Obesity alters pathology and treatment response in inflammatory disease.

Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.

Assessment of MR blood-oxygen-level-dependent (BOLD) cerebrovascular reactivity under general anesthesia in children with moyamoya.

BACKGROUND: Moyamoya is a progressive, non-atherosclerotic cerebral arteriopathy that may present in childhood and currently has no cure. Early diagnosis is critical to prevent a lifelong risk of neurological morbidity. Blood-oxygen-level-dependent (BOLD) MRI cerebrovascular reactivity (CVR) imaging provides a non-invasive, in vivo measure of autoregulatory capacity and cerebrovascular reserve. However, non-compliant or younger children require general anesthesia to achieve BOLD-CVR imaging. OBJECTIVE: To determine the same-day repeatability of BOLD-CVR imaging under general anesthesia in children with moyamoya. MATERIALS AND METHODS: Twenty-eight examination pairs were included (mean patient age = 7.3 ± 4.0 years). Positive and negatively reacting voxels were averaged over signals and counted over brain tissue and vascular territory. The intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, and Bland-Altman plots were used to assess the variability between the scans. RESULTS: There was excellent-to-good (≥ 0.59) within-day repeatability in 18 out of 28 paired studies (64.3%). Wilcoxon signed-rank tests demonstrated no significant difference in the grey and white matter CVR estimates, between repeat scans (all p-values > 0.05). Bland-Altman plots of differences in mean magnitude of positive and negative and fractional positive and negative CVR estimates illustrated a reasonable degree of agreement between repeat scans and no systematic bias. CONCLUSION: BOLD-CVR imaging provides repeatable assessment of cerebrovascular reserve in children with moyamoya imaged under general anesthesia.

Analysis of background echotexture on automated breast ultrasound using BI-RADS and modified classification: Association with clinical features and mammographic density.

PURPOSE: To analyze BE on ABUS using BI-RADS and a modified classification in association with mammographic density and clinical features. METHODS: Menopausal status, parity, and family history of breast cancer were collected for 496 women who underwent ABUS and mammography. Three radiologists independently reviewed all ABUS BE and mammographic density. Statistical analyses including kappa statistics (κ) for interobserver agreement, Fisher's exact test, and univariate and multivariate multinomial logistic regression were performed. RESULTS: BE distribution between the two classifications and between each classification and mammographic density were associated (P < 0.001). BI-RADS homogeneous-fibroglandular (76.8%) and modified heterogeneous BE (71.3%, 75.7%, and 87.5% of mild, moderate, and marked heterogeneous background echotexture, respectively) tended to be dense. BE was correlated between BI-RADS homogeneous-fat and modified homogeneous background (95.1%) and between BI-RADS homogeneous-fibroglandular or heterogeneous (90.6%) and modified heterogeneous (86.9%) (P < 0.001). In multinomial logistic regression, age < 50 years was independently associated with heterogeneous BE (OR, 8.89, P = 0.003, in BI-RADS; OR, 3.74; P = 0.020 in modified classification). CONCLUSION: BI-RADS homogeneous-fat and modified homogeneous BE on ABUS was likely to be mammographically fatty. However, BI-RADS homogeneous-fibroglandular or heterogeneous BE might be classified as any modified BE. Younger age was independently associated with heterogeneous BE.

Three-Dimensional Plasmonic Nanocluster-Driven Light-Matter Interaction for Photoluminescence Enhancement and Picomolar-Level Biosensing.

Plasmonic nanoparticle clusters promise to support unique engineered electromagnetic responses at optical frequencies, realizing a new concept of devices for nanophotonic applications. However, the technological challenges associated with the fabrication of three-dimensional nanoparticle clusters with programmed compositions remain unresolved. Here, we present a novel strategy for realizing heterogeneous structures that enable efficient near-field coupling between the plasmonic modes of gold nanoparticles and various other nanomaterials via a simple three-dimensional coassembly process. Quantum dots embedded in the plasmonic structures display ∼56 meV of a blue shift in the emission spectrum. The decay enhancement factor increases as the total contribution of radiative and nonradiative plasmonic modes increases. Furthermore, we demonstrate an ultracompact diagnostic platform to detect M13 viruses and their mutations from femtoliter volume, sub-100 pM analytes. This platform could pave the way toward an effective diagnosis of diverse pathogens, which is in high demand for handling pandemic situations.

