bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Assessment of the Effects ofIL-1ß-511 C&gt;T Variant on Breast Cancer Risk: An Updated Meta-Analysis of 3331 Cases and 3609 Controls
Authors: Harati-Sadegh Mahdiyeh , Mohammadoo-Khorasani Milad , Sargazi Saman , Saravani Ramin , Shahraki Sheida , Eskandari Ebrahim 
Published: June 2020

AbstractObjectiveGrowing evidence suggests that IL-1β -511C&gt;T, as a functional variant, affects the risk of developing breast cancer (BC); however, the results have not been conclusive. This meta-analysis was conducted to estimate the link between this variant and BC risk.MethodsWe retrieved available publications on IL-1β -511C&gt;T polymorphism by conducting a comprehensive literature search on the Web of Science, MEDLINE, PubMed, Scopus, and Google scholar databases (last search on February 25, 2020).ResultsThe overall analysis indicates that IL-1β -511C&gt;T polymorphism conferred an increased risk of BC under a recessive TT vs CT+CC model by 1.14-fold and showed protection against BC under an overdominant CT vs TT+CC genetic contrast model (odds ratio = 0.84). Stratified analysis based on ethnicity revealed the protective effect of this single-nucleotide polymorphism against BC risk in Caucasian patients.ConclusionOur data results provide a proof of concept for the association of IL-1β -511C&gt;T with BC risk. Larger, well-designed population-based studies are needed to confirm these findings.
Light Chain Predominant Intact Immunoglobulin Monoclonal Gammopathy Disorders: Shorter Survival in Light Chain Predominant Multiple Myelomas
Authors: Singh Gurmukh , Xu Hongyan 
Published: June 2020

Abstract

Background
A proportion of intact immunoglobulin (Ig)–producing multiple myelomas (MMs) was observed to secrete much higher amounts of free light chains (LCs) than usual.

Objectives
To determine the change point between usual and LC-predominant intact Ig-secreting MMs and other monoclonal gammopathic manifestations and the biological significance of the observation.

Methods
We conducted retrospective examination of laboratory findings in 386 MM, 27 smoldering MM, and 179 monoclonal gammopathy of undetermined significance (MGUS) cases that secreted intact Igs. We recorded the highest levels of involved serum free LC, highest ratio of involved to uninvolved LC, highest concentration of involved LC per g of monoclonal Ig, and highest value for ratio of involved to uninvolved LCs divided by the monoclonal Ig concentration. Each data set was sorted into kappa- and lambda LC-associated lesions. Length of time, in months, between diagnosis and last contact with the patients having myeloma was recorded.

Results
Change point analysis of data revealed a subgroup of cases with distinctly higher levels of free LCs. In myelomas, including plasma cell leukemias, 16.4% of myelomas with kappa LCs and 22.3% of myelomas with lambda LCs, the LC secretion was distinctly higher than in the remaining cases, by a combination of 4 parameters, listed herein. Corresponding figures for smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) were 12.5, 27.3, 3.8, and 6.8, respectively. Ten of the 13 (77%) cases of plasma cell leukemia) and all cases of IgD myeloma (n = 4) showed excess secretion of serum free LCs. Among IgG and IgA myelomas, including plasma cell leukemias, the LC-predominant lesions had shorter survival, by an average of 22.5 months.

Conclusions
In total, 18.4% of MMs, including plasma cell leukemias, secrete distinctly higher amounts of serum free LCs than other intact Ig-secreting myelomas and confer significantly lower survival. Quantification of monoclonal serum free LCs may be useful in this subgroup in monitoring progress and potentially in ascertaining minimal residual disease. The findings also stress the need for separate criteria for kappa and lambda LC associated monoclonal gammopathic manifestations. The significantly shorter survival of patients with LC-predominant myelomas warrants consideration in prospective trials of treatments.
Standing Type in Dicey/Marshall Issues of The Berkshire Tragedy
Authors: Atkinson David 
Published: June 2020

Abstract
This article considers six printings of the same ballad, The Berkshire Tragedy, by the same bookseller/printer, the Dicey/Marshall firm, which was the major producer of ballads in London throughout the mid-eighteenth-century. The results are rather startling and demonstrate that the ballad was kept in standing type through five different issues, in spite of a change from four-column to five-column format. These findings add to our knowledge of ballad production in the eighteenth century, and call into question the idea of ballads as ephemera.
Simultaneous multi-telescope observations of FRB 121102
Authors: Caleb M , Stappers B W , Abbott T D , Barr E D , Bezuidenhout M C , Buchner S J , Burgay M , Chen W , Cognard I , Driessen L N , Fender R , Hilmarsson G H , Hoang J , Horn D M , Jankowski F , Kramer M , Lorimer D R , Malenta M , Morello V , Pilia M , Platts E , Possenti A , Rajwade K M , Ridolfi A , Rhodes L , Sanidas S , Serylak M , Spitler L G , Townsend L J , Weltman A , Woudt P A , Wu J 
Published: June 2020

