Biologics : Targets & Therapy最新文献

{"title":"Treating Alpelisib-Induced Hyperinsulinemia in Patients with Advanced Breast Cancer - A Real-Life Experience.","authors":"Ruth Percik,&nbsp;Cecilie Oedegaard Smith,&nbsp;Anca Leibovici,&nbsp;Ayelet Shai","doi":"10.2147/BTT.S395817","DOIUrl":"https://doi.org/10.2147/BTT.S395817","url":null,"abstract":"<p><p>PIK3CA activating mutations are found in 40% of advanced breast cancer and are associated with worse prognosis. PI3K blockage is associated with insulin resistance, leading to hyperglycemia and hyperinsulinemia. Alpelisib is the first PI3K inhibitor used in cancer treatment. Laboratory evidence indicated that alpelisib-induced hyperinsulinemia offsets the drug's efficacy, but insulin levels were not tested in the clinical trials that evaluated alpelisib for breast cancer. Hyperglycemia could also interfere with anti-tumor effects of PI3K inhibitors by inducing Immune tolerance and altered mitochondrial metabolism. We have monitored insulin levels in 4 breast cancer patients with concomitant metabolic syndrome treated with alpelisib, and pre-treated patients with baseline increased insulin levels with pioglitazone, a potent insulin sensitizer, to target both hyperinsulinemia and hyperglycemia, and we report the treatment course of these patients. All patients achieved glycemic control and were able to maintain alpelisib dose intensity. Duration of response to alpelisib was longer than anticipated in this treatment setting. Insulin dynamics confirmed the efficacy of pioglitazone as a specific on-target hypoglycemic and hypo-insulinemic agent in the unique setting of PI3K blockade. Our experience suggests that targeting hyperinsulinemia in patients with is safe and feasible and results in good metabolic and oncologic outcomes.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"61-67"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/64/btt-17-61.PMC10164376.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444801","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":"Why and How Should Ethiopia Establish a Stem Cell Transplant Service? A Review Article.","authors":"Sintayehu Mekonnen,&nbsp;Hawi Farris","doi":"10.2147/BTT.S401289","DOIUrl":"https://doi.org/10.2147/BTT.S401289","url":null,"abstract":"<p><p>Ethiopia is attempting to reduce cancer-related morbidity and mortality through a strategic national cancer control plan but according to Globocan 2020, hematologic malignancies particularly leukemia and non-Hodgkin's lymphoma rank among the top five leading causes of new cancer incidence and cause of death among all age groups in both sexes. Hematopoietic stem-cell transplantation (HSCT) is an advanced treatment modality that makes the only effective treatment for cancer and non-cancer-related hematologic diseases unresponsive to conventional therapy. Patients who need stem cell transplants must travel to abroad countries to get the treatment. Meanwhile, the Ethiopian National Specialty and Subspecialty Roadmap sets the goal of establishing HSCT centers in 2020-2029 GC, yet leaders and planners must start taking steps to put the setup in place. Setting up an HSCT facility is challenging for developing countries due to the high costs, limited infrastructure, and need for intensive medical staff training; however, several nations have been able to start successful stem cell transplant programs. This review summarizes the basic steps and requirements of the program in light of guidelines recommendations and lessons learned from other developing countries. It also highlights possible cost-effective opportunities, bottlenecks, and areas that will require work and investment to make the objective reality in Ethiopia. Provides key information to assist administrators and policymakers to set priorities in planning and making informed decisions to establish and maintain the service.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"33-40"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/8c/btt-17-33.PMC10038007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545572","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":"Adherence to Subcutaneous Anti-Tumour Necrosis Factor Treatment in a Cohort of Patients with Rheumatoid Arthritis Before and After the Implementation of a Comprehensive Care Model.","authors":"Pedro Santos-Moreno,&nbsp;Guillermo Sánchez-Vanegas,&nbsp;Angélica Monterrosa-Blanco,&nbsp;Gabriel-Santiago Rodríguez-Vargas,&nbsp;Manuel Rivero,&nbsp;Pedro Rodriguez,&nbsp;Omar-Javier Calixto,&nbsp;Adriana Rojas-Villarraga,&nbsp;Carlos Alberto Castro","doi":"10.2147/BTT.S385422","DOIUrl":"https://doi.org/10.2147/BTT.S385422","url":null,"abstract":"<p><strong>Purpose: </strong>To assess, in a cohort of patients with rheumatoid arthritis (RA) treated with subcutaneous antitumor necrosis factor drugs (anti-TNFs), the levels of treatment adherence before and after implementing a comprehensive care model (CCM).