bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three prolonged outbreaks of metallo-β-lactamase-producing
Pseudomonas aeruginosa
in an Upper Austrian hospital, 2017–2023
Authors: Cabal Adriana , Hörtenhuber Anna , Salaheddin Yarub , Stöger Anna , Springer Burkhard , Bletz Stefan , Mellmann Alexander , Hyden Patrick , Hartl Rainer , Weinberger Johannes , Conzemius Rick , Hell Markus , Daza-Prieto Beatriz , Lippert Kathrin , Steindl Georg , Köberl-Jelovcan Sandra , Ruppitsch Werner 
Published: August 2024

ABSTRACT

In spring 2022, an increase in metallo-β-lactamase-producing
Pseudomonas aeruginosa
(MBL-Pa) infections was detected in a hospital in Upper Austria. To identify the source of infection and to stop further transmissions, an epidemiological outbreak investigation including whole-genome sequencing (WGS)-based typing was conducted. The final case definition included cases admitted to the hospital between 2020 and 2023 with an MBL-Pa in one of the three genomic clusters identified. In addition, the investigation was extended to include historical cases from 2017. Core genome multilocus sequence typing was performed to assess the genetic relatedness between the isolates. Fifty-four clinical
P. aeruginosa
isolates and eight
P. aeruginosa
isolates from the hospital environment were obtained. All but nine isolates grouped into one of three genomic clusters (ST235/
bla
VIM-1
, ST111/
bla
VIM-2
, or ST621/
bla
IMP-13
), which were considered to be distinct, prolonged outbreaks involving 47 out of 52 cases. The most likely source of infection for cluster 1 (ST111/
bla
VIM-2
) and cluster 2 (ST235/
bla
VIM-1
) was sinks in the intensive care unit (ICU) washroom. Cluster 3 clone (ST621/
bla
IMP-13
) could have originated in the urology ward in 2020 and then spread to the ICU years later. However, the nosocomial origin of this clone could not be proven. In March 2023, following the implementation of control measures (gowning, patient isolation, screening, and daily disinfection), no further MLB-Pa was detected, and the outbreaks were considered to be over. As ICUs play an important role in the transmission of
P. aeruginosa
, emphasis should be placed on genomic surveillance, infection prevention, and control in such wards.

IMPORTANCE

The significance of our work lies in the successful resolution of three prolonged outbreaks of MBL-Pa infections in a hospital in Upper Austria. Through a comprehensive epidemiological investigation coupled with WGS-based typing of
P. aeruginosa
isolates, the study identified three distinct genomic clusters responsible for prolonged outbreaks involving 47 cases. The investigation pinpointed sinks in the ICU washroom as the likely source of infection for two of the clusters. The study demonstrates the effectiveness of control measures such as hand hygiene, gowning, patient isolation, screening, and disinfection in stopping further transmission and bringing the outbreaks to a close. This underscores the critical role of genomic surveillance and control measures, particularly in high-risk settings like ICUs, in reducing nosocomial transmission of MBL-Pa infections.
Dynamic interplay of immune response, metabolome, and microbiota in cows during high-grain feeding: insights from multi-omics analysis
Authors: Castillo-Lopez Ezequias , Ricci Sara , Rivera-Chacon Raul , Sener-Aydemir Arife , Pacífico Cátia , Reisinger Nicole , Schwartz-Zimmermann Heidi E. , Berthiller Franz , Kreuzer-Redmer Susanne , Zebeli Qendrim 
Published: August 2024

