bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Longitudinal Association of Cardiorespiratory Fitness and Adiposity With Clustered Cardiometabolic Risk: A Mediation Analysis
Authors: Silveira João Francisco de Castro , Brand Caroline , Welser Letícia , Gaya Anelise Reis , Burns Ryan Donald , Pfeiffer Karin Allor , Lima Rodrigo Antunes , Andersen Lars Bo , Reuter Cézane Priscila , Pohl Hildegard Hedwig 
Published: August 2023

Purpose: Previous literature has demonstrated the mediating role of adiposity in the association between cardiorespiratory fitness (CRF) and cardiometabolic risk as well as the potential role of CRF in attenuating the adverse consequences associated with excess weight. This study aimed to evaluate the mediating role of CRF and adiposity in the possible association with cardiometabolic risk. Method: Observational 3-year longitudinal study that included 420 children and adolescents (10.50 [2.05] y of age at baseline; 56.2% girls). Body mass index (BMI) was calculated, and CRF was evaluated using field assessments. A clustered cardiometabolic risk score (cMetS) was calculated from glucose, systolic blood pressure, total cholesterol/high-density lipoprotein cholesterol ratio, and triglycerides z scores. Analyses evaluated the mediating role of BMI in the association between CRF and cMetS as well as whether CRF mediated the association between BMI and cMetS. Results: BMI at baseline was directly associated with the cMetS at follow-up (0.102; 95% confidence interval, 0.020 to 0.181), independently of CRF, whereas CRF was only indirectly associated with cMetS at follow-up through BMI (−0.036; 95% confidence interval, −0.070 to −0.009), meaning that the association between CRF and cMetS was explained via the mediation role of BMI. Conclusions: BMI presented direct association with cMetS, whereas CRF exhibited indirect association with cMetS mediated via BMI.
Diversity of
bla
L1-like
genes in
Stenotrophomonas
species: insights from genome analysis of publicly available genome sequences
Authors: Yamada Kageto , Ishii Yoshikazu , Tateda Kazuhiro 
Published: August 2023

ABSTRACT

L1 metallo-β-lactamases produced by
Stenotrophomonas maltophilia
exhibit high diversity. Here, we characterized the genomes of
Stenotrophomonas
species harboring
bla
L1-like
genes using publicly available genome sequences. Our findings provide evidence that
Stenotrophomonas
species with
bla
L1-like
genes constitute a complex comprising many species with high genetic diversity, and similarities between
bla
L1-like
genes are lower than those of the genome. This suggests that the diversity of
bla
L1-like
is attributable to species diversity in
Stenotrophomonas
species harboring
bla
L1-like
and the rapid evolutionary changes in
bla
L1-like
genes.
Diagnostic utility of oropharyngeal swabs as an alternative to lower respiratory tract samples for PCR-based syndromic testing in patients with community-acquired pneumonia
Authors: Serigstad Sondre , Knoop Siri T. , Markussen Dagfinn L. , Ulvestad Elling , Bjørneklett Rune O. , Ebbesen Marit H. , Kommedal Øyvind , Grewal Harleen M. S. 
Published: August 2023

ABSTRACT

Syndromic PCR-based analysis of lower respiratory tract (LRT) samples in patients with community-acquired pneumonia (CAP) improves the bacterial yield and time-to-results compared to culture-based methods. However, obtaining adequate sputum samples can be challenging and is frequently not prioritized in the emergency department (ED). In this study, we assess the concordance of microbiological detections between oropharyngeal- (OP) and LRT samples from patients presenting to the ED with CAP using a syndromic PCR-based respiratory panel [Biofire FilmArray Pneumonia
plus
(FAP
plus
)]. Paired OP- and high-quality LRT samples were collected from 103 patients with confirmed CAP, who had been included in a randomized controlled trial (NCT04660084) or a subsequent observational study at Haukeland University Hospital, and analyzed using the FAP
plus
. The LRT samples were obtained mainly by sputum induction (88%). Using the LRT samples as a reference standard, the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement for the most common bacterial pathogens in CAP,
Streptococcus pneumoniae
and
Haemophilus influenzae
, were 85%, 99% and 95%, and 86%, 98% and 93%, respectively. For
Moraxella catarrhalis,
the PPA was lower (74%), while the NPA was 100%. For bacteria that are less likely causes of uncomplicated CAP (e.g.,
Staphylococcus aureus
and Enterobacterales) the results were more divergent. In conclusion, the FAP
plus
detects the most common CAP pathogens
S. pneumoniae
and
H. influenzae
from OP samples with high PPAs and excellent NPAs when compared with LRT samples. For these pathogens, the PPAs for OP samples were higher than previous reports for nasopharyngeal samples. This suggests that analysis of OP samples with syndromic PCR panels could represent an alternative approach for rapid microbiological testing in the ED, especially in patients where LRT samples are difficult to obtain. Divergent results for bacteria that are less likely to cause uncomplicated CAP do, however, emphasize the need for clinical evaluation of positive test results.
The SlyD metallochaperone targets iron-sulfur biogenesis pathways and the TCA cycle
Authors: Denic Milica , Turlin Evelyne , Zamble Deborah B. , Betton Jean-Michel , Vinella Daniel , De Reuse Hilde 
Published: August 2023

