cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.25040369.v1
title: RNA-Seq and miRNA-Seq data from Epstein-Barr virus-infected tree shrews reveal a ceRNA network contributing to immune microenvironment regulation

description: Epstein-Barr virus (EBV) infection in humans is ubiquitous and associated with various diseases. Remodeling of the immune microenvironment is the primary cause of EBV infection and pathogenesis; however, the underlying mechanism has not been fully elucidated. In this study, we used whole-transcriptome RNA-Seq to detect mRNAs, long non-coding RNAs (lncRNA), and microRNA (miRNA) profiles in the control group, 3 days, and 28 days after EBV infection, based on the tree shrew model that we reported previously. First, we estimated the proportion of 22 cell types in each sample using CIBERSORT software and identified 18 high-confidence DElncRNAs related to immune microenvironment regulation after EBV infection. Functional enrichment analysis of these differentially expressed lncRNAs primarily focused on the autophagy, endocytosis, and ferroptosis signalling pathways. Moreover, EBV infection affects miRNA expression patterns, and many miRNAs are silenced. Finally, three competing endogenous RNA regulatory networks were built using lncRNAs that significantly correlated with immune cell types, miRNAs that responded to EBV infection, and potentially targeted the mRNA of the miRNAs. Among them, MRPL42-AS-5 might act as an hsa-miR-296-5p “sponge” and compete with target mRNAs, thus increasing mRNA expression level, which could induce immune cell infiltration through the cellular senescence signalling pathway against EBV infection. Overall, we conducted a complete transcriptomic analysis of EBV infection in vivo for the first time and provided a novel perspective for further investigation of EBV-host interactions.
DOI: 10.6084/m9.figshare.27258240
title: A <i>Colletotrichum fructicola</i> dual specificity phosphatase CfMsg5 is regulated by the CfAp1 transcription factor during oxidative stress and promotes virulence on <i>Camellia oleifera</i>

description: Anthracnose, caused by <i>Colletotrichum</i> species, induces significant economic damages to crop plants annually, especially for <i>Camellia oleifera</i>. During infection, the counter-defence mechanisms of plant pathogens against ROS-mediated resistance, however, remain poorly understood. By employing Weighted Gene Co-expression Network Analysis (WGCNA), we identified ACTIVATOR PROTEIN-1 (AP-1), a bZIP transcription factor, as significant to infection. And deletion of <i>CfAP1</i> inhibited aerial hyphae formation and growth under oxidative stress. Furthermore, RNA-seq analysis post H<sub>2</sub>O<sub>2</sub> treatment revealed 33 significantly down-regulated genes in the AP-1 deficient strain, including A12032, a dual specificity phosphatase (DSP) homologous to MSG5 from <i>Saccharomyces cerevisiae</i>. This Δ<i>Cfmsg5</i> strain showed enhanced oxidative tolerance, reduced ROS scavenging, and negative regulation of the CWI MAPK cascade under oxygen stress, suggesting its involvement in oxidative signal transduction. Importantly, we provide evidence that CfMsg5 regulates growth, endoplasmic reticulum stress, and several unfolded protein response genes upregulated in Δ<i>Cfmsg5</i>. Collectively, this study identified core components during <i>C. fructicola</i> infection and highlights a potential regulatory module involving CfAp1 and CfMsg5 in response to host ROS bursts. It provides new insights into fungal infection mechanisms and potential targets like <i>CfAP1</i> and <i>CfMSG5</i> for managing anthracnose diseases.
DOI: 10.6084/m9.figshare.27258240.v1
title: A <i>Colletotrichum fructicola</i> dual specificity phosphatase CfMsg5 is regulated by the CfAp1 transcription factor during oxidative stress and promotes virulence on <i>Camellia oleifera</i>

