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Objective: To evaluate the diagnostic performance and reliability of the medial temporal lobe atrophy (MTA) scale in patients with Alzheimer's disease. Methods: A systematic literature search of MEDLINE and EMBASE databases was performed to select studies that evaluated the diagnostic performance or reliability of MTA scale, published up to January 21, 2021. Pooled estimates of sensitivity and specificity were calculated using a bivariate random-effects model. Pooled correlation coefficients for intra- and interobserver agreements were calculated using the random-effects model based on Fisher's Z transformation of correlations. Meta-regression was performed to explain the study heterogeneity. Subgroup analysis was performed to compare the diagnostic performance of the MTA scale and hippocampal volumetry. Results: Twenty-one original articles were included. The pooled sensitivity and specificity of the MTA scale in differentiating Alzheimer's disease from healthy control were 74% (95% CI, 68–79%) and 88% (95% CI, 83–91%), respectively. The area under the curve of the MTA scale was 0.88 (95% CI, 0.84–0.90). Meta-regression demonstrated that the difference in the method of rating the MTA scale was significantly associated with study heterogeneity (p = 0.04). No significant difference was observed in five studies regarding the diagnostic performance between MTA scale and hippocampal volumetry (p = 0.40). The pooled correlation coefficients for intra- and interobserver agreements were 0.85 (95% CI, 0.69–0.93) and 0.83 (95% CI, 0.66–0.92), respectively. Conclusions: Our meta-analysis demonstrated a good diagnostic performance and reliability of the MTA scale in Alzheimer's disease. Key Points: • The pooled sensitivity and specificity of the MTA scale in differentiating Alzheimer's disease from healthy control were 74% and 88%, respectively. • There was no significant difference in the diagnostic performance between MTA scale and hippocampal volumetry. • The reliability of MTA scale was excellent based on the pooled correlation coefficient for intra- and interobserver agreements. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD). Methods: A systematic literature search of the MEDLINE and EMBASE databases was performed, since their inception up to July 28, 2020. Pooled diagnostic yield of diffusion-weighted imaging was calculated using DerSimonian-Laird random-effects model. Pooled diagnostic performance of DWI (sensitivity, specificity, and area under the curve) in diagnosing sCJD among patients with rapidly progressive dementia was calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed. Results: Fifteen original articles with a total of 1144 patients with sCJD were included. The pooled diagnostic yield was 91% (95% confidence interval [CI], 86 to 94%); summary sensitivity, 91% (95% CI, 84 to 95%); and specificity, 97% (95% CI, 94 to 99%). The area under the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI, 0.97–0.99). Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on DWI followed by striatum, thalamus, and cerebellum. Subgroup analysis and meta-regression demonstrated significant heterogeneity among the studies associated with the reference standards used for diagnosis of sCJD. Conclusions: DWI showed excellent diagnostic value in diagnosis of sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia. Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on diffusion-weighted imaging followed by striatum, thalamus, and cerebellum. Key Points: • The pooled diagnostic yield of diffusion-weighted imaging in sporadic Creutzfeldt-Jakob disease was 91%. • The diagnostic performance of diffusion-weighted imaging for predicting sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia was excellent, with pooled sensitivity, 91%, and specificity, 97%. • Simultaneous involvement in the neocortex and striatum was most commonly seen on diffusion-weighted imaging (60%), followed by the neocortex without striatum (30%), thalamus (21%), cerebellum (8%), and striatum without neocortex (7%). [ABSTRACT FROM AUTHOR]

Abstract: We derived the mole fraction of H2 in the troposphere of Titan from an analysis of the H2–N2 dimer S0(0) rotational transition seen near 355cm−1 in spectra recorded by the Composite Infra-Red Spectrometer (CIRS) on the Cassini spacecraft between March 2006 and February 2007. We find a globally-averaged value of (9.6±2.4)×10−4, consistent with the earlier determination based on the Voyager IRIS dataset, and with the value obtained from the Gas Chromatograph Mass Spectrometer (GCMS) experiment on the Huygens probe, but a factor of ∼4 lower than that measured by the Ion and Neutral Mass Spectrometer (INMS) in the 1025–1475km altitude range. Interestingly, the latitudinal distribution of H2 appears to be non-uniform, with a mole fraction above 50°N in excess of 30–70% (±40%) relatively to the globally-averaged value. Such a non-uniform distribution is unexpected since H2 is thought to be chemically inert in the lower atmosphere of Titan. It is proposed that the observed enhancement in the north polar region is caused by downwelling occurring during the winter season in the polar vortex. This interpretation is dependent on the existence of a vertical gradient of the H2 concentration in the stratosphere, as suggested by the differences between the INMS values and those measured by GCMS and CIRS, although such a gradient is not consistent with the present understanding of dynamics and chemistry in Titan''s atmosphere. [Copyright &y& Elsevier]

Removal of hydrophobic organic contaminants (HOCs) using surfactant-enhanced electrokinetic (EK) method was studied in a model system. Kaolinite and phenanthrene were selected as a model clay soil and a representative HOC, respectively. Three different types of surfactants: APG (alkyl polyglucoside), Brij30 (polyoxyethylene-4-lauryl ether), and SDS (sodium dodecyl sulfate), were used to enhance the solubility of HOC. Characteristics of surfactants, such as surface tension, HOC solubility, and biodegradability were measured. In the case of Brij30 solution, phenanthrene solubility was higher than that of others. After 4 days, APG and Brij30 were degraded by 65% and 26% of the initial amount, respectively. However, degradation of SDS was hardly detected. Electroosmotic flow (EOF) of Brij30 solution was lower than others when the 0.1M NaCl was used as electrolyte. Addition of the acetate buffer solution increased the EOF of Brij30 solution and enhanced removal of phenanthrene. Among three different surfactants tested, APG showed the highest removal efficiency. [Copyright &y& Elsevier]

Objectives: To evaluate diagnostic performance of loss of nigral hyperintensity on SWI in differentiating idiopathic Parkinson's disease (IPD) or primary parkinsonism (including IPD and Parkinson-plus syndrome) from healthy/disease controls. Methods: MEDLINE/PubMed and EMBASE databases were searched to identify original articles investigating the diagnostic performance of loss of nigral hyperintensity for differentiating IPD or primary parkinsonism from healthy/disease control, up to April 3, 2020. Pooled sensitivity and specificity were calculated using a bivariate random-effects model. The proportion of nondiagnostic scan, inter- and intrareader agreement, and the proportion of concordance between clinical laterality and imaging asymmetry were also pooled. Results: Nineteen articles covering 2125 patients (1097 with primary parkinsonism, 1028 healthy/disease controls) were included. For discrimination between IPD and healthy/disease controls, pooled sensitivity and specificity were 0.96 (95% CI, 0.91–0.98) and 0.95 (95% CI, 0.92–0.97). For discrimination between primary parkinsonism and healthy/disease controls, pooled sensitivity and specificity were 0.87 (95% CI, 0.75–0.94) and 0.93 (95% CI, 0.85–0.97). The pooled proportion of non-diagnostic scans on random-effects modeling was 4.2% (95% CI, 2.5–6.9%). The inter- and intrareader agreements were almost perfect, with the pooled coefficients being 0.84 (95% CI, 0.78–0.89) and 0.96 (95% CI, 0.89–0.99), respectively. The pooled proportion of concordant cases was 69.3% (95% CI, 58.4–78.4%). Conclusions: Loss of nigral hyperintensity on SWI can differentiate IPD or primary parkinsonism from a healthy/disease control group with high accuracy. However, the proportion of non-diagnostic scans is not negligible and must be taken into account. Key Points: • For discrimination between idiopathic Parkinson's disease and healthy/disease controls, pooled sensitivity and specificity of loss of nigral hyperintensity were 0.96 and 0.95. • For discrimination between primary parkinsonism and healthy/disease controls, pooled sensitivity and specificity of loss of nigral hyperintensity were 0.87 and 0.93. • The pooled proportion of non-diagnostic scans on random-effects modeling was 4.2%. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic performance and interobserver agreement of the callosal angle and Evans' index in idiopathic normal pressure hydrocephalus (iNPH). Methods: A systematic search of MEDLINE and EMBASE was performed to find studies assessing the diagnostic performance or interobserver agreement of the callosal angle and Evans' index in iNPH. Pooled sensitivity and specificity of the two radiologic indices were calculated. The area under the curve (AUC) was obtained based on a hierarchical summary receiver operating characteristic curve. The diagnostic performances of both radiologic indices were compared in subgroup analysis. To evaluate interobserver agreement, the pooled correlation coefficient was calculated. Results: Ten original articles (874 patients) were included. The pooled sensitivity and specificity of the callosal angle in the diagnosis of iNPH were 91% (95% CI, 86–94%) and 93% (95% CI, 89–96%), respectively. The pooled sensitivity and specificity of Evans' index were 96% (95% CI, 47–100%) and 83% (95% CI, 77–88%), respectively. Subgroup analysis demonstrated a significant higher specificity of the callosal angle than that of Evans' index (p < 0.01). The AUC of the callosal angle and Evans' index were 0.97 (95% CI, 0.95–0.98) and 0.87 (95% CI, 0.84–0.90), respectively. The pooled correlation coefficients for the callosal angle and Evans' index were 0.92 (95% CI, 0.82–0.96) and 0.92 (95% CI, 0.83–0.97), respectively. Conclusions: Our meta-analysis demonstrated a high performance of the callosal angle in the diagnosis of iNPH. Evans' index showed reasonable diagnostic performance with high sensitivity but low specificity. Interobserver agreements were excellent in both radiologic indices. Key Points: • Callosal angle showed high diagnostic performance in idiopathic normal pressure hydrocephalus. • Evans' index showed reasonable diagnostic performance with high sensitivity but low specificity. • Interobserver agreements were excellent in both callosal angle and Evans' index. [ABSTRACT FROM AUTHOR]

