bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease
Authors: Velissari Rania , Ilieva Mirolyuba , Dao James , Miller Henry E , Madsen Jens Hedelund , Gorodkin Jan , Aikawa Masanori , Ishii Hideshi , Uchida Shizuka 
Published: October 2023

Abstract
The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.
G2GSnake: a Snakemake workflow for host–pathogen genomic association studies
Authors: Xu Zhi Ming , Naret Olivier , Oumelloul Mariam Ait , Fellay Jacques 
Published: October 2023

Abstract

Summary
Joint analyses of paired host and pathogen genome sequences have the potential to enhance our understanding of host–pathogen interactions. A systematic approach to conduct such a joint analysis is through a “genome-to-genome” (G2G) association study, which involves testing for associations between all host and pathogen genetic variants. Significant associations reveal host genetic factors that might drive pathogen variation, highlighting biological mechanisms likely to be involved in host control and pathogen escape. Here, we present a Snakemake workflow that allows researchers to conduct G2G studies in a reproducible and scalable manner. In addition, we have developed an intuitive R Shiny application that generates custom summaries of the results, enabling users to derive relevant insights.

Availability and implementation
G2GSnake is freely available at: https://github.com/zmx21/G2GSnake under the MIT license.
UDock2: interactive real-time multi-body protein–protein docking software
Authors: Plateau-Holleville Cyprien , Guionnière Simon , Boyer Benjamin , Jiménez-Garcia Brian , Levieux Guillaume , Mérillou Stéphane , Maria Maxime , Montes Matthieu 
Published: October 2023

Abstract

Motivation
Protein–protein docking aims at predicting the geometry of protein interactions to gain insights into the mechanisms underlying these processes and develop new strategies for drug discovery. Interactive and user-oriented manipulation tools can support this task complementary to automated software.

Results
This article presents an interactive multi-body protein–protein docking software, UDock2, designed for research but also usable for teaching and popularization of science purposes due to its high usability. In UDock2, the users tackle the conformational space of protein interfaces using an intuitive real-time docking procedure with on-the-fly scoring. UDock2 integrates traditional computer graphics methods to facilitate the visualization and to provide better insight into protein surfaces, interfaces, and properties.

Availability and implementation
UDock2 is open-source, cross-platform (Windows and Linux), and available at http://udock.fr. The code can be accessed at https://gitlab.com/Udock/Udock2.
Comprehensive microbiome causal mediation analysis using MiMed on user-friendly web interfaces
Authors: Jang Hyojung , Park Solha , Koh Hyunwook 
Published: October 2023

AbstractIt is a central goal of human microbiome studies to see the roles of the microbiome as a mediator that transmits environmental, behavioral, or medical exposures to health or disease outcomes. Yet, mediation analysis is not used as much as it should be. One reason is because of the lack of carefully planned routines, compilers, and automated computing systems for microbiome mediation analysis (MiMed) to perform a series of data processing, diversity calculation, data normalization, downstream data analysis, and visualizations. Many researchers in various disciplines (e.g. clinicians, public health practitioners, and biologists) are not also familiar with related statistical methods and programming languages on command-line interfaces. Thus, in this article, we introduce a web cloud computing platform, named as MiMed, that enables comprehensive MiMed on user-friendly web interfaces. The main features of MiMed are as follows. First, MiMed can survey the microbiome in various spheres (i) as a whole microbial ecosystem using different ecological measures (e.g. alpha- and beta-diversity indices) or (ii) as individual microbial taxa (e.g. phyla, classes, orders, families, genera, and species) using different data normalization methods. Second, MiMed enables covariate-adjusted analysis to control for potential confounding factors (e.g. age and gender), which is essential to enhance the causality of the results, especially for observational studies. Third, MiMed enables a breadth of statistical inferences in both mediation effect estimation and significance testing. Fourth, MiMed provides flexible and easy-to-use data processing and analytic modules and creates nice graphical representations. Finally, MiMed employs ChatGPT to search for what has been known about the microbial taxa that are found significantly as mediators using artificial intelligence technologies. For demonstration purposes, we applied MiMed to the study on the mediating roles of oral microbiome in subgingival niches between e-cigarette smoking and gingival inflammation. MiMed is freely available on our web server (http://mimed.micloud.kr).
Emerging evidence on the role of breast microbiota on the development of breast cancer in high-risk patients
Authors: Actis Silvia , Cazzaniga Massimiliano , Bounous Valentina Elisabetta , D’Alonzo Marta , Rosso Roberta , Accomasso Francesca , Minella Carola , Biglia Nicoletta 
Published: October 2023

