bluuebunny/crossref_metadata_2025_split huggingface dataset:
Institutional escapes, breaks, and continuities: Reframing running away from residential child care institutions
Authors: Bartoszko Aleksandra , Herland Mari D 
Published: November 2024

Abstract
This article offers a novel approach to understand the phenomenon of running away from residential care institutions, challenging prevailing views that pathologize these incidents as individual deviance. Drawing on insights from the sociology of escape and Deleuze and Guattari’s concepts of rhizome and lines of escape, we examine spatial, temporal, and relational dimensions of institutions, revealing the porous nature of institutional boundaries and non-linear characteristics of runaways. By reframing runaways as integral to institutional life rather than isolated events, we argue against reducing them to individual traits. Running away serves as pivotal moments that disrupt and shape institutional norms, highlighting inherent limitations in care. Conceptualizing running away as running-around within the institutional assemblage, we challenge binary inside/outside distinctions and argue that they oversimplify institutional complexity. Our analysis underscores how institutions exert totalizing control through surveillance, while being transformed through acts of running away. Examining the employees’ experiences though five focus group interviews, we critique the conventional perception of institutions as places of care, emphasizing their unbounded and multifaceted social configurations. We discuss how institutional powers shape semiotic systems that govern young people’s behaviour, advocating for a nuanced understanding of residential institutions as rhizomatic formations, where individual actions continually reshape institutional practices and perceptions.
Bivalent RSVpreF Vaccine in Adults 18 to &lt;60 Years Old With High-Risk Conditions
Authors: Davis Matthew , Towner William , DeHaan Elliot , Jiang Qin , Li Wen , Rahman Farah , Patton Michael , Wyper Hayley , Lino Maria Maddalena , Sarwar Uzma N , Majid-Mahomed Zaynah , Mehta Saumil , Howitt William , Cannon Kevin , Kalinina Elena , Cooper David , Swanson Kena A , Anderson Annaliesa S , Gurtman Alejandra , Munjal Iona ,   MONeT Study Team, Almeida Natalia Castillo , Cannon Kevin , Towner William , Davis Joseph , Malkin Elissa , Diemert David , Clark James , Boghara Haresh , Cohen Jonathan , Bailey Mary , Doust Matthew , Carter Michael , Smith William , Onoya Maria , Mehta Saumil , DeAtkine David , Stacey Helen , Howland William , Suplicy Felipe , Dever Michael , Davis Matthew , Mishkin David , Neutel Joel , Hulinsky Ilja , Chaudhry Abid , Juarez Erick , Mauri Monica , Rosen Jeffrey , Howitt William , Klein Terry , Taylor David , Denham Douglas 
Published: November 2024

Abstract

Background
Older individuals and adults with certain chronic or immunocompromising health conditions are at increased risk of severe respiratory syncytial virus (RSV) disease.

Methods
In this phase 3 randomized trial of RSVpreF safety and immunogenicity in 18–59-year-olds at high risk of severe RSV disease, participants were randomized 2:1 to 1 RSVpreF (120 µg) or placebo dose. Primary safety endpoints included reactogenicity events and adverse events (AEs) through 7 days and 1 month after vaccination, respectively, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) throughout the study. In primary analyses, immunogenicity elicited 1 month after RSVpreF was bridged to a randomly selected subset of ≥60-year-olds receiving RSVpreF from the immunogenicity subset in the pivotal phase 3 RENOIR trial, which demonstrated RSVpreF efficacy. Noninferiority was declared if 95% confidence interval (CI) lower bounds were &gt;.667 (neutralizing titer adjusted geometric mean ratios) and &gt;−10% (seroresponse rate differences) for RSV-A and RSV-B.

Results
Overall, 678 participants received RSVpreF (n = 453) or placebo (n = 225). Most reactogenicity events were mild/moderate; severe events occurred in ≤2.0% of participants overall. AE frequencies were similar in RSVpreF (7.1%) and placebo recipients (7.6%). No vaccine-related SAEs or NDCMCs were reported. One month after RSVpreF administration, noninferiority criteria were met in 18–59-year-olds versus ≥60-year-olds for RSV-A and RSV-B neutralizing titers and seroresponse rates.

