bluuebunny/crossref_metadata_2025 huggingface dataset:
CRIPTO promotes extracellular vesicle uptake and activation of cancer associated fibroblasts
Authors: Freeman David W. , Gates Brooke L. , Spendlove Mauri D. , Gulbahce H. Evin , Spike Benjamin T.
Published: March 2024

Expression of CRIPTO, a factor involved in embryonic stem cells, fetal development, and wound healing, is tied to poor prognosis in multiple cancers. Prior studies in triple negative breast cancer (TNBC) models showed CRIPTO blockade inhibits tumor growth and dissemination. Here, we uncover a previously unidentified role for CRIPTO in orchestrating tumor-derived extracellular vesicle (TEV) uptake and fibroblast activation through discrete mechanisms. We found a novel mechanism by which CRIPTO drives aggressive TNBC phenotypes, involving CRIPTO-laden TEVs that program stromal fibroblasts, toward cancer associated fibroblast cell states, which in turn prompt tumor cell invasion. CRIPTO-bearing TEVs exhibited markedly elevated uptake in target fibroblasts and activated SMAD2/3 through NODAL-independent and - dependent mechanisms, respectively. Engineered expression of CRIPTO on EVs enhanced the delivery of bioactive molecules.In vivo, CRIPTO levels dictated TEV uptake in mouse lungs, a site of EV-regulated premetastatic niches important for breast cancer dissemination. These discoveries reveal a novel role for CRIPTO in coordinating heterotypic cellular crosstalk which offers novel insights into breast cancer progression, delivery of therapeutic molecules, and new, potentially targetable mechanisms of heterotypic cellular communication between tumor cells and the TME.
The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination
Authors: Nguyen Doan C. , Hentenaar Ian T. , Morrison-Porter Andrea , Solano David , Haddad Natalie S. , Castrillon Carlos , Lamothe Pedro A. , Andrews Joel , Roberts Danielle , Lonial Sagar , Sanz Ignacio , Lee F. Eun-Hyung
Published: March 2024

The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma cells can be found in the BM. To better understand this paradox, we enrolled 19 healthy adults at 1.5-33 months after SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus-, or SARS-CoV-2-specific antibody secreting cells (ASC) in LLPC (CD19−) and non-LLPC (CD19+) subsets within the BM. All individuals had IgG ASC specific for influenza, tetanus, and SARS-CoV-2 in at least one BM ASC compartment. However, only influenza- and tetanus-specific ASC were readily detected in the LLPC whereas SARS-CoV-2 specificities were mostly excluded. The ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.61, 0.44, and 29.07, respectively. Even in five patients with known PCR-proven history of infection and vaccination, SARS-CoV-2-specific ASC were mostly excluded from the LLPC. These specificities were further validated by using multiplex bead binding assays of secreted antibodies in the supernatants of cultured ASC. Similarly, the IgG ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.66, 0.44, and 23.26, respectively. In all, our studies demonstrate that rapid waning of serum antibodies is accounted for by the inability of mRNA vaccines to induce BM LLPC.
Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms
Authors: Suzuki-Okutani Mie , Okamura Shinya , Tanggis  , Sasaki Hitomi , Lee Suni , Yoshida Akiho , Goto Simon , Matsumoto Mai , Yamawaki Mayuko , Miyazaki Toshiaki , Nakagawa Tatsuya , Ikawa Masahito , Kamitani Wataru , Takekawa Shiro , Yamanishi Koichi , Ebina Hirotaka
Published: March 2024

mRNA vaccines against SARS-CoV-2 were rapidly developed and effective during the pandemic. However, some limitations remain to be resolved, such as the short-lived induced immune response and certain adverse effects. Therefore, there is an urgent need to develop new vaccines that address these issues. While live-attenuated vaccines are a highly effective modality, they pose a risk of adverse effects, including virulence reversion. In the current study, we constructed a live-attenuated vaccine candidate, BK2102, combining naturally occurring virulence-attenuating mutations in theNSP14,NSP1, spike andORF7-8coding regions. Intranasal inoculation with BK2102 induced humoral and cellular immune responses in Syrian hamsters without apparent tissue damage in the lungs, leading to protection against a SARS-CoV-2 D614G and an Omicron BA.5 strains. The neutralizing antibodies induced by BK2102 persisted for up to 364 days, which indicated that they confer long-term protection against infection. Furthermore, we confirmed the safety of BK2102 using transgenic (Tg) mice expressing human ACE2 (hACE2), that are highly susceptible to SARS-CoV-2. BK2102 did not kill the Tg mice, even when virus was administered at a dose of 106plaque-forming units (PFU), while 102PFU of the D614G strain or an attenuated strain lacking the furin cleavage site (FCS) of the spike was sufficient to kill mice. These results suggest that BK2102 is a promising live-vaccine candidate strain that confers long-term protection without significant virulence.
Crystal structure ofBifidobacterium bifidumglycoside hydrolase family 110 α-galactosidase specific for blood group B antigen
Authors: Kashima Toma , Akama Megumi , Wakinaka Takura , Arakawa Takatoshi , Ashida Hisashi , Fushinobu Shinya
Published: March 2024

