bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severity scores, damage indices, and the concept of the colchicine-resistant patient in familial Mediterranean fever
Authors: Er Ozan , Akay Helin , Ozgozen Mehmet Emre , Gulhan Didem , Ugurlu Serdal 
Published: August 2024

ABSTRACT
Familial Mediterranean fever is a common autoinflammatory disease. The primary treatment is colchicine; however, 5–10% of patients do not respond to colchicine and are considered colchicine resistant. Colchicine resistance and disease severity are highly associated, with each used to assess and define the other. In our review, we examined the most commonly used severity scores, damage indices, and definitions of colchicine resistance, revealing both shortcomings and advantages for each. We emphasize the necessity for a new severity score that integrates the definition of colchicine resistance.
Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer
Authors: Kocak Ozer , Kankaya Selin , Kalender Goktug , Citgez Sinharib , Onal Bulent , Dincer Yildiz 
Published: August 2024

Abstract
DNA methylation is an important mechanism in the regulation of gene expression and maintenance of genomic integrity. Aberrant DNA methylation is an early event in carcinogenesis. DNA methyltransferase inhibitors are used to restore aberrant DNA methylation and inhibit tumor growth. Evaluation of DNA methylation level is important for an effective anti-cancer therapy. In the present study, the determination of global DNA methylation levels in patients with urinary bladder cancer was proposed. The methylation-sensitive comet assay determined the global DNA methylation level at the level of single cells. McrBC enzyme, a methylation-sensitive restriction endonuclease, was used for enzymatic digestion to generate additional breaks at methylated sites. % DNA methylation level was significantly higher in patients with bladder cancer compared to the control group. The clinical performance of % DNA methylation analysis by methylation-sensitive comet assay was evaluated by ROC curve. Using the cutoff value of 6.5% DNA methylation, 92% sensitivity, and 42% specificity were obtained. In conclusion, global DNA methylation measured by methylation-sensitive comet assay may be a promising noninvasive biomarker that reduces interventional tests required in the diagnosis and follow-up of urinary bladder cancer.
Discovery of antiphage systems in the lactococcal plasmidome
Authors: Grafakou Andriana , Mosterd Cas , Beck Matthias H , Kelleher Philip , McDonnell Brian , de Waal Paul P , van Rijswijck Irma M H , van Peij Noël N M E , Cambillau Christian , Mahony Jennifer , van Sinderen Douwe 
Published: August 2024

Abstract
Until the late 2000s, lactococci substantially contributed to the discovery of various plasmid-borne phage defence systems, rendering these bacteria an excellent antiphage discovery resource. Recently, there has been a resurgence of interest in identifying novel antiphage systems in lactic acid bacteria owing to recent reports of so-called ‘defence islands’ in diverse bacterial genera. Here, 321 plasmid sequences from 53 lactococcal strains were scrutinized for the presence of antiphage systems. Systematic evaluation of 198 candidates facilitated the discovery of seven not previously described antiphage systems, as well as five systems, of which homologues had been described in other bacteria. All described systems confer resistance against the most prevalent lactococcal phages, and act post phage DNA injection, while all except one behave like abortive infection systems. Structure and domain predictions provided insights into their mechanism of action and allow grouping of several genetically distinct systems. Although rare within our plasmid collection, homologues of the seven novel systems appear to be widespread among bacteria. This study highlights plasmids as a rich repository of as yet undiscovered antiphage systems.
Discovery of numerous novel Helitron-like elements in eukaryote genomes using HELIANO
Authors: Li Zhen , Gilbert Clément , Peng Haoran , Pollet Nicolas 
Published: August 2024

