Geoffrey D Miller, Jenna M Goodrum, America K Flores, Andre K Crouch, Daniel Eichner
{"title":"Detecting EPO in Microvolumetric Capillary Serum Shipped at Ambient Temperature for Antidoping Testing.","authors":"Geoffrey D Miller, Jenna M Goodrum, America K Flores, Andre K Crouch, Daniel Eichner","doi":"10.1002/dta.3831","DOIUrl":"https://doi.org/10.1002/dta.3831","url":null,"abstract":"<p><p>Erythropoietin receptor agonist (ERA) testing for antidoping can be achieved in both urine and blood samples. Recent published work showed the comparability between the two matrices and focused on detectability in microvolumetric capillary serum samples collected using the Tasso+ device. Currently, in the antidoping field, blood samples are required to be shipped under cold, temperature-controlled conditions. However, due to the suggested greater stability of EPO in blood compared to urine, it is believed that blood samples should be viable for ERA analysis if shipped under the ambient, not cold temperature-controlled conditions to which urine samples are subjected. In this collaborative study with the Ultimate Fighting Championship, microvolumetric capillary serum samples were collected in the field and shipped under ambient conditions to the laboratory for ERA analysis. Resulting data showed that endogenous EPO was detectable in 100% of these samples, showing no loss in detectability despite shipping under non-controlled conditions. Further, ERA analyses were conducted in the laboratory on additional in-house collected samples and post-EPO administration samples subjected to various storage and shipping conditions, also showing reliable endogenous and recombinant EPO detectability in all samples except those experiencing extreme temperature (50°C) conditions. Taken together, these data highlight the stability of EPO in blood samples and show that ERA blood samples can be collected in the field and shipped without costly temperature-controlled shipping methods and without a loss in detectability.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Moses Philip, Abdul Khader Karakka Kal, Michael Benedict Subhahar, Tajudheen K Karatt, Fatma Mohammed Graiban, Meleparappil Muhammed Ajeebsanu, Marina Joseph, Shantymol V Jose
{"title":"Investigation Into the Equine Metabolism of Phosphodiesterase-4 Inhibitor Roflumilast for Potential Doping Control.","authors":"Moses Philip, Abdul Khader Karakka Kal, Michael Benedict Subhahar, Tajudheen K Karatt, Fatma Mohammed Graiban, Meleparappil Muhammed Ajeebsanu, Marina Joseph, Shantymol V Jose","doi":"10.1002/dta.3822","DOIUrl":"https://doi.org/10.1002/dta.3822","url":null,"abstract":"<p><p>The phosphodiesterase 4 (PDE4) inhibitors constitute a relatively modern class of medications that are known for inducing bronchodilation and exhibiting anti-inflammatory properties within the body. Due to these properties, there is concern regarding their potential misuse as performance-enhancing substances in competitive sports. This study delves into the metabolic conversion of roflumilast in thoroughbred horses following oral administration and in vitro experimentation using equine liver microsomes and Cunninghamella elegans. High-performance liquid chromatography coupled with a Q Exactive Orbitrap mass spectrometer (HPLC-HRMS) was employed for analysis. The investigation identified 10 metabolites of roflumilast, including six phase I and four phase II metabolites from in vivo studies, and 11 metabolites from in vitro studies, consisting of eight phase I and three phase II metabolites. The identified biotransformation products encompassed processes such as hydroxylation, chlorine substitution, methylation, N-oxide formation, and even the dissociation of methylenecyclopropane and difluoromethane. Furthermore, the study identified three glucuronic acid and one sulfonic acid conjugated phase II metabolites of the investigated drug candidate. The aforementioned findings contribute to the detection and comprehension of the unauthorized utilization of roflumilast in equestrian sports.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mira Sundström, Pirkko Kriikku, Ilkka Ojanperä, Carsten Baessmann, Anna Pelander
{"title":"UHPLC-QTOFMS Urine Drug Screening With Dilute-and-Shoot Sample Preparation and Vacuum-Insulated Probe-Heated Electrospray Ionization.","authors":"Mira Sundström, Pirkko Kriikku, Ilkka Ojanperä, Carsten Baessmann, Anna Pelander","doi":"10.1002/dta.3830","DOIUrl":"https://doi.org/10.1002/dta.3830","url":null,"abstract":"<p><p>We developed a method for comprehensive urine drug screening by applying dilute-and-shoot extraction and vacuum-insulated probe-heated electrospray ionization with ultra-high performance liquid chromatography high-resolution quadrupole time-of-flight mass spectrometry (DS-UHPLC-VIP-HESI-QTOFMS). The method involved five-fold post-hydrolysis dilution of urine samples and chromatography on a C18 UHPLC column prior to QTOFMS analysis. The recently introduced VIP-HESI ion source was chosen