cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13029039.v16
title: Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i> <sub>CTX-M-14b</sub> in Europe

description: Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i> <sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the <i>bla</i> <sub>CTX-M-14b</sub> clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the <i>bla</i> <sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i> <sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
DOI: 10.6084/m9.figshare.12601348.v2
title: Biologically-based modeling of radiation risk and biomarker prevalence for papillary thyroid cancer in Japanese a-bomb survivors 1958 - 2005

description: <i>Purpose:</i> Thyroid cancer of papillary histology (PTC) is the dominant type in radio-epidemiological cohorts established after nuclear accidents or warfare. Studies on post-Chernobyl PTC and on thyroid cancer in the life span study (LSS) of Japanese a-bomb survivors consistently revealed high radiation risk after exposure during childhood and adolescence. For post-Chernobyl risk assessment overexpression of the CLIP2 gene was proposed as molecular biomarker to separate radiogenic from sporadic PTC. Based on such binary marker a biologically-based risk model of PTC carcinogenesis has been developed for observational Chernobyl data. The model featured two independent molecular pathways of disease development, of which one was associated with radiation exposure. To gain credibility the concept for a mechanistic risk model must be based on general biological features which transcend findings in a single cohort. The purpose of the present study is therefore to demonstrate portability of the model concept by application to PTC incidence data in the LSS. By exploiting the molecular two-path concept we improve the determination of the probability of radiation causing cancer (POC). <i>Materials and methods:</i> The current analysis uses thyroid cancer incidence data of the LSS with thyroid cancer diagnoses and papillary histology (n = 292) from the follow-up period between 1958 and 2005. Risk analysis was performed with both descriptive and biologically-based models. <i>Results:</i> Judged by goodness-of-fit all applied models described the data almost equally well. They yielded similar risk estimates in cohorts post-Chernobyl and LSS. The preferred mechanistic model was selected by biological plausibility. It reflected important features of an imperfect radiation marker which are not easily addressed by descriptive models. Precise model predictions of marker prevalence in strata of epidemiological covariables can be tested by molecular measurements. Application of the radiation-related molecular pathway from our preferred model in retrospective risk assessment decreases the threshold dose for 50% POC from 0.33 (95% confidence interval (CI) 0.18; 0.64) Gy to 0.04 (95% CI 0.01; 0.19) Gy for females and from 0.43 (95% CI 0.17; 1.84) Gy to 0.19 (95% CI 0.05; 1.00) Gy for males. These improvements are still not sufficient to separate radiation-induced from sporadic PTC cases at very low doses &lt;0.015 Gy typical for the Fukushima accident. <i>Conclusions:</i> Successful application of our preferred mechanistic model to LSS incidence data confirms and improves the biological two-path concept of radiation-induced PTC. Model predictions suggest further molecular validation studies to consolidate the basis of biologically-based risk estimation.
DOI: 10.6084/m9.figshare.11418321.v1
title: Transcriptional response to metal starvation in the emerging pathogen <i>Mycoplasma genitalium</i> is mediated by Fur-dependent and –independent regulatory pathways

description: Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen <i>Mycoplasma genitalium</i>. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the <i>hrl</i> promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the <i>fur</i> mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the <i>fur</i> mutant by ICP-MS revealed an important role of Fur in nickel acquisition.
DOI: 10.6084/m9.figshare.11999553.v1
title: Live bird markets as evolutionary epicentres of H9N2 low pathogenicity avian influenza viruses in Korea