</p><p><strong>Patients and methods: </strong>An observational study including RA patients under treatment with subcutaneous anti-TNFs (adalimumab, etanercept, and golimumab) selected at convenience was performed; a sample size of 125 patients was calculated. The outcome variable was adherence assessed with the Compliance Questionnaire on Rheumatology (CQR19), measured before and after implementing a CCM. Descriptive and bivariate analyses were performed comparing adherence before and after applying the model (Wilcoxon and McNemar's Chi² test). For multivariate analysis, a generalized linear model adjusted for covariates was performed, where the difference in the proportion of adherence was the outcome measure.</p><p><strong>Results: </strong>A total of 131 RA patients were followed-up for 24 months; average age was 62 years, and 83.9% were women. The median of DAS28 at the beginning of the follow-up was 2.32, and the HAQ was 0.25. At baseline, 87.8% were adherent; after 24 months, 96.2% were adherent according to CQR19. At the end of follow-up, adherence increased with the three types of anti-TNFs treatment. In a matched model adjusted for clinical variables, the CCM was estimated to produce a 9.4% increase in the total percentage of adherent patients. Additionally, a statistically significant increase of 4.5% in the percentage of adherent patients treated with golimumab compared with etanercept and adalimumab was found.</p><p><strong>Conclusion: </strong>A CCM produced an important increase in the percentage of patients with rheumatoid arthritis adherent to treatment after 24 months of follow-up. It is noteworthy that Golimumab patients were more adherent when compared with other current anti-TNFs treatments.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"199-209"},"PeriodicalIF":4.0,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/34/btt-16-199.PMC9699109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40515015","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":"TNF Inhibitors Exert a \"Hidden\" Beneficial Effect in the Cardiovascular Lipoprotein Profile of RA Patients.","authors":"Jaime Calvo Alén,&nbsp;Bernardo Alio Lavin-Gomez,&nbsp;Elena Aurrecoechea,&nbsp;Armando Raul Guerra Ruiz,&nbsp;Víctor Martínez Taboada,&nbsp;Juan Gómez Gerique","doi":"10.2147/BTT.S364191","DOIUrl":"https://doi.org/10.2147/BTT.S364191","url":null,"abstract":"<p><strong>Purpose: </strong>A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests.</p><p><strong>Patients and methods: </strong>RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed.</p><p><strong>Results: </strong>Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed.</p><p><strong>Conclusion: </strong>TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"187-197"},"PeriodicalIF":4.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4c/8d/btt-16-187.PMC9587304.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40680083","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":"Phage Therapy: A Different Approach to Fight Bacterial Infections.","authors":"Zigale Hibstu,&nbsp;Habtamu Belew,&nbsp;Yibeltal Akelew,&nbsp;Hylemariam Mihiretie Mengist","doi":"10.2147/BTT.S381237","DOIUrl":"https://doi.org/10.2147/BTT.S381237","url":null,"abstract":"<p><p>Phage therapy is one of the alternatives to treat infections caused by both antibiotic-sensitive and antibiotic-resistant bacteria, with no or low toxicity to patients. It was started a century ago, although rapidly growing bacterial antimicrobial resistance, resulting in high levels of morbidity, mortality, and financial cost, has initiated the revival of phage therapy. It involves the use of live lytic, bioengineered, phage-encoded biological products, in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body within seven days of clearing an infection. They target specific bacterial strains and cause minimal disruption to the microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying a high phage titer for therapy exposes them and activates the host immune system. To date, no serious side effects have been reported with human phage therapy. In this review, we describe phage-phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, and the therapeutic application of modified phages and phage-encoded products. We also highlight the comparison of antibiotics and lytic phage therapy, the pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling, and current challenges in phage therapy.