bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct gut microbiota profiles may characterize amyloid beta pathology and mild cognitive impairment
Authors: Rouskas Konstantinos , Mamalaki Eirini , Ntanasi Eva , Pantoura Marianna , Anezaki Maria , Emmanouil Christina , Novau-Ferré Nil , Bulló Mònica , Dimas Antigone S , Papandreou Christopher , Yannakoulia Mary , Argiriou Anagnostis , Scarmeas Nikolaos 
Published: May 2024

AbstractGut microbiome composition has been associated with early preclinical Alzheimer’s disease (AD), as reflected by cerebrospinal fluid (CSF) amyloid beta pathology, and with mild cognitive impairment (MCI). However, the presence of distinct microbiota across different disease stages has not been fully characterized. We profiled gut microbiota in 50 nondemented individuals by 16S ribosomal RNA sequencing and taxonomic profiles were compared between amyloid-based (amyloid-normal vs. amyloid-pathology) and clinically- based (cognitively normal vs. MCI) diagnosis groups using linear models (adjusted for sex, age and diet). Elastic net regression model was used to assess the discriminative performance of microbiota for amyloid-pathology and MCI. Microbial diversity measures did not differ across groups. We identified specific genera associated with amyloid-pathology and MCI such asOxalobacter, MarvinbryantiaandEscherichia-Shigella, mostly linked to inflammation. Distinct genera were found to be unique to amyloid-pathology and MCI. Microbiota was shown to have a fairly good discriminative performance. Overall, we suggest the presence of distinct microbiota in early preclinical stage of AD and MCI, which needs to be further explored.
The role of artificial intelligence in the application of the integrated electronic health records and patient-generated health data
Authors: Ye Jiancheng , Hai Jiarui , Song Jiacheng , Wang Zidan 
Published: May 2024

ABSTRACTObjectiveThis scoping review aims to identify and understand the role of artificial intelligence in the application of integrated electronic health records (EHRs) and patient-generated health data (PGHD) in health care, including clinical decision support, health care quality, and patient safety. We focused on the integrated data that combined PGHD and EHR data, and we investigated the role of artificial intelligence (AI) in the application in health care.MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search articles in six databases: PubMed, Embase, Web of Science, Scopus, ACM Digital Library, and IEEE Computer Society Digital Library. In addition, we synthesized seminal sources, including other systematic reviews, reports, and white papers, to inform the context, history, and development of this interdisciplinary research field.ResultsFifty-six publications met the review criteria after screening. The EHR-integrated PGHD introduces benefits to health care, including empowering patients and families to engage via shared decision-making, improving the patient-provider relationship, and reducing the time and cost of clinical visits. AI’s roles include cleaning and management of heterogeneous datasets, assisting in identifying dynamic patterns to improve clinical care processes, and providing more sophisticated algorithms to better predict outcomes and propose precise recommendations based on the integrated data. Challenges mainly stem from the large volume of integrated data, data standards, data exchange and interoperability, security and privacy, interpretation, and meaningful use.ConclusionThe use of PGHD in health care is at a promising stage but needs further work for widespread adoption and seamless integration into health care systems. AI-driven, EHR-integrated PGHD systems can greatly improve clinicians’ abilities to diagnose patients’ health issues, classify risks at the patient level by drawing on the power of integrated data, and provide much-needed support to clinics and hospitals. With EHR-integrated PGHD, AI can help transform health care by improving diagnosis, treatment, and the delivery of clinical care, thus improving clinical decision support, health care quality, and patient safety.
Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation
Authors: Wang Shaobo , Li Wanyu , Wang Lingling , Tiwari Shashi Kant , Bray William , Wu Lujing , Li Na , Hui Hui , Clark Alex E. , Zhang Qiong , Zhang Lingzhi , Carlin Aaron F. , Rana Tariq M. 
Published: May 2024