ABSTRACT
We present 11 detections of FRB 121102 in ∼3 h of observations during its ‘active’ period on the 10th of 2019 September. The detections were made using the newly deployed MeerTRAP system and single pulse detection pipeline at the MeerKAT radio telescope in South Africa. Fortuitously, the Nançay radio telescope observations on this day overlapped with the last hour of MeerKAT observations and resulted in four simultaneous detections. The observations with MeerKAT’s wide band receiver, which extends down to relatively low frequencies (900–1670 MHz usable L-band range), have allowed us to get a detailed look at the complex frequency structure, intensity variations, and frequency-dependent sub-pulse drifting. The drift rates we measure for the full-band and sub-banded data are consistent with those published between 600 and 6500 MHz with a slope of −0.147 ± 0.014 ms−1. Two of the detected bursts exhibit fainter ‘precursors’ separated from the brighter main pulse by ∼28 and ∼34 ms. A follow-up multi-telescope campaign on the 6th and 8th of 2019 October to better understand these frequency drifts and structures over a wide and continuous band was undertaken. No detections resulted, indicating that the source was ‘inactive’ over a broad frequency range during this time.
NuSTAR observations of four nearby X-ray faint AGNs: low luminosity or heavy obscuration?
Authors: Annuar A , Alexander D M , Gandhi P , Lansbury G B , Asmus D , Baloković M , Ballantyne D R , Bauer F E , Boorman P G , Brandt W N , Brightman M , Chen C-T J , Del Moro A , Farrah D , Harrison F A , Koss M J , Lanz L , Marchesi S , Masini A , Nardini E , Ricci C , Stern D , Zappacosta L 
Published: June 2020

ABSTRACT
We present NuSTAR (Nuclear Spectroscopic Telescope Array) observations of four active galactic nuclei (AGNs) located within 15 Mpc. These AGNs, namely ESO 121-G6, NGC 660, NGC 3486, and NGC 5195, have observed X-ray luminosities of L2–10 keV,obs ≲ 1039 erg s−1, classifying them as low-luminosity AGN (LLAGN). We perform broad-band X-ray spectral analysis for the AGN by combining our NuSTAR data with Chandra or XMM–Newton observations to directly measure their column densities (NH) and infer their intrinsic power. We complement our X-ray data with archival and new high-angular resolution mid-infrared (mid-IR) data for all objects, except NGC 5195. Based on our X-ray spectral analysis, we found that both ESO 121-G6 and NGC 660 are heavily obscured (NH &gt; 1023 cm−2; L2–10 keV,int ∼ 1041 erg s−1), and NGC 660 may be Compton thick. We also note that the X-ray flux and spectral slope for ESO 121-G6 have significantly changed over the last decade, indicating significant changes in the obscuration and potentially accretion rate. On the other hand, NGC 3486 and NGC 5195 appear to be unobscured and just mildly obscured, respectively, with L2–10 keV,int &lt; 1039 erg s−1, i.e. genuine LLAGN. Both of the heavily obscured AGNs have Lbol &gt; 1041 erg s−1 and λEdd ≳ 10−3, and are detected in high-angular resolution mid-IR imaging, indicating the presence of obscuring dust on nuclear scale. NGC 3486, however, is undetected in high-resolution mid-IR imaging, and the current data do not provide stringent constraints on the presence or absence of obscuring nuclear dust in the AGN.
Optical studies of two stripped-envelope supernovae – SN 2015ap (Type Ib) and SN 2016P (Type Ic)
Authors: Gangopadhyay Anjasha , Misra Kuntal , Sahu D K , Wang Shan-Qin , Kumar Brajesh , Li Long , Anupama G C , Dastidar Raya , Elias-Rosa N , Kumar Brijesh , Singh Mridweeka , Pandey S B , Sanwal Pankaj , Singh Avinash , Srivastav S , Tartaglia L , Tomasella L 
Published: June 2020

