bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of lichen sclerosus on women’s sexual health from a biopsychosocial perspective: a mixed methods study
Authors: Caspersen Irene S , Højgaard Astrid , Laursen Birgitte S 
Published: March 2023

AbstractBackgroundWomen with lichen sclerosus (LS) may suffer sexually because of dyspareunia, fissures, and introital narrowing. However, the literature remains limited on the biopsychosocial aspects of LS and its impact on sexual health.AimTo examine the biopsychosocial aspects and impact of LS on the sexual health of Danish women with vulvar LS.MethodsThe study was conducted with a mixed methods approach, including women with LS from a Danish patient association. The quantitative sample consisted of 172 women who completed a cross-sectional online survey that included 2 validated questionnaires: the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS). The qualitative sample consisted of 5 women with LS who volunteered for audiotaped, individual, semistructured interviews.OutcomesThis mixed methods study combined data from 2 quantitative questionnaires (FSFI and FSDS) with qualitative interviews to achieve a comprehensive insight into the biopsychosocial aspects of sexual health in women living with LS.ResultsThe sexual function of women with LS was considerably affected, with FSFI scores below the cutoff value of 26.55, indicating a risk of sexual dysfunction. On average, 75% of the women were sexually distressed, with a total FSDS score of 25.47. Furthermore, 68% of the sexually active women were considerably affected in terms of sexual function and sexual distress, thus meeting international criteria for sexual dysfunction. However, a negative impact on sexual function was not always related to sexual distress and vice versa. The qualitative analysis identified 4 overarching themes: (1) decrease in or loss of sexual activity, (2) interference with relationship dynamics, (3) importance of sex and intimacy – loss and restoration, and (4) worries about sexual insufficiency.Clinical ImplicationsInsight into the influence of LS on sexual health is important for health care professionals, including doctors, nurses, sex therapists, and physiotherapists, to provide the best guidance, support, and management for women with LS.Strengths and LimitationsThe strengths of the study are its use of a mixed methods design and the inclusion of sexual function and sexual distress. A limitation is related to the properties of the FSFI regarding women with no sexual activity.ConclusionsLS has a considerable influence on women’s sexual health in terms of sexual function and sexual distress, as supported by quantitative and qualitative measures. Our understanding of the complex interactions among sexual activity, intimate relations, and causes of psychological distress has been enriched.
Self-Fashioning Illusions: Twinship, Subjectivity, and Neo-Victorianism in Christopher Priest’s &#x2028;The Prestige
Authors: Ioannidou Elisavet 
Published: March 2023

Abstract
Examining the conflicting approaches to the fragmentation of the self and the feasibility of self-awareness featured in Christopher Priest’s novel The Prestige (1995), this article reflects on the evaluation, and subsequent reinvention, of the Victorian era in the genre commonly known as neo-Victorian fiction. Alfred Borden, the novel’s Victorian protagonist, fashions himself as a unique and unified individual even though his identity is, in fact, composite and alternatingly shared between twin brothers. In contrast, Andrew Westley, Borden’s twentieth-century descendant, experiences an instinctive sense of division through which he rationalizes his life. Featured in temporally distinct storylines, these conflicting perspectives reflect the tensions at work in the neo-Victorian return to the Victorian past. Silencing multiplicity and negating fragmentation, the Victorian characters echo scholarly objections to the use of the term ‘Victorian’: its apparent assertion of coherence and homogeneity when it is actually called to signify an extremely diverse historical period. Conversely, by means of the twentieth-century protagonist’s need to comprehend and embrace division, a need which is fulfilled through Andrew’s familiarization with and acceptance of his past, the novel acknowledges the multivalence of the ‘Victorian’ and its indisputable connection to the present. Exploring Victorian and twentieth-century appreciations of subjectivity, The Prestige sheds light into neo-Victorianism’s self-fashioning strategies, raising the question whether and to what extent neo-Victorian reconfigurations of the Victorian era (re)discover the past, or operate on our potentially misleading preconceptions about the nineteenth century.
Polishing De Novo Nanopore Assemblies of Bacteria and Eukaryotes With FMLRC2
Authors: Mak Q X Charles , Wick Ryan R , Holt James Matthew , Wang Jeremy R 
Published: March 2023