Human preformed antibodies (Abs), anti-galactose-alpha-1,3-galactose (Gal) and anti- N -glycolylneuraminic acid (Neu5Gc), can react with porcine antigens of wild-type pigs. To provide basic population data of the Abs for potential application in clinical xenotransplantation, we developed enzyme-linked immunosorbent assay methods and investigated the serum titers of anti-Gal and anti-Neu5Gc Abs, including immunoglobulin (Ig) M and IgG along with its subclasses, in humans. Anti-Gal and anti-Neu5Gc Abs serum titers were measured in 380 healthy Korean adults using the in-house enzyme-linked immunosorbent assays. The frequency and median values of anti-Gal and anti-Neu5Gc were measured, and their class and subclass distribution were evaluated. The detection frequencies of anti-Gal were 99.2%, 95.0%, 23.2%, 94.5%, 12.4%, and 3.4% for IgM, IgG, IgG1, IgG2, IgG3, and IgG4, respectively. The detection frequencies of anti-Neu5Gc Abs were 87.4%, 96.6%, 1.6%, 46.3%, 0.0%, and 0.0% for IgM, IgG, IgG1, IgG2, IgG3, and IgG4, respectively. The median values of anti-Gal IgM (1001.6 ng/mL) and IgG (1198.3 ng/mL) were significantly higher than those of anti-Neu5Gc Abs (IgM, 328.4 ng/mL; IgG, 194.7 ng/mL; P <. 001). IgG2 titers of both anti-Gal and anti-Neu5Gc Abs correlated better with the IgG class than the titers of other IgG subclasses. The titers of anti-Gal Abs were higher than those of anti-Neu5Gc Abs. IgG2 was the main IgG subclass in both anti-Gal and anti-Neu5Gc Abs. Variation in the titers of anti-Gal or anti-Neu5Gc Abs may partly explain the biological and immunologic changes that occur in recipients of xenotransplants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the real-world diagnostic performance of high-resolution susceptibility-weighted imaging (HR-SWI) and investigate whether the reader's predictions can be used to find cases where HR-SWI finding and final clinical diagnosis matched. Methods: This retrospective study enrolled patients with suspected Parkinsonism (n = 48) or volunteers with other intracranial pathologies (n = 31) who underwent brain magnetic resonance imaging (MRI) including HR-SWI, which was used to evaluate nigrosome 1 (NG1). All patients with suspected Parkinsonism underwent N-3-fluoropropyl-2-carbomethoxy-3-4-iodophenyl nortropane (FP-CIT) positron emission tomography and a clinical diagnosis was made by a neurologist. The HR-SWI data were qualitatively analyzed by two independent reviewers. A consensus reading was performed and a diagnostic confidence score was assigned. According to final clinical diagnosis, diagnostic sensitivity, specificity, and accuracy were calculated. Receiver operating characteristic (ROC) curve analysis was used to examine whether the diagnostic confidence score could be used to identify HR-SWI finding—final clinical diagnosis matched cases. Results: Of the 48 patients with suspected Parkinsonism, 31 were diagnosed with idiopathic Parkinson's disease, and three with multiple system atrophy. The remaining 14 patients were included in the disease control group. Of the 31 volunteers, 10 subjects were excluded due to possibility of nigrostriatal degeneration and finally 21 subjects were enrolled as controls with non-Parkinsonism pathology (non-PD control). After consensus reading, 25 subjects were classified as true positive and 28 as true negative, according to HR-SWI findings. The calculated diagnostic sensitivity, specificity, and accuracy were 73.5%, 80.0%, and 76.8%, respectively. With using diagnostic concordance score, the area under the ROC curve for the detection of concordance case was 0.83 (95% CI: 0.72–0.91, p < 0.05). Conclusion: The diagnostic performance of NG1 detection using HR-SWI with 3T MRI was within acceptable range. Using the reader's diagnostic confidence could be helpful to find cases which HR-SWI finding and final clinical conclusion match. So HR-SWI may be of added value in the evaluation of suspected Parkinsonism. [ABSTRACT FROM AUTHOR]

Objectives: A combination of T2/FLAIR mismatch sign and advanced imaging parameters may improve the determination of molecular subtypes of diffuse lower-grade glioma. We assessed the diagnostic value of adding the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) to the T2/FLAIR mismatch sign for differentiation of the IDH mutation or 1p/19q codeletion.Materials and Methods: Preoperative conventional, diffusion-weighted, and dynamic susceptibility contrast imaging were performed on 110 patients with diffuse lower-grade gliomas. The study population was classified into three groups using molecular subtype, namely IDH mutation and 1p/19q codeletion (IDHmut-Codel), IDH wild type (IDHwt) and IDH mutation and no 1p/19q codeletion (IDHmut-Noncodel). T2/FLAIR mismatch sign and the histogram parameters of apparent diffusion coefficient (ADC) and normalised cerebral blood volume (nCBV) values were assessed. A multivariate logistic regression model was constructed to distinguish IDHmut-Noncodel from IDHmut-Codel and IDHwt and from IDHwt, and the performance was compared with that of single parameters using the area under the receiver operating characteristics curve (AUC).Results: Positive visual T2/FLAIR mismatch sign and higher nCBV skewness were significant variables to distinguish IDHmut-Noncodel from the other two groups (AUC, 0.88; 95% CI, 0.81-0.96). A lower ADC10 was a significant variable for distinguishing IDHmut-Noncodel from the IDHwt group (AUC, 0.75; 95% CI, 0.62-0.89). Adding ADC or CBV histogram parameters to T2/FLAIR mismatch sign improved performance in distinguishing IDHmut-Noncodel from the other two groups (AUC 0.882 vs. AUC 0.810) or from IDHwt (AUC 0.923 vs. AUC 0.868).Conclusions: The combination of the T2/FLAIR mismatch sign with ADC or CBV histogram parameters can improve the identification of IDHmut-Noncodel diffuse lower-grade gliomas, which can be easily applied in clinical practice.Key Points: • The combination of the T2/FLAIR mismatch sign with the ADC or CBV histogram parameters can improve the identification of IDHmut-Noncodel diffuse lower-grade gliomas. • The multivariable model showed a significantly better performance for distinguishing the IDHmut-Noncodel group from other diffuse lower-grade gliomas than the T2/FLAIR mismatch sign alone or any single parameter. • The IDHmut-Noncodel type was associated with intermediate treatment outcomes; therefore, the identification of IDHmut-Noncodel diffuse lower-grade gliomas could be helpful for determining the clinical approach. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether clinical condition, imaging session, and locations affect repeatability of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) in the brain.Materials and Methods: Three APTw MRI data sets were acquired, involving two intrasession scans and one intersession scan for 19 healthy, 15 glioma, and 12 acute stroke adult participants (mean age 53.8, 54.6, and 68.5, respectively) on a 3T MR scanner. The mean APTw signals from five locations in healthy brain (supratentorial and infratentorial locations) and from entire tumor and stroke lesions (supratentorial location) were calculated. The within-subject coefficient of variation (wCV) and intraclass correlation coefficient (ICC) were calculated for each clinical conditions, image sessions, and anatomic locations. Differences in APTw signals between sessions were analyzed using repeated-measures analysis of variance.Results: The ICC and wCV were 0.96 (95% confidence interval [CI], 0.91-0.99) and 16.1 (12.6-21.3) in glioma, 0.93 (0.82-0.98) and 15.0 (11.4-20.6) in stroke, and 0.84 (0.72-0.91) and 34.0 (28.7-41.0) in healthy brain. There were no significant differences in APTw signal between three sessions, irrespective of disease condition and location. The ICC and wCV were 0.85 (0.68-0.94) and 27.4 (21.8-35.6) in supratentorial, and 0.44 (- 0.18 to 0.76) and 32.7 (25.9 to 42.9) in infratentorial locations. There were significant differences in APTw signal between supra- (mean, 0.49%; 95% CI, 0.38-0.61) and infratentorial locations (1.09%, 0.98-1.20; p < 0.001).Conclusion: The repeatability of APTw signal was excellent in supratentorial locations, while it was poor in infratentorial locations due to severe B0 inhomogeneity and susceptibility which affects MTR asymmetry.Key Points: • In supratentorial locations, APTw MRI showed excellent intrasession and intersession repeatability in brains of healthy controls and patients with glioma, as well as in stroke-affected regions. • APTw MRI showed excellent repeatability in supratentorial locations, but poor repeatability in infratentorial locations. • Considering poor repeatability in the infratentorial locations, the use of APTw MRI in longitudinal assessment in infratentorial locations is not indicated. [ABSTRACT FROM AUTHOR]

Using the LACE data from Apollo 17 we have found measured neon densities consistent with the 20Ne surface number densities reported by Cook et al. (2013) for normal conditions, terminator surface densities of 3 (±1.5) × 103 cm−3. These values are almost an order of magnitude less than those reported by Benna et al. (2015) for CME conditions. Using a Monte Carlo model and assuming the normal solar wind and a photoionization lifetime for Ne of 300 days, our result was more consistent with the Benna (2015) result than our measured result. Two lunations showed an increase in Ne during the night, consistent with the simulation, but two of the lunations showed a decrease in surface number density through the night. We have shown that explaining the Ne distribution is not as simple as assuming dynamic equilibrium with the solar wind and an exosphere accommodated to the local surface temperature. • LACE data from Apollo 17 have been reanalyzed. • The 20Ne nightside surface number densities are 3 (±1.5) × 103 cm−3. • Ne cannot be modeled assuming dynamic equilibrium with the solar wind. [ABSTRACT FROM AUTHOR]

