bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronological changes in etiology, pathological and imaging findings in primary liver cancer from 2001 to 2020
Authors: Tsuzaki Junya , Ueno Akihisa , Masugi Yohei , Tamura Masashi , Yamazaki Seiichiro , Matsuda Kosuke , Kurebayashi Yutaka , Sakai Hiroto , Yokoyama Yoichi , Abe Yuta , Hayashi Koki , Hasegawa Yasushi , Yagi Hiroshi , Kitago Minoru , Jinzaki Masahiro , Sakamoto Michiie 
Published: January 2025

Abstract

Purpose
To achieve a historical perspective, the chronological changes in primary liver cancer over a 20-year period were investigated at a single institution, focusing on shifts in etiology and the impact on imaging and pathological findings using The Liver Imaging Reporting and Data System.

Materials and methods
A retrospective study of surgically resected primary liver cancer in 680 patients from 2001 to 2020 resulted in 434 patients with 482 nodules being analyzed. Dynamic contrast-enhanced computed tomography imaging and the Liver Imaging Reporting and Data System 2018 classification were employed. Two pathologists and two radiologists independently evaluated specimens and images.

Results
This study highlighted a significant decline in cases of viral hepatitis and cirrhosis in primary liver cancer patients but an increase in intrahepatic cholangiocarcinoma and scirrhous hepatocellular carcinoma. Notably, there was a rise in non-viral hepatitis cases, potentially pointing toward an increase in steatohepatitic hepatocellular carcinoma cases in the future. Intrahepatic cholangiocarcinoma, scirrhous hepatocellular carcinoma and steatohepatitic hepatocellular carcinoma tumors exhibited slightly different distributions in the Liver Imaging Reporting and Data System classification compared with ordinary hepatocellular carcinoma, which may reflect the presence of fibrosis and lipid in tumor parenchyma.

Conclusions
Consistent with past reports, this study demonstrated the emergence of primary liver cancer against a backdrop of non-viral and non-cirrhotic liver. Liver Imaging Reporting and Data System has been consistently useful in diagnosing primary liver cancer; however, among the histological subtypes of hepatocellular carcinoma, an increase is anticipated in scirrhous hepatocellular carcinoma and steatohepatitic hepatocellular carcinoma, which may present imaging findings different from those of ordinary hepatocellular carcinoma. This development may necessitate a reevaluation of the current approach for diagnosing and treating hepatocellular carcinoma based solely on imaging.
METTL3 modulates colonic epithelium integrity via maintaining the self-renewal and differentiation of Lgr5+ stem cell
Authors: Ding Chenbo , Yang Xinhui , Liu Hua , Roulis Manolis , Chen Huifang , Chen Yunzhu , Xu Hao , Gao Yimeng , Zhong Jie , Li Hua-Bing , Ye Youqiong , Cai Wei , Hu Weiguo , Wang Zhengting 
Published: January 2025

Abstract
The development and homeostasis of intestinal epithelium are mediated by actively proliferating Lgr5+ stem cells, which possess a remarkable self-renewal and differentiation capacity. Recently, our study demonstrated that m6A methylation was essential for the survival of colonic stem cells. Here, we show that METTL3 expression is downregulated in the colon mucosa in ulcerative colitis (UC) patients and strongly associated with the differentiation and maturation of goblet cells during inflammation. In mice, depletion of Mettl3 significantly inhibits the self-renewal and differentiation of Lgr5+ stem cells, especially the differentiation and maturation of goblet cells, resulting in intestinal dysplasia and spontaneous inflammation. Mechanistically, Mettl3 deletion-mediated m6A loss facilitates the expression levels of Grb10 and Ifrd1 via increasing their mRNA stability. We further demonstrate that the levels of GRB10 and IFRD1 are negatively correlated with METTL3 level in UC samples. Collectively, our data indicate that METTL3 enhances the self-renewal and differentiation of Lgr5+ stem cells during intestinal development and inflammation, and thus it may be a potential therapeutic target for UC treatment.
Durable solutions: to what and for whom?
Authors: Maple Nicholas , Hovil Lucy 
Published: January 2025

