European Journal of Mass Spectrometry最新文献

{"title":"Competing fragmentation processes of <i>O</i>-acetyl-substituted carboxylate anions subjected to collision-induced dissociation.","authors":"J Stuart Grossert, Robert L White","doi":"10.1177/14690667251346668","DOIUrl":"https://doi.org/10.1177/14690667251346668","url":null,"abstract":"<p><p>Carboxylic acids containing an <i>O</i>-acetyl substituent were studied using tandem mass spectrometry (MS/MS). Decarboxylation was observed for deprotonated <i>O</i>-acetylmandelic acid, whereas deprotonated acetoxyacetic acid and acetylsalicylic acid fragmented by two competing pathways. In the lower energy process, the product ion was formed by intramolecular proton abstraction and subsequent neutral loss of ketene (CH₂=C=O) from the <i>O</i>-acetyl group. At higher collision energies, nucleophilic displacement of the <i>O</i>-acetyl group by the carboxylate group of acetoxyacetate yielded acetate (CH₃CO₂^-) as the more abundant product ion. The relative energetics computed for the reaction pathways of acetoxyacetate were consistent with the product ion spectra. Overall, the observation of both the loss of ketene and the formation of acetate ion are characteristic of an <i>O</i>-acetyl group in the precursor carboxylate ion undergoing collision-induced dissociation. The different fragmentation behavior exhibited by <i>O</i>-acetyl mandelate was attributed to the charge stabilizing properties of the phenyl substituent that facilitated decarboxylation. Thus, the fragmentation processes observed depended on the structures of the <i>O</i>-acetyl-substituted carboxylate ions and the associated intramolecular interactions.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"14690667251346668"},"PeriodicalIF":1.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prime mass amino acids: A new numbers based classification of significance to mass spectrometry and protein biology.","authors":"Kevin M Downard","doi":"10.1177/14690667251339718","DOIUrl":"https://doi.org/10.1177/14690667251339718","url":null,"abstract":"<p><p>The nominal mass of amino acid residues calculated from their elemental compositions are defined by prime numbers far more often than chance, and such residues appear to play an important role in the formation and biology of proteins. It is proposed therefore that consideration be given to classifying prime mass amino acids as such, beyond the more common, familiar definitions associated with the other physicochemical properties of amino acids including charged or non-charged, hydrophobic or hydrophilic, polar or non-polar, acidic or basic, aliphatic or aromatic. Greater focus could also be given to such residues during peptide and protein sequencing with mass spectrometry and the construction of structural maps, given their predominantly hydrophobic character and thus their role in protein folding and transmembrane domains. The use of prime numbers to define amino acids based on the sum of the atomic masses from their elemental compositions invokes other recent interest and observations whereby prime numbers were organised in a way that mirrors electrons arranged within the orbitals of an atom. The article links number theory with both the physical and biological sciences, and mass spectrometry, for the first time.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"14690667251339718"},"PeriodicalIF":1.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tandem mass spectrometry fragmentation patterns of sulfo-SDA cross-linked peptides.","authors":"Thomas Powell, Martin Ebner, Andrew Creese","doi":"10.1177/14690667251339717","DOIUrl":"10.1177/14690667251339717","url":null,"abstract":"<p><p>Cross-linking mass spectrometry is rapidly becoming a choice method for determining a protein's higher-order structure as well as capturing inter-protein interactions. In particular, diazirene-based photo-activatable cross-linkers, such as sulfo-SDA have been shown to be effective at generating high-density cross-linking data. Previously, we have shown that this method may be used to study binding orientation between two non-covalently linked complexes; however, several unexpected ions were noted in the MS2 spectra. In this study, the tandem mass spectrometry fragmentation patterns of sulfo-SDA-initiated cross-linked peptides under higher-energy collision induced (HCD), collision induced (CID) and electron transfer with supplementary HCD (EThcD) dissociations are discussed. The analysis revealed substantial insights into localising cross-linking sites, which is essential for accurate determination of protein higher-order structural characteristics.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"14690667251339717"},"PeriodicalIF":1.