ADMET and DMPKPub Date : 2023-01-01DOI: 10.5599/admet.1575
Yachana Gupta, Aditya Sharma Ghrera
{"title":"Development of conducting paper-based electrochemical biosensor for procalcitonin detection.","authors":"Yachana Gupta, Aditya Sharma Ghrera","doi":"10.5599/admet.1575","DOIUrl":"https://doi.org/10.5599/admet.1575","url":null,"abstract":"<p><p>In the present research, an advanced cellulose fiber paper (CFP) based biosensor is developed. This sensor is modified with nanocomposites containing poly(3,4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT:PSS) as the main matrix and functionalized gold nanoparticles (PEDOT:PSS-AuNP@CFP) for the selective and sensitive detection of bacterial infection (BI)-specific biomarker procalcitonin (PCT). Scanning electronic microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction are used to characterize the PEDOT:PSS-AuNP nanocomposite. This biosensor exhibits a high sensitivity of 1.34 μA (pg mL<sup>-1</sup>)<sup>-1</sup> in the linear detection ranges of 1-20×10<sup>4</sup> pg mL<sup>-1</sup>, and a 24-day life span for PCT antigen detection. Anti-PCT antigenic protein is used for immobilization for PCT quantification. The results of electrochemical response studies showed that this conductive paper bioelectrode had good reproducibility, stability, and sensitivity in physiological ranges (1-20×10<sup>4</sup> pg mL<sup>-1</sup>). Further, the proposed bioelectrode is an alternative choice for point-of-care PCT detection.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"11 2","pages":"263-275"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012553","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 simple and fast flow injection amperometry for the determination of methimazole in pharmaceutical preparations using an unmodified boron-doped diamond electrode.","authors":"Adison Meoipun, Kantima Kaewjua, Orawon Chailapakul, Weena Siangproh","doi":"10.5599/admet.1584","DOIUrl":"https://doi.org/10.5599/admet.1584","url":null,"abstract":"<p><p>In this work, an automated flow injection analysis (FIA) connected to a boron-doped diamond electrode (BDDE) was originally developed for the analysis of methimazole in pharmaceutical preparations. At a modification-free BDDE, methimazole was easilly oxidized. For the analysis of the mechanisms occurring at the electrode surface, cyclic voltammetry was employed to evaluate the impact of fundamental experimental parameters, such as pH and scan rate, on the BDDE response. For the quantitative detection, the FIA amperometric approach was constructed and used as a fast and sensitive method. The suggested approach provided a broad linear range of 0.5-50 μmol/L and a low detection limit of 10 nmol/L (signal-to-noise ratio = 3). Furthermore, the BDDE was successfully utilized to quantify methimazole in genuine samples from a variety of medicines, and its performance remained steady after more than 50 tests. The findings of amperometric measurements exhibit excellent repeatability, with relative standard deviations of less than 3.9 and 4.7 % for intra-day and inter-day, respectively. The findings indicated that, compared with traditional approaches, the suggested method has the following advantages: quick analysis time, simplicity, highly sensitive output, and no need for complicated operational processes.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"11 2","pages":"303-315"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710564","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}
ADMET and DMPKPub Date : 2023-01-01DOI: 10.5599/admet.1570
David G Levitt, Michael D Levitt
{"title":"Development and application of a simple pharmacokinetic model that quantitatively describes the distribution and elimination of the commonly measured proteins.","authors":"David G Levitt, Michael D Levitt","doi":"10.5599/admet.1570","DOIUrl":"https://doi.org/10.5599/admet.1570","url":null,"abstract":"<p><p>Increased plasma concentrations of a variety of cellular enzymes (alanine transaminase, aspartate aminotransferase, alkaline phosphatase, amylase, etc.) are commonly used as routine screening tests for a range of conditions. An increased concentration usually is assumed to result from an increased rate of delivery to the plasma. Factors such as decreased metabolism or excretion or altered extravascular distribution usually are ignored. As a prelude to a detailed analysis of all the factors producing altered plasma enzyme levels, we have reviewed the relevant literature describing the pharmacokinetics (PK) of 13 of the commonly measured plasma proteins and developed a PK model that provides a simple physiological description of all the data. Our model starts with the general 3-compartment, 6-parameter system previously developed for albumin and interprets the fluxes in terms of unidirectional sieved protein convectional volume flows from the plasma to the