Abstract
Helitron-like elements (HLEs) are widespread eukaryotic DNA transposons employing a rolling-circle transposition mechanism. Despite their prevalence in fungi, animals, and plant genomes, identifying Helitrons remains a formidable challenge. We introduce HELIANO, a software for annotating and classifying autonomous and non-autonomous HLE sequences from whole genomes. HELIANO overcomes several limitations of existing tools in speed and accuracy, demonstrated through benchmarking and its application to the complex genomes of frogs (Xenopus tropicalis and Xenopus laevis) and rice (Oryza sativa), where it uncovered numerous previously unidentified HLEs. In an extensive analysis of 404 eukaryote genomes, we found HLEs widely distributed across phyla, with exceptions in specific taxa. HELIANO’s application led to the discovery of numerous new HLEs in land plants and identified 20 protein domains captured by certain autonomous HLE families. A comprehensive phylogenetic analysis further classified HLEs into two primary clades, HLE1 and HLE2, and revealed nine subgroups, some of which are enriched within specific taxa. The future use of HELIANO promises to improve the global analysis of HLEs across genomes, significantly advancing our understanding of this fascinating transposon superfamily.
Advancing quantitative PCR with color cycle multiplex amplification
Authors: Chen Wei , Zhang Kerou , Huang Fei , Zhao Lan , Waldren George C , Jiang Qi , Chen Sherry X , Wang Bonnie , Guo Wei , Zhang David Y , Zhang Jinny X 
Published: August 2024

Abstract
Quantitative PCR (qPCR) is the gold standard for detection and quantitation of known DNA targets, but the scarcity of spectrally distinct fluorophores and filter sets limits the number of detectable targets. Here, we introduce color cycle multiplex amplification (CCMA) to significantly increase the number of detectable DNA targets in a single qPCR reaction using standard instrumentation. In CCMA, presence of one DNA target species results in a pre-programmed pattern of fluorescence increases. This pattern is distinguished by cycle thresholds (Cts) through rationally designed delays in amplification. For example, we design an assay wherein Staphylococcus aureus sequentially induces FAM, then Cy5.5, then ROX fluorescence increases with more than 3 cycles between each signal. CCMA offers notably higher potential for multiplexing because it uses fluorescence permutation rather than combination. With 4 distinct fluorescence colors, CCMA theoretically allows the detection of up to 136 distinct DNA target sequences using fluorescence permutation. Experimentally, we demonstrated a single-tube qPCR assay screening 21 sepsis-related bacterial DNA targets in samples of blood, sputum, pleural effusion and bronchoalveolar lavage fluid, with 89% clinical sensitivity and 100% clinical specificity, showing its potential as a powerful tool for advanced quantitative screening in molecular diagnostics.
junctionCounts: comprehensive alternative splicing analysis and prediction of isoform-level impacts to the coding sequence
Authors: Ritter Alexander J , Wallace Andrew , Ronaghi Neda , Sanford Jeremy R 
Published: August 2024

Abstract
Alternative splicing (AS) is emerging as an important regulatory process for complex biological processes. Transcriptomic studies therefore commonly involve the identification and quantification of alternative processing events, but the need for predicting the functional consequences of changes to the relative inclusion of alternative events remains largely unaddressed. Many tools exist for the former task, albeit each constrained to its own event type definitions. Few tools exist for the latter task; each with significant limitations. To address these issues we developed junctionCounts, which captures both simple and complex pairwise AS events and quantifies them with straightforward exon-exon and exon-intron junction reads in RNA-seq data, performing competitively among similar tools in terms of sensitivity, false discovery rate and quantification accuracy. Its partner utility, cdsInsertion, identifies transcript coding sequence (CDS) information via in silico translation from annotated start codons, including the presence of premature termination codons. Finally, findSwitchEvents connects AS events with CDS information to predict the impact of individual events to the isoform-level CDS. We used junctionCounts to characterize splicing dynamics and NMD regulation during neuronal differentiation across four primates, demonstrating junctionCounts’ capacity to robustly characterize AS in a variety of organisms and to predict its effect on mRNA isoform fate.
The Claim for An Institutional Identity in Healthcare Activities: the Italian Case
Authors: Madera Adelaide 
Published: August 2024

Abstract
The aim of this article is to analyse the status of religiously affiliated health facilities in Italy. Many faith-based healthcare institutions are currently entrapped between the expectation to participate in the healthcare public delivery, and the need for a preservation of their religious identity. Indeed, they are facing an increasing risk of a weakening of their religious identity, due to the evolution of civil law regulating ethically controversial issues, which is increasingly distancing from the religious approach, undermining the traditional religious accommodation granted to faith-based healthcare institutions. However, the preservation of their religious ethos requires dealing with a ‘web of relationships’ which includes the founding religious order, patients, practitioners, the State and a ‘highly competitive market’. This article explores the feasibility of an intermediate path between complete immunity and strict non-tolerance of their religious ethos, in the pursuit of the constitutional principles of pluralism, positive neutrality, and subsidiarity.
Viscoelastic performance of bagasse/glass fiber hybrid epoxy composites: effects of fiber hybridization on storage modulus, loss modulus, and damping behavior
Authors: Sumaila Malachy , Samuel Bassey Okon 
Published: August 2024

