Tuberculosis最新文献

{"title":"Low-fitness rpoB mutations in rifampicin-resistant Mycobacterium tuberculosis: Host immunity, compensatory evolution, and diagnostic challenges.","authors":"Mavera Mukhtar, Ashok Aspatwar","doi":"10.1016/j.tube.2026.102812","DOIUrl":"https://doi.org/10.1016/j.tube.2026.102812","url":null,"abstract":"<p><strong>Background: </strong>The rpoB S450L mutation is the most prevalent high-fitness rifampicin resistance-conferring mutation in Mycobacterium tuberculosis. However, numerous alternative rpoB mutations associated with varying fitness costs have been reported, particularly in specific clinical settings. This systematic review critically evaluates the relationship between low-fitness rpoB mutations, host immune status, HIV co-infection, compensatory evolution, and diagnostic discordance.</p><p><strong>Methods: </strong>A systematic literature search was conducted across multiple scientific databases. Studies reporting genetic, phenotypic, structural, or clinical data on rifampicin-resistant M. tuberculosis carrying alternative or borderline rpoB mutations were included. Data were qualitatively synthesized to examine associations among host immune status, bacterial fitness, compensatory evolution, and diagnostic performance.</p><p><strong>Results: </strong>Twenty-one studies met the inclusion criteria. Available clinical evidence indicated a higher prevalence of low-fitness non-S450L rpoB mutations, particularly at codons 430, 435, 441, and 445, among patients with advanced HIV infection. The available evidence suggests that HIV-associated immunosuppression may reduce host-driven purifying selection, facilitating the persistence of low-fitness resistant variants. Genomic and structural studies identified compensatory mutations in rpoA, rpoB, and rpoC that may partially restore bacterial fitness while maintaining rifampicin resistance. Several borderline rpoB mutations also produced discordant results between molecular assays and phenotypic drug susceptibility testing.</p><p><strong>Conclusion: </strong>HIV-associated immunosuppression may influence the evolutionary trajectory of rifampicin-resistant M. tuberculosis by facilitating the persistence of low-fitness rpoB mutations. Integrating molecular diagnostics, genomic surveillance, and host immune profiling may improve the detection and clinical management of rifampicin-resistant tuberculosis, particularly in regions with a high burden of TB-HIV co-infection.</p>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"161 ","pages":"102812"},"PeriodicalIF":2.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel plasma biomarkers for the diagnosis of pulmonary tuberculosis","authors":"Camila P. Sobrinho ,&nbsp;Luana E. Araújo ,&nbsp;Rodrigo L. Meira ,&nbsp;Thainá Horta ,&nbsp;Silvania Cerqueira ,&nbsp;Flávia Marília Fonseca Oliveira ,&nbsp;Jéssica Petrilli ,&nbsp;Sérgio Arruda ,&nbsp;Adriano Queiroz","doi":"10.1016/j.tube.2026.102733","DOIUrl":"10.1016/j.tube.2026.102733","url":null,"abstract":"<div><div>The World Health Organization (WHO) has highlighted the need for new diagnostic tests for pulmonary tuberculosis (TB) that use easily obtainable samples, such as blood, to provide rapid and affordable results suitable for primary healthcare settings. To address this, we evaluated the diagnostic potential of 34 markers quantified by Luminex in supernatants of whole-blood cultures, either stimulated or not with an apolar lipid extract from <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>). The study included 20 patients with pulmonary TB and 20 symptomatic respiratory (SR) non-TB individuals. In unstimulated cultures, eight biomarkers (IL-18, IL-1RA, IL-1β, IL-8, IP-10, MIP-1β, SDF-1α, and TNF-α) differentiated TB patients from SR - non-TB patients, with areas under the ROC curve (AUC) ranging from 0.71 to 0.82. Combinatorial analyses with four-marker panels, namely, IL-18 + IL-1β, IL-1RA + IL-18, IL-18 + IL-1β + IL-1RA and IL-18 + IL-1β + IL-1RA + MIP-1β, revealed AUCs of 0.84–0.90, specificities above 90 % and sensitivities between 70 % and 75 %. The addition of the lipid extract to the whole-blood culture did not improve the discriminatory power of the panels. Validation of the IL-1RA + IL-18 combination by ELISA in an independent group (21 TB patients and 33 SR patients) yielded an AUC of 0.76, a sensitivity of 62 %, a specificity of 88 %, and an accuracy of 78 %. The collective elevation of these cytokines suggests an interplay between pro- and anti-inflammatory pathways in the host response. Although the selected biomarker panels showed moderate diagnostic performance in the ELISA test, other combinations may be useful in helping to predict TB progression or monitor treatment outcomes.