bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salmonella exploits the reactive oxygen species generated by the plant immune system to enhance colonization
Authors: Aldin M Srai , Tzipilevich E 
Published: March 2024

AbstractUnderstanding bacterial interaction with the plant immune system is essential for building a sustainable food system. Discouraging pathogens enhancing beneficial bacteria and preventing food spoilage and contamination by human enteric pathogens. Immune system activation triggers a burst of toxic reactive oxygen species (ROS). We discovered that the food-poisoning bacteriumSalmonellaexploits the plant ROS to enhance biofilm formation and colonization. Scavenging the ROS with antioxidants or inhibiting their production reduces colonization. Further, combining the antioxidant vitamin C and immune system activation with salicylic acid synergistically inhibitedSalmonellacolonization of the plant model Arabidopsis and edible plants. This safe-to-use combination is an eco-friendly method to prevent plant contamination bySalmonella, Listeriaand enteropathogenicE. coli. Finally, we have found that exploiting the plant immunity for enhancing colonization is not exclusive toSalmonellaand diverse beneficialpseudomonasspecies isolated from plants can also exploit the plant immune system, suggesting that it is a general plant colonization strategy.
Deep5hmC: Predicting genome-wide 5-Hydroxymethylcytosine landscape via a multimodal deep learning model
Authors: Ma Xin , Thela Sai Ritesh , Zhao Fengdi , Yao Bing , Wen Zhexing , Jin Peng , Zhao Jinying , Chen Li 
Published: March 2024

Abstract5-hydroxymethylcytosine (5hmC), a critical epigenetic mark with a significant role in regulating tissue-specific gene expression, is essential for understanding the dynamic functions of the human genome. Using tissue-specific 5hmC sequencing data, we introduce Deep5hmC, a multimodal deep learning framework that integrates both the DNA sequence and the histone modification information to predict genome-wide 5hmC modification. The multimodal design of Deep5hmC demonstrates remarkable improvement in predicting both qualitative and quantitative 5hmC modification compared to unimodal versions of Deep5hmC and state-of-the-art machine learning methods. This improvement is demonstrated through benchmarking on a comprehensive set of 5hmC sequencing data collected at four time points during forebrain organoid development and across 17 human tissues. Notably, Deep5hmC showcases its practical utility by accurately predicting gene expression and identifying differentially hydroxymethylated regions in a case-control study of Alzheimer’s disease.
Nucleolar accumulation of APE1 through condensates is mediated by rRNA forming G-quadruplex structures
Authors: Dall’Agnese Giuseppe , Hannett Nancy M. , Overholt Kalon J. , Platt Jesse M. , Henninger Jonathan E. , Marcos-Vidal Asier , Antoniali Giulia , Tell Gianluca 
Published: March 2024

AbstractAPE1 (apurinic/apyrimidinic endodeoxyribonuclease 1) is the main endonuclease of the base excision repair (BER) pathway acting on abasic (AP)-sites in damaged DNA. APE1 is an abundant nuclear protein with a higher concentration than other BER pathway enzymes, and therefore, improper expression and localization of this factor could lead to the accumulation of toxic DNA intermediates. Altered APE1 sub-cellular localization, expression levels, or hyper-acetylation are associated with cancer development suggesting the importance of a fine-tuning mechanism for APE1 nuclear-associated processes. Recent work highlighted multi-functional roles of APE1, including rRNA quality control. However, how rRNA influences the sub-cellular localization and activity of APE1 remains poorly understood, but previously underappreciated APE1-RNA interactions may influence the ability of this protein to form biomolecular condensates and tune APE1 partitioning into nucleoli. Since nucleolar accumulation of ectopic proteins could be the result of overexpression strategies, it is imperative to have cellular models to study APE1 trafficking under physiological conditions. Here we created the first cell line to express fluorescently tagged APE1 at its endogenous locus, enabling live-cell imaging. Live-cell imaging demonstrates that APE1 nucleolar accumulation requires active rRNA transcription. When modeled in vitro, APE1 condensate formation depends on RNA G-quadruplex (rG4) structures in rRNA and is modulated by critical lysine residues of APE1. This study sheds light on the mechanisms underlying APE1 trafficking to the nucleolus and formation of RNA-dependent APE1 nucleolar condensates that may modulate a switch between the activity of this factor in rRNA processing and DNA damage repair.Significance StatementWe created and characterized the first endogenous, fluorescently tagged cell line to study APE1 subcellular trafficking under physiological and stress conditions. Using this cell line, we show that APE1 nucleolar enrichment occurs under physiological conditions and, performingin vitrodroplet assays, we associate APE1 condensates with active transcription of RNA G-quadruplexes, abundantly present in healthy nucleoli. This work deepens our understanding of APE1’s role in healthy cells in the absence of DNA damage and provide a novel mechanism for how this protein responds to stress. Our results suggest that phase separation is an important part of how DNA damage repair proteins switch between their normal physiological functions and their ability to correct DNA lesions.
Increased Risk of Cirrhosis in Patients with Inflammatory Bowel Disease: A Danish registry-based cohort study (1998-2018)
Authors: Deepak Parakkal , McHenry Scott , Sandri Anastasia Karachalia , De Freitas Maiara Brusco , Zamani Mohammad , Yarur Andres J. , Jess Tine 
Published: March 2024

