bluuebunny/crossref_metadata_2025_split huggingface dataset:
An oral commensal attenuates
Pseudomonas aeruginosa
-induced airway inflammation and modulates nitrite flux in respiratory epithelium
Authors: Baty Joshua J. , Stoner Sara N. , McDaniel Melissa S. , Huffines Joshua T. , Edmonds Sara E. , Evans Nicholas J. , Novak Lea , Scoffield Jessica A. 
Published: October 2023

ABSTRACT

Polymicrobial airway infections in persons with cystic fibrosis (pwCF) can positively or negatively impact the course of disease. A major CF pathogen,
Pseudomonas aeruginosa,
often establishes a chronic infection leading to lung deterioration. Interestingly, the presence of certain oral commensal streptococci is correlated with improved outcomes for pwCF. We previously reported that hydrogen peroxide production by these commensals combined with nitrite generates reactive nitrogen intermediates (RNI), which inhibit
P. aeruginosa in vitro
. In this study, we utilized a rat co-infection lung model to assess whether oral commensal-generated RNI can restrict the pathogenesis of a CF isolate of
P. aeruginosa
. We report that the oral commensal
Streptococcus parasanguinis
and nitrite reduce
P. aeruginosa
-induced host inflammation in wild-type rats. To better recapitulate CF-specific airway conditions, we used a bronchial epithelial cell culture model to gain a better understanding of how
S. parasanguinis
and nitrite may influence
P. aeruginosa
burden during a CF infection. Hence, we co-infected wild-type and cystic fibrosis transconductance regulator (CFTR) channel-deficient bronchial epithelial cells with
P. aeruginosa
and
S. parasanguinis
with or without nitrite. Strikingly,
S. parasanguinis
reduced the bacterial burden of
P. aeruginosa
without nitrite, promoted epithelial cell viability, and stimulated nitrite production in the wild-type and CFTR-deficient epithelial cells, where nitrite induction was more apparent in the CFTR mutant cells. Taken together, our study demonstrates that the commensal
S. parasanguinis
may provide protection against
P. aeruginosa
-induced inflammation and cell death, as well as modulate nitrite flux in airway epithelial cells.

IMPORTANCE

Respiratory infections are a leading cause of morbidity and mortality in people with cystic fibrosis (CF). These infections are polymicrobial in nature with overt pathogens and other colonizing microbes present. Microbiome data have indicated that the presence of oral commensal bacteria in the lungs is correlated with improved outcomes. We hypothesize that one oral commensal,
Streptococcus parasanguinis,
inhibits CF pathogens and modulates the host immune response. One major CF pathogen is
Pseudomonas aeruginosa
, a Gram-negative, opportunistic bacterium with intrinsic drug resistance and an arsenal of virulence factors. We have previously shown that
S. parasanguinis
inhibits
P. aeruginosa in vitro
in a nitrite-dependent manner through the production of reactive nitrogen intermediates. In this study, we demonstrate that while this mechanism is evident in a cell culture model of the CF airway, an alternative mechanism by which
S. parasanguinis
may improve outcomes for people with CF is through immunomodulation.
The RND efflux system ParXY affects siderophore secretion in
Pseudomonas putida
KT2440
Authors: Stein Nicola Victoria , Eder Michelle , Burr Fabienne , Stoss Sarah , Holzner Lorenz , Kunz Hans-Henning , Jung Heinrich 
Published: October 2023

ABSTRACT

Tripartite efflux systems transport antimicrobial agents, toxic metabolites, and siderophores from Gram-negative cells into the environment. For example, the main siderophore pyoverdine of the soil bacterium
Pseudomonas putida
KT2440 is secreted into the environment via the PvdRT-OpmQ and MdtABC-OpmB systems. Here, we looked for efflux systems that might be involved in the secretion of pyoverdine in addition to the latter two systems. Screening of different efflux systems revealed that
parX
(encoding the periplasmic adapter protein of the ParXY system) is of particular importance for bacterial growth under iron limitation. Further analysis showed that the deletion of
parX
impairs the production and secretion of pyoverdine, causing the observed growth effect. The effects were dependent on the presence of other tripartite efflux systems and the conditions of iron limitation. The results suggest that ParXY not only plays a role in antibiotic resistance, as shown previously, but also influences the secretion of siderophores in a network of overlapping activities of different tripartite efflux systems.