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102733"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic insights into the adaptation of Mycobacterium bovis to hypoxic conditions","authors":"María Mercedes Bigi ,&nbsp;Magdalena Portela ,&nbsp;Laura Inés Klepp ,&nbsp;Elizabeth Andrea García ,&nbsp;Qi Zhang ,&nbsp;Sen Wang ,&nbsp;Jinlong Bei ,&nbsp;Rosario Durán ,&nbsp;Fabiana Bigi","doi":"10.1016/j.tube.2026.102739","DOIUrl":"10.1016/j.tube.2026.102739","url":null,"abstract":"<div><div>Bovine tuberculosis (bTB) is an important cattle disease with major public health and economic impacts. <em>Mycobacterium bovis</em>, its causative agent, is thought to persist in non-replicative forms within the host, similar to <em>Mycobacterium tuberculosis</em>, leading to chronic or latent infection. In this study, we used the Wayne model—an in vitro system that gradually depletes oxygen—to mimic the hypoxic conditions <em>M. bovis</em> may encounter during latency. Growth analysis showed that part of the bacterial culture remained viable but non-replicative under hypoxia, while another fraction likely lysed, as indicated by declining optical density during late hypoxia and reduced colony-forming units.</div><div>Secreted proteome analysis identified 36 proteins detected exclusively in culture supernatants, with Cut3, SapM, and Cdh accumulating more under hypoxia (p &lt; 0.05, FDR = 0.25). In the cellular proteome, 288 proteins showed differential accumulation (p &lt; 0.05, FDR = 0.25), with 172 more abundant under hypoxia. Under oxygen depletion, <em>M. bovis</em> increased proteins related to nitrogen and lipid metabolism, purine biosynthesis, carbon metabolism, anaplerotic pathways, and several DosR regulon proteins. Aerated cultures showed higher levels of proteins involved in transcription, translation, DNA replication, and virulence. Protein secretion decreased under hypoxia. Overall, <em>M. bovis</em> remodels its proteome to persist in a viable, non-replicative state.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102739"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics reveals phenotypic and functional alterations of erythroid progenitor cells in tuberculosis patients","authors":"Hao Zhang ,&nbsp;Yan Cao ,&nbsp;Ling Yang ,&nbsp;Bowen Liu ,&nbsp;Jingzhi Guan ,&nbsp;Xinjing Wang","doi":"10.1016/j.tube.2026.102746","DOIUrl":"10.1016/j.tube.2026.102746","url":null,"abstract":"<div><div>Anemia is a common complication of tuberculosis (TB), closely associated with impaired host immune function and poor prognosis; however, its impact on the dynamic alterations of erythroid progenitor cells (EPCs) remains largely unexplored. In this study, we integrated and analyzed single-cell transcriptomic data from peripheral blood mononuclear cells (PBMC) of healthy controls, latent tuberculosis (LTB), TB, and disseminated tuberculosis (DTB) cohorts, as well as 18F-FDG-labeled TB lung tissues and adjacent uninvolved regions. At single-cell resolution, we identified ten EPCs clusters within PBMC, among which clusters 2–6 represented DTB-specific subpopulations (EPC_DTB). These EPC_DTB exhibited metabolic reprogramming (including glycolysis, arginine, and lipid metabolism) accompanied by upregulation of IFITM3/JUN and ribosomal genes, consistent with enhanced differentiation. EPC_DTB and EPC_TB interacted with macrophages, dendritic cells, and monocytes through the ANNEXIN and GALECTIN signaling pathways, while these immune cells reciprocally regulated EPCs subsets via the MIF signaling axis. In lung tissues, EPCs (12 clusters) displayed disease-specific characteristics, with clusters 0, 3, and 6 uniquely present in TB lesions. The EPC_High subpopulation within inflammatory foci showed significant upregulation of GZMA, IL32, CCL5, and CHI3L1, whereas EPC_Low communicated with immune cells, epithelial cells, and stromal cells through the MDK–NCL signaling pathway. Moreover, we established an LTB predictive model based on EPC_LTB signature genes in PBMC (GRIK3, S100B, ZDHHC19, and LRRN3). Our study uncovers the heterogeneity of EPCs across different TB stages and tissue compartments, delineates their bidirectional crosstalk with immune cells, and establishes a link among anemia, immune regulation, and EPCs biology, thereby proposing potential diagnostic biomarkers and therapeutic targets.