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CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity. A subset of patients treated with chimeric antigen receptor (CAR) T cells or bispecific T cell engager (BiTE) antibodies display severe neurotoxicity, including fatal cerebral edema associated with T cell infiltration into the brain. Here, we report that mural cells, which surround the endothelium and are critical for blood-brain-barrier integrity, express CD19. We identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm perivascular staining at the protein level. CD19 expression in the brain begins early in development alongside the emergence of mural cell lineages and persists throughout adulthood across brain regions. Mouse mural cells demonstrate lower levels of Cd19 expression, suggesting limitations in preclinical animal models of neurotoxicity. These data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.
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Barreira Hematoencefálica/metabolismo , Células Epiteliais/metabolismo , Imunoterapia Adotiva/efeitos adversos , Animais , Anticorpos Biespecíficos/imunologia , Antígenos CD19/imunologia , Linfócitos B/imunologia , Barreira Hematoencefálica/imunologia , Encéfalo/imunologia , Encéfalo/metabolismo , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia Adotiva/métodos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Músculo Liso Vascular/metabolismo , Neoplasias , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Análise de Célula Única/métodos , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The ability to directly monitor the states of electrons in modern field-effect devices-for example, imaging local changes in the electrical potential, Fermi level and band structure as a gate voltage is applied-could transform our understanding of the physics and function of a device. Here we show that micrometre-scale, angle-resolved photoemission spectroscopy1-3 (microARPES) applied to two-dimensional van der Waals heterostructures4 affords this ability. In two-terminal graphene devices, we observe a shift of the Fermi level across the Dirac point, with no detectable change in the dispersion, as a gate voltage is applied. In two-dimensional semiconductor devices, we see the conduction-band edge appear as electrons accumulate, thereby firmly establishing the energy and momentum of the edge. In the case of monolayer tungsten diselenide, we observe that the bandgap is renormalized downwards by several hundreds of millielectronvolts-approaching the exciton energy-as the electrostatic doping increases. Both optical spectroscopy and microARPES can be carried out on a single device, allowing definitive studies of the relationship between gate-controlled electronic and optical properties. The technique provides a powerful way to study not only fundamental semiconductor physics, but also intriguing phenomena such as topological transitions5 and many-body spectral reconstructions under electrical control.
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Stacking monolayer semiconductors creates moiré patterns, leading to correlated and topological electronic phenomena, but measurements of the electronic structure underpinning these phenomena are scarce. Here, we investigate the properties of the conduction band in moiré heterobilayers of WS2/WSe2 using submicrometer angle-resolved photoemission spectroscopy with electrostatic gating. We find that at all twist angles the conduction band edge is the K-point valley of the WS2, with a band gap of 1.58 ± 0.03 eV. From the resolved conduction band dispersion, we deduce an effective mass of 0.15 ± 0.02 me. Additionally, we observe replicas of the conduction band displaced by reciprocal lattice vectors of the moiré superlattice. We argue that the replicas result from the moiré potential modifying the conduction band states rather than final-state diffraction. Interestingly, the replicas display an intensity pattern with reduced 3-fold symmetry, which we show implicates the pseudo vector potential associated with in-plane strain in moiré band formation.
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PURPOSE: Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit ( B 1 + $$ {\mathrm{B}}_1^{+} $$ ) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome. Novel hardware methods such as dielectric pads have been shown to improve the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity but are currently limited in their corrective effect by the range of high-permittivity materials available and have a fixed shelf life. In this work, an optimized metasurface design is presented that demonstrates in vivo enhancement of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field. METHODS: A prototype metasurface was optimized by an empirical capacitor sweep and by varying the period size. Phantom temperature experiments were performed to evaluate potential metasurface heating effects during scanning. Lastly, in vivo gradient echo images and B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were acquired on five healthy subjects on a 7 T system. Dielectric pads were also used as a comparison throughout the work as a standard comparison. RESULTS: The metasurfaces presented here enhanced the average relative SNR of the gradient echo images by a factor of 2.26 compared to the dielectric pads factor of 1.61. Average B 1 + $$ {\mathrm{B}}_1^{+} $$ values reflected a similar enhancement of 27.6% with the metasurfaces present versus 8.9% with the dielectric pads. CONCLUSION: The results demonstrate that metasurfaces provide superior performance to dielectric padding as shown by B 1 + $$ {\mathrm{B}}_1^{+} $$ maps reflecting their direct effects and resulting enhancements in image SNR at 7 T.
