bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Backwards-step for Gillick: Trans Children’s Inability to Consent to Treatment for Gender Dysphoria—Quincy Bell & Mrs A v The Tavistock and Portman NHS Foundation Trust and Ors [2020] EWHC 3274 (Admin)
Authors: Moreton Kirsty L. 
Published: June 2021

Abstract
The case of Quincy Bell & Mrs A v The Tavistock and Portman NHS Foundation Trust and Ors is a judicial review into the treatment practices of the Gender Identity Development Service (GIDS) run by Tavistock and Portman NHS Foundation Trust (Tavistock). The Divisional Court considered whether children and young people with Gender Dysphoria (GD) can ever be Gillick competent to consent to treatment with Puberty Blockers (PBs), and if so whether GIDS provided sufficient information to support an informed consent. This commentary examines the six key areas of the judgment: the nature of GD and its treatment with PBs; the categorisation of PBs as experimental treatment; the high bar set to achieve Gillick competence; the convergence of information provision and competence; the role of parental consent; and finally the protective jurisdiction of the court. The conclusion of the court that transgender children aged under 16 years will find ‘enormous difficulties’ in reaching the Gillick threshold to be able to consent to PBs, and that even 16- to 17-year olds would benefit from a ‘best interests determination’ from the court, signals judicial thinking which is markedly protectionist. Considering the broad contemporary stance in healthcare of facilitating competence, valuing patient participation, and respecting rights, I argue that this judgment is out of step. It has implications not only for transgender children, but it may also be a worrying signal of a greater general retreat from Gillick and a corresponding advance in emphasis on judicially determined best interests.
Galaxy clustering in harmonic space from the dark energy survey year 1 data: compatibility with real-space results
Authors: Andrade-Oliveira F , Camacho H , Faga L , Gomes R , Rosenfeld R , Troja A , Alves O , Doux C , Elvin-Poole J , Fang X , Friedrich O , Kokron N , Lima M , Miranda V , Pandey S , Porredon A , Sanchez J , Aguena M , Allam S , Annis J , Avila S , Bertin E , Brooks D , Burke D L , Carrasco Kind M , Carretero J , Cawthon R , Chang C , Choi A , Costanzi M , Crocce M , da Costa L N , Pereira M E S , Desai S , Diehl H T , Doel P , Drlica-Wagner A , Everett S , Evrard A E , Ferrero I , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Hinton S R , Hollowood D L , Jain B , James D J , Kuropatkin N , Lahav O , MacCrann N , Maia M A G , March M , Melchior P , Menanteau F , Miquel R , Morgan R , Myles J , Ogando R L C , Palmese A , Paz-Chinchón F , Plazas Malagón A A , Rodriguez-Monroy M , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Soares-Santos M , Suchyta E , Tarle G , To C ,   DES Collaboration
Published: June 2021

ABSTRACT
We perform an analysis in harmonic space of the Dark Energy Survey Year 1 Data (DES-Y1) galaxy clustering photometric data using products obtained for the real-space analysis. We test our pipeline with a suite of lognormal simulations, which are used to validate scale cuts in harmonic space as well as to provide a covariance matrix that takes into account the DES-Y1 mask. We then apply this pipeline to DES-Y1 data taking into account survey property maps derived for the real-space analysis. We compare with real-space DES-Y1 results obtained from a similar pipeline. We show that the harmonic space analysis we develop yields results that are compatible with the real-space analysis for the bias parameters. This verification paves the way to performing a harmonic space analysis for the upcoming DES-Y3 data.
SNe and their impact during the early evolution of Type I Globular Clusters
Authors: Jiménez Santiago , Tenorio-Tagle Guillermo , Silich Sergiy 
Published: June 2021