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"173-186"},"PeriodicalIF":4.0,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/58/btt-16-173.PMC9550173.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33502647","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":"Biosimilars: Science, Implications, and Potential Outlooks in the Middle East and Africa.","authors":"Radwa Ahmed Batran,&nbsp;Mai Elmoshneb,&nbsp;Ahmed Salah Hussein,&nbsp;Omar M Hussien,&nbsp;Fady Adel,&nbsp;Reham Elgarhy,&nbsp;Mosaad I Morsi","doi":"10.2147/BTT.S376959","DOIUrl":"https://doi.org/10.2147/BTT.S376959","url":null,"abstract":"<p><p>Biosimilars are biological products that efficiently replicate the function of the originator products. They have changed the prognosis of millions of patients with many serious conditions. The main engine beyond their development is to bring competition into the marketplace, accordingly further the healthcare systems' sustainability. Furthermore, by lowering financial obstacles to biological treatments, biosimilars play a critical role in budgetary redistribution and, hence, promote better allocation of scarce healthcare resources. Today, biosimilars have become a substantial component of effective biological therapies anywhere in the world. Alike, most Middle East and African countries are encouraging the domestic biosimilars industry, and the whole region is aware of the biosimilars' importance. However, constraints to increasing biosimilars uptake should be addressed.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"161-171"},"PeriodicalIF":4.0,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/72/btt-16-161.PMC9550021.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33502646","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":"Biologic Therapy for Refractory Immune Checkpoint Inhibitor Colitis.","authors":"Nasser M Alorfi,&nbsp;Mansour Marzouq Alourfi","doi":"10.2147/BTT.S367675","DOIUrl":"https://doi.org/10.2147/BTT.S367675","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI) are treatments for several cancer types. Pathogenesis of ICI-induced colitis is not yet clearly explained as it can be disguised as another form such as inflammatory bowel disease or IBD. Recent studies revealed that ICI-induced colitis is a unique form of colitis wherein the synergy of regulatory T cells with the gut microbiome is involved. Diagnosis of colitis can be done via endoscopic lesions and histopathological methods. A patient with colitis can be compared with someone who has IBD. Initial treatment is a corticosteroid. Cooperation between gastroenterologists and oncologists is required to understand further the complete diagnosis and management of different behaviors of ICI-induced colitis. Although immunotherapy provides breakthroughs in treating cancer, adverse effects cannot be prevented and have to be carefully addressed. This study aimed to discuss different biologic therapeutic perspectives in treating refractory immune checkpoint inhibitor-induced colitis. This review provided guidelines, challenges, and suggested protocols for drug immunosuppression.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"119-127"},"PeriodicalIF":4.0,"publicationDate":"2022-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/39/btt-16-119.PMC9362776.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40716014","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":"Is Tofacitinib Effectiveness in Patients with Rheumatoid Arthritis Better After Conventional Than After Biological Therapy? - A Cohort Study in a Colombian Population.","authors":"Pedro Santos-Moreno,&nbsp;Susan Martinez,&nbsp;Linda Ibata,&nbsp;Laura Villarreal,&nbsp;Fernando Rodríguez-Florido,&nbsp;Manuel Rivero,&nbsp;Adriana Rojas-Villarraga,&nbsp;Claudio Galarza-Maldonado","doi":"10.2147/BTT.S361164","DOIUrl":"https://doi.org/10.2147/BTT.S361164","url":null,"abstract":"<p><strong>Purpose: </strong>Tofacitinib is recommended for treatment of rheumatoid arthritis (RA) in patients with moderate to severe disease activity, but there is not enough evidence on its effectiveness after conventional DMARDs vs its use after biologics. The aim was evaluating the effectiveness of tofacitinib in RA as first-line treatment (after conventional DMARDs) in a real-life setting in Colombian (Latin-American) patients.