Purpose: Grading of brain gliomas is of clinical importance, and noninvasive molecular imaging may help differentiate low- and high-grade gliomas. We aimed to evaluate the diagnostic performance of amide proton transfer-weighted (APTw) MRI for differentiating low- and high-grade gliomas on 3-T scanners. Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to March 28, 2018. Original articles evaluating the diagnostic performance of APTw MRI for differentiating low- and high-grade gliomas were selected. The pooled sensitivity and specificity were calculated using a bivariate random-effects model. A coupled forest plot and a hierarchical summary receiver operating characteristic curve were obtained. Heterogeneity was investigated using Higgins inconsistency index (I2) test. Meta-regression was performed. Results: Ten original articles with a total of 353 patients were included. High-grade gliomas showed significantly higher APT signal intensity than low-grade gliomas. The pooled sensitivity and specificity for the diagnostic performance of APTw MRI for differentiating low-grade and high-grade gliomas were 88% (95% CI, 77–94%) and 91% (95% CI, 82–96%), respectively. Higgins I2 statistic demonstrated heterogeneity in the sensitivity (I2 = 68.17%), whereas no heterogeneity was noted in the specificity (I2 = 44.84%). In meta-regression, RF saturation power was associated with study heterogeneity. Correlation coefficients between APT signal intensity and Ki-67 cellular proliferation index ranged from 0.430 to 0.597, indicating moderate correlation. All studies showed excellent interobserver agreement. Conclusions: Although heterogeneous protocols were used, APTw MRI demonstrated excellent diagnostic performance for differentiating low- and high-grade gliomas. APTw MRI could be a reliable technique for glioma grading in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether fast scanned MRI using a 1.5-T scanner is a reliable method for the detection and characterization of acute ischemic stroke in comparison with conventional MRI.Methods: From May 2015 to June 2016, 862 patients (FLAIR, n = 482; GRE, n = 380; MRA, n = 190) were prospectively enrolled in the study, with informed consent and under institutional review board approval. The patients underwent both fast (EPI-FLAIR, ETL-FLAIR, TR-FLAIR, EPI-GRE, parallel-GRE, fast CE-MRA) and conventional MRI (FLAIR, GRE, time-of-flight MRA, fast CE-MRA). Two neuroradiologists independently assessed agreements in acute and chronic ischemic hyperintensity, hyperintense vessels (FLAIR), microbleeds, susceptibility vessel signs, hemorrhagic transformation (GRE), stenosis (MRA), and image quality (all MRI), between fast and conventional MRI. Agreements between fast and conventional MRI were evaluated by generalized estimating equations. Z-scores were used for comparisons of the percentage agreement among fast FLAIR sequences and fast GRE sequences and between conventional and fast MRA.Results: Agreements of more than 80% were achieved between fast and conventional MRI (ETL-FLAIR, 96%; TR-FLAIR, 97%; EPI-GRE, 96%; parallel-GRE, 98%; fast CE-MRA, 86%). ETL- and TR-FLAIR were significantly superior to EPI-FLAIR in the detection of acute ischemic hyperintensity and hyperintense vessels, while parallel-GRE was significantly superior to EPI-GRE in the detection of susceptibility vessel sign (p value < 0.05 for all). There were no significant differences in the other scores and image qualities (p value > 0.05).Conclusions: Fast MRI at 1.5 T is a reliable method for the detection and characterization of acute ischemic stroke in comparison with conventional MRI.Key Points: • Fast MRI at 1.5 T may achieve a high intermethod reliability in the detection and characterization of acute ischemic stroke with a reduction in scan time in comparison with conventional MRI. [ABSTRACT FROM AUTHOR]

Abstract Glutamate excitotoxicity is a pathology in which excessive glutamate can cause neuronal damage and degeneration. It has also been linked to secondary injury mechanisms in traumatic spinal cord injury. Conventional bioanalytical techniques used to characterize glutamate levels in vivo, such as microdialysis, have low spatiotemporal resolution, which has impeded our understanding of this dynamic event. In this study, we present an amperometric biosensor fabricated using a simple direct ink writing technique for the purpose of in vivo glutamate monitoring. The biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multi-walled carbon nanotubes, and a conductive polymer on a flexible substrate. The sensor is designed to measure extracellular dynamics of glutamate and other potential biomarkers during a traumatic spinal cord injury event. Here we demonstrate good sensitivity and selectivity of these rapidly prototyped implantable biosensors that can be inserted into a spinal cord and measure extracellular glutamate concentration. We show that our biosensors exhibit good flexibility, linear range, repeatability, and stability that are suitable for future in vivo evaluation. Highlights • Commercially available nanomaterials mixed to create printable biosensor. • Implantable glutamate biosensors fabricated using direct writing. • Platinum nanoparticle-based devices performed as well as MEMS-fabricated biosensors. • Amperometry at low potential significantly improved the sensitivity and selectivity. • Ex vivo glutamate monitoring demonstrated using rat spinal cord sections. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the imaging features of isocitrate dehydrogenase (IDH) mutant glioma and to assess the diagnostic performance of magnetic resonance imaging (MRI) for prediction of IDH mutation in patients with glioma.Methods: A systematic search of Ovid-MEDLINE and EMBASE up to 10 October 2017 was conducted to find relevant studies. The search terms combined synonyms for 'glioma', 'IDH mutation' and 'MRI'. Studies evaluating the imaging features of IDH mutant glioma and the diagnostic performance of MRI for prediction of IDH mutation in patients with glioma were selected. The pooled summary estimates of sensitivity and specificity and their 95% confidence intervals (CIs) were calculated using a bivariate random-effects model. The results of multiple subgroup analyses are reported.Results: Twenty-eight original articles in a total of 2,146 patients with glioma were included. IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high apparent diffusion coefficient (ADC) value and low relative cerebral blood volume (rCBV) value. For the meta-analysis that included 18 original articles, the summary sensitivity was 86% (95% CI, 79%-91%) and the summary specificity was 87% (95% CI, 78-92%). In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate magnetic resonance spectroscopy (MRS) [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities.Conclusions: IDH mutant glioma consistently demonstrated less aggressive imaging features than IDH wild-type glioma. Despite the variety of different MRI techniques used, MRI showed the potential to non-invasively predict IDH mutation in patients with glioma. 2-Hydroxyglutarate MRS shows higher pooled sensitivity than other imaging modalities.Key Points: • IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high ADC value, and low rCBV value. • The diagnostic performance of MRI for prediction of IDH mutation in patients with glioma is within a clinically acceptable range, the summary sensitivity was 86% (95% CI, 79-91%) and the summary specificity was 87% (95% CI, 78-92%). • In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate MRS [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities. [ABSTRACT FROM AUTHOR]

Objectives Gross total resection for glioblastoma (GBM) has been associated with better prognosis. However, it is not always feasible, and the threshold for the extent of resection required for better prognosis has been controversial. Therefore, we compared the survival and clinical outcomes of patients with GBM who had undergone partial resection (PR) or biopsy. Methods Of the 110 patients, 32 and 78, who had undergone PR and biopsy, respectively, were enrolled to identify any differences in clinical outcomes. No differences were found in patient demographics between the 2 groups, except for tumor location and mean tumor volume (P = 0.02 and P < 0.01, respectively). Propensity score matching between the PR and biopsy groups was performed, in which 20 patients each in the PR and biopsy groups were matched. Results The overall survival (OS) and progression-free survival (PFS) did not differ significantly between the PR and biopsy groups (P = 0.84 and P = 0.48, respectively). After propensity score matching, the differences in OS and PFS between the 2 groups were still not statistically significant (P = 0.51 and P = 0.75, respectively). The hazard ratios for OS and PFS for the PR group compared with biopsy were 0.98 and 0.73, respectively; however, the difference was not statistically significant (P = 0.96 and P = 0.39, respectively). The surgical complication rate was greater in the PR group (14 of 32; 43.7%) than in the biopsy group (9 of 78; 11.5%; P < 0.01). Conclusions PR failed to improve survival compared with biopsy for patients with GBM. Moreover, the surgical complication rate in the PR group was greater than that in the biopsy group. Highlights • GTR of GBM is not always feasible; research is lacking on the beneficial effects on survival of PR GBM compared with biopsy. • We performed PSM to match the PR and biopsy groups to decrease the potential bias and make the 2 groups more comparable. • OS and PFS did not differ significantly between the PR and biopsy groups. • After PSM, the OS and PFS differences between the groups was not statistically significant. • The surgical complication rate was higher in the PR group (43.7%) than in the biopsy group (11.5%). [ABSTRACT FROM AUTHOR]

