cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29590572
title: Anti-HBc IgM associates with acute flare and HBeAg/HBsAg loss in chronic hepatitis B patients with acute exacerbation

description: Acute exacerbation (AE) is common for patients with chronic hepatitis B (CHB). The aim of the study is to investigate the values of hepatitis B core antibody (anti-HBc) IgM in CHB-AE. Patients were screened from a prospective sub-cohort, 419 CHB patients with AE were enrolled and divided into groups according to antiviral treatment history, treatment naïve, withdrawal above or within 6 months, and on-treatment. The prevalence, clinical characteristics of anti-HBc IgM, and its relationship with the outcomes of CHB were assessed. A total of 157 patients (37.5%) were tested positive for anti-HBc IgM, of which patients with antiviral-withdrawal more than 6 months had the highest prevalence (49.3%). Anti-HBc IgM was significantly associated with HBV DNA and ALT, regarding to its prevalence and serum level. Furthermore, serum anti-HBc IgM values varied in different phases of CHB, of which immune active and HBeAg-negative chronic hepatitis phases were significantly higher than that in inactive carriers (<i>p</i> = 0.017 and <i>p</i> = 0.0097, respectively). Anti-HBc IgM could distinguish hepatitis from inactive infection phases in HBeAg-negative patients (AUC 0.841). Anti-HBc IgM levels were significantly higher in subgroup who developed ACLF (<i>p</i> &lt; 0.05), but had no relationship with short-term mortality. Finally, anti-HBc IgM seropositivity was the only predictor of HBeAg seroclearance (OR 3.18, 95% CI 1.30–7.73) and all patients who achieved HBsAg seroclearance within 1-year had a markedly elevated anti-HBc IgM level. In conclusion, our study shows anti-HBc IgM is highly prevalent in CHB patients with AE and would be a new predictor of HBeAg and HBsAg loss in this population.
DOI: 10.6084/m9.figshare.29590572.v1
title: Anti-HBc IgM associates with acute flare and HBeAg/HBsAg loss in chronic hepatitis B patients with acute exacerbation

description: Acute exacerbation (AE) is common for patients with chronic hepatitis B (CHB). The aim of the study is to investigate the values of hepatitis B core antibody (anti-HBc) IgM in CHB-AE. Patients were screened from a prospective sub-cohort, 419 CHB patients with AE were enrolled and divided into groups according to antiviral treatment history, treatment naïve, withdrawal above or within 6 months, and on-treatment. The prevalence, clinical characteristics of anti-HBc IgM, and its relationship with the outcomes of CHB were assessed. A total of 157 patients (37.5%) were tested positive for anti-HBc IgM, of which patients with antiviral-withdrawal more than 6 months had the highest prevalence (49.3%). Anti-HBc IgM was significantly associated with HBV DNA and ALT, regarding to its prevalence and serum level. Furthermore, serum anti-HBc IgM values varied in different phases of CHB, of which immune active and HBeAg-negative chronic hepatitis phases were significantly higher than that in inactive carriers (<i>p</i> = 0.017 and <i>p</i> = 0.0097, respectively). Anti-HBc IgM could distinguish hepatitis from inactive infection phases in HBeAg-negative patients (AUC 0.841). Anti-HBc IgM levels were significantly higher in subgroup who developed ACLF (<i>p</i> &lt; 0.05), but had no relationship with short-term mortality. Finally, anti-HBc IgM seropositivity was the only predictor of HBeAg seroclearance (OR 3.18, 95% CI 1.30–7.73) and all patients who achieved HBsAg seroclearance within 1-year had a markedly elevated anti-HBc IgM level. In conclusion, our study shows anti-HBc IgM is highly prevalent in CHB patients with AE and would be a new predictor of HBeAg and HBsAg loss in this population.
DOI: 10.6084/m9.figshare.29627420
title: Circulated echovirus 18 strains in Guangdong Province and worldwide: A novel perspective on genetic diversity and recombination patterns

