bluuebunny/crossref_metadata_2025_split huggingface dataset:
General principles of communication among nurses in a long-term care unit: a best practice implementation project
Authors: Felizardo Helena , Cardoso Daniela , Nogueira Paula , Bastos Joana , Casimiro Daniela , Nogueira Pedro , Cardoso Ana Filipa , Apóstolo João , Vrbová Tereza , Klugar Miloslav , Klugarová Jitka 
Published: November 2024

ABSTRACT

Introduction:
In health care, effective communication enhances teamwork and safety by minimizing adverse events. Evidence suggests that ongoing education should include communication skills training, as interprofessional communication relies on tools that facilitate seamless interaction.

Objective:
This project aimed to improve communication practices among nurses in a long-term care unit by promoting evidence-based recommendations.

Methods:
This project followed the seven phases proposed by the JBI Evidence Implementation Framework. This framework is grounded in an audit, feedback, and re-audit process, along with a structured approach to addressing barriers to compliance with best practices. JBI's Practical Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP) approach were also used.

Results:
A baseline audit was conducted focusing on three audit criteria. Compliance was measured by observing 250 handovers and administering a questionnaire to 14 nurses. After analyzing the results, the nursing team identified barriers and designed strategies to promote change, such as educational sessions and a focus group. The results of the follow-up audit showed significant improvements across all criteria. Nurses received training in communication for Criterion 1, which improved from 0% to 78%. For Criterion 2, training in teamwork and conflict management improved from 21% to 50%. For Criterion 3, the use of a structured communication tool (ISBAR) during handovers improved from 43.6% to 91%.

Conclusions:
The nursing team's involvement enabled effective change. Adapting ISBAR to a long-term care unit was an unexpected goal. The next objective is to refine and share it with similar units. Integrating communication training into health care institutions’ priorities is crucial, and future audits will ensure sustainability.

Spanish abstract:

http://links.lww.com/IJEBH/A295
The Impact of Health Information Technology on Patient Safety
Authors: Danso Gideon , Lasim Obed Owumbornyi 
Published: November 2024

ABSTRACTIntroductionSince the original Institute of Medicine (IOM) report was published there has been an accelerated development and adoption of health information technology with varying degrees of evidence about the impact of health information technology on patient safety. We conclude that health information technology improves patient’s safety by reducing medication errors, reducing adverse drug reactions, and improving compliance to practice guidelines. There should be no doubt that health information technology is an important tool for improving healthcare quality and safety.MethodA cross-sectional survey was conducted among some health care professionals at St. Gregory Catholic Hospital, Gomoa Buduburam. A self-administered questionnaire was used to elicit information on informed consent, confidentiality and medico legal issues. Data collected was analyzed using SPSS version 20.ResultsA total of 70 health care workers were enrolled on the study representing 70% response rate. The study revealed about 98% knows that Health Information Technology (HIT) is important in delivering care to patients; and 86% of the respondents indicated that HIT has reduced medical errors. About 82% of the responded that HIT has made health care delivery easier and faster and hence reducing awaiting time. About 90% of the responded that HIT has helped in transferring medical records of patient from one facility to the other in case of emergency.ConclusionImpact of Health Information Technology on patient safety and their perception are positive. However, regular training on the update and use of Health Information Technology will be necessary in order to ensure continuous improvement of the quality of health care delivery.
SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness
Authors: Zhou Yiyang , Ahearn Yani P. , Lokugamage Kumari G. , Alvarado R. Elias , Estes Leah K. , Meyers William M. , McLeland Alyssa M. , Morgan Angelica L. , Murray Jordan T. , Walker David H. , Johnson Bryan A. , Routh Andrew L. , Menachery Vineet D. 
Published: November 2024

