cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21155530
title: Compartmentalisation of Hepatitis B virus X gene evolution in hepatocellular carcinoma microenvironment and the genotype-phenotype correlation of tumorigenicity in HBV-related patients with hepatocellular carcinoma

description: Hepatitis B virus (HBV) exists as quasispecies (QS). However, the evolutionary characteristics of haplotypes of HBV X gene in the hepatocellular carcinoma (HCC) microenvironment remain unclear. Mutations across X gene are essential for the tumorigenicity of HBV X protein (HBx). However, the functional phenotypes of many mutant HBx remain unknown. This study aims to compare the characteristics of X gene evolution between tumour and non-tumour tissues in HCC patients and investigate the tumorigenic phenotype of HBx harbouring mutation T81P/S101P/L123S. This study included 24 HCC patients. Molecular cloning of X gene was performed to analyse characteristics of haplotypes in liver tissues. HCC cell lines stably expressing wild-type or mutant HBx and subcutaneous tumour xenograft mouse model were used to assess HBx-T81P/S101P/L123S tumorigenicity. The mean heterogeneity of HBV QS across X gene in tumour tissues was lower than that in non-tumour tissues. A location bias was observed in X gene clones with genotype C or D in tumour tissues compared to those with genotype B. Mutations in genotype-C or – D clones were mainly clustered in the dimerization region and aa110-aa140 within the transactivation region. A novel mutation combination at residues 81, 101 and 123 was identified in tumour tissues. Further, HBx-T81P/S101P/L123S promotes cell proliferation and increases genomic instability, which was mediated by MYC. This study elucidates the compartmentalized evolution patterns of HBV X gene between intra tumour and non-tumour tissues in HCC patients and provides a new mechanism underlying HBV-driven hepatocarcinogenesis, suggesting a potential viral marker for monitoring HCC.
DOI: 10.6084/m9.figshare.21155530.v2
title: Compartmentalisation of Hepatitis B virus X gene evolution in hepatocellular carcinoma microenvironment and the genotype-phenotype correlation of tumorigenicity in HBV-related patients with hepatocellular carcinoma

description: Hepatitis B virus (HBV) exists as quasispecies (QS). However, the evolutionary characteristics of haplotypes of HBV X gene in the hepatocellular carcinoma (HCC) microenvironment remain unclear. Mutations across X gene are essential for the tumorigenicity of HBV X protein (HBx). However, the functional phenotypes of many mutant HBx remain unknown. This study aims to compare the characteristics of X gene evolution between tumour and non-tumour tissues in HCC patients and investigate the tumorigenic phenotype of HBx harbouring mutation T81P/S101P/L123S. This study included 24 HCC patients. Molecular cloning of X gene was performed to analyse characteristics of haplotypes in liver tissues. HCC cell lines stably expressing wild-type or mutant HBx and subcutaneous tumour xenograft mouse model were used to assess HBx-T81P/S101P/L123S tumorigenicity. The mean heterogeneity of HBV QS across X gene in tumour tissues was lower than that in non-tumour tissues. A location bias was observed in X gene clones with genotype C or D in tumour tissues compared to those with genotype B. Mutations in genotype-C or – D clones were mainly clustered in the dimerization region and aa110-aa140 within the transactivation region. A novel mutation combination at residues 81, 101 and 123 was identified in tumour tissues. Further, HBx-T81P/S101P/L123S promotes cell proliferation and increases genomic instability, which was mediated by MYC. This study elucidates the compartmentalized evolution patterns of HBV X gene between intra tumour and non-tumour tissues in HCC patients and provides a new mechanism underlying HBV-driven hepatocarcinogenesis, suggesting a potential viral marker for monitoring HCC.
DOI: 10.5683/sp2/7jtwdz
title: CapnoBase InVivo Dataset

description: The in-vivo dataset contains capnography signals that were recorded during real clinical cases. Information that could possibly identify the source of the data has been removed.
&lt;b&gt;To get access to all files, select &lt;u&gt;all&lt;/u&gt; files before requesting access!&lt;/b&gt;
DOI: 10.6084/m9.figshare.19362548
title: Epidemiology of extrapulmonary tuberculosis among pediatric inpatients in mainland China: a descriptive, multicenter study

