Pub Date : 2025-01-13eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1446339
Xiao Li, Bo Wang, Xiaocong Li, Juan He, Yue Shi, Rui Wang, Dongwei Li, Ding Haitao
Introduction: This study aims to utilize proteomics, bioinformatics, and machine learning algorithms to identify diagnostic biomarkers in the serum of patients with acute and chronic brucellosis.
Methods: Proteomic analysis was conducted on serum samples from patients with acute and chronic brucellosis, as well as from healthy controls. Differential expression analysis was performed to identify proteins with altered expression, while Weighted Gene Co-expression Network Analysis (WGCNA) was applied to detect co-expression modules associated with clinical features of brucellosis. Machine learning algorithms were subsequently used to identify the optimal combination of diagnostic biomarkers. Finally, ELISA was employed to validate the identified proteins.
Results: A total of 1,494 differentially expressed proteins were identified, revealing two co-expression modules significantly associated with the clinical characteristics of brucellosis. The Gaussian Mixture Model (GMM) algorithm identified six proteins that were concurrently present in both the differentially expressed and co-expression modules, demonstrating promising diagnostic potential. After ELISA validation, five proteins were ultimately selected.
Discussion: These five proteins are implicated in the innate immune processes of brucellosis, potentially associated with its pathogenic mechanisms and chronicity. Furthermore, we highlighted their potential as diagnostic biomarkers for brucellosis. This study further enhances our understanding of brucellosis at the protein level, paving the way for future research endeavors.
{"title":"Analysis and validation of serum biomarkers in brucellosis patients through proteomics and bioinformatics.","authors":"Xiao Li, Bo Wang, Xiaocong Li, Juan He, Yue Shi, Rui Wang, Dongwei Li, Ding Haitao","doi":"10.3389/fcimb.2024.1446339","DOIUrl":"10.3389/fcimb.2024.1446339","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to utilize proteomics, bioinformatics, and machine learning algorithms to identify diagnostic biomarkers in the serum of patients with acute and chronic brucellosis.</p><p><strong>Methods: </strong>Proteomic analysis was conducted on serum samples from patients with acute and chronic brucellosis, as well as from healthy controls. Differential expression analysis was performed to identify proteins with altered expression, while Weighted Gene Co-expression Network Analysis (WGCNA) was applied to detect co-expression modules associated with clinical features of brucellosis. Machine learning algorithms were subsequently used to identify the optimal combination of diagnostic biomarkers. Finally, ELISA was employed to validate the identified proteins.</p><p><strong>Results: </strong>A total of 1,494 differentially expressed proteins were identified, revealing two co-expression modules significantly associated with the clinical characteristics of brucellosis. The Gaussian Mixture Model (GMM) algorithm identified six proteins that were concurrently present in both the differentially expressed and co-expression modules, demonstrating promising diagnostic potential. After ELISA validation, five proteins were ultimately selected.</p><p><strong>Discussion: </strong>These five proteins are implicated in the innate immune processes of brucellosis, potentially associated with its pathogenic mechanisms and chronicity. Furthermore, we highlighted their potential as diagnostic biomarkers for brucellosis. This study further enhances our understanding of brucellosis at the protein level, paving the way for future research endeavors.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1446339"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1515972
Lu Li, Darbhe Jayarama Bhat, Hong-Bo Jiang, Jun-Fu Li, Turki M Dawoud, Fangqi Sun, Sukanya Haituk, Ratchadawan Cheewangkoon, Rungtiwa Phookamsak
During investigations of freshwater fungi in Hunan and Yunnan provinces, China, Chaetopsina yunnanensis sp. nov. (Nectriaceae), Parafuscosporella hunanensis sp. nov. (Fuscosporellaceae), and Pleurotheciella yunnanensis sp. nov. (Pleurotheciaceae) were discovered on submerged decaying wood and branches. Based on phylogenetic analyses, C. yunnanensis formed a separate branch with Chaetopsina pinicola and nested among other Chaetopsina species in Nectriaceae (Hypocreales). Furthermore, hitherto known Chaetopsina beijingensis shared the same branch with Chaetopsina fulva, a type species of the genus, demonstrating their conspecific status. Therefore, C. beijingensis is formally synonymized under C. fulva, with an amended species circumscription. Pa. hunanensis formed a well-separated subclade with the ex-type strain of Parafuscosporella mucosa and clustered with other Parafuscosporella within Fuscosporellaceae (Fuscosporellales). In addition, the genus Parafuscosporella is treated as distinct from Vanakripa due to a lack of phylogenetic evidence in clarifying their congeneric status with the latter. Pl. yunnanensis is found to be sister to Pleurotheciella saprophytica, forming a subclade with Pleurotheciella dimorphospora within the Pleurotheciaceae (Pleurotheciales). Morphologically, C. yunnanensis fits well with the generic concept of Chaetopsina in forming a holomorphic state with hyphomycetous asexual morph producing pigmented, setiform conidiophores, phialidic conidiogenous cells, hyaline conidia, and nectria-like sexual morph. Pa. hunanensis fits well with Parafuscosporella in having acrogenous, apiosporous, versicolored, obovoid to obpyriform conidia. In contrast, Pl. yunnanensis resembles Pl. dimorphospora in forming asexual dimorphism with two types of conidia (Type I, brown, muriform/phragmosporous conidia; Type II, hyaline, amerosporous/didymorsporous conidia). The novelty of taxa is explained with detailed descriptions, photo-micrographic illustrations, polymorphism, and multigene phylogenetic analyses of Bayesian inference and maximum likelihood criteria.
