bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staphylococcus aureus
delta toxin modulates both extracellular membrane vesicle biogenesis and amyloid formation
Authors: Wang Xiaogang , Uppu Divakara SSM , Dickey Seth W. , Burgin Dylan J. , Otto Michael , Lee Jean C. 
Published: October 2023

ABSTRACT

Staphylococcus aureus
secretes phenol-soluble modulins (PSMs), a family of small, amphipathic, secreted peptides with multiple biologic activities. Community-acquired
S. aureus
strains produce high levels of PSMs in planktonic cultures, and PSM alpha peptides have been shown to augment the release of extracellular membrane vesicles (MVs). We observed that amyloids, aggregates of proteins characterized by a fibrillar morphology and stained with specific dyes, co-purified with MVs harvested from cell-free culture supernatants of community-acquired
S. aureus
strains. δ-toxin was a major component of amyloid fibrils that co-purified with strain LAC MVs, and δ-toxin promoted the production of MVs and amyloid fibrils in a dose-dependent manner. To determine whether MVs and amyloid fibrils were generated under
in vivo
conditions, we inoculated mice with
S. aureus
harvested from planktonic cultures. Bacterial MVs were isolated and purified from lavage fluids recovered from infected animals. Although δ-toxin was the most abundant PSM in lavage fluids, amyloid fibrils could not be detected in these samples. Our findings expand our understanding of amyloid fibril formation in
S. aureus
cultures, reveal the important roles of δ-toxin in amyloid fibril formation and MV biogenesis, and demonstrate that MVs are generated
in vivo
in a staphylococcal infection model.

IMPORTANCE

Extracellular membrane vesicles (MVs) produced by
Staphylococcus aureus
in planktonic cultures encapsulate a diverse cargo of bacterial proteins, nucleic acids, and glycopolymers that are protected from destruction by external factors. δ-toxin, a member of the phenol soluble modulin family, was shown to be critical for MV biogenesis. Amyloid fibrils co-purified with MVs generated by virulent, community-acquired
S. aureus
strains, and fibril formation was dependent on expression of the
S. aureus
δ-toxin gene (
hld
). Mass spectrometry data confirmed that the amyloid fibrils were comprised of δ-toxin. Although
S. aureus
MVs were produced
in vivo
in a localized murine infection model, amyloid fibrils were not observed in the
in vivo
setting. Our findings provide critical insights into staphylococcal factors involved in MV biogenesis and amyloid formation.
Lactate promotes
Salmonella
intracellular replication and systemic infection via driving macrophage M2 polarization
Authors: Wang Xinyue , Yang Bin , Ma Shuangshuang , Yan Xiaolin , Ma Shuai , Sun Hongmin , Sun Yuyang , Jiang Lingyan 
Published: October 2023

ABSTRACT

Salmonella
is one of the most important enteric pathogens worldwide, which is able to cause lethal systemic infection via survival and replication in host macrophages. Lactate, a byproduct of anaerobic or aerobic glycolysis, can induce macrophage M2 polarization, but the relationship between lactate-mediated macrophage M2 polarization and bacterial infection is poorly understood. Here, we evaluated the role of lactate and lactate-mediated macrophage M2 polarization in the pathogenicity of
Salmonella
. We found that lactate levels were significantly increased in
Salmonella
-infected macrophages, and the increased lactate was derived from the host. Macrophage and mouse infection assays showed that the addition of lactate enhanced
Salmonella
replication within macrophages and the colonization of mouse systemic loci, while pharmacological or genetic inhibition of host lactate production impaired
Salmonella
intracellular replication and its virulence in mice. Further analysis revealed that lactate promotes M2 polarization of
Salmonella
-infected macrophages, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated
Salmonella
growth promotion. Moreover, we showed that macrophage-derived lactate induces the
Salmonella
pathogenicity island (SPI)-2 type III secretion system, leading to increased translocation of the SPI-2 effector SteE, which is responsible for driving M2 polarization. Overall, these findings suggest that lactate promotes
Salmonella
intracellular replication and systemic infection via driving macrophage M2 polarization and highlight the complex interactions between
Salmonella
and macrophages.

