{"title":"Subcellular particles for characterization of host-parasite interactions","authors":"","doi":"10.1016/j.micinf.2024.105314","DOIUrl":"10.1016/j.micinf.2024.105314","url":null,"abstract":"<div><p><span>Parasitic diseases remain a major global health problem for humans. </span>Parasites<span><span><span> employ a variety of strategies to invade and survive within their hosts and to manipulate host defense mechanisms, always in the pathogen's favor. Extracellular vesicles (EVs), membrane-bound </span>nanospheres carrying a variety of bioactive compounds, were shown to be released by the parasites during all stages of the infection, enabling growth and expansion within the host and adaptation to frequently changing environmental stressors. In this review, we discuss how the use of existing nanotechnologies and high-resolution imaging tools assisted in revealing the role of EVs during </span>parasitic infections<span><span>, enabling the quantitation, visualization, and detailed characterization of EVs. We discuss here the cases of malaria, Chagas disease<span> and leishmaniasis as examples of parasitic </span></span>neglected tropical diseases (NTDs). Unraveling the EVs' role in the NTD pathogenesis may enormously contribute to their early and reliable diagnostic, effective treatment, and prevention.</span></span></p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 7","pages":"Article 105314"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NMR spectroscopy can help accelerate antiviral drug discovery programs","authors":"","doi":"10.1016/j.micinf.2024.105297","DOIUrl":"10.1016/j.micinf.2024.105297","url":null,"abstract":"<div><p>Small molecule drugs have an important role to play in combating viral infections, and biophysics support has been central for contributing to the discovery and design of direct acting antivirals. Perhaps one of the most successful biophysical tools for this purpose is NMR spectroscopy when utilized strategically and pragmatically within team workflows and timelines. This report describes some clear examples of how NMR applications contributed to the design of antivirals when combined with medicinal chemistry, biochemistry, X-ray crystallography and computational chemistry. Overall, these multidisciplinary approaches allowed teams to reveal and expose compound physical properties from which design ideas were spawned and tested to achieve the desired successes. Examples are discussed for the discovery of antivirals that target HCV, HIV and SARS-CoV-2.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 7","pages":"Article 105297"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000170/pdfft?md5=57b09fb3bc626418211d24c90dad1ef4&pid=1-s2.0-S1286457924000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibodies anti-rFilF protein has anti-biofilm activity against carbapenem-resistant Acinetobacter baumannii","authors":"Isabel Ladeira Pereira , Thayná Laner Cardoso , Daniela Rodriguero Wozeak , Pamela Scaraffuni Caballero , Stella Buchhorn de Freitas , Amilton Clair Pinto Seixas Neto , Luciano da Silva Pinto , Daiane Drawanz Hartwig","doi":"10.1016/j.micinf.2024.105347","DOIUrl":"10.1016/j.micinf.2024.105347","url":null,"abstract":"<div><p><em>Acinetobacter baumannii</em> is an opportunistic bacterium that causes infection in several sites. Carbapenem-resistant <em>A. baumannii</em> strains (CRAb) lead the World Health Organization's list of 12 pathogens considered a priority for developing new antimicrobials. The pathogenicity of <em>A. baumannii</em> is related to the different virulence factors employed in the colonization of biotic and abiotic surfaces, biofilm formation and multidrug resistance. We analyze the outer membrane protein FilF from <em>A. baumannii in silico</em> and produce it in recombinant form (rFilF). rFilF protein was successfully expressed in <em>Escherichia coli</em> BL21 Star in an insoluble form. Immunization with rFilF induced significant anti-rFilF IgG antibody production in mice, detected by indirect enzyme-linked immunosorbent assay, since the first evaluation until 49th. On the last experimentation day, the predominant immunoglobulin found was IgG1 followed by IgG2a, IgG2b, IgM, IgG3, and IgA. We observe that interleukins 4 and 10 show significant production after the 28th day of experimentation in mice immunized with rFilF. Anti-rFilF pAbs were able to inhibit biofilm formation in nine CRAb strains evaluated, and in the standard strain ATCC® 19606. These results demonstrate the anti-biofilm activity of anti-rFilF antibodies, promising in the development of a non-antibiotic approach based on the control of CRAb strains.