To overcome incompatibility issues and increase the possibility of blood transfusion, technologies that enable efficient conversion of A- and B-type red blood cells to the universal donor O-type is desirable. Although several blood type-converting enzymes have been identified, detailed understanding about their molecular functions is limited. α-Galactosidase fromBifidobacterium bifidumJCM 1254 (AgaBb), belonging to glycoside hydrolase (GH) 110 subfamily A, specifically acts on blood group B antigen. Here we present the crystal structure of AgaBb, including the catalytic GH110 domain and part of the C-terminal uncharacterized regions. Based on this structure, we deduced a possible binding mechanism of blood group B antigen to the active site. Site-directed mutagenesis confirmed that R270 and E380 recognize the fucose moiety in the B antigen. Thermal shift assay revealed that the C-terminal uncharacterized region significantly contributes to protein stability. This region is shared only among GH110 enzymes fromB. bifidumand someRuminococcusspecies. The elucidation of the molecular basis for the specific recognition of blood group B antigen is expected to lead to the practical application of blood group conversion enzymes in the future.
Activation of the imprinted Prader-Willi Syndrome locus by CRISPR-based epigenome editing
Authors: Rohm Dahlia , Black Joshua B. , McCutcheon Sean R. , Barrera Alejandro , Morone Daniel J. , Nuttle Xander , de Esch Celine E. , Tai Derek J.C. , Talkowski Michael E. , Iglesias Nahid , Gersbach Charles A.
Published: March 2024

Summary

Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi Syndrome (PWS) is caused by loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control expression of the PWS geneSNRPNfrom the paternal and maternal chromosomes. We showed that either targeted transcriptional activation or DNA demethylation can activate the silenced maternalSNRPNand downstream PWS transcripts. However, these two approaches function at unique regions, preferentially activating different transcript variants and involving distinct epigenetic reprogramming mechanisms. Remarkably, transient expression of the targeted demethylase leads to stable, long-term maternalSNRPNexpression in PWS iPSCs. This work uncovers targeted epigenetic manipulations to reprogram a disease-associated imprinted locus and suggests possible therapeutic interventions.
Identification of Interaction Partners of Outer Inflammatory Protein A: Computational and Experimental Insights into How Helicobacter pylori Infects Host Cells
Authors: Akcelik-Deveci Sümeyye , Kılıç Elif , Mansur Ozen Nesteren , Timucin Emel , Buyukcolak Yaren , Oktem-Okullu Sinem
Published: March 2024

Adherence to the gastric epithelium is an essential feature ofHelicobacter pylorifor its colonization. Outer membrane proteins (OMPs) play a pivotal role in adherence potentiating the survival of the microbe in the gastric tissue. Among these proteins, Outer inflammatory protein A (OipA) is a critical protein that is known to help bacteria to colonize on the host gastric epithelial cell surface. Although the role of OipA in theH. pyloriattachment and the association between OipA-positiveH. pyloristrains and clinical outcomes have been demonstrated, there is limited information on the structural mechanism of the OipA action in the adherence ofH. pylorito the gastric epithelial cell surface. Our study utilizes experimental and computational methodologies to investigate the interaction partners of OipA on the gastric epithelial cell surface. Initially, we performed a proteomic analysis to decipher the OipA interactome in the human gastric epithelial cells using a pull-down assay of the recombinant OipA and the membrane proteins of the gastric epithelial cells. Proteomic analysis has revealed 704 unique proteins that interacted with OipA. We have further analyzed 16 partners of OipA using molecular modeling tools. Structural findings obtained from the prediction of the protein-protein complexes of OipA and candidate partners unraveled 3 human proteins whose OipA interactions could base an explanation about howH. pylorirecruits OipA for adherence. Altogether, the findings presented here provide insights into novel mechanisms ofH. pyloriand host interactions through OipA, reflecting the potential of these mechanisms and interactions as therapeutic targets to combatH. pyloriinfection.

Key points

Outer membrane proteins (OMPs) are an emerging topic in bacterial infection.

OipA is a candidate for an adherence-receptor network on the gastric epithelial cell surface withH. pylori.

OipA interactome partners on gastric epithelial cell surfaces are valuable therapeutic targets for theH. pyloriinfection.
Epigenetic Mechanisms Regulating the Association betweenOR2L13and Major Psychiatric Disorders
Authors: Du Xiujuan , Zhang Lingli , Ren Tai , He Hua , Zhao Jian , Li Fei
Published: March 2024

Background

Previously, population-based cohort studies have identified the association between epigenetic modifications ofOR2L13related to mental disorders and Gestational diabetes mellitus (GDM). However, the causal nature of these associations remains difficult to establish owing to confounding.

Aims

The purpose of the study was to investigate the causal effect of methylation ofOR2L13and offspring mental health outcomes.

Method

We performed two-sample mendelian randomisation to assess the effect of methylation ofOR2L13on mental disorders. Methylation of 7 CpG sites withinOR2L13related to GDM from two previous studies were used as exposure. Genome wide significant single nucleotide polymorphisms for methylation ofOR2L13retrieved from published data were used as instrumental variables. Their causal impact on major psychiatric disorders was assessed using summary-level data mostly from the Psychiatric Genomics Consortium.