AbstractCoronaviruses (CoVs) maintain large RNA genomes that frequently undergoes mutations and recombination, contributing to their evolution and emergence. In this study, we find that SARS-CoV-2 has greater RNA recombination frequency than other human CoVs. In addition, coronavirus RNA recombination primarily occurs at uridine (U)-enriched RNA sequences. Therefore, we next evaluated the role of SARS-CoV-2 NSP15, a viral endonuclease that targets uridines (EndoU), in RNA recombination and virus infection. Using a catalytically inactivated EndoU mutant (NSP15H234A), we observed attenuated viral replicationin vitroandin vivo. However, the loss of EndoU activity also dysregulated inflammation resulting in similar diseasein vivodespite reduced viral loads. Next-generation sequencing (NGS) demonstrated that loss of EndoU activity disrupts SARS-CoV-2 RNA recombination by reducing viral sub-genomic message but increasing recombination events that contribute to defective viral genomes (DVGs). Overall, the study demonstrates that NSP15 plays a critical role in regulating RNA recombination and SARS-CoV-2 pathogenesis.
Plasma glycome reflects low back pain progression and is not predictive of acute-to-chronic pain transition
Authors: Elgaeva Elizaveta E. , Trbojević-Akmačić Irena , Ugrina Ivo , Vilaj Marija , Slana Anita , Pribic Tea , Tsepilov Yakov A. , Karssen Lennart C. , Aulchenko Yurii S. , Dagostino Concetta , Allegri Massimo , Skelin Andrea , Primorac Dragan , Buyse Klaas , Van Zundert Jan , Lauc Gordan , Williams Frances M.K. , Freidin Maxim B. 
Published: November 2024

AbstractAimsTo investigate if the plasma N-glycome would provide a biomarker of acute-to-chronic low back pain (LBP) transition.Patients & MethodsA prospective longitudinal sample of n = 1,114 individuals enrolled at the first ever episode of LBP and followed-up for three months. Total plasma N-glycome was measured and compared at the baseline and follow-up.ResultsInitial pro-inflammatory patterns of plasma N-glycome change to normal levels between baseline and follow-up in those who resolved from LBP, but not in those who remained at pain after three months. Baseline levels of N-glycans were not predictive of the risk of chronic LBP at follow-up.ConclusionTotal plasma N-glycan levels may reflect ongoing inflammation that is aberrant and promotes ongoing pain and chronicity of symptoms.
Performance characteristics and potential public health impact of improved pre-erythrocytic malaria vaccines targeting childhood burden
Authors: Malinga Josephine , Braunack-Mayer Lydia , Masserey Thiery , Cavelan Aurélien , Chandramohan Daniel , Dicko Alassane , Ouédraogo Jean-Bosco , Kelly Sherrie L , Le Rutte Epke A , Nekkab Narimane , Penny Melissa A 
Published: November 2024

AbstractNew malaria vaccine development builds on groundbreaking recommendations and roll-out of two approved pre-erythrocytic vaccines (PEVs); RTS,S/AS01 and R21/MM. Whilst these vaccines are effective in reducing childhood malaria within yearly routine immunization programs or seasonal vaccination, there is little evidence on how different PEV efficacies, durations of protection, and spacing between doses influence the potential to avert uncomplicated and severe childhood malaria. Mainly, lacking understanding of the required vaccine properties and delivery strategies that lead to an effective childhood vaccine with multi-year protection. We used an individual-based model of malaria transmission informed by trial data to quantify trade-offs between PEV performance properties and impact across different endemicities, deployment schedules, and coverage levels.We found that deploying a vaccine with 90% initial efficacy, with a six to 12-month half-life duration of protection, co-administered with a blood-stage drug, followed by yearly boosters, results in 60-80% yearly incidence reduction, consistent with seasonal RTS,S and R21 trials. Halting vaccination after five years, leads to sustained protection of at least a 35% incidence reduction in children <six years in the 12 months following cessation in settings wherePfPR2-10<30%. Increasing the half-life duration to 12 -18 months or reaching more children provides the same health impact with lower vaccine efficacy. Without a booster (fourth dose), high efficacy (>90%) and longer half-life duration (>12 months) are required to sustain impact beyond primary vaccination, averting up to half the preceding year’s burden. The contribution of each property to the overall impact varies by setting and clinical endpoint, indicating that public health goals should dictate key vaccine performance criteria.Overall, our findings support the need for well-defined target product profiles for long duration vaccines linking priority use cases of where, how, and to whom to deploy new malaria vaccines, to maximize public health impact.
The mitotic CIP2A-TOPBP1 axis facilitates mitotic pathway choice between MiDAS and MMEJ
Authors: Martin Peter R , Nieminuszczy Jadwiga , Kozik Zuza , Jakub Nihal , Lecot Maxime , Vorhauser Julia , Lane Karen A , Kanellou Alexandra , Mansfeld Jörg , Pearl Laurence H , Oliver Antony W , Downs Jessica A , Choudhary Jyoti , Day Matthew , Niedzwiedz Wojciech 
Published: November 2024

