Pub Date : 2025-03-01DOI: 10.1016/j.jinf.2025.106436
C.C.A. Noble , E. McDonald , S. Nicholson , S. Biering-Sørensen , L.F. Pittet , A.L. Byrne , J. Croda , M. Dalcolmo , M.V.G. Lacerda , M. Lucas , D.J. Lynn , C. Prat Aymerich , P.C. Richmond , A. Warris , N. Curtis , N.L. Messina , the BRACE Trial Consortium Group
Objectives
SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac.
Methods
Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac.
Results
In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices.
Conclusions
Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.
{"title":"Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response","authors":"C.C.A. Noble , E. McDonald , S. Nicholson , S. Biering-Sørensen , L.F. Pittet , A.L. Byrne , J. Croda , M. Dalcolmo , M.V.G. Lacerda , M. Lucas , D.J. Lynn , C. Prat Aymerich , P.C. Richmond , A. Warris , N. Curtis , N.L. Messina , the BRACE Trial Consortium Group","doi":"10.1016/j.jinf.2025.106436","DOIUrl":"10.1016/j.jinf.2025.106436","url":null,"abstract":"<div><h3>Objectives</h3><div>SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as <em>CoronaVac</em>. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with <em>CoronaVac</em>.</div></div><div><h3>Methods</h3><div>Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with <em>CoronaVac</em>.</div></div><div><h3>Results</h3><div>In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following <em>CoronaVac</em> vaccination, with variable antibody indices.</div></div><div><h3>Conclusions</h3><div>Anti-N responses to COVID-19 and <em>CoronaVac</em> are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106436"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jinf.2025.106446
Mingyuan Zhang , Yanhang Gao , Fei Kong , Haibing Gao , Yongxiang Yi , Chao Wu , Yongning Xin , Sujun Zheng , Jiajie Lu , Tao Han , Yingren Zhao , Peng Hu , Xiaorong Mao , Qing Xie , Jie Zhang , Jinlin Hou , Zhiliang Gao , Jianqi Lian , Liang Chen , Jia Shang , Junqi Niu
Objectives
GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that inhibits HBV replication by interfering with assembly and disassembly of the virus nucleocapsid, this prospective, open-label, comparative, phase 2b trial evaluated the antiviral activity and safety of GLS4/ritonavir (RTV) combined with entecavir in hepatitis B e antigen-positive patients.
Methods
250 CHB patients were enrolled, including treatment-naïve patients and those interrupted anti-HBV drugs for ≥ 6 months (Part A, n=125), and patients who had taken ETV for ≥1 year and had achieved viral suppression (Part B, n=125). Patients were randomly allocated to receive 120 mg GLS4/100 mg RTV plus 0.5 mg ETV or 0.5 mg ETV monotherapy for 96 weeks.
Results
In the mid-term, in Part A (n=122), greater least-squares mean (LSM) changes from baseline were observed in the GLS4/RTV plus ETV cohort than in ETV monotherapy cohort in HBV DNA (−6.28 vs −5.72 log10 IU/ml, p=0.0005), HBsAg (−0.87 vs −0.65 log10 IU/ml, p=0.0653), HBV pgRNA (−3.83 vs −1.91 log10 copies/ml, p<0.0001); The proportions of both HBV DNA and pgRNA negative patients were 17.3% (13/75, GLS4/RTV plus ETV) and 0% (0/30, ETV monotherapy). In Part B (n=123), greater mean LSM reductions in HBsAg (−0.17 vs −0.06 log10 IU/ml, p=0.0013), HBV pgRNA (−1.61 vs −0.28 log10 copies/ml, p<0.0001) were also observed in the GLS4/RTV+ETV cohort. the proportions of both HBV DNA and pgRNA-negative patients were 71.6% (48/67, GLS4/RTV plus ETV) and 18.9% (7/37, ETV monotherapy), respectively. No patients achieved HBsAg loss at week 48.
GLS4/RTV + ETV were well tolerated, the most common adverse events were elevated alanine aminotransferase levels and hypertriglyceridemia, which were reversed by temporary GLS4/RTV discontinuation.
Conclusions
The primary analysis at week 48 showed that the antiviral efficacy of GLS4/RTV with ETV was clearly superior to that of ETV monotherapy. GLS4/RTV with ETV was well tolerated; further studies evaluating its safety and efficacy are ongoing. (clinical trial identifier: NCT04147208).