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102746"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migrations and Tuberculosis: A comparative study of Mycobacterium tuberculosis genomic population structure in Brazil and Mozambique to historical triangular slave trade knowledge to reconstruct the origins of tuberculosis infections caused by Lineage 1 in Brazil","authors":"Thibaut Morel-Journel ,&nbsp;Christophe Guyeux ,&nbsp;Christophe Sola","doi":"10.1016/j.tube.2026.102734","DOIUrl":"10.1016/j.tube.2026.102734","url":null,"abstract":"<div><div>Lineage 1 is an ancestral lineage of the <em>Mycobacterium tuberculosis</em> complex (MTBC) comprising five sublineages. In a previous study, we suggested that a representative of sublineage L1.1.3, present in both Mozambique and northern Brazil, SIT129, may have been brought to Brazil by sea during the long history of slavery that lasted, between Africa and Brazil, from the early 16th century to the mid-19th century. In this study, using a combination of new comparative genomics results and human migration data extracted from the <span><span>SlaveVoyages.org</span><svg><path></path></svg></span> database, we sought to more precisely reconstruct the scenario for the introduction of L1 genotypes into Brazil. We present results showing substantial similarities between the MTBC population structure in present-day Mozambique and Brazil across three subclades, L1.1.2, L1.1.3, and L1.2.2, and convergent historical data. Indeed, several introductions between the 16th and 19th centuries could explain the higher contemporary prevalence of L1 in northern Brazil. Our data do not allow us to decide between a direct introduction of L1 isolates into northern Brazil and intra-Brazilian transmission from the main southern ports, which seems likely. Other less likely scenarios are also discussed.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102734"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic evaluation of a novel recombinant multi-epitope protein for paucibacillary and multibacillary leprosy","authors":"César N. Pereira ,&nbsp;Raquel S.B. Câmara ,&nbsp;Daniela P. Lage ,&nbsp;Laís V.A. Corrêa ,&nbsp;Camila S. Freitas ,&nbsp;Ana L. Silva ,&nbsp;Nathália C. Galvani ,&nbsp;Mariana M. Cardoso ,&nbsp;Bárbara P.N. Assis ,&nbsp;Miguel A. Chávez-Fumagalli ,&nbsp;Ricardo A. Machado-de-Ávila ,&nbsp;Alexsandro S. Galdino ,&nbsp;Unaí Tupinambás ,&nbsp;Lílian L. Bueno ,&nbsp;Ricardo T. Fujiwara ,&nbsp;Manoel O. da Costa Rocha ,&nbsp;Denise U. Gonçalves ,&nbsp;Myron Christodoulides ,&nbsp;Ana T. Chaves ,&nbsp;Eduardo A.F. Coelho ,&nbsp;Isabela A.G. Pereira","doi":"10.1016/j.tube.2026.102732","DOIUrl":"10.1016/j.tube.2026.102732","url":null,"abstract":"<div><div>The diagnosis of leprosy remains challenging due to its clinical similarity with other infectious diseases and the variable sensitivity and specificity of current laboratory tests. Therefore, the identification and/or development of novel antigens is crucial for improving diagnostic accuracy. In this study, we designed a novel recombinant multi-polypeptide construct, termed M3, which was composed of specific B-cell epitopes from nine <em>Mycobacterium leprae</em> proteins, previously shown to be antigenic in leprosy. The recombinant M3 protein was expressed, purified, and evaluated as an antigen for the diagnosis of both paucibacillary (PB) and multibacillary (MB) disease, by using paired serum and urine samples from 380 participants. ELISA was performed using samples from PB (n = 50) and MB (n = 55) leprosy patients, their household contacts [PBC (n = 30) and MBC (n = 40), respectively], healthy individuals living in endemic region (n = 55), and patients with visceral (n = 30) and tegumentary (n = 45) leishmaniasis, Chagas disease (n = 35), tuberculosis (n = 15), and HIV-infection (n = 25). In serum-based ELISA, M3 showed sensitivity, specificity, positive and negative predictive values, and Youden index of 94.5 %, 100 %, 96.8 %, 97.4 %, and 0.91, respectively; whilst in a urine-based ELISA, the corresponding values were 96.4 %, 100 %, 98.8 %, 98.2 %, and 0.96, respectively. Additionally, paired serum and urine samples from 15 PB and 20 MB patients collected before and after treatment, revealed that anti-M3 antibodies decreased by more than 50 % post-therapy when using both analytes. These pilot findings suggest a potential biological role of the recombinant M3 protein for diagnosis of PB and MB leprosy.