Sandwich spatial saturation for neuromelanin-sensitive MRI: Development and multi-center trial.

Neuromelanin (NM)-sensitive MRI using a magnetization transfer (MT)-prepared T1-weighted sequence has been suggested as a tool to visualize NM contents in the brain. In this study, a new NM-sensitive imaging method, sandwichNM, is proposed by utilizing the incidental MT effects of spatial saturation RF pulses in order to generate consistent high-quality NM images using product sequences. The spatial saturation pulses are located both superior and inferior to the imaging volume, increasing MT weighting while avoiding asymmetric MT effects. When the parameters of the spatial saturation were optimized, sandwichNM reported a higher NM contrast ratio than those of conventional NM-sensitive imaging methods with matched parameters for comparability with sandwichNM (SandwichNM: 23.6 ± 5.4%; MT-prepared TSE: 20.6 ± 7.4%; MT-prepared GRE: 17.4 ± 6.0%). In a multi-vendor experiment, the sandwichNM images displayed higher means and lower standard deviations of the NM contrast ratio across subjects in all three vendors (SandwichNM vs. MT-prepared GRE; Vendor A: 28.4 ± 1.5% vs. 24.4 ± 2.8%; Vendor B: 27.2 ± 1.0% vs. 13.3 ± 1.3%; Vendor C: 27.3 ± 0.7% vs. 20.1 ± 0.9%). For each subject, the standard deviations of the NM contrast ratio across the vendors were substantially lower in SandwichNM (SandwichNM vs. MT-prepared GRE; subject 1: 1.5% vs. 8.1%, subject 2: 1.1 % vs. 5.1%, subject 3: 0.9% vs. 4.0%, subject 4: 1.1% vs. 5.3%), demonstrating consistent contrasts across the vendors. The proposed method utilizes product sequences, requiring no alteration of a sequence and, therefore, may have a wide practical utility in exploring the NM imaging.

Can Bone Erosion in Axial Spondyloarthropathy be Detected by Ultrashort Echo Time Imaging? A Comparison With Computed Tomography in the Sacroiliac Joint.

BACKGROUND: Structural lesion evaluation in axial spondyloarthropathy (SpA) can improve accuracy of diagnosis. However, structural lesions (bone erosions) are difficult to be assessed using conventional MRI compared to computed tomography (CT). PURPOSE: To evaluate the diagnostic performance of ultrashort echo time (UTE) for detecting bone erosion in axial SpA compared to T1WI and three-dimensional double-echo steady-state (3D DESS) imaging using CT as the reference standard. STUDY TYPE: Retrospective. POPULATION: Fourteen patients (eight females, 57.1%) and 14 healthy controls (seven females, 50.0%) who underwent sacroiliac (SI) joint MRI and CT. FIELD STRENGTH/SEQUENCE: 3 T; TSE T1WI, 3D DESS, 2D UTE. ASSESSMENT: The bilateral SI joints were assessed for bone erosion. Three observers scored bone erosion for all three sequences of MRI. CT was used as the gold standard. Diagnostic confidence in axial SpA was measured based on a four-point confidence score. STATISTICAL TESTS: Correlation of erosion scores between CT and MRI were evaluated using Spearman's correlation test. Sensitivity, specificity, and positive-negative predictive values were calculated. Confidence scores were compared using the Wilcoxon sum rank test. Statistical significance was set at P < 0.05. RESULTS: Compared with erosion scores of CT, the correlation coefficients for each MRI sequence showed significant low-to-high positive correlations (0.39-0.72). UTE imaging showed the highest correlation coefficients for all observers (0.70, 0.72, and 0.67, respectively). The specificity of UTE imaging was equal or higher than those of T1WI and 3D DESS for all observers (0.86 vs. 0.71 vs. 0.57; 0.93 vs. 0.71 vs. 0.57; 0.79 vs. 0.79 vs. 0.43). All observers had the highest confidence in interpreting UTE imaging for detecting bone erosion among the three sequences (3.5, 3.4, and 3.3 for UTE; 3.1, 3.0, and 2.6 for T1WI; and 3.2, 2.7, and 2.4 for DESS). DATA CONCLUSION: UTE imaging can detect bone erosions in patients with axial SpA and show higher specificity than conventional T1WI and 3D DESS. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Intravenous Brivaracetam in the Management of Acute Seizures in the Hospital Setting: A Scoping Review.

