ImmunoTargets and Therapy最新文献

{"title":"IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity.","authors":"Melissa Maria Johanna van Gool,&nbsp;Marjolein van Egmond","doi":"10.2147/ITT.S266242","DOIUrl":"https://doi.org/10.2147/ITT.S266242","url":null,"abstract":"<p><p>Mucosal surfaces constitute the frontiers of the body and are the biggest barriers of our body for the outside world. Immunoglobulin A (IgA) is the most abundant antibody class present at these sites. It passively contributes to mucosal homeostasis via immune exclusion maintaining a tight balance between tolerating commensals and providing protection against pathogens. Once pathogens have succeeded in invading the epithelial barriers, IgA has an active role in host-pathogen defense by activating myeloid cells through divers receptors, including its Fc receptor, FcαRI (CD89). To evade elimination, several pathogens secrete proteins that interfere with either IgA neutralization or FcαRI-mediated immune responses, emphasizing the importance of IgA-FcαRI interactions in preventing infection. Depending on the IgA form, either anti- or pro-inflammatory responses can be induced. Moreover, the presence of excessive IgA immune complexes can result in continuous FcαRI-mediated activation of myeloid cells, potentially leading to severe tissue damage. On the one hand, enhancing pathogen-specific mucosal and systemic IgA by vaccination may increase protective immunity against infectious diseases. On the other hand, interfering with the IgA-FcαRI axis by monovalent targeting or blocking FcαRI may resolve IgA-induced inflammation and tissue damage. This review describes the multifaceted role of FcαRI as immune regulator between anti- and pro-inflammatory responses of IgA, and addresses potential novel therapeutic strategies that target FcαRI in disease.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2021-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/df/itt-9-351.PMC7801909.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38755185","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":"Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?","authors":"Francesco Passiglia,&nbsp;Maria Lucia Reale,&nbsp;Valeria Cetoretta,&nbsp;Silvia Novello","doi":"10.2147/ITT.S253581","DOIUrl":"https://doi.org/10.2147/ITT.S253581","url":null,"abstract":"<p><p>The therapeutic targeting of the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis marked a milestone in the treatment of non-small cell lung cancer (NSCLC), leading to unprecedented response duration and long-term survival for a relevant subgroup of patients affected by non-oncogene-addicted, metastatic disease. However, the biological heterogeneity as well as the occurrence of innate/acquired resistance are well-known phenomena which significantly affect the therapeutic response to immunotherapy. To date, we are moving towards the second phase of the \"immune-revolution\", characterized by the advent of new immune-checkpoint inhibitors combinations, aiming to target the main resistance pathways and ultimately increase the number of NSCLC patients who may derive long-term clinical benefit from immunotherapy. In this review, we provide an updated and comprehensive overview of the main PD-1/PD-L1 inhibitors' combination approaches under clinical investigation in non-oncogene addicted, metastatic NSCLC patients, including checkpoints (other than CTLA-4) as well as \"immune-metabolism\" modulators, DNA repair pathway inhibitors, antiangiogenic agents, cytokines, and a new generation of vaccines, with the final aim of identifying the most promising options on the horizon.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/fb/itt-10-9.PMC7872895.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10344101","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":"Acetylcholine Regulates Pulmonary Pathology During Viral Infection and Recovery.","authors":"Alexander P Horkowitz,&nbsp;Ashley V Schwartz,&nbsp;Carlos A Alvarez,&nbsp;Edgar B Herrera,&nbsp;Marilyn L Thoman,&nbsp;Dale A Chatfield,&nbsp;Kent G Osborn,&nbsp;Ralph Feuer,&nbsp;Uduak Z George,&nbsp;Joy A Phillips","doi":"10.2147/ITT.S279228","DOIUrl":"https://doi.org/10.2147/ITT.S279228","url":null,"abstract":"<p><strong>Introduction: </strong>This study was designed to explore the role of acetylcholine (ACh) in pulmonary viral infection and recovery. Inflammatory control is critical to recovery from respiratory viral infection. ACh secreted from non-neuronal sources, including lymphocytes, plays an important, albeit underappreciated, role in regulating immune-mediated inflammation.</p><p><strong>Methods: </strong>ACh and lymphocyte cholinergic status in the lungs were measured over the course of influenza infection and recovery. The role of ACh was examined by inhibiting ACh synthesis in vivo. Pulmonary inflammation was monitored by Iba1 immunofluorescence, using a novel automated algorithm. Tissue repair was monitored histologically.