bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic changes in bleeding sites: Evaluating contrast extravasation on computed tomography and angiography in pelvic fractures
Authors: Inamasu Fumi , Matsumoto Shokei , Senoo Satomi , Shimizu Masayuki 
Published: December 2024

BACKGROUND
Contrast extravasation (“blush”) on contrast-enhanced computed tomography (CECT) indicates active bleeding, but diagnostic angiography (AG) following CECT sometimes differs from the CECT findings in patients with pelvic fractures. This study aimed to evaluate the concordance rate between blush on CECT and AG based on pelvic anatomical location.

METHODS
This retrospective single-center study included patients (18 years or older) with pelvic fractures between 2015 and 2023 who had AG after CECT. Angiography was performed in patients with blush or hematoma on CECT, or unstable hemodynamics due to pelvic fracture. Pelvic bleeding regions were categorized separately into left and right as anterior internal iliac artery and posterior internal iliac artery based on pelvic arterial anatomy. The concordance rate between blush on CECT and AG was assessed using the k statistic.

RESULTS
A total of 87 patients with pelvic fractures were included. Among these, 75 (86%) had blush on CECT, and 12 (14%) had no blush on CECT. The concordance rate was 83% (95% confidence interval, 0.03–0.57; k = 0.30) when assessed on an individual patient basis and 53% (95% confidence interval, 0.24–0.44; k = 0.34) when evaluated by anatomical regions on a unilateral half of the pelvis. The concordance rate for the anatomical hemipelvis evaluation was significantly lower compared with the individual evaluation (p < 0.001). Thirty-three percent of patients with unilateral blush on CECT showed new contralateral blushes during AG.

CONCLUSION
The location of active bleeding often differs between CECT and AG, indicating that bleeding may change intermittently and at various sites over time. This suggests the importance of evaluating both sides of the pelvic arteries during AG rather than solely relying on CECT findings.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Satellite monitoring of long period ocean-induced magnetic field variations
Authors: Finlay Christopher C. , Velímský Jakub , Kloss Clemens , Blangsbøll Rasmus M. 
Published: December 2024

Satellite magnetic field observations have the potential to provide valuable information on dynamics, heat content and salinity throughout the ocean. Here, we present the expected spatio-temporal characteristics of the ocean-induced magnetic field (OIMF) at satellite altitude on periods of months to decades. We compare these to the characteristics of other sources of Earth’s magnetic field, and discuss whether it is feasible for the OIMF to be retrieved and routinely monitored from space. We focus on large length scales (spherical harmonic degrees up to 30) and periods from one month up to 5 years. To characterize the expected ocean signal, we make use of advanced numerical simulations taking high-resolution oceanographic inputs and solve the magnetic induction equation in three dimensions, including galvanic coupling and self-induction effects. We find the time-varying ocean-induced signal dominates over the primary source of the internal field, the core dynamo, at high spherical harmonic degree with the cross-over taking place at degrees 13–19 depending on the considered period. The ionospheric and magnetospheric fields (including their Earth-induced counterparts) have most power on periods shorter than one month and are expected to be mostly zonal in magnetic coordinates at satellite altitude. Based on these findings, we discuss future prospects for isolating and monitoring long period OIMF variations using data collected by present and upcoming magnetic survey satellites.This article is part of the theme issue ‘Magnetometric remote sensing of Earth and planetary oceans’.
Harnessing electromagnetic data for tsunami source estimation: a comprehensive review
Authors: Baba Toshitaka , Lin Zhiheng , Minami Takuto , Toh Hiroaki 
Published: December 2024

Ocean-bottom pressure gauges are widely used for tsunami observations due to their established accuracy and stability. Recent advancements reveal that the magnetic field fluctuates when a large tsunami passes over the ocean, suggesting potential alternatives to pressure gauges in the form of ocean-bottom electromagnetometers (OBEMs). This article offers a comprehensive synthesis of recent findings concerning tsunami magnetic fields and their utility in tsunami source estimation. In addition, we scrutinize the effectiveness of tsunami observations employing OBEMs. Despite the promise of electromagnetometers, it is worth noting that the background noise inherent in electromagnetic observations tends to be approximately 10 times greater than that of pressure observations within the critical tsunami frequency bands. The Earth’s magnetic field sporadically disrupts tsunami magnetic fields, presenting a potential limitation to the utility of electromagnetometers in tsunami detection when compared with pressure gauges. Nevertheless, our investigation underscores the potential of electromagnetic observations in detecting tsunamis propagating over the ocean at magnitudes of a few centimetres. An invaluable advantage of electromagnetometers over pressure monitoring lies in their capability to observe tsunami velocity fields, suggesting a promising avenue for further research and development in tsunami observation technology.
This article is part of the theme issue ‘Magnetometric remote sensing of Earth and planetary oceans’.
Correcting errors in PCR-derived libraries for rare allele detection by reconstructing parental and daughter strand information
Authors: Lim Hyeonseob , Jun Soyeong , Kim Taehoon , Lee Ji Hyun , Bang Duhee 
Published: December 2024