two tissue compartments and equal lymph flows returning to the plasma. This greatly constrains the model such that each protein is characterized by only two adjustable parameters (plasma clearance and sieving factor). In addition to accurately fitting the plasma kinetics, the model can accurately describe the tissue and lymph protein PK. For example, it can describe the thoracic duct lymph protein concentration following an intravenous infusion or the plasma concentration following a subcutaneous tissue injection. This simple model provides a satisfactory framework for the PK of 12 of the 13 proteins investigated. The glycoprotein intestinal alkaline phosphatase is the exception, requiring the addition of a liver recycling compartment involving the asialoglycoprotein receptor.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"11 1","pages":"57-80"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9275820","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":"CuFe<sub>2</sub>O<sub>4</sub> nanoparticles-based electrochemical sensor for sensitive determination of the anticancer drug 5-fluorouracil.","authors":"Peyman Mohammadzadeh Jahani, Maedeh Jafari, Farhad Nazari Ravari","doi":"10.5599/admet.1691","DOIUrl":"https://doi.org/10.5599/admet.1691","url":null,"abstract":"<p><p>A fast and facile electrochemical sensor for the detection of an important anticancer drug, 5-fluorouracil, is fabricated using CuFe<sub>2</sub>O<sub>4</sub> nanoparticles modified screen printed graphite electrode (CuFe<sub>2</sub>O<sub>4</sub> NPs/SPGE). The electrochemical activity of the modified electrode was characterized by chronoamperometry, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV) experiments. The CuFe<sub>2</sub>O<sub>4</sub> NPs improved the electrochemical properties of the electrodes and enhanced their electroanalytical performance. Electrochemical measurements using differential pulse voltammetry showed a wide linear relationship between 5-fluorouracil concentration and peak height within the range 0.1 to 270.0 μM with a low detection limit (0.03 μM). Further, the sensor was testified with a urine sample and 5-fluorouracil injection sample, and the observed remarkable recovery results replicate its practical applicability.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"11 2","pages":"201-210"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012556","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}
ADMET and DMPKPub Date : 2023-01-01DOI: 10.5599/admet.1709
Charaf Laghlimi, Abdelaziz Moutcine, Abdelilah Chtaini, Jalal Isaad, Adil Soufi, Younes Ziat, Hassan Amhamdi, Hamza Belkhanchi
{"title":"Recent advances in electrochemical sensors and biosensors for monitoring drugs and metabolites in pharmaceutical and biological samples.","authors":"Charaf Laghlimi, Abdelaziz Moutcine, Abdelilah Chtaini, Jalal Isaad, Adil Soufi, Younes Ziat, Hassan Amhamdi, Hamza Belkhanchi","doi":"10.5599/admet.1709","DOIUrl":"https://doi.org/10.5599/admet.1709","url":null,"abstract":"<p><p>Various applications of electrochemical sensors and biosensors have been reported in many fields. These include pharmaceuticals, drug detection, cancer detection, and analysis of toxic elements in tap water. Electrochemical sensors are characterised by their low cost, ease of manufacture, rapid analysis, small size and ability to detect multiple elements simultaneously. They also allow the reaction mechanisms of analytes, such as drugs, to be taken into account, giving a first indication of their fate in the body or their pharmaceutical preparation. Several materials are used in the construction of sensors, such as graphene, fullerene, carbon nanotubes, carbon graphite, glassy carbon, carbon clay, graphene oxide, reduced graphene oxide, and metals. This review covers the most recent progress in electrochemical sensors used to analyze drugs and metabolites in pharmaceutical and biological samples. We have highlighted carbon paste electrodes (CPE), glassy carbon electrodes (GCE), screen-printed carbon electrodes (SPCE) and reduced graphene oxide electrodes (rGOE). The sensitivity and analysis speed of electrochemical sensors can be improved by modifying them with conductive materials. Different materials used for modification have been reported and demonstrated, such as molecularly imprinted polymers, multiwalled carbon nanotubes, fullerene (C60), iron(III) nanoparticles (Fe<sub>3</sub>O<sub>4</sub>NP), and CuO micro-fragments (CuO MF). Manufacturing strategies and the detection limit of each sensor have been reported.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"11 2","pages":"151-173"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029918","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}
ADMET and DMPKPub Date : 2022-09-13eCollection Date: 2022-01-01DOI: 10.5599/admet.1335
Pallavi M Shanthappa, Rakshitha Kumar
