Efficient Green Spin Light-Emitting Diodes Enabled by Ultrafast Energy- and Spin-Funneling in Chiral Perovskites.

Introducing molecular chirality into perovskite crystal structures has enabled the control of carrier spin states, giving rise to circularly polarized luminescence (CPL) in thin films and circularly polarized electroluminescence (CPEL) in LEDs. Spin-LEDs can be fabricated either through a spin-filtering layer enabled by chiral-induced spin selectivity or a chiral emissive layer. The former requires a high degree of spin polarization and a compatible spinterface for efficient spin injection, which might not be easily integrated into LEDs. Alternatively, a chiral emissive layer can also generate circularly polarized electroluminescence, but the efficiency remains low and the fundamental mechanism is elusive. In this work, we report an efficient green LED based on quasi-two-dimensional (quasi-2D) chiral perovskites as the emitting layer (EML), where CPEL is directly produced without separate carrier spin injection. The optimized chiral perovskite thin films exhibited strong CPL at 535 nm with a photoluminescence quantum yield (PLQY) of 91% and a photoluminescence dissymmetry factor (glum) of 8.6 × 10-2. Efficient green spin-LEDs were successfully demonstrated, with a large EL dissymmetry factor (gEL) of 7.8 × 10-2 and a maximum external quantum efficiency (EQE) of 13.5% at room temperature. Ultrafast transient absorption (TA) spectroscopic study shows that the CPEL is generated from a rapid energy transfer accompanied by spin transfer from 2D to 3D perovskites. Our study not only demonstrates a reliable approach to achieve high performance spin-LEDs but also reveals the fundamental mechanism of CPEL with an emissive layer of chiral perovskites.

Pseudo-resting-state functional MRI derived from dynamic susceptibility contrast perfusion MRI can predict cognitive impairment in glioma.

BACKGROUND AND PURPOSE: Resting-state functional MRI (rs-fMRI) can be used to estimate functional connectivity (FC) between different brain regions, which may be of value for identifying cognitive impairment in patients with brain tumors. Unfortunately, neither rs-fMRI nor neurocognitive assessments are routinely assessed clinically, mostly due to limitations in exam time and cost. Since DSC perfusion MRI is often used clinically to assess tumor vascularity and similarly uses a gradient echo-EPI sequence for T2*sensitivity, we theorized a "pseudo-rs-fMRI" signal could be derived from DSC perfusion to simultaneously quantify FC and perfusion metrics, and these metrics can be used to estimate cognitive impairment in patients with brain tumors. MATERIALS AND METHODS: N=24 consecutive patients with gliomas were enrolled in a prospective study that included DSC perfusion MRI, rs-fMRI, and neurocognitive assessment. Voxel-wise modeling of contrast bolus dynamics during DSC acquisition was performed and then subtracted from the original signal to generate a residual "pseudo-rs-fMRI" signal. Following the pre-processing of pseudo-rs-fMRI, full rs-fMRI, and a truncated version of the full rs-fMRI (first 100 timepoints) data, the default mode, motor, and language network maps were generated with atlas-based ROIs. Dice scores were calculated for the resting-state network maps from pseudo-rs-fMRI and truncated rs-fMRI using the full rs-fMRI maps as reference. Seed-to-voxel and ROI-to-ROI analyses were performed to assess FC differences between cognitively impaired and non-impaired patients. RESULTS: Dice scores for the group-level and patient-level (mean±SD) default mode, motor, and language network maps using pseudo-rs-fMRI were 0.905/0.689±0.118 (group/patient), 0.973/0.730±0.124, and 0.935/0.665±0.142, respectively. There was no significant difference in Dice scores between pseudo-rs-fMRI and the truncated rs-fMRI default mode (P=0.97) or language networks (P=0.30), but there was a difference in motor networks (P=0.02). A multiple logistic regression classifier applied to ROI-to-ROI FC networks using pseudo-rs-fMRI could identify cognitively impaired patients (Sensitivity=84.6%, Specificity=63.6%, ROC AUC=0.7762±0.0954 (SE), P=0.0221) and performance was not significantly different than full rs-fMRI predictions (AUC=0.8881±0.0733 (SE), P=0.0013, P=0.29 compared to pseudo-rs-fMRI). CONCLUSIONS: DSC perfusion MRI-derived pseudo-rs-fMRI data can be used to perform typical rs-fMRI FC analyses that may identify cognitive decline in patients with brain tumors while still simultaneously performing perfusion analyses.ABBREVIATIONS: AUC = Area under curve; BOLD = Blood oxygenation level dependent; FC = Functional connectivity; MNI = Montreal Neurological Institute; ROC = Receiver operating characteristic; Rs-fMRI = Resting-state functional MRI.

