bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of
glnA
(glutamine synthetase) expression by urea in non-pathogenic and uropathogenic
Escherichia coli
Authors: Urs Karthik , Zimmern Philippe E. , Reitzer Larry 
Published: October 2023

ABSTRACT

Previous transcriptomic studies have shown that
glnA
, which codes for glutamine synthetase (GS), is induced during growth of uropathogenic
E. coli
in urine. GS is at the intersection of carbon and nitrogen metabolism and is, not surprisingly, highly regulated. The
glnALG
operon specifies GS and two regulators of the nitrogen-regulated (Ntr) response, which scavenges nitrogenous compounds during nitrogen limitation. Transcription of
glnA
initiates from the cAMP receptor protein (Crp)-dependent
glnAp1
and the GlnG-dependent
glnAp2
promoters which respond to carbon and nitrogen limitation, respectively. High
glnA
expression is most often associated with nitrogen limitation, and its expression in urine could suggest nitrogen limitation, despite a high concentration of ammonia which suppresses
glnA
expression. To understand the basis for this expression, we compared growth of a non-pathogenic and a uropathogenic strain of
E. coli
in minimal media and a urine-like medium in wild-type,
ΔglnG
and
Δcrp
strains and assessed
glnA
expression with transcriptional and translational fusions, quantitative reverse transcription PCR, direct enzymatic assay, and Western blots. Our results showed that urea induced expression from the Crp-dependent
glnAp1
promoter which produced a transcript that was not translated, inhibited expression from the Ntr
glnAp2
promoter, and did not induce other Ntr genes, i.e., high
glnA
transcription can occur without induction of the Ntr response. We conclude that urea induces
glnA
expression in
E. coli
that is independent of the regulators of the Ntr response.

IMPORTANCE

The bacteria that cause urinary tract infections often become resistant to antibiotic treatment, and genes expressed during an infection could suggest non-antibiotic targets. During growth in urine,
glnA
(specifying glutamine synthetase) expression is high, but our results show that urea induces
glnA
expression independent of the regulation that responds to nitrogen limitation. Although our results suggest that
glnA
is an unlikely target for therapy because of variation in urinary components between individuals, our analysis of
glnA
expression in urine-like environments has revealed previously undescribed layers of regulation. In other words, regulatory mechanisms that are discovered in a laboratory environment do not necessarily operate in the same way in nature.
The expression and function of HSV ICP47 and its promoter in mice
Authors: Velusamy Thilaga , Singh Navneet , Croft Sarah , Smith Stewart , Tscharke David C. 
Published: October 2023

ABSTRACT

Herpes simplex virus (HSV) protein immediate early-infected cell protein (ICP)47 inhibits the transporter associated with antigen presentation, thereby concealing infected cells from the CD8
+
T-cell response in humans. By contrast, in mouse cells, ICP47 was found to be ineffective
in vitro
, despite some evidence for a role of this protein
in vivo
, specifically in the nervous system. Recent evidence suggests that the promoter that drives ICP47 might be active in the establishment of latency and during latency, leading to the possibility that a role might be found in protecting neurons that are latently infected with HSV from T-cell attack. Here, we explored this idea by studying a set of recombinant HSVs that were null for ICP47 protein and/or express Cre recombinase from ICP47 promoters, for use in a Cre-marking mouse model. Using these viruses, we found that contrary to previous studies, the activity of ICP47 in mouse cells is efficient enough to detectably reduce antigen presentation, albeit at levels much lower than in human cells. However,
in vivo
, we found no evidence of ICP47 influencing HSV pathogenesis or latency in a model where the virus does not spread beyond the peripheral nervous system. Finally, we show that the ability of the ICP47 promoter to drive protein expression during HSV latency is dependent on the location that it is placed in a recombinant virus genome and that such expression is undetectable from its native locus.

IMPORTANCE

Immune evasion and latency are key mechanisms that underlie the success of herpesviruses. In each case, interactions between viral and host proteins are required and due to co-evolution, not all mechanisms are preserved across host species, even if infection is possible. This is highlighted by the herpes simplex virus (HSV) protein immediate early-infected cell protein (ICP)47, which inhibits the detection of infected cells by killer T cells and acts with high efficiency in humans, but poorly, if at all in mouse cells. Here, we show that ICP47 retains modest but detectable function in mouse cells, but in an
in vivo
model we found no role during acute infection or latency. We also explored the activity of the ICP47 promoter, finding that it could be active during latency, but this was dependent on genome location. These results are important to interpret HSV pathogenesis work done in mice.
A diagnostic stewardship approach to prevent unnecessary testing of an enteric bacterial molecular panel
Authors: Campodónico Victoria L. , Hanlon Ann , Mikula Michael W. , Miller Jo-Anne , Gherna Michael , Carroll Karen C. , Simner Patricia J. 
Published: October 2023