IMPORTANCE

The important enteropathogen
Salmonella
can cause lethal systemic infection
via
survival and replication in host macrophages. Lactate represents an abundant intracellular metabolite during bacterial infection, which can also induce macrophage M2 polarization. In this study, we found that macrophage-derived lactate promotes the intracellular replication and systemic infection of
Salmonella
. During
Salmonella
infection, lactate
via
the
Salmonella
type III secretion system effector SteE promotes macrophage M2 polarization, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated
Salmonella
growth promotion. This study highlights the complex interactions between
Salmonella
and macrophages and provides an additional perspective on host-pathogen crosstalk at the metabolic interface.
Design of a novel affinity probe using the cell wall-binding domain of a
Listeria monocytogenes
autolysin for pathogen detection
Authors: Lin Min , Dan Hanhong 
Published: October 2023

ABSTRACT

Rapid identification of foods and food-processing environments contaminated with
Listeria monocytogenes
is crucial for controlling human listeriosis, a leading cause of fatality related to foodborne illnesses. The
L. monocytogenes
autolysin IspC anchors to the bacterial surface non-covalently via its C-terminal cell wall-binding domain (CWBD), which contains conserved Gly-Trp (GW) dipeptides. This study explored the binding property of CWBD
IspC
to design an affinity probe for detecting
L. monocytogenes
. Immunogold electron microscopy analysis of a ∆
ispC
mutant and its wild type (WT) revealed that exogenously added CWBD
IspC
bound to surface ligands that were evenly distributed and remained mostly unoccupied in the wild type. CWBD
IspC
detected, via recognizing the cell wall component lipoteichoic acid,
L. monocytogenes
strains primarily belonging to the serotype 4 group, as well as
Listeria innocua
, and
Listeria welshimeri
but did not detect three other
Listeria
spp. (
Listeria seeligeri
,
Listeria ivanovii,
and
Listeria grayi
) nor any non-
Listeria
spp. tested. CWBD
IspC
, when tagged with the enhanced green fluorescent protein, was capable of detecting
L. monocytogenes
by fluorescence microscopy, a colony lift filter assay, and a microtube binding assay. CWBD
IspC
, when covalently attached to magnetic beads, showed the ability to separate
L. monocytogenes
cells with a maximum capture rate of 90 to nearly 100% from 1 × 10
3
to 1 × 10
5
target cells. This study demonstrated for the first time that the CWBD derived from a GW surface protein IspC is a novel antibody alternative for the rapid detection and isolation of
L. monocytogenes
despite binding to two other
Listeria
species.

IMPORTANCE

Human listeriosis is caused by consuming foods contaminated with the bacterial pathogen
Listeria monocytogenes
, leading to the development of a severe and life-threatening foodborne illness. Detection of
L. monocytogenes
present in food and food processing environments is crucial for preventing
Listeria
infection. The
L. monocytogenes
peptidoglycan hydrolase IspC anchors non-covalently to the bacterial surface through its C-terminal cell wall-binding domain (CWBD), CWBD
IspC
. This study explored the surface binding property of CWBD
IspC
to design, construct, characterize, and assess an affinity molecular probe for detecting
L. monocytogenes
. CWBD
IspC
recognized a cell wall ligand lipoteichoic acid that remains evenly displayed and mostly unoccupied on the bacterial surface for interaction with the exogenously added CWBD
IspC
. CWBD
IspC
, when fused to the enhanced green fluorescent protein reporter or covalently conjugated onto magnetic beads, exhibited the functionality as an antibody alternative for rapid detection and efficient separation of the pathogen.
Relationships between fluvial dune cross-set thickness, planview width, and trough geometry
Authors: Cardenas Benjamin T. , Stacey Kaitlyn , Baran Zachary J. 
Published: October 2023

