Machine learning approach for obstructive sleep apnea screening using brain diffusion tensor imaging

Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m²; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m²; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.     

Fast diffusion kurtosis imaging (DKI) with Inherent COrrelation‐based Normalization (ICON) enhances automatic segmentation of heterogeneous diffusion MRI lesion in acute stroke

Diffusion kurtosis imaging (DKI) has been shown to augment diffusion‐weighted imaging (DWI) for the definition of irreversible ischemic injury. However, the complexity of cerebral structure/composition makes the kurtosis map heterogeneous, limiting the specificity of kurtosis hyperintensity to acute ischemia. We propose an Inherent COrrelation‐based Normalization (ICON) analysis to suppress the intrinsic kurtosis heterogeneity for improved characterization of heterogeneous ischemic tissue injury. Fast DKI and relaxation measurements were performed on normal (n = 10) and stroke rats following middle cerebral artery occlusion (MCAO) (n = 20). We evaluated the correlations between mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) derived from the fast DKI sequence and relaxation rates R₁ and R₂, and found a highly significant correlation between MK and R₁ (p < 0.001). We showed that ICON analysis suppressed the intrinsic kurtosis heterogeneity in normal cerebral tissue, enabling automated tissue segmentation in an animal stroke model. We found significantly different kurtosis and diffusivity lesion volumes: 147 ± 59 and 180 ± 66 mm³, respectively (p = 0.003, paired t‐test). The ratio of kurtosis to diffusivity lesion volume was 84% ± 19% (p < 0.001, one‐sample t‐test). We found that relaxation‐normalized MK (RNMK), but not MD, values were significantly different between kurtosis and diffusivity lesions (p < 0.001, analysis of variance). Our study showed that fast DKI with ICON analysis provides a promising means of demarcation of heterogeneous DWI stroke lesions.     

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel‐based analysis are highly dependent on the user‐hypothesis and parameter settings for implementation. In contrast, tract‐based spatial statistics (TBSS) allows for reliable voxel‐wise analysis via the projection of diffusion‐derived parameters onto an alignment‐invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI‐derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2–4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post‐stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post‐stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo‐normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.     

The Role of Circulating T Follicular Helper Cells and Regulatory Cells in Non‐Small Cell Lung Cancer Patients

T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells are identified as the new subset of immune cells. This study aims to investigate the role of circulating Tfh cells (cTfh) and Tfr (cTfr) cells in the pathogenesis of non‐small cell lung cancer (NSCLC). A total of 27 NSCLC patients and 19 age and sex‐matched healthy controls were enrolled. The percentage of cTfh and cTfr was detected by flow cytometric analysis. Compared to healthy controls, a significantly higher percentage of both cTfh and cTfr cells were observed in NSCLC patients (for cTfh, 18.88% ± 16.84% versus 5.98% ± 3.70%, P < 0.01; for cTfr, 2.67% ± 2.20% versus 1.14% ± 0.76%, P < 0.01). Furthermore, there was a positive correlation between cTfh/cTfr ratio and age in NSCLC patients (P < 0.05). When taking age 60 as a cut‐off, the percentage of both cTfh cells and cTfr cells were higher in older patients than younger patients. Moreover, our data showed there was lower percentage of cTfh cells in NSCLC patients with early stage disease (I and II) (12.10% ± 12.22%) than that in advanced stage disease (III and IV) (30.41% ± 17.87%) (P < 0.01). However, no significant relationship was observed between cTfr cells and clinical stage in NSCLC patients. A higher percentage of cTfh cells was observed in patients with squamous cell carcinoma compared with adenocarcinoma (31.70% ± 20.73% versus. 13.48% ± 11.78%, P < 0.05). Taken together, there was significantly higher percentage of cTfh and cTfr cells in NSCLC patients. cTfh and cTfr cells might play an important role in the pathogenesis of NSCLC patients.     