AbstractMitotic DNA double-strand breaks (DSBs) accumulate in response to replication stress or BRCA1/2 deficiency posing a significant threat to genome stability as repair by non-homologous end-joining (NHEJ) and homologous recombination (HR) is inactivated in mitosis. Mitotic cells instead rely on the mechanisms of microhomology mediated end-joining (MMEJ) and mitotic DNA synthesis (MiDAS). However, how these pathways are regulated in mitosis remains unknown. Here we reveal the CIP2A-TOPBP1 complex facilitates recruitment of SMX complex components to mitotic chromatin marked by CIP2A, through a CDK1-dependent interaction between TOPBP1 BRCT 1/2 and SLX4 phospho-threonine1260, that drives MiDAS. Furthermore, CIP2A promotes the recruitment of Polθ to facilitate mitotic MMEJ. This defines a mechanistic framework for mitotic DSB repair, where simultaneous disruption of MiDAS and MMEJ pathways underpins the synthetic lethality observed in BRCA1/2-deficient cells following CIP2A depletion. These findings provide critical insights into mitotic DNA repair and highlights therapeutic opportunities in HR deficient tumours.
Synergistic effects of tRNA modification defects inEscherichia coliK12
Authors: Bacusmo Jo Marie , Babor Jill , Hu Jennifer , Cao Bo , Kellner Stefanie , Szkrybalo Sierra , Yuan Yifeng , Sander Serena , Kuipers Paul , deMott Michael , Mori Hirotada , Dedon Peter , de Crécy-Lagard Valérie 
Published: November 2024

AbstracttRNAs are the central adaptor molecule in translation and require a wide variety of post-transcriptional modifications to fulfill their functions. The model gram-negativeEscherichia coliK-12 is one of the handfuls of bacteria where all the tRNA modifications and corresponding genes have been characterized. This work dissects epistatic relationships between tRNA modification genes inE. coliby conducting a synthetic lethal screen revealing 5 pairs of modifications that cannot be deleted in combination when cells are grown in rich media, and 15 pairs of modifications that lead to growth defects when deleted in combination. ThetruAgene involved in the insertion of Psi residues at positions 38 to 40 in multiple tRNAs gave the highest number of synthetic lethality phenotypes that could be complemented by the expression of thetruAgenein transand in some cases suppressed by the overexpression of target tRNAs. A pilot phenotype screen of strains lacking two tRNA modifications genes viable in rich media lead to the identification of growth conditions that exhibited poor growth. This work lays the foundation to dissect the role of modifications in tRNA quality control.
Immune Evasion, Cell-Cell Fusion, and Spike Stability of the SARS-CoV-2 XEC Variant: Role of Glycosylation Mutations at the N-terminal Domain
Authors: Li Pei , Faraone Julia N. , Hsu Cheng Chih , Chamblee Michelle , Liu Yajie , Zheng Yi-Min , Xu Yan , Carlin Claire , Horowitz Jeffrey C. , Mallampalli Rama K. , Saif Linda J. , Oltz Eugene M. , Jones Daniel , Li Jianrong , Gumina Richard J. , Bednash Joseph S. , Xu Kai , Liu Shan-Lu 
Published: November 2024

SUMMARYSARS-CoV-2 continues to evolve, producing new variants that drive global COVID-19 surges. XEC, a recombinant of KS.1.1 and KP.3.3, contains T22N and F59S mutations in the spike protein’s N-terminal domain (NTD). The T22N mutation, similar to the DelS31 mutation in KP.3.1.1, introduces a potential N-linked glycosylation site in XEC. In this study, we examined the neutralizing antibody (nAb) response and mutation effects in sera from bivalent-vaccinated healthcare workers, BA.2.86/JN.1 wave-infected patients, and XBB.1.5 monovalent-vaccinated hamsters, assessing responses to XEC alongside D614G, JN.1, KP.3, and KP.3.1.1. XEC demonstrated significantly reduced neutralization titers across all cohorts, largely due to the F59S mutation. Notably, removal of glycosylation sites in XEC and KP.3.1.1 substantially restored nAb titers. Antigenic cartography analysis revealed XEC to be more antigenically distinct from its common ancestral BA.2.86/JN.1 compared to KP.3.1.1, with the F59S mutation as a determining factor. Similar to KP.3.1.1, XEC showed reduced cell-cell fusion relative to its parental KP.3, a change attributed to the T22N glycosylation. We also observed reduced S1 shedding for XEC and KP.3.1.1, which was reversed by ablation of T22N and DelS31 glycosylation mutations, respectively. Molecular modeling suggests that T22N and F59S mutations of XEC alters hydrophobic interactions with adjacent spike protein residues, impacting both conformational stability and neutralization. Overall, our findings underscore the pivotal role of NTD mutations in shaping SARS-CoV-2 spike biology and immune escape mechanisms.
MappingPlasmodiumtransitions and interactions in theAnophelesfemale
Authors: Yan Yan , Cheung Elaine , Verzier Lisa H. , Appetecchia Federico , March Sandra , Craven Ailsa R. , Du Esrah , Probst Alexandra S. , Rinvee Tasneem A. , de Vries Laura E. , Kauffman Jamie , Bhatia Sangeeta N. , Nelson Elisabeth , Singh Naresh , Peng Duo , Shaw W. Robert , Catteruccia Flaminia 
Published: November 2024