ABSTRACT

Control of protein folding is a conserved function in all domains of life. The ubiquitous peptidyl-prolyl
cis-trans
isomerases (PPIases) catalyze the
cis
/
trans
-isomerization of peptidyl-prolyl bonds, often a rate-limiting step for protein folding. PPIases are involved in central processes in eucaryotes but their functions in bacteria are poorly understood. We applied a large-scale two-hybrid screen to identify novel targets of SlyD, a metallochaperone PPIase, from the model organism
Escherichia coli
, and the important gastric pathogen
Helicobacter pylori
. SlyD from both organisms interacts with metal-containing proteins including TCA cycle enzymes and with enzymes driving the biogenesis of iron-sulfur (Fe-S) clusters. In
H. pylori
, a ∆
slyD
mutant contains strongly diminished amounts of MisSU, its sole Fe-S biogenesis proteins as well as diminished activity of the Fe-S aconitase.
E. coli
and
H. pylori ∆slyD
mutants are less susceptible to ampicillin and gentamicin antibiotics and under microaerobic conditions to the ROS-producing molecule hypochlorite. In addition, the intracellular ATP content and proton motive force are reduced in the
H. pylori
∆
slyD
mutant, and its gentamicin and hypochlorite susceptibility phenotypes are rescued upon restoration of MisSU expression. Measurement of malate and fumarate in the
H. pylori ∆slyD
mutant suggests that the two enzymes before and after fumarase in the TCA cycle are affected. We conclude that SlyD regulates the activity of TCA cycle enzymes by controlling the efficiency of their Fe-S cluster formation. This is the first report of the role of a bacterial PPIase in central metabolism and susceptibility to stress and antibiotics.

IMPORTANCE

Correct folding of proteins represents a crucial step for their functions. Among the chaperones that control protein folding, the ubiquitous PPIases catalyze the
cis
/
trans
-isomerization of peptidyl-prolyl bonds. Only few protein targets of PPIases have been reported in bacteria. To fill this knowledge gap, we performed a large-scale two-hybrid screen to search for targets of the
Escherichia coli
and
Helicobacter pylori
SlyD PPIase-metallochaperone. SlyD from both organisms interacts with enzymes (i) containing metal cofactors, (ii) from the central metabolism tricarboxylic acid (TCA) cycle, and (iii) involved in the formation of the essential and ancestral Fe-S cluster cofactor.
E. coli
and
H. pylori ∆slyD
mutants present similar phenotypes of diminished susceptibility to antibiotics and to oxidative stress. In
H. pylori
, measurements of the intracellular ATP content, proton motive force, and activity of TCA cycle proteins suggest that SlyD regulates TCA cycle enzymes by controlling the formation of their indispensable Fe-S clusters.
Neoarchean synkinematic metamorphic peak in the Isua supracrustal belt (West Greenland)
Authors: Eskesen Benjamin , Fassmer Kathrin , Münker Carsten , Ulrich Thomas , Szilas Kristoffer , Wagner Simon , Hoffmann J. Elis , Nagel Thorsten J. 
Published: August 2023

