cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.26861602
title: Whole-genome analysis of circulating influenza A virus (H3N2) strains in Shanghai, China from 2005 to 2023

description: Seasonal influenza A virus subtype H3N2 (A/H3N2) circulates globally and has been linked to higher hospitalization rates and summer outbreaks in temperate regions. Here, A/H3N2 circulation in Shanghai, China was systematically studied using data and materials generated by the Shanghai influenza surveillance network from 2005 to 2023. Time-series analysis of incidence and subtyping data showed that A/H3N2 co-circulated with other (sub)types and dominated in multiple seasonal influenza peaks, preferentially in summer. Whole genomes of 528 representative strains were sequenced, and spatiotemporal phylodynamic analysis using these and GISAID-archived sequences demonstrated that in the years before the COVID-19 pandemic, phylogenetically similar strains were circulating locally and elsewhere. However, clade 1a.1 (within 3C.2a.1b.2a), circulated in and only in Shanghai and domestically in 2022, while the sibling clade 2 predominated in other regions. Interestingly, clade 1a.1 was swiftly and completely replaced by clade 2, mostly 2a.3a.1, at the start of 2023. In hemagglutination inhibition and neutralization assays, sera from healthy donors collected in 2022 displayed higher or similar reactivity against 2a.3a.1 compared to 1a.1. By contrast, transcription and replication competence of 2a.3a.1 in MDCK cells was higher than 1a.1. These results indicated that instead of antigenicity differences enabling evasion of pre-existing immunity, higher replicative capability more likely contributed to 2a.3a.1 viruses achieving dominance in China. In addition to summarizing patterns of A/H3N2 local circulation in Shanghai, this work revealed an unusual episode in A/H3N2 global circulation and evolution dynamics in connection to the COVID-19 pandemic and explored possible mechanistic explanations.
DOI: 10.6084/m9.figshare.26861602.v1
title: Whole-genome analysis of circulating influenza A virus (H3N2) strains in Shanghai, China from 2005 to 2023

description: Seasonal influenza A virus subtype H3N2 (A/H3N2) circulates globally and has been linked to higher hospitalization rates and summer outbreaks in temperate regions. Here, A/H3N2 circulation in Shanghai, China was systematically studied using data and materials generated by the Shanghai influenza surveillance network from 2005 to 2023. Time-series analysis of incidence and subtyping data showed that A/H3N2 co-circulated with other (sub)types and dominated in multiple seasonal influenza peaks, preferentially in summer. Whole genomes of 528 representative strains were sequenced, and spatiotemporal phylodynamic analysis using these and GISAID-archived sequences demonstrated that in the years before the COVID-19 pandemic, phylogenetically similar strains were circulating locally and elsewhere. However, clade 1a.1 (within 3C.2a.1b.2a), circulated in and only in Shanghai and domestically in 2022, while the sibling clade 2 predominated in other regions. Interestingly, clade 1a.1 was swiftly and completely replaced by clade 2, mostly 2a.3a.1, at the start of 2023. In hemagglutination inhibition and neutralization assays, sera from healthy donors collected in 2022 displayed higher or similar reactivity against 2a.3a.1 compared to 1a.1. By contrast, transcription and replication competence of 2a.3a.1 in MDCK cells was higher than 1a.1. These results indicated that instead of antigenicity differences enabling evasion of pre-existing immunity, higher replicative capability more likely contributed to 2a.3a.1 viruses achieving dominance in China. In addition to summarizing patterns of A/H3N2 local circulation in Shanghai, this work revealed an unusual episode in A/H3N2 global circulation and evolution dynamics in connection to the COVID-19 pandemic and explored possible mechanistic explanations.
DOI: 10.25549/webster-c100-45324
title: Emergency operations guide, 1984-04

description: Guidebook developed by the Los Angeles Police Department's Tactical Planning Section about essential information for personnel involved in disaster operations, 1984 April. PART OF SERIES: The series includes materials related to the performance of the LAPD prior to and during the 1992 Los Angeles riots. Included are reports and documents pertaining to the department's tactical planning measures for unusual occurrences and emergencies; riot-related statistics and figures; and arrest logs, incident logs, and activities reports maintained during the riots
DOI: 10.6084/m9.figshare.26319108
title: Enterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis

description: Enterovirus A71 (EV-A71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV-A71 and its mechanism, as the current models mainly utilize animal models or immortalized cell lines. In this study, we established a human motor neuron model for EV-A71 infection. Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons. The elevated RNA load in motor neurons correlates with the downregulation of ferritin-encoding genes. Subsequent analysis confirms that neurons infected with EV-A71 undergo ferroptosis, as evidenced by increased levels of labile Fe<sup>2+</sup> and peroxidated lipids. Notably, the Fe<sup>2+</sup> chelator Deferoxamine improves mitochondrial function and promotes survival of motor neurons by 40% after EV-A71 infection. These findings deepen understanding of the molecular pathogenesis of EV-A71 infection, providing insights which suggest that improving mitochondrial respiration and inhibition of ferroptosis can mitigate the impact of EV-A71 infection in the central nervous system.
DOI: 10.6084/m9.figshare.26319108.v1
title: Enterovirus-A71 Preferentially Infects and Replicates in Human Motor Neurons, Inducing Neurodegeneration by Ferroptosis

description: Enterovirus A71 (EV-A71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV-A71 and its mechanism, as the current models mainly utilize animal models or immortalized cell lines. In this study, we established a human motor neuron model for EV-A71 infection. Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons. The elevated RNA load in motor neurons correlates with the downregulation of ferritin-encoding genes. Subsequent analysis confirms that neurons infected with EV-A71 undergo ferroptosis, as evidenced by increased levels of labile Fe<sup>2+</sup> and peroxidated lipids. Notably, the Fe<sup>2+</sup> chelator Deferoxamine improves mitochondrial function and promotes survival of motor neurons by 40% after EV-A71 infection. These findings deepen understanding of the molecular pathogenesis of EV-A71 infection, providing insights which suggest that improving mitochondrial respiration and inhibition of ferroptosis can mitigate the impact of EV-A71 infection in the central nervous system.
DOI: 10.6084/m9.figshare.26319108.v2
title: Enterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis

description: Enterovirus A71 (EV-A71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV-A71 and its mechanism, as the current models mainly utilize animal models or immortalized cell lines. In this study, we established a human motor neuron model for EV-A71 infection. Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons. The elevated RNA load in motor neurons correlates with the downregulation of ferritin-encoding genes. Subsequent analysis confirms that neurons infected with EV-A71 undergo ferroptosis, as evidenced by increased levels of labile Fe<sup>2+</sup> and peroxidated lipids. Notably, the Fe<sup>2+</sup> chelator Deferoxamine improves mitochondrial function and promotes survival of motor neurons by 40% after EV-A71 infection. These findings deepen understanding of the molecular pathogenesis of EV-A71 infection, providing insights which suggest that improving mitochondrial respiration and inhibition of ferroptosis can mitigate the impact of EV-A71 infection in the central nervous system.
DOI: 10.25549/webster-c100-40022
title: Webster scope

description: A report that assesses the 1992 riots using a wide variety of socioeconomic indicators. PART OF SERIES: In addition to analyzing the 1992 riots as a whole, the Webster Commission also divided into several smaller task forces and study groups, each of which addressed one specific aspect of the civil disturbance. The series consists of reports and appendices produced by five of these groups: the Chronology Team, the Public Officials and Community Team, the LAPD Team, the Comparisons Study Group, and the Inter-Agency Team. Also included are two copies of Webster Scope, a report that interprets the riots and their cumulative effects primarily through graphs, charts, statistics, and figures, and several research memoranda that discuss the legality of several riot-response tactics.
DOI: 10.6084/m9.figshare.24592431
title: Monovalent XBB.1.5 booster vaccination induces a broad spectrum of SARS-CoV-2 neutralizing antibodies

description: Monovalent XBB.1.5 booster vaccination induces a broad spectrum of SARS-CoV-2 neutralizing antibodies
DOI: 10.6084/m9.figshare.24592431.v2
title: Monovalent XBB.1.5 booster vaccination induces a broad spectrum of SARS-CoV-2 neutralizing antibodies

description: Monovalent XBB.1.5 booster vaccination induces a broad spectrum of SARS-CoV-2 neutralizing antibodies
DOI: 10.6084/m9.figshare.24942045
title: Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study

