bluuebunny/crossref_metadata_2025_split huggingface dataset:
OzDES reverberation mapping program: Lag recovery reliability for 6-yr C iv analysis
Authors: Penton A , Malik U , Davis T M , Martini P , Yu Z , Sharp R , Lidman C , Tucker B E , Hoormann J K , Aguena M , Allam S , Annis J , Asorey J , Bacon D , Bertin E , Bhargava S , Brooks D , Calcino J , Carnero Rosell A , Carollo D , Carrasco Kind M , Carretero J , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Diehl H T , Eifler T F , Everett S , Ferrero I , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kim A G , Kuehn K , Kuropatkin N , Maia M A G , Marshall J L , Menanteau F , Miquel R , Morgan R , Möller A , Palmese A , Paz-Chinchón F , Plazas A A , Romer A K , Sanchez E , Scarpine V , Scolnic D , Serrano S , Smith M , Suchyta E , Swanson M E C , Tarle G , To C , Uddin S A , Varga T N , Wester W , Wilkinson R D , Lewis G ,   (DES Collaboration)
Published: October 2021

ABSTRACT
We present the statistical methods that have been developed to analyse the OzDES reverberation mapping sample. To perform this statistical analysis we have created a suite of customizable simulations that mimic the characteristics of each source in the OzDES sample. These characteristics include: the variability in the photometric and spectroscopic light curves, the measurement uncertainties, and the observational cadence. By simulating the sources in the OzDES sample that contain the C iv emission line, we developed a set of criteria that rank the reliability of a recovered time-lag depending on the agreement between different recovery methods, the magnitude of the uncertainties, and the rate at which false positives were found in the simulations. These criteria were applied to simulated light curves and these results used to estimate the quality of the resulting Radius–Luminosity relation. We grade the results using three quality levels (gold, silver, and bronze). The input slope of the R–L relation was recovered within 1σ for each of the three quality samples, with the gold standard having the lowest dispersion with a recovered a R–L relation slope of 0.454 ± 0.016 with an input slope of 0.47. Future work will apply these methods to the entire OzDES sample of 771 AGN.
Characterizing the PAH emission in the Orion Bar
Authors: Knight C , Peeters E , Tielens A G G M , Vacca W D 
Published: October 2021

ABSTRACT
We present 5–14 $\mu$m spectra at two different positions across the Orion Bar photodissociation region (PDR) obtained with the Infrared Spectrograph onboard the Spitzer Space Telescope and 3.3 $\mu$m PAH observations obtained with the Stratospheric Observatory for Infrared Astronomy (SOFIA). We aim to characterize emission from Polycyclic Aromatic Hydrocarbon (PAH), dust, atomic and molecular hydrogen, argon, sulfur, and neon as a function of distance from the primary illuminating source. We find that all the major PAH bands peak between the ionization front and the PDR front, as traced by H2, while variations between these bands become more pronounced moving away from this peak into the face-on PDRs behind the PDR front and at the backside of the H ii region. While the relative PAH intensities are consistent with established PAH characteristics, we report unusual behaviours and attribute these to the PDR viewing angle and the strength of the FUV radiation field impinging on the PDRs. We determine the average PAH size which varies across the Orion Bar. We discuss subtle differences seen between the cationic PAH bands and highlight the photochemical evolution of carbonaceous species in this PDR environment. We find that PAHs are a good tracer of environmental properties such as the strength of the FUV radiation field and the PAH ionization parameter.
The search for the farthest quasar: consequences for black hole growth and seed models
Authors: Pacucci Fabio , Loeb Abraham 
Published: October 2021