due to its enhanced ionization efficiency and compatibility with UHPLC-QTOFMS. Extensive data was acquired in positive ion mode with a low collision energy (7 eV) and an elevated collision energy (30 eV), using the broadband collision-induced dissociation data acquisition scan mode that continuously generated high-resolution and accurate mass for parent and fragment qualifier ions, and parent ion isotopic patterns. Compound identification was performed against an in-house database with 1263 compound entries, using an automated post-run reverse target database search with preset identification criteria. Method validation with 56 different drugs showed acceptable results for the limit of identification (median 5 ng/mL), matrix effects (70-130%), repeatability of retention times (< 1%), mass accuracy (< 1 mDa), as well as for specificity and stability. As compared with an established UHPLC-QTOFMS method relying on solid-phase extraction and conventional electrospray ionization, DS-UHPLC-VIP-HESI-QTOFMS produced comparable results from authentic clinical urine samples for most drugs, but showed clearly improved detectability for pregabalin, gabapentin, and ritalinic acid. We anticipate that the new method will be a step forward for laboratories performing routine urine drug screening due to its fast turnaround time, reduced manual workload, cost efficiency, and broad substance coverage.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Max Polke, Marta Concheiro, Gail Cooper, Christian Bogdal, Markus R. Baumgartner, Thomas Krämer, Tina M. Binz
{"title":"Development and validation of a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method including 25 novel synthetic opioids in hair and subsequent analysis of a Swiss opioid consumer cohort","authors":"Max Polke, Marta Concheiro, Gail Cooper, Christian Bogdal, Markus R. Baumgartner, Thomas Krämer, Tina M. Binz","doi":"10.1002/dta.3663","DOIUrl":"10.1002/dta.3663","url":null,"abstract":"<p>Major public health concern is raised by the evidence that common drugs like heroin are now frequently laced or replaced with highly potent novel synthetic opioids (NSOs). The objective of this study was to explore the prevalence and patterns of NSOs in a cohort of Swiss opioid users by hair analysis. Hair analysis is considered an ideal tool for retrospective consumption monitoring. Hair samples from 439 opioid users in Zurich were analyzed. Study inclusion required a previous positive hair test result for heroin metabolites, oxycodone, fentanyl, methadone, or tramadol. The samples were extracted with a two-step extraction procedure, followed by a targeted LC–MS/MS (QTRAP® 6500+) analysis in multiple reaction monitoring mode for a total of 25 NSOs. The method underwent full validation and demonstrated good selectivity and sensitivity with limits of detection (LOD) as low as 0.1 pg/mg. The analyzed sample cohort demonstrated a positivity rate for NSOs of 2.5%, including the following NSOs: butyrylfentanyl, acrylfentanyl, furanylfentanyl, methoxyacetylfentanyl, ocfentanil, U-47700, isobutyrylfentanyl and benzylfentanyl. Furthermore, we were able to identify specific consumption patterns among drug users. The results indicate that hair analysis is a valuable tool for investigating the prevalence of NSOs in drug-using populations, which seems to be low in the case of Swiss opioid users. Nevertheless, the results highlight the need for sensitive analytical detection methods in forensic toxicology to identify and monitor substance distribution in different populations.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1384-1391"},"PeriodicalIF":2.6,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dta.3663","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Loria, Andreas Breenfeldt Andersen, Jacob Bejder, Thomas Bonne, Silke Grabherr, Tiia Kuuranne, Nicolas Leuenberger, Nikolai Baastrup Nordsborg
{"title":"mRNA biomarkers sensitive and specific to micro-dose erythropoietin treatment at sea level and altitude","authors":"Francesco Loria, Andreas Breenfeldt Andersen, Jacob Bejder, Thomas Bonne, Silke Grabherr, Tiia Kuuranne, Nicolas Leuenberger, Nikolai Baastrup Nordsborg","doi":"10.1002/dta.3665","DOIUrl":"10.1002/dta.3665","url":null,"abstract":"<p>Recombinant human erythropoietin (rhEPO) is prohibited by the World Anti-Doping Agency. rhEPO abuse can be indirectly detected via the athlete biological passport (ABP). However, altitude exposure challenges interpretation of the ABP. This study investigated whether 5′-aminolevulinate synthase 2 (<i>ALAS2</i>) and carbonic anhydrase 1 (<i>CA1</i>) in capillary dried blood spots (DBSs) are sensitive and specific markers of rhEPO treatment at altitude. <i>ALAS2</i> and <i>CA1</i> expression was monitored in DBS collected weekly before, during, and after a 3-week period at sea level or altitude. Participants were randomly assigned to receive 20 IU kg bw<sup>−1</sup> epoetin alpha (rhEPO) or placebo injections every second day for 3 weeks while staying at