bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complexity of the neutrophil transcriptome in early and severe rheumatoid arthritis. A role for microRNAs?
Authors: Alarcon Michele Fresneda , Abdullah Genna Ali , Beggs John Alexander , Kynoch Isobel , Sellin Andrew , Cross Andrew , Haldenby Sam , Antczak Philipp , Gutiérrez Eva Caamaño , Wright Helen Louise 
Published: December 2024

ABSTRACTNeutrophils are innate immune cells that drive the progression of rheumatoid arthritis (RA) through the release of reactive oxygen species (ROS), neutrophil extracellular traps (NETs) and proteases that damage host tissues. Neutrophil activation is regulated, in part, by dynamic changes in gene expression. In this study we have used RNAseq to measure the transcriptomes of neutrophils from people with severe, methotrexate-refractory RA and healthy controls. We identified a dynamic gene expression profile in people with severe RA. This is dominated by a type-I interferon-induced gene expression signature as well as activation of genes regulating neutrophil degranulation, NET production, response to ROS and oxidative stress. Whilst we did not detect significantly elevated levels of interferon-alpha in RA blood sera, we identified increased expression in RA neutrophils of miR-96- 5p and miR-183-5p which regulate activation of the interferon pathway as members of the miR-183C cluster. We also detected significantly elevated NET debris in RA blood sera (p<0.05). Using gene set variation analysis we explored the heterogeneity of neutrophil gene expression in RA and identified subsets of patients with gene expression profiles reflecting enhanced neutrophil degranulation and cytotoxicity, tissue inflammation or activation by interferons. Comparison with published single-cell RNAseq datasets identified RA transcriptomes where neutrophils were polarised by genes relating to early or late cell maturity, with significant genes in each polarised state being regulated by miR-146a- 5p, miR-155-5p, miR-183-5p or miR-96-5p. Overall our study demonstrates the heterogeneity of the RA neutrophil transcriptome and proposes miRNA-driven mechanisms for regulating the activated neutrophil phenotype in RA.
Closing Gaps in Evidence-Based Care for Acute Myocardial Infarction in northern Tanzania: Insights from a Prospective Study
Authors: Adisa Olanrewaju , Brown Erin E , Sakita Francis M , Temu Gloria , Rugakingira Anzibert , Lameck Godfrey , Shayo Frida M , Mmbaga Blandina T , Thielman Nathan M , Bloomfield Gerald S , Bettger Janet P , Hertz Julian T 
Published: December 2024

AbstractBackgroundThe burden of Acute Myocardial Infarction (AMI) is growing in sub-Saharan Africa. In Tanzania, uptake of diagnostic testing and evidence-based therapy for AMI is suboptimal. We aimed to describe current gaps in evidence-based AMI care in a Tanzanian emergency department (ED) and estimate the potential benefit of closing key performance gaps.MethodsAdults presenting with chest pain or dyspnea to the Kilimanjaro Christian Medical Centre (KCMC) ED were prospectively enrolled from February to September 2023 and their diagnostic tests and treatments were recorded. Thirty days following enrollment, a follow-up telephone survey was administered to assess mortality and medication use. Key performance metrics included the proportion of participants receiving both electrocardiography (ECG) and cardiac biomarker testing, as well as the proportion of participants with AMI receiving evidence-based therapies. To estimate the benefits of closing performance gaps, the the annualized number of participants not receiving each element evidence-based therapy was divided by published numbers needed to treat (NNTs) for each intervention. An exploratory analysis was conducted using performance metrics at KCMC and published national incidence data to estimate the potential benefits of closing performance gaps in AMI care at scale across Tanzania.ResultsOf 275 enrolled participants, 41 (14.9%) met criteria for AMI. Of participants, 91 (33.1%) received both ECG and cardiac biomarker testing. Of participants with AMI, 14 (34%) received aspirin, 11 (27%) received clopidogrel, and 2 (5%) received heparin. At 30-day follow-up, 25 (61%) participants with AMI were still alive, of whom 3 (12%) were taking dual antiplatelet therapy. Closing the diagnostic gap at KCMC could lead to the identification of an estimated 121 additional AMI cases annually. Aggregate estimated total benefit for closing gaps in uptake of aspirin, clopidogrel, heparin, and dual-antiplatelet therapy would result in approximately 6 deaths prevented and 33 serious cardiovascular events prevented at KCMC annually. Closing performance gaps at scale across Tanzania would result in approximately 69,206 additional AMI cases identified, 3,003 deaths prevented, and 11,405 serious cardiovascular events prevented annually.ConclusionsClosing diagnostic and treatment gaps in AMI care in northern Tanzania presents an opportunity to increase case identification, save lives, and prevent cardiovascular events and rehospitalizations.
COVID-19 Vaccine Acceptance and Hesitancy in Cameroon: A Systematic Review and Meta-analysis
Authors: Cheuyem Fabrice Zobel Lekeumo , Amani Adidja , Nkodo Iyawa Clarisse Alma , Boukeng Lionel Bethold Keubou , Edzamba Michel Franck , Nouko Ariane , Guissana Edwige Omona , Ngos Christelle Sandrine , Achangwa Chabeja , Mouangue Christian 
Published: December 2024

