bluuebunny/crossref_metadata_2025_split huggingface dataset:
A vaccine candidate based on baculovirus displaying chikungunya virus E1-E2 envelope confers protection against challenge in mice
Authors: Caillava Ana J. , Alfonso Victoria , Tejerina Cibello Malena , Demaria María Agostina , Coria Lorena M. , Cassataro Juliana , Taboga Oscar A. , Alvarez Diego E. 
Published: October 2024

ABSTRACT

Chikungunya fever is a re-emerging mosquito-borne disease caused by the chikungunya virus (CHIKV) and produces acute arthritis that can progress to chronic disease with arthralgia. The first approved live-attenuated chikungunya vaccine has only recently become available for use in humans in the USA, but the access in endemic regions remains unmet. Here, we exploited the baculovirus display technology to develop a vectored vaccine candidate that exposes the CHIKV membrane proteins E1 and E2 on the baculovirus surface. Using recombinant baculovirus as vector vaccines has both productive and regulatory advantages: they are safe for handling and easy to produce in high titers and are non-pathogenic and non-replicative in mammals but have strong adjuvant properties by inducing humoral and cellular immune responses. CHIKV E1 and E2 envelope proteins with their own signal and transmembrane sequences were expressed on the surface of budded baculovirus virions. Immunization of C57BL/6 mice with non-adjuvanted recombinant baculovirus induced IgG antibodies against E2 with a predominant IgG2c subtype, neutralizing antibodies and a specific IFN-γ CD8
+
T-cell response. Immunization with a second dose significantly boosted the antibody response, and mice immunized with two doses of the vaccine candidate were completely protected against challenge with CHIKV showing no detectable viremia or signs of disease. Altogether, baculovirus display of CHIKV envelope proteins served as an efficient vaccine platform against CHIKV.

IMPORTANCE
The global spread of chikungunya virus (CHIKV) has disproportionately impacted the Americas that experienced a fourfold increase in 2023 in cases and deaths compared with the same period in 2022. The disease is characterized by acute fever and debilitating joint pain that can become chronic. Despite the socioeconomic burden related to the high morbidity rates of CHIKV infection, a vaccine for CHIKV is currently approved only in the USA. Vaccines are the most effective preventive measure against viral diseases, and advances in the development of different vaccine platforms such as nucleic acids and viral vectors have prompted the rapid deployment of vaccines to contain the COVID-19 pandemic. Here, we report the use of baculovirus display as a strategy for the design of a novel vaccine that provides sterilizing immunity in a mouse model of chikungunya disease. Our results encourage further research regarding the potential of baculovirus as platforms for human vaccine design.
First insights into the prevalence, genetic characteristics, and pathogenicity of
Bacillus cereus
from generations worldwide
Authors: Tong Cuihong , Xiao Danyu , Li Qi , Gou Jing , Wang Shuang , Zeng Zhenling , Xiong Wenguang 
Published: October 2024

ABSTRACT

Bacillus cereus
, a global threat, is one of the major causes of toxin-induced foodborne diseases. However, a comprehensive assessment of the prevalence and characteristics of
B. cereus
worldwide is still lacking. Here, we applied whole-genome sequence analysis to 191
B. cereus
collected in Africa, America, Asia, Europe, and Oceania from the 1900s to 2022, finding that CC142 dominated the global
B. cereus
clonal complex. The results provided direct evidence that
B. cereus
could spread through the food chain and intercontinentally.
B. cereus
from different generations worldwide showed coherence in the antibiotic-resistant gene and virulence and biofilm gene profiles, although with high genomic heterogeneity. The
BCI-BCII-vanZF-fosB
profiles and virulence and biofilm genes were detected at high rates, and we emphasized that
B. cereus
would pose a serious challenge to global public health and clinical treatment.

