bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global torques and stochasticity as the drivers of massive black hole pairing in the young Universe
Authors: Bortolas Elisa , Capelo Pedro R , Zana Tommaso , Mayer Lucio , Bonetti Matteo , Dotti Massimo , Davies Melvyn B , Madau Piero 
Published: August 2020

ABSTRACT
The forthcoming Laser Interferometer Space Antenna (LISA) will probe the population of coalescing massive black hole (MBH) binaries up to the onset of structure formation. Here, we simulate the galactic-scale pairing of ∼106 M⊙ MBHs in a typical, non-clumpy main-sequence galaxy embedded in a cosmological environment at z = 7–6. In order to increase our statistical sample, we adopt a strategy that allows us to follow the evolution of six secondary MBHs concomitantly. We find that the magnitude of the dynamical-friction-induced torques is significantly smaller than that of the large-scale, stochastic gravitational torques arising from the perturbed and morphologically evolving galactic disc, suggesting that the standard dynamical friction treatment is inadequate for realistic galaxies at high redshift. The dynamical evolution of MBHs is very stochastic, and a variation in the initial orbital phase can lead to a drastically different time-scale for the inspiral. Most remarkably, the development of a galactic bar in the host system either significantly accelerates the inspiral by dragging a secondary MBH into the centre, or ultimately hinders the orbital decay by scattering the MBH in the galaxy outskirts. The latter occurs more rarely, suggesting that galactic bars overall promote MBH inspiral and binary coalescence. The orbital decay time can be an order of magnitude shorter than what would be predicted relying on dynamical friction alone. The stochasticity and the important role of global torques have crucial implications for the rates of MBH coalescences in the early Universe: both have to be accounted for when making predictions for the upcoming LISA observatory.
Repeated mergers and ejection of black holes within nuclear star clusters
Authors: Fragione Giacomo , Silk Joseph 
Published: August 2020

ABSTRACT
Current stellar evolution models predict a dearth of black holes (BHs) with masses $\gtrsim \! 50\, \rm M_\odot$ and $\lesssim \! 5\, \rm M_\odot$, and intermediate-mass black holes (IMBHs; $\sim \! 10^2\!-\! 10^5\rm\, M_\odot$) have not yet been detected beyond any reasonable doubt. A natural way to form massive BHs is through repeated mergers, detectable via gravitational wave emission with current LIGO/Virgo or future LISA and ET observations. Nuclear star clusters (NSCs) have masses and densities high enough to retain most of the merger products, which acquire a recoil kick at the moment of merger. We explore the possibility that IMBHs may be born as a result of repeated mergers in NSCs, and show how their formation pathways depend on the NSC mass and density, and BH spin distribution. We find that BHs in the pair-instability mass gap can be formed and observed by LIGO/Virgo, and show that the typical mass of the ejected massive BHs is 400–$500\, \rm M_\odot$, with velocities of up to a few thousand $\, \rm km\, s^{-1}$. Eventually, some of these IMBHs can become the seeds of supermassive BHs, observed today in the centres of galaxies. In dwarf galaxies, they could potentially solve the abundance, core-cusp, too-big-to-fail, ultra-faint, and baryon-fraction issues via plausible feedback scenarios.
On the expanding roles of tRNA fragments in modulating cell behavior
Authors: Magee Rogan , Rigoutsos Isidore 
Published: August 2020

AbstractThe fragments that derive from transfer RNAs (tRNAs) are an emerging category of regulatory RNAs. Known as tRFs, these fragments were reported for the first time only a decade ago, making them a relatively recent addition to the ever-expanding pantheon of non-coding RNAs. tRFs are short, 16–35 nucleotides (nts) in length, and produced through cleavage of mature and precursor tRNAs at various positions. Both cleavage positions and relative tRF abundance depend strongly on context, including the tissue type, tissue state, and disease, as well as the sex, population of origin, and race/ethnicity of an individual. These dependencies increase the urgency to understand the regulatory roles of tRFs. Such efforts are gaining momentum, and comprise experimental and computational approaches. System-level studies across many tissues and thousands of samples have produced strong evidence that tRFs have important and multi-faceted roles. Here, we review the relevant literature on tRF biology in higher organisms, single cell eukaryotes, and prokaryotes.
A ribosomal RNA fragment with 2′,3′-cyclic phosphate and GTP-binding activity acts as RIG-I ligand
Authors: Jung Stephanie , von Thülen Tina , Yang Ines , Laukemper Viktoria , Rupf Benjamin , Janga Harshavardhan , Panagiotidis Georgios-Dimitrios , Schoen Andreas , Nicolai Marina , Schulte Leon N , Obermann Hannah-Lena , Weber Friedemann , Kaufmann Andreas , Bauer Stefan 
Published: August 2020

