Journal of magnetic resonance最新文献

{"title":"Super-resolution NMR spectroscopy","authors":"Luca Wenchel ,&nbsp;Olivia Gampp ,&nbsp;Roland Riek","doi":"10.1016/j.jmr.2024.107746","DOIUrl":"10.1016/j.jmr.2024.107746","url":null,"abstract":"<div><p>Spectral resolution is one of the limiting factors in nuclear magnetic resonance (NMR) spectroscopy of biological systems where signal overlap often interferes with chemical shift assignment as well as dynamics and structure analysis. This problem can be addressed in part by using higher magnetic field NMR spectrometers operating at up to 1.2 GHz ¹H frequency to enhance the resolution proportionally with the field strength, and by deuteration in combination with transverse relaxation-optimized spectroscopy that reduces the transverse relaxation rate and proportionally the resonance linewidth of the peaks yielding higher spectral resolution. As a complement or alternative to these expensive and often insufficient approaches, we present here a generally applicable method to reduce the linewidth of peaks in indirect dimensions of multi-dimensional NMR spectra by increasing the number of scans per time increment exponentially as a function of time in order to compensate, in part, the decay of the signal caused by transverse relaxation. This enables to achieve a user-defined linewidth of the peaks without undue increase of the noise. Optimization by including in the number of scans also a cosine apodization function as well as processing spectra with an exponential-cosine window function in the direct dimension results typically in a resolution enhancement (linewidth reduction) by a factor of 1.5–2 in comparison to a standard measurement with a constant number of scans per time increment. This is comparable to the 2-fold resolution enhancement that can be obtained by going from a 600 MHz ¹H frequency NMR spectrometer to a 1.2 GHz instrument, or from 1.2 GHz to a spectrum measured hypothetically at 2.4 GHz ¹H frequency. A factor of two resolution enhancement causes thereby a signal to noise loss of a factor of three. The sensitivity gain by dynamic number of scan sampling is thereby ∼20 % over the use of a digital apodization function.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"366 ","pages":"Article 107746"},"PeriodicalIF":2.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1090780724001307/pdfft?md5=a4a8c026a704df7c0d6034901bc7234d&pid=1-s2.0-S1090780724001307-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of undersampling on preclinical lung T2* mapping with 3D radial UTE MRI at 7 T","authors":"Ian R. Stecker ,&nbsp;Abdullah S. Bdaiwi ,&nbsp;Peter J. Niedbalski ,&nbsp;Neelakshi Chatterjee ,&nbsp;Md M. Hossain ,&nbsp;Zackary I. Cleveland","doi":"10.1016/j.jmr.2024.107741","DOIUrl":"10.1016/j.jmr.2024.107741","url":null,"abstract":"<div><p>Lung diseases are almost invariably heterogeneous and progressive, making it imperative to capture temporally and spatially explicit information to understand the disease initiation and progression. Imaging the lung with MRI—particularly in the preclinical setting—has historically been challenging because of relatively low lung tissue density, rapid cardiac and respiratory motion, and rapid transverse (T₂*) relaxation. These limitations can largely be mitigated using ultrashort-echo-time (UTE) sequences, which are intrinsically robust to motion and avoid significant T₂* decay. A significant disadvantage of common radial UTE sequences is that they require inefficient, center-out k-space sampling, resulting in long acquisition times relative to conventional Cartesian sequences. Therefore, pulmonary images acquired with radial UTE are often undersampled to reduce acquisition time. However, undersampling reduces image SNR, introduces image artifacts, and degrades true image resolution. The level of undersampling is further increased if offline gating techniques like retrospective gating are employed, because only a portion (∼40–50%) of the data is used in the final image reconstruction. Here, we explore the impact of undersampling on SNR and T₂* mapping in mouse lung imaging using simulation and in-vivo data. Increased scatter in both metrics was noticeable at around 50% sampling. Parenchymal apparent SNR only decreased slightly (average decrease ∼ 1.4) with as little as 10% sampling. Apparent T₂* remained similar across undersampling levels, but it became significantly increased (p &lt; 0.05) below 80% sampling. These trends suggest that undersampling can generate quantifiable, but moderate changes in the apparent value of T₂*. Moreover, these approaches to assess the impact of undersampling are straightforward to implement and can readily be expanded to assess the quantitative impact of other MR acquisition and reconstruction parameters.