bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualization of immune pathways that enhance the neutralizing antibody response to vaccines after primary immunization
Authors: Verma Anita , De Pascalis Roberto , Mocca Christopher P. , Li Xiaohong , Burns Drusilla L. 
Published: February 2024

ABSTRACT

We examined the relationship between the association of a vaccine antigen with immune cells in secondary lymphoid organs shortly after immunization and the resulting neutralizing antibody response induced by that antigen using three antigenic forms of anthrax protective antigen (PA) that induce qualitatively different antibody responses. The three PA forms used were wild-type PA, which binds to anthrax toxin receptors and elicits a robust antibody response that includes both neutralizing and non-neutralizing antibodies; a receptor-binding-deficient (RBD) mutant form of PA, which does not bind cellular receptors and elicits only barely detectable antibody responses; and an engineered chimeric form of PA, which binds cholera toxin receptors and elicits a robust total antibody response but a poor neutralizing antibody response. We found that both wild-type PA and the PA chimera associated with immune cells in secondary lymphoid organs after immunization, but the RBD mutant PA exhibited minimal association, revealing a relationship between antigen binding to toxin receptors on immune cells after immunization and subsequent antibody responses. A portion of wild-type PA that bound to immune cells was cell surface-associated and maintained its native conformation. Much lower amounts of conformationally intact PA chimera were associated with immune cells after immunization, correlating with the lower neutralizing antibody response elicited by the PA chimera. Thus, binding of an antigen to receptors on immune cells in secondary lymphoid organs after immunization and maintenance of conformational integrity of the cell-associated antigen help dictate the magnitude of the resulting neutralizing antibody response, but not necessarily the total antibody response.

IMPORTANCE
Many vaccines protect by the induction of antibodies that neutralize the action of the pathogen. Here, we followed the fate of three antigenic forms of a vaccine antigen in secondary lymphoid organs after immunization to investigate events leading to a robust neutralizing antibody response. We found that the magnitude of the neutralizing antibody response, but not the total antibody response, correlates with the levels of conformationally intact antigen associated with immune cells in secondary lymphoid organs after primary immunization. We believe that these results provide important insights into the genesis of neutralizing antibody responses induced by vaccine antigens and may have implications for vaccine design.
Complete genome sequence of
Fusobacterium vincentii
strain TDC100 isolated from an apical periodontitis lesion
Authors: Yonezawa Hideo , Kokubu Eitoyo , Kikuchi Yuichiro , Ishihara Kazuyuki 
Published: February 2024

ABSTRACT

This study reports the complete genome sequence of
Fusobacterium vincentii
strain TDC100. The complete circular chromosome of strain TDC100 was obtained and assembled using a combination of short- and long-read sequencing.
Draft genome of
Staphylococcus capitis
O112, isolated from the cheek swab of a healthy female
Authors: Jablonska Sandra , Kula Alex , Putonti Catherine 
Published: February 2024

ABSTRACT

Staphylococcus capitis
is a Gram-positive bacterium that is part of the normal human flora, found in multiple anatomical sites. Here, we present the 2.5-Mbp draft genome of
S. capitis
O112, isolated from a cheek swab collected from a healthy female.
PEXEL is a proteolytic maturation site for both exported and non-exported
Plasmodium
proteins
Authors: Fierro Manuel A. , Muheljic Ajla , Sha Jihui , Wohlschlegel James , Beck Josh R. 
Published: February 2024

ABSTRACT

Obligate intracellular malaria parasites dramatically remodel their erythrocyte host through effector protein export to create a niche for survival. Most exported proteins contain a pentameric

P
lasmodium

ex
port
el
ement (PEXEL)/host-targeting motif that is cleaved in the parasite ER by the aspartic protease Plasmepsin V (PMV). This processing event exposes a mature N terminus required for translocation into the host cell and is not known to occur in non-exported proteins. Here, we report that the non-exported parasitophorous vacuole protein UIS2 contains a
bona fide
PEXEL motif that is processed in the
P. falciparum
blood stage. While the N termini of exported proteins containing the PEXEL and immediately downstream ~10 residues are sufficient to mediate translocation into the RBC, the equivalent UIS2 N terminus does not promote the export of a reporter. Curiously, the UIS2 PEXEL contains an unusual aspartic acid at the fourth position, which constitutes the extreme N-terminal residue following PEXEL cleavage (P1′, RIL↓DE). Using a series of chimeric reporter fusions, we show that Asp at P1′ is permissive for PMV processing but abrogates export. Moreover, mutation of this single UIS2 residue to alanine enables export, reinforcing that the mature N terminus mediates export, not PEXEL processing
per se
. Prompted by this observation, we further show that PEXEL sequences in the N termini of other non-exported rhoptry proteins are also processed, suggesting that PMV may be a more general secretory maturase than previously appreciated, similar to orthologs in related apicomplexans. Our findings provide new insight into the unique N-terminal constraints that mark proteins for export.

