Toxicological Sciences最新文献

{"title":"GanCtrl: a generative AI approach to derive study-aligned synthetic controls for reducing concurrent control animal use.","authors":"Mansi Chandra, Xi Chen, Ting Li, Weida Tong","doi":"10.1093/toxsci/kfag099","DOIUrl":"10.1093/toxsci/kfag099","url":null,"abstract":"<p><p>Minimizing the use of animals as concurrent controls in in vivo studies directly supports the 3Rs principles of Replacement, Reduction, and Refinement. Current virtual control group (VCG) approaches primarily rely on historical control data, but their utility may be limited by cross-study variability from differences in study design, laboratory practices, and data heterogeneity. We propose GanCtrl, a generative AI approach to infer study-specific control data directly from time-matched treatment data. By generating synthetic controls analogous to concurrent controls, GanCtrl aims to mitigate biological, temporal, and technical biases inherent in VCG approaches based on historical control data. GanCtrl was applied to rat repeat-dose toxicity studies to simulate 38 clinical pathology endpoints under control conditions using corresponding treatment data. Synthetic controls closely approximated real concurrent controls, with differences smaller than intra- and inter-laboratory baseline variation and comparable to biological replicate variability, while also preserving the typical magnitude and distribution of control responses across studies. Importantly, synthetic controls enabled detection of drug-induced clinical pathology signals and maintained biologically relevant endpoint relationships, such as ALT-AST. For practical utility, toxicity assessments using GanCtrl-derived synthetic controls were compared with those using real concurrent controls and benchmarked against VCGs constructed from single-laboratory or combined multi-laboratory historical data. Although both approaches performed comparably in the single-laboratory setting, GanCtrl outperformed VCGs when data from multiple laboratories were combined. These findings suggest that GanCtrl offers a potential approach for generating VCGs that may reduce the use of concurrent control animals and advance the 3Rs.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to be seen: optimizing your manuscript for AI search.","authors":"Alison Harrill","doi":"10.1093/toxsci/kfag084","DOIUrl":"https://doi.org/10.1093/toxsci/kfag084","url":null,"abstract":"","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"209 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649304","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":"Towards Bayesian-based quantitative adverse outcome pathways using in vitro data from open literature and continuous variables: a case example for liver fibrosis.","authors":"Robin Durnik, Tereza Juchelkova, Helge Hecht, Levi M T Winkelman, Joost B Beltman, Xavier Coumoul, Florence Jornod, Karine Audouze, Ludek Blaha, Lola Bajard","doi":"10.1093/toxsci/kfag090","DOIUrl":"10.1093/toxsci/kfag090","url":null,"abstract":"<p><p>As toxicology shifts towards nonanimal testing, quantitative models are essential to predict adverse health effects from molecular or cellular perturbations. Quantitative Adverse Outcome Pathways (qAOPs) represent such models, building on mechanistic knowledge and quantifying the key event relationships (KERs) described in AOPs. Despite the recognized need, the number of qAOPs remains limited. Bayesian-based approaches are often chosen for developing qAOP for their flexibility, but most use discretized variables, limiting their predictive power. In addition, these models are mainly built from newly generated data, underexploiting the large amount of information available. This study successfully leverages data from public literature and presents an innovative framework based on continuous variables to develop a Bayesian-based quantitative model for a central KER towards liver fibrosis. The model predicts the probability of the expression fold change for two key markers of hepatic stellate cell activation (aSMA and COL1A1), given the effects on tissue injury, using in vitro data from several chemicals. We propose a newly developed workflow to assist in knowledge identification, organization, and extraction from scientific literature and chemical databases. Based on in vitro data and in vivo information from the Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System) database, we estimate a biologically relevant range in COL1A1 fold change that indicates an activated state of stellate cells and high liver fibrosis odds ratios. Our study provides a case example of integrating published data and continuous variables to build a Bayesian-based model, which constitutes an essential step towards predicting liver fibrosis from in vitro data.