bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of thermal winds on the outbursts evolution of LMXB systems
Authors: Avakyan A L , Lipunova G V , Malanchev K L
Published: November 2023

Theoretical models of accretion discs and observational data indicate that the X-ray emission from the inner parts of an accretion disc can irradiate its outer regions and induce a thermal wind, which carries away the mass and angular momentum from the disc. Our aim is to investigate the influence of the thermal wind on the outburst light curves of black hole X-ray binary systems. We carry out numerical simulations of a non-stationary disc accretion with wind using upgraded open code freddi. We assume that the wind launches only from the ionized part of the disc and may turn off if the latter shrinks fast enough. Our estimates of the viscosity parameter α are shifted downward compared to a scenario without a wind. Generally, correction of α depends on the spectral hardness of central X-rays and the disc outer radius, but unlikely to exceed a factor of 10 in the case of a black hole low-mass X-ray binary (BH LMXB). We fit 2002 outburst of BH LMXB 4U 1543 − 47 taking into account the thermal wind. The mass-loss in the thermal wind is of order of the accretion rate on the central object at the peak of the outburst. New estimate of the viscosity parameter α for the accretion disc in this system is about two times lower than the previous one. Additionally, we calculate evolution of the number of hydrogen atoms towards 4U 1543 − 47 due to the thermal wind from the hot disc.
Detection and preliminary characterization of polluted white dwarfs from Gaia EDR3 and LAMOST
Authors: Badenas-Agusti Mariona , Vanderburg Andrew , Blouin Simon , Dufour Patrick , Viaña Javier , Seager Sara , Wang Sharon X
Published: November 2023

We present a catalogue of 62 polluted white dwarfs observed by the 9th Low-Resolution Data Release of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST LRS DR9v1; R≈1800) and the Early Data Release 3 (EDR3) of the Gaia Mission. Among these stellar remnants, 30 are new discoveries with previously unknown traces of calcium pollution. To generate our catalogue, we used a data base of 4324 unique Gaia EDR3 white dwarf candidates with LAMOST LRS DR9v1 observations, many of which have been spectroscopically confirmed by other telescopes. For these stars, we developed a quantitative method to detect calcium absorption in their spectra between 3900–4000 Å, which we then validated through visual inspection and multiple literature cross-checks. Our catalogue provides the astrometric and photometric properties of the white dwarf candidates, incorporates supplementary data (e.g. Montreal White Dwarf Database, MWDD; PanSTARRS; the Hubble Space Telescope), and indicates the possibility of calcium pollution in their atmospheres. For our final sample of polluted white dwarfs, we also determine the main atmospheric properties of 23 sources with effective temperatures Teff ≤ 25 000 K and no existing calcium abundances in the MWDD. Our analysis represents a first step towards measuring the full atmospheric composition of these stars and learning about the bulk properties of their accreted material. As we venture into the era of wide-field spectroscopic surveys, our work highlights the importance of combining large-scale data bases for identifying and characterizing new polluted white dwarfs.
Image restoration with point-spread function regularization and active learning
Authors: Jia Peng , Lv Jiameng , Ning Runyu , Song Yu , Li Nan , Ji Kaifan , Cui Chenzhou , Li Shanshan
Published: November 2023

Large-scale astronomical surveys can capture numerous images of celestial objects, including galaxies and nebulae. Analysing and processing these images can reveal the intricate internal structures of these objects, allowing researchers to conduct comprehensive studies on their morphology, evolution, and physical properties. However, varying noise levels and point-spread functions can hamper the accuracy and efficiency of information extraction from these images. To mitigate these effects, we propose a novel image restoration algorithm that connects a deep-learning-based restoration algorithm with a high-fidelity telescope simulator. During the training stage, the simulator generates images with different levels of blur and noise to train the neural network based on the quality of restored images. After training, the neural network can restore images obtained by the telescope directly, as represented by the simulator. We have tested the algorithm using real and simulated observation data and have found that it effectively enhances fine structures in blurry images and increases the quality of observation images. This algorithm can be applied to large-scale sky survey data, such as data obtained by the Large Synoptic Survey Telescope (LSST), Euclid, and the Chinese Space Station Telescope (CSST), to further improve the accuracy and efficiency of information extraction, promoting advances in the field of astronomical research.
The first comprehensive study of a giant nebula around a radio-quiet quasar in the z < 1 Universe
Authors: Liu Zhuoqi , Johnson Sean D , Li Jennifer I-Hsiu , Rudie Gwen C , Schaye Joop , Chen Hsiao-Wen , Brinchmann Jarle , Cantalupo Sebastiano , Chen Mandy C , Kollatschny Wolfram , Maseda Michael V , Mishra Nishant , Muzahid Sowgat
Published: November 2023