IMPORTANCE

Host erythrocyte remodeling by malaria parasite-exported effector proteins is critical to parasite survival and disease pathogenesis. In the deadliest malaria parasite
Plasmodium falciparum
, most exported proteins undergo proteolytic maturation via recognition of the pentameric

P
lasmodium

ex
port
el
ement (PEXEL)/host-targeting motif by the aspartic protease Plasmepsin V, which exposes a mature N terminus that is conducive for export into the erythrocyte host cell. While PEXEL processing is considered a unique mark of exported proteins, we demonstrate that PEXEL motifs are present and processed in non-exported proteins. Importantly, we show that specific residues at the variable fourth position of the PEXEL motif inhibit export despite being permissive for processing, reinforcing that features of the mature N terminus, and not PEXEL cleavage, identify cargo for export. This opens the door to further inquiry into the nature and evolution of the PEXEL motif.
Refined understanding of the impact of the
Mycobacterium tuberculosis
complex diversity on the intrinsic susceptibility to pretomanid
Authors: Rupasinghe Praharshinie , Reenaers Rabab , Vereecken Jens , Mulders Wim , Cogneau Sari , Merker Matthias , Niemann Stefan , Vally Omar Shaheed , Rigouts Leen , Köser Claudio U. , Decroo Tom , de Jong Bouke C. 
Published: February 2024

ABSTRACT

Previous work reported unprecedented differences in the intrinsic
in vitro
susceptibility of the
Mycobacterium tuberculosis
complex (MTBC) to pretomanid (Pa) using the Mycobacteria Growth Indicator Tube (MGIT) system. We tested 125 phylogenetically diverse strains from all known MTBC lineages (
1
–
9
) without known Pa resistance mutations and four strains with known resistance mutations as controls. This confirmed that MTBC, unlike most bacteria-antimicrobial combinations, displayed substantial differences in the intrinsic susceptibility relative to the technical variation of Pa MIC testing. This was also the case for the Middlebrook 7H11 (7H11) medium, demonstrating that these differences were not specific to MGIT. Notably, lineage 1 was confirmed to have intrinsically elevated MICs compared with lineages 2, 3, 4, and 7 (L2–4/7), underlining the urgent need for WHO to publish its decision of whether lineage 1 should be deemed treatable by BPaL(M), the now preferred all-oral regimen for treating rifampin-resistant tuberculosis. Lineages 5 and 6, which are most frequent in West Africa, responded differently to Pa, with lineage 5 being more similar to L2–4/7 and lineage 6 being more susceptible. More data are needed to determine whether 7H11 MICs are systematically lower than those in MGIT.

IMPORTANCE

This study confirmed that the
Mycobacterium tuberculosis
complex lineage 1, responsible for 28% of global tuberculosis cases, is less susceptible to pretomanid (Pa). It also refined the understanding of the intrinsic susceptibilities of lineages 5 and 6, most frequent in West Africa, and lineages 8 and 9. Regulators must review whether these
in vitro
differences affect the clinical efficacy of the WHO-recommended BPaL(M) regimen and set breakpoints for antimicrobial susceptibility testing accordingly. Notably, regulators should provide detailed justifications for their decisions to facilitate public scrutiny.
A 6-year retrospective study of clinical features, microbiology, and genomics of Shiga toxin-producing
Escherichia coli
in children who presented to a tertiary referral hospital in Costa Rica
Authors: Perez-Corrales Cristian , Peralta-Barquero Valeria , Duarte-Martinez Francisco , Oropeza-Barrios Gletty 
Published: February 2024

ABSTRACT

Shiga-toxin-producing
Escherichia coli
(STEC) is associated with diarrhea and hemolytic uremic syndrome (HUS). STEC infections in Costa Rica are rarely reported in children. We gathered all the records of STEC infections in children documented at the National Children’s Hospital, a tertiary referral hospital, from 2015 to 2020. Clinical, microbiological, and genomic information were analyzed and summarized. A total of 3,768 diarrheal episodes were reviewed. Among them, 31 STEC were characterized (29 fecal, 1 urine, and 1 bloodstream infection). The prevalence of diarrheal disease due to STEC was estimated at 0.8% (
n
= 29/3,768), and HUS development was 6.4% (
n
= 2/31). The
stx1
gene was found in 77% (
n
= 24/31) of STEC strains.
In silico
genomic predictions revealed a predominant prevalence of serotype O118/O152:H2, accompanied by a cluster exhibiting allele differences ranging from 33 to 8, using a core-genome multilocus sequence typing (cgMLST) approach. This is the first study using a genomic approach for STEC infections in Costa Rica.