Abstract
We present petrological data and seven Lu-Hf garnet–amphibole–whole rock ages obtained from a single garnet-hornblende-mica schist sample from the Isua supracrustal belt (West Greenland). Garnets grew during prograde metamorphism toward regional amphibolite-facies peak conditions, and a mylonitic foliation formed during and after garnet growth. Garnet crystals show typical prograde zoning with no visible traces of a relict garnet generation. They do show various degrees of retrogression. While some crystals are perfectly euhedral with only minor chemical alteration along cracks, others are elongated in the foliation and either grew in this shape or were deformed. Six garnet splits were separated from crushed single crystals and one from a crushed bulk sample. Individual three-point garnet–hornblende–whole rock ages scatter between 2.603 ± 0.018 Ga and 2.432 ± 0.059 Ga for single garnets. The garnet split from the bulk sample defines an age of 2.463 ± 0.031 Ga, the data point farthest from the regression line for all data points (2.551 ± 0.074 Ga, mean square of weighted deviates = 25). We interpret these data to indicate partial retrogression of a Neoarchean garnet population not significantly older than the oldest obtained three-point age. Well-preserved garnet zoning, regional peak temperatures well below the closing temperature of the Lu-Hf system, and the small scatter of Lu-Hf ages preclude an interpretation of the observed metamorphism and deformation as being Eoarchean in age.
Can quantifying the relative intensity of a person’s free-living physical activity predict how they respond to a physical activity intervention? Findings from the PACES RCT
Authors: Rowlands Alex V , Orme Mark W , Maylor Ben , Kingsnorth Andrew , Herring Louisa , Khunti Kamlesh , Davies Melanie , Yates Tom 
Published: August 2023

ObjectivesTo determine whether quantifying both the absolute and relative intensity of accelerometer-assessed physical activity (PA) can inform PA interventions. We hypothesised that individuals whose free-living PA is at a low relative intensity are more likely to increase PA in response to an intervention, as they have spare physical capacity.MethodWe conducted a secondary data analysis of a 12-month randomised controlled trial, Physical Activity after Cardiac EventS, which was designed to increase PA but showed no improvement. Participants (N=239, 86% male; age 66.4 (9.7); control N=126, intervention N=113) wore accelerometers for 7 days and performed the incremental shuttle walk test (ISWT) at baseline and 12 months. PA intensity was expressed in absolute terms (intensity gradient) and relative to acceleration at maximal physical capacity (predicted from an individual’s maximal ISWT walking speed). PA outcomes were volume and absolute intensity gradient.ResultsAt baseline, ISWT performance was positively correlated with PA volume (r=0.50, p<0.001) and absolute intensity (r=0.50, p<0.001), but negatively correlated with relative intensity (r=−0.13, p=0.025). Relative intensity of PA at baseline moderated the change in absolute intensity (p=0.017), but not volume, of PA postintervention. Low relative intensity at baseline was associated with increased absolute intensity gradient (+0.5 SD), while high relative intensity at baseline was associated with decreased absolute intensity gradient (−0.5 SD).ConclusionThose with low relative intensity of PA were more likely to increase their absolute PA intensity gradient in response to an intervention. Quantifying absolute and relative PA intensity of PA could improve enables personalisation of interventions.
Socioeconomic status, maternal risk factors, and gestational diabetes mellitus across reproductive years: a Finnish register-based study
Authors: Roustaei Zahra , Anttonen Sanna , Räisänen Sari , Gissler Mika , Heinonen Seppo 
Published: August 2023

IntroductionTo evaluate the degree to which socioeconomic differences in gestational diabetes mellitus (GDM) are accounted for by differences in maternal risk factors, to assess whether age-related risks of GDM differ across socioeconomic groups, and to identify priority populations for future interventions.Research design and methodsWe performed a register-based study using data from the Finnish Medical Birth Register and Statistics Finland on the 474 166 women who gave birth in Finland from 2008 to 2015. We collected information on GDM based on the International Classification of Diseases 10th Revision codes O24.4 and O24.9. We used multivariable models to examine the association between socioeconomic status, maternal risk factors, and GDM. We further tested interaction on multiplicative and additive scales.ResultsThe incidence of GDM was 8.7% in 2008–2011 and 12.5% in 2012–2015. Lower socioeconomic levels than upper level employees were associated with an increased risk of GDM. Up to 64.0% of socioeconomic differences in GDM were attributed to body mass index and 5.5% to smoking. There was evidence for effect modification. Relative to women in the upper level category who were aged less than 19 years, GDM adjusted ORs (95% CIs) for women 35 years or older in upper level versus long-term unemployed groups were 3.28 (2.08–5.18) and 5.29 (3.35–8.35), respectively.ConclusionsThere is a paradox that socioeconomic advantage increases the incidence of GDM at the population level while reducing the incidence of GDM within the population. Nevertheless, socioeconomic differences in GDM persist and widen with increasing maternal age, even after accounting for maternal risk factors.
Biomodulating healing after arthroscopic rotator cuff repair: the protocol of a randomised proof of concept trial (BIOHACK)
Authors: Allaart Laurens Jan Houterman , Lech James , Macken Arno Alexander , Kling Agathe , Lafosse Laurent , Lafosse Thibault , van den Bekerom Michel P J , Buijze Geert Alexander 
Published: August 2023