Abstract
Cancer is a multi-factorial disease, and the etiology of breast cancer (BC) is due to a combination of both genetic and environmental factors. Breast tissue shows a unique microbiota, Proteobacteria and Firmicutes are the most abundant bacteria in breast tissue, and several studies have shown that the microbiota of healthy breast differs from that of BC. Breast microbiota appears to be correlated with different characteristics of the tumor, and prognostic clinicopathologic features. It also appears that there are subtle differences between the microbial profiles of the healthy control and high-risk patients. Genetic predisposition is an extremely important risk factor for BC. BRCA1/2 germline mutations and Li-Fraumeni syndrome are DNA repair deficiency syndromes inherited as autosomal dominant characters that substantially increase the risk of BC. These syndromes exhibit incomplete penetrance of BC expression in carrier subjects. The action of breast microbiota on carcinogenesis might explain why women with a mutation develop cancer and others do not. Among the potential biological pathways through which the breast microbiota may affect tumorigenesis, the most relevant appear to be DNA damage caused by colibactin and other bacterial-derived genotoxins, β-glucuronidase-mediated estrogen deconjugation and reactivation, and HPV-mediated cancer susceptibility. In conclusion, in patients with a genetic predisposition, an unfavorable breast microbiota may be co-responsible for the onset of BC. Prospectively, the ability to modulate the microbiota may have an impact on disease onset and progression in patients at high risk for BC.
Diagnostic miRNA Signatures in Paired Tumor, Plasma, and Urine Specimens From Renal Cell Carcinoma Patients
Authors: Bustos Matias A , Gottlieb Josh , Choe Jane , Suyeon Ryu , Lin Selena Y , Allen Warren M , Krasne David L , Wilson Timothy G , Hoon Dave S B , Linehan Jennifer A 
Published: October 2023

Abstract

Background
The incidence of patients diagnosed with renal cell carcinoma (RCC) is increasing. There are no approved biofluid biomarkers for routine diagnosis of RCC patients. This retrospective study aims to identify cell-free microRNA (cfmiR) signatures in urine samples that can be utilized as biomarkers for early diagnosis of sporadic RCC patients.

Methods
Tissue, plasma, and urine samples (n = 221) from 56 sporadic RCC patients and respective normal healthy donors were profiled for 2083 microRNAs (miRs) using the next-generation sequencing-based HTG EdgeSeq miR Whole Transcriptome Assay. DESeq2 (FC |1.2|, false discovery rate &lt;0.05) was performed to identify differentially expressed miRs. Data from RCC tissue samples of The Cancer Genome Atlas database were used for miR validation.

Results
We found a 10-miR signature that distinguished RCC tissues from remote normal kidney tissue or benign kidney lesion samples. Additionally, we identified subtype-specific miRs (miR-122-5p, miR-210-3p, and miR-21-3p) and miRs specific for all RCC subtypes (miR-106b-3p, miR-629-5p, and miR-885-5p). We observed that miR-155-5p was associated with tumor size. Using The Cancer Genome Atlas data sets, we validated the miRs found in RCC tissue samples. In plasma or urine analysis, we found cfmiRs that were consistently and significantly upregulated in RCC tissue samples. A 15-cfmiR signature was proposed in urine samples of RCC patients, of which miR-1275 was consistently upregulated in tissue, plasma, and urine samples.