Abstract
The RNA helicase RIG-I plays a key role in sensing pathogen-derived RNA. Double-stranded RNA structures bearing 5′-tri- or diphosphates are commonly referred to as activating RIG-I ligands. However, endogenous RNA fragments generated during viral infection via RNase L also activate RIG-I. Of note, RNase-digested RNA fragments bear a 5′-hydroxyl group and a 2′,3′-cyclic phosphate. How endogenous RNA fragments activate RIG-I despite the lack of 5′-phosphorylation has not been elucidated. Here we describe an endogenous RIG-I ligand (eRL) that is derived from the internal transcribed spacer 2 region (ITS2) of the 45S ribosomal RNA after partial RNase A digestion in vitro, RNase A protein transfection or RNase L activation. The immunostimulatory property of the eRL is dependent on 2′,3′-cyclic phosphate and its sequence is characterized by a G-quadruplex containing sequence motif mediating guanosine-5′-triphosphate (GTP) binding. In summary, RNase generated self-RNA fragments with 2′,3′-cyclic phosphate function as nucleotide-5′-triphosphate binding aptamers activating RIG-I.
Replisome bypass of transcription complexes and R-loops
Authors: Brüning Jan-Gert , Marians Kenneth J 
Published: August 2020

AbstractThe vast majority of the genome is transcribed by RNA polymerases. G+C-rich regions of the chromosomes and negative superhelicity can promote the invasion of the DNA by RNA to form R-loops, which have been shown to block DNA replication and promote genome instability. However, it is unclear whether the R-loops themselves are sufficient to cause this instability or if additional factors are required. We have investigated replisome collisions with transcription complexes and R-loops using a reconstituted bacterial DNA replication system. RNA polymerase transcription complexes co-directionally oriented with the replication fork were transient blockages, whereas those oriented head-on were severe, stable blockages. On the other hand, replisomes easily bypassed R-loops on either template strand. Replication encounters with R-loops on the leading-strand template (co-directional) resulted in gaps in the nascent leading strand, whereas lagging-strand template R-loops (head-on) had little impact on replication fork progression. We conclude that whereas R-loops alone can act as transient replication blocks, most genome-destabilizing replication fork stalling likely occurs because of proteins bound to the R-loops.
NCBP3 positively impacts mRNA biogenesis
Authors: Dou Yuhui , Barbosa Isabelle , Jiang Hua , Iasillo Claudia , Molloy Kelly R , Schulze Wiebke Manuela , Cusack Stephen , Schmid Manfred , Le Hir Hervé , LaCava John , Jensen Torben Heick 
Published: August 2020

AbstractThe nuclear Cap-Binding Complex (CBC), consisting of Nuclear Cap-Binding Protein 1 (NCBP1) and 2 (NCBP2), associates with the nascent 5′cap of RNA polymerase II transcripts and impacts RNA fate decisions. Recently, the C17orf85 protein, also called NCBP3, was suggested to form an alternative CBC by replacing NCBP2. However, applying protein–protein interaction screening of NCBP1, 2 and 3, we find that the interaction profile of NCBP3 is distinct. Whereas NCBP1 and 2 identify known CBC interactors, NCBP3 primarily interacts with components of the Exon Junction Complex (EJC) and the TRanscription and EXport (TREX) complex. NCBP3-EJC association in vitro and in vivo requires EJC core integrity and the in vivo RNA binding profiles of EJC and NCBP3 overlap. We further show that NCBP3 competes with the RNA degradation factor ZC3H18 for binding CBC-bound transcripts, and that NCBP3 positively impacts the nuclear export of polyadenylated RNAs and the expression of large multi-exonic transcripts. Collectively, our results place NCBP3 with the EJC and TREX complexes in supporting mRNA expression.
Thirdhand Smoke Contamination and Infant Nicotine Exposure in a Neonatal Intensive Care Unit: An Observational Study
Authors: Northrup Thomas F , Stotts Angela L , Suchting Robert , Khan Amir M , Green Charles , Klawans Michelle R , Quintana Penelope J E , Hoh Eunha , Hovell Melbourne F , Matt Georg E 
Published: August 2020

Abstract

Introduction
Thirdhand smoke (THS) is ultrafine particulate matter and residue resulting from tobacco combustion, with implications for health-related harm (eg, impaired wound healing), particularly among hospitalized infants. Project aims were to characterize nicotine (THS proxy) transported on neonatal intensive care unit (NICU) visitors and deposited on bedside furniture, as well as infant exposure.