BACKGROUND: Clinical considerations for drug treatment of acute seizures involve variables such as safety, tolerability, drug-drug interactions, dosage, route of administration, and alterations in pharmacokinetics because of critical illness. Therapy options that are easily and quickly administered without dilution, well tolerated, and effective are needed for the treatment of acute seizures. The objective of this review is to focus on the clinical considerations relating to the use of intravenous brivaracetam (IV BRV) for the treatment of acute seizures in the hospital, focusing on critically ill patients. METHODS: This was a scoping literature review of PubMed from inception to April 13, 2021, and search of the American Academy of Neurology (AAN) 2021 Annual Meeting website for English language publications/conference abstracts reporting the results of IV BRV use in hospitalized patients, particularly in the critical care setting. Outcomes of interest relating to the clinical pharmacology, safety, tolerability, efficacy, and effectiveness of IV BRV were reviewed and are discussed. RESULTS: Twelve studies were included for analysis. One study showed that plasma concentrations of IV BRV 15 min after the first dose were similar between patients receiving IV BRV as bolus or infusion. IV BRV was generally well tolerated in patients with acute seizures in the hospital setting, with a low incidence of individual TEAEs classified as behavioral disorders. IV BRV demonstrated efficacy and effectiveness and had a rapid onset, with clinical and electrophysiological improvement in seizures observed within minutes. Although outside of the approved label, findings from several studies suggest that IV BRV reduces seizures and is generally well tolerated in patients with status epilepticus. CONCLUSIONS: IV BRV shows effectiveness, and is generally well tolerated in the management of acute seizures in hospitalized patients where rapid administration is needed, representing a clinically relevant antiseizure medication for potential use in the critical care setting.

Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging Assessment of Optic Pathway Function in Patients With Anterior Visual Pathway Compression.

BACKGROUND: In patients with sellar or parasellar tumors, it is crucial to evaluate visual field impairment in the preoperative stage and to predict visual field improvement after the surgery. The purpose of this study was to investigate the associations of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters in the optic radiations with preoperative and postoperative visual field impairment. METHODS: This prospective study included 81 participants with sellar or parasellar tumors. Multishell diffusion imaging and a visual field impairment score (VFIS) were acquired before and after the surgery. The multishell diffusion-weighted imaging was acquired to measure the neurite density and neurite orientation dispersion, as well as the diffusivity. DTI parameters were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD). NODDI provided intracellular volume fraction (Vic), the orientation dispersion index, and isotropic volume fraction (Viso). The associations of DTI and NODDI parameters in the optic radiations with VFIS were investigated, adjusting for age, tumor height, and symptom duration. RESULTS: Among 162 optic radiations, 117 were functionally impaired in the preoperative stage. FA and Vic had significant negative correlations, whereas MD and RD had significant positive correlations with the VFIS (all P < 0.001). In the preoperative stage, lower FA (P = 0.001; odds ratio = 0.750) and Vic (P = 0.003; OR = 0.827) and higher MD (P = 0.007; OR = 1.244) and RD (P < 0.001; OR = 1.361) were significantly associated with the presence of visual field impairment. For the degree of postoperative improvement, preoperative lower Vic (P = 0.034; OR = 0.910) and higher MD (P = 0.037; OR = 1.103) and RD (P = 0.047; OR = 1.090) were significantly associated with more postoperative improvement. CONCLUSIONS: DTI and NODDI parameters in the optic radiations were correlated with VFIS and associated with preoperative visual field impairments and postoperative improvement. It may help in predicting visual field improvement after the surgery in patients with sellar or parasellar tumors.

Mental health profiles of autistic children and youth during the COVID-19 pandemic.

