bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sagas and genre: A case for application of network analysis to manuscripts preserving Old Norse-Icelandic saga literature
Authors: Kapitan Katarzyna Anna , Wills Tarrin 
Published: April 2023

Abstract
This study applies statistical approaches to the analysis of the genre relationships of Old Norse-Icelandic literature in order to expand our understanding of the relationships between works, their transmission, and their possible modes of reception, as manifested in the extant manuscripts. This article contributes to the ongoing discussion of the genre boundaries of Old Norse-Icelandic literature and presents an alternative method of engaging with this material in the form of computer-assisted analysis, i.e. data visualization and network analysis. Using data collected from major online databases of Old Norse-Icelandic manuscripts, we present the most complete to date network of co-occurrences in manuscripts of works belonging to a number of literary genres. The present study empirically demonstrates the manifoldness of the connections between the Old Norse-Icelandic works which transcend traditional scholarly genre boundaries. The study identifies two main communities within the network: a community of romances, or works of narrative fiction, which includes mainly legendary sagas (fornaldarsögur) and chivalric sagas (riddarasögur), and a community of historicizing narratives, or pseudo-history, which includes mainly sagas of Icelanders (Íslendingasögur) and kings’ sagas (konungasögur).
Abundances of CNO elements in z ∼ 0.3–0.4 Lyman continuum leaking galaxies
Authors: Izotov Y I , Schaerer D , Worseck G , Berg D , Chisholm J , Ravindranath S , Thuan T X 
Published: April 2023

ABSTRACT
We present observations with the Space Telescope Imaging Spectrograph onboard the Hubble Space Telescope (HST) of 11 Lyman continuum (LyC) leaking galaxies at redshifts, z, in the range 0.29–0.43, with oxygen abundances 12+log(O/H) = 7.64–8.16, stellar masses M⋆ ∼ 107.8–109.8 M⊙, and O32 = [O iii] λ5007/[O ii] λ3727 of ∼ 5–20 aiming to detect the C iii] λ1908 emission line. We combine these observations with the optical Sloan Digital Sky Survey (SDSS) spectra for the determination of carbon, nitrogen, and oxygen abundances. Our sample was supplemented by 31 galaxies from the literature, for which carbon, nitrogen, and oxygen abundances can be derived from the HST and SDSS spectra. These additional galaxies, however, do not have LyC observations. We find that log(C/O) for the entire sample at 12+log(O/H) &lt; 8.1 does not depend on metallicity, with a small dispersion of ∼0.13 dex around the average value of ∼−0.75 dex. On the other hand, the log(N/O) in galaxies at z &gt; 0.1, including LyC leakers, is systematically higher compared to the rest of the sample with lower metallicity. We find that log(C/O) slightly decreases with increasing M⋆ from ∼ −0.65 at M⋆ = 106 M⊙ to ∼ −0.80 at M⋆ = 109–1010 M⊙, whereas log(N/O) is considerably enhanced at M⋆ &gt; 108 M⊙. The origin of these trends remains basically unknown. A possible solution would be to assume that the upper mass limit of the stellar initial mass function in more massive galaxies is higher. This would result in a higher production of oxygen and a larger fraction of massive stars with stellar wind polluting the interstellar medium with nitrogen.
Gas distribution in ODISEA sources from ALMA long-baseline observations in 12CO(2-1)
Authors: Antilen Juanita , Casassus Simon , Cieza Lucas A , González-Ruilova Camilo 
Published: April 2023

ABSTRACT
The 12CO rotational lines in protoplanetary discs are good tracers of the total spatial extension of the gas component, and potentially planet–disc interactions. We present ALMA long baseline observations of the 12CO(2-1) line of 10 protoplanetary discs from the Ophiuchus DIsc Survey Employing ALMA (ODISEA) project, aiming to set constraints on the gas distribution of these sources. The position angle of the gaseous disc can be inferred for five sources using high-velocity channels, which trace the gas in the inner part of the disc. We compare the high-velocity PAs to the orientations inferred from the continuum, representative of the orientation over ∼53 to 256 au in these resolved discs. We find a significant difference in orientation for DoAr 44, which is evidence of a tilted inner disc. Eight discs show evidence of gas inside inner dust cavities or gaps, and the disc of ISO-Oph 196 is not detected in 12CO(2-1), except for the compact signal located inside its dust cavity. Our observations also point out a possible outflow in WLY 2-63.
Esearch3D: propagating gene expression in chromatin networks to illuminate active enhancers
Authors: Heer Maninder , Giudice Luca , Mengoni Claudia , Giugno Rosalba , Rico Daniel 
Published: April 2023