Abstract
Sedimentary structures provide critical information for the reconstruction of ancient environments of Earth and other planets. Fluvial dune cross sets, structures that record dune migration via the filling of leading troughs along ancient riverbeds, are particularly useful. Most quantitative methods for interpreting cross sets require thickness measurements, but the growth of planview imaging of sedimentary rocks on Earth and Mars has introduced a need for methods to interpret planview exposures of cross sets. Here, we measured 359 cross-set widths exposed along ancient channel belts of the Cretaceous Cedar Mountain Formation exposed in Utah, USA, and compared these widths to published thicknesses (n = 350). We found that the mean cross-set width was 1.29 m, 9.3 times the mean thickness. The normalized distributions of widths and thicknesses were statistically similar and thus contained similar paleoenvironmental information. Numerical experiments representing a series of trough cut-and-fill structures show that cross-set reworking is equally important in setting width as thickness and that the observed cross-set widths could be explained by a gamma-distributed range of trough widths with a mean of 2.96 ± 0.25 m, ~2.3 times cross-set width. Given the similarity of dune-field geometries across depositional settings and planetary boundary conditions, we suggest this cross-set width-to-thickness relationship could be useful for interpreting other cross sets exposed in planview.
Seizures in hospitalised paediatric patients with SARS-CoV-2 and comparison of severity with seizures in hospitalised paediatric patients with other respiratory viruses during the COVID-19 pandemic: a population-based cohort study
Authors: Anastasopoulou Stavroula , Svensson Eva , Wickström Ronny , Hertting Olof , Rinder Malin Ryd , Bennet Rutger , Eriksson Margareta 
Published: October 2023

ObjectiveTo study seizures in patients hospitalised due to SARS-CoV-2 infection, and compare their severity with seizures in patients hospitalised due to other viral respiratory tract infections (RTIs).DesignObservational population-based cohort study.SettingNorthern Stockholm.PatientsPatients aged 1 month–18 years hospitalised due to SARS-CoV-2 with and without seizures, and patients of the same age hospitalised due to other viral RTIs with seizures, between 1 March 2020 and 30 June 2022.Main outcome measuresThe prevalence of seizures in hospitalised patients due to SARS-CoV-2, the evaluation of assumed predictors of seizures and the comparison of severity markers in patients with SARS-CoV-2 versus other RTIs.Results32 of 239 included patients (13.4%) admitted due to SARS-CoV-2 infection had seizures. Central nervous system (CNS) disease and the omicron period had significantly increased OR for seizures (OR: 5.12; CI: 2.06 to 12.72 and OR: 3.01; CI: 1.15 to 7.88, respectively). Seizures in patients with SARS-CoV-2 were more common in children older than 5 years (p=0.001), even in the absence of fever (p=0.007), as compared with other viral RTIs. The duration of hospitalisation was longer in patients with seizures due to other viral RTIs (p=0.023). There was no significant difference regarding severity markers of seizures between the two groups.ConclusionsCNS disease and the omicron period were risk factors for seizures in patients with SARS-CoV-2, who were older than patients with other RTIs. The severity of seizures was comparable between the two groups; hospitalisation was however longer in patients with other RTIs.
Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review
Authors: Slack Emma , Pears Katrina Anne , Rankin Judith , Newton Julia L , Pearce Mark 
Published: October 2023

ObjectivesTo identify, synthesise and appraise evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and pregnancy.DesignMixed-methods systematic review, using convergent segregated design.Data sourcesMEDLINE, EMBASE, Scopus, PsycINFO, CINAHL, MedRxiv, PROSPERO and grey literature sources through 6 August 2023.Eligibility criteriaWe included original research studies, expert opinion and grey literature reporting on ME/CFS and pregnancy/post partum (up to 2 years), risk of pregnancy outcomes with ME/CFS or experiences during pregnancy for mother, partner or health and social care professionals following ME/CFS during pregnancy, all where the evidence was relevant to a confirmed ME/CFS diagnosis prior to pregnancy.Data extraction and synthesisThree independent reviewers completed all screening, data extraction and quality assessment. Risk of bias was assessed using the mixed-methods appraisal tool V.2018. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses. Findings were integrated through configuration.ResultsSearches identified 3675 articles, 16 met the inclusion criteria: 4 quantitative (1 grey), 11 qualitative (9 grey) and 1 grey mixed-methods study. Of the four quantitative studies that reported on ME/CFS severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one found most women had no change in ME/CFS symptoms and one found ME/CFS improved; this difference in symptom severity across studies was supported by the qualitative evidence. The qualitative literature also highlighted the importance of individualised care throughout pregnancy and birth, and the need for additional support during family planning, pregnancy and with childcare. Only one quantitative study reported on pregnancy outcomes, finding decreased vaginal births and higher rates of spontaneous abortions and developmental and learning delays associated with pregnancies in those with ME/CFS.ConclusionsCurrent evidence on ME/CFS in pregnancy is limited and findings inconclusive. More high-quality research is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy.
Content or context? A study protocol for a three-arm parallel randomised controlled trial of Re-PROGRAM, a brief internet-based intervention for patients with functional seizures
Authors: Higson Lana , O'Brien Terence J , Rayner Genevieve , Alpitsis Rubina , Winton-Brown Toby 
Published: October 2023