Abstract
The three durable solutions (resettlement, local integration, and repatriation) are out of reach to most refugees. Even when they are offered, they are often watered down or repackaged, so that their durability has been undermined. This paper examines their contemporary role and framing and proposes an urgent recalibration of our understanding of the solutions based around three interlinked elements. First, to recover the core function of all three durable solutions, namely the (re)gaining of citizenship; in order, second, to shift the conversation away from assumptions about the sedentary nature of durable solutions; which, third, draws out a greater understanding of the potential collaboration and connections between these traditional solutions and ground-level solutions that refugees create for themselves. We argue that not only are each of these elements important in and of themselves, but they also need to be viewed as indivisible.
Design and in vitr
o anticancer assessment of a click chemistry-derived dinuclear copper artificial metallo-nuclease
Authors: Poole Simon , Aning Obed Akwasi , McKee Vickie , Catley Thomas , Nielsen Aaraby Yoheswaran , Thisgaard Helge , Johansson Pegah , Menounou Georgia , Hennessy Joseph , Slator Creina , Gibney Alex , Pyne Alice , McGorman Bríonna , Westerlund Fredrik , Kellett Andrew 
Published: January 2025

Abstract
Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres—central for enhancing AMN activity—to bind DNA, via two phenanthroline ligands separated by an aliphatic linker. DNA-binding experiments, involving circular dichroism spectroscopy, agarose gel electrophoresis and fluorescence quenching, revealed a preference for binding with adenine-thymine-rich DNA. The oxidative cleavage mechanism of Cu2-BPL-C6 was then elucidated using in vitro molecular and biophysical assays, including in-liquid atomic force microscopy analysis, revealing potent DNA cleavage mediated via superoxide and hydrogen peroxide oxidative pathways. Single-molecule analysis with peripheral blood mononuclear cells identified upregulated single-strand DNA lesions in Cu2-BPL-C6-treated cells. Using specific base excision repair (BER) enzymes, we showed that Endo IV selectively repairs these lesions indicating that the complex generates apurinic and apyrimidinic adducts. Broad spectrum anticancer evaluation of BPL-C6 was performed by the National Cancer Institute’s 60 human cell line screen (NCI-60) and revealed selectivity for certain melanoma, breast, colon and non-small cell lung cancer cell lines.
Unveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus
Authors: Tsvetkov Vladimir , Mir Bartomeu , Alieva Rugiya , Arutyunyan Alexander , Oleynikov Ilya , Novikov Roman , Boravleva Elizaveta , Kamzeeva Polina , Zatsepin Timofei , Aralov Andrey , González Carlos , Zavyalova Elena 
Published: January 2025

Abstract
Non-canonical nucleic acid structures play significant roles in cellular processes through selective interactions with proteins. While both natural and artificial G-quadruplexes have been extensively studied, the functions of i-motifs remain less understood. This study investigates the artificial aptamer BV42, which binds strongly to influenza A virus hemagglutinin and unexpectedly retains its i-motif structure even at neutral pH. However, BV42 conformational heterogeneity hinders detailed structural analysis. Molecular dynamics simulations and chemical modifications of BV42 helped us to identify a potential binding site, allowing for aptamer redesign to eliminate the conformational diversity while retaining binding affinity. Nuclear magnetic resonance spectroscopy confirmed the i-motif/duplex junction with the three-cytosine loop nearby. This study highlights the unique structural features of the functional i-motif and its role in molecular recognition of the target.
High hydrostatic pressure promotes gene transcription via a cystathionine-β-synthase domain-containing protein in the hyperthermophilic archaeon Pyrococcus yayanosii
Authors: Li Cong , Li Siyuan , Song Qinghao , Da Lin-tai , Xu Jun 
Published: January 2025

