bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Genome Sequencing Compared to a Gene Panel in Infants with a Suspected Genetic Disorder: An Economic Evaluation
Authors: Lavelle Tara A. , Maron Jill L. , Kingsmore Stephen F. , Lin Ching-Hsuan , Zhu Yingying , Sweigart Benjamin , Reed Dallas , Gelb Bruce D. , Vockley Jerry , Davis Jonathan M. 
Published: October 2024

AbstractIntroductionRapid genome sequencing (rGS) provides high diagnostic yield for critically ill infants with suspected genetic disorders, but it has high upfront costs and insufficient insurance coverage. Assessing the long-term costs of rGS is important for guiding coverage decisions. This study compares 1-year healthcare costs for: 1) early rGS (within 7 days of admission) for all infants, and 2) early targeted neonatal gene sequencing (NewbornDx) for all infants, followed by rGS after 7 days for undiagnosed infants.MethodsThe Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a multicenter, prospective study that enrolled 400 hospitalized infants under one year with suspected genetic disorders. All participants underwent both rGS and NewbornDx. Using study data, we developed and populated a decision tree to compare 1-year costs for early rGS versus early NewbornDx followed by later rGS if necessary.ResultsThe diagnostic yield and upfront testing costs were higher for rGS (49%; $12,297) than NewbornDx (27%; $2,449; p<0.05). Over 1 year, early rGS was estimated to save $158,592 per patient (95% CI: $63,701-$253,292) compared to early NewbornDx with later rGS if necessary.DiscussionEarly rGS results in substantial cost savings, highlighting the need to expand reimbursement to improve access.
Data quality and Big Data in the health industry: a scoping review protocol
Authors: Santos Lívia C. T , Bublitz Frederico M. 
Published: October 2024

ABSTRACTIntroductionBig Data is characterized by the large volume of data, the variety of types and formats, the speed with which they are generated, and the veracity and value that can be extracted from the data. However, the result obtained with this technology will depend on the quality of the information obtained from the data. Big Data has great potential in healthcare and can be used to advance diagnosis, treatment, and healthcare management. Health data is highly vulnerable due to its sensitive nature, as it contains personal and confidential information. If exposed or compromised, it could lead to privacy violations, inaccuracies, misuse, incorrect diagnoses, or misguided decision-making in patient care. It is important to prioritize confidentiality, adhere to regulatory compliance, and maintain data integrity; for that, it is essential to use efficient methods to obtain quality data and make them able to reach the proposed objective.ObjectiveIn this context, the scoping review protocol aims to identify and map existing strategies, methods, or models that improve the quality of medical and health data in Big Data environments. This review explores the methods to support the effective use of Big Data in healthcare while addressing the challenges to maintain data integrity and ensure safe decision-making.Methods and analysisThis scoping review will be conducted based on the six-step process outlined in the framework proposed by Levac et al. in “Scoping Studies: Advancing the methodology” and will be reported following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. The research team will use Data Quality, Big Data, and Health terms to search for primary studies in the Scopus Document Search, IEEE Xplore Digital Library, and ACM Digital Library databases.
Revealing Hidden Threats: Marine Invertebrate Invasions in the Banc d’Arguin National Park (PNBA), Mauritania, Explored Through DNA Barcoding
Authors: Moura Carlos J. , Sidina Ebaye , Serrão Ester 
Published: October 2024

