Pharmaceuticals (Basel, Switzerland)最新文献

{"title":"\"K-Powder\" Exposure during Adolescence Elicits Psychiatric Disturbances Associated with Oxidative Stress in Female Rats.","authors":"Sabrina de Carvalho Cartágenes,&nbsp;Cinthia Cristina Sousa de Menezes da Silveira,&nbsp;Bruno Gonçalves Pinheiro,&nbsp;Luanna Melo Pereira Fernandes,&nbsp;Sarah Viana Farias,&nbsp;Natália Harumi Correa Kobayashi,&nbsp;Pablo Henrique Franco Santos de Souza,&nbsp;Alejandro Ferraz do Prado,&nbsp;Maria Karolina Martins Ferreira,&nbsp;Rafael Rodrigues Lima,&nbsp;Edivaldo Herculano Correa de Oliveira,&nbsp;Francisco Canindé Ferreira de Luna,&nbsp;Rommel Mário Rodríguez Burbano,&nbsp;Enéas Andrade Fontes-Júnior,&nbsp;Cristiane do Socorro Ferraz Maia","doi":"10.3390/ph15111373","DOIUrl":"https://doi.org/10.3390/ph15111373","url":null,"abstract":"<p><p>Ketamine, also called 'K-powder' by abusers, an analog of phencyclidine, primarily acts as an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, therapeutically used as an anesthetic agent. Ketamine also stimulates the limbic system, inducing hallucinations and dissociative effects. At sub-anesthetic doses, ketamine also displays hallucinatory and dissociative properties, but not loss of consciousness. These behavioral consequences have elicited its recreational use worldwide, mainly at rave parties. Ketamine is generally a drug of choice among teenagers and young adults; however, the harmful consequences of its recreational use on adolescent central nervous systems are poorly explored. Thus, the aim of the present study was to characterize the behavioral and biochemical consequences induced by one binge-like cycle of ketamine during the early withdrawal period in adolescent female rats. Adolescent female Wistar rats (<i>n</i> = 20) received intraperitoneally administered ketamine (10 mg/kg/day) for 3 consecutive days. Twenty-four hours after the last administration of ketamine, animals were submitted to behavioral tests in an open field, elevated plus-maze, and forced swimming test. Then, animals were intranasally anesthetized with 2% isoflurane and euthanized to collect prefrontal cortex and hippocampus to assess lipid peroxidation, antioxidant capacity against peroxyl radicals, reactive oxygen species, reduced glutathione, and brain-derived neurotrophic factor (BDNF) levels. Our results found that 24 h after recreational ketamine use, emotional behavior disabilities, such as anxiety- and depression-like profiles, were detected. In addition, spontaneous ambulation was reduced. These negative behavioral phenotypes were associated with evidence of oxidative stress on the prefrontal cortex and hippocampus.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464711","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":"Reactivity of Covalent Fragments and Their Role in Fragment Based Drug Discovery.","authors":"Kirsten McAulay,&nbsp;Alan Bilsland,&nbsp;Marta Bon","doi":"10.3390/ph15111366","DOIUrl":"https://doi.org/10.3390/ph15111366","url":null,"abstract":"<p><p>Fragment based drug discovery has long been used for the identification of new ligands and interest in targeted covalent inhibitors has continued to grow in recent years, with high profile drugs such as osimertinib and sotorasib gaining FDA approval. It is therefore unsurprising that covalent fragment-based approaches have become popular and have recently led to the identification of novel targets and binding sites, as well as ligands for targets previously thought to be 'undruggable'. Understanding the properties of such covalent fragments is important, and characterizing and/or predicting reactivity can be highly useful. This review aims to discuss the requirements for an electrophilic fragment library and the importance of differing warhead reactivity. Successful case studies from the world of drug discovery are then be examined.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691273","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":"A Systematic Review and Meta-Analysis of Premenstrual Syndrome with Special Emphasis on Herbal Medicine and Nutritional Supplements.","authors":"Arshiya Sultana,&nbsp;Md Belal Bin Heyat,&nbsp;Khaleequr Rahman,&nbsp;Radhika Kunnavil,&nbsp;Mohamed Joonus Aynul Fazmiya,&nbsp;Faijan Akhtar,&nbsp;Sumbul,&nbsp;Juan Luis Vidal Mazón,&nbsp;Carmen Lili Rodríguez,&nbsp;Isabel De La Torre Díez","doi":"10.3390/ph15111371","DOIUrl":"https://doi.org/10.3390/ph15111371","url":null,"abstract":"<p><p>Herbal medicine and nutritional supplements are suggested to treat premenstrual somatic and psycho-behavioural symptoms in clinical guidelines; nonetheless, this is at present based on poor-quality trial evidence. Hence, we aimed to design a systematic review and meta-analysis for their effectiveness in alleviating premenstrual symptoms. The published randomized controlled trials (RCTs) were extracted from Google scholar, PubMed, Scopus and PROSPERO databases. The risk of bias in randomized trials was assessed by Cochrane risk-of-bias tool<i>.