bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T-cell Effector Function in Mice: Implications for Combination with Immunotherapy
Authors: Tyler Paul M. , Servos Mariah M. , de Vries Romy C. , Klebanov Boris , Kashyap Trinayan , Sacham Sharon , Landesman Yosef , Dougan Michael , Dougan Stephanie K. 
Published: February 2017

Abstract
Selinexor (KPT-330) is a first-in-class nuclear transport inhibitor currently in clinical trials as an anticancer agent. To determine how selinexor might affect antitumor immunity, we analyzed immune homeostasis in mice treated with selinexor and found disruptions in T-cell development, a progressive loss of CD8 T cells, and increases in inflammatory monocytes. Antibody production in response to immunization was mostly normal. Precursor populations in bone marrow and thymus were unaffected by selinexor, suggesting that normal immune homeostasis could recover. We found that a high dose of selinexor given once per week preserved nearly normal immune functioning, whereas a lower dose given 3 times per week did not restore immune homeostasis. Both naïve and effector CD8 T cells cultured in vitro showed impaired activation in the presence of selinexor. These experiments suggest that nuclear exportins are required for T-cell development and function. We determined the minimum concentration of selinexor required to block T-cell activation and showed that T-cell–inhibitory effects of selinexor occur at levels above 100 nmol/L, corresponding to the first 24 hours post-oral dosing. In a model of implantable melanoma, selinexor treatment at 10 mg/kg with a 4-day drug holiday led to intratumoral IFNγ+, granzyme B+ cytotoxic CD8 T cells that were comparable with vehicle-treated mice. Overall, selinexor treatment leads to transient inhibition of T-cell activation, but clinically relevant once and twice weekly dosing schedules that incorporate sufficient drug holidays allow for normal CD8 T-cell functioning and development of antitumor immunity. Mol Cancer Ther; 16(3); 428–39. ©2017 AACR.
See related article by Farren et al., p. 417
Prognostic Relevance of Tumor Purity and Interaction with MGMT Methylation in Glioblastoma
Authors: Schulze Heuling Eva , Knab Felix , Radke Josefine , Eskilsson Eskil , Martinez-Ledesma Emmanuel , Koch Arend , Czabanka Marcus , Dieterich Christoph , Verhaak Roel G. , Harms Christoph , Euskirchen Philipp 
Published: February 2017

Abstract
Promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, is a critical biomarker in glioblastoma (GBM), as treatment decisions and clinical trial inclusion rely on its accurate assessment. However, interpretation of results is complicated by poor interassay reproducibility as well as a weak correlation between methylation status and expression levels of MGMT. This study systematically investigates the influence of tumor purity on tissue subjected to MGMT analysis. A quantitative, allele-specific real-time PCR (qAS-PCR) assay was developed to determine genotype and mutant allele frequency of telomerase promoter (pTERT) mutations as a direct measure of tumor purity. We studied tumor purity, pTERT mutation by Sanger sequencing, MGMT methylation by pyrosequencing, IDH1 mutation status, and clinical parameters in a cohort of high-grade gliomas (n = 97). The qAS-PCR reliably predicted pTERT genotype and tumor purity compared with independent methods. Tumor purity positively and significantly correlated with the extent of methylation in MGMT methylated GBMs. Extent of MGMT methylation differed significantly with respect to pTERT mutation hotspot (C228T vs. C250T). Interestingly, frontal lobe tumors showed greater tumor purity than those in other locations. Above all, tumor purity was identified as an independent prognostic factor in GBM. In conclusion, we determined mutual associations of tumor purity with MGMT methylation and pTERT mutations and found that the extent of MGMT methylation reflects tumor purity. In turn, tumor purity is prognostic in IDH1 wild-type GBM.
Implications: Tumor purity is an independent prognostic marker in glioblastoma and is associated with the extent of MGMT methylation. Mol Cancer Res; 15(5); 532–40. ©2017 AACR.
Prediction of major and clinically relevant bleeding in patients with VTE treated with edoxaban or vitamin K antagonists
Authors: Raskob Gary , Büller Harry , Grosso Michael , Zhang George , Winters Shannon , Cohen Alexander , Di Nisio Marcello 
Published: February 2017