We present the first comprehensive study of a giant, ≈70 kpc-scale nebula around a radio-quiet quasar at z < 1. The analysis is based on deep integral field spectroscopy with Multi-Unit Spectroscopic Explorer of the field of HE 0238−1904, a luminous quasar at z = 0.6282. The nebula emits strongly in [O ii], $\rm H \beta$, and [O iii], and the quasar resides in an unusually overdense environment for a radio-quiet system. The environment likely consists of two groups which may be merging, and in total have an estimated dynamical mass of Mdyn ≈ 4 × 1013 to 1014 M⊙. The nebula exhibits largely quiescent kinematics and irregular morphology. The nebula may arise primarily through interaction-related stripping of circumgalactic and interstellar medium (CGM/ISM) of group members, with some potential contributions from quasar outflows. The simultaneous presence of the giant nebula and a radio-quiet quasar in a rich environment suggests a correlation between such circum-quasar nebulae and environmental effects. This possibility can be tested with larger samples. The upper limits on the electron number density implied by the [O ii] doublet ratio range from $\log (n_{\rm e, [O\,{\small II}]} /\mathrm{cm}^{-3})<1.2$ to 2.8. However, assuming a constant quasar luminosity and negligible projection effects, the densities implied from the measured line ratios between different ions (e.g. [O ii], [O iii], and [Ne v]) and photoionization simulations are often 10−400 times larger. This large discrepancy can be explained by quasar variability on a time-scale of ≈104−105 yr.
Free-form and hybrid lens models for SDSS J1004+4112: substructure and central image time delay constraints
Authors: Perera Derek , Williams Liliya L R , Liesenborgs Jori , Ghosh Agniva , Saha Prasenjit
Published: November 2023

SDSS J1004+4112 is a well-studied gravitational lens with a recently measured time delay between its first and fourth arriving quasar images. Using this new constraint, we present updated free-form lens reconstructions using the lens inversion method grale, which only uses multiple image and time delay data as inputs. In addition, we obtain hybrid lens reconstructions by including a model of the brightest cluster galaxy as a Sersic lens. For both reconstructions, we use two sets of images as input: one with all identified images, and the other a revised set leaving out images that have been potentially misidentified. We also develop a source position optimization Markov chain Monte Carlo (MCMC) routine, performed on completed grale runs, that allows each model to better match observed image positions and time delays. All the reconstructions produce similar mass distributions, with the hybrid models finding a steeper profile in the centre. Similarly, all the mass distributions are fitted by the Navarro–Frenk–White profile, finding results consistent with previous parametric reconstructions and those derived from Chandra X-ray observations. We identify an ∼5 × 1011 M⊙ substructure apparently unaffiliated with any cluster member galaxy and present in all our models, and study its reality. Using our free-form and hybrid models, we predict a central quasar image time delay of ∼2980 ± 270 and ∼3280 ± 215 d, respectively. A potential future measurement of this time delay will, while being an observational challenge, further constrain the steepness of the central density profile.
A cool, magnetic white dwarf accreting planetary debris
Authors: Vennes Stéphane , Kawka Adela , Klein Beth L , Zuckerman B , Weinberger Alycia J , Melis Carl
Published: November 2023

We present an analysis of spectroscopic data of the cool, highly magnetic, and polluted white dwarf 2MASS J0916−4215. The atmosphere of the white dwarf is dominated by hydrogen, but numerous spectral lines of magnesium, calcium, titanium, chromium, iron, and strontium, along with Li i, Na i, Al i, and K i lines, are found in the incomplete Paschen–Back regime, most visibly, in the case of Ca ii lines. Extensive new calculations of the Paschen–Back effect in several spectral lines are presented and results of the calculations are tabulated for the Ca ii H&K doublet. The abundance pattern shows a large lithium and strontium excess, which may be viewed as a signature of planetary debris akin to Earth’s continental crust accreted on to the star, although the scarcity of silicon indicates possible dilution in bulk Earth material. Accurate abundance measurements proved sensitive to the value of the broadening parameter due to collisions with neutral hydrogen ($\Gamma$H i), particularly in saturated lines such as the resonance lines of Ca i and Ca ii. We found that $\Gamma$H i if formulated with values from the literature could be overestimated by a factor of 10 in most resonance lines.
J-PLUS: galaxy-star-quasar classification for DR3
Authors: von Marttens R , Marra V , Quartin M , Casarini L , Baqui P O , Alvarez-Candal A , Galindo-Guil F J , Fernández-Ontiveros J A , del Pino Andrés , Díaz-García L A , López-Sanjuan C , Alcaniz J , Angulo R , Cenarro A J , Cristóbal-Hornillos D , Dupke R , Ederoclite A , Hernández-Monteagudo C , Marín-Franch A , Moles M , Sodré L , Varela J , Vázquez Ramió H
Published: November 2023

The Javalambre Photometric Local Universe Survey (J-PLUS) is a 12-band photometric survey using the 83-cm JAST telescope. Data Release 3 includes 47.4 million sources. J-PLUS DR3 only provides star-galaxy classification so that quasars are not identified from the other sources. Given the size of the data set, machine learning methods could provide a valid alternative classification and a solution to the classification of quasars. Our objective is to classify J-PLUS DR3 sources into galaxies, stars, and quasars, outperforming the available classifiers in each class. We use an automated machine learning tool called TPOT to find an optimized pipeline to perform the classification. The supervised machine learning algorithms are trained on the crossmatch with SDSS DR18, LAMOST DR8, and Gaia. We checked that the training set of about 660 thousand galaxies, 1.2 million stars, and 270 thousand quasars is both representative and contain a minimal presence of contaminants (less than 1 per cent). We considered 37 features: the 12 photometric bands with respective errors, 6 colours, 4 morphological parameters, galactic extinction with its error, and the PSF relative to the corresponding pointing. With TPOT genetic algorithm, we found that XGBoost provides the best performance: the AUC for galaxies, stars, and quasars is above 0.99 and the average precision is above 0.99 for galaxies and stars and 0.96 for quasars. XGBoost outperforms the classifiers already provided in J-PLUS DR3 and also classifies quasars.
Fisher forecast for the BAO measurements from the CSST spectroscopic and photometric galaxy clustering
Authors: Ding Zhejie , Yu Yu , Zhang Pengjie
Published: November 2023