AbstractBackgroundThe development of effective vaccines was a promising tool for ending the pandemic. However, the success of a vaccination programme depends heavily on achieving significant community acceptance. In Cameroon, numerous studies have investigated the level of acceptance, hesitancy and perception of COVID-19 vaccines, with mixed results. To provide a comprehensive understanding of these parameters, this meta-analysis aimed to estimate the pooled proportion of COVID-19 vaccine acceptance, hesitancy and perception in Cameroon.MethodsA systematic search of online databases, including PubMed, Google Scholar, and ScienceDirect, was conducted to identify relevant research articles. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The extracted data were compiled in a Microsoft Excel spreadsheet and analyzed using R statistical software (version 4.3.3). The pooled proportion of COVID-19 vaccine acceptance, hesitancy, and perception was calculated using random effects meta-analysis. Funnel plots, Egger’s and Begg’s tests were used to assess publication bias.ResultsOf the 1243 records identified through the database search, 20 research articles were included in the systematic review and meta-analysis. The random-effects model showed that the that approximately 31.21% (95% CI: 23.49-38.94) of the Cameroonian population was willing to accept the COVID-19 vaccine. More than two-thirds of the population (68.49%; 95% CI: 60.65-76.34) were vaccine hesitant. Half of the participants (51.81%; 95% CI: 42.70-60.93), had a negative perception of the COVID-19 vaccine. The acceptance rate progressed from the first semester of 2021 (27.21%; 95% CI: 10.38-44.05) to the first semester of 2022 (45.56%; 95% CI: 25-66.12). The pooled vaccine acceptance rate was 29.29% (95% CI: 19.86-38.72) for the general population and 39.24% (95% CI: 22.84-55.64) for healthcare workers. The pooled vaccine hesitancy rate was 70.39% (95% CI: 61.30-79.80) for the general population and 57.42 % (95% CI: 4.05-71.80) for healthcare workersConclusionDespite progress in vaccine acceptance, targeted interventions are still needed to address vaccine hesitancy in the country. Strategies such as improving access to accurate information, building trust in institutions, and strengthening community engagement are crucial to increasing COVID-19 vaccine uptake.
Coral anthozoan-specific opsins employ a novel chloride counterion for spectral tuning
Authors: Sakai Yusuke , Sen Saumik , Sugihara Tomohiro , Kakeyama Yukiya , Iwasaki Makoto , Schertler Gebhard F.X. , Deupi Xavier , Koyanagi Mitsumasa , Terakita Akihisa 
Published: December 2024