Quantification of the in vivo brain ultrashort-T2* component in healthy volunteers.

PURPOSE: Recent work has shown MRI is able to measure and quantify signals of phospholipid membrane-bound protons associated with myelin in the human brain. This work seeks to develop an improved technique for characterizing this brain ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component in vivo accounting for T 1 $$ {\mathrm{T}}_1 $$ weighting. METHODS: Data from ultrashort echo time scans from 16 healthy volunteers with variable flip angles (VFA) were collected and fitted into an advanced regression model to quantify signal fraction, relaxation time, and frequency shift of the ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component. RESULTS: The fitted components show intra-subject differences of different white matter structures and significantly elevated ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ signal fraction in the corticospinal tracts measured at 0.09 versus 0.06 in other white matter structures and significantly elevated ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ frequency shift in the body of the corpus callosum at - $$ - $$ 1.5 versus - $$ - $$ 2.0 ppm in other white matter structures. CONCLUSION: The significantly different measured components and measured T 1 $$ {\mathrm{T}}_1 $$ relaxation time of the ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component suggest that this method is picking up novel signals from phospholipid membrane-bound protons.

Quantification of T2-FLAIR Mismatch in Nonenhancing Diffuse Gliomas Using Digital Subtraction.

BACKGROUND AND PURPOSE: The T2-FLAIR mismatch sign on MR imaging is a highly specific imaging biomarker of isocitrate dehydrogenase (IDH)-mutant astrocytomas, which lack 1p/19q codeletion. However, most studies using the T2-FLAIR mismatch sign have used visual assessment. This study quantified the degree of T2-FLAIR mismatch using digital subtraction of fluid-nulled T2-weighted FLAIR images from non-fluid-nulled T2-weighted images in human nonenhancing diffuse gliomas and then used this information to assess improvements in diagnostic performance and investigate subregion characteristics within these lesions. MATERIALS AND METHODS: Two cohorts of treatment-naïve, nonenhancing gliomas with known IDH and 1p/19q status were studied (n = 71 from The Cancer Imaging Archive (TCIA) and n = 34 in the institutional cohort). 3D volumes of interest corresponding to the tumor were segmented, and digital subtraction maps of T2-weighted MR imaging minus T2-weighted FLAIR MR imaging were used to partition each volume of interest into a T2-FLAIR mismatched subregion (T2-FLAIR mismatch, corresponding to voxels with positive values on the subtraction maps) and nonmismatched subregion (T2-FLAIR nonmismatch corresponding to voxels with negative values on the subtraction maps). Tumor subregion volumes, percentage of T2-FLAIR mismatch volume, and T2-FLAIR nonmismatch subregion thickness were calculated, and 2 radiologists assessed the T2-FLAIR mismatch sign with and without the aid of T2-FLAIR subtraction maps. RESULTS: Thresholds of ≥42% T2-FLAIR mismatch volume classified IDH-mutant astrocytoma with a specificity/sensitivity of 100%/19.6% (TCIA) and 100%/31.6% (institutional); ≥25% T2-FLAIR mismatch volume showed 92.0%/32.6% and 100%/63.2% specificity/sensitivity, and ≥15% T2-FLAIR mismatch volume showed 88.0%/39.1% and 93.3%/79.0% specificity/sensitivity. In IDH-mutant astrocytomas with ≥15% T2-FLAIR mismatch volume, T2-FLAIR nonmismatch subregion thickness was negatively correlated with the percentage T2-FLAIR mismatch volume (P < .0001) across both cohorts. The percentage T2-FLAIR mismatch volume was higher in grades 3-4 compared with grade 2 IDH-mutant astrocytomas (P < .05), and ≥15% T2-FLAIR mismatch volume IDH-mutant astrocytomas were significantly larger than <15% T2-FLAIR mismatch volume IDH-mutant astrocytoma (P < .05) across both cohorts. When evaluated by 2 radiologists, the additional use of T2-FLAIR subtraction maps did not show a significant difference in interreader agreement, sensitivity, or specificity compared with a separate evaluation of T2-FLAIR and T2-weighted MR imaging alone. CONCLUSIONS: T2-FLAIR digital subtraction maps may be a useful, automated tool to obtain objective segmentations of tumor subregions based on quantitative thresholds for classifying IDH-mutant astrocytomas using the percentage T2 FLAIR mismatch volume with 100% specificity and exploring T2-FLAIR mismatch/T2-FLAIR nonmismatch subregion characteristics. Conversely, the addition of T2-FLAIR subtraction maps did not enhance the sensitivity or specificity of the visual T2-FLAIR mismatch sign assessment by experienced radiologists.

