cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21754646
title: Epidemiological characteristics and molecular features of carbapenem-resistant <i>Enterobacter</i> strains in China: a multicenter genomic study

description: Epidemiological characteristics and molecular features of carbapenem-resistant <i>Enterobacter</i> (CR-<i>Ent</i>) species remain unclear in China. In this study, we performed a genomic study on 92 isolates from <i>Enterobacter</i>-caused infections from a multicenter study in China. Whole genome sequencing (WGS) was used to determine the genome sequence of 92 non-duplicated CR-<i>Ent</i> strains collected from multiple tertiary health centres. The precise species of <i>Enterobacter</i> strains were identified by average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH). Molecular features of high-risk CR-<i>Ent</i> sequence type (ST) lineages and carbapenemase-encoding plasmids were determined. The result revealed that the most common human-source CR-<i>Ent</i> species in China was <i>E. xiangfangensis</i> (66/92, 71.93%), and the proportion of carbapenemase-producing <i>Enterobacter</i> (CP-<i>Ent</i>) in CR-<i>Ent</i> was high (72/92, 78.26%) in comparison to other global regions. Furthermore, ST171 and ST116 <i>E. xiangfangensis</i> were the major lineages of CP-<i>Ent</i> strains, and ST171 <i>E. xiangfangensis</i> was more likely to cause infections in older patients. Genomic analysis also highlighted the likelihood of intra-hospital/inter-hospital clonal transmission of ST171 and ST116 <i>E. xiangfangensis</i>. In addition, the <i>bla</i><sub>NDM</sub>-harbouring IncX3-type plasmid was identified as the prevalent carbapenemase-encoding plasmid carried by CR-<i>Ent</i> strains, and was experimentally confirmed to be able to self-transfer with high frequency. This study detailed the genomic and clinical characteristics of CR-<i>Ent</i> in China in the form of multicenter for the first time. The high risk of carbapenemase-producing ST171 and ST116 <i>E. xiangfangensis</i>, and the <i>bla</i><sub>NDM</sub>-harbouring IncX3-type plasmid were detected and emphasized.
DOI: 10.6084/m9.figshare.21754646.v1
title: Epidemiological characteristics and molecular features of carbapenem-resistant <i>Enterobacter</i> strains in China: a multicenter genomic study

description: Epidemiological characteristics and molecular features of carbapenem-resistant <i>Enterobacter</i> (CR-<i>Ent</i>) species remain unclear in China. In this study, we performed a genomic study on 92 isolates from <i>Enterobacter</i>-caused infections from a multicenter study in China. Whole genome sequencing (WGS) was used to determine the genome sequence of 92 non-duplicated CR-<i>Ent</i> strains collected from multiple tertiary health centres. The precise species of <i>Enterobacter</i> strains were identified by average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH). Molecular features of high-risk CR-<i>Ent</i> sequence type (ST) lineages and carbapenemase-encoding plasmids were determined. The result revealed that the most common human-source CR-<i>Ent</i> species in China was <i>E. xiangfangensis</i> (66/92, 71.93%), and the proportion of carbapenemase-producing <i>Enterobacter</i> (CP-<i>Ent</i>) in CR-<i>Ent</i> was high (72/92, 78.26%) in comparison to other global regions. Furthermore, ST171 and ST116 <i>E. xiangfangensis</i> were the major lineages of CP-<i>Ent</i> strains, and ST171 <i>E. xiangfangensis</i> was more likely to cause infections in older patients. Genomic analysis also highlighted the likelihood of intra-hospital/inter-hospital clonal transmission of ST171 and ST116 <i>E. xiangfangensis</i>. In addition, the <i>bla</i><sub>NDM</sub>-harbouring IncX3-type plasmid was identified as the prevalent carbapenemase-encoding plasmid carried by CR-<i>Ent</i> strains, and was experimentally confirmed to be able to self-transfer with high frequency. This study detailed the genomic and clinical characteristics of CR-<i>Ent</i> in China in the form of multicenter for the first time. The high risk of carbapenemase-producing ST171 and ST116 <i>E. xiangfangensis</i>, and the <i>bla</i><sub>NDM</sub>-harbouring IncX3-type plasmid were detected and emphasized.
DOI: 10.6084/m9.figshare.22730058
title: Probable airborne transmission of <i>Burkholderia pseudomallei</i> causing an urban outbreak of melioidosis during typhoon season in Hong Kong, China