sea level (rhEPO, <i>n</i> = 25; placebo, <i>n</i> = 9) or altitude (rhEPO, <i>n</i> = 12; placebo, <i>n</i> = 27). <i>ALAS2</i> and <i>CA1</i> expression increased up to 300% and 200%, respectively, upon rhEPO treatment at sea-level and altitude (<i>P</i>-values <0.05). When a blinded investigator interpreted the results, <i>ALAS2</i> and <i>CA1</i> expression had a sensitivity of 92%. Altitude did not confound the interpretation. Altitude affected <i>ALAS2</i> and <i>CA1</i> expression less than actual ABP markers when compared between sea level and altitude results. An individual athlete passport-like approach simulation confirmed the biomarker potential of <i>ALAS2</i> and <i>CA1</i>. <i>ALAS2</i> and <i>CA1</i> were sensitive and specific biomarkers of micro-dose rhEPO treatment at sea level and altitude. Altitude seemed less a confounding factor for these biomarkers, especially when they are combined. Thus, micro-dose rhEPO injections can be detected in a longitudinal blinded setting using mRNA biomarkers in DBS.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1392-1401"},"PeriodicalIF":2.6,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Detlef Thieme, Kai Weigel, Patricia Anielski, Aniko Krumbholz, Frank Sporkert, Annekathrin M. Keiler
{"title":"Elimination profile of low-dose chlortalidone and its detection in hair for doping analysis—Implication for unintentional non-therapeutic exposure","authors":"Detlef Thieme, Kai Weigel, Patricia Anielski, Aniko Krumbholz, Frank Sporkert, Annekathrin M. Keiler","doi":"10.1002/dta.3661","DOIUrl":"10.1002/dta.3661","url":null,"abstract":"<p>Chlortalidone (CLT) is a thiazide-type diuretic with high affinity for the erythrocyte carbonic anhydrase. Therapeutically, it is mostly used to treat edema and hypertension due to liver cirrhosis, heart insufficiency, or renal dysfunction. Although diuretics and masking agents are prohibited by the World Anti-Doping Agency (WADA) at all times in sports, substances belonging to this category are constantly detected in athlete samples, according to WADA's annual testing figures. Within this group of structurally diverse compounds, a threshold of 20 ng/mL has been introduced for six substances solely due to their presence as contaminants in other permitted drugs because of pharmaceutical production processes. In a recent presumptive doping case with a low urinary CLT concentration, the question of unintentional doping, for example, by contaminated non-steroidal anti-inflammatory drug intake, arose. To examine this potential scenario, a co-elimination of low-dose CLT and hydrochlorothiazide (HCTA; 20 × 50 μg, 0.2 mg/day each) was conducted on five consecutive days in two volunteers. Urine samples were subjected to liquid chromatography-tandem mass spectrometry (LC–MS/MS). Moreover, we examined the incorporation of CLT in scalp hair. HCTA is rapidly excreted renally in comparatively high concentrations. In contrast, the elimination of CLT is considerably slower (terminal elimination half-life extended by a factor of 12) and, consequently, much less concentrated in corresponding urine samples (45 and 53 ng/mL, respectively). Conversely, a higher hair incorporation of chlorthalidone was observed with simultaneous dosing of both. The results suggest that an unintentional intake of sub-therapeutic CLT doses due to contamination might result in an adverse analytical finding.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1378-1383"},"PeriodicalIF":2.6,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dta.3661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bethan Davies, Richard Paul, David Osselton, Richard Evers, Timothy Woolley
{"title":"Absence of new psychoactive substances in wastewater from South Wales, UK, revealed by optimised liquid chromatography-time-of-flight analysis","authors":"Bethan Davies, Richard Paul, David Osselton, Richard Evers, Timothy Woolley","doi":"10.1002/dta.3659","DOIUrl":"10.1002/dta.3659","url":null,"abstract":"<p>New psychoactive substances are produced and marketed to mimic the effects of their illicit counterparts and to attempt to evade drug tests and prosecution. Here, we present the optimisation, validation and application of an analytical method using liquid chromatography–time-of-flight mass spectrometry to detect and quantify 37 new psychoactive substances and illicit substances in wastewater from South Wales, UK, using a targeted analysis method. Sample preparation was performed using solid-phase extraction with Oasis HLB cartridges. The LC separation was performed using a YMC-Triart Phenyl 450 bar column (12 nm, 5 μm, 100 × 3 mm) which provided good separation and resolution for all targeted analytes with a run time of 9 min. The method was validated using the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recovery and matrix effects. The method was then applied to influent wastewater samples collected from two wastewater treatment plants in Wales, UK.