{"title":"Emulsifier-modified sunflower oil-sunflower wax oleogel as growth modulator of probiotics","authors":"Deepti Bharti , Senthilguru Kulanthaivel , Prashant Mishra , Neha Jain , Kunal Pal , Indranil Banerjee","doi":"10.1016/j.bbadva.2025.100147","DOIUrl":"10.1016/j.bbadva.2025.100147","url":null,"abstract":"<div><div>The efficiency of oleogel as an oral delivery vehicle of probiotics depends on the chemical composition and gelator used. However, the gelators, which are surfactant in nature often interact with the probiotics and alter the therapeutic outcome. Keeping this perspective in mind, here we have developed oleogel of sunflower oil containing 5% (w/w) of sunflower wax and different emulsifiers, namely Span80 (S), Tween 80(T), stearyl alcohol (SA), and Span60 (SP), and checked their influence on probiotics in-vitro. Using confocal laser scanning microscopy, it was found that adding different emulsifiers changed the length and arrangement of the gelator network. SA and SP-modified oleogels, used at a concentration of 0.05% (w/v), demonstrated enhanced growth and metabolic activity of <em>Lactiplantibacillus pentosus</em>, which was employed as a model probiotic. Furthermore, the mucin adhesion test and scanning electron microscopy confirmed the negligible effect of those oleogels on the activity and morphology of the probiotic, respectively. When the secretome of such probiotics was applied to the colonic cell line, no negative effects were seen. This study implied that sunflower oil-sunflower wax oleogels modified using different emulsifiers can modulate probiotic growth.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2025-01-01Epub Date: 2025-02-16DOI: 10.1016/j.bbadva.2025.100150
Keita Yamada
{"title":"Minor acidic glycans: Review of focused glycomics methods","authors":"Keita Yamada","doi":"10.1016/j.bbadva.2025.100150","DOIUrl":"10.1016/j.bbadva.2025.100150","url":null,"abstract":"<div><div>Glycans are modified by acidic molecules, including sialic acid, sulfates, phosphates, and glucuronic acid, forming acidic glycans. Among these, sialylated glycans form major components of deuterostome glycomes, and their structure and function have been widely studied. The other acidic glycans, comprising minor components of the glycome, are often overlooked by glycomics and glycoproteomics methods, although they are implicated in conditions such as inflammatory diseases, neurological diseases, and viral infections. Therefore, minor acidic glycans are high-priority targets for glycomics, and analytical techniques focused on minor acidic glycans are being developed. This review examines the methods of enriching the minor acidic glycans from biological glycomes and examines their structure, providing examples of the application of these techniques in biological and clinical samples.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2025-01-01Epub Date: 2025-02-19DOI: 10.1016/j.bbadva.2025.100151
Quan-en Yang , Nicole Lee , Nicole Johnson , Jennifer Hong , Jenny (Qinghua) Zhao , Xiulian Sun , Jian Zhang
{"title":"Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy","authors":"Quan-en Yang , Nicole Lee , Nicole Johnson , Jennifer Hong , Jenny (Qinghua) Zhao , Xiulian Sun , Jian Zhang","doi":"10.1016/j.bbadva.2025.100151","DOIUrl":"10.1016/j.bbadva.2025.100151","url":null,"abstract":"<div><div>Biological drugs with gene and cell therapy potentials, including natural or rationally created biomacromolecules, recombinant proteins/enzymes, gene-carrying DNA/RNA fragments, oncolytic viruses, plasmid and viral vectors or other gene delivering vehicles with specific therapeutic genes and gene manipulation tools, and genetically modified and reprogrammed human cells comprise a large fraction of drug development candidates in modern precision and regeneration medicine. These drugs have displayed unique capabilities in treating patients with previously incurable diseases. However, most of the drug preparations have complex multimolecular structures and require specific biomanufacturing systems and many other additional biological active materials for drug synthesis, cell expansion, and production enhancement. Thus, the final products would have to be subjected to sequential extensive purification processes to exclude impurities and to concentrate the drug products after manufacturing. The quality evaluation for each drug product is an individualized process and must be specifically designed and performed according to the characteristics of the drug and its manufacturing and purification methods. Some of the Quality Control (QC) assays may be very costly and time-consuming, frequently with inconsistent test results from batch-to-batch. This review focuses on QC assessment strategy development for common gene and cell therapy drugs which use prokaryotic or eukaryotic cells for manufacturing or cell factories for <em>in vitro</em> expansions, especially for drug identification and concentration determination, impurity detection and quantification, drug potency, stability, and safety evaluations; and discusses some key issues for drug quality assessments in different categories and emphasizes the importance of individualized QC strategy design.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2025-01-01Epub Date: 2025-04-27DOI: 10.1016/j.bbadva.2025.100161
