cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.9378752.v2
title: Carriage and potential long distance transmission of <i>Listeria monocytogenes</i> by migratory black-headed gulls in Dianchi Lake, Kunming

description: <i>Listeria monocytogenes</i> is a high risk pathogen which can cause invasive diseases in humans. We previously reported that black-headed gulls from Dianchi Lake of Kunming carrying <i>L. monocytogenes</i>, while the characteristics of these isolates and the relationship with habitats of migratory gulls have not been explored. In this study, we investigated the prevalence and molecular characteristics of <i>Listeria monocytogenes</i> from black-headed gulls in Dianchi Lake, and phylogenetic analysis based on core genome SNPs was used to determine the genetic relationship of the strains from Dianchi Lake and other regions. Occurrence of <i>L. monocytogenes</i> in black-headed gull feces in 2016, 2017 and 2018 was 1.0%, 1.0% and 0.6% respectively. The predominant serotype of 28 isolates was 4b, while the predominant sequence types were ST145 and ST201. Based on their prevalence and genomic relationships, ST5 and ST87 were likely to be sourced locally while ST145 and ST201 were likely to be non-local. <i>L. monocytogenes</i> may travel along the bird migration route leading to transmission over a large geographical span carried by black-headed gull. Although the prevalence of <i>L. monocytogenes</i> was low, its carriage by the migratory black-headed gulls poses potential public health risks in regions where the migratory birds passage and reside.
DOI: 10.6084/m9.figshare.10620929.v2
title: Dual activity of PNGM-1 pinpoints the evolutionary origin of subclass B3 metallo-<i>β</i>-lactamases: a molecular and evolutionary study

description: Resistance to <i>β</i>-lactams is one of the most serious problems associated with Gram-negative infections. <i>β</i>-Lactamases are able to hydrolyze <i>β</i>-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-<i>β</i>-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.
DOI: 10.6084/m9.figshare.9783305
title: H3N2 avian influenza viruses detected in live poultry markets in China bind to human-type receptors and transmit in guinea pigs and ferrets

description: The H3N2 influenza viruses became widespread in humans during the 1968 H3N2 pandemic and have been a major cause of influenza epidemics ever since. Different lineages of H3N2 influenza viruses are also commonly found in animals. If a different lineage of H3N2 virus jumps to humans, a human influenza pandemic could occur with devastating consequences. Here, we studied the genetics, receptor-binding properties, and replication and transmission in mammals of 15 H3N2 avian influenza viruses detected in live poultry markets in China. We found that the H3N2 avian influenza viruses are complicated reassortants with distinct replication phenotypes in mice. Five viruses replicated efficiently in mice and bound to both human-type and avian-type receptors. These viruses transmitted efficiently to direct-contact guinea pigs, and three of them also transmitted among guinea pigs and ferrets via respiratory droplets. Moreover, ferret antiserum induced by human H3N2 viruses did not react with any of the H3N2 avian influenza viruses. Our study demonstrates that the H3N2 avian influenza viruses pose a clear threat to human health and emphasizes the need for continued surveillance and evaluation of the H3N2 influenza viruses circulating in nature.
DOI: 10.6084/m9.figshare.7937198
title: Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion

description: Rapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing <i>Mycobacterium tuberculosis</i>, the pathological signiﬁcance of microRNAs, as biomarkers of tuberculosis, in autophagosome maturation is unclear. Here, these microRNAs were investigated by Solexa sequencing and qPCR validation, and a potential diagnostic model was established by logistic regression. Besides that, the mechanism of one of the microRNAs involved in the occurrence of tuberculosis was studied. The results showed that the expression of miR-423-5p, miR-17-5p, and miR-20b-5p were signiﬁcantly increased in the serum of patients with tuberculosis. The combination of these three microRNAs established a model to diagnose tuberculosis with an accuracy of 78.18%, and an area under the curve value of 0.908. Bioinformatics analysis unveiled miR-423-5p as the most likely candidate in regulating autophagosome maturation. The up-regulation of miR-423-5p could inhibit autophagosome maturation through suppressing autophagosome–lysosome fusion in macrophages. Further investigations showed that <i>VPS33A</i> was the direct target of miR-423-5p, and the two CUGCCCCUC domains in <i>VPS33A</i> 3’-UTR were the direct regulatory sites for miR-423-5p. In addition, an inverse correlation between <i>VPS33A</i> and miR-423-5p was found in peripheral blood mononuclear cells of patients with tuberculosis. Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, our ﬁndings suggests that miR-423-5p could suppress autophagosome–lysosome fusion by post-transcriptional regulation of <i>VPS33A</i>, which might be important for the occurrence of active tuberculosis.
DOI: 10.6084/m9.figshare.7937198.v1
title: Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion

description: Rapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing <i>Mycobacterium tuberculosis</i>, the pathological signiﬁcance of microRNAs, as biomarkers of tuberculosis, in autophagosome maturation is unclear. Here, these microRNAs were investigated by Solexa sequencing and qPCR validation, and a potential diagnostic model was established by logistic regression. Besides that, the mechanism of one of the microRNAs involved in the occurrence of tuberculosis was studied. The results showed that the expression of miR-423-5p, miR-17-5p, and miR-20b-5p were signiﬁcantly increased in the serum of patients with tuberculosis. The combination of these three microRNAs established a model to diagnose tuberculosis with an accuracy of 78.18%, and an area under the curve value of 0.908. Bioinformatics analysis unveiled miR-423-5p as the most likely candidate in regulating autophagosome maturation. The up-regulation of miR-423-5p could inhibit autophagosome maturation through suppressing autophagosome–lysosome fusion in macrophages. Further investigations showed that <i>VPS33A</i> was the direct target of miR-423-5p, and the two CUGCCCCUC domains in <i>VPS33A</i> 3’-UTR were the direct regulatory sites for miR-423-5p. In addition, an inverse correlation between <i>VPS33A</i> and miR-423-5p was found in peripheral blood mononuclear cells of patients with tuberculosis. Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, our ﬁndings suggests that miR-423-5p could suppress autophagosome–lysosome fusion by post-transcriptional regulation of <i>VPS33A</i>, which might be important for the occurrence of active tuberculosis.
DOI: 10.6084/m9.figshare.9783305.v1
title: H3N2 avian influenza viruses detected in live poultry markets in China bind to human-type receptors and transmit in guinea pigs and ferrets

description: The H3N2 influenza viruses became widespread in humans during the 1968 H3N2 pandemic and have been a major cause of influenza epidemics ever since. Different lineages of H3N2 influenza viruses are also commonly found in animals. If a different lineage of H3N2 virus jumps to humans, a human influenza pandemic could occur with devastating consequences. Here, we studied the genetics, receptor-binding properties, and replication and transmission in mammals of 15 H3N2 avian influenza viruses detected in live poultry markets in China. We found that the H3N2 avian influenza viruses are complicated reassortants with distinct replication phenotypes in mice. Five viruses replicated efficiently in mice and bound to both human-type and avian-type receptors. These viruses transmitted efficiently to direct-contact guinea pigs, and three of them also transmitted among guinea pigs and ferrets via respiratory droplets. Moreover, ferret antiserum induced by human H3N2 viruses did not react with any of the H3N2 avian influenza viruses. Our study demonstrates that the H3N2 avian influenza viruses pose a clear threat to human health and emphasizes the need for continued surveillance and evaluation of the H3N2 influenza viruses circulating in nature.
DOI: 10.6084/m9.figshare.9783305.v2
title: H3N2 avian influenza viruses detected in live poultry markets in China bind to human-type receptors and transmit in guinea pigs and ferrets

description: The H3N2 influenza viruses became widespread in humans during the 1968 H3N2 pandemic and have been a major cause of influenza epidemics ever since. Different lineages of H3N2 influenza viruses are also commonly found in animals. If a different lineage of H3N2 virus jumps to humans, a human influenza pandemic could occur with devastating consequences. Here, we studied the genetics, receptor-binding properties, and replication and transmission in mammals of 15 H3N2 avian influenza viruses detected in live poultry markets in China. We found that the H3N2 avian influenza viruses are complicated reassortants with distinct replication phenotypes in mice. Five viruses replicated efficiently in mice and bound to both human-type and avian-type receptors. These viruses transmitted efficiently to direct-contact guinea pigs, and three of them also transmitted among guinea pigs and ferrets via respiratory droplets. Moreover, ferret antiserum induced by human H3N2 viruses did not react with any of the H3N2 avian influenza viruses. Our study demonstrates that the H3N2 avian influenza viruses pose a clear threat to human health and emphasizes the need for continued surveillance and evaluation of the H3N2 influenza viruses circulating in nature.
DOI: 10.6084/m9.figshare.7937303
title: Hepatitis B virus mutation pattern rtL180M+A181C+M204V may contribute to entecavir resistance in clinical practice