Although advanced magnetic resonance imaging (MRI) techniques provide useful information for the differential diagnosis of intra-axial mass-like lesions, the specific diagnostic role of multimodal MRI over conventional magnetic resonance imaging (CMRI) alone in the differential diagnosis of mass-like lesions from a large heterogeneous cohort has not been studied. In this study, we aimed to determine the added value of a joint approach of diffusion-weighted imaging (DWI) and dynamic-susceptibility-contrast perfusion imaging (DSC-PWI) for diagnosis of intra-axial mass-like lesions, comparing them with CMRI alone. Furthermore, we performed these evaluations in a manner simulating clinical practice. Our institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 1038 patients with intra-axial mass-like lesions were retrospectively recruited according to their histological and clinico-radiological diagnoses made between January 2005 and December 2014. All patients underwent CMRI, DWI and DSC-PWI. The diagnostic accuracy and confidence in diagnosing each type of intra-axial mass-like lesions, and for differentiating the intra-axial brain tumors from non-neoplastic lesions, were compared according to the MRI protocols. The disease-specific sensitivity of joint approach differed according to specific disease entities in diagnosing each disease category. Joint approach provided the best diagnostic accuracy for discriminating intra-axial brain tumors from non-neoplastic lesions, with high diagnostic accuracy (95.3–96.7%), specificity (82–84.0%), positive-predictive-value (97.0–97.3%), and negative-predictive-value (84.8–92.7%), with the reader’s confidence values being significantly improved over those on CMRI alone (all p-values < 0.001). In conclusion, joint approach of DWI, DSC-PWI to CMRI helps to differentiate non-neoplastic lesions from intra-axial brain tumors, and improves diagnostic confidence compared with CMRI alone. The benefit from the combined imaging differs for each disease category; thus joint approach needs to be customized according to clinical suspicion. [ABSTRACT FROM AUTHOR]

Objectives: Differentiation of glioma from brain metastasis is clinically crucial because it affects the clinical outcome of patients and alters patient management. Here, we present a systematic review and meta-analysis of the currently available data on perfusion magnetic resonance imaging (MRI) for differentiating glioma from brain metastasis, assessing MRI protocols and parameters.Methods: A computerised search of Ovid-MEDLINE and EMBASE databases was performed up to 3 October 2017, to find studies on the diagnostic performance of perfusion MRI for differentiating glioma from brain metastasis. Pooled summary estimates of sensitivity and specificity were obtained using hierarchical logistic regression modelling. We conducted meta-regression and subgroup analyses to explain the effects of the study heterogeneity.Results: Eighteen studies with 900 patients were included. The pooled sensitivity and specificity were 90% (95% CI, 84-94%) and 91% (95% CI, 84-95%), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.96 (95% CI, 0.94-0.98). The meta-regression showed that the percentage of glioma in the study population and the study design were significant factors affecting study heterogeneity. In a subgroup analysis including patients with glioblastoma only, the pooled sensitivity was 92% (95% CI, 84-97%) and the pooled specificity was 94% (95% CI, 85-98%).Conclusions: Although various perfusion MRI techniques were used, the current evidence supports the use of perfusion MRI to differentiate glioma from brain metastasis. In particular, perfusion MRI showed excellent diagnostic performance for differentiating glioblastoma from brain metastasis.Key Points: • Perfusion MRI shows high diagnostic performance for differentiating glioma from brain metastasis. • The pooled sensitivity was 90% and pooled specificity was 91%. • Peritumoral rCBV derived from DSC is a relatively well-validated. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas.Materials and Methods: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNRmax and APTmax) and 90% histogram values (TNR90 and APT90).Results: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APTmax (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNRmax (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05).Conclusions: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism.Key Points: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the value of multiparametric MRI for determination of early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma.Methods: A computerized search of Ovid-MEDLINE and EMBASE up to 1 October 2017 was performed to find studies on the diagnostic performance of multiparametric MRI for differentiating true progression from pseudoprogression. The beginning search date was not specified. Pooled estimates of sensitivity and specificity were obtained using hierarchical logistic regression modeling. We performed meta-regression and sensitivity analyses to explain the effects of the study heterogeneity.Results: Nine studies including 456 patients were included. Pooled sensitivity and specificity were 84 % (95 % CI 74-91) and 95 % (95 % CI 83-99), respectively. Area under the hierarchical summary receiver operating characteristic curve was 0.95 (95 % CI 0.92-0.96). Meta-regression showed true progression in the study population, the mean age and the reference standard were significant factors affecting heterogeneity.Conclusion: Multiparametric MRI may be used as a potential surrogate endpoint for assessment of early treatment response, especially in the differentiation of true progression from pseudoprogression. However, based on the current evidence, monoparametric and multiparametric MRI perform equally in the clinical context. Further evaluation will be needed.Key Points: • Multiparametric MRI shows high diagnostic performance for early treatment response in glioblastoma. • Multiparametric MRI could differentiate true progression from pseudoprogression in newly diagnosed glioblastoma. • The normalized rCBV derived from DSC was the most commonly used parameter. [ABSTRACT FROM AUTHOR]

Electrospun WO 3 nanofibers (NFs) with hierarchically interconnected porosity (HP_WO 3 NFs) are designed by using dual sacrificial templates including zero-dimensional (0D) polystyrene (PS) colloids and one-dimensional (1D) multi-walled carbon nanotubes (MWCNTs). Multi-dimensionally interconnected pore-loaded structures offer much enhanced surface area and abundant gas penetration pathway into the inner sensing layers, which are essential requirements for effective gas adsorption-desorption reactions, fast gas diffusion, and high gas response. Moreover, such porous WO 3 NFs are homogeneously decorated by Pt nanoparticles (Apo-Pt) encapsulated in a protein nanocage, i.e., apoferritin, which enables uniform catalyst sensitization in interior and exterior of highly gas accessible NFs. The HP_WO 3 NFs sensitized by Apo-Pt (Apo-Pt@HP_WO 3 NFs) exhibited highly selective and sensitive acetone response (R air /R gas  = 10.80 ± 0.06 @ 1 ppm) under high humidity atmosphere (90% RH). To investigate the potential suitability as exhaled breath analyzers, we tested three sensor arrays consisting of mesoporous WO 3 NFs templated by MWCNTs (MP_WO 3 NFs), HP_WO 3 NFs, and Apo-Pt@HP_WO 3 NFs. The result revealed that targeted acetone molecules were clearly classified against six different interfering molecules (H 2 S, C 7 H 8 , C 2 H 5 OH, CO, NH 3 and CH 4 ) through principle component analysis (PCA), confirming excellent acetone selectivity of the designed sensor arrays. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long‐term survival of the graft. MD‐3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM‐1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long‐term survival of adult wild‐type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD‐3 mAb and maintenance with anti‐CD154 mAb and sirolimus. Methods: Eleven rhesus monkeys were assigned to three groups. Group 1 (n = 4) involved treatment with MD‐3 induction, short‐term (<4 months) administration of anti‐CD154 mAb, and maintenance therapy with sirolimus. Group 2 (n = 4) involved treatment with MD‐3 induction and long‐term maintenance therapy with anti‐CD154 mAb and sirolimus. Group 3 (n = 3) involved only maintenance therapy with anti‐CD154 mAb and sirolimus. Diabetes was induced in monkeys by streptozotocin, and pig islets (61 000‐112 000 IEQ/kg for each transplant; up to 280 000 IEQ/kg per recipient) were infused through the portal vein. The in vivo functional potency of the isolated islets was tested by minimal model transplant in streptozotocin‐induced diabetic NOD/SCID mice, and the mean AUC of blood glucose level divided by the number of follow‐up days was calculated. Results: The islet grafts survived more than 6 months (between 225 and 727 days) in nine of 12 transplants of MD‐3‐treated groups 1 and 2, whereas in the absence of MD‐3 mAb, survival was <40 days. In three transplants of the MD‐3‐treated Group 2, functional graft survival was only for 104, 125, and 154 days. In these cases, a retrospective analysis suggested that the relatively short survival duration was associated with the relatively high AUC value in the NOD/SCID bioassay. Notably, when retransplantation was performed in Group 3, blood glucose control was extended up to 956 days, which was supported by MD‐3 mAb‐based suppression of adaptive immunity. No replication of cytomegalovirus genes was observed. Conclusions: Long‐term survival of pig islet xenografts and successful retransplantation were achieved with MD‐3 mAb‐based immunosuppression regimen in this pig‐to‐monkey transplantation model. It should be emphasized that these encouraging results were achieved following the transplantation of islets from pigs that had not been genetically modified. Considering that it is possible to further substantially reduce the destruction of grafted islet using genetically modified pig islet, the islet requirement could be reduced and much longer graft survival can be achieved. [ABSTRACT FROM AUTHOR]

Abstract: Background: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti‐CD154 monoclonal antibody (mAb) in pig‐to‐non‐human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti‐CD40 (2C10R4) mAb‐based studies have not been reported. Methods: Nine streptozotocin (STZ)‐induced diabetic rhesus monkeys were transplanted with adult porcine islets isolated from designated pathogen‐free (DPF) miniature pigs. They were treated with anti‐CD40 mAb‐based immunosuppressive regimen and were divided into 3 groups: anti‐CD40 only group (n = 2), belatacept group (anti‐CD40 mAb+belatacept, n = 2), and tacrolimus group (anti‐CD40 mAb+tacrolimus, n = 5). All monkeys received anti‐thymocyte globulin (ATG), cobra venom factor (CVF), adalimumab, and sirolimus. Blood glucose levels (BGL) and serum porcine C‐peptide concentrations were measured. Humoral and cellular immune responses were assessed by ELISA and ELISPOT, respectively. Liver biopsy and subsequent immunohistochemistry were conducted. Results: All animals restored normoglycemia immediately after porcine islet transplantation and finished the follow‐up without any severe adverse effects except for one animal (R092). Most animals maintained their body weight. Median survival, as defined by a serum porcine C‐peptide concentration of >0.15 ng/mL, was 31, 27, and 60 days for anti‐CD40 only, belatacept, and tacrolimus groups, respectively. Anti‐αGal IgG levels in serum and the number of interferon‐γ secreting T cells in peripheral blood mononuclear cells did not increase in most animals. Conclusion: These results showed that anti‐CD40 mAb combined with tacrolimus was effective in prolonging porcine islet graft survival, but anti‐CD40 mAb was not as effective as anti‐CD154 mAb in terms of preventing early islet loss. [ABSTRACT FROM AUTHOR]