SummaryBetter understanding of risk factors for major bleeding events during anticoagulant treatment for venous thromboembolism (VTE) may help physicians when deciding on intensity and duration of treatment. The primary aim of this study was to identify risk factors for major and clinically relevant bleeding in patients receiving the oral factor Xa inhibitor edoxaban or warfarin for the treatment of acute VTE. We analysed data from 8240 patients who received ≥1 dose of study drug in the Hokusai-VTE study. Bleeding risk factors were evaluated in 4118 patients who received edoxaban and significant variables were combined in a prediction model. We used the C-statistic to estimate model discrimination and bootstrap techniques for internal validation. Major bleeding occurred in 56/4118 (1.4 %) patients given edoxaban and in 66/4122 (1.6 %) patients given warfarin. Clinically relevant bleeding occurred in 349 (8.5 %) and 423 (10.3 %), respectively. Significant risk factors for major bleeding during edoxaban treatment were female sex, concomitant antiplatelet therapy, haemoglobin ≤10 g/dl, history of arterial hypertension, and systolic blood pressure >160 mmHg. The discrimination of the model was high (C-statistic: 0.71) for major bleeding, lower for clinically relevant bleeding (C-statistic: 0.62) and when the model was applied to patients receiving warfarin (C-statistic 0.60). In conclusion, we identified five main predictors of major bleeding in patients receiving edoxaban for the treatment of acute VTE. A risk model based on these factors predicted an increased risk of bleeding with good discrimination.Supplementary Material to this article is available online at www.thrombosis-online.com.
Sex Differences in 1-Year All-Cause Rehospitalization in Patients After Acute Myocardial Infarction
Authors: Dreyer Rachel P. , Dharmarajan Kumar , Kennedy Kevin F. , Jones Philip G. , Vaccarino Viola , Murugiah Karthik , Nuti Sudhakar V. , Smolderen Kim G. , Buchanan Donna M. , Spertus John A. , Krumholz Harlan M. 
Published: February 2017

Background:
Compared with men, women are at higher risk of rehospitalization in the first month after discharge for acute myocardial infarction (AMI). However, it is unknown whether this risk extends to the full year and varies by age. Explanatory factors potentially mediating the relationship between sex and rehospitalization remain unexplored and are needed to reduce readmissions. The aim of this study was to assess sex differences and factors associated with 1-year rehospitalization rates after AMI.

Methods:
We recruited 3536 patients (33% women) ≥18 years of age hospitalized with AMI from 24 US centers into the TRIUMPH study (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients’ Health Status). Data were obtained by medical record abstraction and patient interviews, and a physician panel adjudicated hospitalizations within the first year after AMI. We compared sex differences in rehospitalization using a Cox proportional hazards model, following sequential adjustment for covariates and testing for an age-sex interaction.

Results:
One-year crude all-cause rehospitalization rates for women were significantly higher than men after AMI (hazard ratio, 1.29 for women; 95% confidence interval, 1.12−1.48). After adjustment for demographics and clinical factors, women had a persistent 26% higher risk of rehospitalization (hazard ratio, 1.26; 95% confidence interval, 1.08−1.47). However, after adjustment for health status and psychosocial factors (hazard ratio, 1.14; 95% confidence interval, 0.96−1.35), the association was attenuated. No significant age-sex interaction was found for 1-year rehospitalization, suggesting that the increased risk applied to both older and younger women.

Conclusions:
Regardless of age, women have a higher risk of rehospitalization compared with men over the first year after AMI. Although the increased risk persisted after adjustment for clinical factors, the poorer health and psychosocial state of women attenuated the difference.
Toxicity of ethanol solutions and vapours against Meloidogyne incognita
Authors: Silva Julio C.P. , Campos Vicente P. , Freire Eduardo S. , Terra Willian C. , Lopez Liliana E. 
Published: February 2017

Ethanol (EtOH) is less harmful to humans than currently available nematicide molecules. This study evaluated the efficacy of EtOH in controllingMeloidogyne incognitain vitroand in lettuce plants under glasshouse conditions. Aqueous EtOH solutions (5-70% volume) and their vapours caused an acute nematicidal effectin vitroin second-stage juveniles (J2) ofM. incognitaand reduced hatching of J2. There was a large reduction of galls and eggs in the root system when 40 ml of EtOH was applied toM. incognita-infested soil at concentrations of 40 and 70%. Water exposed to EtOH vapours for 1 h became toxic, and a 12-h exposure caused 100% J2 mortality. Use of a plastic cover did not increase the efficiency of EtOH in controllingM. incognitain lettuce plants. The observed EtOH effects indicate its prospective use in controlling plant-parasitic nematodes, especially in glasshouses.
Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice
Authors: Li Huihui , Choesang Tenzin , Bao Weili , Chen Huiyong , Feola Maria , Garcia-Santos Daniel , Li Jie , Sun Shuming , Follenzi Antonia , Pham Petra , Liu Jing , Zhang Jinghua , Ponka Prem , An Xiuli , Mohandas Narla , Fleming Robert E. , Rivella Stefano , Li Guiyuan , Ginzburg Yelena Z. 
Published: February 2017

