bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motility-dependent processes in
Toxoplasma gondii
tachyzoites and bradyzoites: same same but different
Authors: Kent Robyn S. , Ward Gary E. 
Published: February 2025

ABSTRACT

During infection,
Toxoplasma gondii
tachyzoites must be able to move in order to migrate through tissues, cross biological barriers, and penetrate into and egress from cells they infect. Bradyzoite-stage parasites, which establish infection in naïve hosts, also require motility to escape from cysts after they are ingested and to subsequently migrate to the gut wall, where they either invade cells of the intestinal epithelium or squeeze between these cells to infect the underlying tissue. Little is known about the motility of bradyzoites, which we analyze in detail here and compare to the well-characterized motility and motility-dependent processes of tachyzoites. Unexpectedly, bradyzoites were found to be as motile as tachyzoites in a three-dimensional model extracellular matrix, and they showed increased invasion into and transmigration across monolayers of certain cell types, consistent with their need to establish infection in the gut. The motility of the two stages was inhibited to the same extent by cytochalasin D and KNX-002, compounds known to target the parasite’s actomyosin-based motor. Other compounds that impact tachyzoite motility (tachyplegin and enhancer 5) have a reduced effect on bradyzoites. Furthermore, rapid bradyzoite egress from infected cells is not triggered by treatment with calcium ionophores, as it is with tachyzoites. The similarities and differences between these two life cycle stages highlight the need to characterize both tachyzoites and bradyzoites for a more complete understanding of the role of motility in the parasite life cycle and the effect that motility-targeting therapeutics will have on disease establishment and progression.

IMPORTANCE

Toxoplasma gondii
is a parasite that chronically infects around one-third of the world's population.
Toxoplasma
uses motility for multiple purposes during infection, including extracellular migration, invasion into host cells, and host cell egress. These motility-dependent processes have been extensively studied in the life cycle stage responsible for acute infection, the tachyzoite. In contrast, motility and motility-dependent processes are poorly understood in bradyzoite-stage parasites, which are responsible for both establishing infection after consumption of infected meat and initiating potentially life-threatening reactivated infections in the brains of immunocompromised individuals. We show here that the motility and motility-dependent processes of bradyzoites are similar in many respects to those of tachyzoites but markedly different in others. The results of this study highlight the need to consider both life cycle stages in attempts to develop drugs targeting parasite motility and the signaling processes that regulate motility-dependent processes during infection by these important human pathogens.
Identification and characterization of archaeal pseudomurein biosynthesis genes through pangenomics
Authors: Lupo Valérian , Roomans Célyne , Royen Edmée , Ongena Loïc , Jacquemin Olivier , Mullender Coralie , Kerff Frédéric , Baurain Denis 
Published: February 2025

ABSTRACT

The peptidoglycan (PG, or murein) is a mesh-like structure, which is made of glycan polymers connected by short peptides and surrounds the cell membrane of nearly all bacterial species. In contrast, there is no PG counterpart that would be universally found in Archaea but rather various polymers that are specific to some lineages. Methanopyrales and Methanobacteriales are two orders of Euryarchaeota that harbor pseudomurein (PM), a structural analog of the bacterial PG. Owing to the differences between PG and PM biosynthesis, some have argued that the origin of both polymers is not connected. However, recent studies have revealed that the genomes of PM-containing Archaea encode homologs of the bacterial genes involved in PG biosynthesis, even though neither their specific functions nor the relationships within the corresponding inter-domain phylogenies have been investigated so far. In this work, we devised a pangenomic bioinformatic pipeline to identify proteins for PM biosynthesis in Archaea without prior genetic knowledge. The taxonomic distribution and evolutionary relationships of the candidate proteins were studied in detail in Archaea and Bacteria through HMM sequence mining and phylogenetic inference of the Mur domain-containing family, the ATP-grasp superfamily, and the MraY-like family. Our results show that archaeal muramyl ligases are of bacterial origin but diversified through a mixture of horizontal gene transfers and gene duplications. However, in the ATP-grasp and MraY-like families, the archaeal members were not found to originate from Bacteria. Our pangenomic approach further identified five new genes potentially involved in PM synthesis and that would deserve functional characterization.