Purpose: Distinguishing non-neoplastic pituitary stalk lesions (non-NPSLs) from neoplastic pituitary stalk lesions (NPSLs) is a major concern in guiding treatment for a thickened pituitary stalk. Our study aimed to aid provide preoperative diagnostic assistance by combining clinical and magnetic resonance imaging (MRI) findings to distinguish non-NPSLs from NPSLs. Materials and methods: We recruited 158 patients with thickened pituitary stalk lesions visible on MRI. Laboratory findings included hypopituitarism, diabetes insipidus (DI), and hyperprolactinemia. MR images were assessed for anterior–posterior thickness (mm), diffuse pituitary stalk thickening, cystic changes, a high T1 signal, and glandular or extrasellar involvement. A diagnostic model was developed using a recursive partitioning logistic regression analysis. The model was validated in an independent dataset comprising 63 patients, and its diagnostic performance was compared with that of the original radiological reports. Results: A univariate analysis found significant associations of DI (P = 0.006), absence of extrasellar involvement (P = 0.002), and lower stalk thickness (P = 0.031) with non-NPSLs. A diagnostic model was created using the following parameters (in order of priority): 1) lack of extrasellar involvement, 2) stalk thickness < 5.3 mm, and 3) presence of DI. The diagnostic performance (area under the curve; AUC) of this model in the independent set was 0.813, representing a significant improvement over the original radiological reports (AUC: 0.713, P = 0.029). Conclusion: The joint diagnostic approach based on clinical and imaging-based factors robustly distinguished non-NPSLs from NPSLs. This approach could guide treatment strategies and prevent unnecessary surgery in patients with non-NPSL. [ABSTRACT FROM AUTHOR]

Objectives: To compare three-dimensional high-resolution magnetic resonance imaging (3D HR-MRI) and digital subtraction angiography (DSA) for diagnosing and evaluating stenosis in the entire circle of Willis.Methods: The study included 516 intracranial arteries from 43 patients with intracranial artery stenosis (ICAS) who underwent both 3D HR-MRI and DSA within 1 month. Two readers independently diagnosed atherosclerosis, dissection, moyamoya disease and vasculitis, rated their diagnostic confidence for each vessel and measured the luminal diameters. Reference standard was made from clinico-radiologic diagnosis. Diagnostic accuracy, diagnostic confidence, the degree of stenosis and luminal diameter were assessed and compared between both modalities.Results: For atherosclerosis, 3D HR-MRI showed better diagnostic accuracy (P = .03-.003), sensitivity (P = .006-.01) and positive predictive value (P ≤ .001-.006) compared to DSA. Overall, the readers were more confident of their diagnosis of ICAS when using 3D HR-MRI (reader 1, P ≤ .001-.007; reader 2, P ≤ .001-.015). 3D HR-MRI showed similar degree of stenosis (P > .05) and higher luminal diameter (P < .05) compared to DSA.Conclusions: 3D HR-MRI might be useful to evaluate atherosclerosis, with better diagnostic confidence and comparable stenosis measurement compared to DSA in the entire circle of Willis.Key Points: • 3D HR-MRI showed better diagnostic accuracy for atherosclerosiscompared to DSA • 3D HR-MRI showed better overall diagnostic confidence for stenosiscompared to DSA • 3D HR-MRI and DSA showed similar degree of stenosis. [ABSTRACT FROM AUTHOR]

Background The use of different 3D T1-weighted magnetic resonance (T1 MR) imaging protocols induces image incompatibility across multicenter studies, negating the many advantages of multicenter studies. A few methods have been developed to address this problem, but significant image incompatibility still remains. Thus, we developed a novel and convenient method to improve image compatibility. Methods W-score standardization creates quality reference values by using a healthy group to obtain normalized disease values. We developed a protocol-specific w-score standardization to control the protocol effect, which is applied to each protocol separately. We used three data sets. In dataset 1, brain T1 MR images of normal controls (NC) and patients with Alzheimer’s disease (AD) from two centers, acquired with different T1 MR protocols, were used (Protocol 1 and 2, n = 45/group). In dataset 2, data from six subjects, who underwent MRI with two different protocols (Protocol 1 and 2), were used with different repetition times, echo times, and slice thicknesses. In dataset 3, T1 MR images from a large number of healthy normal controls (Protocol 1: n = 148, Protocol 2: n = 343) were collected for w-score standardization. The protocol effect and disease effect on subjects' cortical thickness were analyzed before and after the application of protocol-specific w-score standardization. Results As expected, different protocols resulted in differing cortical thickness measurements in both NC and AD subjects. Different measurements were obtained for the same subject when imaged with different protocols. Multivariate pattern difference between measurements was observed between the protocols. Classification accuracy between two protocols was nearly 90%. After applying protocol-specific w-score standardization, the differences between the protocols substantially decreased. Most importantly, protocol-specific w-score standardization reduced both univariate and multivariate differences in the images while maintaining the AD disease effect. Compared to conventional regression methods, our method showed the best performance for in terms of controlling the protocol effect while preserving disease information. Conclusions Protocol-specific w-score standardization effectively resolved the concerns of conventional regression methods. It showed the best performance for improving the compatibility of a T1 MR post-processed feature, cortical thickness. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations. Materials and methods: In this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student’s t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy. Results: The mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis. Conclusion: Multiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function. [ABSTRACT FROM AUTHOR]

Chemical sensors have been essential components in recent years due to the gathering attention in environmental monitoring and healthcare. In this review, the authors comprehensively highlight recent progresses on the 1D chemiresistive-type sensors based on semiconductor metal oxides (SMOs) and optical-type sensors, which are prepared by electrospinning technique. In the part of chemiresistive-type sensors, diverse synthesis techniques for 1D SMO nanofibrous structure are presented with controlled microstructure and surface morphology. In addition, unique functionalization routes of emerging nanocatalysts encapsulated by bio-inspired templates are described for the next generation catalyst on the 1D SMO nanofibers (NFs). For the optical-type sensors, new classes of 1D NFs employing specific absorption and emission properties are introduced. In particular, diverse 1D NF-based colorimetric and fluorescence sensors as well as Raman and surface-enhanced Raman scattering sensors are covered in the view point of material preparation and optical sensing properties. Finally, the authors prospect future research directions to overcome current limitations and challenges to achieve high performance chemical sensors. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence of cerebrovascular stenosis and white matter lesions on preoperative magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) in liver transplantation candidates.Methods: This retrospective study included 1,460 consecutive patients with liver cirrhosis (LC) who underwent MRA with/without brain MRI for pretransplantation evaluation. These patients were matched with 5,331 controls using propensity scores, and the prevalences of significant cerebrovascular stenosis and white matter lesions were compared.Results: A matched analysis of 1,264 pairs demonstrated that the prevalence of significant stenosis was comparable between LC patients and controls (2.2% vs. 1.4%, P = 0.143). LC and most of LC-related parameters were not associated with stenosis. Significant white matter lesions were more common in LC patients (2.8% vs. 1.3%, P = 0.036). A high Model for End-Stage Liver Disease (MELD) score (OR 1.11, CI 1.03-1.20, P = 0.008, for infarction; OR 1.1, CI 1.04-1.16, P = 0.001, for haemorrhage) and stroke history (OR 179.06, CI 45.19-709.45, P < 0.001) were predictors of perioperative stroke.Conclusions: LC patients and control subjects demonstrated similar cerebrovascular stenosis prevalences, whereas white matter lesions were more common in LC patients. A high MELD score and stroke history contribute as predictors of perioperative stroke.Key Points: • Routine preoperative MR imaging in liver transplantation candidates may not be necessary. • Liver cirrhosis patients and control subjects had similar prevalences of significant cerebrovascular stenosis. • Liver cirrhosis and cirrhosis-related parameters were not correlated with significant cerebrovascular stenosis. • Significant white matter lesions were more frequent in liver cirrhosis patients. [ABSTRACT FROM AUTHOR]

Objective: To determine if perfusion in surgical cavity wall enhancement (SCWE) obtained in early post-treatment MR imaging can stratify time-to-progression (TTP) in glioblastoma. Materials and methods: This study enrolled 60 glioblastoma patients with more than 5-mm-thick SCWEs as detected on contrast-enhanced MR imaging after concurrent chemoradiation therapy. Two independent readers categorized the shape and perfusion state of SCWEs as nodular or non-nodular and as having positive or negative perfusion compared with the contralateral grey matter on arterial spin labeling (ASL). The perfusion fraction on ASL within the contrast-enhancing lesion was calculated. The independent predictability of TTP was analyzed using the Kaplan-Meier method and Cox proportional hazards modelling. Results: The perfusion fraction was higher in the non-progression group, significantly for reader 2 (P = 0.03) and borderline significantly for reader 1 (P = 0.08). A positive perfusion state and (P = 0.02) a higher perfusion fraction of the SCWE were found to become an independent predictor of longer TTP (P = 0.001 for reader 1 and P < 0.001 for reader 2). The contrast enhancement pattern did not become a TTP predictor. Conclusion: Assessment of perfusion in early post-treatment MR imaging can stratify TTP in patients with glioblastoma for adjuvant temozolomide therapy. Positive perfusion in SCWEs can become a predictor of a longer TTP. [ABSTRACT FROM AUTHOR]