Conclusions
This integrative study found diagnostic miRs/cfmiRs for RCC patients, which were validated using The Cancer Genome Atlas data sets. Distinctive cfmiR signatures found in urine may have clinical utility for the diagnosis of RCC.
Extraintestinal Manifestations of Inflammatory Bowel Disease Are Associated With Increased Biologic Cycling
Authors: Alizadeh Madeline , Ali Osman , Cross Raymond K 
Published: October 2023

Abstract

Background
Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are a common, frequently debilitating complication of the disease. Biologics are indicated and often required in patients with EIMs to control disease; however, little is known about whether patients with EIMs cycle through more therapies than their counterparts without EIMs.

Methods
To address this question, we performed a retrospective analysis of patients enrolled in the Study of Prospective Adult Research Cohort with IBD registry seen at our University Medical Center, on data from December 2016 to January 2021. Four hundred fifty-six participants with information on EIMs and biologic use available were included, and demographic and clinical characteristics were analyzed.

Results
Three hundred thirty-eight and 118 participants without and with EIMs were identified, respectively. Those with EIMs were likelier to have biologic exposure, and cycle through more biologics, both in univariate and multivariate analyses controlling for age, disease duration, sex, corticosteroid use, and IBD type (P-value = .006). In a subanalysis of patients with Crohn’s disease (CD), EIMs were associated with increased biologic cycling in ileocolonic disease (P-value = .050).

Conclusions
To our knowledge, this is the first study assessing biologic cycling in patients with EIMs. Our findings that patients with EIMs are likelier to cycle through biologics, particularly CD patients with ileocolonic disease, highlights the need for more research on which biologics may be most effective for specific subsets of IBD patients, including those with concurrent EIMs. The presence of EIMs is a marker of harder-to-treat IBD and may indicate earlier initiation of advanced therapies.
Gender, Security, and Atomic Destruction in Louisa Hall’s Trinity
Authors: Kollin Susan 
Published: October 2023

Abstract
Louisa Hall’s Trinity examines environmental risk and responsibility, restoring to memory the networks of power and security that shaped the life of J. Robert Oppenheimer, the so-called “father of the atomic age.” Extending work in feminist theories of exposure, Indigenous critiques of nuclear colonization, and studies of environmental agency and accountability, I trace the author’s use of fictional biography as a means of investigating disavowal, detachment, and the drive for mastery. Focusing on systems of silence and security underwriting the development of the bomb, Hall addresses everyday experiences of gender, race, and sexuality as meaningful in the world of atomic science and as useful tools for grappling with the uncertainties and vulnerabilities of environmental risk in the atomic age.
Hypertension-mediated organ damage involving multiple sites is an independent risk factor for cardiovascular events
Authors: Lembo Maria , Pacella Daniela , Manzi Maria Virginia , Morisco Carmine , La Mura Lucia , Mancusi Costantino , Bardi Luca , Trimarco Valentina , Trimarco Bruno , Izzo Raffaele , Esposito Giovanni 
Published: October 2023

Abstract

Aims
Chronic pressure overload determines functional and structural alterations, leading to hypertension-mediated organ damage (HMOD), affecting multiple districts. We aim at evaluating the prognostic impact of the absence vs. presence of HMOD in one or more sites and of blood pressure (BP) and metabolic control in hypertensive patients.

Methods and results
The study included 7237 hypertensive patients from the Campania Salute Network Registry, followed up for 5.3 ± 4.5 years. As HMOD, we analysed the presence of left ventricular hypertrophy, carotid plaques, and chronic kidney disease (CKD-EPI ≥3 stage) and evaluated the impact of zero vs. one vs. two vs. three sites of HMOD on the occurrence of major adverse cardiovascular events (MACEs). Blood pressure control and Metabolic Score for Insulin Resistance (METS-IR) were also considered. Optimal BP control was achieved in 57.3% patients. Major adverse cardiovascular events occurred in 351 (4.8%) patients. The MACE rate in patients without HMOD was 2.7%, whereas it was 4.7, 7.9, and 9.8% in patients with one, two, and three sites with HMOD, respectively. By using Cox multivariate models, adjusted for age, BP control, mean heart rate, mean METS-IR, number of HMOD sites, and drugs, MACE was found to be significantly associated with ageing, mean METS-IR, anti-platelet therapy, and multiple sites with HMOD, whereas a negative association was found with renin–angiotensin system inhibitor drugs.