description: Anthracnose, caused by <i>Colletotrichum</i> species, induces significant economic damages to crop plants annually, especially for <i>Camellia oleifera</i>. During infection, the counter-defence mechanisms of plant pathogens against ROS-mediated resistance, however, remain poorly understood. By employing Weighted Gene Co-expression Network Analysis (WGCNA), we identified ACTIVATOR PROTEIN-1 (AP-1), a bZIP transcription factor, as significant to infection. And deletion of <i>CfAP1</i> inhibited aerial hyphae formation and growth under oxidative stress. Furthermore, RNA-seq analysis post H<sub>2</sub>O<sub>2</sub> treatment revealed 33 significantly down-regulated genes in the AP-1 deficient strain, including A12032, a dual specificity phosphatase (DSP) homologous to MSG5 from <i>Saccharomyces cerevisiae</i>. This Δ<i>Cfmsg5</i> strain showed enhanced oxidative tolerance, reduced ROS scavenging, and negative regulation of the CWI MAPK cascade under oxygen stress, suggesting its involvement in oxidative signal transduction. Importantly, we provide evidence that CfMsg5 regulates growth, endoplasmic reticulum stress, and several unfolded protein response genes upregulated in Δ<i>Cfmsg5</i>. Collectively, this study identified core components during <i>C. fructicola</i> infection and highlights a potential regulatory module involving CfAp1 and CfMsg5 in response to host ROS bursts. It provides new insights into fungal infection mechanisms and potential targets like <i>CfAP1</i> and <i>CfMSG5</i> for managing anthracnose diseases.
DOI: 10.6084/m9.figshare.24566672
title: Enhanced infectivity of bovine viral diarrhoea virus (BVDV) in arginase-producing bovine monocyte-derived macrophages

description: Macrophages are important cells of the innate immunity that play a major role in Bovine Viral Diarrhoea Virus (BVDV) pathogenesis. Macrophages are not a homogenous population; they exist in different phenotypes, typically divided into two main categories: classically (pro-inflammatory) and alternatively activated (anti-inflammatory) or M1 and M2, respectively. The role of bovine macrophage phenotypes on BVDV infection is still unclear. This study characterized the interaction between BVDV and monocyte-derived macrophages (Mo-Mφ) collected from healthy cattle and polarized to an M1 or M2 state by using LPS, INF-γ, IL-4, or azithromycin. Arginase activity quantitation was utilized as a marker of the M2 Mo-Mφ spectrum. There was a significant association between arginase activity and the replication rate of BVDV strains of different genotypes and biotypes. Inhibition of arginase activity also reduced BVDV infectivity. Calves treated with azithromycin-induced Mo-Mφ of the M2 state produced high levels of arginase. Interestingly, azithromycin administered <i>in vivo</i> increased the susceptibility of macrophages to BVDV infection <i>ex vivo</i>. Mo-Mφ from pregnant dams and calves produced higher arginase levels than those from non-pregnant adult animals. The increased infection of arginase-producing alternatively activated bovine macrophages with BVDV supports the need to delve into a possible leading role of M2 macrophages in establishing the immune-suppressive state during BVDV convalescence.
DOI: 10.6084/m9.figshare.24566672.v1
title: Enhanced infectivity of bovine viral diarrhoea virus (BVDV) in arginase-producing bovine monocyte-derived macrophages

description: Macrophages are important cells of the innate immunity that play a major role in Bovine Viral Diarrhoea Virus (BVDV) pathogenesis. Macrophages are not a homogenous population; they exist in different phenotypes, typically divided into two main categories: classically (pro-inflammatory) and alternatively activated (anti-inflammatory) or M1 and M2, respectively. The role of bovine macrophage phenotypes on BVDV infection is still unclear. This study characterized the interaction between BVDV and monocyte-derived macrophages (Mo-Mφ) collected from healthy cattle and polarized to an M1 or M2 state by using LPS, INF-γ, IL-4, or azithromycin. Arginase activity quantitation was utilized as a marker of the M2 Mo-Mφ spectrum. There was a significant association between arginase activity and the replication rate of BVDV strains of different genotypes and biotypes. Inhibition of arginase activity also reduced BVDV infectivity. Calves treated with azithromycin-induced Mo-Mφ of the M2 state produced high levels of arginase. Interestingly, azithromycin administered <i>in vivo</i> increased the susceptibility of macrophages to BVDV infection <i>ex vivo</i>. Mo-Mφ from pregnant dams and calves produced higher arginase levels than those from non-pregnant adult animals. The increased infection of arginase-producing alternatively activated bovine macrophages with BVDV supports the need to delve into a possible leading role of M2 macrophages in establishing the immune-suppressive state during BVDV convalescence.
DOI: 10.6084/m9.figshare.27098247
title: Ctr9 promotes virulence of <i>Candida albicans</i> by regulating methionine metabolism

