bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is specialized metabolite regulation specialized?
Authors: Kliebenstein Daniel J 
Published: May 2023

Abstract
Recent technical and theoretical advances have generated an explosion in the identification of specialized metabolite pathways. In comparison, our understanding of how these pathways are regulated is relatively lagging. This and the relatively young age of specialized metabolite pathways has partly contributed to a default and common paradigm whereby specialized metabolite regulation is theorized as relatively simple with a few key transcription factors and the compounds are non-regulatory end-products. In contrast, studies into model specialized metabolites, such as glucosinolates, are beginning to identify a new understanding whereby specialized metabolites are highly integrated into the plants’ core metabolic, physiological, and developmental pathways. This model includes a greatly extended compendium of transcription factors controlling the pathway, key transcription factors that co-evolve with the pathway and simultaneously control core metabolic and developmental components, and finally the compounds themselves evolve regulatory connections to integrate into the plants signaling machinery. In this review, these concepts are illustrated using studies in the glucosinolate pathway within the Brassicales. This suggests that the broader community needs to reconsider how they do or do not integrate specialized metabolism into the regulatory network of their study species.
Use of Levetiracetam for Post-Traumatic Seizure Prophylaxis in Combat-Related Traumatic Brain Injury
Authors: Atwood Rex , Walker Patrick , Walper Daniel , Elster Eric , Bradley Matthew 
Published: May 2023

ABSTRACT

Introduction
Post-traumatic seizure (PTS) prophylaxis is recommended in patients with traumatic brain injury (TBI) at high risk for PTSs, but consensus on the optimal pharmacologic therapy has not yet been established. Levetiracetam is frequently used for seizure prophylaxis in combat-related TBI, but its efficacy and safety in this patient population has not yet been described.

Methods
A retrospective cohort of 687 consecutive casualties transferred to the CONUS from October 2010 to December 2015 was analyzed. Seventy-one patients with combat-related injuries and radiographic evidence of skull fractures or intracranial hemorrhage were included. Data collection included demographics and injury characteristics including initial Glasgow Coma Scale, computed tomography findings, interventions, and 6-month Glasgow Outcome Score.

Results
All patients in this cohort were male, with an average age of 25 (median 24; Interquartile range (IQR) 4.5) and an average Injury Severity Score of 28 (median 27; IQR 15). The most common mechanism of injury was explosive blast (76%). Penetrating TBI was common (51%). Most patients (88.7%) were administered seizure prophylaxis. Of these, the majority (61/63) received levetiracetam, and the additional two were administered phenytoin. The remaining 11.3% of patients were deemed not to require seizure prophylaxis. The incidence of seizures while on prophylaxis was low (2.8%) and occurred in patients who suffered transcranial gunshot wounds and ultimately died. No serious adverse effects were attributed to levetiracetam.

Conclusions
Levetiracetam appears to be a safe and effective medication for PTS prophylaxis in combat casualties. The rate of PTSs in combat-related TBI on appropriate prophylaxis is low.
Rapidly evolving Galactic plane outbursts in NEOWISE: revisiting the Galactic nova rate with the first all-sky search in the mid-infrared
Authors: Zuckerman Liam , De Kishalay , Eilers Anna-Christina , Meisner Aaron M , Panagiotou Christos 
Published: May 2023