ABSTRACT
The iron composition of globular clusters (GCs) is homogeneous in all but a few massive clusters, despite the presence of multiple stellar populations. Hence, most if not all the supernovae (SN) ejecta was not used to form stars. Here by means of semi-analytic and numerical studies we address this issue considering both stellar winds and supernovae feedback during the early evolution of proto-globular clusters. We calculate the ability of stellar winds to form a global wind that removes the gas left over from star formation. The innermost radius from which such a global wind can be formed, the superwind radius RSW, is a function of the cloud parameters and the star formation efficiency. In the case of complete gas expulsion (RSW = 0), the SN ejecta merge with shock-heated winds and exit the cluster. On the other hand, when RSW &gt; 0, supernova remnants (SNRs) become pressure-confined if evolving within a critical radius Rblow, and mix their products with the residual gas. However, outside of this central zone the SNRs experience blowout. In such cases, the thermalized ejecta escapes the cluster, making the SN products unavailable for the formation of new stars. We estimated the metallicity enhancement (Δ[Fe/H]) of the leftover gas and discuss the conditions required to produce secondary stellar populations with Δ[Fe/H] in the range observed in the majority of GCs.
The origins of off-centre massive black holes in dwarf galaxies
Authors: Bellovary Jillian M , Hayoune Sarra , Chafla Katheryn , Vincent Donovan , Brooks Alyson , Christensen Charlotte R , Munshi Ferah D , Tremmel Michael , Quinn Thomas R , Van Nest Jordan , Sligh Serena K , Luzuriaga Michelle 
Published: June 2021

ABSTRACT
Massive black holes often exist within dwarf galaxies, and both simulations and observations have shown that a substantial fraction of these may be off-centre with respect to their hosts. We trace the evolution of off-centre massive black holes (MBHs) in dwarf galaxies using cosmological hydrodynamical simulations, and show that the reason for off-centre locations is mainly due to galaxy–galaxy mergers. We calculate dynamical time-scales and show that off-centre MBHs are unlikely to sink to their galaxys’ centres within a Hubble time, due to the shape of the hosts’ potential wells and low stellar densities. These wandering MBHs are unlikely to be detected electromagnetically, nor is there a measurable dynamical effect on the galaxy’s stellar population. We conclude that off-centre MBHs may be common in dwarfs, especially if the mass of the MBH is small or the stellar mass of the host galaxy is large. However, detecting them is extremely challenging, because their accretion luminosities are very low and they do not measurably alter the dynamics of their host galaxies.
Chemical signatures of a warped protoplanetary disc
Authors: Young Alison K , Alexander Richard , Walsh Catherine , Nealon Rebecca , Booth Alice , Pinte Christophe 
Published: June 2021

ABSTRACT
Circumstellar discs may become warped or broken into distinct planes if there is a stellar or planetary companion with an orbit that is misaligned with respect to the disc. There is mounting observational evidence for protoplanetary discs with misaligned inner discs and warps that may be caused by such interactions with a previously undetected companion, giving us a tantalizing indication of possible planets forming there. Hydrodynamical and radiative transfer models indicate that the temperature varies azimuthally in warped discs due to the variable angle at which the disc surface faces the star and this impacts the disc chemistry. We perform chemical modelling based on a hydrodynamical model of a protoplanetary disc with an embedded planet orbiting at a 12° inclination to the disc. Even for this small misalignment, abundances of species including CO and HCO+ vary azimuthally and this results in detectable azimuthal variations in submillimetre line emission. Azimuthal variations in line emission may therefore indicate the presence of an unseen embedded companion. Non-axisymmetric chemical abundances should be considered when interpreting molecular line maps of warped or shadowed protoplanetary discs.
Establishment of a specific in vivo Cu(Ⅰ) reporting system based on metallothionein screening
Authors: Ma Mingjun , Qiu Botao , Jin Jing , Wang Jiaru , Nie Yuzhe , Liang Yang , Yu Ze , Teng Chun-Bo 
Published: June 2021

