bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral epithelial-macrophage crosstalk permits secondary bacterial infections
Authors: Lane Sidney , White Tristan L. A. , Walsh Erin E. , Cattley Richard T. , Cumberland Rachel , Hawse William F. , Delgoffe Greg M. , Badylak Stephen F. , Bomberger Jennifer M. 
Published: September 2023

ABSTRACT

Extracellular vesicles (EVs) are produced by most known cell types as a form of intercellular communication to influence the physiological function of neighboring cells. During respiratory viral-bacterial coinfection, the preceding antiviral response can lead to an impaired antibacterial response, driven by miscommunication between cells responding to viruses and cells responding to bacteria. Previous studies have shown that antiviral signaling can influence EV cargo and promote antiviral defense in the recipient cell; however, how antiviral EVs may influence host defense against coinfecting microorganisms, specifically bacteria, is not known. Herein, we demonstrated that EVs released from the respiratory epithelium during antiviral signaling alter macrophage inflammatory signaling, induce anti-inflammatory metabolic reprogramming, and impair antibacterial activity against
Staphylococcus aureus
, a common coinfecting bacterial pathogen. Further proteomic analysis revealed that antiviral EVs are preferentially loaded with pyruvate kinase M2 (PKM2), a metabolic enzyme with immunomodulatory effects, and treatment with antiviral EVs leads to increased PKM2 in macrophages. Moreover, we showed that antiviral EV-treated macrophages displayed enhanced oxidative phosphorylation, a metabolic profile consistent with impaired
S. aureus
clearance, and that this metabolic state is phenocopied in macrophages treated with a PKM2 activator. Taken together, our findings identify EVs as a component of the epithelial antiviral response that contributes to impaired bacterial clearance through epithelial-macrophage crosstalk and suggest a role for EVs in driving disease progression during respiratory coinfection.

IMPORTANCE

Miscommunication of antiviral and antibacterial immune signals drives worsened morbidity and mortality during respiratory viral-bacterial coinfections. Extracellular vesicles (EVs) are a form of intercellular communication with broad implications during infection, and here we show that epithelium-derived EVs released during the antiviral response impair the antibacterial activity of macrophages, an innate immune cell crucial for bacterial control in the airway. Macrophages exposed to antiviral EVs display reduced clearance of
Staphylococcus aureus
as well as altered inflammatory signaling and anti-inflammatory metabolic reprogramming, thus revealing EVs as a source of dysregulated epithelium-macrophage crosstalk during coinfection. As effective epithelium-macrophage communication is critical in mounting an appropriate immune response, this novel observation of epithelium-macrophage crosstalk shaping macrophage metabolism and antimicrobial function provides exciting new insight and improves our understanding of immune dysfunction during respiratory coinfections.
The E301R protein of African swine fever virus functions as a sliding clamp involved in viral genome replication
Authors: Li Su , Ge Hailiang , Li Yanhua , Zhang Kehui , Yu Shaoxiong , Cao Hongwei , Wang Yanjin , Deng Hao , Li Jiaqi , Dai Jingwen , Li Lian-Feng , Luo Yuzi , Sun Yuan , Geng Zhi , Dong Yuhui , Zhang Heng , Qiu Hua-Ji 
Published: September 2023

