bluuebunny/crossref_metadata_2025_split huggingface dataset:
The phage-encoded PIT4 protein affects multiple two-component systems of
Pseudomonas aeruginosa
Authors: Schroven Kaat , Putzeys Leena , Kerremans Alison , Ceyssens Pieter-Jan , Vallino Marta , Paeshuyse Jan , Haque Farhana , Yusuf Ahmed , Koch Matthias D. , Lavigne Rob 
Published: November 2023

ABSTRACT

Two-component systems (TCSs) control a large proportion of virulence factors in
Pseudomonas aeruginosa
. Yet, investigations on inhibitors of regulatory pathways of TCSs remain scarce, despite their potential in anti-virulence strategies. This work elucidates the molecular mechanism of PIT4, a protein encoded by the lytic
P. aeruginosa
phage LSL4. Single-copy expression of this early phage gene inhibits bacterial motility, in particular twitching motility, and reduces the virulence of
P. aeruginosa
in HeLa cells. Differential gene expression and a yeast two-hybrid screen showed that PIT4 interacts with components of different two-component systems. In one-on-one interaction assays, it was confirmed that PIT4 specifically interacts with the histidine kinase domains of FleS, PilS, and PA2882. This identified phage mechanism therefore demonstrates the ability of phage proteins to simultaneously target and impact multiple pathways and hints toward a biological function as an infection-exclusion mechanism. This work highlights the potential of previously unknown phage proteins in virulence regulation of multidrug resistant pathogens that could in future be exploited for anti-virulence strategies and biotechnological applications.

IMPORTANCE

More and more
Pseudomonas aeruginosa
isolates have become resistant to antibiotics like carbapenem. As a consequence,
P. aeruginosa
ranks in the top three of pathogens for which the development of novel antibiotics is the most crucial. The pathogen causes both acute and chronic infections, especially in patients who are the most vulnerable. Therefore, efforts are urgently needed to develop alternative therapies. One path explored in this article is the use of bacteriophages and, more specifically, phage-derived proteins. In this study, a phage-derived protein was studied that impacts key virulence factors of the pathogen via interaction with multiple histidine kinases of TCSs. The fundamental insights gained for this protein can therefore serve as inspiration for the development of an anti-virulence compound that targets the bacterial TCS.
Porcine deltacoronavirus enters ST cells by clathrin-mediated endocytosis and does not require Rab5, Rab7, or Rab11
Authors: Li Shiqian , Xiao Dai , Zhang Luwen , Chen Rui , Song Daili , Wen Yiping , Wu Rui , Zhao Qin , Du Senyan , Yan Qigui , Cao Sanjie , Huang Xiaobo 
Published: November 2023

ABSTRACT
Porcine deltacoronavirus (PDCoV) is a newly emerged enteric pathogen that causes diarrhea, dehydration, vomiting, and in suckling piglets, a high rate of death. Here, we used endocytosis inhibitors, dominant-negative mutants, and small interfering RNA (siRNA) interference to investigate PDCoV entry into swine testicle (ST) cells. Results showed that chlorpromazine, dynasore, and methyl-β-cyclodextrin (MβCD) inhibited PDCoV internalization; immunofluorescence assay (IFA) of dominant-negative (DN) mutants and siRNA interference further demonstrated these results, indicating that PDCoV utilizes clathrin-mediated endocytosis and requires dynamin and cholesterol to enter ST cells. The role of endosomes in PDCoV infection was also investigated and we found that PDCoV does not require Rab5, Rab7, or Rab11 for productive infection, indicating that the transport of PDCoV in ST cells does not require the participation of the endosomal system. Our findings will provide additional understanding of the entry mechanisms of PDCoV and possible antiviral targets.

IMPORTANCE
Porcine deltacoronavirus (PDCoV) is a newly emerged enteric virus threatening pig industries worldwide. Our previous work showed that PDCoV enters porcine kidney (PK-15) cells through a caveolae-dependent pathway, but the entry mechanism for PDCoV into swine testicle (ST) cells remains unclear. Mechanisms of virus entry can be different with different virus isolates and cell types. Here, we determined that PDCoV enters ST cells via clathrin-mediated endocytosis. Additionally, we found that PDCoV entry does not require Rab5, Rab7, or Rab11. These findings provide additional understanding of the entry mechanisms of PDCoV and possible antiviral targets.
Real-world evaluation of the Lucira Check-It COVID-19 loop-mediated amplification (LAMP) test
Authors: Simms Elizabeth , McCracken Gregory R. , Hatchette Todd F. , McNeil Shelly A. , Davis Ian , Whelan Noella , Keenan Angela , LeBlanc Jason J. , Patriquin Glenn 
Published: November 2023