ABSTRACT
The Galactic nova rate is intimately linked to our understanding of its chemical enrichment and progenitor channels of Type Ia supernovae. Yet past estimates have varied by more than an order of magnitude (≈10–300 yr−1), owing to limitations in both discovery methods as well as assumptions regarding the Galactic dust distribution and extragalactic stellar populations. Recent estimates utilizing synoptic near-infrared surveys have begun to provide a glimpse of a consensus (≈25–50 yr−1); however, a consistent estimate remains lacking. Here, we present the first all-sky search for Galactic novae using 8 yr of data from the Near Earth Object WISE (NEOWISE) mid-infrared (MIR) survey. Operating at 3.4 and 4.6 µm where interstellar extinction is negligible, the 6-month cadence NEOWISE data set offers unique sensitivity to discover slowly evolving novae across the entire Galaxy. Using a novel image subtraction pipeline together with systematic selection criteria, we identify a sample of 49 rapidly evolving MIR outbursts as candidate Galactic novae. While 27 of these sources are known novae, the remaining are previously missed nova candidates discovered in this work. The unknown events are spatially clustered along the densest and most heavily obscured regions of the Galaxy where previous novae are severely underrepresented. We use simulations of the NEOWISE survey strategy, the pipeline detection efficiency, and our criteria to derive a Galactic nova rate of $47.9^{+3.1}_{-8.3}$ yr−1. The discovery of these exceptionally bright (yet overlooked) nova candidates confirms emerging suggestions that optical surveys have been highly incomplete in searches for Galactic novae, highlighting the potential for MIR searches in revealing the demographics of Galactic stellar outbursts.
UNCOVERing the extended strong lensing structures of Abell 2744 with the deepest JWST imaging
Authors: Furtak Lukas J , Zitrin Adi , Weaver John R , Atek Hakim , Bezanson Rachel , Labbé Ivo , Whitaker Katherine E , Leja Joel , Price Sedona H , Brammer Gabriel B , Wang Bingjie , Marchesini Danilo , Pan Richard , Dayal Pratika , van Dokkum Pieter , Feldmann Robert , Fujimoto Seiji , Franx Marijn , Khullar Gourav , Nelson Erica J , Mowla Lamiya A 
Published: May 2023

ABSTRACT
We present a new parametric lens model for the massive galaxy cluster Abell 2744 based on new ultra-deep JWST imaging taken in the framework of the UNCOVER program. These observations constitute the deepest JWST images of a lensing cluster to date, adding to existing deep Hubble Space Telescope (HST) images and the recent JWST Early Release Science and Director’s Discretionary Time data taken for this field. The wide field of view of UNCOVER (∼45 arcmin2) extends beyond the cluster’s well-studied central core and reveals a spectacular wealth of prominent lensed features around two massive cluster sub-structures in the north and north-west, where no multiple images were previously known. We identify 75 new multiple images and candidates of 17 sources, 43 of which allow us, for the first time, to constrain the lensing properties and total mass distribution around these extended cluster structures using strong lensing (SL). Our model yields an effective Einstein radius of θE, main = 23.2 ± 2.3 arcsec for the main cluster core (for zs = 2), enclosing a mass of M(&lt; θE, main) = (7.7 ± 1.1) × 1013 M⊙, and θE, NW = 13.1 ± 1.3 arcsec for the newly discovered north-western SL structure enclosing M(&lt; θE, NW) = (2.2 ± 0.3) × 1013 M⊙. The northern clump is somewhat less massive with θE, N = 7.4 ± 0.7 arcsec enclosing M(&lt; θE, N) = (0.8 ± 0.1) × 1013 M⊙. We find the northern sub-structures of Abell 2744 to broadly agree with the findings from weak lensing analyses and align with the filamentary structure found by these previous studies. Our model in particular reveals a large area of high magnification values between the various cluster structures, which will be paramount for lensed galaxy studies in the UNCOVER field. The model is made publicly available to accompany the first UNCOVER data release.
Multidimensional profiling reveals GATA1-modulated stage-specific chromatin states and functional associations during human erythropoiesis
Authors: Li Dong , Zhao Xin-Ying , Zhou Shuo , Hu Qi , Wu Fan , Lee Hsiang-Ying 
Published: May 2023

Abstract
Mammalian erythroid development can be divided into three stages: hematopoietic stem and progenitor cell (HSPC), erythroid progenitor (Ery-Pro), and erythroid precursor (Ery-Pre). However, the mechanisms by which the 3D genome changes to establish the stage-specific transcription programs that are critical for erythropoiesis remain unclear. Here, we analyze the chromatin landscape at multiple levels in defined populations from primary human erythroid culture. While compartments and topologically associating domains remain largely unchanged, ∼50% of H3K27Ac-marked enhancers are dynamic in HSPC versus Ery-Pre. The enhancer anchors of enhancer–promoter loops are enriched for occupancy of respective stage-specific transcription factors (TFs), indicating these TFs orchestrate the enhancer connectome rewiring. The master TF of erythropoiesis, GATA1, is found to occupy most erythroid gene promoters at the Ery-Pro stage, and mediate conspicuous local rewiring through acquiring binding at the distal regions in Ery-Pre, promoting productive erythroid transcription output. Knocking out GATA1 binding sites precisely abrogates local rewiring and corresponding gene expression. Interestingly, knocking down GATA1 can transiently revert the cell state to an earlier stage and prolong the window of progenitor state. This study reveals mechanistic insights underlying chromatin rearrangements during development by integrating multidimensional chromatin landscape analyses to associate with transcription output and cellular states.
Phosphorylation status of MUS81 is a modifier of Olaparib sensitivity in BRCA2-deficient cells
Authors: Blandino Francesca , Malacaria Eva , Figlioli Carolina , Noto Alessandro , Pugliese Giusj Monia , Franchitto Annapaola , Pichierri Pietro 
Published: May 2023