Objectives: Canadian province-wide lockdowns have challenged children's mental health (MH) during the COVID-19 pandemic, with autistic children being at particular risk. The purpose of our study was to identify sub-groups of autistic children with distinct mental health change profiles, to understand the child-, parent-, and system-specific factors associated with such profiles in order to ultimately inform future interventions. Methods: Data were drawn from a large Canadian cohort (N=1,570) across Ontario, resulting in 265 autistic children (mean age=10.9 years, 76% male). K-means clustering analyses were employed to partition distinct MH profiles in six MH measures (mood, anxiety, OCD symptoms, irritability, inattention, hyperactivity) and group differences were examined with reference to the above factors. Additionally, we investigated the characteristics of children who accessed acute MH services. Results: The optimal number of clusters was two; one included those experiencing MH deterioration across all six MH measures (61.3%, 95% confidence interval [CI]=54.9 to 67.4), and a second included youth that did not experience MH changes (38.7%, 95%CI=32.6 to 45.1). Child-specific factors associated with MH deterioration included higher pre-existing internalizing symptoms, high levels of COVID stress. Parental MH challenges and system-specific factors, such as the loss of learning supports, access to physicians and material deprivation, were also associated with MH deterioration. Access to acute MH services were primarily associated with financial insecurity and loss of services. Conclusions: More than half of autistic children experienced MH deterioration, and person-specific (pre-existing MH, COVID related stress), parent-specific (Parent MH) and system-level (loss of services and material deprivation) characteristics were associated with such decline, providing clinical and policy opportunities for intervention at multiple levels.

Fabrication of Chiral M13 Bacteriophage Film by Evaporation-Induced Self-Assembly.

Biomacromolecules are likely to undergo self-assembly and show specific collective behavior concentrated in the medium. Although the assembly procedures have been studied for unraveling their mysteries, there are few cases to directly demonstrate the collective behavior and phase transition process in dynamic systems. In the contribution, the drying process of M13 droplet is investigated, and can be successfully simulated by a doctor blade coating method. The morphologies in the deposited film are measured by atomic force microscopy and the liquid crystal phase development is captured in real time using polarized optical microscope. Collective behaviors near the contact line are characterized by the shape of meniscus curve and particle movement velocity. With considering rheological properties and flow, the resultant chiral film is used to align gold nanorods, and this approach can suggest a way to use M13 bacteriophage as a scaffold for the multi-functional chiral structures.

So You Want to Image Myelin Using MRI: An Overview and Practical Guide for Myelin Water Imaging.

Myelin water imaging (MWI) is an MRI imaging biomarker for myelin. This method can generate an in vivo whole-brain myelin water fraction map in approximately 10 minutes. It has been applied in various applications including neurodegenerative disease, neurodevelopmental, and neuroplasticity studies. In this review we start with a brief introduction of myelin biology and discuss the contributions of myelin in conventional MRI contrasts. Then the MRI properties of myelin water and four different MWI methods, which are categorized as T2 -, T2 *-, T1 -, and steady-state-based MWI, are summarized. After that, we cover more practical issues such as availability, interpretation, and validation of these methods. To illustrate the utility of MWI as a clinical research tool, MWI studies for two diseases, multiple sclerosis and neuromyelitis optica, are introduced. Additional topics about imaging myelin in gray matter and non-MWI methods for myelin imaging are also included. Although technical and physiological limitations exist, MWI is a potent surrogate biomarker of myelin that carries valuable and useful information of myelin. Evidence Level: 5 Technical Efficacy: 1 J. MAGN. RESON. IMAGING 2021;53:360-373.

Dynamic contrast-enhanced and diffusion-weighted MRI of invasive breast cancer for the prediction of sentinel lymph node status.