Altered Iron and Microstructure in Huntington's Disease Subcortical Nuclei: Insight From 7T MRI.

BACKGROUND: Pathophysiological changes of Huntington's disease (HD) can precede symptom onset by decades. Robust imaging biomarkers are needed to monitor HD progression, especially before the clinical onset. PURPOSE: To investigate iron dysregulation and microstructure alterations in subcortical regions as HD imaging biomarkers, and to associate such alterations with motor and cognitive impairments. STUDY TYPE: Prospective. POPULATION: Fourteen individuals with premanifest HD (38.0 ± 11.0 years, 9 females; far-from-onset N = 6, near-onset N = 8), 21 manifest HD patients (49.1 ± 12.1 years, 11 females), and 33 age-matched healthy controls (43.9 ± 12.2 years, 17 females). FIELD STRENGTH/SEQUENCE: 7 T, T1 -weighted imaging, quantitative susceptibility mapping, and diffusion tensor imaging. ASSESSMENT: Volume, susceptibility, fractional anisotropy (FA), and mean diffusivity (MD) within subcortical brain structures were compared across groups, used to establish HD classification models, and correlated to clinical measures and cognitive assessments. STATISTICAL TESTS: Generalized linear model, multivariate logistic regression, receiver operating characteristics with the area under the curve (AUC), and likelihood ratio test comparing a volumetric model to one that also includes susceptibility and diffusion metrics, Wilcoxon paired signed-rank test, and Pearson's correlation. A P-value <0.05 after Benjamini-Hochberg correction was considered statistically significant. RESULTS: Significantly higher striatal susceptibility and FA were found in premanifest and manifest HD preceding atrophy, even in far-from-onset premanifest HD compared to controls (putamen susceptibility: 0.027 ± 0.022 vs. 0.018 ± 0.013 ppm; FA: 0.358 ± 0.048 vs. 0.313 ± 0.039). The model with additional susceptibility, FA, and MD features showed higher AUC compared to volume features alone when differentiating premanifest HD from HC (0.83 vs. 0.66), and manifest from premanifest HD (0.94 vs. 0.83). Higher striatal susceptibility significantly correlated with cognitive deterioration in HD (executive function: r = -0.600; socioemotional function: r = -0.486). DATA CONCLUSION: 7 T MRI revealed iron dysregulation and microstructure alterations with HD progression, which could precede volume loss, provide added value to HD differentiation, and might be associated with cognitive changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

pH-Weighted amine chemical exchange saturation transfer echo planar imaging visualizes infiltrating glioblastoma cells.

