Journal of Magnetic Resonance Open最新文献

{"title":"Hyperpolarized 13C NMR for longitudinal in-cell metabolism using a mobile 3D cell culture system","authors":"T.B.W. Mathiassen ,&nbsp;A.E. Høgh ,&nbsp;M. Karlsson ,&nbsp;S. Katsikis ,&nbsp;K. Wang ,&nbsp;M. Pennestri ,&nbsp;J.H. Ardenkjær-Larsen ,&nbsp;P.R. Jensen","doi":"10.1016/j.jmro.2023.100131","DOIUrl":"10.1016/j.jmro.2023.100131","url":null,"abstract":"<div><p>Hyperpolarization with the dissolution dynamic nuclear polarization (dDNP) technique yields &gt; 10,000-fold signal increases for NMR-active nuclei (e.g. ¹³C). Hyperpolarized ¹³C-labeled metabolic tracer molecules thus allow real-time observations of biochemical pathways in living cellular systems without interfering background. This methodology lends itself to the direct observation of altered intracellular reaction chemistry imparted for instance by drug treatment, infections, or other diseases. A reoccurring challenge for longitudinal cell studies of mammalian cells with NMR and dDNP-NMR is maintaining cell viability in the NMR spectrometer. 3D cell culture methods are increasing in popularity because they provide a physiologically more relevant environment compared to 2D cell cultures. Based on such strategies a mobile 3D culture system was devised. The clinical drug etoposide was used to treat cancer cells (HeLa) and the resulting altered metabolism was measured using hyperpolarized [1–¹³C]pyruvate. We show that sustaining the cell cultivation in cell incubators and only transferring the cells to the NMR spectrometer for the few minutes required for the dDNP-NMR measurements is an attractive alternative to cell maintenance in the NMR tube. High cell viability is sustained, and experimental throughput is many doubled.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100131"},"PeriodicalIF":2.624,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666441023000390/pdfft?md5=1fb698b32491f80f5153bc638f0b5899&pid=1-s2.0-S2666441023000390-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86035083","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 brisk walk through the fields of relaxation, saturation, and exchange: From solid state NMR to in-vivo imaging","authors":"Elena Vinogradov","doi":"10.1016/j.jmro.2023.100130","DOIUrl":"10.1016/j.jmro.2023.100130","url":null,"abstract":"<div><p>Novel MRI contrast methods, such as Chemical Exchange Saturation Transfer (CEST), rely on previously developed theory and approaches, often introduced first in solidstate NMR. Understanding or at least connecting the basic principles and original works to the modern-day contrast methods in MRI is instructive. The work brings together concepts in relaxation, saturation, and spin lock experiments in the dynamic (exchanging) systems. The work describes how basic principles and theory are translated and being applied to MRI contrast, including MT and CEST. Finally, we review select papers generalizing concepts of relaxation under periodic RF.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100130"},"PeriodicalIF":2.624,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666441023000389/pdfft?md5=5cac507629ee325b6dadfb0d3027b863&pid=1-s2.0-S2666441023000389-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80779800","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":"Analytical descriptions of (multiple-contact) cross-polarization dynamics and spin-lattice relaxation in solid alanine","authors":"Jérôme Hirschinger,&nbsp;Jésus Raya","doi":"10.1016/j.jmro.2023.100128","DOIUrl":"10.1016/j.jmro.2023.100128","url":null,"abstract":"<div><p>In this work, several exact and approximate analytical solutions to the quantum master equation are derived using both classical and non-classical coupling models to describe the kinetics of Hartmann-Hahn cross-polarization (HHCP) and multiple-contact CP (MC<img>CP). Moreover, the analytical solution originally obtained by Naito and McDowell [J. Chem. Phys. 84 (1986) 4181.] is shown to be incorrect and the different regimes of spin diffusion and <span><math><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi></mrow></msub></math></span> relaxation are characterized by the amplitude of the second stage of the HHCP dynamics and the HHCP/MC<img>CP crossing time. The analysis of the ¹H–¹³C HHCP and MC<img>CP dynamics together with (Lee-Goldburg) ¹H <span><math><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi></mrow></msub></math></span> relaxation experimental data provides a consistent picture of spin dynamics in solid alanine and explains the apparent discrepancies previously observed between <span><math><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi></mrow></msub></math></span> and <span><math><msub><mi>T</mi><mn>1</mn></msub></math></span> relaxation measurements. The CH and CH₃ protons relax as expected <em>via</em> spin diffusion towards the NH₃ protons but the assumption of common proton spin temperature, in which the bottleneck of relaxation is at the NH₃ sites, generally valid for <span><math><msub><mi>T</mi><mn>1</mn></msub></math></span> relaxation breaks down for <span><math><msub><mi>T</mi><mrow><mn>1</mn><mi>ρ</mi></mrow></msub></math></span> relaxation. A diffusion-limited situation in which nuclear Zeeman energy is transferred to the lattice faster than can be supplied by spin diffusion is observed instead.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100128"},"PeriodicalIF":2.624,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666441023000365/pdfft?md5=8634b4f0bfee2e20f4a4370925e073c3&pid=1-s2.0-S2666441023000365-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78948571","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":"Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1–13C]pyruvate in vivo","authors":"Keilian MacCulloch ,&nbsp;Austin Browning ,&nbsp;David O. Guarin Bedoya ,&nbsp;Stephen J. McBride ,&nbsp;Mustapha B. Abdulmojeed ,&nbsp;Carlos Dedesma ,&nbsp;Boyd M. Goodson ,&nbsp;Matthew S. Rosen ,&nbsp;Eduard Y. Chekmenev ,&nbsp;Yi-Fen Yen ,&nbsp;Patrick TomHon ,&nbsp;Thomas Theis","doi":"10.1016/j.jmro.2023.100129","DOIUrl":"https://doi.org/10.1016/j.jmro.2023.100129","url":null,"abstract":"<div><p>Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, <em>in vivo</em> detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected <em>in vivo</em>, specifically using hyperpolarized [1–¹³C]pyruvate. Biocompatible formulations of hyperpolarized [1–¹³C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected <em>in vivo</em>. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100129"},"PeriodicalIF":2.624,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3266171","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":"CPMAS NMR platform for direct compositional analysis of mycobacterial cell-wall complexes and whole cells","authors":"Xinyu Liu ,&nbsp;Jasna Brčić ,&nbsp;Gail H. Cassell ,&nbsp;Lynette Cegelski","doi":"10.1016/j.jmro.2023.100127","DOIUrl":"10.1016/j.jmro.2023.100127","url":null,"abstract":"<div><p>Tuberculosis and non-tuberculosis mycobacterial infections are rising each year and often result in chronic incurable disease. Important antibiotics target cell-wall biosynthesis, yet some mycobacteria are alarmingly resistant or tolerant to currently available antibiotics. This resistance is often attributed to assumed differences in composition of the complex cell wall of different mycobacterial strains and species. However, due to the highly crosslinked and insoluble nature of mycobacterial cell walls, direct comparative determinations of cell-wall composition pose a challenge to analysis through conventional biochemical analyses. We introduce an approach to directly observe the chemical composition of mycobacterial cell walls using solid-state NMR spectroscopy. ¹³C CPMAS spectra are provided of individual components (peptidoglycan, arabinogalactan, and mycolic acids) and of <em>in situ</em> cell-wall complexes. We assigned the spectroscopic contributions of each component in the cell-wall spectrum. We uncovered a higher arabinogalactan-to-peptidoglycan ratio in the cell wall of <em>M. abscessus</em>, an organism noted for its antibiotic resistance, relative to <em>M. smegmatis</em>. Furthermore, differentiating influences of different types of cell-wall targeting antibiotics were observed in spectra of antibiotic-treated whole cells. This platform will be of value in evaluating cell-wall composition and antibiotic activity among different mycobacteria and in considering the most effective combination treatment regimens.