ABSTRACT
The quest for high-redshift quasars has led to a series of record-breaking sources, with the current record holder at z = 7.642. Here, we show how future detections of z &gt; 8 quasars impact the constraints on the parameters for black hole growth and seed models. Using broad flat priors on the growth parameters (Eddington ratio $\, {f_{\rm Edd}}$, duty cycle ${\cal D}$, seed mass M•,seed, and radiative efficiency ϵ), we show that the large uncertainties in their determination decrease by a factor ∼5 when a quasar’s detection redshift goes from z = 9 to z = 12. In this high-redshift regime, ϵ tends to the lowest value allowed, and the distribution for M•,seed peaks well inside the heavy seed domain. Remarkably, two quasars detected at z &gt; 7 with low accretion rates (J1243+0100 and J0313–1806) already tighten the available parameter space, requiring $M_{\rm \bullet , seed} \gt 10^{3.5} \, {\rm M_\odot }$ and ϵ &lt; 0.1. The radiative efficiency is a crucial unknown, with factor ∼2 changes able to modify the predicted mass by ∼3 orders of magnitude already at z ∼ 9. The competing roles of inefficient accretion (decreasing ϵ) and black hole spin-up (increasing ϵ) significantly impact growth models. Finally, we suggest that yields currently predicted by upcoming quasar surveys (e.g. Euclid) will be instrumental for determining the most-likely seed mass regime. For example, assuming thin-disc accretion, a detection of a quasar with $M_\bullet \sim 10^{10} \, {\rm M_\odot }$ by z ∼ 9–10 would exclude the entire parameter space available for light seeds and dramatically reduce the one for heavy seeds.
Immunogenicity of sarilumab and impact on safety and efficacy in Japanese patients with rheumatoid arthritis: analysis of two Phase 3 randomised clinical trials
Authors: Tanaka Yoshiya , Takahashi Toshiya , Sumi Mariko , Hagino Owen , Van Hoogstraten Hubert , Xu Christine , Kato Naoto , Kameda Hideto 
Published: October 2021

ABSTRACT

Objectives
To describe the immunogenicity profile of sarilumab in Japanese patients with rheumatoid arthritis (RA).

Methods
Patients enrolled in the KAKEHASI and HARUKA studies were included in our analysis. In these studies, patients received sarilumab 150 mg or 200 mg every 2 weeks for 52 or 28 weeks in combination with methotrexate (MTX) (KAKEHASI), or for 52 weeks as monotherapy or in combination with non-MTX conventional synthetic disease-modifying anti-rheumatic drugs (HARUKA). Anti-drug antibodies (ADAs) and neutralising antibodies (NAbs) were assessed in the pooled population.

Results
Positive ADA assay responses occurred in 10/149 (7.1%) patients treated with sarilumab 150 mg and 13/185 (7.0%) patients treated with sarilumab 200 mg, with persistent responses in 2 (1.4%) and 4 (2.2%) patients, respectively. Peak ADA titre was 30. No patients treated with the 150 mg dose and one patient (0.5%) treated with the 200 mg dose exhibited NAbs. There was no evidence of an association between ADA formation and hypersensitivity reactions or reduced efficacy.

Conclusions
ADAs, which occurred at a low frequency and titre, did not affect the safety or efficacy of sarilumab 150 or 200 mg administered as monotherapy or combination therapy in Japanese patients with RA in the KAKEHASI or HARUKA studies.
Evolutionary repair reveals an unexpected role of the tRNA modification m1G37 in aminoacylation
Authors: Clifton Ben E , Fariz Muhammad A , Uechi Gen-Ichiro , Laurino Paola 
Published: October 2021

Abstract
The tRNA modification m1G37, introduced by the tRNA methyltransferase TrmD, is thought to be essential for growth in bacteria because it suppresses translational frameshift errors at proline codons. However, because bacteria can tolerate high levels of mistranslation, it is unclear why loss of m1G37 is not tolerated. Here, we addressed this question through experimental evolution of trmD mutant strains of Escherichia coli. Surprisingly, trmD mutant strains were viable even if the m1G37 modification was completely abolished, and showed rapid recovery of growth rate, mainly via duplication or mutation of the proline-tRNA ligase gene proS. Growth assays and in vitro aminoacylation assays showed that G37-unmodified tRNAPro is aminoacylated less efficiently than m1G37-modified tRNAPro, and that growth of trmD mutant strains can be largely restored by single mutations in proS that restore aminoacylation of G37-unmodified tRNAPro. These results show that inefficient aminoacylation of tRNAPro is the main reason for growth defects observed in trmD mutant strains and that proS may act as a gatekeeper of translational accuracy, preventing the use of error-prone unmodified tRNAPro in translation. Our work shows the utility of experimental evolution for uncovering the hidden functions of essential genes and has implications for the development of antibiotics targeting TrmD.
Chromatin loading of MCM hexamers is associated with di-/tri-methylation of histone H4K20 toward S phase entry
Authors: Hayashi-Takanaka Yoko , Hayashi Yuichiro , Hirano Yasuhiro , Miyawaki-Kuwakado Atsuko , Ohkawa Yasuyuki , Obuse Chikashi , Kimura Hiroshi , Haraguchi Tokuko , Hiraoka Yasushi 
Published: October 2021