</p><p><strong>Results: </strong>Pulmonary ACh remained constant through the early stage of infection and increased during the peak of the acquired immune response. As the concentration of ACh increased, cholinergic lymphocytes appeared in the BAL and lungs. Cholinergic capacity was found primarily in CD4 T cells, but also in B cells and CD8 T cells. The cholinergic CD4⁺ T cells bound to influenza-specific tetramers and were retained in the resident memory regions of the lung up to 2 months after infection. Histologically, cholinergic lymphocytes were found in direct physical contact with activated macrophages throughout the lung. Inflammation was monitored by ionized calcium-binding adapter molecule 1 (Iba1) immunofluorescence, using a novel automated algorithm. When ACh production was inhibited, mice exhibited increased tissue inflammation and delayed recovery. Histologic examination revealed abnormal tissue repair when ACh was limited.</p><p><strong>Conclusion: </strong>These findings point to a previously unrecognized role for ACh in the transition from active immunity to recovery and pulmonary repair following respiratory viral infection.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/9b/itt-9-333.PMC7751717.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39088816","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":"Complement Inhibition for the Treatment of Myasthenia Gravis.","authors":"Renato Mantegazza, Fiammetta Vanoli, Rita Frangiamore, Paola Cavalcante","doi":"10.2147/ITT.S261414","DOIUrl":"10.2147/ITT.S261414","url":null,"abstract":"<p><p>Generalized myasthenia gravis (gMG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Approximately 80-90% of patients display antibodies directed against the nicotinic acetylcholine receptor (AChR). A major drive of AChR antibody-positive MG pathology is represented by complement activation. The role of the complement cascade has been largely demonstrated in patients and in MG animal models. Complement activation at the NMJ leads to focal lysis of the post-synaptic membrane, disruption of the characteristic folds, and reduction of AChR. Given that the complement system works as an activation cascade, there are many potential targets that can be considered for therapeutic intervention. Preclinical studies have confirmed the efficacy of complement inhibition in ameliorating MG symptoms. Eculizumab, an antibody directed towards C5, has recently been approved for the treatment of AChR antibody-positive gMG. Other complement inhibitors, targeting C5 as well, are currently under phase III study. Complement inhibitors, however, may present prohibitive costs. Therefore, the identification of a subset of patients more or less prone to respond to such therapies would be beneficial. For such purpose, there is a critical need to identify possible biomarkers predictive of therapeutic response, a field not yet sufficiently explored in MG. This review aims to give an overview of the complement cascade involvement in MG, the evolution of complement-inhibiting therapies and possible biomarkers useful to tailor and monitor complement-directed therapies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/61/itt-9-317.PMC7751298.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39088815","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":"Development of Anti-<i>Yersinia pestis</i> Human Antibodies with Features Required for Diagnostic and Therapeutic Applications.","authors":"Antonietta M Lillo, Nileena Velappan, Julia M Kelliher, Austin J Watts, Samuel P Merriman, Grace Vuyisich, Laura M Lilley, Kent E Coombs, Tara Mastren, Munehiro Teshima, Benjamin W Stein, Gregory L Wagner, Srinivas Iyer, Andrew R M Bradbury, Jennifer Foster Harris, Armand E Dichosa, Stosh A Kozimor","doi":"10.2147/ITT.S267077","DOIUrl":"10.2147/ITT.S267077","url":null,"abstract":"<p><strong>Background: </strong><i>Yersinia pestis</i> is a category A infective agent that causes bubonic, septicemic, and pneumonic plague. Notably, the acquisition of antimicrobial or multidrug resistance through natural or purposed means qualifies <i>Y. pestis</i> as a potential biothreat agent. Therefore, high-quality antibodies designed for accurate and sensitive <i>Y. pestis</i> diagnostics, and therapeutics potentiating or replacing traditional antibiotics are of utmost need for national security and public health preparedness.</p><p><strong>Methods: </strong>Here, we describe a set of human monoclonal immunoglobulins (IgG1s) targeting <i>Y. pestis</i> fraction 1 (F1) antigen, previously derived from in vitro evolution of a phage-display library of single-chain antibodies (scFv). We extensively characterized these antibodies and their effect on bacterial and mammalian cells via: ELISA, flow cytometry, mass spectrometry, spectroscopy, and various metabolic assays.