AbstractThe Banc d’Arguin National Park (PNBA) in Mauritania, a globally significant biodiversity hotspot, faces growing threats from human activities and biological invasions. This study aimed to document marine invertebrate diversity in the PNBA and identify non-native and potentially invasive species. Samples were collected during expeditions in 2021 and 2022, using scuba-diving, drag dredging, and manual intertidal collection across depths of 0 to 20 meters. Through DNA barcoding of COI and 16S genes, 17 species from three phyla—Cnidaria, Bryozoa, and Arthropoda— were identified, with several cryptic taxa detected. Evidence of human-mediated introduction was found in hydroids (Bougainvillia, Pennaria, Obelia), bryozoans (Amathia, Bugula, Schizoporella), and barnacles (Amphibalanus), suggesting invasions from regions like Brazil, and the Indo-Pacific. Notably,Amathia brasiliensisandAmathia cf. vidoviciwere recorded for the first time in West Africa, alongside the detection of two otherAmathiaspecies, raising concerns about their potential impact on the PNBA’s biodiversity and ecosystem services. The presence of these exotic species, likely introduced via international maritime traffic and fishing activities, highlights the park’s vulnerability. The study underscores the utility of DNA barcoding for detecting cryptic diversity and tracking species dispersal, recommending urgent conservation measures and biosecurity protocols to protect the PNBA’s unique marine ecosystems.
Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates
Authors: Totty Michael S. , Juanes Rita Cervera , Bach Svitlana V. , Ameur Lamya Ben , Valentine Madeline R. , Simons Evan , Romac McKenna , Trinh Hoa , Henderson Krystal , Del Rosario Ishbel , Tippani Madhavi , Miller Ryan A. , Kleinman Joel E. , Page Stephanie Cerceo , Saunders Arpiar , Hyde Thomas M. , Martinowich Keri , Hicks Stephanie C. , Costa Vincent D. 
Published: October 2024

ABSTRACTThe amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular and anatomical features that are specialized in the amygdala of primates versus other vertebrates requires a systematic, anatomically-resolved molecular analysis of constituent cell populations. We analyzed five nuclear subdivisions of the primate amygdala with single-nucleus RNA sequencing in macaques, baboons, and humans to examine gene expression profiles for excitatory and inhibitory neurons and confirmed our results with single-molecule FISH analysis. We identified distinct subtypes ofFOXP2+interneurons in the intercalated cell masses and protein-kinase C-δ interneurons in the central nucleus. We also establish that glutamatergic, pyramidal-like neurons are transcriptionally specialized within the basal, lateral, or accessory basal nuclei. Understanding the molecular heterogeneity of anatomically-resolved amygdalar neuron types provides a cellular framework for improving existing models of how amygdalar neural circuits contribute to cognition and mental health in humans by using nonhuman primates as a translational bridge.
TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling
Authors: Kim Daein , Bhargava Ragini , Wang Shih-Chun , Lee Doohyung , Patel Riya , Oh Sungtaek , Bowman Ray W. , Na Chan Hyun , O’Sullivan Roderick J. , Miller Kyle M. 
Published: October 2024

AbstractAn inability to replicate the genome can cause replication stress and genome instability. Here, we develop BLOCK-ID, a proteomic method to identify and visualize proteins at stressed replication forks. This approach successfully identified novel mediators of the replication stress response, including the chromatin acetylation reader protein TRIM24. In validating TRIM24 function, we uncovered its crucial role in coordinating Alternative Lengthening of Telomeres (ALT), a cancer-specific telomere extension pathway involving replication stress. Our data reveal that TRIM24 is directed to telomeres via a p300/CBP-dependent acetylation chromatin signaling cascade, where it organizes ALT-associated PML bodies (APBs) to promote telomere DNA synthesis. Strikingly, we demonstrate that when artificially tethered at telomeres, TRIM24 can stimulate new telomere DNA synthesis in a SUMO-dependent manner, independently of p300/CBP or PML-dependent APBs. Thus, this study identifies a TRIM24 chromatin signaling pathway required for ALT telomere maintenance.
DNA-Dependent Protein Kinase Inhibitors PI-103 and Samotolisib Augment CRISPR/Cas9 Knockin Efficiency in Human T Cells
Authors: Džafo Emina , Hafezi Morteza , Giordano Attianese Greta Maria Paola , Reichenbach Patrick , Grillet Stephane , Scholten Kirsten , Coukos George , Irving Melita , Gentner Bernhard 
Published: October 2024