Objectives: To determine if gemistocytic grade II astrocytoma (GemA) and its MR imaging characteristics are associated with a shorter time-to-progression (TTP) compared with non-gemistocytic grade II astrocytoma (non-GemA).Materials and Methods: We enrolled 78 patients who were followed up more than 5 years (29 pathologically proven GemA and 49 non-GemA) during a 10-year period. Contrast-enhanced T1-weighted, diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC), and MR spectroscopy (MRS) and clinical data were retrospectively reviewed. Clinical and MR imaging features were analyzed as possible prognostic factors of high-grade transformation, and multivariate analysis of TTP was performed using Cox proportional modeling.Results: GemA showed more frequent high-grade features than non-GemA, including diffusion restriction (P < .001), increased choline/creatine (P = .02), and increased choline/NAA ratio (P = .015). Patients with GemA had a significantly shorter median TTP (53.1 vs 68 months; P < .001). A gemistocytic histopathology (hazard ratio = 3.42; P = .015) and low ADC (hazard ratio = 3.61; P = .001) were independently associated with a shorter TTP.Conclusions: GemA can present with MR imaging findings mimicking high-grade glioma at initial diagnosis and transforms to high-grade disease earlier than non-GemA. Low ADC on DWI might be useful in stratifying the risk of progression in patients with grade II astrocytoma.Key Points: • Gemistocytic grade II astrocytoma (GemA) showed more frequent high-grade features than non-GemA. • Patients with GemA had a significantly shorter median TTP than non-GemA. • Gemistocytic histopathology and low ADC were independently associated with shorter TTP. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine whether diffusion and perfusion imaging parameters demonstrate different diagnostic values for predicting pseudoprogression between glioblastoma subgroups stratified by O6-mythylguanine-DNA methyltransferase (MGMT) promoter methylation status.Methods: We enrolled seventy-five glioblastoma patients that had presented with enlarged contrast-enhanced lesions on magnetic resonance imaging (MRI) one month after completing concurrent chemoradiotherapy and undergoing MGMT promoter methylation testing. The imaging parameters included 10 or 90 % histogram cutoffs of apparent diffusion coefficient (ADC10), normalized cerebral blood volume (nCBV90), and initial area under the time signal-intensity curve (IAUC90). The results of the areas under the receiver operating characteristic curve (AUCs) with cross-validation were compared between MGMT methylation and unmethylation groups.Results: MR imaging parameters demonstrated a trend toward higher accuracy in the MGMT promoter methylation group than in the unmethylation group (cross-validated AUCs = 0.70-0.95 and 0.56-0.87, respectively). The combination of MGMT methylation status with imaging parameters improved the AUCs from 0.70 to 0.75-0.90 for both readers in comparison with MGMT methylation status alone. The probability of pseudoprogression was highest (95.7 %) when nCBV90 was below 4.02 in the MGMT promoter methylation group.Conclusions: MR imaging parameters could be stronger predictors of pseudoprogression in glioblastoma patients with the methylated MGMT promoter than in patients with the unmethylated MGMT promoter.Key Points: • The glioblastoma subgroup was stratified according to MGMT promoter methylation status. • Diagnostic values of diffusion and perfusion parameters for predicting pseudoprogression were compared. • Imaging parameters showed higher diagnostic accuracy in the MGMT promoter methylation group. • Imaging parameters were independent to MGMT promoter methylation status for predicting pseudoprogression. • Imaging biomarkers might demonstrate different diagnostic values according to MGMT promoter methylation. [ABSTRACT FROM AUTHOR]

Objectives: To determine the added value of amide proton transfer (APT) imaging to conventional and perfusion MRI for differentiating tumour progression (TP) from the treatment-related effect (TE) in patients with post-treatment glioblastomas.Methods: Sixty-five consecutive patients with enlarging contrast-enhancing lesions following concurrent chemoradiotherapy were assessed using contrast-enhanced T1-weighted MRI (CE-T1WI), 90th percentile histogram parameters of normalized cerebral blood volume (nCBV90) and APT asymmetry value (APT90). Diagnostic performance was determined using the area under the receiver operating characteristic curve (AUC) and cross validations.Results: There were statistically significant differences in the mean APT90 between the TP and the TE groups (3.87-4.01 % vs. 1.38-1.41 %; P < .001). Compared with CE-T1WI alone, the addition of APT90 to CE-T1WI significantly improved cross-validated AUC from 0.58-0.74 to 0.89-0.91 for differentiating TP from TE. The combination of CE-T1WI, nCBV90 and APT90 resulted in greater diagnostic accuracy for differentiating TP from TE than the combination of CE-T1WI and nCBV90 (cross-validated AUC, 0.95-0.97 vs. 0.84-0.91). The inter-reader agreement between the expert and trainee was excellent for the measurements of APT90 (intraclass correlation coefficient, 0.94).Conclusion: Adding APT imaging to conventional and perfusion MRI improves the diagnostic performance for differentiating TP from TE.Key Points: • APT imaging could provide a reliable distinction between TP and TE • Adding APT imaging to CE-T1WI improved the diagnostic accuracy versus CE-T1WI alone • Multimodal imaging using CE-T1WI, perfusion and APT imaging led to accurate diagnosis • The inter-reader agreement of APT histogram parameters was excellent. [ABSTRACT FROM AUTHOR]

Background and Purpose: Quantitative measurements, as well as qualitative characterizations, of the vessel walls of the small intracranial arteries became clinically available and reliable beyond the resolution limit of 1.5 T high-resolution magnetic resonance imaging (HR-MRI) with the development of 3 T HR-MRI. We present the quantitative dissection findings of spontaneous and unruptured acute intracranial artery dissection (SID) using 3 T HR-MRI and investigate the differences between each cerebral artery.Methods: Twenty-eight lesions (anterior cerebral artery = 6; middle cerebral artery = 4; vertebral artery = 18) from 26 patients (17 male and 9 female patients; mean age = 47 years; age range = 32-74 years) with presumptive diagnoses of SID were included. The diagnosis was determined based on the clinical features, findings on luminal angiography (such as digital subtraction angiography, computed tomography, or magnetic resonance angiography), and HR-MRI. HR-MRI was performed within one month from onset. The neuroimaging indices (maximal outer diameter and area, remodeling index and modified remodeling index, and wall thickness and wall area index) of aneurysmal dilatation and the signal intensities of the intramural hematomas were rated using HR-MRI. The results were compared between each cerebral artery.Results: The maximal outer diameter and area, remodeling index and modified remodeling index, and wall thickness index and length were significantly different between anterior and posterior circulation (P < .05). The mean relative signal intensities of the intramural hematoma showed consistent values, regardless of the cerebral arteries, without significant difference.Conclusions: Neuroimaging indices of aneurysmal dilatation may be adjunctive indicators in the evaluation of SID. [ABSTRACT FROM AUTHOR]

The influence of iron oxide, FeO x , on Pt for CO oxidation was investigated. A film of FeO x , nominally 0.8-nm thick, was added to a Pt/Al 2 O 3 catalyst by Atomic Layer Deposition. The film was found to wet the Pt surface after oxidation at 773 K and 973 K, as shown by aberration-corrected, transmission electron microscopy. In-situ infrared spectra and CO chemisorption measurements showed that the addition of the FeO x greatly suppressed CO adsorption but enhanced CO oxidation rates due to FeO x -Pt interfaces. The FeO x layer also improved the stability of the catalyst by mitigating the sintering of Pt particles at 973 K. • Atomic-scale FeO x overlayer augments the CO oxidation activity and thermal stability of the Pt/Al 2 O 3 at 973 K. • TEM and CO chemisorption shows that FeO x overlayer wets the Pt surface and greatly suppresses CO adsorption on Pt. • In-situ infrared spectra shows that CO oxidation occurs without CO adsorption on FeO x -overcoated Pt catalyst. • FeO x overlayers near Pt enhances CO oxidation rates through the FeO x -Pt interfaces. [ABSTRACT FROM AUTHOR]

Background Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates ( NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. Methods Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University ( SNU) miniature pigs with immunosuppression by anti-thymoglobulin ( ATG), cobra venom factor, anti- CD154 monoclonal antibody ( mAb), and sirolimus. CD4+ CD25high CD127low autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40- CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. Results After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40- CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. Conclusions Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to- NHP islet xenotransplantation setting. [ABSTRACT FROM AUTHOR]

Background: Although high-resolution magnetic resonance imaging (HR-MRI) has been used as a strong imaging method for diagnosing intracranial vertebral artery dissection (IVAD), the diagnosis is sometimes challenging because a dissection has geometric changes in the natural course. The radiologic features may change or disappear over time, which makes the diagnosis confusing. Our study was to present radiological findings according to the stages in spontaneous and unruptured, IVAD on 3T HR-MRI and to guide the age estimation of IVAD with the distinguishing findings according to the stages. Methods: From January 2011 to July 2014, the 41 vertebral arteries (M:F = 18: 12; age range 32-67 years) were retrospectively enrolled. Spontaneous, unruptured IVAD was diagnosed if it had a clear onset based on clinical and radiological findings. The stages were classified as acute (0-3 days), early subacute (3-10 days), late subacute (10-60 days) and chronic stage (>60 days; recovery and nonrecovery groups) according to the time intervals from symptom onset, based on the prior published studies. HR-MR findings were assessed and compared in the intimal flap, double lumen, aneurysmal dilatation (maximal outer diameter, maximal wall thickness, wall thickness index and remodeling index), intramural hematoma (relative signal intensity) and vessel wall enhancement according to the stages with qualitative and quantitative methods. Two radiologists analyzed the HR-MR findings with consensus reading. Results: IVAD was classified into acute (n = 6), early subacute (n = 8), late subacute (n = 16) and chronic (n = 11) stages. HR-MR dissection findings such as intimal flap, double lumen, aneurysmal dilatation and intramural hematoma significantly decreased from the earlier stages to the chronic stage (p < 0.05). The quantitative indices in aneurysmal dilatation and the relative signal intensity of intramural hematoma showed significant higher values in the earlier stages followed by a significant decrease in the chronic stage recovery group (p < 0.05). The degree of vessel wall enhancement was higher in the earlier stage and decreased in the chronic stage (p < 0.05), but mild vessel wall enhancement was identified 900 days after symptom onset. Conclusion: The 3T HR-MRI reveals the vessel wall characteristics and provides distinguishing findings between earlier stages and the chronic stage in spontaneous and unruptured IVAD. Characterization of these radiological findings according to stages may assist with the age estimation of the dissection and may help to understand IVAD as a whole. [ABSTRACT FROM AUTHOR]