Purpose/introductionOver the last decades, there has been increasing interest in biological stimulation or bioaugmentation after rotator cuff repair. So far, there is no consensus on the appropriate composition of biologicals or which patients would benefit most, and moreover, these biologicals are often expensive. However, there are other, non-pharmacological strategies that are also believed to achieve biological stimulation. This randomised controlled trial evaluates the possible cumulative effect of pragmatic application of cryobiomodulation, photobiomodulation and electrobiomodulation—collectively called biomodulation—on the bone-to-tendon healing process after rotator cuff repair.MethodsIn this randomised, controlled proof of concept study, 146 patients undergoing arthroscopic repair of a full thickness posterosuperior or anterosuperior rotator cuff tear will be 1:1 randomly assigned to either a control group or to the additional biomodulation protocol group. The adjuvant biomodulation protocol consists of seven self-applicable therapies and will be administered during the first 6 weeks after surgery. Primary outcome will be healing of the rotator cuff as evaluated by the Sugaya classification on MRI at 1-year postoperatively.Ethics and disseminationThis study has been accepted by the National Ethical Review Board CPP Sud-Est IV in France and has been registered at Clinicaltrials.gov. The results of this study will be published in a peer-reviewed journal.Trial registration numberNCT04618484.
Cost-effectiveness analysis of serplulimab combined with chemotherapy in the treatment of extensive-stage small-cell lung cancer from the perspective of the healthcare system in China
Authors: Long Yunchun , Xu Yuan , Liao Li , Zhou Yujie , Wang Hao 
Published: August 2023

ObjectiveThe ASTRUM-005 trial showed that serplulimab plus chemotherapy (SEP) significantly extended survival time compared with chemotherapy in the treatment of small cell lung cancer. But the survival benefits of SEP came at high costs, and its economy is not clear. Therefore, this study aimed to evaluate the cost-effectiveness of SEP from the perspective of the Chinese healthcare system.DesignA partition survival model was built to simulate the outcomes. The clinical data came from the ASTRUM-005 trial, and only direct medical costs were included in the model. The utility values referred to the published literature. Scenario analyses 1 and 2 explored outcomes in the presence of a patient assistance plan (PAP) and different simulation periods, respectively. Scenario analysis 3 compared the cost-effectiveness of atezolizumab plus chemotherapy (AEP) with SEP by network meta-analysis. Sensitivity analyses were conducted to assess the robustness of the results.Outcome measuresTotal costs, incremental costs, life years, quality-adjusted life years (QALYs), incremental QALYs and incremental cost-effectiveness ratio (ICER).ResultsCompared with chemotherapy, SEP achieved an additional 0.34 QALYs at incremental costs of US$41 682.63, with an ICER of US$122 378.86/QALY. When PAP was available, ICER was US$58 316.46/QALY. In the simulation time of 5 years and 20 years, the ICER was US$132 637.97/QALY and US$118 054.59/QALY, respectively. When compared with AEP, SEP not only reduced the costs by US$47 244.87 but also gained 0.07 QALYs more. Sensitivity analyses showed that the price of serplulimab and the utility value of the progression-free survival stage were the main influencing parameters, and the results were stable.ConclusionsCompared with chemotherapy, SEP was not cost-effective from the perspective of the Chinese healthcare system. However, SEP was absolutely dominant in comparison with AEP.
TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy
Authors: Tvingsholm Siri Amanda , Frej Marcus Svensson , Rafa Vibeke Mindahl , Hansen Ulla Kring , Ormhøj Maria , Tyron Alexander , Jensen Agnete W P , Kadivar Mohammad , Bentzen Amalie Kai , Munk Kamilla K , Aasbjerg Gitte N , Ternander Jeppe S H , Heeke Christina , Tamhane Tripti , Schmess Christian , Funt Samuel A. , Kjeldsen Julie Westerlin , Kverneland Anders Handrup , Met Özcan , Draghi Arianna , Jakobsen Søren Nyboe , Donia Marco , Marie Svane Inge , Hadrup Sine Reker 
Published: August 2023

