bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic broad-band X-ray study of super-Eddington accretion on to supermassive black holes – I. X-ray continuum
Authors: Tortosa Alessia , Ricci Claudio , Ho Luis C , Tombesi Francesco , Du Pu , Inayoshi Kohei , Wang Jian-Min , Shangguan Jinyi , Li Ruancun 
Published: December 2022

ABSTRACT
We present the first systematic broad-band X-ray study of super-Eddington accretion onto supermassive black holes with simultaneous NuSTAR and XMM–Newton or Swift/XRT observations of a sample of eight super-Eddington accreting Active Galactic Nuclei (AGNs) with Eddington ratio 1 &lt; λ Edd &lt; 426. We find that the super-Eddington accreting massive black holes (SEAMBHs) show a steep primary continuum slope as expected for sources accreting in the super-Eddington regime, mostly dominated by relativistic reflection. The iron K α emission lines of the sources of our sample show relativistic broadening. In addition, the equivalent widths of the narrow components of the iron K α lines follow the ‘X-ray Baldwin’ effect, also known as the ‘Iwasawa–Taniguchi’ effect. We found a statistically significant correlation between the photon index of the primary power law and the Eddington ratio, consistent with past studies. Moreover, as expected for super-Eddington sources, the median value of the reflection fraction of the sources we analysed is a factor ∼ 2 higher than the median reflection fraction value of the type 1 AGN from the BASS sample. We are able to estimate the coronal temperature for three sources of our sample: Mrk 382 (kTe = 7.75 keV), PG 0026+129 (kTe = 39 keV), and IRAS 04416+1215 (kTe = 2.95 keV). Looking at the position of the SEAMBHs sources of our sample in the compactness–temperature diagram it appears that in super-Eddington AGN, as for lower Eddington ratio AGN, the X-ray corona is controlled by pair production and annihilation.
The metallicity’s fundamental dependence on both local and global galactic quantities
Authors: Baker William M , Maiolino Roberto , Belfiore Francesco , Curti Mirko , Bluck Asa F L , Lin Lihwai , Ellison Sara L , Thorp Mallory , Pan Hsi-An 
Published: December 2022

ABSTRACT
We study the scaling relations between gas-phase metallicity, stellar mass surface density (Σ*), star formation rate surface density (ΣSFR), and molecular gas surface density ($\Sigma _{{\rm H}_2}$) in local star-forming galaxies on scales of a kpc. We employ optical integral field spectroscopy from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, and ALMA data for a subset of MaNGA galaxies. We use partial correlation coefficients and Random Forest regression to determine the relative importance of local and global galactic properties in setting the gas-phase metallicity. We find that the local metallicity depends primarily on Σ* (the resolved mass–metallicity relation, rMZR), and has a secondary anticorrelation with ΣSFR (i.e. a spatially resolved version of the ‘Fundamental Metallicity Relation’, rFMR). We find that $\Sigma _{{\rm H}_2}$ is less important than ΣSFR in determining the local metallicity. This result indicates that gas accretion, resulting in local metallicity dilution and local boosting of star formation, is unlikely to be the primary origin of the rFMR. The local metallicity depends also on the global properties of galaxies. We find a strong dependence on the total stellar mass (M*) and a weaker (inverse) dependence on the total SFR. The global metallicity scaling relations, therefore, do not simply stem out of their resolved counterparts; global properties and processes, such as the global gravitational potential well, galaxy-scale winds and global redistribution/mixing of metals, likely contribute to the local metallicity, in addition to local production and retention.
A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair
Authors: Bralić Amer , Tehseen Muhammad , Sobhy Mohamed A , Tsai Chi-Lin , Alhudhali Lubna , Yi Gang , Yu Jina , Yan Chunli , Ivanov Ivaylo , Tsutakawa Susan E , Tainer John A , Hamdan Samir M 
Published: December 2022

AbstractNucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding showed XPG acts by switching ssDNA translocation to dsDNA unwinding as a likely committed step. Pertinent to the NER pathway regulation, XPG incision activity is suppressed during coreTFIIH translocation on DNA but is licensed when coreTFIIH stalls at the lesion or when ATP hydrolysis is blocked. Moreover, ≥15 nucleotides of 5′-ssDNA is a prerequisite for efficient translocation and incision. Our results unveil a paired coordination mechanism in which key lesion scanning and DNA incision steps are sequentially coordinated, and damaged patch removal is only licensed after generation of ≥15 nucleotides of 5′-ssDNA, ensuring the correct ssDNA bubble size before cleavage.
Freddie: annotation-independent detection and discovery of transcriptomic alternative splicing isoforms using long-read sequencing
Authors: Orabi Baraa , Xie Ning , McConeghy Brian , Dong Xuesen , Chauve Cedric , Hach Faraz 
Published: December 2022