description: Echovirus 18 (E18) has re-emerged as a global public health concern in recent years because of its association with severe neonatal systemic diseases that pose a risk of high mortality. The lack of effective intervention strategies for E18 infections is largely attributed to limited knowledge regarding molecular epidemiology and recombination patterns. In this study, we obtained seven full-length E18 sequences from infants in Guangdong Province and combined them with representative sequences from GenBank. Using this expanded dataset, we analysed the molecular epidemiological features, genetic characteristics, and recombination patterns of E18. Global statistics reveal a distinct double-peak pattern in the frequency of E18 infections throughout the year in the Northern Hemisphere. All strains isolated from clinical specimens were classified as genotype C2, which has emerged as the predominant circulating strain in Guangdong Province and globally. Several potential recombination events with E30 were identified among these seven strains, particularly in the P2 and P3 non-structural regions. This study offers new insights into the global dissemination, genetic diversity, and phylodynamics of E18, potentially providing valuable information for designing antiviral vaccines and the implementation of sustainable surveillance strategies to enhance virus prevention and control during public health crises.
DOI: 10.6084/m9.figshare.29627420.v1
title: Circulated echovirus 18 strains in Guangdong Province and worldwide: A novel perspective on genetic diversity and recombination patterns

description: Echovirus 18 (E18) has re-emerged as a global public health concern in recent years because of its association with severe neonatal systemic diseases that pose a risk of high mortality. The lack of effective intervention strategies for E18 infections is largely attributed to limited knowledge regarding molecular epidemiology and recombination patterns. In this study, we obtained seven full-length E18 sequences from infants in Guangdong Province and combined them with representative sequences from GenBank. Using this expanded dataset, we analysed the molecular epidemiological features, genetic characteristics, and recombination patterns of E18. Global statistics reveal a distinct double-peak pattern in the frequency of E18 infections throughout the year in the Northern Hemisphere. All strains isolated from clinical specimens were classified as genotype C2, which has emerged as the predominant circulating strain in Guangdong Province and globally. Several potential recombination events with E30 were identified among these seven strains, particularly in the P2 and P3 non-structural regions. This study offers new insights into the global dissemination, genetic diversity, and phylodynamics of E18, potentially providing valuable information for designing antiviral vaccines and the implementation of sustainable surveillance strategies to enhance virus prevention and control during public health crises.
DOI: 10.6084/m9.figshare.29377870
title: A dual fluorescence channel RAA-based CRISPR-Cas12a/Cas13a system for highly sensitive detection of <i>Gyrovirus galga1</i> and <i>Gyrovirus homsa1</i>

description: <i>Gyrovirus galga1</i> (GyG1) and <i>Gyrovirus homsa1</i> (GyH1) are the second and third most common gyroviruses identified, respectively, after chicken anaemia virus. They were first reported in 2011 and are currently prevalent worldwide. However, limited research on these pathogens and a lack of prevention and control strategies have necessitated the establishment of a rapid diagnostic technique to address new challenges in infectious diseases. Recombinase acid amplification (RAA) combined with CRISPR – Cas12a or CRISPR – Cas13a technology has major advantages for highly sensitive and rapid diagnosis. Specific targets can activate CRISPR–Cas trans-cleavage activity, resulting in non-specific cleavage of single-stranded DNA by the CRISPR – Cas12a complex and RNA cleavage by the CRISPR – Cas13a complex. In this study, for the first time, we combined RAA-based CRISPR – Cas12a and CRISPR – Cas13a systems for simultaneous differential diagnosis of GyG1 and GyH1 infection. The results showed that dual fluorescence channel RAA-based CRISPR – Cas12a/Cas13a technology could detect GyG1 and GyH1 within one hour, with a minimum detection limit of 1.5 copies of the target DNA standard/µL and no cross-reactivity with other avian pathogens. In addition, this method could be used for clinical detection, with the results exhibiting high consistency with those obtained by qPCR. These findings demonstrate that our RAA-based CRISPR – Cas12a/Cas13a dual-channel detection system can detect two different subtypes of gyrovirus in a sample with good specificity and high sensitivity, improving the detection efficiency and providing a new technique for the study of viral infection dynamics.
DOI: 10.6084/m9.figshare.29377870.v1
title: A dual fluorescence channel RAA-based CRISPR-Cas12a/Cas13a system for highly sensitive detection of <i>Gyrovirus galga1</i> and <i>Gyrovirus homsa1</i>