Masaaki Matsubara , Mayumi Ishihara , Michael Tiemeyer , Kazuhiro Aoki , René Ranzinger
{"title":"DANGO: An MS data annotation tool for glycolipidomics","authors":"Masaaki Matsubara , Mayumi Ishihara , Michael Tiemeyer , Kazuhiro Aoki , René Ranzinger","doi":"10.1016/j.bbadva.2025.100161","DOIUrl":"10.1016/j.bbadva.2025.100161","url":null,"abstract":"<div><div>Glycosphingolipids are essential components of all eukaryotic cells and play a major role in a broad range of cellular and biological processes, including growth, cell signaling, survival, differentiation, and disease. Glycosphingolipid structural diversity arises from heterogeneity in both the glycan and lipid moieties. Most currently available computational tools for annotating mass spectrometry data for glycosphingolipids primarily focus on glycan structure analysis, although a tool for annotating intact glycosphingolipids has recently been reported. Developing tools that integrate both glycan-centric analytical approaches and dynamic lipid composition changes, which influence functional membrane characteristics, would be highly beneficial. We have developed a glycosphingolipid computational tool, named DANGO (Data ANnotation system for GlycolipidOmics), for the automated annotation of glycolipidomic datasets. DANGO supports processing and annotation of mass spectrometry data to characterize both the glycan and lipid (ceramide) moieties (http://www.ms-dango.org/). DANGO annotates MS datasets using a glycosphingolipid database, which is created from a curated or user-defined glycan and ceramide collection, and proposes candidate structures to the user that match the experimental data. DANGO is implemented as an extension of GRITS Toolbox (http://www.grits-toolbox.org), employing functionalities such as display routines for post-processing and organized annotation of data and relevant metadata. Implementation of a novel filter algorithm in DANGO reduces false-positive identifications, resulting in enhanced reliability and shortened computational time for acquiring glycosphingolipid structural annotation. The labor-intensive manual annotation of mass spectrometry datasets has been the only approach to confident assignment of glycosphingolipid structural identity. DANGO provides intuitive workflows for enhancing the annotation of glycosphingolipidomic data.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2025-01-01Epub Date: 2025-03-04DOI: 10.1016/j.bbadva.2025.100152
Takayuki Omoto , Nao Yamakawa , Di Wu , Hitoshi Mori , Ushio Takeda , Masaya Hane , Ken Kitajima , Chihiro Sato
{"title":"An enhanced dual detection of DMB-labeled sialic acids using high-resolution accurate mass spectrometry and fluorescence detection","authors":"Takayuki Omoto , Nao Yamakawa , Di Wu , Hitoshi Mori , Ushio Takeda , Masaya Hane , Ken Kitajima , Chihiro Sato","doi":"10.1016/j.bbadva.2025.100152","DOIUrl":"10.1016/j.bbadva.2025.100152","url":null,"abstract":"<div><div>Sialic acids are important glycan components not only in the conformation of the structure but also in functions of many biological activities. Detection methods for sialic acid have been developed, and fluorescent labeling of sialic acids with 1,2-diamino-4,5-methylenedioxybenzene (DMB) is the best method for its analysis. However, identifying and quantifying sialic acids using mass spectrometry (MS) remains difficult because of the diversity of sialic acids, including <em>O</em>-acetylation. In this study, we initially focused on enhancing the liquid chromatography (LC) separation of DMB-labeled sialic acids in bovine submaxillary mucin (BSM). We successfully achieved highly resolutive separation of 14 types of sialic acids, including multiply <em>O</em>-acetylated species, using a CAPCELL CORE C18 column. These structures were subsequently confirmed through collision-induced dissociation (CID) fragmentation. We then assessed MS and fluorescence detection (FLD) sensitivity using Neu5Ac, Neu5Gc, and Kdn standards, determining detection limits of 32 fmol for MS and 320 amol for FLD, with 320 fmol needed for CID-based structural analysis. These findings highlight the complementary nature of fluorescence and mass spectrometry techniques for DMB-labeled sialic acids identification and quantification. We also examined both CID and electron-activated dissociation (EAD) on the ZenoTOF 7600. CID fragment analysis revealed C5-specific diagnostic fragment ions for Neu5Ac, Neu5Gc, and Kdn. EAD spectra predominantly induced fragmentation of the fluorescent DMB core, regardless of applied variable kinetic energies. This study also led to the discovery of a new structure, Neu5Gc7,8,9Ac<sub>3</sub>, alongside the previously reported Neu5,7,8,9Ac<sub>4</sub> in BSM.