ABSTRACT
We present the photometric and spectroscopic studies of a Type Ib SN 2015ap and a Type Ic SN 2016P. SN 2015ap is one of the bright (MV = −18.04 mag) Type Ib while SN 2016P lies at an average value among the Type Ic SNe (MV = −17.53 mag). Bolometric light-curve modelling of SNe 2015ap and 2016P indicates that both the SNe are powered by 56Ni + magnetar model with 56Ni masses of 0.01 and 0.002 M⊙, ejecta masses of 3.75 and 4.66 M⊙, spin period P0 of 25.8 and 36.5 ms, and magnetic field Bp of 28.39 × 1014 and 35.3 × 1014 G, respectively. The early spectra of SN 2015ap show prominent lines of He with a ‘W’ feature due to Fe complexes while other lines of Mg ii, Na i, and Si ii are present in both SNe 2015ap and 2016P. Nebular phase [O i] profile indicates an asymmetric profile in SN 2015ap. The [O i]/[Ca ii] ratio and nebular spectral modelling of SN 2015ap hint towards a progenitor mass between 12 and 20 M⊙.
Water transport throughout the TRAPPIST-1 system: the role of planetesimals
Authors: Đošović Vladimir , Novakovć Bojan , Vukotć Branislav , Ćirković Milan M 
Published: June 2020

ABSTRACT
Observational data suggest that a belt of planetesimals is expected close to the snow line in protoplanetary discs. Assuming there is such a belt in the TRAPPIST-1 system, we examine possibilities of water delivery to the planets via planetesimals from the belt. The study is accomplished by numerical simulations of dynamical evolution of a hypothetical planetesimal belt. Our results show that the inner part of the belt is dynamically unstable and planetesimals located in this region are quickly scattered away, with many of them entering the region around the planets. The main dynamical mechanism responsible for the instability are close encounters with the outermost planet Trappist-1h. A low-order mean-motion resonance 2:3 with Trappist-1h, located in the same region, also contributes to the objects transport. In our nominal model, the planets have received a non-negligible amount of water, with the smallest amount of 15 per cent of the current Earth’s water amount (EWA) being delivered to the planet 1b, while the planets Trappist-1e and Trappist-1g have received more than 60 per cent of the EWA. We have found that while the estimated efficiency of water transport to the planets is robust, the amount of water delivered to each planet may vary significantly, depending on the initial masses and orbits of the planets. The estimated dynamical ‘half-lives’ have shown that the impactors’ source region should be emptied in less then 1 Myr. Therefore, the obtained results suggest that the transport of planetesimals through the system preferably occurs during an early phase of the planetary system evolution.
A fully-automated method discovers loss of mouse-lethal and human-monogenic disease genes in 58 mammals
Authors: Turakhia Yatish , Chen Heidi I , Marcovitz Amir , Bejerano Gill 
Published: June 2020

Abstract
Gene losses provide an insightful route for studying the morphological and physiological adaptations of species, but their discovery is challenging. Existing genome annotation tools focus on annotating intact genes and do not attempt to distinguish nonfunctional genes from genes missing annotation due to sequencing and assembly artifacts. Previous attempts to annotate gene losses have required significant manual curation, which hampers their scalability for the ever-increasing deluge of newly sequenced genomes. Using extreme sequence erosion (amino acid deletions and substitutions) and sister species support as an unambiguous signature of loss, we developed an automated approach for detecting high-confidence gene loss events across a species tree. Our approach relies solely on gene annotation in a single reference genome, raw assemblies for the remaining species to analyze, and the associated phylogenetic tree for all organisms involved. Using human as reference, we discovered over 400 unique human ortholog erosion events across 58 mammals. This includes dozens of clade-specific losses of genes that result in early mouse lethality or are associated with severe human congenital diseases. Our discoveries yield intriguing potential for translational medical genetics and evolutionary biology, and our approach is readily applicable to large-scale genome sequencing efforts across the tree of life.
Anti-inflammatory functions of the glucocorticoid receptor require DNA binding
Authors: Escoter-Torres Laura , Greulich Franziska , Quagliarini Fabiana , Wierer Michael , Uhlenhaut Nina Henriette 
Published: June 2020

Abstract
The glucocorticoid receptor is an important immunosuppressive drug target and metabolic regulator that acts as a ligand-gated transcription factor. Generally, GR’s anti-inflammatory effects are attributed to the silencing of inflammatory genes, while its adverse effects are ascribed to the upregulation of metabolic targets. GR binding directly to DNA is proposed to activate, whereas GR tethering to pro-inflammatory transcription factors is thought to repress transcription. Using mice with a point mutation in GR’s zinc finger, that still tether via protein–protein interactions while being unable to recognize DNA, we demonstrate that DNA binding is essential for both transcriptional activation and repression. Performing ChIP-Seq, RNA-Seq and proteomics under inflammatory conditions, we show that DNA recognition is required for the assembly of a functional co-regulator complex to mediate glucocorticoid responses. Our findings may contribute to the development of safer immunomodulators with fewer side effects.
Poly(A) binding KPAF4/5 complex stabilizes kinetoplast mRNAs in Trypanosoma brucei
Authors: Aphasizheva Inna , Yu Tian , Suematsu Takuma , Liu Qiushi , Mesitov Mikhail V , Yu Clinton , Huang Lan , Zhang Liye , Aphasizhev Ruslan 
Published: June 2020

