embryogenesis. Our findings thereby uncover a novel regulatory mechanism by which Smurf1 controls the TGF-β and Activin cascade and identify VprBP as a critical determinant of embryonic mesoderm induction.
Neogenin-loss in neural crest cells results in persistent hyperplastic primary vitreous formation
Authors: Lin Sen , Liu Wei , Chen Chun-Lin , Sun Dong , Hu Jin-Xia , Li Lei , Ye Jian , Mei Lin , Xiong Wen-Cheng 
Published: July 2019

AbstractNeogenin is a transmembrane receptor critical for multiple cellular processes, including neurogenesis, astrogliogenesis, endochondral bone formation, and iron homeostasis. Here we present evidence that loss of neogenin contributes to pathogenesis of persistent hyperplastic primary vitreous (PHPV) formation, a genetic disorder accounting for ~ 5% of blindness in the USA. Selective loss of neogenin in neural crest cells (as observed in Wnt1-Cre; Neof/f mice), but not neural stem cells (as observed in GFAP-Cre and Nestin-Cre; Neof/f mice), resulted in a dysregulation of neural crest cell migration or delamination, exhibiting features of PHPV-like pathology (e.g. elevated retrolental mass), unclosed retinal fissure, and microphthalmia. These results demonstrate an unrecognized function of neogenin in preventing PHPV pathogenesis, implicating neogenin regulation of neural crest cell delamination/migration and retinal fissure formation as potential underlying mechanisms of PHPV.
Absolute colours and phase coefficients of trans-Neptunian objects: correlations and populations
Authors: Alvarez-Candal Alvaro , Ayala-Loera Carmen , Gil-Hutton Ricardo , Ortiz José Luis , Santos-Sanz Pablo , Duffard René 
Published: July 2019

ABSTRACT
The study of the visible colours of the trans-Neptunian objects opened a discussion almost 20 yr ago which, in spite of the increase in the amount of available data, seems far from subside. Visible colours impose constraints to the current theories of the early dynamical evolution of the Solar system such as the environment of formation, initial surface composition, and how (if) they were scattered to regions closer to the inner planets. In this paper, we present an updated version of our data base of absolute colours and relative phase coefficients for 117 objects. We define the absolute colours as the difference of the absolute magnitudes HV − HR, and the relative phase coefficient as the difference of the slopes of the phase curves Δβ. These were obtained joining our own observations plus data from the literature. The methodology has been introduced in previous works and here we expand in some interesting results, in particular the strong anticorrelation found between HV − HR and Δβ, which means that redder objects have steeper phase curves in the R filter, while bluer objects have steeper phase curves in the V filter. We analyse a series of results published in the literature in view of our data base, which is free of phase effects, and show that their statistical meaning is not very strong. We point out that phase-colouring and observational errors play an important role in the understanding of these proposed relationships.
Investigation of Na+ and K+ Transport in Halophytes: Functional Analysis of the HmHKT2;1 Transporter from Hordeum maritimum and Expression under Saline Conditions
Authors: Hmidi Dorsaf , Messedi Dorsaf , Corratgï¿½-Faillie Claire , Marhuenda Thï¿½o , Fizames Cï¿½cile , Zorrig Walid , Abdelly Chedly , Sentenac Hervï¿½ , Vï¿½ry Anne-Aliï¿½nor 
Published: July 2019

Abstract
Control of K+ and Na+ transport plays a central role in plant adaptation to salinity. In the halophyte Hordeum maritimum, we have characterized a transporter gene, named HmHKT2;1, whose homolog HvHKT2;1 in cultivated barley, Hordeum vulgare, was known to give rise to increased salt tolerance when overexpressed. The encoded protein is strictly identical in two H. maritimum ecotypes, from two biotopes (Tunisian sebkhas) affected by different levels of salinity. These two ecotypes were found to display distinctive responses to salt stress in terms of biomass production, Na+ contents, K+ contents and K+ absorption efficiency. Electrophysiological analysis of HmHKT2;1 in Xenopus oocytes revealed distinctive properties when compared with HvHKT2;1 and other transporters from the same group, especially a much higher affinity for both Na+ and K+, and an Na+–K+ symporter behavior in a very broad range of Na+ and K+ concentrations, due to reduced K+ blockage of the transport pathway. Domain swapping experiments identified the region including the fifth transmembrane segment and the adjacent extracellular loop as playing a major role in the determination of the affinity for Na+ and the level of K+ blockage in these HKT2;1 transporters. The analysis (quantitative reverse transcription-PCR; qRT-PCR) of HmHKT2;1 expression in the two ecotypes submitted to saline conditions revealed that the levels of HmHKT2;1 transcripts were maintained constant in the most salt-tolerant ecotype whereas they decreased in the less tolerant one. Both the unique functional properties of HmHKT2;1 and the regulation of the expression of the encoding gene could contribute to H. maritimum adaptation to salinity.
MORPHOFUNCTIONAL EVALUATION OF MACULAR-FOVEAL CAPILLARIES
Authors: Pilotto Elisabetta , Leonardi Francesca , Deganello Davide , Convento Enrica , Midena Edoardo , Frizziero Luisa 
Published: July 2019

Purpose:
To analyze the macular function of eyes with macular-foveal capillaries (MFC), a condition characterized by the absence of the foveal avascular zone (FAZ), identified by optical coherence tomography angiography.