ABSTRACT

African swine fever virus (ASFV) is a complex nucleocytoplasmic, large DNA virus that infects both domestic pigs and wild boar, but little is known about the process of genomic replication. The E301R protein (pE301R) from ASFV was previously predicted as a proliferating cell nuclear antigen (PCNA)-like protein through clamping DNA polymerase to the DNA duplex, but its exact structure and functions remain uncharacterized. Here, the crystal structure of pE301R revealed that it is composed of structurally similar head and tail domains and shares significant structural similarities to the DNA polymerase processivity factors, including sliding clamp and eukaryotic PCNA. More specifically, we demonstrated that pE301R exhibited multiple oligomeric states (with dimers and tetramers dominant), and the tetramers are consistent with the ring-shaped homotetramers in a head-to-tail manner generated by crystal packing. We also showed that pE301R interacted with the ASFV genome and viral DNA polymerase O174L. Furthermore, knockdown of
E301R
by specific small interfering RNAs (siRNAs) significantly decreased the virus genomic replication. Interestingly, the downregulation of PCNA by siRNAs significantly decreased the cell viability, whereas the inhibitory effect was reversed by pE301R overexpression. Notably, we demonstrated that overexpression of PCNA partially restored ASFV replication upon transfection of siRNAs targeting
E301R
. More importantly, T2 amino alcohol, a PCNA-specific inhibitor, markedly inhibited ASFV replication at the stage of viral genome replication. Taken together, we revealed that pE301R functions as a sliding clamp in ASFV genomic replication and can be used as a potential antiviral target.

IMPORTANCE

Sliding clamp is a highly conserved protein in the evolution of prokaryotic and eukaryotic cells. The sliding clamp is required for genomic replication as a critical co-factor of DNA polymerases. However, the sliding clamp analogs in viruses remain largely unknown. We found that the ASFV E301R protein (pE301R) exhibited a sliding clamp-like structure and similar functions during ASFV replication. Interestingly, pE301R is assembled into a unique ring-shaped homotetramer distinct from sliding clamps or proliferating cell nuclear antigens (PCNAs) from other species. Notably, the
E301R
gene is required for viral life cycle, but the pE301R function can be partially restored by the porcine PCNA. This study not only highlights the functional role of the ASFV pE301R as a viral sliding clamp analog, but also facilitates the dissection of the complex replication mechanism of ASFV, which provides novel clues for developing antivirals against ASF.
Terpenes modulate bacterial and fungal growth and sorghum rhizobiome communities
Authors: Chou Ming-Yi , Andersen Trine B. , Mechan Llontop Marco E. , Beculheimer Nick , Sow Alassane , Moreno Nick , Shade Ashley , Hamberger Bjoern , Bonito Gregory 
Published: September 2023

ABSTRACT

Terpenes are among the oldest and largest class of plant-specialized bioproducts that are known to affect plant development, adaptation, and biological interactions. While their biosynthesis, evolution, and function in aboveground interactions with insects and individual microbial species are well studied, how different terpenes impact plant microbiomes belowground is much less understood. Here we designed an experiment to assess how belowground exogenous applications of monoterpenes (1,8-cineole and linalool) and a sesquiterpene (nerolidol) delivered through an artificial root system impacted its belowground bacterial and fungal microbiome. We found that the terpene applications had significant and variable impacts on bacterial and fungal communities, depending on terpene class and concentration; however, these impacts were localized to the artificial root system and the fungal rhizosphere. We complemented this experiment with pure culture bioassays on responsive bacteria and fungi isolated from the sorghum rhizobiome. Overall, higher concentrations (200 µM) of nerolidol were inhibitory to
Ferrovibrium
and tested Firmicutes. While fungal isolates of
Penicillium
and
Periconia
were also more inhibited by higher concentrations (200 µM) of nerolidol,
Clonostachys
was enhanced at this higher level and together with
Humicola
was inhibited by the lower concentration tested (100 µM). On the other hand, 1,8-cineole had an inhibitory effect on
Orbilia
at both tested concentrations but had a promotive effect at 100 µM on
Penicillium
and
Periconia
. Similarly, linalool at 100 µM had significant growth promotion in
Mortierella
, but an inhibitory effect for
Orbilia
. Together, these results highlight the variable direct effects of terpenes on single microbial isolates and demonstrate the complexity of microbe-terpene interactions in the rhizobiome.