AbstractDNA replication is a key step in initiating cell proliferation. Loading hexameric complexes of minichromosome maintenance (MCM) helicase onto DNA replication origins during the G1 phase is essential for initiating DNA replication. Here, we examined MCM hexamer states during the cell cycle in human hTERT-RPE1 cells using multicolor immunofluorescence-based, single-cell plot analysis, and biochemical size fractionation. Experiments involving cell-cycle arrest at the G1 phase and release from the arrest revealed that a double MCM hexamer was formed via a single hexamer during G1 progression. A single MCM hexamer was recruited to chromatin in the early G1 phase. Another single hexamer was recruited to form a double hexamer in the late G1 phase. We further examined relationship between the MCM hexamer states and the methylation levels at lysine 20 of histone H4 (H4K20) and found that the double MCM hexamer state was correlated with di/trimethyl-H4K20 (H4K20me2/3). Inhibiting the conversion from monomethyl-H4K20 (H4K20me1) to H4K20me2/3 retained the cells in the single MCM hexamer state. Non-proliferative cells, including confluent cells or Cdk4/6 inhibitor-treated cells, also remained halted in the single MCM hexamer state. We propose that the single MCM hexamer state is a halting step in the determination of cell cycle progression.
Probing the stability of the SpCas9–DNA complex after cleavage
Authors: Aldag Pierre , Welzel Fabian , Jakob Leonhard , Schmidbauer Andreas , Rutkauskas Marius , Fettes Fergus , Grohmann Dina , Seidel Ralf 
Published: October 2021

Abstract
CRISPR–Cas9 is a ribonucleoprotein complex that sequence-specifically binds and cleaves double-stranded DNA. Wildtype Cas9 and its nickase and cleavage-incompetent mutants have been used in various biological techniques due to their versatility and programmable specificity. Cas9 has been shown to bind very stably to DNA even after cleavage of the individual DNA strands, inhibiting further turnovers and considerably slowing down in-vivo repair processes. This poses an obstacle in genome editing applications. Here, we employed single-molecule magnetic tweezers to investigate the binding stability of different Streptococcus pyogenes Cas9 variants after cleavage by challenging them with supercoiling. We find that different release mechanisms occur depending on which DNA strand is cleaved. After initial target strand cleavage, supercoils are only removed after the collapse of the R-loop. We identified several states with different stabilities of the R-loop. Most importantly, we find that the post-cleavage state of Cas9 exhibits a higher stability than the pre-cleavage state. After non-target strand cleavage, supercoils are immediately but slowly released by swiveling of the non-target strand around Cas9 bound to the target strand. Consequently, Cas9 and its non-target strand nicking mutant stay stably bound to the DNA for many hours even at elevated torsional stress.
Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi
Authors: Liu Tianshuo , Pyle Anna M 
Published: October 2021

Abstract
Fungal pathogens represent an expanding global health threat for which treatment options are limited. Self-splicing group II introns have emerged as promising drug targets, but their development has been limited by a lack of information on their distribution and architecture in pathogenic fungi. To meet this challenge, we developed a bioinformatic workflow for scanning sequence data to identify unique RNA structural signatures within group II introns. Using this approach, we discovered a set of ubiquitous introns within thermally dimorphic fungi (genera of Blastomyces, Coccidioides and Histoplasma). These introns are the most biochemically reactive group II introns ever reported, and they self-splice rapidly under near-physiological conditions without protein cofactors. Moreover, we demonstrated the small molecule targetability of these introns by showing that they can be inhibited by the FDA-approved drug mitoxantrone in vitro. Taken together, our results highlight the utility of structure-based informatic searches for identifying riboregulatory elements in pathogens, revealing a striking diversity of reactive self-splicing introns with great promise as antifungal drug targets.
PharmacoDB 2.0: improving scalability and transparency of in vitro pharmacogenomics analysis
Authors: Feizi Nikta , Nair Sisira Kadambat , Smirnov Petr , Beri Gangesh , Eeles Christopher , Esfahani Parinaz Nasr , Nakano Minoru , Tkachuk Denis , Mammoliti Anthony , Gorobets Evgeniya , Mer Arvind Singh , Lin Eva , Yu Yihong , Martin Scott , Hafner Marc , Haibe-Kains Benjamin 
Published: October 2021