AbstractAnimal opsins are G protein coupled receptors that have evolved to sense light by covalently binding a retinal chromophore via a protonated (positively charged) Schiff base. A negatively charged amino acid in the opsin, acting as a counterion, stabilises the proton on the Schiff base, which is essential for sensitivity to visible light. In this study, we investigate the spectroscopic properties of a unique class of opsins from a reef-building coral belonging to the anthozoan-specific opsin II group (ASO-II opsins), which intriguingly lack a counterion residue at any of established sites. Our findings reveal that, unlike other known animal opsins, the protonated state of the Schiff base in visible light-sensitive ASO-II opsins is highly dependent on exogenously supplied chloride ions (Cl−). By using structural modelling and QM/MM calculations to interpret spectroscopy data, we conclude that, in the dark state, ASO-II opsins employ environmental Cl−as their native counterion, while a nearby polar residue, Glu292 in its protonated neutral form, facilitates Cl−binding. In contrast, Glu292 plays a crucial role in maintaining the protonation state of the Schiff base in the light-activated protein, serving as the counterion in the photoproduct. Furthermore, Glu292 is involved in G protein activation of the ASO-II opsin, suggesting that this novel counterion system coordinates multiple functional properties.
Notch signaling stabilizes lengths of motile cilia in multiciliated cells in the lung
Authors: Joy Neenu , Deshpande Aditya , Lingamallu Sai Manoz , Prabantu Vasam Manjveekar , Naveenkumar CN , Bharathkumar K , Bhat Sukanya , Alvarado-Martinez Zabdiel , Livraghi-Butrico Alessandra , Hagood James S. , Boucher Richard C. , Lafkas Daniel , Byrd Kevin M. , Narayanan Shridhar , Shandil R.K. , Guha Arjun 
Published: December 2024

ABSTRACTAirway multiciliated cells (MCs) maintain respiratory health by clearing mucus and trapped particles through the beating of motile cilia. While it is known that ciliary lengths decrease along the proximal-distal (P-D) axis of the tracheobronchial tree, how this is regulated is unclear. Here, we demonstrate that canonical Notch signaling in MCs plays a critical role in stabilizing ciliary length. Inhibition of Notch signaling in MCs results in ciliary shortening in the trachea, lengthening in the distal airway, and to region-specific alterations in gene expression. We probe how environmental challenges impact MC homeostasis using germ-free andMycobacterium tuberculosis(M. tb) infection models. While germ-free conditions do not perturb ciliary lengths,M. tbinfection leads to lengthening of distal airway cilia, correlating with a downregulation of Notch signaling. These findings reveal that ciliary length and the P-D gradient in the airways are actively regulated, with Notch signaling serving as a stabilizing mechanism.
Mycobacterial EsxG·EsxH (TB9.8·TB10.4) peptides as a subunit vaccine to booster BCG vaccination in an experimental model of pulmonary Tuberculosis
Authors: Martínez-Olivares Constanza Estefania , Lozano-Ordaz Vasti , Mata-Espinosa Dulce , Barrios-Payán Jorge Alberto , Ortiz-Cabrera Ángel Elías , Rodríguez-Miguez Yadira Rocio , Hernández-Pando Rogelio 
Published: December 2024

AbstractThe attenuatedMycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine is currently the only validated vaccine against tuberculosis (TB). In a previous study, we conducted anin-silicoselection of four peptides (G1, G2, H1, and H2) derived from the mycobacterial protein antigens TB10.9·TB10.4 (EsxG·EsxH). Bioinformatic analysis and molecular dynamic simulations predicted these epitopes could be loaded into a MHC-II complex, inducing T and B cell activation. The present study aimed to experimentally validate these peptides as subunit vaccines by determining their cytotoxicity, immunogenicity, and protective efficacy againstMycobacterium tuberculosis(Mtb) in mice when administered as a booster to BCG vaccination. Mice were vaccinated with BCG and, two months later, were subcutaneously immunized with either peptide G1, G2, H1, or H2. One-month post-immunization, mice were challenged with the reference strain H37Rv of moderate virulence or the hypervirulent clinical isolate 09005186. After vaccination and before the challenge, the spleen and lung cells were harvested and stimulatedin vitrowith the corresponding peptide to measure cytokine expression in CD4+, and CD8+T cells, as well as the phenotypes of activated effector T cells, proliferative senescence, central and periphery memory CD4+and CD8+cells. Additionally, specific IgG antibody titers elicited by each peptide were measured using ELISA. Compared with animals vaccinated only with BCG, boosting BCG vaccination with these peptides provided enhanced protection by significantly prolonging the mice survival, reducing the bacillary load, and decreasing tissue damage (pneumonia). These findings contribute to the broader understanding of peptide-based subunit vaccines and highlight the potential for tailored approaches to enhance protective immunity.
SalmonellaTyphimurium Manipulates Syntaxin 7 to Navigate Endo-Lysosomal Trafficking in Host Cells
Authors: Vij Rhea , Chatterjee Ritika , Nair Abhilash Vijay , Singh Anmol , Hajra Dipasree , Gangi Setty Subba Rao , Chakravortty Dipshikha 
Published: December 2024