ABSTRACT

This study explores the dynamics of immune gene expression, ruminal metabolome, and gut microbiota in cows due to the duration of high-grain feeding, shedding light on host response and microbial dynamics in parallel. Cows consumed forage for a week, then gradually transitioned to a high-grain diet, which they consumed for 4 weeks. Immune response was evaluated in ruminal papillae by expression of genes related to the nuclear factor-kappaB (NFkB) pathway and correlated with the microbiota. Rumen metabolome was evaluated with high-performance liquid chromatography coupled with mass spectrometry and anion-exchange chromatography. Rumen and fecal microbiota were evaluated with 16S rRNA gene amplicon sequencing. In the rumen, expression of inflammation-associated genes increased with the duration on high grain, indicating activation of pro-inflammatory cascades; microbial diversity decreased with a high-grain diet but stabilized after week 3 on high grain. Changes in microbial relative abundance and metabolite enrichment were observed throughout the 4 weeks on high grain, with increments in propionogenic taxa (i.e.,
Succinivibrionaceae
). Metabolite enrichment analysis showed that at the start of high-grain feeding, simple carbohydrates were enriched; then, these were substituted by their fermentation products. There were correlations between certain ruminal bacterial taxa (i.e.,
Ruminococcaceae
UCG-005) and expression of genes of the NFkB pathway, suggesting the influence of these taxa on host immune response. In feces, microbial diversity and several
Ruminococcaceae
members initially declined but recovered by weeks 3 and 4. Overall, despite the stabilization of microbial diversity, changes in microbial relative abundance and proinflammatory genes were observed throughout high-grain feeding, suggesting that cows need more than 4 weeks to fully adjust once consuming a high-grain diet.

IMPORTANCE
Despite the stepwise diet transition typically assumed to serve for animal adaptation, expression of signaling receptors, mediators, and downstream targets of nuclear factor-kappaB pathway were found throughout the 4 weeks on high grain, which correlated with changes in the rumen microbial profile. In addition, although microbial diversity recovered in the feces and stabilized in the rumen in week 3 on high grain, we observed changes in microbial relative abundance throughout the 4 weeks on high grain, suggesting that cows need more than 4 weeks to adjust once consuming this diet. Findings are particularly important to consider when planning experiments involving dietary changes.
Real-time flow cytometry to assess qualitative and quantitative responses of oral pathobionts during exposure to antiseptics
Authors: Chatzigiannidou I. , Heyse J. , Props R. , Rubbens P. , Mermans F. , Teughels W. , Van de Wiele T. , Boon N. 
Published: August 2024

ABSTRACT

Antiseptics are widely used in oral healthcare to prevent or treat oral diseases, such as gingivitis and periodontitis. However, the incidence of bacteria being tolerant to standard antiseptics has sharply increased over the last few years. This stresses the urgency for surveillance against tolerant organisms, as well as the discovery of novel antimicrobials. Traditionally, susceptibility to antimicrobials is assessed by broth micro-dilution or disk diffusion assays, both of which are time-consuming, labor-intensive, and provide limited information on the mode of action of the antimicrobials. The abovementioned limitations highlight the need for the development of new methods to monitor and further understand antimicrobial susceptibility. In this study, we used real-time flow cytometry, combined with membrane permeability staining, as a quick and sensitive technology to study the quantitative and qualitative responses of two oral pathobionts to different concentrations of chlorhexidine (CHX), cetylpyridinium chloride (CPC), or triclosan. Apart from the real-time monitoring of cell damage, we further applied a phenotypic fingerprinting method to differentiate between the bacterial subpopulations that arose due to treatment. We quantified the pathobiont damage rate of different antiseptics at different concentrations within 15 minutes of exposure and identified the conditions under which the bacteria were most susceptible. Moreover, we detected species-specific and treatment-specific phenotypic subpopulations. This proves that real-time flow cytometry can provide information on the susceptibility of different microorganisms in a short time frame while differentiating between antiseptics and thus could be a valuable tool in the discovery of novel antimicrobial compound, while at the same time deciphering their mode of action.

IMPORTANCE
With increasing evidence that microorganisms are becoming more tolerant to standard antimicrobials, faster and more accessible antimicrobial susceptibility testing methods are needed. However, traditional susceptibility assays are laborious and time-consuming. To overcome the abovementioned limitations, we introduce a novel approach to define antimicrobial susceptibility in a much shorter time frame with the use of real-time flow cytometry. Furthermore, phenotypic fingerprinting analysis can be applied on the data to study the way antiseptics affect the bacterial cell morphology over time and, thus, gain information on the mode of action of a certain compound.
Orthologs of
Plasmodium
ICM1 are dispensable for Ca
2+
mobilization in
Toxoplasma gondii
Authors: Cabral Gabriel , Ren Bingjian , Bisio Hugo , Otey Dawson , Soldati-Favre Dominique , Brown Kevin M. 
Published: August 2024