Automatic identification of sleep and wakefulness using single‐channel EEG and respiratory polygraphy signals for the diagnosis of obstructive sleep apnea

Polysomnography (PSG) is necessary for the accurate estimation of total sleep time (TST) and the calculation of the apnea–hypopnea index (AHI). In type III home sleep apnea testing (HSAT), TST is overestimated because of the lack of electrophysiological sleep recordings. The aim of this study was to evaluate the accuracy and reliability of a novel automated sleep/wake scoring algorithm combining a single electroencephalogram (EEG) channel with actimetry and HSAT signals. The study included 160 patients investigated by PSG for suspected obstructive sleep apnea (OSA). Each PSG was recorded and scored manually using American Academy of Sleep Medicine (AASM) rules. The automatic sleep/wake‐scoring algorithm was based on a single‐channel EEG (FP2‐A1) and the variability analysis of HSAT signals (airflow, snoring, actimetry, light and respiratory inductive plethysmography). Optimal detection thresholds were derived for each signal using a training set. Automatic and manual scorings were then compared epoch by epoch considering two states (sleep and wake). Cohen's kappa coefficient between the manual scoring and the proposed automatic algorithm was substantial, 0.74 ± 0.18, in separating wakefulness and sleep. The sensitivity, specificity and the positive and negative predictive values for the detection of wakefulness were 76.51% ± 21.67%, 95.48% ± 5.27%, 81.84% ± 15.42% and 93.85% ± 6.23% respectively. Compared with HSAT signals alone, AHI increased by 22.12% and 27 patients changed categories of OSA severity with the automatic sleep/wake‐scoring algorithm. Automatic sleep/wake detection using a single‐channel EEG combined with HSAT signals was a reliable method for TST estimation and improved AHI calculation compared with HSAT.     

Comparison of Intravenous with Oral Busulfan in Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Regimens for Pediatric Acute Leukemia

Recent reports revealed that intravenous (iv) busulfan (BU) may not only reduce early nonrelapse mortality (NRM) but also improve overall survival (OS) probability in adults. Therefore, we retrospectively compared outcomes for 460 children with acute leukemia who underwent hematopoietic stem cell transplantation with either iv-BU (n = 198) or oral busulfan (oral-BU) (n = 262) myeloablative conditioning. OS at 3 years was 53.4% ± 3.7% with iv-BU and 55.1% ± 3.1% with oral-BU; the difference was not statistically significant (P = .77). OS at 3 years in 241 acute lymphoblastic leukemia and 219 acute myeloid leukemia patients was 56.4% ± 5.5% with iv-BU and 54.6% ± 4.1 with oral-BU (P = .51) and 51.0% ± 5.0% with iv-BU and 55.8% ± 4.8% with oral-BU (P = .83), respectively. Cumulative incidence of relapse at 3 years with iv-BU was similar to that with oral-BU (39.0% ± 3.6% and 36.4% ± 3.1%, respectively; P = .67). Cumulative incidence of NRM at 3 years was 16.6% ± 2.7% with iv-BU and 18.3% ± 2.5% with oral-BU (P = .51). Furthermore, multivariate analysis showed no significant survival advantage with iv-BU. In conclusion, iv-BU failed to show a significant survival advantage in children with acute leukemia.     

An EEG-based functional connectivity measure for automatic detection of alcohol use disorder

BackgroundThe abnormal alcohol consumption could cause toxicity and could alter the human brain’s structure and function, termed as alcohol used disorder (AUD). Unfortunately, the conventional screening methods for AUD patients are subjective and manual. Hence, to perform automatic screening of AUD patients, objective methods are needed. The electroencephalographic (EEG) data have been utilized to study the differences of brain signals between alcoholics and healthy controls that could further developed as an automatic screening tool for alcoholics.MethodIn this work, resting-state EEG-derived features were utilized as input data to the proposed feature selection and classification method. The aim was to perform automatic classification of AUD patients and healthy controls. The validation of the proposed method involved real-EEG data acquired from 30 AUD patients and 30 age-matched healthy controls. The resting-state EEG-derived features such as synchronization likelihood (SL) were computed involving 19 scalp locations resulted into 513 features. Furthermore, the features were rank-ordered to select the most discriminant features involving a rank-based feature selection method according to a criterion, i.e., receiver operating characteristics (ROC). Consequently, a reduced set of most discriminant features was identified and utilized further during classification of AUD patients and healthy controls. In this study, three different classification models such as Support Vector Machine (SVM), Naïve Bayesian (NB), and Logistic Regression (LR) were used.ResultsThe study resulted into SVM classification accuracy = 98%, sensitivity = 99.9%, specificity = 95%, and f-measure = 0.97; LR classification accuracy = 91.7%, sensitivity = 86.66%, specificity = 96.6%, and f-measure = 0.90; NB classification accuracy = 93.6%, sensitivity = 100%, specificity = 87.9%, and f-measure = 0.95.ConclusionThe SL features could be utilized as objective markers to screen the AUD patients and healthy controls.     