IMPORTANCE

Gram-negative bacteria from the
Pseudomonas
group are survivors in various environmental niches. For example, the bacteria secrete siderophores to capture ferric ions under deficiency conditions. Tripartite efflux systems are involved in the secretion of siderophores, which are also important for antibiotic resistance. For one of these efflux systems, the resistance-nodulation-cell division transporter ParXY from the model organism
Pseudomonas putida
KT2440, we show that it influences the secretion of the siderophore pyoverdine in addition to its already known involvement in antibiotic resistance. Phenotypically, its role in pyoverdine secretion is only apparent when other pyoverdine secretion systems are inactive. The results confirm that the different tripartite efflux systems have overlapping substrate specificities and can at least partially functionally substitute for each other, especially in important physiological activities such as supplying the cell with iron ions. This fact must be taken into account when developing specific inhibitors for tripartite efflux systems.
RNAseq analysis of
Cellvibrio japonicus
during starch utilization differentiates between genes encoding carbohydrate active enzymes controlled by substrate detection or growth rate
Authors: Garcia Cecelia A. , Gardner Jeffrey G. 
Published: October 2023

ABSTRACT

Bacterial utilization of starch is increasingly of interest as the importance and contributions of animal gut microbiomes become more defined. Consequently, identifying and characterizing the bacterial enzymes responsible for the degradation, transport, and metabolism of starch will enable developments in pharmaceutical, biotechnological, and culinary industries searching for novel prebiotics, carrier molecules, and low glycemic index sweeteners. The current challenge is that bacteria proficient at starch utilization often have hundreds of carbohydrate active enzymes, and it is unclear which are essential for starch utilization using only homology-based bioinformatics or computational methods. Complementary experimental data are also needed, especially to understand the regulation of bacterial starch utilization. We have completed an RNAseq analysis of the Gram-negative bacterium
Cellvibrio japonicus
and found that it has sophisticated regulation that includes substrate sensing and growth rate components for genes that encode starch-degrading enzymes. Among the 22 genes predicted to encode starch-active enzymes,
C. japonicus
has 10 alpha-amylases, 4 alpha-glucosidases, 2 pullulnases, and 2 cyclomaltodextrin glucanotransferases, 15 of which were up-regulated during exponential growth on starch and 8 up-regulated in stationary phase. Growth analyses with an enzyme secretion deficient mutant of
C. japonicus
suggested that secreted amylases are essential for this bacterium to degrade starch. Our approach of coupling a physiological growth assay with transcriptomic data provides a platform to identify targets for further genetic or biochemical analysis that can be broadly applied to other starch-utilizing bacteria.

IMPORTANCE

Understanding the bacterial metabolism of starch is important as this polysaccharide is a ubiquitous ingredient in foods, supplements, and medicines, all of which influence gut microbiome composition and health. Our RNAseq and growth data set provides a valuable resource to those who want to better understand the regulation of starch utilization in Gram-negative bacteria. These data are also useful as they provide an example of how to approach studying a starch-utilizing bacterium that has many putative amylases by coupling transcriptomic data with growth assays to overcome the potential challenges of functional redundancy. The RNAseq data can also be used as a part of larger meta-analyses to compare how
C. japonicus
regulates carbohydrate active enzymes, or how this bacterium compares to gut microbiome constituents in terms of starch utilization potential.
A conserved metabolic signature associated with response to fast-acting anti-malarial agents
Authors: Simwela Nelson V. , Guiguemde W. Armand , Straimer Judith , Regnault Clement , Stokes Barbara H. , Tavernelli Luis E. , Yokokawa Fumiaki , Taft Benjamin , Diagana Thierry T. , Barrett Michael P. , Waters Andrew P. 
Published: October 2023