Abstract
In Trypanosoma brucei, mitochondrial pre-mRNAs undergo 3′-5′ exonucleolytic processing, 3′ adenylation and uridylation, 5′ pyrophosphate removal, and, often, U-insertion/deletion editing. The 3′ modifications are modulated by pentatricopeptide repeat (PPR) Kinetoplast Polyadenylation Factors (KPAFs). We have shown that KPAF3 binding to the 3′ region stabilizes properly trimmed transcripts and stimulates their A-tailing by KPAP1 poly(A) polymerase. Conversely, poly(A) binding KPAF4 shields the nascent A-tail from uridylation and decay thereby protecting pre-mRNA upon KPAF3 displacement by editing. While editing concludes in the 5′ region, KPAF1/2 dimer induces A/U-tailing to activate translation. Remarkably, 5′ end recognition and pyrophosphate hydrolysis by the PPsome complex also contribute to mRNA stabilization. Here, we demonstrate that KPAF4 functions as a heterodimer with KPAF5, a protein lacking discernable motifs. We show that KPAF5 stabilizes KPAF4 to enable poly(A) tail recognition, which likely leads to mRNA stabilization during the editing process and impedes spontaneous translational activation of partially-edited transcripts. Thus, KPAF4/5 represents a poly(A) binding element of the mitochondrial polyadenylation complex. We present evidence that RNA editing substrate binding complex bridges the 5′ end-bound PPsome and 3′ end-bound polyadenylation complexes. This interaction may enable mRNA circularization, an apparently critical element of mitochondrial mRNA stability and quality control.
A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics
Authors: Deprey Kirsten , Batistatou Nefeli , Kritzer Joshua A 
Published: June 2020

AbstractRNA therapeutics are a promising strategy to treat genetic diseases caused by the overexpression or aberrant splicing of a specific protein. The field has seen major strides in the clinical efficacy of this class of molecules, largely due to chemical modifications and delivery strategies that improve nuclease resistance and enhance cell penetration. However, a major obstacle in the development of RNA therapeutics continues to be the imprecise, difficult, and often problematic nature of most methods used to measure cell penetration. Here, we review these methods and clearly distinguish between those that measure total cellular uptake of RNA therapeutics, which includes both productive and non-productive uptake, and those that measure cytosolic/nuclear penetration, which represents only productive uptake. We critically analyze the benefits and drawbacks of each method. Finally, we use key examples to illustrate how, despite rigorous experimentation and proper controls, our understanding of the mechanism of gymnotic uptake of RNA therapeutics remains limited by the methods commonly used to analyze RNA delivery.
Intact RNA structurome reveals mRNA structure-mediated regulation of miRNA cleavage in vivo
Authors: Yang Minglei , Woolfenden Hugh C , Zhang Yueying , Fang Xiaofeng , Liu Qi , Vigh Maria L , Cheema Jitender , Yang Xiaofei , Norris Matthew , Yu Sha , Carbonell Alberto , Brodersen Peter , Wang Jiawei , Ding Yiliang 
Published: June 2020

AbstractMicroRNA (miRNA)-mediated cleavage is involved in numerous essential cellular pathways. miRNAs recognize target RNAs via sequence complementarity. In addition to complementarity, in vitro and in silico studies have suggested that RNA structure may influence the accessibility of mRNAs to miRNA-induced silencing complexes (miRISCs), thereby affecting RNA silencing. However, the regulatory mechanism of mRNA structure in miRNA cleavage remains elusive. We investigated the role of in vivo RNA secondary structure in miRNA cleavage by developing the new CAP-STRUCTURE-seq method to capture the intact mRNA structurome in Arabidopsis thaliana. This approach revealed that miRNA target sites were not structurally accessible for miRISC binding prior to cleavage in vivo. Instead, we found that the unfolding of the target site structure plays a key role in miRISC activity in vivo. We found that the single-strandedness of the two nucleotides immediately downstream of the target site, named Target Adjacent nucleotide Motif, can promote miRNA cleavage but not miRNA binding, thus decoupling target site binding from cleavage. Our findings demonstrate that mRNA structure in vivo can modulate miRNA cleavage, providing evidence of mRNA structure-dependent regulation of biological processes.
Assessment of the Subarachnoid Hemorrhage International Trialists (SAHIT) Models for Dichotomized Long-Term Functional Outcome Prediction After Aneurysmal Subarachnoid Hemorrhage in a United Kingdom Multicenter Cohort Study
Authors: Hostettler Isabel C , Pavlou Menelaos , Ambler Gareth , Alg Varinder S , Bonner Stephen , Walsh Daniel C , Bulters Diederik , Kitchen Neil , Brown Martin M , Grieve Joan , Houlden Henry , Werring David J ,   on behalf of the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators
Published: June 2020