Methods:
Eight eyes with MFC at optical coherence tomography angiography and normal visual acuity were consecutively recruited. Eight eyes of healthy subjects were enrolled as healthy controls. All eyes underwent optical coherence tomography, optical coherence tomography angiography, best-correct visual acuity, low-luminance visual acuity, contrast sensitivity measurement, colour vision tests, and both mesopic and scotopic microperimetry.

Results:
Best-corrected visual acuity, low-luminance visual acuity, contrast sensitivity, and colour vision tests did not differ between the two groups. At mesopic microperimetry, both foveal retinal sensitivity and mean mesopic retinal sensitivity of the central 1° were statistically inferior in MFC versus control eyes (P < 0.0001 and P < 0.0001, respectively). At scotopic microperimetry, a dense foveal scotoma, normally present in control eyes, was completely lacking in MFC eyes. Scotopic foveal retinal sensitivity was statistically superior in MFC versus control eyes (P = 0.009).

Conclusion:
The absence of the foveal dense scotoma in scotopic conditions underlines that the foveal rod-free zone is not present when capillaries are present in this area. An anomalous foveal distribution of photoreceptors, with both rods and cones present in this area, may be postulated in MFC eyes.
UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES
Authors: Whist Eline , Symes Richard J. , Chang John H. , Chowdhury Vivek , Lim Li-Anne , Grigg John R. , Lin Ming-Lee , Karaconji Tanya , Giblin Michael , Symons Andrew , Lim Lyndell L. , McCluskey Peter J. 
Published: July 2019

Background/Purpose:
To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma.

Methods:
A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified.

Results:
Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment.

Conclusion:
We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.
Readiness for Behavior Change in Patients Living With Ischemic Heart Disease
Authors: ESHAH Nidal F. 
Published: July 2019

ABSTRACTBackgroundReadiness for behavioral change may be evaluated by assessing the patient's stage of change, as described in the transtheoretical model. Identifying readiness to change in patients with ischemic heart disease may enhance the effectiveness of interventions that target risk reduction and lifestyle modification.PurposeThis study was designed to assess the readiness of patients with ischemic heart disease to change health behaviors as well as to identify the factors that significantly predict this change.MethodsA descriptive correlation design approach was adopted, and a convenience sample of 122 patients with ischemic heart disease was recruited from an outpatient cardiac clinic. Readiness for behavioral change was evaluated by assessing the stages of change of the participants, as described in the transtheoretical model. Data on readiness to change were collected using the “readiness for lifestyle change inventory.”ResultsA total of 62.2% and 43.4% of the participants were in the precontemplation phase of change for “cease smoking” and “be physically active,” respectively; about 33% of the patients were in the maintenance phase for “control weight”; 36.1% were in the maintenance phase for “reduce consumption of high-fat foods”; and 51.6% and 57.4% were in the maintenance phase for “eat fruits and vegetables” and “practice relaxation,” respectively. Participants who were overweight or obese showed higher readiness to practice physical activity, and those with high cholesterol levels showed a higher readiness to reduce the amount of fat in their diet. Higher income was found to predict higher readiness to eat fruits and vegetables.ConclusionsPatients are not adequately ready to change their health-related behaviors. Higher cardiovascular risk predicts higher readiness to change health behaviors.
Cognitive and Behavioral Differentiation of Those With Borderline Personality Disorder and Bipolar Disorder
Authors: Bayes Adam J. , Parker Gordon B. 
Published: July 2019

Abstract
The current study sought to identify features offering differentiation of borderline personality disorder (BPD) from bipolar disorder (BP). Participants were clinically assessed and assigned diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders criteria. A 113-item self-report questionnaire was completed, comprising cognitive and behavioral constructs weighted to a borderline personality style. A total of n = 53 participants were assigned to BPD, n = 83 to BP, with comorbid participants excluded. Twenty items were highly endorsed (>95%) by the BPD group, with most of the features capturing emotional dysregulation (ED) and identity disturbance; however, many items were also highly endorsed by the participants with BP. Thirty-eight items offered differentiation of BPD from BP, with identity disturbance overrepresented. The study findings indicate that the transdiagnostic nature of ED (a feature of both conditions) means it is less useful for diagnostic decisions, whereas identity disturbance is both intrinsic to BPD and offers specificity in differentiation from BP.