Abstract
This study aimed to investigate the viscoelastic properties of bagasse/glass fiber multilayered hybrid reinforced epoxy composites, focusing on how fiber hybridization affects dynamic mechanical performance. Epoxy composites with various layering sequences, including all-glass (AG), all-bagasse (AB), bagasse-glass-bagasse (BGB), and glass-bagasse-glass (GBG), were fabricated and analyzed using dynamic mechanical analysis (DMA) to measure storage modulus (E′), loss modulus (E″), and damping factor (tan δ). The results showed that hybrid composites (GBG and BGB) experienced a decrease in storage modulus by approximately 25% compared to AG, indicating enhanced polymer molecular chain mobility and improved interfacial adhesion between bagasse fibers and the epoxy matrix. The glass transition temperature (Tg) was slightly lower in hybrid composites, with GBG at 61°C and BGB at 60°C, compared to 62°C for AG. In terms of energy dissipation, AG exhibited the highest loss modulus peak at 62°C, while AB showed the lowest with a Tg at 53°C. The damping factor analysis revealed that AB had the highest damping peak (tan δ = 0.9) at 61°C, although this occurred at a lower temperature than the AG composite (tan δ = 0.7 at 76°C). These findings suggest that bagasse and glass fiber hybrid composites offer tailored viscoelastic properties, making them suitable for applications in automotive components, aerospace structures, and sports equipment.
The British Political Tradition and Constitutional Policy: The Offer of Deliberative Mini Publics
Authors: Coulter Steph , McKee Rebecca , Pannell Jack , Sargeant Jess 
Published: August 2024

AbstractThe Review of the UK Constitution was an eighteen-month project assessing the functioning of the UK constitution resulting in a set of practical, innovative, and robust recommendations. This article draws out one theme from this research, the offer of Deliberative Mini Publics (DMPs) in the process of constitutional change in the UK. Using Marsh, Richards, and Smith’s ‘Asymmetric Power Model’ as a mechanism for understanding the centralised and top–down nature of British democracy, we argue that the integration of DMPs can offer an opportunity to mitigate some of the core problems with the functioning of the UK constitution and produce better constitutional policy.
Natural Variation in Sexual Traits and Gene Expression between Selfing and Outcrossing Arabidopsis lyrata Suggests Sexual Selection at Work
Authors: İltaş Ömer , Čertner Martin , Lafon Placette Clément 
Published: August 2024

Abstract
Flowering plants show significant diversity in sexual strategies, profoundly impacting the evolution of sexual traits and associated genes. Sexual selection is one of the primary evolutionary forces driving sexual trait variation, particularly evident during pollen–pistil interactions, where pollen grains compete for fertilization and females select mating partners. Multiple mating may intensify competition among pollen donors for siring, while in contrast, self-fertilization reduces sire–sire competition, relaxing the sexual selection pressure. Traits involved in male–male competition and female choice are well described, and molecular mechanisms underlying pollen development and pollen–pistil interactions have been extensively studied in the model species Arabidopsis thaliana. However, whether these molecular mechanisms are involved in sexual selection in nature remains unclear. To address this gap, we measured intrinsic pollen performance and its interaction with female choice and investigated the associated gene expression patterns in a selfing and an outcrossing population of Arabidopsis lyrata. We found that pollen germination and pollen tube growth were significantly higher in outcrossers than selfers, and this difference was accompanied by changes in the expression of genes involved in vesicle transport and cytoskeleton. Outcrosser mother plants showed a negative impact on pollen tube growth compared to selfer mother plants, together with a difference of expression for genes involved in auxin and stress response, suggesting a potential mechanism for female choice through molecular cross talk at the post-pollination stage. Our study provides insight into the impact of sexual selection on the evolution of sexual gene expression in plants.
Alternating between even and odd ploidy levels switches on and off the recombination control, even near the centromeres
Authors: Boideau Franz , Huteau Virginie , Maillet Loeiz , Brunet Anael , Coriton Olivier , Deniot Gwenaëlle , Trotoux Gwenn , Taburel-Lodé Maryse , Eber Frédérique , Gilet Marie , Baron Cécile , Boutte Julien , Richard Gautier , Aury Jean-Marc , Belser Caroline , Labadie Karine , Morice Jérôme , Falentin Cyril , Martin Olivier , Falque Matthieu , Chèvre Anne-Marie , Rousseau-Gueutin Mathieu 
Published: August 2024