BACKGROUND: Although sentinel lymph node biopsy (SLNB) is the current standard for identifying lymph metastasis in breast cancer patients, there are complications of SLNB. PURPOSE: To evaluate preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) of invasive breast cancer for predicting sentinel lymph node metastasis. STUDY TYPE: Retrospective. POPULATION: In all, 309 patients who underwent clinically node-negative invasive breast cancer surgery FIELD STRENGTH/SEQUENCE: 3.0T, DCE-MRI, DWI. ASSESSMENT: We collected clinicopathologic variables (age, histologic and nuclear grade, extensive intraductal carcinoma component, lymphovascular invasion, and immunohistochemical profiles) and preoperative MRI features (tumor size, background parenchymal enhancement, internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, quantitative kinetic parameters, tumoral apparent diffusion coefficient [ADC], peritumoral maximal ADC, and peritumoral-tumoral ADC ratio). STATISTICAL TESTS: Multivariate logistic regressions were performed to determine independent variables associated with SLN metastasis, and the area under the receiver operating characteristic curve (AUC) was analyzed for those variables. RESULTS: 41 (13.3%) of the patients showed SLN metastasis. With MRI, tumor size (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06-1.17), heterogeneous (OR, 5.33; 95% CI, 1.71-16.58), and rim (OR, 15.54; 95% CI, 2.12-113.72) enhancement and peritumoral-tumoral ADC ratio (OR, 72.79; 95% CI, 7.15-740.82) were independently associated with SLN metastasis. Clinicopathologic variables independently associated with SLN metastasis included age (OR, 0.96; 95% CI, 0.92-0.99) and CD31 (OR, 2.90; 95% CI, 1.04-8.92). The area under the curve (AUC) of MRI features (0.80; 95% CI, 0.73-0.87) was significantly higher than for clinicopathologic variables (0.68; 95% CI, 0.60-0.77; P = 0.048) and was barely below statistical significance for combined MRI features with clinicopathologic variables (0.84; 95% CI 0.78-0.90, P = 0.057). DATA CONCLUSION: Preoperative internal enhancement on DCE-MRI and peritumoral-tumoral ADC ratio on DWI might be useful for predicting SLN metastasis in patients with invasive breast cancer. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:615-626.

Safety and efficacy of midazolam nasal spray for the treatment of intermittent bouts of increased seizure activity in the epilepsy monitoring unit: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Midazolam nasal spray (MDZ-NS) is indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern, in patients 12 years of age and older with epilepsy. This trial evaluated safety and efficacy of MDZ-NS in patients with epilepsy who were admitted to the epilepsy monitoring unit for seizure characterization/presurgical evaluation. METHODS: In this randomized, double-blind, placebo-controlled phase 3 trial (P261-301; NCT01999777), eligible patients with ≥2 seizures in the 6-hour window preceding trial medication administration for whom treatment was appropriate based on investigator's judgment were randomized (1:1) to MDZ-NS 5 mg or placebo. Efficacy outcomes were proportion of patients seizure-free for 6 hours after treatment and time to first seizure within 6 hours. Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs). RESULTS: Sixty-two patients were randomized (MDZ-NS n = 31; placebo n = 31), received trial medication, and completed the trial. A higher proportion of patients on MDZ-NS than placebo were seizure-free for 6 hours following treatment (54.8% vs 38.7%); however, the 16.1% difference was not statistically significant (P = .1972). The Kaplan-Meier curve of time to first seizure showed separation of both groups in favor of MDZ-NS from ~1.5 hours post-dose and throughout the 6-hour Treatment phase. Median time to first seizure was not estimable for MDZ-NS (>50% of patients had no seizure) and 3.9 hours for placebo (P = .1388). TEAEs with MDZ-NS were generally comparable to those with placebo. There were no deaths, serious TEAEs, or discontinuations due to TEAEs. SIGNIFICANCE: Although the observed treatment difference may be clinically meaningful, statistical significance was not demonstrated. Results suggest that MDZ-NS 5 mg may provide improvement over placebo, with efficacy maintained for ≥6 hours post-dose. MDZ-NS was well tolerated in this population.

LI-RADS v2014 categorization of hepatocellular carcinoma: Intraindividual comparison between gadopentetate dimeglumine-enhanced MRI and gadoxetic acid-enhanced MRI.

OBJECTIVES: To use Liver Imaging Reporting and Data System (LI-RADS) categorization and features of hepatocellular carcinomas (HCCs) to intraindividually compare gadopentetate dimeglumine-enhanced magnetic resonance imaging (Gd-DTPA-MRI) and gadoxetic acid-enhanced MRI (Gd-EOB-MRI), before and after applying modified major features. METHODS: Of 77 HCCs in 64 patients analysed, 17 HCCs were confirmed histopathologically and 46 patients had cirrhosis. Gd-EOB-MRI and Gd-DTPA-MRI were evaluated for the presence of major and ancillary features by two radiologists. LI-RADS categorization was done for Gd-DTPA-MRI (LI-RADS-DTPA) and for Gd-EOB-MRI before and after applying modified major features (hepatobiliary phase [HBP] hypointensity as an additional major feature, LI-RADS-EOBm1; HBP hypointense rim as capsule appearance, LI-RADS-EOBm2; and transitional phase [TP] hypointensity as washout appearance, LI-RADS-EOBm3). Sensitivities of LR-5 categorization for the diagnosis of HCC were compared. RESULTS: Washout (p=0.012) and capsule appearance (p<0.001) were less frequently observed on Gd-EOB-MRI. Sensitivity for LR-5 categorization was significantly higher with LI-RADS-DTPA compared with LI-RADS-EOB (p=0.001) and LI-RADS-EOBm2 (p=0.004), while sensitivity for LR-5 categorization with LI-RADS-EOBm1 (p=0.210) and LI-RADS-EOBm3 (p=0.727) was comparable. CONCLUSION: Modifying LI-RADS for use with Gd-EOB-MRI, such as applying HBP hypointensity as an additional major feature or using TP hypointensity as washout appearance, can improve the sensitivity for the detection of HCC. KEY POINTS: • Adding HBP hypointensity as additional major feature improved sensitivity of LR-5 categorization. • Adding TP hypointensity as modified washout appearance improved sensitivity of LR-5 categorization. • Sensitivities for LR-5 classification were comparable between LI-RADS-DTPA, LI-RADS-EOBm1, and LI-RADS-EOBm3.