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107741"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141838804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal Ions: I. Local interactions of the electron spin","authors":"Yu.E. Kandrashkin","doi":"10.1016/j.jmr.2024.107728","DOIUrl":"10.1016/j.jmr.2024.107728","url":null,"abstract":"<div><p>The anisotropic Zeeman interaction of an ion, and the strong hyperfine interaction with its own nucleus, can significantly influence its interactions with the local environment. These effects, including the reduction of the effective magnetic moment of the electron spin and the phase memory decay rate, are studied theoretically. Analytical expressions describing the mean magnetic moment of the electron spin are obtained. The results of the theoretical analysis and accompanying numerical computations show that the strong hyperfine interaction of the ion reduces its effective magnetic moment. In particular, a 7% reduction is found for the scandium endofullerene Sc₂@C₈₀(CH₂Ph) under conditions typical of an X-band EPR experiment.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107728"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Shot MRI in parahydrogen hyperpolarized samples","authors":"L. Buljubasich","doi":"10.1016/j.jmr.2024.107740","DOIUrl":"10.1016/j.jmr.2024.107740","url":null,"abstract":"<div><p>The site-specific signal enhancement provided by parahydrogen induced polarization (PHIP) may be combined with magnetic resonance imaging (MRI) to study chemical and biomolecular processes. However, imaging of hydrogen nuclei (<span><math><msup><mrow></mrow><mrow><mn>1</mn></mrow></msup></math></span>H) is hampered by background signals arising from the presence of thermally polarized nuclei. Additionally, fast imaging sequences are commonly based on multiple radio-frequency pulses, where the signals resulting from PHIP oscillate due to the evolution with a <span><math><mi>J</mi></math></span>-coupling Hamiltonian. In this article, an innovative imaging scheme for single-scan MRI is presented that effectively detects hyperpolarized components while simultaneously canceling out thermal contributions. This method is based on the quenching of inherent oscillations of PHIP-originated signals due to <span><math><mi>J</mi></math></span>-couplings during the multipulse sequence and the suppression of thermal signals by spin dynamics and a tailored restructuring of the <span><math><mi>k</mi></math></span>-space. A series of numerical simulations on specific two- and three-spin systems serve to support the feasibility of the approach. Furthermore, this theoretical study demonstrates the potential of combining hyperpolarization and long-lived states (PHIP and LLS) in the selected molecules, which could be seen as a preliminary step towards the development of fast imaging techniques, for example in the field of biomolecular research.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107740"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential of water channels for developing genetically encoded reporters and biosensors for diffusion-weighted MRI","authors":"Asish N. Chacko ,&nbsp;Austin D.C. Miller ,&nbsp;Kaamini M. Dhanabalan ,&nbsp;Arnab Mukherjee","doi":"10.1016/j.jmr.2024.107743","DOIUrl":"10.1016/j.jmr.2024.107743","url":null,"abstract":"<div><p>Genetically encoded reporters for magnetic resonance imaging (MRI) offer a valuable technology for making molecular-scale measurements of biological processes within living organisms with high anatomical resolution and whole-organ coverage without relying on ionizing radiation. However, most MRI reporters rely on synthetic contrast agents, typically paramagnetic metals and metal complexes, which often need to be supplemented exogenously to create optimal contrast. To eliminate the need for synthetic contrast agents, we previously introduced aquaporin-1, a mammalian water channel, as a new reporter gene for the fully autonomous detection of genetically labeled cells using diffusion-weighted MRI. In this study, we aimed to expand the toolbox of diffusion-based genetic reporters by modulating aquaporin membrane trafficking and harnessing the evolutionary diversity of water channels across species. We identified a number of new water channels that functioned as diffusion-weighted reporter genes. In addition, we show that loss-of-function variants of yeast and human aquaporins can be leveraged to design first-in-class diffusion-based sensors for detecting the activity of a model protease within living cells.