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Desenho de Equipamento , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Imageamento por Ressonância Magnética/instrumentação , Humanos , Perna (Membro)/diagnóstico por imagem , Adulto , Aumento da Imagem/métodos , Feminino , Masculino , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Razão Sinal-RuídoRESUMO
PURPOSE: The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD+) levels in the human brain in vivo by means of downfield proton MRS (DF 1H MRS). METHODS: DF 1H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally selective excitation and spatially selective localization to determine cerebral NAD+ levels on two back-to-back days: once after an overnight fast (baseline) and once 4 h after oral ingestion of nicotinamide riboside (900 mg). Additionally, two more baseline scans were performed following the same paradigm to assess test-retest reliability of the NAD+ levels in the absence of NR. RESULTS: NR supplementation increased mean NAD+ concentration compared to the baseline (0.458 ± 0.053 vs. 0.392 ± 0.058 mM; p < 0.001). The additional two baseline scans demonstrated no differences in mean NAD+ concentrations (0.425 ± 0.118 vs. 0.405 ± 0.082 mM; p = 0.45), and no difference from the first baseline scan (F(2, 16) = 0.907; p = 0.424). CONCLUSION: These preliminary results confirm that acute NR supplementation increases cerebral NAD+ levels in healthy human volunteers and shows the promise of DF 1H MRS utility for robust detection of NAD+ in humans in vivo.
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Encéfalo , Suplementos Nutricionais , NAD , Niacinamida , Compostos de Piridínio , Humanos , Niacinamida/análogos & derivados , NAD/metabolismo , Masculino , Compostos de Piridínio/farmacocinética , Adulto , Feminino , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Reprodutibilidade dos Testes , Adulto Jovem , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância MagnéticaRESUMO
PURPOSE: In vivo quantification of lactate has numerous applications in studying the pathology of both cerebral and musculoskeletal systems. Due to its low concentration (~0.5-1 mM), and overlap with lipid signals, traditional 1H MR spectra acquired in vivo using a small voxel and short echo time often result in an inadequate signal to detect and resolve the lactate peak, especially in healthy human volunteers. METHODS: In this study, using a semi-LASER acquisition with long echo time (TE = 288 ms) and large voxel size (80 × 70 × 20 mm3), we clearly visualize the combined signal of lactate and threonine. Therefore, we call the signal at 1.33 ppm Lac+ and quantify Lac+ concentration from water suppressed spectra in healthy human brains in vivo. Four participants (22-37 years old; mean age = 28 ± 5.4; three male, one female) were scanned on four separate days, and on each day four measurements were taken. Intra-day values are calculated for each participant by comparing the four measurements on a single day. Inter-day values were calculated using the mean intra-day measurements. RESULTS: The mean intra-participant Lac+ concentration, standard deviation (SD), and coefficient of variation (CV) ranged from 0.49 to 0.61 mM, 0.02 to 0.07 mM, and 4% to 13%, respectively, across four volunteers. The inter-participant Lac+ concentration, SD, and CV was 0.53 mM, ±0.06 mM, and 11%. CONCLUSION: Repeatability is shown in Lac+ measurement in healthy human brain using a long echo time semi-LASER sequence with a large voxel in about 3.5 min at 3 T.