Key PointsApotransferrin decreases TfR1 expression and alters TfR1 trafficking to normalize enucleation in β-thalassemic erythroid precursors. Decreased TfR1 upregulates hepcidin in an iron- and ERFE-independent manner, resulting in iron-restricted β-thalassemic erythropoiesis.
Distinct functions of CXCR4, CCR2, and CX3CR1 direct dendritic cell precursors from the bone marrow to the lung
Authors: Nakano Hideki , Lyons-Cohen Miranda R , Whitehead Gregory S , Nakano Keiko , Cook Donald N 
Published: February 2017

Abstract
Precursors of dendritic cells (pre-DCs) arise in the bone marrow (BM), egress to the blood, and finally migrate to peripheral tissue, where they differentiate to conventional dendritic cells (cDCs). Upon their activation, antigen-bearing cDCs migrate from peripheral tissue to regional lymph nodes (LNs) in a manner dependent on the chemokine receptor, CCR7. To maintain immune homeostasis, these departing cDCs must be replenished by new cDCs that develop from pre-DCs, but the molecular signals that direct pre-DC trafficking from the BM to the blood and peripheral tissues remain poorly understood. In the present study, we found that pre-DCs express the chemokine receptors CXCR4, CCR2, and CX3CR1, and that each of these receptors has a distinct role in pre-DC trafficking. Flow cytometric analysis of pre-DCs lacking CXCR4 revealed that this receptor is required for the retention of pre-DCs in the BM. Analyses of mice lacking CCR2 or CX3CR1, or both, revealed that they promote pre-DC migration to the lung at steady state. CCR2, but not CX3CR1, was required for pre-DC migration to the inflamed lung. Thus, these multiple chemokine receptors cooperate in a step-wise fashion to coordinate the trafficking of pre-DCs from the BM to the circulation and peripheral tissues.
Matricellular proteins tune myeloid-derived suppressor cell recruitment and function in breast cancer
Authors: Chiodoni Claudia , Sangaletti Sabina , Colombo Mario P 
Published: February 2017

Abstract
Solid tumor progression is often associated with the expansion of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells that actively foster tumor growth and metastatic dissemination through a plethora of mechanisms, including, but not limited to, their major suppressive activity on the immune response. Indeed, MDSCs may sustain tumor progression by dynamically remodeling the tumor microenvironment through the production of angiogenic factors and metalloproteases, by helping the establishment of a premetastatic niche, and by promoting stemness and epithelial-to-mesenchymal transition (EMT) features in tumor cells. MDSCs are also regulated by a growing list of factors that mainly comprise 2 sets of signals: those responsible for their expansion and recruitment, such as GM-, M-, and G-CSF and other growth factors, and those relevant for the induction of their suppressive activity, which include proinflammatory cytokines and transcription factors. We review here a new class of MDSC regulators—matricellular proteins—with a particular focus on osteopontin (OPN) and secreted acidic cysteine-rich glycoprotein (SPARC), which seem to affect the expansion/recruitment and the immune-suppressive activity of MDSCs. Matricellular proteins function indirectly on MDSCs through the induction of other mediators when produced by tumor cells and cell autonomously when expressed—likely in an intracellular form—directly by MDSCs.
The Impact of Family Income on Child Achievement: Evidence from the Earned Income Tax Credit: Reply
Authors: Dahl Gordon B. , Lochner Lance 
Published: February 2017

Dahl and Lochner (2012) provides some of the first causal evidence of the effects of family income on child achievement using changes in the Earned Income Tax Credit. Unfortunately, a coding error in the creation of total family income affects the first stage estimates and inflates the instrumental variable (IV) estimates. Importantly, it does not affect the reduced-form estimates or alter statistical significance of the IV estimates. This response shows that correcting this error does not alter the core findings or main message of the paper. (JEL H24, H31, I21, I38, J13)
‘Where do you want to have your baby?’ Women's narratives of how they chose their birthplace
Authors: Woog Chantal Louise 
Published: February 2017

