Drug metabolism and personalized therapy最新文献

{"title":"Safinamide dual molecular mechanisms: sodium channel and glutamate modulation as a translational rationale for neuropathic pain - A narrative review.","authors":"Utpal Bhui, Radheshyam Pal, Amit Chakraborty, Sathvik Belagodu Sridhar, Uttam Prasad Panigrahy, Shubhrajit Mantry, Bimlesh Kumar","doi":"10.1515/dmpt-2026-0021","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0021","url":null,"abstract":"<p><strong>Introduction: </strong>Neuropathic pain is a chronic and debilitating condition characterized by maladaptive changes in peripheral and central nervous system pathways. It is driven by abnormal neuronal excitability and excitatory neurotransmission. Among the key contributors are voltage-gated sodium channels (VGSCs) and glutamatergic mechanisms, both of which play pivotal roles in peripheral and central sensitization.</p><p><strong>Content: </strong>This narrative review was conducted through a structured literature search of PubMed/MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, Google Scholar, and relevant gray literature sources. Search terms included safinamide, Xadago, sodium channels, Nav1.7, Nav1.8, glutamate, NMDA, AMPA, mGluR, EAAT, neuropathic pain, and neuropathy. English-language <i>in vitro</i>, animal, and human studies were considered, and evidence was synthesized according to mechanistic relevance, preclinical findings, clinical pain outcomes, and translational limitations.</p><p><strong>Summary: </strong>Through selective interaction with inactivated sodium channel states that are common in hyperexcitable neurons and presynaptic regulation of glutamate without interfering with normal transmission. Safinamide is able to suppress ectopic discharges, decrease central sensitization, and alleviate neuroinflammation. Preclinical models reveal the strong dose-dependent antinociceptive activity, the restoration of sodium current densities, and the decreased evoked glutamate overflow. There are clinical studies of the populations with the PD that demonstrate that pain-related outcomes improve significantly and depend on the improvement of motor symptoms to a lesser extent. Safinamide's balanced profile has the potential benefits of improved tolerability and multimodal activity compared to conventional sodium channel blockers or direct NMDA antagonists.</p><p><strong>Outlook: </strong>Although the existing clinical evidence outside the context of Parkinson's disease is still scarce, its pharmacodynamic characteristics make it possible to develop further studies in a variety of neuropathic pain syndromes using biomarker-based, randomized controlled trials.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812433","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":"<i>Withania somnifera</i> ameliorates endoplasmic reticulum stress in human hepatocellular carcinoma HepG2 cells.","authors":"Eshita Sharma, Dilip Mehta, Anand Bhaskar, Aswathi Biju, Juhi Srivastava, Sujit Nair","doi":"10.1515/dmpt-2025-0096","DOIUrl":"https://doi.org/10.1515/dmpt-2025-0096","url":null,"abstract":"<p><strong>Objectives: </strong>Endoplasmic reticular (ER) stress plays an important role in gene modulation and the consequent release of several inflammatory mediators i.e., cytokines and proteases, key players associated with systemic-induced inflammation in various liver diseases. Natural products containing bioactive compounds have emerged as better therapeutic agents, attributed to their affordability as well as inherent biological properties. <i>Withania somnifera</i> (WS, Ashwagandha) is recognized for its immunomodulatory activities in Ayurveda.</p><p><strong>Methods: </strong>The present study investigated the effects of WS in uninduced and tunicamycin (Tm)-stimulated inflammation as well as ER stress response in HepG2 cells. The cells were optimized for Tm stress induction time, concentration as well as treatment mode (pre-, co- or post-).</p><p><strong>Results: </strong>There was a substantial increase in ER stress and inflammation response after 24 h at 40 μg/mL in the pretreatment group. WS treatment significantly inhibited ER stress response and inflammation in uninduced and Tm-induced stress groups in a dose-dependent approach. The activation of PERK/eIF2α/ATF4 and IRE1α/JNK signaling cascades was inhibited by WS in both uninduced and Tm-stimulated cells. The molecular pathways involved in suppression of hepatic inflammation included NF-κB, P38 and MAPK JNK which showed inhibition by WS. Suppression of inflammatory cytokine production <i>viz</i>. IL-1β, IL-6, and IL-18 was observed in both uninduced and stress-induced cells.</p><p><strong>Conclusions: </strong>This study suggests that WS is a potential candidate to prevent inflammation and ER stress response against ER-stress triggered inflammation in HepG2 ER cells.