AbstractBackground and AimsPrior studies suggest an increased risk of non-alcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD). We aimed to investigate the risk of cirrhosis in a nationwide cohort of IBD patients compared to a matched non-IBD population.MethodsPatients diagnosed with IBD without prior cirrhosis during 1998-2018 were identified in the Danish health registries and were matched 1:10 to persons without IBD. Cox regression was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).ResultsWithin the study population of 495,220 persons, a total of 2,741 cirrhosis cases were identified during follow-up, with a higher proportion of cases among patients with IBD (0.9%) compared to non-IBD persons (0.5%). Patients with IBD had a significantly higher risk of cirrhosis compared to non-IBD persons (adjusted HR (aHR) (95% CI): 1.84 (1.64-2.04)). The leading etiology of cirrhosis in IBD was NAFLD (51.6%), followed by alcohol (39.0%). The risk of cirrhosis among IBD patients (compared to non-IBD persons) was more pronounced among those diagnosed with IBD ≤ 40 years of age (aHR (95% CI): 3.08 (2.45-3.87); vs. > 40 years of age, 1.63 (1.45-1.84); p-value <0.001) and CD patients (aHR (95% CI): 2.20 (1.80-2.67); vs. 1.72 (1.52-1.95) among UC; p-value 0.04).ConclusionIBD was associated with an increased risk of incident cirrhosis, especially in patients aged ≤ 40 years at IBD diagnosis and in patients with CD. These findings point towards a need for focused screening for cirrhosis among IBD patients, especially in certain groups.
Amino acid profiling of COVID-19 patients blood serum
Authors: Russkikh Ya.V. , Sushentseva N.N. , Popov O.S. , Apalko S.V. , Shimansky V.S. , Asinovskaya A.Yu. , Mosenko S.V. , Sarana A.M. , Scherbak S.G. 
Published: March 2024

ABSTRACTMain objectives of this study were to analyse metabolomic profile features of patients with COVID-19 using mass spectrometry techniques while taking into account the clinical and laboratory history, and to study the relationship between the severity of COVID-19 symptoms and the concentration of primary metabolites, primarily amino acids. We used frozen blood serum samples of 935 COVID-19 patients from the City Hospital No. 40 biobank collection. Metabolomic profile was studied by HPLS-MS/MS method. R programming language was used for statistical data processing. The difference of metabolic profile of patients with COVID-19 depending on the severity of the disease was revealed based on the performed analysis - for 52 out of 84 detected compounds there were differences with reliability p<0,01. Statistically significant differences in concentration were recorded for organic acids, amino acids and their derivatives. Using samples from the biobank collection, a metabolomic study of the biomaterial of patients hospitalised with the diagnosis of COVID-19 was carried out. According to the results obtained, kynurenine, phenylalanine and acetylcarnitine were associated with the severity of COVID-19 infection.
Welsh hospital admissions due to dog bites and strikes (2014-2022)
Authors: Owczarczak-Garstecka Sara C , Oxley James A , Tulloch John SP 
Published: March 2024