{"title":"Efficacy and safety of GLS4 with entecavir vs entecavir alone in chronic hepatitis B patients: A multicenter clinical trial","authors":"Mingyuan Zhang , Yanhang Gao , Fei Kong , Haibing Gao , Yongxiang Yi , Chao Wu , Yongning Xin , Sujun Zheng , Jiajie Lu , Tao Han , Yingren Zhao , Peng Hu , Xiaorong Mao , Qing Xie , Jie Zhang , Jinlin Hou , Zhiliang Gao , Jianqi Lian , Liang Chen , Jia Shang , Junqi Niu","doi":"10.1016/j.jinf.2025.106446","DOIUrl":"10.1016/j.jinf.2025.106446","url":null,"abstract":"<div><h3>Objectives</h3><div>GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that inhibits HBV replication by interfering with assembly and disassembly of the virus nucleocapsid, this prospective, open-label, comparative, phase 2b trial evaluated the antiviral activity and safety of GLS4/ritonavir (RTV) combined with entecavir in hepatitis B e antigen-positive patients.</div></div><div><h3>Methods</h3><div>250 CHB patients were enrolled, including treatment-naïve patients and those interrupted anti-HBV drugs for ≥ 6 months (Part A, n=125), and patients who had taken ETV for ≥1 year and had achieved viral suppression (Part B, n=125). Patients were randomly allocated to receive 120 mg GLS4/100 mg RTV plus 0.5 mg ETV or 0.5 mg ETV monotherapy for 96 weeks.</div></div><div><h3>Results</h3><div>In the mid-term, in Part A (n=122), greater least-squares mean (LSM) changes from baseline were observed in the GLS4/RTV plus ETV cohort than in ETV monotherapy cohort in HBV DNA (−6.28 vs −5.72 log10 IU/ml, p=0.0005), HBsAg (−0.87 vs −0.65 log10 IU/ml, p=0.0653), HBV pgRNA (−3.83 vs −1.91 log10 copies/ml, p<0.0001); The proportions of both HBV DNA and pgRNA negative patients were 17.3% (13/75, GLS4/RTV plus ETV) and 0% (0/30, ETV monotherapy). In Part B (n=123), greater mean LSM reductions in HBsAg (−0.17 vs −0.06 log10 IU/ml, p=0.0013), HBV pgRNA (−1.61 vs −0.28 log10 copies/ml, p<0.0001) were also observed in the GLS4/RTV+ETV cohort. the proportions of both HBV DNA and pgRNA-negative patients were 71.6% (48/67, GLS4/RTV plus ETV) and 18.9% (7/37, ETV monotherapy), respectively. No patients achieved HBsAg loss at week 48.</div><div>GLS4/RTV + ETV were well tolerated, the most common adverse events were elevated alanine aminotransferase levels and hypertriglyceridemia, which were reversed by temporary GLS4/RTV discontinuation.</div></div><div><h3>Conclusions</h3><div>The primary analysis at week 48 showed that the antiviral efficacy of GLS4/RTV with ETV was clearly superior to that of ETV monotherapy. GLS4/RTV with ETV was well tolerated; further studies evaluating its safety and efficacy are ongoing. (clinical trial identifier: NCT04147208).</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106446"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.jinf.2025.106453
Maxime Danjean , Laure Surgers , Guilhem Royer , Vanessa Demontant , Hadrien Kimseng , Amandine Caillault , Bryan Jimenez-Araya , Sarah Seng , Elisabeth Trawinski , Hayette Rougier , Jean-Winoc Decousser , Hervé Jacquier , Anders Boyd , Paul-Louis Woerther
Objectives
We characterized the genetic proximity of Sequence Type (ST) 131, 1193 and 14 Extended-Spectrum Beta-Lactamase-producing E. coli (ESBL-Ec) to assess human determinants of carriage in community settings.
Methods
In this cross-sectional study, we included individuals seeking care at a sexually transmitted infection (STI) or HIV outpatient clinic. ESBL-Ec were compared using phylogeny, core-genome Multi-Locus Sequence Typing and Single-Nucleotide Polymorphism (SNP) determination. Determinants were compared between STs and correlated to genetic distances.
Results
103 individuals carried 112 strains of ST131 (n=63), ST14 (n=26) and ST1193 (n=23). Compared to ST131, ST14 isolates were more commonly found in individuals with any STI (p=0.031), men who have sex with men (p<0.001) and recent antibiotic use (p=0.021); whereas ST1193 isolates were more commonly found in individuals who engaged in insertive anal sex in <6 months (p=0.017). ST131 isolates showed high genomic diversity, while other STs evidenced a high level of proximity. SNPs data indicated the likely spread of a single ST14 (range=1;32) and some ST1193 clusters (range=2;111), which were linked to ST-specific sexual behaviors.
Conclusions
In populations of those at risk of acquiring STI, ST14 and ST1193 ESBL-Ec are emerging. Specific sexual transmissions routes are likely to play a role in their spread.