{"title":"ProAll-D: protein allergen detection using long short term memory - a deep learning approach.","authors":"Pallavi M Shanthappa, Rakshitha Kumar","doi":"10.5599/admet.1335","DOIUrl":"https://doi.org/10.5599/admet.1335","url":null,"abstract":"<p><strong>Background: </strong>An allergic reaction is the immune system's overreacting to a previously encountered, typically benign molecule, frequently a protein. Allergy reactions can result in rashes, itching, mucous membrane swelling, asthma, coughing, and other bizarre symptoms. To anticipate allergies, a wide range of principles and methods have been applied in bioinformatics. The sequence similarity approach's positive predictive value is very low and ineffective for methods based on FAO/WHO criteria, making it difficult to predict possible allergens.</p><p><strong>Method: </strong>This work advocated the use of a deep learning model LSTM (Long Short-Term Memory) to overcome the limitations of traditional approaches and machine learning lower performance models in predicting the allergenicity of dietary proteins. A total of 2,427 allergens and 2,427 non-allergens, from a variety of sources, including the Central Science Laboratory and the NCBI are used. The data was divided 80:20 for training and testing purposes. These techniques have all been implemented in Python. To describe the protein sequences of allergens and non-allergens, five E-descriptors were used. E1 (hydrophilic character of peptides), E2 (length), E3(propensity to form helices), E4(abundance and dispersion), and E5 (propensity of beta strands) are used to make the variable-length protein sequence to uniform length using ACC transformation. A total of eight machine learning techniques have been taken into consideration.</p><p><strong>Results: </strong>The Gaussian Naive Bayes as accuracy of 64.14 %, Radius Neighbour's Classifier with 49.2 %, Bagging Classifier was 85.8 %, ADA Boost was 76.9 %, Linear Discriminant Analysis has 76.13 %, Quadratic Discriminant Analysis was 84.2 %, Extra Tree Classifier was 90%, and LSTM is 91.5 %.</p><p><strong>Conclusion: </strong>As the LSTM, has an AUC value of 91.5 % is regarded best in predicting allergens. A web server called ProAll-D has been created that successfully identifies novel allergens using the LSTM approach. Users can use the link https://doi.org/10.17632/tjmt97xpjf.1 to access the ProAll-D server and data.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"231-240"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466458","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}
ADMET and DMPKPub Date : 2022-09-13eCollection Date: 2022-01-01DOI: 10.5599/admet.1317
Riyam F Ghazi, Mohammed H Al-Mayahy
{"title":"Levothyroxine sodium loaded dissolving microneedle arrays for transdermal delivery.","authors":"Riyam F Ghazi, Mohammed H Al-Mayahy","doi":"10.5599/admet.1317","DOIUrl":"https://doi.org/10.5599/admet.1317","url":null,"abstract":"<p><p>Levothyroxine (LT-4) sodium has shown variable bioavailability following oral administration. This can be assigned to the significant influence of gastrointestinal conditions, food and drugs administered concomitantly on the rate and extent of absorption from the gastrointestinal tract. Thus, the aim of this research study was to establish an efficient transdermal delivery system of LT-4 sodium via the application of hyaluronic acid dissolving microneedles. Microneedles-based drug delivery system consists of sharp-tip needles that puncture the top layers of the skin in a minimally invasive manner to create physical channels through which therapeutic molecules can easily diffuse into/across the skin. Hyaluronic acid polymer at different ratios (5-60 %) was used to prepare microneedle arrays (100 needles per array) using a micromoulding technique. Characterisation tests were carried out to select the optimum formulation. F11 formula containing 50% w/v hyaluronic acid and 1% v/v Tween 80 formula showed an appropriate needle shape with dimensions of 432 ± 6.4 μm in height and a tip diameter of 9.8 ± 1.3 μm. The microneedle arrays demonstrated a suitable mechanical strength after applying a force of 32 N per array and an excellent insertion ability both in Parafilm M® and human skin. The in vivo dissolution of microneedles was started rapidly within 5 minutes following the insertion in the skin and completed at 1 hour. Ex vivo permeation study using human skin has shown a significant improvement in LT-4 sodium delivery across the skin compared to control preparations (drug solution and microneedle free film). The microneedle array F11 has significantly (P ≤ 0.05) increased LT-4 sodium permeation through the skin (cumulative permeated amount of 32 ± 2 μg/cm<sup>2</sup>) in comparison to the control solution (cumulative permeated amount of 0.7 ± 0.07 μg/cm<sup>2</sup>) and the microneedle free film (cumulative permeated amount of 0.1 ± 0.02 μg/cm<sup>2</sup>) over 7 hours. The findings from the irritation test revealed that mild erythema was produced from the application of microneedle arrays which disappeared within 24 hours. Accordingly, dissolving hyaluronic acid microneedles could be a feasible and effective approach to delivering LT-4 sodium transdermally without causing significant skin damage.