</i> The main outcome parameters were analysed separately based on the Premenstrual Symptom Screening Tool and PMTS and DRSP scores. Secondary parameters of somatic, psychological, and behavioural subscale symptoms of PSST were also analysed. Data synthesis was performed assuming a random-effects model, and standardized mean difference (SMDs) was analysed using SPSS version 28.0.0 (IBM, Armonk, NY, USA). A total of 754 articles were screened, and 15 RCTs were included (<i>n</i> = 1211 patients). Primary results for participants randomized to an intervention reported reduced PSST (<i>n</i> = 9), PMTS (<i>n</i> = 2), and DSR (<i>n</i> = 4) scores with (SMD = -1.44; 95% CI: -1.72 to -1.17), (SMD = -1.69; 95% CI: -3.80 to 0.42) and (SMD = 2.86; 95% CI: 1.02 to 4.69) verses comparator with substantial heterogeneity. Physical (SMD = -1.61; 95% CI = -2.56 to -0.66), behavioural (SMD = -0.60; 95% CI = -1.55 to0.35) and mood (SMD = 0.57; 95% CI = -0.96 to 2.11) subscale symptom groupings of PSST displayed similar findings. Fifty-three studies (<i>n</i> = 8) were considered at low risk of bias with high quality. Mild adverse events were reported by four RCTs. Based on the existing evidence, herbal medicine and nutritional supplements may be effective and safe for PMS.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691275","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":"Effects of Dexmedetomidine on Basic Cardiac Electrophysiology in Adults; a Descriptive Review and a Prospective Case Study.","authors":"Reino Pöyhiä,&nbsp;Teija Nieminen,&nbsp;Ville W T Tuompo,&nbsp;Hannu Parikka","doi":"10.3390/ph15111372","DOIUrl":"https://doi.org/10.3390/ph15111372","url":null,"abstract":"<p><p>Dexmedetomidine (DEX) is a commonly used sedative agent with no or minimal effects on breathing. DEX may also be beneficial in myocardial protection. Since the mechanisms of cardiac effects are not well known, we carried out a descriptive review and examined the effects of DEX on myocardial electrical conduction in a prospective and controlled manner. For the review, clinical studies exploring DEX in myocardial protection published between 2020-2022 were explored. A case study included 11 consecutive patients at a median (range) age of 48 (38-59), scheduled for elective radiofrequency ablation of paroxysmal atrial fibrillation. A bolus dose of DEX 1 µg/kg given in 15 min was followed by a continuous infusion of 0.2-0.7 µg/kg/h. Direct intracardiac electrophysiologic measurements, hemodynamics and oxygenation were measured before and after the DEX bolus. Experimental studies show that DEX protects the heart both via stabilizing cardiac electrophysiology and reducing apoptosis and autophagy after cell injury. The clinical evidence shows that DEX provides cardiac protection during different surgeries. In a clinical study, DEX increased the corrected sinus node recovery time, prolongated the atrioventricular (AV) nodal refractory period and cycle length producing AV nodal Wenckebach retrograde conduction block. DEX has a putative role in organ protection against hypoxic, oxidative and reperfusion injury. DEX slows down the firing of the sinus node and prolongs AV refractoriness.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691276","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":"Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties.","authors":"Yuqiang Li,&nbsp;Dan Wang,&nbsp;Heming Ge,&nbsp;Cenap Güngör,&nbsp;Xuejun Gong,&nbsp;Yongheng Chen","doi":"10.3390/ph15111369","DOIUrl":"https://doi.org/10.3390/ph15111369","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a subpopulation of cancer cells possessing stemness characteristics that are closely associated with tumor proliferation, recurrence and resistance to therapy. Recent studies have shown that different cytoskeletal components and remodeling processes have a profound impact on the behavior of CSCs. In this review, we outline the different cytoskeletal components regulating the properties of CSCs and discuss current and ongoing therapeutic strategies targeting the cytoskeleton. Given the many challenges currently faced in targeted cancer therapy, a deeper comprehension of the molecular events involved in the interaction of the cytoskeleton and CSCs will help us identify more effective therapeutic strategies to eliminate CSCs and ultimately improve patient survival.