Abstract
Cystathionine-β-synthase (CBS) domains are ubiquitously prevalent in all kingdoms of life. Remarkably, in archaea, proteins consisting of solely CBS domains are widespread. However, the biological functions of CBS proteins in archaea are still unknown. Here, we identified a high hydrostatic pressure regulator (HhpR) that comprises four CBS domains serving as a transcriptional activator via specifically binding to the UAS (upstream activating sequence) motif situated within the promoter region of an operon in a hyperthermophilic archaeon Pyrococcus yayanosii under high hydrostatic pressure (HHP). By combining molecular dynamics simulations, in vitro and in vivo assays, we revealed the potential binding interfaces between HhpR and its specific DNA binding site. Particularly, one stem–loop region in HhpR (termed as ‘Arm’) was found to play a critical role in regulating the transcription activity, and the 192 position in the Arm region is an essential site in dictating the conformational changes of HhpR at HHP condition. Our work provides novel insights into the structure–function relationship of CBS-containing proteins that participate in archaeal gene regulation as general transcriptional activators.
Quadruplet codon decoding-based versatile genetic biocontainment system
Authors: Choi Yun-Nam , Kim Donghyeon , Lee Seongbeom , Shin Ye Rim , Lee Jeong Wook 
Published: January 2025

Abstract
Biological resources, such as sequence information, genetic traits, materials and strains, pose risks when inadvertently released or deliberately misused. To address these concerns, we developed Quadruplet COdon DEcoding (QCODE), a versatile genetic biocontainment strategy that introduces a quadruplet codon (Q-codon) causing frameshifts, hindering proper gene expression. Strategically incorporating Q-codons in multiple genes prevents genetic trait escape, unallowed proliferation of microbial strains and unauthorized leakages of genetic materials. This multifaceted strategy, integrating Q-codons for genetic traits, materials and strains, ensures robust biocontainment across various levels. Notably, our system maintains sequence protection, safeguarding genetic sequence information against unauthorized access. The QCODE approach offers a versatile, efficient and compact solution to enhance biosecurity in diverse biological research settings.
tRNA thiolation optimizes appressorium-mediated infection by enhancing codon-specific translation in Magnaporthe oryzae
Authors: Zhang Xinrong , He Rongrong , Li Yinan , Ren Shuchao , Xiang Shikun , Zheng Jing , Qu Zhiguang , Zhou Shu , Zhou Zhipeng , Chen Xiao-Lin 
Published: January 2025

Abstract
Thiolation, a post-transcriptional modification catalyzed by Uba4-Urm1-Ncs2/Ncs6 pathway in three specific transfer RNAs (tRNAs), is conserved from yeast to humans and plays an important role in enhancing codon–anticodon interaction and translation efficiency. Yet, except for affecting effector secretion, its roles in plant pathogenic fungi are not fully understood. Here, we used Magnaporthe oryzae as a model system to illustrate the vital role of s2U34 modification on the appressorium-mediated virulence. The absence of tRNA thiolation leads to diminished translation elongation at AAA/CAA/GAA but not their synonymous codons, resulting in reduced levels of key proteins enriched in these codons, which are critical for appressorium development and function. Importantly, overexpressing these proteins can partially mitigate the defects resulting from NCS2 deletion. Our study sheds light on the s2U34 modification’s role in plant pathogenic fungi, enhancing our understanding of translational control beyond effector secretion.
Epidemiology of Lyme Disease as Identified Through Electronic Health Records in a Large Midwestern Health System, 2016–2019
Authors: Kugeler Kiersten J , Scotty Erica , Hinckley Alison F , Hook Sarah A , Nawrocki Courtney C , Nikolai Anne M , Linz Alexandra M , Meece Jennifer , Schotthoefer Anna M 
Published: January 2025

Abstract

Background
Lyme disease is the most common vector-borne disease in the United States; however, its frequency is not reliably measured through surveillance. Electronic health records (EHR) might capture the frequency and characteristics of Lyme disease cases more accurately. We queried EHR from 1 health system to describe the epidemiology of Lyme disease cases in Wisconsin during 2016–2019.