ABSTRACT

Apicomplexan parasites mobilize ionic calcium (Ca
2+
) from intracellular stores to promote microneme secretion and facilitate motile processes including gliding motility, invasion, and egress. Recently, a multipass transmembrane protein, ICM1, was found to be
i
mportant for
c
alcium
m
obilization in
Plasmodium falciparum
and
P. berghei
. Comparative genomics and phylogenetics have revealed putative ICM orthologs in
Toxoplasma gondii
and other apicomplexans.
T. gondii
possesses two ICM-like proteins, which we have named TgICM1-L (TGGT1_305470) and TgICM2-L (TGGT1_309910). TgICM1-L and TgICM2-L localized to undefined puncta within the parasite cytosol. TgICM1-L and TgICM2-L are individually dispensable in tachyzoites, suggesting a potential compensatory relationship between the two proteins may exist. Surprisingly, mutants lacking both TgICM1-L and TgICM2-L are fully viable, exhibiting no obvious defects in growth, microneme secretion, invasion, or egress. Furthermore, loss of TgICM1-L, TgICM2-L, or both does not impair the parasite’s ability to mobilize Ca
2+
. These findings suggest that additional proteins may participate in Ca
2+
mobilization or import in Apicomplexa, reducing the dependence on ICM-like proteins in
T. gondii
. Collectively, these results highlight similar yet distinct mechanisms of Ca
2+
mobilization between
T. gondii
and
Plasmodium
.

IMPORTANCE

Ca
2+
signaling plays a crucial role in governing apicomplexan motility; yet, the mechanisms underlying Ca
2+
mobilization from intracellular stores in these parasites remain unclear. In
Plasmodium
, the necessity of ICM1 for Ca
2+
mobilization raises the question of whether this mechanism is conserved in other apicomplexans. Investigation into the orthologs of
Plasmodium
ICM1 in
T. gondii
revealed a differing requirement for ICM proteins between the two parasites. This study suggests that
T. gondii
employs ICM-independent mechanisms to regulate Ca
2+
homeostasis and mobilization. Proteins involved in Ca
2+
signaling in apicomplexans represent promising targets for therapeutic development.
New species, new records, and common species of
Diderma
(Physarales,
Didymiaceae
) from China
Authors: Li Xuefei , Tuo Yonglan , Hu Jiajun , Li You , Dai Dan , Sossah Frederick Leo , Wang Jiajia , Guo Yanfang , Liu Shuyan , Ma Haixia , Zhang Bo , Li Xiao , Li Yu 
Published: August 2024

ABSTRACT

Myxomycetes are fungus-like organisms that play a significant role in ecological processes, however, their taxonomic diversity and distribution in China are poorly understood.
Diderma
is an important genus within the Class Myxogastria that has received little attention in China. This study provides new insights into the geographic range of
Diderma
species in China and identifies previously unreported and newly recorded species. Our results reveal that the geographic distribution of
Diderma
species in China is more diverse than previously thought, with four previously unreported species found in Liaoning, Hubei, Sichuan, and Gansu provinces. In addition, we describe five new
Diderma
species that are distinct from previously known species, namely
Diderma annuliferum
,
Diderma gansuense
,
Diderma roseum
,
Diderma jilinense
, and
Diderma flexocapillitium
. We identified these species using a combination of morphological characterization, DNA sequencing, and phylogenetic analysis. Our findings have important implications for understanding Myxomycete biodiversity in China and can inform future research on the ecology, biogeography, and evolution of these fascinating organisms. Specifically, our study highlights the need for continued exploration of underrepresented areas to gain a more comprehensive understanding of the diversity and distribution of Myxomycetes in China.