description: Live bird markets (LBMs) in Korea have been recognized as a reservoir, amplifier, and source of avian influenza viruses (AIVs); however, little was known about the role of LBMs in the epidemiology of AIVs in Korea until recently. Through 10 years of surveillance (2006–2016) we have isolated and sequenced H9N2 viruses in Korean LBMs. To understand how H9N2 evolves and spreads in Korea, a statistical Bayesian phylogenetic model was used. Phylogenetic analysis suggests that three separate introductions of progenitor gene pools, Korean domestic duck-origin and two wild aquatic bird-origin AIVs, contributed to the generation of the five genotypes of H9N2 viruses in Korea. Phylogenetic reconstruction of ecological states infer that the LBMs are where chickens become infected with the virus, with domestic ducks playing a major role in the transmission and evolution of the H9N2 viruses. Three increases in the genetic diversity of H9N2 viruses were observed and coincided with transitions in host species and the locations (domestic farm, LBM, slaughterhouse, and wild aquatic bird habitat) where the viruses were isolated, accompanying genetic reassortment. Following the introduction of a wild aquatic bird-origin AIVs in 2008, six genes of the Korean lineage H9N2 virus were replaced with genes originating from wild aquatic birds, and viruses with this new genotype became predominant in Korean LBMs.
DOI: 10.6084/m9.figshare.11902206.v1
title: Tick-borne encephalitis foci in northeast Italy revealed by combined virus detection in ticks, serosurvey on goats and human cases

description: Tick-borne encephalitis (TBE) is a severe zoonotic neurological disease endemic in northeast Italy since 1992. In the Province of Trento, a sharp increase in TBE incidence has been recorded since 2012, despite the vaccination efforts. To assess current TBE infection hazard in this area, we applied an integrated approach combining the distribution of human cases, the seroprevalence of tick-borne encephalitis virus (TBEV) in sentinel hosts and the screening of questing ticks for TBEV. A total of 706 goat sera from 69 farms were screened for TBEV-specific antibodies resulting in 5 positive farms, while the location of human cases was provided by the local Public Health Agency. Tick sampling was concentrated in areas where TBEV circulation was suggested by either seroprevalence in goats or human cases, resulting in 2,410 <i>Ixodes ricinus</i> collected and analyzed by real-time RT–PCR. Four tick samples from 2 areas with record of human cases were positive to TBEV corresponding to a 0.17% prevalence in the region, while risk areas suggested by serology on goats were not confirmed by tick screening. Our results revealed an increase in TBEV prevalence in ticks and the emergence of new active TBE foci, compared to previous surveys, and demonstrated the importance of an integrated approach for TBE risk assessment. A phylogenetic analysis of the partial E gene confirmed that the European TBEV subtype is circulating in northeast Italy and suggested that the different Italian TBEV strains originated independently as a result of different introductions from neighbouring countries, presumably through migratory birds.
DOI: 10.6084/m9.figshare.13034798.v1
title: Multicenter evaluation of two chemiluminescence and three lateral flow immunoassays for the diagnosis of COVID-19 and assessment of antibody dynamic responses to SARS-CoV-2 in Taiwan

description: This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4–99.0%), Abbott Test (94.0%, 89.1–96.8%), Wondfo Test (91.4%, 85.8–94.9%), ASK Test (97.4%, 93.4–99.0%), and Dynamiker Test (90.1%, 84.3–94.0%) after &gt;21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3–99.7%) for the Roche Test, 97.9% (95% CI, 94.8–99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1–100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.
DOI: 10.6084/m9.figshare.12085149.v1
title: Rsp promotes the transcription of virulence factors in an <i>agr</i>-independent manner in <i>Staphylococcus aureus</i>

description: <i>Staphylococcus aureus</i> is a major human pathogen that causes a great diversity of community- and hospital-acquired infections. Rsp, a member of AraC/XylS family of transcriptional regulators (AFTRs), has been reported to play an important role in the regulation of virulence determinants in <i>S. aureus</i> via an <i>agr</i>-dependent pathway. Here we demonstrated that Rsp could bind to the <i>rsp</i> promoter to positively regulate its own expression. We then constructed an isogenic <i>rsp</i> deletion strain and compared the haemolysis in the wild-type and <i>rsp</i> mutant strains. Our results indicated that the <i>rsp</i> mutant strain displayed decreased haemolytic activity, which was correlated with a dramatic decrease in the expression of <i>hla</i> and <i>psm</i>. Furthermore, we analysed the regulatory effects of Rsp in the <i>agr</i> mutant strain and found that they are <i>agr</i>-independent. Electrophoretic mobility shift assay indicated that Rsp can directly bind to the promoter regions of <i>hla</i> and <i>psm</i>. The mouse model of subcutaneous abscess showed that the <i>rsp</i> mutant strain displayed a significant defect in virulence compared to the wild-type strain. These findings reveal that Rsp positively regulates the virulence of <i>S. aureus</i> by promoting the expression of <i>hla</i> and <i>psm</i> through direct binding to their promoter regions.
DOI: 10.6084/m9.figshare.12601348.v1
title: Biologically-based modeling of radiation risk and biomarker prevalence for papillary thyroid cancer in Japanese a-bomb survivors 1958–2005