description: Between January 2015 and October 2022, 38 patients with culture-confirmed melioidosis were identified in the Kowloon West (KW) Region, Hong Kong. Notably, 30 of them were clustered in the Sham Shui Po (SSP) district, which covers an estimated area of 2.5 km<sup>2</sup>. Between August and October 2022, 18 patients were identified in this district after heavy rainfall and typhoons. The sudden upsurge in cases prompted an environmental investigation, which involved collecting 20 air samples and 72 soil samples from residential areas near the patients. A viable isolate of <i>Burkholderia pseudomallei</i> was obtained from an air sample collected at a building site five days after a typhoon. <i>B. pseudomallei</i> DNA was also detected in 21 soil samples collected from the building site and adjacent gardening areas using full-length 16S rRNA gene sequencing, suggesting that <i>B. psuedomallei</i> is widely distributed in the soil environment surrounding the district. Core genome-multilocus sequence typing showed that the air sample isolate was phylogenetically clustered with the outbreak isolates in KW Region. Multispectral satellite imagery revealed a continuous reduction in vegetation region in SSP district by 162,255 m<sup>2</sup> from 2016 to 2022, supporting the hypothesis of inhalation of aerosols from the contaminated soil as the transmission route of melioidosis during extreme weather events. This is because the bacteria in unvegetated soil are more easily spread by winds. In consistent with inhalational melioidosis, 24 (63.2%) patients had pneumonia. Clinicians should be aware of melioidosis during typhoon season and initiate appropriate investigation and treatment for patients with compatible symptoms.
DOI: 10.6084/m9.figshare.22730058.v1
title: Probable airborne transmission of <i>Burkholderia pseudomallei</i> causing an urban outbreak of melioidosis during typhoon season in Hong Kong, China

description: Between January 2015 and October 2022, 38 patients with culture-confirmed melioidosis were identified in the Kowloon West (KW) Region, Hong Kong. Notably, 30 of them were clustered in the Sham Shui Po (SSP) district, which covers an estimated area of 2.5 km<sup>2</sup>. Between August and October 2022, 18 patients were identified in this district after heavy rainfall and typhoons. The sudden upsurge in cases prompted an environmental investigation, which involved collecting 20 air samples and 72 soil samples from residential areas near the patients. A viable isolate of <i>Burkholderia pseudomallei</i> was obtained from an air sample collected at a building site five days after a typhoon. <i>B. pseudomallei</i> DNA was also detected in 21 soil samples collected from the building site and adjacent gardening areas using full-length 16S rRNA gene sequencing, suggesting that <i>B. psuedomallei</i> is widely distributed in the soil environment surrounding the district. Core genome-multilocus sequence typing showed that the air sample isolate was phylogenetically clustered with the outbreak isolates in KW Region. Multispectral satellite imagery revealed a continuous reduction in vegetation region in SSP district by 162,255 m<sup>2</sup> from 2016 to 2022, supporting the hypothesis of inhalation of aerosols from the contaminated soil as the transmission route of melioidosis during extreme weather events. This is because the bacteria in unvegetated soil are more easily spread by winds. In consistent with inhalational melioidosis, 24 (63.2%) patients had pneumonia. Clinicians should be aware of melioidosis during typhoon season and initiate appropriate investigation and treatment for patients with compatible symptoms.
DOI: 10.6084/m9.figshare.22323729.v2
title: Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade

description: SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.
DOI: 10.6084/m9.figshare.30837294
title: Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles

description: Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.
DOI: 10.6084/m9.figshare.30837294.v1
title: Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles

description: Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.
DOI: 10.5061/dryad.m51q0
title: Data from: Hypoglycemia Following intravenous insulin plus glucose for hyperkalemia in patients with impaired renal function

description: Background: Hypoglycemia is a serious complication following the
 administration of insulin for hyperkalemia. We determined the incidence of
 hypoglycemia and severe hypoglycemia (blood glucose &lt;70 or ≤40
 mg/dl, respectively) in a cohort of AKI and non-dialysis dependent CKD
 patients who received an intravenous infusion of insulin plus glucose to
 treat hyperkalemia. Methods: We retrospectively reviewed charts of all AKI
 and non-dialysis dependent CKD patients who received 10 U of insulin plus
 50 g glucose to treat hyperkalemia from December 1, 2013 to May 31, 2015
 at our Department. Results: One hundred sixty four episodes of
 hyperkalemia were treated with insulin plus glucose and were eligible for
 analysis. Serum potassium levels dropped by 1.18 ± 1.01 mmol/l. Eleven
 treatments (6.1%) resulted in hypoglycemia and two (1.2%) in severe
 hypoglycemia. A lower pretreatment blood glucose tended to associate with
 a higher subsequent risk of hypoglycemia. Age, sex, renal function, an
 established diagnosis of diabetes or previous treatment were not
 associated with the development of this complication. We did not register
 any significant adverse events. Conclusion: Our intravenous regimen
 combining an infusion of insulin plus glucose effectively reduced serum
 potassium levels compared to previous studies and associated a low risk of
 symptomatic hypoglycemia and other complications.
description: S1
DOI: 10.6084/m9.figshare.21629544
title: Epidemiology, evolution, and biological characteristics of H6 avian influenza viruses in China