IMPORTANCE

This study first emphasized the prevalence, genetic characteristics, and pathogenicity of
Bacillus cereus
worldwide from the 1900s to 2022 using whole-genome sequence analysis. The CC142 dominated the global
Bacillus cereus
clonal complex. Moreover, we revealed a close evolutionary relationship between the isolates from different sources.
B. cereus
isolates from different generations worldwide showed coherence in potential pathogenicity, although with high genomic heterogeneity. The
BCI-BCII-vanZF-fosB
profiles and virulence and biofilm genes were detected at high rates, and we emphasized that
B. cereus
would pose a serious challenge to global public health and clinical treatment.
Multi-omics analysis reveals the core microbiome and biomarker for nutrition degradation in alfalfa silage fermentation
Authors: Wang Yuan , Sun Yunlei , Huang KeXin , Gao Yu , Lin Yufan , Yuan Baojie , Wang Xin , Xu Gang , Nussio Luiz Gustavo , Yang Fuyu , Ni Kuikui 
Published: October 2024

ABSTRACT

Alfalfa (
Medicago sativa
L.) is one of the most extensively cultivated forage crops globally, and its nutritional quality critically influences the productivity of dairy cows. Silage fermentation is recognized as a crucial technique for the preservation of fresh forage, ensuring the retention of its vital nutrients. However, the detailed microbial components and their functions in silage fermentation are not fully understood. This study integrated large-scale microbial culturing with high-throughput sequencing to thoroughly examine the microbial community structure in alfalfa silage and explored the potential pathways of nutritional degradation via metagenomic analysis. The findings revealed an enriched microbial diversity in silage, indicated by the identification of amplicon sequence variants. Significantly, the large-scale culturing approach recovered a considerable number of unique microbes undetectable by high-throughput sequencing. Predominant genera, such as
Lactiplantibacillus
,
Leuconostoc
,
Lentilactobacillus
,
Weissella
, and
Liquorilactobacillus
, were identified based on their abundance and prevalence. Additionally, genes associated with Enterobacteriaceae were discovered, which might be involved in pathways leading to the production of ammonia-N and butyric acid. Overall, this study offers a comprehensive insight into the microbial ecology of silage fermentation and provides valuable information for leveraging microbial consortia to enhance fermentation quality.

IMPORTANCE
Silage fermentation is a microbial-driven anaerobic process that efficiently converts various substrates into nutrients readily absorbable and metabolizable by ruminant animals. This study, integrating culturomics and metagenomics, has successfully identified core microorganisms involved in silage fermentation, including those at low abundance. This discovery is crucial for the targeted cultivation of specific microorganisms to optimize fermentation processes. Furthermore, our research has uncovered signature microorganisms that play pivotal roles in nutrient metabolism, significantly advancing our understanding of the intricate relationships between microbial communities and nutrient degradation during silage fermentation.
Evaluation of the CARBA PAcE test, a colorimetric imipenem hydrolysis test for rapid detection of carbapenemase activity
Authors: Rakovitsky Nadya , Lurie-Weinberger Mor N. , Temkin Elizabeth , Hameir Amichay , Efrati-Epchtien Reut , Wulffhart Liat , Keren Paz Alona , Schwartz David , Carmeli Yehuda 
Published: October 2024

ABSTRACT

There is an urgent need for accurate and fast diagnostic tests to identify carbapenemase-producing bacteria. Here, we evaluated a colorimetric imipenem hydrolysis test, called the CARBA PAcE test, to detect carbapenemase-producing Gram-negative bacteria (GNB). We tested a collection of 270 GNB isolates with a characterized carbapenemase content. Our testing set included 205 carbapenemase-producing, carbapenemase-resistant
Enterobacterales
(
CP CRE
) with 40
Klebsiella pneumoniae
carbapenemase (KPC), 49 New Delhi metallo beta lactamase (NDM), 49 OXA-48-like, 15 Verona integron-mediated metallo-β-lactamase (VIM), three IMP, 43 IMI, six isolates producing more than one carbapenemase, and 65 non-carbapenemase-producing
Enterobacterales
(20 ESBL producers, 35 non-carbapenemase-producing, carbapenem-resistant [non-CP CRE], and 10 carbapenem-susceptible
Enterobacterales
[non-CP, non-CSE, third-generation cephalosporin and carbapenem susceptible]). We compared the performances of the CARBA PAcE test, the qualitative colorimetric β-CARBA test, and the modified CarbaNP test to a gold standard of carbapenemase gene detection by PCR. Specificities of all tests were high: 95.4% (62/65) for CARBA PAcE test, 98.5% (64/65) for β-CARBA test, and 100% (65/65) for the modified CarbaNP test. Sensitivity varied by carbapenemase: all three tests had a sensitivity of 100% for NDM, VIM, and IMP and 97.5% for KPC. Sensitivity to detect IMI was 0% for the CARBA PAcE and β-CARBA tests and 11.6% for the modified CarbaNP test. Sensitivity to detect OXA-48-like was 89.7% for the CARBA PAcE test, 87.7% for the β-CARBA test, and 14.2% for the modified CarbaNP test. Reading the results of the CARBA PAcE assay was difficult. The CARBA PAcE assay is highly sensitive for detecting NDM, VIM, IMP, and KPC, but slightly less sensitive for OXA-48-like. It does not detect IMI. It is highly specific, and its overall diagnostic accuracy is similar to that of β-CARBA. Its operational advantages are rapid turnaround time, ease of use, and long shelf life, but reading of results is subjective.

