cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27098389
title: Association of hepatitis B core antibody level and hepatitis B surface antigen clearance in HBeAg-negative patients with chronic hepatitis B

description: Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, <i>n</i> = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, <i>n</i> = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, <i>p</i> = 0.208) and seroconversion (21.1% vs. 10.6%, <i>p</i> = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, <i>p</i> &lt; 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, <i>p</i> &lt; 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.
DOI: 10.6084/m9.figshare.27098389.v1
title: Association of hepatitis B core antibody level and hepatitis B surface antigen clearance in HBeAg-negative patients with chronic hepatitis B

description: Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, <i>n</i> = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, <i>n</i> = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, <i>p</i> = 0.208) and seroconversion (21.1% vs. 10.6%, <i>p</i> = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, <i>p</i> &lt; 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, <i>p</i> &lt; 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.
DOI: 10.6084/m9.figshare.25792923
title: Norepinephrine may promote the progression of <i>Fusobacterium nucleatum</i> related colorectal cancer via quorum sensing signalling

description: <i>Fusobacterium nucleatum (F. nucleatum)</i> is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of <i>F. nucleatum</i> in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of <i>F. nucleatum</i> related CRC (<i>p</i> &lt; 0.01). <i>In vitro</i> studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of <i>F. nucleatum</i>. Moreover, chronic stress significantly increased the colon tumour burden of Apc<sup>Min/+</sup> mice infected with <i>F. nucleatum</i> (<i>p</i> &lt; 0.01), which was decreased by a catecholamine inhibitor (<i>p</i> &lt; 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of <i>F. nucleatum</i> related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.
DOI: 10.6084/m9.figshare.25792923.v1
title: Norepinephrine may promote the progression of <i>Fusobacterium nucleatum</i> related colorectal cancer via quorum sensing signalling

description: <i>Fusobacterium nucleatum (F. nucleatum)</i> is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of <i>F. nucleatum</i> in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of <i>F. nucleatum</i> related CRC (<i>p</i> &lt; 0.01). <i>In vitro</i> studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of <i>F. nucleatum</i>. Moreover, chronic stress significantly increased the colon tumour burden of Apc<sup>Min/+</sup> mice infected with <i>F. nucleatum</i> (<i>p</i> &lt; 0.01), which was decreased by a catecholamine inhibitor (<i>p</i> &lt; 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of <i>F. nucleatum</i> related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.
DOI: 10.6084/m9.figshare.26143815
title: Unraveling host-pathogen dynamics in a murine model of septic peritonitis induced by vancomycin-resistant <i>Enterococcus faecium</i>

description: Vancomycin-resistant <i>Enterococcus faecium</i> (<i>E. faecium</i>) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing <i>E. faecium</i>, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and <i>E. faecium</i> in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II<sup>+</sup> recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that <i>E. faecium</i> triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.
DOI: 10.6084/m9.figshare.26143815.v2
title: Unraveling host-pathogen dynamics in a murine model of septic peritonitis induced by vancomycin-resistant <i>Enterococcus faecium</i>

description: Vancomycin-resistant <i>Enterococcus faecium</i> (<i>E. faecium</i>) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing <i>E. faecium</i>, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and <i>E. faecium</i> in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II<sup>+</sup> recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that <i>E. faecium</i> triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.
DOI: 10.6084/m9.figshare.24756277
title: Pathogenicity and virulence of <i>Acinetobacter baumannii</i>: Factors contributing to the fitness in healthcare settings and the infected host

description: <i>Acinetobacter baumannii</i> is a common cause of healthcare-associated infections and hospital outbreaks, particularly in intensive care units. Much of the success of <i>A. baumannii</i> relies on its genomic plasticity, which allows rapid adaptation to adversity and stress. The capacity to acquire novel antibiotic resistance determinants and the tolerance to stresses encountered in the hospital environment promote <i>A. baumannii</i> spread among patients and long-term contamination of the healthcare setting. This review explores virulence factors and physiological traits contributing to <i>A. baumannii</i> infection and adaptation to the hospital environment. Several cell-associated and secreted virulence factors involved in <i>A. baumannii</i> biofilm formation, cell adhesion, invasion, and persistence in the host, as well as resistance to xeric stress imposed by the healthcare settings, are illustrated to give reasons for the success of <i>A. baumannii</i> as a hospital pathogen.
DOI: 10.6084/m9.figshare.24756277.v1
title: Pathogenicity and virulence of <i>Acinetobacter baumannii</i>: Factors contributing to the fitness in healthcare settings and the infected host

