bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft genome sequence of carbapenems-resistant
Acinetobacter baumannii
Hakim RU_CBWP strain isolated from a pond surface water in Bangladesh
Authors: Khan Muhib Ullah , Romance M. , Polash Md. Arif-Uz-Zaman , Zahan Nusrat , Ali Md. Sumon , Raihan Jafor , Sarker Subir , Haque Md. Hakimul 
Published: June 2024

ABSTRACT

We have revealed the genomic sequence of
Acinetobacter baumannii
strain Hakim RU_CBWP isolated from pond surface water. Our assembled genome covers 3.787 Mb with 45.5629× coverage, showcasing an average GC content of 38.60%. This genome contains two CRISPR arrays, 17 prophages, 22 antibiotic resistance genes, and 20 virulence factor genes.
Oligomycin-producing
Streptomyces
sp. newly isolated from Swiss soils efficiently protect
Arabidopsis thaliana
against
Botrytis cinerea
Authors: Louviot Fanny , Abdelrahman Ola , Abou-Mansour Eliane , L'Haridon Floriane , Allard Pierre-Marie , Falquet Laurent , Weisskopf Laure 
Published: June 2024

ABSTRACT

Botrytis cinerea
is a necrotrophic phytopathogen able to attack more than 200 different plant species causing strong yield losses worldwide. Many synthetic fungicides have been developed to control this disease, resulting in the rise of fungicide-resistance
B. cinerea
strains. The aim of this study was to identify
Streptomyces
strains showing antagonistic activity against
B. cinerea
to contribute to plant protection in an environmentally friendly way. We isolated 15 Actinomycete strains from 9 different Swiss soils. The culture filtrates of three isolates showing antifungal activity inhibited spore germination and delayed mycelial growth of
B. cinerea
. Infection experiments showed that
Arabidopsis thaliana
plants were more resistant to this pathogen after leaf treatment with the
Streptomyces
filtrates. Bioassay-guided isolation of the active compounds revealed the presence of germicidins A and B as well as of oligomycins A, B, and E. While germicidins were mostly inactive, oligomycin B reduced the mycelial growth of
B. cinerea
significantly. Moreover, all three oligomycins inhibited this fungus’ spore germination, suggesting that these molecules might contribute to the
Streptomyces
’s ability to protect plants against infection by the broad host-pathogen
Botrytis cinerea
.

IMPORTANCE

This study reports the isolation of new
Streptomyces
strains with strong plant-protective potential mediated by their production of specialized metabolites. Using the broad host range pathogenic fungus
Botrytis cinerea
, we demonstrate that the cell-free filtrate of selected
Streptomyces
isolates efficiently inhibits different developmental stages of the fungus, including mycelial growth and the epidemiologically relevant spore germination. Beyond
in vitro
experiments, the strains and their metabolites also efficiently protected plants against the disease caused by this pathogen. This work further identifies oligomycins as active compounds involved in the observed antifungal activity of the strains. This work shows that we can harness the natural ability of soil-borne microbes and of their metabolites to efficiently fight other microbes responsible for significant crop losses. This opens the way to the development of environmentally friendly health protection measures for crops of agronomical relevance, based on these newly isolated strains or their metabolic extracts containing oligomycins.
A metabolomics perspective on clorobiocin biosynthesis: discovery of bromobiocin and novel derivatives through LC-MS
E
-based molecular networking
Authors: Janzing Niklas B. M. , Niehoff Maurice , Sander Wolfram , Senges Christoph H. R. , Schäkermann Sina , Bandow Julia E. 
Published: June 2024