The China Space Station Telescope (CSST) is a forthcoming Stage IV galaxy survey. It will simultaneously undertake the photometric redshift (photo-z) and slitless spectroscopic redshift (spec-z) surveys mainly for weak lensing and galaxy clustering studies. The two surveys cover the same sky area and overlap on the redshift range. At z > 1, due to the sparse number density of the spec-z sample, it limits the constraints on the scale of baryon acoustic oscillations (BAO). By cross-correlating the spec-z sample with the high density photo-z sample, we can effectively enhance the constraints on the angular diameter distances DA(z) from the BAO measurement. Based on the Fisher matrix, we forecast a >30 per cent improvement on constraining DA(z) from the joint analysis of the spec-z and cross galaxy power spectra at 1.0 < z < 1.2. Such improvement is generally robust against different systematic effects including the systematic noise and the redshift success rate of the spec-z survey, as well as the photo-z error. We also show the BAO constraints from other Stage-IV spectroscopic surveys for the comparison with CSST. Our study can be a reference for the future BAO analysis on real CSST data. The methodology can be applied to other surveys with spec-z and photo-z data in the same survey volume.
MOG as symmetry breaking in scalar–vector–tensor gravity
Authors: Rouhani Shahin , Rahvar Sohrab
Published: November 2023

The Modified Gravity Model (MOG) has been proposed as a solution to the dark matter problem, but it does not meet the gauge invariant condition. The aim of this work is to propose a gauge-invariant theory, which suggests that symmetry can break at a low temperature in the Universe, leading to the MOG theory. This theory has the potential to alter the dynamics of the early and late Universe and naturally produce cosmological inflation.
Mitonuclear Sex Determination? Empirical Evidence from Bivalves
Authors: Smith Chase H , Mejia-Trujillo Raquel , Breton Sophie , Pinto Brendan J , Kirkpatrick Mark , Havird Justin C
Published: November 2023

Genetic elements encoded in nuclear DNA determine the sex of an individual in many animals. In certain bivalve lineages that possess doubly uniparental inheritance (DUI), mitochondrial DNA (mtDNA) has been hypothesized to contribute to sex determination. In these cases, females transmit a female mtDNA to all offspring, while male mtDNA (M mtDNA) is transmitted only from fathers to sons. Because M mtDNA is inherited in the same way as Y chromosomes, it has been hypothesized that mtDNA may be responsible for sex determination. However, the role of mitochondrial and nuclear genes in sex determination has yet to be validated in DUI bivalves. In this study, we used DNA, RNA, and mitochondrial short noncoding RNA (sncRNA) sequencing to explore the role of mitochondrial and nuclear elements in the sexual development pathway of the freshwater mussel Potamilus streckersoni (Bivalvia: Unionida). We found that the M mtDNA sheds a sncRNA partially within a male-specific mitochondrial gene that targets a pathway hypothesized to be involved in female development and mitophagy. RNA-seq confirmed the gene target was significantly upregulated in females, supporting a direct role of mitochondrial sncRNAs in gene silencing. These findings support the hypothesis that M mtDNA inhibits female development. Genome-wide patterns of genetic differentiation and heterozygosity did not support a nuclear sex-determining region, although we cannot reject that nuclear factors are involved with sex determination. Our results provide further evidence that mitochondrial loci contribute to diverse, nonrespiratory functions and additional insights into an unorthodox sex-determining system.
AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences
Authors: Varadi Mihaly , Bertoni Damian , Magana Paulyna , Paramval Urmila , Pidruchna Ivanna , Radhakrishnan Malarvizhi , Tsenkov Maxim , Nair Sreenath , Mirdita Milot , Yeo Jingi , Kovalevskiy Oleg , Tunyasuvunakool Kathryn , Laydon Agata , Žídek Augustin , Tomlinson Hamish , Hariharan Dhavanthi , Abrahamson Josh , Green Tim , Jumper John , Birney Ewan , Steinegger Martin , Hassabis Demis , Velankar Sameer
Published: November 2023