IntroductionFunctional seizures (FS) mimic epilepsy but are not caused by epileptic electrical activity in the brain and are believed to have a psychological origin. There is a well-documented gap between the needs of patients with FS and available therapeutic resources. While there is potential for reducing seizure burden in patients via psychosocial intervention, there is no evidence-based care pathway or consistent availability of treatment and no effective pharmacological treatment. The objective of this study is to investigate the clinical efficacy and tolerability of a novel internet-based intervention in reducing seizure frequency.Methods and analysisA 3-arm parallel randomised controlled trial will compare the efficacy of brief guided internet-based therapy to unguided internet-based therapy and to standard care. Approximately 100 participants with FS will be recruited, with diagnostic criteria based on gold standard video-electroencephalogram (v-EEG) monitoring; patients will be randomly assigned to one of the three study arms. The primary study outcome will be FS frequency at 6 weeks and at follow-up (6 and 12 months) compared with baseline. Seizure frequency will be modelled using Poisson regression. Secondary outcomes include psychosocial functioning, healthcare resource usage, anxiety, depression, somatisation and life impact. Between-group differences will be evaluated using analysis of variance. Analysis of covariance will estimate within-group changes on secondary outcomes. Cognitive and psychological factors will be used as predictors of seizure reduction in exploratory analyses. A qualitative survey using a semi-structured interview will use thematic analyses to explore participants’ treatment experiences, their impressions of FS management and perceived mechanisms for change.Ethics and disseminationThe study was approved by the Human Research and Ethics Committee of the Alfred Hospital Human Research Ethics Committee as part of the Australian Multisite Ethics approval system. Results of the study will be presented at national and international conferences and published in peer-reviewed journals.Trial registration numberACTRN12622000262707.
Prognostic models based on lymph node density for primary gastrointestinal melanoma: a SEER population-based analysis
Authors: Zeng Jiaqi , Zhu Lin , Zhou Guanzhou , Pan Fei , Yang Yunsheng 
Published: October 2023

ObjectiveThis study aimed to construct prognostic models to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with primary gastrointestinal melanoma (PGIM).DesignAn observational and retrospective study.SettingData were obtained from the Surveillance, Epidemiology and End Results (SEER) programme database, encompassing a broad geographical and demographic spectrum of patients across the USA.ParticipantsA total of 991 patients diagnosed with PGIM were included in this study.MethodsA total of 991 patients with PGIM were selected from the SEER database. They were further divided into a training cohort and a validation cohort. Independent prognostic factors were identified by Cox regression analysis. Two prognostic models were constructed based on the results of multivariable Cox regression analysis. The concordance index (C-index) and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the discriminative ability. Calibration curves were plotted to evaluate the agreement between the probability as predicted by the models and the actual probability. Risk stratification was developed given the model.ResultsBy the multivariable Cox regression analysis, we identified four independent risk factors (age, stage, lymph node density and surgery) for OS, and three independent risk factors (stage, lymph node density and surgery) for CSS, which were used to construct prognostic models. C-index, time-dependent AUC, calibration curves and Kaplan-Meier curves of risk stratification indicated that these two models had good discriminative ability, predictive ability as well as clinical value.ConclusionsThe prognostic models of OS and CSS had satisfactory accuracy and were of clinical value in evaluating the prognosis of patients with PGIM.
Randomised controlled trial of preconception lifestyle intervention on maternal and offspring health in people with increased risk of gestational diabetes: study protocol for the BEFORE THE BEGINNING trial
Authors: Sujan Md Abu Jafar , Skarstad Hanna Margrethe Storheil , Rosvold Guro , Fougner Stine Lyngvi , Nyrnes Siri Ann , Iversen Ann-Charlotte , Follestad Turid , Salvesen Kjell Å , Moholdt Trine 
Published: October 2023