description: H6 avian influenza virus (AIV) is one of the most prevalent AIV subtypes in birds globally. To investigate the current situation and characteristics of H6 AIVs circulating in China, we analysed the epidemiology, genetic evolution and pathogenic features of this subtype. During 2000-2021, H6 subtype AIVs spread widely through Southern China and presented high host diversity. On analysing 171 H6 viruses isolated during 2009-2021, dynamic reassortments were observed among H6 and other co-circulating AIV subtypes, and these generated a total of 16 different genotypes. A few H6N6 strains possessed L226 and S228 mutations of hemagglutinin (H3 numbering), which may enhance the affinity of H6 viruses to human receptors. H6N6 viruses also exhibited divergent pathogenicity and growth profiles <i>in vivo</i> and <i>in vitro</i>. Some of the H6N6 viruses could infect mice without mammalian adaptation, and even caused death in this species. Therefore, our study demonstrated that the H6 AIVs posed a potential threat to human health and highlighted the urgent need for continued surveillance and evaluation of the H6 influenza viruses circulating in the field.
DOI: 10.6084/m9.figshare.21629544.v2
title: Epidemiology, evolution, and biological characteristics of H6 avian influenza viruses in China

description: H6 avian influenza virus (AIV) is one of the most prevalent AIV subtypes in birds globally. To investigate the current situation and characteristics of H6 AIVs circulating in China, we analysed the epidemiology, genetic evolution and pathogenic features of this subtype. During 2000-2021, H6 subtype AIVs spread widely through Southern China and presented high host diversity. On analysing 171 H6 viruses isolated during 2009-2021, dynamic reassortments were observed among H6 and other co-circulating AIV subtypes, and these generated a total of 16 different genotypes. A few H6N6 strains possessed L226 and S228 mutations of hemagglutinin (H3 numbering), which may enhance the affinity of H6 viruses to human receptors. H6N6 viruses also exhibited divergent pathogenicity and growth profiles <i>in vivo</i> and <i>in vitro</i>. Some of the H6N6 viruses could infect mice without mammalian adaptation, and even caused death in this species. Therefore, our study demonstrated that the H6 AIVs posed a potential threat to human health and highlighted the urgent need for continued surveillance and evaluation of the H6 influenza viruses circulating in the field.
DOI: 10.6084/m9.figshare.22323729
title: Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade

description: SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.
DOI: 10.6084/m9.figshare.21778970
title: A comparative analysis exposes an amplification delay distinctive to SARS-CoV-2 Omicron variants of clinical and public health relevance

description: Mutations in the SARS-CoV-2 genome may negatively impact a diagnostic test, have no effect, or turn into an opportunity for rapid molecular screening of variants. Using an in-house Emergency Use Authorized RT-qPCR-based COVID-19 diagnostic assay, we combined sequence surveillance of viral variants and computed PCR efficiencies for mismatched templates. We found no significant mismatches for the <i>N</i>, <i>E</i>, and <i>S</i> set of assay primers until the Omicron variant emerged in late November 2021. We found a single mismatch between the Omicron sequence and one of our assay’s primers caused a &gt; 4 cycle delay during amplification without impacting overall assay performance. Starting in December 2021, clinical specimens received for COVID-19 diagnostic testing that generated a Cq delay greater than 4 cycles were sequenced and confirmed as Omicron. Clinical samples without a Cq delay were largely confirmed as the Delta variant. The primer-template mismatch was then used as a rapid surrogate marker for Omicron. Primers that correctly identified Omicron were designed and tested, which prepared us for the emergence of future variants with novel mismatches to our diagnostic assay's primers. Our experience demonstrates the importance of monitoring sequences, the need for predicting the impact of mismatches, their value as a surrogate marker, and the relevance of adapting one's molecular diagnostic test for evolving pathogens.
DOI: 10.6084/m9.figshare.21778970.v1
title: A comparative analysis exposes an amplification delay distinctive to SARS-CoV-2 Omicron variants of clinical and public health relevance

description: Mutations in the SARS-CoV-2 genome may negatively impact a diagnostic test, have no effect, or turn into an opportunity for rapid molecular screening of variants. Using an in-house Emergency Use Authorized RT-qPCR-based COVID-19 diagnostic assay, we combined sequence surveillance of viral variants and computed PCR efficiencies for mismatched templates. We found no significant mismatches for the <i>N</i>, <i>E</i>, and <i>S</i> set of assay primers until the Omicron variant emerged in late November 2021. We found a single mismatch between the Omicron sequence and one of our assay’s primers caused a &gt; 4 cycle delay during amplification without impacting overall assay performance. Starting in December 2021, clinical specimens received for COVID-19 diagnostic testing that generated a Cq delay greater than 4 cycles were sequenced and confirmed as Omicron. Clinical samples without a Cq delay were largely confirmed as the Delta variant. The primer-template mismatch was then used as a rapid surrogate marker for Omicron. Primers that correctly identified Omicron were designed and tested, which prepared us for the emergence of future variants with novel mismatches to our diagnostic assay's primers. Our experience demonstrates the importance of monitoring sequences, the need for predicting the impact of mismatches, their value as a surrogate marker, and the relevance of adapting one's molecular diagnostic test for evolving pathogens.