IMPORTANCE

Methanobrevibacter smithii
is an archaea commonly found in the human gut, but its presence alongside pathogenic bacteria during infections has led some researchers to consider it as an opportunistic pathogen. Fortunately, endoisopeptidases isolated from phages, such as PeiW and PeiP, can cleave the cell walls of
M. smithii
and other pseudomurein-containing archaea. However, additional research is required to identify effective anti-archaeal agents to combat these opportunistic microorganisms. A better understanding of the pseudomurein cell wall and its biosynthesis is necessary to achieve this goal. Our study sheds light on the origin of cell wall structures in those microorganisms, showing that the archaeal muramyl ligases responsible for its formation have bacterial origins. This discovery challenges the conventional view of the cell-wall architecture in the last archaeal common ancestor and shows that the distinction between “common origin” and “convergent evolution” can be blurred in some cases.
Gut commensal
Alistipes shahii
improves experimental colitis in mice with reduced intestinal epithelial damage and cytokine secretion
Authors: Lin Xiaoying , Xu Mingchao , Lan Ruiting , Hu Dalong , Zhang Suping , Zhang Shuwei , Lu Yao , Sun Hui , Yang Jing , Liu Liyun , Xu Jianguo 
Published: February 2025

ABSTRACT

The commensal bacterium
Alistipes shahii
is a core microbe of the human gut microbiome and its abundance is negatively correlated with inflammatory bowel diseases (IBDs). However, its fundamental role in regulating inflammatory response remains unknown. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we examined the effect of
A. shahii
strain As360 intervention on host inflammatory response and found that
A. shahii
As360 alleviated disease activity index, colon shortening, and colonic histopathological lesion. The levels of tight junction proteins (mainly ZO1 and claudin-1) were decreased in DSS-induced colitis mice, whereas the levels of these proteins were elevated in colitis mice with
A. shahii
As360 treatment. In addition,
A. shahii
As360 treatment led to alterations in cytokine release, especially an increase of IL10. It also led to reduced expressions of
mtor
and
Nlrp3
and increased expression of mTOR inhibitor
Ddit4
at the transcriptional level. 16S rRNA amplicon sequencing found that
Bacteroides
, a producer of short-chain fatty acids (SCFAs), was enriched in the fecal samples of mice with
A. shahii
treatment. Metabolic analyses found that, following
A. shahii
As360 treatment, the SCFAs in the fecal content was increased whereas lactic acid was decreased in the cecal content. These findings suggest that supplementation with
A. shahii
As360 is a promising strategy to prevent colitis.

IMPORTANCE

As one of the core microbes and keystone species in the human gut,
Alistipes shahii
has the potential to inhibit inflammation and improve inflammatory bowel diseases (IBDs) conditions. In this study, we experimentally demonstrated that oral administration of
A. shahii
As360 alleviated symptoms of colitis, altered the release of cellular inflammatory factors, reduced the intestinal epithelial barrier damage, and changed gut microbiota and fecal metabolites. These findings provide a deeper understanding of the beneficial effects of
A. shahii
and its perspective for better strategies to prevent IBD.
Dissemination of
bla
NDM
-harboring plasmids in carbapenem-resistant and hypervirulent
Klebsiella pneumoniae
Authors: Gu Yihai , Wang Xiao , Zhang Wei , Weng Rui , Shi Qiucheng , Hou Xuan , Wang Hui , Deng Minghui , Mou Jian , Jiang Yan 
Published: February 2025

ABSTRACT

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) is a global public health threat, and CRKP strains carrying
bla
NDM
plasmids are of particular concern. Here, the antimicrobial resistance and molecular epidemiological characteristics of 59 CRKP strains isolated from patients receiving care at a tertiary hospital in China from 2019 to 2021 were determined through antimicrobial resistance testing and genomic sequence analysis. We analyzed the genetic characteristics and transmissibility of
bla
NDM
-harboring plasmids through S1-digested pulsed field gel electrophoresis, Southern blotting, and conjugation assays. The virulence levels of the strains were evaluated using a
Galleria mellonella
larvae infection model. All the CRKP strains were multidrug resistant, but none were resistant to colistin or tigecycline. A total of eight sequence types (STs) were detected in these CRKPs, with ST11 (39/59) and ST15 (12/59) being the most common. Among the carbapenemase genes,
bla
KPC
(39/59) and
bla
NDM
(18/59) were the most common, with
bla
KPC-2
transmitted mainly through ST11 clones and
bla
NDM-5
transmitted through ST15 clones. The
bla
NDM
-harboring plasmids primarily belong to the incompatibility type IncX3 (14/18). IS
26
-mediated gene recombination, sequence insertion, and plasmid integration were observed to occur during the dissemination process. The resistance gene profile mediated by
bla
NDM
-harboring plasmids can be transferred through conjugation, which have almost no fitness cost and is extremely stable after passage. Six of these strains presented carbapenem resistance combined with hypervirulence (CR-hvKP), including ST23-KL1, ST218-KL57, ST17-KL112, and ST147-KL64. Additionally,
bla
NDM
-harboring plasmids can disseminate rapidly over large surface areas and persist for a long time in medical institutions, leading to outbreaks of highly resistant clones associated with CR-hvKP.