{"title":"Extensive dissemination of ESBL-producing Clonal Complex 14 Escherichia coli is likely spread through sexual transmission among men who have sex with men at risk of sexually transmitted infections","authors":"Maxime Danjean , Laure Surgers , Guilhem Royer , Vanessa Demontant , Hadrien Kimseng , Amandine Caillault , Bryan Jimenez-Araya , Sarah Seng , Elisabeth Trawinski , Hayette Rougier , Jean-Winoc Decousser , Hervé Jacquier , Anders Boyd , Paul-Louis Woerther","doi":"10.1016/j.jinf.2025.106453","DOIUrl":"10.1016/j.jinf.2025.106453","url":null,"abstract":"<div><h3>Objectives</h3><div>We characterized the genetic proximity of Sequence Type (ST) 131, 1193 and 14 Extended-Spectrum Beta-Lactamase-producing <em>E. coli</em> (ESBL-Ec) to assess human determinants of carriage in community settings.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, we included individuals seeking care at a sexually transmitted infection (STI) or HIV outpatient clinic. ESBL-Ec were compared using phylogeny, core-genome Multi-Locus Sequence Typing and Single-Nucleotide Polymorphism (SNP) determination. Determinants were compared between STs and correlated to genetic distances.</div></div><div><h3>Results</h3><div>103 individuals carried 112 strains of ST131 (<em>n</em>=63), ST14 (<em>n</em>=26) and ST1193 (<em>n</em>=23). Compared to ST131, ST14 isolates were more commonly found in individuals with any STI (<em>p</em>=0.031), men who have sex with men (<em>p</em><0.001) and recent antibiotic use (<em>p</em>=0.021); whereas ST1193 isolates were more commonly found in individuals who engaged in insertive anal sex in <6 months (<em>p</em>=0.017). ST131 isolates showed high genomic diversity, while other STs evidenced a high level of proximity. SNPs data indicated the likely spread of a single ST14 (range=1;32) and some ST1193 clusters (range=2;111), which were linked to ST-specific sexual behaviors.</div></div><div><h3>Conclusions</h3><div>In populations of those at risk of acquiring STI, ST14 and ST1193 ESBL-Ec are emerging. Specific sexual transmissions routes are likely to play a role in their spread.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106453"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/j.jinf.2025.106452
Hao Chen , Yang Xu , Yafei Li , Hui-Qi Qu, Hakon Hakonarson, Jin Li, Qianghua Xia
{"title":"Genomic variation and impact on the proteins of Mpox virus","authors":"Hao Chen , Yang Xu , Yafei Li , Hui-Qi Qu, Hakon Hakonarson, Jin Li, Qianghua Xia","doi":"10.1016/j.jinf.2025.106452","DOIUrl":"10.1016/j.jinf.2025.106452","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106452"},"PeriodicalIF":14.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/j.jinf.2025.106451
Yi Song , Yu-Nong Gong , Kuan-Fu Chen , David K. Smith , Hassan Zaraket , Seweryn Bialasiewicz , Sarah Tozer , Paul KS Chan , Evelyn SC Koay , Hong Kai Lee , Kok Keng Tee , Pieter LA Fraaij , Lance Jennings , Matti Waris , Hidekazu Nishimura , Aripuana Watanabe , Theo Sloots , Jen Kok , Dominic E. Dwyer , Marion PG Koopmans , Tommy TY Lam
Objectives
Human parainfluenza viruses (hPIV) are a common cause of acute respiratory infections, especially in children under five years and the elderly. hPIV can be subclassified as types 1–4: these showed various seasonality patterns worldwide, and it is unclear how climatic factors might consistently explain their global epidemiology.
Methods
This study collected time-series incidence data from the literature and hPIV surveillance programs worldwide (47 locations). Wavelet analysis and circular statistics were used to detect the seasonality and the months of peak incidence for each hPIV type. Relationships between climatic drivers and incidence peaks were assessed using a generalized estimating equation.
Results
The average positive rate of hPIV among patients with respiratory symptoms was 5.6% and ranged between 0.69–3.48% for different types. In the northern temperate region, the median peak incidence months for hPIV1, hPIV2, and hPIV4 were from September to October, while for hPIV3, it was in late May. Seasonal peaks of hPIV3 were associated with higher monthly temperatures and lower diurnal temperatures range throughout the year; hPIV4 peaks appeared to correlate with lower monthly temperatures and higher precipitation throughout the year. Different hPIV types exhibit different patterns of global epidemiology and transmission.
Conclusions
Climate drivers may play a role in hPIV transmission. More comprehensive and coherent surveillance of hPIV types would enable more in-depth analyses and inform the timing of preventive measures.