Abstract
The MUS81 complex is crucial for preserving genome stability through resolution of branched DNA intermediates in mitosis and also for the processing of deprotected replication forks in BRCA2-deficient cells. Because of the existence of two different MUS81 complexes in mammalian cells that act in M- or S-phase, whether and how the PARPi sensitivity of BRCA2-deficient cells is affected by loss of MUS81 function is unclear. Here, using a mutant of MUS81 that impairs its function in M-phase, we show that viability of BRCA2-deficient cells but not their PARPi sensitivity requires a fully-functional MUS81 complex in mitosis. In contrast, expression of a constitutively-active MUS81 is sufficient to confer PARPi resistance. From a mechanistic point of view, our data indicate that deregulated action of the mitotic active form of MUS81 in S-phase leads to the cleavage of stalled replication forks before their reversal, bypassing fork deprotection, and engaging a Polθ-dependent DSBs repair. Collectively, our findings describe a novel mechanism leading to PARPi resistance that involves unscheduled MUS81-dependent cleavage of intact, unreversed replication forks. Since this cleavage occurs mimicking the phosphorylated status of S87 of MUS81, our data suggest that hyperphosphorylation of this residue in S-phase might represent a novel biomarker to identify resistance to PARPi.
Active in vivo translocation of the Methanosarcina mazei Gö1 Casposon
Authors: Gehlert Finn O , Nickel Lisa , Vakirlis Nikolaos , Hammerschmidt Katrin , Vargas Gebauer Herman I , Kießling Claudia , Kupczok Anne , Schmitz Ruth A 
Published: May 2023

Abstract
Casposons are transposable elements containing the CRISPR associated gene Cas1solo. Identified in many archaeal genomes, casposons are discussed as the origin of CRISPR-Cas systems due to their proposed Cas1solo-dependent translocation. However, apart from bioinformatic approaches and the demonstration of Cas1solo integrase and endonuclease activity in vitro, casposon transposition has not yet been shown in vivo. Here, we report on active casposon translocations in Methanosarcina mazei Gö1 using two independent experimental approaches. First, mini-casposons, consisting of a R6Kγ origin and two antibiotic resistance cassettes, flanked by target site duplications (TSDs) and terminal inverted repeats (TIRs), were generated, and shown to actively translocate from a suicide plasmid and integrate into the chromosomal MetMaz-C1 TSD IS1a. Second, casposon excision activity was confirmed in a long-term evolution experiment using a Cas1solo overexpression strain in comparison to an empty vector control under four different treatments (native, high temperature, high salt, mitomycin C) to study stress-induced translocation. Analysis of genomic DNA using a nested qPCR approach provided clear evidence of casposon activity in single cells and revealed significantly different casposon excision frequencies between treatments and strains. Our results, providing the first experimental evidence for in vivo casposon activity are summarized in a modified hypothetical translocation model.
Coronary Artery Disease in Persons With Human Immunodeficiency Virus Without Detectable Viral Replication
Authors: Knudsen Andreas D , Fuchs Andreas , Benfield Thomas , Gerstoft Jan , Køber Lars , Trøseid Marius , Kofoed Klaus F , Nielsen Susanne D 
Published: May 2023

Abstract

Background
We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 6, IL-1β, and high-sensitivity C-reactive protein (hsCRP), were associated with CAD.

Methods
From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as &gt;0% stenosis, and obstructive CAD as ≥50% stenosis.

Results
Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels &gt;2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1β was not associated with CAD.