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability studies of glycopyrronium bromide and <i>in vitro</i> toxicity evaluation of its major transformation products by LC-MS/MS and NMR.","authors":"Bala Manikantha Adimoolam, Aruna Jangam, S Babu Dadinaboyina, Srinivas Ragampeta, Jagadeshwar Reddy Thota","doi":"10.1177/14690667251339714","DOIUrl":"https://doi.org/10.1177/14690667251339714","url":null,"abstract":"<p><p>Characterization of impurities is very important in drug chemistry and process development. Due to these transformation products (TPs), the drug may lose its stability, safety and efficiency. Hence, it is imperative to develop a selective analytical method enabling chromatographic separation of drug and their TPs. Glycopyrronium bromide is a quaternary ammonium drug that acts as an anticholinergic agent and is used to treat chronic obstructive pulmonary disease. Glycopyrronium bromide was forced to degrade under various conditions, according to the International Council for Harmonisation Q1A (R2) guidelines. The resulting TPs were further separated on an Accucore C18 (150 × 4.6 mm, 2.6 μm) column using a gradient program. Glycopyrronium bromide yielded two TPs under acid and base hydrolytic stress conditions. Structural characterization of both TP1 and TP2 was carried out by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in combination with HRMS. Further, the TPs were isolated using semi-preparative HPLC, and their structures were confirmed by ¹H and ¹³C NMR spectroscopy. <i>In vitro</i> toxicity studies of isolated TPs were carried out using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method and they were found non-toxic.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"14690667251339714"},"PeriodicalIF":1.1,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased preponderance of glutamatergic dysregulation in atypical facial pain.","authors":"Tajdeen Faaheera Fathima, Ramya Suresh, Ramya Ramadoss, Sandhya Sundar, Suganya Panneer Selvam, Pratibha Ramani, Krishnaswamy Nitya, Kasi Rajan Hema Shree","doi":"10.1177/14690667251327131","DOIUrl":"10.1177/14690667251327131","url":null,"abstract":"<p><p><b>Background:</b> Orofacial pain, encompassing a broad spectrum of conditions, arises from the intricate interplay of sensory, cognitive, and emotional components. Accurate diagnosis and management are challenging due to the complexity of orofacial anatomy. Saliva, a non-invasive diagnostic fluid, offers significant potential for identifying biomarkers associated with pain and systemic diseases. <b>Objective:</b> This study aims to investigate the salivary proteome profile in individuals with orofacial pain to identify potential biomarkers for improved diagnostic accuracy and therapeutic interventions. <b>Methods:</b> Saliva samples were collected and processed from individuals experiencing orofacial pain. Proteomic profiling was conducted using advanced mass spectrometry techniques. Identified proteins and metabolites were analyzed to determine their relevance to immune responses, inflammation, and metabolic pathways. Statistical evaluations were performed to identify significant differences in biomarker expression. <b>Results:</b> Key immune-related proteins, such as immunoglobulin A (360.7075 m/z) and lysozyme C (315.8543 m/z), were identified, highlighting their roles in mucosal immunity and antimicrobial defense. Essential amino acids, including leucine (207.1007 m/z) and tyrosine (126.9058 m/z), emphasized their importance in protein synthesis and metabolic pathways. Lipid metabolites like deoxycholic acid (259.8098 m/z) and linoleic acid (183.9124 m/z) suggested active lipid metabolism. Elevated uric acid levels (248.9720 m/z) indicated oxidative stress and chronic inflammation. <b>Conclusion:</b> Saliva's proteomic profile provides valuable insights into the mechanisms underlying orofacial pain. Identified biomarkers have potential applications in diagnostics and personalized therapeutic strategies. Future studies should focus on validating these findings in larger cohorts to enhance clinical applicability.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"63-69"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of linear quadrupoles operated with amplitude-asymmetric sinusoidal waveforms.","authors":"Alexander I Ivanov, Alexey A Sysoev, Andrew N Konenkov, Nikolai V Konenkov","doi":"10.1177/14690667251315048","DOIUrl":"10.1177/14690667251315048","url":null,"abstract":"<p><p>The stability regions formed by the asymmetric sinusoidal shape of the periodic supply potential of the quadrupole mass filter are calculated, with the signal duty cycle <math><mi>d</mi><mo>=</mo><mn>0.5</mn></math>. Two cases are considered, when <math><msub><mi>A</mi><mn>1</mn></msub><mo><</mo><mspace></mspace><msub><mi>A</mi><mn>2</mn></msub></math> and <math><msub><mi>A</mi><mn>1</mn></msub><mo>></mo><msub><mi>A</mi><mn>2</mn></msub></math>, where <math><msub><mi>A</mi><mn>1</mn></msub></math> and <math><msub><mi>A</mi><mn>2</mn></msub></math> are the amplitudes of the positive and negative parts of the sinusoid. Stability islands are revealed, where the QMF operation is possible by changing amplitude <math><msub><mi>A</mi><mn>2</mn></msub></math> without DC potential. For the values <math><msub><mi>A</mi><mn>1</mn></msub><mo>=</mo><mn>1</mn></math> and <math><msub><mi>A</mi><mn>2</mn></msub><mo>=</mo><mn>0.8</mn></math>, the mass selected instability mode with a resolution of about 7000 is found. In this island, the potential well depth reaches its maximum along the <i>Y</i> coordinate. At the amplitudes <math><msub><mi>A</mi><mn>1</mn></msub><mo>=</mo><mn>1</mn></math> and <math><msub><mi>A</mi><mn>2</mn></msub><mo>=</mo><mn>1.8</mn><mo>-</mo><mn>2.0</mn></math>, stability regions are formed, the operation in which allows reaching <math><msub><mi>R</mi><mrow><mn>0.5</mn></mrow></msub><mo>=</mo><mn>2000</mn></math>. The results of the transmission and excitation contours modeling confirm the validity of the method for calculating the stability diagrams of a linear quadrupole with asymmetric sinusoidal waveform.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"21-28"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">Basics of utilizing NH<ns0:math><ns0:msubsup><ns0:mrow /><ns0:mn>4</ns0:mn><ns0:mo>+</ns0:mo></ns0:msubsup></ns0:math> ions for accurate phthalate ester quantification via selected ion flow tube mass spectrometry in food.","authors":"Manjeet Bhatia","doi":"10.1177/14690667241310351","DOIUrl":"10.1177/14690667241310351","url":null,"abstract":"<p><p>Phthalate esters, frequently used as plasticizers in consumer products, raise concerns because of potential health effects. Using density functional theory (DFT) with B₃LYP and 6-311++G(d, p) basis sets, their properties, such as dipole moment, polarizability, proton affinity and ionization energy of phthalate esters are obtained. Reaction kinetics and thermodynamics of popular reagent ions like H₃O<math><msup><mrow></mrow><mo>+</mo></msup></math>, NH<math><msubsup><mrow></mrow><mn>4</mn><mo>+</mo></msubsup></math>, NO<math><msup><mrow></mrow><mo>+</mo></msup></math> and O<math><msubsup><mrow></mrow><mn>2</mn><mo>+</mo></msubsup><mrow><msup><mrow></mrow><mo>∙</mo></msup></mrow></math> are computed to know the feasibility of the reactions with such ions. Proton affinity and ionization energy indicate high susceptibility to proton and charge transfer reactions. High dipole moments contribute to elevated rate coefficients in proton transfer reaction mass spectrometry (PTR-MS) and selected ion flow tube mass spectrometry (SIFT-MS). PTR-MS rates are influenced by drift tube conditions, supported by high center-of-mass collisional energy of E<math><msub><mrow></mrow><mrow><mi>cm</mi></mrow></msub></math> = 0.28 eV. SIFT-MS rates diminish with rising temperature. The high kinetic energy data of H₃O<math><msup><mrow></mrow><mo>+</mo></msup></math>, NO<math><msup><mrow></mrow><mo>+</mo></msup></math> and O<math><msubsup><mrow></mrow><mn>2</mn><mo>+</mo></msubsup><mrow><msup><mrow></mrow><mo>∙</mo></msup></mrow></math> suggests that simple proton transfer and charge transfer reactions are overruled due to very high internal energy which could lead to extensive fragmentation of phthalate esters. The energetic profile of NH<math><msubsup><mrow></mrow><mn>4</mn><mo>+</mo></msubsup></math> ions indicates their suitability for quantifying phthalate esters using NH<math><msubsup><mrow></mrow><mn>4</mn><mo>+</mo></msubsup></math>-CI-MS techniques.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"29-37"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-of-flight mass spectrometry with a pulsed glow discharge-A versatile tool in modern analytical chemistry: From elemental and isotopic analysis of solids to determination of VOCs and inorganic compounds in ambient air.","authors":"Alexander Ganeev, Victoria Chuchina, Anna Gubal, Denis Kravtsov, Evgenia Iakovleva, Mikhail Yavor, Alexander Berdnikov, Alexander Frolov, Mika Sillanpää, Qing Ye, Jin Han, Marat Myradimov, Alexander Stroganov","doi":"10.1177/14690667251328836","DOIUrl":"10.1177/14690667251328836","url":null,"abstract":"<p><p>This article describes the key achievements over the past 10 years in the microsecond pulsed glow discharge mass spectrometry applied to the analysis of solids and gaseous mixtures. The solid-state analysis allows studying solid materials with different conductivities, including direct simultaneous quantitation of light elements with high ionization energy (N, O, F, Cl, etc.), heavy elements (U, Th, etc.), and isotope analysis. Dielectric materials analysis is considered in details with special emphasis on sample preparation approaches. Particular attention is focused on a new application of the technique for detection of volatile organic and inorganic compounds in gas mixtures (model gas mixtures, ambient air and exhaled air). This approach has prospects for solving medical and environmental problems as well as for process gas monitoring. Several applications (He determination in deuterium, detection of VOCs, Xe and other inorganic compounds in air) are presented as examples. Using the high resolution (6000 for Pb, <i>m</i>/<i>z</i> 208) of Lumas PGD-301 time-of-flight mass spectrometer helps to eliminate most of the interferences and thereby improves the analytical performance. Combination of high energy electron ionization with soft Penning and other ionization mechanisms allows to detect almost all known elements and molecules.