{"title":"New insights into freshwater ascomycetes: discovery of novel species in diverse aquatic habitats.","authors":"Lu Li, Darbhe Jayarama Bhat, Hong-Bo Jiang, Jun-Fu Li, Turki M Dawoud, Fangqi Sun, Sukanya Haituk, Ratchadawan Cheewangkoon, Rungtiwa Phookamsak","doi":"10.3389/fcimb.2024.1515972","DOIUrl":"10.3389/fcimb.2024.1515972","url":null,"abstract":"<p><p>During investigations of freshwater fungi in Hunan and Yunnan provinces, China, <i>Chaetopsina yunnanensis</i> sp. nov. (Nectriaceae), <i>Parafuscosporella hunanensis</i> sp. nov. (Fuscosporellaceae), and <i>Pleurotheciella yunnanensis</i> sp. nov. (Pleurotheciaceae) were discovered on submerged decaying wood and branches. Based on phylogenetic analyses, <i>C. yunnanensis</i> formed a separate branch with <i>Chaetopsina pinicola</i> and nested among other <i>Chaetopsina</i> species in Nectriaceae (Hypocreales). Furthermore, hitherto known <i>Chaetopsina beijingensis</i> shared the same branch with <i>Chaetopsina fulva</i>, a type species of the genus, demonstrating their conspecific status. Therefore, <i>C. beijingensis</i> is formally synonymized under <i>C. fulva</i>, with an amended species circumscription. <i>Pa. hunanensis</i> formed a well-separated subclade with the ex-type strain of <i>Parafuscosporella mucosa</i> and clustered with other <i>Parafuscosporella</i> within Fuscosporellaceae (Fuscosporellales). In addition, the genus <i>Parafuscosporella</i> is treated as distinct from <i>Vanakripa</i> due to a lack of phylogenetic evidence in clarifying their congeneric status with the latter. <i>Pl. yunnanensis</i> is found to be sister to <i>Pleurotheciella saprophytica</i>, forming a subclade with <i>Pleurotheciella dimorphospora</i> within the Pleurotheciaceae (Pleurotheciales). Morphologically, <i>C. yunnanensis</i> fits well with the generic concept of <i>Chaetopsina</i> in forming a holomorphic state with hyphomycetous asexual morph producing pigmented, setiform conidiophores, phialidic conidiogenous cells, hyaline conidia, and nectria-like sexual morph. <i>Pa. hunanensis</i> fits well with <i>Parafuscosporella</i> in having acrogenous, apiosporous, versicolored, obovoid to obpyriform conidia. In contrast, <i>Pl. yunnanensis</i> resembles <i>Pl. dimorphospora</i> in forming asexual dimorphism with two types of conidia (Type I, brown, muriform/phragmosporous conidia; Type II, hyaline, amerosporous/didymorsporous conidia). The novelty of taxa is explained with detailed descriptions, photo-micrographic illustrations, polymorphism, and multigene phylogenetic analyses of Bayesian inference and maximum likelihood criteria.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1515972"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Antibiotic overuse is driving a global rise in antibiotic resistance, highlighting the need for robust antimicrobial stewardship (AMS) initiatives to improve prescription practices. While antimicrobials are essential for treating sepsis and preventing surgical site infections (SSIs), they can inadvertently disrupt the gut microbiota, leading to postoperative complications. Treatment methods vary widely across nations due to differences in drug choice, dosage, and therapy duration, affecting antibiotic resistance rates, which can reach up to 51% in some countries. In Romania and the Republic of Moldova, healthcare practices for surgical antibiotic prophylaxis differ significantly despite similarities in genetics, culture, and diet. Romania's stricter healthcare regulations result in more standardized antibiotic protocols, whereas Moldova's limited healthcare funding leads to less consistent practices and greater variability in treatment outcomes.
Methods: This study presents the results of a prospective cross-border investigation involving 86 colorectal cancer patients from major oncological hospitals in Romania and Moldova. We analyzed fecal samples collected from patients before and 7 days post-antibiotic treatment, focusing on the V3-V4 region of the 16S rRNA gene.
Results: Our findings indicate that inconsistent antibiotic prophylaxis policies-varying in type, dosage, or therapy duration-significantly impacted the gut microbiota and led to more frequent dysbiosis compared to stricter prophylactic antibiotic practices (single dose, single product, limited time).
Discussion: We emphasize the need for standardized antibiotic prophylaxis protocols to minimize dysbiosis and its associated risks, promoting more effective antimicrobial use, particularly in low- and middle-income countries (LMICs).