Conclusions
RSVpreF was well tolerated with no safety concerns and demonstrated immunobridging to efficacy in 18–59-year-olds at high risk of severe RSV disease versus ≥60-year-olds in whom efficacy was previously demonstrated, supporting use of RSVpreF to prevent RSV-associated disease in this population. NCT05842967.
Use of artificial intelligence to predict outcomes in mild aortic valve stenosis
Authors: Julakanti Raghav R , Padang Ratnasari , Scott Christopher G , Dahl Jordi , Al-Shakarchi Nader J , Metzger Coby , Lanyado Alon , Jackson John I , Nkomo Vuyisile T , Pellikka Patricia A 
Published: November 2024

Abstract

Aims
Aortic stenosis (AS) is a common and progressive disease, which, if left untreated, results in increased morbidity and mortality. Monitoring and follow-up care can be challenging due to significant variability in disease progression. This study aimed to develop machine learning models to predict the risks of disease progression and mortality in patients with mild AS.

Methods and results
A comprehensive database including 9611 patients with serial transthoracic echocardiograms was collected from a single institution across three clinical sites. The data set included parameters from echocardiograms, electrocardiograms, laboratory values, and diagnosis codes. Data from a single clinical site were preserved as an independent test group. Machine learning models were trained to identify progression to severe stenosis and all-cause mortality and tested in their performance for endpoints at 2 and 5 years. In the independent test group, the AS progression model differentiated those with progression to severe AS within 2 and 5 years with an area under the curve (AUC) of 0.86 for both. The feature of greatest importance was aortic valve mean gradient, followed by other valve haemodynamic measurements including valve area and dimensionless index. The mortality model identified those with mortality within 2 and 5 years with an AUC of 0.84 and 0.87, respectively. Smaller reduced-input validation models had similarly robust findings.

Conclusion
Machine learning models can be used in patients with mild AS to identify those at high risk of disease progression and mortality. Implementation of such models may facilitate real-time, patient-specific follow-up recommendations.
Impact of family mutual aid system for personal medical insurance accounts on paediatric patients’ outpatient utilization patterns and costs: a difference-in-differences analysis
Authors: Liu Xinyi , Gao Chunhui , Wei Mingyue , Li Guohong , Fan Xianqun 
Published: November 2024

Abstract
This study explores the effect of the transformation of paediatric healthcare through the implementation of the Family Mutual Aid System (FMAS) for personal medical insurance accounts among paediatric patients at a children’s hospital (Hospital A in Shanghai, China). We conducted a cohort study in the endocrinology department of Hospital A from August 2021 to July 2023 to assess the impact of FMAS enrolment on patients’ annual outpatient visits, annual outpatient expenditures, and the allocation of these costs among the basic medical insurance pooling fund and patients’ out-of-pocket expenses, with a further subdivision into online and offline consultations. Analysis employed a weighted difference-in-differences approach within a fixed-effects model following propensity score matching. The study encompassed 10 975 paediatric patients, divided into those enrolled in FMAS (observation group) and those not (control group). Enrolment in FMAS was associated with a statistically significant increase in annual outpatient visits by an average of 1.107, predominantly attributed to an uptick in offline consultations. Additionally, there was a substantial 38.9% rise in annual outpatient costs. Detailed analysis revealed a 52.5% increase in costs covered by the medical insurance pooling fund, while patients’ out-of-pocket expenses decreased by an average of 69.2%. These findings highlight the beneficial effects of FMAS enrolment on healthcare service utilization and the risk-sharing mechanisms of medical insurance.
One Health bottom-up analysis of the dissemination pathways concerning critical priority carbapenemase- and ESBL-producing Enterobacterales from storks and beyond
Authors: Martínez-Álvarez Sandra , Höfle Ursula , Châtre Pierre , Alonso Carla Andrea , Asencio-Egea María Ángeles , François Pauline , Cardona-Cabrera Teresa , Zarazaga Myriam , Madec Jean-Yves , Haenni Marisa , Torres Carmen 
Published: November 2024

Abstract

Background
‘One Health’ initiatives to tackle the rising risk of antimicrobial resistance (AMR) have flourished due to increasing detection of Enterobacterales producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases (CPs).

Objectives
This study aimed to conduct an in-depth holistic analysis of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) isolates recovered from landfill-foraging white stork faecal samples and clinical isolates from a nearby hospital.

Methods
Faecal samples (n = 211) were collected from storks foraging at two landfills in Spain. Ec/Kp stork isolates were recovered on selective media and whole-genome sequencing (WGS), together with isolates obtained from the nearby hospital. These genomic data were compared with public genomes from different contexts (clinical, environmental, or animal hubs) to understand global transmission dynamics.