AbstractViral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show that the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation of key proteins in multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits of the host oligosaccharyltransferase (OST) complex and blocks its interaction with the spike protein, which results in misfolding and retention of spike protein in the endoplasmic reticulum likely due to decreasedN-glycan transfer, and reduces the assembly and release of infectious virions. Consistent with these observations, pharmacological inhibition of the OST complex with NGI-1 potently inhibits glycosylation of other viral proteins, including MERS-CoV spike protein, HIV-1 gp160, and IAV hemagglutinin, and prevents the production of infectious virions. Our results identify a novel strategy by which ISGs restrict virus infection and provide a rationale for targeting glycosylation as a broad antiviral therapeutic strategy.HighlightsThe interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo.ER-localized GBP5 restricts N-linked glycosylation of SARS-CoV-2 spike protein, leading to protein misfolding and preventing transport to the Golgi apparatus.GBP5 binds to OST complex accessory proteins and potentially blocks access of the catalytic subunit to the spike protein.GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2Pharmacological inhibition of OST blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV.SignificanceViral infection induces production of type I interferons and expression of interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. We found that the interferon-stimulated gene GBP5 is induced by SARS-CoV-2 infection in vitro and in vivo. GBP5 inhibits N-glycosylation of key proteins in multiple viruses, including SARS-CoV-2. Importantly, pharmacological inhibition of Oligosaccharyltransferase (OST) Complex blocks host cell infection by SARS-CoV-2, variants of concern, HIV-1, and IAV, indicating future translational application of our findings.
Downstream metabolites of (+)-cis-12-oxo-phytodienoic acid function as noncanonical bioactive jasmonates inArabidopsis thaliana
Authors: Saito Rina , Nishizato Yuho , Kitajima Tsumugi , Nakayama Misuzu , Takaoka Yousuke , Kato Nobuki , Ueda Minoru 
Published: May 2024

Abstract(+)-cis-12-oxo-phytodienoic acid (cis-OPDA) is a biosynthetic precursor of the plant hormone (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile). It functions as an endogenous chemical signal independent of the JA-Ile receptor COI1-JAZ inArabidopsis thaliana. The bioactive form ofcis-OPDA that induces COI1-JAZ-independent gene expression remains unknown.In this study, we hypothesized that the genuine bioactive forms ofcis-OPDA are the downstream metabolites, which upregulate the expression of the OPDA marker genes such asZAT10/ERF5in a JA-Ile-independent manner. These downstream metabolites function independently of the JA-Ile-COI1-JAZ-MYCs canonical jasmonate signaling module, and its electrophilic nature is essential for its bioactivity.
Quantification ofLegionella pneumophilain building potable water systems: a meta-analysis comparing qPCR and culture-based detection methods
Authors: Sylvestre Émile , Rhoads William J. , Julian Timothy R. , Hammes Frederik 
Published: May 2024

AbstractQuantitative polymerase chain reaction (qPCR) offers a rapid, automated, and potentially on-site method for quantifyingL. pneumophilain building potable water systems, complementing and potentially replacing traditional culture-based techniques. However, the application of qPCR in assessing human health risks is complicated by its tendency to overestimate such risks due to the detection of genomic copies that do not correspond to viable, infectious bacteria. This study examines the relationship betweenL. pneumophilameasurements obtained via qPCR and culture-based methods, aiming to understand and establish qPCR-to-culture concentration ratios needed to inform associated health risks. We developed a Poisson lognormal ratio model and a random-effects meta-analysis to analyze variations in qPCR-to-culture ratios within and across sites. Our findings indicate these ratios typically vary from 1:1 to 100:1, with ratios close to 1:1 predicted at all sites. Consequently, adopting a default 1:1 conversion factor appears necessary as a cautious approach to convert qPCR concentrations to culturable concentrations for use in models of associated health risks, for example, through quantitative microbial risk assessment (QMRA) frameworks. Where this approach may be too conservative, targeted sampling and the applications of viability-qPCR could improve the accuracy of qPCR-based QMRA. Standardizing qPCR and culture-based methods and reporting site-specific environmental factors that affect the culturability ofL. pneumophilawould improve the understanding of the relationship between the two methods. The ratio model introduced here shifts us beyond simple correlation analyses, facilitating investigations of temporal and spatial heterogeneities in the relationship. This analysis is a step forward in the integration of QMRA and molecular biology, as the framework demonstrated here forL. pneumphilais applicable to other pathogens monitored in the environment.
“I didn’t come into nursing to be attacked and constantly abused”: A qualitative study of exposure to violence for nurses across ethnic groups in the United Kingdom
Authors: Chui Zoe , Caton Emma , Naqvi Habib , Baker Edward , Onwumere Juliana , Lee Geraldine A , Hatch Stephani L 
Published: May 2024