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Encéfalo , Ácido Láctico , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Reprodutibilidade dos Testes , Ácido Láctico/metabolismo , Ácido Láctico/análise , Espectroscopia de Ressonância Magnética/métodosRESUMO
BACKGROUND: Skeletal muscle mitochondrial oxidative phosphorylation (mtOXPHOS) is important for ATP generation and its dysfunction leads to exercise intolerance. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a useful, noninvasive technique for mtOXPHOS assessment but has limitations. Creatine-weighted chemical exchange saturation transfer (CrCEST) MRI is a potential alternative to assess muscle bioenergetics. PURPOSE: To evaluate the interscan repeatability, intra- and interobserver reproducibility of CrCEST during mild plantar flexion exercise. STUDY TYPE: Retrospective. SUBJECTS: Twenty healthy volunteers (age 37.6 ± 12.4 years, 11 females). FIELD STRENGTH/SEQUENCE: 3 T/CEST imaging using gradient echo readout. ASSESSMENT: τCrCEST (postexercise Cr recovery time) was assessed in two scans for each participant, following mild plantar flexion exercises targeting the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles. Three observers measured τCrCEST for interobserver reproducibility. Three readings by one observer were used to measure intraobserver reproducibility. Two scans were used for within-participant interscan repeatability. STATISTICAL TESTS: Paired t tests, intraclass correlation coefficient (ICC), and Pearson correlation were conducted. Bland-Altman plots were used to analyze the interobserver variability. A P-value of 0.05 was considered statistically significant. RESULTS: There was excellent intra- (ICC ∈ 0.94 - 0.98 $$ \in \left[0.94-0.98\right] $$ ) and interobserver (ICC ∈ 0.9 - 0.98 $$ \in \left[0.9-0.98\right] $$ ) reproducibility, with moderate interscan repeatability for τCrCEST in LG and MG (ICC ∈ 0.54 - 0.74 $$ \in \left[0.54-0.74\right] $$ ) and poor-to-moderate interscan repeatability in Sol (ICC ∈ 0.24 - 0.53 $$ \in \left[0.24-0.53\right] $$ ). Excellent interobserver reproducibility was confirmed by Bland-Altman plots (fixed bias P-value ∈ 0.08 - 0.87 $$ \in \left[0.08-0.87\right] $$ ). DATA CONCLUSION: CrCEST MRI shows promise in assessing muscle bioenergetics by evaluating τCrCEST during mild plantar flexion exercise with reasonable reliability, particularly in LG and MG. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.
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Photoluminescence has widely been used to study excitons in semiconducting transition metal dichalcogenide (MX2) monolayers, demonstrating strong light-matter interactions and locked spin and valley degrees of freedom. In heterobilayers composed of overlapping monolayers of two different MX2, an interlayer exciton can form, with the hole localised in one layer and the electron in the other. These interlayer excitons are long-lived, field-tunable, and can be trapped by moiré patterns formed at small twist angles between the layers. Here we demonstrate that emission from radiative recombination of interlayer excitons can be observed by cathodoluminescence from a WSe2/MoSe2heterobilayer encapsulated in hexagonal boron nitride. The higher spatial resolution of cathodoluminescence, compared to photoluminescence, allows detailed analysis of sample heterogeneity at the 100 s of nm lengthscales over which twist angles tend to vary in dry-transfer fabricated heterostructures.
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Diverse emergent correlated electron phenomena have been observed in twisted-graphene layers. Many electronic structure predictions have been reported exploring this new field, but with few momentum-resolved electronic structure measurements to test them. We use angle-resolved photoemission spectroscopy to study the twist-dependent (1° < θ < 8°) band structure of twisted-bilayer, monolayer-on-bilayer, and double-bilayer graphene (tDBG). Direct comparison is made between experiment and theory, using a hybrid k·p model for interlayer coupling. Quantitative agreement is found across twist angles, stacking geometries, and back-gate voltages, validating the models and revealing field-induced gaps in twisted graphenes. However, for tDBG at θ = 1.5 ± 0.2°, close to the magic angle θ = 1.3°, a flat band is found near the Fermi level with measured bandwidth Ew = 31 ± 5 meV. An analysis of the gap between the flat band and the next valence band shows deviations between experiment (Δh = 46 ± 5 meV) and theory (Δh = 5 meV), indicative of lattice relaxation in this regime.
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As the ageing population grows and forms a significant category of over 65s in many societies, along with it comes the risk of developing physical and psychological degenerative changes. This presents many challenges for health and social care services in not only identifying those at risk but also managing that risk to try to preserve health and independence for as long as possible. Screening for frailty has supported services to identify those that may be at risk of hospitalisation, requiring long term care or support services at home in older age. Frailty can be exacerbated by the risk of nutritional deficiencies and more severe malnutrition. Therefore, screening for frailty should also include a nutritional assessment, which can be supported by a recognition of the need for nutritional support along with other holistic frailty management.