description: <i>Gyrovirus galga1</i> (GyG1) and <i>Gyrovirus homsa1</i> (GyH1) are the second and third most common gyroviruses identified, respectively, after chicken anaemia virus. They were first reported in 2011 and are currently prevalent worldwide. However, limited research on these pathogens and a lack of prevention and control strategies have necessitated the establishment of a rapid diagnostic technique to address new challenges in infectious diseases. Recombinase acid amplification (RAA) combined with CRISPR – Cas12a or CRISPR – Cas13a technology has major advantages for highly sensitive and rapid diagnosis. Specific targets can activate CRISPR–Cas trans-cleavage activity, resulting in non-specific cleavage of single-stranded DNA by the CRISPR – Cas12a complex and RNA cleavage by the CRISPR – Cas13a complex. In this study, for the first time, we combined RAA-based CRISPR – Cas12a and CRISPR – Cas13a systems for simultaneous differential diagnosis of GyG1 and GyH1 infection. The results showed that dual fluorescence channel RAA-based CRISPR – Cas12a/Cas13a technology could detect GyG1 and GyH1 within one hour, with a minimum detection limit of 1.5 copies of the target DNA standard/µL and no cross-reactivity with other avian pathogens. In addition, this method could be used for clinical detection, with the results exhibiting high consistency with those obtained by qPCR. These findings demonstrate that our RAA-based CRISPR – Cas12a/Cas13a dual-channel detection system can detect two different subtypes of gyrovirus in a sample with good specificity and high sensitivity, improving the detection efficiency and providing a new technique for the study of viral infection dynamics.
DOI: 10.6084/m9.figshare.30460201
title: The GCN-2/eIF-2α/ATF-4 signaling pathway is involved in <i>C. elegans</i> defense against <i>Salmonella enterica</i> infection

description: In response to external or endogenous stress, eukaryotic cells can activate a common adaptive pathway called the integrated stress response (ISR). The ISR reduces global protein translation but upregulates the expression of stress response proteins to either restore cellular homeostasis or, in case of severe or prolonged stress, promote cell death. The bZIP transcription factor ATF4 plays a deciding role in cellular fate upon ISR activation, but the precise mechanisms underlying such decision-making remain unclear. Although bacterial infection has previously been observed to induce the ISR, the effects of this pathway on bacterial pathogenesis and host defense are not well understood. The functions of ATF4 in this process remain even more elusive. Using the <i>Caenorhabditis elegans</i> model to explore the bacterial infection-induced ISR, we found that infection with <i>Salmonella enterica</i> induced the GCN-2/eIF-2α/ATF-4 signaling pathway to modulate host defense against the infection. More specifically, ATF-4 suppressed the expression of ribosomal protein genes in response to <i>S. enterica</i> exposure, reducing worm survival against the pathogen. Because ribosomal proteins are directly involved in protein translation, our data revealed an important, novel mechanism by which ATF-4 mediates the reduction of global translation under stress by inhibiting the expression of ribosomal proteins. ATF-4 also regulates components of mitochondrial electron transport and collagen genes in response to <i>S. enterica</i> infection; both regulations are linked to stress resistance and longevity. Overall, we have identified specific molecular mechanisms through which ATF-4 determines cell fate upon ISR activation, revealing how this pathway influences host outcomes during bacterial infection. ATF-4 mediates the integrated stress response to pathogen infection through regulating genes encoding ribosomal proteins, collagens, and components of mitochondrial electron transport.
DOI: 10.6084/m9.figshare.30460201.v1
title: The GCN-2/eIF-2α/ATF-4 signaling pathway is involved in <i>C. elegans</i> defense against <i>Salmonella enterica</i> infection