AbstractMolecular barcoding methods enable high-sensitivity detection of circulating tumor DNA that is rarely present in liquid biopsy samples. Many methods involve ligation of molecular barcodes to DNA prior to hybridization capture, enabling recovery of starting molecules. Development of polymerase chain reaction (PCR)-based methods could facilitate more cost- and labor- effective detection; however, tracking molecular identity can be difficult, as new barcodes overwrite old barcodes in each cycle. We developed a sensitive genotyping method based on a peer-to-peer network-derived identifier for error reduction in amplicon sequencing (SPIDER-seq) and enable molecular identity tracking with PCR-derived libraries using overwritten barcodes. SPIDER-seq detected mutations at frequences as low as 0.125% after only two consecutive general PCR cycles and systematically analyzed the error pattern in the peer-to-peer network. Our method could facilitate the rapid detection of mutations associated with various cancers.
Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs
Authors: Ghosh Soumita , Lahens Nick , Barekat Kayla , Tang Soon-Yew , Theken Katherine N. , Ricciotti Emanuela , Sengupta Arjun , Joshi Robin , Bushman Frederic D. , Weljie Aalim , Grosser Tilo , FitzGerald Garret A 
Published: December 2024

AbstractNon-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase -2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.
Combined analysis of chromatin accessibility, promoter interactions and whole genome sequencing solved the missing heritability in gastric cancer
Authors: São José C. , Ferreira M. , Cordova L. , Pedro A. , Senz J. , Garcia-Pelaez J. , Lobo S. , Gullo I. , André A. , Kaurah P. , Puntieri F. , Glaser J. , Huntsman D. , Mundlos S. , Schrader K. , Oliveira C. 
Published: December 2024

AbstractMissing heritability in hereditary diffuse gastric cancer (HDGC) ranges from 60 to 90%. These HDGC-like families, despite complying with HDGC clinical criteria, lackCDH1andCTNNA1actionable germline variants, and are not offered HDGC-targeted life-saving disease prevention measures. Herein, we explored novel HDGC predisposition mechanisms affecting theCDH1-regulatory network. We called single-nucleotide (SNV) and copy-number variants (CNV) from 19 HDGC-like probands from whole-genome sequencing data and performed gene-ontology analysis. Chromatin enhancer marks andCDH1promoter interactions were evaluated in normal stomach by ChIP-seq, ATAC-seq and 4C-seq, variant causality was assessed by RT-PCR, immunohistochemistry and microsatellite instability (MSI) analysis in tumours. Functional analysis was performed using CRISPR-Cas9, RT-PCR and flow cytometry in cell lines, and enhancer assays using mouse embryos. Within theCDH1topologically associating domain (TAD), we found two deletions in Family F4 and F9. F4 carried a heterozygousCDH320kb-CNV triggeringCDH1mRNA/protein loss in homozygosity by CRISPR-Cas9 editing, similarly to aCDH1coding deletion. This 20kb sequence encloses two hypomorphic tissue-specific regulatory elements (REs), each contributing 50% toCDH1expression regulation. F9 carried a heterozygous 39bp-intergenic CNV downstream ofCDH1, triggeringCDH1mRNA/protein loss by CRISPR-Cas9. F15, presenting gastric but not colorectal cancer, carried anMLH1heterozygous 2.7Kb germline CNV overlapping a stomach-specific RE found by ChIP-seq. The gastric tumour of mixed histology displayed Microsatellite instability (MSI), reducedMLH1mRNA and protein, and reducedCDH1and E-cadherin protein. CRISPR-Cas9 clones mimicking theMLH1heterozygous CNV, triggered loss ofMLH1andCDH1/E-cadherin mRNA and protein, similar to a coding deletion. Beyond theCDH1TAD and tumour risk syndrome genes, multiple deletions of stomach accessible chromatin sequences were found in particularly young-affected individuals from additional 6 families. This oligogenic pattern impaired specifically mucin genes and multiple immune-related pathways. Herein, we pinpointed novel mechanisms behind HDGC predisposition. One involves deletions ofCDH1-REs in the TAD or stomach-specificCDH1-REs in theMLH1locus. The second involves multiple deletions of stomach REs affecting mucin and immune-related genes, favouring a gastric immune-deficient phenotype. Altogether, by combining stomach-specific chromatin accessibility and promoter interactions with whole genome sequencing, we solved the missing heritability in 47% of HDGC-like families within our cohort.
Constrained hypermutation and absence of TERT promoter mutations in Lynch syndrome-associated urothelial cancer
Authors: Nikkola Jussi , Ryyppö Lauri , Vuorinen Juuso , Moilanen Lauri , Ahtiainen Maarit , Pylvänäinen Kirsi , Selin Hanna , Virtanen Tuomo , Nykter Matti , Veitonmäki Thea , Mecklin Jukka-Pekka , Seppälä Toni T. , Annala Matti 
Published: December 2024