BACKGROUND: Given the invasive nature of glioblastoma, tumor cells exist beyond the contrast-enhancing (CE) region targeted during treatment. However, areas of non-enhancing (NE) tumors are difficult to visualize and delineate from edematous tissue. Amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) is a pH-sensitive molecular magnetic resonance imaging technique that was evaluated in its ability to identify infiltrating NE tumors and prognosticate survival. METHODS: In this prospective study, CEST-EPI was obtained in 30 patients and areas with elevated CEST contrast ("CEST+" based on the asymmetry in magnetization transfer ratio: MTRasym at 3 ppm) within NE regions were quantitated. Median MTRasym at 3 ppm and volume of CEST + NE regions were correlated with progression-free survival (PFS). In 20 samples from 14 patients, image-guided biopsies of these areas were obtained to correlate MTRasym at 3 ppm to tumor and non-tumor cell burden using immunohistochemistry. RESULTS: In 15 newly diagnosed and 15 recurrent glioblastoma, higher median MTRasym at 3ppm within CEST + NE regions (P = .007; P = .0326) and higher volumes of CEST + NE tumor (P = .020; P < .001) were associated with decreased PFS. CE recurrence occurred in areas of preoperative CEST + NE regions in 95.4% of patients. MTRasym at 3 ppm was correlated with presence of tumor, cell density, %Ki-67 positivity, and %CD31 positivity (P = .001; P < .001; P < .001; P = .001). CONCLUSIONS: pH-weighted amine CEST-EPI allows for visualization of NE tumor, likely through surrounding acidification of the tumor microenvironment. The magnitude and volume of CEST + NE tumor correlates with tumor cell density, degree of proliferating or "active" tumor, and PFS.

Simultaneous quantification of perfusion, permeability, and leakage effects in brain gliomas using dynamic spin-and-gradient-echo echoplanar imaging MRI.

OBJECTIVE: To determine the feasibility and biologic correlations of dynamic susceptibility contrast (DSC), dynamic contrast enhanced (DCE), and quantitative maps derived from contrast leakage effects obtained simultaneously in gliomas using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) during a single contrast injection. MATERIALS AND METHODS: Thirty-eight patients with enhancing brain gliomas were prospectively imaged with dynamic SAGE-EPI, which was processed to compute traditional DSC metrics (normalized relative cerebral blood flow [nrCBV], percentage of signal recovery [PSR]), DCE metrics (volume transfer constant [Ktrans], extravascular compartment [ve]), and leakage effect metrics: ΔR2,ss* (reflecting T2*-leakage effects), ΔR1,ss (reflecting T1-leakage effects), and the transverse relaxivity at tracer equilibrium (TRATE, reflecting the balance between ΔR2,ss* and ΔR1,ss). These metrics were compared between patient subgroups (treatment-naïve [TN] vs recurrent [R]) and biological features (IDH status, Ki67 expression). RESULTS: In IDH wild-type gliomas (IDHwt-i.e., glioblastomas), previous exposure to treatment determined lower TRATE (p = 0.002), as well as higher PSR (p = 0.006), Ktrans (p = 0.17), ΔR1,ss (p = 0.035), ve (p = 0.006), and ADC (p = 0.016). In IDH-mutant gliomas (IDHm), previous treatment determined higher Ktrans and ΔR1,ss (p = 0.026). In TN-gliomas, dynamic SAGE-EPI metrics tended to be influenced by IDH status (p ranging 0.09-0.14). TRATE values above 142 mM-1s-1 were exclusively seen in TN-IDHwt, and, in TN-gliomas, this cutoff had 89% sensitivity and 80% specificity as a predictor of Ki67 > 10%. CONCLUSIONS: Dynamic SAGE-EPI enables simultaneous quantification of brain tumor perfusion and permeability, as well as mapping of novel metrics related to cytoarchitecture (TRATE) and blood-brain barrier disruption (ΔR1,ss), with a single contrast injection. CLINICAL RELEVANCE STATEMENT: Simultaneous DSC and DCE analysis with dynamic SAGE-EPI reduces scanning time and contrast dose, respectively alleviating concerns about imaging protocol length and gadolinium adverse effects and accumulation, while providing novel leakage effect metrics reflecting blood-brain barrier disruption and tumor tissue cytoarchitecture. KEY POINTS: • Traditionally, perfusion and permeability imaging for brain tumors requires two separate contrast injections and acquisitions. • Dynamic spin-and-gradient-echo echoplanar imaging enables simultaneous perfusion and permeability imaging. • Dynamic spin-and-gradient-echo echoplanar imaging provides new image contrasts reflecting blood-brain barrier disruption and cytoarchitecture characteristics.

Activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrence of glioblastoma.