Results

LowerOR2L13methylation was casually associated with a higher risk of PD in offspring [cg03748376: odds ratio (OR)=0.81, 95% confidence interval (CI) =0.68–0.97, P =0.02]. However, little evidence was found for a causal relationship between the methylation levels ofOR2L13and autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), bipolar disorder (BD) and obsessive-compulsive disorder (OCD).

Conclusions

Evidence from our study supported a causal effect of lowerOR2L13methylation on PD risk.
Challenges in identifying and quantifying country-level participation in multi-country randomised controlled trials involving Ireland as a collaborating partner
Authors: Larkin James , Alanza Uchechukwu , Raj Nagarajan Vikneswaran , Collins Maurice , Termanini Sami , Farrington Emmet , Clyne Barbara , Fahey Tom , Moriarty Frank
Published: March 2024

Background and Objective

Randomised controlled trials (RCTs) provide vital information about healthcare interventions. Accurate reporting is vital for effective RCT dissemination. This study aimed to assess the reporting quality of multi-country RCTs, using Ireland as a case study, examining trial characteristics, adherence to reporting standards and the reporting of participation from Ireland.

Study Design and Setting

This is a secondary analysis of RCTs identified in a previous observational study of RCTs where ≥80% of participants were recruited in Ireland. This current study focuses on multi-country RCTs with Ireland as a participating country. The current study involved an additional screening process according to these inclusion criteria: RCTs conducted on humans in a healthcare setting with centres based in Ireland, and <80% of participants recruited in Ireland. The primary outcome variables were trial characteristics and reporting rates for: trial registration, use of standardised reporting guidelines, number of Irish centres and number of participants recruited in Ireland. Descriptive statistics were used for analysis.

Results

Overall, 239 RCTs were included. The most common intervention was a drug (74.9% of RCTs). The most common setting was an ambulatory setting (74.1% of RCTs). The most common clinical domain was the cardiovascular system (18.0% of RCTs). Among RCTs published after the CONSORT reporting guideline was published (1996), 8.3% referred to a standardised reporting guideline. Among RCTs published after the International Committee of Medical Journal Editors mandated clinical trial registration (2005), 81.8% provided registration numbers. Number of Irish centres was reported in 75.3% (N=180) of RCTs. Number of participants recruited in Ireland was reported in 27.2% (N=65) of RCTs.

Conclusion

Our findings show deficits in reporting quality for multi-country RCTs, particularly in referring to reporting guidelines and reporting number of participants for the examined country. Institutions should create policies to ensure transparent RCT dissemination.
Determining the feasibility of linked claims and vaccination data for a Covid-vaccine pharmaco-epidemiological study in Germany – RiCO feasibility study protocol
Authors: Timmesfeld Nina , Ihle Peter , Denz Robin , Meiszl Katharina , Scholz Katrin , Oberle Doris , Drechsel-Bäuerle Ursula , Keller-Stanislawski Brigitte , Diebner Hans H. , Meyer Ingo
Published: March 2024

In Germany, there has been no population-level pharmaco-epidemiological study on the safety of the Covid-19 vaccines. One factor preventing such a study so far relates to challenges combining the different relevant data bodies on vaccination with suitable outcome data, specifically statutory health insurance claims data. Individual identifiers used across these data bodies are of unknown quality and reliability for data linkage. As part of a larger pharmaco-vigilance study on the COVID-19 vaccines, called RiCO (German "Risikoevaluation der COVID-19-Impfstoffe”, Englisch "Risk assessment of COVID-19 vaccines”), a feasibility study is being conducted to determine the overall confidence level with which existing data can be analysed in relation to the safety of the COVID-19 vaccine. This RiCO feasibility study will establish a dataflow combining claims data and vaccination data for a sub-sample of the total German population, describe data quality for each data set from the various sources, estimate the proportion of the different linkage errors and will develop various approaches for linking the data in addition to the simple form of linkage using a common identifier in order to reduce possible linkage errors. These last three points are the core objective of the feasibility study. A secondary objective is to test the viability of the required dataflow involving multiple stakeholders from different parts of the healthcare system. Results will be published and used to plan the actual pharmaco-vigilance study on the COVID-19 vaccines for Germany, as well as future research on the role of COVID vaccines as risk or protective factors for long-term COVID-19 effects.

Strength and limitations

Potential for a population-level pharmaco-epidemiological study on the safety of the Covid-19 vaccines for Germany, based on vaccination data combined with statutory health insurance claims data.

Introduction and estimation of quality metrics pertaining to the linkability of the various data bodies existing in Germany.

Direct measurement of linkage error based on the available identifiers is not possible, proxy metrics and descriptive analytics need to be used.