description: Pediatric tuberculosis (TB) is a serious infectious disease that affects many children worldwide and is more likely to be extrapulmonary than adult TB. However, the clinical and epidemiological profile, and cost burden of pediatric extrapulmonary TB (EPTB) in China remain unknown. Here, we conducted a descriptive, multicenter study of pediatric TB patients from 22 hospitals across all six regions in China from October 2015 to December 2018. Of 4,654 patients, 54.23% (2,524) had pulmonary TB (PTB), 17.76% (827) had EPTB, and 28.00% (1,303) had concurrent extrapulmonary and pulmonary TB (combined TB). Compared with PTB, EPTB and combined TB were associated with lower hospitalization frequency (2.43 and 2.21 vs. 3.16 times), longer length of stay (10.61 and 11.27 vs. 8.56 days), and higher rate of discharge against medical advice (8.46% and 9.44% vs. 5.67%). EPTB was associated with higher mortality (0.97% vs. 0.24% and 0.31%), higher rate of low birth weight (17.69% vs. 6.79% and 6.22%), worse diagnosis at the first visit (21.16% vs. 34.67% and 44.47%), and worse hospitalization plan situation (4.35% vs. 7.81% and 7.44%), compared with PTB and combined TB. EPTB and combined TB had higher financial burdens (17.67% and 16.94% vs. 13.30%) and higher rates of catastrophic expenditure (8.22% and 9.59% vs. 5.03%), compared with PTB. Meningitis TB (34.18%) was the most frequent form of total extrapulmonary infection and had the highest cost burden and rate of catastrophic expenditure. In conclusion, improved screening approaches for pediatric EPTB are needed to reduce diagnostic challenges and financial burden.
DOI: 10.6084/m9.figshare.19362548.v2
title: Epidemiology of extrapulmonary tuberculosis among pediatric inpatients in mainland China: a descriptive, multicenter study

description: Pediatric tuberculosis (TB) is a serious infectious disease that affects many children worldwide and is more likely to be extrapulmonary than adult TB. However, the clinical and epidemiological profile, and cost burden of pediatric extrapulmonary TB (EPTB) in China remain unknown. Here, we conducted a descriptive, multicenter study of pediatric TB patients from 22 hospitals across all six regions in China from October 2015 to December 2018. Of 4,654 patients, 54.23% (2,524) had pulmonary TB (PTB), 17.76% (827) had EPTB, and 28.00% (1,303) had concurrent extrapulmonary and pulmonary TB (combined TB). Compared with PTB, EPTB and combined TB were associated with lower hospitalization frequency (2.43 and 2.21 vs. 3.16 times), longer length of stay (10.61 and 11.27 vs. 8.56 days), and higher rate of discharge against medical advice (8.46% and 9.44% vs. 5.67%). EPTB was associated with higher mortality (0.97% vs. 0.24% and 0.31%), higher rate of low birth weight (17.69% vs. 6.79% and 6.22%), worse diagnosis at the first visit (21.16% vs. 34.67% and 44.47%), and worse hospitalization plan situation (4.35% vs. 7.81% and 7.44%), compared with PTB and combined TB. EPTB and combined TB had higher financial burdens (17.67% and 16.94% vs. 13.30%) and higher rates of catastrophic expenditure (8.22% and 9.59% vs. 5.03%), compared with PTB. Meningitis TB (34.18%) was the most frequent form of total extrapulmonary infection and had the highest cost burden and rate of catastrophic expenditure. In conclusion, improved screening approaches for pediatric EPTB are needed to reduce diagnostic challenges and financial burden.
DOI: 10.6084/m9.figshare.19900326
title: Comparative miRNA transcriptomics of macaques and mice reveals <i>MYOC</i> is an inhibitor for <i>Cryptococcus neoformans</i> invasion into the brain

description: Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART­naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen <i>Cryptococcus neoformans</i>. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during <i>C. neoformans</i> infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage “Trojan Horse” in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by <i>MYOC</i>, was found to be a novel enhancer for the macrophage “Trojan Horse,” and an enhanced fungal burden was achieved in the brains of <i>MYOC</i>-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and <i>MYOC</i> in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by <i>C. neoformans</i> and other pathogenic microorganisms.
DOI: 10.6084/m9.figshare.19900326.v2
title: Comparative miRNA transcriptomics of macaques and mice reveals <i>MYOC</i> is an inhibitor for <i>Cryptococcus neoformans</i> invasion into the brain