Radiomics in peritumoral non-enhancing regions: fractional anisotropy and cerebral blood volume improve prediction of local progression and overall survival in patients with glioblastoma.

PURPOSE: The peritumoral non-enhancing region (NER) is frequently not removed during the surgical resection of glioblastoma, with most recurrences occurring within the original treatment field. This study determined whether radiomics analysis of the NER can predict local recurrence and overall survival in patients with glioblastoma. METHODS: Preoperative magnetic resonance imaging (MRI) scans from 83 consecutive patients with glioblastoma were retrospectively reviewed and grouped into training (n = 59) and test sets (n = 24). A total of 6472 radiomic features were extracted from contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images and from fractional anisotropy (FA) and normalized cerebral blood volume (CBV) maps. A diagnostic model to predict 6-month progression was tested using the area under the receiver operating characteristics curve (AUC) and compared with the single parameters of FA and CBV. A survival model was tested using Harrell's C-index and compared with clinical models that included age, sex, Karnofsky performance score, and extent of surgical resection. RESULTS: Four FA features and six CBV features were selected for the diagnostic model; no features were extracted from conventional MRI. Combined FA and CBV radiomics showed better predictive value for local progression (AUC, 0.79; 95% CI, 0.67-0.90) than single imaging radiomics (AUC, 0.70-0.76) or single imaging parameters (AUC, 0.51-0.54). The combined model (C-index, 0.87) improved prognostication when added to clinical models (C-index, 0.72). CONCLUSION: Radiomics features using FA and CBV in the NER have the potential to improve prediction of local progression and overall survival in patients with glioblastoma.

Projection of the Years of Life Lost, Years Lived with Disability, and ​Disability-Adjusted Life Years in Korea for 2030.

BACKGROUND: Projection of future trends in disease burden can facilitate setting of priorities for health policies and resource allocation. We report here projections of disease-specific mortality and the burdens of various diseases in Korea from 2016 to 2030. METHODS: Separate age- and sex-specific projection models for 21 major cause clusters from 2016 to 2030 were developed by applying coherent functional data models based on historical trends from 2002 to 2015. The age- and sex-specific years of life lost (YLL) for each cause cluster were projected based on the projected number of deaths. Years lived with disability (YLD) projections were derived using the 2015 age- and sex-specific YLD to YLL ratio. The disability-adjusted life years (DALYs) was the sum of YLL and YLD. RESULTS: The total number of deaths is projected to increase from 275,777 in 2015 to 421,700 in 2030, while the age-standardized death rate is projected to decrease from 586.9 in 2015 to 447.3 in 2030. The largest number of deaths is projected to be a result of neoplasms (75,758 deaths for males; 44,660 deaths for females), followed by cardiovascular and circulatory diseases (34,795 deaths for males; 48,553 deaths for females). The three leading causes of DALYs for both sexes are projected to be chronic respiratory diseases, musculoskeletal disorders, and other non-communicable diseases (NCDs). CONCLUSION: We demonstrate that NCDs will continue to account for the majority of the disease burden in Korea in the future.

Clinical and Genetic Analysis of an Infertile Male with 46,XX/46,XY Chimerism.