The AlphaFold Database Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) has significantly impacted structural biology by amassing over 214 million predicted protein structures, expanding from the initial 300k structures released in 2021. Enabled by the groundbreaking AlphaFold2 artificial intelligence (AI) system, the predictions archived in AlphaFold DB have been integrated into primary data resources such as PDB, UniProt, Ensembl, InterPro and MobiDB. Our manuscript details subsequent enhancements in data archiving, covering successive releases encompassing model organisms, global health proteomes, Swiss-Prot integration, and a host of curated protein datasets. We detail the data access mechanisms of AlphaFold DB, from direct file access via FTP to advanced queries using Google Cloud Public Datasets and the programmatic access endpoints of the database. We also discuss the improvements and services added since its initial release, including enhancements to the Predicted Aligned Error viewer, customisation options for the 3D viewer, and improvements in the search engine of AlphaFold DB.
Human Ageing Genomic Resources: updates on key databases in ageing research
Authors: de Magalhães João Pedro , Abidi Zoya , dos Santos Gabriel Arantes , Avelar Roberto A , Barardo Diogo , Chatsirisupachai Kasit , Clark Peter , De-Souza Evandro A , Johnson Emily J , Lopes Inês , Novoa Guy , Senez Ludovic , Talay Angelo , Thornton Daniel , To Paul Ka Po
Published: November 2023

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).
Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription
Authors: Tang Yingke , Behrens Ryan T , St Gelais Corine , Wu Siqi , Vivekanandan Saravanan , Razin Ehud , Fang Pengfei , Wu Li , Sherer Nathan , Musier-Forsyth Karin
Published: November 2023

Human lysyl-tRNA synthetase (LysRS) was previously shown to be re-localized from its normal cytoplasmic location in a multi-aminoacyl-tRNA synthetase complex (MSC) to the nucleus of HIV-1 infected cells. Nuclear localization depends on S207 phosphorylation but the nuclear function of pS207-LysRS in the HIV-1 lifecycle is unknown. Here, we show that HIV-1 replication was severely reduced in a S207A-LysRS knock-in cell line generated by CRISPR/Cas9; this effect was rescued by S207D-LysRS. LysRS phosphorylation up-regulated HIV-1 transcription, as did direct transfection of Ap4A, an upstream transcription factor 2 (USF2) activator that is synthesized by pS207-LysRS. Overexpressing an MSC-derived peptide known to stabilize LysRS MSC binding inhibited HIV-1 replication. Transcription of HIV-1 proviral DNA and other USF2 target genes was reduced in peptide-expressing cells. We propose that nuclear pS207-LysRS generates Ap4A, leading to activation of HIV-1 transcription. Our results suggest a new role for nuclear LysRS in facilitating HIV-1 replication and new avenues for antiviral therapy.
Differing structures and dynamics of two photolesions portray verification differences by the human XPD helicase
Authors: Fu Iwen , Geacintov Nicholas E , Broyde Suse
Published: November 2023

Ultraviolet light generates cyclobutane pyrimidine dimer (CPD) and pyrimidine 6−4 pyrimidone (6−4PP) photoproducts that cause skin malignancies if not repaired by nucleotide excision repair (NER). While the faster repair of the more distorting 6–4PPs is attributed mainly to more efficient recognition by XPC, the XPD lesion verification helicase may play a role, as it directly scans the damaged DNA strand. With extensive molecular dynamics simulations of XPD-bound single-strand DNA containing each lesion outside the entry pore of XPD, we elucidate strikingly different verification processes for these two lesions that have very different topologies. The open book-like CPD thymines are sterically blocked from pore entry and preferably entrapped by sensors that are outside the pore; however, the near-perpendicular 6−4PP thymines can enter, accompanied by a displacement of the Arch domain toward the lesion, which is thereby tightly accommodated within the pore. This trapped 6−4PP may inhibit XPD helicase activity to foster lesion verification by locking the Arch to other domains. Furthermore, the movement of the Arch domain, only in the case of 6−4PP, may trigger signaling to the XPG nuclease for subsequent lesion incision by fostering direct contact between the Arch domain and XPG, and thereby facilitating repair of 6−4PP.
To let go or not to let go: how ParA can impact the release of the chromosomal anchoring in Caulobacter crescentus
Authors: Puentes-Rodriguez Stephanie G , Norcross John D , Mera Paola E
Published: November 2023

Chromosomal maintenance is vital for the survival of bacteria. In Caulobacter crescentus, chromosome replication initiates at ori and segregation is delayed until the nearby centromere-like region parS is replicated. Our understanding of how this sequence of events is regulated remains limited. The segregation of parS has been shown to involve multiple steps including polar release from anchoring protein PopZ, slow movement and fast ParA-dependent movement to the opposite cell pole. In this study, we demonstrate that ParA’s competing attractions from PopZ and from DNA are critical for segregation of parS. Interfering with this balance of attractions—by expressing a variant ParA-R195E unable to bind DNA and thus favoring interactions exclusively between ParA-PopZ—results in cell death. Our data revealed that ParA-R195E’s sole interactions with PopZ obstruct PopZ’s ability to release the polar anchoring of parS, resulting in cells with multiple parS loci fixed at one cell pole. We show that the inability to separate and segregate multiple parS loci from the pole is specifically dependent on the interaction between ParA and PopZ. Collectively, our results reveal that the initial steps in chromosome segregation are highly regulated.
DescribePROT in 2023: more, higher-quality and experimental annotations and improved data download options
Authors: Basu Sushmita , Zhao Bi , Biró Bálint , Faraggi Eshel , Gsponer Jörg , Hu Gang , Kloczkowski Andrzej , Malhis Nawar , Mirdita Milot , Söding Johannes , Steinegger Martin , Wang Duolin , Wang Kui , Xu Dong , Zhang Jian , Kurgan Lukasz
Published: November 2023