IMPORTANCE

This study provides a comprehensive description of clinical, microbiological, genomic, and demographic data from patients who attended the only pediatric hospital in Costa Rica with Shiga-toxin-producing
Escherichia coli
(STEC) infections. Despite the low prevalence of STEC infections, we found a predominant serotype O118/O152:H2, highlighting the pivotal role of genomics in understanding the epidemiology of public health threats such as STEC. Employing a genomic approach for this pathogen for the first time in Costa Rica, we identified a higher prevalence of STEC in children under 2 years old, especially those with gastrointestinal comorbidities, residing in densely populated regions. Limitations such as potential geographic bias and lack of strains due to direct molecular diagnostics are acknowledged, emphasizing the need for continued surveillance to uncover the true extent of circulating serotypes and potential outbreaks in Costa Rica.
Microbiome composition and function within the Kellet’s whelk perivitelline fluid
Authors: Daniels Benjamin N. , Nurge Jenna , De Smet Chanel , Sleeper Olivia , White Crow , Davidson Jean M. , Fidopiastis Pat 
Published: February 2024

ABSTRACT

Microbiomes have gained significant attention in ecological research, owing to their diverse interactions and essential roles within different organismal ecosystems. Microorganisms, such as bacteria, archaea, and viruses, have profound impact on host health, influencing digestion, metabolism, immune function, tissue development, and behavior. This study investigates the microbiome diversity and function of Kellet’s whelk (
Kelletia kelletii
) perivitelline fluid (PVF), which sustains thousands of developing
K. kelletii
embryos within a polysaccharide and protein matrix. Our core microbiome analysis reveals a diverse range of bacteria, with the
Roseobacter
genus being the most abundant. Additionally, genes related to host-microbe interactions, symbiosis, and quorum sensing were detected, indicating a potential symbiotic relationship between the microbiome and Kellet’s whelk embryos. Furthermore, the microbiome exhibits gene expression related to antibiotic biosynthesis, suggesting a defensive role against pathogenic bacteria and potential discovery of novel antibiotics. Overall, this study sheds light on the microbiome’s role in Kellet’s whelk development, emphasizing the significance of host-microbe interactions in vulnerable life history stages. To our knowledge, ours is the first study to use 16S sequencing coupled with RNA sequencing (RNA-seq) to profile the microbiome of an invertebrate PVF.

IMPORTANCE
This study provides novel insight to an encapsulated system with strong evidence of symbiosis between the microbial inhabitants and developing host embryos. The Kellet’s whelk perivitelline fluid (PVF) contains microbial organisms of interest that may be providing symbiotic functions and potential antimicrobial properties during this vulnerable life history stage. This study, the first to utilize a comprehensive approach to investigating Kellet’s whelk PVF microbiome, couples 16S rRNA gene long-read sequencing with RNA-seq. This research contributes to and expands our knowledge on the roles of beneficial host-associated microbes.
Personal strategies to reduce the effects of landscape fire smoke on asthma-related outcomes: a protocol for systematic review and meta-analysis
Authors: Beyene Tesfalidet , Gibson Peter G , Murphy VE , Jensen Megan E , McDonald Vanessa M 
Published: February 2024

IntroductionLandscape fire smoke (LFS) contains several hazardous air pollutants that are known to be detrimental to human health. People with asthma are more vulnerable to the health impact of LFS than general populations. The aim of this review is to investigate the effectiveness of personal strategies to reduce the effect of LFS on asthma-related outcomes.Methods and analysisWe will electronically search databases such as Medline, Embase, CINAHL and Cochrane Clinical Trials Register to identify eligible articles for the review. Screening of search results and data extraction from included studies will be completed by two independent reviewers. The risk of bias (RoB 2) will be assessed using the Risk of Bias Assessment Tool for Non-Randomised Studies for observational studies, the Cochrane Collaboration tool for assessing the RoB 2 for randomised controlled trials (RCTs) and the Risk Of Bias In Nonrandomized Studies of Interventions tool for non-RCTs. A random-effect meta-analysis will be performed to determine the pooled summary of findings of the included studies. If meta-analysis is not possible, we will conduct a narrative synthesis. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Ethics and disseminationThis study will synthesise the available evidence obtained from published studies and as such, no ethical approval is required. The review will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42022341120.
How the commercial virtual care industry gathers, uses and values patient data: a Canadian qualitative study
Authors: Spithoff Sheryl , McPhail Brenda , Vesely Leslie , Rowe Robyn K , Mogic Lana , Grundy Quinn 
Published: February 2024

