bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ensembl 2025
Authors: Dyer Sarah C , Austine-Orimoloye Olanrewaju , Azov Andrey G , Barba Matthieu , Barnes If , Barrera-Enriquez Vianey Paola , Becker Arne , Bennett Ruth , Beracochea Martin , Berry Andrew , Bhai Jyothish , Bhurji Simarpreet Kaur , Boddu Sanjay , Branco Lins Paulo R , Brooks Lucy , Ramaraju Shashank Budhanuru , Campbell Lahcen I , Martinez Manuel Carbajo , Charkhchi Mehrnaz , Cortes Lucas A , Davidson Claire , Denni Sukanya , Dodiya Kamalkumar , Donaldson Sarah , El Houdaigui Bilal , El Naboulsi Tamara , Falola Oluwadamilare , Fatima Reham , Genez Thiago , Martinez Jose Gonzalez , Gurbich Tatiana , Hardy Matthew , Hollis Zoe , Hunt Toby , Kay Mike , Kaykala Vinay , Lemos Diana , Lodha Disha , Mathlouthi Nourhen , Merino Gabriela Alejandra , Merritt Ryan , Mirabueno Louisse Paola , Mushtaq Aleena , Hossain Syed Nakib , Pérez-Silva José G , Perry Malcolm , Piližota Ivana , Poppleton Daniel , Prosovetskaia Irina , Raj Shriya , Salam Ahamed Imran Abdul , Saraf Shradha , Saraiva-Agostinho Nuno , Sinha Swati , Sipos Botond , Sitnik Vasily , Steed Emily , Suner Marie-Marthe , Surapaneni Likhitha , Sutinen Kyösti , Tricomi Francesca Floriana , Tsang Ian , Urbina-Gómez David , Veidenberg Andres , Walsh Thomas A , Willhoft Natalie L , Allen Jamie , Alvarez-Jarreta Jorge , Chakiachvili Marc , Cheema Jitender , da Rocha Jorge Batista , De Silva Nishadi H , Giorgetti Stefano , Haggerty Leanne , Ilsley Garth R , Keatley Jon , Loveland Jane E , Moore Benjamin , Mudge Jonathan M , Naamati Guy , Tate John , Trevanion Stephen J , Winterbottom Andrea , Flint Bethany , Frankish Adam , Hunt Sarah E , Finn Robert D , Freeberg Mallory A , Harrison Peter W , Martin Fergal J , Yates Andrew D 
Published: December 2024

Abstract
Ensembl (www.ensembl.org) is an open platform integrating publicly available genomics data across the tree of life with a focus on eukaryotic species related to human health, agriculture and biodiversity. This year has seen a continued expansion in the number of species represented, with &gt;4800 eukaryotic and &gt;31 300 prokaryotic genomes available. The new Ensembl site, currently in beta, has continued to develop, currently holding &gt;2700 eukaryotic genome assemblies. The new site provides genome, gene, transcript, homology and variation views, and will replace the current Rapid Release site; this represents a key step towards provision of a single integrated Ensembl site. Additional activities have included developing improved regulatory annotation for human, mouse and agricultural species, and expanding the Ensembl Variant Effect Predictor tool. To learn more about Ensembl, help and documentation are available along with an extensive training program that can be accessed via our training pages.
The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma
Authors: Berardi Andrea , Kaestner Charlotte Leonie , Ghitti Michela , Quilici Giacomo , Cocomazzi Paolo , Li Jianping , Ballabio Federico , Zucchelli Chiara , Knapp Stefan , Licht Jonathan D , Musco Giovanna 
Published: December 2024

Abstract
Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 (H3K27me3). This is the first PHD tandem cassette known to decode the methylation status of H3K27. Importantly, in a NSD2-dependent MM cellular model, we show that expression of NSD2 mutants, engineered to disrupt the interaction between H3K27me3 and PHDVC5HCH, display in comparison to wild-type NSD2: incomplete loss of H3K27 methylation throughout the genome, decreased activation of adhesive properties and cell adhesion genes, and a decrease of the corresponding H3K27ac signal at promoters. Collectively, these data suggest that the PHDVC5HCH domain of NSD2 plays an important role in modulating gene expression and chromatin modification, providing new opportunities for pharmacological intervention.
Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy
Authors: Hwang Taejoo , Sitko Lukasz Karol , Khoirunnisa Ratih , Navarro-Aguad Fernanda , Samuel David M , Park Hajoong , Cheon Banyoon , Mutsnaini Luthfiyyah , Lee Jaewoong , Otlu Burçak , Takeda Shunichi , Lee Semin , Ivanov Dmitri , Gartner Anton 
Published: December 2024