The DescribePROT database of amino acid-level descriptors of protein structures and functions was substantially expanded since its release in 2020. This expansion includes substantial increase in the size, scope, and quality of the underlying data, the addition of experimental structural information, the inclusion of new data download options, and an upgraded graphical interface. DescribePROT currently covers 19 structural and functional descriptors for proteins in 273 reference proteomes generated by 11 accurate and complementary predictive tools. Users can search our resource in multiple ways, interact with the data using the graphical interface, and download data at various scales including individual proteins, entire proteomes, and whole database. The annotations in DescribePROT are useful for a broad spectrum of studies that include investigations of protein structure and function, development and validation of predictive tools, and to support efforts in understanding molecular underpinnings of diseases and development of therapeutics. DescribePROT can be freely accessed at http://biomine.cs.vcu.edu/servers/DESCRIBEPROT/.
The forkhead DNA-binding domain binds specific G2-rich RNA sequences
Authors: Zutterling Caroline , Todeschini Anne-Laure , Fourmy Deborah , Busso Didier , Veaute Xavier , Ducongé Frédéric , Veitia Reiner A
Published: November 2023

Transcription factors contain a DNA-binding domain ensuring specific recognition of DNA target sequences. The family of forkhead (FOX) transcription factors is composed of dozens of paralogs in mammals. The forkhead domain (FHD) is a segment of about 100 amino acids that binds an A-rich DNA sequence. Using DNA and RNA PCR-SELEX, we show that recombinant FOXL2 proteins, either wild-type or carrying the oncogenic variant C134W, recognize similar DNA-binding sites. This suggests that the oncogenic variant does not alter the intrinsic sequence-specificity of FOXL2. Most importantly, we show that FOXL2 binds G2-rich RNA sequences whereas it virtually fails to bind similar sequences in DNA chemistry. Interestingly, a statistically significant subset of genes responding to the knock-down of FOXL2/Foxl2 harbor such G2-rich sequences and are involved in crucial signaling pathways and cellular processes. In addition, we show that FOXA1, FOXO3a and chimeric FOXL2 proteins containing the FHD of the former are also able to interact with some of the preferred FOXL2-binding sequences. Our results point to an unexpected and novel characteristic of the forkhead domain, the biological relevance of which remains to be explored.
The Neurogenome study: Comprehensive molecular profiling to optimize treatment for Danish glioblastoma patients
Authors: Nørøxe Dorte Schou , Maarup Simone , Fougner Vincent , Muhic Aida , Møller Søren , Urup Thomas , Lü Maya Jeje Schuang , Weischenfeldt Joachim , Hansen Adam Espe , Skovgaard Poulsen Hans , Lassen Ulrik , Hasselbalch Benedikte
Published: November 2023

Background

Glioblastoma is an aggressive brain cancer with no possibility for cure. Treatment and survival have only improved slightly since 2005 when the current regime was implemented. The limited improvements in the treatment of glioblastoma may reflect our poor understanding of the disease. We hypothesize that systematically collected translational data will improve knowledge and hereby treatment.

Methods

We have been performing whole exome sequencing in glioblastoma tumor tissue since 2016 and whole genome sequencing (WGS) since 2020 with the aim of offering experimental treatment.

Results

We have sequenced 400+ GBM patients and from these 100+ are paired tumor samples from relapse surgery. To develop genomic profiling and to increase the information on each patient´s contribution, we have initiated the Neurogenome study as of June 2022. The Neurogenome protocol is a national, comprehensive, translational, and omic protocol. It is a continuation of 2 previous protocols from 2016 and forth in our department, but with more substudies added, focusing on the translational and clinical utility. We collect and analyze data from an out-patient clinic in a systematic approach to a number of subprojects ranging from basic science to applied clinical science, including clinical trials.

Conclusions

The protocol will act as a backbone for future projects in the national research center, Danish Comprehensive Cancer Center—Brain Tumor Center with the overall aim to select eligible patients for experimental treatment based upon genomic alterations. The article will present the Neurogenome setup and a presentation of selected projects that are based upon inclusion.
How Complete Are Tobacco Sales Data? Assessing the Comprehensiveness of US Tobacco Product Retail Sales Data Through Comparisons to Excise Tax Collections
Authors: Liber Alex C , Faraji Maryam , Ranganathan Radhika , Friedman Abigail S
Published: November 2023

Introduction

Sales data analyses are increasingly used to guide tobacco regulatory science. However, such data do not cover specialist retailers like vape shops or tobacconists. Understanding the extent of the cigarette and electronic nicotine delivery system (ENDS) markets covered by sales data is critical to establishing such analyses’ generalizability and potential biases.

Methods

Using retail sales data from Information Resources Incorporated (IRI) and Nielsen, we conduct tax gap analyses comparing states’ cigarette and ENDS tax revenue to tax collection estimates based on retail sales data. For the 23 US states in both retail sales datasets, cigarette tax gap analyses were conducted for each year from 2018 to 2020. Four (Louisiana, North Carolina, Ohio, and Washington) of those 23 states levied per-unit ENDS taxes and provided monthly tax revenue data covering January 2018 to October 2021, where we conducted monthly tax gap analyses for both cigarettes and ENDS.