AbstractIntracellular pathogens rely on manipulating host endocytic pathways to ensure survival.LegionellaandChlamydiaexploit host SNARE proteins, withLegionellacleaving syntaxin 17 (STX17) andChlamydiainteracting with VAMP8 and VAMP7. Similarly,Salmonellatargets the host’s endosomal fusion machinery, using SPI effectors like SipC and SipA to interact with syntaxin 6 (STX6) and syntaxin 8 (STX8), respectively, maintaining its vacuolar niche. Recent evidence highlights syntaxin 7 (STX7), a Qa-SNARE involved in endo-lysosomal fusion, as a potentialSalmonellatarget. BioID screening revealed STX7 interactions with SPI-2 effectors SifA and SopD2, suggesting a critical role inSalmonellapathogenesis. We investigated the role of STX7 inSalmonella-containing vacuole (SCV) biogenesis and pathogenesis in macrophages and epithelial cells. Our findings indicate that STX7 levels and localization differ between these cell types during infection, reflecting the distinct survival strategies ofSalmonella. Live cell imaging showed that STX7 is recruited to SCVs at different infection stages, with significantly altered distribution in HeLa cells at the late stage of infection. STX7 knockdown resulted in reduced bacterial survival, which was rescued upon overexpression of STX7 in both HeLa and RAW264.7 cells, suggestingSalmonellahijacks STX7 to evade lysosomal fusion and secure nutrients for intracellular replication. These results underscore the essential role of STX7 in maintaining SCVs and facilitatingSalmonellasurvival. Further, the temporal expression of STX7 adaptor/binding partners in macrophages showed dynamic interactions with STX7 facilitatingSalmonellainfection and survival in host cells. Together, our study highlights STX7 as a critical host factor exploited bySalmonella, providing insights into the molecular mechanisms underlying its pathogenesis in macrophages and epithelial cells. These findings may in form strategies for targeting host-pathogen interactions to combatSalmonellainfections.
A novel membrane stress-response that blocks chromosomal replication by targeting the DnaA initiator via the ClpP protease
Authors: Gbolahan Alabi , Li Tong , Saxena Rishit , Wolcott Karen , Sohail Aamna , Ahmad Ishika , Chattoraj Dhruba K. , Crooke Elliott , Saxena Rahul 
Published: December 2024

AbstractInEscherichia coli, membrane-stress due to interrupted lipoprotein (Lpp) maturation impairs DNA replication and arrests cell growth. How the two disparate processes of Lpp maturation and DNA replication are connected remains unclear. We demonstrate that upon membrane-stress the Rcs stress-response pathway is activated and the replication initiator DnaA is lost, which explains the replication block. However, the Lon protease, a key regulator of the Rcs pathway, is not required for the DnaA loss. We further ruled out the involvement of (p)ppGpp, one of the major mediators of stress-response in bacteria. However, upon deletion of the ClpP protease gene, DnaA was stable, replication initiated, and there was no cell-growth arrest. In wildtype cells, overexpression of DnaA was lethal even without the membrane-stress apparently from hyper-initiation. The hyper-initiation was restrained in Δcrpcells, and overexpression of DnaA was able to overcome the growth-arrest. Δfiscells, which were earlier found resistant to the membrane-stress, showed DnaA stability and normal replication upon induction of the membrane-stress. We conclude that DnaA loss suffices to explain the growth-arrest upon the membrane-stress. The stress-response pathway described here appears novel because of its independence from Lon and (p)ppGpp, which have been implicated in other stress-responses that block DNA replication.SignificanceThe seminal observation that DNA replication-stress can block cell division inE. coli(SOS response), introduced the concept of checkpoint control in the cell cycle. Here, we describe a novel checkpoint control that functions in the opposite direction: membrane-stress causing replication block. We show how two apparently unrelated outcomes of reducing a membrane phospholipid, accumulation of a precursor lipoprotein (pLpp) and block of replication initiation, could be linked. The pLpp accumulation stresses the membrane that causes a response culminating in activating the ClpP protease that blocks replication by targeting the initiator DnaA. DnaA being vital and highly conserved, the detail understanding of the response pathway is likely to open new avenues to treat bacterial infection.
Paratope mapping of tilvestamab, an anti-AXL function blocking antibody, using high-throughput bacterial expression of secreted scFv-ompY fusion proteins
Authors: Christakou Eleni , Kursula Petri , Micklem David 
Published: December 2024