Abstract
In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ∼40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We first demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair (MMR) knockout in conjunction with additional repair deficiencies uncovers cryptic mutational patterns. We next report how distinct mutational signatures are induced by TMZ upon sequential inactivation of DNA repair pathways, mirroring the acquisition of chemotherapy resistance by glioblastomas. The most toxic adduct induced by TMZ, O6-meG, is directly repaired by the O6-methylguanine-DNA methyltransferase (MGMT). In MGMT-/- cells, MMR leads to cell death and limits mutagenesis. MMR deficiency results in TMZ resistance, allowing the accumulation of ∼105 C &gt; T substitutions corresponding to signature SBS11. Under these conditions, N3-methyladenine (3-meA), processed by base excision repair (BER), limits cell survival. Without BER, 3-meA is read through via error-prone TLS, causing T &gt; A substitutions but not affecting survival. Blocking BER after abasic site formation results in large deletions and TMZ hypersensitization. Our findings reveal potential vulnerabilities of TMZ-resistant tumors.
An sRNA overexpression library reveals AbnZ as a negative regulator of an essential translocation module in Caulobacter crescentus
Authors: Velasco-Gomariz Manuel , Sulzer Johannes , Faber Franziska , Fröhlich Kathrin S 
Published: December 2024

Abstract
Small RNAs (sRNAs) play a crucial role in modulating target gene expression through short base-pairing interactions and serve as integral components of many stress response pathways and regulatory circuits in bacteria. Transcriptome analyses have facilitated the annotation of dozens of sRNA candidates in the ubiquitous environmental model bacterium Caulobacter crescentus, but their physiological functions have not been systematically investigated so far. To address this gap, we have established CauloSOEP, a multi-copy plasmid library of C. crescentus sRNAs, which can be studied in a chosen genetic background and under select conditions. Demonstrating the power of CauloSOEP, we identified sRNA AbnZ to impair cell viability and morphology. AbnZ is processed from the 3′ end of the polycistronic abn mRNA encoding the tripartite envelope-spanning efflux pump AcrAB-NodT. A combinatorial approach revealed the essential membrane translocation module TamAB as a target of AbnZ, implying that growth inhibition by AbnZ is linked to repression of this system.
Vaping-Specific Nicotine Dependence Across Days Among a National Sample of US Young Adults Who Vape
Authors: Parks Michael J , Arterberry Brooke J , Patrick Megan E 
Published: December 2024

Abstract

Introduction
Vaping has increased among young adults (YAs), and nicotine dependence prevalence has increased among YAs who vape, in the US. Research on nicotine dependence symptoms (NDS) among YAs who vape remains limited, and accurately measuring NDS and their severity remains a challenge. To date, no research has considered day-to-day NDS, as previous research focuses on retrospective measures.

Aims and Methods
Daily data came from the Monitoring the Future Vaping Supplement; out of 1244 YAs, we analyzed data from 150 (Mage = 19 [SE = 0.44]; 71.2% non-Hispanic white; 57.8% male) who vaped nicotine at least once during 14 daily surveys (n = 882 nicotine vaping days). The vaping-specific Hooked on Nicotine Checklist measured NDS on nicotine vaping days. Dichotomous and count measures of NDS were used at the day level and aggregated to the person level. Descriptive analyses and multilevel regression models were used. Weights ensured generalizability and adjusted for attrition.

Results
Any NDS were reported on 64.5% of nicotine vaping days (average 1.93 symptoms); 43.3% of nicotine vaping days had more than 1 NDS. Results across persons (rather than days) showed any NDS on 53.8% of nicotine vaping days, and 45.4% YAs reported between 1 and 2 symptoms per vaping day; 23.3% reported 2 + symptoms on average. Multilevel models showed nontrivial variance across days and persons in NDS, and regular vaping at baseline predicted NDS.

Conclusions
Vaping-specific NDS varied across days and persons for any NDS and NDS severity. Future research should consider daily NDS fluctuations, identifying factors that confer risk to inform NDS prevention and treatment among YAs who vape.