Results

Across states covered by both sales datasets, annual mean cigarette sales in IRI and Nielsen account for 92.3% (95% CI = 88.3% to 96.2%) and 84.0% (95% CI = 79.3% to 88.7%) of state cigarette tax revenue, respectively. Monthly average coverage rates for ENDS sales were lower, ranging from 42.3% to 86.1% for IRI and 43.6% to 88.5% for Nielsen, but remained stable over time.

Conclusions

IRI and Nielsen sales data capture almost the entire US cigarette market and a substantial but lower portion of the US ENDS market. With proper care to address shortcomings, sales data analyses can capture changes in the US market for these tobacco products.

Implications

Policy evaluations and analyses using e-cigarette and cigarette sales data are often criticized because these data do not cover online sales or sales by specialty retailers like tobacconists. Cigarette sales data consistently cover nearly 90% of taxed sales, while e-cigarette sales data cover around 50% of taxed volumes. Retail sales data capture nearly all cigarette sales and a substantial portion of ENDS sales with relatively stable rates of coverage over time, supporting their continued use in tobacco surveillance and policy evaluation work.
Seeing Through the Blind: Belief About Treatment Randomization and Smoking Cessation Outcome Among People With Current or Past Major Depressive Disorder Who Smoke in a Placebo-Controlled Trial of Varenicline
Authors: Schnoll Robert , Wileyto E Paul , Bauer Anna-Marika , Fox Erica N , Blumenthal Daniel , Hosie Quinn Mackenzie , Leone Frank , Huffman Mark D , Khan Sadiya S , Gollan Jacqueline K , Papandonatos George D , Hitsman Brian
Published: November 2023

Introduction

Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial.

Aims and Methods

175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed.

Results

Treatment arm belief was significantly associated with actual arm assignment (χ2(2) = 13.0, p = .002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, versus “not sure” (RR = 3.05 [1.41–6.60], p = .005). Participants in the placebo arm were just as likely to believe they were taking placebo versus “not sure” (χ2[2] = 0.75, p = .69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR = 5.91 [2.06–16.92], p = .001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline (B = 0.077 [0.002–0.192], p < .05).

Conclusions

Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

Trial Registration

Data come from the trial NCT02378714.

Implications

The present study adds to the sparse literature on blind integrity, particularly in the field of tobacco cessation. Randomized clinical trial participants can discern their assignment to varenicline, and believing that one received varenicline was associated with significantly higher cessation rates. Identifying treatment arm allocation may be associated with changes in the rewarding aspects of smoking that have been well documented with varenicline use. Masking allocation to varenicline is challenging. The effects of this medication in clinical trials may represent both pharmacological effects and participants’ abilities to recognize that they are receiving the medication.
Long-term Dalbavancin for Suppression of Gram-Positive Chronic Left Ventricular Assist Device Infections
Authors: Rowe Sarah , Green Sarah , Albrecht Benjamin , Pouch Stephanie M
Published: November 2023

Background

Infection is the leading cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). Prolonged suppressive therapy should be strongly considered and is often used in patients with recurrent infections when source control cannot be achieved. Dalbavancin is a promising option in patients with LVADs requiring prolonged durations of antibiotic therapy, especially when no oral alternatives are available.

Methods

This case series included 8 patients receiving dalbavancin for the long-term suppression of gram-positive infections at Emory University Hospital and Emory St Joseph's Hospital.

Results

The overall incidence of breakthrough infections occurred in 5 of the 8 patients included in the study. One patient experienced an early breakthrough infection within 1 month of dalbavancin initiation. Another experienced a breakthrough infection within 3 and 6 months of dalbavancin initiation, and the final 3 patients experienced a breakthrough infection within 6 and 12 months. The average duration of dalbavancin suppression therapy among all patients was 229 days, and no adverse effects were reported.

Conclusions

Dalbavancin is a promising option in patients who require long-term suppression for chronic gram-positive LVAD infections, given its unique pharmacokinetic profile and excellent tissue penetration. The use of biweekly dalbavancin infusions in our 8 patients prevented infection for an extended period of time despite some of the patients not being able to consistently receive infusions. Larger studies are needed to determine the efficacy and safety of using dalbavancin for long-term suppression of gram-positive LVAD infections.
Rapid Diagnosis of Hemophagocytic Lymphohistiocytosis Triggered by Disseminated BCG Infection in Infants With Severe Combined Immunodeficiency: Case Report
Authors: Zou Ting-Ting , Liao Qiong , Liu Yang , Guo Qin , Zhu Yu , Wan Chao-min
Published: November 2023