IMPORTANCE

The appearance of plasmids carrying
bla
NDM
and the rise of carbapenem-resistant hypervirulent
Klebsiella pneumoniae
(CR-hvKP) have significantly escalated the public health risk associated with Carbapenem-resistant
Klebsiella pneumoniae
(CRKP). In this study, we described the resistance rates, virulence factors, and molecular epidemiology of 59 CRKP isolated from patients at a tertiary hospital in China from 2019 to 2021. Beyond this, we also assessed the characteristics of
bla
NDM
-harboring plasmids and their dissemination patterns among CRKP, especially some CR-hvKP. Our research contributes to the field of
bla
NDM
dissemination studies, prompting researchers to formulate strict measures to prevent and control the development of
bla
NDM
-harboring plasmids, which is instrumental in the clinical development of targeted treatment plans.
Equitable access to quality trauma systems in Ghana: a qualitative study
Authors: Kunfah Sheba Mary Pognaa , Yakubu Mustapha , Ofori-Appiah Bernard , Ayingayure Emmanuel , Odland Maria Lisa , Yempabe Tolgou , Buunaaim Alexis Dun Bo-ib , Konadu-Yeboah Dominic , Ignatowicz Agnieszka , Davies Justine , Stephen Tabiri 
Published: February 2025

ObjectivesTo explore the barriers to accessing quality trauma care after injury in Ghana.DesignA qualitative study using semi-structured interviews and focus group discussions in one rural and one urban setting. Interviews and focus group discussions were audio recorded, transcribed and thematically analysed using the four-delay framework.Participants53 patient participants (n=39 men, n=14 women, mean age=41, SD=15.6, n=38 rural participants, n=15 urban participants) who had an injury not more than 6 months preceding the start of the study.Settings15 individual interviews (n=15) and 2 focus group discussions (n=23) were conducted in Yendi (rural setting in Ghana) and 10 individual interviews (n=10) and 1 focus group discussion (n=5) in the Tamale metropolis (urban setting in Ghana).ResultsOur findings showed that when an injury occurred, participants faced multiple barriers across all delays which prevented them from accessing quality injury care. Barriers were a mix of individual, community-level and health-system factors that were interrelated in many ways. Financial difficulties were one of the prominent barriers mentioned by the participants in both settings.ConclusionThis study shows that multiple factors cause an injured patient to delay in seeking care, reaching care, receiving care and remaining in care. Therefore, there is a pressing need for comprehensive, community-driven strategies to strengthen health literacy at the community level. There is also a need for facility-based strategies that would improve the availability of medical and human resources to augment access to quality trauma care. Additionally, if policymakers focus on removing financial barriers to trauma care and strengthening referral systems, especially in the remote and rural areas, it would greatly improve access to quality trauma care in Ghana.
HPV vaccination among young adults in Switzerland: a cross-sectional study
Authors: El-Hadad Samia , Sachs Maike Katja , Barrense-Dias Yara , Granell Joan Carles Suris , Niggli Angela , Leeners Brigitte 
Published: February 2025

ObjectiveThis study aimed to evaluate the human papillomavirus (HPV) vaccination status among a representative sample of young adults (YAs) with a special focus on the catch-up vaccination uptake among the male population in Switzerland.Design and settingData were extracted from an online self-administered questionnaire survey, conducted as a representative cross-sectional study in 2017. To understand correlations between vaccination uptake and sociodemographic characteristics, sexual health, and sexual behaviour, we performed bivariate analysis and multivariate regression analysis.ParticipantsOut of a total of 7142 participants, 2155 female and 996 male cisgender participants remained for statistical evaluation after excluding homosexual/bisexual study participants, those with gender dysphoria or those without knowledge of their vaccination status.OutcomesThe primary outcome of this study was to investigate HPV vaccination rates among female and male YAs in Switzerland. As secondary outcomes, we assessed uptake of catch-up vaccination and identified key factors influencing HPV vaccination uptake.ResultsVaccination rates were significantly higher in the female group (40.9%), while not wanting to be vaccinated and doubting benefits and necessity of the vaccine were main reasons for non-vaccination. Vaccination coverage among male YAs was very low (7.8%), primarily due to insufficient information. Parents not being Swiss-born, a higher family socioeconomic status and having had a gynaecological visit at a younger age correlated with HPV vaccination uptake for female YAs. In the male group, participants with a higher number of lifetime partners and a younger age at first steady partnership were more likely to report a positive vaccination status. Knowledge about the benefits of catch-up vaccination was very limited among both genders.ConclusionsThe lack of knowledge about benefits of HPV vaccination contributes to low vaccine uptake, especially occurring among the male population, must be addressed. Given the number of people who reported not knowing whether they were vaccinated or not, it is crucial to ensure that there is a thorough discussion about HPV and the protection the vaccine provides when presenting for vaccination.
Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis
Authors: Støy Sidsel , Eriksen Lotte Lindgreen , Lauszus Johanne Sloth , Damsholt Søren , Baunwall Simon Mark Dahl , Erikstrup Christian , Vilstrup Hendrik , Jepsen Peter , Hvas Christian , Thomsen Karen Louise 
Published: February 2025