AbstractThe human malaria parasite,Plasmodium falciparum, relies onAnophelesmosquitoes for transmission. Once ingested during blood feeding, most parasites die in the mosquito midgut lumen or during epithelium traversal. How surviving ookinetes interact with midgut cells and form oocysts is unknown, yet these steps are essential to initiate a remarkable, similarly uncharacterized growth process culminating in the production of thousands of infectious sporozoites. Here, using single-cell RNA sequencing of both parasites and mosquito cells across four time points and two metabolic conditions, we unveil key processes shaping developmental transitions and mosquito-parasite interactions occurring in the midgut. In depth functional analyses reveal processes regulating oocyst growth and identify the transcription factorPfSIP2 as essential for sporozoite infection of human hepatocytes. By combining the analysis of shared mosquito-parasite barcodes with confocal microscopy, we discover that parasites preferentially interact with midgut progenitor cells during epithelial crossing, potentially using their basal location as an exit landmark. Additionally, we unveil tight connections between extracellular late oocysts and surrounding muscle cells that may ensure parasites adhere to the midgut without damaging it. Ultimately, our study provides fundamental insight into the molecular events characterizing previously inaccessible biological transitions and mosquito-parasite interactions, and identifies candidates for transmission-blocking strategies.
Dynamic metabolic modeling of ATP allocation during viral infection
Authors: Lu Alvin , Dukovski Ilija , Segrè Daniel 
Published: November 2024

SummaryViral pathogens, like SARS-CoV-2, hijack the host’s macromolecular production machinery, imposing an energetic burden that is distributed across cellular metabolism. To explore the dynamic metabolic tension between the host’s survival and viral replication, we developed a computational framework that uses genome-scale models to perform dynamic Flux Balance Analysis of human cell metabolism during virus infections. Relative to previous models, our framework addresses the physiology of viral infections of non-proliferating host cells through two new features. First, by incorporating the lipid content of SARS-CoV-2 biomass, we discovered activation of previously overlooked pathways giving rise to new predictions of possible drug targets. Furthermore, we introduce a dynamic model that simulates the partitioning of resources between the virus and the host cell, capturing the extent to which the competition depletes the human cells from essential ATP. By incorporating viral dynamics into our COMETS framework for spatio-temporal modeling of metabolism, we provide a mechanistic, dynamic and generalizable starting point for bridging systems biology modeling with viral pathogenesis. This framework could be extended to broadly incorporate phage dynamics in microbial systems and ecosystems.
Structural basis of the catalytic and allosteric mechanism of bacterial acetyltransferase PatZ
Authors: Park Jun Bae , Lee Gwanwoo , Han Yu-Yeon , Kim Dongwook , Heo Kyoo , Kim Jeesoo , Park Juhee , Yun Hyosuk , Lee Chul Won , Cho Hyun-Soo , Kim Jong-Seo , Steinegger Martin , Seok Yeong-Jae , Roh Soung-Hun 
Published: November 2024

