bluuebunny/crossref_metadata_2025_split huggingface dataset:
Belgian dietitians′ knowledge, perceptions and willingness‐to‐recommend of genetically modified food and organisms
Authors: De Mesmaeker Mathias , Tran Duc , Verbeecke Vincent , Ameye Florien , Dubaere Pauline , Strobbe Simon , Van Der Straeten Dominique , De Steur Hans 
Published: September 2023

AbstractBackgroundDietitians play a critical role in the public's relationship with food and are often overlooked as an important stakeholder group in the general debate about sustainable food. Genetically modified organisms (GMOs) are one type of modern food source that could contribute to a more sustainable food system. This case study is the first to examine the knowledge, perception and willingness‐to‐recommend (WTR) genetically modified (GM) foods by dietitians in Europe.MethodsAn online survey was addressed to all members of the Flemish Association of Dietitians (Belgium) in 2021, resulting in a sample of 98 valid responses. Multivariate linear regression included sociodemographic, knowledge, and attitudinal factors as the independent variables to explain dietitians' WTR.ResultsFlemish dietitians had limited knowledge of GMOs; only about half of the GM questions were answered correctly. Most dietitians (53%–76%) would recommend GMOs with positive effects on human nutrition or sustainability, whereas few dietitians (19%–27%) would recommend other GMO applications. Trust in GMO information sources and perceived GM benefits significantly influenced a positive WTR of GM foods. Predominant negative information about GM foods was significantly associated with dietitians' low trust and WTR such foods.ConclusionsCountering the predominantly negative portrayal with more neutral and factual information could improve trust, which in turn could positively influence dietitians' perceptions towards GMOs. By further examining the knowledge and perception of dietitians worldwide GMOs and gene‐edited products, new insights could be could gathered into the positioning of this underexposed stakeholder group.
Equilibrium reporting strategy: Two rate classes and full insurance
Authors: Cao Jingyi , Li Dongchen , Young Virginia R. , Zou Bin 
Published: September 2023

AbstractWe propose a multiperiod insurance model under a bonus–malus system with two rate classes and consider an insured who has purchased full insurance for her losses. To explore the potential advantage of underreporting her insurable losses, the insured follows a barrier strategy and only reports lossses above the barrier to the insurer. We obtain a unique equilibrium declaration strategy in closed form for a risk‐neutral insured who maximizes her expected wealth, and in semiclosed form for a risk‐averse insured who maximizes her expected exponential utility of wealth, both over an exogenous random horizon. We find that the equilibrium barriers for the two classes are equal and strictly greater than zero, offering a theoretical explanation for the underreporting of insurable losses, a form of ex post moral hazard. Finally, we consider the case of three rate classes and show, through numerical examples, that the equilibrium barriers are not equal.
A risk science perspective on vaccines
Authors: Glette‐Iversen Ingrid , Aven Terje , Flage Roger 
Published: September 2023

AbstractVaccines can be seen as one of the greatest successes in modern medicine. Good examples are the vaccines against smallpox, polio, and measles. Unfortunately, vaccines can have side effects, but the risks are considered by the health authorities and experts to be small compared to their benefits. Nevertheless, there are many who are skeptical of vaccination, something which has been very clearly demonstrated in relation to the COVID‐19 disease. Risk is the key concept when evaluating a vaccine, in relation to both its ability to protect against the disease and its side effects. However, risk is a challenging concept to measure, which makes communication about vaccines’ performance and side effects difficult. The present article aims at providing new insights into vaccine risks—the understanding, perception, communication, and handling of them—by adopting what is here referred to as a contemporary risk science perspective. This perspective clarifies the relationships between the risk concept and terms like uncertainty, knowledge, and probability. The skepticism toward vaccines is multifaceted, and influenced by concerns that extend beyond the effectiveness and safety of the vaccines. However, by clarifying the relationships between key concepts of risk, particularly how uncertainty affects risk and its characterization, we can improve our understanding of this issue.
Strongyloides infection screening in transplant candidates: What is the best strategy?
Authors: Gryschek Ronaldo Cesar Borges , Corral Marcelo Andreetta , Sitta Renata Barnabé , Gottardi Maiara , Pierrotti Ligia Camera , Costa Silvia Figueiredo , Abdala Edson , Chieffi Pedro Paulo , de Paula Fabiana Martins 
Published: September 2023

AbstractBackgroundThe potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern.MethodsIn this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates.ResultsBy parasitological techniques, 10% of fecal samples were positive. Anti‐Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme‐linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR).ConclusionThe set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.
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Selective efferent vagal stimulation in heart failure
Authors: Booth Lindsea C. , Saseetharan Baagavi , May Clive N. , Yao Song T. 
Published: September 2023