description: <i>Candida albicans</i>, a part of normal flora, is an opportunistic fungal pathogen and causes severe health issues in immunocompromised patients. Its pathogenicity is intricately linked to the transcriptional regulation of its metabolic pathways. Paf1 complex (Paf1C) is a crucial transcriptional regulator that is highly conserved in eukaryotes. The objective of this study was to explore the role of Paf1C in the metabolic pathways and how it influences the pathogenicity of <i>C. albicans</i>. Paf1C knockout mutant strains of <i>C. albicans</i> (<i>ctr9</i>Δ/Δ, <i>leo1</i>Δ/Δ, and <i>cdc73</i>Δ/Δ) were generated using the CRISPR-Cas9 system. To investigate the effect of Paf1C on pathogenicity, macrophage interaction assays and mouse survival tests were conducted. The growth patterns of the Paf1C knockout mutants were analyzed through spotting assays and growth curve measurements. Transcriptome analysis was conducted under yeast conditions (30°C without serum) and hyphal conditions (37°C with 10% FBS), to further elucidate the role of Paf1C in the pathogenicity of <i>C. albicans</i>. <i>CTR9</i> deletion resulted in the attenuation of <i>C. albicans</i> virulence, in macrophage and mouse models. Furthermore, we confirmed that the reduced virulence of the <i>ctr9</i>Δ/Δ mutant can be attributed to a decrease in <i>C. albicans</i> cell abundance. Moreover, transcriptome analysis revealed that metabolic processes required for cell proliferation are impaired in <i>ctr9</i>Δ/Δ mutant. Notably, <i>CTR9</i> deletion led to the downregulation of methionine biosynthetic genes and the cAMP-PKA signaling pathway-related hypha essential genes, which are pivotal for virulence. Our results suggest that Ctr9-regulated methionine metabolism is a crucial factor for determining <i>C. albicans</i> pathogenicity.
DOI: 10.6084/m9.figshare.27098247.v1
title: Ctr9 promotes virulence of <i>Candida albicans</i> by regulating methionine metabolism

description: <i>Candida albicans</i>, a part of normal flora, is an opportunistic fungal pathogen and causes severe health issues in immunocompromised patients. Its pathogenicity is intricately linked to the transcriptional regulation of its metabolic pathways. Paf1 complex (Paf1C) is a crucial transcriptional regulator that is highly conserved in eukaryotes. The objective of this study was to explore the role of Paf1C in the metabolic pathways and how it influences the pathogenicity of <i>C. albicans</i>. Paf1C knockout mutant strains of <i>C. albicans</i> (<i>ctr9</i>Δ/Δ, <i>leo1</i>Δ/Δ, and <i>cdc73</i>Δ/Δ) were generated using the CRISPR-Cas9 system. To investigate the effect of Paf1C on pathogenicity, macrophage interaction assays and mouse survival tests were conducted. The growth patterns of the Paf1C knockout mutants were analyzed through spotting assays and growth curve measurements. Transcriptome analysis was conducted under yeast conditions (30°C without serum) and hyphal conditions (37°C with 10% FBS), to further elucidate the role of Paf1C in the pathogenicity of <i>C. albicans</i>. <i>CTR9</i> deletion resulted in the attenuation of <i>C. albicans</i> virulence, in macrophage and mouse models. Furthermore, we confirmed that the reduced virulence of the <i>ctr9</i>Δ/Δ mutant can be attributed to a decrease in <i>C. albicans</i> cell abundance. Moreover, transcriptome analysis revealed that metabolic processes required for cell proliferation are impaired in <i>ctr9</i>Δ/Δ mutant. Notably, <i>CTR9</i> deletion led to the downregulation of methionine biosynthetic genes and the cAMP-PKA signaling pathway-related hypha essential genes, which are pivotal for virulence. Our results suggest that Ctr9-regulated methionine metabolism is a crucial factor for determining <i>C. albicans</i> pathogenicity.
DOI: 10.6084/m9.figshare.25477711
title: Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