Abstract
Cancer pharmacogenomics studies provide valuable insights into disease progression and associations between genomic features and drug response. PharmacoDB integrates multiple cancer pharmacogenomics datasets profiling approved and investigational drugs across cell lines from diverse tissue types. The web-application enables users to efficiently navigate across datasets, view and compare drug dose–response data for a specific drug-cell line pair. In the new version of PharmacoDB (version 2.0, https://pharmacodb.ca/), we present (i) new datasets such as NCI-60, the Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) dataset, as well as updated data from the Genomics of Drug Sensitivity in Cancer (GDSC) and the Genentech Cell Line Screening Initiative (gCSI); (ii) implementation of FAIR data pipelines using ORCESTRA and PharmacoDI; (iii) enhancements to drug–response analysis such as tissue distribution of dose–response metrics and biomarker analysis; and (iv) improved connectivity to drug and cell line databases in the community. The web interface has been rewritten using a modern technology stack to ensure scalability and standardization to accommodate growing pharmacogenomics datasets. PharmacoDB 2.0 is a valuable tool for mining pharmacogenomics datasets, comparing and assessing drug–response phenotypes of cancer models.
msRepDB: a comprehensive repetitive sequence database of over 80 000 species
Authors: Liao Xingyu , Hu Kang , Salhi Adil , Zou You , Wang Jianxin , Gao Xin 
Published: October 2021

Abstract
Repeats are prevalent in the genomes of all bacteria, plants and animals, and they cover nearly half of the Human genome, which play indispensable roles in the evolution, inheritance, variation and genomic instability, and serve as substrates for chromosomal rearrangements that include disease-causing deletions, inversions, and translocations. Comprehensive identification, classification and annotation of repeats in genomes can provide accurate and targeted solutions towards understanding and diagnosis of complex diseases, optimization of plant properties and development of new drugs. RepBase and Dfam are two most frequently used repeat databases, but they are not sufficiently complete. Due to the lack of a comprehensive repeat database of multiple species, the current research in this field is far from being satisfactory. LongRepMarker is a new framework developed recently by our group for comprehensive identification of genomic repeats. We here propose msRepDB based on LongRepMarker, which is currently the most comprehensive multi-species repeat database, covering &gt;80 000 species. Comprehensive evaluations show that msRepDB contains more species, and more complete repeats and families than RepBase and Dfam databases. (https://msrepdb.cbrc.kaust.edu.sa/pages/msRepDB/index.html).
Genomicus in 2022: comparative tools for thousands of genomes and reconstructed ancestors
Authors: Nguyen Nga Thi Thuy , Vincens Pierre , Dufayard Jean François , Roest Crollius Hugues , Louis Alexandra 
Published: October 2021

Abstract
Genomicus is a database and web-server dedicated to comparative genomics in eukaryotes. Its main functionality is to graphically represent the conservation of genomic blocks between multiple genomes, locally around a specific gene of interest or genome-wide through karyotype comparisons. Since 2010 and its first release, Genomicus has synchronized with 60 Ensembl releases and seen the addition of functions that have expanded the type of analyses that users can perform. Today, five public instances of Genomicus are supporting a total number of 1029 extant genomes and 621 ancestral reconstructions from all eukaryotes kingdoms available in Ensembl and Ensembl Genomes databases complemented with four additional instances specific to taxonomic groups of interest. New visualization and query tools are described in this manuscript. Genomicus is freely available at http://www.genomicus.bio.ens.psl.eu/genomicus.
MLL1 is regulated by KSHV LANA and is important for virus latency
Authors: Tan Min , Li Shijun , Juillard Franceline , Chitas Rute , Custódio Tânia F , Xue Han , Szymula Agnieszka , Sun Qiming , Liu Bing , Álvarez Ángel L , Chen She , Huang Jing , Simas J Pedro , McVey Colin E , Kaye Kenneth M 
Published: October 2021