AbstractAlternative splicing (AS) is an important mechanism in the development of many cancers, as novel or aberrant AS patterns play an important role as an independent onco-driver. In addition, cancer-specific AS is potentially an effective target of personalized cancer therapeutics. However, detecting AS events remains a challenging task, especially if these AS events are novel. This is exacerbated by the fact that existing transcriptome annotation databases are far from being comprehensive, especially with regard to cancer-specific AS. Additionally, traditional sequencing technologies are severely limited by the short length of the generated reads, which rarely spans more than a single splice junction site. Given these challenges, transcriptomic long-read (LR) sequencing presents a promising potential for the detection and discovery of AS. We present Freddie, a computational annotation-independent isoform discovery and detection tool. Freddie takes as input transcriptomic LR sequencing of a sample alongside its genomic split alignment and computes a set of isoforms for the given sample. It then partitions the input reads into sets that can be processed independently and in parallel. For each partition, Freddie segments the genomic alignment of the reads into canonical exon segments. The goal of this segmentation is to be able to represent any potential isoform as a subset of these canonical exons. This segmentation is formulated as an optimization problem and is solved with a dynamic programming algorithm. Then, Freddie reconstructs the isoforms by jointly clustering and error-correcting the reads using the canonical segmentation as a succinct representation. The clustering and error-correcting step is formulated as an optimization problem—the Minimum Error Clustering into Isoforms (MErCi) problem—and is solved using integer linear programming (ILP). We compare the performance of Freddie on simulated datasets with other isoform detection tools with varying dependence on annotation databases. We show that Freddie outperforms the other tools in its accuracy, including those given the complete ground truth annotation. We also run Freddie on a transcriptomic LR dataset generated in-house from a prostate cancer cell line with a matched short-read RNA-seq dataset. Freddie results in isoforms with a higher short-read cross-validation rate than the other tested tools. Freddie is open source and available at https://github.com/vpc-ccg/freddie/.
The structure, binding and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3
Authors: Hall Daniel , Giaimo Benedetto Daniele , Park Sung-Soo , Hemmer Wiebke , Friedrich Tobias , Ferrante Francesca , Bartkuhn Marek , Yuan Zhenyu , Oswald Franz , Borggrefe Tilman , Rual Jean-François , Kovall Rhett A 
Published: December 2022

Abstract
The Notch pathway transmits signals between neighboring cells to elicit downstream transcriptional programs. Notch is a major regulator of cell fate specification, proliferation, and apoptosis, such that aberrant signaling leads to a pleiotropy of human diseases, including developmental disorders and cancers. The pathway signals through the transcription factor CSL (RBPJ in mammals), which forms an activation complex with the intracellular domain of the Notch receptor and the coactivator Mastermind. CSL can also function as a transcriptional repressor by forming complexes with one of several different corepressor proteins, such as FHL1 or SHARP in mammals and Hairless in Drosophila. Recently, we identified L3MBTL3 as a bona fide RBPJ-binding corepressor that recruits the repressive lysine demethylase LSD1/KDM1A to Notch target genes. Here, we define the RBPJ-interacting domain of L3MBTL3 and report the 2.06 Å crystal structure of the RBPJ–L3MBTL3–DNA complex. The structure reveals that L3MBTL3 interacts with RBPJ via an unusual binding motif compared to other RBPJ binding partners, which we comprehensively analyze with a series of structure-based mutants. We also show that these disruptive mutations affect RBPJ and L3MBTL3 function in cells, providing further insights into Notch mediated transcriptional regulation.
Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of gene regulatory programs in cancers
Authors: Castro-Mondragon Jaime A , Aure Miriam Ragle , Lingjærde Ole Christian , Langerød Anita , Martens John W M , Børresen-Dale Anne-Lise , Kristensen Vessela N , Mathelier Anthony 
Published: December 2022

AbstractMost cancer alterations occur in the noncoding portion of the human genome, where regulatory regions control gene expression. The discovery of noncoding mutations altering the cells’ regulatory programs has been limited to few examples with high recurrence or high functional impact. Here, we show that transcription factor binding sites (TFBSs) have similar mutation loads to those in protein-coding exons. By combining cancer somatic mutations in TFBSs and expression data for protein-coding and miRNA genes, we evaluate the combined effects of transcriptional and post-transcriptional alterations on the regulatory programs in cancers. The analysis of seven TCGA cohorts culminates with the identification of protein-coding and miRNA genes linked to mutations at TFBSs that are associated with a cascading trans-effect deregulation on the cells’ regulatory programs. Our analyses of cis-regulatory mutations associated with miRNAs recurrently predict 12 mature miRNAs (derived from 7 precursors) associated with the deregulation of their target gene networks. The predictions are enriched for cancer-associated protein-coding and miRNA genes and highlight cis-regulatory mutations associated with the dysregulation of key pathways associated with carcinogenesis. By combining transcriptional and post-transcriptional regulation of gene expression, our method predicts cis-regulatory mutations related to the dysregulation of key gene regulatory networks in cancer patients.
PARG and BRCA1–BARD1 cooperative function regulates DNA repair pathway choice during gametogenesis
Authors: Trivedi Shalini , Blazícková Jitka , Silva Nicola 
Published: December 2022