AbstractPatients diagnosed with heart failure have high rates of mortality and morbidity. Based on promising preclinical studies, vagal nerve stimulation has been trialled in these patients using whole nerve electrical stimulation, but the results have been mixed. This is, at least in part, due to an inability to selectively recruit the activity of specific fibres within the vagus with whole nerve electrical stimulation, as well as not knowing which the ‘therapeutic’ fibres are. This symposium review focuses on a population of cardiac‐projecting efferent vagal fibres with cell bodies located within the dorsal motor nucleus of the vagus nerve and a new method of selectively targeting these projections as a potential treatment in heart failure.
Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen,
Candida albicans
Authors: Giuraniuc C. V. , Parkin C. , Almeida M. C. , Fricker M. , Shadmani P. , Nye S. , Wehmeier S. , Chawla S. , Bedekovic T. , Lehtovirta-Morley L. , Richards D. M. , Gow N. A. , Brand A. C. 
Published: September 2023

ABSTRACT

Calcium (Ca
2+
) is an important second messenger for activating stress response signaling and cell adaptation in eukaryotic cells yet intracellular Ca
2+
-dynamics in fungi are poorly understood due to lack of effective real-time Ca
2+
reporters. We engineered the GCaMP6f construct for use in the fungal pathogen,
Candida albicans
, and used live-cell imaging to observe both dynamic Ca
2+
spiking and slower changes in non-spiking Ca
2+
-GCaMP signals elicited by stress or gene deletion. Short-term exposure to membrane, osmotic or oxidative stress generated immediate stress-specific responses and repeated exposure revealed differential recovery signatures. Osmotic stress caused yeast cell shrinkage and no adaptation response, where Ca
2+
-GCaMP spiking was inhibited by 1 M NaCl but not by 0.666 M CaCl
2.
Treatment with sodium dodecylsulfate (SDS) caused a spike-burst, raised the non-spiking Ca
2+
-GCaMP signals, and caused significant cell death, but surviving cells adapted over subsequent exposures. Treatment with 5 mM H
2
O
2
abolished spiking and caused transient non-GCaMP-related autofluorescence, but cells adapted such that spiking returned and autofluorescence diminished on repeated exposure. Adaptation to H
2
O
2
was dependent on Cap1, extracellular Ca
2+
, and calcineurin but not on its downstream target, Crz1. Ca
2+
-dynamics were not affected by H
2
O
2
in the
hog1
Δ or
yvc1
Δ mutants, suggesting a pre-adapted, resistant state, possibly due to changes in membrane permeability. Live-cell imaging of Ca
2+
-GCaMP responses in individual cells has, therefore, revealed the dynamics of Ca
2+
-influx, signaling and homeostasis, and their role in the temporal stress response signatures of
C. albicans
.

IMPORTANCE

Intracellular calcium signaling plays an important role in the resistance and adaptation to stresses encountered by fungal pathogens within the host. This study reports the optimization of the GCaMP fluorescent calcium reporter for live-cell imaging of dynamic calcium responses in single cells of the pathogen,
Candida albicans
, for the first time. Exposure to membrane, osmotic or oxidative stress generated both specific changes in single cell intracellular calcium spiking and longer calcium transients across the population. Repeated treatments showed that calcium dynamics become unaffected by some stresses but not others, consistent with known cell adaptation mechanisms. By expressing GCaMP in mutant strains and tracking the viability of individual cells over time, the relative contributions of key signaling pathways to calcium flux, stress adaptation, and cell death were demonstrated. This reporter, therefore, permits the study of calcium dynamics, homeostasis, and signaling in
C. albicans
at a previously unattainable level of detail.
AP2XII-1 is a negative regulator of merogony and presexual commitment in
Toxoplasma gondii
Authors: Fan Fuqiang , Xue Lilan , Yin Xiaoyan , Gupta Nishith , Shen Bang 
Published: September 2023

ABSTRACT

A transition from the asexual to sexual development in the widespread intracellular pathogen
Toxoplasma gondii
requires stage switching in its feline (definitive) host, but the mechanisms governing this process remain elusive. Here, we demonstrate a novel apicomplexan-specific transcription factor,
Tg
AP2XII-1, that controls the transition of the acutely infectious tachyzoite stage to a presexual merozoite stage. The AP2XII-1 deletion mutants are elongated and replicate as merozoites by endopolygeny instead of endodyogeny, by which tachyzoites proliferate. Besides, the parasites lacking AP2XII-1 show a merozoite-type transcriptional profile. Indeed, AP2XII-1 directly targets many stage-specific genes via its interaction with the MORC complex, eventually repressing a repertoire of sex-related transcripts in tachyzoites. In conclusion, our work identifies AP2XII-1 as a merogony repressor, provides insight into the sexual commitment of
T. gondii
, and opens a gateway to culture the presexual stages of a model parasitic protist.