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2025-01-01Epub Date: 2025-01-07DOI: 10.1016/j.bbadva.2025.100138
Helena Torpy , The Huong Chau , Sayantani Chatterjee , Anastasia Chernykh , David J. Torpy , Emily J. Meyer , Morten Thaysen-Andersen
{"title":"Impact of different pathogen classes on the serum N-glycome in septic shock","authors":"Helena Torpy , The Huong Chau , Sayantani Chatterjee , Anastasia Chernykh , David J. Torpy , Emily J. Meyer , Morten Thaysen-Andersen","doi":"10.1016/j.bbadva.2025.100138","DOIUrl":"10.1016/j.bbadva.2025.100138","url":null,"abstract":"<div><div>The morbidity and mortality of sepsis remain high. Clinicians lack effective markers to rapidly diagnose sepsis and identify the underlying pathogen infection particularly for patients with candidaemia or cases of culture-negative sepsis where culture-based diagnostics are inadequate. In our search for new lines of potential sepsis biomarkers, we here explore the impact of various classes of infectious agents on the serum <em>N</em>-glycome in a septic shock cohort. Comparative <em>N</em>-glycomics was performed on sera collected from 49 septic shock patients infected with viral (n = 9), bacterial (n = 37) or fungal (n = 3) pathogens using an established PGC-LC-MS/MS method. Aberrant serum <em>N</em>-glycosylation features were observed in patients with fungal infection relative to the other infection sub-groups including i) altered expression of prominent α2,6-sialylated biantennary <em>N</em>-glycan isomers, ii) elevated levels of IgG-type <em>N</em>-glycosylation and iii) a global shift in the serum <em>N</em>-glycome involving altered glycan type distribution and considerable changes in core fucosylation and α2,6-sialylation. Septic shock patients infected with bacterial and viral pathogens exhibited similar global serum <em>N</em>-glycome features and therefore could not be stratified based on their serum <em>N</em>-glycosylation. Subtle and less consistent serum <em>N</em>-glycome differences were observed between septic shock patients infected with different bacterial pathogens. In conclusion, our study has tested the impact of different pathogen classes on the serum <em>N</em>-glycome in a septic shock cohort, and reports that fungal infection impacts the host serum <em>N</em>-glycome differently compared to bacterial or viral infections thus potentially opening avenues for glycan-based biomarkers to better diagnose patients with candidaemia.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2024-01-01Epub Date: 2024-09-27DOI: 10.1016/j.bbadva.2024.100121
Daniel E. Otzen
{"title":"Editorial: Research methods in biochemistry and biophysics","authors":"Daniel E. Otzen","doi":"10.1016/j.bbadva.2024.100121","DOIUrl":"10.1016/j.bbadva.2024.100121","url":null,"abstract":"","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"6 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2024-01-01Epub Date: 2024-11-30DOI: 10.1016/j.bbadva.2024.100126
Sunmyoung Lee , Louis-David Leclercq , Yann Guerardel , Christine M. Szymanski , Thomas Hurtaux , Tamara L. Doering , Takane Katayama , Kiyotaka Fujita , Kazuhiro Aoki , Kiyoko F. Aoki-Kinoshita
{"title":"MicroGlycoDB: A database of microbial glycans using Semantic Web technologies","authors":"Sunmyoung Lee , Louis-David Leclercq , Yann Guerardel , Christine M. Szymanski , Thomas Hurtaux , Tamara L. Doering , Takane Katayama , Kiyotaka Fujita , Kazuhiro Aoki , Kiyoko F. Aoki-Kinoshita","doi":"10.1016/j.bbadva.2024.100126","DOIUrl":"10.1016/j.bbadva.2024.100126","url":null,"abstract":"<div><div>Glycoconjugates are present on microbial surfaces and play critical roles in modulating interactions with the environment and the host. Extensive research on microbial glycans, including elucidating the structural diversity of the glycan moieties of glycoconjugates and polysaccharides, has been carried out to investigate the function of glycans in modulating the interactions between the host and microbes, to explore their potential applications in the therapeutic targeting of