Abstract
Meiotic chromosome segregation relies on programmed DNA double-strand break induction. These are in turn repaired by homologous recombination, generating physical attachments between the parental chromosomes called crossovers. A subset of breaks yields recombinant outcomes, while crossover-independent mechanisms repair the majority of lesions. The balance between different repair pathways is crucial to ensure genome integrity. We show that Caenorhabditis elegans BRC-1/BRCA1-BRD-1/BARD1 and PARG-1/PARG form a complex in vivo, essential for accurate DNA repair in the germline. Simultaneous depletion of BRC-1 and PARG-1 causes synthetic lethality due to reduced crossover formation and impaired break repair, evidenced by hindered RPA-1 removal and presence of aberrant chromatin bodies in diakinesis nuclei, whose formation depends on spo-11 function. These factors undergo a similar yet independent loading in developing oocytes, consistent with operating in different pathways. Abrogation of KU- or Theta-mediated end joining elicits opposite effects in brc-1; parg-1 doubles, suggesting a profound impact in influencing DNA repair pathway choice by BRC-1-PARG-1. Importantly, lack of PARG-1 catalytic activity suppresses untimely accumulation of RAD-51 foci in brc-1 mutants but is only partially required for fertility. Our data show that BRC-1/BRD-1–PARG-1 joint function is essential for genome integrity in meiotic cells by regulating multiple DNA repair pathways.
BELL1 interacts with CRABS CLAW and INNER NO OUTER to regulate ovule and seed development in pomegranate
Authors: Zhao Yujie , Wang Yuying , Yan Ming , Liu Cuiyu , Yuan Zhaohe 
Published: December 2022

Abstract
Pomegranate (Punica granatum) flowers are classified as bisexual flowers and functional male flowers. Functional male flowers have sterile pistils that show abnormal ovule development. In previous studies, we identified INNER NO OUTER (INO), CRABS CLAW (CRC), and BELL1 (BEL1), which were specifically expressed in bisexual and functional male flowers. However, the functions of ovule identity genes and the mechanism underlying ovule sterility in pomegranate remain unknown. Here, we found that the integument primordia formed and then ceased developing in the ovules of functional male flowers with a vertical diameter of 8.1–13.0 mm. Megaspore mother cells were observed in bisexual flowers when the vertical diameters of flowers were 10.1–13.0 mm, but not in functional male flowers. We analyzed the expression patterns of ovule-related genes in pomegranate ovule sterility and found that PgCRC mRNA was highly expressed at a critical stage of ovule development in bisexual flowers. Ectopic expression of PgCRC and PgINO was sufficient to increase seed number in transgenic lines. PgCRC partially complemented the Arabidopsis (Arabidopsis thaliana) crc mutant, and PgINO successfully rescued the seeds set in the Arabidopsis ino mutant. The results of yeast two-hybrid assays, bimolecular fluorescence complementation assays, and genetic data analyses showed that PgCRC and PgINO directly interact with PgBEL1. Our results also showed that PgCRC and PgINO could not interact directly with MADS-box proteins and that PgBEL1 interacted with SEPALLATA proteins. We report the function of PgCRC and PgINO in ovule and seed development and show that PgCRC and PgINO interact with PgBEL1. Thus, our results provide understanding of the genetic regulatory networks underlying ovule development in pomegranate.
Infantile Takayasu: clinical features and long-term outcome
Authors: Miller-Barmak Adi , Sztajnbok Flavio , Balik Zeynep , Borzutzky Arturo , Fogel Leslie A , Goldzweig Ofra , Ozen Seza , Butbul Aviel Yonatan 
Published: December 2022

Abstract

Objectives
Takayasu arteritis (TAK) is a large-vessel vasculitis rarely reported in children and infants. Most articles on paediatric TAK have not focused on infants. We present the largest case series of infantile TAK, aiming to identify its demographic and clinical characteristics and compare them with existing data on older children.

Methods
We conducted an international multicentre retrospective cohort study. Epidemiological and clinical data were collected from patients’ charts from six rheumatology centres. All patients met both the EULAR/PReS 2008 criteria and the 1990 ACR/EULAR criteria and were diagnosed with TAK at age &lt;5 years.