Implications
NDS and its severity varied across days and persons, demonstrating the utility of daily data. The results were generally similar for experiencing any NDS and NDS severity, but there was slightly more variability across days for any NDS. Intervention and treatment strategies could utilize approaches that identify and address daily symptoms to help curb nicotine dependence. Future research and treatment efforts should also consider the immediate contexts and potential factors that explain particularly elevated NDS on a given day.
Effects of a Low-Protein Diet on Kidney Function in Patients With Chronic Kidney Disease: An Umbrella Review of Systematic Reviews and Meta-analyses of Randomized Controlled Trials
Authors: Amiri Khosroshahi Reza , Zare Marzieh , Zeraattalab-Motlagh Sheida , Kiany Fatemeh , Talebi Sepide , Mohammadi Hamed 
Published: December 2024

Abstract

Context
Chronic kidney disease (CKD) stands out as one of the most widespread diseases globally. Dietary interventions, such as adopting a low-protein diet (LPD), play a crucial role as a key approach in impeding the advancement of CKD.

Objective
The objective of this umbrella review was to provide understanding into the effects of an LPD on kidney function among individuals with CKD, along with evaluating the certainty of the available evidence.

Data Sources
Searches for relevant studies were conducted without limitations through databases such as PubMed, Scopus, Web of Science, and Google Scholar, encompassing findings up to June 2023.

Data Extraction
The effect sizes for each meta-analysis were recalibrated using a random-effects model. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Data Analysis
Twenty-five meta-analyses including 47 randomized controlled trials were included in this study. Moderate certainty of the evidence suggests that LPDs may reduce glycated hemoglobin (HbA1c) and phosphorus levels, and the risk of progressing to end-stage renal disease in patients with CKD. Moreover, notable outcomes include increased glomerular filtration rate and decreased levels of serum albumin, blood urea nitrogen, and bicarbonate, although the certainty of evidence is low. In addition, LPDs can substantially decrease proteinuria, urine urea, and parathyroid hormone (PTH), although with very low certainty. The effects on serum creatinine, calcium, systolic blood pressure, and diastolic blood pressure are statistically nonsignificant, with the certainty of evidence ranging from low to moderate.

Conclusion
LPDs demonstrated beneficial effects on renal function in patients with CKD, which is supported by moderate to very low certainty evidence.

Systematic Review Registration
PROSPERO registration no. CRD42023473647.
Who lacks voter identification? The electoral implications of the Elections Act 2022
Authors: Fieldhouse Edward , Scott Ralph , Prosser Christopher , Bailey Jack , Mellon Jonathan 
Published: December 2024

Abstract
The Elections Act 2022 requires voters to present photo identification at general elections in Great Britain and local elections in England. In this article, we use data from the British Election Study Internet Panel to identify who does and does not own the necessary photo documents and how this affected turnout in the 2023 and 2024 local elections, as well as the 2024 General Election. We find that around 5% of the voting-age population lack valid voter identification and that this is related to age, education, socio-economic status, and social grade. The data also give us a reliable indication of the party-political impact of the photo ID requirement. We find that conservative voters are more likely to hold valid photo identification than supporters of other parties. We also find that a small but significant proportion of registered voters (between 1.2% and 2.4%) reported either being turned away or dissuaded from voting at these elections because of the requirement.
CAX-INTERACTING PROTEIN4 depletion causes early lethality and pre-mRNA missplicing in Arabidopsis
Authors: Aceituno-Valenzuela Uri , Fontcuberta-Cervera Sara , Micol-Ponce Rosa , Sarmiento-Mañús Raquel , Ruiz-Bayón Alejandro , Ponce María Rosa 
Published: December 2024