description: Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART­naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen <i>Cryptococcus neoformans</i>. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during <i>C. neoformans</i> infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage “Trojan Horse” in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by <i>MYOC</i>, was found to be a novel enhancer for the macrophage “Trojan Horse,” and an enhanced fungal burden was achieved in the brains of <i>MYOC</i>-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and <i>MYOC</i> in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by <i>C. neoformans</i> and other pathogenic microorganisms.
DOI: 10.6084/m9.figshare.17099727
title: Replicative transposition contributes to the evolution and dissemination of KPC-2-producing plasmid in <i>Enterobacterales</i>

description: <i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing <i>Enterobacterales</i> are prevalent worldwide and pose an alarming threat to public health. The incidence and transmission of <i>bla</i><sub>KPC-2</sub> gene via horizontal gene transfer (e.g. transposition) have been well documented. However, the dynamics of transposon structure bearing <i>bla</i><sub>KPC-2</sub> and their exact effects on the evolution and dissemination of <i>bla</i><sub>KPC-2</sub> gene are not well characterized. Here, we collected all 161 carbapenem-resistant <i>Enterobacterales</i> (CRE) isolates during the early stage of CRE pandemic. We observed that the prevalence of KPC-2-producing <i>Enterobacterales</i> was mediated by multiple species and sequence types (STs), and that <i>bla</i><sub>KPC-2</sub> gene was located on three diverse variants of Tn<i>1721</i> in multi-drug resistance (MDR) region of plasmid. Notably, the outbreak of KPC-2-producing plasmid is correlated with the dynamics of transposon structure. Furthermore, we experimentally demonstrated that replicative transposition of Tn<i>1721</i> and IS<i>26</i> promotes horizontal transfer of <i>bla</i><sub>KPC-2</sub> and the evolution of KPC-2-producing plasmid. The Tn<i>1721</i> variants appearing concurrently with the peak of an epidemic (A2- and B-type) showed higher transposition frequencies and a certain superior ability to propagation. Overall, our work suggests replicative transposition contributes to the evolution and transmission of KPC-2-producing plasmid and highlights its important role in the inter- and intra-species dissemination of <i>bla</i><sub>KPC-2</sub> gene in <i>Enterobacterales</i>.
DOI: 10.6084/m9.figshare.17099727.v2
title: Replicative transposition contributes to the evolution and dissemination of KPC-2-producing plasmid in <i>Enterobacterales</i>

description: <i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing <i>Enterobacterales</i> are prevalent worldwide and pose an alarming threat to public health. The incidence and transmission of <i>bla</i><sub>KPC-2</sub> gene via horizontal gene transfer (e.g. transposition) have been well documented. However, the dynamics of transposon structure bearing <i>bla</i><sub>KPC-2</sub> and their exact effects on the evolution and dissemination of <i>bla</i><sub>KPC-2</sub> gene are not well characterized. Here, we collected all 161 carbapenem-resistant <i>Enterobacterales</i> (CRE) isolates during the early stage of CRE pandemic. We observed that the prevalence of KPC-2-producing <i>Enterobacterales</i> was mediated by multiple species and sequence types (STs), and that <i>bla</i><sub>KPC-2</sub> gene was located on three diverse variants of Tn<i>1721</i> in multi-drug resistance (MDR) region of plasmid. Notably, the outbreak of KPC-2-producing plasmid is correlated with the dynamics of transposon structure. Furthermore, we experimentally demonstrated that replicative transposition of Tn<i>1721</i> and IS<i>26</i> promotes horizontal transfer of <i>bla</i><sub>KPC-2</sub> and the evolution of KPC-2-producing plasmid. The Tn<i>1721</i> variants appearing concurrently with the peak of an epidemic (A2- and B-type) showed higher transposition frequencies and a certain superior ability to propagation. Overall, our work suggests replicative transposition contributes to the evolution and transmission of KPC-2-producing plasmid and highlights its important role in the inter- and intra-species dissemination of <i>bla</i><sub>KPC-2</sub> gene in <i>Enterobacterales</i>.
DOI: 10.6084/m9.figshare.20415830
title: Correlation of <i>Moraxella catarrhalis</i> macrolide susceptibility with the ability to adhere and invade human respiratory epithelial cells