1.AbstractThe adoptive cell transfer ofex vivoexpanded tumor infiltrating lymphocytes (i.e., TIL therapy) is a promising clinical strategy and recently FDA approved for melanoma but has major limitations including that not all tumors are inflamed. Moreover, tumor-specific clones can be rare and in an exhausted state due to the suppressive tumor microenvironment. These obstacles can be overcome by engineering autologous peripheral blood T cells with pre-selected T cell receptors (TCRs) by viral vector-mediated gene insertion. While viral transduction is highly efficient, the insertional site is not specific and persistence of the T cells is oftentimes limited. In contrast, site-specific integration of the TCR into the TCR α chain (TRAC) locus by CRISPR/Cas9 has been shown to enable more consistent and physiological levels of exogenous TCR expression coupled with superior persistence and tumor control in preclinical studies. Here, we sought to improve the efficiency of CRISPR/Cas9 mediated TCR knockin (KI) into theTRAClocus of primary human T cells. In addition to the previously reported DNA-dependent protein kinase inhibitor M3814, we demonstrate that PI-103 and samotolisib markedly increase KI efficiency in a process that is GMP-compatible, while CC-115 had a variable effect. Importantly, PI-103 and samotolisib do not negatively impact cell viability, fold-expansion nor T cell phenotype and we conclude that they are suitable for the generation of gene-modified T cells for clinical use.
Analysis of RNA/DNA Hybrid Profiles in Blood From Autistic Patients Reveals Differences in mRNA and non-coding RNA Regions
Authors: Kianmehr Leila , MokhtarZadeh Kasra , Yilmaz Zeynep , Duman Ecmel Mehmetbeyoglu , Taheri Serpil , Rassoulzadegan Minoo 
Published: October 2024

AbstractDNA/RNA hybrids are present in normal cellular physiology, but when misregulated in the genome, they can contribute to human pathologies such as neurodevelopmental disorders and cancer. These hybrid structures are often abundant in repetitive genomic sequences such as telomeres and centromeres, contributing to evolutionary conserved phenomena. However, excessive accumulation can lead to DNA damage and genomic instability.Studies of autism spectrum disorders (ASDs) have revealed genome-wide disruptions, including mutations and significant deregulation of gene expression. Surprisingly, the common underlying factors remain unidentified. ASDs, which are of hereditary origin and more prevalent among boys, manifest themselves during development through disorders of various origins.In this study, we used whole-genome transcriptomic analysis of DNA/RNA hybrids from blood samples of autistic patients and healthy controls. we identified differences between numerous hybrid genomic regions with varying sequence compositions. Additionally, we observed local specificity in genomic regions, where RNA could either inhibit or enhance transcription. Our analysis of short RNAs hybridized with DNA revealed a striking example of transcriptional activity, where each gene is stably transcribed. We propose that non-coding RNAs originating from exons, introns or intergenic regions bind to DNA as hybrids (DNA/RNA) and influence gene expression. The specific levels of these short RNAs may regulate their own transcription, likely affecting cell fate.
Context-dependent epigenome rewiring during neuronal differentiation
Authors: Manelli Vera , Diwakar Jeisimhan , Beşkardeş Sude , Alonso-Gil Dácil , Forné Ignasi , Chong Faye , Imhof Axel , Bonev Boyan 
Published: October 2024

AbstractTranscription factors (TFs) are pivotal in orchestrating lineage decisions and their binding is often accompanied by chromatin remodeling. However, a comprehensive understanding of how cellular and epigenetic contexts influence TF binding and the subsequent activation of lineage-specific programs remains lacking. Here, we dissected the molecular mechanisms underlying the binding of one such TF – Neurog2 and its functional consequences in two cell-types: mouse embryonic stem cells and neural progenitor cells. Our findings reveal that cell-type-specific chromatin accessibility and motif syntax are key determinants for TF binding. While Neurog2 binding primarily leads to chromatin opening, DNA demethylation and increased chromatin interactions, we also uncovered strong indirect, cell-type-specific effects, which ultimately result in vastly different epigenetic landscape. Furthermore, we identify shared and cell-type-specific Neurog2 interactors, including the SWI/SNF and NuRD complexes. Our study shed light on how cellular environment can modulate TF function to establish lineage identity during development.
Elevated Ubiquitin Phosphorylation by PINK1 Contributes to Proteasomal Impairment and Promotes Neurodegeneration
Authors: Chen Cong , Gao Tong-Yao , Yi Hua-Wei , Zhang Yi , Wang Tong , Lou Zhi-Lin , Wei Tao-Feng , Lu Yun-Bi , Li Ting-Ting , Tang Chun , Zhang Wei-Ping 
Published: October 2024