{"title":"Impact of antibiotic prophylaxis on gut microbiota in colorectal surgery: insights from an Eastern European stewardship study.","authors":"Irina Cezara Văcărean-Trandafir, Roxana-Maria Amărandi, Iuliu Cristian Ivanov, Loredana Mihaiela Dragoș, Mihaela Mențel, Ştefan Iacob, Ana-Maria Muşină, Elena-Roxana Bărgăoanu, Cristian Ene Roată, Ștefan Morărașu, Valeri Țuțuianu, Marcel Ciobanu, Mihail-Gabriel Dimofte","doi":"10.3389/fcimb.2024.1468645","DOIUrl":"10.3389/fcimb.2024.1468645","url":null,"abstract":"<p><strong>Introduction: </strong>Antibiotic overuse is driving a global rise in antibiotic resistance, highlighting the need for robust antimicrobial stewardship (AMS) initiatives to improve prescription practices. While antimicrobials are essential for treating sepsis and preventing surgical site infections (SSIs), they can inadvertently disrupt the gut microbiota, leading to postoperative complications. Treatment methods vary widely across nations due to differences in drug choice, dosage, and therapy duration, affecting antibiotic resistance rates, which can reach up to 51% in some countries. In Romania and the Republic of Moldova, healthcare practices for surgical antibiotic prophylaxis differ significantly despite similarities in genetics, culture, and diet. Romania's stricter healthcare regulations result in more standardized antibiotic protocols, whereas Moldova's limited healthcare funding leads to less consistent practices and greater variability in treatment outcomes.</p><p><strong>Methods: </strong>This study presents the results of a prospective cross-border investigation involving 86 colorectal cancer patients from major oncological hospitals in Romania and Moldova. We analyzed fecal samples collected from patients before and 7 days post-antibiotic treatment, focusing on the V3-V4 region of the 16S rRNA gene.</p><p><strong>Results: </strong>Our findings indicate that inconsistent antibiotic prophylaxis policies-varying in type, dosage, or therapy duration-significantly impacted the gut microbiota and led to more frequent dysbiosis compared to stricter prophylactic antibiotic practices (single dose, single product, limited time).</p><p><strong>Discussion: </strong>We emphasize the need for standardized antibiotic prophylaxis protocols to minimize dysbiosis and its associated risks, promoting more effective antimicrobial use, particularly in low- and middle-income countries (LMICs).</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1468645"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-13eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1529159
Zhiyuan Wang, Yang Chen, Yanyan Chen, Rui Chen, Weiwei Wang, Shichen Hu, Yihai Li, Hongjun Chen, Ping Wei, Xiumiao He
Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role. However, the underlying mechanisms that enable IBDV to block the IRF7 pathway remain unclear. In this study, we found that IRF7 and IFN-β expression were suppressed in DF-1 cells during infection with very virulent IBDV (vvIBDV), but not with attenuated IBDV, while the virus continued to replicate. Overexpression of IRF7 inhibits IBDV replication while knocking down IRF7 promotes IBDV replication. Overexpression of IRF7 couldn't compensate the IRF7 protein level in vvIBDV-infected cells, which suggested that IRF7 protein was degraded by IBDV infection. By using inhibitors, the degradation of IRF7 was found to be related to the proteasome pathway. Further study revealed that IRF7 was observed to interact and colocalize with the IBDV VP3 protein. Consistent with IBDV infection results, IBDV VP3 protein was observed to inhibit the IRF7-IFN-β expression, affect the degradation of IRF7 protein via proteasome pathway. All these results suggest that the IBDV exploits IRF7 by affecting its expression and proteasome degradation via the viral VP3 protein to facilitate viral replication in the cells. These findings revealed a novel mechanism that IBDV uses to evade host antiviral defense.
{"title":"Infectious bursal disease virus affecting interferon regulatory factor 7 signaling through VP3 protein to facilitate viral replication.","authors":"Zhiyuan Wang, Yang Chen, Yanyan Chen, Rui Chen, Weiwei Wang, Shichen Hu, Yihai Li, Hongjun Chen, Ping Wei, Xiumiao He","doi":"10.3389/fcimb.2024.1529159","DOIUrl":"10.3389/fcimb.2024.1529159","url":null,"abstract":"<p><p>Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role. However, the underlying mechanisms that enable IBDV to block the IRF7 pathway remain unclear. In this study, we found that IRF7 and IFN-β expression were suppressed in DF-1 cells during infection with very virulent IBDV (vvIBDV), but not with attenuated IBDV, while the virus continued to replicate. Overexpression of IRF7 inhibits IBDV replication while knocking down IRF7 promotes IBDV replication. Overexpression of IRF7 couldn't compensate the IRF7 protein level in vvIBDV-infected cells, which suggested that IRF7 protein was degraded by IBDV infection. By using inhibitors, the degradation of IRF7 was found to be related to the proteasome pathway. Further study revealed that IRF7 was observed to interact and colocalize with the IBDV VP3 protein. Consistent with IBDV infection results, IBDV VP3 protein was observed to inhibit the IRF7-IFN-β expression, affect the degradation of IRF7 protein via proteasome pathway. All these results suggest that the IBDV exploits IRF7 by affecting its expression and proteasome degradation via the viral VP3 protein to facilitate viral replication in the cells. These findings revealed a novel mechanism that IBDV uses to evade host antiviral defense.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1529159"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1471974
Ruoyu Yao, Guofen Xu, Xiujuan Fu, Wenrui Zhang, Han Wang, Yu Chen, Jia Yao
Background and aims: The impact of coronavirus disease 2019 (COVID-19) on patients with acute-on-chronic liver failure (ACLF) remains unclear. To investigate the clinical characteristics of patients with ACLF complicated with COVID-19 in order to provide evidence for the precise treatment of this patient population.