IMPORTANCE

The discovery of five new
Diderma
species and the revelation of their diverse distribution expand our understanding of Myxomycete diversity and provide a foundation for future studies on the ecology and biogeography of these organisms. These findings contribute to our knowledge of microbial diversity and have practical implications for conserving underrepresented areas and maintaining healthy ecosystems.
Development of a triplex RT-qPCR assay for simultaneous quantification of Japanese encephalitis, Murray Valley encephalitis, and West Nile viruses for environmental surveillance
Authors: Liu Yawen , Smith Wendy J , Gebrewold Metasebia , Simpson Stuart L. , Wang Xinhong , Ahmed Warish 
Published: August 2024

ABSTRACT

The co-circulation of mosquito-borne Japanese encephalitis virus (JEV), Murray Valley encephalitis virus (MVEV), and West Nile virus (WNV) has impacted human and animal health in multiple countries worldwide. To facilitate early warnings and surveillance of the presence of these viral infectious agents in the environment, a triplex reverse transcription-quantitative PCR (RT-qPCR) was developed for simultaneous quantification of JEV, MVEV, and WNV in potential hotspots such as piggery and urban wastewater and environmental water samples. The performance of the developed triplex RT-qPCR assay was compared with that of simplex counterparts, all using the same primer and probe sequences. The quantifiable results showed a concordance rate of 93.9%–100% (Cohen’s kappa) between the triplex and simplex assays. The mean concentrations of exogenous JEV, MVEV, and WNV using the triplex and simplex RT-qPCR assays were remarkably similar in piggery/urban wastewater and environmental water samples. However, the impacts of the matrix effects (i.e., sample composition and PCR inhibition) of environmental water samples on the accurate quantification of these viruses need to be considered. Taken together, this newly developed triplex RT-qPCR assay of JEV, MVEV, and WNV will allow for a more rapid and cost-efficient sample analysis and data interpretation. The application of the triplex assay for environmental surveillance may be a valuable tool to complement the existing disease and mosquito surveillance approaches used to safeguard the health of both humans and animals.

IMPORTANCE
The co-circulation of mosquito-borne Japanese encephalitis virus (JEV), Murray Valley encephalitis virus (MVEV), and West Nile virus (WNV) poses significant threats to human and animal health globally. In this study, a triplex RT-qPCR assay was developed for simultaneous quantification of these viruses in wastewater and environmental water samples. Results demonstrated high concordance and sensitivity of the newly developed triplex RT-qPCR assay compared to simplex assays, indicating its efficacy for environmental surveillance. This cost-effective and rapid assay offers a vital tool for timely monitoring of mosquito-borne viruses in environmental samples, enhancing our ability to mitigate potential outbreaks and safeguard public health.
Clinical value of guideline recommended molecular targets and genome targeted cancer therapies: cross sectional study
Authors: Tibau Ariadna , Hwang Thomas J , Avorn Jerry , Kesselheim Aaron S 
Published: August 2024

Abstract

Objective
To assess the clinical benefit and actionability of molecular targets for genome targeted cancer drugs recommended for clinical practice by the National Comprehensive Cancer Network (NCCN).

Design
Cross sectional study.

Participants/setting
Genome targeted cancer drugs recommended by NCCN guidelines in the advanced setting.

Main outcome measures
Molecular target actionability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit of genome targeted oncology therapies was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets at ESCAT category level I associated with studies showing substantial clinical benefit by ESMO-MCBS (grades 4-5) were designated as high benefit, and those linked to studies achieving an ESMO-MCBS grade of 3 were categorized as being of promising but unproven benefit.

Results
411 recommendations related to 74 genome targeted drugs targeting 50 driver alterations were examined. Most recommendations (346/411; 84%) were associated with clinical trials of various phases, but 16% (65/411) relied on only case reports or pre-clinical studies. However, clinical trials mostly comprised phase I or phase II (271/346; 78%), single arm (262/346; 76%) studies. The primary endpoint assessed in most trials was overall response rate (271/346; 78%) rather than survival. ESCAT tier I targetability encompassed 60% (246/411) of target recommendations, 35% (142/411) were classified as tier II or III, and 6% (23/411) had their relevance yet to be determined (tiers IV to X). When ESMO-MCBS was applied to 267 scorable trials, only 12% (32/267) showed substantial clinical benefit (grades 4-5) and 45% (121/267) were grade 3. When both frameworks were combined, 12% (32/267) of trials supported a determination of high benefit and 33% (88/267) indicated promising but unproven benefit. Of the 118 interventions endorsed by NCCN authors as preferred, 62 (53%) applied to treatments with high or promising but unproven benefit.