Abstract
Meiotic recombination is a key biological process in plant evolution and breeding, as it generates genetic diversity in each generation through the formation of crossovers (COs). However, due to their importance in genome stability, COs are highly regulated in frequency and distribution. We previously demonstrated that this strict regulation of COs can be modified, both in terms of CO frequency and distribution, in allotriploid Brassica hybrids (2n = 3x = 29; AAC) resulting from a cross between Brassica napus (2n = 4x = 38; AACC) and Brassica rapa (2n = 2x = 20; AA). Using the recently updated B. napus genome now including pericentromeres, we demonstrated that COs occur in these cold regions in allotriploids, as close as 375 kb from the centromere. Reverse transcription quantitative PCR (RT-qPCR) of various meiotic genes indicated that Class I COs are likely involved in the increased recombination frequency observed in allotriploids. We also demonstrated that this modified recombination landscape can be maintained via successive generations of allotriploidy (odd ploidy level). This deregulated meiotic behavior reverts to strict regulation in allotetraploid (even ploidy level) progeny in the second generation. Overall, we provide an easy way to manipulate tight recombination control in a polyploid crop.
Dosage sensitivity shapes balanced expression and gene longevity of homoeologs after whole-genome duplications in angiosperms
Authors: Shi Tao , Gao Zhiyan , Chen Jinming , Van de Peer Yves 
Published: August 2024

Abstract
Following whole-genome duplication (WGD), duplicate gene pairs (homoeologs) can evolve varying degrees of expression divergence. However, the determinants influencing these relative expression level differences (RFPKM) between homoeologs remain elusive. In this study, we analyzed the RFPKM between homoeologs in 3 angiosperms, Nymphaea colorata, Nelumbo nucifera, and Acorus tatarinowii, all having undergone a single WGD since the origin of angiosperms. Our results show significant positive correlations in RFPKM of homoeologs among tissues within the same species, and among orthologs across these 3 species, indicating convergent expression balance/bias between homoeologous gene copies following independent WGDs. We linked RFPKM between homoeologs to gene attributes associated with dosage-balance constraints, such as protein–protein interactions, lethal-phenotype scores in Arabidopsis (Arabidopsis thaliana) orthologs, domain numbers, and expression breadth. Notably, homoeologs with lower RFPKM often had more interactions and higher lethal-phenotype scores, indicating selective pressures favoring balanced expression. Also, homoeologs with lower RFPKM were more likely to be retained after WGDs in angiosperms. Within Nelumbo, greater RFPKM between homoeologs correlated with increased cis- and trans-regulatory differentiation between species, highlighting the ongoing escalation of gene expression divergence. We further found that expression degeneration in 1 copy of homoeologs is inclined toward nonfunctionalization. Our research highlights the importance of balanced expression, shaped by dosage-balance constraints, in the evolutionary retention of homoeologs in plants.
Exogenous application of the apocarotenoid retinaldehyde negatively regulates auxin-mediated root growth
Authors: Xu Kang , Zeng Haoran , Lin Feiyang , Yumoto Emi , Asahina Masashi , Hayashi Ken-ichiro , Fukaki Hidehiro , Ito Hisashi , Watahiki Masaaki K 
Published: August 2024