Methods: A total of 34 ACLF patients with COVID-19 admitted to these three hospitals from December 2022 to August 2023 were included as the ACLF+COVID-19 group. Additionally, 34 age-, gender-, etiology-, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score-matched ACLF patients were screened from 286 ACLF patients as the ACLF group. From 382 COVID-19 patients, 34 were selected as the COVID-19 group, matching the ACLF+COVID-19 group in age, gender, and illness severity. Clinical features of these three groups were compared, with the primary measure being the 28-day mortality rate in the ACLF patients and the secondary measures including clinical symptoms, laboratory tests, comorbidities, and complications in three groups.
Results: Compared with the ACLF group, the ACLF+COVID-19 group had significantly higher incidence rates of fever, cough, sputum production, fatigue, and hypoxemia (all p<0.01). Patients in the ACLF+COVID-19 group were more likely to have hepatic encephalopathy (p=0.015), lower platelet count (p=0.016) and elevated IL-6 level (p=0.026), and higher MELD-Na score (p=0.041) one week after admission, but without a significant increase in 28-day mortality rate (p=0.16).
Conclusions: ACLF patients with COVID-19 have increased risk for thrombocytopenia, more obvious inflammatory response, and rapid disease progression 1 week after admission, but the 28-day mortality rate is similar to that of ACLF patients without COVID-19.
{"title":"Clinical characteristics and the role of IL-6 in acute-on-chronic liver failure patients with or without COVID-19: a multicenter paired cohort study.","authors":"Ruoyu Yao, Guofen Xu, Xiujuan Fu, Wenrui Zhang, Han Wang, Yu Chen, Jia Yao","doi":"10.3389/fcimb.2024.1471974","DOIUrl":"10.3389/fcimb.2024.1471974","url":null,"abstract":"<p><strong>Background and aims: </strong>The impact of coronavirus disease 2019 (COVID-19) on patients with acute-on-chronic liver failure (ACLF) remains unclear. To investigate the clinical characteristics of patients with ACLF complicated with COVID-19 in order to provide evidence for the precise treatment of this patient population.</p><p><strong>Methods: </strong>A total of 34 ACLF patients with COVID-19 admitted to these three hospitals from December 2022 to August 2023 were included as the ACLF+COVID-19 group. Additionally, 34 age-, gender-, etiology-, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score-matched ACLF patients were screened from 286 ACLF patients as the ACLF group. From 382 COVID-19 patients, 34 were selected as the COVID-19 group, matching the ACLF+COVID-19 group in age, gender, and illness severity. Clinical features of these three groups were compared, with the primary measure being the 28-day mortality rate in the ACLF patients and the secondary measures including clinical symptoms, laboratory tests, comorbidities, and complications in three groups.</p><p><strong>Results: </strong>Compared with the ACLF group, the ACLF+COVID-19 group had significantly higher incidence rates of fever, cough, sputum production, fatigue, and hypoxemia (all p<0.01). Patients in the ACLF+COVID-19 group were more likely to have hepatic encephalopathy (p=0.015), lower platelet count (p=0.016) and elevated IL-6 level (p=0.026), and higher MELD-Na score (p=0.041) one week after admission, but without a significant increase in 28-day mortality rate (p=0.16).</p><p><strong>Conclusions: </strong>ACLF patients with COVID-19 have increased risk for thrombocytopenia, more obvious inflammatory response, and rapid disease progression 1 week after admission, but the 28-day mortality rate is similar to that of ACLF patients without COVID-19.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1471974"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1496126
Lilian de Oliveira Guimarães, Geovani de Oliveira Ribeiro, Roseane da Couto, Endrya do Socorro Foro Ramos, Vanessa Dos Santos Morais, Juliana Telles-de-Deus, Vanessa Christe Helfstein, Jesus Maia Dos Santos, Xutao Deng, Eric Delwart, Ramendra Pati Pandey, Vera Lucia Fonseca de Camargo-Neves, Antonio Charlys da Costa, Karin Kirchgatter, Élcio Leal
Background: Mosquito-borne diseases have a significant public health threat worldwide, with arboviruses accounting for a high proportion of infectious diseases and mortality annually. Brazil, in particular, has been suffering outbreaks of diseases transmitted by mosquito viruses, notably those of the Aedes genus, such as dengue, Zika, and chikungunya. Against this background, the São Paulo Zoo is an intriguing ecological niche to explore the virome of mosquitoes, potentially shedding light on the dynamics of arbovirus transmission within a confined setting.