description: Thyroid cancer of papillary histology (PTC) is the dominant type in radio-epidemiological cohorts established after nuclear accidents or warfare. Studies on post-Chernobyl PTC and on thyroid cancer in the life span study (LSS) of Japanese a-bomb survivors consistently revealed high radiation risk after exposure during childhood and adolescence. For post-Chernobyl risk assessment overexpression of the CLIP2 gene was proposed as molecular biomarker to separate radiogenic from sporadic PTC. Based on such binary marker a biologically-based risk model of PTC carcinogenesis has been developed for observational Chernobyl data. The model featured two independent molecular pathways of disease development, of which one was associated with radiation exposure. To gain credibility the concept for a mechanistic risk model must be based on general biological features which transcend findings in a single cohort. The purpose of the present study is therefore to demonstrate portability of the model concept by application to PTC incidence data in the LSS. By exploiting the molecular two-path concept we improve the determination of the probability of radiation causing cancer (POC). The current analysis uses thyroid cancer incidence data of the LSS with thyroid cancer diagnoses and papillary histology (<i>n</i> = 292) from the follow-up period between 1958 and 2005. Risk analysis was performed with both descriptive and biologically-based models. Judged by goodness-of-fit all applied models described the data almost equally well. They yielded similar risk estimates in cohorts post-Chernobyl and LSS. The preferred mechanistic model was selected by biological plausibility. It reflected important features of an imperfect radiation marker which are not easily addressed by descriptive models. Precise model predictions of marker prevalence in strata of epidemiological covariables can be tested by molecular measurements. Application of the radiation-related molecular pathway from our preferred model in retrospective risk assessment decreases the threshold dose for 50% POC from 0.33 (95% confidence interval (CI) 0.18; 0.64) Gy to 0.04 (95% CI 0.01; 0.19) Gy for females and from 0.43 (95% CI 0.17; 1.84) Gy to 0.19 (95% CI 0.05; 1.00) Gy for males. These improvements are still not sufficient to separate radiation-induced from sporadic PTC cases at very low doses &lt;0.015 Gy typical for the Fukushima accident. Successful application of our preferred mechanistic model to LSS incidence data confirms and improves the biological two-path concept of radiation-induced PTC. Model predictions suggest further molecular validation studies to consolidate the basis of biologically-based risk estimation.
DOI: 10.6084/m9.figshare.12853628.v1
title: Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors

description: Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine, <i>Salvia miltiorrhiza</i> (Danshen), were screened for anti-EV-A71. We identified a natural product, rosmarinic acid (RA), as a potential inhibitor of EV-A71 by cell-based antiviral assay and <i>in vivo</i> mouse model. Results also show that RA may affect the early stage of viral infection and may target viral particles directly, thereby interfering with virus-P-selectin glycoprotein ligand-1 (PSGL1) and virus-heparan sulfate interactions without abolishing the interaction between the virus and scavenger receptor B2 (SCARB2). Sequencing of the plaque-purified RA-resistant viruses revealed a N104K mutation in the five-fold axis of the structural protein VP1, which contains positively charged amino acids reportedly associated with virus-PSGL1 and virus-heparan sulfate interactions via electrostatic attraction. The plasmid-derived recombinant virus harbouring this mutation was confirmed to be refractory to RA inhibition. Receptor pull-down showed that this non-positively charged VP1-N104 is critical for virus binding to heparan sulfate. As the VP1-N104 residue is conserved among different EV-A71 strains, RA may be useful for inhibiting EV-A71 infection, even for emergent virus variants. Our study provides insight into the molecular mechanism of virus-host interactions and identifies a promising new class of inhibitors based on its antiviral activity and broad spectrum effects against a range of EV-A71.
DOI: 10.6084/m9.figshare.12301067.v1
title: Unexpected rabies variant identified in kinkajou (<i>Potos flavus</i>), Mato Grosso, Brazil