IntroductionGestational diabetes mellitus (GDM) is associated with increased risk for type 2 diabetes in the mother and cardiometabolic diseases in the child. The preconception period is an optimal window to adapt the lifestyle for improved outcomes for both mother and child. Our aim is to determine the effect of a lifestyle intervention, initiated before and continued throughout pregnancy, on maternal glucose tolerance and other maternal and infant cardiometabolic outcomes.Methods and analysisThis ongoing randomised controlled trial has included 167 females aged 18–39 years old at increased risk for GDM who are contemplating pregnancy. The participants were randomly allocated 1:1 to an intervention or control group. The intervention consists of exercise (volume is set by a heart rate-based app and corresponds to ≥ 1 hour of weekly exercise at ≥ 80% of individual heart rate maximum), and time-restricted eating (≤ 10 hours/day window of energy intake). The primary outcome measure is glucose tolerance in gestational week 28. Maternal and offspring outcomes are measured before and during pregnancy, at delivery, and at 6–8 weeks post partum. Primary and secondary continuous outcome measures will be compared between groups based on the ‘intention to treat’ principle using linear mixed models.Ethics and disseminationThe Regional Committees for Medical and Health Research Ethics in Norway has approved the study (REK 143756). The anonymised results will be submitted for publication and posted in a publicly accessible database of clinical study results.Trial registration numberClinical trial govNCT04585581.
Efficacy and safety of lenvatinib–transcatheter arterial chemoembolisation sequential therapy followed by surgical resection for intermediate-stage hepatocellular carcinoma beyond Up-to-7 criteria: a study protocol for a multicentre, single-arm, prospective study
Authors: Oshita Ko , Kobayashi Tsuyoshi , Namba Yosuke , Fukuhara Sotaro , Matsubara Keiso , Takei Daisuke , Nakano Ryosuke , Okamoto Wataru , Sakai Hiroshi , Tanimine Naoki , Nakahara Takashi , Kuroda Shintaro , Tahara Hiroyuki , Ohira Masahiro , Kawaoka Tomokazu , Ide Kentaro , Imamura Michio , Aikata Hiroshi , Ohdan Hideki 
Published: October 2023

IntroductionThe feasibility and efficacy of surgical resection following systemic therapy for intermediate-stage hepatocellular carcinoma (HCC) beyond the Up-to-7 criteria is unclear. The combination of lenvatinib (LEN) and transcatheter arterial chemoembolisation (TACE), termed LEN–TACE sequential therapy, has shown a high response rate and survival benefit in patients with intermediate-stage HCC. This trial aims to evaluate the efficacy and safety of LEN–TACE sequential therapy and the feasibility of surgical resection for intermediate-stage HCC beyond the Up-to-7 criteria.Methods and analysisThis is a multicentre, single-arm, prospective clinical trial. Thirty patients with intermediate-stage HCC beyond the Up-to-7 criteria will be enrolled. Patients eligible for this study will undergo LEN–TACE sequential therapy in which LEN is administered for 4 weeks, followed by TACE, and then further LEN for another 4 weeks. Patients will be assessed for efficacy of LEN–TACE sequential therapy and resectability, and surgical resection will be performed if the HCC is considered radically resectable. The primary outcome of this study is the resection rate after LEN–TACE sequential therapy. The secondary outcomes are the objective response rate of LEN–TACE sequential therapy, safety, curative resection rate, overall survival and recurrence-free survival.Ethics and disseminationThis trial was approved by the Institutional Review Board of Hiroshima University, Japan (approval no. CRB210003), and has been registered with the Japan Registry of Clinical Trials (jRCTs061220007). The results of this study will be submitted for publication in a peer-reviewed journal and shared with the scientific community at international conferences.Trial registration numberjRCTs061220007 (https://jrct.niph.go.jp/latest-detail/jRCTs061220007).