Abstract
Most cell type-specific genes are regulated by the interaction of enhancers with their promoters. The identification of enhancers is not trivial as enhancers are diverse in their characteristics and dynamic in their interaction partners. We present Esearch3D, a new method that exploits network theory approaches to identify active enhancers. Our work is based on the fact that enhancers act as a source of regulatory information to increase the rate of transcription of their target genes and that the flow of this information is mediated by the folding of chromatin in the three-dimensional (3D) nuclear space between the enhancer and the target gene promoter. Esearch3D reverse engineers this flow of information to calculate the likelihood of enhancer activity in intergenic regions by propagating the transcription levels of genes across 3D genome networks. Regions predicted to have high enhancer activity are shown to be enriched in annotations indicative of enhancer activity. These include: enhancer-associated histone marks, bidirectional CAGE-seq, STARR-seq, P300, RNA polymerase II and expression quantitative trait loci (eQTLs). Esearch3D leverages the relationship between chromatin architecture and transcription, allowing the prediction of active enhancers and an understanding of the complex underpinnings of regulatory networks. The method is available at: https://github.com/InfOmics/Esearch3D and https://doi.org/10.5281/zenodo.7737123.
AFM-based force spectroscopy unravels stepwise formation of the DNA transposition complex in the widespread Tn3 family mobile genetic elements
Authors: Fernandez Maricruz , Shkumatov Alexander V , Liu Yun , Stulemeijer Claire , Derclaye Sylvie , Efremov Rouslan G , Hallet Bernard , Alsteens David 
Published: April 2023

Abstract
Transposon Tn4430 belongs to a widespread family of bacterial transposons, the Tn3 family, which plays a prevalent role in the dissemination of antibiotic resistance among pathogens. Despite recent data on the structural architecture of the transposition complex, the molecular mechanisms underlying the replicative transposition of these elements are still poorly understood. Here, we use force-distance curve-based atomic force microscopy to probe the binding of the TnpA transposase of Tn4430 to DNA molecules containing one or two transposon ends and to extract the thermodynamic and kinetic parameters of transposition complex assembly. Comparing wild-type TnpA with previously isolated deregulated TnpA mutants supports a stepwise pathway for transposition complex formation and activation during which TnpA first binds as a dimer to a single transposon end and then undergoes a structural transition that enables it to bind the second end cooperatively and to become activated for transposition catalysis, the latter step occurring at a much faster rate for the TnpA mutants. Our study thus provides an unprecedented approach to probe the dynamic of a complex DNA processing machinery at the single-particle level.
Insplico: effective computational tool for studying splicing order of adjacent introns genome-wide with short and long RNA-seq reads
Authors: Gohr André , Iñiguez Luis P , Torres-Méndez Antonio , Bonnal Sophie , Irimia Manuel 
Published: April 2023

Abstract
Although splicing occurs largely co-transcriptionally, the order by which introns are removed does not necessarily follow the order in which they are transcribed. Whereas several genomic features are known to influence whether or not an intron is spliced before its downstream neighbor, multiple questions related to adjacent introns' splicing order (AISO) remain unanswered. Here, we present Insplico, the first standalone software for quantifying AISO that works with both short and long read sequencing technologies. We first demonstrate its applicability and effectiveness using simulated reads and by recapitulating previously reported AISO patterns, which unveiled overlooked biases associated with long read sequencing. We next show that AISO around individual exons is remarkably constant across cell and tissue types and even upon major spliceosomal disruption, and it is evolutionarily conserved between human and mouse brains. We also establish a set of universal features associated with AISO patterns across various animal and plant species. Finally, we used Insplico to investigate AISO in the context of tissue-specific exons, particularly focusing on SRRM4-dependent microexons. We found that the majority of such microexons have non-canonical AISO, in which the downstream intron is spliced first, and we suggest two potential modes of SRRM4 regulation of microexons related to their AISO and various splicing-related features. Insplico is available on gitlab.com/aghr/insplico.
Novel mechanisms for the removal of strong replication-blocking HMCES- and thiazolidine-DNA adducts in humans
Authors: Sugimoto Yohei , Masuda Yuji , Iwai Shigenori , Miyake Yumi , Kanao Rie , Masutani Chikahide 
Published: April 2023