{"title":"Global epidemiology, seasonality and climatic drivers of the four human parainfluenza virus types","authors":"Yi Song , Yu-Nong Gong , Kuan-Fu Chen , David K. Smith , Hassan Zaraket , Seweryn Bialasiewicz , Sarah Tozer , Paul KS Chan , Evelyn SC Koay , Hong Kai Lee , Kok Keng Tee , Pieter LA Fraaij , Lance Jennings , Matti Waris , Hidekazu Nishimura , Aripuana Watanabe , Theo Sloots , Jen Kok , Dominic E. Dwyer , Marion PG Koopmans , Tommy TY Lam","doi":"10.1016/j.jinf.2025.106451","DOIUrl":"10.1016/j.jinf.2025.106451","url":null,"abstract":"<div><h3>Objectives</h3><div>Human parainfluenza viruses (hPIV) are a common cause of acute respiratory infections, especially in children under five years and the elderly. hPIV can be subclassified as types 1–4: these showed various seasonality patterns worldwide, and it is unclear how climatic factors might consistently explain their global epidemiology.</div></div><div><h3>Methods</h3><div>This study collected time-series incidence data from the literature and hPIV surveillance programs worldwide (47 locations). Wavelet analysis and circular statistics were used to detect the seasonality and the months of peak incidence for each hPIV type. Relationships between climatic drivers and incidence peaks were assessed using a generalized estimating equation.</div></div><div><h3>Results</h3><div>The average positive rate of hPIV among patients with respiratory symptoms was 5.6% and ranged between 0.69–3.48% for different types. In the northern temperate region, the median peak incidence months for hPIV1, hPIV2, and hPIV4 were from September to October, while for hPIV3, it was in late May. Seasonal peaks of hPIV3 were associated with higher monthly temperatures and lower diurnal temperatures range throughout the year; hPIV4 peaks appeared to correlate with lower monthly temperatures and higher precipitation throughout the year. Different hPIV types exhibit different patterns of global epidemiology and transmission.</div></div><div><h3>Conclusions</h3><div>Climate drivers may play a role in hPIV transmission. More comprehensive and coherent surveillance of hPIV types would enable more in-depth analyses and inform the timing of preventive measures.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106451"},"PeriodicalIF":14.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.jinf.2025.106450
Qianyu Feng , Jinjin Wang , Xinyu Wang , Jiao Tian , Linlin Zhang , Dilara Dilmurat , Mengjia Liu , Junhong Ai , Guoshuang Feng , Yueping Zeng , Ran Wang , Zhengde Xie
Background
Community acquired pneumonia (CAP) is a major global public health concern among children, with viral pathogens playing a significant role. Despite this, national multicenter studies on viral community acquired pneumonia (VCAP) in hospitalized children remain scarce. The study employed a multicenter approach to investigate the clinical epidemiology and burden of VCAP in hospitalized children across China.
Method
Data were extracted from the face sheets of discharge medical records (FSMRs) within the FuTang Update Medical Records (FUTURE) database, spanning 2016 to 2022. VCAP cases from 33 tertiary children's hospitals were identified and analyzed. Epidemiological characteristics, length of stay (LOS), and hospitalization costs were compared using appropriate statistical methods.
Results
Between January 2016 to December 2022, 72,905 hospitalized cases of CAP with confirmed diagnoses of viral pathogens were documented, accounting 4.07% of all CAP cases (72,905/1791,343). Respiratory syncytial virus (RSV) was the leading cause, responsible for 57.21% of cases, followed by adenovirus, parainfluenza virus, human rhinovirus and influenza virus. The male-to-female ratio was 1.69:1, and infants under 1 year of age represented 59.84% of hospitalizations. Temporal trends showed an increase in VCAP hospitalizations from 2016 to 2019, a decline in 2020, followed by a resurgence in 2021 and 2022. Seasonally, the majority of cases occurred during winter (December to February, 41.67%), while summer (June to August) had the lowest proportion (16.80%). A total of 40 deaths were reported, representing a mortality rate of 0.05%. The median LOS was 7 days, with a median hospitalization cost of 907.38 USD.
Conclusions
Although the proportion of CAP cases in children with confirmed viral pathogen in China is relatively low, VCAP remains a significant health burden for children. RSV is the most prevalent viral cause of VCAP, particularly affecting infants under 1 year of age, while adenovirus is associated with the highest mortality, longest LOS, and highest hospitalization costs. VCAP cases peak during the winter months. While the prognosis is generally favorable, the disease continues to pose a considerable public health challenge.
{"title":"Clinical epidemiological characteristics of hospitalized pediatric viral community-acquired pneumonia in China","authors":"Qianyu Feng , Jinjin Wang , Xinyu Wang , Jiao Tian , Linlin Zhang , Dilara Dilmurat , Mengjia Liu , Junhong Ai , Guoshuang Feng , Yueping Zeng , Ran Wang , Zhengde Xie","doi":"10.1016/j.jinf.2025.106450","DOIUrl":"10.1016/j.jinf.2025.106450","url":null,"abstract":"<div><h3>Background</h3><div>Community acquired pneumonia (CAP) is a major global public health concern among children, with viral pathogens playing a significant role. Despite this, national multicenter studies on viral community acquired pneumonia (VCAP) in hospitalized children remain scarce. The study employed a multicenter approach to investigate the clinical epidemiology and burden of VCAP in hospitalized children across China.</div></div><div><h3>Method</h3><div>Data were extracted from the face sheets of discharge medical records (FSMRs) within the FuTang Update Medical Records (FUTURE) database, spanning 2016 to 2022. VCAP cases from 33 tertiary children's hospitals were identified and analyzed. Epidemiological characteristics, length of stay (LOS), and hospitalization costs were compared using appropriate statistical methods.</div></div><div><h3>Results</h3><div>Between January 2016 to December 2022, 72,905 hospitalized cases of CAP with confirmed diagnoses of viral pathogens were documented, accounting 4.07% of all CAP cases (72,905/1791,343). Respiratory syncytial virus (RSV) was the leading cause, responsible for 57.21% of cases, followed by adenovirus, parainfluenza virus, human rhinovirus and influenza virus. The male-to-female ratio was 1.69:1, and infants under 1 year of age represented 59.84% of hospitalizations. Temporal trends showed an increase in VCAP hospitalizations from 2016 to 2019, a decline in 2020, followed by a resurgence in 2021 and 2022. Seasonally, the majority of cases occurred during winter (December to February, 41.67%), while summer (June to August) had the lowest proportion (16.80%). A total of 40 deaths were reported, representing a mortality rate of 0.05%. The median LOS was 7 days, with a median hospitalization cost of 907.38 USD.</div></div><div><h3>Conclusions</h3><div>Although the proportion of CAP cases in children with confirmed viral pathogen in China is relatively low, VCAP remains a significant health burden for children. RSV is the most prevalent viral cause of VCAP, particularly affecting infants under 1 year of age, while adenovirus is associated with the highest mortality, longest LOS, and highest hospitalization costs. VCAP cases peak during the winter months. While the prognosis is generally favorable, the disease continues to pose a considerable public health challenge.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106450"},"PeriodicalIF":14.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.jinf.2025.106449
Xiaochen Wang , Kaishan Jiang , Wenjin Xing , Qiudan Xin , Qiongjie Hu , Shiji Wu , Ziyong Sun , Hongyan Hou , Yi Ren , Feng Wang
Background
Distinguishing between active tuberculosis disease (TBD) and latent tuberculosis infection (TBI) is crucial for TB control but remains challenging.