Methods: In this study, we conducted a comprehensive metagenomic analysis of mosquitoes collected from diverse habitats within the zoo, focusing on the Aedes, Anopheles, and Culex genera. From 1,039 contigs of viral origin, we identified 229 viral species infecting mosquitoes, with the orders Picornavirales, Nodamuvirales and Sobelivirales being the most prevalent and abundant. The difference in virome composition was primarily driven by mosquito host species rather than specific collection sites or trap height.
Results: Despite environmental disparities, the virome remained remarkably uniform across different areas of the zoo, emphasizing the strong association between mosquito species and their viral communities. Furthermore, we identified a core virome shared among mosquito species, highlighting potential cross-species transmission events and underscoring the need for targeted surveillance and control measures.
Conclusion: These results contribute to our understanding of the interplay between mosquitoes, the environment, and viruses, providing valuable insights for disease intervention strategies in mosquito-borne diseases.
{"title":"Exploring mosquito virome dynamics within São Paulo Zoo: insights into mosquito-virus-environment interactions.","authors":"Lilian de Oliveira Guimarães, Geovani de Oliveira Ribeiro, Roseane da Couto, Endrya do Socorro Foro Ramos, Vanessa Dos Santos Morais, Juliana Telles-de-Deus, Vanessa Christe Helfstein, Jesus Maia Dos Santos, Xutao Deng, Eric Delwart, Ramendra Pati Pandey, Vera Lucia Fonseca de Camargo-Neves, Antonio Charlys da Costa, Karin Kirchgatter, Élcio Leal","doi":"10.3389/fcimb.2024.1496126","DOIUrl":"10.3389/fcimb.2024.1496126","url":null,"abstract":"<p><strong>Background: </strong>Mosquito-borne diseases have a significant public health threat worldwide, with arboviruses accounting for a high proportion of infectious diseases and mortality annually. Brazil, in particular, has been suffering outbreaks of diseases transmitted by mosquito viruses, notably those of the <i>Aedes</i> genus, such as dengue, Zika, and chikungunya. Against this background, the São Paulo Zoo is an intriguing ecological niche to explore the virome of mosquitoes, potentially shedding light on the dynamics of arbovirus transmission within a confined setting.</p><p><strong>Methods: </strong>In this study, we conducted a comprehensive metagenomic analysis of mosquitoes collected from diverse habitats within the zoo, focusing on the <i>Aedes</i>, <i>Anopheles</i>, and <i>Culex</i> genera. From 1,039 contigs of viral origin, we identified 229 viral species infecting mosquitoes, with the orders <i>Picornavirales</i>, <i>Nodamuvirales</i> and <i>Sobelivirales</i> being the most prevalent and abundant. The difference in virome composition was primarily driven by mosquito host species rather than specific collection sites or trap height.</p><p><strong>Results: </strong>Despite environmental disparities, the virome remained remarkably uniform across different areas of the zoo, emphasizing the strong association between mosquito species and their viral communities. Furthermore, we identified a core virome shared among mosquito species, highlighting potential cross-species transmission events and underscoring the need for targeted surveillance and control measures.</p><p><strong>Conclusion: </strong>These results contribute to our understanding of the interplay between mosquitoes, the environment, and viruses, providing valuable insights for disease intervention strategies in mosquito-borne diseases.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1496126"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1505207
Xiangqun Zhang, Na Shang, Da Zhang, Junyuan Wu, Shubin Guo
Background: Community-acquired pneumonia (CAP) poses a significant health threat to the elderly population, leading to high morbidity and mortality rates. Serum ferritin, a critical indicator of iron metabolism, plays a pivotal role in inflammation and immune regulation. Nevertheless, its specific prognostic relevance in elderly patients with CAP remains unclear. This study aimed to evaluate the predictive capacity of serum ferritin in determining the prognosis of elderly patients with CAP and to investigate its effectiveness when combined with the sequential organ failure assessment (SOFA) or CURB-65 (confusion, uremia, respiratory rate, blood pressure, aged ≥65 years) scores.
Methods: This retrospective cohort study included 451 elderly patients (aged ≥65 years) diagnosed with CAP according to established criteria. Serum ferritin concentrations were measured upon admission and various prognostic indicators such as 28-day mortality, mechanical ventilation requirement, and vasopressor administration were analyzed in conjunction with white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lactate (Lac), SOFA scores, and CURB-65 scores. The independent predictive value of ferritin was assessed through receiver operating characteristic (ROC) curve analysis and multivariate logistic regression.
Results: Among the 451 patients, 99 (22%) died within 28 days. The area under the curve (AUC) of serum ferritin for predicting 28-day mortality was 0.75 (95%CI: 0.695-0.805). Ferritin outperformed WBC, CRP, and PCT in predictive performance, and its performance was comparable to Lac. When combined with SOFA or CURB-65 scores, the AUC of ferritin for predicting 28-day mortality increased to 0.84 and 0.847, respectively (P<0.001). Moreover, the AUC of ferritin for predicting vasopressor administration was 0.707, which increased to 0.864 and 0.822 when combined with SOFA or CURB-65 scores, respectively (P<0.001). Ferritin could predict mechanical ventilation requirement with an AUC of 0.618, but it was not an independent risk factor, and its predictive ability was not significantly different from other indicators.