Abstract
Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-Å crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors.
EWAS Open Platform: integrated data, knowledge and toolkit for epigenome-wide association study
Authors: Xiong Zhuang , Yang Fei , Li Mengwei , Ma Yingke , Zhao Wei , Wang Guoliang , Li Zhaohua , Zheng Xinchang , Zou Dong , Zong Wenting , Kang Hongen , Jia Yaokai , Li Rujiao , Zhang Zhang , Bao Yiming 
Published: October 2021

Abstract
Epigenome-Wide Association Study (EWAS) has become a standard strategy to discover DNA methylation variation of different phenotypes. Since 2018, we have developed EWAS Atlas and EWAS Data Hub to integrate a growing volume of EWAS knowledge and data, respectively. Here, we present EWAS Open Platform (https://ngdc.cncb.ac.cn/ewas) that includes EWAS Atlas, EWAS Data Hub and the newly developed EWAS Toolkit. In the current implementation, EWAS Open Platform integrates 617 018 high-quality EWAS associations from 910 publications, covering 51 phenotypes, 275 diseases and 104 environmental factors. It also provides well-normalized DNA methylation array data and the corresponding metadata from 115 852 samples, which involve 707 tissues, 218 cell lines and 528 diseases. Taking advantage of integrated knowledge and data in EWAS Atlas and EWAS Data Hub, EWAS Open Platform equips with EWAS Toolkit, a powerful one-stop site for EWAS enrichment, annotation, and knowledge network construction and visualization. Collectively, EWAS Open Platform provides open access to EWAS knowledge, data and toolkit and thus bears great utility for a broader range of relevant research.
Palmaris brevis spasm syndrome in manual workers using vibratory tools
Authors: Cooke R 
Published: October 2021

Summary
Palmaris brevis spasm syndrome (PBSS) appears to reflect benign muscle hyperactivity, with unprovoked recurrent spasm of the muscle and consequent dimpling of the hypothenar eminence. Two cases are reported, being the first known report of the condition among manual workers or those using vibratory tools. Each was diagnosed during routine health surveillance for hand–arm vibration syndrome. With hand cramps being a frequent report among vibration-exposed workers, this condition should be considered in such cases, although the lack of reports means that the frequency of the condition is unknown. One of the employees described more frequent episodes of spasm during periods of increased manual work. Diagnosis is possible by witnessing the characteristic spasm, or by viewing photographs of it. Functional impairment is not usual, except for the brief duration of an attack. There is no consensus regarding appropriate treatment.
Underascertainment of COVID-19 cases among first responders: a seroepidemiological study
Authors: Backhaus I , Hermsen D , Timm J , Boege F , Lübke N , Göbels K , von der Lieth D , Dragano N 
Published: October 2021

Abstract

Background
Providing frontline support places first responders at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Aims
This study was aimed to determine the anti-SARS-CoV-2 seroprevalence in a cohort of first responders (i.e. firefighters/paramedics), to detect the underascertainment rate and to assess risk factors associated with seropositivity.

Methods
We conducted a serological survey among 745 first responders in Germany during 27 November and 4 December 2020 to determine the anti-SARS-CoV-2 seroprevalence using Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Mannheim, Germany). As part of the examination, participants were asked to provide information on coronavirus disease 2019 (COVID-19)-like-symptoms, information on sociodemographic characteristics and workplace risk factors for a SARS-CoV-2 infection and any prior COVID-19 infection. Descriptive statistics and logistic regression analysis were performed and seroprevalence estimates were adjusted for test sensitivity and specificity.

Results
The test-adjusted seroprevalence was 4% (95% CI 3.1–6.2) and the underascertainment rate was 2.3. Of those tested SARS-CoV-2 antibody positive, 41% were aware that they had been infected in the past. Seropositivity was elevated among paramedics who worked in the emergency rescue team providing first level of pre-hospital emergency care (6% [95% CI 3.4–8.6]) and those directly exposed to a COVID-19 case (5% [95% CI 3.5–8.1]). Overall, the seroprevalence and the underascertainment rate were higher among first responders than among the general population.

Conclusions
The high seroprevalence and underascertainment rate highlight the need to mitigate potential transmission within and between first responders and patients. Workplace control measures such as increased and regular COVID-19-testing and the prompt vaccination of all personnel are necessary.