description: <i>Acinetobacter baumannii</i> is a common cause of healthcare-associated infections and hospital outbreaks, particularly in intensive care units. Much of the success of <i>A. baumannii</i> relies on its genomic plasticity, which allows rapid adaptation to adversity and stress. The capacity to acquire novel antibiotic resistance determinants and the tolerance to stresses encountered in the hospital environment promote <i>A. baumannii</i> spread among patients and long-term contamination of the healthcare setting. This review explores virulence factors and physiological traits contributing to <i>A. baumannii</i> infection and adaptation to the hospital environment. Several cell-associated and secreted virulence factors involved in <i>A. baumannii</i> biofilm formation, cell adhesion, invasion, and persistence in the host, as well as resistance to xeric stress imposed by the healthcare settings, are illustrated to give reasons for the success of <i>A. baumannii</i> as a hospital pathogen.
DOI: 10.6084/m9.figshare.26143815.v1
title: Unraveling host-pathogen dynamics in a murine Model of septic peritonitis induced by vancomycin-resistant <i>Enterococcus faecium</i>

description: Vancomycin-resistant <i>Enterococcus faecium</i> (<i>E. faecium</i>) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing <i>E. faecium</i>, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and <i>E. faecium</i> in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II<sup>+</sup> recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that <i>E. faecium</i> triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.
DOI: 10.6084/m9.figshare.25624538
title: Comprehensive evaluation of immune dysregulation in secondary hemophagocytic lymphohistiocytosis

description: Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets. Simultaneously, cytokine levels and routine laboratory indicators were also collected. In sHLH patients, lymphocyte subset absolute numbers were significantly impaired, accompanied by T cell hyperactivation, B cell hyperactivation, and increased plasmablast proliferation. Prognostic analysis revealed that lower CD8+ T cell percentages, elevated APTT, IL-6, IL-10 levels, and increased CD4+CD28null T cell proportions were associated with poor patient outcomes. The study demonstrates dysregulation in the counts and phenotypes of lymphocyte subsets in sHLH patients. Several key factors, including IL-6, IL-10, APTT, and various T cell percentages, have potential as prognostic markers and therapeutic targets in sHLH.
DOI: 10.6084/m9.figshare.25624538.v1
title: Comprehensive evaluation of immune dysregulation in secondary hemophagocytic lymphohistiocytosis

description: Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets. Simultaneously, cytokine levels and routine laboratory indicators were also collected. In sHLH patients, lymphocyte subset absolute numbers were significantly impaired, accompanied by T cell hyperactivation, B cell hyperactivation, and increased plasmablast proliferation. Prognostic analysis revealed that lower CD8+ T cell percentages, elevated APTT, IL-6, IL-10 levels, and increased CD4+CD28null T cell proportions were associated with poor patient outcomes. The study demonstrates dysregulation in the counts and phenotypes of lymphocyte subsets in sHLH patients. Several key factors, including IL-6, IL-10, APTT, and various T cell percentages, have potential as prognostic markers and therapeutic targets in sHLH.
DOI: 10.6084/m9.figshare.24580573
title: Protective efficacy of a novel recombinant influenza virus carrying partial human metapneumovirus F protein epitopes

description: Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infections in infants and children. Currently, no approved HMPV vaccine is available. We developed a novel recombinant influenza virus, which carried partial HMPV F protein (HMPV-F) epitopes, utilizing reverse genetics. The novel single-stranded RNA virus, termed rFLU-HMPV/F-NA, was synthesized in the neuraminidase (NA) fragment of influenza virus A/PuertoRico/8/34 (PR8). The morphological characteristics of rFLU-HMPV/F-NA were consistent with the wild-type flu virus. The virus could passage in specific pathogen-free (SPF) chicken embryos for at least five consecutive generations with haemagglutinin (HA) titres of 2<sup>8–</sup><sup>9</sup> or 8–9LogTCID<sub>50</sub>/mL. BALB/c mice were intranasally immunized at 21-day intervals with 10<sup>4</sup> TCID<sub>50</sub> (low-dose group) or 10<sup>6</sup> TCID<sub>50</sub> (high-dose group) rFLU-HMPV/F-NA, and PBS or PR8 vaccine was used for the control group. rFLU-HMPV/F-NA induced robust humoral, mucosal, and cellular immune responses in vivo in a dose-dependent manner. More importantly, wt clinical HMPV isolate challenge studies showed that rFLU-HMPV/F-NA provided significant immune protection against HMPV infection compared to the PBS or PR8 vaccine control group, as shown by improved histopathological changes and reduced viral titres in the lungs of immunized mice post-challenge. These findings demonstrate that rFLU-HMPV/F-NA has potential as a promising HMPV candidate vaccine and warrants further investigation into its control of HMPV infection.
DOI: 10.6084/m9.figshare.24580573.v1
title: Protective efficacy of a novel recombinant influenza virus carrying partial human metapneumovirus F protein epitopes