ABSTRACT

After stool culture was replaced by an enteric bacterial panel (EBP) at the Johns Hopkins Hospital (JHH), many EBPs were ordered >3 days after admission (EBP >3 days) with low yield. To reduce unnecessary testing, a hard stop for ordering EBP >3 days was established with the option to override the restriction. The present study retrospectively evaluates the usefulness of overriding that restriction. A retrospective chart review was performed on all patients with an EBP >3 days at the JHH from November 2021 to October 2022. The override provided only one new diagnosis of
Salmonella
infection in a patient who developed diarrhea within 3 days of admission but was not tested by EBP until day 5. There were no positive EBPs >3 days in patients without diarrhea or who developed diarrhea >3 days after admission (diarrhea >3 days). Most patients with requests to override the restriction were also tested for
Clostridioides difficile
. All patients positive for
C. difficile
received treatment and their
C. difficile
positive test resulted
>
1 day before the EBP was run. There were no differences in yield in patients
>
65 years of age with significant comorbidities or associated with neutropenia, leukocytosis, human immunodeficiency virus status, or lactoferrin positivity. There were no positive tests in patients receiving stool softeners within the previous 48 hours of testing. Overriding the hard stop should not be approved in patients without diarrhea or with diarrhea >3 days, who received stool softeners within the previous 48 hours or have not been tested for more common causes of hospital-acquired diarrhea.

IMPORTANCE

Testing for enteric bacterial pathogens in patients hospitalized for more than 3 days is almost always inappropriate. Our study validates the utility of the 3-day rule and the use of clinical decision support tools to decrease unnecessary testing of enteropathogenic bacteria other than
C. difficile
. Overriding the restriction was very low yield. Our study highlights the importance of diagnostic stewardship and further refines the criteria for allowing providers to override the restriction while monitoring the impact of the interventions.
Anatomy of the Band Structure of the Newest Apparent Near-Ambient Superconductor LuH3 – xNx
Authors: Pavlov N. S. , Shein I. R. , Pervakov K. S. , Pudalov V. M. , Nekrasov I. A. 
Published: October 2023

Recently it was claimed that nitrogen-doped lutetium hydride exhibited a near-ambient superconducting transition with a temperature of 294 K at a pressure of only 10 kbar, this pressure being several orders of magnitude lower than previously demonstrated for hydrides under pressure. In this paper, we investigate within DFT + U the electronic structure of both parent lutetium hydride LuH3 and nitrogen doped lutetium hydride LuH2.75N0.25. We calculated corresponding bands, density of states and Fermi surfaces with and without spin-orbit coupling (SOC). It is shown that in the stoichiometric system the Lu-5$$d$$ states cross the Fermi level while the H-$$1s$$ states make almost no contribution at the Fermi level. However, with nitrogen doping, the N‑$$2p$$ states enter the Fermi level in large quantities and bring together a significant contribution from the H‑$$1s$$ states. The presence of N-$$2p$$ and H-$$1s$$ states at the Fermi level in a doped compound can facilitate the emergence of superconductivity. Surprisingly, SOC splits quite significantly (0.1–0.25 eV) nitrogen bands in LuH2.75N0.25 just below the Fermi level. For instance, nitrogen doping almost doubles the value of DOS at the Fermi level. Simple BCS analysis shows that the nitrogen doping of LuH3 can provide $${{T}_{c}}$$ more than 100 K and even increase it with further hole doping.
Are maternal vaccines effective and safe for mothers and infants? A systematic review and meta-analysis of randomised controlled trials
Authors: de Bruin Odette , Phijffer Emily , Ahmadizar Fariba , van der Maas Nicoline , Wildenbeest Joanne , Sturkenboom Miriam , Bont Louis , Bloemenkamp Kitty 
Published: October 2023

IntroductionMaternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants. We aimed to provide an up-to-date overview of the efficacy and safety of all available maternal vaccines.MethodsWe searched PubMed, Embase, CENTRAL and ClinicalTrials.gov on 1 February 2022, for phase III and IV randomised controlled trials (RCTs) that compared maternal vaccination against any pathogen with placebo or no vaccination. Primary outcomes were laboratory-confirmed or clinically confirmed disease in mothers and infants. Secondary safety outcomes included intrauterine growth restriction, stillbirth, maternal death, preterm birth, congenital malformations and infant death. Random effects meta-analysis were used to calculate pooled risk ratio’s (RR). Quality appraisal was performed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).ResultsSix RCTs on four maternal vaccines, influenza, tetanus, diphtheria and pertussis (Tdap), pneumococcal and respiratory syncytial virus (RSV) were eligible. The overall risk of bias and certainty of evidence varied from low to high. Maternal influenza vaccination significantly reduced the number of laboratory-confirmed influenza cases (RR 0.58, 95% CI 0.42 to 0.79, event rate 57 vs 98, 2 RCTs, n=6003, I2=0%), and clinically confirmed influenza cases in mothers (RR 0.88, 95% CI 0.78 to 0.99, event rate 418 vs 472, 2 RCTs, n=6003, I2=0%), and laboratory-confirmed influenza in infants (RR 0.66, 95% CI 0.52 to 0.85, event rate 98 vs 148, 2 RCTs, n=5883, I2=0%), although this was not significant for clinically confirmed influenza in infants (RR 0.99, 95% CI 0.94 to 1.05, event rate 1371 vs 1378, 2 RCTs, n=5883, I2=0%). No efficacy data were available on maternal Tdap vaccination. Maternal pneumococcal vaccination did not reduce laboratory-confirmed and clinically confirmed middle ear disease (RR 0.49, 95% CI 0.24 to 1.02, event rate 9 vs 18, 1 RCT, n=133 and RR 0.88 95% CI 0.69 to 1.12, event rate 42 vs 47, 1 RCT, n=133, respectively), and clinically confirmed lower-respiratory tract infection (LRTI) (RR 1.08, 95% CI 0.82 to 1.43, event rate 18 vs 34, 1 RCT, n=70) in infants. Maternal RSV vaccination did not reduce laboratory-confirmed RSV LRTI in infants (RR 0.75, 95% CI 0.56 to 1.01, event rate 103 vs 71, 1 RCT, n=4527). There was no evidence of a significant effect of any of the maternal vaccines on the reported safety outcomes.ConclusionsThe few RCTs with low event rates suggest that, depending on the type of maternal vaccine, the vaccine might effectively prevent disease and within its size does not show safety concerns in mothers and infants.PROSPERO registration numberCRD42021235115.
Geospatial patterns of progress towards UNAIDS ‘95-95-95’ targets and community vulnerability in Zambia: insights from population-based HIV impact assessments
Authors: Cuadros Diego F , Chowdhury Tuhin , Milali Masabho , Citron Daniel T , Nyimbili Sulani , Vlahakis Natalie , Savory Theodora , Mulenga Lloyd , Sivile Suilanji , Zyambo Khozya Davie , Bershteyn Anna 
Published: October 2023

IntroductionIn sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the ‘95-95-95’ targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the ‘95-95-95’ indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps.MethodsThis study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimised hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access and social determinants of healthcare utilisation. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioural covariates and the three main outcomes of study.ResultsVaried progress towards the ‘95-95-95’ targets were observed in different regions of Zambia. Each ‘95’ displayed a unique geographical pattern, independent of HIV prevalence, resulting in four distinct geographical clusters. Factors associated with gaps in the ‘95s’ include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on antiretroviral therapy and having detectable viral loads.ConclusionsOur study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographical patterns and levels of performance in the ‘95-95-95’ targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors and developing innovative strategies to improve local HIV care continuum outcomes.
NISCAHN: a phase II trial of nivolumab in patients with salivary gland carcinoma (Unicancer ORL-08)
Authors: Fayette Jérôme , Even Caroline , Digue Laurence , Geoffrois Lionnel , Rolland Fréderic , Cupissol Didier , Guigay Joel , Le Tourneau Christophe , Dillies Anne Françoise , Zanetta Sylvie , Bozec Laurence , Borel Christian , Couchon-Thaunat Sophie , Costes-Martineau Valérie , Sudaka-Bahadoran Anne , Jallut Isabelle , Garic Florence , Lardy-Cleaud Audrey , Chabaud Sylvie 
Published: October 2023

ObjectiveSalivary gland cancers (SGC) are rare cancers with currently no standard treatment for recurrent/metastatic disease. Based on checkpoint inhibitors benefit in a broad range of tumours, NIvolumab in Salivary gland CArcinoma of the Head and Neck (NISCAHN) evaluated nivolumab efficacy in SGC.Methods and analysisIn this phase II single-stage Fleming design, patients with SGC with a progressive disease progression within 6 months prior to entering the study, were divided into ACC (adenoid cytic carcinoma) and non-ACC. All received nivolumab for a maximum of 12 months. The primary endpoint was the non-progression rate at 6 months (NPR6m) according to Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), tumour growth rate, safety and quality of life (health-related quality of life).Results46 patients with ACC and 52 patients without ACC were enrolled over 1 year. Median follow-up was respectively 29.2 months and 16.9 months for patients with ACC and non-ACC. In the ACC cohort, with 15/45 patients non-progressive at 6 months, the primary endpoint was met (33.3%; 95% CI 21.8 to NE). Nivolumab failed to demonstrate efficacy in the non-ACC cohort (NPR6m: 14.0%; 7/50 patients). ORR, PFS and OS were 8.7% (95% CI 2.4 to 20.8), 5.3 (95% CI 3.2 to 5.6) and 17.2 months (95% CI 12.5-NE) in the ACC cohort, and 3.8% (95% CI 0.5 to 13.2), 1.8 (95% CI 1.7 to 3.5) and 11.5 months (95% CI 7.5 to 14.8) in the non-ACC cohort. Nivolumab safety profile was consistent with previous reports.ConclusionNivolumab has limited efficacy in SGC. Differential results were observed in the two cohorts. The primary endpoint was met in the ACC cohort and no new safety signals were identified.Trial registration numberEudraCT number: 2016-001794-32/NCT03132038.
Use of immersive virtual reality for stress reduction during botulinum toxin injection for spasticity (RVTOX): a study protocol of a randomised control trial
Authors: Bougeard Marie , Hauret Isabelle , Pelletier-Visa Mathilde , Plan-Paquet Anne , Givron Pascale , Badin Marin , Pereira Bruno , Lanhers Charlotte , Coudeyre Emmanuel 
Published: October 2023