AbstractAs the accuracy and throughput of nanopore sequencing improve, it is increasingly common to perform long-read first de novo genome assemblies followed by polishing with accurate short reads. We briefly introduce FMLRC2, the successor to the original FM-index Long Read Corrector (FMLRC), and illustrate its performance as a fast and accurate de novo assembly polisher for both bacterial and eukaryotic genomes.
Droplet microfluidic chip-ICP–MS-based single-cell analysis for study of cellular behavior of macrophages to thimerosal
Authors: Ma Junrong , He Man , Chen Beibei , Hu Bin 
Published: March 2023

Abstract
Thimerosal (THI) is widely used as an antimicrobial preservative, but can hydrolyze to ethylmercury, causing potentially neurotoxicity. In this work, a THP-1 cell line was used to investigate the biological behavior of THI. An on-line droplet microfluidic chip system combined with time-resolved inductively coupled plasma mass spectrometry was used to quantify Hg in single THP-1 cells. The cellular uptake and elimination behaviors of THI were studied, and the toxicity of THI in terms of redox balance was discussed. The results showed that a small number of cells (&lt;5%) exhibited a high uptake content (&gt;200 fg/cell) for THI, and most of the cells (68.8–85.8% for different exposure groups at 25 h) exhibited a relatively low uptake content (&lt;20 fg/cell). After stopping exposure to THI, the cells showed an elimination process for Hg, which was rapid in the first several hours and gradually slowed down. When the elimination time was 25 h, 7.4–26.3% of the cells in different exposure groups still contained a detectable amount of Hg (&gt;2 fg/cell), indicating Hg could not be eliminated completely, which may cause cumulative toxicity to macrophages. Moreover, it was found that exposure to THI even at 50 ng/mL can cause cellular oxidative stress behavior, leading to an increase in reactive oxygen species level and a decrease in glutathione level. This trend would continue for a period of time after stopping THI exposure. With the elimination of Hg, the redox balance of cells showed a tendency to stabilize and restore, but cannot be restored to normal status, indicating a long-term chronic toxicity of THI to THP-1 cells.
Fitness functions for RNA structure design
Authors: Ward Max , Courtney Eliot , Rivas Elena 
Published: March 2023

Abstract
An RNA design algorithm takes a target RNA structure and finds a sequence that folds into that structure. This is fundamentally important for engineering therapeutics using RNA. Computational RNA design algorithms are guided by fitness functions, but not much research has been done on the merits of these functions. We survey current RNA design approaches with a particular focus on the fitness functions used. We experimentally compare the most widely used fitness functions in RNA design algorithms on both synthetic and natural sequences. It has been almost 20 years since the last comparison was published, and we find similar results with a major new result: maximizing probability outperforms minimizing ensemble defect. The probability is the likelihood of a structure at equilibrium and the ensemble defect is the weighted average number of incorrect positions in the ensemble. We find that maximizing probability leads to better results on synthetic RNA design puzzles and agrees more often than other fitness functions with natural sequences and structures, which were designed by evolution. Also, we observe that many recently published approaches minimize structure distance to the minimum free energy prediction, which we find to be a poor fitness function.
Structural and functional insights into the activation of the dual incision activity of UvrC, a key player in bacterial NER
Authors: Seck Anna , De Bonis Salvatore , Stelter Meike , Ökvist Mats , Senarisoy Müge , Hayek Mohammad Rida , Le Roy Aline , Martin Lydie , Saint-Pierre Christine , Silveira Célia M , Gasparutto Didier , Todorovic Smilja , Ravanat Jean-Luc , Timmins Joanna 
Published: March 2023