An attempt at linkage with the vaccination data could only be made using data from one smaller statutory health insurance, which may limit the extent to which the data can be analysed.
Systematic Review of Large Language Models for Patient Care: Current Applications and Challenges
Authors: Busch Felix , Hoffmann Lena , Rueger Christopher , van Dijk Elon HC , Kader Rawen , Ortiz-Prado Esteban , Makowski Marcus R , Saba Luca , Hadamitzky Martin , Kather Jakob Nikolas , Truhn Daniel , Cuocolo Renato , Adams Lisa C , Bressem Keno K
Published: March 2024

The introduction of large language models (LLMs) into clinical practice promises to improve patient education and empowerment, thereby personalizing medical care and broadening access to medical knowledge. Despite the popularity of LLMs, there is a significant gap in systematized information on their use in patient care. Therefore, this systematic review aims to synthesize current applications and limitations of LLMs in patient care using a data-driven convergent synthesis approach. We searched 5 databases for qualitative, quantitative, and mixed methods articles on LLMs in patient care published between 2022 and 2023. From 4,349 initial records, 89 studies across 29 medical specialties were included, primarily examining models based on the GPT-3.5 (53.2%, n=66 of 124 different LLMs examined per study) and GPT-4 (26.6%, n=33/124) architectures in medical question answering, followed by patient information generation, including medical text summarization or translation, and clinical documentation. Our analysis delineates two primary domains of LLM limitations: design and output. Design limitations included 6 second-order and 12 third-order codes, such as lack of medical domain optimization, data transparency, and accessibility issues, while output limitations included 9 second-order and 32 third-order codes, for example, non-reproducibility, non-comprehensiveness, incorrectness, unsafety, and bias. In conclusion, this study is the first review to systematically map LLM applications and limitations in patient care, providing a foundational framework and taxonomy for their implementation and evaluation in healthcare settings.
Evaluation of efficacy of formic acid and thermal remediation for management ofTropilaelapsandVarroamites in central Thailand
Authors: Sankovitz Madison , Steinhauer Nathalie , Yemor Tanawat , Cook Steven C. , Evans Jay D. , Ramsey Samuel D.
Published: March 2024

The western honey bee,Apis mellifera, faces a new threat from the spread of parasiticTropilaelaps(Tropi) mites, specificallyT. mercedesae, which adds additional complexity to an apicultural landscape heavily impacted byVarroa destructor. In this study conducted in central Thailand, we investigated the efficacy of two methods of applying formic acid and a thermal remediation technique in controlling Tropi mites andVarroa, focusing our attention on the reproductive stage of the mites which is restricted to capped brood cells. Results revealed that both formic acid treatments (Formic Pro and liquid formic acid) demonstrated an immediate and substantial reduction in live Tropi andVarroapopulations, maintaining near-zero levels for the 3- week duration of the study. In contrast, thermal remediation, employing heating pads, exhibited a more gradual decline, achieving an 85.42% reduction in Tropi mites and a 92.33% reduction inVarroamites by week three. Notably, heat-treated colonies experienced an unexpected resurgence in mite populations during week two. The findings contribute valuable insights into potential strategies for mitigating the threat of Tropi mites and highlight the urgency of further research to safeguard global honey bee populations.
Bsp22 protein polymerization drives dynamic adaptation of theBordetellatype III secretion system injectisome
Authors: Malcova Ivana , Kamanova Jana
Published: March 2024

Many gram-negative bacteria are equipped with a type III secretion system (T3SS) injectisome, enabling the direct translocation of effector proteins from the bacterial cytoplasm into host cells. In the case ofBordetella bronchiseptica, a respiratory pathogen of diverse mammals, the T3SS injectisome exhibits a unique needle tip filament formed by the Bsp22 protein, essential for bacterial persistence in mice. Here, we usedB. bronchisepticaandB. pertussiswith in-frame insertions of short peptide tags into the Bsp22 to elucidate its formation and characteristics via super-resolution imaging with fluorophore-labeled nanobodies and biarsenic probes. We report that on abiotic surfaces, Bsp22 forms flexible filaments that protrude up to several µm from bacterial cells. In these conditions, Bsp22 filaments grow continuously without any apparent growth control, with Bsp22 subunits being added at the distal end. Remarkably, during host cell infection, the growth of Bsp22 filaments is constrained, accompanied by downregulated Bsp22 protein production. When infecting HeLa cells, some Bsp22 filaments form a short physical bridge between the bacterium and the host cell surface. In nasal epithelium, whereB. bronchisepticacolonization is specifically restricted to ciliated cells, Bsp22 filaments align parallel to the cilia, pointing towards the cell apical surface. These results highlight the context-specific and environment-influenced dynamic modulation of the length and orientation ofBordetellaneedle tip filament, uncovering the adaptability of theBordetellaT3SS injectisome in response to conditions encountered during host cell infection.
Lords of the flies: Dipteran migrants are diverse, abundant and ecologically important
Authors: Hawkes Will L. , Menz Myles H.M. , Wotton Karl R.
Published: March 2024

Insect migrants are hugely abundant and recent studies have identified Diptera as the major component of many migratory assemblages, often totalling up to 90% of all individuals. Despite this, studies into their migratory behaviour have been widely eschewed in favour of the more ‘charismatic’ migrant insects such as butterflies, dragonflies, and moths. Here we review the available literature on Dipteran migration and identify 13 lines of evidence that we use to determine migratory behaviour. Using this approach, we find species from 60 out of 130 Dipteran families that show evidence of migration, with Syrphidae fulfilling 12 of these criteria, followed by the Tephritidae with 10. In contrast to these groups, 22 families fulfilled just two lines of evidence or fewer, underlining the need for more research into the migratory characteristics of these groups. In total, 622 species of Diptera were found to have migratory behaviour (0.5% of the total Dipteran species count), a figure rising to 3% for the Syrphidae, a percentage mirrored by other animal taxa such as butterflies, noctuid moths, and bats. Research was biased to locations in Europe (49% of publications) and while vast regions remain understudied, our review identified major flyways used by Dipteran migrants across all biogeographic realms. Finally, we detail the ecological and economic roles of these migrants and review how these services are being affected by anthropogenic change through population declines and phenological shifts. Overall, this review highlights how little is known about Dipteran migration and how vital their migratory behaviour may be to the health of global ecosystems.
Integrativein vivoanalysis of the ethanolamine utilization bacterial microcompartment inEscherichia coli.
Authors: Jallet Denis , Soldan Vanessa , Shayan Ramteen , Stella Alexandre , Ismail Nour , Zenati Rania , Cahoreau Edern , Burlet-Schiltz Odile , Balor Stéphanie , Millard Pierre , Heux Stéphanie
Published: March 2024