IntroductionLiver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.Methods and analysisIn this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.Ethics and disseminationThe Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.Trial registration numberClinicalTrials.gov study identifierNCT04932577.
Daily SARS-CoV-2 testing after travel-related close contact notifications during elite sporting events hosted in the UK: a longitudinal study
Authors: Davies Madeleine , Hill Jerry , Goggins Luke , Peirce Nicholas , Smith Jenifer , Boulter Matthew , Fowler Tom Alan , Buchan Iain , Calder James D F 
Published: February 2025

Isolation requirements for COVID-19 close contacts risked discouraging elite athletes and support staff from travelling to international sports events hosted in the UK during 2021.ObjectivesThe purpose of this study, in collaboration with the UK Health Security Agency, was to develop and implement a risk assessment and workplace daily testing approach in elite sporting events, for individuals who would otherwise be excluded by quarantine.MethodsLongitudinal study of athletes and staff identified as close contacts during travel (ie, flights, train) to specific international sports events. A risk assessment was undertaken, and participants were categorised as at ‘low’ or ‘high’ risk of developing SARS-CoV-2 based on their exposure circumstances. High-risk individuals remained in 10-day isolation, whereas those of low risk underwent daily symptom and lateral flow testing, enhanced workplace mitigation and selected work activities were permitted.ResultsOf 29 514 event personnel, 202 travel-related close contacts were reported to the study team, of which 126 were eligible from 40 events in 7 sports. Of the individuals assessed, 105 (83.3%) were classified as low risk, while 21 (16.7%) were classified as high risk. No low-risk individuals tested positive in over 280 rapid antigen tests.ConclusionInternational sports events rely on athlete and support staff availability, with economic consequences of event cancellation or postponement. Our study showed no detection of SARS-CoV-2 in low-risk close contacts, and enabled their sustained participation. This multidisciplinary intervention appears to have been effective, enabling large-scale event continuation, while minimising risk to athletes, employees and the wider public.
Updated evidence on selection and implementation of an invasive treatment strategy for older patients with non-ST-segment elevation myocardial infarction
Authors: Gill Kieran , Kunadian Vijay 
Published: February 2025

Non-ST-segment elevation myocardial infarction (NSTEMI) is the most common acute coronary syndrome diagnosis in older patients. In the UK, there are ~20 000 NSTEMI cases annually in patients aged ≥75 years. Despite therapeutic advances in pharmacological and invasive management, studies show that older patients with NSTEMI experience worse in-hospital and long-term outcomes than younger patients, suggesting a clear need for robust evidence in this cohort.The European Society of Cardiology guidelines recommend that invasive management should be considered holistically with no specified age cut-offs. However, older patients are less likely to receive invasive management due to a paucity of evidence from trials that represent contemporary clinical characteristics of older adults. Recruiting older patients realistic of those encountered in clinical practice is hugely challenging. Chronological age alone does not reflect the heterogeneity of the older population; ~30% of older patients with NSTEMI are frail, ~65% are cognitively impaired and most live with at least two additional comorbidities that can influence risk. Weighing the risk of an NSTEMI in an older adult against competing risks attributable to underlying frailty, comorbidities and cognitive impairment poses a key challenge.Recently, the SENIOR-RITA trial showed that invasive management in older patients with NSTEMI is safe and reduces non-fatal myocardial infarction and subsequent revascularisation but does not improve mortality. Individualised risk assessment and shared decision-making is necessary to guide these nuanced decisions. This review discusses the latest evidence regarding invasive management in the older population with NSTEMI, including the impact of geriatric syndromes on clinical outcomes.