AbstractTargeting AXL with a highly selective antibody presents a promising approach for inhibiting AXL and potentially improving cancer treatment. An essential step in antibody optimisation is the mapping of paratope residues to epitope residues. In this study, we identify the residues of tilvestamab, a function-blocking anti-AXL monoclonal antibody (mAb), that are essential for its binding to the extracellular domain of AXL. A single-chain variable fragment (scFv) fused to osmotically inducible protein Y (osmY) was designed to enable the secretion of soluble scFv-osmY mutants, which could be directly subjected to high-throughput biolayer interferometry (BLI) screening for binding to the AXL Ig1 domain. Each CDR residue of scFv was mutated to Ala, while additional mutations were made on the basis of predicted contribution to binding. We generated Alphafold3 predictions for the scFv(tilvestamab)-AXL Ig1 complex to gain insights into the molecular interactions of the essential residues, as determined by the experimental data. Our study reveals that tilvestamab binds to the Ig1 domain of AXL, with twelve residues on scFv (tilvestamab) contributing most to binding. Glu2 near the N terminus of AXL is essential for binding. The data give a structural view into the AXL-tilvestamab complex and allow for further optimisation of the binding interface.
Genes and pathways determining flowering time variation in temperate adapted sorghum
Authors: Mangal Harshita , Linders Kyle , Turkus Jonathan , Shrestha Nikee , Long Blake , Cebert Ernst , Kuang Xianyan , Torres-Rodriguez J. Vladimir , Schnable James C. 
Published: December 2024

ABSTRACTThe timing of the transition from vegetative to reproductive growth is determined by a complex genetic architecture integrating signals from a diverse set of external and internal stimuli and plays a key role in determining plant fitness and adaptation. However, significant divergence in the identities and functions of many flowering time pathway components has been reported among plant species. Here we employ a combination of genome and transcriptome wide association studies to identify genetic determinants of variation in flowering time across multiple environments in a large panel of primarily photoperiod-insensitive sorghum (Sorghum bicolor), a major crop that has, to date, been the subject of substantially less genetic investigation than its relatives. Gene families that form core components of the flowering time pathway in other species, FT-like and SOC1-like genes, appear to play similar roles in sorghum, but the genes identified are not orthologous to the primary FT-like or SOC1-like genes which play similar roles in related species. The aging pathway appears to play a significant role in determining non-photoperiod determined variation in flowering time in sorghum. Two components of this pathway were identified in a transcriptome wide association study, while a third was identified via genome wide association. Our results demonstrate that, while the functions of larger gene families are conserved, functional data from even closely related species is not a reliable guide to which gene copies will play roles in determining natural variation in flowering time.
How does financial reporting quality mediate ESG performance to investment efficiency?
Authors: Maiyarni Reka , Utama Sidharta , Djakman Chaerul D. , Mita Aria Farah 
Published: December 2024

Purpose
This study aims to assess the direct and indirect effects of environmental, social and governance (ESG) performance on investment efficiency by investigating the role of financial reporting quality in mediating this relationship.

Design/methodology/approach
To obtain a more comprehensive measurement of ESG performance, this study used both Refinitiv Eikon and Bloomberg ESG scores, while previous studies typically used one ESG score measurement. The test was conducted on cross-country samples of 5,980 observations over 2016–2023. The mediation effect was tested using the three-stage least squares method developed by Baron and Kenny (1986). The Oster test was done to address endogeneity issues that become a matter of concern in determining the estimation model used in this study.

Findings
Empirical results show that ESG performance positively affects investment efficiency, and financial reporting quality mediates the positive effects of ESG performance on investment efficiency. The results of this study indicate that ESG performance will reduce agency problems, thus increasing investment efficiency. This implies that high ESG performance and good financial reporting quality are determining factors for companies to invest more efficiently.

Originality/value
This study reveals how ESG performance affects investment efficiency mediated by financial reporting quality, which has never been discussed in other studies. ESG performance was measured by using the average of Bloomberg ESG score and Refinitiv Eikon ESG score to complement previous studies that generally used one ESG score measurement.