Methods
Cross-sectional data were collected from participants in a metropolitan NICU. Participants completed a survey and carbon monoxide breath sample, and 41.9% (n = 88) of participants (n = 210) were randomly selected for finger-nicotine wipes during a study phase when all bedside visitors were screened for nicotine use and finger-nicotine levels. During an overlapping study phase, 80 mother–infant dyads consented to bedside furniture-nicotine wipes and an infant urine sample (for cotinine analyses).

Results
Most nonstaff visitors’ fingers had nicotine above the limit of quantification (&gt;LOQ; 61.9%). Almost all bedside furniture surfaces (93.8%) and infant cotinine measures (93.6%) had values &gt;LOQ, regardless of household nicotine use. Participants who reported using (or lived with others who used) nicotine had greater furniture-nicotine contamination (Mdn = 0.6 [interquartile range, IQR = 0.2–1.6] µg/m2) and higher infant cotinine (Mdn = 0.09 [IQR = 0.04–0.25] ng/mL) compared to participants who reported no household-member nicotine use (Mdn = 0.5 [IQR = 0.2–0.7] µg/m2; Mdn = 0.04 [IQR = 0.03–0.07] ng/mL, respectively). Bayesian univariate regressions supported hypotheses that increased nicotine use/exposure correlated with greater nicotine contamination (on fingers/furniture) and infant THS exposure.

Conclusions
Potential furniture-contamination pathways and infant-exposure routes (eg, dermal) during NICU hospitalization were identified, despite hospital prohibitions on tobacco/nicotine use. This work highlights the surreptitious spread of nicotine and potential THS-related health risks to vulnerable infants during critical stages of development.

Implications
THS contamination is underexplored in medical settings. Infants who were cared for in the NICU are vulnerable to health risks from THS exposure. This study demonstrated that 62% of nonstaff NICU visitors transport nicotine on their fingers to the NICU. Over 90% of NICU (bedside) furniture was contaminated with nicotine, regardless of visitors’ reported household-member nicotine use or nonuse. Over 90% of infants had detectable levels of urinary cotinine during NICU hospitalizations. Results justify further research to better protect infants from unintended THS exposure while hospitalized.
Regulation of DELLA Proteins by Post-translational Modifications
Authors: Blanco-Touri��n Noel , Serrano-Mislata Antonio , Alabad� David 
Published: August 2020

AbstractDELLA proteins are the negative regulators of the gibberellin (GA) signaling pathway. GAs have a pervasive effect on plant physiology, influencing processes that span the entire life cycle of the plant. All the information encoded by GAs, either environmental or developmental in origin, is canalized through DELLAs, which modulate the activity of many transcription factors and transcriptional regulators. GAs unlock the signaling pathway by triggering DELLA polyubiquitination and degradation by the 26S proteasome. Recent reports indicate, however, that there are other pathways that trigger DELLA polyubiquitination and degradation independently of GAs. Moreover, results gathered during recent years indicate that other post-translational modifications (PTMs), namely phosphorylation, SUMOylation and glycosylation, modulate DELLA function. The convergence of several PTMs in DELLA therefore highlights the strict regulation to which these proteins are subject. In this review, we summarize these discoveries and discuss DELLA PTMs from an evolutionary perspective and examine the possibilities these and other post-translational regulations offer to improve DELLA-dependent agronomic traits.
Hypogammaglobulinemia after rituximab for rheumatoid arthritis is not rare and is related with good response: 13 years real-life experience
Authors: Evangelatos Gerasimos , Fragoulis George E , Klavdianou Kalliopi , Moschopoulou Melina , Vassilopoulos Dimitrios , Iliopoulos Alexios 
Published: August 2020

Abstract

Objectives
Rituximab (RTX) use in the treatment of RA can be complicated by decrease in IgG, IgM or IgA levels (hypogammaglobulinemia-HGG). The aim of this study was to define the frequency of HGG in RA patients treated with RTX and to identify associations between its occurrence and patients’ characteristics, disease outcomes and serious infections rate.

Methods
RA patients treated with RTX in two rheumatology centers from January 2007 to January 2020 were retrospectively examined. Demographical, clinical and laboratory parameters were recorded at baseline and at last visit.