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1370-1377"},"PeriodicalIF":2.6,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dta.3659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139739964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interest of hair tests to discriminate a tail end of a doping regimen from a meat contamination in case of challenging an antidoping rule violation. III. Case report involving boldenone","authors":"Pascal Kintz, Laurie Gheddar","doi":"10.1002/dta.3656","DOIUrl":"10.1002/dta.3656","url":null,"abstract":"","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1366-1369"},"PeriodicalIF":2.6,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139733991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arianna Giorgetti, Annette Zschiesche, Olwen Groth, Belal Haschimi, Martin Scheu, Guido Pelletti, Paolo Fais, Frank Musshoff, Volker Auwärter
{"title":"ADB-HEXINACA—a novel synthetic cannabinoid with a hexyl substituent: phase I metabolism in authentic urine samples, a case report and prevalence on the German market","authors":"Arianna Giorgetti, Annette Zschiesche, Olwen Groth, Belal Haschimi, Martin Scheu, Guido Pelletti, Paolo Fais, Frank Musshoff, Volker Auwärter","doi":"10.1002/dta.3657","DOIUrl":"10.1002/dta.3657","url":null,"abstract":"<p>Synthetic cannabinoid receptor agonists (SCRAs) are one of the largest groups of new psychoactive substances (NPS). Yet, another novel analog started spreading on the NPS market around 2021. Soon after, the substance could be analytically characterized in herbal material as ADB-HEXINACA, an SCRA containing a hexyl-substituted tail on the indazole core. Here, we present suitable urinary markers to prove the consumption of this analog, a case report of acute polydrug intoxication and data on its prevalence in Germany. Anticipated phase I metabolites were detected in 12 authentic urine samples that were collected for abstinence control and analyzed by ultra-performance liquid chromatography coupled to a time-of-flight mass spectrometer (UPLC-qToF-MS). The results of in vivo samples were confirmed by analysis of in vitro incubates with pooled human liver microsomes (pHLMs). Forensic samples were used to assess the prevalence of ADB-HEXINACA. Thirty-two phase I metabolites were detected in the authentic urine samples. The main metabolites resulted from amide hydrolysis in combination with either monohydroxylation or ketone formation at the hexyl moiety (M15 and M26), the monitoring of which is recommended as a proof of consumption. ADB-HEXINACA was detected in 3.5% of SCRA positive urine samples collected for abstinence control in Freiburg up to December 2022 and in 5.5% of the SCRA positive blood/serum samples. The hexyl substituent of ADB-HEXINACA allows for the detection of specific urinary biomarkers suggested as analytical targets to confirm its prior intake. ADB-HEXINACA had a rather low prevalence in Germany, alternating months of higher prevalence with periods of total absence.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1350-1365"},"PeriodicalIF":2.6,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dta.3657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Polet, Peter Van Eenoo, Lance Brooker, Claire Edey, Vanessa Agon, Janelle Grainger, Gemma Payne, Catrin Goebel
{"title":"Prevalence of nandrolone preparations with endogenous carbon isotope ratios in Australia","authors":"Michael Polet, Peter Van Eenoo, Lance Brooker, Claire Edey, Vanessa Agon, Janelle Grainger, Gemma Payne, Catrin Goebel","doi":"10.1002/dta.3654","DOIUrl":"10.1002/dta.3654","url":null,"abstract":"<p>Nandrolone and its prohormones, including 19-norandrost-4-ene-3,17-dione and 19-norandrost-4-ene-3β,17β-diol, are anabolic steroids forbidden at all times in sports according to the World Anti<span>-</span>Doping Code Prohibited List and its metabolite 19-norandrosterone (19NA) is the preferred urinary target compound to identify their abuse. In recent years, an increasing number of 19NA isotope ratio mass spectrometry (IRMS) cases have arisen that, based on the initial testing procedure, were likely to result in an adverse analytical finding but were concluded negative after IRMS analysis. The current study was therefore set up to gain a better insight on the prevalence of nandrolone preparations with endogenous carbon isotope ratio values in Australia. Suitable workplace (non-athlete) urine samples that had previously been reported positive for 19NA were identified and analysed on IRMS. A total of 82% of the samples that were analysed were reported with enriched carbon isotope ratios of 19NA (i.e., 19NA greater than −26‰). This indicates that there is a high prevalence of nandrolone-containing anabolic androgenic steroid preparations in Australia that have ‘endogenous’ carbon isotope ratios which reduces the ability to identify exogenous nandrolone.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"16 11","pages":"1345-1349"},"PeriodicalIF":2.6,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}