Abstract
Apurinic/apyrimidinic (AP) sites are DNA lesions created under normal growth conditions that result in cytotoxicity, replication-blocks, and mutations. AP sites are susceptible to β-elimination and are liable to be converted to DNA strand breaks. HMCES (5-hydroxymethylcytosine binding, ES cell specific) protein interacts with AP sites in single stranded (ss) DNA exposed at DNA replication forks to generate a stable thiazolidine protein-DNA crosslink and protect cells against AP site toxicity. The crosslinked HMCES is resolved by proteasome-mediated degradation; however, it is unclear how HMCES-crosslinked ssDNA and the resulting proteasome-degraded HMCES adducts are processed and repaired. Here, we describe methods for the preparation of thiazolidine adduct-containing oligonucleotides and determination of their structure. We demonstrate that the HMCES-crosslink is a strong replication blocking adduct and that protease-digested HMCES adducts block DNA replication to a similar extent as AP sites. Moreover, we show that the human AP endonuclease APE1 incises DNA 5′ to the protease-digested HMCES adduct. Interestingly, while HMCES-ssDNA crosslinks are stable, the crosslink is reversed upon the formation of dsDNA, possibly due to a catalytic reverse reaction. Our results shed new light on damage tolerance and repair pathways for HMCES-DNA crosslinks in human cells.
The ADAR1 editome reveals drivers of editing-specificity for ADAR1-isoforms
Authors: Kleinova Renata , Rajendra Vinod , Leuchtenberger Alina F , Lo Giudice Claudio , Vesely Cornelia , Kapoor Utkarsh , Tanzer Andrea , Derdak Sophia , Picardi Ernesto , Jantsch Michael F 
Published: April 2023

AbstractAdenosine deaminase acting on RNA ADAR1 promotes A-to-I conversion in double-stranded and structured RNAs. ADAR1 has two isoforms transcribed from different promoters: cytoplasmic ADAR1p150 is interferon-inducible while ADAR1p110 is constitutively expressed and primarily localized in the nucleus. Mutations in ADAR1 cause Aicardi – Goutières syndrome (AGS), a severe autoinflammatory disease associated with aberrant IFN production. In mice, deletion of ADAR1 or the p150 isoform leads to embryonic lethality driven by overexpression of interferon-stimulated genes. This phenotype is rescued by deletion of the cytoplasmic dsRNA-sensor MDA5 indicating that the p150 isoform is indispensable and cannot be rescued by ADAR1p110. Nevertheless, editing sites uniquely targeted by ADAR1p150 remain elusive. Here, by transfection of ADAR1 isoforms into ADAR-less mouse cells we detect isoform-specific editing patterns. Using mutated ADAR variants, we test how intracellular localization and the presence of a Z-DNA binding domain-α affect editing preferences. These data show that ZBDα only minimally contributes to p150 editing-specificity while isoform-specific editing is primarily directed by the intracellular localization of ADAR1 isoforms. Our study is complemented by RIP-seq on human cells ectopically expressing tagged-ADAR1 isoforms. Both datasets reveal enrichment of intronic editing and binding by ADAR1p110 while ADAR1p150 preferentially binds and edits 3’UTRs.
BRAF
V600E/RAS Mutations and Lynch Syndrome in Patients With MSI-H/dMMR Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors
Authors: Colle Raphael , Lonardi Sara , Cachanado Marine , Overman Michael J , Elez Elena , Fakih Marwan , Corti Francesca , Jayachandran Priya , Svrcek Magali , Dardenne Antoine , Cervantes Baptiste , Duval Alex , Cohen Romain , Pietrantonio Filippo , André Thierry 
Published: April 2023

Abstract

Background
We pooled data from 2 cohorts of immune checkpoint inhibitors-treated microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer patients to evaluate the prognostic value of RAS/BRAFV600E mutations and Lynch syndrome (LS).

Patients and Methods
Patients were defined as LS-linked if germline mutation was detected and as sporadic if loss of MLH1/PMS2 expression with BRAFV600E mutation and/or MLH1 promoter hypermethylation, or biallelic somatic MMR genes mutations were found. Progression-free survival (PFS) and overall survival (OS) were adjusted on prognostic modifiers selected on unadjusted analysis (P &lt; .2) if limited number of events.