IMPORTANCE
We evaluated the ability of the CARBA PAcE test to detect carbapenemases in 274 Gram-negative isolates with a known carbapenemase content. Specificity was high for all carbapenemases tested (96.9%). Sensitivity was high for KPC, NDM, VIM, and IMP (97.5-100%); but lower for OXA-48-like (89.7%). Activity of IMI could not be detected. Taken together, our results indicate that CARBA PAcE is a useful alternative in regions where NDM and KPC are predominant. The limitations of the test are difficulty in reading results and incompatibility with mSuperCARBA.
High rate of macrolide resistance and closely genetically related
Mycobacterium abscessus
complex strains identified among both cystic fibrosis and non-cystic fibrosis patients within two countries
Authors: Dohál Matúš , Dvořáková Věra , Hromádková Michaela , Pinková Martina , Amlerová Jana , Schwarz Marek , Spitaleri Andrea , di Marco Federico , Hnilicová Jarmila , Gondáš Eduard , Rasmussen Michael E. , Porvazník Igor , Solovič Ivan , Cirillo Daniela M. , Mokrý Juraj 
Published: October 2024

ABSTRACT

Mycobacterium abscessus
is an emerging opportunistic pathogen affecting patients with chronic lung diseases, primarily cystic fibrosis (CF), or those under immunosuppression. Hence, investigations into the epidemiology and transmission of
M. abscessus
and accurate antibiotic susceptibility data are essential for the effective treatment of infections caused by this pathogen. This retrospective nationwide study included all clinical
M. abscessus
isolates (
n
= 59) from 29 patients diagnosed in the Czech Republic and Slovakia between 2018 and 2023. Whole genome sequencing (WGS) was performed to identify clusters and classify isolates into predominant circulating clones (DCC). Subspecies identification of unique isolates showed subspecies
abscessus
as the most prevalent (69.0%). The results of drug-susceptibility testing showed that 65.5% of all isolates were resistant to at least three antibiotics tested. CF patients under 24 years of age were the most at-risk group for
M. abscessus
infection. WGS identified seven clusters (including two cross-border) comprising CF and non-CF patients with a total clustering rate of 48.3%. One cluster involved patients infected with subspecies
massiliense
strains differing by 0 single nucleotide polymorphisms hospitalized in the same center. Furthermore, we identified representatives of all major DCCs. This study revealed predominant
Mycobacterium abscessus
complex clones circulating in the Czech Republic and Slovakia. The results show the high discriminatory power of WGS in the molecular epidemiology of
M. abscessus
and provide supporting evidence of direct or indirect cross-transmission of subspecies
massiliense
among both CF and non-CF patients.

