Biologics : Targets & Therapy最新文献

{"title":"Targeting Metabolic Reprogramming of T-Cells for Enhanced Anti-Tumor Response","authors":"Y. T. Dabi, H. Andualem, S. T. Degechisa, S. T. Gizaw","doi":"10.2147/BTT.S365490","DOIUrl":"https://doi.org/10.2147/BTT.S365490","url":null,"abstract":"Abstract Cancer immunotherapy is an effective treatment option against cancer. One of the approaches of cancer immunotherapy is the modification of T cell-based anti-tumor immune responses. T-cells, a type of adaptive immune response cells responsible for cell-mediated immunity, have long been recognized as key regulators of immune-mediated anti-tumor immunity. T-cell activities have been reported to be suppressed or enhanced by changes in cell metabolism. Moreover, metabolic reprogramming during activation of T cells is required for the development of distinct differentiation profiles of these cells, which may allow the development of long-term cell-mediated anti-tumor immunity. However, T cells have been shown to undergo metabolic exhaustion in tumor microenvironment (TME) as it poses several obstacles to their function. Applications of several mechanistic solutions to improve the efficacy of T cell-based therapies including chimeric antigen receptor (CAR) T cell therapy are yet to be determined. Modifying the metabolic properties of these cells and employing them in cancer immunotherapy is a potential strategy for improving their anti-tumor activity and therapeutic efficacy. To give an insight, in this review paper, we endeavoured to cover metabolic reprogramming in cancer and T cells, signalling mechanisms involved in immuno-metabolic regulation, the effects of the TME on T cell metabolic fitness, and targeting metabolic reprogramming of T cells for an enhanced anti-tumor response.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"35 - 45"},"PeriodicalIF":4.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42016582","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}

{"title":"Progress in Biological Therapies for Adult-Onset Still’s Disease","authors":"P. Galozzi, S. Bindoli, A. Doria, P. Sfriso","doi":"10.2147/BTT.S290329","DOIUrl":"https://doi.org/10.2147/BTT.S290329","url":null,"abstract":"Abstract Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"21 - 34"},"PeriodicalIF":4.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47547261","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}

{"title":"Continuous Use of Etanercept During Pregnancy Does Not Affect TNF-Alpha Levels in Umbilical Cord Blood","authors":"Masayuki Nishide, Mayu Yagita, A. Kumanogoh","doi":"10.2147/BTT.S358449","DOIUrl":"https://doi.org/10.2147/BTT.S358449","url":null,"abstract":"Abstract TNF-alpha-targeted therapies during pregnancy is a topic of interest in rheumatology. Etanercept (ETN) is expected to have lower transplacental transfer, however, clinical evidence is lacking on the usefulness and safeness of continuing etanercept throughout pregnancy. We here described the first reported case of relapsing polychondritis where continuous use of ETN throughout pregnancy was required. The patient was a pregnant Japanese woman who presented with bilateral ear cartilage redness, swelling, saddle nose and severe subglottic oedema. Due to severe systemic and life-threatened disease, we decided to continue using ETN throughout pregnancy and resulted in successful vaginal delivery. The treatment with ETN was successful and TNF-alpha levels in umbilical cord blood were not affected. The infant did not have any signs of chondritis although levels of anti-type 2 collagen antibodies in maternal and umbilical cord blood were similar, suggesting that anti-type 2 collagen antibodies crossed the placenta. This case is an important clinical experience that strengthens the safety to continue ETN during the entire pregnancy if necessary.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"17 - 19"},"PeriodicalIF":4.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46134943","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}

{"title":"A Non-Interventional Multicenter Study of First-Line Bevacizumab in Combination with Chemotherapy in Patients with Metastatic Colorectal Cancer in Lebanon","authors":"S. Temraz, F. Nasr, J. Kattan, D. Abigerges, W. Moukadem, F. Farhat, L. Maatouk, G. Chahine, A. Shamseddine","doi":"10.2147/BTT.S340525","DOIUrl":"https://doi.org/10.2147/BTT.S340525","url":null,"abstract":"Purpose When combined with chemotherapy, bevacizumab improves progression-free survival (PFS) in metastatic colorectal cancer (mCRC). This observational trial was designed to assess the safety and efficacy of bevacizumab plus first-line chemotherapy in a real-world setting in Lebanon. Patients and Methods A non-interventionaL multicenter study of first-LIne AVastin® (bevacizumab) in combination with chEmotherapy in patients with metastatic colorectal cancer (LLIVE) is a multicenter, prospective, Lebanon-based, observational study that enrolled mCRC patients who received first-line bevacizumab plus chemotherapy combination. The primary end point of the study was PFS. Secondary endpoints comprised the overall response rate (ORR) and the safety and tolerability of bevacizumab. Results A total of 196 patients were enrolled between July 2010 and August 2013. The median duration of follow-up was 11 months. Median duration of bevacizumab treatment was 4 months with FOLFOX being the chiefly chemotherapy regimen used in the first-line setting (26%). Median PFS was 8.22 months (95% confidence interval (CI): 7.005–9.443). The ORR was 50.3% (complete response 7.5%, partial response 42.8%). The most common adverse event encountered was hypertension (28%) followed by epistaxis (4.8%), diarrhea (4%), anemia (4%) and headache (4%). Grade 3/4 adverse events occurred in 15.2% of patients. Conclusion The trial further substantiated the efficacy and safety of bevacizumab and chemotherapy in the first-line treatment of mCRC patients in Lebanon.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"7 - 15"},"PeriodicalIF":4.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48063634","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}

{"title":"A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances.","authors":"Maheeba Abdulla,&nbsp;Nafeesa Mohammed","doi":"10.2147/BTT.S380027","DOIUrl":"https://doi.org/10.2147/BTT.S380027","url":null,"abstract":"<p><p>Inflammatory bowel diseases are considered immune disorders with a complex genetic architecture involving constantly changing endogenous and exogenous factors. The rapid evolution of genomic technologies and the emergence of newly discovered molecular actors are compelling the research community to reevaluate the knowledge and molecular processes. The human intestinal tract contains intestinal human microbiota consisting of commensal, pathogenic, and symbiotic strains leading to immune responses that can contribute and lead to both systemic and intestinal disorders including IBD. In this review, we attempted to highlight some updates of the new IBD features related to genomics, microbiota, new emerging therapies and some major established IBD risk factors.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 ","pages":"129-140"},"PeriodicalIF":4.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/ae/btt-16-129.PMC9481278.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9925276","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":"Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who Switched to an Infliximab Biosimilar or Remained on Originator Infliximab.","authors":"Timothy Fitzgerald, Richard Melsheimer, Marie-Hélène Lafeuille, Patrick Lefebvre, Laura Morrison, Kimberly Woodruff, Iris Lin, Bruno Emond","doi":"10.2147/BTT.S285610","DOIUrl":"10.2147/BTT.S285610","url":null,"abstract":"<p><strong>Objective: </strong>To compare switching and discontinuation patterns of patients stable on originator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on originator IFX (continuers) in the United States.</p><p><strong>Methods: </strong>Symphony Health Solutions' Patient Transactional Datasets (10/2012-03/2019) were used to identify adults with ≥2 claims for either rheumatoid arthritis (RA), psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, or inflammatory bowel disease (IBD); and ≥1 claim for originator or biosimilar IFX. The index date was the first IFX biosimilar claim for switchers or a random originator IFX claim for continuers. All patients were required to have ≥5 originator IFX claims during the 12 months pre-index (prevalent population). The subset of patients with ≥12 months of observation prior to the first originator IFX claim was also analyzed (incident population). Switchers were matched 1:3 to continuers. Discontinuation was defined as having ≥120 days between 2 consecutive index treatment claims.</p><p><strong>Results: </strong>Prevalent switchers (N=1109) were 3.57-times more likely than continuers (N=3327) to switch to another originator biologic (hazard ratio [HR]=3.57, p<0.001). Of 249 prevalent switchers who switched to another originator biologic, 200 (80.3%) switched back to originator IFX. Incident switchers (N=571) were 2.55-times more likely than continuers (N=1713) to switch to another originator biologic (HR=2.55, p<0.001). Of 118 incident switchers who switched to another originator biologic, 90 (76.3%) switched back to originator IFX. Prevalent switchers were 1.25-times more likely than continuers to discontinue index therapy (HR=1.25, p<0.001). Similar results were observed in RA (prevalent population; switching: HR=3.49, p<0.001; discontinuation: HR=1.23, p=0.009) and IBD (prevalent population; switching: HR=3.82, p<0.001; discontinuation: HR=1.29, p=0.003) subgroups.