</p><p><strong>Patients and methods: </strong>Retrospective cohort study conducted at a specialized center for RA management. A complete statistical analysis was performed to compare the values of the change in the DAS28 at months 3, 6, and 12 in both treatment groups.</p><p><strong>Results: </strong>A total of 152 RA patients who received tofacitinib: first-line 85 patients (55.9%) after failure on conventional DMARDs or second-line 67 patients (44.1%) after failure on biologic DMARDs. Comparative analysis of response to treatment showed a reduction in DAS28 at 3, 6, and 12 months in both study groups without statistical differences, but a higher proportion of first-line patients achieved remission (45% vs 23%). Nonresponse at three months were associated with no response at six months of follow-up. Baseline DAS28 was significantly associated with response at 12 months (OR: 1.87, 95%CI: 1.06-3.30, <i>p</i>-value 0.028). In second-line patients, response to tofacitinib was not related to number of biologic DMARDs previously used.</p><p><strong>Conclusion: </strong>Tofacitinib is an effective treatment option for patients with RA, maybe better after conventional DMARDs than after biologic therapy failure. Further studies are required to determine the role of tofacitinib in different lines of RA treatment and in other groups of patients.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"107-117"},"PeriodicalIF":4.0,"publicationDate":"2022-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/ad/btt-16-107.PMC9289171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40612094","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":"Successful Treatment of an Adult with Atopic Dermatitis and Lamellar Ichthyosis Using Dupilumab.","authors":"Faisal K Binkhonain,&nbsp;Sara Aldokhayel,&nbsp;Hessah BinJadeed,&nbsp;Abdulaziz Madani","doi":"10.2147/BTT.S362391","DOIUrl":"https://doi.org/10.2147/BTT.S362391","url":null,"abstract":"<p><p>Lamellar ichthyosis (LI) is a rare autosomal cornification disorder, with most cases due to a mutation in the transglutaminase-1 (TGM1) gene on chromosome 14. Patients with LI usually present with a collodion membrane and mild erythroderma at birth, with the collodion membranes shedding within the first weeks of life and being replaced by a generalized scale. Typically, LI is managed with oral retinoids, emollients, and keratolytic agents, eg, lactic acid. We report an LI case associated with atopic dermatitis and asthma that showed a marked improvement with dupilumab treatment. This finding is highly significant as it may represent a breakthrough in the treatment of LI, thus more research is needed to investigate the potential benefits of dupilumab for the treatment of ichthyosis, such as the effects observed in our patient.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"85-88"},"PeriodicalIF":4.0,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/63/btt-16-85.PMC9236574.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40405565","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":"Biological Therapies for the Management of Enteric Disease: Considerations for the Clinician.","authors":"Adam Saleh,&nbsp;Usman Ansari,&nbsp;Shaadi Abughazaleh,&nbsp;Kerri Glassner,&nbsp;Bincy P Abraham","doi":"10.2147/BTT.S335697","DOIUrl":"https://doi.org/10.2147/BTT.S335697","url":null,"abstract":"<p><p>Several biologic therapies have been approved for enteric diseases. We evaluate each biologic's role based on their mechanism of action in treating these conditions. This review examines data on efficacy and safety, as well as considerations for using these therapies in clinical practice in inflammatory bowel diseases, enteric infections-specifically <i>Clostridioides difficile</i> colitis-and potentially in the increasingly prevalent disorder of eosinophilic esophagitis. When choosing an appropriate therapy, it is important to assess patient severity, as most biologics are approved for those with moderate to severe disease activity. With many years of data from clinical trials and real-world experience, these therapies have been shown to improve outcomes overall in enteric diseases, contributing to more options for our patients.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":" ","pages":"67-83"},"PeriodicalIF":4.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/2e/btt-16-67.PMC9211072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391172","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}