Results
Eighty-three patients (84.3% females) with a mean age of 63.2 years were enrolled. They had baseline DAS28(CRP) of 5.2  (1.1) and received a median (range) of 8 (2–20) RTX cycles. A total of 43.4%, 24.1% and 31.3% developed ‘any HGG’, ‘low IgG’ and ‘low IgM’, respectively. Lower baseline IgG and IgM levels were predictors of ‘low IgG’ and ‘low IgM’ occurrence, respectively. Patients who developed ‘low IgM’ exhibited lower DAS28(CRP) and increased rates of remission and low disease activity compared with those with normal IgM levels. Patients who maintained normal IgG were receiving methotrexate more frequently. No differences were observed in serious infections rate among subgroups.

Conclusion
HGG occurred in 43% of RTX-treated patients. Patients who developed low IgG or low IgM had lower baseline levels than those who did not. Concomitant DMARD and corticosteroid therapy was not associated with HGG. Low IgM, but not low IgG, development was associated with better disease outcomes. HGG was not associated with an increased incidence of serious infections.
EFFECTIVE INDOOR DOSE OF GAMMA RADIATION FROM BUILDING MATERIALS: COMPARISON OF SEVERAL METHODS FOR ESTIMATION AND POSSIBLE UNDERESTIMATE
Authors: Krmar M , Milić K , Arsenić I , Hansman J 
Published: August 2020

Abstract
This paper compares several methods for estimation of the effective indoor dose of gamma radiation from building materials. It was found that specific dose ratios proposed for 3 cm thick layers in one recommendation gives 2.8 times lower value of gamma dose than other methods. The most common case is that granite has an elevated content of natural radionuclides and it is usually used in the form of decorative layers. If the decision about restricted or non-restricted use of granite as a building material is based on method which underestimate gamma dose, there is reasonable concern that materials having elevated concentrations of natural radionuclides than allowed will be used in dwellings. In addition, it is pointed out that existing regulations allow in some cases non-restricted use of building materials even in the case when their activity concentrations exceed exception limits.
Multivariate model for cooperation: bridging social physiological compliance and hyperscanning
Authors: Sciaraffa Nicolina , Liu Jieqiong , Aricò Pietro , Flumeri Gianluca Di , Inguscio Bianca M S , Borghini Gianluca , Babiloni Fabio 
Published: August 2020

AbstractThe neurophysiological analysis of cooperation has evolved over the past 20 years, moving towards the research of common patterns in neurophysiological signals of people interacting. Social physiological compliance (SPC) and hyperscanning represent two frameworks for the joint analysis of autonomic and brain signals, respectively. Each of the two approaches allows to know about a single layer of cooperation according to the nature of these signals: SPC provides information mainly related to emotions, and hyperscanning that related to cognitive aspects. In this work, after the analysis of the state of the art of SPC and hyperscanning, we explored the possibility to unify the two approaches creating a complete neurophysiological model for cooperation considering both affective and cognitive mechanisms We synchronously recorded electrodermal activity, cardiac and brain signals of 14 cooperative dyads. Time series from these signals were extracted, and multivariate Granger causality was computed. The results showed that only when subjects in a dyad cooperate there is a statistically significant causality between the multivariate variables representing each subject. Moreover, the entity of this statistical relationship correlates with the dyad’s performance. Finally, given the novelty of this approach and its exploratory nature, we provided its strengths and limitations.
Integrating immunotherapy in the (neo)adjuvant setting of early breast cancer
Authors: Chan Jack J. , Tan Tira J.Y. , Dent Rebecca A. 
Published: August 2020

Purpose of review
Breast cancer is a relative latecomer in the success story of immuno-oncology. In this review, we focus on the preclinical and clinical lines of evidence to justify the evaluation of immune checkpoint inhibition (ICI) for the curative-intent treatment of breast cancer, the latest and ongoing trials of (neo)adjuvant immunotherapy, and practical considerations in clinical practice associated with this new treatment paradigm.

Recent findings
Insights from the immunobiology of breast cancer have paved the way for the new frontier of immunotherapy in this malignancy, starting from advanced stages and moving onto curable cases. Tumor-infiltrating lymphocyte quantification and PD-L1 immunohistochemistry are forerunners of predictive biomarkers for sensitivity to ICI in breast cancers. Preliminary results from phase III trials of combinatorial immunochemotherapy to treat early high-risk or locally advanced triple-negative breast cancer are encouraging for pathological complete response. Additional efficacy and patient-reported outcomes of (neo)adjuvant immunochemotherapy trials are awaited.