ABSTRACT

In hospitals during the COVID-19 pandemic, laboratory testing was important to reduce SARS-CoV-2 transmissions, particularly for high-risk settings like the emergency department and pre-operative settings and for the safe return to work of exposed healthcare workers (HCWs). For these applications, delayed test results from laboratory nucleic acid amplification tests (NAATs) posed a barrier to maximizing efficient patient flow and minimizing staffing shortages. This quality improvement project sought to evaluate the performance of the Lucira Check-It COVID-19 Test, a rapid diagnostic test that used NAAT technology (NAAT-RDT). Using 10-fold serial dilutions of SARS-CoV-2, the analytical sensitivity of the NAAT-RDT was assessed against standard NAATs used for routine diagnostic testing. Clinical performance was assessed at two Nova Scotia hospitals in 405 cases with paired swabs tested by NAAT-RDT and laboratory-based NAATs. These represented three distinct populations: patients presenting to the emergency department (
n
= 208), patients in the pre-operative setting (
n
= 158), and patients presenting to community testing sites (
n
= 38). The analytical sensitivity of the NAAT-RDT and other laboratory NAATs was comparable. During clinical evaluation, the overall sensitivity and specificity were 92.9% and 98.3%, respectively, with little variation between settings. The Lucira NAAT-RDT is a portable and self-contained device that provides an easily interpreted result within 30 minutes following a bilateral nasal swab collection. Its performance was shown to be acceptable for use in three settings in this quality improvement project, facilitating patient flow and management.

IMPORTANCE
In hospitals during the COVID-19 pandemic, laboratory testing was important to reduce SARS-CoV-2 transmissions, while facilitating patient flow in the emergency department and pre-operative settings, and allowing for the safe return to work of exposed healthcare workers. Delayed test results from laboratory nucleic acid amplification tests (NAATs) posed a barrier to maximizing efficient patient flow and minimizing staffing shortages. This quality improvement project sought to evaluate the analytical and clinical performance of the Lucira Check-It COVID-19 Test, a point-of-care test that used NAAT technology, in the perioperative setting, emergency department, and community testing sites. We found the Lucira Check-It to have comparable performance to laboratory NAATs. It can be employed with little training for specimen collection, processing, and interpretation, and at a cost justifiable from the resources saved from avoiding sample transport and laboratory testing.
The diagnostic accuracy of the GeneXpert ESBL-
ampC
prototype assay for rapid PCR-based detection of extended-spectrum beta-lactamase genes directly from urine
Authors: Tops Sofie C. M. , Schapendonk Claire E. P. , Coolen Jordy P. M. , Tenover Fred C. , Tickler Isabella A. , Melchers Willem J. G. , Wertheim Heiman F. L. 
Published: November 2023

ABSTRACT

The emerging prevalence of extended-spectrum beta-lactamase (ESBL) producing Enterobacterales has implications for the empirical treatment of common infections, such as complicated urinary tract infections. To provide adequate treatment, while avoiding empirical therapy with last resort carbapenems, rapid identification of ESBL-containing pathogens is desirable. Routine urine samples were collected between February and July 2021 in two Dutch clinical medical microbiology laboratories according to a predefined list containing certain culture characteristics. All urine samples were screened for the presence of ESBL genes (
bla
CTX-M2
,
bla
CTX-M14
, and
bla
CTX-M15
) with random-access quantitative PCR (qPCR) using the Cepheid GeneXpert ESBL-
ampC
prototype assay. The qPCR and microbiological culture results were compared. After the calculation of the sensitivity and specificity, discrepancies were investigated by whole-genome sequencing. In total, 276 urine samples were available for ESBL analysis (94 ESBL culture positive and 182 ESBL culture negative). The sensitivity and specificity for detection of ESBL genes were 90.4% and 98.4%, respectively. In nine samples (9.6%), no ESBL genes were detected with GeneXpert, while in the microbiological culture, an ESBL-positive organism was isolated. This was mainly explained by non-GeneXpert ESBL genes:
bla
SHV
-family (
n
= 6; 75.0%),
bla
TEM
-family (
n
= 1; 12.5%), and
bla
SRT
-family (
n
= 1; 12.5%). The positive and negative predictive values in a hypothetical clinical scenario with a 15% ESBL prevalence were 0.91 and 0.98, respectively. Regarding
ampC
, the specificity appears to be satisfactory, but the sensitivity is low. The Cepheid GeneXpert ESBL assay could be beneficial for the fast and accurate detection of ESBL genes in regions where the epidemiology of ESBL genes coincides with the targets in the panel.