Abstract
Copper is one of the indispensable trace metal elements in organisms, but excess copper means cytotoxicity. Cells protect themselves by storing excess copper in copper-binding proteins. Metallothioneins (MTs) are a group of low-molecular-weight, cysteine-rich proteins, which are well known in sensing and binding the overcharged Zn(Ⅱ), Cd(Ⅱ), and Cu(Ⅰ) in cells. However, there are few reports on MTs that can specifically respond to intracellular copper ions in mammals in real-time. Here, we screened copper-response MTs in pancreatic cancer cells through data-mining, RNA-seq, and qPCR analysis. We found that MT1E, MT1F, and MT1X mRNA were significantly upregulated after exogenous copper ions induction. By constructing the stable cell lines with MT1E, MT1F, or MT1X promoter-driven EGFP as reporters, we found that only PMT1F-EGFP could specifically and stably report the intracellular Cu(Ⅰ) changes in multiple cell lines, including Panc-1, 8988T, 293T, HepG2, and normal hepatic cells, indicating that PMT1F-EGFP is an ideal in vivo Cu(Ⅰ) reporter. Using the PMT1F-EGFP reporter, we found that MEK inhibitors (U0126) and Astragaloside IV could significantly increase intracellular copper ions. According to these results, that PMT1F-EGFP reporter can sense intracellular copper change and can be used to screen copper-target drugs and study copper-related cellular physiology and pathology.
INO80 promotes H2A.Z occupancy to regulate cell fate transition in pluripotent stem cells
Authors: Yu Hongyao , Wang Jiajia , Lackford Brad , Bennett Brian , Li Jian-liang , Hu Guang 
Published: June 2021

AbstractThe INO80 chromatin remodeler is involved in many chromatin-dependent cellular functions. However, its role in pluripotency and cell fate transition is not fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the transition toward and maintenance of the primed state. In the naïve state, INO80 pre-marked gene promoters that would adopt bivalent histone modifications by H3K4me3 and H3K27me3 upon transition into the primed state. In the primed state, in contrast to its known role in H2A.Z exchange, INO80 promoted H2A.Z occupancy at these bivalent promoters and facilitated H3K27me3 installation and maintenance as well as downstream gene repression. Together, our results identified an unexpected function of INO80 in H2A.Z deposition and gene regulation. We showed that INO80-dependent H2A.Z occupancy is a critical licensing step for the bivalent domains, and thereby uncovered an epigenetic mechanism by which chromatin remodeling, histone variant deposition and histone modification coordinately control cell fate.
The dynamic cycle of bacterial translation initiation factor IF3
Authors: Nakamoto Jose A , Evangelista Wilfredo , Vinogradova Daria S , Konevega Andrey L , Spurio Roberto , Fabbretti Attilio , Milón Pohl 
Published: June 2021

Abstract
Initiation factor IF3 is an essential protein that enhances the fidelity and speed of bacterial mRNA translation initiation. Here, we describe the dynamic interplay between IF3 domains and their alternative binding sites using pre-steady state kinetics combined with molecular modelling of available structures of initiation complexes. Our results show that IF3 accommodates its domains at velocities ranging over two orders of magnitude, responding to the binding of each 30S ligand. IF1 and IF2 promote IF3 compaction and the movement of the C-terminal domain (IF3C) towards the P site. Concomitantly, the N-terminal domain (IF3N) creates a pocket ready to accept the initiator tRNA. Selection of the initiator tRNA is accompanied by a transient accommodation of IF3N towards the 30S platform. Decoding of the mRNA start codon displaces IF3C away from the P site and rate limits translation initiation. 70S initiation complex formation brings IF3 domains in close proximity to each other prior to dissociation and recycling of the factor for a new round of translation initiation. Altogether, our results describe the kinetic spectrum of IF3 movements and highlight functional transitions of the factor that ensure accurate mRNA translation initiation.
Directed evolution of orthogonal RNA–RBP pairs through library-vs-library in vitro selection
Authors: Fukunaga Keisuke , Yokobayashi Yohei 
Published: June 2021