description: Micro RNAs (miRNAs) have been implicated in the regulation of maturation, proliferation, differentiation, and activation of immune cells. In this study, we demonstrated that miR-29a antagonizes IFN-γ production at early times post-LSDV infection in cattle. miR-29a was predicted to target upstream IFN-γ regulators, and its inhibition resulted in enhanced IFN-γ production in sensitized peripheral blood mononuclear cells (PBMCs). Further, stimulation of PBMCs with LSDV antigen exhibited lower levels of miR-29a, concomitant with a potent cell-mediated immune response (CMI), characterized by an increase in LSDV-specific CD8+ T cell counts and enhanced levels of IFN-γ, which eventually facilitated virus clearance. In addition, a few immunocompromised cattle (developed secondary LSDV infection at ~ 6 months) that failed to mount a potent cell-mediated immune response, were shown to maintain higher miR-29a levels. Furthermore, as compared to the sensitized crossbred cattle, PBMCs from sensitized Rathi (a native Indian breed) animals exhibited lower levels of miR-29a along with an increase in CD8+ T cell counts and enhanced levels of IFN-γ. Finally, we analysed that a ≥ 60% decrease in miR-29a expression levels in the PBMCs of sensitized cattle correlated with a potent CMI response. In conclusion, miR-29a expression is involved in antagonizing the IFN-γ response in LSDV-infected cattle and may serve as a novel biomarker for the acute phase of LSDV infection, as well as predicting the functionality of T cells in sensitized cattle. In addition, Rathi cattle mount a more potent CMI response against LSDV than crossbred cattle.
DOI: 10.6084/m9.figshare.25477711.v1
title: Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

description: Micro RNAs (miRNAs) have been implicated in the regulation of maturation, proliferation, differentiation, and activation of immune cells. In this study, we demonstrated that miR-29a antagonizes IFN-γ production at early times post-LSDV infection in cattle. miR-29a was predicted to target upstream IFN-γ regulators, and its inhibition resulted in enhanced IFN-γ production in sensitized peripheral blood mononuclear cells (PBMCs). Further, stimulation of PBMCs with LSDV antigen exhibited lower levels of miR-29a, concomitant with a potent cell-mediated immune response (CMI), characterized by an increase in LSDV-specific CD8+ T cell counts and enhanced levels of IFN-γ, which eventually facilitated virus clearance. In addition, a few immunocompromised cattle (developed secondary LSDV infection at ~ 6 months) that failed to mount a potent cell-mediated immune response, were shown to maintain higher miR-29a levels. Furthermore, as compared to the sensitized crossbred cattle, PBMCs from sensitized Rathi (a native Indian breed) animals exhibited lower levels of miR-29a along with an increase in CD8+ T cell counts and enhanced levels of IFN-γ. Finally, we analysed that a ≥ 60% decrease in miR-29a expression levels in the PBMCs of sensitized cattle correlated with a potent CMI response. In conclusion, miR-29a expression is involved in antagonizing the IFN-γ response in LSDV-infected cattle and may serve as a novel biomarker for the acute phase of LSDV infection, as well as predicting the functionality of T cells in sensitized cattle. In addition, Rathi cattle mount a more potent CMI response against LSDV than crossbred cattle.
DOI: 10.6084/m9.figshare.25514161
title: Emergence and circulation of enterovirus B species in infants in southern China: A multicenter retrospective analysis

description: Enteroviruses (EV) are common and can cause severe diseases, particularly in young children. However, the information of EV infection in infants in China is limited due to the vast population size and extensive geographical area of the country. Here, we conducted a retrospective multicenter analysis of available EV data to assess the current epidemiological situation in the infant population in southern China. The study enrolled infants with suspected EV infection from 34 hospitals across 12 cities in southern China between 2019 to 2022, and the confirmation of EV was done using RT-PCR and VP1 gene sequencing. Out of 1221 infants enrolled, 330 (27.03%) were confirmed as EV-infected. Of these, 260 (78.79%) were newborns aged 0–28 days. The EV belonged to three species: EV-B (80.61%), EV-A (11.82%), and human rhinovirus (7.58%). Newborns were more susceptible to EV-B than older infants (<i>p</i> &lt; 0.001). Within EV-B, we identified 15 types, with coxsackievirus (CV) B3 (20.91%), echovirus (E) 11 (19.70%), and E18 (16.97%) being the most common. The predominant EV types changed across different years. EV infection in infants followed a seasonal pattern, with a higher incidence from May to August. Furthermore, perinatal mother-to-child EV transmission in 12 mother-newborn pairs were observed. Our study is the first to demonstrate the emergence and widespread circulation of EV-B species, mainly CVB3, E11, and E18, in southern China, primarily affecting young infants. This research provides valuable insights for future epidemic assessment, prediction, as well as the elimination of mother-to-child transmission.
DOI: 10.6084/m9.figshare.25514161.v1
title: Emergence and circulation of enterovirus B species in infants in southern China: A multicenter retrospective analysis