description: In response to external or endogenous stress, eukaryotic cells can activate a common adaptive pathway called the integrated stress response (ISR). The ISR reduces global protein translation but upregulates the expression of stress response proteins to either restore cellular homeostasis or, in case of severe or prolonged stress, promote cell death. The bZIP transcription factor ATF4 plays a deciding role in cellular fate upon ISR activation, but the precise mechanisms underlying such decision-making remain unclear. Although bacterial infection has previously been observed to induce the ISR, the effects of this pathway on bacterial pathogenesis and host defense are not well understood. The functions of ATF4 in this process remain even more elusive. Using the <i>Caenorhabditis elegans</i> model to explore the bacterial infection-induced ISR, we found that infection with <i>Salmonella enterica</i> induced the GCN-2/eIF-2α/ATF-4 signaling pathway to modulate host defense against the infection. More specifically, ATF-4 suppressed the expression of ribosomal protein genes in response to <i>S. enterica</i> exposure, reducing worm survival against the pathogen. Because ribosomal proteins are directly involved in protein translation, our data revealed an important, novel mechanism by which ATF-4 mediates the reduction of global translation under stress by inhibiting the expression of ribosomal proteins. ATF-4 also regulates components of mitochondrial electron transport and collagen genes in response to <i>S. enterica</i> infection; both regulations are linked to stress resistance and longevity. Overall, we have identified specific molecular mechanisms through which ATF-4 determines cell fate upon ISR activation, revealing how this pathway influences host outcomes during bacterial infection. ATF-4 mediates the integrated stress response to pathogen infection through regulating genes encoding ribosomal proteins, collagens, and components of mitochondrial electron transport.
DOI: 10.6084/m9.figshare.29534075
title: Contribution of a LysM domain-containing protein regulated by VicRK to <i>Streptococcus sanguinis</i> virulence

description: <i>Streptococcus sanguinis</i> is a commensal member of the oral microbiome involved in opportunistic cardiovascular infections. In the present study, we investigated the contribution of <i>ssa_0094</i>, a gene strongly regulated by the two-component system VicRK, to functions associated with biofilm formation, immune evasion, and cardiovascular virulence. <i>In silico</i> analysis showed that <i>ssa_0094</i> encodes a protein with a LysM domain, which is highly conserved among <i>S. sanguinis</i>. Although not an ubiquitous gene, several commensal streptococcal species of the oronasopharynx and zoonotic strains of <i>Streptococcus suis</i> harbor <i>ssa_0094</i> homologues. A <i>ssa_0094</i> isogenic mutant (SK0094) showed defects in initiating biofilms on saliva-coated surfaces, reduced hydrophobicity, and lower production of amyloid-like components when compared to the parent strain (SK36) or to the complemented mutant (SK0094+), although it showed mild changes in DNA release and production of H<sub>2</sub>O<sub>2</sub>. Deletion of <i>ssa_0094</i> also impaired <i>S. sanguinis</i> binding to multiple human glycoproteins of plasma and/or extracellular matrix (ECM) (plasminogen, fibronectin, fibrinogen, fibrin, type I collagen, and elastin) and promoted clear increases in C3b deposition and in induction of NEtosis by neutrophils of peripheral blood. Moreover, SK0094 showed impaired invasiveness into HCAEC cells and reduced <i>ex vivo</i> persistence in human blood, but no clear change in virulence in a <i>Galleria mellonella</i> infection model. These findings indicate that <i>ssa_0094</i> is highly conserved within <i>S. sanguinis</i> strains and required for biofilm initiation as well as for multiple functions of immune evasion and cardiovascular virulence in <i>S. sanguinis</i> in a host-specific fashion.
DOI: 10.6084/m9.figshare.29534075.v2
title: Contribution of a LysM domain-containing protein regulated by VicRK to <i>Streptococcus sanguinis</i> virulence

description: <i>Streptococcus sanguinis</i> is a commensal member of the oral microbiome involved in opportunistic cardiovascular infections. In the present study, we investigated the contribution of <i>ssa_0094</i>, a gene strongly regulated by the two-component system VicRK, to functions associated with biofilm formation, immune evasion, and cardiovascular virulence. <i>In silico</i> analysis showed that <i>ssa_0094</i> encodes a protein with a LysM domain, which is highly conserved among <i>S. sanguinis</i>. Although not an ubiquitous gene, several commensal streptococcal species of the oronasopharynx and zoonotic strains of <i>Streptococcus suis</i> harbor <i>ssa_0094</i> homologues. A <i>ssa_0094</i> isogenic mutant (SK0094) showed defects in initiating biofilms on saliva-coated surfaces, reduced hydrophobicity, and lower production of amyloid-like components when compared to the parent strain (SK36) or to the complemented mutant (SK0094+), although it showed mild changes in DNA release and production of H<sub>2</sub>O<sub>2</sub>. Deletion of <i>ssa_0094</i> also impaired <i>S. sanguinis</i> binding to multiple human glycoproteins of plasma and/or extracellular matrix (ECM) (plasminogen, fibronectin, fibrinogen, fibrin, type I collagen, and elastin) and promoted clear increases in C3b deposition and in induction of NEtosis by neutrophils of peripheral blood. Moreover, SK0094 showed impaired invasiveness into HCAEC cells and reduced <i>ex vivo</i> persistence in human blood, but no clear change in virulence in a <i>Galleria mellonella</i> infection model. These findings indicate that <i>ssa_0094</i> is highly conserved within <i>S. sanguinis</i> strains and required for biofilm initiation as well as for multiple functions of immune evasion and cardiovascular virulence in <i>S. sanguinis</i> in a host-specific fashion.
DOI: 10.6084/m9.figshare.29582154
title: Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases <i>Helicobacter pylori</i> density in the murine stomach