Results
Of 466 included patients, 305 (65.4%) and 161 (34.5%) received, respectively, anti-PD1 alone and anti-PD1+anti-CTLA4 in the total population, 111 (24.0%) were treated in first-line; 129 (28.8%) were BRAFV600E-mutated and 153 (32.8%) RAS-mutated. Median follow-up was 20.9 months. In adjusted analysis of the whole population (PFS/OS events = 186/133), no associations with PFS and OS were observed for BRAFV600E-mutated (PFS HR= 1.20, P = .372; OS HR = 1.06, P = .811) and RAS-mutated patients (PFS HR = 0.93, P = .712, OS HR = 0.75, P = .202). In adjusted analysis in the Lynch/sporadic status-assigned population (n = 242; PFS/OS events = 80/54), LS-liked patients had an improved PFS compared to sporadic cases (HR = 0.49, P = .036). The adjusted HR for OS was 0.56 with no significance (P = .143). No adjustment on BRAFV600E mutation was done due to collinearity.

Conclusion
In this cohort, RAS/BRAFV600E mutations were not associated with survival while LS conferred an improved PFS.
Association Between Immune-Related Adverse Events and Survival in Patients with Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab
Authors: Fukushima Taito , Morimoto Manabu , Kobayashi Satoshi , Ueno Makoto , Uojima Haruki , Hidaka Hisashi , Kusano Chika , Chuma Makoto , Numata Kazushi , Tsuruya Kota , Arase Yoshitaka , Kagawa Tatehiro , Hattori Nobuhiro , Ikeda Hiroki , Watanabe Tsunamasa , Tanaka Katsuaki , Maeda Shin 
Published: April 2023

Abstract

Background
Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab.

Patients and Methods
We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group).

Results
Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P = .055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P = .036). Grade 1/2 irAEs significantly prolonged PFS (P = .014) and OS (P = .003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P = .003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P = .017) on multivariate analysis.

Conclusion
The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.
Investigation of mid-infrared long-term variability of dusty AGB stars using multi-epoch scan data of AKARI and WISE
Authors: Tachibana Kengo , Miyata Takashi , Kamizuka Takafumi , Ohsawa Ryou , Takita Satoshi , Nakagawa Akiharu , Ita Yoshifusa , Uchiyama Mizuho 
Published: April 2023

Abstract
Asymptotic giant branch (AGB) stars are one of the main sources of dust in the Universe. They form and supply dust triggered by stellar pulsations, but the details of the mechanism are still unknown. Among all AGB stars, dusty AGB stars are the most important in terms of dust supply because they contain the star with a high mass-loss rate. To investigate the relationship between the pulsation and the dust supply for such dusty AGB stars, long-term mid-infrared monitoring is necessary. In this study, we combine data from a infrared astronomical satellites AKARI and WISE to generate mid-infrared long-term observation data. This collected data enables us to investigate the variability of dusty AGB stars with a variability period of more than several hundred days (&gt;250 d). Furthermore, we determine the mid-infrared variability amplitudes of 169 O-rich AGB stars and 28 OH/IR stars in our Galaxy, as well as data at other wavelengths. This study is the largest study on mid-infrared variability. Additionally, we discover a positive correlation between the variability amplitude A18μm in the 18μm band and the $\mathit {W3}-\mathit {W4}$ infrared color which is the measure of the dust supply. Also, we find that this relationship is independent of the variability period and mode. Finally, we calculate the radiative transfer of circumstellar dust from AGB stars. The result of our calculations showed that $A_{18\mu \rm {m}}$ is strongly affected by the luminosity change ratio of the central star. These experimental results imply that the luminosity change ratio has a strong influence on the dust supply of AGB star.
Loss of Chloroplast GNAT Acetyltransferases Results in Distinct Metabolic Phenotypes in Arabidopsis
Authors: Ivanauskaite Aiste , Rantala Marjaana , Laihonen Laura , Konert Minna M , Schwenner Naike , Mühlenbeck Jens S , Finkemeier Iris , Mulo Paula 
Published: April 2023