AbstractUbiquitin (Ub), a key player of protein turnover, can be phosphorylated by PINK1 kinase to generate S65-phosphorylated ubiquitin (pUb). Elevated pUb levels have been observed in aged human brains and human brains with Parkinson’s disease. However, how pUb is involved in neurodegeneration remains elusive. Here we show that elevation of pUb is pervasive in a multitude of neurodegenerative conditions, including Alzheimer’s disease, aging, and ischemic injury. In cultured cells, proteasomal inhibition by MG132 leads to sPINK1 accumulation, the cytosolic fragment of PINK1, thus promoting Ub phosphorylation. Elevated pUb impairs proteasomal degradation by disrupting covalent ubiquitin chain elongation and noncovalent proteasome-substrate interaction. Conversely,pink1knockout mitigates protein aggregation in both aging and ischemic mouse brains, as well as cells treated with MG132. Using AAV2/9 vector to specifically express sPINK1 in mouse hippocampus neurons, we observed cumulative pUb elevation, accompanied by protein aggregation, proteostasis disturbance, neuronal injury, neuroinflammation, and cognitive impairment. These sPINK1-induced impairments were reversed by co-expressing Ub/S65A phospho-null Ub mutant but exacerbated by Ub/S65E phospho-mimic mutant. As such, pUb elevation can result from declined proteasomal activity in neurodegenerative conditions, while a constant elevation of pUb actively drives neurodegeneration by further inhibiting proteasomal degradation. Our study reveals a new pathogenic pathway of neurodegeneration, highlighting the pUb-mediated feedforward loop as a promising therapeutic target for pharmaceutical intervention.
Heterogeneity and Metabolic Diversity amongEnterococcusSpecies during Long-term Colonization
Authors: Karlsson Philip A. , Zhang Taoran , Järhult Josef D. , Joffré Enrique , Wang Helen 
Published: October 2024

ABSTRACTUrinary tract infections (UTIs), traditionally dominated by Gram-negative pathogens, are increasingly complicated by antimicrobial-resistantEnterococcusspp. in hospital settings. This study screened urine samples from 210 ICU patients at Uppsala University Hospital (June 2020 - September 2021), identifying 39 unique PhenePlate™-RF types acrossE. faecium,E. faecalis, andE. durans.E. faeciumisolates showed considerable genetic diversity, primarily within clonal complex 17 (CC17), known for its virulence and antibiotic resistance. We identified multiple lineages and sequence types (STs), such as in patient HWP143, who had isolates from both ST80 and ST22 (an ancestral CC17 lineage). Notably, metabolic adaptations, such as increased L-arabinose metabolism, and shifts in antibiotic resistance were observed. Variations and similarities in plasmid content between individual linages suggest horizontal gene transfer.E. faecalisisolates exhibited less genetic diversity but significant metabolic variability across patients and mixed infections, as seen in patient HWP051, colonized by both ST16 (CC58) and ST287.E. durans, though less common, shared important metabolic traits withE. faeciumand displayed polyclonal characteristics, highlighting its potential role in UTIs and the complexity of enterococcal infections.E. duranswas sometimes misidentified, underscoring the need for accurate identification methods. This research underscores the importance of understanding genetic and metabolic diversity, plasmid variations, and horizontal gene transfer inEnterococcusspp., which influence antibiotic resistance, virulence, and ultimately, treatment outcomes.IMPORTANCE STATEMENTOur study uncovers novel insights into the genetic and metabolic diversity ofEnterococcusspecies within individual patients, focusing onE. faecium,E. faecalis, andE. durans. Unlike prior studies, which often focused on single lineages, we reveal multiple clones and lineages across individual patients, including clones from clonal complex 17 and the emerging sequence type (ST) 192, highlighting notable metabolic adaptations and shifts in antibiotic resistance. The detection of mixed colonization with varied ST-types, andE. duransmisidentification by MALDI-TOF, later corrected by sequencing, further emphasizes the challenges inEnterococcusspecies identification. For the first time, we demonstrate likely horizontal gene transfer amongE. faecium,E. faecalis, andE. duranswithin the same patient, underscoring the dynamic nature of these infections. Our findings have significant implications for understanding the complexity ofEnterococcusinfections, stressing the need to consider genetic and metabolic diversity to improve disease management and treatment outcomes.
Shh signaling directs dorsal ventral patterning in the regeneratingX. tropicalisspinal cord
Authors: Angell Swearer Avery , Perkowski Samuel , Wills Andrea 
Published: October 2024