description: There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan–Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57–381) person-years/100,000. The SIR was 5.59 (95%CI:1.81–13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (<i>P</i> &gt; 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (<i>P</i> &lt; 0.001). Furthermore, the value of the IGRA assay decreased after treatment (<i>P</i> &lt; 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.
DOI: 10.6084/m9.figshare.24942045.v2
title: Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study

description: There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan–Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57–381) person-years/100,000. The SIR was 5.59 (95%CI:1.81–13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (<i>P</i> &gt; 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (<i>P</i> &lt; 0.001). Furthermore, the value of the IGRA assay decreased after treatment (<i>P</i> &lt; 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.
DOI: 10.6084/m9.figshare.25164464
title: RES-Xre toxin-antitoxin locus <i>knaAT</i> maintains the stability of the virulence plasmid in <i>Klebsiella pneumoniae</i>

description: Hypervirulent <i>Klebsiella pneumoniae</i> isolates have been increasingly reported worldwide<i>,</i> especially hypervirulent drug-resistant variants owing to the acquisition of a mobilizable virulence plasmid by a carbapenem-resistant strain. This pLVPK-like mobilizable plasmid encodes various virulence factors; however, information about its genetic stability is lacking. This study aimed to investigate the type II toxin-antitoxin (TA) modules that facilitate the virulence plasmid to remain stable in <i>K. pneumoniae</i>. More than 3,000 TA loci in 2,000 <i>K. pneumoniae</i> plasmids were examined for their relationship with plasmid cargo genes. TA loci from the RES-Xre family were highly correlated with virulence plasmids of hypervirulent <i>K. pneumoniae</i>. Overexpression of the RES toxin KnaT, encoded by the virulence plasmid-carrying RES-Xre locus <i>knaAT,</i> halts the cell growth of <i>K. pneumoniae</i> and <i>E. coli</i>, whereas co-expression of the cognate Xre antitoxin KnaA neutralizes the toxicity of KnaT. <i>knaA</i> and <i>knaT</i> were co-transcribed, representing the characteristics of a type II TA module. The <i>knaAT</i> deletion mutation gradually lost its virulence plasmid in <i>K. pneumoniae,</i> whereas the stability of the plasmid in <i>E. coli</i> was enhanced by adding <i>knaAT</i>, which revealed that the <i>knaAT</i> operon maintained the genetic stability of the large virulence plasmid in <i>K. pneumoniae</i>. String tests and mouse lethality assays subsequently confirmed that a loss of the virulence plasmid resulted in reduced pathogenicity of <i>K. pneumoniae</i>. These findings provide important insights into the role of the RES-Xre TA pair in stabilizing virulence plasmids and disseminating virulence genes in <i>K. pneumonia</i>e.
DOI: 10.6084/m9.figshare.25164464.v2
title: RES-Xre toxin-antitoxin locus <i>knaAT</i> maintains the stability of the virulence plasmid in <i>Klebsiella pneumoniae</i>

description: Hypervirulent <i>Klebsiella pneumoniae</i> isolates have been increasingly reported worldwide<i>,</i> especially hypervirulent drug-resistant variants owing to the acquisition of a mobilizable virulence plasmid by a carbapenem-resistant strain. This pLVPK-like mobilizable plasmid encodes various virulence factors; however, information about its genetic stability is lacking. This study aimed to investigate the type II toxin-antitoxin (TA) modules that facilitate the virulence plasmid to remain stable in <i>K. pneumoniae</i>. More than 3,000 TA loci in 2,000 <i>K. pneumoniae</i> plasmids were examined for their relationship with plasmid cargo genes. TA loci from the RES-Xre family were highly correlated with virulence plasmids of hypervirulent <i>K. pneumoniae</i>. Overexpression of the RES toxin KnaT, encoded by the virulence plasmid-carrying RES-Xre locus <i>knaAT,</i> halts the cell growth of <i>K. pneumoniae</i> and <i>E. coli</i>, whereas co-expression of the cognate Xre antitoxin KnaA neutralizes the toxicity of KnaT. <i>knaA</i> and <i>knaT</i> were co-transcribed, representing the characteristics of a type II TA module. The <i>knaAT</i> deletion mutation gradually lost its virulence plasmid in <i>K. pneumoniae,</i> whereas the stability of the plasmid in <i>E. coli</i> was enhanced by adding <i>knaAT</i>, which revealed that the <i>knaAT</i> operon maintained the genetic stability of the large virulence plasmid in <i>K. pneumoniae</i>. String tests and mouse lethality assays subsequently confirmed that a loss of the virulence plasmid resulted in reduced pathogenicity of <i>K. pneumoniae</i>. These findings provide important insights into the role of the RES-Xre TA pair in stabilizing virulence plasmids and disseminating virulence genes in <i>K. pneumonia</i>e.
DOI: 10.6084/m9.figshare.25343537
title: Evaluation of outbreak persistence caused by multidrug-resistant and echinocandin-resistant <i>Candida parapsilosis</i> using multidimensional experimental and epidemiological approaches