Conclusions
In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD.
Constitutional Adjudication in the European Legal Space
Authors: von Bogdandy Armin , Grabenwarter Christoph , Huber Peter M 
Published: May 2023

Abstract
This chapter highlights the characteristics, challenges, and perspectives of constitutional adjudication in Europe. It is the concluding chapter to the two respective volumes of the Max Planck Handbooks. Though there are many different institutionalizations and trajectories, all the relevant courts increasingly share features for their involvement in and their responsibility for the European legal space. The positive foundation of this common responsibility are the values established in Article 2 TEU. This responsibility is, however, being subjected to a severe test today; indeed the main challenge these courts face today is authoritarianism. To combat this rise of authoritarianism, this chapter argues, they must form a more perfect union.
Buyers’ Sourcing Strategies and Suppliers’ Markups in Bangladeshi Garments
Authors: Cajal-Grossi Julia , Macchiavello Rocco , Noguera Guillermo 
Published: May 2023

AbstractWe study differences in markups earned by Bangladeshi garment exporters across buyers with different sourcing strategies and make three contributions. First, we distinguish buyers with a relational versus a spot sourcing strategy and show that a buyer’s sourcing strategy is correlated across products and origins. Buyer fixed effects explain most of the variation in sourcing strategies, suggesting that these depend on organizational capabilities. Second, we use novel data that match quantities and prices of the two main variable inputs in the production of garments (fabric and labor on sewing lines) to specific export orders. We derive conditions under which these data allow measurement of within exporter-product-time differences in markups across orders produced for different buyers. Third, we show that exporters earn higher markups on otherwise identical orders produced for relational, as opposed to spot, buyers. A sourcing model with imperfect contract enforcement, idiosyncratic shocks to exporters, and buyers that adopt different sourcing strategies trading off higher prices and reliable supply rationalizes this and other observed facts in the industry. We discuss alternative explanations and policy implications.
DAS28-γGT for the prediction of major cardiovascular events in rheumatoid arthritis: results from the ESPOIR cohort
Authors: Dupont Anne , Constantin Arnaud , Soubrier Martin , Rincheval Nathalie , Avouac Jérôme 
Published: May 2023

Abstract

Objective
To validate the predictive value of the DAS28 γ-glutamyl transferase (DAS28-γGT) for the occurrence of major cardiovascular (CV) events (MACE) in the ‘Etude et Suivi des Polyarthrites Indifférenciées Récentes’ ESPOIR cohort.

Methods
Analysis of 13-year outcome from the ESPOIR cohort. RA patients with missing data for baseline γGT activity and those not followed-up to 1 year were excluded. Baseline DAS28-γGT was calculated using the following formula: 0.56*√TJ-28 + 0.28 * √SJ-28 + 2*ln(γGT) + 0.014 * GH. Our primary outcome was the merit of the DAS28-γGT in predicting the occurrence of MACE.

Results
Among the 696 patients [536 women, mean (s.d.) age of 49 (12) years], 34 MACE were recorded, with a mean time to event of 71 (44) months. Receiver operating characteristic curve analysis indicated that a DAS28-γGT &gt;9.4 had the best sensitivity and specificity for the diagnosis of MACE during the observation period. DAS28-γGT &gt;9.4 was predictive of the occurrence of MACE, with a hazard ratio (HR) of 3.11 (95% CI 1.41, 5.43). Multivariate Cox analyses confirmed higher DAS28-γGT (HR 2.44, 95% CI 1.05, 5.64) together with age (HR 1.04, 95% CI 1.01, 1.07) and diabetes mellitus (HR 4.12, 95% CI 1.55, 10.95) as independent predictors of MACE. There was a dose effect of the DAS28-γGT for MACE-risk prediction, which was in line with the application of the Framingham risk score.