Objectives: To determine the diagnostic superiority of parametric response mapping of apparent diffusion coefficient (ADCPR) for predicting glioblastoma treatment response, compared to single time point measurement.Methods: Fifty post-treatment glioblastoma patients were enrolled. ADCPR was calculated from serial apparent diffusion coefficient (ADC) maps acquired before and at the time of first detection of an enlarged contrast-enhancing lesion on voxel-by-voxel basis. The percentage-decrease in ADCPR and tenth percentile histogram cutoff value of ADC (ADC10) were compared at subsequent 3-month and 1-year follow-ups.Results: The percentage-decrease in ADCPR was significantly higher in the progression group (mean = 33.2-38.3 %) than in the stable-response group (mean = 9.7 %) at 3 months follow-up (corrected p < 0.001 for both readers). ADCPR significantly improved area under the receiver operating characteristic curve from 0.67 to 0.88 (corrected p = 0.037) and from 0.70 to 0.92 (corrected p = 0.020) for both readers, respectively, compared to ADC10 at 3-month follow-up, but did not significantly improve at 1-year follow-up. The inter-reader agreement was higher for ADCPR than ADC10 (intraclass correlation coefficient, 0.93 versus 0.86).Conclusion: Voxel-based ADCPR appears to be a superior imaging biomarker than ADC, particularly for predicting early tumour progression in patients with glioblastoma.Key Points: • Treatment response pattern of glioblastoma was evaluated using voxel-based ADCPR and ADC10. • Voxel-based ADCPR was more accurate in predicting treatment response pattern than ADC10. • Inter-reader agreement was higher in ADCPR calculation than in ADC10 calculation. • Voxel-based ADCPR can be a predictor of early treatment response pattern for glioblastoma. [ABSTRACT FROM AUTHOR]

Background: Although the prognosis of ischemic stroke is highly dependent on the lesion location, it has rarely been quantitatively utilized. We investigated the usefulness of regional extent of ischemic lesion (rEIL) predicting the improvement of visual field defect (VFD) in patients with posterior cerebral artery infarction. Methods: The rEILs were measured in each individual cortex after transforming the lesions to a standard atlas. Significant improvement of VFD was tentatively defined as 20% improvement at 3 months after stroke. The performances of clinical and imaging variables predicting significant improvement were measured by support vector machine. The maximum performance of variables predicting the significant improvement was compared between subgroups of variables (clinical, baseline severity and lesion volume) and the effect of adding rEIL to those subgroups of variables was evaluated. Results: A total of 35 patients were enrolled in this study. Left PCA infarct, MR-time from onset, rEILs in the lingual, calcarine, and cuneus cortices were good prognostic indicators of hemi-VFD (performance for predicting the significant improvement: 72.8±11.8%, 66.1±11.2%, respectively). A combination of the rEILs of each cortical subregions demonstrated a better predictive performance for hemi-VFD (83.8±9.5%) compared to a combination of clinical variables (72.8±11.8; p<0.001), baseline severity (63.0±11.9%; p<0.001), or lesion volume (62.6±12.7%; p<0.001). Adding a rEIL to other variables improved the prognostic prediction for hemi-VFD (74.4±11.6% to 91.3±7.7%; p<0.001). Conclusions: An estimation of rEIL provides useful information regarding the ischemic lesion location. rEIL accurately predicts the significant improvement of VFD and enhances the prediction power when combined with other variables. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the accuracy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MR imaging for distinguishing tumor recurrence from post-treatment effect as alternatives to dynamic-susceptibility contrast-enhanced (DSC) perfusion MR imaging when the DSC image is uninterpretable. Materials and Methods: This retrospective study was approved by our institutional review board. Seventy one post-treatment glioblastoma patients who showed enlarged contrast-enhancing lesions on follow-up MR images after concurrent chemoradiotherapy and uninterpretable DSC images for corresponding enhancing lesions, underwent additional DWI and DCE MR imaging. The primary outcome was the frequency of interpretable DWI and DCE MR cases in these 71 patients. The secondary outcome was the area under the receiver operating characteristic curve (AUC) of DWI and DCE imaging parameters for distinguishing tumor recurrence from post-treatment effect in selected patients with interpretable DWI and DCE images. The imaging parameters were quantified as 10% cumulative histogram cutoff of apparent diffusion coefficient (ADC10) and 90% cumulative histogram cutoff of initial area under the time signal intensity curve (IAUC90). The AUCs were cross-validated by using leave-one-out method. Results: Of the 71 patients, the uninterpretable DSC images were associated with treatment-related hemorrhage within the corresponding enhancing lesions (n = 54, 76.1%) and a near skull base location (n = 17, 23.9%). The frequencies of interpretable DWI and DCE image were 51 (71.8%) and 59 (83.1%) of the 71 cases with uninterpretable DSC images, respectively. Of the 45 selected patients with interpretable DWI and DCE images, the combination of DWI with DCE imaging showed a superior diagnostic performance than DWI or DCE imaging alone for differentiating tumor recurrence from post-treatment effect (cross-validated AUC: 0.78 versus 0.55 and 0.73 for reader 1; cross-validated AUC: 0.78 versus 0.53 and 0.75 for reader 2, respectively). Cross-validated accuracy of the single and combined imaging parameters also showed the highest for the combination of DWI with DCE MR imaging (72.9% for reader 1; 72.5% for reader 2) and the lowest for DWI alone (54.0% for reader 1; 56.4% for reader 2). Inter-reader agreement for DCE imaging was higher than that for DWI (intraclass correlation coefficient: 0.95 versus 0.87). Conclusion: DCE MR imaging could be a superior and more reproducible imaging biomarker than DWI for differentiating tumor recurrence from post-treatment effect in patients with post-treatment glioblastoma when DSC MR images are not interpretable. [ABSTRACT FROM AUTHOR]

Tailoring of semiconducting metal oxide nanostructures, which possess controlled pore size and concentration, is of great value to accurately detect various volatile organic compounds in exhaled breath, which act as potential biomarkers for many health conditions. In this work, we have developed a very simple and robust route for controlling both the size and distribution of spherical pores in electrospun WO3 nanofibers (NFs) via a sacrificial templating route using polystyrene colloids with different diameters (200 nm and 500 nm). A tentacle-like structure with randomly distributed pores on the surface of electrospun WO3 NFs were achieved, which exhibited improved surface area as well as porosity. Porous WO3 NFs with enhanced surface area exhibited high gas response (Rair/Rgas = 43.1 at 5 ppm) towards small and light H2S molecules. In contrast, porous WO3 NFs with maximized pore diameter showed a high response (Rair/Rgas = 2.8 at 5 ppm) towards large and heavy acetone molecules. Further enhanced sensing performance (Rair/Rgas = 65.6 at 5 ppm H2S) was achieved by functionalizing porous WO3 NFs with 0.1 wt% non-oxidized graphene (NOGR) flakes by forming a Schottky barrier (ΔΦ = 0.11) at the junction between the WO3 NFs (Φ = 4.56 eV) and NOGR flakes (Φ = 4.67 eV), which showed high potential for the diagnosis of halitosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Brain tumor cellularity has been assessed by using apparent diffusion coefficient (ADC). However, the ADC value might be influenced by both perfusion and true molecular diffusion, and the perfusion effect on ADC can limit the reliability of ADC in the characterization of tumor cellularity, especially, in hypervascular brain tumors. In contrast, the IVIM technique estimates parameter values for diffusion and perfusion effects separately. The purpose of our study was to compare ADC and IVIM for differentiating among glioblastoma, metastatic tumor, and primary CNS lymphoma (PCNSL) focusing on diffusion-related parameter. Materials and Methods: We retrospectively reviewed the data of 128 patients with pathologically confirmed glioblastoma (n = 55), metastasis (n = 31), and PCNSL (n = 42) prior to any treatment. Two neuroradiologists independently calculated the maximum IVIM-f (fmax) and minimum IVIM-D (Dmin) by using 16 different b-values with a bi-exponential fitting of diffusion signal decay, minimum ADC (ADCmin) by using 0 and 1000 b-values with a mono-exponential fitting and maximum normalized cerebral blood volume (nCBVmax). The differences in fmax, Dmin, nCBVmax, and ADCmin among the three tumor pathologies were determined by one-way ANOVA with multiple comparisons. The fmax and Dmin were correlated to the corresponding nCBV and ADC using partial correlation analysis, respectively. Results: Using a mono-exponential fitting of diffusion signal decay, the mean ADCmin was significantly lower in PCNSL than in glioblastoma and metastasis. However, using a bi-exponential fitting, the mean Dmin did not significantly differ in the three groups. The mean fmax significantly increased in the glioblastomas (reader 1, 0.103; reader 2, 0.109) and the metastasis (reader 1, 0.105; reader 2, 0.107), compared to the primary CNS lymphomas (reader 1, 0.025; reader 2, 0.023) (P < .001 for each). The correlation between fmax and the corresponding nCBV was highest in glioblastoma group, and the correlation between Dmin and the corresponding ADC was highest in primary CNS lymphomas group. Conclusion: Unlike ADC value derived from a mono-exponential fitting of diffusion signal, diffusion-related parametric value derived from a bi-exponential fitting with separation of perfusion effect doesn’t differ among glioblastoma, metastasis, and PCNSL. [ABSTRACT FROM AUTHOR]