Bacterial microcompartments (BMCs) are self-assembling protein megacomplexes that encapsulate metabolic pathways. Although approximately 20% of sequenced bacterial genomes contain operons encoding putative BMCs, few have been thoroughly characterized, nor any in the most studiedEscherichia colistrains. We used an interdisciplinary approach to gain deep molecular and functional insights into the ethanolamine utilization (Eut) BMC system encoded by theeutoperon inE. coliK-12. Theeutgenotype was linked with the ethanolamine utilization phenotype using deletion and overexpression mutants. The subcellular dynamics and morphology of theE. coliEut BMC were characterizedin cellulaby fluorescence microscopy and electron (cryo)microscopy. The minimal proteome reorganization required for ethanolamine utilization and thein vivostochiometric composition of the Eut BMC were determined by quantitative proteomics. Finally, the first flux map connecting the Eut BMC with central metabolismin cellulawas obtained by genome scale modelling and13C-fluxomics. Our results reveal that, contrary to previous suggestions, ethanolamine serves both as a nitrogen and a carbon source inE. coliK-12, while also contributing significant metabolic overflow. Overall, this study provides a quantitative molecular and functional understanding of the BMCs involved in ethanolamine assimilation byE. coli.

Importance

The properties of BMCs make them an ideal tool to build orthogonal network structures with minimal interactions with native metabolic and regulatory networks. However, this requires an understanding of how BMCs work natively. In this study, we combined genetic manipulation, multi-omics, modelling and microscopy to address this issue for Eut BMCs. We show that the Eut BMC inE. coliturns ethanolamine into usable carbon and nitrogen substrates to sustain growth. These results improve our understanding of compartmentalization in a widely used bacterial chassis.
Systematic classification of phage receptor-binding proteins predicts surface glycopolymer structure inStaphylococcuspathogens
Authors: Krusche Janes , Beck Christian , Lehmann Esther , Gerlach David , Wolz Christiane , Peschel Andreas
Published: March 2024

Wall teichoic acids (WTAs) are major surface polymers of staphylococcal pathogens and commensals, whose variable structure governs interaction with host receptors, immunoglobulins, and bacteriophages. The ribitol phosphate (RboP) WTA type contributes to virulence, for instance inStaphylococcus aureus, but we lack comprehensive knowledge of WTA types and cognate phages.

We developed a computational pipeline to identify the receptor-binding proteins (RBPs) in 335 Staphylococcus phage genomes, yielding multiple distinct RBP clusters. Notably, many phages had two separate RBPs with in part different WTA preferences. RBP representatives differed in specificity for RboP WTA glycosylation types, recapitulating the specificity of the corresponding phage. Based on these results, we created a publicly available bioinformatic tool to predict phage host specificity based on RBP similarity.

The RboP WTA specific Φ13-RBP also revealed that the presence of RboP WTA on non-aureus staphylococci is more common than previously thought. Our approach facilitates the characterization of opportunistic Staphylococcus pathogens according to WTA types, which has major implications for phage-mediated interspecies horizontal gene transfer and future phage therapies.
Biological Control of Green Mold in Simulated Post-harvest Chain of Citrus Fruit: Efficacy ofCandida oleophilaStrain O and Molecular Insight into Elicitation of Host Immune System
Authors: Rovetto Ermes Ivan , Spada Federico LA , Boumlasy Soumia EL , Conti Taguali Sebastiano , Riolo Mario , Pane Antonella , Cacciola Santa Olga
Published: March 2024

Managing post-harvest decays in citrus fruit without relying on conventional pesticides presents a significant challenge in modern Plant Pathology. This study aimed to evaluate the efficacy of the biological control agentCandida oleophilastrain O in controlling green mold caused byPenicillium digitatumthroughout various stages of the post-harvest supply chain. Using a series ofin vivoexperiments, different scenarios ofP. digitatuminfections in clementine tangerine, orange, and lemon fruit were examined, with treatments applied before, during or after infection. The study simulated typical conditions of the citrus supply chain, including picking, processing in packinghouses, and transportation, as well as cold storage and shelf-life phases. Results indicated thatC. oleophilaexhibited significant efficacy in reducing green mold symptoms, even at shelf-life temperatures, making it a practical alternative to conventional fungicides. Additionally, the study provided insights into the molecular mechanisms underlying the defensive response of citrus fruit toC. oleophilatreatment, with up-regulation of defense-related genes observed across different fruit types. Overall, this study underscores the potential ofC. oleophilaas a sustainable and effective solution for managing post-harvest decays in citrus fruit within the complexities of the supply chain.
Dynamical generation of the scalar
f0(500)
,
f0(980)
, and
K0*(700)
resonances in the
Ds+→K+π+π−
reaction
Authors: Dai L. R. , Oset E.
Published: March 2024