AbstractBacterial nucleotide excision repair (NER), mediated by the UvrA, UvrB and UvrC proteins is a multistep, ATP-dependent process, that is responsible for the removal of a very wide range of chemically and structurally diverse DNA lesions. DNA damage removal is performed by UvrC, an enzyme possessing a dual endonuclease activity, capable of incising the DNA on either side of the damaged site to release a short single-stranded DNA fragment containing the lesion. Using biochemical and biophysical approaches, we have probed the oligomeric state, UvrB- and DNA-binding abilities and incision activities of wild-type and mutant constructs of UvrC from the radiation resistant bacterium, Deinococcus radiodurans. Moreover, by combining the power of new structure prediction algorithms and experimental crystallographic data, we have assembled the first model of a complete UvrC, revealing several unexpected structural motifs and in particular, a central inactive RNase H domain acting as a platform for the surrounding domains. In this configuration, UvrC is maintained in a ‘closed’ inactive state that needs to undergo a major rearrangement to adopt an ‘open’ active state capable of performing the dual incision reaction. Taken together, this study provides important insight into the mechanism of recruitment and activation of UvrC during NER.
Proteomic analyses reveal new features of the box H/ACA RNP biogenesis
Authors: Schlotter Florence , Mérouani Salim , Flayac Justine , Kogey Valentyne , Issa Amani , Dodré Maxime , Huttin Alexandra , Branlant Christiane , Bertrand Edouard , Labialle Stéphane , Vandermoere Franck , Verheggen Céline , Massenet Séverine 
Published: March 2023

Abstract
The conserved H/ACA RNPs consist of one H/ACA RNA and 4 core proteins: dyskerin, NHP2, NOP10, and GAR1. Its assembly requires several assembly factors. A pre-particle containing the nascent RNAs, dyskerin, NOP10, NHP2 and NAF1 is assembled co-transcriptionally. NAF1 is later replaced by GAR1 to form mature RNPs. In this study, we explore the mechanism leading to the assembly of H/ACA RNPs. We performed the analysis of GAR1, NHP2, SHQ1 and NAF1 proteomes by quantitative SILAC proteomic, and analyzed purified complexes containing these proteins by sedimentation on glycerol gradient. We propose the formation of several distinct intermediate complexes during H/ACA RNP assembly, notably the formation of early protein-only complexes containing at least the core proteins dyskerin, NOP10, and NHP2, and the assembly factors SHQ1 and NAF1. We also identified new proteins associated with GAR1, NHP2, SHQ1 and NAF1, which can be important for box H/ACA assembly or function. Moreover, even though GAR1 is regulated by methylations, the nature, localization, and functions of these methylations are not well known. Our MS analysis of purified GAR1 revealed new sites of arginine methylations. Additionally, we showed that unmethylated GAR1 is correctly incorporated in H/ACA RNPs, even though with less efficiency than methylated ones.
Recent advancements in the structural biology of human telomerase and their implications for improved design of cancer therapeutics
Authors: Welfer Griffin A , Freudenthal Bret D 
Published: March 2023

Abstract
Telomerase is a specialized reverse transcriptase that synthesizes telomeric repeats at the ends of linear chromosomes. Telomerase is transiently expressed in germ and stem cells, but nearly all somatic cells silence it after differentiating. However, the vast majority of cancer cells reactivate and constitutively express telomerase to maintain replicative immortality. Because of this, telomerase has remained a promising broad-spectrum chemotherapeutic target for over 30 years. However, various challenges associated with obtaining high-resolution structural data for telomerase have limited the development of rationally designed structure-based therapeutics. Various techniques and model systems have been utilized to advance our understanding of the structural biology of telomerase. In particular, multiple high-resolution cryogenic electron microscopy (cryo-EM) structures published within the past few years have revealed new components of the telomerase complex with near atomic resolution structural models. Additionally, these structures have provided details for how telomerase is recruited to telomeres and its mechanism of telomere synthesis. With these new pieces of evidence, and the promising outlook for future refinements to our current models, the possibility of telomerase specific chemotherapeutics is becoming more tangible than ever. This review summarizes these recent advancements and outlines outstanding questions in the field.
ICI efficacy information portal: a knowledgebase for responder prediction to immune checkpoint inhibitors
Authors: Chen Jiamin , Rebibo Daniel , Cao Jianquan , Mok Simon Yat-Man , Patel Neel , Tseng Po-Cheng , Zhang Zhenghao , Yip Kevin Y 
Published: March 2023