Background National guidelines endorse the provision of birthplace choice for women with low-risk pregnancies. Despite the availability of different options (birth centre, home and hospital) and substantial evidence highlighting the benefits of birth outside a hospital setting, the majority of women choose to give birth in a hospital. Aims This study aimed to: explore how low-risk, first-time mothers chose where to give birth to their babies; and gain an in-depth understanding of what factors influenced women's experiences of decision-making. Methods A qualitative study with a narrative approach was used. Data were collected using an online questionnaire. Participants were recruited from a social networking site. A purposive sample of nine low-risk, first-time mothers, all of whom were given a choice of birthplace (at least two options), was used. Findings Two core themes emerged that were considered to influence women's decisions on birthplace: women's expectations of birth, perception of safety and protecting the birthing process; and the influence of the midwife, antenatal education and the partner. Conclusion The study reveals that women make choices based on a variety of reasons. However, the findings presented suggest that most women give birth in a hospital as it is still widely considered to be the safest place for women and babies—both by couples themselves and by many health professionals. The challenge is to address this generation of women who believe that hospital is the most appropriate place to give birth, despite evidence to the contrary, and ultimately promote the normality of pregnancy and childbirth.
On the Astron UV Space Mission Data
Authors: Kilpio E. Yu. , Mironov A. V. , Malkov O. Yu. 
Published: February 2017

Abstract
The Soviet UV space mission Astron, launched in 1983, had been operational for eight years as the largest ultraviolet space telescope during its lifetime. Astron provided a lot of observational material for various types of astrophysical objects, but unfortunately these data were not widely available and, as a result, unduly forgotten. Here we present some results of our comparison of the Astron data to the modern UV stellar data, such as the NGSL spectral library, discuss the precision and accuracy achieved with Astron, and make some conclusions on potential application areas of these data.
A New Revision of the HDEC (Henry Draper Extension Charts) Catalog
Authors: Ashimbaeva N. , Sementsov V. 
Published: February 2017

Abstract
A new version of the HDEC (Henry Draper Extension Charts) catalog is presented. The catalog includes 88,548 entries, more than 3500 of which (components of binary systems) were earlier corrupted by an algorithmic error (1579 multiple systems were revealed). Spectral classification of these objects has been corrected manually using the CDS data. We also corrected some mistakes of the catalog detected by the measurement model and cross-matching with other CDS catalogs, and, in some cases, by the authors of the catalog and through collaboration of the HDEC users.
Half a Century after the Outburst of the Symbiotic Nova V1016 Cyg
Authors: Arkhipova V. P. , Taranova O. G. , Ikonnikova N. P. , Esipov V. F. , Komissarova G. V. , Shenavrin V. I. 
Published: February 2017

Abstract
We present the results of our long-term UBV JHKLM photometry and spectroscopic monitoring of the symbiotic nova V1016 Cyg. After its outburst in 1964, the star showed fading in the U, B, V bands at a rate of about 0.03 mag per year. The behavior of the B − V and U − B color indices reflects variations of the emission lines, fading of the erupted component, weakening and reddening of the cool giant. Also, monotonic color and brightness variations in the infrared (IR) were observed at a scale of several thousand days. After 2004, the yearly mean IR brightness showed a decline and IR colors, reddening, due to the increase of the optical depth of the dust. The parameters of the cool star and of the dust envelope were estimated. The pulsation period of the Mira-type variable was refined, P = 465±5 days. The Mira’s photospheric temperature varied from 2100 to 2700 K in the pulsation cycle. The mass of the dust shell has grown twice during the recent decade, at a dust penetration rate of ∆M
dust ~ 10−7
M
⊙/yr. Our spectroscopic monitoring of V1016 Cyg over 1995−2013 showed variations in the emission line strengths. The absolute fluxes of most lines decreased after 2000, whereas the relative intensities of [O III], [Ar III], [Fe VII], [Ca VII] lines with respect to Hβ are increasing after the possible minimum that could happen in the 1990s. An essential flux decline (approximately ten-fold between 1995 and 2013) in the Raman scattered O VI line at λ6825 shows the change of conditions in its formation zone, due to absorption of O VI 1032 Å quanta in the new dust shell of the cool component.
Stäackel-type Dynamic Model of the Galaxy Based on Maser Kinematic Data
Authors: Gromov A. O. , Nikiforov I. I. , Ossipkov L. P. 
Published: February 2017