Methods
Single-cell RNA sequencing was conducted on purified Mycobacterium tuberculosis (MTB)-specific CD154+CD4+ T cells.
Results
We observe a superior role of CD154 in detecting MTB infection, whereas its ability in distinguishing TBD from TBI is still limited due to patient heterogeneity. Single-cell RNA sequencing of MTB-specific CD154+CD4+ T cells identifies 10 distinct clusters, including Treg, T_act, Th1_pex, Th1_eff, Tfh, T_na, Th17_ex, Th2, NKT, and Th1_cyt. Notably, effector and apoptotic Th1 cells are predominant in CD154+CD4+ T cells of TBD. However, Tfh cells are the primary component in TBI. Most Th1_pex cells are positioned at the end of the developmental trajectory and are regulated by key genes associated with apoptosis and early exhaustion, such as GADD45B, FOS, and EZH2. Oxidative stress-induced metabolic disorder, marked by increased metabolism of nitrogen, cysteine, and glutathione, also contributes to the apoptosis of Th1_pex cells. Using seven features including NA, CM, EM, EMRA, CXCR3+ Th1, IFN-γ+ Th1, and Tfh of CD154+CD4+ T cells, both TBD and TBI can be classified into different subtypes, and a further established random forest model can accurately differentiate TBD from TBI. Additionally, the key checkpoints of exhausted MTB-specific Th1 cells are identified and blocking ADORA2A efficiently restores their function.
Conclusions
We depict the cellular compositions, transcriptional characteristics, and developmental trajectories of MTB-specific CD154+CD4+ T cells from TBI to TBD, putting forward a new direction in the diagnosis and prognosis of disease.
{"title":"Clustering Mycobacterium tuberculosis-specific CD154+CD4+ T cells for distinguishing tuberculosis disease from infection based on single-cell RNA-seq analysis","authors":"Xiaochen Wang , Kaishan Jiang , Wenjin Xing , Qiudan Xin , Qiongjie Hu , Shiji Wu , Ziyong Sun , Hongyan Hou , Yi Ren , Feng Wang","doi":"10.1016/j.jinf.2025.106449","DOIUrl":"10.1016/j.jinf.2025.106449","url":null,"abstract":"<div><h3>Background</h3><div>Distinguishing between active tuberculosis disease (TBD) and latent tuberculosis infection (TBI) is crucial for TB control but remains challenging.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing was conducted on purified <em>Mycobacterium tuberculosis</em> (MTB)-specific CD154<sup>+</sup>CD4<sup>+</sup> T cells.</div></div><div><h3>Results</h3><div>We observe a superior role of CD154 in detecting MTB infection, whereas its ability in distinguishing TBD from TBI is still limited due to patient heterogeneity. Single-cell RNA sequencing of MTB-specific CD154<sup>+</sup>CD4<sup>+</sup> T cells identifies 10 distinct clusters, including Treg, T_act, Th1_pex, Th1_eff, Tfh, T_na, Th17_ex, Th2, NKT, and Th1_cyt. Notably, effector and apoptotic Th1 cells are predominant in CD154<sup>+</sup>CD4<sup>+</sup> T cells of TBD. However, Tfh cells are the primary component in TBI. Most Th1_pex cells are positioned at the end of the developmental trajectory and are regulated by key genes associated with apoptosis and early exhaustion, such as GADD45B, FOS, and EZH2. Oxidative stress-induced metabolic disorder, marked by increased metabolism of nitrogen, cysteine, and glutathione, also contributes to the apoptosis of Th1_pex cells. Using seven features including NA, CM, EM, EMRA, CXCR3<sup>+</sup> Th1, IFN-γ<sup>+</sup> Th1, and Tfh of CD154<sup>+</sup>CD4<sup>+</sup> T cells, both TBD and TBI can be classified into different subtypes, and a further established random forest model can accurately differentiate TBD from TBI. Additionally, the key checkpoints of exhausted MTB-specific Th1 cells are identified and blocking ADORA2A efficiently restores their function.</div></div><div><h3>Conclusions</h3><div>We depict the cellular compositions, transcriptional characteristics, and developmental trajectories of MTB-specific CD154<sup>+</sup>CD4<sup>+</sup> T cells from TBI to TBD, putting forward a new direction in the diagnosis and prognosis of disease.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106449"},"PeriodicalIF":14.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.jinf.2025.106447
Nadia Mazarakis , Zheng Quan Toh , Eleanor Neal , Kathryn Bright , Skyy Luu , Leanne Quah , Yan Yung Ng , Cattram Nguyen , John Hart , Lien Anh Ha Do , Anna Rudel , Shashini Dassanayake , Rachel A. Higgins , Darren Suryawijaya Ong , Fran Justice , Kerryn A. Moore , Emma Watts , Siddhartha Mahanty , Kanta Subbarao , Kim Mulholland , Paul V. Licciardi
Objectives
We conducted a randomised controlled trial (RCT) to compare immunogenicity, reactogenicity and safety one month after a fourth COVID-19 mRNA or protein vaccine dose.