IMPORTANCE

This study highlights the importance of understanding
Mycobacterium abscessus
transmission because it poses a growing threat to vulnerable populations, especially young cystic fibrosis patients. Investigating how it spreads and which antibiotics work best is crucial for effective treatment. This research used whole genome sequencing to track
M. abscessus
and found evidence of potential transmission between patients, including across borders. The findings suggest that dominant strains are circulating and some patients may be infected through direct or indirect contact. This knowledge can inform infection control and treatment strategies.
Genomic and phenotypic characterization of
Pseudomonas aeruginosa
isolates from two Mexican cystic fibrosis attention centers
Authors: Núñez-García Luis Ángel , Feliciano-Guzmán José Manuel , Mireles-Davalos Christian Daniel , López-Sántiz José Raúl , Ovando-Fonseca Jesús Elías , Becerril-Vargas Eduardo , Jiménez-Martínez María Elena , Rodríguez-Medina Nadia , Garza-Ramos Ulises , Córdova-Fletes Carlos , Garza-González Elvira 
Published: October 2024

ABSTRACT

Thirty-nine clinical isolates of
Pseudomonas aeruginosa
collected from 11 cystic fibrosis (CF) patients at two CF attention centers over 10 years were subjected to whole genome sequencing (WGS). Phenotypic tests (i.e., elastase, motility, biofilm, growth rate, and antibiotic susceptibility) were performed to correlate results. A single strain of
P. aeruginosa
was found to persist over time in longitudinal isolates. No transmission between patients or centers was observed. A tendency to lack genes related to pyoverdine, flagellum, pili, and O-antigen was observed, whereas those related to biofilm, phenazine, and pyochelin were conserved among isolates. In a patient with a 10-year follow-up, a single strain of
P. aeruginosa
persisted and showed a gradual decrease in elastase activity and growth rate, demonstrating an adaptive phenotype.

IMPORTANCE

This study investigates the genomic and phenotypic characteristics of
Pseudomonas aeruginosa
isolates from Mexican cystic fibrosis (CF) patients, an underrepresented group in CF research. To our knowledge, it is the first to use whole genome sequencing (WGS) to study longitudinally collected
P. aeruginosa
isolates from this population, evaluating both genomic features and clonal relationships. Remarkably, the study includes samples from one patient over 10 years, offering an extended observation time compared to existing literature. Unlike similar studies, which often lack phenotypic testing, this research incorporates various virulence-related phenotypic assays, enhancing our understanding of gene-to-phenotype correlations. Two potential mechanisms for the loss of elastolytic activity were identified. Furthermore, we conduct an in-depth mobilome analysis, an area that remains largely unexplored in CF contexts. Whole genome sequencing data are publicly available through the NCBI SRA database, facilitating further re-analysis for studies on
P. aeruginosa
in CF, as well as epidemiological and population structure research.
Design and evaluation of a visual genomic explainer: a mixed-methods study
Authors: Butler Grainne , Andersen Camilla , Buttery Jim , Gupta Asheeta , Martyn Melissa M , Stark Zornitza , Wilkins Ella , Jayasinghe Kushani , Quinlan Catherine 
Published: October 2024

ObjectiveTo design and assess a visual genomic explainer focusing on plain language and engaging imagery. The explainer aimed to support doctors’ comprehension of complex genomic concepts and results and act as a resource promoting the integration of genomic testing into mainstream care.DesignProspective genomic resource development and questionnaire.SettingRegional and tertiary hospitals in Australia and Ireland, private and community-based clinicians in Australia.ParticipantsRecruitment of paediatricians and nephrologists in Australia and paediatricians in Ireland was multi-faceted. Emails with survey links were circulated through training bodies, advanced trainee networks, departmental heads, and professional societies.Main outcome measuresComprehension, engagement and perception of the visual explainer.ResultsMost clinicians surveyed (95% (53) Australian group, 100% (29) Irish group) felt that genomics would be a useful tool in their practice. 77% of Australian paediatric respondents and 73% of Irish paediatric respondents felt that genomics was underutilised. Challenges encountered with genomic testing included poor patient comprehension of the testing process and results along with difficulties perceived by clinicians in explaining complex results. 89% of Australian paediatricians and 100% of Irish paediatricians surveyed would recommend the use of the explainer to other professionals in their field.ConclusionThis genomic resource was acceptable to clinicians and could be a useful tool to support paediatricians integrating genomic testing into mainstream care.
Huntington’s disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration
Authors: Koriath Carolin Anna Maria , Guntoro Fernando , Norsworthy Penelope , Dolzhenko Egor , Eberle Michael , Hensman Moss Davina J , Flower Michael , Hummerich Holger , Rosser Anne Elizabeth , Tabrizi Sarah J , Mead Simon , Wild Edward J 
Published: October 2024