Conclusion: Admission serum ferritin is an independent predictor for the prognosis of elderly patients with CAP, and it exhibits a strong ability to predict the 28-day mortality and vasopressor administration. The combination of ferritin with SOFA and CURB-65 scores significantly improves the prognostic predictive potency.
{"title":"The independent predictive value of admission serum ferritin concentration for prognosis in elderly patients with community-acquired pneumonia in the emergency department.","authors":"Xiangqun Zhang, Na Shang, Da Zhang, Junyuan Wu, Shubin Guo","doi":"10.3389/fcimb.2024.1505207","DOIUrl":"10.3389/fcimb.2024.1505207","url":null,"abstract":"<p><strong>Background: </strong>Community-acquired pneumonia (CAP) poses a significant health threat to the elderly population, leading to high morbidity and mortality rates. Serum ferritin, a critical indicator of iron metabolism, plays a pivotal role in inflammation and immune regulation. Nevertheless, its specific prognostic relevance in elderly patients with CAP remains unclear. This study aimed to evaluate the predictive capacity of serum ferritin in determining the prognosis of elderly patients with CAP and to investigate its effectiveness when combined with the sequential organ failure assessment (SOFA) or CURB-65 (confusion, uremia, respiratory rate, blood pressure, aged ≥65 years) scores.</p><p><strong>Methods: </strong>This retrospective cohort study included 451 elderly patients (aged ≥65 years) diagnosed with CAP according to established criteria. Serum ferritin concentrations were measured upon admission and various prognostic indicators such as 28-day mortality, mechanical ventilation requirement, and vasopressor administration were analyzed in conjunction with white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lactate (Lac), SOFA scores, and CURB-65 scores. The independent predictive value of ferritin was assessed through receiver operating characteristic (ROC) curve analysis and multivariate logistic regression.</p><p><strong>Results: </strong>Among the 451 patients, 99 (22%) died within 28 days. The area under the curve (AUC) of serum ferritin for predicting 28-day mortality was 0.75 (95%CI: 0.695-0.805). Ferritin outperformed WBC, CRP, and PCT in predictive performance, and its performance was comparable to Lac. When combined with SOFA or CURB-65 scores, the AUC of ferritin for predicting 28-day mortality increased to 0.84 and 0.847, respectively (<i>P</i><0.001). Moreover, the AUC of ferritin for predicting vasopressor administration was 0.707, which increased to 0.864 and 0.822 when combined with SOFA or CURB-65 scores, respectively (<i>P</i><0.001). Ferritin could predict mechanical ventilation requirement with an AUC of 0.618, but it was not an independent risk factor, and its predictive ability was not significantly different from other indicators.</p><p><strong>Conclusion: </strong>Admission serum ferritin is an independent predictor for the prognosis of elderly patients with CAP, and it exhibits a strong ability to predict the 28-day mortality and vasopressor administration. The combination of ferritin with SOFA and CURB-65 scores significantly improves the prognostic predictive potency.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1505207"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Treatment methods in traditional Chinese medicine (TCM) are foundational to their theoretical, methodological, formulaic, and pharmacological systems, significantly contributing to syndrome differentiation and therapy. The principle of "promoting urination to regulate bowel movements" is a common therapeutic approach in TCM. The core concept is "promoting the dispersion and drainage of water dampness, regulating urination to relieve diarrhea," yet its scientific underpinning remains unclear. Modern medical treatment for watery diarrhea primarily focuses on electrolyte replenishment, as diuretics may lead to dehydration and other side effects. Some reports suggest that this TCM approach lacks scientific validity. Microecology, an area associated with the origins of TCM, is closely related to the development, diagnosis, and treatment of diarrhea. The renal-intestinal axis offers a molecular biological basis for examining associated pathological mechanisms, advancing therapeutic targets such as "treating the intestine to address kidney issues" and highlighting the interactions within the "renal-intestinal microbiota-liquid metabolism" framework, thus providing an endogenous mechanism to support "treating the intestine through the kidney." An increasing number of studies have shown that the intestinal microbiota and its metabolites, as unique mediators, are involved in the physiological and pathological changes of the body. Therefore, this study explores the relationship between fluid metabolism and diarrhea from the perspective of the intestinal microbiota and its metabolites, aiming to elucidate the biological mechanisms underlying the "promoting urination to regulate bowel movements" therapeutic approach and to clarify the scientific basis for treating diarrhea via the renal-intestinal axis. This research provides new insights for the study of TCM microbiology.