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808457","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":"Assessment of the impact of valproic acid co-administration on clozapine plasma concentrations in Tunisian patients.","authors":"Syrine Ben Hammamia, Safa Souissi, Mariem Bettoumia, Mouna Ben Sassi, Khouloud Ferchichi, Mouna Daldoul, Hanene El Jebari, Mohamed Zouari, Issam Salouage, Rim Charfi, Riadh Daghfous, Emna Gaies, Sameh Trabelsi","doi":"10.1515/dmpt-2026-0018","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0018","url":null,"abstract":"<p><strong>Objectives: </strong>Reports on drug-drug interactions between Valproic Acid (VPA) and Clozapine (CLZ) are very inconsistent. Previous reports demonstrate that VPA may exhibit either inhibitory or inductive effects or have no effect on CLZ pharmacokinetics. The aim of this study was to investigate the impact of VPA on plasma CLZ concentrations in a series of Tunisian patients.</p><p><strong>Methods: </strong>This retrospective study was conducted from 2010 to 2025 at the Clinical Pharmacology Department of the Tunisian National Pharmacovigilance Center and included samples of patients treated by CLZ for schizophrenia.</p><p><strong>Results: </strong>A total of 1,035 samples were analyzed: 814 corresponded to CLZ monotherapy and 221 to combined of VPA and CLZ therapy. The median CLZ plasma concentration-to-dose ratio (C/D ratio) was significantly higher in the monotherapy group than in the combination group (0.87 vs. 0.75 ng/mL per mg/day; p<0.05). Within the combination group, the CLZ C/D ratio was significantly lower in men than in women (0.67 vs. 1.16 ng/mL per mg/day; p<0.05).</p><p><strong>Conclusions: </strong>Our study demonstrates a significant inductive effect of VPA on CLZ metabolism, which may be influenced by factors such as gender. Hence, clinicians should be aware of the critical need for CLZ monitoring in clinical practice to personalize treatment adjustment.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808518","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":"Association of <i>HTR2A</i> (rs6313) gene polymorphism with autism spectrum disorder in Jordanian children: a case-control study.","authors":"Wiam Khalil, Elaf Adel Al-Dalabeeh, Malek Zihlif","doi":"10.1515/dmpt-2026-0022","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0022","url":null,"abstract":"<p><strong>Objectives: </strong>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a significant genetic component, often linked to disruptions in the serotonergic system. The <i>HTR2A</i> gene, specifically the rs6313 (102T>C) polymorphism, is a primary candidate for investigating ASD susceptibility. The aim of this study is to investigate the association of rs6313 polymorphism with susceptibility to ASD in the Jordanian population.</p><p><strong>Methods: </strong>In this case-control study, 99 Jordanian children with ASD and 109 neurotypical controls were genotyped using PCR-RFLP. Genotype and allele frequencies were analyzed under multiple genetic models.</p><p><strong>Results: </strong>No statistically significant differences were found between cases and controls regarding genotype (p=0.54) or allele frequencies (p=0.3284). The distribution adhered to Hardy-Weinberg equilibrium in both groups.</p><p><strong>Conclusions: </strong>Our findings suggest no significant association between the HTR2A rs6313 and ASD susceptibility in the Jordanian population. These results emphasize the need for larger, multi-marker studies to account for regional genetic diversity.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808472","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":"Clinical implementation of pharmacogenetics in Spain: the Spanish Society of Pharmacogenetics and Pharmacogenomics (SEFF) strategy as a roadmap for precision medicine.","authors":"Francisco Abad-Santos, Cristina Rodriguez-Antona, Adrián LLerena","doi":"10.1515/dmpt-2026-0045","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0045","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812367","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":"Impact of TNF-alpha -308 G/A polymorphism on response to TNF inhibitors in Tunisian patients with inflammatory rheumatic diseases.","authors":"Ines Mahmoud, Syrine Zanned, Leila Rouached, Selma Bouden, Moalla Myriam, Siwar Ben Dhia, Rawdha Tekaya, Aicha Ben Tekaya, Leila Abdelmoula, Imen Sfar","doi":"10.1515/dmpt-2025-0087","DOIUrl":"https://doi.org/10.1515/dmpt-2025-0087","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the impact of the TNF-α promoter SNP -308G/A on therapeutic response, serum drug levels, and immunogenicity of TNF inhibitors in chronic inflammatory rheumatic diseases.</p><p><strong>Methods: </strong>This cross-sectional, multicentric study included 73 patients: 32 with rheumatoid arthritis (RA) and 41 with spondyloarthritis (SpA). Serum drug levels (SDL) and anti-drug antibodies (ADA) were quantified by ELISA (Promonitor^®). Genotyping for SNP -308 was performed via PCR-RFLP. Therapeutic response was assessed at 6 months using delta DAS28 and EULAR response in RA and delta BASDAI, BASDAI20 and BASDAI50 responses in SpA patients.