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105347"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Donor screening for fecal microbiota transplantation with a direct stool testing-based strategy: a prospective cohort study","authors":"Debora Rondinella , Gianluca Quaranta , Tommaso Rozera , Pasquale Dargenio , Giovanni Fancello , Irene Venturini , Alessandra Guarnaccia , Serena Porcari , Stefano Bibbò , Maurizio Sanguinetti , Antonio Gasbarrini , Luca Masucci , Giovanni Cammarota , Gianluca Ianiro","doi":"10.1016/j.micinf.2024.105341","DOIUrl":"10.1016/j.micinf.2024.105341","url":null,"abstract":"<div><p>Fecal microbiota transplantation (FMT) is effective against recurrent <em>Clostridioides difficile</em> infection (rCDI), but its safety is jeopardized by the potential transmission of pathogens, so international guidelines recommend either a quarantine or a direct stool testing. Whereas reports of the quarantine-based approach are emerging, data on the direct testing-based approach are not available. Our aim is to report outcomes of a donor screening framework for FMT including direct stool testing.</p><p>In this prospective cohort study, all donor candidates recruited at our FMT centre underwent a four-step screening process to be enrolled as actual donors. Each collected stool donation was then evaluated with a direct stool testing including a molecular assay for gut pathogens and a culture assay for multi-drug resistant organisms (MDRO).</p><p>From January 2019 to June 2023, 72 of 227 candidates (32%) were considered eligible and provided 277 stool donations. Ninety-nine donations (36%) were discarded for positivity to intestinal pathogens, most commonly enteropathogenic <em>Escherichia coli</em> (n = 37) and <em>Blastocystis hominis</em> (n = 20). Overall, 337 stool aliquots were obtained from 165 approved donations. All suspensions were used for patients with rCDI, and no serious adverse events or clinically evident infections were observed at 12 weeks after procedures.</p><p>In our study, screening of donor faeces including direct stool testing led to the discard of a considerable rate of stool donations but was also extremely safe. This approach may represent a reliable strategy to guarantee the safety of FMT programs, especially in countries with high prevalence of MDRO.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105341"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000716/pdfft?md5=5c2186591be258d997c7c256ea148c99&pid=1-s2.0-S1286457924000716-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuhong Chen , Jianqiang Ni , Chuanbin Wang , Xinyan Zhai , Tingrong Luo , Yi-Ping Li , Youchuan Wei , Yuliang Liu
{"title":"The proteomic analysis uncovers the cellular responses to the African swine fever virus membrane proteins p54, p17, and pB117L","authors":"Yuhong Chen , Jianqiang Ni , Chuanbin Wang , Xinyan Zhai , Tingrong Luo , Yi-Ping Li , Youchuan Wei , Yuliang Liu","doi":"10.1016/j.micinf.2024.105348","DOIUrl":"10.1016/j.micinf.2024.105348","url":null,"abstract":"<div><p>African swine fever virus (ASFV) infection causes African swine fever (ASF), a highly contagious and fatal disease that poses severe threat to swine production. To gain insights into the host responses to ASFV, we generated recombinant adenovirus Ad5 expressing viral membrane proteins p54, p17, and pB117L individually and infected an alveolar cell line, 3D4/21, with these recombinant viruses. Then, the cell lysates were analyzed using label-free quantification proteomic analysis method. A total of 2158 differentially expressed proteins (DEPs) were identified, of which 817, 466, and 875 proteins were from Ad5-p54-, Ad5-p17-, Ad5-pB117L-infected 3D4/21 cells, respectively. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed distinct yet interconnecting patterns of protein interaction networks. Specifically, the Ad5-p54 virus infection enriched the DEPs primarily involved in the metabolic pathways, endocytosis, adherens junction, and SNARE interactions in vesicular transport. The Ad5-p17 virus infection enriched the DEPs in endocytosis, ubiquitin-mediated proteolysis, N-Glycan biosynthesis, and apoptosis, while the Ad5-pB117L virus infection enriched the DEPs in metabolic pathways, endocytosis, oxidative phosphorylation, and focal adhesion. In summary, these results provide a comprehensive proteinomics analysis of the cellular responses to three ASFV membrane proteins, thus facilitating our understanding of ASFV pathogenesis.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105348"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000789/pdfft?md5=19258e15cfc39b5a36435f7e27ac5455&pid=1-s2.0-S1286457924000789-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justyna Śmiałek-Bartyzel , Monika Bzowska , Paweł Mak