pathogenic species, and in the use as probiotics in gut microbiomes. However, glycan-related information is dispersed across numerous databases and a vast amount of literature, which makes it laborious and time-consuming to identify and gather the relevant information about microbial glycosylation. This challenge can be addressed by a comprehensive database, which could offer insight into the fundamental processes underlying glycosylation. We have developed a MicroGlycoDB database to provide integrated glycan information on important model microorganisms. The data is described using Semantic Web Technologies, which allow microbial glycan data to be represented in a structured format accessible by machines, thus facilitating data sharing and integration with other resources that catalog features such as pathways, diseases, or interactions. This semantic data based on ontologies will contribute to the discovery of new knowledge in the field of microbiology, along with the expansion of information on the glycosylation of other microorganisms.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"6 ","pages":"Article 100126"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BBA AdvancesPub Date : 2024-01-01Epub Date: 2024-05-17DOI: 10.1016/j.bbadva.2024.100116
Anna Aldinio-Colbachini, Andrea Fasano, Chloé Guendon, Aurore Jacq-Bailly, Jérémy Wozniak, Carole Baffert, Arlette Kpebe, Christophe Léger, Myriam Brugna, Vincent Fourmond
{"title":"Corrigendum to “Transport limited adsorption experiments give a new lower estimate of the turnover frequency of Escherichia coli hydrogenase 1” BBA Advances 3 (2023) 100090","authors":"Anna Aldinio-Colbachini, Andrea Fasano, Chloé Guendon, Aurore Jacq-Bailly, Jérémy Wozniak, Carole Baffert, Arlette Kpebe, Christophe Léger, Myriam Brugna, Vincent Fourmond","doi":"10.1016/j.bbadva.2024.100116","DOIUrl":"10.1016/j.bbadva.2024.100116","url":null,"abstract":"","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"5 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667160324000048/pdfft?md5=cdd2a719a385328bd1c5cd1ea02d3094&pid=1-s2.0-S2667160324000048-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of protein glycosylation in an Asgard archaeon","authors":"Satoshi Nakagawa , Hiroyuki Imachi , Shigeru Shimamura , Saeko Yanaka , Hirokazu Yagi , Maho Yagi-Utsumi , Hiroyuki Sakai , Shingo Kato , Moriya Ohkuma , Koichi Kato , Ken Takai","doi":"10.1016/j.bbadva.2024.100118","DOIUrl":"https://doi.org/10.1016/j.bbadva.2024.100118","url":null,"abstract":"<div><p>Archaeal cells are typically enveloped by glycosylated S-layer proteins. Archaeal protein glycosylation provides valuable insights not only into their adaptation to their niches but also into their evolutionary trajectory. Notably, thermophilic <em>Thermoproteota</em> modify proteins with <em>N</em>-glycans that include two GlcNAc units at the reducing end, resembling the \"core structure\" preserved across eukaryotes. Recently, Asgard archaea, now classified as members of the phylum <em>Promethearchaeota,</em> have offered unprecedented opportunities for understanding the role of archaea in eukaryogenesis. Despite the presence of genes indicative of protein <em>N</em>-glycosylation in this archaeal group, these have not been experimentally investigated. Here we performed a glycoproteome analysis of the firstly isolated Asgard archaeon <em>Promethearchaeum syntrophicum</em>. Over 700 different proteins were identified through high-resolution LC-MS/MS analysis, however, there was no evidence of either the presence or glycosylation of putative S-layer proteins. Instead, <em>N</em>-glycosylation in this archaeon was primarily observed in an extracellular solute-binding protein, possibly related to chemoreception or transmembrane transport of oligopeptides. The glycan modification occurred on an asparagine residue located within the conserved N-X-S/T sequon, consistent with the pattern found in other archaea, bacteria, and eukaryotes. Unexpectedly, three structurally different <em>N</em>-glycans lacking the conventional core structure were identified in this archaeon, presenting unique compositions that included atypical sugars. Notably, one of these sugars was likely HexNAc modified with a threonine residue, similar to modifications previously observed in mesophilic methanogens within the <em>Methanobacteriati</em>. Our findings advance our understanding of Asgard archaea physiology and evolutionary dynamics.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"6 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667160324000061/pdfft?md5=f2facf0349cd217ae593decc0231d59b&pid=1-s2.0-S2667160324000061-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}