</p><p><strong>Results: </strong>Two of our anti-F1 IgG (αF1Ig 2 and αF1Ig 8) stood out for high production yield, specificity, and stability. These two antibodies were additionally attractive in that they displayed picomolar affinity, did not compete when binding <i>Y. pestis</i>, and retained immunoreactivity upon chemical derivatization. Most importantly, these antibodies detected <1,000 <i>Y. pestis</i> cells in sandwich ELISA, did not harm respiratory epithelial cells, induced <i>Y. pestis</i> agglutination at low concentration (350 nM), and caused apparent reduction in cell growth when radiolabeled at a nonagglutinating concentration (34 nM).</p><p><strong>Conclusion: </strong>These antibodies are amenable to the development of accurate and sensitive diagnostics and immuno/radioimmunotherapeutics.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/ITT.S267077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38690171","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":"All are Equal, Some are More Equal: Targeting IL 12 and 23 in IBD - A Clinical Perspective.","authors":"André Jefremow,&nbsp;Markus F Neurath","doi":"10.2147/ITT.S282466","DOIUrl":"https://doi.org/10.2147/ITT.S282466","url":null,"abstract":"Abstract Chronic inflammatory diseases like inflammatory bowel diseases (IBD) or psoriasis represents a worldwide health burden. Researchers provided great achievements in understanding the origin of these diseases leading to improved therapeutic options. The discovery of cytokines like tumor necrosis factor-α or transforming growth factor-β are examples for these efforts. Interleukin 12 (IL 12) and interleukin 23 (IL 23) represent different important cytokines in this regard. They both belong to the interleukin 12 family and are related by sharing the subunit p40. Ustekinumab is an antibody that blocks p40 and thereby interleukins 12 and 23. Trials showed promising results in treating IBD patients with this drug. Consequently, new questions arose about the distinct features of IL 12 and 23. This review focuses on these interleukins regarding their functions in the healthy and inflamed gut and provides an overview about the results from in vitro and in vivo studies as well as clinical trials.","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/ITT.S282466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38335592","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":"Immunotherapeutic Targets and Therapy for Renal Cell Carcinoma.","authors":"Pierangela Sepe,&nbsp;Alessia Mennitto,&nbsp;Francesca Corti,&nbsp;Giuseppe Procopio","doi":"10.2147/ITT.S240889","DOIUrl":"10.2147/ITT.S240889","url":null,"abstract":"<p><p>Over the last 20 years, different therapies have been considered as the mainstay for the treatment of patients with metastatic renal cell carcinoma (mRCC). Since angiogenesis is a key mechanism in the pathogenesis of renal carcinoma, research is still focusing on the inhibition of new vessel growth through the development of novel and potent tyrosine kinase inhibitors (TKIs), such as cabozantinib. On the other hand, a new therapeutic scenario has opened up in the forefront with immunotherapy. Immune checkpoint inhibitors (ICIs), which already represent a standard treatment option in pretreated mRCC patients, are revolutionizing the frontline therapeutic armamentarium of mRCC. Upfront combination immunotherapy as well as combinations of immunotherapy with targeted agents showed to significantly improved outcomes of mRCC patients compared to single-agent TKIs. ICIs are associated with long-lasting responses. Nonetheless, several unmet needs remain, as a small proportion of patients shows primary refractoriness to immunotherapy. Multiple treatment strategies combining different mechanisms of action or targeting immune escape pathways are emerging with the aim to improve response rates and survival outcomes. This review summarizes current immunotherapeutic targets and therapies approved for mRCC, while examining mechanisms of resistance and future directions, with the aim to address novel treatment strategies and help in improving the management of this tumor.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/ITT.S240889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38736779","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":"Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.","authors":"Rhea Singh, Courtney E Heron, Rima I Ghamrawi, Lindsay C Strowd, Steven R Feldman","doi":"10.2147/ITT.S229667","DOIUrl":"10.2147/ITT.S229667","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a common chronic, inflammatory skin condition. The pathogenesis of AD involves many cytokines that utilize the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling cascade; therefore, JAK inhibitors may be used in the treatment of AD. This review aims to evaluate the pathophysiology, efficacy, and safety of JAK inhibitors and their emerging role as a therapeutic option for patients with AD.