AbstractObjectiveTo describe the incidence and victim demographics of Welsh hospital admissions due to dog bites and strikes from 2014 to 2022.Study designDescriptive analysis of Welsh hospital admissions data.MethodsResidents of Wales admitted to a Welsh National Health Service (NHS) hospital for a dog bite or strike, were identified using ICD-10 codes. The annual incidence of dog bite admissions between 2014 and 2022 was calculated and stratified by child–adult status, sex, and Local Health Boards. Trends over time were analysed using Chi-square test for trends.ResultsHospital admissions due to dog bites and strikes have significantly increased from 16.3 per 100,000 to 23.7 per 100,000 population in 2022. This was driven by an increase in non-geriatric adults, and an increase in three Local Health Boards. The Swansea Bay area has the highest incidence in Wales (56.1 admissions per 100,000).ConclusionsWales has a higher incidence of dog bites than England or the Republic of Ireland. Work in the communities where incidence is exceptionally high is needed to understand the reasons behind having the highest incidence of dog bites in the British Isles and to establish the most efficacious methods for bite prevention.
Comprehensive Evaluation of Artificial Intelligence Models for Diagnosis of Multiple Sclerosis Using Information from Retinal Layers Multicenter OCT Images
Authors: Khodabandeh Zahra , Rabbani Hossein , Bidabadi Neda Shirani , Bonyani Mehdi , Kafieh Rahele 
Published: March 2024

AbstractMultiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. Optical coherence tomography (OCT) is a retinal imaging technology with great promise as a possible MS biomarker. Unlike other ophthalmologic diseases, the variations in shape of raw cross-sectional OCTs in MS are subtle and not differentiable from healthy controls (HCs). More detailed information like thickness of particular layers of retinal tissues or surface of individual retinal boundaries are more appropriate discriminators for this purpose. Artificial Intelligence (AI) has demonstrated a robust performance in feature extraction and classification of retinal OCTs in different ophthalmologic diseases using OCTs. We explore a comprehensive range of AI models including (1) feature extraction with autoencoder (AE) and shallow networks for classification, (2) classification with deep networks designed from scratch, and (3) fine-tuning of pretrained networks (as a generic model of the visual world) for this specific application. We also investigate different input data including thickness and surfaces of different retinal layers to find the most representative data for discrimination of MS. Moreover, channel-wise combination and mosaicing of multiple inputs are examined to find the better merging model. To address interpretability requirement of AI models in clinical applications, the visualized contribution of each input data to the classification performance is shown using occlusion sensitivity and Grad-CAM approaches. The data used in this study includes 38 HC and 78 MS eyes from two independent public and local datasets. The effectiveness and generalizability of the classification methods are demonstrated by testing the network on these independent datasets. The most discriminative topology for classification, utilizing the proposed deep network designed from scratch, is determined when the inputs consist of a channel-wise combination of the thicknesses of the three layers of the retina, namely the retinal fiber layer (RNFL), ganglion cell and inner plexiform layer (GCIP), and inner nuclear layer (INL). This structure resulted in balanced-accuracy of 97.3, specificity of 97.3, recall 97.4%, and g-mean of 97.3% in discrimination of MS and HC OCTs.
XBB.1.5 mRNA COVID-19 Vaccination and Inpatient or Emergency Department Visits Among Adults Infected with SARS-CoV-2 JN.1 and XBB-Lineage Variants
Authors: Levy Matthew E. , Chilunda Vanessa , Heaton Phillip R. , McKeen Deran , Goldman Jason D. , Davis Richard E. , Schandl Cynthia A. , Glen William B. , McEwen Lisa M. , Cirulli Elizabeth T. , Wyman Dana , Rossi Andrew Dei , Dai Hang , Isaksson Magnus , Washington Nicole L. , Basler Tracy , Tsan Kevin , Nguyen Jason , Ramirez Jimmy , Sandoval Efren , Lee William , Lu James , Luo Shishi 
Published: March 2024

ABSTRACTWithin a multi-state viral genomic surveillance program, we conducted a case-control analysis comparing prior receipt of XBB.1.5-adapted mRNA vaccination between SARS-CoV-2-infected adults with inpatient/ED visits (proxy for severe illness) vs outpatient visits. Among 6,551 patients from September 2023-January 2024, 6.1% with inpatient/ED visits vs 12.0% with outpatient visits had received XBB.1.5 vaccination (aOR=0.41; 95%CI:0.32-0.53). This protective association was weaker among JN.1 (aOR=0.62; 95%CI:0.40-0.96) vs XBB-lineage (aOR=0.28; 95%CI:0.18-0.43) variant infections (interaction, p=0.003). XBB.1.5 vaccination was also protective specifically compared to BA.4/BA.5-adapted mRNA vaccination (aOR=0.60; 95%CI:0.45-0.79). XBB.1.5 vaccines protect against severe illness, but protection may be weaker against JN.1 vs XBB-lineage variants.
Single cell sequencing of pig lungs reveals immune responses underlying influenza infection and oseltamivir therapy
Authors: de Carvalho Madrid Darling Melany , Gu Weihong , Warren Wesley C. , Driver John P. 
Published: March 2024