Abstract
Zinc knuckle (ZCCHC) motif-containing proteins are present in unicellular and multicellular eukaryotes, and most ZCCHC proteins with known functions participate in the metabolism of various classes of RNA, such as mRNAs, ribosomal RNAs, and microRNAs. The Arabidopsis (Arabidopsis thaliana) genome encodes 69 ZCCHC-containing proteins; however, the functions of most remain unclear. One of these proteins, CAX-INTERACTING PROTEIN 4 (CXIP4, encoded by AT2G28910), has been classified as a PTHR31437 family member. This family includes human Splicing regulatory glutamine/lysine-rich protein 1 (SREK1)-interacting protein 1 (SREK1IP1), which is thought to function in pre-mRNA splicing and RNA methylation. Metazoan SREK1IP1-like and plant CXIP4-like proteins only share a ZCCHC motif, and their functions remain almost entirely unknown. Here, we studied two loss-of-function alleles of Arabidopsis CXIP4: cxip4-1 is likely null and shows early lethality, and cxip4-2 is hypomorphic and viable, with pleiotropic morphological defects. The cxip4-2 mutant exhibited deregulation of defense genes and upregulation of transcription factor genes, some of which might explain its developmental defects. The cxip4-2 mutant also exhibited increased intron retention events, being more evident in cxip4-1. The specific functions of misspliced genes, such as those involved in “gene silencing by DNA methylation” and “mRNA polyadenylation factor” suggest that CXIP4 has additional functions. In cxip4-2 plants, polyadenylated RNAs accumulate in the nucleus; these could be misspliced mRNAs. The CXIP4 protein localizes to the nucleus in a pattern resembling nuclear speckles rich in splicing factors. Therefore, CXIP4 is required for plant development and survival and mRNA maturation.
A glutamine synthetase-Dof transcription factor module regulates nitrogen remobilization from source to sink tissues in tea plants
Authors: Liu Mei-Ya , Jiao Zixin , Lou Heqiang , Tang Dandan , Tian Xinyue , Zhou Bo-Wen , Ruan Jianyun , Fernie Alisdair R , Zhang Qunfeng 
Published: December 2024

Abstract
Nitrogen (N) remobilization from mature leaves to new shoots (NSs) is closely related to the quality of green tea in the spring season, which subsequently determines its economic value. However, the underlying N remobilization mechanism remains poorly understood. Here, we demonstrate that &gt;80% of the recovered 15N was partitioned in the first mature leaves that supply NSs. N-remobilization efficiency (NRE) from mature leaves to NSs varied significantly among tea cultivars. N-fertilization level and NRE showed a significantly positive correlation. Based on weighted gene co-expression network analysis, glutamate metabolism-related genes, including glutamine synthetase genes, CsGSs, were dissected from the interaction network of hub genes regulating N remobilization. Gene expression patterns and the localization of CsGS1.1 in the cytosol and vascular tissue suggest its potential role in N remobilization. Consistent with these findings, source-to-sink N remobilization at the reproductive stage was enhanced in transgenic CsGS1.1-overexpressing plants. Furthermore, we demonstrated that the Dof transcription factor CsDof16 directly binds to the −526 to −426 region of the CsGS1.1 promoter, thereby activating its transcription and regulating N remobilization. Taken together, our findings suggest that the CsDof16-CsGS1.1 module regulates the remobilization of N in the form of glutamate/glutamine from mature leaves to NSs, constituting an important control point in the regulation of source-to-sink N partitioning in tea plants. Our findings can be employed to reduce fertilizer application and promote the development of sustainable tea production.
Rhizophagus irregularis regulates RiCPSI and RiCARI expression to influence plant drought tolerance
Authors: Wang Zhihao , Zhang Shiqi , Liang Jingwei , Chen Hui , Jiang Zhijian , Hu Wentao , Tang Ming 
Published: December 2024

Abstract
Arbuscular mycorrhizal fungi (AMF) can transfer inorganic nitrogen (N) from the soil to host plants to cope with drought stress, with arginine synthesis and NH4+ transport being pivotal processes. However, the regulatory mechanism underlying these processes remains unclear. Here, we found that drought stress upregulated expression of genes involved in the N transfer pathway and putrescine and glutathione synthesis in the mycorrhizal structures of Rhizophagus irregularis within alfalfa (Medicago sativa) roots, i.e. carbamoyl phosphate synthase (RiCPSI), arginase (RiCARI), urease (RiURE), ornithine decarboxylase (RiODC), and glutamate-cysteine ligase (RiGCL). Furthermore, we confirmed that RiCPSI is a carbamoyl phosphate synthase. Silencing RiCARI via host-induced gene silencing inhibited arbuscule formation, suppressed putrescine and glutathione synthesis, and altered arginine metabolism within R. irregularis-plant symbiosis, leading to a substantial reduction in the drought tolerance of M. sativa. Conversely, silencing RiCPSI decreased arginine, putrescine, and glutathione synthesis in R. irregularis but did not adversely affect NH4+ transfer from fungi to the host plant and drought tolerance of M. sativa. Interestingly, overexpressing RiCPSI via our host-induced gene overexpressing system enhanced arginine, putrescine, and glutathione synthesis in R. irregularis, reduced arbuscule abundance, and improved drought tolerance of M. sativa. Our findings demonstrate that under drought stress, the nitrogen transfer from AMF to the host plant was improved. This is accompanied by increased arginine, putrescine, and glutathione synthesis within R. irregularis, driven by the upregulation of RiCPSI and RiCARI expression in mycorrhizal structures within the roots. These molecular adjustments collectively contribute to enhanced drought tolerance in R. irregularis-plant symbiosis.
Propelling sustainable energy: Multi-omics analysis of pennycress FATTY ACID ELONGATION1 knockout for biofuel production
Authors: Rasoul Amira , Johnston Christopher R , LaChance Jordan , Sedbrook John C , Alonso Ana Paula 
Published: December 2024