ObjectivesTo understand and report on the direct-to-consumer virtual care industry in Canada, focusing on how companies collect, use and value patient data.DesignQualitative study using situational analysis methodology.SettingCanadian for-profit virtual care industry.Participants18 individuals employed by or affiliated with the Canadian virtual care industry.MethodsSemistructured interviews were conducted between October 2021 and January 2022 and publicly available documents on websites of commercial virtual care platforms were retrieved. Analysis was informed by situational analysis, a constructivist grounded theory methodology, with a continuous and iterative process of data collection and analysis; theoretical sampling and creation of theoretical concepts to explain findings.ResultsParticipants described how companies in the virtual care industry highly valued patient data. Companies used data collected as patients accessed virtual care platforms and registered for services to generate revenue, often by marketing other products and services. In some cases, virtual care companies were funded by pharmaceutical companies to analyse data collected when patients interacted with a healthcare provider and adjust care pathways with the goal of increasing uptake of a drug or vaccine. Participants described these business practices as expected and appropriate, but some were concerned about patient privacy, industry influence over care and risks to marginalised communities. They described how patients may have agreed to these uses of their data because of high levels of trust in the Canadian health system, problematic consent processes and a lack of other options for care.ConclusionsPatients, healthcare providers and policy-makers should be aware that the direct-to-consumer virtual care industry in Canada highly values patient data and appears to view data as a revenue stream. The industry’s data handling practices of this sensitive information, in the context of providing a health service, have implications for patient privacy, autonomy and quality of care.
Investigating healthcare workforce recruitment and retention: a mixed-methods study protocol
Authors: Alkan Erkan , Cushen-Brewster Noreen , Anyanwu Philip 
Published: February 2024

IntroductionAlthough the sustainability of the health workforce has been identified as essential to achieving health and wider development objectives, challenges with securing and retaining the healthcare workforce persist. In the UK, there are notable shortages across a wide range of National Health Service (NHS) staff groups, with a high staff turnover indicating retention issues in the healthcare workforce. In addition, gaps exist in understanding the root cause of individual organisation’s workforce deficiencies and how their practice environment factors interact to impact workforce recruitment and retention.Methods and analysisAn exploratory mixed-methods approach will be conducted to investigate the impact of organisational practice environment factors on healthcare workforce recruitment and retention in two Integrated Care Systems (ICS) in the East of England. We will conduct an online survey of newly qualified and established nurses and allied health professionals using a questionnaire adapted from two validated instruments. Our calculation suggests a sample size of 373 participants, we will aim to surpass this in our recruitment to strengthen the statistical analyses. Multilevel linear regression models will be fitted to evaluate the association between organisational practice environmental factors and staff recruitment and retention. The qualitative interviews will explore the experiences and perspectives of staff and senior leaders to explain the survey results and any significant associations therein. Also, the interviews will explore how to strengthen the partnership between higher education institutions, Health Education England, health and care service providers, NHS nursing and allied health professional staff to enhance recruiting and retaining staff. An exploratory inductive coding and analysis will follow Braun and Clarke’s recommendations to generate key themes from transcribed interview data.Ethics and disseminationEthical approval has been obtained through the University of Suffolk Research Ethics Committee (approval number: RETH(S)22/051). Findings from our work will be disseminated through publications in peer-reviewed journals; presentations at stakeholders’ events, professional and academic conferences; and short reports for stakeholders, including participating ICSs.
Adequacy of cancer-related pain management using the Pain Management Index among patients with cancer in the Northwest oncology centres of Ethiopia: an institutional-based cross-sectional study
Authors: Mihiretie Endalamaw Aschale , Siyum Tewodros Solomon , Tamene Fasil Bayafers 
Published: February 2024

ObjectiveThe aim of this study was to assess the adequacy of cancer-related pain (CRP) management and associated factors among patients with cancer in the Northwest oncology centres of Ethiopia.Design and settingAn institutional-based multicentre cross-sectional study was conducted among patients with cancer in the Northwest oncology centres of Ethiopia from May to July 2022.ParticipantsAll oncology patients at selected hospitals who fulfilled the inclusion criteria during the data collection period were the study population.Main outcome measuresThe main outcome of this study was the adequacy of CRP management, which was measured by the Pain Management Index (PMI). A systematic random sampling technique was used to select representatives from each study area. Data entry and analysis were done using EpiData V.4.6.1 and SPSS V.26, respectively. Binary logistic regression was conducted to determine independent predictors of the adequacy of CRP management. A p value of <0.05 was considered statistically significant.ResultsFrom a total of 422 included respondents, about 67.5% of the participants had adequate CRP management (95% CI 62.8 to 72). Good performance status (adjusted OR (AOR)=0.44; 95% CI 0.24 to 0.80), presence of comorbidity (AOR=3.28; 95% CI 1.68 to 6.38) and pain history (AOR=0.33; 95% CI 0.01 to 0.11) were significantly associated with the adequacy of cancer pain management.ConclusionUsing PMI status in the Northwest oncology centre of Ethiopia, more than two-thirds of patients with CRP obtained adequate pain management. The adequacy of CRP management was found to be influenced by factors like comorbidity, past pain history and Eastern cooperative oncology group performance status.