AbstractLynch syndrome (LS) is a hereditary condition characterized by defective DNA mismatch repair (MMR) and high incidence of several cancers, including urothelial cancers (UC) of the upper urinary tract and bladder. We set out to study the somatic landscape of LS-associated urothelial cancer (LS-UC) by analyzing 41 surgical tumor samples and 3 urine DNA samples from 34 LS-UC patients. We show that telomerase reverse transcriptase (TERT) promoter mutations found in 83% of sporadic UC are almost completely absent (5%) in LS-UC (p < 0.00001). Instead, all LS-UC carried a 5-methylcytosine deamination (CG>TG) and microsatellite instability driven mutation landscape characterized by highly frequentARID1A(82%),FGFR3(80%), and KMT2D (78%) mutations, as well as preferential usage of CG>TG mutation hotspots. We propose that the scarcity ofTERTpromoter mutations in LS-UC is due to inability to create the necessary GABP binding motif (5’-GGAA) through CG>TG mutation or microsatellite instability. Our data shows that LS-UC represents a disease entity with unique genomic characteristics.
Identification of genetic variation in genes linked to buparvaquone resistance in Theileria sp infecting dairy cattle in India.
Authors: Musale Pankaj , Khilari Ajinkya , Gade Rohini , Dhanikachalam Velu , Jadhav Santoshkumar , Bajpai Manali , Turakani Bhagya , Joshi Akshay , Prajapati Amar , Srivastava Anand , Swaminathan Marimutthu , Joshi Sachin , Shanmugam Dhanasekaran 
Published: December 2024

Buparvaquone (BQO) is used for treatment of bovine theileriosis, a tickborne disease caused by parasites of the heileria genus. Studies on T. annulata have linked the mechanism of BQO resistance predominantly to genetic variations in the parasite cytochrome b (cytb) gene. In addition, cryptic mechanisms of resistance involving the parasite peptidyl-prolyl isomerase (pin1) and dihydroorotate dehydrogenase (dhodh) genes require assessment. In India, where bovine theileriosis is endemic, and BQO is widely used for treatment, monitoring and establishing the link between genetic variations in cytb, dhodh and pin1 genes and BQO resistance is essential. In this study, multiplexed PCR amplification and nanopore sequencing approaches were used for genotyping the complete gene loci of the target genes. Analysis of 420 T. annulata field samples collected from seven different states of India revealed the presence of previously reported variations S129G, A146T and P253S in cytb and A53P in pin1, which are linked to BQO resistance. The role of A146T, a highly prevalent variation which mostly co-occurred with I203V, in BQO resistance needs to be evaluated. From 60 samples having T. orientalis infection, the genetic variations identified from the three genes were found to be mostly natural variations based on the reference genotypes and were distinct from T. annulata variations. This study has revealed the presence of BQO resistance-linked cytb gene mutations in T. annulata infecting dairy cattle in India and establishes a nanopore sequencing method for molecular surveillance of genetic variation in field samples.
Microtubule stiffening by doublecortin-domain protein ZYG-8 contributes to spindle orientation duringC. eleganszygote division
Authors: Cueff Louis , Pastezeur Sylvain , Huet Ewen , Coquil Méline , Savary Titouan , Pécréaux Jacques , Bouvrais Hélène 
Published: December 2024