Abstract
A dynamic model of the Galaxy is constructed based on kinematic data for masers with trigonometric parallaxes. Maser data is used to compute the model potential in the Galactic plane. The potential is then generalized to three dimensions assuming the existence of a third quadratic integral of motion. The resulting Galactic model potential is of Stäckel’s type. The corresponding space density function is determined from Poisson’s equation.
Discovery, Observational Data and the Orbit of the Transneptunian Object (420356) Praamžius
Authors: Černis K. , Boyle R. P. , Wlodarczyk I. 
Published: February 2017

AbstractA project for astrometric and photometric observations of asteroids with the VATT telescope on Mt. Graham is described. One of the most important results is the discovery of the Transneptunian object (420356) Praamžius. We computed its orbit applying 198 optical observations from 2003 February 1 to 2016 January 30. We also followed its orbit searching for minimal distances to Neptune between the years 17 000 and −13 000. Combined with the apparent brightness, the orbit gives the absolute magnitude
Phase-Space Model of a Collisionless Stellar Cylinder Embedded in a Rotating Halo
Authors: Kondratyev B. P. , Kireeva E. N. 
Published: February 2017

Abstract
The phase-space model of a stellar cylindrical bar embedded in a rotating triaxial halo is constructed. The equations of motion of an individual star in the bar are derived and solved. The model has three integrals of motion and the condition of the cylinder boundary conservation is derived. The model is found to represent a four-dimensional ellipsoid in six-dimensional phase space. The phase-space distribution function of stars is derived, which depends on isolating integrals of motion. The centroid velocity field describes longitudinal shear averaged flows in the cylinder. Two non-zero components of the velocity dispersion tensor depend quadratically on coordinates and vanish at the surface of the cylindrical bar.
Kernel Density Estimation in the Study of Star Clusters
Authors: Seleznev Anton F. 
Published: February 2017

Abstract
The kernel estimator method is used to evaluate the surface and spatial star number density in star clusters. Both density maps and radial density profiles are plotted. These estimates are used to derive the cluster size, the number of cluster stars and the cluster mass, and to study the cluster structure. The kernel estimator is also used to plot the luminosity function, mass function, the velocity distribution, and Hess diagrams for star clusters. The advantages of the kernel estimator method and technical details of its use are illustrated by modern results for the open cluster NGC 4337.
Swing Amplification and Global Modes Reciprocity in Models with Cusps
Authors: Polyachenko E. V. 
Published: February 2017

Abstract
We use 3D N-body simulations to analyze the onset of the bar in cuspy models, and argue that the role of swing amplification is twofold. Amplified shot noise due to disk discreteness hampers the bar formation, while induced resonance perturbations allow the bar amplitude to overcome shots. The bar pattern speed and the growth rate obtained in N-body simulations agree well with the global mode analysis.
Outer Rings in Early-Type Disk Galaxies: Star Formation Rate
Authors: Kostiuk I. P. , Sil’chenko O. K. 
Published: February 2017

Abstract
The total ring star formation rates and their surface densities are determined for 34 early-type disk galaxies with outer stellar rings which were detected in the UV with the GALEX space telescope. The total level of the integrated star formation rate in the outer rings appears to be low – less than 0.1 M
⊙ yr−1, with typical surface densities from 10−4 to 10−3
M
⊙ yr−1 kpc−2.
Critical comments to a recent EFLM recommendation for the review of reference intervals
Authors: Haeckel Rainer , Wosniok Werner , Arzideh Farhad , Zierk Jakob , Gurr Eberhard , Streichert Thomas 
Published: February 2017

AbstractIn a recent EFLM recommendation on reference intervals by Henny et al., the direct approach for determining reference intervals was proposed as the only presently accepted “gold” standard. Some essential drawbacks of the direct approach were not sufficiently emphasized, such as unacceptably wide confidence limits due to the limited number of observations claimed and the practical usability for only a limited age range. Indirect procedures avoid these disadvantages of the direct approach. Furthermore, indirect approaches are well suited for reference limits with large variations during lifetime and for common reference limits.