IMPORTANCE

Sexual development is vital for the transmission, genetic hybridization, and population evolution of apicomplexan pathogens, which include several clinically relevant parasites, such as
Plasmodium, Eimeria,
and
Toxoplasma gondii
. Previous studies have demonstrated different morphological characteristics and division patterns between asexual and sexual stages of the parasites. However, the primary regulation is poorly understood. A transition from the asexual to the sexual stage is supposedly triggered/accompanied by rewiring of gene expression and controlled by transcription factors and chromatin modulators. Herein, we discovered a tachyzoite-specific transcriptional factor AP2XII-1, which represses the presexual development in the asexual tachyzoite stage of
T. gondii
. Conditional knockdown of AP2XII-1 perturbs tachyzoite proliferation by endodyogeny and drives a transition to a morphologically and transcriptionally distinct merozoite stage. The results also suggest a hierarchical transcriptional regulation of sexual development by AP2 factors and provide a path to culturing merozoites and controlling inter-host transmission of
T. gondii
.
Complete genome sequence of seven virulent Newcastle disease virus isolates of sub-genotype XIII.1.1 from Tanzania
Authors: Goraichuk Iryna V. , Msoffe Peter L. M. , Chiwanga Gaspar H. , Dimitrov Kiril M. , Afonso Claudio L. , Suarez David L. 
Published: September 2023

ABSTRACT
We report the complete genome sequences of seven virulent Newcastle disease viruses (NDVs) that were isolated from chickens from live bird markets in the Arusha, Iringa, Mbeya, and Tanga regions of Tanzania in 2012. Phylogenetic analysis revealed that all isolates belong to sub-genotype XIII.1.1.
Clinical
rel
mutations in
Staphylococcus aureus
prime pathogen expansion under nutrient stress
Authors: Chen Edwin , Shaffer Marla G. , Bilodeau Robert E. , West Raymond E. , Oberly Patrick J. , Nolin Thomas D. , Culyba Matthew J. 
Published: September 2023

ABSTRACT

Persistent infection by
Staphylococcus aureus
has been linked to the bacterial stringent response (SR), a conserved stress response pathway regulated by the Rel protein. Rel synthesizes (p)ppGpp “alarmones” in response to amino acid starvation, which enables adaptation to stress by modulating bacterial growth and virulence. We previously identified five novel protein-altering mutations in
rel
that arose in patients with persistent methicillin-resistant
S. aureus
bacteremia. The mutations mapped to both the enzymatic and regulatory protein domains of Rel. Here, we set out to characterize the phenotype of these mutations to understand how they may have been selected
in vivo
. After introducing each mutation into
S. aureus
strain JE2, we analyzed growth, fitness, and antibiotic profiles. Despite being located in different protein domains, we found that all of the mutations converged on the same phenotype. Each shortened the time of lag phase growth and imparted a fitness advantage in nutritionally depleted conditions. Through quantification of intracellular (p)ppGpp, we link this phenotype to increased SR activation, specifically during the stationary phase of growth. In contrast to two previously identified clinical
rel
mutations, we find that our
rel
mutations do not cause antibiotic tolerance. Instead, our findings suggest that
in vivo
selection was due to an augmented SR that primes cells for growth in nutrient-poor conditions, which may be a strategy for evading host-imposed nutritional immunity.

Importance

Host and pathogen compete for available nutrition during infection. For bacteria, the stringent response (SR) regulator Rel responds to amino acid deprivation by signaling the cell to modulate its growth rate, metabolism, and virulence. In this report, we characterize five
rel
mutations that arose during cases of persistent methicillin-resistant
Staphylococcus aureus
bacteremia. We find that all of the mutations augmented SR signaling specifically under nutrient-poor conditions, enabling the cell to more readily grow and survive. Our findings reveal a strategy used by bacterial pathogens to evade the nutritional immunity imposed by host tissues during infection.
Clostridium scindens
secretome suppresses virulence gene expression of
Clostridioides difficile
in a bile acid-independent manner
Authors: Saenz Carmen , Fang Qing , Gnanasekaran Thiyagarajan , Trammell Samuel Addison Jack , Buijink Jesse Arnold , Pisano Paola , Wierer Michael , Moens Frédéric , Lengger Bettina , Brejnrod Asker , Arumugam Manimozhiyan 
Published: September 2023