Background To understand humoral responses elicited after xenotransplantation, we compared the induction of anti-non-Gal antibodies vs. anti-Gal antibodies in non-human primates ( NHPs) after intraportal porcine islet transplantation ( PITX). Methods Anti-Gal and anti-non-Gal IgGs were analyzed in serial plasma samples of NHP recipients after PITX by enzyme-linked immunosorbent assay ( ELISA) using synthetic Gal and by flow cytometry using α-1,3-galactosyltransferase gene knockout ( GTKO) porcine endothelial cells, respectively. Anti-non-Gal IgG was detected in some recipients after PITX. The specificity of anti-non-Gal IgG was investigated by two-dimensional electrophoresis of the protein extract from GTKO porcine endothelial cells, Western blot analysis of recipient pre- and post- PITX plasma, and MALDI- TOF/ TOF mass spectrometry, revealing albumin, a non-glycosylated protein in the serum supplement of the islets solution, as a putative antigen for anti-non-Gal IgG. The binding of IgG antibodies to human albumin ( HA), bovine albumin ( BA), porcine albumin ( PA), and Gal was compared by ELISA in pre- and post- PITX plasma samples of 30 NHP recipients subjected to intraportal PITX, which were grouped according to the use of CD40- CD154 blockade and sirolimus. Results One of the immunoblot-matched spots was identified as BA by mass spectrometry. By ELISA, the plasma used in the immunoblot analysis revealed strong IgG binding to BA and PA, but not to HA. Anti- PA, anti- BA, and anti-Gal antibodies in NHP recipients 1 month after PITX were detected in 5 (100%), 3 (60%), and 5 (100%), respectively, of the 5 recipients receiving various immunosuppression ( IS) without CD40- CD154 blockade (group I) and in 0 (0%), 0 (0%), and 4 (16%), respectively, of the 25 recipients receiving IS with CD40- CD154 blockade and sirolimus (group II). This finding revealed significant differences between the groups (P < 0.0001, P = 0.0011 and P = 0.0013, respectively). Interestingly, among 15 recipients achieving graft survival longer than 1 month in group II, anti- PA IgG was detected in only 1 recipient (6.7%) 180 days after PITX. However, an increase in anti-Gal IgG was detected in 7 recipients (46.7%) despite maintenance IS with anti- CD154 and sirolimus. This result indicates that anti-Gal IgG is more frequently induced than anti- PA IgG (P = 0.0352). Moreover, induction IS with anti- CD154 and sirolimus suppressed anti-Gal IgG, but not anti- PA and anti- BA IgG, responses in sensitized recipients given a repeat transplantation. Conclusions In NHP recipients of PITX, anti- PA and anti- BA IgG antibodies are elicited by porcine serum included as a supplement in porcine islet preparation. IS including CD40- CD154 blockade and sirolimus suppresses these antibody responses in naïve recipients, but not in sensitized recipients. The elicitation of anti-xenogenic albumin antibodies, a humoral response to a model protein antigen, is distinct from that of anti-Gal antibodies, a response to carbohydrate antigen. [ABSTRACT FROM AUTHOR]

To develop an international consensus regarding the appropriate conditions for undertaking clinical trials in xenocorneal transplantation, here we review specific ethical, logistical, scientific, and regulatory issues regarding xenocorneal transplantation, and propose guidelines for conduct of clinical xenocorneal transplantation trials. These proposed guidelines are modeled on the published consensus statement of the International Xenotransplantation Association regarding recommended guidelines for conduct of clinical islet xenotransplantation. It is expected that this initial consensus statement will be revised over time in response to scientific advances in the field, and changes in the regulatory framework based on accumulating clinical experience. [ABSTRACT FROM AUTHOR]

[Display omitted] • A practice-scale sandwich-type honeycomb catalyst discharge reactor was developed. • High-throughput without significant pressure drop condition was obtained. • 94.5 % IPA was removed using the honeycomb catalyst discharge reactor. • Uniform discharge was created using Pd/Al2O3/honeycomb combined with plasma. • Byproducts formation and IPA oxidation pathways were elucidated. A practical-scale sandwich-type honeycomb catalyst reactor incorporating non-thermal plasma was developed for the high-throughput removal of isopropanol (IPA) from air. The Pd/γ-Al 2 O 3 /honeycomb catalyst was fabricated by coating a cordierite monolith with γ-alumina powder on which to support the palladium (Pd). The supported catalyst showed good activity and the combination of the honeycomb structure with plasma produced a uniform plasma inside the catalyst chamber. The influence of different parameters, including the energy density (SIE), humidity, initial concentration, and flow rate, on the plasma characteristics and IPA removal efficiency was investigated. The results showed that the SIE has the strongest effect on the IPA removal efficiency. The efficiency of IPA removal was 94.5% and the CO2 selectivity was 85% for an SIE of 180 J/L. Using optical emission spectroscopy, we found that the increased formation of atomic oxygen and reactive species plays an essential role in the oxidation of IPA by plasma catalysis. The main byproducts were identified by GC-MS, which indicated that acetone is the major liquid product. A plausible reaction mechanism for the plasma-catalytic oxidation of IPA is proposed based on the intermediates and byproducts. [ABSTRACT FROM AUTHOR]

FSGS is the second most common cause of idiopathic NS in children. It often progresses to ESRD and commonly recurs after KT. To investigate the risk factors and the prognosis of recurrence in pediatric idiopathic FSGS in Korea, retrospective review of 43 KT in 38 children with idiopathic FSGS of last two decades was conducted. The patients presented at the median age of 5.1 yr (range 1.1-13.8 yr) and received KT 5.7 yr later (range 1.3-17.6 yr). FSGS recurred in 20 allografts immediately after transplantation, only in those who presented with NS but not in those who presented with AUA. The risk factors for recurrence were age of onset >5 yr and progression to ESRD within six yr but not sooner than 18 months. CR was achieved in 13 patients with FSGS recurrence and sustained in nine without subsequent relapse over a median of six and a half yr (0.6-20.7 yr). Pediatric idiopathic FSGS presenting with NS recurred in more than half of patients after transplantation. Interestingly, more rapid progression within less than 18 months did not predict recurrence. To identify high-risk patients of recurrence, an international cooperative study would be necessary. [ABSTRACT FROM AUTHOR]

Background There is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF Tacrolimus) in solid organ transplantation. Methods A prospective, randomized study of 126 de novo renal transplant patients was conducted to compare the efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n = 63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition. Crossover study was carried out in 66 patients at 6 months. Results On Day 10, 117 patients completed PK profiles (54 GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C0 (9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL, P = 0.80) but significantly higher dose-normalized Cmax (309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg, P < 0.001). The dose-normalized AUC0–12 tended to be higher in the GEN tacrolimus than in the REF tacrolimus group (1513.4 ± 935.4 versus 1262.5 ± 593.5 ng.h/mL/mg/kg, P = 0.084). Because of this early and high Cmax with a rapid decline in GEN tacrolimus concentration, the trough concentration was maintained lower than that of REF tacrolimus. At 6 months, GEN tacrolimus showed equivalent dose-normalized AUC0–12 (1882.2 ± 935.6 versus 1718.1 ± 946.3 ng.h/mL/mg/kg, P = 0.429) but still higher dose-normalized Cmax (346.3 ± 184.4 versus 273.2 ± 148.9 ng/mL/mg/kg, P = 0.056), despite a reduced trough concentration (5.7 ± 1.6 versus 6.9 ± 2.2 ng/mL, P = 0.004). PK profiles evaluated at 9 months showed that generic substitution also resulted in an ‘early and high Cmax’. Efficacy and safety data were comparable over the 9-month study period. Conclusions Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) are difficult to differentiate especially in the early stages. We aimed to investigate the diagnostic performance of the magnetic resonance parkinsonism index (MRPI) in differentiating PSP from PD. A systematic literature search of PubMed-MEDLINE and EMBASE was performed to identify original articles evaluating the diagnostic performance of the MRPI in differentiating PSP from PD published up to 20 February 2021. The pooled sensitivity, specificity, and 95% CI were calculated using the bivariate random-effects model. The area under the curve (AUC) was calculated using a hierarchical summary receiver operating characteristic (HSROC) model. Meta-regression was performed to explain the effects of heterogeneity. A total of 14 original articles involving 484 PSP patients and 1243 PD patients were included. In all studies, T1-weighted images were used to calculate the MRPI. Among the 14 studies, nine studies used 3D T1-weighted images. The pooled sensitivity and specificity for the diagnostic performance of the MRPI in differentiating PSP from PD were 96% (95% CI, 87–99%) and 98% (95% CI, 91–100%), respectively. The area under the HSROC curve was 0.99 (95% CI, 0.98–1.00). Heterogeneity was present (sensitivity: I2 = 97.29%; specificity: I2 = 98.82%). Meta-regression showed the association of the magnet field strength with heterogeneity. Studies using 3 T MRI showed significantly higher sensitivity (100%) and specificity (100%) than those of studies using 1.5 T MRI (sensitivity of 98% and specificity of 97%) (p < 0.01). Thus, the MRPI could accurately differentiate PSP from PD and support the implementation of appropriate management strategies for patients with PSP. [ABSTRACT FROM AUTHOR]