INTRODUCTION: Hypoxia inducible factor 2-alpha (HIF2α) mediates cellular responses to hypoxia and is over-expressed in glioblastoma (GBM). PT2385 is an oral HIF2α inhibitor with in vivo activity against GBM. METHODS: A two-stage single-arm open-label phase II study of adults with GBM at first recurrence following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium. PT2385 was administered at the phase II dose (800 mg b.i.d.). The primary outcome was objective radiographic response (ORR = complete response + partial response, CR + PR); secondary outcomes were safety, overall survival (OS), and progression free survival (PFS). Exploratory objectives included pharmacokinetics (day 15 Cmin), pharmacodynamics (erythropoietin, vascular endothelial growth factor), and pH-weighted amine- chemical exchange saturation transfer (CEST) MRI to quantify tumor acidity at baseline and explore associations with drug response. Stage 1 enrolled 24 patients with early stoppage for ≤ 1 ORR. RESULTS: Of the 24 enrolled patients, median age was 62.1 (38.7-76.7) years, median KPS 80, MGMT promoter was methylated in 46% of tumors. PT2385 was well tolerated. Grade ≥ 3 drug-related adverse events were hypoxia (n = 2), hyponatremia (2), lymphopenia (1), anemia (1), and hyperglycemia (1). No objective radiographic responses were observed; median PFS was 1.8 months (95% CI 1.6-2.5) and OS was 7.7 months (95% CI 4.9-12.6). Drug exposure varied widely and did not differ by corticosteroid use (p = 0.12), antiepileptics (p = 0.09), or sex (p = 0.37). Patients with high systemic exposure had significantly longer PFS (6.7 vs 1.8 months, p = 0.009). Baseline acidity by pH-weighted CEST MRI correlated significantly with treatment duration (R2 = 0.49, p = 0.017). Non-enhancing infiltrative disease with high acidity gave rise to recurrence. CONCLUSIONS: PT2385 monotherapy had limited activity in first recurrent GBM. Drug exposure was variable. Signals of activity were observed in GBM patients with high systemic exposure and acidic lesions on CEST imaging. A second-generation HIF2α inhibitor is being studied.

Lifetime Enhancement and Degradation Study of Blue OLEDs Using Deuterated Materials.

Significant lifetime enhancement, up to an eight-fold increase in T90, has been demonstrated in blue organic light-emitting diode (OLED) devices through the deuteration of host and hole transport materials. We observed a progressive increase in T90 using a series of anthracene-based hydrocarbon hosts with incremental deuteration in the emitting layer. In addition, we realized further lifetime improvement using a deuterated hole-transport layer along with the deuterated emitting layer. To elucidate the deuteration effects, we utilized laser desorption/ionization-time-of-flight (LDI-TOF) mass spectrometry for in situ UV irradiation to induce photodegradation and immediate chemical analysis of the resultant photodegradation species. Adducts between the host and moieties from transport materials were identified in UV-degraded films comprising a mixture of host and transport materials, indicating that similar species could be produced in OLED devices using these materials. Deuteration, in effect, mediated the formation of these adduct species, presumably electroluminescence quenchers, and thus improved the device lifetime. An approximate agreement was obtained between the kinetic isotope effect of the photodegradation reactions and the enhancement in device lifetime with deuteration.

Comparison of quantitative susceptibility mapping methods for iron-sensitive susceptibility imaging at 7T: An evaluation in healthy subjects and patients with Huntington's disease.

Quantitative susceptibility mapping (QSM) is a promising tool for investigating iron dysregulation in neurodegenerative diseases, including Huntington's disease (HD). Many diverse methods have been proposed to generate accurate and robust QSM images. In this study, we evaluated the performance of different dipole inversion algorithms for iron-sensitive susceptibility imaging at 7T on healthy subjects of a large age range and patients with HD. We compared an iterative least-squares-based method (iLSQR), iterative methods that use regularization, single-step approaches, and deep learning-based techniques. Their performance was evaluated by comparing: (1) deviations from a multiple-orientation QSM reference; (2) visual appearance of QSM maps and the presence of artifacts; (3) susceptibility in subcortical brain regions with age; (4) regional brain susceptibility with published postmortem brain iron quantification; and (5) susceptibility in HD-affected basal ganglia regions between HD subjects and healthy controls. We found that single-step QSM methods with either total variation or total generalized variation constraints (SSTV/SSTGV) and the single-step deep learning method iQSM generally provided the best performance in terms of correlation with iron deposition and were better at differentiating between healthy controls and premanifest HD individuals, while deep learning QSM methods trained with multiple-orientation susceptibility data created QSM maps that were most similar to the multiple orientation reference and with the best visual scores.