Importance
Terpenes represent one of the largest and oldest classes of plant-specialized metabolism, but their role in the belowground microbiome is poorly understood. Here, we used a “rhizobox” mesocosm experimental set-up to supply different concentrations and classes of terpenes into the soil compartment with growing sorghum for 1 month to assess how these terpenes affect sorghum bacterial and fungal rhizobiome communities. Changes in bacterial and fungal communities between treatments belowground were characterized, followed by bioassays screening on bacterial and fungal isolates from the sorghum rhizosphere against terpenes to validate direct microbial responses. We found that microbial growth stimulatory and inhibitory effects were localized, terpene specific, dose dependent, and transient in time. This work paves the way for engineering terpene metabolisms in plant microbiomes for improved sustainable agriculture and bioenergy crop production.
Molecular characterization of highly prevalent
Escherichia coli
and
Escherichia marmotae
resistant to extended-spectrum cephalosporins in European starlings (
Sturnus vulgaris
) in Tunisia
Authors: Souguir Meriem , Châtre Pierre , Drapeau Antoine , François Pauline , Azaiez Sana , Ncir Sana , Madec Jean-Yves , Mansour Wejdene , Haenni Marisa 
Published: September 2023

ABSTRACT

European starlings are widespread migratory birds that have already been described as carrying bacteria resistant to extended-spectrum cephalosporins (ESC-R). These birds are well known in Tunisia because they spend the wintertime in this country and are hunted for human consumption. The goal of our study was to estimate the proportion of ESC-R in these birds and to characterize the collected isolates using whole-genome sequencing. Results showed that 21.5% (42/200) of the birds carried either an extended-spectrum beta-lactamase (ESBL) or an acquired AmpC gene. Diverse
bla
CTX-M
genes were responsible for the ESBL phenotype,
bla
CTX-M-14
being the most prevalent, while only
bla
CMY-2
and one
bla
CMY-62
were found in AmpC-positive isolates. Likewise, different genetic determinants carried these resistance genes, including IncHI2, and IncF plasmids for
bla
CTX-M
genes and IncI1 plasmids for
bla
CMY-2
genes. Three chromosomally encoded
bla
CTX-M-15
genes were also identified. Surprisingly, species identification revealed a large proportion (32.7%) of
Escherichia marmotae
isolates. This species is phenotypically indistinguishable from
Escherichia coli
and has obviously the same capacity to acquire ESC-R genes. Our data also strongly suggest that at least the IncHI2/pST3 plasmid can spread equally between
E. coli
and
E. marmotae
. Given the potential transmission routes between humans and animals, either by direct contact with dejections or through meat preparation, it is important to closely monitor antimicrobial resistance in European starlings in Tunisia and to set up further studies to identify the sources of contamination of these birds.

IMPORTANCE
The One Health concept highlighted knowledge gaps in the understanding of the transmission routes of resistant bacteria. A major interest was shown in wild migratory birds since they might spread resistant bacteria over long distances. Our study brings further evidence that wild birds, even though they are not directly submitted to antibiotic treatments, can be heavily contaminated by resistant bacteria. Our results identified numerous combinations of resistance genes, genetic supports, and bacterial clones that can spread vertically or horizontally and maintain a high level of resistance in the bird population. Some of these determinants are widespread in humans or animals (IncHI2/pST3 plasmids and pandemic clones), while some others are less frequent (atypical IncI1 plasmid and minor clones). Consequently, it is essential to be aware of the risks of transmission and to take all necessary measures to prevent the proportions of resistant isolates from increasing uncontrollably.
Endoscopic stone management in an ectopic ureter inserting into the prostatic urethra
Authors: Heijkoop Bridget , Lahoud John , Wong Eddy Lee Hao 
Published: September 2023

We report a case of successful endoscopic stone management in a patient with ectopic ureteric insertion. The patient had a complete duplex collecting system, with the upper moiety ureter inserting ectopically into his prostatic urethra, and an obstructing ureteric stone in the distal portion of the ectopic ureter. This made both characterisation of the patient’s anatomy and initial emergency stone management challenging.The case offers several learning points for clinicians who may encounter similar situations. By describing the challenges of managing this patient’s presentation, we highlight considerations in imaging interpretation and operative approach that may help the reader manage a similar presentation to their practice. Additionally, we remind the urologist to consider the implications of an ectopic duplex ureter on future procedures, such as transurethral resection of the prostate or radical prostatectomy.
Observational study on the timing and method of interruption by hospital consultants during the opening statement in outpatient consultations
Authors: Mulder-Vos Inge , Driever Ellen M , Brand Paul L P 
Published: September 2023