ABSTRACTGCN5-relatedN-Acetyltransferases (GNATs) play a crucial role in regulating bacterial metabolism by acetylating specific target proteins. Despite their importance in bacterial physiology, the mechanisms underlying GNATs’ enzymatic and regulatory functions remain poorly understood. In this study, we elucidated the structures ofEscherichia coliPatZ, a type I GNAT, and investigated its ligand interactions, catalytic processes, and allosterism. PatZ functions as a homotetramer, with each subunit comprising a catalytic domain and a regulatory domain. Our findings reveal that the regulatory domain is essential for acetyltransferase activity, as it not only induces cooperative conformational changes in the catalytic domain but also directly contributes to the formation of substrate binding pockets. Furthermore, a protein structure-based analysis on the evolution of bacterial GNAT types reveals a distinct pattern of the regulatory domain across phyla, underscoring the regulatory domain’s critical role in responding to cellular energy status.SIGNIFICANCE STATEMENTPost-translational modifications, particularly acetylation mediated by GCN5-related N-Acetyltransferases (GNATs), play a crucial role in bacterial physiology. Protein acetyltransferase Z (PatZ) is a key GNAT with diverse substrates, essential for understanding the bacterial acetylome. This study employs cryogenic electron microscopy, X-ray crystallography, and biochemical analyses to elucidate the mechanistic regulation ofEscherichia coliPatZ. Our high-resolution structures reveal PatZ’s homo-tetrameric architecture, with each subunit comprising regulatory and GNAT domains. We characterize ligand-PatZ interactions, demonstrating ligand-induced conformational changes that facilitate allosteric regulation of the catalytic domain. Furthermore, our analyses elucidate the regulatory domain’s contribution to substrate binding pocket formation, potentially enhancing substrate specificity. Structure-based phylogenetic analysis provides insights into the evolution of diverse regulatory domains in the GNAT superfamily across bacterial taxonomy. This first visualization of PatZ advances our mechanistic understanding of bacterial physiology, offering novel insights into GNAT-mediated bacterial adaptations.HIGHLIGHTS-E. coliPatZ forms a homotetramer, with each subunit possessing a GNAT catalytic domain and a regulatory domain.- Cooperative binding of acetyl-CoA to the regulatory domains is a prerequisite for inducing the structural compatibility of the catalytic domain with a substrate.- Diverse regulatory domains in GNATs evolved to adapt to varied metabolic conditions across bacterial taxonomy.
Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation
Authors: Chen Wenqian , Yang Jie , Lander Gabriel C. 
Published: November 2024

AbstractThe human ClpXP complex (hClpXP) plays a central role in mitochondrial protein quality control by degrading misfolded or unneeded proteins. While bacterial ClpXP complexes have been extensively characterized, the molecular determinants underlying hClpXP assembly and regulation are not as well understood. We determined cryo-electron microscopy (cryo-EM) structures of hClpP in isolation and in complex with hClpX, revealing how hClpX binding promotes rearrangement of an asymmetric hClpP heptamer to assemble as a symmetric tetradecamer. Our hClpXP structure also highlights the stabilizing role of a previously uncharacterized eukaryotic ClpX sequence, referred to as the E-loop, and its importance in ATPase activity and hexamer assembly. We further show that peptide interaction with the hClpP proteolytic active site promotes the complex to adopt a proteolytically competent conformation. Together, these findings advance our understanding of the molecular mechanisms defining hClpXP activation and function.
Peripheral immune profiles in individuals at genetic risk for amyotrophic lateral sclerosis and Alzheimer’s disease
Authors: Deecke Laura , Ohlei Olena , Goldeck David , Homann Jan , Toepfer Sarah , Demuth Ilja , Bertram Lars , Pawelec Graham , Lill Christina M. 
Published: November 2024

AbstractThe immune system plays a crucial role in the pathogenesis of neurodegenerative diseases. Here, we explored whether blood immune cell profiles are already altered in healthy individuals with a genetic predisposition to amyotrophic lateral sclerosis (ALS) or Alzheimer’s disease (AD).Using multicolor flow cytometry, we analyzed 92 immune cell phenotypes in the blood of 448 healthy participants from the Berlin Aging Study II. We calculated polygenic risk scores (PGS) using genome-wide significant SNPs from recent large genome-wide association studies on ALS and AD. Linear regression analyses were then performed of the immune cell types on the PGS in both the overall sample and a subgroup of older participants (>60 years).While we did not find any significant associations between immune cell subtypes and ALS and AD PGS when controlling for the false discovery rate (FDR=0.05), we observed several nominally significant results (p<0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (p=0.006). Other immune cell subtypes associated with ALS risk included PD-1+ CD8+ and CD57+ CD4+ early-memory T cells, non-classical monocytes, and myeloid dendritic cells. For AD, naïve CD57+ CD8+ T cells, and mature NKG2A+ natural killer cells showed nominally significant associations.We did not observe immune cell changes in individuals with high genetic risk for ALS or AD, suggesting immune alterations may arise later in disease progression. Additional studies are required to validate our nominally significant findings.