Amine-weighted chemical exchange saturation transfer magnetic resonance imaging in brain tumors.

Amine-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is particularly valuable as an amine- and pH-sensitive imaging technique in brain tumors, targeting the intrinsically high concentration of amino acids with exchangeable amine protons and reduced extracellular pH in brain tumors. Amine-weighted CEST MRI contrast is dependent on the glioma genotype, likely related to differences in degree of malignancy and metabolic behavior. Amine-weighted CEST MRI may provide complementary value to anatomic imaging in conventional and exploratory therapies in brain tumors, including chemoradiation, antiangiogenic therapies, and immunotherapies. Continual improvement and clinical testing of amine-weighted CEST MRI has the potential to greatly impact patients with brain tumors by understanding vulnerabilities in the tumor microenvironment that may be therapeutically exploited.

Low rank off-resonance correction for double half-echo k-space acquisitions.

The present study describes a model-based approach for correcting off-resonance in the context of double half-echo k-space acquisitions. This technique employs center-out readouts in forward and reverse directions to reduce echo-times but is sensitive to off-resonance, which manifests as pixel shifts in both directions. Demodulating the k-space signal with a constant off-resonance term per slice removes pixel shifts and results in a marked reduction in blurring. Phantom and in vivo datasets are demonstrated from low bandwidth sodium imaging.

A Knowledge-Based Discovery Approach Couples Artificial Neural Networks With Weight Engineering to Uncover Immune-Related Processes Underpinning Clinical Traits of Breast Cancer.

Immune-related processes are important in underpinning the properties of clinical traits such as prognosis and drug response in cancer. The possibility to extract knowledge learned by artificial neural networks (ANNs) from omics data to explain cancer clinical traits is a very attractive subject for novel discovery. Recent studies using a version of ANNs called autoencoders revealed their capability to store biologically meaningful information indicating that autoencoders can be utilized as knowledge discovery platforms aside from their initial assigned use for dimensionality reduction. Here, we devise an innovative weight engineering approach and ANN platform called artificial neural network encoder (ANNE) using an autoencoder and apply it to a breast cancer dataset to extract knowledge learned by the autoencoder model that explains clinical traits. Intriguingly, the extracted biological knowledge in the form of gene-gene associations from ANNE shows immune-related components such as chemokines, carbonic anhydrase, and iron metabolism that modulate immune-related processes and the tumor microenvironment play important roles in underpinning breast cancer clinical traits. Our work shows that biological "knowledge" learned by an ANN model is indeed encoded as weights throughout its neuronal connections, and it is possible to extract learned knowledge via a novel weight engineering approach to uncover important biological insights.

Lipids associated with plant-bacteria interaction identified using a metabolomics approach in an Arabidopsis thaliana model.

Background: Systemic acquired resistance (SAR) protects plants against a wide variety of pathogens. In recent decades, numerous studies have focused on the induction of SAR, but its molecular mechanisms remain largely unknown. Methods: We used a metabolomics approach based on ultra-high-performance liquid chromatographic (UPLC) and mass spectrometric (MS) techniques to identify SAR-related lipid metabolites in an Arabidopsis thaliana model. Multiple statistical analyses were used to identify the differentially regulated metabolites. Results: Numerous lipids were implicated as potential factors in both plant basal resistance and SAR; these include species of phosphatidic acid (PA), monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG). Conclusions: Our findings indicate that lipids accumulated in both local and systemic leaves, while other lipids only accumulated in local leaves or in systemic leaves. PA (16:0_18:2), PE (34:5) and PE (16:0_18:2) had higher levels in both local leaves inoculated with Psm ES4326 or Psm avrRpm1 and systemic leaves of the plants locally infected with Psm avrRpm1 or Psm ES4326. PC (32:5) had high levels in leaves inoculated with Psm ES4326. Other differentially regulated metabolites, including PA (18:2_18:2), PA (16:0_18:3), PA (18:3_18:2), PE (16:0_18:3), PE (16:1_16:1), PE (34:4) and TGs showed higher levels in systemic leaves of the plants locally infected with Psm avrRpm1 or Psm ES4326. These findings will help direct future studies on the molecular mechanisms of SAR.