Conclusion
The DAS28-γGT was identified in this large prospective cohort as an independent predictor of MACE in patients with RA. The DAS28-γGT is a simple and useful tool to evaluate CV risk in routine and warn the clinician about the CV risk burden in patients with RA.
Surveillance within the Law: A Critique of the Legal Framework for Surveillance of Digital Communications by Law Enforcement Authorities in Botswana
Authors: Balule Badala Tachilisa , Dambe Baboki Jonathan 
Published: May 2023

Abstract
Surveillance of digital communications invokes both commendation and criticism. Whereas it may serve justifiable and legitimate purposes, it is also susceptible to abuse if it is undertaken in the absence of adequate safeguards. In 2022, Botswana enacted the Criminal Procedure and Evidence (Controlled Investigations) Act. The Act is intended to regulate the surveillance of digital communications for law enforcement purposes. This article assesses whether the Act provides adequate procedural safeguards to protect against undue infringement of fundamental rights, particularly, the right to privacy. In this regard, the article examines how the constitutionally entrenched right to privacy has been interpreted and applied by the courts in Botswana. Consequently, the article interrogates whether the surveillance of digital communications under the auspices of the Criminal Procedure and Evidence (Controlled Investigations) Act falls within the parameters of justifiable inroads into the right to privacy. The analysis of the Act is undertaken drawing inspiration from international jurisprudence on how to balance the necessity for surveillance with respect for fundamental rights.
Inferring Historical Introgression with Deep Learning
Authors: Zhang Yubo , Zhu Qingjie , Shao Yi , Jiang Yanchen , Ouyang Yidan , Zhang Li , Zhang Wei 
Published: May 2023

Abstract
Resolving phylogenetic relationships among taxa remains a challenge in the era of big data due to the presence of genetic admixture in a wide range of organisms. Rapidly developing sequencing technologies and statistical tests enable evolutionary relationships to be disentangled at a genome-wide level, yet many of these tests are computationally intensive and rely on phased genotypes, large sample sizes, restricted phylogenetic topologies, or hypothesis testing. To overcome these difficulties, we developed a deep learning-based approach, named ERICA, for inferring genome-wide evolutionary relationships and local introgressed regions from sequence data. ERICA accepts sequence alignments of both population genomic data and multiple genome assemblies, and efficiently identifies discordant genealogy patterns and exchanged regions across genomes when compared with other methods. We further tested ERICA using real population genomic data from Heliconius butterflies that have undergone adaptive radiation and frequent hybridization. Finally, we applied ERICA to characterize hybridization and introgression in wild and cultivated rice, revealing the important role of introgression in rice domestication and adaptation. Taken together, our findings demonstrate that ERICA provides an effective method for teasing apart evolutionary relationships using whole genome data, which can ultimately facilitate evolutionary studies on hybridization and introgression.
Community-Level Social Vulnerability and Patterns of Adolescent Injury
Authors: Kwon Eustina G. , Herrera-Escobar Juan P. , Bulger Eileen M. , Rice-Townsend Samuel E. , Nehra Deepika 
Published: May 2023

Objective:
To describe adolescent injuries by the community-level social vulnerability, focusing on injuries related to interpersonal violence.

Background:
The Center for Disease Control and Prevention’s social vulnerability index (SVI) is a tool used to characterize community-level vulnerability.

Methods:
Injured adolescent trauma patients (13–17 years old) cared for at a large Level I trauma center over a 10-year period were identified. Injuries were classified by intent as either intentional or unintentional. Census tract level SVI was calculated by composite score and for 4 subindex scores (socioeconomic, household composition/disability, minority/language, housing type/transportation). Patients were stratified by SVI quartile with the lowest quartile designated as low-, the middle two quartiles as average-, and the highest quartile as high vulnerability. The primary outcome was odds of intentional injury. Demographic and injury characteristics were compared by SVI and intent. Multivariable logistic regression was used to estimate the adjusted odds of intentional injury associated with SVI.

Results:
A total of 1993 injured adolescent patients (1676 unintentional and 317 intentional) were included. The composite SVI was higher in the intentional injury cohort (mean, SD: 66.7, 27.8 vs. 50.5, 30.2; P < 0.001) as was each subindex SVI. The high SVI cohort comprised 31% of the study population, 49% of intentional injuries, and 51% of deaths. The high SVI cohort had significantly increased unadjusted (odds ratio, 4.5; 95% confidence interval, 3.0–6.6) and adjusted (odds ratio, 1.8; 95% confidence interval, 1.6–2.8) odds of intentional injury.

Conclusions:
Adolescents living in the highest SVI areas experience significantly higher odds of intentional injury. SVI and SVI subindex details may provide direction for community-level interventions to decrease the impact of violent injury among adolescents.