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107743"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1090780724001277/pdfft?md5=e871041d5317f3019b5d00b1c5657e72&pid=1-s2.0-S1090780724001277-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of dielectric properties and their impact on MAS-DNP NMR applications","authors":"Faith J. Scott ,&nbsp;Thierry Dubroca ,&nbsp;Robert W. Schurko ,&nbsp;Stephen Hill ,&nbsp;Joanna R. Long ,&nbsp;Frédéric Mentink-Vigier","doi":"10.1016/j.jmr.2024.107742","DOIUrl":"10.1016/j.jmr.2024.107742","url":null,"abstract":"<div><p>The dielectric properties of materials play a crucial role in the propagation and absorption of microwave beams employed in Magic Angle Spinning − Dynamic Nuclear Polarization (MAS-DNP) NMR experiments. Despite ongoing optimization efforts in sample preparation, routine MAS-DNP NMR applications often fall short of theoretical sensitivity limits. Offering a different perspective, we report the refractive indices and extinction coefficients of diverse materials used in MAS-DNP NMR experiments, spanning a frequency range from 70 to 960 GHz. Knowledge of their dielectric properties enables the accurate simulation of electron nutation frequencies, thereby guiding the design of more efficient hardware and sample preparation of biological or material samples. This is illustrated experimentally for four different rotor materials (sapphire, yttria-stabilized zirconia (YSZ), aluminum nitride (AlN), and SiAlON ceramics) used for DNP at 395 GHz/¹H 600 MHz. Finally, electromagnetic simulations and state-of-the-art MAS-DNP numerical simulations provide a rational explanation for the observed magnetic field dependence of the enhancement when using nitroxide biradicals, offering insights that will improve MAS-DNP NMR at high magnetic fields.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107742"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Field-domain rapid-scan EPR at 240 GHz for studies of protein functional dynamics at room temperature","authors":"Brad D. Price ,&nbsp;Antonín Sojka ,&nbsp;Shiny Maity ,&nbsp;I. Marcelo Chavez ,&nbsp;Matthieu Starck ,&nbsp;Maxwell Z. Wilson ,&nbsp;Songi Han ,&nbsp;Mark S. Sherwin","doi":"10.1016/j.jmr.2024.107744","DOIUrl":"10.1016/j.jmr.2024.107744","url":null,"abstract":"<div><p>We present field-domain rapid-scan (RS) electron paramagnetic resonance (EPR) at 8.6<!--> <!-->T and 240<!--> <!-->GHz. To enable this technique, we upgraded a home-built EPR spectrometer with an FPGA-enabled digitizer and real-time processing software. The software leverages the Hilbert transform to recover the in-phase (<span><math><mi>I</mi></math></span>) and quadrature (<span><math><mi>Q</mi></math></span>) channels, and therefore the raw absorptive and dispersive signals, <span><math><msup><mrow><mi>χ</mi></mrow><mrow><mo>′</mo></mrow></msup></math></span> and <span><math><msup><mrow><mi>χ</mi></mrow><mrow><mo>′</mo><mo>′</mo></mrow></msup></math></span>, from their combined magnitude (<span><math><msqrt><mrow><msup><mrow><mi>I</mi></mrow><mrow><mn>2</mn></mrow></msup><mo>+</mo><msup><mrow><mi>Q</mi></mrow><mrow><mn>2</mn></mrow></msup></mrow></msqrt></math></span>). Averaging a magnitude is simpler than real-time coherent averaging and has the added benefit of permitting long-timescale signal averaging (up to at least <span><math><mrow><mn>2</mn><mo>.</mo><mn>5</mn><mo>×</mo><mn>1</mn><msup><mrow><mn>0</mn></mrow><mrow><mn>6</mn></mrow></msup></mrow></math></span> scans) because it eliminates the effects of source-receiver phase drift. Our rapid-scan (RS) EPR provides a signal-to-noise ratio that is approximately twice that of continuous wave (CW) EPR under the same experimental conditions, after scaling by the square root of acquisition time. We apply our RS EPR as an extension of the recently reported time-resolved Gd-Gd EPR (TiGGER) [Maity et al., 2023], which is able to monitor inter-residue distance changes during the photocycle of a photoresponsive protein through changes in the Gd-Gd dipolar couplings. RS, opposed to CW, returns field-swept spectra as a function of time with 10<!--> <!-->ms time resolution, and thus, adds a second dimension to the static field transients recorded by TiGGER. We were able to use RS TiGGER to track time-dependent and temperature-dependent kinetics of AsLOV2, a light-activated phototropin domain found in oats. The results presented here combine the benefits of RS EPR with the improved spectral resolution and sensitivity of Gd chelates at high magnetic fields. In the future, field-domain RS EPR at high magnetic fields may enable studies of other real-time kinetic processes with time resolutions that are otherwise difficult to access in the solution state.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"366 ","pages":"Article 107744"},"PeriodicalIF":2.