AbstractBackgroundWorkplace violence is a serious threat to staff safety and leads to mental and physical health problems that have negative consequences for the recruitment and retention of nurses, amid the worst staffing crisis in the history of the National Health Service (NHS) in the United Kingdom.ObjectivesThis study aims to explore the social context of violence for hospital-based and community nurses from different ethnic groups, the types of violence experienced or witnessed both in and outside the workplace, and the impact of violence on mental and physical health.MethodsSemi-structured interviews were conducted online with 12 hospital-based and community nurses recruited across London. Interview data were analysed using reflexive thematic analysis.ResultsThe sample comprised seven hospital nurses and five community nurses. Four themes were identified from the analysis: i) the social context in which nurses from different ethnic groups are exposed to community violence; ii) the types of workplace violence experienced or witnessed by hospital-based and community nurses from different ethnic groups; iii) nurses’ perceptions of the factors contributing to workplace violence iv) how violence impacts mental and physical health outcomes for hospital-based and community nurses from different ethnic groups. Based on the social ecological framework and the sociological theory of stress, we have used these findings to present a conceptual stress process model of violence exposure for nurses.ConclusionsHospital-based and community nurses from different ethnic groups are exposed to violence both in and outside the workplace which negatively affects their mental and physical health. Whilst interventions aimed at improving personal safety and security measures in hospitals are valuable, interventions to address the social and institutional factors that put nurses at risk of violence exposure are needed. Further research using wider criteria for violence to include witnessing and hearing about violent events are needed to advance our understanding of how nurses are affected by multiple sources and types of violence in both their work and personal lives.What is already knownWorkplace violence is widespread and can lead to mental and physical health problems for healthcare staff.Nurses are one of the occupational groups most vulnerable to workplace violence and are consistently in short supply.What this paper addsFindings informed the development of a conceptual stress process model of violence exposure for nurses.Nurses perceived their gender, age and ethnicity as contributing factors to workplace violence.Witnessing or experiencing violence both in and outside the workplace has serious negative consequences at the individual and organisational levels.
Potential Pathways of Spread of Highly Pathogenic Avian Influenza A/H5N1 Clade 2.3.4.4b Across Dairy Farms in the United States
Authors: Stone Haley , Jindal Mehak , Lim Samsung , Dawson Rebecca , Quigley Ashley , Scotch Matthew , MacIntyre C. Raina 
Published: May 2024

AbstractThe emergence of Highly Pathogenic Avian Influenza (HPAI) A/H5N1 clade 2.3.4.4b has led to an unprecedented intercontinental spread, affecting a broad spectrum of avian and mammalian species. Recent outbreaks in US dairy farms, underscore the urgent need to understand the transmission pathways. The study aimed to evaluate the modes of introduction and transmission to dairy farms, through geospatial and exposure analyses. Our findings favour a singular introduction over multiple independent introductions, with non-waterfowl species exhibiting the highest dairy farm exposure, which is a major shift from historical waterfowl spread. Moreover, bidirectional spread between cattle and poultry highlights the intricate nature of disease transmission within the agricultural ecosystem. Additional factors such as livestock trade, poultry litter feed and contaminated milking machinery likely contributed to the amplification of the outbreaks throughout the United States. As large-scale outbreaks persist in the United States, the likelihood of a human pandemic increases, making it imperative to enact and sustain heightened surveillance measures across all potentially impacted species.
TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress
Authors: Hwang Sseu-Pei , Liao Han , Barondeau Katherine , Han Xinyi , Herbert Cassandra , McConie Hunter , Shekar Amirtha , Pestov Dimitri , Limbach Patrick A , Chang Jeffrey T , Denicourt Catherine 
Published: May 2024

SUMMARYtRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and Nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA, as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing m22G solely at position 27 of tRNA-Tyr-GUA. Surprisingly, TRMT1L depletion also impaired the deposition of acp3U and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA levels, coinciding with a reduction in global translation rates and hypersensitivity to oxidative stress. Our results establish TRMT1L as the elusive methyltransferase catalyzing the m22G27 modification on tRNA Tyr, resolving a long-standing gap of knowledge and highlighting its potential role in a tRNA modification circuit crucial for translation regulation and stress response.
DGCR8haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects
Authors: Colomer-Boronat A , Knol LI , Peris G , Sanchez L , Peluso S , Tristan-Ramos P , Gazquez-Gutierrez A , Chin P , Gordon K , Barturen G , Hill RE , Garcia-Perez JL , Ivens A , Macias S , Heras SR 
Published: May 2024

AbstractThe 22q11.2 deletion syndrome (22qDS) is caused by a microdeletion in chromosome 22, includingDGCR8, an essential gene for miRNA production. The contribution of humanDGCR8hemizygosity to the disease is still unclear. In this study, we generated two human pluripotent cell models containing a single functionalDGCR8allele to elucidate its role on 22qDS.DGCR8+/-cells show increased apoptosis as well as self-renewal and differentiation defects in both the naïve and primed states. The expression of primate-specific miRNAs was largely affected, due to impaired miRNA processing and chromatin accessibility.DGCR8+/-cells also displayed a pronounced reduction in human endogenous retrovirus class H (HERVH) expression, a primate-specific retroelement essential for pluripotency maintenance. Importantly, the reintroduction of primate-specific miRNAs as well as the miR-371-3 cluster rescued the cellular and molecular phenotypes ofDGCR8+/-cells. Our results suggest thatDGCR8is haploinsufficient in humans and that miRNAs and transposable elements may have co-evolved in primates as part of an essential regulatory network to maintain stem cell identity.
Extracellular Vimentin is a Damage-Associated Molecular Pattern Protein Serving as an Agonist of TLR4 in Human Neutrophils
Authors: Suprewicz Łukasz , Fiedoruk Krzysztof , Skłodowski Karol , Zakrzewska Magdalena , Walewska Alicja , Deptuła Piotr , Lesiak Agata , Okła Sławomir , Galie Peter A. , Patteson Alison E. , Janmey Paul A. , Bucki Robert 
Published: May 2024