{"title":"Pro-inflammatory properties of aureocin A53","authors":"Justyna Śmiałek-Bartyzel , Monika Bzowska , Paweł Mak","doi":"10.1016/j.micinf.2024.105365","DOIUrl":"10.1016/j.micinf.2024.105365","url":null,"abstract":"<div><p>Aureocin A53 is a peptide bacteriocin produced by an opportunistic pathogen <em>Staphylococcus aureus</em> strain A53. The spatial structure of aureocin, unlike its amino acid sequence, is similar to the bacteriocin BacSp222, which was recently found to have the ability to induce the inflammatory response in the host cells. The presented research aimed to verify such properties also for aureocin A53. We demonstrated that the synthetic aureocin has slight cytotoxic activity towards murine monocytic-macrophage cells. This molecule was also able to activate murine P388.D1 and RAW 264.7 cells to IFN-γ-dependent production of nitric oxide and to activate production of the pro-inflammatory cytokine - TNF. We also proved that the observed pro-inflammatory activity of the studied bacteriocin is related to the stimulation of the TLR2/TLR6 heterodimer and, consequently, activation of the NF-κB transcription factor. To sum up, A53 is the second bacteriocin described in the literature, showing the pro-inflammatory activity against murine macrophage-like cells.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105365"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924001011/pdfft?md5=5e9b9997e8982e314bfe2ca7e5411958&pid=1-s2.0-S1286457924001011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enam Reyaz , Rati Tandon , Mirza Adil Beg , Ranadhir Dey , Niti Puri , Poonam Salotra , Hira L. Nakhasi , A. Selvapandiyan
{"title":"Proteome profile of Leishmania donovani Centrin1−/− parasite-infected human macrophage cell line and its implications in determining possible mechanisms of protective immunity","authors":"Enam Reyaz , Rati Tandon , Mirza Adil Beg , Ranadhir Dey , Niti Puri , Poonam Salotra , Hira L. Nakhasi , A. Selvapandiyan","doi":"10.1016/j.micinf.2024.105340","DOIUrl":"10.1016/j.micinf.2024.105340","url":null,"abstract":"<div><p>Our developed cell division-specific ‘centrin’ gene deleted <em>Leishmania donovani</em> (<em>LdCen1</em><sup><em>−/−</em></sup>) the causative parasite of the fatal visceral-leishmaniasis (VL), exhibits a selective growth arrest at the intracellular stage and is anticipated as a live attenuated vaccine candidate against VL. <em>LdCen1</em><sup><em>−/−</em></sup> immunization in animals has shown increased IFN-γ secreting CD4+ and CD8+ T cells along with protection conferred by a protective proinflammatory immune response. A label-free proteomics approach has been employed to understand the physiology of infection and predict disease interceptors during <em>Leishmania</em>-host interactions. Proteomic modulation after infection of human macrophage cell lines suggested elevated annexin A6, implying involvement in various biological processes such as membrane repair, transport, actin dynamics, cell proliferation, survival, differentiation, and inflammation, thereby potentiating its immunological protective capacity. Additionally, S100A8 and S100A9 proteins, known for maintaining homeostatic balance in regulating the inflammatory response, have been upregulated after infection. The inhibitory clade of serpins, known to inhibit cysteine proteases (CPs), was upregulated in host cells after 48 h of infection. This is reflected in the diminished expression of CPs in the parasites during infection. Such proteome analysis confirms <em>LdCen1</em><sup><em>−/−</em></sup> efficacy as a vaccine candidate and predicts potential markers in future vaccine development strategies against infectious diseases.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105340"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jae-Hun Ahn , Do-Hyeon Jung , Dong-Yeon Kim , Tae-Sung Lee , Yeong-Jun Kim , Yun-Ji Lee , In-Su Seo , Wan-Gyu Kim , Young Jin Cho , Sung Jae Shin , Jong-Hwan Park
{"title":"Impact of IL-1β on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production","authors":"Jae-Hun Ahn , Do-Hyeon Jung , Dong-Yeon Kim , Tae-Sung Lee , Yeong-Jun Kim , Yun-Ji Lee , In-Su Seo , Wan-Gyu Kim , Young Jin Cho , Sung Jae Shin , Jong-Hwan Park","doi":"10.1016/j.micinf.2024.105351","DOIUrl":"10.1016/j.micinf.2024.105351","url":null,"abstract":"<div><p><em>Mycobacterium abscessus</em> (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1β maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1β in the host's defense against MAB. The IL-1β production by MAB was completely abolished in NLRP3, but not NLRC4, deficient macrophages. The NLRP3 inflammasome components, which are ASC and caspase-1 were also found to be essential for IL-1β production in response to MAB. NLRP3 and IL-1β deficiency did not affect the intracellular growth of MAB in macrophages, and the bacterial burden in lungs of NLRP3- and IL-1β-deficient mice was also comparable to the burden observed in WT mice. In contrast, IL-1β deficiency ameliorated lung pathology in MAB-infected mice. Notably, the lung homogenates of IL-1β-deficient mice had reduced levels of IL-17, but not IFN-γ and IL-4 when compared with WT counterparts. Furthermore, <em>in vitro</em> co-culture analysis showed that IL-1β signaling was essential for IL-17 production in response to MAB. Finally, we observed that the anti-IL-17 antibody administration moderately mitigated MAB-induced lung pathology. These findings indicated that IL-1β production contribute to MAB-induced lung pathology via the elevation of IL-17 production.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105351"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paula Arbildi , Ana Clara Muniz-Lagos , Eugenia Fernández , Rosina Giorgi , Kai Wiater , Gustavo Mourglia-Ettlin , Verónica Fernández
