Frontiers in molecular medicine最新文献

{"title":"High-titer human packaging cells producing γ-retroviral vectors pseudotyped with engineered baboon endogenous retrovirus (BaEV) envelope proteins.","authors":"Angelina Hallik, Mona Pißarreck, Mats Jürgen Grummel, Yasemin van Heuvel, Jörn Stitz","doi":"10.3389/fmmed.2026.1888550","DOIUrl":"10.3389/fmmed.2026.1888550","url":null,"abstract":"<p><p>Lentiviral, α-retroviral, and γ-retroviral vector particles pseudotyped with envelope (Env) proteins of baboon endogenous retrovirus (BaEV) were shown to mediate highly efficient gene transfer into a range of primary human hematopoietic cell types in gene therapeutic strategies. However, the fusogenicity of utilized Env proteins mediated syncytia formation, hindering the establishment of stable viral packaging cell lines (VPCLs). Consequently, we used another BaEV Env variant, termed BaEV-TR-previously reported not to induce cell-to-cell fusion-and assessed its utility in stable producer cell line development. The absence of syncytia formation was reconfirmed in human 293T and HT1080 cell lines. Using HT1080 host cells, the stable VPCL HT/BaEV-TR was established. Conducting a Western blot analysis, BaEV-TR protein incorporation into vector particles was readily detected. Murine leukemia virus (MLV) pseudotype vectors efficiently transduced a variety of human target cell lines, reaching high vector titers of more than 3.0 × 10⁶ transducing units per mL (TU/mL) in 293T target cells. In summary, this proof-of-concept study underlines the utility of the Env variant BaEV-TR for the establishment of stable pseudotype VPCLs and the utilization of HT1080 cells as an alternative to frequently used 293T host cells.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1888550"},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882593","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":"Circulating tumour DNA in mCRPC: bridging tumour biology and real-time treatment monitoring.","authors":"Chimbabantu Kaoma, Mike Sathekge, Joseph Chalwe, Kgomotso Mokoala, Mankgopo Kgatle","doi":"10.3389/fmmed.2026.1852641","DOIUrl":"https://doi.org/10.3389/fmmed.2026.1852641","url":null,"abstract":"<p><p>Metastatic castration-resistant prostate cancer (mCRPC) is associated with poor prognosis. Currently, treatment selection and response assessment in mCRPC still rely largely on prostate-specific antigen (PSA) and imaging tools, which may be insensitive and biologically noninformative. Liquid biopsy (LB), particularly circulating tumor DNA (ctDNA), offers a minimally invasive and reproducible approach for real-time assessment of tumor burden and tumor genomics. Across major treatment classes, ctDNA tumor fraction has shown consistent prognostic value, while selected genomic alterations may provide therapy-specific predictive information. Early on-treatment ctDNA kinetics are also emerging as dynamic markers of response, although prospective validation is required before routine clinical implementation. In this narrative review, we synthesize current evidence on ctDNA biology, detection methods, and its clinical utility across key mCRPC treatment classes, including androgen receptor pathway inhibitors (ARPIs), taxane chemotherapy, PARP inhibitors, and PSMA-targeted radioligand therapy (RLT). We critically examine ctDNA tumor fraction as a pan-therapy prognostic biomarker, genomic alterations as potential predictors of treatment sensitivity or resistance, early kinetic changes as surrogate markers of response, and the biological and technical limitations that currently restrict clinical adoption. Overall, the current evidence base for ctDNA in mCRPC remains predominantly prognostic rather than definitively predictive. Its integration into routine clinical practice will require prospective biomarker-driven trials, assay standardization, and a clear demonstration of clinical utility. At present, ctDNA is best positioned as a complementary tool for risk stratification and disease monitoring, with the potential to evolve into a clinically actionable biomarker for treatment decision-making.