BackgroundGenetic testing for Huntington’s disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.MethodsClinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.ResultsHDPC prevalence was estimated at 2.3–2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified oneATXN1expansion in a patient with HDPC.ConclusionsThe HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.
Characterisation ofNeisseria gonorrhoeaestrain differences in patients with multisite infection
Authors: Miari Victoria F , Blakiston Matthew R , Solanki Priya , Gundogdu Ozan , Stabler Richard A 
Published: October 2024

BackgroundNeisseria gonorrhoeae, the aetiological agent of gonorrhoea, is an increasing global health priority due to high levels of antimicrobial resistance (AMR). It is estimated that up to 42% of patients are infected at multiple anatomical sites simultaneously. Previous studies identified that 7%–40% of those with multisite infection have different strains infecting different sites, with potentially different antimicrobial susceptibility profiles. This study aims to estimate the proportion of patients with multisite infection through differential antimicrobial susceptibility testing (AST) profiles and sequence-based molecular methods.MethodsThis was a cross-sectional study of multisite gonococcal isolates provided by three National Health Service laboratories. Minimum inhibitory concentrations (MICs) for cefixime, ceftriaxone, azithromycin, ciprofloxacin, tetracycline and spectinomycin were determined. Possible multistrain infections were defined as isolates with a significant difference in MIC to at least one antimicrobial. Whole genome sequencing (WGS) was performed to determine multistrain infection throughN. gonorrhoeaemultiantigen sequence typing (NG-MAST),N. gonorrhoeaesequence typing for antimicrobial resistance (NG-STAR), multilocus sequencing typing (MLST) and single nucleotide polymorphism (SNP) phylogeny, and to compare AST profiles with identified AMR genes.ResultsNinety-one isolates were collected from 41 patients with multisite infections. Of these 41 patients, 6 (14.6%) hadN. gonorrhoeaeisolates with discordant MICs. WGS-based typing confirmed that four out of six patients were infected with different gonococcal strains. The relatedness of isolates with the same MLST across multiple patients was differentiated using SNP-based analysis, and this included the identification of a potential transmission event. WGS-based AMR prediction for all antimicrobials tested correlated well with the phenotypic data.ConclusionThis study demonstrates that potentially a significant proportion of patients with multisite infections are infected with multiple gonococcal strains, with differing AST profiles, at different anatomical sites. This has implications for patient sampling, susceptibility testing protocols, AMR surveillance and potentially appropriate antibiotic therapy.
Early Career South African Occupational Therapists’ Perceptions of Person–Environment Fit in Work–Life Areas That Influence Work Stress
Authors: de Witt Patricia , Bruce Morgann , Botha Marica , Franzsen Denise 
Published: October 2024

Introduction: Poor fit between the work environment and work expectations is associated with high levels of workplace‐related stress. Work stress in occupational therapy has been attributed to the nature of the profession and various other workplace‐related factors. Workplace‐related stress leading to burnout has been found to be higher in early career occupational therapists with less than 5 years of experience. This study explored workplace factors that result in poor person–work environment fit in six work–life areas in South African early career occupational therapists.Methods: A descriptive electronic survey design was used to access a sample of South African 261 occupational therapists with 2–5 years of work experience. The Area of Work–Life Survey (AWS) considers six work–life areas: control, workload, community, rewards, values, and fairness, which were used to collect data. Data were analysed to determine low, moderate, and high work environment fit for workplace factors including employment setting, field of practice, years’ experience, time with current organization, and hours worked.Results: Of the six work–life areas, only the scores for workload fell below the norm for the respondents. All six work–life areas were impacted by employment settings, with respondents in public health hospitals and clinics indicating significantly low person–environment fit in most areas. Respondents in physical rehabilitation had a significantly low fit for workload, as did years of experience, length of time with organization, and hours worked. Fairness had a low fit for physical rehabilitation and medicolegal fields of practice.Conclusion: Workload impacted workplace‐related stress in respondents with scores below the norm on the AWS for this work–life area. Although some work‐related factors affected workplace‐related stress, the overall scores for the other work–life areas were above the norm, with only respondents in public service settings and in the field of physical rehabilitation reporting low work environment fit.