cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12853628.v2
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.13012474
title: Two types of colistin heteroresistance in <i>Acinetobacter baumannii</i> isolates

description: In this study, we investigated the colistin heteroresistance patterns in <i>Acinetobacter baumannii</i> isolates. To identify colistin heteroresistance, population analysis profiling was performed for six <i>in vitro</i> colistin-susceptible <i>A. baumannii</i> isolates. Survival rates with and without prior exposure to colistin (at concentrations between 0 and 32 mg/L) were measured in media with and without colistin. Amino acid substitutions were also detected in colonies that survived in media with 4 mg/L colistin without further antibiotic treatment in six <i>A. baumannii</i> isolates. A stability test was also performed to investigate whether colistin resistance is maintained without antibiotic treatment. Although only three isolates showed typical colistin heteroresistance pattern, colistin-resistant populations were identified even without prior exposure to colistin in all <i>A. baumannii</i> isolates. Nearly all colonies of typical colistin-heteroresistant isolates (Type I heteroresistance) that survived after exposure to high colistin concentrations were found to be colistin-resistant, whereas no resistant colonies were identified in the other isolates (Type II heteroresistance). Stability tests showed that most of the surviving populations in media with 4 mg/L colistin without further antibiotic exposure failed to preserve resistance to colistin. Colistin-resistant populations also showed either no change in amino acid sequences, or diverse amino acid substitutions. We identified two types of colistin heteroresistance in <i>A. baumannii</i> isolates. Because Type I colistin-heteroresistant <i>A. baumannii</i> isolates could not be eradicated <i>in vitro</i> by high concentrations of colistin, differentiating two colistin heteroresistance types would be important for the treatment of <i>A. baumannii</i> infections using colistin.
DOI: 10.6084/m9.figshare.13012474.v1
title: Two types of colistin heteroresistance in <i>Acinetobacter baumannii</i> isolates

description: In this study, we investigated the colistin heteroresistance patterns in <i>Acinetobacter baumannii</i> isolates. To identify colistin heteroresistance, population analysis profiling was performed for six <i>in vitro</i> colistin-susceptible <i>A. baumannii</i> isolates. Survival rates with and without prior exposure to colistin (at concentrations between 0 and 32 mg/L) were measured in media with and without colistin. Amino acid substitutions were also detected in colonies that survived in media with 4 mg/L colistin without further antibiotic treatment in six <i>A. baumannii</i> isolates. A stability test was also performed to investigate whether colistin resistance is maintained without antibiotic treatment. Although only three isolates showed typical colistin heteroresistance pattern, colistin-resistant populations were identified even without prior exposure to colistin in all <i>A. baumannii</i> isolates. Nearly all colonies of typical colistin-heteroresistant isolates (Type I heteroresistance) that survived after exposure to high colistin concentrations were found to be colistin-resistant, whereas no resistant colonies were identified in the other isolates (Type II heteroresistance). Stability tests showed that most of the surviving populations in media with 4 mg/L colistin without further antibiotic exposure failed to preserve resistance to colistin. Colistin-resistant populations also showed either no change in amino acid sequences, or diverse amino acid substitutions. We identified two types of colistin heteroresistance in <i>A. baumannii</i> isolates. Because Type I colistin-heteroresistant <i>A. baumannii</i> isolates could not be eradicated <i>in vitro</i> by high concentrations of colistin, differentiating two colistin heteroresistance types would be important for the treatment of <i>A. baumannii</i> infections using colistin.
DOI: 10.6084/m9.figshare.12853718
title: Population structure-guided profiling of antibiotic resistance patterns in clinical <i>Listeria monocytogenes</i> isolates from Germany identifies <i>pbpB3</i> alleles associated with low levels of cephalosporin resistance