ABSTRACT

Characterizing the mode of action of anti-malarial compounds that emerge from high-throughput phenotypic screens is central to understanding how parasite resistance to these drugs can emerge. Here, we have employed untargeted metabolomics to inform on the mechanism of action of anti-malarial leads with different speed of kill profiles being developed by the Novartis Institute of Tropical Diseases (NITD). Time-resolved global changes in malaria parasite metabolite profiles upon drug treatment were quantified using liquid chromatography-based mass spectrometry and compared to untreated controls. Using this approach, we confirmed previously reported metabolomics profiles of the fast-killing (2.5 h) drug dihydroartemisinin (DHA) and the slower killing atovaquone. A slow-acting anti-malarial lead from NITD of imidazolopiperazine (IZP) class, GNF179, elicited little or no discernable metabolic change in malaria parasites in the same 2.5-h window of drug exposure. In contrast, fast-killing drugs, DHA and the spiroindolone (NITD246), elicited similar metabolomic profiles both in terms of kinetics and content. DHA and NITD246 induced peptide losses consistent with disruption of hemoglobin catabolism and also interfered with the pyrimidine biosynthesis pathway. Two members of the recently described class of anti-malarial agents of the 5-aryl-2-amino-imidazothiadiazole class also exhibited a fast-acting profile that featured peptide losses indicative of disrupted hemoglobin catabolism. Our screen demonstrates that structurally unrelated, fast-acting anti-malarial compounds generate similar biochemical signatures in
Plasmodium
pointing to a common mechanism associated with rapid parasite death. These profiles may be used to identify and possibly predict the mode of action of other fast-acting drug candidates.

IMPORTANCE
In malaria drug discovery, understanding the mode of action of lead compounds is important as it helps in predicting the potential emergence of drug resistance in the field when these drugs are eventually deployed. In this study, we have employed metabolomics technologies to characterize the potential targets of anti-malarial drug candidates in the developmental pipeline at NITD. We show that NITD fast-acting leads belonging to spiroindolone and imidazothiadiazole class induce a common biochemical theme in drug-exposed malaria parasites which is similar to another fast-acting, clinically available drug, DHA. These biochemical features which are absent in a slower acting NITD lead (GNF17) point to hemoglobin digestion and inhibition of the pyrimidine pathway as potential action points for these drugs. These biochemical themes can be used to identify and inform on the mode of action of fast drug candidates of similar profiles in future drug discovery programs.
Pneumatic Transport System REGATA-2 for Automation of Activation Analysis at the IREN Facility, FLNP JINR
Authors: Lobachev V. V. , Dmitriev A. Yu. , Borzakov S. B. , Smirnov A. A. , Zhironkin I. S. , Golubkov E. A. , Shvetsov V. N. 
Published: October 2023

Abstract
The IREN facility at the Frank Laboratory of Neutron Physics (FLNP) of the Joint Institute for Nuclear Research (JINR) is used for experiments to determine elemental composition of various samples by neutron activation analysis (NAA). A pneumatic transport system (PTS) REGATA-2 was implemented to automate the delivery of containers with samples to the irradiation position and back. The article describes the characteristics of the PTS, its adaptation for operation at the IREN facility, and also plans for subsequent modernization and future prospects. After the assembling of the system, the optimal parameters were chosen for irradiating the typical samples, and a calibration was created for a high-purity germanium detector, which let to consider the volume nature of the samples. Samples of archaeological ceramics from Kazakhstan were studied using the PTS. The features of the IREN facility let to use not only a neutron, but also a gamma-producing target. The first experiments on the qualitative determination of elements by gamma-activation analysis (GAA) were carried out, and the prospects for using the facility for these purposes were confirmed. The creation of the PTS let to automate the process of irradiation samples and increase the efficiency of research in NAA and GAA, especially for short-lived isotopes. It also reduces the negative impact of radiation on the human body.
A critical analysis of COVAX alliance and corresponding global health governance and policy issues: a scoping review
Authors: Pushkaran Anjali , Chattu Vijay Kumar , Narayanan Prakash 
Published: October 2023