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"213-230"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466455","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":"Silver(I) complexes with phenolic Schiff bases: Synthesis, antibacterial evaluation and interaction with biomolecules.","authors":"Natalia Loginova, Maxim Gvozdev, Nikolai Osipovich, Alina Khodosovskaya, Tatiana Koval'chuk-Rabchinskaya, Galina Ksendzova, Dzmitry Kotsikau, Anatoly Evtushenkov","doi":"10.5599/admet.1167","DOIUrl":"https://doi.org/10.5599/admet.1167","url":null,"abstract":"<p><p>Novel Ag(I) complexes (<b>2a</b>-<b>2c</b>) with phenolic Schiff bases were synthesized using 4,6-di-tert-butyl-3-(((5-mercapto-1,3,4-thiadiazol-2-yl)imino)methyl)benzene-1,2-diol (<b>1a</b>), 4,6-di-tert-butyl-3-(((4-mercaptophenyl)imino)methyl)benzene-1,2-diol (<b>1b</b>), and 4,6-di-tert-butyl-3-(((3-mercaptophenyl)imino)methyl)benzene-1,2-diol (<b>1c</b>). They were examined by elemental analysis, FT-IR, UV-Vis, <sup>1</sup>H-NMR spectroscopy, XRD, cyclic voltammetry, conductivity measurements, and biological methods. The complexes are characterized by distorted geometry of the coordination cores AgN<sub>2</sub>S<sub>2</sub> (<b>2c</b>), AgNS (<b>2b</b>) and AgS<sub>2</sub> (<b>2a</b>). These stable complexes were not typified by the intramolecular redox reaction in organic solvents resulting in the formation of silver nanoparticles (AgNPs). Antibacterial activity of <b>1a</b>-<b>1c</b> and <b>2a</b>-<b>2c</b> was evaluated in comparison with AgNPs and commonly used antibiotics. All the complexes were more active than the ligands against the bacteria tested (14), but they were less active than AgNPs and commonly used antibiotics. Both <b>1a</b>-<b>1c</b> and their complexes <b>2a</b>-<b>2c</b> exhibited the capability for the bovine heart Fe(III)-Cyt c reduction. The ligands <b>1b</b> and <b>1c</b> were characterized by the highest reduction rate among the compounds under study, and they showed a higher reducing ability (determined by cyclic voltammetry) as compared with that of their Ag(I) complexes <b>2b</b> and <b>2c</b>.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"197-212"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466456","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}
ADMET and DMPKPub Date : 2022-09-13eCollection Date: 2022-01-01DOI: 10.5599/admet.1170
U C Mithin, Rinku Buragohain, Pradip K Das, Tapan K Mandal, Rabindra N Hansda, Siddhartha N Joardar, Indranil Samanta, Tapas K Sar
{"title":"Pharmacokinetics of ceftriaxone-tazobactam (8:1) combination in healthy and <i>Escherichia coli</i> induced diarrhoeic birds.","authors":"U C Mithin, Rinku Buragohain, Pradip K Das, Tapan K Mandal, Rabindra N Hansda, Siddhartha N Joardar, Indranil Samanta, Tapas K Sar","doi":"10.5599/admet.1170","DOIUrl":"https://doi.org/10.5599/admet.1170","url":null,"abstract":"<p><p>Antibiotic-resistant <i>Escherichia coli</i> infection of poultry causes significant economic losses. Extended spectrum β lactamases (ESBL) producing <i>E. coli</i> was inoculated in a broiler, Rhode Island Red and Haringhata Black birds orally at 56×10<sup>8</sup> c.f.u. mL<sup>-1</sup> for induction of diarrhoea. Pharmacokinetics of ceftriaxone-tazobactam combination (8:1) was studied following a single intramuscular injection at 28.125 mg kg<sup>-1</sup> and the combination was administered twice daily to treat such infection. Plasma concentration of both ceftriaxone persisted up to 8 h in experimental birds and maintained an approximate ratio of 8:1 with tazobactam for a period of 2 h, 0.25 h and 0.75 h, respectively in a broiler, Rhode Island Red and Haringhata Black birds. The <i>K</i> <sub>el</sub> was significantly lower in all experimental birds compared to healthy birds. Efficacy study was conducted in diarrhoeic birds by administration of ceftriaxone-tazobactam combination at 28.125 mg kg<sup>-1</sup> body weight twice daily intramuscularly for three days which caused an increase in specific antibody titre in the broiler on 5<sup>th</sup> day and in Rhode Island Red birds 10<sup>th</sup> day. However, Haringhata black birds were inherently showed more resistance towards the infection. The combination of ceftriaxone and tazobactam in the ratio of 8:1 can be an effective treatment to combat ESBL producing <i>E. coli</i> infections.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 3","pages":"180-196"},"PeriodicalIF":2.5,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466457","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}