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464710","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":"Exploration of <i>Solanum xanthocarpum</i> Schrad. & Wendl. against <i>Mycobacterium avium</i> Subspecies <i>paratuberculosis</i> and Assessment of Its Immunomodulatory and Anti-Inflammatory Potential.","authors":"Varsha Srivastava,&nbsp;Manthena Navabharath,&nbsp;Saurabh Gupta,&nbsp;Shoor Vir Singh,&nbsp;Sayeed Ahmad","doi":"10.3390/ph15111367","DOIUrl":"https://doi.org/10.3390/ph15111367","url":null,"abstract":"<p><p><i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP), being a dairy-borne pathogen, resistant of pasteurization and other sterilization techniques, is a major cause for development of inflammatory bowel disorders such as Johne's disease (JD) in dairy animals and Crohn's Disease (CD) in humans, for which no therapy is available to date. In the absence of effective therapy or a vaccine, management of CD has been accomplished by removal of the affected intestines. However, usually, even after removal of 2/3 of the intestine, CD reoccurs. Hence, there exists a need to develop an alternative therapy for such infection. The potential of herbals remains unexplored against MAP and related infections. Therefore, the conducted study is a novel initiative for the evaluation of anti-mycobacterial activity of bioactive extracts of <i>Solanum xanthocarpum</i> Schrad. & Wendl. against MAP infection. The said plant was authenticated according to the Ayurvedic Pharmacopoeia of India. Qualitative and quantitative evaluation of the extracts were done using chromatographic and spectroscopic techniques. Preliminary in vitro pharmacological assessments revealed the immunomodulatory and anti-inflammatory potential of the extracts. REMA assay was conducted to determine their anti-MAP activity along with determination of the best active extract. The hydro-alcoholic extract showed the best inhibition of MAP, providing a potential ray of hope against this emerging major pathogen of animals, and associated with Crohn's disease and other autoimmune disorders in human beings.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691272","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":"Can PSMA-Targeting Radiopharmaceuticals Be Useful for Detecting Hepatocellular Carcinoma Using Positron Emission Tomography? An Updated Systematic Review and Meta-Analysis.","authors":"Alessio Rizzo,&nbsp;Manuela Racca,&nbsp;Domenico Albano,&nbsp;Francesco Dondi,&nbsp;Francesco Bertagna,&nbsp;Salvatore Annunziata,&nbsp;Giorgio Treglia","doi":"10.3390/ph15111368","DOIUrl":"https://doi.org/10.3390/ph15111368","url":null,"abstract":"<p><strong>Background: </strong>Several studies proposed the use of positron emission tomography (PET) with Prostate-Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in hepatocellular carcinoma (HCC). Our aim is to calculate the detection rate (DR) of this examination in HCC with a meta-analysis.</p><p><strong>Methods: </strong>A comprehensive literature search of studies on the DR of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HCC was performed. Original articles evaluating these imaging examinations both in newly diagnosed HCC patients and HCC patients with disease relapse were included. Pooled DR including 95% confidence intervals (95% CI) was calculated. Statistical heterogeneity was also assessed using the I² test.</p><p><strong>Results: </strong>The meta-analysis of six selected studies (126 patients) provided a DR of 85.9% for PET imaging with PSMA-targeting radiopharmaceuticals in the diagnosis of HCC. Moderate statistical heterogeneity among the included studies was found (I² = 56%).</p><p><strong>Conclusions: </strong>The quantitative data provided demonstrate the high DR of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HCC lesion detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in HCC.