</p><p><strong>Results: </strong>In RA, the heterozygous G/A genotype was significantly associated with a greater reduction in median DAS28 compared to G/G (p=0.039) and a higher proportion of good EULAR responders (p=0.154). In SpA, G/A carriers showed larger decreases in BASDAI scores though differences were not statistically significant. Across both diseases, the G/A genotype was associated with significantly higher median serum drug levels (p=0.032). No association was observed between SNP -308G/A and ADA positivity.</p><p><strong>Conclusions: </strong>The TNF-α -308G/A polymorphism may be a predictive marker of TNF inhibitor efficacy in RA, potentially influencing serum drug levels while immunogenicity appears unaffected. Larger prospective studies are needed to confirm these findings and explore additional determinants of TNF inhibitor response.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561063","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":"MicroRNA sequencing reveals modulation of neurodegenerative miRNAs by <i>Withania somnifera</i> in human neuroblastoma SK-N-SH cells.","authors":"Shanavas Syed Mohamed Puhari, Dilip Mehta, Anand Bhaskar, Vivek Basudkar, Praful Saha, Saiprasad Ajgaonkar, Aswathi Biju, Jash Trivedi, S Dhananya, Manju Moorthy, Gopalakrishna Ramaswamy, Yundong Zhou, Sujit Nair","doi":"10.1515/dmpt-2026-0006","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0006","url":null,"abstract":"<p><strong>Objectives: </strong><i>Withania somnifera</i> (WS) is known for its adaptogenic benefits; however, its beneficial effects in neurodegenerative diseases have not been fully explored. MicroRNAs (miRNAs) are small noncoding RNAs whose role(s) in modulating the effects of WS in neurodegeneration are yet unknown. This study aimed to investigate the impact of WS on miRNA expression in the SK-N-SH human neuroblastoma cell line.</p><p><strong>Methods: </strong>We employed high-throughput sequencing to identify miRNAs with altered expression following dose-dependent and temporal treatment with WS.</p><p><strong>Results: </strong>Our findings revealed that miRNA expression profiles were significantly altered in WS-treated cells. In the dose comparison (100 μg/mL vs. 50 μg/mL), 21 miRNAs were modulated at 3 h (18 upregulated and 3 downregulated), whereas 7 miRNAs were modulated at 9 h (3 upregulated and 4 downregulated). In the temporal comparison (9 h vs. 3 h), 9 miRNAs were modulated at 50 μg/mL (6 upregulated and 3 downregulated), whereas 30 miRNAs were modulated at 100 μg/mL (4 upregulated and 26 downregulated). Bioinformatics analyses, including target prediction and functional enrichment, revealed that these WS-modulated differentially expressed miRNAs were significantly enriched in neurodegenerative, apoptotic, and inflammatory pathways. Finally, 51 novel miRNAs were identified post-WS treatment.</p><p><strong>Conclusions: </strong>Taken together, our results indicate that WS may be beneficial in neurodegenerative disease and healthy aging by modulating noncoding miRNAs.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469561","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":"The impact of antihistamine use on allergic reactions in pregnancy.","authors":"Maria Zofia Lisiecka, Joanna Luczak","doi":"10.1515/dmpt-2026-0014","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0014","url":null,"abstract":"<p><p>Allergic diseases are common among women of reproductive age, which necessitates the use of antihistamine therapy during pregnancy while ensuring safety for both the mother and the foetus. The study aimed to determine the safety profile, pharmacological characteristics, and clinical consequences of antihistamine use during pregnancy for the maternal-foetal system. A systematic review of scientific publications for the period 2020-2025 was carried out using the PRISMA methodology with a search in five international databases, which allowed us to select 45 relevant sources analyzing pathophysiology, pharmacology, and clinical consequences. It has been established that maternal immunoglobulins of class E are transported across the placental barrier, where they may sensitise foetal mast cells <i>in utero</i>. Hormonal changes during pregnancy induce polarisation of the immune response towards Th2 with progressive suppression of eosinophils by 17-22 % in the second trimester and by 20-42 % in the third trimester. Population cohort studies covering more than 1.2 million pregnancies have found no statistically significant associations between the use of second-generation antihistamines and major congenital malformations, spontaneous abortions or premature births. Physiological changes during pregnancy modify the pharmacokinetic parameters of drugs, reducing plasma protein concentrations by 20-40 %, However, cetirizine and loratadine demonstrate a favourable safety profile based on data from more than 186,000 exposures in Scandinavian registries, and the relative infant dose remains below the 5 % safety threshold. The findings support the use of second-generation antihistamines as first-line therapy for allergic diseases in pregnancy and provide an evidence base for selecting safe pharmacological agents at different gestational stages.