Abstract
Acetylation is one of the most common chemical modifications found on a variety of molecules ranging from metabolites to proteins. Although numerous chloroplast proteins have been shown to be acetylated, the role of acetylation in the regulation of chloroplast functions has remained mainly enigmatic. The chloroplast acetylation machinery in Arabidopsis thaliana consists of eight General control non-repressible 5 (GCN5)-related N-acetyltransferase (GNAT)–family enzymes that catalyze both N-terminal and lysine acetylation of proteins. Additionally, two plastid GNATs have also been reported to be involved in the biosynthesis of melatonin. Here, we have characterized six plastid GNATs (GNAT1, GNAT2, GNAT4, GNAT6, GNAT7 and GNAT10) using a reverse genetics approach with an emphasis on the metabolomes and photosynthesis of the knock-out plants. Our results reveal the impact of GNAT enzymes on the accumulation of chloroplast-related compounds, such as oxylipins and ascorbate, and the GNAT enzymes also affect the accumulation of amino acids and their derivatives. Specifically, the amount of acetylated arginine and proline was significantly decreased in the gnat2 and gnat7 mutants, respectively, as compared to the wild-type Col-0 plants. Additionally, our results show that the loss of the GNAT enzymes results in increased accumulation of Rubisco and Rubisco activase (RCA) at the thylakoids. Nevertheless, the reallocation of Rubisco and RCA did not have consequent effects on carbon assimilation under the studied conditions. Taken together, our results show that chloroplast GNATs affect diverse aspects of plant metabolism and pave way for future research into the role of protein acetylation.
The benefits of making peace with pain: chronic pain acceptance moderates the indirect effect of perceived burdensomeness between pain severity and suicidal cognitions
Authors: Hale Willie , Vacek Sarah , Crabtree Meghan , Grelle Kaitlin , Bryan Craig J , McGeary Donald D , Kanzler Kathryn E 
Published: April 2023

Abstract

Objective
The purpose of this study was (1) to examine the degree to which perceived burdensomeness mediates the relationship between pain severity and suicidal cognitions and (2) to determine whether this mediated relationship was moderated by pain acceptance. We predicted that high levels of pain acceptance would buffer relationships on both paths of the indirect effect.

Methods
Two-hundred seven patients with chronic pain completed an anonymous self-report battery of measures, including the Chronic Pain Acceptance Questionnaire, the Interpersonal Needs Questionnaire, the Suicidal Cognitions Scale, and the pain severity subscale of the West Haven–Yale Multidimensional Pain Inventory. Conditional process models were examined with Mplus.

Results
Chronic pain acceptance significantly moderated both paths of the mediation model. Results from the conditional indirect effect model indicated that the indirect effect was significant for those with low (b = 2.50, P = .004) and medium (b = 0.99, P = .01) but not high (b = 0.08, P = .68) levels of pain acceptance and became progressively stronger as pain acceptance scores decreased. The nonlinear indirect effect became nonsignificant at acceptance scores 0.38 standard deviation above the mean—a clinically attainable treatment target.

Conclusions
Higher acceptance mitigated the relationship between pain severity and perceived burdensomeness and the relationship between perceived burdensomeness and suicidal cognitions in this clinical sample of patients experiencing chronic pain. Findings indicate that any improvement in pain acceptance can be beneficial, and they provide clinicians with a clinical cut-point that might indicate lower vs higher suicide risk.
Managing Diversity in Nigeria’s Fourth Republic National Assembly: Integrated Parties versus Ethno-Regional Balancing
Authors: Demarest Leila , Langer Arnim 
Published: April 2023

Abstract
Since independence, Nigeria has adopted federalism to manage the country’s deep ethno-regional divisions, but federalism has not averted instability and return to military rule in the past. This highlights the need for additional factors and mechanisms to secure and stabilize civilian rule in Nigeria. The country’s ethnic party ban ensures that parties in power have a broad basis across the territory. Theoretically, these “integrated” parties are often argued to foster intergroup compromise and political stability. Yet in our case study of intergroup relations in Nigeria’s National Assembly, we demonstrate that the country’s broad-based parties do not play a strong role in organizing intergroup cooperation. Despite this, the Assembly has not experienced substantial policy gridlock. We argue that instead of integrated parties, ethno-regional balancing (i.e., a practice whereby key positions in parliament are allocated to different groupings) is a much more important stabilizing factor in Nigeria’s federal parliament.