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691274","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":"The Anxiolytic Activity of <i>Schinus terebinthifolia</i> Leaf Lectin (SteLL) Is Dependent on Monoaminergic Signaling although Independent of the Carbohydrate-Binding Domain of the Lectin.","authors":"Bárbara Raíssa Ferreira de Lima,&nbsp;Leydianne Leite de Siqueira Patriota,&nbsp;Amanda de Oliveira Marinho,&nbsp;Jainaldo Alves da Costa,&nbsp;Thiago Henrique Napoleão,&nbsp;Michelle Melgarejo da Rosa,&nbsp;Patrícia Maria Guedes Paiva","doi":"10.3390/ph15111364","DOIUrl":"https://doi.org/10.3390/ph15111364","url":null,"abstract":"<p><p>The potential of plant lectins (carbohydrate-binding proteins) for the treatment of neurological disorders such as anxiety and depression has started to be reported in the last few years. <i>Schinus terebinthifolia</i> leaves contain a lectin called SteLL, which has displayed antimicrobial, immunomodulatory, antitumor, and analgesic activities. However, the effects of SteLL on the Central Nervous System (CNS) have not yet been determined. In this study, we investigated the in vivo anxiolytic effect of SteLL in mice using the open field (OF) and elevated plus maze (EPM) tests. In the OF, SteLL (1, 2, and 4 mg/kg, i.p.) did not interfere with the number of crossings but significantly reduced the number of rearings. In the EPM, SteLL 4 mg/kg and the combination SteLL (1 mg/kg) plus diazepam (1 mg/kg) significantly increased the time spent in the open arms while reducing the time spent in the closed arms. The anxiolytic effect of SteLL did not seem to be dependent on the carbohydrate-binding domain of the lectin. Nevertheless, the SteLL effect in the EPM was reversed by the pretreatment with the pharmacological antagonists of the α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and the D1 dopamine receptor. Overall, our results suggest that the anxiolytic effect of SteLL is dependent on the monoaminergic signaling cascade.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691270","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":"Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury.","authors":"José M Alonso,&nbsp;Alejandro Escobar-Peso,&nbsp;Israel Fernández,&nbsp;Alberto Alcázar,&nbsp;José Marco-Contelles","doi":"10.3390/ph15111363","DOIUrl":"https://doi.org/10.3390/ph15111363","url":null,"abstract":"<p><p>In our search for new neuroprotective agents for stroke therapy to improve the pharmacological profile of the compound quinolylnitrone QN23, we have prepared and studied sixteen new, related and easily available quinolylnitrones. As a result, we have identified compounds QN4 and QN15 as promising candidates showing high neuroprotection power in a cellular experimental model of ischemia. Even though they were found to be less active than our current lead compound QN23, QN4 and QN15 provide an improved potency and, particularly for QN4, an expanded range of tolerability and improved solubility compared to the parent compound. A computational DFT-based analysis has been carried out to understand the antioxidant power of quinolylnitrones QN23, QN4 and QN15. Altogether, these results show that subtle, simple modifications of the quinolylnitrone scaffold are tolerated, providing high neuroprotective activity and optimization of the pharmacological potency required for an improved design and future drug developments in the field.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40676339","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":"A Review of the Safety of Interleukin-17A Inhibitor Secukinumab.","authors":"Vishnu Eshwar,&nbsp;Ashwin Kamath,&nbsp;Rajeshwari Shastry,&nbsp;Ashok K Shenoy,&nbsp;Priyanka Kamath","doi":"10.3390/ph15111365","DOIUrl":"https://doi.org/10.3390/ph15111365","url":null,"abstract":"<p><p>Secukinumab is an anti-interleukin (IL)-17A IgG1-κ monoclonal antibody approved for psoriasis, psoriatic arthritis, and ankylosing spondylitis. Its efficacy is well documented, but the complete safety profile of secukinumab, especially on long-term use, needs to be studied. IL-17 inhibitors increase the risk of infections, especially respiratory tract infections and candidiasis, and inflammatory bowel disease; the causal relationships are well described. However, evidence regarding the other adverse events is scarce, and causal associations between the adverse events and the biologic remain unresolved. This review aims to present a narrative perspective on the safety of secukinumab and identify some key areas where the safety of secukinumab may potentially be useful in understanding the scope of secukinumab therapy and making informed clinical decisions.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691271","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}