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469619","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":"MDMA-induced CYP2D6 inhibition: concentration-dependent variability using dextromethorphan as a probe.","authors":"Faezeh Ahmadi, Hoda Lavasani, Mohammadhosein Keshvadi, Youssef Daali, Mohammadreza Rouini, Sanaz Jamshidfar, Yalda H Ardakani","doi":"10.1515/dmpt-2025-0029","DOIUrl":"10.1515/dmpt-2025-0029","url":null,"abstract":"<p><strong>Objectives: </strong>Ecstasy is commonly abused due to entactogenic effects. Although our previous studies on isolated perfused rat model confirmed inhibition of CYP2D6 by MDMA, the time for enzyme recovery was different when mirtazapine and tramadol were used as substrates. Therefore, present study intended to investigate CYP2D6 inhibition by MDMA using dextromethorphan as a well-known probe. Two different concentrations of dextromethorphan were used at therapeutic and saturated level to clarify observations.</p><p><strong>Methods: </strong>Thirty-two rats were divided into two groups (dextromethorphan concentration: 2 µM or 300 µM). Each group was divided into four subgroups. Except for control, three treatment subgroups received a single dose of MDMA (1 mg/kg) 1 h, 1 week, and 1 month before liver perfusion, respectively.</p><p><strong>Results: </strong>Mean metabolic ratio using therapeutic dextromethorphan concentration showed a statistically significant decrease only in the 1-hour group compared to control. The results of the mean metabolic ratio using the saturated concentration showed a reduction in all treatment groups (p-value<0.05).</p><p><strong>Conclusions: </strong>It can be concluded that the isoenzyme behavior can be completely different using therapeutic vs. saturated probe concentrations. The best explanation for the duality observed in metabolic behavior seems to be the dependence of the metabolite on enzymatic pathway.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"103-108"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257732","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":"Allergic reactions to anaesthetics in surgery: current challenges and perspectives.","authors":"Maria Zofia Lisiecka, Joanna Luczak","doi":"10.1515/dmpt-2026-0008","DOIUrl":"https://doi.org/10.1515/dmpt-2026-0008","url":null,"abstract":"<p><strong>Introduction: </strong>This study was conducted to assess the current state of issues related to AR to anaesthetics used in surgical procedures.</p><p><strong>Contents: </strong>A literature review of scientific publications in allergology and anaesthesiology was performed, evaluating the allergenic profile of modern anaesthetics and analysing approaches to preventing AR during surgery.</p><p><strong>Summary: </strong>Currently, the most commonly used local anaesthetics are amides, including lidocaine, bupivacaine, articaine, mepivacaine, ropivacaine, and levobupivacaine. These are considered safer in terms of allergenicity compared to their ester-based predecessors - novocaine, benzocaine, and tetracaine - as their metabolites rarely act as allergens. Among general anaesthetics, intravenous agents such as propofol, midazolam, etomidate, and ketamine, as well as inhalational agents including sevoflurane, isoflurane, desflurane, and xenon, are widely used. These are generally safer than their predecessor, thiopental, with xenon currently exhibiting the highest safety profile due to its inert chemical properties. Muscle relaxants have the highest allergenic potential, as their mechanism of action - blocking acetylcholine receptors - can lead to cell damage and the release of immune-stimulating substances. The only representative of depolarising muscle relaxants is succinylcholine, while non-depolarising agents include atracurium, cisatracurium, vecuronium, rocuronium, pancuronium, and mivacurium.</p><p><strong>Outlook: </strong>Preventive measures to reduce the risk of AR include: a detailed patient history and diagnostic testing using skin tests, provocation tests, and/or blood tests for Immunoglobulin E (IgE); replacement of the allergenic drug with a safer alternative if an allergy is confirmed; close monitoring for allergic manifestations during surgery, with professional preparedness for resuscitation in cases of anaphylaxis; postoperative patient monitoring to detect potential delayed AR; documentation of all AR for future reference. The findings of this study may be applied in clinical practice to mitigate the risks of AR associated with anaesthetic use during surgical interventions.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149077","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}