Abstract
RNA-binding proteins (RBPs) and their RNA ligands play many critical roles in gene regulation and RNA processing in cells. They are also useful for various applications in cell biology and synthetic biology. However, re-engineering novel and orthogonal RNA–RBP pairs from natural components remains challenging while such synthetic RNA–RBP pairs could significantly expand the RNA–RBP toolbox for various applications. Here, we report a novel library-vs-library in vitro selection strategy based on Phage Display coupled with Systematic Evolution of Ligands by EXponential enrichment (PD-SELEX). Starting with pools of 1.1 × 1012 unique RNA sequences and 4.0 × 108 unique phage-displayed L7Ae-scaffold (LS) proteins, we selected RNA–RBP complexes through a two-step affinity purification process. After six rounds of library-vs-library selection, the selected RNAs and LS proteins were analyzed by next-generation sequencing (NGS). Further deconvolution of the enriched RNA and LS protein sequences revealed two synthetic and orthogonal RNA–RBP pairs that exhibit picomolar affinity and &gt;4000-fold selectivity.
Discovery of a pre-mRNA structural scaffold as a contributor to the mammalian splicing code
Authors: Saha Kaushik , Fernandez Mike Minh , Biswas Tapan , Joseph Simpson , Ghosh Gourisankar 
Published: June 2021

Abstract
The specific recognition of splice signals at or near exon-intron junctions is not explained by their weak conservation and instead is postulated to require a multitude of features embedded in the pre-mRNA strand. We explored the possibility of 3D structural scaffold of AdML—a model pre-mRNA substrate—guiding early spliceosomal components to the splice signal sequences. We find that mutations in the non-cognate splice signal sequences impede recruitment of early spliceosomal components due to disruption of the global structure of the pre-mRNA. We further find that the pre-mRNA segments potentially interacting with the early spliceosomal component U1 snRNP are distributed across the intron, that there is a spatial proximity of 5′ and 3′ splice sites within the pre-mRNA scaffold, and that an interplay exists between the structural scaffold and splicing regulatory elements in recruiting early spliceosomal components. These results suggest that early spliceosomal components can recognize a 3D structural scaffold beyond the short splice signal sequences, and that in our model pre-mRNA, this scaffold is formed across the intron involving the major splice signals. This provides a conceptual basis to analyze the contribution of recognizable 3D structural scaffolds to the splicing code across the mammalian transcriptome.
Fear Avoidance Beliefs Are Associated With Perceived Disability in Persons With Vestibular Disorders
Authors: Dunlap Pamela M , Sparto Patrick J , Marchetti Gregory F , Furman Joseph M , Staab Jeffrey P , Delitto Anthony , Klatt Brooke N , Whitney Susan L 
Published: June 2021

Abstract

Objective
The purpose of this study was to determine the association between fear-avoidance beliefs and disability in 3 months in people with vestibular disorders while accounting for demographic and clinical characteristics.

Methods
This prospective cohort study included people aged 18 to 100 years who reported dizziness. Participants were recruited from a balance disorders clinic and outpatient physical therapy clinics. All participants completed the Vestibular Activities Avoidance Instrument (VAAI) and the Hospital Anxiety and Depression Scale at baseline and the Vestibular Activities and Participation measure (VAP), dizziness Visual Analogue Scale (VAS), and 12-item Short Form Health Questionnaire at baseline and 3-month follow-up. A modified version of the VAAI included 9 items abstracted from the 81-item VAAI. The relationships between 9-item VAAI scores and follow-up measures of disability were assessed using Spearman correlation coefficients. Linear regression models were analyzed to determine the effect of fear-avoidance beliefs on follow-up VAP score while accounting for baseline outcome measures.

Results
All participants (n = 404) completed the baseline assessment (mean age = 54 years), and 286 (71%) completed the 3-month assessment. The mean 9-item VAAI score was 25 (SD = 14) at baseline and was significantly associated with VAP (ρ = 0.54), 12-item Short Form Health Questionnaire component scores (ρ = −0.53; −0.44), and dizziness VAS at follow-up (ρ = 0.37). Approximately 38% of the variation in VAP score at follow-up was predicted by age, number of medications, 9-item VAAI score, dizziness VAS, and Hospital Anxiety and Depression Scale-depression score when considered together (R2 = 0.38).