ObjectiveTo analyse verbal interruptions by Dutch hospital consultants during the patient’s opening statement in medical encounters.DesignCross-sectional descriptive study.SettingIsala teaching hospital in Zwolle, the Netherlands.Participants94 consultations by 27 consultants, video recorded in 2018 and 2019.Main outcome measuresPhysicians’ verbal interruptions during patients’ opening statements, rate of completion of patients’ opening statements, time to first interruption and the effect of gender, age and physician specialty on the rate and type of physicians’ verbal interruptions.ResultsPatients were interrupted a median of 9 times per minute during their opening statement, the median time to the first interruption was 6.5 s. Most interruptions (67%) were backchannels (such as ‘hm hm’ or ‘go on’), considered to be encouraging the patient to continue. In 52 consultations (55%), patients could not finish their opening statement due to a floor changing interruption by the consultant. The median time to such an interruption was 31.4 s, on average 20 s shorter than a finished opening statement (p=0.004). Female consultants used more backchannels (median 9, IQR 5–12) than male consultants (median 7, IQR 2–11, p=0.028).ConclusionsHospital-based consultants use various ways to interrupt patients during their opening statements. Most of these interruptions are encouraging backchannels. Still, consultants change the conversational floor in more than half of their patients during their opening statements after a median of 31 s.
Index hospital cost of adverse events following thoracic surgery: a systematic review of economic literature
Authors: Jones Daniel , Kumar Srishti , Anstee Caitlin , Gingrich Molly , Simone Alexander , Ahmadzai Zubair , Thavorn Kednapa , Seely Andrew 
Published: September 2023

ObjectivesAdverse events (AEs) following thoracic surgery place considerable strain on healthcare systems. A rigorous evaluation of the economic impact of thoracic surgical AEs remains lacking and is required to understand the value of money of formal quality improvement initiatives. Our objective was to conduct a systematic review of all available literature focused on specific cost of postoperative AEs following thoracic surgery.DesignSystematic review of the economic literature was performed, following recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Data sourcesAn economic search filter developed by the Canadian Agency for Drugs and Technologies in Health was applied, and MEDLINE, Embase and The Cochrane Library were searched from inception to January 2022.Eligibility criteriaWe included English articles involving adult patients who underwent a thoracic surgical procedure with estimated costs of postoperative complications. Eligible study designs included comparative observational studies, randomised control trials, decision analytic or cost-prediction models, cost analyses, cost or burden of illness studies, economic evaluation studies and systematic reviews and/or meta-analyses of cost analyses and cost of illness studies.Data extraction and synthesisTwo reviewers independently screened titles and abstracts in the first stage and full-text articles of included studies in the second stage. Disagreements during abstract and full-text screening stages were resolved via discussion until a consensus was reached. Studies were appraised for methodological quality using the Critical Appraisal Skills Program checklist.Results3349 studies were identified: 20 met inclusion criteria. Most were conducted in the USA (12/20), evaluating AE impact on hospital expenditures (18/20). 68 procedure-specific AE mean costs were characterised (USD$). The most commonly described were anastomotic leak (mean:range) (USD$49 278:$6 176–$133 002) and pneumonia ($12 258:$2608–$34 591) following esophagectomy, and prolonged air leak ($2556:$571–$3573), respiratory failure ($19 062:$11 841–$37 812), empyema ($30 189:$23 784–$36 595), pneumonia ($15 362:$2542–$28 183), recurrent laryngeal nerve injury ($16 420:$4224–$28 616) and arrhythmia ($6835:$5833–$8659) following lobectomy.ConclusionsHospital costs associated with AEs following thoracic surgery are substantial and varied. Quantifying costs of AEs enable future economic evaluation studies, which could help prioritising value-directed quality improvement to optimally improve outcomes and reduce costs.
Incidence of constipation and associated factors in the period of lockdown during COVID-19 pandemic: protocol for a systematic review and meta-analysis
Authors: Zhang Juan Juan , Sun Ran , Guo Sha , Yang Sha 
Published: September 2023