{"title":"Immunization with a Mu-class glutathione transferase from Echinococcus granulosus induces efficient antibody responses and confers long-term protection against secondary cystic echinococcosis","authors":"Paula Arbildi , Ana Clara Muniz-Lagos , Eugenia Fernández , Rosina Giorgi , Kai Wiater , Gustavo Mourglia-Ettlin , Verónica Fernández","doi":"10.1016/j.micinf.2024.105364","DOIUrl":"10.1016/j.micinf.2024.105364","url":null,"abstract":"<div><p>Cystic echinococcosis, a zoonosis caused by cestodes belonging to the <em>Echinococcus granulosus sensu lato</em> (s.l.) genetic complex, affects humans and diverse livestock species. Although a veterinary vaccine exhibiting high levels of antibody-mediated protection has successfully reached the market, the large genetic diversity among parasite isolates and their particular host preferences, makes still necessary the search for novel vaccine candidates. Glutathione transferases (GSTs) constitute attractive targets for immunoprophylaxis due to their outstanding relevance in helminth detoxification processes, against both exogenous and endogenous stressors. Among the six GSTs known to be expressed in <em>E. granulosus</em> s.l., EgGST1 (Mu-class), EgGST2 (Sigma-class), and EgGST3 (a still non-classifiable isoenzyme), show the highest proteomic expression. Therefore, their recombinant forms -rEgGST1, rEgGST2 and rEgGST3- were herein analyzed regarding their potential to induce long-term antiparasite protection in mice. Only immunization with rEgGST1 induced long-lasting protection; and accordingly, rEgGST1-specific antibodies enhanced the parasite killing through both the classical activation of the host complement system and the antibody-dependent cellular cytotoxicity by macrophages. These results support further testing of rEgGST1 as a vaccine candidate in diverse hosts due to the broad expression of EgGST1 in different parasite stages and tissues.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105364"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of different immunomodulating liposome-based adjuvants and injection sites on immunogenicity in pigs","authors":"Evelína Šťastná , Gitte Erbs , Kerstin Skovgaard , Jeanne Toft Jakobsen , Mick Bailey , Gabriel Kristian Pedersen , Gregers Jungersen","doi":"10.1016/j.micinf.2024.105346","DOIUrl":"10.1016/j.micinf.2024.105346","url":null,"abstract":"<div><p>Vaccine adjuvants, such as liposome-based cationic adjuvant formulations (CAFs), are able to boost immune responses and, by incorporation of distinct immunomodulators, steer immunity towards a desired direction in mice, non-human primates and humans, while less studied in pigs. Here we used commercial pigs to investigate polarizing adjuvant effects of CAFs with immunomodulators: C-type lectin receptor ligands trehalose-6,6ʼ-dibehenate and monomycolyl glycerol, toll-like receptor 3 ligand Poly(I:C) or retinoic acid. Vaccines were formulated with a recombinant <em>Chlamydia</em> model protein antigen and administered via three injection routes. All adjuvants significantly increased antigen-specific IgG in serum, compared to non-adjuvanted antigen. Administering the vaccines through intramuscular and intraperitoneal routes induced significantly higher antigen-specific IgG and IgA serum antibodies, than the perirectal route. Although immunizations triggered cell-mediated immunity, no significant differences between adjuvants or injection sites were detected. Genes depicting T cell subtypes revealed only minor differences. Our findings suggest that specific signatures of the tested adjuvant immunomodulation do not translate well from mice to pigs in standard two-dose immunizations. This study provides new insights into immune responses to CAFs in pigs, and highlights that adjuvant development should ideally be carried out in the intended species of interest or in models with high predictive validity/translational value.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"26 5","pages":"Article 105346"},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000765/pdfft?md5=d28093bc6978156731bd85958e64fa71&pid=1-s2.0-S1286457924000765-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}