High‐resolution diffusion tensor imaging in cervical spondylotic myelopathy: a preliminary follow‐up study

Diffusion imaging is a promising technique as it can provide microstructural tissue information and thus potentially show viable changes in spinal cord. However, the traditional single‐shot imaging method is limited as a result of various image artifacts. In order to improve measurement accuracy, we used a newly developed, multi‐shot, high‐resolution, diffusion tensor imaging (DTI) method to investigate diffusion metric changes and compare them with T₂‐weighted (T2W) images before and after decompressive surgery for cervical spondylotic myelopathy (CSM). T2W imaging, single‐shot DTI and multi‐shot DTI were employed to scan seven patients with CSM before and 3 months after decompressive surgery. High signal intensities were scored using the T2 W images. DTI metrics, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were quantified and compared pre‐ and post‐surgery. In addition, the relationship between imaging metrics and neurological assessments was examined. The reproducibility of multi‐shot DTI was also assessed in 10 healthy volunteers. Post‐surgery, the mean grade of cervical canal stenosis was reduced from grade 3 to normal after 3 months. Compared with single‐shot DTI, multi‐shot DTI provided better images with lower artifact levels, especially following surgery, as a result of reduced artifacts from metal implants. The new method also showed acceptable reproducibility. Both FA and RD values from the new acquisition showed significant differences post‐surgery (FA, p = 0.026; RD, p = 0.048). These changes were consistent with neurological assessments. In contrast, T2W images did not show significant changes before and after surgery. Multi‐shot diffusion imaging showed improved image quality over single‐shot DWI, and presented superior performance in diagnosis and recovery monitoring for patients with CSM compared with T2W imaging. DTI metrics can reflect the pathological conditions of spondylotic spinal cord quantitatively and may serve as a sensitive biomarker for potential CSM management.     

In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

Diffusion magnetic resonance imaging (MRI) exhibits contrast that identifies macro‐ and microstructural changes in neurodegenerative diseases. Previous studies have shown that MR diffusion tensor imaging (DTI) can observe changes in spinal cord white matter in animals and humans affected with symptomatic amyotrophic lateral sclerosis (ALS). The goal of this preclinical work was to investigate the sensitivity of DTI for the detection of signs of tissue damage before symptoms appear. High‐field MRI data were acquired using a 9.4‐T animal scanner to examine the spinal cord of an ALS mouse model at pre‐ and post‐symptomatic stages (days 80 and 120, respectively). The MRI results were validated using yellow fluorescent protein (YFP) via optical microscopy of spinal cord tissue slices collected from the YFP,G93A‐SOD1 mouse strain. DTI maps of diffusion‐weighted imaging (DWI) signal intensity, mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were computed for axial slices of the lumbar region of the spinal cord. Significant changes were observed in FA (6.7% decrease, p < 0.01), AD (19.5% decrease, p < 0.01) and RD (16.1% increase, p < 0.001) at postnatal day 80 (P80). These differences were correlated with changes in axonal fluorescence intensity and membrane cellular markers. This study demonstrates the value of DTI as a potential tool to detect the underlying pathological progression associated with ALS, and may accelerate the discovery of therapeutic strategies for patients with this disease.     

Fibrin Glue Therapy for Severe Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation.     

Validation of cardiac diffusion tensor imaging sequences: A multicentre test–retest phantom study

Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish the accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI among 10 centres internationally. Phantoms comprising 0%–20% polyvinylpyrrolidone (PVP) were scanned with DTI using a product pulsed gradient spin echo (PGSE; N = 10 sites) sequence, and a custom motion-compensated spin echo (SE; N = 5) or stimulated echo acquisition mode (STEAM; N = 5) sequence suitable for cardiac DTI in vivo. A second identical scan was performed 1–9 days later, and the data were analysed centrally. The average mean diffusivities (MDs) in 0% PVP were (1.124, 1.130, 1.113) x 10⁻³ mm²/s for PGSE, SE and STEAM, respectively, and accurate to within 1.5% of reference data from the literature. The coefficients of variation in MDs across sites were 2.6%, 3.1% and 2.1% for PGSE, SE and STEAM, respectively, and were similar to previous studies using only PGSE. Reproducibility in MD was excellent, with mean differences in PGSE, SE and STEAM of (0.3 ± 2.3, 0.24 ± 0.95, 0.52 ± 0.58) x 10⁻⁵ mm²/s (mean ± 1.96 SD). We show that custom sequences for cardiac DTI provide accurate, precise, repeatable and reproducible measurements. Further work in anisotropic and/or deforming phantoms is warranted.     