Diagnostic and Prognostic Value of pH- and Oxygen-Sensitive Magnetic Resonance Imaging in Glioma: A Retrospective Study.

Characterization of hypoxia and tissue acidosis could advance the understanding of glioma biology and improve patient management. In this study, we evaluated the ability of a pH- and oxygen-sensitive magnetic resonance imaging (MRI) technique to differentiate glioma genotypes, including isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion, and epidermal growth factor receptor (EGFR) amplification, and investigated its prognostic value. A total of 159 adult glioma patients were scanned with pH- and oxygen-sensitive MRI at 3T. We quantified the pH-sensitive measure of magnetization transfer ratio asymmetry (MTRasym) and oxygen-sensitive measure of R2' within the tumor region-of-interest. IDH mutant gliomas showed significantly lower MTRasym × R2' (p < 0.001), which differentiated IDH mutation status with sensitivity and specificity of 90.0% and 71.9%. Within IDH mutants, 1p/19q codeletion was associated with lower tumor acidity (p < 0.0001, sensitivity 76.9%, specificity 91.3%), while IDH wild-type, EGFR-amplified gliomas were more hypoxic (R2' p = 0.024, sensitivity 66.7%, specificity 76.9%). Both R2' and MTRasym × R2' were significantly associated with patient overall survival (R2': p = 0.045; MTRasym × R2': p = 0.002) and progression-free survival (R2': p = 0.010; MTRasym × R2': p < 0.0001), independent of patient age, treatment status, and IDH status. The pH- and oxygen-sensitive MRI is a clinically feasible and potentially valuable imaging technique for distinguishing glioma subtypes and providing additional prognostic value to clinical practice.

Paradoxical Association Between Relative Cerebral Blood Volume Dynamics Following Chemoradiation and Increased Progression-Free Survival in Newly Diagnosed IDH Wild-Type MGMT Promoter Methylated Glioblastoma With Measurable Disease.

Background and Purpose: While relative cerebral blood volume (rCBV) may be diagnostic and prognostic for survival in glioblastoma (GBM), changes in rCBV during chemoradiation in the subset of newly diagnosed GBM with subtotal resection and the impact of MGMT promoter methylation status on survival have not been explored. This study aimed to investigate the association between rCBV response, MGMT methylation status, and progression-free (PFS) and overall survival (OS) in newly diagnosed GBM with measurable enhancing lesions. Methods: 1,153 newly diagnosed IDH wild-type GBM patients were screened and 53 patients (4.6%) had measurable post-surgical tumor (>1mL). rCBV was measured before and after patients underwent chemoradiation. Patients with a decrease in rCBV >10% were considered rCBV Responders, while patients with an increase or a decrease in rCBV <10% were considered rCBV Non-Responders. The association between change in enhancing tumor volume, change in rCBV, MGMT promotor methylation status, and PFS or OS were explored. Results: A decrease in tumor volume following chemoradiation trended towards longer OS (p=0.12; median OS=26.8 vs. 16.3 months). Paradoxically, rCBV Non-Responders had a significantly improved PFS compared to Responders (p=0.047; median PFS=9.6 vs. 7.2 months). MGMT methylated rCBV Non-Responders exhibited a significantly longer PFS compared to MGMT unmethylated rCBV Non-Responders (p<0.001; median PFS=0.5 vs. 7.1 months), and MGMT methylated rCBV Non-Responders trended towards longer PFS compared to methylated rCBV Responders (p=0.089; median PFS=20.5 vs. 13.8 months). Conclusions: This preliminary report demonstrates that in newly diagnosed IDH wild-type GBM with measurable enhancing disease after surgery (5% of patients), an enigmatic non-response in rCBV was associated with longer PFS, particularly in MGMT methylated patients.

Risk of COVID-19 Transmission Aboard Aircraft: An Epidemiological Analysis Based on the National Health Information Platform.