description: Recently, the prevalence of macrolide-resistant <i>Moraxella catarrhalis</i> has been reported, especially among Chinese children. The fitness cost of resistance is reported to render the resistant bacteria less virulent. To investigate the correlation between macrolide susceptibility of <i>M. catarrhalis</i> and pathogenicity, the whole genome of 70 <i>M. catarrhalis</i> isolates belonging to four clonal complexes with different macrolide susceptibilities was sequenced. The gene products were annotated with the Gene Ontology terms. Based on 46 extracted essential virulence genes, 19 representative isolates were selected to infect type II alveolar cells (A549 cells). The ability of these isolates to adhere and invade human epithelial cells and to produce cytokines was comparatively analysed. Furthermore, mice were infected with a pair of <i>M. catarrhalis</i> isolates with different pathogenic behaviours and macrolide susceptibilities to examine pulmonary clearance, histological findings, and the production of cytokines. The percentages of annotations for binding, metabolic process, cellular process, and cell were non-significantly different between the macrolide-resistant and macrolide-susceptible groups. The presence of <i>uspA2</i>, <i>uspA2H</i>, <i>pilO</i>, <i>lbpB</i>, <i>lex1</i>, <i>modM</i>, <i>mboIA</i>, and <i>mboIB</i> significantly differed among the four clonal complexes and macrolide susceptibility groups. Furthermore, compared with those in macrolide-susceptible isolates, the adhesion ability was stronger (<i>P</i> = 0.0019) and the invasion ability was weaker (<i>P</i> &lt; 0.0001) in the macrolide-resistant isolates. Mouse experiments revealed that pulmonary macrophages elicit immune responses against <i>M. catarrhalis</i> infection by significantly upregulating the Csf2, Il4, Il13, Il1b, Il6, Tnf, and Il18. Therefore, <i>M. catarrhalis</i> populations exhibited diverse pathogenicity <i>in vitro</i> and <i>in vivo</i>.
DOI: 10.6084/m9.figshare.20415830.v2
title: Correlation of <i>Moraxella catarrhalis</i> macrolide susceptibility with the ability to adhere and invade human respiratory epithelial cells

description: Recently, the prevalence of macrolide-resistant <i>Moraxella catarrhalis</i> has been reported, especially among Chinese children. The fitness cost of resistance is reported to render the resistant bacteria less virulent. To investigate the correlation between macrolide susceptibility of <i>M. catarrhalis</i> and pathogenicity, the whole genome of 70 <i>M. catarrhalis</i> isolates belonging to four clonal complexes with different macrolide susceptibilities was sequenced. The gene products were annotated with the Gene Ontology terms. Based on 46 extracted essential virulence genes, 19 representative isolates were selected to infect type II alveolar cells (A549 cells). The ability of these isolates to adhere and invade human epithelial cells and to produce cytokines was comparatively analysed. Furthermore, mice were infected with a pair of <i>M. catarrhalis</i> isolates with different pathogenic behaviours and macrolide susceptibilities to examine pulmonary clearance, histological findings, and the production of cytokines. The percentages of annotations for binding, metabolic process, cellular process, and cell were non-significantly different between the macrolide-resistant and macrolide-susceptible groups. The presence of <i>uspA2</i>, <i>uspA2H</i>, <i>pilO</i>, <i>lbpB</i>, <i>lex1</i>, <i>modM</i>, <i>mboIA</i>, and <i>mboIB</i> significantly differed among the four clonal complexes and macrolide susceptibility groups. Furthermore, compared with those in macrolide-susceptible isolates, the adhesion ability was stronger (<i>P</i> = 0.0019) and the invasion ability was weaker (<i>P</i> &lt; 0.0001) in the macrolide-resistant isolates. Mouse experiments revealed that pulmonary macrophages elicit immune responses against <i>M. catarrhalis</i> infection by significantly upregulating the Csf2, Il4, Il13, Il1b, Il6, Tnf, and Il18. Therefore, <i>M. catarrhalis</i> populations exhibited diverse pathogenicity <i>in vitro</i> and <i>in vivo</i>.
DOI: 10.6084/m9.figshare.20118841
title: Severity of SARS-CoV-2 Omicron BA.2 infection in unvaccinated hospitalized children: comparison to influenza and parainfluenza infections