AbstractTissue development and regeneration rely on the deployment of embryonic signals to drive progenitor activity and thus generate complex cell diversity and organization. One such signal is Sonic Hedgehog (Shh), which establishes the dorsal-ventral (D/V) axis of the spinal cord during embryogenesis. However, the existence of this D/V axis and its dependence on Shh signaling during regeneration varies by species. Here we investigate the function of Shh signaling in patterning the D/V axis during spinal cord regeneration inXenopus tropicalistadpoles. We find that neural progenitor markers Msx1/2, Nkx6.1, and Nkx2.2 are confined to dorsal, intermediate and ventral spatial domains, respectively, in both the uninjured and regenerating spinal cord. These domains are altered by perturbation of Shh signaling. Additionally, we find that these D/V domains are more sensitive to Shh perturbation during regeneration than uninjured tissue. The renewed sensitivity of these neural progenitor cells to Shh signals represents a regeneration specific response and raises questions about how responsiveness to developmental patterning cues is regulated in mature and regenerating tissues.
Investigating the determinants of consumer confidence and online impulse buying intentions: an experimental study
Authors: Jamil Raja Ahmed , Qayyum Abdul , Ahmad Zia , Shah Adnan Muhammad 
Published: October 2024

PurposeThis study examines the effects of risk reduction, seller reputation, eWOM and warranties on consumer confidence and online impulse buying intentions through the lens of the stimulus-organism-response (SOR) model. It also explores the role of installment options in online impulse buying.Design/methodology/approachWe performed a between-subjects experiment (installment vs. no-installment option). Data were collected from 199 consumers and analyzed using SmartPLS 3.3.9.FindingsThe results show that risk reduction, eWOM and warranty positively affect consumer confidence (CC) in online shopping and that CC positively predicts online impulse buying intentions. It was also found that the effect of CC on online impulse buying intentions was stronger when consumers were offered an installment option than a no-installment option.Practical implicationsFindings suggest that online sellers should invest more resources in building consumer confidence, which affects online impulse buying intentions. Moreover, online sellers should offer installment options to consumers, thereby reaping stronger effects of consumer confidence on online impulse buying intentions.Originality/valueEmploying the experimental approach, this study makes a novel attempt to examine the role of the installment option in fostering online impulse buying intentions among Pakistani consumers. Likewise, this is one of the early studies to explore the effects of risk reduction, seller reputation, eWOM and warranties on CC among Pakistani consumers using the SOR model.
The socio-spatial dynamics of coliving: examining fractality, visual integration and copresence in a large-scale purpose-built shared living building
Authors: Alyedreessy Emad 
Published: October 2024

Purpose“Coliving” is a rapidly developing cohousing typology, characterised by high-density private micro-units integrated with shared, mixed-use amenity spaces. This research examines the interrelationship between spatial configuration, space typologies and the frequency and intensity of copresence within a large coliving building-also known as large-scale purpose-built shared living (LSPBSL).Design/methodology/approachUsing a UK-based case study, quantitative methods drawn from space syntax theory-namely, visibility graph analysis (VGA) and systematically structured ethnographic observations-were adopted to measure visual integration (HH) and copresence.FindingsA positive correlation (rs = 0.43, p = 0.07) and no statistically significant difference in distribution (V = 76, p = 0.70) was identified between macro- and micro-level visual integration (HH), indicating that “fractality” exists in the building. Positive correlations were also identified between visual (HH) and spatial (1/RRA) integration (rs = 0.62, p < 0.01); visual integration and copresence frequency (rs = 0.55, p = 0.12); copresence frequency and intensity (rs = 0.63, p < 0.01) and copresence intensity (CI) and frequencies of large group interactions.Originality/valueNo existing research examines the relationship between spatial configurations and the frequencies, intensities and patterns of copresence within coliving buildings. Thus, this article contributes to spatial theory by (1) identifying correlations between these variables within an uncharted spatial context, and (2) introducing a novel syntactic concept – “fractality” – alongside a method for its calculation. By identifying the space typologies and spatial configurations that facilitate the greatest opportunities for social encounter, this study also contributes towards our knowledge of shared living environments.