Summary
The prospect of integrating ICI in the treatment of early-stage breast cancer is promising. Questions regarding patient selection, the choice of ICI agent and combination partner in escalation strategies, sequencing and duration of treatments, cost-effectiveness and mechanisms of resistance remain to be answered by future research.
Child Temperament Outcomes After Laser Surgery for Twin-Twin Transfusion Syndrome
Authors: Chmait Hikmat R. , Chon Andrew H. , Korst Lisa M. , Putnam Samuel P. , Llanes Arlyn , Vanderbilt Douglas L. 
Published: August 2020

ABSTRACT:

Objective:
Twin-twin transfusion syndrome (TTTS) is a severe pregnancy complication of monochorionic (identical) twins that results in markedly discordant in utero environments for each twin. The aim of this study was to test for differences in temperament between former donor (hypovolemic, smaller) and recipient (hypervolemic, larger) twins with TTTS.

Methods:
Parents of dual survivors aged 3 to 7 years who underwent in utero laser surgery for TTTS were surveyed using the Children's Behavior Questionnaire-Very Short Form (CBQ-VSF). The CBQ-VSF assessed 3 traits: Surgency, Negative Affect, and Effortful Control. Differences in traits between donor and recipients were assessed using a paired t test.

Results:
We studied 85 twin pairs treated in utero for TTTS. There were no statistically significant differences in Surgency, Negative Affect, or Effortful Control between recipients and donors, although score differences for each trait varied widely among sibling pairs.

Conclusion:
Despite varied in utero environments, no temperament differences between donor and recipient monozygotic twins were found for the population as a whole. This finding may be of some reassurance to parents whose pregnancies are complicated by TTTS.
Effectiveness of a 595-nm Pulsed Dye Laser for the Treatment of Basal Cell Carcinoma Using One Double-Stacked Pulse Session: A Randomized, Double-Blinded Controlled Trial
Authors: Chow Maggie , Eimpunth Sasima , Hamman Michael Shane , Jiang Shang I. Brian 
Published: August 2020

BACKGROUND
Surgical and nonsurgical methods are used for treating basal cell carcinoma (BCC). Few randomized controlled trials exist on the effectiveness of the pulsed dye laser (PDL) on BCC treatment.

OBJECTIVE
We investigated the effectiveness of PDL treatment in a single session for the management of nodular and superficial BCCs on the trunk and extremities of adults using a randomized, double-blind, controlled technique.

METHODS
We used settings of fluence 7.5 J/cm2, 3-ms pulse duration, no dynamic cooling, 10-mm spot size, 10% overlap between pulses, and 2 stacked pulses on a 595-nm wavelength laser. Histopathologic clearance on excision of tumor with 4-mm margins was the primary outcome measure.

RESULTS
Twenty-four patients were included in the study, with 14 in the laser treatment group and 10 patients in the sham/control group. In total, 10/14 (71.4%) of the tumors in the treatment group were successfully treated with no residual tumor on excisional specimen histology, compared with 3/10 (30.0%) of the control group (p = .045).

CONCLUSION
Our study shows that PDL may be an effective treatment for low-risk BCCs of the trunk and extremities, but the cure rate is lower than those of other treatments for BCC. Thus, PDL under the current settings cannot be recommended.
Anatomic Characteristics and Treatment of the Midcheek Groove by Deep Filling
Authors: Du Yuyang , Zhong Yuan , Wang Zhizhou , Sui Hongjin , Luo Sai 
Published: August 2020

BACKGROUND
Because the anatomic mechanisms underlying the formation of the midcheek groove are unclear, treatments to date have resulted in unsatisfactory outcomes.

OBJECTIVE
This study investigated the anatomical foundation of the midcheek groove and evaluated appropriate treatment methods.

MATERIALS AND METHODS
Six cadaver hemifacial specimens were subjected to gross anatomic dissection and 6 to P45 sheet plastination. Based on the anatomic results, the area under the orbicularis oculi muscle (OOM) was selected for deep filling. Patients were evaluated by measuring 3D depth, regrading, and self-assessment.

RESULTS
The medial band was observed to be an important structure of the OOM, with the facial projection overlapping the midcheek groove trace. Two of the 6 P45 specimens were found to have compact fibroelastic bundles (CFBs) between the medial band and the dermis. Deep filling of the area under the OOM significantly reduced the depth of each section in all 34 patients (p < .001). Grades 3 and 4 midcheek grooves were downgraded distinctively. Most subjects expressed satisfaction with outcomes.

CONCLUSION
Formation of the midcheek groove is associated with the passage of CFBs. Deep filling of the area under the OOM effectively improves the midcheek grooves.