Pub Date : 2024-09-24DOI: 10.1016/j.drudis.2024.104191
Zahra Maani , Leila Rahbarnia , Ali Bahadori , Khalil Maleki Chollou , Safar Farajnia
HIV-derived TAT peptide, with a high penetration rate into cells and its nonimmunogenic and minimally toxic nature, is an attractive tool for enhancing the biodistribution of drugs and their systemic administration. Despite the presence of numerous promising preclinical investigations illustrating its capability to specifically target distinct tissues and deliver a diverse range of pharmacological agents, the efficacy of various clinical trials incorporating TAT has been impeded by several considerable obstacles. Hence, there is much need for an in-depth investigation concerning the application of TAT in drug delivery mechanisms. In this review, we have elucidated the structure of TAT and its utility in the proficient delivery of various types of bioactive molecules.
艾滋病病毒衍生的 TAT 肽具有较高的细胞渗透率、非免疫原性和毒性小的特点，是增强药物生物分布和全身用药的一种极具吸引力的工具。尽管有大量前景看好的临床前研究表明，TAT 能够特异性地靶向不同的组织，并递送各种药剂，但采用 TAT 进行的各种临床试验的疗效一直受到一些重大障碍的阻碍。因此，亟需对 TAT 在给药机制中的应用进行深入研究。在这篇综述中，我们阐明了 TAT 的结构及其在熟练递送各类生物活性分子方面的作用。
{"title":"Spotlight on HIV-derived TAT peptide as a molecular shuttle in drug delivery","authors":"Zahra Maani , Leila Rahbarnia , Ali Bahadori , Khalil Maleki Chollou , Safar Farajnia","doi":"10.1016/j.drudis.2024.104191","DOIUrl":"10.1016/j.drudis.2024.104191","url":null,"abstract":"<div><div>HIV-derived TAT peptide, with a high penetration rate into cells and its nonimmunogenic and minimally toxic nature, is an attractive tool for enhancing the biodistribution of drugs and their systemic administration. Despite the presence of numerous promising preclinical investigations illustrating its capability to specifically target distinct tissues and deliver a diverse range of pharmacological agents, the efficacy of various clinical trials incorporating TAT has been impeded by several considerable obstacles. Hence, there is much need for an in-depth investigation concerning the application of TAT in drug delivery mechanisms. In this review, we have elucidated the structure of TAT and its utility in the proficient delivery of various types of bioactive molecules.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104191"},"PeriodicalIF":6.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicroRNA-29b (miR-29b) is known for its therapeutic potential as an antifibrotic and anticancer agent. In fibrotic conditions, miR-29b inhibits fibrogenesis by downregulating crucial regulators such as collagens, extracellular matrix proteins and the transforming growth factor-β pathway. Similarly, in cancer, it acts as a tumor suppressor by downregulating various oncogenes and signaling pathways involved in cancer progression, such as Wnt–β-catenin, p38–mitogen-activated protein kinase and nuclear factor-κB. However, the upregulation of these pathways suppresses miR-29b, contributing to fibrosis and cancer development. Preclinical research and clinical trials have shown that delivering exogenous miR-29b mimics can restore its expression, attenuating tumorigenesis and fibrogenesis. This review discusses miR-29b’s potential and its possible therapeutic development for cancer and fibrotic disorders.
{"title":"Downregulation of microRNA-29b in cancer and fibrosis: molecular insights and clinical implications","authors":"Pratik Pramod Shinde, Deepak Chitkara, Anupama Mittal","doi":"10.1016/j.drudis.2024.104190","DOIUrl":"10.1016/j.drudis.2024.104190","url":null,"abstract":"<div><div>MicroRNA-29b (miR-29b) is known for its therapeutic potential as an antifibrotic and anticancer agent. In fibrotic conditions, miR-29b inhibits fibrogenesis by downregulating crucial regulators such as collagens, extracellular matrix proteins and the transforming growth factor-β pathway. Similarly, in cancer, it acts as a tumor suppressor by downregulating various oncogenes and signaling pathways involved in cancer progression, such as Wnt–β-catenin, p38–mitogen-activated protein kinase and nuclear factor-κB. However, the upregulation of these pathways suppresses miR-29b, contributing to fibrosis and cancer development. Preclinical research and clinical trials have shown that delivering exogenous miR-29b mimics can restore its expression, attenuating tumorigenesis and fibrogenesis. This review discusses miR-29b’s potential and its possible therapeutic development for cancer and fibrotic disorders.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104190"},"PeriodicalIF":6.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glioblastoma multiforme (GBM) is the most common CNS cancer, it has dismal survival rates despite several effective mediators: intensified cytotoxic therapy, chimeric antigen receptor (CAR)-T cell therapy, viral therapy, adoptive cell therapy, immune checkpoint blockade therapy, radiation therapy and vaccine therapy. This review examines the basic concepts underlying immune targeting and examines products such as checkpoint blockade drugs, CAR-T cells, oncolytic viruses, combinatory multimodal immunotherapy and cancer vaccines. New approaches to overcoming current constraints and challenges in GBM therapy are discussed, based on recent studies into these tactics, findings from ongoing clinical trials, as well as previous trial results.