Abstract
The aviation industry’s growing interest in renewable jet fuel has encouraged the exploration of alternative oilseed crops. Replacing traditional fossil fuels with a sustainable, domestically sourced crop can substantially reduce carbon emissions, thus mitigating global climate instability. Pennycress (Thlaspi arvense L.) is an emerging oilseed intermediate crop that can be grown during the offseason between maize (Zea mays) and soybean (Glycine max) to produce renewable biofuel. Pennycress is being domesticated through breeding and mutagenesis, providing opportunities for trait enhancement. Here, we employed metabolic engineering strategies to improve seed oil composition and bolster the plant's economic competitiveness. FATTY ACID ELONGATION1 (FAE1) was targeted using CRISPR-Cas 9 gene editing to eliminate very long chain fatty acids (VLCFAs) from pennycress seed oil, thereby enhancing its cold flow properties. Through an integrated multiomics approach, we investigated the impact of eliminating VLCFAs in developing and mature plant embryos. Our findings revealed improved cold-germination efficiency in fae1, with seedling emergence occurring up to 3 d earlier at 10 °C. However, these alterations led to a tradeoff between storage oil content and composition. Additionally, these shifts in lipid biosynthesis were accompanied by broad metabolic changes, such as the accumulation of glucose and ADP-glucose quantities consistent with increased starch production. Furthermore, shifts to shorter FA chains triggered the upregulation of heat shock proteins, underscoring the importance of VLCFAs in stress signaling pathways. Overall, this research provides crucial insights for optimizing pennycress seed oil while preserving essential traits for biofuel applications.
ChatGPT versus expert feedback on clinical reasoning questions and their effect on learning: a randomized controlled trial
Authors: Çiçek Feray Ekin , Ülker Müşerref , Özer Menekşe , Kıyak Yavuz Selim 
Published: December 2024

Abstract

Purpose
To evaluate the effectiveness of ChatGPT-generated feedback compared to expert-written feedback in improving clinical reasoning skills among first-year medical students.

Methods
This is a randomized controlled trial conducted at a single medical school and involved 129 first-year medical students who were randomly assigned to two groups. Both groups completed three formative tests with feedback on urinary tract infections (UTIs; uncomplicated, complicated, pyelonephritis) over five consecutive days as a spaced repetition, receiving either expert-written feedback (control, n = 65) or ChatGPT-generated feedback (experiment, n = 64). Clinical reasoning skills were assessed using Key-Features Questions (KFQs) immediately after the intervention and 10 days later. Students’ critical approach to artificial intelligence (AI) was also measured before and after disclosing the AI involvement in feedback generation.

Results
There was no significant difference between the mean scores of the control (immediate: 78.5 ± 20.6 delayed: 78.0 ± 21.2) and experiment (immediate: 74.7 ± 15.1, delayed: 76.0 ± 14.5) groups in overall performance on Key-Features Questions (out of 120 points) immediately (P = .26) or after 10 days (P = .57), with small effect sizes. However, the control group outperformed the ChatGPT group in complicated urinary tract infection cases (P &lt; .001). The experiment group showed a significantly higher critical approach to AI after disclosing, with medium-large effect sizes.

Conclusions
ChatGPT-generated feedback can be an effective alternative to expert feedback in improving clinical reasoning skills in medical students, particularly in resource-constrained settings with limited expert availability. However, AI-generated feedback may lack the nuance needed for more complex cases, emphasizing the need for expert review. Additionally, exposure to the drawbacks in AI-generated feedback can enhance students’ critical approach towards AI-generated educational content.