description: Enteroviruses (EV) are common and can cause severe diseases, particularly in young children. However, the information of EV infection in infants in China is limited due to the vast population size and extensive geographical area of the country. Here, we conducted a retrospective multicenter analysis of available EV data to assess the current epidemiological situation in the infant population in southern China. The study enrolled infants with suspected EV infection from 34 hospitals across 12 cities in southern China between 2019 to 2022, and the confirmation of EV was done using RT-PCR and VP1 gene sequencing. Out of 1221 infants enrolled, 330 (27.03%) were confirmed as EV-infected. Of these, 260 (78.79%) were newborns aged 0–28 days. The EV belonged to three species: EV-B (80.61%), EV-A (11.82%), and human rhinovirus (7.58%). Newborns were more susceptible to EV-B than older infants (<i>p</i> &lt; 0.001). Within EV-B, we identified 15 types, with coxsackievirus (CV) B3 (20.91%), echovirus (E) 11 (19.70%), and E18 (16.97%) being the most common. The predominant EV types changed across different years. EV infection in infants followed a seasonal pattern, with a higher incidence from May to August. Furthermore, perinatal mother-to-child EV transmission in 12 mother-newborn pairs were observed. Our study is the first to demonstrate the emergence and widespread circulation of EV-B species, mainly CVB3, E11, and E18, in southern China, primarily affecting young infants. This research provides valuable insights for future epidemic assessment, prediction, as well as the elimination of mother-to-child transmission.
DOI: 10.6084/m9.figshare.30011118.v1
title: Continuity of care for patients with chronic lymphocytic leukemia: an analysis of real-world data

description: Aims This study hypothesized that greater continuity of care (CoC) would be associated with lower all-cause healthcare resource utilization and improved overall survival (OS) among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) among patients who received covalent Bruton tyrosine kinase inhibitor (cBTKi)-based therapy. Methods Optum’s de-identified Clinformatics® Data Mart Database was used for this retrospective study. Patient-level CoC measured by continuity of hematologist/oncologist provider care was evaluated using published measures; the Herfindahl-Hirschman Index (HHI) was the primary measure (range 0 = no continuity to 1.0 = complete continuity). Outcomes included all-cause emergency room (ER) visits, inpatient hospitalizations, and OS. Multivariable regression models (logistic, negative binomial, and Cox proportional hazards), adjusted for baseline covariates, were conducted to evaluate the relationship of CoC with outcomes. Results In total, 5,990 patients were included in the analysis; median follow-up was 31.8 months. Median HHI was 0.7210 (interquartile range = 0.4749, 1.0000). With higher CoC, there were lower odds of having an ER visit (HHI odds ratio [OR] = 0.89; 95% confidence interval [CI]: 0.87-0.91; p &lt; 0.0001), lower number of ER visits (HHI rate ratio [RR] = 0.93; 95%CI 0.92-0.94; p &lt; 0.0001), lower odds of inpatient hospitalization (HHI OR = 0.85; 95%CI: 0.84-0.87; p &lt; 0.0001), and lower number of hospitalizations (HHI RR = 0.89; 95%CI: 0.88-0.90; p &lt; 0.0001) . There was no significant difference in the hazard of death (HHI hazard ratio = 0.99 (95%CI: 0.97-1.01) p = 0.18. Limitations Causality cannot be inferred in this retrospective study. Conclusions Greater CoC was significantly associated with reduced ER visits and reduced hospitalization, among patients diagnosed with CLL who received cBTKi therapy. While interpretation may be limited in the retrospective design, sensitivity and post-hoc analyses support this relationship. The findings from this study suggest the importance of maintaining a consistent oncologist/hematologist for the patient with CLL to reduce these healthcare events; however, causality cannot be inferred from this study. This retrospective real-world database study investigated the continuity of oncology provider care among patients with CLL, to understand the relationship between continuity of care (CoC) and healthcare resource utilization and patient outcomes. This study found that higher CoC was associated with lower healthcare resource utilization, but inconsistent findings were observed with overall survival. While a causal relationship cannot be determined, these findings suggest the importance of maintaining consistent oncologist/hematologist care for the patient with CLL.