We develop a model aimed at understanding the three mass distributions of pairs of mesons in the Cabibbo-suppressed Ds+→K+π+π− decay recently measured with high statistics by the BESIII collaboration. The largest contributions to the process come from the Ds+→K+ρ0 and Ds+→K*0π+ decay modes, but the Ds+→K0*(1430)π+ and Ds+→K+f0(1370) modes also play a moderate role and all of them are introduced empirically. Instead, the contribution of the f0(500), f0(980), and K0*(700) resonances is introduced dynamically by looking at the decay modes at the quark level, hadronizing qq¯ pairs to give two mesons, and allowing these mesons to interact, for which we follow the chiral unitary approach, to finally produce the K+π+π− final state. While the general features of the mass distributions are fairly obtained, we pay special attention to the specific effects created by the light scalar resonances, which are visible in the low mass region of the π+π−(f0(500)) and K+π−(K0*(700)) mass distributions and a narrow peak for π+π− distribution corresponding to f0(980) excitation. The contribution of these three resonances is generated by only one parameter. We see the agreement found in these regions as further support for the nature of the light scalar states as dynamically generated from the interaction of pseudoscalar mesons.

Published by the American Physical Society
2024
To assess or not to assess an entrepreneurship competence in vocational education and training? Results from a case study of Italy
Authors: Morselli Daniele
Published: March 2024

Purpose

This article focuses on the assessment of entrepreneurship competence by selected vocational teachers in Italy. The exploratory research question addresses the extent to which entrepreneurship assessments are competence based, and the research seeks to identify fully fledged assessment programmes with both a formative and summative component, and the use of assessment rubrics. It also explores the extent to which entrepreneurship competence is referred to in school documentation and later assessed, and the tools and strategies used for such assessment.

Design/methodology/approach

This case study is part of a larger European research project promoted by Cedefop; in Italy it focused on six selected vocational IVET and CVET programmes and apprenticeship schemes. It used a wide range of instruments to ensure triangulation and multiple perspectives: analysed policy documents and undertook online interviews with experts and policy makers. At VET providers' premises it deployed: analysis of school documents; observations of learning environments; interviews and focus groups with (in schools) teachers, directors and vice directors, learners and alumni (in companies) instructors, company tutors and employers, apprentices and alumni.

Findings

Assessment tasks were rarely embedded within fully fledged assessment programmes involving both formative and summative tasks, and assessment rubric for grading. Most of the time, entrepreneurship programmes lacked self-assessment, peer assessment and structured feedback and did not involve learners in the assessment process. Some instructors coached the students, but undertook no clear formative assessment. These findings suggest institutions have a testing culture with regard to assessment, at the level of both policy and practice. In most cases, entrepreneurship competence was not directly assessed, and learning outcomes were only loosely related to entrepreneurship.

Research limitations/implications

One limitation concerned the selection of the VET providers: these were chosen not on a casual basis, but because they ran programmes that were relevant to the development of entrepreneurship competence.

Practical implications

At the policy level, there is a need for new guidelines on competence development and assessment in VET, guidelines that are more aligned with educational research on competence development. To ensure the development of entrepreneurship competence, educators need in-service training and a community of practice.

Originality/value

So far, the literature has concentrated on entrepreneurship education at the tertiary level. Little is known about how VET instructors assess entrepreneurship competence. This study updates the picture of policy and practice in Italy, illustrating how entrepreneurship competence is developed in selected IVET and CVET programmes and apprenticeships.
G‐quadruplex is involved in the regulation of BmSGF1 expression in the Silkworm, Bombyx mori
Authors: Chen Yanfei , Li Jin , Niu Kangkang , Peng Yuling , Song Qisheng , Feng Qili
Published: March 2024

Advanced DNA structures, such as the G‐quadruplex (G4) and the i‐motif, are widely but not randomly present in the genomes of many organisms. A G4 structure was identified in the promoter of the silk gland factor‐1 gene (SGF1), which is the main regulatory gene for silk production in Bombyx mori. In this study, a BmSGF1 G4−/− homozygous mutant was generated with the G4 sequence knocked out. The promoter activity of BmSGF1 was lowered in the BmSGF1 G4−/− mutant. Pyridostatin (PDS) stabilized the G4 structure and increased the promoter activity of BmSGF1, whereas anti‐sense oligonucleotide (ASO) complementary to the G4 sequence suppressed the promoter activity of BmSGF1. Compared with wild‐type larvae, the deletion of the BmSGF1 G4 structure decreased both the expression of BmSGF1 and the fibroin heavy chain gene BmFib‐H in the posterior silk gland and the weight of the cocoons. Overall, these results suggest that the promoter G4 structure of BmSGF1 participates in the transcription regulation of the BmSGF1 gene in the silkworm.
Serum levels of CXCL5 are decreased and correlate with circulating platelet counts in systemic lupus erythematosus
Authors: Zhang Liang , Zhao Liling , Du Keqian , Chen Juan , Ding Huihua , Petersen Frank , Ye Shuang , Lin Zhiming , Yu Xinhua
Published: March 2024

Objective

To identify disease‐specific serum chemokine profiles and potential anti‐inflammatory chemokines in three rheumatic diseases.