description: A second case of a novel rabies variant described once in a capuchin monkey from Mato Grosso, Brazil, was discovered in a rabid wild kinkajou from the same region, indicating a public health risk following exposure to either of the two animals.
DOI: 10.6084/m9.figshare.12146112.v2
title: Jamestown Canyon virus in Massachusetts: clinical case series and vector screening

description: Jamestown Canyon virus (JCV) is a neuroinvasive arbovirus that is found throughout North America and increasingly recognized as a public health concern. From 2004 to 2012, an average of 1.7 confirmed cases were reported annually in the United States, whereas from 2013 to 2018 this figure increased over seventeen-fold to 29.2 cases per year. The rising number of reported human infections highlights the need for better understanding of the clinical manifestations and epidemiology of JCV. Here, we describe nine patients diagnosed with neuroinvasive JCV infection in Massachusetts from 2013, the year of the first reported case in the state, to 2017. Because current diagnostic testing relies on serology, which is complicated by cross-reactivity with related orthobunyaviruses and can be negative in immunosuppressed patients, we developed and evaluated an RT-qPCR assay for detection of JCV RNA. We tested this on the available archived serum from two patients, but did not detect viral RNA. JCV is transmitted by multiple mosquito species and its primary vector in Massachusetts is unknown, so we additionally applied the RT-qPCR assay and confirmatory RNA sequencing to assess JCV prevalence in a vector candidate, <i>Ochlerotatus canadensis</i>. We identified JCV in 0.6% of mosquito pools, a similar prevalence to neighboring Connecticut. We assembled the first Massachusetts JCV genome directly from a mosquito sample, finding high identity to JCV isolates collected over a 60-year period. Further studies are needed to reconcile the low vector prevalence and low rate of viral evolutionary change with the increasing number of reported cases.
DOI: 10.6084/m9.figshare.5032250
title: Microscopic recognition and identification of fish meal in compound feeds

description: Fish meal is an accepted ingredient in compound feed. Unauthorised application is primarily enforced by visual inspection, i.e., microscopy. In order to document the visually available diversity, fragments of bones and scales of 17 teleost fish species belonging to seven different orders were investigated for their diversity in the presence of structural elements: lacunae and canaliculae in bone fragments and type of growth rings and teeth of scale fragments. Despite the classical division into cellular bones and acellular bones of teleost fish, i.e., whether or not possessing osteocytes, the current examinations revealed patterns of lacunae, in some types accompanied with canaliculae, in all 17 species investigated. In total seven types of bone structures were defined, and six types of scale structures. Profiles with the relative frequency of each bone type per species were established. The share of acellular bone fragments appeared to be related to the evolutionary position of the species. Results of proficiency tests for the detection of fish meal reveal that in most cases the sensitivity and specificity for the detection of fish meal ranges from sufficient to perfect. Only some specified circumstances can hamper proper recognition and identification, most notably salmon bone fragments mimicking bone fragments from terrestrial animals, and pieces of hydrolysed proteins or minerals mimicking acellular fish bone fragments. The expertise gained in this study would help to improve the distinction between fish meal and terrestrial animal material in compound feed, and it supports the application of the species-to-species ban with respect to the valorisation of by-products from fish farms in aquafeed. In a broader perspective, the current expertise might be helpful to detect fraud throughout the feed/food production chain. The matrix of characteristics versus species is implemented in a data model running in the expert system ‘Determinator’ for facilitating identification.