ABSTRACTTo address the role of microtubule flexural rigidity in spindle positioning during cell division, we used theCaenorhabditis eleganszygote. We showed that ZYG-8DCLK1, its unique Doublecortin-family member, rigidifies microtubules, as evidenced by more bent microtubules when targeting this protein. Microtubules also exhibited larger maximal curvatures and increased tortuosity. Functionally, we observed increased amplitudes of anaphase spindle-pole oscillations followingzyg-8(RNAi)and even greater inzyg-8(or484ts)mutants preventing microtubule binding. Interestingly, the mutants exhibited incorrect final spindle position and orientation. Overly soft microtubules impaired spindle centring force, upsetting the pulling versus pushing force balance. We strengthened these findings by depleting PTL-1Tau, a protein that rigidifies microtubules. In conclusion, sufficient microtubule rigidity is essential during mitosis to ensure effective cortical pushing, thereby accurately orienting the spindle and guaranteeing correct daughter cell fates. Microtubule rigidity is likely controlled in human mitoses as well, consistent with reported DCLK1 and Tau deregulations in various cancers.
The mycobacterial nucleoid-associated protein NapM exhibits stress-induced septal localization and modulates cell envelope gene expression
Authors: Milcarz Kornel , Hołówka Joanna , Pawełczyk Jakub , Paściak Mariola , Lavrynchuk Yaroslav , Płociński Przemysław , Zakrzewska-Czerwińska Jolanta 
Published: December 2024

AbstractThe bacterial chromosome is organized in a hierarchical and dynamic manner to facilitate various DNA transactions. Nucleoid-associated proteins (NAPs) are the most abundant small-scale chromosomal organizers, playing roles in maintaining chromosomal DNA integrity, gene regulation, DNA replication, and DNA repair. In this study, we characterize the recently identified mycobacterial NAP, NapM inMycobacterium smegmatis. Our study shows that NapM exhibits a distinctive septal localization in response to stress affecting cell envelope integrity and modulates the expression of approximately one-third ofM. smegmatisgenes, including those involved in cell envelope biosynthesis. Our findings suggest that NapM regulates mycobacterial cell division under stress, enabling this saprophyte to adapt to constantly changing environmental conditions.
Thermodynamic Parameter Estimation for Modified Oligonucleotides Using Molecular Dynamics Simulations
Authors: Park Soon Woo , Lee Junehawk , Park Jung Woo , Kim Moon Ki , Seo Sangjae 
Published: December 2024

AbstractThis study investigates the thermodynamic parameters of 1,300 RNA/DNA hybrid duplexes, including both natural and chemically modified forms, using molecular dynamics (MD) simulations. Modified duplexes consist of phosphorothioate (PS) backbones and 2′-O-methoxyethyl (MOE) modifications, both commonly used in therapeutic oligonucleotides. Hybridization enthalpy and entropy were calculated from MD trajectories using molecular mechanics Poisson-Boltzmann surface area (MMPBSA) and molecular mechanics generalized Born surface area (MMGBSA) approaches. To address discrepancies with experimental data, we established empirical relationships by comparing calculated values with known experimental results of natural hybrid duplexes, then extended these relationships to the entire dataset. The corrected parameters were subsequently used to generate nearest-neighbor (NN) models, allowing for experimentally reliable melting temperature predictions. In this process, MMGBSA demonstrated superior predictive performance with high convergence and consistency for both natural and modified duplexes. Specifically, MMGBSA captured the stabilizing effects of the MOE modification with minimal bias, while MMPBSA exhibited greater variability and limited reliability. These findings highlight the potential of MMGBSA for accurate thermodynamic modeling of both natural and modified nucleic acids, providing a robust framework and experimentally meaningful insights for applications in nucleic acid-based therapeutic design and biotechnology.
Normative models reveal distinct cortical abnormalities to dimensions of psychopathologies in preadolescents
Authors: Deng Qingkun , Levitis Elizabeth , Adams Rick A , Altmann Andre 
Published: December 2024