ABSTRACTDespite pigs being an important species in influenza A virus (IAV) epidemiology and a reliable model of human IAV infections, many aspects of the porcine pulmonary immune system remain poorly understood. Here, we characterized the single cell landscape of lung leukocytes of healthy pigs and then compared them to pigs infected with 2009 pandemic H1N1 IAV with or without oseltamivir antiviral therapy. Our data show conserved features as well as species-specific differences in cell types and cell states compared to human and mouse lung leukocytes. IAV infection induced a robust antiviral transcriptional response in multiple lymphoid and myeloid cell types, as well as distinct patterns of cell-cell cross talk. Oseltamivir treatment reduced these responses. Together our findings describe key events in the pulmonary anti-IAV response of pigs that open new avenues to develop IAV vaccines and therapies. They should also enable the better use of pigs as a model for human IAV infection and immunity.
Spectral Characterization of a Blue Light-Emitting Micro-LED Platform and Microbial Chromophores for Therapeutic Applications in Skin Conditions
Authors: Serrage Hannah J. , Eling Charlotte J. , Alves Pedro U. , Mcbain Andrew J. , O’neill Catherine , Laurand Nicolas 
Published: March 2024

AbstractThe therapeutic application of blue light (380 – 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin, termed the skin microbiome. In conditions including acne vulgaris, blue light is thought to address this imbalance through the selective photoexcitation of microbial species expressing wavelength-specific chromophores, differentially affecting skin commensals and thus altering the relative species composition. However, the abundance and diversity of these chromophores across the skin microbiota remains poorly understood. Similarly, devices utilised for studies are often bulky and poorly characterised which if translated to therapy could result in reduced patient compliance. Here, we present a clinically viable micro-LED illumination platform with peak emission 450 nm (17 nm FWHM) and adjustable irradiance output to a maximum 0.55±0.01 W/cm2, dependent upon the concentration of titanium dioxide nanoparticles applied to an accompanying flexible light extraction substrate. Utilising spectrometry approaches, we characterised the abundance of prospective blue light chromophores across skin commensal bacteria isolated from healthy volunteers. Of the strains surveyed 62.5% exhibited absorption peaks within the blue light spectrum, evidencing expression of carotenoid pigments (18.8%, 420 – 483 nm;Micrococcus luteus, Kocuriaspp.), porphyrins (12.5%, 402 – 413 nm;Cutibacteriumspp.) and potential flavins (31.2%, 420 – 425 nm;StaphylococcusandDermacoccusspp.). We also present evidence of the capacity of these species to diminish irradiance output when combined with the micro-LED platform and in turn how exposure to low-dose blue light causes shifts in observed absorbance spectra peaks. Collectively these findings highlight a crucial deficit in understanding how microbial chromophores might shape response to blue light and in turn evidence of a micro-LED illumination platform with potential for clinical applications.
Development of Broad-spectrum β-cyclodextrins-Based Nanomaterials Against Influenza Viruses
Authors: Zwygart Arnaud Charles-Antoine , Medaglia Chiara , Zhu Yong , Tarbet E Bart , Jonna Westover , Fage Clément , Le Roy Didier , Roger Thierry , Constant Samuel , Huang Song , Stellacci Francesco , Silva Paulo Jacob , Tapparel Caroline 
Published: March 2024

AbstractIn recent decades, epidemics and pandemics have multiplied throughout the world, with viruses generally being the primary agents responsible. Among these, influenza viruses play a key role, as they cause severe respiratory distress, representing a major threat to public health. To enhance the response to viral disease outbreaks, there is a need for ready-to-use broad-spectrum antivirals. We have engineered macromolecules (named CD-SA) consisting of a β-cyclodextrin (CD) scaffold modified with hydrophobic linkers in the primary face, onto which unitary sialic acid (SA) epitopes are covalently grafted, this to mimic influenza virus host receptors. In this study, we demonstrated that CD-SA, with a unitary SA, without extensive polysaccharides or specific connectivity, acts as a potent virucidal antiviral against several variants of human influenza type A and type B viruses. We also assessed the genetic barrier to resistance of CD-SAin vitroand successfully delayed emergence of resistance by combining CD-SA with interferon-λ1 (IFN λ1). Finally, we completed the characterization of the antiviral activity by conducting bothex vivoandin vivostudies, demonstrating a potent antiviral effect in human airway epithelia and in a mouse model of infection, higher than that of Oseltamivir, a currently approved anti-influenza antiviral.
SalmonellaTyphimurium infection inhibits macrophage IFNβ signaling in a TLR4-dependent manner
Authors: Shuster Michael , Lyu Zhihui , Augenstreich Jacques , Mathur Shrestha , Ganesh Akshaya , Ling Jiqiang , Briken Volker 
Published: March 2024