ABSTRACT

Clostridioides difficile
infection (CDI) is a major health concern and one of the leading causes of hospital-acquired diarrhea in many countries.
C. difficile
infection is challenging to treat as
C. difficile
is resistant to multiple antibiotics. Alternative solutions are needed as conventional treatment with broad-spectrum antibiotics often leads to recurrent CDI. Recent studies have shown that specific microbiota-based therapeutics such as bile acids (BAs) are promising approaches to treat CDI.
Clostridium scindens
encodes the bile acid-induced (
bai
) operon that carries out 7-alpha-dehydroxylation of liver-derived primary BAs to secondary BAs. This biotransformation is thought to increase the antibacterial effects of BAs on
C. difficile
. Here, we used an automated multistage fermentor to study the antibacterial actions of
C. scindens
and BAs on
C. difficile
in the presence/absence of a gut microbial community derived from healthy human donor fecal microbiota. We observed that
C. scindens
inhibited
C. difficile
growth when the medium was supplemented with primary BAs. Transcriptomic analysis indicated upregulation of
C. scindens bai
operon and suppressed expression of
C. difficile
exotoxins that mediate CDI. We also observed BA-independent antibacterial activity of the secretome from
C. scinden
s cultured overnight in a medium without supplementary primary BAs, which suppressed growth and exotoxin expression in
C. difficile
mono-culture. Further investigation of the molecular basis of our observation could lead to a more specific treatment for CDI than current approaches.

IMPORTANCE

There is an urgent need for new approaches to replace the available treatment options against
Clostridioides difficile
infection (CDI). Our novel work reports a bile acid-independent reduction of
C. difficile
growth and virulence gene expression by the secretome of
Clostridium scindens
. This potential treatment combined with other antimicrobial strategies could facilitate the development of alternative therapies in anticipation of CDI and in turn reduce the risk of antimicrobial resistance.
Music medicine to improve the tolerability of onabotulinumtoxinA injections for chronic migraine: an open-label prospective cohort study
Authors: Ray Jason , Raviskanthan Subahari 
Published: September 2023

IntroductionOnabotulinumtoxinA for migraine involves 31 injected repeated every 12 weeks. Tolerability is a significant factor impacting discontinuation. Music medicine has not been studied previously as an intervention to improve the tolerability of injections.MethodologyA single-centre prospective cohort study was undertaken. Following baseline, patients had music played during the procedure. Change in Visual Analogue Score (VAS) was assessed as the primary outcome.ResultsOver 6 months, 50 patients were recruited with a median age of 42, and median duration of therapy of 13.5 months. ‘Quiet calm classical music’ was associated with a significant reduction in VAS (z=−4.7, p<0.001). Duration of therapy, disease state or headache frequency had no correlation with change in VAS.ConclusionMusic medicine is associated with a significant reduction in the procedural pain of onabotulinumtoxinA injections in prospective study. Further study is required to explore other modifiable factors to improve patient experience.
Development and validation of a tool to predict high-need, high-cost patients hospitalised with ischaemic heart disease
Authors: Nkemdirim Okere Arinze , Moussa Richard K , Ali Askal , Diaby Vakaramoko K 
Published: September 2023

ObjectiveTo develop and validate a tool to predict patients with ischaemic heart disease (IHD) at risk of excessive healthcare resource utilisation.DesignA retrospective cohort study.SettingWe identified patients through the State of Florida Agency for Health Care Administration (N=586 518) inpatient dataset.ParticipantsAdult patients (at least 40 years of age) admitted to the hospital with a diagnosis of IHD between 1 January 2007 and 31 December 2016.Primary outcome measuresWe identified patients whose healthcare utilisation is higher than presumed (analysis of residuals) and used logistic regression (binary and multinomial) in estimating the predictive models to classify individual as high-need, high-care (HNHC) patients relative to inpatient visits (frequency of hospitalisation), cost and hospital length of stay. Discrimination power, prediction accuracy and model improvement for the binary logistic model were assessed using receiver operating characteristic statistic, the Brier score and the log-likelihood (LL)-based pseudo-R2, respectively. LL-based pseudo-R2and Brier score were used for multinomial logistic models.ResultsThe binary logistic model had good discrimination power (c-statistic=0.6496), an accuracy of probabilistic predictions (Brier score) of 0.0621 and an LL-based pseudo-R2of 0.0338 in the development cohort. The model performed similarly in the validation cohort (c-statistic=0.6480), an accuracy of probabilistic predictions (Brier score) of 0.0620 and an LL-based pseudo-R2of 0.0380. A user-friendly Excel-based HNHC risk predictive tool was developed and readily available for clinicians and policy decision-makers.ConclusionsThe Excel-based HNHC risk predictive tool can accurately identify at-risk patients for HNHC based on three measures of healthcare expenditures.
Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases – an open, multicentre, randomised non-inferiority phase 3 trial
Authors: Alkner Sara , de Boniface Jana , Lundstedt Dan , Mjaaland Ingvil , Ryden Lisa , Vikstrom Johan , Bendahl Pär-Ola , Holmberg Erik , Sackey Helena , Wieslander Elinore , Karlsson Per 
Published: September 2023

IntroductionModern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.Methods and analysisIn this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I–III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.Ethics and disseminationThe trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.Trial registration numberNCT05634889.