description: <b>Background and Aims:</b> Entecavir (ETV) resistance of hepatitis B virus (HBV) conventionally requires rt184, 202, or 250 mutations plus lamivudine-resistance mutation (rtM204V/I ± L180M). This study aimed to clarify whether rtL180M+A181C+M204V mutations may contribute to HBV ETV resistance. <b>Methods:</b> Serum samples were collected from 22,009 patients who underwent resistance testing in Beijing 302 Hospital from 2007 to 2016. HBV reverse transcriptase (RT) gene was screened by direct sequencing and verified by clonal sequencing. Phenotypic analysis was performed for evaluating replication capacity and drug susceptibility. <b>Results:</b> Classical ETV-resistance mutations of HBV were detected in 1252 patients who were receiving ETV therapy. The rtA181C mutation was detected with rtL180M+M204V mutations in 18 lamivudine-experienced ETV-treated patients, and the emergence of the mutations was associated with virological breakthrough or inadequate virological response to ETV. Patient-derived representative rtA181C-containing mutants, rtL180M+A181C+M204V, rtL180M+A181C+M204V+M250V, and rtL180M+A181C+S202G+M204V, exhibited 45.7%, 25.9%, and 25.0% replication capacity and 85.6-, 356.1-, and 307.1-fold decreased susceptibility to ETV respectively compared to the wild-type strain, while the three mutants remained sensitive to tenofovir (TDF). Artificial elimination of rtA181C largely restored the rtL180M+A181C+M204V mutant’s sensitivity to ETV. Molecular modelling of viral RT binding to ETV showed that the rtL180M+A181C+M204V mutant had a less stable conformation compared to rtL180M+M204V mutant. In clinical practice, undetectable serum HBV DNA was achieved in two of five longitudinally followed rtA181C-positive patients who received switching-to TDF therapy, but not in the other three who received add-on adefovir therapy during observation. <b>Conclusions:</b> Both clinical and experimental data support rtL180M+A181C+M204V as a novel non-classical ETV-resistance mutation pattern.
DOI: 10.6084/m9.figshare.7937303.v2
title: Hepatitis B virus mutation pattern rtL180M+A181C+M204V may contribute to entecavir resistance in clinical practice

description: <b>Background and Aims:</b> Entecavir (ETV) resistance of hepatitis B virus (HBV) conventionally requires rt184, 202, or 250 mutations plus lamivudine-resistance mutation (rtM204V/I ± L180M). This study aimed to clarify whether rtL180M+A181C+M204V mutations may contribute to HBV ETV resistance. <b>Methods:</b> Serum samples were collected from 22,009 patients who underwent resistance testing in Beijing 302 Hospital from 2007 to 2016. HBV reverse transcriptase (RT) gene was screened by direct sequencing and verified by clonal sequencing. Phenotypic analysis was performed for evaluating replication capacity and drug susceptibility. <b>Results:</b> Classical ETV-resistance mutations of HBV were detected in 1252 patients who were receiving ETV therapy. The rtA181C mutation was detected with rtL180M+M204V mutations in 18 lamivudine-experienced ETV-treated patients, and the emergence of the mutations was associated with virological breakthrough or inadequate virological response to ETV. Patient-derived representative rtA181C-containing mutants, rtL180M+A181C+M204V, rtL180M+A181C+M204V+M250V, and rtL180M+A181C+S202G+M204V, exhibited 45.7%, 25.9%, and 25.0% replication capacity and 85.6-, 356.1-, and 307.1-fold decreased susceptibility to ETV respectively compared to the wild-type strain, while the three mutants remained sensitive to tenofovir (TDF). Artificial elimination of rtA181C largely restored the rtL180M+A181C+M204V mutant’s sensitivity to ETV. Molecular modelling of viral RT binding to ETV showed that the rtL180M+A181C+M204V mutant had a less stable conformation compared to rtL180M+M204V mutant. In clinical practice, undetectable serum HBV DNA was achieved in two of five longitudinally followed rtA181C-positive patients who received switching-to TDF therapy, but not in the other three who received add-on adefovir therapy during observation. <b>Conclusions:</b> Both clinical and experimental data support rtL180M+A181C+M204V as a novel non-classical ETV-resistance mutation pattern.
DOI: 10.6084/m9.figshare.7937303.v3
title: Hepatitis B virus mutation pattern rtL180M+A181C+M204V may contribute to entecavir resistance in clinical practice