ABSTRACT

Clorobiocin is a well-known, highly effective inhibitor of DNA gyrase belonging to the aminocoumarin antibiotics. To identify potentially novel derivatives of this natural product, we conducted an untargeted investigation of clorobiocin biosynthesis in the known producer
Streptomyces roseochromogenes
DS 12.976 using LC-MS
E
, molecular networking, and analysis of fragmentation spectra. Previously undescribed clorobiocin derivatives uncovered in this study include bromobiocin, a variant halogenated with bromine instead of chlorine, hydroxylated clorobiocin, carrying an additional hydroxyl group on its 5-methyl-pyrrole 2-carboxyl moiety, and two other derivatives with modifications on their 3-dimethylallyl 4-hydroxybenzoate moieties. Furthermore, we identified several compounds not previously considered clorobiocin pathway products, which provide new insights into the clorobiocin biosynthetic pathway. By supplementing the medium with different concentrations of potassium bromide, we confirmed that the clorobiocin halogenase can utilize bromine instead of chlorine. The reaction, however, is impeded such that non-halogenated clorobiocin derivatives accumulate. Preliminary assays indicate that the antibacterial activity of bromobioin against
Bacillus subtilis
and efflux-impaired
Escherichia coli
matches that of clorobiocin. Our findings emphasize that yet unexplored compounds can be discovered from established strains and biosynthetic gene clusters by means of metabolomics analysis and highlight the utility of LC-MS
E
-based methods to contribute to unraveling natural product biosynthetic pathways.

IMPORTANCE

The aminocoumarin clorobiocin is a well-known gyrase inhibitor produced by the gram-positive bacterium
Streptomyces roseochromogenes
DS 12.976. To gain a deeper understanding of the biosynthetic pathway of this complex composite of three chemically distinct entities and the product spectrum, we chose a metabolite-centric approach. Employing high-resolution LC-MS
E
analysis, we investigated the pathway products in extracted culture supernatants of the natural producer. Novel pathway products were identified that expand our understanding of three aspects of the biosynthetic pathway, namely the modification of the noviose, transfer and methylation of the pyrrole 2-carboxyl moiety, and halogenation. For the first time, brominated products were detected. Their levels and the levels of non-halogenated products increased in medium supplemented with KBr. Based on the presented data, we propose that the enzyme promiscuity contributes to a broad product spectrum.
Transcriptional responses of brain endothelium to
Plasmodium falciparum
patient-derived isolates
in vitro
Authors: Askonas Caroline , Storm Janet , Camarda Grazia , Craig Alister , Pain Arnab 
Published: June 2024

ABSTRACT

A hallmark of cerebral malaria (CM) is sequestration of
Plasmodium falciparum
-infected erythrocytes (IE) within the brain microvasculature. Binding of IE to endothelium reduces microvascular flow and, combined with an inflammatory response, perturbs endothelial barrier function, resulting in breakdown of the blood-brain barrier (BBB). Cytoadherence leads to activation of the endothelium and alters a range of cell processes affecting signaling pathways, receptor expression, coagulation, and disruption of BBB integrity. Here, we investigated whether CM-derived parasites elicit differential effects on human brain microvascular endothelial cells (HBMECs), as compared to uncomplicated malaria (UM)-derived parasites. Patient-derived IE from UM and CM clinical cases, as well as non-binding skeleton-binding protein 1 knockout parasites, were overlaid onto tumour necrosis factor (TNF)-activated HBMECs. Gene expression analysis of endothelial responses was performed using probe-based assays of a panel of genes involved in inflammation, apoptosis, endothelial barrier function, and prostacyclin synthesis pathway. We observed a significant effect on endothelial transcriptional responses in the presence of IE, yet there was no significant correlation between HBMEC responses and type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and level of IE binding to HBMECs, as we detected the same change in endothelial responses when employing both binding and non-binding parasites. Our results suggest that interaction of IE with endothelial cells in this co-culture model induces some endothelial responses that are independent of clinical origin and independent of the expression of the major variant antigen
Plasmodium falciparum
erythrocyte membrane protein 1 on the IE surface.

IMPORTANCE

Cerebral malaria (CM) is the most prevalent and deadly complication of severe
Plasmodium falciparum
infection. A hallmark of this disease is sequestration of
P. falciparum
-infected erythrocytes (IE) in brain microvasculature that ultimately results in breakdown of the blood-brain barrier. Here, we compared the effect of
P. falciparum
parasites derived from uncomplicated malaria (UM) and CM cases on the relative gene expression of human brain microvascular endothelial cells (HBMECs) for a panel of genes. We observed a significant effect on the endothelial transcriptional response in the presence of IE, yet there is no significant correlation between HBMEC responses and the type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and the level of IE binding to HBMECs. Our results suggest that interaction of IE with endothelial cells induces endothelial responses that are independent of clinical origin and not entirely driven by surface
Plasmodium falciparum
erythrocyte membrane protein 1 expression.
Efficacy of rifapentine and other rifamycins against
Coxiella burnetii in vitro
Authors: Miller Halie K. , Kersh Gilbert J. 
Published: June 2024