IntroductionBotulinum toxin injection is a common way to help reduce spasticity in the body caused by central neurological damage such as cerebral stroke, multiple sclerosis or traumatic brain injury. The pain felt during the injection causes most patients to experience significant stress for further injections, the level of which is variable between patients.Immersive virtual reality is a digital technique that simulates the three-dimensional spatial and sound environment around a person said to be immersed in this virtualised world. The effectiveness of virtual reality comes from the intensity of this multisensory immersion, known as the feeling of presence (ie, subjective experience of being in one place or one environment, even when you are physically in another one).Only one research article in paediatrics has shown that immersive reality technique has a positive impact on the level of pain and agitation suffered during botulinum toxin injections. The purpose of this study is therefore to evaluate with sufficient assurance the following research hypothesis: virtual reality can help adults cope with the stress and pain of botulinum toxin treatment injection.Methods and analysisThe research hypothesis will be tested using a randomised stepped-wedge method versus a non-invasive technique (headset with virtual reality session) to its control (headset with no image nor audio).The design leads to considering the injection as a statistical unit as all participants will undergo the standard condition, the control technique and virtual reality technique.Ethics and disseminationPatients will be fully and fairly informed in terms of their understanding of the objectives and constraints of the study and the possible risks involved. They will also be entitled to refuse the study and/or withdraw, and this refusal will have no impact on their follow-up as part of their pathology. Dissemination of the results of this study will be through peer-reviewed publications, and national and international conferences.Ethics were approved by the Comité de Protection des Personnes Nord-Ouest in January 2022.Trial registration numberNCT05364203.
Investigating mortality and morbidity associated with UrINary incontinence during Older Womens Secondary Care Admissions and exploring nurses experiences of delivering related care (U-INconti): a mixed methods research protocol
Authors: Iles-Smith Heather , McMillan Isobel May , Evans-Cheung Trina , Haas Eckersley Ruth , Russell Margaret , Wood Julie , McCarthy Robyn Emelda , Rosson Lyndsey , Doxford-Hook Liz , Fu Yu , McGowan Linda 
Published: October 2023

IntroductionUrinary incontinence (UI) is associated with increasing age and is more frequently experienced by women. Despite 40% prevalence in the community, little is known about the prevalence/incidence of UI in older women during hospital admission. UI during hospital admissions, within this group, has also been under-researched in terms of its relationship to specific clinical conditions and mortality rates. Given that UI has serious implications for both patient care and women’s general health and well-being on discharge, this protocol describes a planned research project which aims to determine mortality, morbidity, prevalence and incidence of UI in older women (≥55 years) during hospital admission to inform nursing practice. Additionally, it aims to explore the experience of nurses who deliver women’s care.Methods and analysisThis is an explanatory mixed-methods study consisting of two phases: (1) retrospecitive analysis of electronic patient care records (EPCR) to determine prevalence/incidence of UI, clinical conditions most likely associated with UI and any associations between UI and death, (2) nurse interviews to explore views, knowledge and perceptions of performing the nursing assessment and providing care for older women (≥55 years) with UI during admission. EPCR will be gained from a National Health Service (NHS) teaching hospital. Nurse interviews will be conducted with nurses from an alternative but similar-sized NHS hospital.Ethics and disseminationEthical approval is provided by the University of Salford Ethics Committee and regulatory approval by the NHS Health Research Authority (Integrated Research Application System project ID: 303118). Local NHS trust approval to access electronic care records for the purposes of analysis of anonymised data has been provided by one of the two collaborating NHS hospitals. Findings will be disseminated through open-access geriatric or urogynaecology journals and presented to relevant stakeholders at local, national and international meetings including scientific meetings such as the UK Continence Society and International Continence Society.