</p><p><strong>Conclusion: </strong>Patients switching from originator to biosimilar IFX were more likely to switch to another originator biologic (notably back to originator IFX) and discontinue index treatment than those remaining on originator IFX; however, reasons for switching are unknown.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"15 ","pages":"1-15"},"PeriodicalIF":5.3,"publicationDate":"2021-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/f3/btt-15-1.PMC7797299.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343101","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":"How Can We Engineer CAR T Cells to Overcome Resistance?","authors":"Maya Glover,&nbsp;Stephanie Avraamides,&nbsp;John Maher","doi":"10.2147/BTT.S252568","DOIUrl":"https://doi.org/10.2147/BTT.S252568","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy has achieved unrivalled success in the treatment of B cell and plasma cell malignancies, with five CAR T cell products now approved by the US Food and Drug Administration (FDA). However, CAR T cell therapies for solid tumours have not been nearly as successful, owing to several additional challenges. Here, we discuss mechanisms of tumour resistance in CAR T cell therapy and the emerging strategies that are under development to engineer CAR T cells to overcome resistance.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"15 ","pages":"175-198"},"PeriodicalIF":4.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/56/btt-15-175.PMC8141613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578933","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":"Glycopeptides as Potential Interventions for COVID-19.","authors":"Desalegn Getnet Demsie,&nbsp;Abadi Kahsu Gebre,&nbsp;Ebrahim M Yimer,&nbsp;Niguse Meles Alema,&nbsp;Ephrem Mebrahtu Araya,&nbsp;Abere Tilahun Bantie,&nbsp;Mengesha Dessie Allene,&nbsp;Hagazi Gebremedhin,&nbsp;Adane Yehualaw,&nbsp;Chernet Tafere,&nbsp;Haileslassie Tesfay Tadese,&nbsp;Bekalu Amare,&nbsp;Etsay Weldekidan,&nbsp;Desye Gebrie","doi":"10.2147/BTT.S262705","DOIUrl":"https://doi.org/10.2147/BTT.S262705","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19), an infectious disease that primarily attacks the human pulmonary system, is caused by a viral strain called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak emerged from Wuhan, China, and later spread throughout the world. Until the first week of May 2020, over 3.7 million cases had been reported worldwide and more than 258,000 had died due to the disease. So far, off label use of various drugs has been tried in many clinical settings, however, at present, there is no vaccine or antiviral treatment for human and animal coronaviruses. Therefore, repurposing of the available drugs may be promising to control emerging infections of SARS-COV2; however, new interventions are likely to require months to years to develop. Glycopeptides, which are active against gram-positive bacteria, have demonstrated significant activity against viral infections including SARS-COV and MERS-COV and have a high resemblance of sequence homology with SARS-COV2. Recent in vitro studies have also shown promising activities of aglycon derivative of glycopeptides and teicoplanin against SARS-COV2. Hydrophobic aglycon derivatives and teicoplanin, with minimal toxicity to human cell lines, inhibit entry and replication of SARS-COV2. These drugs block proteolysis of polyprotein a/b with replicase and transcription domains. Teicoplanin use was associated with complete viral clearance in a cohort of patients with severe COVID-19 symptoms. This review attempts to describe the activity, elucidate the possible mechanisms and potential clinical applications of existing glycopeptides against corona viruses, specifically SARS-COV2.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"14 ","pages":"107-114"},"PeriodicalIF":4.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S262705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849878","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":"Efficacy And Safety Of Adalimumab Biosimilar (Exemptia) In Moderate-To-Severe Steroid-Refractory Ulcerative Colitis Patients: Real-Life Outcomes In Resource-Constrained Setting At 24-Weeks Follow-Up.","authors":"Alok Chandra, Ravi Kanth, Sandeep Thareja","doi":"10.2147/BTT.S214518","DOIUrl":"10.2147/BTT.S214518","url":null,"abstract":"<p><strong>Background: </strong>Adalimumab (ADA) is approved for the management of lcerative colitis (UC) not responding to conventional therapy. Use of biologics in resource-constrained settings is very challenging. Currently, real-life data on the safety and efficacy of ADA biosimilar (Exemptia) in steroid-refractory UC patients are limited.</p><p><strong>Aim and objectives: </strong>To assess the efficacy and safety of ADA biosimilar (Exemptia) to treat steroid-refractory difficult-to-treat UC patients in a resource-constrained Indian setting at 24-weeks follow-up.