Methods
This RCT recruited healthy adults in Melbourne, Australia, who had previously received three COVID-19 vaccine doses at least six months prior and had no SARS-CoV-2 infection in the last three months. The participants were randomised (1:1) to receive the bivalent mRNA vaccine (mRNA-1273.214/mRNA-1273.222, hereafter Moderna) or protein vaccine (NVX-CoV-2373, hereafter Novavax) as a fourth dose. A self-selected control group who elected not to receive an additional dose were also included. The co-primary endpoints compared immunogenicity at 28 days post-vaccination measured as binding antibodies (IgG against Ancestral and Omicron subvariants; BA.1, BA.4/5 and JN.1) between the two vaccine groups, and reactogenicity within one-week post-vaccination. ClinicalTrials.gov Identifier: NCT05543356.
Results
Between Feb 28 and Oct 4, 2023, 496 participants were enrolled into the study. Participants were randomised into either the bivalent mRNA Moderna (n=177) or protein Novavax (n=176) vaccine groups, with n=143 allocated to the control group. The geometric mean ratio (GMR) of anti-Spike binding IgG antibody levels were higher for the Moderna vaccine compared to the Novavax vaccine at 28 days post-vaccination for all variants tested, including Ancestral (GMR: 2.11, 95% CI: 1.88 – 2.37), BA.1 (GMR: 2.32, 95% CI 2.04 – 2.63), BA.4/5 (GMR: 2.32, 95% CI: 2.04 – 2.65), and JN.1 (GMR: 2.40, 95% CI: 2.14 – 2.70). The frequency of any local and systemic reactions (grades 1–4) was higher for the Moderna vaccine (159/177; 89.8%) compared to the Novavax vaccine (130/176; 73.9%). Serious reactions (grade 3–4) between the groups were similar (11/177; 6.2%, versus 9/176; 5.1%, respectively).
Conclusion
At day 28 post-vaccination, higher immunogenicity was observed following Moderna vaccination compared to Novavax vaccination when given as a fourth dose in healthy adults for Ancestral and Omicron subvariants, including JN.1. However, local and systemic reactogenicity was higher in the Moderna vaccine group compared with the Novavax vaccine group. These results may have important implications for ongoing booster strategies.
{"title":"The immunogenicity, reactogenicity, and safety of a bivalent mRNA or protein COVID-19 vaccine given as a fourth dose","authors":"Nadia Mazarakis , Zheng Quan Toh , Eleanor Neal , Kathryn Bright , Skyy Luu , Leanne Quah , Yan Yung Ng , Cattram Nguyen , John Hart , Lien Anh Ha Do , Anna Rudel , Shashini Dassanayake , Rachel A. Higgins , Darren Suryawijaya Ong , Fran Justice , Kerryn A. Moore , Emma Watts , Siddhartha Mahanty , Kanta Subbarao , Kim Mulholland , Paul V. Licciardi","doi":"10.1016/j.jinf.2025.106447","DOIUrl":"10.1016/j.jinf.2025.106447","url":null,"abstract":"<div><h3>Objectives</h3><div>We conducted a randomised controlled trial (RCT) to compare immunogenicity, reactogenicity and safety one month after a fourth COVID-19 mRNA or protein vaccine dose.</div></div><div><h3>Methods</h3><div>This RCT recruited healthy adults in Melbourne, Australia, who had previously received three COVID-19 vaccine doses at least six months prior and had no SARS-CoV-2 infection in the last three months. The participants were randomised (1:1) to receive the bivalent mRNA vaccine (mRNA-1273.214/mRNA-1273.222, hereafter Moderna) or protein vaccine (NVX-CoV-2373, hereafter Novavax) as a fourth dose. A self-selected control group who elected not to receive an additional dose were also included. The co-primary endpoints compared immunogenicity at 28 days post-vaccination measured as binding antibodies (IgG against Ancestral and Omicron subvariants; BA.1, BA.4/5 and JN.1) between the two vaccine groups, and reactogenicity within one-week post-vaccination. ClinicalTrials.gov Identifier: NCT05543356.</div></div><div><h3>Results</h3><div>Between Feb 28 and Oct 4, 2023, 496 participants were enrolled into the study. Participants were randomised into either the bivalent mRNA Moderna (n=177) or protein Novavax (n=176) vaccine groups, with n=143 allocated to the control group. The geometric mean ratio (GMR) of anti-Spike binding IgG antibody levels were higher for the Moderna vaccine compared to the Novavax vaccine at 28 days post-vaccination for all variants tested, including Ancestral (GMR: 2.11, 95% CI: 1.88 – 2.37), BA.1 (GMR: 2.32, 95% CI 2.04 – 2.63), BA.4/5 (GMR: 2.32, 95% CI: 2.04 – 2.65), and JN.1 (GMR: 2.40, 95% CI: 2.14 – 2.70). The frequency of any local and systemic reactions (grades 1–4) was higher for the Moderna vaccine (159/177; 89.8%) compared to the Novavax vaccine (130/176; 73.9%). Serious reactions (grade 3–4) between the groups were similar (11/177; 6.2%, versus 9/176; 5.1%, respectively).</div></div><div><h3>Conclusion</h3><div>At day 28 post-vaccination, higher immunogenicity was observed following Moderna vaccination compared to Novavax vaccination when given as a fourth dose in healthy adults for Ancestral and Omicron subvariants, including JN.1. However, local and systemic reactogenicity was higher in the Moderna vaccine group compared with the Novavax vaccine group. These results may have important implications for ongoing booster strategies.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106447"},"PeriodicalIF":14.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.jinf.2025.106448