Conclusion
In hypertensive patients, the risk of MACE increases with the incremental number of districts involved by HMOD, independent of BP control and despite the significant impact of metabolic dysregulation. Hypertension-mediated organ damage involving multiple sites is the deleterious consequence of hypertension and dysmetabolism but, when established, it represents an independent cardiovascular risk factor for MACE occurrence.
Child Penalties in Politics
Authors: Fiva Jon H , King Max-Emil M 
Published: October 2023

Abstract
Women tend to experience a substantial decline in their labour income after their first child is born, while men do not. Do such ‘child penalties’ also exist in the political arena? Using comprehensive administrative data from Norway, we find that women are less likely than men to secure elected office after their first child is born. The effects already manifest from the nomination stage, where mothers receive less favourable rankings on party lists relative to comparable fathers. This paper broadens our understanding of a fundamental social issue in political representation and demonstrates how motherhood even affects positively selected women.
Validation of Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons in the EPIC-Norfolk prospective population cohort
Authors: van Trier Tinka J , Snaterse Marjolein , Boekholdt S Matthijs , Scholte op Reimer Wilma J M , Hageman Steven H J , Visseren Frank L J , Dorresteijn Jannick A N , Peters Ron J G , Jørstad Harald T 
Published: October 2023

Abstract

Aims
The European Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models are recommended to identify individuals at high 10-year risk for cardiovascular disease (CVD). Independent validation and assessment of clinical utility is needed. This study aims to assess discrimination, calibration, and clinical utility of low-risk SCORE2 and SCORE2-OP.

Methods and results
Validation in individuals aged 40–69 years (SCORE2) and 70–79 years (SCORE2-OP) without baseline CVD or diabetes from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population study. We compared 10-year CVD risk estimates with observed outcomes (cardiovascular mortality, non-fatal myocardial infarction, and stroke). For SCORE2, 19 560 individuals (57% women) had 10-year CVD risk estimates of 3.7% [95% confidence interval (CI) 3.6–3.7] vs. observed 3.8% (95% CI 3.6–4.1) [observed (O)/expected (E) ratio 1.0 (95% CI 1.0–1.1)]. The area under the curve (AUC) was 0.75 (95% CI 0.74–0.77), with underestimation of risk in men [O/E 1.4 (95% CI 1.3–1.6)] and overestimation in women [O/E 0.7 (95% CI 0.6–0.8)]. Decision curve analysis (DCA) showed clinical benefit. Systematic Coronary Risk Evaluation 2-Older Persons in 3113 individuals (58% women) predicted 10-year CVD events in 10.2% (95% CI 10.1–10.3) vs. observed 15.3% (95% CI 14.0–16.5) [O/E ratio 1.6 (95% CI 1.5–1.7)]. The AUC was 0.63 (95% CI 0.60–0.65) with underestimation of risk across sex and risk ranges. Decision curve analysis showed limited clinical benefit.

Conclusion
In a UK population cohort, the SCORE2 low-risk model showed fair discrimination and calibration, with clinical benefit for preventive treatment initiation decisions. In contrast, in individuals aged 70–79 years, SCORE2-OP demonstrated poor discrimination, underestimated risk in both sexes, and limited clinical utility.
Length of hospital stay for elective electrophysiological procedures: a survey from the European Heart Rhythm Association
Authors: Boriani Giuseppe , Imberti Jacopo F , Leyva Francisco , Casado-Arroyo Ruben , Chun Julian , Braunschweig Frieder , Zylla Maura M , Duncker David , Farkowski Michał M , Pürerfellner Helmut , Merino José L 
Published: October 2023

Abstract

Aims
Electrophysiological (EP) operations that have traditionally involved long hospital lengths of stay (LOS) are now being undertaken as day case procedures. The coronavirus disease-19 pandemic served as an impetus for many centres to shorten LOS for EP procedures. This survey explores LOS for elective EP procedures in the modern era.