AbstractBackgroundVimentin is a type III intermediate filament protein, that plays an important role in cytoskeletal mechanics. It is now known that vimentin also plays important roles outside the cell. Recent studies show the controlled release of vimentin into the extracellular environment, where it functions as a signaling molecule. Such observations are expanding our current knowledge of vimentin as a structural cellular component towards additional roles as an active participant in cell signaling.MethodsOur study investigates the immunological roles of extracellular vimentin (eVim) and its citrullinated form (CitVim) as a damage-associated molecular pattern (DAMP) engaging the Toll-like receptor 4 (TLR4) of human neutrophils. We usedin vitroassays to study neutrophil migration through endothelial cell monolayers and activation markers such as NADPH oxidase subunit 2 (NOX2/gp91phox). The comparison of eVim with CitVim and its effect on human neutrophils was extended to the induction of extracellular traps (NETs) and phagocytosis of pathogens.ResultsBoth eVim and CitVim interact with and trigger TLR4, leading to increased neutrophil migration and adhesion. CitVim stimulated the enhanced migratory ability of neutrophils, activation of NF-κB, and induction of NET formation mainly mediated through reactive oxygen species (ROS)-dependent and TLR4-dependent pathways. In contrast, neutrophils exposed to non-citrullinated vimentin exhibited higher efficiency in favoring pathogen phagocytosis, such asEscherichia coliandCandida albicans, compared to CitVim.ConclusionsOur study identifies new functions of eVim in its native and modified forms as an extracellular matrix DAMP and highlights its importance in the modulation of immune system functions. The differential effects of eVim and CitVim on neutrophil functions highlight their potential as new molecular targets for therapeutic strategies aimed at differential regulation of neutrophil activity in different pathological conditions. This, in turn, opens new windows of therapeutic intervention in inflammatory and immunological diseases characterized by immune system dysfunction, in which eVim and CitVim play a key role.
A neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making
Authors: Clairis N. , Barakat A. , Brochard Jules , Xin Lijing , Sandi C. 
Published: May 2024

AbstractMotivation levels vary across individuals, yet the underlying mechanisms driving these differences remain elusive. The dorsomedial prefrontal cortex/dorsal anterior cingulate cortex (dmPFC/dACC) and the anterior insula (aIns) play crucial roles in effort-based decision-making. Here, we investigate the influence of lactate, a key metabolite involved in energy metabolism and signaling, on decisions involving both physical and mental effort, as well as its effects on neural activation. Using proton magnetic resonance spectroscopy and functional MRI in 63 participants, we find that higher lactate levels in the dmPFC/dACC are associated with reduced motivation for physical effort, a relationship mediated by neural activity within this region. Additionally, plasma and dmPFC/dACC lactate levels correlate, suggesting a systemic influence on brain metabolism. Supported by path analysis, our results highlight lactate’s role as a modulator of dmPFC/dACC activity, hinting at a neurometabolic mechanism that integrates both peripheral and central metabolic states with brain function in effort-based decision-making.
Tn-seq of theCandida glabratareference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin
Authors: Nickels Timothy J. , Gale Andrew P. , Harrington Abigail A. , Timp Winston , Cunningham Kyle W. 
Published: May 2024

ABSTRACTC. glabratais an opportunistic pathogen that can resist common antifungals and rapidly acquire multidrug resistance. A large amount of genetic variation exists between isolates, which complicates generalizations. Portable Tn-seq methods can efficiently provide genome-wide information on strain differences and genetic mechanisms. Using theHermestransposon, the CBS138 reference strain and a commonly studied derivative termed 2001 were subjected to Tn-seq in control conditions and after exposure to varying doses of the clinical antifungal micafungin. The approach revealed large differences between these strains, including a 131 kb tandem duplication and a variety of fitness differences. Additionally, both strains exhibited up to 1000-fold increased transposon accessibility in subtelomeric regions relative to the BG2 strain, indicative of open subtelomeric chromatin in these isolates and large epigenetic variation within the species. Unexpectedly, the Pdr1 transcription factor conferred resistance to micafungin through targets other thanCDR1. Other micafungin resistance pathways were also revealed including mannosyltransferase activity and biosynthesis of the lipid precursor sphingosine, the drugging of which by SDZ 90-215 or myriocin enhanced the potency of micafunginin vitro. These findings provide insights into complexity of theC. glabrataspecies as well as strategies for improving antifungal efficacy.SummaryCandida glabrata is an emerging pathogen with large genetic diversity and genome plasticity. The type strain CBS138 and a laboratory derivative were mutagenized with theHermestransposon and profiled using Tn-seq. Numerous genes that regulate innate and acquired resistance to an important clinical antifungal were uncovered, including a pleiotropic drug resistance gene (PDR1) and a duplication of part of one chromosome. Compounds that target PDR1 and other genes may augment the potency of existing antifungals.