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1852641"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759925","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":"Impact of plant-based interventions on gynecological cancers: a narrative review of mechanistic interplays and clinical evidence.","authors":"Fidelis Batale Fabrael, John Sotunsa, Kehinde Samuel Olaniyi, Onome Bright Oghenetega, Oluwatobi Adewale, Blessing Monica Akindele, Faith Olanrewaju, Nekabari Lekpa Gbimadee, Seyi Olayemi, Abosede Oreoluwa Bolaji, Marvellous Osewe Iyobhebhe, Emmanuel Mololuwa Adegbotoluwa, Emmanuel Damilare Folahanmi, John Ahmadu Kaisar, Precious Adeoye Oyedokun","doi":"10.3389/fmmed.2026.1832188","DOIUrl":"10.3389/fmmed.2026.1832188","url":null,"abstract":"<p><p>Gynecological cancers account for approximately 1.4 million new cases and 680,000 deaths annually. Cervical, ovarian, endometrial, vulvar, and vaginal cancers collectively impose a major and disproportionate burden on women in low- and middle-income countries. Conventional treatments, including surgery, platinum-based chemotherapy, and radiotherapy, are limited by systemic toxicity, acquired chemoresistance, recurrence, and financial inaccessibility in resource-limited settings. Approximately 80 percent of patients with advanced ovarian cancer eventually develop platinum resistance, and cervical cancer persists as a leading cause of cancer death in regions with inadequate screening and vaccination infrastructure. Plant-derived phytochemicals have attracted substantial scientific attention as adjunct or complementary anticancer strategies. This review synthesizes preclinical, epidemiological, and emerging clinical evidence for alkaloids, flavonoids, terpenoids, polyphenols, coumarins, and organosulfur compounds in gynecological cancer prevention and management. These compounds modulate multiple oncogenic pathways relevant to gynecological malignancies: tumor cell proliferation, intrinsic and extrinsic apoptosis, angiogenesis, oxidative stress, inflammation, hormone receptor signaling, HPV E6/E7 oncoprotein expression, and epigenetic regulation. Paclitaxel, a taxane terpenoid, serves as the definitive proof of concept that plant-derived compounds can achieve gold-standard clinical status in gynecological oncology. Critical barriers limit clinical translation for most non-approved phytochemicals: oral bioavailability is poor, botanical preparations are unstandardized, randomized trial data in gynecological cancer populations are scarce, and herb-drug interaction profiles are incompletely characterized. Nanoformulation approaches, including liposomal encapsulation, PLGA nanoparticles, and phytosomes, offer practical routes to overcome these pharmacokinetic obstacles. Future work should prioritize biomarker-embedded clinical trials, molecular subtype-stratified patient selection, and rigorous evaluation of phytochemical-chemotherapy combination regimens.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1832188"},"PeriodicalIF":0.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407249","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":"Blood biomarkers and atrial remodeling in patients at risk of atrial fibrillation.","authors":"Filip Loncaric, Ilana Forado Benatar, Maria Mimbrero Guillamon, Loredana Nunno, Rafael Jimenez-Arjona, Laia Tirapu, Sílvia Montserrat, Laura Sanchis, Adelina Doltra, Bart Bijnens, Marta Sitges","doi":"10.3389/fmmed.2026.1801523","DOIUrl":"10.3389/fmmed.2026.1801523","url":null,"abstract":"<p><strong>Introduction: </strong>Arterial hypertension and endurance training are related to left atrial (LA) remodeling and risk of atrial fibrillation (AF). Serum blood biomarkers have been explored in relation to cardiovascular risk. Our aim was to assess the influence of patient and echocardiographic characteristics on serum blood biomarkers in individuals at risk for AF.</p><p><strong>Methods: </strong>A population of 511 subjects was analyzed: 286 endurance athletes and 225 patients with arterial hypertension. Participants underwent 2D and 3D echocardiography with speckle-tracking analysis. Blood samples were obtained to evaluate biomarkers of myocardial damage (Brain Natriuretic Peptide, troponin I, Oncostatin M, heart-type Fatty Acid-Binding Protein and Placenta Growth Factor), vascular endothelial dysfunction (Endothelial cell-specific molecule 1), and fibrosis (Matrix Metalloproteinase 1, 2 and 9, C-X-C motif chemokine ligand 6 and 16, and Galectin-3 (Gal-3)). Linear regression models were fitted to discern the relationship of patient and echo characteristics and serum biomarker levels.</p><p><strong>Results: </strong>The results revealed the significant influence of age, gender, body mass index and renal function on biomarker levels. Parameters of myocardial damage showed a limited range of values in our cohort with no differences between groups. Biomarkers of fibrosis were uniformly elevated in hypertension, with Gal-3 levels independently associated with LA reservoir strain.</p><p><strong>Conclusion: </strong>Serum levels of fibrosis biomarkers differ between populations at risk for AF. In hypertension Gal-3 levels are associated with LA reservoir function, making it a potential biomarker for LA remodeling in this setting. Clinical follow-up is needed to relate these findings with clinical outcomes.