Methods and results
An online survey consisting of 27 multiple-choice questions was completed by 245 respondents from 35 countries. With respect to de novo cardiac implantable electronic device (CIED) implantations, day case procedures were reported for 79.5% of implantable loop recorders, 13.3% of pacemakers (PMs), 10.4% of implantable cardioverter defibrillators (ICDs), and 10.2% of cardiac resynchronization therapy (CRT) devices. With respect to CIED generator replacements, day case procedures were reported for 61.7% of PMs, 49.2% of ICDs, and 48.2% of CRT devices. With regard to ablations, day case procedures were reported for 5.7% of atrial fibrillation (AF) ablations, 10.7% of left-sided ablations, and 17.5% of right-sided ablations. A LOS ≥ 2 days for CIED implantation was reported for 47.7% of PM, 54.5% of ICDs, and 56.9% of CRT devices and for 54.5% of AF ablations, 42.2% of right-sided ablations, and 46.1% of left-sided ablations. Reimbursement (43–56%) and bed availability (20–47%) were reported to have no consistent impact on the organization of elective procedures.

Conclusion
There is a wide variation in the LOS for elective EP procedures. The LOS for some procedures appears disproportionate to their complexity. Neither reimbursement nor bed availability consistently influenced LOS.
Chromosome structure and DNA replication dynamics during the life cycle of the predatory bacterium Bdellovibrio bacteriovorus
Authors: Pląskowska Karolina , Zakrzewska-Czerwińska Jolanta 
Published: October 2023

Abstract
Bdellovibrio bacteriovorus, an obligate predatory Gram-negative bacterium that proliferates inside and kills other Gram-negative bacteria, was discovered more than 60 years ago. However, we have only recently begun to understand the detailed cell biology of this proficient bacterial killer. Bdellovibrio bacteriovorus exhibits a peculiar life cycle and bimodal proliferation, and thus represents an attractive model for studying novel aspects of bacterial cell biology. The life cycle of B. bacteriovorus consists of two phases: a free-living nonreplicative attack phase and an intracellular reproductive phase. During the reproductive phase, B. bacteriovorus grows as an elongated cell and undergoes binary or nonbinary fission, depending on the prey size. In this review, we discuss: (1) how the chromosome structure of B. bacteriovorus is remodeled during its life cycle; (2) how its chromosome replication dynamics depends on the proliferation mode; (3) how the initiation of chromosome replication is controlled during the life cycle, and (4) how chromosome replication is spatiotemporally coordinated with the proliferation program.
Genomic Insights into Mollusk Terrestrialization: Parallel and Convergent Gene Family Expansions as Key Facilitators in Out-of-the-Sea Transitions
Authors: Aristide Leandro , Fernández Rosa 
Published: October 2023

Abstract
Animals abandoned their marine niche and successfully adapted to life on land multiple times throughout evolution, providing a rare opportunity to study the mechanisms driving large scale macroevolutionary convergence. However, the genomic factors underlying this process remain largely unknown. Here, we investigate the macroevolutionary dynamics of gene repertoire evolution during repeated transitions out of the sea in mollusks, a lineage that has transitioned to freshwater and terrestrial environments multiple independent times. Through phylogenomics and phylogenetic comparative methods, we examine ∼100 genomic data sets encompassing all major molluskan lineages. We introduce a conceptual framework for identifying and analyzing parallel and convergent evolution at the orthogroup level (groups of genes derived from a single ancestral gene in the species in question) and explore the extent of these mechanisms. Despite deep temporal divergences, we found that parallel expansions of ancient gene families played a major role in facilitating adaptation to nonmarine habitats, highlighting the relevance of the preexisting genomic toolkit in facilitating adaptation to new environments. The expanded functions primarily involve metabolic, osmoregulatory, and defense-related systems. We further found functionally convergent lineage-exclusive gene gains, while family contractions appear to be driven by neutral processes. Also, genomic innovations likely contributed to fuel independent habitat transitions. Overall, our study reveals that various mechanisms of gene repertoire evolution—parallelism, convergence, and innovation—can simultaneously contribute to major evolutionary transitions. Our results provide a genome-wide gene repertoire atlas of molluskan terrestrialization that paves the way toward further understanding the functional and evolutionary bases of this process.