Abstract
Root development is essential for plant survival. The lack of carotenoid biosynthesis in the phytoene desaturase 3 (pds3) mutant results in short primary roots (PRs) and reduced lateral root formation. In this study, we showed that short-term inhibition of PDS by fluridone suppresses PR growth in wild type, but to a lesser extent in auxin mutants of Arabidopsis (Arabidopsis thaliana). Such an inhibition of PDS activity increased endogenous indole-3-acetic acid levels, promoted auxin signaling, and partially complemented the PR growth of an auxin-deficient mutant, the YUCCA 3 5 7 8 9 quadruple mutant (yucQ). The exogenous application of retinaldehyde (retinal), an apocarotenoid derived from β-carotene, complemented the fluridone-induced suppression of root growth, as well as the short roots of the pds3 mutant. Retinal also partially complemented the auxin-induced suppression of root growth. These results suggest that retinal may play a role in regulating root growth by modulating endogenous auxin levels.
Associations between 1930s HOLC grades and estimated population burden of cardiovascular disease risk factors in 2020
Authors: Wei Hanxue , Spoer Benjamin R , Titus Andrea R , Lampe Taylor M , Gourevitch Marc N , Faber Jacob W , Korzeniewski Steven J , Bauer Samantha J , Thorpe Lorna E 
Published: August 2024

Abstract
Studies have recently begun to explore the potential long-term health impacts of homeownership policies implemented in the New Deal era. We investigated the association between assigned grades of lending risk by the Home Owners’ Load Corporation (HOLC) maps from the 1930s and present-day prevalence of three cardiovascular risk factors (diabetes and obesity in 2020, and hypertension in 2019), estimated at the census tract level in the United States. To minimize potential confounding, we adjusted for sociodemographic data from the time period when HOLC maps were made. We calculated propensity scores (predicted probability of receiving a HOLC grade) and created a pseudo-population using inverse probability weighting. We then employed marginal structural models to estimate prevalence differences comparing A vs. B, B vs. C, and C vs. D HOLC grades. Adjusting only for regions, a less desirable HOLC grade was associated with higher estimated prevalence rates of present-day cardiovascular risk factors; however, most differences were no longer significant after applying propensity score methods. The one exception was that the prevalence of diabetes, hypertension, and obesity were all higher in C vs. B graded census tracts, while no differences were observed for C and D and A and B comparisons. These results contribute to a small body of evidence that suggests historical “yellowlining” (as C grade was in color yellow) may have had persistent impacts on neighborhood-level cardiovascular risk factors 80 years later.
Mantis: High-throughput 4D imaging and analysis of the molecular and physical architecture of cells
Authors: Ivanov Ivan E , Hirata-Miyasaki Eduardo , Chandler Talon , Cheloor-Kovilakam Rasmi , Liu Ziwen , Pradeep Soorya , Liu Chad , Bhave Madhura , Khadka Sudip , Arias Carolina , Leonetti Manuel D , Huang Bo , Mehta Shalin B 
Published: August 2024

Abstract
High-throughput dynamic imaging of cells and organelles is essential for understanding complex cellular responses. We report Mantis, a high-throughput 4D microscope that integrates two complementary, gentle, live-cell imaging technologies: remote-refocus label-free microscopy and oblique light-sheet fluorescence microscopy. Additionally, we report shrimPy (Smart High-throughput Robust Imaging and Measurement in Python), an open-source software for high-throughput imaging, deconvolution, and single-cell phenotyping of 4D data. Using Mantis and shrimPy, we achieved high-content correlative imaging of molecular dynamics and the physical architecture of 20 cell lines every 15 min over 7.5 h. This platform also facilitated detailed measurements of the impacts of viral infection on the architecture of host cells and host proteins. The Mantis platform can enable high-throughput profiling of intracellular dynamics, long-term imaging and analysis of cellular responses to perturbations, and live-cell optical screens to dissect gene regulatory networks.
An exploration of interview breaks in child forensic interviews
Authors: Danby Meaghan C , Sharman Stefanie J 
Published: August 2024

Abstract
Child forensic interview guidelines commonly recommend that interviewers take breaks during interviews to improve children’s comfort and to review the evidence obtained. However, instructions vary on how, when, and why to take breaks. Recent studies have also raised concerns about whether the feedback that interviewers receive during breaks reduces the quality of their post-break questioning. To establish interviewers’ use of breaks and compare their pre- versus post-break questioning, we recruited 54 police child interviewers. Participants provided a recent child interview and completed a questionnaire about their use of breaks in that interview. Breaks were rarely used for children’s comfort but were commonly used to review the evidence obtained. While interviewers’ questioning was proportionally more specific and less open-ended post-break (compared to pre-break), post-break open-ended questioning was positively associated with receiving advice from a colleague monitoring the interview about best practice techniques. Therefore, it is important that interview monitors have child interviewing knowledge.