description: Numbers of listeriosis illnesses have been increasing in Germany and the European Union during the last decade. In addition, reports on the occurrence of antibiotic resistance in <i>Listeria monocytogenes</i> in clinical and environmental isolates are accumulating. The susceptibility towards 14 antibiotics was tested in a selection of clinical <i>L. monocytogenes</i> isolates to get a more precise picture of the development and manifestation of antibiotic resistance in the <i>L. monocytogenes</i> population. Based on the population structure determined by core genome multi locus sequence typing (cgMLST) 544 out of 1220 sequenced strains collected in Germany between 2009 and 2019 were selected to cover the phylogenetic diversity observed in the clinical <i>L. monocytogenes</i> population. All isolates tested were susceptible towards ampicillin, penicillin and co-trimoxazole – the most relevant antibiotics in the treatment of listeriosis. Resistance to daptomycin and ciprofloxacin was observed in 493 (91%) and in 71 (13%) of 544 isolates, respectively. While all tested strains showed resistance towards ceftriaxone, their resistance levels varied widely between 4 mg/L and &gt;128 mg/L. An allelic variation of the penicillin binding protein gene <i>pbpB3</i> was identified as the cause of this difference in ceftriaxone resistance levels. This study is the first population structure-guided analysis of antimicrobial resistance in recent clinical isolates and confirms the importance of penicillin binding protein B3 (PBP B3) for the high level of intrinsic cephalosporin resistance of <i>L. monocytogenes</i> on a population-wide scale.
DOI: 10.6084/m9.figshare.12853718.v1
title: Population structure-guided profiling of antibiotic resistance patterns in clinical <i>Listeria monocytogenes</i> isolates from Germany identifies <i>pbpB3</i> alleles associated with low levels of cephalosporin resistance

description: Numbers of listeriosis illnesses have been increasing in Germany and the European Union during the last decade. In addition, reports on the occurrence of antibiotic resistance in <i>Listeria monocytogenes</i> in clinical and environmental isolates are accumulating. The susceptibility towards 14 antibiotics was tested in a selection of clinical <i>L. monocytogenes</i> isolates to get a more precise picture of the development and manifestation of antibiotic resistance in the <i>L. monocytogenes</i> population. Based on the population structure determined by core genome multi locus sequence typing (cgMLST) 544 out of 1220 sequenced strains collected in Germany between 2009 and 2019 were selected to cover the phylogenetic diversity observed in the clinical <i>L. monocytogenes</i> population. All isolates tested were susceptible towards ampicillin, penicillin and co-trimoxazole – the most relevant antibiotics in the treatment of listeriosis. Resistance to daptomycin and ciprofloxacin was observed in 493 (91%) and in 71 (13%) of 544 isolates, respectively. While all tested strains showed resistance towards ceftriaxone, their resistance levels varied widely between 4 mg/L and &gt;128 mg/L. An allelic variation of the penicillin binding protein gene <i>pbpB3</i> was identified as the cause of this difference in ceftriaxone resistance levels. This study is the first population structure-guided analysis of antimicrobial resistance in recent clinical isolates and confirms the importance of penicillin binding protein B3 (PBP B3) for the high level of intrinsic cephalosporin resistance of <i>L. monocytogenes</i> on a population-wide scale.
DOI: 10.6084/m9.figshare.13313278
title: A novel <i>Sporothrix brasiliensis</i> genomic variant in Midwestern Brazil: evidence for an older and wider sporotrichosis epidemic

description: Sporotrichosis is a subcutaneous infection caused by fungi from the genus <i>Sporothrix</i>. It is transmitted by inoculation of infective particles found in plant-contaminated material or diseased animals, characterizing the classic sapronotic and emerging zoonotic transmission, respectively. Since 1998, southeastern Brazil has experienced a zoonotic sporotrichosis epidemic caused by <i>S. brasiliensis</i>, centred in the state of Rio de Janeiro. Our observation of feline sporotrichosis cases in Brasília (Midwestern Brazil), around 900 km away from Rio de Janeiro, led us to question whether the epidemic caused by <i>S. brasiliensis</i> has spread from the epicentre in Rio de Janeiro, emerged independently in the two locations, or if the disease has been present and unrecognized in Midwestern Brazil. A retrospective analysis of 91 human and 4 animal cases from Brasília, ranging from 1993 to 2018, suggests the occurrence of both sapronotic and zoonotic transmission. Molecular typing of the calmodulin locus identified <i>S. schenckii</i> as the agent in two animals and all seven human patients from which we were able to recover clinical isolates. In two other animals, the disease was caused by <i>S. brasiliensis</i>. Whole-genome sequence typing of seven <i>Sporothrix</i> spp. strains from Brasília and Rio de Janeiro suggests that <i>S. brasiliensis</i> isolates from Brasília are genetically distinct from those obtained at the epicentre of the outbreak in Rio de Janeiro, both in phylogenomic and population genomic analyses. The two <i>S. brasiliensis</i> populations seem to have separated between 2.2 and 3.1 million years ago, indicating independent outbreaks or that the zoonotic <i>S. brasiliensis</i> outbreak might have started earlier and be more widespread in South America than previously recognized.
DOI: 10.6084/m9.figshare.13313278.v1
title: A novel <i>Sporothrix brasiliensis</i> genomic variant in Midwestern Brazil: evidence for an older and wider sporotrichosis epidemic