Philippe Ndzomo , Ala-Eddine Deghmane , Serges Tchatchouang , Rosanne Ngome , Aude Terrade , Mélanie Denizon , Michaël Falguieres , Oumar Doucoure , Tania Crucitti , Onana Boyomo , Michael Marks , Sara Eyangoh , Muhamed-Kheir Taha
Background
Haemophilus ducreyi, traditionally recognized as the etiological agent of chancroid, a genital ulcer disease, is increasingly being identified as a significant cause of cutaneous ulcers in yaws-endemic regions across the South Pacific, Southeast Asia, and Sub-Saharan Africa. Despite its clinical relevance, this pathogen remains poorly characterized, and comprehensive genetic tools for analyzing isolate relationships are still lacking.
Methods
In this study, we present a follow-up of our previous research and developed a multilocus sequence typing (MLST) approach based on six of the seven loci from the Haemophilus influenzae MLST scheme and applied it to 82 primary clinical samples, previously confirmed to contain H. ducreyi, without culture. We also performed whole-genome sequencing (WGS) and antibiotic susceptibility testing on four cultured isolates obtained from cutaneous ulcers in yaws endemic health districts of Cameroon.
Results
Antibiotic susceptibility testing of H. ducreyi cultured isolates revealed sensitivity to all tested antibiotics, including ceftriaxone, azithromycin, and ciprofloxacin. MLST analysis, using data extracted from WGS and directly from clinical samples, identified 38 complete profiles across the six loci (34 from direct samples and four from cultured isolates), identifying 14 distinct sequence types (STs). BURST analysis of the six MLST genes grouped the STs into two distinct clonal complexes. An additional, polymorphism was observed in the ftsI gene, which encodes the penicillin-binding protein 3.
Conclusions
This study highlights the need for genetic typing of H. ducreyi strains circulating in the yaws-endemic regions of Cameroon. The developed MLST scheme offered effective strain discrimination and provided valuable insights into their genetic relationships in these areas.
{"title":"Genetic characterization of Haemophilus ducreyi from non-genital skin lesions in Cameroon","authors":"Philippe Ndzomo , Ala-Eddine Deghmane , Serges Tchatchouang , Rosanne Ngome , Aude Terrade , Mélanie Denizon , Michaël Falguieres , Oumar Doucoure , Tania Crucitti , Onana Boyomo , Michael Marks , Sara Eyangoh , Muhamed-Kheir Taha","doi":"10.1016/j.jinf.2025.106448","DOIUrl":"10.1016/j.jinf.2025.106448","url":null,"abstract":"<div><h3>Background</h3><div><em>Haemophilus ducreyi</em>, traditionally recognized as the etiological agent of chancroid, a genital ulcer disease, is increasingly being identified as a significant cause of cutaneous ulcers in yaws-endemic regions across the South Pacific, Southeast Asia, and Sub-Saharan Africa. Despite its clinical relevance, this pathogen remains poorly characterized, and comprehensive genetic tools for analyzing isolate relationships are still lacking.</div></div><div><h3>Methods</h3><div>In this study, we present a follow-up of our previous research and developed a multilocus sequence typing (MLST) approach based on six of the seven loci from the <em>Haemophilus influenzae</em> MLST scheme and applied it to 82 primary clinical samples, previously confirmed to contain <em>H. ducreyi</em>, without culture. We also performed whole-genome sequencing (WGS) and antibiotic susceptibility testing on four cultured isolates obtained from cutaneous ulcers in yaws endemic health districts of Cameroon<em>.</em></div></div><div><h3>Results</h3><div>Antibiotic susceptibility testing of <em>H. ducreyi</em> cultured isolates revealed sensitivity to all tested antibiotics, including ceftriaxone, azithromycin, and ciprofloxacin. MLST analysis, using data extracted from WGS and directly from clinical samples, identified 38 complete profiles across the six loci (34 from direct samples and four from cultured isolates), identifying 14 distinct sequence types (STs). BURST analysis of the six MLST genes grouped the STs into two distinct clonal complexes. An additional, polymorphism was observed in the <em>ftsI</em> gene, which encodes the penicillin-binding protein 3.</div></div><div><h3>Conclusions</h3><div>This study highlights the need for genetic typing of <em>H. ducreyi</em> strains circulating in the yaws-endemic regions of Cameroon. The developed MLST scheme offered effective strain discrimination and provided valuable insights into their genetic relationships in these areas.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106448"},"PeriodicalIF":14.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1016/j.jinf.2025.106445
Xu Wang , Yan Kui , Chui-Zhao Xue , Qian Wang , Can-Jun Zheng , Jiang-Shan Zhao , Ya-Ming Yang , Xiao-Feng Jiang , Qu-Zhen Gong-Sang , Xiao Ma , Yu Feng , Xiang-Lin Wu , Sa Chen , Fan-Ka Li , Wen-Jie Yu , Ben-Fu Li , Bai-Xue Liu , Ying Wang , Li-Ying Wang , Shi-Jie Yang , Jian-Ping Cao
Objectives
We evaluated the epidemiological characteristics of echinococcosis, a global public health threat, in China to inform global control efforts.