</p><p><strong>Methods: </strong>A PubMed search of Phase I, II, and III clinical trials was conducted for relevant literature published between January 2015 and June 2020 utilizing the key terms: JAK inhibitors, atopic dermatitis, efficacy, safety, and treatment. The search was subsequently expanded to include additional terms.</p><p><strong>Results: </strong>In multiple Phase II and III clinical trials, JAK inhibitors were more efficacious than placebo or vehicle controls and slightly more efficacious in direct comparisons to corticosteroids. Overall, JAK inhibitors have a moderate safety profile for use in AD. Some of the more severe theoretical adverse events included thrombosis and reactivation of viral infections. While data remain limited for the long-term efficacy and safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results.</p><p><strong>Discussion: </strong>Short-term data suggest that both topical and oral JAK inhibitors are efficacious and safe for use in patients with AD, although cases of thrombosis and viral disease have been reported. While the current standard treatments for AD are likely preferred, failed therapy with these agents or corticosteroid phobia may be indications for the use of JAK inhibitors in patients with AD.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/f9/itt-9-255.PMC7667501.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38615716","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":"Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases.","authors":"Yoshiya Tanaka,&nbsp;Kana Hoshino-Negishi,&nbsp;Yoshikazu Kuboi,&nbsp;Fumitoshi Tago,&nbsp;Nobuyuki Yasuda,&nbsp;Toshio Imai","doi":"10.2147/ITT.S277991","DOIUrl":"https://doi.org/10.2147/ITT.S277991","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disorder that affects joints and is characterized by synovial hyperplasia and bone erosion associated with neovascularization and infiltration of proinflammatory cells. The introduction of biological disease-modifying anti-rheumatic drugs has dramatically changed the treatment of RA over the last 20 years. However, fewer than 50% of RA patients enter remission, and 10-15% are treatment refractory. There is currently no cure for RA. Fractalkine (FKN, also known as CX3CL1) is a cell membrane-bound chemokine that can be induced on activated vascular endothelial cells. FKN has dual functions as a cell adhesion molecule and a chemoattractant. FKN binds specifically to the chemokine receptor CX3CR1, which is selectively expressed on subsets of immune cells such as patrolling monocytes and killer lymphocytes. The FKN-CX3CR1 axis is thought to play important roles in the initiation of the inflammatory cascade and can contribute to exacerbation of tissue injury in inflammatory diseases. Accordingly, studies in animal models have shown that inhibition of the FKN-CX3CR1 axis not only improves rheumatic diseases but also reduces associated complications, such as pulmonary fibrosis and cardiovascular disease. Recently, a humanized anti-FKN monoclonal antibody, E6011, showed promising efficacy with a dose-dependent clinical response and favorable safety profile in a Phase 2 clinical trial in patients with RA (NCT02960438). Taken together, the preclinical and clinical results suggest that E6011 may represent a new therapeutic approach for rheumatic diseases by suppressing a major contributor to inflammation and mitigating concomitant cardiovascular and fibrotic diseases. In this review, we describe the role of the FKN-CX3CR1 axis in rheumatic diseases and the therapeutic potential of anti-FKN monoclonal antibodies to fulfill unmet clinical needs.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/ITT.S277991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38595485","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":"GM-CSF: A Promising Target in Inflammation and Autoimmunity.","authors":"Kevin M C Lee, Adrian A Achuthan, John A Hamilton","doi":"10.2147/ITT.S262566","DOIUrl":"10.2147/ITT.S262566","url":null,"abstract":"<p><p>The cytokine, granulocyte macrophage-colony stimulating factor (GM-CSF), was firstly identified as being able to induce in vitro the proliferation and differentiation of bone marrow progenitors into granulocytes and macrophages. Much preclinical data have indicated that GM-CSF has a wide range of functions across different tissues in its action on myeloid cells, and GM-CSF deletion/depletion approaches indicate its potential as an important therapeutic target in several inflammatory and autoimmune disorders, for example, rheumatoid arthritis. In this review, we discuss briefly the biology of GM-CSF, raise some current issues and questions pertaining to this biology, summarize the results from preclinical models of a range of inflammatory and autoimmune disorders and list the latest clinical trials evaluating GM-CSF blockade in such disorders.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2020-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/1b/itt-9-225.PMC7605919.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38663694","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}