ABSTRACT

Since 1999, doxycycline and hydroxychloroquine have been the recommended treatment for chronic Q fever, a life-threatening disease caused by the bacterial pathogen,
Coxiella burnetii
. Despite the duration of its use, the treatment is not ideal due to the lengthy treatment time, high mortality rate, resistant strains, and the potential for contraindicated usage. A literature search was conducted to identify studies that screened large panels of drugs against
C. burnetii
to identify novel targets with potential efficacy against
C. burnetii
. Twelve candidate antimicrobials approved for use in humans by the US Food and Drug Administration were selected and minimum inhibitory concentrations (MICs) were determined against the low virulence strain Nine Mile phase II. Rifabutin and rifaximin were the best performing antibiotics tested with MICs of ≤0.01 µg mL
−1
. Further screening of these top candidates was conducted alongside two drugs from the same class, rifampin, well-characterized
,
and rifapentine, not previously reported against
C. burnetii
. These were screened against virulent strains of
C. burnetii
representing three clinically relevant genotypes. Rifapentine was the most effective in the human monocytic leukemia cell line, THP-1, with a MIC ≤0.01 µg mL
−1
. In the human kidney epithelial cell line, A-498, efficacy of rifapentine, rifampin, and rifabutin varied across
C. burnetii
strains with MICs between ≤0.001 and 0.01 µg mL
−1
. Rifampin, rifabutin, and rifapentine were all bactericidal against
C. burnetii
; however, rifabutin and rifapentine demonstrated impressive bactericidal activity as low as 0.1 µg mL
−1
and should be further explored as alternative Q fever treatments given their efficacy
in vitro
.

IMPORTANCE

This work will help inform investigators and physicians about potential alternative antimicrobial therapies targeting the causative agent of Q fever,
Coxiella burnetii
. Chronic Q fever is difficult to treat, and alternative antimicrobials are needed. This manuscript explores the efficacy of rifamycin antibiotics against virulent strains of
C. burnetii
representing three clinically relevant genotypes
in vitro
. Importantly, this study determines the susceptibility of
C. burnetii
to rifapentine, which has not been previously reported. Evaluation of the bactericidal activity of the rifamycins reveals that rifabutin and rifapentine are bactericidal at low concentrations, which is unusual for antibiotics against
C. burnetii
.
Genomic and phenotypic studies among
Clostridioides difficile
isolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea
Authors: Meléndez-Sánchez D. , Hernández Laura , Ares Miguel , Méndez Tenorio A. , Flores-Luna Lourdes , Torres Javier , Camorlinga-Ponce M. 
Published: June 2024

ABSTRACT

Clostridioides difficile
(
C. difficile
) is widely distributed in the intestinal tract of humans, animals, and in the environment. It is the most common cause of diarrhea associated with the use of antimicrobials in humans and among the most common healthcare-associated infections worldwide. Its pathogenesis is mainly due to the production of toxin A (TcdA), toxin B (TcdB), and a binary toxin (CDT), whose genetic variants may be associated with disease severity. We studied genetic diversity in 39
C
.
difficile
isolates from adults and children attended at two Mexican hospitals, using different gene and genome typing methods and investigated their association with
in vitro
expression of toxins. Whole-genome sequencing in 39 toxigenic
C. difficile
isolates were used for multilocus sequence typing,
tcdA
, and
tcdB
typing sequence type, and phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity in cell-culture assays. Clustering of strains by genome-wide phylogeny matched clade classification, forming different subclusters within each clade. The toxin profile
tcdA+/tcdB+/cdt+
and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which TcdA2 and TcdB2 were more prevalent. Prevalent clades and toxin subtypes in strains from children differed from those in adult strains. Toxin gene expression or cytotoxicity was not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity among
C. difficile
isolates from patients with healthcare-associated diarrhea.