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100127"},"PeriodicalIF":2.624,"publicationDate":"2023-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666441023000353/pdfft?md5=b8e77d4be33bc168b0286ba8cff3b61a&pid=1-s2.0-S2666441023000353-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85315161","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":"Affordable amino acid α/β-deuteration and specific labeling for NMR signal enhancement: Evaluation on the kinase p38α","authors":"Rania Ghouil ,&nbsp;Chafiaa Bouguechtouli ,&nbsp;Hélène Chérot ,&nbsp;Agathe Marcelot ,&nbsp;Maxime Roche ,&nbsp;Francois-Xavier Theillet","doi":"10.1016/j.jmro.2023.100126","DOIUrl":"https://doi.org/10.1016/j.jmro.2023.100126","url":null,"abstract":"<div><p>Although very effective in decreasing NMR relaxation of large proteins, homogeneous deuteration can be costly, and anyway unsuitable for recombinant production in metazoan systems. We sought to explore other deuteration schemes, which would be adapted to protein expression in mammalian cells. Here, we evaluate the benefits of the deuteration on alpha- and beta-positions of amino acids for a typical middle size protein domain, namely the model 40 kDa-large kinase p38α. We report the position-specific deuteration of free amino acids by using enzyme-assisted H/D exchange, executed by the cystathionine gamma-synthase and a newly designed high-performance mutant E325A. Then, we used cell-free expression in bacterial extracts to avoid any scrambling and back-protonation of the tested isotopically labelled amino acids (Ala, Leu, Lys, Ser, Asp, Glu, Gly). Our results show signal enhancements up to three in ¹H-¹⁵N spectra when these α/β-deuterated amino acids are integrated. Because our approach relies on single ²H_α/β-¹⁵N-amino acid labeling, an additional three-fold increase in sensitivity is obtained by the possible use of moderate resolution SOFAST-HMQC instead of the classical HSQC or TROSY experiments. This allows recording residue-resolved solution ¹H-¹⁵N NMR spectra of 100 μg of p38α in one hour with S/N∼10.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100126"},"PeriodicalIF":2.624,"publicationDate":"2023-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1826370","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":"A primer to polarizing agent design: Quantum mechanical understanding of cross effect magic-angle spinning Dynamic Nuclear Polarization","authors":"Lydia Gkoura ,&nbsp;Asif Equbal","doi":"10.1016/j.jmro.2023.100125","DOIUrl":"10.1016/j.jmro.2023.100125","url":null,"abstract":"<div><p>Dynamic Nuclear Polarization (DNP) is transforming the landscape of solid-state characterization for both biological solids and functional materials. By transferring electron spin polarization to coupled nuclear spins under microwave irradiation, DNP increases NMR sensitivity by several orders of magnitude. However, the mechanism of DNP transfer and its efficiency under magic-angle spinning (MAS) significantly differs from that under static conditions. This primer article provides a comprehensive and pedagogical explanation of the theoretical aspects of MAS-DNP, with a specific focus on the cross-effect mechanism. A clear understanding of the nuances of MAS-DNP is crucial for improving its efficiency and extending its application to high magnetic fields and fast MAS conditions. To this end, the article proposes a guideline for synthetic chemists to develop DNP polarizing agents under these experimental conditions.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100125"},"PeriodicalIF":2.624,"publicationDate":"2023-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266644102300033X/pdfft?md5=04fd482932dc3eae839d2bc3109ace6b&pid=1-s2.0-S266644102300033X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86288119","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":"Modelling of T1 dispersion effects on fluid polarization in oil flow","authors":"Rutger R. Tromp,&nbsp;Leo Pel,&nbsp;David M.J. Smeulders","doi":"10.1016/j.jmro.2023.100124","DOIUrl":"https://doi.org/10.1016/j.jmro.2023.100124","url":null,"abstract":"<div><p>In this article we use numerical simulations to study the effect of <em>T</em>₁ dispersion on fluid polarization buildup in oil flow to characterize the sensitivity of both a conventional NMR concept (ROI located inside the polarization magnet) and a Earth's field NMR concept (ROI outside and downstream of the polarization magnet) to <em>T</em>₁ dispersion of flowing samples. As a polarization field in both concepts we use a 90 cm long Halbach magnet. The <em>T</em>₁ dispersion behavior of the oils is based on a set of crude oils that span a viscosity range of 0.7 cP up to 2·10⁴ cP and <em>T</em>₁ relaxation measurements for Larmor frequencies between 10 kHz and 20 MHz. Numerical simulations based on solving the Bloch-Torrey equation for the longitudinal magnetization component show that fluid polarization levels in a ROI of a Earth's field NMR system concept are much more strongly affected by <em>T</em>₁ dispersion than in the conventional NMR system concept. As a result, we may conclude that the Earth's field NMR system design is less robust for measuring flowing samples that show strong <em>T</em>₁ dispersion behavior. In comparison, the conventional