</p><p><strong>Materials and methods: </strong>This was a retrospective single-center study to evaluate the efficacy and safety of ADA biosimilar (Exemptia) in steroid-refractory UC patients. All the eligible patients who received induction dose of 160 mg at week 0, 80 mg at week 2 and 40 mg at week 4 and 40 mg every 4 weeks as maintenance regimen from 01 September 2017 to 31 Jan 2019 were retrospectively included in this single-center analysis. Those patients who had shown sub-optimal response at 12 weeks received 40 mg every 2 weeks as maintenance therapy. Outcomes in terms of clinical remission, clinical response and mucosal healing were evaluated in the short term at 12 weeks and 24 weeks.</p><p><strong>Results: </strong>Twenty-five patients were retrospectively included between the time period of 1 September 2017 to 31 July 2018 with a mean age of 35 years. ADA biosimilar was effective in inducing clinical remission in 16% patients at 12 and 24 weeks, clinical response was seen in 48% at week 12 and 44% at week 24. The mean baseline total Mayo score (TMS) for all patients was 10.16 which decreased to a mean score of 5.72 at 12 weeks and 5.52 at 24 weeks with therapy with the decrease of the score being statistically significant both at 12 and 24 weeks (p<0.05). Two patients (8%) developed pulmonary tuberculosis (TB). ADA biosimilar frequency was accelerated to once in 2 weeks in 14 (56%) patients who did not show an optimal response at 12 weeks. Of these 14 patients, 5 were responders and 9 were non-responders at 12 weeks. At 24 weeks, 6 patients showed clinical response and 7 were non-responders, while one patient had developed TB.</p><p><strong>Conclusion: </strong>ADA biosimilar (Exemptia) therapy is a safe and cost-effective alternative to original biologics in difficult-to-treat UC patients in resource-constrained Indian setting with comparable efficacy. Maintenance therapy at four weekly intervals can be considered in those patients who have shown an early clinical response at 12 weeks to minimize costs, but more studies are needed to confirm the same.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 1","pages":"191-200"},"PeriodicalIF":5.3,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46186136","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":"Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats.","authors":"Nur Samsu, Setyawati Soeharto, Muhaimin Rifai, Achmad Rudijanto","doi":"10.2147/BTT.S214820","DOIUrl":"10.2147/BTT.S214820","url":null,"abstract":"<p><strong>Background: </strong>Podocyte injury and its subsequent detachment play a critical role in the development and progression of diabetic nephropathy (DN). The objective of this study was to investigate the effect of rosmarinic acid (RA) in preventing podocyte detachment and inhibiting the progression of DN in streptozotocin (STZ)-induced diabetic in rats.</p><p><strong>Methods: </strong>We used 20 adult male Wistar rats as experimental animals, which were randomly divided into 5 groups (n=4 per group): nondiabetic rat group (negative control) and 4 groups of STZ-induced diabetic rats, namely, 1 group untreated diabetic rats (positive control) and 3 groups treated diabetic rats with RA 75 mg/kg, telmisartan (TMS) 1 mg/kg and combination of RA 75 mg/kg with TMS 1 mg/kg), respectively. After 8 weeks of therapy, urinary levels of podocin, nephrin and albumin and also serum cystatin C levels were examined by ELISA. The expression of p65 nuclear factor-kB by immunohistochemistry whereas expression of podocin and nephrin glomerulus were examined by immunofluorescence.</p><p><strong>Results: </strong>In the treated diabetic groups, we found that urinary level of podocin and nephrin, albumin urine excretion and serum cystatin C levels were significantly lower than the positive control group. Compared to negative controls, the group of treated diabetic rats did not differ significantly in preventing increased excretion of urinary nephrin and podocin. Meanwhile, treatment with RA monotherapy was significantly better than TMS or a combination of RA with TMS in reducing albumin excretion and preventing decreased kidney function.</p><p><strong>Conclusion: </strong>In STZ-induced diabetic rats, RA can prevent podocyte detachment. Treatment with RA and TMS either monotherapy or in combination can inhibit the development and progression of DN. However, the combination of both did not show a synergistic effect, even have higher urinary albumin excretion and worse kidney function compared to the RA monotherapy.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"13 ","pages":"179-190"},"PeriodicalIF":5.3,"publicationDate":"2019-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/be/btt-13-179.PMC6722456.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41190498","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}