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1801523"},"PeriodicalIF":0.0,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201292","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":"Editorial: Targeted cancer therapy through metabolic pathways.","authors":"Prasanna Srinivasan Ramalingam, Md Sadique Hussain, Shreyas Ramchandra Gaikwad, Sivakumar Arumugam","doi":"10.3389/fmmed.2026.1842647","DOIUrl":"10.3389/fmmed.2026.1842647","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1842647"},"PeriodicalIF":0.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984714","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":"Mapping the future of medicine through digital twins.","authors":"Frank Emmert-Streib, Shailesh Tripathi, Olli Yli-Harja","doi":"10.3389/fmmed.2026.1840371","DOIUrl":"10.3389/fmmed.2026.1840371","url":null,"abstract":"<p><p>Digital twins are rapidly gaining popularity in medicine and the health sciences, as they offer not merely a new method but a versatile paradigm capable of addressing a wide range of healthcare challenges. In this paper, we provide a focused survey of these developments and highlight promising approaches across several fields, including general health systems, cardiology, oncology, and mental health. We also discuss the key challenges and future directions for general medical digital twin systems.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1840371"},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936073","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":"Sirtuin 1 is a key molecular link between cellular senescence and heart failure.","authors":"Jan Krekora, Jarosław Drożdż, Janusz Blasiak","doi":"10.3389/fmmed.2026.1818104","DOIUrl":"10.3389/fmmed.2026.1818104","url":null,"abstract":"<p><p>Cellular senescence, a state where cells permanently exit the cycle but remain metabolically active, plays a role in cardiovascular diseases (CVD), including heart failure (HF). Senescent cells accumulate in aging and stressed heart tissue, releasing pro-inflammatory cytokines, chemokines, and enzymes that affect endothelial cells. This ongoing inflammation exacerbates cardiac damage, induces endothelial dysfunction, and triggers secondary senescence across various cardiac cell types. Senescent cardiomyocytes contribute to reduced systolic function by causing mitochondrial damage, impaired contractility, and metabolic dysfunction, leading to lower cardiac output and symptoms such as fatigue and exercise intolerance in HF patients. Additionally, inflammation from senescent endothelial cells and loss of microvasculature impair coronary blood flow and oxygen delivery, worsening symptoms such as shortness of breath, angina-like discomfort, and fluid retention by disrupting cardiac energy metabolism and increasing filling pressures. A key factor linking cellular senescence with HF is sirtuin 1 (SIRT1), a histone deacetylase with antioxidant activity. SIRT1 acts as a hormetic regulator in the heart, being beneficial within a narrow range but potentially harmful when overstimulated. As drugs targeting senescence are emerging to treat CVD, it is important to evaluate how SIRT1 may influence the connection between senescence and HF to improve anti-senescent therapies. In this narrative/perspective review, we explore the molecular mechanisms underlying senescence in HF development and how SIRT1 might modulate these processes for therapeutic benefit.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1818104"},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147936145","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":"Molecular mechanisms underlying psoriasis and depression: an integrated analysis using mendelian randomization, transcriptomics, and single-cell sequencing.","authors":"Baojun De, Wenfeng Bao, Nagongbilige Hea, Jun Fang","doi":"10.3389/fmmed.2026.1770665","DOIUrl":"10.3389/fmmed.2026.1770665","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis, an immune-mediated systemic inflammatory disease affecting skin, vessels, and joints, often co-occurs with depression. Routine depression screening is vital, as mood disorders link to inflammation, visible lesions, and functional limitations.</p><p><strong>Methods: </strong>The study integrated Mendelian randomization (MR), transcriptomics, and single-cell omics via public databases to explore comorbidity mechanisms.</p><p><strong>Results: </strong>MR identified 340 psoriasis-related and 307 depression-related eQTL-gene associations; 9 intersected. LASSO found 4 key Genes (<i>MAP3K20, WARS2, TBXAS1, ABHD15</i>), enriched in IL-17/NF-κB/FoxO pathways, cholesterol metabolism, and synaptic cycling. They correlated with immune infiltration, ferroptosis, and specific cell localization. Folic acid (from CTD) targeted 3 genes.