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Fragilidade , Desnutrição , Humanos , Idoso , Fragilidade/diagnóstico , Idoso Fragilizado/psicologia , Estado Nutricional , Desnutrição/diagnóstico , Desnutrição/prevenção & controle , Avaliação NutricionalRESUMO
PURPOSE: The nuclear Overhauser effect (NOE) quantification from the steady-state NOE imaging suffers from multiple confounding non-NOE-specific sources, including direct saturation, magnetization transfer, and relevant chemical exchange species, and is affected by B0 and B1 + inhomogeneities. The B0 -dependent and B1 + -dependent data needed for deconvolving these confounding effects would increase the scan time substantially, leading to other issues such as patient tolerability. Here, we demonstrate the feasibility of brain lipid mapping using an easily implementable transient NOE (tNOE) approach. METHODS: This 7T study used a frequency-selective inversion pulse at a range of frequency offsets between 1.0 and 5.0 parts per million (ppm) and -5.0 and -1.0 ppm relative to bulk water peak. This was followed by a fixed/variable mixing time and then a single-shot 2D turbo FLASH readout. The feasibility of tNOE measurements is demonstrated on bovine serum albumin phantoms and healthy human brains. RESULTS: The tNOE measurements from bovine serum albumin phantoms were found to be independent of physiological pH variations. Both bovine serum albumin phantoms and human brains showed broad tNOE contributions centered at approximately -3.5 ppm relative to water peak, with presumably aliphatic moieties in lipids and proteins being the dominant contributors. Less prominent tNOE contributions of approximately +2.5 ppm relative to water, presumably from aromatic moieties, were also detected. These aromatic signals were free from any CEST signals. CONCLUSION: In this study, we have demonstrated the feasibility of tNOE in human brain at 7 T. This method is more scan-time efficient than steady-state NOE and provides NOE measurement with minimal confounders.
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Encéfalo , Imageamento por Ressonância Magnética , Humanos , Algoritmos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos de Viabilidade , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Soroalbumina Bovina , Água/metabolismo , Imagens de FantasmasRESUMO
PURPOSE: Nuclear Overhauser effect (NOE) is based on dipolar cross-relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on determining the reproducibility of NOE magnetization transfer ratio (NOEMTR ) and isolated or relayed NOE (rNOE) contributions to the NOE MRI of the healthy human brain at 7 Tesla (T). METHODS: We optimized the B 1 + $$ {\mathrm{B}}_1^{+} $$ amplitude and length of the saturation pulse by acquiring NOE images with different B 1 + $$ {\mathrm{B}}_1^{+} $$ values with multiple saturation lengths. Repeated NOE MRI measurements were made on five healthy volunteers by using optimized saturation pulse parameters including correction of B0 and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities. To isolate the individual contributions from z-spectra, we have fit the NOE z-spectra using multiple Lorentzians and calculated the total contribution from each pool contributing to the overall NOEMTR contrast. RESULTS: We found that a saturation amplitude of 0.72 µT and a length of 3 s provided the highest contrast. We found that the mean NOEMTR value in gray matter (GM) was 26%, and in white matter (WM) was 33.3% across the 3D slab of the brain. The mean rNOE contributions from GM and WM values were 8.9% and 9.6%, which were â¼10% of the corresponding total NOEMTR signal. The intersubject coefficient of variations (CoVs) of NOEMTR from GM and WM were 4.5% and 6.5%, respectively, whereas the CoVs of rNOE were 4.8% and 5.6%, respectively. The intrasubject CoVs of the NOEMTR range was 2.1%-4.2%, and rNOE range was 2.9%-10.5%. CONCLUSION: This work has demonstrated an excellent reproducibility of both inter- and intrasubject NOEMTR and rNOE metrics in healthy human brains at 7 T.