IntroductionThe lifestyle and habit changes that have emerged as a result of quarantine measures may have had a negative impact on defecation habits. However, there is a lack of data on combined estimates of its occurrence and prevalence.Methods and analysisWe will conduct a systematic search for observational studies on PubMed/MEDLINE, Web of Science, Cochrane Library, EMBASE, CNKI, SinoMed, VIP China Science and Technology Journal database, Chinese Biomedical Databases and Wanfang Data. The search will include literature published from the inception of the databases to September 2022. Two authors will independently screen articles and extract data based on predefined inclusion and exclusion criteria. The risk of bias in the included studies will be evaluated using the Newcastle-Ottawa Scale for observational studies. Statistical analysis will be performed using Review Manager software V.5.4 and STATA V.16.0 software. Heterogeneity among studies will be assessed using the Q statistical test and I2statistical tests. In case of significant heterogeneity, subgroup analysis and sensitivity analysis will be conducted to explore the source of heterogeneity. Sensitivity analyses will also be performed to assess the reliability of the study findings. If feasible, a meta-analysis will be conducted. Otherwise, a descriptive synthesis will be performed using a best-evidence synthesis approach. The primary outcome of interest will be the prevalence of constipation. The secondary outcomes will involve examining the association of risk factors. To evaluate potential publication bias, we will use both the Begg funnel plot and Egger’s weighted regression statistics. Furthermore, to accurately assess the quality of evidence for our primary outcome, we will employ the Grading of Recommendations Assessment, Development and Evaluation system.Ethics and disseminationThis systematic review protocol will only consider published studies available in databases and will not include individual patient data. Therefore, ethical approval is not required, and the findings will be published in a peer-reviewed journal.PROSPER registration numberCRD42022366176.
Endovascular ultrasound renal denervation to lower blood pressure in young hypertensive women planning pregnancy: study protocol for a multicentre randomised, blinded and sham controlled proof of concept study
Authors: Gosse Philippe , Sentilhes Loïc , Boulestreau Romain , Doublet Julien , Gaudissard Julie , Azizi Michel , Cremer Antoine 
Published: September 2023

IntroductionA major issue confronting clinicians treating hypertension in pregnancy is the limited number of pharmacological options. Endovascular catheter-based renal denervation (RDN) is a new method to lower blood pressure (BP) in patients with hypertension by reducing the activity of the renal sympathetic nervous system. Drugs that affect this system are safe in pregnant women. So there is reasonable evidence that RDN performed before pregnancy should not have deleterious effects for the fetus. Because the efficacy of RDN may be greater in younger patients and in women, we may expect a larger proportion of BP normalisation in young hypertensive women, but this remains to be proven. Our primary objective is to quantify the proportion of BP normalisation with RDN in this population.Methods and analysisWHY-RDN is a multicentre randomised sham-controlled trial conducted in six French hypertension centres that will include 80 women with essential hypertension treated or untreated, who are planning a pregnancy in the next 2 years and will be randomly assigned to RDN or classic renal arteriography and sham RDN in a ratio of 1:1. The primary outcome is the normalisation of 24-hour BP (<130/80 mm Hg) at 2-month post procedure off treatment. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected responder rates of 24% and 3% in the treatment and control group, respectively. Secondary outcomes include the absence of adverse outcomes for a future pregnancy, the variations of BP in ambulatory and home BP measurements and the evaluation of treatment prescribed.Ethics and disseminationWHY-RDN has been approved by the French Ethics Committee (Tours, Region Centre, Ouest 1- number 2021T1-28 HPS). This project is being carried out in accordance with national and international guidelines. The findings of this study will be disseminated by publication.Trial registration numberClinicalTrials.gov,NCT05563337.