{"title":"Investigating the biological significance of the TCM principle \"promoting urination to regulate bowel movements\" through the influence of the intestinal microbiota and their metabolites on the renal-intestinal axis.","authors":"Donglin Yu, Junxi Shen, Liwen Li, Qi Long, Shiqin Xie, Mengsi Zhou, Qianghong Tian, Ying Cai","doi":"10.3389/fcimb.2024.1523708","DOIUrl":"10.3389/fcimb.2024.1523708","url":null,"abstract":"<p><p>Treatment methods in traditional Chinese medicine (TCM) are foundational to their theoretical, methodological, formulaic, and pharmacological systems, significantly contributing to syndrome differentiation and therapy. The principle of \"promoting urination to regulate bowel movements\" is a common therapeutic approach in TCM. The core concept is \"promoting the dispersion and drainage of water dampness, regulating urination to relieve diarrhea,\" yet its scientific underpinning remains unclear. Modern medical treatment for watery diarrhea primarily focuses on electrolyte replenishment, as diuretics may lead to dehydration and other side effects. Some reports suggest that this TCM approach lacks scientific validity. Microecology, an area associated with the origins of TCM, is closely related to the development, diagnosis, and treatment of diarrhea. The renal-intestinal axis offers a molecular biological basis for examining associated pathological mechanisms, advancing therapeutic targets such as \"treating the intestine to address kidney issues\" and highlighting the interactions within the \"renal-intestinal microbiota-liquid metabolism\" framework, thus providing an endogenous mechanism to support \"treating the intestine through the kidney.\" An increasing number of studies have shown that the intestinal microbiota and its metabolites, as unique mediators, are involved in the physiological and pathological changes of the body. Therefore, this study explores the relationship between fluid metabolism and diarrhea from the perspective of the intestinal microbiota and its metabolites, aiming to elucidate the biological mechanisms underlying the \"promoting urination to regulate bowel movements\" therapeutic approach and to clarify the scientific basis for treating diarrhea via the renal-intestinal axis. This research provides new insights for the study of TCM microbiology.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1523708"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acinetobacter baumannii has emerged as a critical global health threat due to its exceptional survival skills in adverse environment and its ability to acquire antibiotic resistance, presenting significant challenges for infection treatment and control. The World Health Organization has classified carbapenem-resistant A. baumannii as a "Critical Priority" pathogen to guide research and the development of control and prevention strategies. Epidemiological surveillance methodologies provide the tools necessary for classifying A. baumannii into international clonal lineages, facilitating the analysis of molecular characteristics, global dissemination, and evolution. This study provides a detailed analysis of the molecular epidemiology of A. baumannii in Mexico, focusing on identifying the main international clonal lineages. Genomic analyses of 146 genomes, along with information from previous studies, identified 24 different sequence types according to the Oxford Scheme. The major international clone IC2 (CC208) was identified and harbors β-lactamases OXA-66, ADC-30, OXA-72, and is predicted to possess the OCL1 locus. The international clone IC5 (CC205) carries β-lactamase OXA-65, along with ADC-214 and OXA-239, with OCL10 predicted in 82.2% of the genomes. The international clone IC7 (CC229) harbors β-lactamase OXA-64, as well as ADC-174 and ADC-214, with OCL6 and OCL7 loci predicted. These international clones were identified in different periods and regions of Mexico and are likely to be widely distributed throughout the country. The analysis of each lineage reveals distinct molecular characteristics, including sequence types, capsule typing, outer core loci, and specific antibiotic resistance profiles. Understanding these features is crucial for elucidating their roles in infection dynamics, resistance mechanisms, and their impact on clinical outcomes.
{"title":"Genomic analysis of the main epidemiological lineages of <i>Acinetobacter baumannii</i> in Mexico.","authors":"Barrios-Camacho Humberto, Lozano-Aguirre Luis, Duran-Bedolla Josefina","doi":"10.3389/fcimb.2024.1499839","DOIUrl":"10.3389/fcimb.2024.1499839","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> has emerged as a critical global health threat due to its exceptional survival skills in adverse environment and its ability to acquire antibiotic resistance, presenting significant challenges for infection treatment and control. The World Health Organization has classified carbapenem-resistant <i>A. baumannii</i> as a \"Critical Priority\" pathogen to guide research and the development of control and prevention strategies. Epidemiological surveillance methodologies provide the tools necessary for classifying <i>A. baumannii</i> into international clonal lineages, facilitating the analysis of molecular characteristics, global dissemination, and evolution. This study provides a detailed analysis of the molecular epidemiology of <i>A. baumannii</i> in Mexico, focusing on identifying the main international clonal lineages. Genomic analyses of 146 genomes, along with information from previous studies, identified 24 different sequence types according to the Oxford Scheme. The major international clone IC2 (CC208) was identified and harbors β-lactamases OXA-66, ADC-30, OXA-72, and is predicted to possess the OCL1 locus. The international clone IC5 (CC205) carries β-lactamase OXA-65, along with ADC-214 and OXA-239, with OCL10 predicted in 82.2% of the genomes. The international clone IC7 (CC229) harbors β-lactamase OXA-64, as well as ADC-174 and ADC-214, with OCL6 and OCL7 loci predicted. These international clones were identified in different periods and regions of Mexico and are likely to be widely distributed throughout the country. The analysis of each lineage reveals distinct molecular characteristics, including sequence types, capsule typing, outer core loci, and specific antibiotic resistance profiles. Understanding these features is crucial for elucidating their roles in infection dynamics, resistance mechanisms, and their impact on clinical outcomes.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1499839"},"PeriodicalIF":4.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-09eCollection Date: 2024-01-01DOI: 10.3389/fcimb.2024.1482787
Xiaolin Ma, Yuting Wu, Ri De, Hailan Yao, Feng He, Yi Wang, Wei Wang, Chao Yan, Qinwei Song, Chunjie Guo, Li Wen, Linqing Zhao, Ling Cao, Chunmei Zhu
Background: The pathogenic distribution of co-infections and immunological status of patients infected with human adenovirus serotypes 3 or 7 (HAdV-3 or HAdV-7) were poorly understood.