Methods
Within a cohort of persons evaluated for Lyme disease, we applied a Lyme disease case definition based on first-line antibiotics within 14 days of a Lyme disease diagnosis code or test order or on the same day as a related keyword in clinical notes. We compared characteristics of cases to those of cases reported through surveillance and reviewed medical charts to assess case definition validity.

Results
Among 67 289 possible Lyme disease events in the cohort, 13 494 (20.1%) met our Lyme disease case definition. Cases were more common among males, children 5–9 years, older adults, White non-Hispanic persons, and in the summer months. EHR-based Lyme disease incidence was 4–8 times that reported through surveillance. The EHR definition had moderately high sensitivity (83.4%) and specificity (71.1%) for confirmed and probable Lyme disease.

Conclusions
EHR queries show promise to capture the incidence of Lyme disease more completely and provide more robust clinical information than public health surveillance. Demographic and seasonal characteristics of EHR-identified cases were comparable to those identified through surveillance. Further algorithm refinement might improve accuracy of measuring Lyme disease in EHR systems.
Brain-inspired wiring economics for artificial neural networks
Authors: Zhang Xin-Jie , Moore Jack Murdoch , Gao Ting-Ting , Zhang Xiaozhu , Yan Gang 
Published: January 2025

Abstract
Wiring patterns of brain networks embody a trade-off between information transmission, geometric constraints, and metabolic cost, all of which must be balanced to meet functional needs. Geometry and wiring economy are crucial in the development of brains, but their impact on artificial neural networks (ANNs) remains little understood. Here, we adopt a wiring cost-controlled training framework that simultaneously optimizes wiring efficiency and task performance during structural evolution of sparse ANNs whose nodes are located at arbitrary but fixed positions. We show that wiring cost control improves performance across a wide range of tasks, ANN architectures and training methods, and can promote task-specific structural modules. An optimal wiring cost range provides both enhanced predictive performance and high values of topological properties, such as modularity and clustering, which are observed in real brain networks and known to improve robustness, interpretability, and performance of ANNs. In addition, ANNs trained using wiring cost can emulate the connection distance distribution observed in the brains of real organisms (such as Ciona intestinalis and Caenorhabditis elegans), especially when achieving high task performance, offering insights into biological organizing principles. Our results shed light on the relationship between topology and task specialization of ANNs trained within biophysical constraints, and their geometric resemblance to real neuronal-level brain maps.
Partner (in)congruence in gender role attitudes and relationship satisfaction
Authors: Park Haeyoung Gideon , Qin Helena Yuchen , Horne Rebecca M , Impett Emily A , Yorgason Jeremy B , Cheung Felix 
Published: January 2025

Abstract
The societal shift toward greater gender equality has led to increased variability in people’s gender role attitudes, or the belief that men and women should occupy distinct family roles (i.e. men as breadwinners and women as homemakers). Existing evidence on the association between gender role attitudes and relationship well-being remains inconclusive with mixed findings, likely because past research has not adequately considered the direction and degree of (in)congruencies between partners within the relationship. Using longitudinal samples of 1,327 couples from the United States and 5,856 couples from Germany tracked over 2 and 13 years, respectively, we employed dyadic response surface analysis to examine how different patterns of partner (in)congruencies in gender role attitudes predict relationship well-being in mixed-gender relationships. The results showed that, for US men and German men and women, the direction of incongruence between partners’ gender role attitudes mattered: relationship satisfaction was higher when men adopted more egalitarian attitudes than women (or conversely, when women adopted more traditional attitudes than men) compared with the reverse. Relationship satisfaction was also higher when both partners showed congruence in extreme gender role attitudes (either strongly traditional or egalitarian) than when either partner endorsed more neutral attitudes. US women reported higher relationship satisfaction only when either partner endorsed more egalitarian attitudes. Although past research emphasizes the benefits of partner similarity for relationship well-being, our findings highlight the importance of both similarity and complementarity in gender role attitudes, potentially subject to cultural and contextual factors.
Effects of double data extraction on errors in evidence synthesis: a crossover, multicenter, investigator-blinded, randomized controlled trial
Authors: Tang Lijun , Wang Ruoxi , Doi Suhail A R , Furuya-Kanamori Luis , Lin Lifeng , Qin Zongshi , Tao Fangbiao , Xu Chang 
Published: January 2025

Abstract

Objectives
The objective was to investigate the role of double extraction in reducing data errors in evidence synthesis for pharmaceutical and non-pharmaceutical interventions.