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversible disruption of proresolving lipid mediator pathways and erythroid homeostasis by PM2.5.","authors":"Haley Asplund, Heinrich H Dreyer, Timothy E O'Toole, Petra Haberzettl, Daniel J Conklin, Jason Hellmann, Brian E Sansbury","doi":"10.1093/toxsci/kfag092","DOIUrl":"10.1093/toxsci/kfag092","url":null,"abstract":"<p><p>Ambient particulate matter (PM2.5) exposure is a major environmental risk factor for cardiopulmonary disease, but its effects on erythroid homeostasis remain incompletely understood. Although prior in vitro work indicates that PM2.5 can damage circulating red blood cells (RBCs), whether exposure alters erythropoiesis and the coordinated clearance of senescent RBCs has not been fully explored. Using a mouse model of whole-body exposure to concentrated ambient PM2.5 (CAP), we investigated associations between inhaled PM on erythroid output, splenic macrophage function, and lipid mediator signaling. CAP exposure was associated with suppressed erythropoietin levels, reduced circulating reticulocytes, and decreased erythroid precursor populations in the bone marrow, consistent with impaired erythropoiesis. Despite preserved splenic architecture, CAP-exposed mice exhibited reduced splenic iron and heme content, consistent with diminished erythrocyte turnover and processing. Targeted lipidomic profiling revealed broad suppression of proresolving lipid mediators in the spleen, with lipoxin A4 (LXA4) among the most consistently reduced species. Expression of the LXA4 receptor, ALX/FPR2, was also downregulated with prolonged exposure. Importantly, removal of CAP and return to filtered air resulted in normalization of splenic lipid mediator profiles, restoration of LXA4 levels, and recovery of erythroid parameters, including reticulocyte abundance and RBC stress markers. Together, these findings suggest that altered resolution signaling contributes to PM2.5-induced disruption of erythroid homeostasis and implicate macrophage-lipid mediator pathways in the hematologic response to environmental stress.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethylene glycol monomethyl ether altered rat sperm small RNAs with critical developmental roles.","authors":"Yuan Pu, August Guang, Xinran Qi, Poonam Mehta, Saadhya Bahudodda, Angela R Stermer, Daniel J Spade","doi":"10.1093/toxsci/kfag091","DOIUrl":"10.1093/toxsci/kfag091","url":null,"abstract":"<p><p>Ethylene glycol monomethyl ether (EGME) is a testicular germ cell toxicant that selectively targets spermatocytes. In rats, male-only EGME exposure reduces mating success and can lead to an increase in resorbed fetuses. In a previous study, 5-d exposure to 50, 60, or 75 mg/kg/d EGME in male rats led to a decrease in sperm motility and increase in retained spermatid heads with a lowest observed adverse effect level (LOAEL) of 75 mg/kg/d. At 60 mg/kg/d, EGME exposure altered the proportion of sperm small RNA reads mapped to different small RNA categories and the distribution of read lengths. To understand the possible role of sperm sncRNAs in EGME-mediated reduction in spermatogenesis, fertility, and embryonic development, we analyzed sperm sncRNA data from EGME-treated male rats to identify differential expression at the individual RNA level. EGME treatment resulted in dose-dependent increases in the expression levels of microRNAs (miRNAs), piRNAs, and tRNA-derived small RNAs (tsRNAs), and mixture of dose-dependent increases and decreases in abundance of rsRNA reads. We identified 12 miRNAs that were differentially expressed at all EGME doses, with a monotonic, dose-dependent increase. High-confidence targets of these 12 miRNAs are known to be expressed in preimplantation embryos and statistically enriched for Gene Ontology (GO) biological processes related to early development, such as cell fate commitment and regulation of developmental growth. These results demonstrated that the EGME-induced changes in sperm sncRNA levels were reproducible, dose-dependent, and provided a putative mechanism of paternal EGME effects on embryonic development, which will be investigated in future studies.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward internal threshold for toxicological concern: in vitro hepatocyte metabolism testing of 207 chemicals using cryopreserved suspended hepatocytes for physiologically based pharmacokinetic modeling.","authors":"Corie A Ellison, Anne Marie Api, Richard A Becker, Sherry Black, Kaushal Joshi, Dan Selechnik","doi":"10.1093/toxsci/kfag086","DOIUrl":"10.1093/toxsci/kfag086","url":null,"abstract":"<p><p>In vitro hepatic metabolic clearance data were generated for a diverse set of 207 chemicals to advance the collaborative initiative to establish an internal Threshold of Toxicological Concern (iTTC). The data reported herein are being used for chemical-specific physiologically based pharmacokinetic (PBPK) modeling to convert oral No Observable Adverse Effect Levels (NOAELs) into estimates of internal exposure. Hepatocyte assays were conducted at 2 concentrations (0.1 and 1 µM) using