description: <b>Background and Aims:</b> Entecavir (ETV) resistance of hepatitis B virus (HBV) conventionally requires rt184, 202, or 250 mutations plus lamivudine-resistance mutation (rtM204V/I ± L180M). This study aimed to clarify whether rtL180M+A181C+M204V mutations may contribute to HBV ETV resistance. <b>Methods:</b> Serum samples were collected from 22,009 patients who underwent resistance testing in Beijing 302 Hospital from 2007 to 2016. HBV reverse transcriptase (RT) gene was screened by direct sequencing and verified by clonal sequencing. Phenotypic analysis was performed for evaluating replication capacity and drug susceptibility. <b>Results:</b> Classical ETV-resistance mutations of HBV were detected in 1252 patients who were receiving ETV therapy. The rtA181C mutation was detected with rtL180M+M204V mutations in 18 lamivudine-experienced ETV-treated patients, and the emergence of the mutations was associated with virological breakthrough or inadequate virological response to ETV. Patient-derived representative rtA181C-containing mutants, rtL180M+A181C+M204V, rtL180M+A181C+M204V+M250V, and rtL180M+A181C+S202G+M204V, exhibited 45.7%, 25.9%, and 25.0% replication capacity and 85.6-, 356.1-, and 307.1-fold decreased susceptibility to ETV respectively compared to the wild-type strain, while the three mutants remained sensitive to tenofovir (TDF). Artificial elimination of rtA181C largely restored the rtL180M+A181C+M204V mutant’s sensitivity to ETV. Molecular modelling of viral RT binding to ETV showed that the rtL180M+A181C+M204V mutant had a less stable conformation compared to rtL180M+M204V mutant. In clinical practice, undetectable serum HBV DNA was achieved in two of five longitudinally followed rtA181C-positive patients who received switching-to TDF therapy, but not in the other three who received add-on adefovir therapy during observation. <b>Conclusions:</b> Both clinical and experimental data support rtL180M+A181C+M204V as a novel non-classical ETV-resistance mutation pattern.
DOI: 10.6084/m9.figshare.7937507
title: Diversity of phenotypically non-dermatophyte, non-<i>Aspergillus</i> filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing

description: Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-<i>Aspergillus</i> fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of &gt;1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.
DOI: 10.6084/m9.figshare.7937507.v2
title: Diversity of phenotypically non-dermatophyte, non-<i>Aspergillus</i> filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing

description: Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-<i>Aspergillus</i> fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of &gt;1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.
DOI: 10.6084/m9.figshare.7937507.v1
title: Diversity of phenotypically non-dermatophyte, non-<i>Aspergillus</i> filamentous fungi causing nail infections: importance of accurate identification and antifungal susceptibility testing

description: Onychomycosis is most commonly caused by dermatophytes. In this study, we examined the spectrum of phenotypically non-dermatophyte and non-<i>Aspergillus</i> fungal isolates recovered over a 10-year period from nails of patients with onychomycosis in Hong Kong. A total of 24 non-duplicated isolates recovered from 24 patients were included. The median age of the patients was 51 years, and two-thirds of them were males. One-third and two-thirds had finger and toe nail infections respectively. Among these 24 nail isolates, 17 were confidently identified as 13 different known fungal species, using a polyphasic approach. These 13 species belonged to 11 genera and ≥9 families. For the remaining seven isolates, multilocus sequencing did not reveal their definite species identities. These seven potentially novel species belonged to four different known and three potentially novel genera of seven families. 33.3%, 41.7% and 95.8% of the 24 fungal isolates possessed minimum inhibitory concentrations of &gt;1 µg/mL to terbinafine, itraconazole and fluconazole, respectively, the first line treatment of onychomycosis. A high diversity of moulds was associated with onychomycosis. A significant proportion of the isolates were potentially novel fungal species. To guide proper treatment, molecular identification and antifungal susceptibility testing should be performed for these uncommonly isolated fungal species.