description: There has been a rapid surge of hospitalization due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants globally. The severity of Omicron BA.2 in unexposed, unvaccinated, hospitalized children is unknown. We investigated the severity and clinical outcomes of COVID-19 infection during the Omicron wave in uninfected, unvaccinated hospitalized children and in comparison with influenza and parainfluenza viral infections. This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes for the Omicron BA.2-dominant fifth wave (5–28 February 2022, n = 1144), and influenza and parainfluenza viruses (1 January 2015–31 December 2019, n = 32212 and n = 16423, respectively) in children 0–11 years old. Two deaths (0.2%) out of 1144 cases during the initial Omicron wave were recorded. Twenty-one (1.8%) required PICU admission, and the relative risk was higher for Omicron than influenza virus (n = 254, 0.8%, adjusted RR = 2.1, 95%CI 1.3–3.3, <i>p</i> = 0.001). The proportion with neurological complications was 15.0% (n = 171) for Omicron, which was higher than influenza and parainfluenza viruses (n = 2707, 8.4%, adjusted RR = 1.6, 95%CI 1.4–1.9 and n = 1258, 7.7%, adjusted RR = 1.9, 95%CI 1.6–2.2, <i>p</i> &lt; 0.001 for both, respectively). Croup occurred for Omicron (n = 61, 5.3%) more than influenza virus (n = 601, 1.9%, adjusted RR = 2.0, 95%CI 1.5–2.6, <i>p</i> &lt; 0.001) but not parainfluenza virus (n = 889, 5.4%). Our findings showed that for hospitalized children who had no past COVID-19 or vaccination, Omicron BA.2 was not mild. Omicron BA.2 appeared to be more neuropathogenic than influenza and parainfluenza viruses. It targeted the upper airways more than influenza virus.
DOI: 10.6084/m9.figshare.20118841.v2
title: Severity of SARS-CoV-2 Omicron BA.2 infection in unvaccinated hospitalized children: comparison to influenza and parainfluenza infections

description: There has been a rapid surge of hospitalization due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants globally. The severity of Omicron BA.2 in unexposed, unvaccinated, hospitalized children is unknown. We investigated the severity and clinical outcomes of COVID-19 infection during the Omicron wave in uninfected, unvaccinated hospitalized children and in comparison with influenza and parainfluenza viral infections. This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes for the Omicron BA.2-dominant fifth wave (5–28 February 2022, n = 1144), and influenza and parainfluenza viruses (1 January 2015–31 December 2019, n = 32212 and n = 16423, respectively) in children 0–11 years old. Two deaths (0.2%) out of 1144 cases during the initial Omicron wave were recorded. Twenty-one (1.8%) required PICU admission, and the relative risk was higher for Omicron than influenza virus (n = 254, 0.8%, adjusted RR = 2.1, 95%CI 1.3–3.3, <i>p</i> = 0.001). The proportion with neurological complications was 15.0% (n = 171) for Omicron, which was higher than influenza and parainfluenza viruses (n = 2707, 8.4%, adjusted RR = 1.6, 95%CI 1.4–1.9 and n = 1258, 7.7%, adjusted RR = 1.9, 95%CI 1.6–2.2, <i>p</i> &lt; 0.001 for both, respectively). Croup occurred for Omicron (n = 61, 5.3%) more than influenza virus (n = 601, 1.9%, adjusted RR = 2.0, 95%CI 1.5–2.6, <i>p</i> &lt; 0.001) but not parainfluenza virus (n = 889, 5.4%). Our findings showed that for hospitalized children who had no past COVID-19 or vaccination, Omicron BA.2 was not mild. Omicron BA.2 appeared to be more neuropathogenic than influenza and parainfluenza viruses. It targeted the upper airways more than influenza virus.
DOI: 10.15468/dl.mkbbsm
title: Occurrence Download

description: A dataset containing 39194 species occurrences available in GBIF matching the query:
{
 "Geometry" : [
 "POLYGON ((-105.4188 21.59913, -105.2688 21.59913, -105.2688 21.74913, -105.4188 21.74913, -105.4188 21.59913))"
 ]
}

 The dataset includes 39194 records from 52 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0040896-251025141854904/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.