Methods: This study involved a retrospective analysis of respiratory specimens collected from enrolled children with lower respiratory tract infections (LRTIs), positive for HAdV-3 or HAdV-7 from January 2017 to December 2019. Demographic data, clinical features, laboratory and radiographic findings were compared to delineate the impact of co-infections, and immune responses on clinical severity of HAdV-3 or HAdV-7 infections.
Results: Among 1311cases enrolled, there were 66 infected with HAdV-3 and 58 with HAdV-7. HAdV-7-infected patients exhibited more prolonged fever (100% vs 89.4%, p=0.014), pneumonia (100% vs 89.4%, p=0.014), hypoxia (34.5% vs 12.1%, p=0.003), higher propensity for aspartate aminotransferase exceeding 80U/L (21.1% vs 4.7%, p=0.006), D-Dimer exceeding 1.65mg/L (64.9% vs 12.5%, p<0.001), consolidation (50.0% vs 27.4%, p=0.011), and pleural effusion (32.8% vs 6.5%, p<0.001), co-infections with Mycoplasma pneumoniae (77.1% vs 32.6%, p<0.001), and multiple infections (56.8% vs 41.3%, p=0.007), compared to those with HAdV-3 infections. Immune cell analysis indicated that HAdV-7 infections led to a more pronounced decrease in CD3+ T cells (1596.8 vs 2444.8 cells/𝛍l, p=0.042), CD8+ cytotoxic T cells (668.6 vs 774.0 cells/µl, p=0.045), and increased NK cell percentages (11.5% vs 9.0%, p=0.044) compared to HAdV-3 infections.
Conclusions: Hospitalized children with HAdV-7-associated LRTIs exhibit greater severity, multiple infections, and significant potential for greater cellular immune dysregulation compared to those with HAdV-3 infection, indicating a more severe clinical course and distinct pathogenic profiles.
{"title":"Impact of co-infections and immune responses on clinical severity of human adenovirus 3 and 7 infections in hospitalized children with lower respiratory tract infections: a comparative study.","authors":"Xiaolin Ma, Yuting Wu, Ri De, Hailan Yao, Feng He, Yi Wang, Wei Wang, Chao Yan, Qinwei Song, Chunjie Guo, Li Wen, Linqing Zhao, Ling Cao, Chunmei Zhu","doi":"10.3389/fcimb.2024.1482787","DOIUrl":"10.3389/fcimb.2024.1482787","url":null,"abstract":"<p><strong>Background: </strong>The pathogenic distribution of co-infections and immunological status of patients infected with human adenovirus serotypes 3 or 7 (HAdV-3 or HAdV-7) were poorly understood.</p><p><strong>Methods: </strong>This study involved a retrospective analysis of respiratory specimens collected from enrolled children with lower respiratory tract infections (LRTIs), positive for HAdV-3 or HAdV-7 from January 2017 to December 2019. Demographic data, clinical features, laboratory and radiographic findings were compared to delineate the impact of co-infections, and immune responses on clinical severity of HAdV-3 or HAdV-7 infections.</p><p><strong>Results: </strong>Among 1311cases enrolled, there were 66 infected with HAdV-3 and 58 with HAdV-7. HAdV-7-infected patients exhibited more prolonged fever (100% vs 89.4%, <i>p</i>=0.014), pneumonia (100% vs 89.4%, <i>p</i>=0.014), hypoxia (34.5% vs 12.1%, <i>p</i>=0.003), higher propensity for aspartate aminotransferase exceeding 80U/L (21.1% vs 4.7%, <i>p</i>=0.006), D-Dimer exceeding 1.65mg/L (64.9% vs 12.5%, <i>p</i><0.001), consolidation (50.0% vs 27.4%, <i>p</i>=0.011), and pleural effusion (32.8% vs 6.5%, p<0.001), co-infections with <i>Mycoplasma pneumoniae</i> (77.1% vs 32.6%, <i>p</i><0.001), and multiple infections (56.8% vs 41.3%, <i>p</i>=0.007), compared to those with HAdV-3 infections. Immune cell analysis indicated that HAdV-7 infections led to a more pronounced decrease in CD3+ T cells (1596.8 vs 2444.8 cells/𝛍l, p=0.042), CD8+ cytotoxic T cells (668.6 vs 774.0 cells/µl, <i>p</i>=0.045), and increased NK cell percentages (11.5% vs 9.0%, <i>p</i>=0.044) compared to HAdV-3 infections.</p><p><strong>Conclusions: </strong>Hospitalized children with HAdV-7-associated LRTIs exhibit greater severity, multiple infections, and significant potential for greater cellular immune dysregulation compared to those with HAdV-3 infection, indicating a more severe clinical course and distinct pathogenic profiles.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1482787"},"PeriodicalIF":4.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}