Results
Twelve patients were included (50% female). Median age of symptom onset was 11 months, with a diagnostic delay of 4 months. The most common symptoms at presentation were hypertension, blood pressure differences between limbs, and fever. The most commonly involved arteries were the abdominal aorta and renal artery. Medications included steroids, conventional and biologic DMARDs, and other immunosuppressive therapies. Half of the patients received biologic agents, of which infliximab had the highest complete remission rate (40%). Other medications resulting in complete remission were CYC (40%) and MTX (38%). Invasive procedures were required for 58% of patients. The most common complications were cardiac (50%), stroke (42%), and serious infections (33%). No patients died.

Conclusion
This study presents the largest series of infantile TAK. Compared with other reported series on older children, infants with TAK have more severe disease and were more likely to receive biologic agents, develop complications, and require invasive interventions.
Populist Female MPs and the Discourse around Gender and Gender-based Violence in the Italian Twittersphere during the Pandemic
Authors: Giorgi Alberta , Loner Enzo 
Published: December 2022

AbstractRecent research exploring the relationships between gender and populism has shown that populist parties, mainly right-wing, usually do not advance a women-friendly agenda and do not provide women-favorable environments. Nevertheless, concerns about women’s rights and combating violence against women are gaining space within populist discourse. In this contribution, we analyze the tweets of populist female MPs in the Italian Parliament to explore their discourse on gender issues, paying particular attention to gender-based violence and the internal differences in the discourse of populist female MPs. The results show how right-wing female MPs promote a “right-wing” version of women’s rights, especially when dealing with gender-based violence. The results also point out the differences in populist discourse on gender and gender-based violence in different varieties of populism.
Dengue and COVID-19 co-infections: an important consideration in the tropics
Authors: Dalugama Chamara , Seneviratne Suranjith L 
Published: December 2022

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected &gt;370 million individuals worldwide. Dengue is endemic in many countries and leads to epidemics at frequent intervals. In the tropics and subtropics, it is possible that individuals may be concurrently infected with both dengue and SARS-CoV-2. Differentiation between the two infections may be difficult from both a clinical and laboratory perspective. We have outlined the currently published findings (as of the end of December 2021) on patients with dengue and SARS-CoV-2 co-infections and have discussed the observed outcomes and management of such patients. Co-infections were more common in males &gt;25 y of age, fever was not universal, 30–50% had medical comorbidities such as diabetes mellitus or hypertension and the case fatality rate was 16–28%.
A Bacterial Wilt Disease Caused by a New Bacterial Pathogen of Guar Belonging to the Genus Pantoea Identified in Texas
Authors: Obasa Ken , Ravelombola Waltram , Avila Jaqueline 
Published: December 2022

Guar ( Cyamopsis tetragonoloba [L.] Taub) or cluster bean is a legume plant that is cultivated mainly for its galactomannan (guar gum) extracted from the seed endosperm. In 2021, a disease outbreak among germplasms in the Texas A&M AgriLife Research Guar Breeding Program located in Vernon, Texas, was observed. Symptoms of the disease were similar to bacterial blight caused by Xanthomonas axonopodis pv . cyamopsidis and included black necrotic streaks on stems and petioles, vascular necrosis, wilting, and eventual death of affected plants. The disease incidence ranged from 75 to 90% in each of the affected germplasms. Diagnosis of affected germplasms consistently recovered bacteria that were identified on the basis of their 16S rRNA partial gene sequence as belonging to the genus Pantoea. Two independent pathogenicity assays and the satisfaction of Koch's postulate under greenhouse experimental conditions determined that the Pantoea isolates were the causal agent of the disease. Investigations of the disease etiology also led to the discovery that the Pantoea sp. can be seedborne. Additionally, although the disease symptoms share similarities with those of bacterial blight in guar, they differ in the absence of the large angular necrotic lesions on leaves that are characteristic of the later stage of the bacterial blight infection. However, infection by the Pantoea sp. similarly resulted in the eventual death of affected plants. Whole-genome pairwise alignments and multilocus sequence analysis of the isolate indicate that it is most closely related to P. vagans, but also distinct genetically, and tentatively designated as Pantoae sp. isolate B550. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Preoperative frailty screening, assessment and management
Authors: Cappe Maximilien , Laterre Pierre-François , Dechamps Mélanie 
Published: December 2022

Purpose of review
To highlight the importance of frailty assessment in thoracic surgery patients.

Recent findings
Frailty results from an accelerated loss of functional reserve associated with ageing and leads to increased vulnerability following surgery. It is a complex and multidimensional syndrome involving physiological and psychosocial systems. Frailty is a separate entity from comorbidities and disabilities. Frailty is associated with an increased risk of complications and a higher mortality rate after thoracic surgery. Patients can easily be screened for frailty and frail patients can benefit from further assessment of all areas of frailty secondarily. Prehabilitation and rehabilitation can help limit frailty-related complications after thoracic surgery.

Summary
Frailty should be part of the routine preoperative evaluation for thoracic surgery. Frailty must be considered in assessing eligibility for surgery and in planning prehabilitation and rehabilitation if necessary.