Results
A wide range of blaESBL/blapAmpC (blaCTX-M/blaSHV-12/blaDHA) were detected in 71 stork samples (33.6%), while blaCP (blaKPC/blaNDM/blaOXA-48/blaVIM) were identified in 28 (13.3%) samples. Clonal and plasmid transmissions were evidenced inside and between both landfills. Mapping against 10 624 public Ec/Kp genomes and from those of nearby hospital revealed that identical strains (&lt;10 allelic differences with Ec-ST38/ST131 and Kp-ST512 lineages) and epidemic plasmids (full identity/coverage with IncN/blaKPC-2, IncF/blaKPC-3, IncX3/blaNDM-7, IncL/blaOXA-48) were found from clinical isolates in countries located along the storks’ migration routes.

Conclusions
Storks may be contaminated by bacterial isolates from a likely human origin and become non-human reservoirs of critical genes, which can be dispersed over long distances. Identifying strains/plasmids along the stork’s routes that are identical or closely related to those described here opens new perspectives for large-scale research to understand the AMR transmission dynamics.
In vitro monitoring of drug resistance emergence during stepwise induction of bedaquiline and clofazimine, alone and in combination: a phenotypic and genotypic analysis
Authors: Chen Suting , Shang Yuanyuan , Zheng Jifang , Huo Fengmin , Xue Yi , Zhao Liping , Jiang Guanglu , Chu Naihui , Huang Hairong 
Published: November 2024

Abstract

Objectives
The co-resistance between bedaquiline and clofazimine raises significant concerns, as they are commonly co-administered as core drugs in drug-resistant TB regimens. The present study aimed to monitor drug resistance-associated gene mutations and the phenotypic change in Mycobacterium tuberculosis (Mtb) under a stepwise drug resistance induction in vitro using bedaquiline, clofazimine or combined drugs.

Methods
Drug-resistant Mtb strains were gradually induced in vitro on a drug-containing solid medium with a 2-fold increasing concentration of bedaquiline, clofazimine and their combination. The MIC of the induced drug-resistant Mtb strains was determined. The drug resistance-associated genes, including Rv0678, Rv1979c, atpE and pepQ, were sequenced and analysed.

Results
Unlike exposure to bedaquiline alone or the combination of these two drugs, clofazimine alone resulted in drug resistance gene mutations occurring later, specifically in the fourth round of induction as opposed to the second round of induction. Besides, nucleotide deletion or insertion in Rv0678 was the main mutation type for induction under the two-drug combination, while single-nucleotide polymorphisms (SNPs) in Rv0678 were the major mutation types when induced by bedaquiline or clofazimine alone. Rv0678 mutation happened at a relatively lower bedaquiline concentration exposure alone, while atpE mutation occurred at a higher bedaquiline concentration. Regardless of the drug exposure manner, a strong correlation between bedaquiline MICs and clofazimine MICs was observed in all drug resistance strains.

Conclusions
Combined exposure to bedaquiline and clofazimine developed Rv0678 mutation as early as exposure to bedaquiline alone. However, rather than SNPs, deletion and insertion were the dominant mutation types in dual-drug exposure strain.
SV4GD: a comprehensive structural variation database specially for genetic diseases
Authors: Shi Lei , Zhang Sainan , Li Ying , Li Hailong , Wang Xin , Du Meiyu , Zhang Meiyi , Ke Liyan , Zhang Yueni , Xu Chao , Tan Senwei , Zhang Zitong , Zhang Duoyi , Wang Jiaping , Qi Changlu , Liu Xingwang , Wang Xin , Qian Kai , Cheng Liang , Zhang Xue 
Published: November 2024

Abstract
Structural variations (SVs) contribute to a large extent to genomic diversity and are highly relevant for various human genetic diseases. The sensitivity and specificity of SV identification have significantly improved with the development and widespread application of high-throughput sequencing, making clinical diagnosis and treatment more accurate. Therefore, the SV4GD (Structural Variation for Genetic Diseases, https://bio-computing.hrbmu.edu.cn/SV4GD/), a manually curated database, was constructed to provide a comprehensive, standardized and user-friendly data resource for selective batch browsing, searching, downloading and comparing those genetic disease-relevant SVs. This database compiles 10 305 records of germline structural variants from 58 human neoplastic diseases and 232 non-neoplastic genetic diseases, including 2695 disease-related SVs, and other 7610 pending research SVs detected from patients. SV4GD provides a browser and search engine to query for the detailed information of SVs, human genetic diseases and the clinical information of patients, providing an easy-to-use online tool for clinical and molecular genetics research.
Rfam 15: RNA families database in 2025
Authors: Ontiveros-Palacios Nancy , Cooke Emma , Nawrocki Eric P , Triebel Sandra , Marz Manja , Rivas Elena , Griffiths-Jones Sam , Petrov Anton I , Bateman Alex , Sweeney Blake 
Published: November 2024