{"title":"From promise to progress: the dynamic landscape of glioblastoma immunotherapy","authors":"Muhammad Ijaz , Zia Ullah , Bilal Aslam , Mohsin Khurshid , Pengfei Chen , Bing Guo","doi":"10.1016/j.drudis.2024.104188","DOIUrl":"10.1016/j.drudis.2024.104188","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is the most common CNS cancer, it has dismal survival rates despite several effective mediators: intensified cytotoxic therapy, chimeric antigen receptor (CAR)-T cell therapy, viral therapy, adoptive cell therapy, immune checkpoint blockade therapy, radiation therapy and vaccine therapy. This review examines the basic concepts underlying immune targeting and examines products such as checkpoint blockade drugs, CAR-T cells, oncolytic viruses, combinatory multimodal immunotherapy and cancer vaccines. New approaches to overcoming current constraints and challenges in GBM therapy are discussed, based on recent studies into these tactics, findings from ongoing clinical trials, as well as previous trial results.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104188"},"PeriodicalIF":6.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.drudis.2024.104187
Nicolas Gaigeard , Anaïs Cardon , Benoit Le Goff , Jérôme Guicheux , Marie-Astrid Boutet
Osteoarthritis (OA) is an incurable, painful, and debilitating joint disease affecting over 500 million people worldwide. The OA joint tissues are infiltrated by various immune cells, particularly macrophages, which are able to induce or perpetuate inflammation. Notably, synovitis and its macrophage component represent a target of interest for developing treatments. In this review, we describe the latest advances in understanding the heterogeneity of macrophage origins, phenotypes, and functions in the OA joint and the effect of current symptomatic therapies on these cells. We then highlight the therapeutic potential of anticytokines/chemokines, nano- and microdrug delivery, and future strategies to modulate macrophage functions in OA.
骨关节炎（OA）是一种无法治愈、令人痛苦和衰弱的关节疾病，影响着全球 5 亿多人。OA 关节组织被各种免疫细胞浸润，尤其是巨噬细胞，它们能够诱发或延续炎症。值得注意的是，滑膜炎及其巨噬细胞成分是开发治疗方法的一个目标。在这篇综述中，我们将介绍在了解 OA 关节中巨噬细胞的起源、表型和功能的异质性以及目前的对症疗法对这些细胞的影响方面取得的最新进展。然后，我们将重点介绍抗细胞因子/凝血因子、纳米和微药物递送的治疗潜力，以及调节 OA 中巨噬细胞功能的未来策略。
{"title":"Unveiling the macrophage dynamics in osteoarthritic joints: From inflammation to therapeutic strategies","authors":"Nicolas Gaigeard , Anaïs Cardon , Benoit Le Goff , Jérôme Guicheux , Marie-Astrid Boutet","doi":"10.1016/j.drudis.2024.104187","DOIUrl":"10.1016/j.drudis.2024.104187","url":null,"abstract":"<div><div>Osteoarthritis (OA) is an incurable, painful, and debilitating joint disease affecting over 500 million people worldwide. The OA joint tissues are infiltrated by various immune cells, particularly macrophages, which are able to induce or perpetuate inflammation. Notably, synovitis and its macrophage component represent a target of interest for developing treatments. In this review, we describe the latest advances in understanding the heterogeneity of macrophage origins, phenotypes, and functions in the OA joint and the effect of current symptomatic therapies on these cells. We then highlight the therapeutic potential of anticytokines/chemokines, nano- and microdrug delivery, and future strategies to modulate macrophage functions in OA.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104187"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.drudis.2024.104189
Fadi E. Pulous , Barbara Steurer , Frank W. Pun , Man Zhang , Feng Ren , Alex Zhavoronkov
Metabolic and transcriptional reprogramming are crucial hallmarks of carcinogenesis that present exploitable vulnerabilities for the development of targeted anticancer therapies. Through controlling the balance of the cellular methionine (MET) metabolite pool, MET adenosyl transferase 2 alpha (MAT2A) regulates crucial steps during metabolism and the epigenetic control of transcription. The aberrant function of MAT2A has been shown to drive malignant transformation through metabolic addiction, transcriptional rewiring, and immune modulation of the tumor microenvironment (TME). Moreover, MAT2A sustains the survival of 5′-methylthioadenosine phosphorylase (MTAP)-deficient tumors, conferring synthetic lethality to cancers with MTAP loss, a genetic alteration that occurs in ∼15% of all cancers. Thus, the pharmacological inhibition of MAT2A is emerging as a desirable therapeutic strategy to combat tumor growth. Here, we review the latest insights into MAT2A biology, focusing on its roles in both metabolic addiction and gene expression modulation in the TME, outline the current landscape of MAT2A inhibitors, and highlight the most recent clinical developments and opportunities for MAT2A inhibition as a novel anti-tumor therapy.