IntroductionThe COVAX alliance is a novel approach to international partnership in global health intended to achieve the worthy goal of ‘COVID-19 vaccine equity’. This study aimed to identify the implementation challenges and framework gaps of COVAX and to explore the interconnected global health policy and governance gaps in ensuring equity, accessibility and affordability of vaccines.MethodsA scoping review was conducted to identify the implementation challenges and framework gaps of COVAX and related global health policy and governance gaps. A search was carried out in PubMed, Scopus, Springer Link and Embase databases. Manually searched the grey literature, such as official reports and articles. EndNote V.20 was used to manage the evidence screening, and data extraction was carried out in Microsoft Excel.ResultsSearches of four electronic databases and official UN, GAVI and WHO websites identified 4686 pieces of evidence. The 937 duplicates were removed, and the remaining 3749 articles were screened for the title and abstract. Most articles were eliminated as they do not address global COVAX or COVID-19 vaccine equity. The remaining 53 pieces of evidence were reviewed for full text, and ultimately 40 articles found eligible were included in the scoping review.ConclusionsThe implementation challenges of COVAX were attributed mainly to the phenomenon of vaccine nationalism by rich countries. The future global health policy and governance structure must be re-examined to address the inadequacies of such novel super public-and-private partnership models.
Prediction of refractive error and its progression: a machine learning-based algorithm
Authors: Barraza-Bernal Maria J , Ohlendorf Arne , Sanz Diez Pablo , Feng Xiancai , Yang Li-Hua , Lu Mei-Xia , Wahl Siegfried , Kratzer Timo 
Published: October 2023

ObjectiveMyopia is the refractive error that shows the highest prevalence for younger ages in Southeast Asia and its projection over the next decades indicates that this situation will worsen. Nowadays, several management solutions are being applied to help fight its onset and development, nonetheless, the applications of these techniques depend on a clear and reliable assessment of risk to develop myopia.Methods and analysisIn this study, population-based data of Chinese children were used to develop a machine learning-based algorithm that enables the risk assessment of myopia’s onset and development. Cross-sectional data of 12 780 kids together with longitudinal data of 226 kids containing age, gender, biometry and refractive parameters were used for the development of the models.ResultsA combination of support vector regression and Gaussian process regression resulted in the best performing algorithm. The Pearson correlation coefficient between prediction and measured data was 0.77, whereas the bias was −0.05 D and the limits of agreement was 0.85 D (95% CI: −0.91 to 0.80D).DiscussionThe developed algorithm uses accessible inputs to provide an estimate of refractive development and may serve as guide for the eye care professional to help determine the individual best strategy for management of myopia.
Increasing staff time for patient facing care on an inpatient geriatric unit through modification of multidisciplinary board rounds: a quality improvement project
Authors: Britton Hannah 
Published: October 2023

BackgroundNHS staff recruitment and retention have failed to keep pace with service demands and workforce burn-out is of significant concern. This quality improvement project (QIP) aimed to increase staff time for patient facing care through reducing duplication of hospital board rounds within a 36-bedded NHS inpatient geriatric ward.InterventionThirty-minute board rounds were reduced from twice daily (Monday–Friday) at 08:30 hours and midday to once daily at midday with the aim of freeing up staff time for patient care. A multidisciplinary team (MDT) safety briefing at 08:30 hours lasting 5–10 min was implemented to enable review of shift pressures and identification of patients who are unwell, newly admitted or due for discharge. Safety briefing format was amended to further support staff prioritisation.MethodsThis QIP was underpinned by the model for improvement, using Plan-Do-Study-Act cycles. Data were collected through a staff questionnaire alongside calculation of staff time spent at board rounds and safety huddles. Staff verbal feedback and questionnaire results were also used to improve and modify process’. Patient discharge data were collated via trust metrics as a balancing measure.ResultsThrough board round modification, 25 hours of MDT time was saved each week, with all responding staff reporting increased time for patient facing care following QIP implementation. >85% of questionnaire respondents agreed that board round changes resulted in improvement. Balancing measures collected as part of the project also revealed an increase in weekly ward discharges from an average of 15.75–17.5 confirming no negative impact on patient flow following board round amendments.ConclusionWhile significant staffing shortages continue, local innovations focused on staff time may have the potential to support effective use of limited resources.
Non-operative treatment of acute appendicitis in children: clinical efficacy of amoxicillin-clavulanic acid in a retrospective single-centre study
Authors: Picard Clémence , Abbo Olivier , Munzer Caroline , Ricco Lucas , Dubois Damien , Lemoine Cécile , Claudet Isabelle , Bréhin Camille 
Published: October 2023