cryopreserved cells from multiple species, ensuring applicability to existing mammalian toxicity studies. The metabolic clearance measurements across chemicals varied significantly, ranging from 0 to 4,294 µl/min/106 cells at 0.1 µM and from 0 to 2,351 µl/min/106 cells at 1 µM. A substantial proportion of the chemicals (68% at 0.1 µM and 62% at 1 µM) exhibited clearance values below 30 µl/min/106 cells. Additionally, we observed a strong correlation (R = 0.8) between intrinsic clearance (CLint) values determined at the 2 concentrations. These data contribute to establishing robust iTTC values that can be utilized for: (i) extrapolating from an oral in vivo study to dermal and inhalation exposures, (ii) risk-based screening of aggregate exposures of a given substance from multiple routes of exposures, and (iii) risk-based screening of human biomonitoring results.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of a metabolism-dependent aryl hydrocarbon receptor off-target activation for a drug development candidate and a screening strategy for de-risking backups.","authors":"Amy G Aslamkhan, Wen Kang, Karin Otte, Alex Tamburino, Paul J Ciaccio, Beatrice Sacre-Salem, Zoltan Erdos, Yuexia Liang, Richard W Gundersdorf, Bridget Becker, Keith Q Tanis, Todd Pippert, Pam Lane, Binod Jacob, Kimberly B Bleicher, Zhibin Wang, Ming Su, Stephen Pacchione, David Candito, Vladimir Simov, Peter H Fuller, Matthew J Fell, J Michael Ellis, Robert Foti, Kara M Pearson, Frank D Sistare, Warren E Glaab","doi":"10.1093/toxsci/kfag083","DOIUrl":"10.1093/toxsci/kfag083","url":null,"abstract":"<p><p>During lead optimization, off-target activation of the aryl hydrocarbon receptor (AhR) was identified for Compound 25. AhR is a xenobiotic-responsive transcription factor associated with adverse outcomes in rodents (and potentially humans) and modulation of drug metabolism. In rats, marked hepatic induction of AhR target genes, Cyp1a1 and Cyp1a2, was observed following repeat dosing and increased with study duration. Compound 25 was inactive in conventional AhR luciferase reporter assays but induced robust Cyp1a1 expression in metabolically competent rat and human HEPATOPAC cultures, suggesting a metabolism-dependent mechanism. Extensive metabolite profiling demonstrated that Compound 25 undergoes complex oxidative and conjugative metabolism; however, specific AhR-active metabolite(s) could not be identified. AhR involvement was confirmed in vivo using AhR knockout and wild-type rats, in which Cyp1a1/2 induction occurred exclusively in wild-type animals. Chromatin immunoprecipitation further demonstrated increased AhR binding at Cyp1a1/2 promoters following Compound 25 treatment. In rat HEPATOPAC cultures, siRNA-mediated knockdown of Por and Cyb5a attenuated Cyp1a1 induction, supporting a requirement for metabolic competence. Consistent with AhR pathway engagement, induction of CYP1A1 in human HEPATOPAC was reduced by the AhR antagonist CH223191. Collectively, these findings demonstrate that AhR activation associated with Compound 25 is dependent on metabolic transformation and may not be detected in conventional reporter assays lacking metabolic capacity. This work highlights the value of metabolically competent hepatocyte models, combined with short-duration in vivo studies, for identifying and mitigating metabolism-dependent AhR liabilities during drug discovery.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520929","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":"Systematic comparison of temporal hepatotoxicant-induced gene network responses across 3 liver test systems.","authors":"Tamara Y Danilyuk, Marou Schouten, Elsje J Burgers, Barira Islam, Joost B Beltman, Peter Bouwman, Giulia Callegaro, Bob van de Water","doi":"10.1093/toxsci/kfag088","DOIUrl":"10.1093/toxsci/kfag088","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) arises from dynamic and time-dependent cellular stress responses that remain insufficiently captured by conventional single-timepoint toxicogenomic assessments. We systematically characterized temporal and concentration-dependent transcriptomic responses to the clinically relevant hepatotoxicants ketoconazole, diclofenac, and nitrofurantoin across 3 human liver in vitro models: primary human hepatocytes (PHH), hiPSC-derived hepatocyte-like cells (HLC), and HepG2 cells. Time-resolved RNA sequencing (0 to 48 h) combined with likelihood ratio testing identified time-responsive genes (TRGs), which were subsequently integrated into TXG-MAPr gene co-expression modules to enable mechanistic interpretation at the network level. Across all models and compounds, a conserved core stress response was observed, characterized by activation of ER stress (ATF4), oxidative stress (NRF2), and heat shock (HSF1) pathways, whereas distinct model-specific adaptive programs reflected differences in metabolic competence and differentiation status. Mapping TRGs onto co-expression