Medial meniscus extrusion as a predictor for a poor prognosis in patients with spontaneous osteonecrosis of the knee

BackgroundRisk factors for the progression of spontaneous osteonecrosis of the knee (SONK) remain unclear. The purpose of this study was to investigate the association between magnetic resonance imaging (MRI) findings of the meniscus and the prognosis of SONK.MethodsA total of 78 consecutive patients (female 85%; mean age 75.6 ± 7.2 years old) diagnosed with SONK were included. Of these, 30 patients did not receive surgery within 1 year from the onset of SONK (conservative group), while the remaining 48 patients underwent unicompartmental knee arthroplasty due to worsening of symptoms (UKA group). Using MRI findings obtained within 3 months of the onset, we compared the types of meniscus tear and medial meniscus extrusion between the conservative group and UKA group. We performed a receiver operating characteristics (ROC) analysis to estimate the cut-off value.ResultsPatients in the UKA group showed greater medial meniscus extrusion (absolute value, 4.2 mm ± 1.9 vs. 2.8 mm ± 1.2, P = 0.001; relative percentage of extrusion (RPE), 45.7% ± 21.5 vs. 30.7% ± 12.9, P = 0.001) and a higher prevalence of radial tear (P = 0.021) than those in the conservative group. In the multivariate analysis, RPE remained a relevant independent factor (P = 0.035) for future UKA. An ROC analysis found that the cut-off point of RPE was 33% (sensitivity, 81.2%; specificity, 63.3%).ConclusionRPE was a predictor of the prognosis of patients who underwent UKA within 1 year after the onset of SONK. Our results suggest that patients with RPE ≥ 33% are at high risk for progression.     

Increased killer B cells in chronic HCV infection may lead to autoimmunity and increased viral load

Regulatory B (B_reg) cells are characterized by various membrane markers and the secretion of different inhibitory cytokines. A new subset of B_reg cells was identified as CD5^hi Fas‐ligand (FasL)^hi. Their main reported role is to suppress anti‐viral and anti‐tumour immune responses, and, hence they have been dubbed ‘killer’ B cells. In this study, we aim to assess the role of these cells in chronic hepatitis C virus (HCV) infection, and determine if they contribute to the increased viral load and persistence of HCV and its related autoimmunity. (i) FasL expression on CD5^hi B cells is increased significantly in HCV‐infected patients compared to healthy individuals [28·06 ± 6·71 mean fluorescence intensity (MFI) ± standard error of the mean (s.e.m.), median = 27·9 versus 10·87 ± 3·97 MFI ± s.e.m., median = 10·3, respectively, P <  0·0001]. (ii) Killer B cells from HCV patients increased autologous CD4⁺ T cell apoptosis compared to the apoptosis in healthy individuals [39·17% ± 7·18% mean ± standard deviation (s.d.), median = 39·6 versus 25·92 ± 8·65%, mean ± s.d., median = 24·1%, P <  0·0001, respectively]. A similar increase was observed in CD8⁺ T cell apoptosis (54·67 ± 15·49% mean ± s.d., median = 57·3 versus 21·07% ± 7·4%, mean ± s.d., median = 20%, P = 0·0006, respectively). (iii) By neutralizing FasL with monoclonal anti‐FasL antibodies, we have shown that the induction of apoptosis by killer B cells is FasL‐dependent. (iv) Increased expression of FasL on CD5^hi B cells is correlated positively with an increased viral load and the presence of anti‐nuclear antibodies and rheumatoid factor in HCV. This is the first study in which killer B cells have been suggested to play a pathogenic role in HCV. They seem to be involved in HCV's ability to escape efficient immune responses.     

Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time‐consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi‐automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post‐marathon and follow‐up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi‐automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out‐of‐phase Dixon images at baseline. These segmentations were longitudinally propagated for the post‐marathon and follow‐up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi‐automatic segmentations. Bland‐Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ₃). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland‐Altman analysis showed that the 95% limits of agreement for MD, FA and λ₃ ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA and λ₃ (r = 0.99, p < 60; 0.0001). In conclusion, the supervised semi‐automatic segmentation framework successfully quantified DTI indices in the upper‐leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.     