Hemophagocytic lymphohistiocytosis triggered by disseminated Bacillus Calmette-Guerin infection is rare. Targeted next-generation sequencing for tuberculosis can rapidly identify different strains of Mycobacterium tuberculosis complex as well as drug resistance genes. Herein we report 2 cases of hemophagocytic lymphohistiocytosis in whom targeted next-generation sequencing rapidly identified Bacillus Calmette-Guerin as the infectious trigger.
Cryptochrome 1b represses gibberellin signaling to enhance lodging resistance in maize
Authors: Chen Shizhan , Fan Xiaocong , Song Meifang , Yao Shuaitao , Liu Tong , Ding Wusi , Liu Lei , Zhang Menglan , Zhan Weimin , Yan Lei , Sun Guanghua , Li Hongdan , Wang Lijian , Zhang Kang , Jia Xiaolin , Yang Qinghua , Yang Jianping
Published: November 2023

Maize (Zea mays L.) is one of the most important crops worldwide. Photoperiod, light quality, and light intensity in the environment can affect the growth, development, yield, and quality of maize. In Arabidopsis (Arabidopsis thaliana), cryptochromes are blue-light receptors that mediate the photocontrol of stem elongation, leaf expansion, shade tolerance, and photoperiodic flowering. However, the function of maize cryptochrome ZmCRY in maize architecture and photomorphogenic development remains largely elusive. The ZmCRY1b transgene product can activate the light signaling pathway in Arabidopsis and complement the etiolation phenotype of the cry1-304 mutant. Our findings show that the loss-of-function mutant of ZmCRY1b in maize exhibits more etiolation phenotypes under low blue light and appears slender in the field compared with wild-type plants. Under blue and white light, overexpression of ZmCRY1b in maize substantially inhibits seedling etiolation and shade response by enhancing protein accumulation of the bZIP transcription factors ELONGATED HYPOCOTYL 5 (ZmHY5) and ELONGATED HYPOCOTYL 5-LIKE (ZmHY5L), which directly upregulate the expression of genes encoding gibberellin (GA) 2-oxidase to deactivate GA and repress plant height. More interestingly, ZmCRY1b enhances lodging resistance by reducing plant and ear heights and promoting root growth in both inbred lines and hybrids. In conclusion, ZmCRY1b contributes blue-light signaling upon seedling de-etiolation and integrates light signals with the GA metabolic pathway in maize, resulting in lodging resistance and providing information for improving maize varieties.
Microtubule-associated proteins MAP65-1 and SUN18/IQD26 coordinately regulate tomato fruit shape by affecting cell division
Authors: Bao Zhiru , Guo Ye , Meng Xiangxu , Shi Chunmei , Ouyang Bo , Qu Xiaolu , Wang Pengwei
Published: November 2023

Microtubule-associated proteins MAP65-1 and SUN18 function additively in fruit shape regulation by modulating cell division patterns but not changing cell morphology.
Common co-morbidities in polymyalgia rheumatica and giant cell arteritis: cross-sectional study in UK Biobank
Authors: Chatzigeorgiou Charikleia , Taylor John C , Elliott Faye , O’Sullivan Eoin P , Morgan Ann W , Barrett Jennifer H , Mackie Sarah L
Published: November 2023

Objective

The aim was to determine prevalent co-morbidities in cases with PMR or GCA compared with matched controls.

Methods

This was a nested, cross-sectional case–control study within the UK Biobank, which recruited participants aged 40–69 years. Case status was defined as self-reported prior diagnosis of PMR or GCA. Ten controls per case were matched for age, sex, ethnicity and assessment centre. Associations with selected self-reported co-morbidities were studied using conditional logistic regression.

Results

Of PMR (n = 1036) or GCA (n = 102) cases, 72% were female, 98% White, and 58% reported current use of glucocorticoids. Mean age was 63 years. At the time of the assessment visit, compared with controls, PMR/GCA cases were more likely to report poor general health and at least several days of low mood in the past 2 weeks. PMR was associated with hypothyroidism [odds ratio (OR) = 1.34; 95% CI = 1.07, 1.67] and ever-use of HRT (OR = 1.26; 95% CI = 1.07, 1.47). Regarding common co-morbidities, PMR and GCA were both associated with hypertension (PMR: OR = 1.21; 95% CI = 1.06, 1.39; GCA: OR = 1.86; 95% CI = 1.23, 2.81) and cataract (PMR: OR = 1.51; 95% CI = 1.19, 1.93; GCA: OR = 3.84; 95% CI = 2.23, 6.60). Additionally, GCA was associated with depression (OR = 3.05; 95% CI = 1.59, 5.85). Neither condition was associated with diabetes.

Conclusion

Participants with a history of PMR/GCA, including those not currently taking glucocorticoids, rated their health as poorer than matched controls. Some previously described disease associations (hypothyroidism and early menopause) were replicated. Hypertension and cataract, both of which can be exacerbated by long-term glucocorticoid therapy, were over-represented in both diseases, particularly GCA.
Targeted, actionable and fair: Reviewer reports as feedback and its effect on ECR career choices
Authors: Derrick Gemma Elizabeth , Zimmermann Alessandra , Greaves Helen , Best Jonathan , Klavans Richard
Published: November 2023