description: <i>Helicobacter pylori</i> is the most common gastric pathogen. <i>H. pylori</i> is prone to develop antibiotic resistance and recurrence after therapy makes treatment problematic. <i>H. pylori</i> can be detected attached to the gastric epithelial cells; however, it is mostly found within the gastric mucus. <i>Helicobacter</i> species infections impair the mucus barrier by decreasing the binding ability of the mucins, decreasing the growth-limiting activity of mucins and decreasing mucin production. The current study aimed to restore mucin production in the male C57BL/6 mouse <i>H. pylori</i> (SS1) infection model and evaluate its effects on <i>H. pylori</i> density. Mice infected with SS1 were treated with (R)-α-methylhistamine (RαMH) or interleukin-4 (IL4). Treatment with RαMH or IL4 restored mucin production and decreased gastric <i>H. pylori</i> density compared to mock-treated infected mice. Treatment with RαMH and IL4 did not affect serum anti-<i>H. pylori</i> IgG levels, expression of antimicrobial peptides or <i>H. pylori</i> virulence factors. Further, RαMH did not have cytotoxic effects on <i>H. pylori</i>. However, the expression of cytokines (<i>Tnf</i> and <i>Il4)</i>, factors related to mucus production (<i>Tff1</i>, <i>Spedf, Stat6,</i> and <i>Ptgs1</i>), and mucin O-glycan sialylation levels differed between mice treated with RαMH and IL4. This suggests that increased mucus production can have similar effects on pathogen density in spite of differences in the local niche. In conclusion, agents that stimulate mucin production in the gastric mucosa have the potential to aid in the removal of pathogens from the gastric niche.
DOI: 10.6084/m9.figshare.29582154.v1
title: Treatment with (R)-α-methylhistamine or IL4 stimulates mucin production and decreases <i>Helicobacter pylori</i> density in the murine stomach

description: <i>Helicobacter pylori</i> is the most common gastric pathogen. <i>H. pylori</i> is prone to develop antibiotic resistance and recurrence after therapy makes treatment problematic. <i>H. pylori</i> can be detected attached to the gastric epithelial cells; however, it is mostly found within the gastric mucus. <i>Helicobacter</i> species infections impair the mucus barrier by decreasing the binding ability of the mucins, decreasing the growth-limiting activity of mucins and decreasing mucin production. The current study aimed to restore mucin production in the male C57BL/6 mouse <i>H. pylori</i> (SS1) infection model and evaluate its effects on <i>H. pylori</i> density. Mice infected with SS1 were treated with (R)-α-methylhistamine (RαMH) or interleukin-4 (IL4). Treatment with RαMH or IL4 restored mucin production and decreased gastric <i>H. pylori</i> density compared to mock-treated infected mice. Treatment with RαMH and IL4 did not affect serum anti-<i>H. pylori</i> IgG levels, expression of antimicrobial peptides or <i>H. pylori</i> virulence factors. Further, RαMH did not have cytotoxic effects on <i>H. pylori</i>. However, the expression of cytokines (<i>Tnf</i> and <i>Il4)</i>, factors related to mucus production (<i>Tff1</i>, <i>Spedf, Stat6,</i> and <i>Ptgs1</i>), and mucin O-glycan sialylation levels differed between mice treated with RαMH and IL4. This suggests that increased mucus production can have similar effects on pathogen density in spite of differences in the local niche. In conclusion, agents that stimulate mucin production in the gastric mucosa have the potential to aid in the removal of pathogens from the gastric niche.