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1090780724001289/pdfft?md5=f06bb2dfd5a7dd417b03580fd438e9ff&pid=1-s2.0-S1090780724001289-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal ions: II. Super-hyperfine interactions with surrounding nuclei","authors":"Yu. E. Kandrashkin","doi":"10.1016/j.jmr.2024.107732","DOIUrl":"10.1016/j.jmr.2024.107732","url":null,"abstract":"<div><p>The anisotropic Zeeman and strong hyperfine interactions of a Kramers ion can significantly affect its magnetic properties as well as the interactions with the nearby nuclei. The interactions with the local environment are described in the preceding article. In the current work, the change of the spin states of distant nuclei is studied. Analytical expressions describing the depth of the electron spin echo envelope modulation (ESEEM) are obtained for the ions with anisotropic Zeeman and strong hyperfine interactions. Due to the g-tensor anisotropy, the electron Zeeman interaction axis is tilted in respect to the direction of the external magnetic field which makes non-collinear with the Zeeman interaction axes of the ion and the nearby nuclei and significantly modifies the nuclear spin states. Thus, the isotropic hyperfine interaction, and particularly the Fermi contact interaction can directly contribute to the ESEEM. An additional factor, that can significantly modify the ESEEM signal is the mixing of the multiple oscillations arising when several nuclei occur in optimal conditions for the generation of the nuclear coherence. This situation arises when several EPR transitions of the ion covering a wide range of magnetic fields are examined.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107732"},"PeriodicalIF":2.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal Ions: III. Analysis of the local interactions in a single crystal of 173Yb3+ doped Y5SiO5","authors":"Yu.E. Kandrashkin","doi":"10.1016/j.jmr.2024.107731","DOIUrl":"10.1016/j.jmr.2024.107731","url":null,"abstract":"<div><p>The electron spin echo envelope modulation (ESEEM) technique is a direct method to probe the nuclear spin coherences induced by electron spin transitions. Recently, this approach was used to study an isotopically pure Y₂SiO₅ crystal doped with ¹⁷³Yb³⁺ ions, and the presence of the Fermi contact interaction was proposed to explain the frequency comb detected in the two-pulse ESEEM experiment [Solovarov N. K. et al. <em>JETP Letters</em> 115 (6): 362–67]. Here we simulate the Fourier images of the ESEEM data. The numerical analysis shows that the modulation is mainly due to the nuclear spin coherences induced by the dipole–dipole interactions. However, the correlation between the experimental and simulated data is better when the super-hyperfine interactions of the nearby yttrium nuclei have an additional isotropic contribution. The analysis of the rescaled X-band ESEEM spectra shows that for the EPR transitions at magnetic fields &gt; 100 mT, the main contribution to the modulation comes from the oscillations of the individual nuclei and the effect of interference between coherences originating from several nuclei is not strong. Further experiments to distinguish the sources of the echo modulation are discussed.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107731"},"PeriodicalIF":2.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141602378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective correlations between aliphatic 13C nuclei in protein solid-state NMR","authors":"Hang Xiao ,&nbsp;Weijing Zhao ,&nbsp;Yan Zhang ,&nbsp;Huimin Kang ,&nbsp;Zhengfeng Zhang ,&nbsp;Jun Yang","doi":"10.1016/j.jmr.2024.107730","DOIUrl":"10.1016/j.jmr.2024.107730","url":null,"abstract":"<div><p>Solid-state nuclear magnetic resonance (NMR) is a potent tool for studying the structures and dynamics of insoluble proteins. It starts with signal assignment through multi-dimensional correlation experiments, where the aliphatic ¹³Cα-¹³Cβ correlation is indispensable for identifying specific residues. However, developing efficient methods for achieving this correlation is a challenge in solid-state NMR. We present a simple band-selective zero-quantum (ZQ) recoupling method, named POST-C4₁₆¹ (PC4), which enhances ¹³Cα-¹³Cβ correlations under moderate magic-angle spinning (MAS) conditions. PC4 requires minimal ¹³C radio-frequency (RF) field and proton decoupling, exhibits high stability against RF variations, and achieves superior efficiency. Comparative tests on various samples, including the formyl-Met-Leu-Phe (fMLF) tripeptide, microcrystalline β1 immunoglobulin binding domain of protein G (GB1), and membrane protein of mechanosensitive channel of large conductance from <em>Methanosarcina acetivorans</em> (MaMscL), demonstrate that PC4 selectively enhances ¹³Cα-¹³Cβ correlations by up to 50 % while suppressing unwanted correlations, as compared to the popular dipolar-assisted rotational resonance (DARR). It has addressed the long-standing need for selective ¹³C–¹³C correlation methods. We anticipate that this simple but efficient PC4 method will have immediate applications in structural biology by solid-state NMR.</p></div>","PeriodicalId":16267,"journal":{"name":"Journal of magnetic resonance","volume":"365 ","pages":"Article 107730"},"PeriodicalIF":2.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}