Donor Lymphocyte Infusion for the Treatment of Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Because the efficacy of donor lymphocyte infusion (DLI) for acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains uncertain, especially in the Asian population, a nationwide registry study was retrospectively performed by the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation to identify the factors affecting the patient survival after DLI. Among 143 adult AML patients who received DLI for the treatment of first hematological relapse after HSCT, the overall survival rates at 1 year, 2 years, and 5 years were 32% ± 4%, 17% ± 3%, and 7% ± 3%, respectively. Complete remission (CR) at the time of DLI, which was obtained in 8% of the patients, was the strongest predictive factor for survival after DLI. Therefore, long-term survival after DLI was achieved almost exclusively in patients who successfully achieved a CR before DLI, indicating the limited efficacy of DLI in a minority of patients.     

Histological Changes in Alveolar Bone After Onlay Augmentation Using the Casing Method

Numerous studies on alveolar bone augmentation have been reported. However, it remains challenging to obtain favorable new bone, especially for onlay bone augmentation. For successful onlay bone augmentation, it is necessary to use a graft material with high bone‐forming activity and wound stabilization. We performed onlay bone augmentation on the buccal surface of mandibular alveolar bone in dogs, using a polyethylene terephthalate (PET) case (Casing method). The aim of this study was to histologically examine the feasibility of Casing method for external onlay bone augmentation. Beagle dogs were selected for this study. At 12 weeks after tooth extraction, a PET case was placed on the buccal surface of mandibular alveolar bone and filled with a mixture of hydroxyapatite and β‐tricalcium phosphate (β‐TCP) particles (volume ratio 1:1) impregnated with crushed autogenous bone (superfine bone powder) suspended in plasma. At 4, 8, and 16 weeks after bone graft, nondecalcified sections were histologically examined. At 4 weeks, new bone formation on the particle surfaces was observed on the original bone side of the PET case. At 16 weeks, bone formation was observed in almost all areas inside the case. The percentage of the augmented area (including new bone and particles surrounded by new bone; was significantly greater at 16 weeks (85.7% ± 6.0%) than at 4 weeks (10.5% ± 4.8%) or 8 weeks (69.6% ± 15.6%). The results of this study suggest that onlay bone augmentation using the Casing method has considerable potential to yield histologically favorable new bone formation. Anat Rec, 301:1148–1158, 2018. © 2018 Wiley Periodicals, Inc.     

B-cell responses to vaccination with BNT162b2 and mRNA-1273 6 months after second dose

ObjectivesTo examine the state of B-cell immunity 6 months after the second vaccination against SARS-CoV-2 in comparison to the state observed 2 weeks after vaccination.MethodsSera of 439 participants, whose immune responses to two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273) were previously characterized, was examined for anti-S1 IgG and IgA, anti-NCP IgG and neutralizing antibodies (nAb), and antinuclear antibodies (ANA).ResultsLevels of all examined markers decreased significantly from 2 weeks to 6 months after second vaccination (anti-S1 IgG: 3744 ± 2571.4 vs. 253 ± 144 binding antibody units (BAU)/mL; anti-S1 IgA: 12 ± 0 vs. 1.98 ± 1.75 optical density (OD) ratio; nAb: 100% ± 0% vs. 82% ± 19.3%), the vast majority of participants retaining reactive levels of anti-S1 IgG (436/439) and anti-S1 IgA (334/439) at 6 months. Immune responses were stronger for mRNA-1273 compared with BNT162b2 (anti-S1 IgG: 429 ± 289 vs. 243 ± 143 BAU/mL; anti-S1 IgA: 5.38 ± 3.91 vs. 1.89 ± 1.53 OD ratio; nAb: 90.5% ± 12.6% vs. 81% ± 19.3%). There was no meaningful influence of sex and age on the examined markers. There was a strong correlation between anti-S1 IgG and the surrogate neutralization assay (rho = 0.91, p <0.0001), but not for for IgA and the surrogate neutralization assay (rho = 0.52, p <0.0001). There was a ceiling effect for the association between anti-S1 IgG titres and the inhibition of binding between S1 and ACE2. ANA prevalence was unchanged from 2 weeks to 6 months after the second vaccination (87/498 vs. 77/435), as were the median ANA titres (1:160 vs. 1:160).DiscussionAlthough the clinical consequences of decreasing anti-SARS-CoV-2 antibody titres cannot be estimated with certainty, a lowered degree of clinical protection against SARS-CoV-2 is possible. Persistently stronger responses to mRNA-1273 suggest that it might confer greater protection than BNT162b2, even 6 months after the second vaccination. Neither examined vaccinations induced ANA within the examined time frame.     