IMPORTANCE

Clostridioides difficile
is a toxin-producing bacterial pathogen recognized as the most common cause of diarrhea acquired primarily in healthcare settings. This bacterial species is diverse; its global population has been divided into five different clades using multilocus sequence typing, and strains may express different toxin subtypes that may be related to the clades and, importantly, to the severity and progression of disease. Genotyping of children strains differed from adults suggesting toxins might present a reduced toxicity. We studied extensively cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinical
C. difficile
isolates. Most isolates presented a
tcdA+/ tcdB+/cdt
+ pattern, with high diversity in cytotoxicity and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence of
C. difficile
better and find markers for better clinical use
Health consequences of the Urmia Lake crisis: the baseline study protocol
Authors: Sadeghi-Bazargani Homayoun , Saadatkhah Mortaza , Farahbakhsh Mostafa , Sarraf Behrouz Sari , Abbasnezhad Ommolbanin , Mohebbi Iraj , Mohammadi Gholamhassan , EntezarMahdi Rasoul , Pourasghar Faramarz 
Published: June 2024

IntroductionClimate change may affect human health due to various mechanisms including overexposure to environmental pollution or dispersed particles. Lake Urmia (LU) drying in recent years has turned into a crisis with particle distribution as its main manifest. It is told that this crisis may affect the health of neighbouring residents. In this paper, we elaborate on a research protocol developed to assess the potential health consequences of LU drying (LUD) by investigating the distribution of physical and mental health conditions/disorders among residents of LU’s surrounding provinces with different exposure levels to LUD outcomes.Methods and analysisThe target population of this study is the residents of the LU basin from East Azerbaijan and West Azerbaijan provinces of Iran. A total of 803 households and 2783 people are studied in 86 clusters. Cluster sampling is applied. The weighting of the samples is based on a satellite map of the density of suspended particles such that people living in areas with higher risk have a higher chance of selection. Various types of measurements are done in three major groups including self-reported health, clinical interview/examination and paraclinical assays.Ethics and disseminationIn this project, all procedures are in accordance with the ethical standards of the Ethics Committee of Tabriz University of Medical Sciences. Moreover, an informed consent letter is obtained from all participants included in the study. The results from this study will be disseminated in international journals and implemented in the primary care guidelines and national policy documents on managing the potential health consequences of LUD.
Early provision of clinical information with an ‘opt in’ approach improves patient experience in tonsillectomy referrals
Authors: Philp Nichola , Maqsood Raeesah , Joshyulla-Prasanna Adithya , van der Meer Robert Bauke , Douglas Catriona M , Wood Margaret , Rymaszewski Lech 
Published: June 2024

Patients referred by their general practitioner (GP) with a definite diagnosis, for example, recurrent sore throat for consideration of tonsillectomy in adults, may wait for months without receiving any further clinical information from the hospital until their outpatient consultation. Prompt provision of condition-specific information after referral has received little attention despite considerable potential to enhance patients’ understanding, thereby relieving uncertainty and anxiety, and facilitating shared decision-making.This study aimed to report the experience of patients with recurrent tonsillitis who had been sent a booklet outlining the benefits and risks of tonsillectomy immediately after GP referral.Greater Glasgow and Clyde Health Board received 218 referrals of patients aged 16–40 to discuss tonsillectomy between January and August 2022. Every patient was sent a 16-page booklet by post and given the choice to opt in for a consultation.165 (76%) patients opted in, and 53 (24%) did not. Feedback was obtained from 143 patients (66%) from both groups. 99% found the information booklet easy to understand, 97% would recommend it to a friend with recurrent tonsillitis, 93% felt their questions had been answered and 92% believed it helped them to decide whether to proceed with tonsillectomy. Socioeconomic deprivation did not influence the outcome.In conclusion, most patients found provision of clinical information immediately after vetting of the referral to be beneficial, irrespective of whether they opted in for a consultation. This concept has broad applicability across all specialties, and the principles can be readily adopted and adapted by clinicians and managers in local units.
Evaluating the participation of junior members and patient and healthcare professionals representatives in EULAR task forces: results from an international survey
Authors: Juge Pierre-Antoine , Kragstrup Tue Wenzel , Perez-Garcia Luis Fernando , Frãzao-Mateus Elsa , Makri Souzi , Boyd Peter , Primdahl Jette , Ferreira Ricardo J O , Vliet Vlieland Theodora P M , Ndosi Mwidimi , Kiltz Uta , Landewé Robert , Lauper Kim , de Hooge Manouk 
Published: June 2024