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102732"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Dysregulated IFN-γ, IL-6 and TNF α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB”","authors":"Prashant Ramdas Kokiwar,&nbsp;Ambreen Singh Chauhan,&nbsp;A. Kavya,&nbsp;Archana Dhyani","doi":"10.1016/j.tube.2026.102737","DOIUrl":"10.1016/j.tube.2026.102737","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102737"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to comments for: Dysregulated IFN-γ, IL-6 and TNF-α after COVID-19 is suggestive of lowered innate immune responses to SARS-CoV-2 and MTB","authors":"Uzair Abbas ,&nbsp;Kiran Iqbal Masood ,&nbsp;Tulaib Iqbal ,&nbsp;Shama Qaiser ,&nbsp;Martin Rottenberg ,&nbsp;Bushra Jamil ,&nbsp;Rabia Hussain ,&nbsp;Zahra Hasan","doi":"10.1016/j.tube.2026.102738","DOIUrl":"10.1016/j.tube.2026.102738","url":null,"abstract":"","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102738"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of programmed cell death pathways in the host response to Mycobacterium tuberculosis: Insights from gene expression analysis in active pulmonary tuberculosis patients","authors":"Qifeng Li ,&nbsp;Maierheba Kuerbanjiang ,&nbsp;Jianfeng Zhang ,&nbsp;Dan Chen ,&nbsp;Gaofeng Sun ,&nbsp;Zhigang Liu","doi":"10.1016/j.tube.2026.102741","DOIUrl":"10.1016/j.tube.2026.102741","url":null,"abstract":"<div><div>Tuberculosis, primarily caused by <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), remains a leading global health issue. We investigate the interplay between <em>Mtb</em> infection and various programmed cell death (PCD) in active pulmonary tuberculosis (ATB). Using GSE19491 and GSE107994 datasets, we identified 1306 overlapping differentially expressed genes (DEGs) in peripheral blood from ATB patients and healthy controls. Gene set variation analysis revealed that, except for cuproptosis, the PCD pathways: necroptosis, apoptosis, pyroptosis, and ferroptosis were significantly elevated in ATB patients. Weighted Gene Co-expression Network Analysis further identified 392 PCD-associated hub genes. KEGG and GO analyses highlighted key functional enrichments in immune responses, cellular stress, and PCD pathways. Moreover, we found a positive correlation between PCD types and specific immune cell populations. Additionally, by integrating DEGs of peripheral blood samples and lung granuloma tissues with PCD-associated hub genes, we identified 30 PCD-related genes in ATB patients. RT-qPCR results demonstrated significantly elevated GCLC, RBCK1, ZEB1, and EIF2AK2 levels, alongside lowered PLA2G4C and CAMK2G levels in patients’ peripheral blood. These findings underscore the critical role of PCD pathways in modulating the immune response during <em>Mtb</em> infection. Future mechanistic studies are required to definitively establish the causal roles of these pathways in regulating cell death and bacterial control.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102741"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse zoonosis in bovine tuberculosis: The neglected threat of Mycobacterium tuberculosis infection in cattle","authors":"Vaishnavi Vivekanandan ,&nbsp;Arun K ,&nbsp;Sindhu Hasini Doredla ,&nbsp;Harini Ramanujam ,&nbsp;Ranjani Singaraj ,&nbsp;Kannan Palaniyandi","doi":"10.1016/j.tube.2026.102731","DOIUrl":"10.1016/j.tube.2026.102731","url":null,"abstract":"<div><div>Tuberculosis (TB), caused by members of the <em>Mycobacterium tuberculosis</em> complex (MTBC), remains a significant global health concern. While zoonotic transmission of <em>M. bovis</em> from cattle to humans is well documented, reverse zoonotic transmission of <em>M. tuberculosis</em> from humans to cattle has received far less attention. This review provides the first comprehensive synthesis of <em>M. tuberculosis</em> infections in cattle, drawing on evidence from farms, households, and slaughterhouses where human–animal contact is most intense. Available data indicate that such spillover events are uncommon compared with <em>M. bovis</em> infection, and that infectious humans—via aerosols or sputum-contaminated feed or environments—represent the primary, and likely exclusive source of infection for cattle, as no sustained cattle-to-cattle transmission has been reported. Experimental <em>M. tuberculosis</em> infection in cattle consistently demonstrates an attenuated phenotype, with mild pathology and low bacterial loads. However, the identification of multidrug-resistant and pre–extensively drug-resistant <em>M. tuberculosis</em> strains in cattle raises a potential future concern regarding cross-species transmission, despite the fact that transmission back to humans has not been observed yet. Enhancing routine molecular diagnostics is vital for precise MTBC differentiation and a better grasp of cross-species transmission dynamics. A unified One Health strategy, which combines human, animal, and environmental monitoring, is essential to track and address this emerging threat.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102731"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}