networks revealed coordinated temporal activation patterns and highlighted both shared and system-specific transcriptional programs. Concentration-response analysis at 24 h demonstrated that module-level transcriptomic points of departure (tPODs) were highly reproducible across models for a subset of functionally annotated networks, particularly ER stress modules associated with hepatocellular injury in vivo. Notably, these modules showed substantial gene-level concordance across systems, supporting their biological robustness and translational relevance. These findings establish that time-resolved, network-based transcriptomics provides mechanistically grounded, reproducible, and quantitative endpoints that enhance cross-system comparability and offer a scalable framework for regulatory toxicology and next-generation chemical risk assessment.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Words matter in toxicology and risk assessment as they impact risk communication.","authors":"Curtis D Klaassen","doi":"10.1093/toxsci/kfag074","DOIUrl":"10.1093/toxsci/kfag074","url":null,"abstract":"<p><p>Clear, consistent language is essential in toxicology and risk assessment because terminology directly affects risk communication and understanding. The original concept of a \"No Harm Dose of Reasonable Certainty\" (NHDoRC) for an amount of chemical to which people can be exposed without detrimental effects is a plain language expression that clearly describes regulatory intent. However, the subsequent introduction and use of many related technical terms, such as NOAEL, BMD, RP, and PoD, with almost the same meaning, can confuse non-experts and even scientists working in different regulatory entities. Similarly, ADI, RfD, TDI, MRL, HBGV, and RV are all different abbreviations used in toxicology and risk assessment to describe the \"acceptable\" human dose in the context of food, water, and environmental chemicals. Likewise, the frequent use of terms such as margin of exposure (MoE) and margin of safety (MoS) interchangeably further complicates communication, as they are mathematically (and toxicologically) quite different. NOAEL and BMD10 are sometimes used interchangeably, but they usually represent two different points on the dose-response curve. Because of the many complications in the terminology used in risk assessment, a committee should be established to harmonize terminology across agencies and the wider risk assessment community, including industry and academia. The recommendations from such a committee would improve clarity, transparency, regulatory efficiency, and public trust in chemical risk assessment.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259672","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":"Integrating mechanistic data to contextualize in vivo apical observations using the developmental neurotoxicity in vitro battery.","authors":"Brianna L Jackson, Yaoxing Wu, Kian Afsharian, Christopher Schlosser, Angela H Hofstra, Laura M Minnema, Jördis Klose, Ellen Fritsche, Manasvinee Mayil Vahanan, Timothy J Shafer, Kelly E Carstens, Agnes L Karmaus","doi":"10.1093/toxsci/kfag089","DOIUrl":"10.1093/toxsci/kfag089","url":null,"abstract":"<p><p>Regulatory toxicity studies traditionally rely on in vivo apical endpoints for hazard characterization and risk assessment; when available, relevant and reliable in vitro assays are anticipated to aid this interpretation. Developmental neurotoxicity (DNT)-related parameters such as brain morphometry can be especially challenging to interpret, based on technical challenges such as sample preparation artifacts. This study employed the Developmental Neurotoxicity In Vitro Battery (DNT-IVB), designed to provide functional insights on key neurodevelopmental processes (KNDPs), to provide context for equivocal brain morphometry effects observed in a legacy in vivo DNT study conducted with acibenzolar-S-methyl (ASM), a plant host defense inducer. ASM and its major mammalian metabolite, acibenzolar acid (AA), were tested in all 17 in vitro assays comprised within the current iteration of the DNT-IVB. In vitro testing concentrations were derived to match the existing in vivo DNT study by applying physiologically based pharmacokinetic (PBPK) modeling with adjustment for rat versus human toxicokinetics. All concentration-response DNT-IVB assay data were analyzed using the US EPA ToxCast Pipeline. ASM showed no effect on any KNDP in vitro. AA was active only in the rat network formation assay with low potency AC50 ranges of 96.1 to 150 µM that modeling shows will not be achieved in vivo at doses where the apical effects in question were observed. This case study demonstrates the potential of the DNT-IVB to be used as a tool to assess equivocal findings from in vivo DNT studies and contribute to a weight of evidence to support conclusions on chemical-mediated DNT.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}