description: Sporotrichosis is a subcutaneous infection caused by fungi from the genus <i>Sporothrix</i>. It is transmitted by inoculation of infective particles found in plant-contaminated material or diseased animals, characterizing the classic sapronotic and emerging zoonotic transmission, respectively. Since 1998, southeastern Brazil has experienced a zoonotic sporotrichosis epidemic caused by <i>S. brasiliensis</i>, centred in the state of Rio de Janeiro. Our observation of feline sporotrichosis cases in Brasília (Midwestern Brazil), around 900 km away from Rio de Janeiro, led us to question whether the epidemic caused by <i>S. brasiliensis</i> has spread from the epicentre in Rio de Janeiro, emerged independently in the two locations, or if the disease has been present and unrecognized in Midwestern Brazil. A retrospective analysis of 91 human and 4 animal cases from Brasília, ranging from 1993 to 2018, suggests the occurrence of both sapronotic and zoonotic transmission. Molecular typing of the calmodulin locus identified <i>S. schenckii</i> as the agent in two animals and all seven human patients from which we were able to recover clinical isolates. In two other animals, the disease was caused by <i>S. brasiliensis</i>. Whole-genome sequence typing of seven <i>Sporothrix</i> spp. strains from Brasília and Rio de Janeiro suggests that <i>S. brasiliensis</i> isolates from Brasília are genetically distinct from those obtained at the epicentre of the outbreak in Rio de Janeiro, both in phylogenomic and population genomic analyses. The two <i>S. brasiliensis</i> populations seem to have separated between 2.2 and 3.1 million years ago, indicating independent outbreaks or that the zoonotic <i>S. brasiliensis</i> outbreak might have started earlier and be more widespread in South America than previously recognized.
DOI: 10.6084/m9.figshare.12301067
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.12301067.v3
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
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.13291832
title: A multi-family cluster of COVID-19 associated with asymptomatic and pre-symptomatic transmission in Jixi City, Heilongjiang, China, 2020

description: We investigated a multi-family cluster of 22 cases in Jixi, where pre-symptomatic and asymptomatic transmission resulted in at least 41% of household infections of SARS-CoV-2. Our study illustrates the challenge of controlling COVID-19 due to the presence of asymptomatic and pre-symptomatic transmission even when extensive testing and contact tracing are conducted.
DOI: 10.6084/m9.figshare.11694969
title: Modulation of lethal HPAIV H5N8 clade 2.3.4.4B infection in AIV pre-exposed mallards

description: In 2016/2017, a severe epidemic of HPAIV H5N8 clade 2.3.4.4 group B (H5N8B) affected Europe. To analyse the role of mallards in the spatiotemporal dynamics of global HPAIV H5N8B dispersal, mallards (<i>Anas platyrhynchos</i>), naturally exposed to various AIV and therefore seropositive, were challenged with H5N8B. All experiments were controlled by infection and co-housing of seronegative juvenile Pekin ducklings. All ducks that survived the first infection were re-challenged 21 dpi with the homologous H5N8B strain. After the first H5N8B infection, seropositive mallards showed only mild clinical symptoms. Moderate to low viral shedding, occurring particularly from the oropharynx and lasting for 7 days maximum, led to severe clinical disease of all contact ducklings. All challenged seronegative Pekin ducks and contact ducklings died or had to be euthanized. H5-specific antibodies were detected in surviving birds within 2 weeks. Virus and viral RNA could be isolated from several water samples until 6 and 9 dpi, respectively. Conversely, upon re-infection with homologous H5N8B neither inoculated nor contact ducklings showed any clinical symptoms, nor was an antibody titer increase of seropositive mallards or any seroconversion of contact ducklings observed. Mallard ducks naturally pre-exposed to LPAIV can play a role as a clinically unsuspicious virus reservoir for H5N8B effective in virus transmission. Mallards with homologous immunity did not contribute to virus transmission.
DOI: 10.6084/m9.figshare.11694969.v1
title: Modulation of lethal HPAIV H5N8 clade 2.3.4.4B infection in AIV pre-exposed mallards