BackgroundThe success rate of non-operative treatment (NOT) of acute uncomplicated appendicitis (AUA) in children varies from 65% to 95%. There are no recommendations on the appropriate antibiotic therapy.ObjectiveTo determine the clinical efficacy of amoxicillin-clavulanic acid for NOT of AUA in children.MethodsDesign: Cross-sectional study in a single medical centre. Settings: Emergency department and Paediatric Visceral Surgery department of the Children Hospital in Toulouse, France. Patients: Patients 5–15 years old who were diagnosed with appendicitis, (1) With abdominal pain and a first episode of acute appendicitis, (2) With no radiological or ultrasound evidence of appendicolith, appendiceal perforation, pelvic abscess nor peritonitis, and (3) With non-septic general aspect, were included. Interventions: NOT consisted of hospital admission. The antibiotic treatment was a combination of amoxicillin and clavulanic acid (80 mg/kg/day of amoxicillin): intravenous regimen during 48 hours followed by oral route during 7 days. Main outcome measure: Success rate of amoxicillin-clavulanic acid NOT in children with AUA at 2 years.ResultsThe initial success rate of amoxicillin-clavulanic acid NOT in children with AUA was 100% (104/104 patients). The success rate at 2 years was 85.6% (89/104) at discharge. None of the 15 patients who underwent surgery after recurrence of appendicitis presented with peritonitis, appendiceal perforation nor pelvic abscess.ConclusionNarrowed antibiotic therapy with amoxicillin and clavulanic acid seems to be an alternative to surgery in children with AUA. It is necessary to wait for the results of ongoing studies to confirm these results.
Oregon Death with Dignity Act access: 25 year analysis
Authors: Regnard Claud , Worthington Ana , Finlay Ilora 
Published: October 2023

Objectives
Assisted dying has been legally available in Oregon in the USA for 25 years, since when official reports have been published each year detailing the number of people who have used this option as well as sociodemographic and information about the process. The aim of this study was to examine changes over time in these data.

Methods
We collated and reviewed data on 2454 assisted deaths included in annual reports on assisted deaths published by the Oregon Health Authority from 1998 to 2022. Descriptive statistics were used to describe time trends.

Results
The number of assisted deaths in Oregon increased from 16 in 1998 to 278 in 2022. Over this time, patients’ health funding status changed from predominantly private (65%) to predominantly government support (79.5%), and there was an increase in patients feeling a burden and describing financial concerns as reasons for choosing an assisted death. There has been a reduction in the length of the physician–patient relationship from 18 weeks in 2010 to 5 weeks in 2022, and the proportion referred for psychiatric assessment remains low (1%). Data are frequently missing, particularly around complications.

Conclusions
The number and characteristics of people accessing assisted deaths, and the process, have changed since data collection started in 1998. Prospective studies are needed to examine the relationship between socioeconomic factors and the desire for an assisted death in Oregon.
Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm
Authors: Kim Hae Rang , Kim Min Jeoung , Kim Sunyeup , Chang Myung Soo , Kim Dong Joon , Kim Byung Moon , Park Keun Young , Kim Yong Bae , Lee Christopher Seungkyu , Byeon Suk Ho , Kim Sung Soo , Lee Seung Won , Kim Yong Joon 
Published: October 2023

Background
To evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA).

Methods
Incident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent treatment: observation (n=208 993), microsurgical clipping (n=14 168) and endovascular treatment (EVT) groups (n=30 079). The incidence and the incident time of RAO were analysed. HRs of RAO and associated risk factors were evaluated. Additionally, a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of UIAs.

Results
In the nationwide cohort analysis, the incidence of RAO was significantly higher in EVT group than in observation and clipping groups, especially within 60 days (early RAO (within 60 days): HR=4.00, 95% CI: 2.44 to 6.56); delayed RAO (after 60 days): HR=1.74, 95% CI: 1.13 to 2.68). Multivariable analysis showed that the presence of chronic kidney disease (p=0.009) and use of a balloon microcatheter during the procedure (p=0.013) were associated with a higher risk of RAO. In hospital cohort analysis, 11 (0.8%) cases of RAO occurred after EVT, whereas none occurred after microsurgical clipping (p<0.001). Patients with RAO were younger and received balloon microcatheters more frequently than their counterparts. Ten cases of RAO (90.9%) occurred in paraclinoid aneurysms, where EVT was preferred over microsurgical clipping.

Conclusions
Performing EVT for UIA may increase the risk of subsequent RAO. Care should be taken when treating paraclinoid aneurysms with balloon microcatheters.