description: Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infections in infants and children. Currently, no approved HMPV vaccine is available. We developed a novel recombinant influenza virus, which carried partial HMPV F protein (HMPV-F) epitopes, utilizing reverse genetics. The novel single-stranded RNA virus, termed rFLU-HMPV/F-NA, was synthesized in the neuraminidase (NA) fragment of influenza virus A/PuertoRico/8/34 (PR8). The morphological characteristics of rFLU-HMPV/F-NA were consistent with the wild-type flu virus. The virus could passage in specific pathogen-free (SPF) chicken embryos for at least five consecutive generations with haemagglutinin (HA) titres of 2<sup>8–</sup><sup>9</sup> or 8–9LogTCID<sub>50</sub>/mL. BALB/c mice were intranasally immunized at 21-day intervals with 10<sup>4</sup> TCID<sub>50</sub> (low-dose group) or 10<sup>6</sup> TCID<sub>50</sub> (high-dose group) rFLU-HMPV/F-NA, and PBS or PR8 vaccine was used for the control group. rFLU-HMPV/F-NA induced robust humoral, mucosal, and cellular immune responses in vivo in a dose-dependent manner. More importantly, wt clinical HMPV isolate challenge studies showed that rFLU-HMPV/F-NA provided significant immune protection against HMPV infection compared to the PBS or PR8 vaccine control group, as shown by improved histopathological changes and reduced viral titres in the lungs of immunized mice post-challenge. These findings demonstrate that rFLU-HMPV/F-NA has potential as a promising HMPV candidate vaccine and warrants further investigation into its control of HMPV infection.
DOI: 10.6084/m9.figshare.27455206
title: Hidden liver-joint axis: HBV infection causes rheumatoid arthritis via TRAFD1 with imbalance of HBV X protein and trans-ferulic acid

description: Liver metabolites are involved in the progression of rheumatoid arthritis (RA), indicating a connection between the liver and joints. However, the impact and mechanism of Hepatitis B virus (HBV), a hepatotropic virus, on RA are still unclear. We investigated the correlation between HBV and RA using Mendelian randomization analysis. Single-cell transcriptome analysis was conducted to investigate changes in cell subtypes in synovial tissue of HBV-RA patients. Fibroblast-like synoviocytes (FLS) were used to create a cell model, and the transcriptome was examined to identify the key downstream molecules of FMT regulated by HBx. CIA model was constructed using HBV transgenic, HBx transgenic, and TRADF1 knockout mice to investigate the impact and mechanism of HBV on CIA. The results of our study revealed a significant positive correlation between HBV and RA. The functional studies identified a crucial role of fibroblast-myofibroblast transition (FMT) in the progression of RA. The results suggest that HBV-encoded HBx may promote FMT in RA by upregulating TRAFD1. Furthermore, trans-ferulic acid (TFA) was identified by screening for common metabolites in the liver, joints, and peripheral blood using the metabolome and WGCNA. Interestingly, we found that TFA ameliorated HBx-induced RA by suppressing TRAFD1 expression. Our study demonstrates that hidden liver-joint axis, an imbalance between TFA and HBx, plays a critical role in HBV-induced RA, which could be a potential strategy for preventing RA development.
DOI: 10.6084/m9.figshare.27455206.v1
title: Hidden liver-joint axis: HBV infection causes rheumatoid arthritis via TRAFD1 with imbalance of HBV X protein and trans-ferulic acid

description: Liver metabolites are involved in the progression of rheumatoid arthritis (RA), indicating a connection between the liver and joints. However, the impact and mechanism of Hepatitis B virus (HBV), a hepatotropic virus, on RA are still unclear. We investigated the correlation between HBV and RA using Mendelian randomization analysis. Single-cell transcriptome analysis was conducted to investigate changes in cell subtypes in synovial tissue of HBV-RA patients. Fibroblast-like synoviocytes (FLS) were used to create a cell model, and the transcriptome was examined to identify the key downstream molecules of FMT regulated by HBx. CIA model was constructed using HBV transgenic, HBx transgenic, and TRADF1 knockout mice to investigate the impact and mechanism of HBV on CIA. The results of our study revealed a significant positive correlation between HBV and RA. The functional studies identified a crucial role of fibroblast-myofibroblast transition (FMT) in the progression of RA. The results suggest that HBV-encoded HBx may promote FMT in RA by upregulating TRAFD1. Furthermore, trans-ferulic acid (TFA) was identified by screening for common metabolites in the liver, joints, and peripheral blood using the metabolome and WGCNA. Interestingly, we found that TFA ameliorated HBx-induced RA by suppressing TRAFD1 expression. Our study demonstrates that hidden liver-joint axis, an imbalance between TFA and HBx, plays a critical role in HBV-induced RA, which could be a potential strategy for preventing RA development.