BackgroundAdoptive cell therapy (ACT) has shown promising results for the treatment of cancer and viral infections. Successful ACT relies on ex vivo expansion of large numbers of desired T-cells with strong cytotoxic capacity and in vivo persistence, which constitutes the greatest challenge to current ACT strategies. Here, in this study, we present a novel technology for ex vivo expansion of antigen-specific T-cells; artificial antigen-presenting scaffolds (Ag-scaffolds) consisting of a dextran-polysaccharide backbone, decorated with combinations of peptide-Major Histocompatibility Complex (pMHC), cytokines and co-stimulatory molecules, enabling coordinated stimulation of antigen-specific T-cells.MethodsThe capacity of Ag-scaffolds to expand antigen-specific T-cells was explored in ex vivo cultures with peripheral blood mononuclear cells from healthy donors and patients with metastatic melanoma. The resulting T-cell products were assessed for phenotypic and functional characteristics.ResultsWe identified an optimal Ag-scaffold for expansion of T-cells for ACT, carrying pMHC and interleukin-2 (IL-2) and IL-21, with which we efficiently expanded both virus-specific and tumor-specific CD8+ T cells from peripheral blood of healthy donors and patients, respectively. The resulting T-cell products were characterized by a high frequency of antigen-specific cells with high self-renewal capacity, low exhaustion, a multifunctional cytokine profile upon antigen-challenge and superior tumor killing capacity. This demonstrates that the coordinated stimuli provided by an optimized stoichiometry of TCR engaging (pMHC) and stimulatory (cytokine) moieties is essential to obtain desired T-cell characteristics. To generate an ‘off-the-shelf’ multitargeting Ag-scaffold product of relevance to patients with metastatic melanoma, we identified the 30 most frequently recognized shared HLA-A0201-restricted melanoma epitopes in a cohort of 87 patients. By combining these in an Ag-scaffold product, we were able to expand tumor-specific T-cells from 60–70% of patients with melanoma, yielding a multitargeted T-cell product with up to 25% specific and phenotypically and functionally improved T cells.ConclusionsTaken together, the Ag-scaffold represents a promising new technology for selective expansion of antigen-specific CD8+ T cells directly from blood, yielding a highly specific and functionally enhanced T-cell product for ACT.
Reactivation of low avidity tumor-specific CD8+T cells associates with immunotherapeutic efficacy of anti-PD-1
Authors: Sugiyarto Gessa , Lau Doreen , Hill Samuel Luke , Arcia-Anaya David , Boulanger Denise S M , Parkes Eileen E , James Edward , Elliott Tim 
Published: August 2023

BackgroundCD8+T cells are a highly diverse population of cells with distinct phenotypic functions that can influence immunotherapy outcomes. Further insights on the roles of CD8+specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy.MethodsCT26 models were treated with anti-PD-1 on days 3, 6 and 9 following subcutaneous tumor implantation generating variable responses during early tumor development. Tetramer staining was performed to determine the frequency and avidity of CD8+T cells targeting the tumor-specific epitope GSW11 and confirmed with tetramer competition assays. Functional characterization of high and low avidity GSW11-specific CD8+T cells was conducted using flow cytometry and bulk RNA-seq. In vitro cytotoxicity assays and in vivo adoptive transfer experiments were performed to determine the cytotoxicity of high and low avidity populations.ResultsTreatment success with anti-PD-1 was associated with the preferential expansion of low avidity (Tetlo) GSW11-specific CD8+T cells with Vβ TCR expressing clonotypes. High avidity T cells (Tethi), if present, were only found in progressing PD-1 refractory tumors. Tetlodemonstrated precursor exhausted or progenitor T cell phenotypes marked by higher expression of Tcf-1 and T-bet, and lower expression of the exhaustion markers CD39, PD-1 and Eomes compared with Tethi, whereas Tethicells were terminally exhausted. Transcriptomics analyses showed pathways related to TCR signaling, cytotoxicity and oxidative phosphorylation were significantly enriched in Tetlofound in both regressing and progressing tumors compared with Tethi, whereas genes related to DNA damage, apoptosis and autophagy were downregulated. In vitro studies showed that Tetloexhibits higher cytotoxicity than Tethi. Adoptive transfer of Tetloshowed more effective tumor control than Tethi, and curative responses were achieved when Tetlowas combined with two doses of anti-PD-1.ConclusionsTargeting subdominant T cell responses with lower avidity against pMHC affinity neoepitopes showed potential for improving PD-1 immunotherapy. Future interventions may consider expanding low avidity populations via vaccination or adoptive transfer.