</p><p><strong>Conclusion: </strong>These 4 genes mediate comorbidity via inflammation, immune metabolism, and ferroptosis. Folic acid pathways have therapeutic value, laying a foundation for precision therapy.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1770665"},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790559","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":"HIF1α reinforces PPARγ-dependent metabolic rechanneling to support lipid accumulation in adipocytes.","authors":"Chaonan Zhu, Meiqian Wu, Minh Duc Pham, Yue Wang, Arka Provo Das, Yijie Mao, Peter Mirtschink, Ting Yuan, Jaya Krishnan","doi":"10.3389/fmmed.2026.1716464","DOIUrl":"10.3389/fmmed.2026.1716464","url":null,"abstract":"<p><strong>Introduction: </strong>Adipose tissue hypoxia is a hallmark of obesity and partly contributes to metabolic dysfunction through effects on differentiated adipocytes. Although hypoxia-inducible factor 1α (HIF1α) is a key transcriptional mediator of hypoxic responses, its state-dependent metabolic role remains incompletely defined in mature adipocytes. Herein, we investigate how HIF1α regulates lipid metabolism in differentiated adipocytes under nutrient excess conditions.</p><p><strong>Methods: </strong>An adipocyte-specific Hif1α knockout mouse model was subjected to high-fat diet feeding <i>in vivo</i>. Adipose mass, adipocyte size, glucose tolerance, and insulin sensitivity were assessed. Metabolic and enzymatic analyses focused on lipid anabolic pathways, including glycolysis-linked glycerolipid biosynthesis and PPARγ-dependent programs.</p><p><strong>Results: </strong>Adipocyte-specific deletion of Hif1α attenuated adipocyte hypertrophy, resulting in reduced adipose mass as well as improved systemic glucose tolerance and insulin sensitivity during high-fat diet feeding. Mechanistically, HIF1α reinforced PPARγ-dependent lipid anabolic programs by coordinating glycolytic flux with glycerolipid biosynthesis to promote the rechanneling of glucose-derived intermediates into triacylglyceride synthesis.</p><p><strong>Discussion: </strong>Together, these findings provide metabolic and enzymatic validations of a late-stage, state-dependent HIF1α-PPARγ lipid storage program and implicate the glycerol-3-phosphate dehydrogenase 1 (GPD1)-glycerol-3-phosphate acyltransferase (GPAT) axis as a key molecular executor of hypertrophic lipid accumulation in differentiated adipocytes.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1716464"},"PeriodicalIF":0.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438134","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":"CD19 exon 2 skipping is a potential prognostic correlate of anti-CD19 CAR-T therapy relapse.","authors":"Søren Helweg Dam, Giorgia Moranzoni, Magnus Haraldson Høie, Signe Modvig, Karin A W Wadt, Bodil Als-Nielsen, Kjeld Schmiegelow, Kristoffer Vitting-Seerup, Mike Bogetofte Barnkob, Lars Rønn Olsen","doi":"10.3389/fmmed.2026.1763390","DOIUrl":"10.3389/fmmed.2026.1763390","url":null,"abstract":"<p><p>Relapse following anti-CD19 chimeric antigen receptor (CAR) T cell therapy remains a concern in the treatment of refractory B-cell malignancies. Although the CD19<b>Δ</b>exon2 splice variant has been linked to treatment failure, reliable pre-treatment biomarkers for relapse risk are lacking. Here, we analyzed RNA-sequencing data from a small publicly available cohort of four anti-CD19 CAR-T-treated B-cell acute lymphoblastic leukemia patients, including one responder, one non-responder, and two who relapsed after initial response. We quantified the percent spliced in (PSI) of CD19 exon 2, as a proxy for CD19<b>Δ</b>exon2 abundance before and after treatment. The patient with the lowest pre-treatment exon 2 PSI (i.e., highest estimated abundance of CD19<b>Δ</b>exon2) experienced the earliest relapse, whereas the complete responder showed no detectable exon 2 skipping. In silico protein structure modeling indicated reduced structural stability of the FMC63 epitope region in the CD19<b>Δ</b>exon2 variant, supporting a potential mechanistic link between exon 2 exclusion and antigen escape. Analysis of larger RNA-sequencing datasets from CAR-T treatment-naïve B-cell malignancies and healthy tissues revealed low-level exon 2 skipping in some individuals across both malignant and normal B cells. These findings suggest that CD19 exon 2 skipping may correlate with relapse after CAR-T therapy, and its presence in treatment-naïve individuals highlights its potential for evaluation as an RNA- or qPCR-based biomarker in future studies.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"6 ","pages":"1763390"},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313220","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}