Methods

The discovery cohort included 18 patients with rheumatoid arthritis (RA), 20 patients with primary Sjögren's syndrome (pSS), 24 patients with systemic lupus erythematosus (SLE) and 28 healthy subjects. Findings from the discovery cohort were validated in two replication cohorts, consisting of 23 patients with SLE matched with 23 healthy subjects and 62 patients with SLE, 16 patients with ANCA‐associated vasculitis (AAV), and 32 healthy controls, respectively. Serum levels of chemokines were determined using multiplex assay or ELISA.

Results

In the discovery cohort, serum levels of multiple chemokines were increased in one or more diseases in comparison to healthy subjects, including CCL2, CCL20, CXCL9, CXCL10, and CXCL11 in SLE, CCL2, CCL4, and CXCL11 in pSS, and CCL2, CCL4, and CXCL9 in RA. Notably, serum levels of CCL3 (p = .0003) and CXCL5 (p = .0003) were decreased in SLE. The SLE‐specific decrease in CXCL5 serum levels was confirmed in the two replication cohorts, with p = .0034 and p = .0006, respectively. Moreover, a positive correlation between serum levels of CXCL5 and circulating platelet counts (R = .71, p = .00018) in SLE observed in the discovery cohort was confirmed in both replication cohorts (R = .52, p = .011 and R = .49, p = .00005, respectively).

Conclusion

In the present study, we demonstrate that serum levels of CXCL5 are decreased in patients with SLE and positively correlated with circulating platelet count. These findings suggest that platelet‐associated CXCL5 is presumably involved in the development of SLE.
Finger cuff versus invasive and noninvasive arterial pressure measurement in pregnant patients with obesity
Authors: Eley Victoria , Llewellyn Stacey , Pelecanos Anita , Callaway Leonie , Smith Matthew , van Zundert Andre , Stowasser Michael
Published: March 2024

Background

Pregnant patients with obesity may have compromised noninvasive blood pressure (NIBP) measurement. We assessed the accuracy and trending ability of the ClearSight™ finger cuff (FC) with invasive arterial monitoring (INV) and arm NIBP, in obese patients having cesarean delivery.

Methods

Participants were aged ≥18 years, ≥34 weeks gestation, and body mass index (BMI) ≥ 40 kg m−2. FC, INV, and NIBP measurements were obtained across 5‐min intervals. The primary outcome was agreement of FC measurements with those of the reference standard INV, using modified Bland–Altman plots. Secondary outcomes included comparisons between FC and NIBP and NIBP versus INV, with four‐quadrant plots performed to report discordance rates and evaluate trending ability.

Results

Twenty‐three participants had a median (IQR) BMI of 45 kg m−2 (44–48). When comparing FC and INV the mean bias (SD, 95% limits of agreement) for systolic blood pressure (SBP) was 16 mmHg (17, −17.3 to 49.3 mmHg), for diastolic blood pressure (DBP) −0.2 mmHg (10.5, −20.7 to 20.3), and for mean arterial pressure (MAP) 5.2 mmHg (11.1, −16.6 to 27.0 mmHg). Discordance occurred in 54 (26%) pairs for SBP, 41 (23%) for DBP, and 41 (21.7%) for MAP. Error grid analysis showed 92.1% of SBP readings in Zone A (no‐risk zone). When comparing NIBP and INV, the mean bias (95% limits of agreement) for SBP was 13.0 mmHg (16.7, −19.7 to 29.3), for DBP 5.9 mmHg (11.9, −17.4 to 42.0), and for MAP 8.2 mmHg (11.9, −15.2 to 31.6). Discordance occurred in SBP (84 of 209, 40.2%), DBP (74 of 187, 39.6%), and MAP (63 of 191, 33.0%).

Conclusions

The FC and NIBP techniques were not adequately in agreement with INV. Trending capability was better for FC than NIBP. Clinically important differences may occur in the setting of the perfusion‐dependent fetus.
Amplitude‐integrated electroencephalography showed no differences in cerebral activity between preterm singletons and twins in the first 4 weeks of life
Authors: Schreiner Christina , Staudt Anna , Kiechl‐Kohlendorfer Ursula , Griesmaier Elke
Published: March 2024

Aim

Genetic influences on cerebral activity have been described previously, but data are scarce in preterms. We aimed to investigate whether a genetic influence causes amplitude‐integrated electroencephalography (aEEG) signals to differ between singletons and twin preterm newborns.

Methods

This was a retrospective single‐centre study conducted at Innsbruck Medical University Hospital, Austria. Preterm infants born before 32 weeks of gestation between 6 November 2010 and 6 December 2022 were eligible for the study. The aEEG was analysed for the total maturation score, its component scores and the number of sleep–wake cycles per hour.

Results

We enrolled 240 preterm twin infants (57.5% male) with a mean gestational age of 30 (range: 24–32) weeks and a mean birth weight of 1324 (range: 600–2116) grams. We compared 240 singleton matched preterms. No differences were found between preterm singletons and twin preterm infants regarding the total maturation and component scores, or the number of sleep–wake cycles. aEEG showed no difference between monozygotic and dizygotic twins.