Identification of task parameters from movement-related cortical potentials

The study investigates the accuracy in discriminating rate of torque development (RTD) and target torque (TT) (task parameters) from electroencephalography (EEG) signals generated during imaginary motor tasks. Signals were acquired from nine healthy subjects during four imaginary isometric plantar-flexions of the right foot involving two RTDs (ballistic and moderate) and two TTs (30 and 60% of the maximal voluntary contraction torque), each repeated 60 times in random order. The single-trial EEG traces were classified with a pattern recognition approach based on wavelet coefficients as features and support vector machine (SVM) as classifier. Average misclassification rates were (mean ± SD) 16 ± 9% and 26 ± 13% for discrimination of the two TTs under ballistic and moderate RTDs, respectively. RTDs could be discriminated with misclassification rates of 16 ± 11% and 19 ± 10% under high and low TT, respectively. These results indicate that differences in both TT and RTD can be detected from single-trial EEG traces during imaginary tasks.     

Three‐dimensional echo planar spectroscopic imaging for differentiation of true progression from pseudoprogression in patients with glioblastoma

Accurate differentiation of true progression (TP) from pseudoprogression (PsP) in patients with glioblastomas (GBMs) is essential for planning adequate treatment and for estimating clinical outcome measures and future prognosis. The purpose of this study was to investigate the utility of three‐dimensional echo planar spectroscopic imaging (3D‐EPSI) in distinguishing TP from PsP in GBM patients. For this institutional review board approved and HIPAA compliant retrospective study, 27 patients with GBM demonstrating enhancing lesions within six months of completion of concurrent chemo‐radiation therapy were included. Of these, 18 were subsequently classified as TP and 9 as PsP based on histological features or follow‐up MRI studies. Parametric maps of choline/creatine (Cho/Cr) and choline/N‐acetylaspartate (Cho/NAA) were computed and co‐registered with post‐contrast T₁‐weighted and FLAIR images. All lesions were segmented into contrast enhancing (CER), immediate peritumoral (IPR), and distal peritumoral (DPR) regions. For each region, Cho/Cr and Cho/NAA ratios were normalized to corresponding metabolite ratios from contralateral normal parenchyma and compared between TP and PsP groups. Logistic regression analyses were performed to obtain the best model to distinguish TP from PsP. Significantly higher Cho/NAA was observed from CER (2.69 ± 1.00 versus 1.56 ± 0.51, p = 0.003), IPR (2.31 ± 0.92 versus 1.53 ± 0.56, p = 0.030), and DPR (1.80 ± 0.68 versus 1.19 ± 0.28, p = 0.035) regions in TP patients compared with those with PsP. Additionally, significantly elevated Cho/Cr (1.74 ± 0.44 versus 1.34 ± 0.26, p = 0.023) from CER was observed in TP compared with PsP. When these parameters were incorporated in multivariate regression analyses, a discriminatory model with a sensitivity of 94% and a specificity of 87% was observed in distinguishing TP from PsP. These results indicate the utility of 3D‐EPSI in differentiating TP from PsP with high sensitivity and specificity.     

High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome

Klinefelter syndrome (KS) occurs in 1:600 males and is associated with high morbidity and mortality due to diabetes and cardiovascular disease. Up to 50% of men with KS have metabolic syndrome, a cluster of features conferring increased risk for diabetes and cardiovascular disease. These cardiometabolic (CM) risk features have not been studied in adolescents with KS. The objective of this cohort study was to compare CM risk features in adolescents with KS to controls matched for sex, age, and BMI z score. Fifty males with KS (age 10–17 years) were well‐matched to male controls (n = 50) for age (14.0 ± 1.7 vs. 14.0 ± 1.5 years) and BMI z score (0.3 ± 1.3 vs. 0.4 ± 1.2). Three CM risk features were present in 30% of adolescents with KS compared to 12% of controls (RR 2.5, 95% CI 1.1–5.9, p = .048). The KS group had significantly lower HDL cholesterol (p = .006), higher triglycerides (p < .001), and greater waist circumference percentile (p < .001). Despite a normal BMI, the prevalence of CM risk features was very high in adolescents with KS, particularly for central adiposity and dyslipidemia. The pathophysiology of this metabolic profile independent of obesity needs further investigation to facilitate prevention of the high morbidity of cardiovascular disease and diabetes in this population. ClinicalTrials.gov identifiers: NCT01585831 and NCT02723305.