Abstract
The Rfam database, a widely used repository of non-coding RNA families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26 106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes. Sixty-five RNA families were enhanced using experimentally determined 3D structures, improving the accuracy of consensus secondary structures and annotations. R-scape covariation analysis was used to refine structural predictions in 26 families. Gene Ontology (GO) and Sequence Ontology annotations were comprehensively updated, increasing GO term coverage to 75% of families. The release adds 14 new Hepatitis C Virus RNA families and completes microRNA family synchronization with miRBase, resulting in 1603 microRNA families. New data types, including FULL alignments, have been implemented. Integration with APICURON for improved curator attribution and multiple website enhancements further improve user experience. These updates significantly expand Rfam’s coverage and improve annotation quality, reinforcing its critical role in RNA research, genome annotation and the development of machine learning models. Rfam is freely available at https://rfam.org.
CRISPRoffT: comprehensive database of CRISPR/Cas off-targets
Authors: Wang Grant , Liu Xiaona , Wang Aoqi , Wen Jianguo , Kim Pora , Song Qianqian , Liu Xiaona , Zhou Xiaobo 
Published: November 2024

Abstract
The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) programmable nuclease system continues to evolve, with in vivo therapeutic gene editing increasingly applied in clinical settings. However, off-target effects remain a significant challenge, hindering its broader clinical application. To enhance the development of gene-editing therapies and the accuracy of prediction algorithms, we developed CRISPRoffT (https://ccsm.uth.edu/CRISPRoffT/). Users can access a comprehensive repository of off-target regions predicted and validated by a diverse range of technologies across various cell lines, Cas enzyme variants, engineered sgRNAs (single guide RNAs) and CRISPR editing systems. CRISPRoffT integrates results of off-target analysis from 74 studies, encompassing 29 experimental prediction techniques, 368 guide sequences, 226 164 potential guide and off-target pairs and 8840 validated off-targets. CRISPRoffT features off-target data from different CRISPR approaches (knockout, base editing and prime editing) applied under diverse experimental conditions, including 85 different Cas/guide RNA (gRNA) combinations used across 34 different human and mouse cell lines. CRISPRoffT provides results of comparative analyses for individual guide sequences, genes, cell types, techniques and Cas/gRNA combinations under different conditions. CRISPRoffT is a unique resource providing valuable insights that facilitate the safety-driven design of CRISPR-based therapeutics, inform experimental design, advance the development of computational off-target prediction algorithms and guide RNA design algorithms.
iDog: a multi-omics resource for canids study
Authors: Liu Yanhu , Wang Yibo , Sun Jiani , Kong Demian , Zhou Bowen , Ding Mengting , Meng Yuyan , Duan Guangya , Cui Ying , Fan Zhuojing , Zhang Ya-Ping , Zhao Wenming , Tang Bixia 
Published: November 2024

Abstract
iDog (https://ngdc.cncb.ac.cn/idog/) is a comprehensive public resource for domestic dogs (Canis lupus familiaris) and wild canids, designed to integrate multi-omics data and provide data services for the worldwide canine research community. Notably, iDog 2.0 features a 15-fold increase in genomic samples, including 29.55 million single nucleotide polymorphisms (SNPs) and 16.54 million insertions/deletions (InDels) from 1929 modern samples and 29.09 million SNPs from 111 ancient Canis samples. Additionally, 43487 breed-specific SNPs and 530 disease/trait-associated variants have been identified and integrated. The platform also includes data from 141 BioProjects involving gene expression analyses and a single-cell transcriptome module containing data from 105 057 Beagle hippocampus cells. iDog 2.0 also includes an epignome module that evaluates DNA methylation patterns across 547 samples and chromatin accessibility across 87 samples for the analysis of gene expression regulation. Additionally, it provies phenotypic data for 897 dog diseases, 3207 genotype-to-phenotype (G2P) pairs, and 349 dog disease-associated genes, along with two newly constructed ontologies for breed and disease standardization. Finally, 13 new analytical tools have been added. Given these enhancements, the updated iDog 2.0 is an invaluable resource for the global cannie research community.
NCBI RefSeq: reference sequence standards through 25 years of curation and annotation
Authors: Goldfarb Tamara , Kodali Vamsi K , Pujar Shashikant , Brover Vyacheslav , Robbertse Barbara , Farrell Catherine M , Oh Dong-Ha , Astashyn Alexander , Ermolaeva Olga , Haddad Diana , Hlavina Wratko , Hoffman Jinna , Jackson John D , Joardar Vinita S , Kristensen David , Masterson Patrick , McGarvey Kelly M , McVeigh Richard , Mozes Eyal , Murphy Michael R , Schafer Susan S , Souvorov Alexander , Spurrier Brett , Strope Pooja K , Sun Hanzhen , Vatsan Anjana R , Wallin Craig , Webb David , Brister J Rodney , Hatcher Eneida , Kimchi Avi , Klimke William , Marchler-Bauer Aron , Pruitt Kim D , Thibaud-Nissen Françoise , Murphy Terence D 
Published: November 2024