Conclusion

Compared to singletons, twin infants born preterm showed no differences in aEEG signals in the first 4 weeks of life. Future studies should include more complex non‐invasive functional neuroimaging methods to gain more insight into this important topic.
A virtuous cycle between meaning in daily life and state mindfulness as well as the unique role of depression among young adults: A diary study
Authors: Lian Yangyu , Zhang Wenrui , He Ting , Wang Yulong , Lin Xiuyun
Published: March 2024

The positive association between meaning in life (MIL) and mindfulness has been supported; however, previous research has been limited to the trait level. To explore the dynamics of mindfulness and MIL in the state level, the present study used the experience sampling method (ESM) and conducted a dynamic structural equation model (DSEM). In addition, we examined the moderation of baseline depression in this dynamic relationship and the protective role of the dynamics on depression. We recruited 184 college students (Mage = 21.58, 33.15% male), who reported three times a day for 14 consecutive days, and analyzed the 7726 collected responses. Firstly, a virtuous cycle between mindfulness and MIL was proven. Besides, the baseline depressive symptoms moderated the predictive of mindfulness on MIL, suggesting state mindfulness gave people with more depressive symptoms more meaningful in daily life. Lastly, the result also demonstrated the positive prediction of mindfulness on MIL and alleviated the worsening of depressive symptoms within 2 weeks. The findings extended the relationship between MIL and mindfulness from trait level to state level, enriching the self‐determination theory, and examined the unique effect of depressive symptoms in the dynamics.
The relationship of pain intensity and opioid craving with delayed methadone dose: A preliminary study of individuals with opioid use disorder
Authors: MacLean R. Ross , Spinola Suzanne , Pittman Brian , Meyerovich Julia , Szollosy Sara K. , Wolkowicz Noah R. , Minnix Stacy , Sofuoglu Mehmet
Published: March 2024

Aims

Despite a strong theoretical link between opioid craving and pain, little is known about the temporal relationship between pain and craving and the acute experience of pain in the context of methadone treatment. Using a cross‐over design, the current study evaluated the time course of pain and craving and objective experience of pain as a function of the last methadone dose.

Methods

Participants (n = 20) presented for the study in the morning and either received methadone dose as scheduled or delayed dose until the afternoon. During the 4‐h study visit, participants completed a series of tasks, including repeated assessment of pain and craving at 0, +40, +70, +130, +160 and +240 min and a cold pressor test (CPT) at +15 and +220 min.

Results

Separate mixed model results demonstrated no effect of dosing condition on craving; however, there was a significant dosing condition by time interaction (F(5,209) = 3.38, P = .006) such that pain increased over time in the delayed methadone condition but decreased in time in the scheduled methadone condition. A mixed model predicting self‐reported pain revealed a three‐way interaction between dosing condition, craving and time (F(5,197) = 2.39, P = .039) explained by a positive association between craving and pain at each time point (except 240 min) in delayed condition (P‐range = .004–.0001). A separate mixed model on CPT data indicated a significant condition by time interaction such that pain threshold decreased in the delayed, but not scheduled, condition (F(1,57) = 4.01, P = .050).

Conclusions

These preliminary findings highlight the potential for increased risks after even a short delay in receiving a methadone dose.
Metabolomics profile and machine learning prediction of treatment responses in immune thrombocytopenia: A prospective cohort study
Authors: Li Yang , Sun Ting , Chen Jia , Liu Xiaofan , Fu Rongfeng , Xue Feng , Liu Wei , Ju Mankai , Dai Xinyue , Li Huiyuan , Wang Wentian , Chi Ying , Li Ting , Shao Shuai , Yang Renchi , Chen Yunfei , Zhang Lei
Published: March 2024

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by antibody‐mediated platelet destruction and impaired platelet production. The mechanisms underlying ITP and biomarkers predicting the response of drug treatments are elusive. We performed a metabolomic profiling of bone marrow biopsy samples collected from ITP patients admission in a prospective study of the National Longitudinal Cohort of Hematological Diseases. Machine learning algorithms were conducted to discover novel biomarkers to predict ITP patient treatment responses. From the bone marrow biopsies of 91 ITP patients, we quantified a total of 4494 metabolites, including 1456 metabolites in the positive mode and 3038 metabolites in the negative mode. Metabolic patterns varied significantly between groups of newly diagnosed and chronic ITP, with a total of 876 differential metabolites involved in 181 unique metabolic pathways. Enrichment factors and p‐values revealed the top metabolically enriched pathways to be sphingolipid metabolism, the sphingolipid signalling pathway, ubiquinone and other terpenoid–quinone biosynthesis, thiamine metabolism, tryptophan metabolism and cofactors biosynthesis, the phospholipase D signalling pathway and the phosphatidylinositol signalling system. Based on patient responses to five treatment options, we screened several metabolites using the Boruta algorithm and ranked their importance using the random forest algorithm. Lipids and their metabolism, including long‐chain fatty acids, oxidized lipids, glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine biosynthesis, helped differentiate drug treatment responses. In conclusion, this study revealed metabolic alterations associated with ITP in bone marrow supernatants and a potential biomarker predicting the response to ITP.