IMPORTANCE
Early identification of complicated urinary tract infections caused by ESBL-producing Enterobacterales has the potential to limit the use of carbapenems to those patients without alternative antibiotic options and avoid the empirical use of carbapenems in patients without ESBL-producing bacteria. The purpose for such a test will differ by setting and ESBL prevalence rates. Countries with low ESBL rates and cephalosporins as empiric treatment (e.g., The Netherlands) will need a rule-in test to decide to use carbapenems, while countries with high ESBL rates and empiric carbapenem treatment will need a rule-out test for ESBLs to de-escalate therapy early. Anyway, such as a test would—at least theoretically—improve patient care and reduce selective pressure for the emergence of carbapenem resistance.
An Effective Synthetic Approach to of 2-([5'-Aryl-2,2'-bipyridin]-6-yl)-5-aryl-1,3,4-oxadiazoles
Authors: Valieva M. I. , Starnovskaya E. S. , Kopchuk D. S. , Sharafieva E. R. , Slovesnova N. V. , Kovalev I. S. , Nosova E. V. , Zyryanov G. V. , Chupakhin O. N. 
Published: November 2023

Abstract
A convenient synthetic approach to 2-(2,2'-bipyridin-6-yl)-1,3,4-oxadiazole derivatives is proposed, which involves the preparation of 5-aryl-2,2'-bipyridine-6-carboxylic acid esters by the “1,2,4-triazine” methodology and the subsequent construction of the 1,3,4-oxadiazole ring via the modification of the ester group.
Rare case of central congenital hypothyroidism due to aTSHβmutation presenting with macro-orchidism
Authors: Karguppikar Madhura Bharat , Schoenmakers Nadia , Khadilkar Vaman , Khadilkar Anuradha 
Published: November 2023

A male infant was brought to our paediatric endocrine unit with typical clinical features of congenital hypothyroidism (CH) and striking macro-orchidism. On evaluation, free T3, free T4 and thyroid stimulating hormone (TSH) were found to be low, suggestive of congenital CH. Cortisol was within reference range and prolactin was mildly elevated. No suspicious lesions were encountered on neurosonography. On commencing treatment with thyroxine, clinical features of hypothyroidism showed dramatic improvement with regression of testicular enlargement. Genetic analysis revealed deletion of theTSHβgene.Our case highlights a rare presentation of central CH with macro-orchidism in a genetically proven deletion ofTSHβgene. Macro-orchidism has been widely reported inIGSF-1mutations leading to central CH; however, central CH and macro-orchidism have not been reported in association withTSHβdeletions.
Minimally invasive fenestration for decompression of C2-C3 spinal stenosis
Authors: Hebda Patrycja Weronika , Majewski Olaf 
Published: November 2023

Conventional techniques in neurosurgery such as laminectomy have been extensively displaced by minimally invasive types, owing to the character of complexity of cervical spinal region. Spinal canal stenosis at C2-C3 level is documented in the literature with the majority being caused by intervertebral disc herniations.This case reports a patient who presented with classical myelopathy symptoms and significant thickening of ligamentum flavum, while minimal spondylosis was detected at C2-C3 level. The decompression was performed from posterior approach and limited to the removal of ligamentum flavum with minimal resection of adjacent laminae, no fixation and no disc evacuation. After surgery, there was a significant improvement with preserved spinal stability.Although the anterior approach is more common for cervical spine, universal access site has not been defined in literature. We suggest that minimal decompression produces desirable effects with no need for fusion and preserving adequate stability of spinal complex.
Building upon the sugar beverage tax in Mexico: a modelling study of tax alternatives to increase benefits
Authors: Salgado Hernández Juan Carlos , Basto-Abreu Ana , Junquera-Badilla Isabel , Moreno-Aguilar Luis Alberto , Barrientos-Gutiérrez Tonatiuh , Colchero M. Arantxa 
Published: November 2023

IntroductionIn 2014, Mexico implemented a one peso-per-litre tax to sugar-sweetened beverage (SSB). Even though this tax reduced household purchases and predicted population health gains, the magnitude is lower compared with taxes implemented in other settings. In this study, we assessed what would happen if Mexico modified its existing tax to get higher benefits based on currently implemented taxes elsewhere.MethodsFor each tax scenario, we estimated net benefits as the difference between healthcare savings and lost jobs. We created hypothetical scenarios in which the current tax doubled or would be modified based on existing tax designs around the world including specific taxes (sugar-density or volumetric) and ad-valorem taxes.ResultsWe found that the largest benefits would correspond to a tax increase of 7.4 Mexican pesos (0.45 US dollars (USD)) per SSB litre, following the current tax in Bahrain (the highest tax rate option). This tax is predicted to yield net benefits equivalent to USD 24.7 billion after 10 years of the tax redesign. We also found that sugar-density taxes can result in larger net benefits since, in addition to reductions in consumption associated with responses to prices, they induce product reformulation. Middle-income households are the most benefited group because they reported the highest baseline prevalence of obesity and the largest price elasticity.ConclusionPolicymakers should consider pursuing a tax reform adding to the current tax, with significant increases in prices linked to a sugar-density strategy to reach a higher benefit.
Antibiotic prescription for children with acute respiratory tract infections in rural primary healthcare in Guangdong province, China: a cross-sectional study
Authors: He Diqiong , Li Feifeng , Wang Jiong , Zhuo Chao , Zou Guanyang 
Published: November 2023