ObjectiveEuropean Alliance of Associations for Rheumatology (EULAR) task forces (TF) requires participation of ≥2 junior members, a health professional in rheumatology (HPR) and two patient research partners for the development of recommendations or points to consider. In this study, participation of these junior and representative members was compared with the one of traditional TF members (convenor, methodologist, fellow and expert TF members).MethodsAn online survey was developed and emailed to previous EULAR TF members. The survey comprised multiple-choice, open-ended and 0–100 rating scale (fully disagree to fully agree) questions.ResultsIn total, 77 responded, 48 (62%) women. In total, 46 (60%) had participated as a junior or representative TF member. Most junior/representative members reported they felt unprepared for their first TF (10/14, 71%). Compared with traditional members, junior/representative members expressed a significantly higher level of uncertainty about their roles within the TF (median score 23 (IQR 7.0–52.0) vs 7 (IQR 0.0–21.0)), and junior/representative members felt less engaged by the convenor (54% vs 71%). Primary factors that facilitated interaction within a TF were experience, expertise and preparation (54%), a supportive atmosphere (42%) and a clear role (12%).ConclusionJuniors, patients and HPR experience various challenges when participating in a EULAR TF. These challenges differ from and are generally less pronounced than those experienced by traditional TF members. The convenor should introduce the participants to the tasks, emphasise the value of their contributions and how to prepare accordingly for the TF meeting.
Factors Associated with Poor Mental Health in Patients with Axial Spondyloarthritis: Results from the International Map of Axial Spondyloarthritis (IMAS)
Authors: Garrido-Cumbrera Marco , Navarro-Compán Victoria , Poddubnyy Denis , Sommerfleck Fernando , Makri Souzi , Correa-Fernández José , Akerkar Shashank , Lowe Jo , Karam Elie , Bundy Christine 
Published: June 2024

BackgroundThis study aims to assess the prevalence of poor mental health in axial spondyloarthritis (axSpA) and its associated factors in a large sample of patients from the International Map of Axial Spondyloarthritis (IMAS) study from around the globe.MethodsIMAS is a cross-sectional online survey (2017–2022) that includes 5557 unselected patients with axSpA worldwide. Mental health was evaluated by the 12-item General Health Questionnaire (GHQ-12) and the cut-off point for poor mental health was set at 3. Logistic regression analysis was used to evaluate relationships between the investigated factors and poor mental health (GHQ-12≥3) in patients with axSpA (n=4335).ResultsOf 5351 patients, the mean of GHQ-12 was 4.7 and 59.4% were having poor mental health, being 69.9% in South Africa, 63.7% in Latin America, 60.8% in Europe, 54.3% in North America and 51.8% in Asia. Overall, 40.5% and 37.2% of patients experienced anxiety and depression. The factors associated with poor mental health were younger age (OR=0.99), female gender (OR=1.16), being on sick leave or unemployed (OR=1.63), non-physical activity (OR=1.22), smoking (OR=1.20), higher Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] (OR=1.42), functional limitation (OR=1.02) and shorter symptoms duration (OR=0.98).ConclusionsGlobally, 6 in 10 patients with axSpA had poor mental health, with a higher proportion in South Africa and lower in Asia. The factors associated with poor mental health include domains such as younger age, female gender, employment difficulties, harmful habits, disease burden and symptom duration. A holistic management approach to axSpA should encompass both physical and mental health.
LHCb potential to discover long-lived new physics particles with lifetimes above 100 ps
Authors: Gorkavenko Volodymyr , Jashal Brij Kishor , Kholoimov Valerii , Kyselov Yehor , Mendoza Diego , Ovchynnikov Maksym , Oyanguren Arantza , Svintozelskyi Volodymyr , Zhuo Jiahui 
Published: June 2024

AbstractFor years, it has been believed that the main LHC detectors can play only a limited role of a lifetime frontier experiment exploring the parameter space of long-lived particles (LLPs)—hypothetical particles with tiny couplings to the Standard Model. This paper demonstrates that the LHCb experiment may become a powerful lifetime frontier experiment if it uses the new algorithm reconstructing tracks that do not allow hits in the LHCb vertex tracker. In particular, for many LLP scenarios, LHCb may be as sensitive as the proposed experiments beyond the main LHC detectors for various LLP models, including heavy neutral leptons, dark scalars, dark photons, and axion-like particles.