Design
Crossover randomized controlled trial (RCT).

Setting
University and hospital with teaching programs in evidence-based medicine.

Participants
One hundred eligible participants were randomly assigned in a 1:1 ratio to perform data extraction tasks for either 10 RCTs of pharmaceutical interventions or 10 RCTs of non-pharmaceutical interventions, followed by a crossover pattern and a further cross-checking process (double extraction). Only data on binary adverse outcomes were extracted.

Intervention
Double data extraction versus single extraction.

Primary and secondary outcome measures
The primary outcome was the error rate before and after the cross-checking process. The secondary outcome was the absolute difference in error rates. Error rates were assessed at both the study level and the cell level.

Results
Error rates in the pharmaceutical and non-pharmaceutical groups were 64.65% and 59.90%, respectively, with an absolute difference of 4.75% and an odds ratio (OR) of 1.29 [95% confidence interval (CI): 1.06–1.57, P = .01] when measured at the study level. After cross-checking, error rates decreased to 44.88% and 39.54%, with the difference between the two groups remaining at 5.34%, and an OR of 1.27 (95%CI: 1.1–1.46; P &lt; .01). Similar differences were observed when measured at the cell level.

Conclusion
Although double extraction reduced data errors, the error rate remained high after the process. Evidence synthesis research may consider triple data extraction to further minimize potential data errors.

Trial registration number
Chinese Clinical Trial Registry Center (Identifier: ChiCTR2200062206).
Global and regional burden of cardiovascular diseases attributable to non-optimal temperatures: findings from the global burden of disease study 2021
Authors: Jena Diptismita , Padhi Bijaya Kumar 
Published: January 2025

Abstract

Background
Cardiovascular diseases (CVD) are leading contributors to global morbidity and mortality, significantly influenced by non-optimal temperatures. This study projects the impact of temperature fluctuations on CVD through 2050, considering environmental and climate changes.

Methods
Using Global Burden of Disease (GBD) study data, we analysed age-standardized death rates and disability-adjusted life years (ASR DALYs) related to non-optimal temperatures. We applied Estimated Annual Percentage Change (EAPC) for trend analysis and Auto-Regressive Integrated Moving Average (ARIMA) models for forecasting CVD mortality and DALYs from 2022 to 2050.

Results
EAPC analysis revealed a decline in CVD mortality rates, with a decrease of −0.32% for males (95% CI: −0.39 to −0.24%) and −0.42% for females (95% CI: −0.48 to −0.36%), indicating reduced mortality from non-optimal temperatures. Regions with higher Socio-Demographic Index showed more significant declines. ARIMA forecasts predict a substantial increase in CVD burden with deaths projected to rise from 1.2 million in 2022 to 1.9 million by 2050, and DALYs expected to increase from 2.4 million to over 3 million during the same period.

Conclusion
The projected rise in CVD due to temperature variability highlights the need for robust health systems integrated with climate action to mitigate risks. This research underscores the importance of advancing SDG 3.4 to reduce non-communicable disease mortality and emphasizes climate considerations in health planning per SDG 13.
Expanding the genomic diversity of human anelloviruses
Authors: Modha Sejal , Hughes Joseph , Orton Richard J , Lytras Spyros 
Published: January 2025

Abstract
Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: Alphatorquevirus, Betatorquevirus, and Gammatorquevirus, while we also present new genomes of the under-sampled Hetorquevirus, Memtorquevirus, and Samektorquevirus genera. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same genus and only 15 inter-genus recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination; however, events between distant viruses or ones producing chimaeric ORF1s likely lead to nonviable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses’ rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain nonstandard viral genomes. However, low-read depth of the metagenomically assembled contigs may partly explain the lack of some features. Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.