Methods
Descriptive, statistical, cluster, spatial, and trend analyses were used to evaluate the epidemiology at national, provincial, and county levels based on 2004–2022 nationwide surveillance data from China.
Results
Between 2004 and 2022, China recorded 72,676 cystic echinococcosis (CE) cases, 11,465 alveolar echinococcosis (AE) cases, and 5703 others, with an average annual cases per million (ANpM) of 3.45. Females had a higher incidence (ANpM = 3.87) than males (3.05), with most cases (41.15%) in the 30–49 age group, mainly among herders (38.76%) and farmers (37.82%). Seven provinces (Xizang, Qinghai, Xinjiang, Ningxia, Gansu, Sichuan, and Inner Mongolia) accounted for 98.12% of cases, with the Tibetan Plateau showing the highest rates (ANpMs = 155.51 for CE, 46.95 for AE). Surgery and case fatality rates were 39.45% and 5.23% in key surveillance regions (KSRs). Prevalence among residents (0.20%), livestock (1.33%), rodents (1.30%), and dogs (1.26%) declined with increased control funding in KSRs. Between 2023 and 2030, there will be an estimated 20,096 new cases and 45,323 cases requiring treatment.
Conclusion
The prevalence of echinococcosis has been alleviated in China, but significant control challenges remain, requiring sustained and targeted control measures.
{"title":"Past, present and future epidemiology of echinococcosis in China based on nationwide surveillance data 2004–2022","authors":"Xu Wang , Yan Kui , Chui-Zhao Xue , Qian Wang , Can-Jun Zheng , Jiang-Shan Zhao , Ya-Ming Yang , Xiao-Feng Jiang , Qu-Zhen Gong-Sang , Xiao Ma , Yu Feng , Xiang-Lin Wu , Sa Chen , Fan-Ka Li , Wen-Jie Yu , Ben-Fu Li , Bai-Xue Liu , Ying Wang , Li-Ying Wang , Shi-Jie Yang , Jian-Ping Cao","doi":"10.1016/j.jinf.2025.106445","DOIUrl":"10.1016/j.jinf.2025.106445","url":null,"abstract":"<div><h3>Objectives</h3><div>We evaluated the epidemiological characteristics of echinococcosis, a global public health threat, in China to inform global control efforts.</div></div><div><h3>Methods</h3><div>Descriptive, statistical, cluster, spatial, and trend analyses were used to evaluate the epidemiology at national, provincial, and county levels based on 2004–2022 nationwide surveillance data from China.</div></div><div><h3>Results</h3><div>Between 2004 and 2022, China recorded 72,676 cystic echinococcosis (CE) cases, 11,465 alveolar echinococcosis (AE) cases, and 5703 others, with an average annual cases per million (ANpM) of 3.45. Females had a higher incidence (ANpM = 3.87) than males (3.05), with most cases (41.15%) in the 30–49 age group, mainly among herders (38.76%) and farmers (37.82%). Seven provinces (Xizang, Qinghai, Xinjiang, Ningxia, Gansu, Sichuan, and Inner Mongolia) accounted for 98.12% of cases, with the Tibetan Plateau showing the highest rates (ANpMs = 155.51 for CE, 46.95 for AE). Surgery and case fatality rates were 39.45% and 5.23% in key surveillance regions (KSRs). Prevalence among residents (0.20%), livestock (1.33%), rodents (1.30%), and dogs (1.26%) declined with increased control funding in KSRs. Between 2023 and 2030, there will be an estimated 20,096 new cases and 45,323 cases requiring treatment.</div></div><div><h3>Conclusion</h3><div>The prevalence of echinococcosis has been alleviated in China, but significant control challenges remain, requiring sustained and targeted control measures.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106445"},"PeriodicalIF":14.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}