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Algoritmos , Neoplasias Encefálicas , Humanos , Reprodutibilidade dos Testes , Interpretação de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , PrótonsRESUMO
PURPOSE: The purpose of this study was to characterize the 1 H downfield MR spectrum from 8.0 to 10.0 ppm of human skeletal muscle at 7 T and determine the T1 and cross-relaxation rates of observed resonances. METHODS: We performed downfield MRS in the calf muscle of 7 healthy volunteers. Single-voxel downfield MRS was collected using alternately selective or broadband inversion-recovery sequences and spectrally selective 90° E-BURP RF pulse excitation centered at 9.0 ppm with bandwidth = 600 Hz (2.0 ppm). MRS was collected using TIs of 50-2500 ms. We modeled recovery of the longitudinal magnetization of three observable resonances using two models: (1) a three-parameter model accounting for the apparent T1 recovery and (2) a Solomon model explicitly including cross-relaxation effects. RESULTS: Three resonances were observed in human calf muscle at 7 T at 8.0, 8.2, and 8.5 ppm. We found broadband (broad) and selective (sel) inversion recovery T1 = mean ± SD (ms): T1-broad,8.0ppm = 2108.2 ± 664.5, T1-sel,8.0ppm = 753.6 ± 141.0 (p = 0.003); T1-broad,8.2ppm = 2033.5 ± 338.4, T1-sel,8.2ppm = 135.3 ± 35.3 (p < 0.0001); and T1-broad,8.5ppm = 1395.4 ± 75.4, T1-sel,8.5ppm = 107.1 ± 40.0 (p < 0.0001). Using the Solomon model, we found T1 = mean ± SD (ms): T1-8.0ppm = 1595.6 ± 491.1, T1-8.2ppm = 1737.2 ± 963.7, and T1-8.5ppm = 849.8 ± 282.0 (p = 0.04). Post hoc tests corrected for multiple comparisons showed no significant difference in T1 between peaks. The cross-relaxation rate σAB = mean ± SD (Hz) of each peak was σAB,8.0ppm = 0.76 ± 0.20, σAB,8.2ppm = 5.31 ± 2.27, and σAB,8.5ppm = 7.90 ± 2.74 (p < 0.0001); post hoc t-tests revealed the cross-relaxation rate of the 8.0 ppm peak was significantly slower than the peaks at 8.2 ppm (p = 0.0018) and 8.5 ppm (p = 0.0005). CONCLUSION: We found significant differences in effective T1 and cross-relaxation rates of 1 H resonances between 8.0 and 8.5 ppm in the healthy human calf muscle at 7 T.
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Músculo Esquelético , Humanos , Espectroscopia de Ressonância Magnética , Músculo Esquelético/diagnóstico por imagemRESUMO
PURPOSE: The purpose of this study was to identify and characterize newly discovered resonances appearing in the downfield proton MR spectrum (DF 1 H MRS) of the human calf muscle in vivo at 7T. METHODS: Downfield 1 H MRS was performed on the calf muscle of five healthy volunteers at 7T. A spectrally selective 90° E-BURP RF pulse with an excitation center frequency at 10.3 ppm and an excitation bandwidth of 2 ppm was used for DF 1 H MRS acquisition. RESULTS: In all participants, we observed new resonances at 9.7, 10.1, 10.3, and 10.9 ppm in the DF 1 H MRS. Phantom experiments at 37°C strongly suggest the new resonance at 9.7 ppm could be from H2-proton of the nicotinamide rings in nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) while the resonance at 10.1 ppm could be attributed to the indole -NH proton of L-tryptophan. We observed that the resonances at 10.1 and 10.9 ppm are significantly suppressed when the water resonance is saturated, indicating that these peaks have either 1 H chemical exchange or cross-relaxation with water. Conversely, the resonances at 9.7 and 10.3 ppm exhibit moderate signal reduction in the presence of water saturation. CONCLUSION: We have identified new proton resonances in vivo in human calf muscle occurring at chemical shifts of 9.7, 10.1, 10.3, and 10.9 ppm. These preliminary results are promising for investigating the role of NR/NMN and L-tryptophan metabolism in understanding the de novo and salvage pathways of NAD+ synthesis in skeletal muscle.