ObjectivesThe objective of this study is to understand the characteristics and patterns of the first antibiotic prescriptions for children with acute respiratory infections (ARIs) in rural primary healthcare (PHC) in Guangdong province, China.DesignCross-sectional study.Setting and participantsWe used prescription data generated from the electronic medical record system of 37 township hospitals in two counties of Shaoguan City, Guangdong province. 46 699 first prescriptions for ARIs in children aged 0–18 years were screened from 444 979 outpatient prescriptions recorded between November 2017 and October 2018.Outcome measuresDescriptive analyses were used to report sociodemographic characteristics and antibiotic prescribing profiles. χ2analysis and binary logistic regression were used to analyse the factors associated with antibiotic prescriptions in children.ResultsOf the 46 699 sampled cases, 83.00% (n=38 759) received at least one antibiotic as part of their first prescription. Of the 38 759 sampled cases treated with antibiotics, 40.76% (n=15 799), 56.15% (n=21 762) and 31.59% (n=12 244) received parenteral antibiotics, broad-spectrum antibiotics and two or more kinds of antibiotics, respectively. Multivariable analysis showed that children aged ≤5 years were less likely to be prescribed with antibiotics than those aged 16–18 years (OR 0.545, p<0.001). Those with health insurance were more likely to be prescribed with antibiotics than those without health insurance (OR 1.677, p<0.001).ConclusionsMisuse and overuse of antibiotics were found in the prescriptions of children with ARIs in rural PHC. Antibiotic stewardship programme should be established to reduce the level of antibiotic prescriptions among children with ARIs in rural PHC, especially regarding the prescriptions of broad-spectrum antibiotics and parenteral antibiotics, tailored to different ages, sex and health insurance groups.
SalmonellaVaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohort
Authors: Hanumunthadu Brama , Kanji Nasir , Owino Nelly , Ferreira Da Silva Carla , Robinson Hannah , White Rachel , Ferruzzi Pietro , Nakakana Usman , Canals Rocio , Pollard Andrew J , Ramasamy Maheshi 
Published: November 2023

IntroductionInvasive non-typhoidal Salmonellosis (iNTS) is mainly caused bySalmonella entericaserovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidalSalmonellaeserovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containingS. Typhimurium andS. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.Method and analysisTheSalmonellaVaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities ofS. Typhimurium andS. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.Ethics and disseminationEthical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.Trial registration numberEudraCT Number: 2020-000510-14.
Role of excessive weight in intraocular pressure: a systematic review and meta-analysis
Authors: Waspodo Noro , Giffari Makkaraka Moh Anfasa , Nislawati Ririn , Ismail Abrar , Taufik Fadillah Zainal Ahmad , Lolok Giordano Bandi 
Published: November 2023

ObjectiveThis systematic review and meta-analysis aimed to analyse the effect of excess body weight on intraocular pressure (IOP) values.Method and analysisA literature search from PubMed, Medline and ScienceDirect Databases on 18 May 2023 was conducted by three reviewers, then filtered each study based on inclusion and exclusion criteria. For the quality assessment of included studies, the Newcastle–Ottawa Scale was adapted. Meta-analysis was performed using RevMan V.5.4 by entering the IOP values of each group to measure the mean difference.ResultsFrom 2656 studies, there were 9 studies that matched the criteria and then were included to perform a quantitative meta-analysis. The results showed a mean difference of 0.93 (95% CI: 0.67 to 1.18) of the excessive weight group against the normal weight group. This suggests that there is a significant relationship between excess body weight and increasing values of IOP.ConclusionIt can be concluded that excessive body weight tends to lead to higher IOP, which means that high IOP becomes a major risk factor for glaucoma.
Role of genetic polymorphisms in clopidogrel response variability: a systematic review
Authors: Lopez Jose , Mark Justin , Duarte Gustavo J , Shaban Mohammed , Sosa Franklin , Mishra Rishabh , Jain Swati , Tran An , Khizar Asma , Karpel Daniel , Acosta Giancarlo , Rodriguez-Guerra Miguel 
Published: November 2023

IntroductionClopidogrel is a P2Y12inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.Areas coveredAs a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.Experts’ commentaryOur findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.