AbstractType I Interferons (IFNs) generally have a protective role during viral infections, but their function during bacterial infections is dependent on the bacterial species.Legionella pneumophila,Shigella sonneiandMycobacterium tuberculosiscan inhibit type I IFN signaling. Here we examined the role of type I IFN, specifically IFNβ, in the context ofSalmonella entericaserovar Typhimurium (STm) macrophage infections and the capacity of STm to inhibit type I IFN signaling. We demonstrate that IFNβ has no effect on the intracellular growth of STm in infected bone marrow derived macrophages (BMDMs) derived from C57BL/6 mice. STm infection inhibits IFNβ signaling but not IFNγ signaling in a murine macrophage cell line. We show that this inhibition is independent of the type III and type VI secretion systems expressed by STm and is also independent of bacterial phagocytosis. The inhibition is Toll-like receptor 4 (TLR4)-dependent as the TLR4 ligand, lipopolysaccharide (LPS), alone is sufficient to inhibit IFNβ-mediated signaling and STm-infected, TLR4-deficient BMDMs do not exhibit inhibited IFNβ signaling. In summary, we show that macrophages exposed to STm have reduced IFNβ signaling via crosstalk with TLR4 signaling, and that IFNβ signaling does not affect cell autonomous host defense against STm.
Spatial patterns ofHyalomma marginatum-borne pathogens in the Occitanie region (France), a focus on the intriguing dynamics ofRickettsia aeschlimannii
Authors: Charlotte Joly-Kukla , Célia Bernard , David Bru , Clémence Galon , Carla Giupponi , Karine Huber , Hélène Jourdan-Pineau , Laurence Malandrin , Ignace Rakotoarivony , Camille Riggi , Laurence Vial , Sara Moutailler , Thomas Pollet 
Published: March 2024

ABSTRACTHyalomma marginatumis an invasive tick species recently established in mainland southern France. This tick is known to host a diverse range of human and animal pathogens such asRickettsia aeschlimannii,Theileria equi,Anaplasma phagocytophilum,Anaplasma marginale,Ehrlichia minasensis, Crimean-Congo hemorrhagic fever and West Nile virus. While information about the dynamics of these pathogens is crucial to assess disease risk and develop effective monitoring strategies, few data on the spatial dynamics of these pathogens are currently available. We thus collected ticks in 27 sites in the Occitanie region to characterize spatial patterns ofH. marginatum- borne pathogens. Several pathogens have been detected:Theileria equi(9.2%),Theileria orientalis(0.2%),Anaplasma phagocytophilum(1.6%),Anaplasma marginale(0.8%) andRickettsia aeschlimannii(87.3%). Interestingly, we found a spatial clustered distribution for the pathogenR. aeschlimanniibetween two geographically isolated areas with infection rates and bacterial loads significantly lower in Hérault/Gard departments (infection rate 78.6% in average) compared to Aude/Pyrénées-Orientales departments (infection rate 92.3% in average). At a smaller scale,R. aeschlimanniiinfection rates varied from one site to another, ranging from 29% to 100%. Overall, such high infection rates (87.3% in average) and the effective maternal transmission ofR. aeschlimanniimight suggest a role as a tick symbiont inH. marginatum. Moreover, currently identified as a human pathogen, such results also question about its pathogenic status in humans given the low number of human cases. Further studies are thus needed to understand both the status and the role ofR. aeschlimanniiinH. marginatumticks.IMPORTANCETicks are obligatory hematophagous arthropods which transmit pathogens of medical and veterinary importance. Their infections cause serious health issues in humans and considerable economic loss in domestic animals. Information about the presence of pathogens in ticks and their dynamics is crucial to assess disease risk for public and animal health. Analysing tick-borne pathogens in ticks collected in 27 sites in the regions Occitanie, our results highlight clear spatial patterns in theHyalomma marginatum-borne pathogen distribution and strengthen the postulate that it is essential to develop effective monitoring strategies and consider the spatial scale to better characterize the circulation of tick-borne pathogens.