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NAD , Prótons , Humanos , Triptofano , Músculo Esquelético/diagnóstico por imagem , ÁguaRESUMO
PURPOSE: Nuclear Overhauser effect magnetization transfer ratio (NOEMTR ) is a technique used to investigate brain lipids and macromolecules in greater detail than other techniques and benefits from increased contrast at 7 T. However, this contrast can become degraded because of B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities present at ultra-high field strengths. High-permittivity dielectric pads (DP) have been used to correct for these inhomogeneities via displacement currents generating secondary magnetic fields. The purpose of this work is to demonstrate that dielectric pads can be used to mitigate B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities and improve NOEMTR contrast in the temporal lobes at 7 T. METHODS: Partial 3D NOEMTR contrast images and whole brain B 1 + $$ {\mathrm{B}}_1^{+} $$ field maps were acquired on a 7 T MRI across six healthy subjects. Calcium titanate DP, having a relative permittivity of 110, was placed next to the subject's head near the temporal lobes. Pad corrected NOEMTR images had a separate postprocessing linear correction applied. RESULTS: DP provided supplemental B 1 + $$ {\mathrm{B}}_1^{+} $$ to the temporal lobes while also reducing the B 1 + $$ {\mathrm{B}}_1^{+} $$ magnitude across the posterior and superior regions of the brain. This resulted in a statistically significant increase in NOEMTR contrast in substructures of the temporal lobes both with and without linear correction. The padding also produced a convergence in NOEMTR contrast toward approximately equal mean values. CONCLUSION: NOEMTR images showed significant improvement in temporal lobe contrast when DP were used, which resulted from an increase in B 1 + $$ {\mathrm{B}}_1^{+} $$ homogeneity across the entire brain slab. DP-derived improvements in NOEMTR are expected to increase the robustness of the brain substructural measures both in healthy and pathological conditions.
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Encéfalo , Cabeça , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico , Campos Magnéticos , 5-Metiltetra-Hidrofolato-Homocisteína S-MetiltransferaseRESUMO
Declines in soil multifunctionality (e.gsoil capacity to provide food and energy) are closely related to changes in the soil microbiome (e.g., diversity) Determining ecological drivers promoting such microbiome changes is critical knowledge for protecting soil functions. However, soil-microbe interactions are highly variable within environmental gradients and may not be consistent across studies. Here we propose that analysis of community dissimilarity (ß-diversity) is a valuable tool for overviewing soil microbiome spatiotemporal changes. Indeed, ß-diversity studies at larger scales (modelling and mapping) simplify complex multivariate interactions and refine our understanding of ecological drivers by also giving the possibility of expanding the environmental scenarios. This study represents the first spatial investigation of ß-diversity in the soil microbiome of New South Wales (800,642 km2 ), Australia. We used metabarcoding soil data (16S rRNA and ITS genes) as exact sequence variants (ASVs) and UMAP (Uniform Manifold Approximation and Projection) as the distance metric. ß-Diversity maps (1000-m resolution)-concordance correlations of 0.91-0.96 and 0.91-0.95 for bacteria and fungi, respectively-showed soil biome dissimilarities driven primarily by soil chemistry-pH and effective cation exchange capacity (ECEC)-and cycles of soil temperature-land surface temperature (LST-phase and LST-amplitude). Regionally, the spatial patterns of microbes parallel the distribution of soil classes (e.g., Vertosols) beyond spatial distances and rainfall, for example. Soil classes can be valuable discriminants for monitoring approaches, for example pedogenons and pedophenons. Ultimately, cultivated soils exhibited lower richness due to declines in rare microbes which might compromise soil functions over time.
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Microbiota , Solo , Austrália , Temperatura , RNA Ribossômico 16S/genética , Microbiologia do Solo , Microbiota/genéticaRESUMO
BACKGROUND: There is a need to evaluate if and how telerehabilitation approaches might co-exist within healthcare in the long-term. Our aim was to implement and evaluate a multidisciplinary group-based telerehabilitation approach for people engaging in neurological rehabilitation. METHODS: NeuroRehabilitation OnLine (NROL) was adapted and implemented within an existing healthcare system as a programme of repeating six-week blocks. A robust evaluation was undertaken simultaneously using a convergent parallel design underpinned by implementation frameworks. This included service data, and patient and staff interviews. Implementation success was conceptualised using the outcomes of appropriateness, acceptability and sustainability. RESULTS: Eight NROL blocks delivered 265 sessions with 1347 patient contacts, and NROL continues as part of standard practice. The approach was appropriate for varied demographics and had positive patient opinions and outcomes for many. Staff perceived NROL provided a compatible means to increase therapy and help meet targets, despite needing to mitigate some challenges when fitting the approach within the existing system. NROL was considered acceptable due to good attendance (68%), low drop-out (12%), and a good safety record (one non-injury fall). It was accepted as a new way of working across rehabilitation disciplines as an 'extra layer of therapy'. NROL had perceived advantages in terms of patient and staff resource (e.g. saving time, energy and travel). NROL provided staffing efficiencies (ratio 0.6) compared to one-to-one delivery. Technology difficulties and reluctance were surmountable with dedicated technology assistance. Leadership commitment was considered key to enable the efforts needed for implementation and sustained use. CONCLUSION: Pragmatic implementation of group-based telerehabilitation was possible as an adjunct to neurological rehabilitation within an existing healthcare system. The compelling advantages reported of having NROL as part of rehabilitation supports the continued use of this telerehabilitation approach. This project provides an exemplar of how evaluation can be run concurrently with implementation, applying a data driven rather than anecdotal approach to implementation.