Conclusion
According to the ESCAT and ESMO-MCBS frameworks, about one eighth of genome based treatments for solid cancer were rated as likely to offer a high benefit to patients, whereas around a third were identified as offering a promising but unproven substantial benefit. Ensuring that NCCN recommendations are aligned with expected clinical benefits is crucial for promoting informed, evidence based, genomic guided treatment decisions.
Mainstreaming genetics into Italian prenatal care: exploring the future implementation of non-invasive prenatal testing (NIPT) in the Italian National Healthcare System using stakeholder interviews
Authors: Sesa Giulia , Czabanowska Katarzyna , Kok Kristiaan , Vrijenhoek Terry 
Published: August 2024

IntroductionNon-invasive prenatal testing (NIPT) has revolutionised the way prenatal testing is performed globally. Italy is one of the European countries considering incorporating NIPT nationwide into the publicly funded healthcare system. Given the extensive autonomy granted to the private sector, that not all technological applications result in equal benefits, and that only a few Italian regions currently offer NIPT through the public healthcare system free of charge, it is crucial to consider how to implement such a technology in the Italian public healthcare sector.MethodsA qualitative study consisting of 12 semistructured interviews was performed. The study population included gynaecologists, geneticists, bioethicists, health economists and public health professionals. Non-probability sampling techniques were used to recruit the study’s participants. Content analysis was employed to analyse the data.ResultsFrom the interviews, it emerged that a contingent implementation of NIPT for major chromosomal aneuploidies screening seems the most cost-effective and logical in the Italian context. No consensus was reached on fetal sex and sex chromosome aneuploidies screening. Most interviewees disagreed with making whole-genome/whole-exome sequencing available through the public sector. The high appreciation of NIPT, its potential to advance fundamental objectives of healthcare systems and its compatibility with the Italian prenatal testing culture are among the factors that may facilitate the transition of NIPT from the private to the public sector. Mainstreaming NIPT in the public healthcare system is challenged by its high costs, current offer, lack of prioritisation and regional differences.ConclusionsWhile transitions take time and are challenging to achieve, this study shows that the current prenatal testing structure and practice would only need modest adjustments to accommodate NIPT, offering hope for the future. Future studies could expand this research by involving a broad range of stakeholders and investigating the effects of various NIPT implementation strategies presently employed across Italian regions.
Prevalence of intracerebral thrombus detected by optical coherence tomography in patients with posterior circulation stroke or transient ischemic attack
Authors: Xu Ran , Yang Bin , Wang Tao , Zhang Xiao , Li Tianhua , Feng Yao , Guo Xiaofan , Jia Jinzhu , Ma Yan , Dmytriw Adam A , Jia Haibo , Jiao Liqun 
Published: August 2024

BackgroundThe incidence of thrombosis in patients with intracranial atherosclerotic stenosis (ICAS) remains unclear. Optical coherence tomography (OCT) has the potential to explore the vessel wall structure of posterior-circulation ICAS because of its relatively straight anatomical structure compared with that of the anterior cerebral arteries. This study aimed to determine the prevalence and characteristics of thrombosis in the posterior-circulation ICAS using OCT.MethodsThis prospective study was conducted on 135 patients with posterior-circulation arterial stenosis who underwent OCT. All patients were symptomatic and had a severely stenotic lesion (70–99%) in the vetebrobasilar artery. The enrolled patients were classified according to the presence of in situ thrombus as defined by OCT. Clinical data and OCT characteristics were compared.ResultsEighty-two patients diagnosed with posterior-circulation ICAS were enrolled. In situ thrombi were identified in 34 patients. Clinically, patients with in situ thrombus were more prone to cerebral infarctions than transient ischemic attacks. The percentage area of stenosis in the non-thrombus group was significantly lower than that in the thrombus group. The thrombus burden, mean flow area, mean thrombus area, maximum lipid arc, and mean lumen area were significantly different among white, red, and mixed thrombi.ConclusionsWe achieved in vivo vessel wall structural analysis of posterior-circulation ICAS with the largest sample size. We also revealed the true incidence of in situ thrombosis and potential corresponding clinical events of posterior-circulation ICAS for the first time.