description: <i>Candida parapsilosis</i> is known to cause severe and persistent outbreaks in clinical settings. Patients infected with multidrug-resistant <i>C. parapsilosis</i> (MDR Cp) isolates were identified in a large Turkish hospital from 2017–2020. We subsequently identified three additional patients infected with MDR Cp isolates in 2022 from the same hospital and two echinocandin-resistant (ECR) isolates from a single patient in another hospital. The increasing number of MDR and ECR isolates contradicts the general principle that the severe fitness cost associated with these phenotypes could prevent their dominance in clinical settings. Here, we employed a multidimensional approach to systematically assess the fitness costs of MDR and ECR <i>C. parapsilosis</i> isolates. Whole-genome sequencing revealed a novel MDR genotype infecting two patients in 2022. Despite severe <i>in vitro</i> defects, the levels and tolerances of the biofilms of our ECR and MDR isolates were generally comparable to those of susceptible wild-type isolates. Surprisingly, the MDR and ECR isolates showed major alterations in their cell wall components, and some of the MDR isolates consistently displayed increased tolerance to the fungicidal activities of primary human neutrophils and were more immunoevasive during exposure to primary human macrophages. Our systemic infection mouse model showed that MDR and ECR <i>C. parapsilosis</i> isolates had comparable fungal burden in most organs relative to susceptible isolates. Overall, we observed a notable increase in the genotypic diversity and frequency of MDR isolates and identified MDR and ECR isolates potentially capable of causing persistent outbreaks in the future.
DOI: 10.6084/m9.figshare.25343537.v1
title: Evaluation of outbreak persistence caused by multidrug-resistant and echinocandin-resistant <i>Candida parapsilosis</i> using multidimensional experimental and epidemiological approaches

description: <i>Candida parapsilosis</i> is known to cause severe and persistent outbreaks in clinical settings. Patients infected with multidrug-resistant <i>C. parapsilosis</i> (MDR Cp) isolates were identified in a large Turkish hospital from 2017–2020. We subsequently identified three additional patients infected with MDR Cp isolates in 2022 from the same hospital and two echinocandin-resistant (ECR) isolates from a single patient in another hospital. The increasing number of MDR and ECR isolates contradicts the general principle that the severe fitness cost associated with these phenotypes could prevent their dominance in clinical settings. Here, we employed a multidimensional approach to systematically assess the fitness costs of MDR and ECR <i>C. parapsilosis</i> isolates. Whole-genome sequencing revealed a novel MDR genotype infecting two patients in 2022. Despite severe <i>in vitro</i> defects, the levels and tolerances of the biofilms of our ECR and MDR isolates were generally comparable to those of susceptible wild-type isolates. Surprisingly, the MDR and ECR isolates showed major alterations in their cell wall components, and some of the MDR isolates consistently displayed increased tolerance to the fungicidal activities of primary human neutrophils and were more immunoevasive during exposure to primary human macrophages. Our systemic infection mouse model showed that MDR and ECR <i>C. parapsilosis</i> isolates had comparable fungal burden in most organs relative to susceptible isolates. Overall, we observed a notable increase in the genotypic diversity and frequency of MDR isolates and identified MDR and ECR isolates potentially capable of causing persistent outbreaks in the future.
DOI: 10.6084/m9.figshare.27060509
title: Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in <i>Brucella abortus</i>

description: Brucellosis, caused by the intracellular pathogen <i>Brucella</i>, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in <i>Brucella</i>. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in <i>B. abortus</i>. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in <i>B. abortus</i> by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of <i>arsR2</i> attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic <i>Brucella</i> species.