description: In 2016/2017, a severe epidemic of HPAIV H5N8 clade 2.3.4.4 group B (H5N8B) affected Europe. To analyse the role of mallards in the spatiotemporal dynamics of global HPAIV H5N8B dispersal, mallards (<i>Anas platyrhynchos</i>), naturally exposed to various AIV and therefore seropositive, were challenged with H5N8B. All experiments were controlled by infection and co-housing of seronegative juvenile Pekin ducklings. All ducks that survived the first infection were re-challenged 21 dpi with the homologous H5N8B strain. After the first H5N8B infection, seropositive mallards showed only mild clinical symptoms. Moderate to low viral shedding, occurring particularly from the oropharynx and lasting for 7 days maximum, led to severe clinical disease of all contact ducklings. All challenged seronegative Pekin ducks and contact ducklings died or had to be euthanized. H5-specific antibodies were detected in surviving birds within 2 weeks. Virus and viral RNA could be isolated from several water samples until 6 and 9 dpi, respectively. Conversely, upon re-infection with homologous H5N8B neither inoculated nor contact ducklings showed any clinical symptoms, nor was an antibody titer increase of seropositive mallards or any seroconversion of contact ducklings observed. Mallard ducks naturally pre-exposed to LPAIV can play a role as a clinically unsuspicious virus reservoir for H5N8B effective in virus transmission. Mallards with homologous immunity did not contribute to virus transmission.
DOI: 10.6084/m9.figshare.13291832.v1
title: A multi-family cluster of COVID-19 associated with asymptomatic and pre-symptomatic transmission in Jixi City, Heilongjiang, China, 2020

description: We investigated a multi-family cluster of 22 cases in Jixi, where pre-symptomatic and asymptomatic transmission resulted in at least 41% of household infections of SARS-CoV-2. Our study illustrates the challenge of controlling COVID-19 due to the presence of asymptomatic and pre-symptomatic transmission even when extensive testing and contact tracing are conducted.
DOI: 10.6084/m9.figshare.12301067.v2
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.21918894.v1
title: human_milk_cis_eQTL_summary_stats.tab.gz

description: Human milk eQTL summary statistics in tabix format
DOI: 10.6084/m9.figshare.21929250.v1
title: Empirical Study on High Performance Computing (HPC) Performance Bug Analysis - Replication Package

description: Summary results of labeled data added.
DOI: 10.6084/m9.figshare.21929466
title: Supplementary Material for: IMPACT OF THE COVID-19 PANDEMIC ON CERVICAL CANCER SCREENING IN SÃO PAULO STATE, BRAZIL

description: INTRODUCTION: The early identification of precursor lesions followed by appropriate treatment prevents development of cervical cancer and its consequences OBJECTIVE: The present study evaluated the influence of the Covid-19 pandemic on cervical cancer screening by comparing the quantity of tests to detect cervical cellular changes performed in Sao Paulo state in 2019, prior to the detection of SARS-CoV-2 in Brazil, to the first (2020) and second (2021) years following its appearance. MATERIALS AND METHODS: Data from Fundação Oncocentro de São Paulo (FOSP), the agency that analyses approximately 220,000 Pap tests annually, was reviewed. RESULTS: A median of 1835 Papanicolaou (Pap) tests were performed in 55 municipalities in 2019. This was reduced to 815 tests in 2020, a 56% decrease (p = 0.0026). In 2021, the median number was 1745, a 53% increase over 2020 levels (p = 0.0233). The 26 municipalities with &gt;1000 tests in 2020 had a median reduction from 4433 in 2019 to 2580 in 2020 (p = 0. 0046). The 29 municipalities with &lt;1000 tests had a median reduction from 951 in 2019 to 554 in 2020 (p &lt; 0.0001). There was a 44% reduction in the number of follow-up cytological evaluations from 2019 to 2020, followed by a 30% increase the following year. However, the percentage of women with a normal finding or with any abnormality remained unchanged. The findings from a histological evaluation of women in Sao Paulo city indicated that the percent of cases positive for CIN-1 (p&lt;0.0410) and CIN-3 (p&lt;0.0012) increased in 2020 and 2021 as compared to 2019 levels. CONCLUSION: A reduction in testing for cervical cancer in the first year of the Covid-19 pandemic, accompanied by an elevated incidence of precancerous lesions in each of the first two years following its initiation, may portend a subsequent increased occurrence of cervical cancer in Brazil.