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COVID-19 , Telerreabilitação , Humanos , Telerreabilitação/métodos , Pandemias , COVID-19/epidemiologia , Atenção à Saúde , Instalações de SaúdeRESUMO
The number of individuals living with chronic obstructive pulmonary disease (COPD) is increasing, but nutritional care can be inconsistent, especially in those with stable COPD. Historically, poor appetite and weight loss have been considered the norm during the progression of COPD into the later stage. However, it is imperative that nutritional assessment, support and management is undertaken from diagnosis, because malnutrition can lead to exacerbations of COPD and increased hospitalisation. Poor nutrition in individuals with COPD has been shown to predict an increase in mortality and with the care of patients taking place principally in the community, the nutritional aspects of care should be assessed, monitored and managed, in accordance with the latest guidance. The lack of a nutritional Quality Outcome Framework indicator for COPD can leave nutrition overlooked, but evidence shows that screening, assessment and planning can have an overall positive impact.
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Desnutrição , Doença Pulmonar Obstrutiva Crônica , Humanos , Desnutrição/etiologia , Desnutrição/prevenção & controle , Estado Nutricional , Doença Pulmonar Obstrutiva Crônica/complicações , Apoio Nutricional , Avaliação NutricionalRESUMO
In the technique presented here, dubbed 'qMRS', we quantify the change in 1H MRS signal following administration of 2H-labeled glucose. As in recent human DMRS studies, we administer [6,6'-2H2]-glucose orally to healthy subjects. Since 2H is not detectable by 1H MRS, the transfer of the 2H label from glucose to a downstream metabolite leads to a reduction in the corresponding 1H MRS resonance of the metabolite, even if the total concentration of both isoforms remains constant. Moreover, introduction of the deuterium label alters the splitting pattern of the proton resonances, making indirect detection of the deuterated forms- as well as the direct detection of the decrease in unlabeled form- possible even without a 2H coil. Because qMRS requires only standard 1H MRS acquisition methods, it can be performed using commonly implemented single voxel spectroscopy (SVS) and chemical shift imaging (CSI) sequences. In this work, we implement qMRS in semi-LASER based CSI, generating dynamic maps arising from the fitted spectra, and demonstrating the feasibility of using qMRS and qCSI to monitor dynamic metabolism in the human brain using a 7T scanner with no auxiliary hardware.
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Glucose , Imageamento por Ressonância Magnética , Deutério , Glucose/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
PURPOSE: To explore the presence of new resonances beyond 9.4 ppm from the human brain, down-field proton MRS was performed in vivo in the human brain on 6 healthy volunteers at 7 T. METHODS: To maximize the SNR, a large voxel was placed within the brain to cover the maximal area in such a way that sinus cavities were avoided. A spectrally selective 90° E-BURP pulse with an excitation bandwidth of 2 ppm was used to probe the spectral chemical shift range between 9.1 and 10.5 ppm. The E-BURP pulse was integrated with PRESS spatial localization to obtain non-water-suppressed proton MR spectra from the desired spectral region. RESULTS: In the down-field proton MRS obtained from all of the volunteers scanned, we identified a new peak consistently resonating at 10.1 ppm. Protons associated with this resonance are in cross-relaxation with the bulk water, as demonstrated by the water saturation and deuterium exchange experiments. CONCLUSION: Based on the chemical shift, this new peak was identified as the indole (-NH) proton of l-tryptophan (l-TRP) and was further confirmed from phantom experiments on l-TRP. These promising preliminary results potentially pave the way to investigate the role of cerebral metabolism of l-TRP in healthy and disease conditions.