OBJECTIVES: This study aims to investigate the risk of COVID-19 transmission on aircraft. METHODS: We obtained data on all international flights to Lanzhou, China, from June 1, 2020, to August 1, 2020, through the Gansu Province National Health Information Platform and the official website of the Gansu Provincial Center for Disease Control and Prevention. We then performed the statistical analysis. RESULTS: Three international flights arrived in Lanzhou. The flights had a total of 700 passengers, of whom 405 (57.9%) were male, and 80 (11.4%) were children under the age of 14 years. Twenty-seven (3.9%) passengers were confirmed to have COVID-19. Confirmed patients were primarily male (17, 65.4%) with a median age of 27.0 years. Most confirmed cases were seated in the middle rows of economy class or near public facility areas such as restrooms and galleys. The prevalence of COVID-19 did not differ between passengers sitting in the window, aisle, or middle seats. However, compared with passengers sitting in the same row up to 2 rows behind a confirmed case, passengers seated in the 2 rows in front of a confirmed case were at a slightly higher risk of being infected. CONCLUSIONS: COVID-19 may be transmitted during a passenger flight, although there is still no direct evidence.

Visualization of tumor heterogeneity and prediction of isocitrate dehydrogenase mutation status for human gliomas using multiparametric physiologic and metabolic MRI.

This study aimed to differentiate isocitrate dehydrogenase (IDH) mutation status with the voxel-wise clustering method of multiparametric magnetic resonance imaging (MRI) and to discover biological underpinnings of the clusters. A total of 69 patients with treatment-naïve diffuse glioma were scanned with pH-sensitive amine chemical exchange saturation transfer MRI, diffusion-weighted imaging, fluid-attenuated inversion recovery, and contrast-enhanced T1-weighted imaging at 3 T. An unsupervised two-level clustering approach was used for feature extraction from acquired images. The logarithmic ratio of the labels in each class within tumor regions was applied to a support vector machine to differentiate IDH status. The highest performance to predict IDH mutation status was found for 10-class clustering, with a mean area under the curve, accuracy, sensitivity, and specificity of 0.94, 0.91, 0.90, and 0.91, respectively. Targeted biopsies revealed that the tissues with labels 7-10 showed high expression levels of hypoxia-inducible factor 1-alpha, glucose transporter 3, and hexokinase 2, which are typical of IDH wild-type glioma, whereas those with labels 1 showed low expression of these proteins. In conclusion, A machine learning model successfully predicted the IDH mutation status of gliomas, and the resulting clusters properly reflected the metabolic status of the tumors.

Diffusion MRI is an early biomarker of overall survival benefit in IDH wild-type recurrent glioblastoma treated with immune checkpoint inhibitors.

BACKGROUND: Diffusion MRI estimates of the apparent diffusion coefficient (ADC) have been shown to be useful in predicting treatment response in patients with glioblastoma (GBM), with ADC elevations indicating tumor cell death. We aimed to investigate whether the ADC values measured before and after treatment with immune checkpoint inhibitors (ICIs) and the changes in these ADC values could predict overall survival (OS) in patients with recurrent IDH wild-type GBM. METHODS: Forty-four patients who met the following inclusion criteria were included in this retrospective study: (i) diagnosed with recurrent IDH wild-type GBM and treated with either pembrolizumab or nivolumab and (ii) availability of diffusion data on pre- and post-ICI MRI. Tumor volume and the median relative ADC (rADC) with respect to the normal-appearing white matter within the enhancing tumor were calculated. RESULTS: Median OS among all patients was 8.1 months (range, 1.0-22.5 months). Log-rank test revealed that higher post-treatment rADC was associated with a significantly longer OS (median, 10.3 months for rADC ≥ 1.63 versus 6.1 months for rADC < 1.63; P = .02), whereas tumor volume, pretreatment rADC, and changes in rADC after treatment were not significantly associated with OS. Cox regression analysis revealed that post-treatment rADC significantly influenced OS (P = .02, univariate analysis), even after controlling for age and sex (P =.01, multivariate analysis), and additionally controlling for surgery after ICI treatment (P = .045, multivariate analysis). CONCLUSIONS: Elevated post-treatment rADC may be an early imaging biomarker for OS benefits in GBM patients receiving ICI treatment.