Abstract
Immune checkpoint inhibitors (ICIs) have led to durable responses in cancer patients, yet their efficacy varies significantly across cancer types and patients. To stratify patients based on their potential clinical benefits, there have been substantial research efforts in identifying biomarkers and computational models that can predict the efficacy of ICIs, and it has become difficult to keep track of all of them. It is also difficult to compare findings of different studies since they involve different cancer types, ICIs, and various other details. To make it easy to access the latest information about ICI efficacy, we have developed a knowledgebase and a corresponding web-based portal (https://iciefficacy.org/). Our knowledgebase systematically records information about latest publications related to ICI efficacy, predictors proposed, and datasets used to test them. All information recorded is checked carefully by a manual curation process. The web-based portal provides functions to browse, search, filter, and sort the information. Digests of method details are provided based on the original descriptions in the publications. Evaluation results of the effectiveness of the predictors reported in the publications are summarized for quick overviews. Overall, our resource provides centralized access to the burst of information produced by the vibrant research on ICI efficacy.
R-loops, type I topoisomerases and cancer
Authors: Saha Sourav , Pommier Yves 
Published: March 2023

Abstract
R-loops are abundant and dynamic structures ubiquitously present in human cells both in the nuclear and mitochondrial genomes. They form in cis in the wake of transcription complexes and in trans apart from transcription complexes. In this review, we focus on the relationship between R-loops and topoisomerases, and cancer genomics and therapies. We summarize the topological parameters associated with the formation and resolution of R-loops, which absorb and release high levels of genomic negative supercoiling (Sc-). We review the deleterious consequences of excessive R-loops and rationalize how human type IA (TOP3B) and type IB (TOP1) topoisomerases regulate and resolve R-loops in coordination with helicase and RNase H enzymes. We also review the drugs (topoisomerase inhibitors, splicing inhibitors, G4 stabilizing ligands) and cancer predisposing genes (BRCA1/2, transcription, and splicing genes) known to induce R-loops, and whether stabilizing R-loops and thereby inducing genomic damage can be viewed as a strategy for cancer treatment.
DELongSeq for efficient detection of differential isoform expression from long-read RNA-seq data
Authors: Hu Yu , Gouru Anagha , Wang Kai 
Published: March 2023

Abstract
Conventional gene expression quantification approaches, such as microarrays or quantitative PCR, have similar variations of estimates for all genes. However, next-generation short-read or long-read sequencing use read counts to estimate expression levels with much wider dynamic ranges. In addition to the accuracy of estimated isoform expression, efficiency, which measures the degree of estimation uncertainty, is also an important factor for downstream analysis. Instead of read count, we present DELongSeq, which employs information matrix of EM algorithm to quantify uncertainty of isoform expression estimates to improve estimation efficiency. DELongSeq uses random-effect regression model for the analysis of DE isoform, in that within-study variation represents variable precision in isoform expression estimation and between-study variation represents variation in isoform expression levels across samples. More importantly, DELongSeq allows 1 case versus 1 control comparison of differential expression, which has specific application scenarios in precision medicine (such as before versus after treatment, or tumor versus stromal tissues). Through extensive simulations and analysis of several RNA-Seq datasets, we show that the uncertainty quantification approach is computationally reliable, and can improve the power of differential expression (DE) analysis of isoforms or genes. In summary, DELongSeq allows for efficient detection of differential isoform/gene expression from long-read RNA-Seq data.
TiSA: TimeSeriesAnalysis—a pipeline for the analysis of longitudinal transcriptomics data
Authors: Lefol Yohan , Korfage Tom , Mjelle Robin , Prebensen Christian , Lüders Torben , Müller Bruno , Krokan Hans , Sarno Antonio , Alsøe Lene ,   CONSORTIUM LEMONAID, Berdal Jan-Erik , Sætrom Pål , Nilsen Hilde , Domanska Diana 
Published: March 2023