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"3-20"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-ESI-MS/MS method for the accurate quantification of eight nitrosamines in pharmaceutical products.","authors":"Ibrahim Danis, Durisehvar Ozer Unal","doi":"10.1177/14690667251328823","DOIUrl":"10.1177/14690667251328823","url":null,"abstract":"<p><p>In 2018, the Food and Drug Administration and the European Medicines Agency identified nitrosamine impurities in certain drugs, prompting detailed investigations by international regulatory authorities. According to ICH M7 (R1) guidelines, nitrosamines are classified as Class 1 substances, the most hazardous category, based on their carcinogenic and mutagenic properties. They are also recognized as probable human carcinogens by the International Agency for Research on Cancer. Since nitrosamine-induced DNA damage poses significant health risks, identifying potential nitrosamines in pharmaceutical products is crucial. In this study, a simple and efficient extraction method was designed to minimize matrix effects. These effects were evaluated using calibration curves prepared for each drug product in their respective matrices. The developed method was performed using an Agilent 1260 series HPLC system and an Agilent 6460 triple quadrupole tandem mass spectrometer. An Inertsil ODS-3 C18 (5 µm, 4.6 × 150 mm) column was employed for chromatographic separation. A triple quadrupole mass detector with electrospray ionization was used for detection, and multiple reaction monitoring was employed for quantification. The correlation coefficients (r²) were at least 0.999 for all eight nitrosamines. Limit of detection and limit of quantification values were determined as 0.05-0.8 ng/mL and 0.1-2.0 ng/mL, respectively. Validation results demonstrated satisfactory selectivity, accuracy, precision, and stability. The results demonstrated that the developed method is capable of reliably detecting potential nitrosamines present in pharmaceutical products at trace levels. This method contributes significantly to pharmaceutical safety and can serve as a valuable tool for future analyses.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"51-62"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of unknown oxidation degradation products of Rimegepant by HPLC and triple quadrupole mass spectrometry.","authors":"Narayana Reddy Godi, Sireesha Dodda, Nagavardhana Reddy Vanga, Kumarswamy Ummiti","doi":"10.1177/14690667251328804","DOIUrl":"10.1177/14690667251328804","url":null,"abstract":"<p><p>Rimegepant is a calcitonin gene-related peptide receptor antagonist that has been licensed for migraine headache treatment in the United States, the European Union, the United Kingdom, Hong Kong, Australia, and Kuwait. The oxidation stress study of the Rimegepant drug substance revealed the presence of five impurities. Rimegepant degraded by 5% under the selected oxidation conditions, meeting regulatory expectations. Four out of five impurities are enhanced by more than 1%. This research aims to characterize these oxidation degradation products utilizing the triple quadrupole mass spectroscopic technique. The Rimegepant oxidation degradation products were identified using an optimized chromatographic method that relies on reverse-phase HPLC with PDA detection. This technique utilized a Waters Xbridge C18 column with an eluent mixture of acetonitrile and 0.1% formic acid in water. The oxidation products of Rimegepant have been effectively separated, with a resolution above 3.0. Triple quadrupole mass spectrometry analysis characterized the five degradation products, which showed three N-oxide impurities with masses <i>m</i>/<i>z</i> 566, <i>m</i>/<i>z</i> 550, and <i>m</i>/<i>z</i> 548, as well as two hydrolysis products with masses, <i>m</i>/<i>z</i> 218, <i>m</i>/<i>z</i> 290. These new impurities deserve special attention because the drug's potency and related impurity levels determine any pharmaceutical medication product's quality, safety, and effectiveness.</p>","PeriodicalId":12007,"journal":{"name":"European Journal of Mass Spectrometry","volume":" ","pages":"38-50"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}