NMR system design is relatively insensitive to the effect of <em>T</em>₁ dispersion, as <em>T</em>₁ dispersion effects were found to form a relatively small correction to the magnetization buildup. The conventional NMR system design consequently is the preferred implementation of a NMR system that operates on fluids with strong <em>T</em>₁ dispersion behavior. We show that in the presence of <em>T</em>₁ dispersion <em>s</em> = <em>vT</em>₁(0)/<em>L_m*</em> may be used as a governing parameter for fluid polarization buildup, where <em>T</em>₁(0) is the <em>T</em>₁ relaxation time in the center of the polarization magnet, and we show how an modified analytical uniform field model can be used to describe fluid polarization for a uniform flow velocity distribution in the presence of <em>T</em>₁ dispersion with an accuracy within 1% for the samples and field distribution considered in this study at industrially relevant flow velocities.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100124"},"PeriodicalIF":2.624,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3451238","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":"Background removal from rapid-scan EPR spectra of nitroxide-based spin labels by minimizing non-quadratic cost functions","authors":"Florian Johannsen,&nbsp;Malte Drescher","doi":"10.1016/j.jmro.2023.100121","DOIUrl":"https://doi.org/10.1016/j.jmro.2023.100121","url":null,"abstract":"<div><p>Rapid-scan electron paramagnetic resonance spectroscopy is an emerging technique which substantially improves the signal-to-noise ratio and time resolution compared to conventional continuous-wave experiments. This allows the investigation of spin-labeled biomolecules and their structural dynamics on much shorter time scales than usually accessible. The EPR spectrum however is superimposed by a strong background that is caused by microphonic effects of the alternating magnetic field. This article discusses the use of non-quadratic cost functions for background removal of rapid-scan spectra. The method is validated for the most prominent type of spin-probes in the field of biochemistry: the nitroxide spin-label.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"16 ","pages":"Article 100121"},"PeriodicalIF":2.624,"publicationDate":"2023-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1826466","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":"Steady-State Free Precession sequences for high and low field NMR spectroscopy in solution: Challenges and opportunities","authors":"Tiago Bueno Moraes ,&nbsp;Flávio Vinícius Crizóstomo Kock ,&nbsp;Kahlil Schwanka Salome ,&nbsp;Andersson Barison ,&nbsp;Andre Simpson ,&nbsp;Luiz Alberto Colnago","doi":"10.1016/j.jmro.2022.100090","DOIUrl":"https://doi.org/10.1016/j.jmro.2022.100090","url":null,"abstract":"<div><p>The receptivity of NMR spectroscopy is low when compared to other techniques. Historically, increasing the strength of the static magnetic field has been the major approach to increase NMR sensitivity. In recent years several polarization transfer protocols have been used to enhance the signal-to-noise ratio (SNR), although they require special accessories and/or sample preparation. In this paper, we consider both the challenges and opportunities of steady-state free precession (SSFP) pulse sequences as a simple and efficient alternative to enhance SNR, in standard high-resolution and benchtop low-resolution NMR spectrometers. The maximum gain in these sequences is obtained with the shortest time between the pulses (Tp). However, when Tp&lt;T₂, the SSFP signal contains FID and echo components which lead to phase, intensity, and truncation artifacts on spectra obtained by Fast Fourier transform (FT). Several phase alternation SSFP sequences were used to cancel the echo component and minimize these problems in the FT spectra. Krylov base diagonalization method (KBDM) was used to eliminate the phase and truncation problems in spectra acquired by SSFP pulse sequences and can be a viable alternative to FT. The experiments were performed in high and low resolution (bench top) NMR spectrometers and significant enhancements in SNR of low receptivity nuclei such as ¹³C and ¹⁵N could be achieved. The SSFP sequences were also shown to enhance SNR in nuclei with high receptivity such as ¹⁹F and ³¹P, in very dilute samples, as is common in environmental and biological samples.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":"14 ","pages":"Article 100090"},"PeriodicalIF":2.624,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1826375","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}