Abstract
Improved transcriptomic sequencing technologies now make it possible to perform longitudinal experiments, thus generating a large amount of data. Currently, there are no dedicated or comprehensive methods for the analysis of these experiments. In this article, we describe our TimeSeries Analysis pipeline (TiSA) which combines differential gene expression, clustering based on recursive thresholding, and a functional enrichment analysis. Differential gene expression is performed for both the temporal and conditional axes. Clustering is performed on the identified differentially expressed genes, with each cluster being evaluated using a functional enrichment analysis. We show that TiSA can be used to analyse longitudinal transcriptomic data from both microarrays and RNA-seq, as well as small, large, and/or datasets with missing data points. The tested datasets ranged in complexity, some originating from cell lines while another was from a longitudinal experiment of severity in COVID-19 patients. We have also included custom figures to aid with the biological interpretation of the data, these plots include Principal Component Analyses, Multi Dimensional Scaling plots, functional enrichment dotplots, trajectory plots, and complex heatmaps showing the broad overview of results. To date, TiSA is the first pipeline to provide an easy solution to the analysis of longitudinal transcriptomics experiments.
TIS Transformer: remapping the human proteome using deep learning
Authors: Clauwaert Jim , McVey Zahra , Gupta Ramneek , Menschaert Gerben 
Published: March 2023

AbstractThe correct mapping of the proteome is an important step towards advancing our understanding of biological systems and cellular mechanisms. Methods that provide better mappings can fuel important processes such as drug discovery and disease understanding. Currently, true determination of translation initiation sites is primarily achieved by in vivo experiments. Here, we propose TIS Transformer, a deep learning model for the determination of translation start sites solely utilizing the information embedded in the transcript nucleotide sequence. The method is built upon deep learning techniques first designed for natural language processing. We prove this approach to be best suited for learning the semantics of translation, outperforming previous approaches by a large margin. We demonstrate that limitations in the model performance are primarily due to the presence of low-quality annotations against which the model is evaluated against. Advantages of the method are its ability to detect key features of the translation process and multiple coding sequences on a transcript. These include micropeptides encoded by short Open Reading Frames, either alongside a canonical coding sequence or within long non-coding RNAs. To demonstrate the use of our methods, we applied TIS Transformer to remap the full human proteome.
Single-cell gene set enrichment analysis and transfer learning for functional annotation of scRNA-seq data
Authors: Franchini Melania , Pellecchia Simona , Viscido Gaetano , Gambardella Gennaro 
Published: March 2023

AbstractAlthough an essential step, cell functional annotation often proves particularly challenging from single-cell transcriptional data. Several methods have been developed to accomplish this task. However, in most cases, these rely on techniques initially developed for bulk RNA sequencing or simply make use of marker genes identified from cell clustering followed by supervised annotation. To overcome these limitations and automatize the process, we have developed two novel methods, the single-cell gene set enrichment analysis (scGSEA) and the single-cell mapper (scMAP). scGSEA combines latent data representations and gene set enrichment scores to detect coordinated gene activity at single-cell resolution. scMAP uses transfer learning techniques to re-purpose and contextualize new cells into a reference cell atlas. Using both simulated and real datasets, we show that scGSEA effectively recapitulates recurrent patterns of pathways’ activity shared by cells from different experimental conditions. At the same time, we show that scMAP can reliably map and contextualize new single-cell profiles on a breast cancer atlas we recently released. Both tools are provided in an effective and straightforward workflow providing a framework to determine cell function and significantly improve annotation and interpretation of scRNA-seq data.