Previous studies of the use of peer review for the allocation of competitive funding agencies have concentrated on questions of efficiency and how to make the ‘best’ decision, by ensuring that successful applicants are also the more productive or visible in the long term. This paper examines the components of feedback received from an unsuccessful grant application, is associated with motivating applicants career decisions to persist (reapply for funding at T1), or to switch (not to reapply, or else leave academia). This study combined data from interviews with unsuccessful ECR applicants (n = 19) to The Wellcome Trust 2009–19, and manual coding of reviewer comments received by applicants (n = 81). All applicants received feedback on their application at T0 with a large proportion of unsuccessful applicants reapplying for funding at T1. Here, peer-review-comments-as-feedback sends signals to applicants to encourage them to persist (continue) or switch (not continue) even when the initial application has failed. Feedback associated by unsuccessful applicants as motivating their decision to resubmit had three characteristics: actionable; targeted; and fair. The results lead to identification of standards of feedback for funding agencies and peer-reviewers to promote when providing reviewer feedback to applicants as part of their peer review process. The provision of quality reviewer-reports-as-feedback to applicants, ensures that peer review acts as a participatory research governance tool focused on supporting the development of individuals and their future research plans.
Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry
Authors: Miyazaki Yusuke , Funada Masashi , Nakayamada Shingo , Sonomoto Koshiro , Tanaka Hiroaki , Hanami Kentaro , Fukuyo Shunsuke , Kubo Satoshi , Yamaguchi Ayako , Miyagawa Ippei , Todoroki Yasuyuki , Ueno Masanobu , Tanaka Yoshiya
Published: November 2023

Objective

To determine the safety and efficacy of anifrolumab in patients with systemic lupus erythematosus (SLE) classified based on the Lupus Low Disease Activity State (LLDAS) in real-world clinical practice.

Methods

This retrospective observational study involved SLE patients who started anifrolumab therapy. The primary end point was the retention rate over 26 weeks after initiating anifrolumab therapy; 45 patients followed up for 12 weeks or longer were analysed in the following groups to determine the safety and efficacy up to week 12 after treatment initiation: (i) non-LLDAS achievement group and (ii) minor flare group. Safety and efficacy were compared between the minor flare group and the standard of care (SoC) group (treated by adding glucocorticoids [GCs] or immunosuppressants) after adjustment with inverse probability of treatment weighting using propensity score (PS-IPTW).

Results

The retention rate of anifrolumab was 89.7% at week 26.The LLDAS achievement rates at week 12 were 42.9% and 66.7% in the non-LLDAS achievement and minor flare groups, respectively. In both groups, GC doses and SELENA–SLEDAI score significantly decreased. When the anifrolumab group with minor flare was compared with the SoC group or the GC dose increase group, the GC dose and SLEDAI score were significantly lower in the anifrolumab group than in either of the other groups; there was no significant difference in LLDAS achievement.

Conclusion

At week 26 after initiating anifrolumab therapy, ∼90% of patients remained on therapy. Anifrolumab might lower disease activity without initiating GCs and reduce GC doses, especially in patients who experience minor flares after LLDAS achievement.
Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction
Authors: Di Matteo Andrea , De Lorenzis Enrico , Duquenne Laurence , Nam Jacqueline L , Garcia-Montoya Leticia , Harnden Kate , Chowdhury Rahaymin , Wakefield Richard J , Emery Paul , Mankia Kulveer
Published: November 2023

Objectives

To investigate, in anti-CCP antibody–positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of US for the prediction of inflammatory arthritis. Furthermore, to define a concise US protocol for feasible risk prediction.

Methods

Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months. Multivariable binary regression models for inflammatory arthritis development at 24 months evaluated routine clinical variables associated with inflammatory arthritis alone (‘clinical’ model) and combined with a 36-joint US scanning protocol (‘clinical-US extended’ model). A ‘clinical-US short’ model was also developed.

Results

At 24 months, 92/417 (22.1%) CCP+ at-risk developed inflammatory arthritis (median time 7 months, interquartile range 3–12). The ‘clinical-US extended’ model performed better than the ‘clinical’ model [area under the curve (AUC) 0.788 vs AUC 0.731, respectively, P < 0.001] with an odds ratio for inflammatory arthritis development of 3.18 (95% CI 1.80–5.63) for US synovitis and 2.54 (95% CI 1.21–5.37) for bone erosions. The ‘clinical-US short’ model, which retained the wrists, knees and MTP5 joints, performed better (AUC 0.782) than the ‘clinical’ model (P < 0.001) and similarly (difference in Akaike information criteria <2) to the ‘clinical-US extended’ model.

Conclusions

US provides valuable information for predicting progression to inflammatory arthritis in CCP+ individuals both alone and in addition to clinical variables. US synovitis was associated with a 3-fold increase risk of inflammatory arthritis development. A concise US protocol of six joints provides clinically feasible risk prediction in CCP+ at-risk.
Oklo natural fission reactors and dynamical models of dark energy
Authors: Davis E D
Published: November 2023

Bounds on the cosmological variation of the fine structure constant α inferred from Oklo neutron capture data are sometimes taken cum grano salis. It is possible to quantify uncertainties related to the treatment of excitation, deformation and the Coulomb interaction. On the basis of this analysis, it is concluded that Oklo data imply the relative change in α over the last 1.9 billion years is < 0.01 ppm (95% CL). Accommodation of this constraint represents a challenge to dark energy models that predict that fundamental constants do change.