Conclusion
Fear-avoidance beliefs are associated with measures of disability at 3 months and are predictive of activity limitations and participation restrictions at 3 months when controlling for age, medications, baseline dizziness, and depression symptom severity in people with vestibular disorders.

Impact
Measurement of fear-avoidance beliefs may provide important prognostic information, suggesting that an assessment of fear-avoidance beliefs could be used by clinicians to identify individuals at greater risk of disability after a vestibular disorder.

Lay Summary
Fear-avoidance beliefs in people who have vestibular disorders are associated with disability at 3 months and predict limitations in daily activities at 3 months.
Fraud, specialization, and efficiency in peer review
Authors: Garcia J A , Rodriguez-Sanchez Rosa , Fdez-Valdivia J 
Published: June 2021

Abstract
Reviewers are humans and might be affected by cognitive biases when information overload comes into play. In fact, no amount of scientific training will completely mask the human impulses to partisanship. And the consequence is that authors may receive incorrect editorial decisions in their submissions to peer-reviewed journals. For instance, the journal editor issues a substantial revision when in fact a moderate one would suffice. This would be over-revision in peer review. In this situation, there exists a fraud cost if the journal editor tries to request the author to make a substantial revision when in fact a moderate one would be sufficient. Thus, in this article, we identify a set of conditions under which the peer review process involves equilibrium fraud and over-revision. An equilibrium in peer review is efficient if the first peer-reviewed journal to which the author submits their research paper makes a truthful editorial decision, which the author accepts. When the fraud cost is sufficiently high, there exists an efficient equilibrium. Otherwise, when the fraud cost cannot sustain an efficient equilibrium, it may arise a specialization equilibrium in which the author first submits the manuscript to a top journal which makes a truthful editorial decision. This specialization equilibrium may explain why academic journals with higher quality standards more often attract authors who write articles of higher quality. Finally, when the fraud cost is not too large, we show that a new type of equilibrium emerges in our model, equilibria involving costly fraud, in which the first peer-reviewed journal to which the research paper is submitted always requests substantial revisions. If the review time and the probability of very serious concerns from reviewers were large, the author would prefer to send the research paper to one single peer-reviewed journal even if that would involve over-revision. In the fraud equilibrium, the author’s revision cost is high and independent of the true quality of the manuscript.
The different responses of universities to introduction of performance-based research funding
Authors: Abramo Giovanni , D’Angelo Ciriaco Andrea 
Published: June 2021

Abstract
Governments and organizations design performance-based research funding systems (PBRFS) for strategic aims, such as to selectively allocate scarce resources and stimulate research efficiency. In this work, we analyze the relative change in research productivity of Italian universities after the introduction of such a system, featuring financial and reputational incentives. Using a bibliometric approach, we compare the relative research performance of universities before and after the introduction of PBRFS, at the overall, discipline and field levels. The findings show convergence in the universities’ performance, due above all to the remarkable improvement of the lowest performers. Geographically, the universities of the south (vs central and northern Italy) achieved the greatest improvement in relative performance. The methodology, and results, should be of use to university management and policy-makers.
New developments in Sjogren’s syndrome
Authors: Thalayasingam Nishanthi , Baldwin Kelly , Judd Claire , Ng Wan-Fai 
Published: June 2021

Abstract
SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely empirical and offer only symptomatic relief for patients. There are no proven treatments that alter disease progression or treat the systemic manifestations of disease. B-cell depletion is used in patients with systemic disease but its overall clinical efficacy has not been demonstrated in two large randomized controlled trials. Studies are now focussing on alternative strategies to target B-cells, including co-stimulation targets, with promising data. It is increasingly clear that clinical trials in SS will require patient stratification and relevant and sensitive outcome measures to identify successful treatment modalities.