{"title":"MAT2A inhibition combats metabolic and transcriptional reprogramming in cancer","authors":"Fadi E. Pulous , Barbara Steurer , Frank W. Pun , Man Zhang , Feng Ren , Alex Zhavoronkov","doi":"10.1016/j.drudis.2024.104189","DOIUrl":"10.1016/j.drudis.2024.104189","url":null,"abstract":"<div><div>Metabolic and transcriptional reprogramming are crucial hallmarks of carcinogenesis that present exploitable vulnerabilities for the development of targeted anticancer therapies. Through controlling the balance of the cellular methionine (MET) metabolite pool, MET adenosyl transferase 2 alpha (MAT2A) regulates crucial steps during metabolism and the epigenetic control of transcription. The aberrant function of MAT2A has been shown to drive malignant transformation through metabolic addiction, transcriptional rewiring, and immune modulation of the tumor microenvironment (TME). Moreover, MAT2A sustains the survival of 5′-methylthioadenosine phosphorylase (MTAP)-deficient tumors, conferring synthetic lethality to cancers with MTAP loss, a genetic alteration that occurs in ∼15% of all cancers. Thus, the pharmacological inhibition of MAT2A is emerging as a desirable therapeutic strategy to combat tumor growth. Here, we review the latest insights into MAT2A biology, focusing on its roles in both metabolic addiction and gene expression modulation in the TME, outline the current landscape of MAT2A inhibitors, and highlight the most recent clinical developments and opportunities for MAT2A inhibition as a novel anti-tumor therapy.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104189"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.drudis.2024.104185
Devaraj Ezhilarasan
{"title":"Beyond resmetirom approval for NAFLD: what has to be done?","authors":"Devaraj Ezhilarasan","doi":"10.1016/j.drudis.2024.104185","DOIUrl":"10.1016/j.drudis.2024.104185","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104185"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.drudis.2024.104186
Richard J. Webb , Maha Al-Asmakh , Maciej Banach , Mohsen Mazidi
The use of proteomics in human studies investigating stroke and myocardial infarction (MI) has been increasing, prompting a review of the literature. This revealed proteinaceous biomarkers of stroke from thrombi, brain tissue, cells, and particles, some of which cross the blood–brain barrier (BBB). Several proteins were also implicated in coronary artery disease (CAD), which often underlies MI, cholesterol transportation, and inflammation. Furthermore, the platelet proteome revealed itself as a potential therapeutic target, along with differentially expressed proteins associated with MI progression. Moreover, proteomic data enhanced the performance of conventional risk scores and causal protein discovery has improved interventions and drug development for patients with MI and other conditions. These findings suggest that proteomics holds much promise for future stroke and MI research.