Abstract
Reference sequences and annotations serve as the foundation for many lines of research today, from organism and sequence identification to providing a core description of the genes, transcripts and proteins found in an organism's genome. Interpretation of data including transcriptomics, proteomics, sequence variation and comparative analyses based on reference gene annotations informs our understanding of gene function and possible disease mechanisms, leading to new biomedical discoveries. The Reference Sequence (RefSeq) resource created at the National Center for Biotechnology Information (NCBI) leverages both automatic processes and expert curation to create a robust set of reference sequences of genomic, transcript and protein data spanning the tree of life. RefSeq continues to refine its annotation and quality control processes and utilize better quality genomes resulting from advances in sequencing technologies as well as RNA-Seq data to produce high-quality annotated genomes, ortholog predictions across more organisms and other products that are easily accessible through multiple NCBI resources. This report summarizes the current status of the eukaryotic, prokaryotic and viral RefSeq resources, with a focus on eukaryotic annotation, the increase in taxonomic representation and the effect it will have on comparative genomics. The RefSeq resource is publicly accessible at https://www.ncbi.nlm.nih.gov/refseq.
CAZac: an activity descriptor for carbohydrate-active enzymes
Authors: Lombard Vincent , Henrissat Bernard , Garron Marie-Line 
Published: November 2024

Abstract
The Carbohydrate-Active enZYme database (CAZy; www.cazy.org) has been providing the reference classification of carbohydrate-active enzymes (CAZymes) for &gt;30 years. Based on literature survey, the sequence-based families of CAZymes are enriched with functional data by using the International Union of Biochemistry and Molecular Biology Enzyme Commission (EC) number system. However, this system was not developed to search or compare functional information. To better harness functional information, we have developed CAZac (CAZyme activity descriptor), a multicriterion system that describes CAZymes’ mechanisms, glycosidic bond orientations, subsites and inter-residue connectivities. This new system, implemented for glycoside hydrolases, glycoside phosphorylases, transglycosidases, polysaccharide lyases and lytic polysaccharide monooxygenases allows complex searches in the CAZy database to uncover the evolution of substrate specificity and mechanisms of CAZymes across families.
EPCO-06. DIFFUSE MIDLINE GLIOMAS: FROM CELL CYCLE TO THERAPEUTIC OPPORTUNITIES
Authors: Hains Anastasia , Marques Joana , Chetal Kashish , Junior Carlos Biagi , Gonzalez-Sandoval Adriana , Pillai Renjitha , Gatto Alberto , Sadreyev Ruslan , Filbin Mariella , Van Rechem Capucine 
Published: November 2024

Abstract
The fatal Diffuse Midline Gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling of differentiation. As replication timing influences gene expression, cell fate, and cellular response to therapeutics, we undertook a multi-omics approach (Repli-seq, cell cycle RNA-seq, single cell RNA-seq) in DMG cells (H3.1K27M and H3.3K27M subgroups) and tumors in comparison to normal brain to gain an appreciation for targetable pathways in DMG. DMG cells presented differential replication timing in each subgroup, which, in turn, correlated with significant differential gene expression including the cholesterol biosynthesis pathway. Consistent with these findings, DMG tumors presented high replication stress and cholesterol biosynthesis pathway signatures. Moreover, DMG cells were specifically vulnerable to an inhibitor of the cholesterol pathway and to a replication stress therapy, singly and in combination. In conclusion, this combinatorial genomics approach revealed insights into therapeutic opportunities for this incurable disease.