Abstract

BACKGROUND
Long-term outcome after subarachnoid hemorrhage, beyond the first few months, is difficult to predict, but has critical relevance to patients, their families, and carers.

OBJECTIVE
To assess the performance of the Subarachnoid Hemorrhage International Trialists (SAHIT) prediction models, which were initially designed to predict short-term (90 d) outcome, as predictors of long-term (2 yr) functional outcome after aneurysmal subarachnoid hemorrhage (aSAH).

METHODS
We included 1545 patients with angiographically-proven aSAH from the Genetic and Observational Subarachnoid Haemorrhage (GOSH) study recruited at 22 hospitals between 2011 and 2014. We collected data on age, WNFS grade on admission, history of hypertension, Fisher grade, aneurysm size and location, as well as treatment modality. Functional outcome was measured by the Glasgow Outcome Scale (GOS) with GOS 1 to 3 corresponding to unfavorable and 4 to 5 to favorable functional outcome, according to the SAHIT models. The SAHIT models were assessed for long-term outcome prediction by estimating measures of calibration (calibration slope) and discrimination (area under the receiver-operating characteristic curve [AUC]) in relation to poor clinical outcome.

RESULTS
Follow-up was standardized to 2 yr using imputation methods. All 3 SAHIT models demonstrated acceptable predictive performance for long-term functional outcome. The estimated AUC was 0.71 (95% CI: 0.65-0.76), 0.73 (95% CI: 0.68-0.77), and 0.74 (95% CI: 0.69-0.79) for the core, neuroimaging, and full models, respectively; the calibration slopes were 0.86, 0.84, and 0.89, indicating good calibration.

CONCLUSION
The SAHIT prediction models, incorporating simple factors available on hospital admission, show good predictive performance for long-term functional outcome after aSAH.
Do Politicians Discriminate against Ethnic Minority Constituents? A Field Experiment on Social Interactions between Citizens and Swedish Local Politicians
Authors: Larsson Taghizadeh Jonas , Åström Angelica , Adman Per 
Published: June 2020

Abstract
In ethnically diverse societies, are citizens treated equally by their political representatives? Several field experiments find that politicians discriminate in their daily communication with voters. However, these studies only focus on the USA and South Africa and may overestimate the degree of discrimination by ignoring sex and socio-economic status. We address these shortcomings by investigating ethnic discrimination in Sweden. In an email experiment, all 812 municipal commissioners were randomly contacted by voters with Arabic- or Swedish-sounding names. Our results do not show any clear signs of discrimination; thus, previous results might not be generalisable to Sweden or similar democracies.
Muon and electron g − 2 and the origin of the fermion mass hierarchy
Authors: Haba Naoyuki , Shimizu Yasuhiro , Yamada Toshifumi 
Published: June 2020

Abstract
We present a model that gives a natural explanation to the charged lepton mass hierarchy and study the contributions to the electron and the muon $g-2$. In the model, we introduce lepton-flavor-dependent $U(1)_F$ symmetry and three additional Higgs doublets with $U(1)_F$ charges, to realize that each generation of charged leptons couples to one of the three additional Higgs doublets. The $U(1)_F$ symmetry is softly broken by $+1$ charges, and the smallness of the soft breaking naturally gives rise to the hierarchy of the Higgs vacuum expectation values, which then accounts for the charged lepton mass hierarchy. Since electron and muon couple to different scalar particles, each scalar contributes to the electron and the muon $g-2$ differently. We survey the space of parameters of the Higgs sector and find that there are sets of parameters that explain the muon $g-2$ discrepancy. On the other hand, we cannot find parameter sets that can explain the $g-2$ discrepancy within 2 $\sigma$. Here, the $U(1)_F$ symmetry suppresses charged lepton flavor violation.