AbstractBackgroundEvidence suggests a non-specific mapping between psychiatric disorders and underlying neurobiological substrates. A dimensional psychopathology framework may prove useful for organizing observed neurobiological alterations along broad psychopathological dimensions.MethodsWe applied latent class analysis, with an additional constraint on classification uncertainty, to identify clinical cohorts of symptomatic homogeneity to represent the high-risk end of specific psychopathological dimensions (i.e., internalizing/externalizing,p-factor), using baseline data (N= 11860) from the Adolescent Brain and Cognitive Development (ABCD) Study. These cohorts were compared against neurotypical individuals in deviations from the normality of cortical development, quantified using autoencoder-based normative models, to reveal cortical abnormalities.ResultsWe identified cortical thickness related to psychopathologies in the ABCD data, particularly to externalizing syndromes, and revealed distinct structural abnormalities to broad psychopathological dimensions.ConclusionThis study highlights the value of person-centered analytic techniques, combined with normative modeling, to complement traditional associational methodologies in revealing neurobiological correlates of dimensional psychopathologies.
Purinergic Receptor P2Y13Controls Activation and Mode of Division in Subependymal Adult Neural Stem Cells
Authors: Paniagua-Herranz Lucía , Serrano-López Julia , Llorente-Sáez Celia , Pérez-Sanz Marina Leonor , de Agustín-Durán David , Duart-Abadia Pere , Domingo-Muelas Ana , Vincelle-Nieto África , Bragado Paloma , Manzano-Franco Diana , Arribas-Blázquez Marina , Olivos-Oré Luis Alcides , Gascón Sergio , Gutierrez-Uzquiza Álvaro , Pérez-Sen Raquel , Delicado Esmerilda G. , Gómez-Villafuertes Rosa , Reyes-Palomares Armando , Artalejo Antonio R. , Fariñas Isabel , Ortega Felipe 
Published: December 2024

ABSTRACTThe subependymal zone (SEZ) of the mammalian brain is the most active germinal area that continues to generate newborn neurons throughout life. This area harbors a population of neural stem cells (NSCs) that can be found in different states of activation, each differing in proliferative capacity and molecular signature: quiescent NSCs (qNSCs), primed NSCs (pNSCs), and activated NSCs (aNSCs). There is currently a void in terms of the specific markers available to effectively discern between these transient states. Likewise, the molecular signaling mechanisms controlling the transition from quiescence to activation remain largely unexplored, as do the factors influencing the decision between differentiation and self-renewal during NSC division. Here, we present evidence that the metabotropic P2Y13purinergic receptor plays a critical role in regulating adult neurogenesis. We found that P2Y13is specifically expressed in NSCs within the adult SEZ and that its levels can be used to distinguish qNSCs from aNSCs. Functionally, P2Y13signaling promotes NSC activation, enhancing lineage progression, while dampening their self-renewal capacity. Conversely, pharmacological blockade or genetic silencing of the P2Y13receptor favors NSC quiescence. Thus, we identified the metabotropic P2Y13purinergic receptor as a pivotal modulator of NSC dynamics, influencing both the balance between NSC quiescence and activation and the mode of NSC division at the subependymal zone.
Mapping Chromatin Interactions of ZBP1 and ADAR1 Z-Alpha Domains: A ChIP-Seq Based Comparison
Authors: Hamrick Dennis , Sharma Manjita , Grow Edward 
Published: December 2024

AbstractThe DNA double helix typically exists in the canonical B-form conformation, but this structure often can adopt the unique alternative form known as Z-DNA. In Z-DNA, the DNA helix winds to the left in a zigzag pattern instead of the right-handed B-DNA form. Z-DNA is thought to play a key role in transcription, but it is unclear whether is a positive or negative regulator of RNA polymerase activity. Additionally, several studies have shown how Z-DNA contributes to DNA damage or genome instability. However, the precise role of Z-DNA in the genome remains unclear. To address this question, we mapped Z-DNA using a ChIP-Seq assay with two Z-DNA biosensors: Zaa-Zbp1, comprised of a dimerized Z-alpha Z-DNA binding domains from Z-DNA binding protein 1 (Zbp1), and Zaa-Adar1, comprised of dimerized Z-alpha domains from Adenosine deaminase acting on RNA 1 (Adar1). We found that these Zaa probes possessed similar binding profiles when analyzed with motif analysis, but gene ontology analysis revealed that these Z-alpha domains bound to heterogeneous genes, with Zaa-Zbp1 most strongly binding to genes in the RHOQ-GTPase pathway and Zaa-Adar1 binding to genes involved in the M phase of the cell cycle.