{"title":"Application of proteomics for novel drug discovery and risk prediction optimisation in stroke and myocardial infarction: a review of in-human studies","authors":"Richard J. Webb , Maha Al-Asmakh , Maciej Banach , Mohsen Mazidi","doi":"10.1016/j.drudis.2024.104186","DOIUrl":"10.1016/j.drudis.2024.104186","url":null,"abstract":"<div><div>The use of proteomics in human studies investigating stroke and myocardial infarction (MI) has been increasing, prompting a review of the literature. This revealed proteinaceous biomarkers of stroke from thrombi, brain tissue, cells, and particles, some of which cross the blood–brain barrier (BBB). Several proteins were also implicated in coronary artery disease (CAD), which often underlies MI, cholesterol transportation, and inflammation. Furthermore, the platelet proteome revealed itself as a potential therapeutic target, along with differentially expressed proteins associated with MI progression. Moreover, proteomic data enhanced the performance of conventional risk scores and causal protein discovery has improved interventions and drug development for patients with MI and other conditions. These findings suggest that proteomics holds much promise for future stroke and MI research.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104186"},"PeriodicalIF":6.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.drudis.2024.104183
Godfrey Mayoka, Peter Mubanga Cheuka
{"title":"Early career researchers’ experiences in drug discovery in Africa","authors":"Godfrey Mayoka, Peter Mubanga Cheuka","doi":"10.1016/j.drudis.2024.104183","DOIUrl":"10.1016/j.drudis.2024.104183","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104183"},"PeriodicalIF":6.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.drudis.2024.104164
Amit Kumar , Shashi Kashyap , Farhan Mazahir , Rajeev Sharma , Awesh K. Yadav
Molecularly imprinted polymers (MIPs) are polymeric matrices that can mimic natural recognition entities, such as antibodies and biological receptors. Molecular imprinting of therapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high drug-loading capacity and good control of payload release. MIPs possess considerable promise as synthetic recognition elements in ‘theranostics’. Moreover, the high affinity and specificity of MIPs make them more advantageous than other polymer-based nanocomposites. This review summarizes the present state-of-the-art of MIP-based delivery systems for the targeted delivery of bioactives, with current challenges and future perspectives.
{"title":"Unveiling the potential of molecular imprinting polymer-based composites in the discovery of advanced drug delivery carriers","authors":"Amit Kumar , Shashi Kashyap , Farhan Mazahir , Rajeev Sharma , Awesh K. Yadav","doi":"10.1016/j.drudis.2024.104164","DOIUrl":"10.1016/j.drudis.2024.104164","url":null,"abstract":"<div><div>Molecularly imprinted polymers (MIPs) are polymeric matrices that can mimic natural recognition entities, such as antibodies and biological receptors. Molecular imprinting of therapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high drug-loading capacity and good control of payload release. MIPs possess considerable promise as synthetic recognition elements in ‘theranostics’. Moreover, the high affinity and specificity of MIPs make them more advantageous than other polymer-based nanocomposites. This review summarizes the present state-of-the-art of MIP-based delivery systems for the targeted delivery of bioactives, with current challenges and future perspectives.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104164"},"PeriodicalIF":6.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.drudis.2024.104182
Surina Bo , Mu Dan , Wei Li , Chen Chen
Diabetes is a complex, multifactorial disease that is caused by a pathological combination of insulin resistance and pancreatic islet dysfunction. Polysaccharides are extensively dispersed in nature and have a very complicated structure with various biological properties. Natural polysaccharides have potentially extraordinary beneficial health effects on managing metabolic diseases such as diabetes, obesity and cardiovascular disease. Thus, a systematic review of the latest research into and possible regulatory mechanisms of natural polysaccharides for type 2 diabetes mellitus treatment is of great significance for a better understanding of their pharmaceutical value. We discuss the regulatory mechanisms of natural polysaccharides for the treatment of diabetes, and especially their role in reshaping dysfunctional gut microbiota. Natural polysaccharides could be developed as new and safe antidiabetic drugs, and detailed mechanistic studies could further clarify the molecular targets of polysaccharides in the treatment of diabetes.
{"title":"The regulatory mechanism of natural polysaccharides in type 2 diabetes mellitus treatment","authors":"Surina Bo , Mu Dan , Wei Li , Chen Chen","doi":"10.1016/j.drudis.2024.104182","DOIUrl":"10.1016/j.drudis.2024.104182","url":null,"abstract":"<div><div>Diabetes is a complex, multifactorial disease that is caused by a pathological combination of insulin resistance and pancreatic islet dysfunction. Polysaccharides are extensively dispersed in nature and have a very complicated structure with various biological properties. Natural polysaccharides have potentially extraordinary beneficial health effects on managing metabolic diseases such as diabetes, obesity and cardiovascular disease. Thus, a systematic review of the latest research into and possible regulatory mechanisms of natural polysaccharides for type 2 diabetes mellitus treatment is of great significance for a better understanding of their pharmaceutical value. We discuss the regulatory mechanisms of natural polysaccharides for the treatment of diabetes, and especially their role in reshaping dysfunctional gut microbiota. Natural polysaccharides could be developed as new and safe antidiabetic drugs, and detailed mechanistic studies could further clarify the molecular targets of polysaccharides in the treatment of diabetes.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104182"},"PeriodicalIF":6.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003076/pdfft?md5=0e0518270b681b81f1885e4f5c0b10f9&pid=1-s2.0-S1359644624003076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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