The sex chromosome-discordant chimerism 46,XX/46,XY is rarely found in humans with a phenotypically normal appearance, and this lack of phenotypic changes and the rarity of chimerism make it difficult to identify its exact incidence. Here, we report a case of this sex chromosome-discordant chimerism diagnosed by cytogenic and molecular analyses of peripheral blood in a phenotypically normal male who was referred to our facility for infertility. Based on the karyotype, fluorescence in situ hybridisation (FISH) and short tandem repeat (STR) analyses, the type of this chimerism was determined to be tetragametic presenting four alleles at two loci on chromosomes 16 and 21.

Comparison of transient severe motion in gadoxetate disodium and gadopentetate dimeglumine-enhanced MRI: effect of modified breath-holding method.

OBJECTIVES: To compare the occurrence of transient severe motion (TSM) between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI and between gadoxetate disodium-enhanced MRI scans obtained with and without the application of a modified breath-holding technique. METHODS: We reviewed 80 patients who underwent two magnetic resonance examinations (gadoxetate disodium-enhanced MRI and gadopentetate dimeglumine-enhanced MRI) with the application of a modified breath-holding technique (dual group). This group was compared with 100 patients who underwent gadoxetate disodium-enhanced MRI without the application of the modified breath-holding technique (single group). Patient risk factors and motion scores (1 [none] to 5 [non-diagnostic]) for each dynamic-phase imaging were analysed. RESULTS: In the dual group, mean motion scores did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI (p=0.096-0.807) in any phase. However, in all phases except the late dynamic phase, mean motion scores of the dual group were significantly lower than those in the single group. TSM incidence did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI in the dual group (3.8% vs. 1.3%, p=0.620). CONCLUSION: With proper application of the modified breath-holding technique, TSM occurrence with gadoxetate disodium-enhanced MRI was comparable to that associated with gadopentetate dimeglumine-enhanced MRI. KEY POINTS: • The modified breath-holding method significantly reduced the incidence of TSM. • Gadoxetate disodium and gadopentetate dimeglumine showed comparable motion scores. • TSM incidence was comparable between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI.

The neural correlates of attachment security in typically developing children.

This study investigated neural correlates of children's attachment security using functional magnetic resonance imaging. Fifty-one boys' attachment styles (age mean = 9.5 years, SD = 0.61) were assessed with the Separation Anxiety Test (SAT). We created an fMRI version of the SAT to activate children's attachment system in fMRI environment and contrasted two conditions in which children were instructed to infer the specific feeling of the boy in the picture or to identify objects or physical activities. In the final fMRI analysis (N = 21), attachment security could be detected at the neural level corresponding to the behavioural differences in the attachment interview. Securely attached children showed greater activation in the frontal, limbic and basal ganglia area which included the dorsolateral prefrontal cortex, amygdala, cingulate cortex and striatum, compared to other children who had lower quality of attachment. These regions have a key role in socio-emotional information processing and also represent a brain network related to approach and avoidance motivation in humans. Especially the striatum, strongly linked to reward processing underpinning social approach and avoidance motivation, showed the largest effects in these differences and also positively correlated with emotional openness scores in SAT. This suggests that the quality of attachment configures the approach and avoidance motivational system in our brain mediated by the striatum.

Optical Tracking Data Validation and Orbit Estimation for Sparse Observations of Satellites by the OWL-Net.

An Optical Wide-field patroL-Network (OWL-Net) has been developed for maintaining Korean low Earth orbit (LEO) satellites' orbital ephemeris. The OWL-Net consists of five optical tracking stations. Brightness signals of reflected sunlight of the targets were detected by a charged coupled device (CCD). A chopper system was adopted for fast astrometric data sampling, maximum 50 Hz, within a short observation time. The astrometric accuracy of the optical observation data was validated with precise orbital ephemeris such as Consolidated Prediction File (CPF) data and precise orbit determination result with onboard Global Positioning System (GPS) data from the target satellite. In the optical observation simulation of the OWL-Net for 2017, an average observation span for a single arc of 11 LEO observation targets was about 5 min, while an average optical observation separation time was 5 h. We estimated the position and velocity with an atmospheric drag coefficient of LEO observation targets using a sequential-batch orbit estimation technique after multi-arc batch orbit estimation. Post-fit residuals for the multi-arc batch orbit estimation and sequential-batch orbit estimation were analyzed for the optical measurements and reference orbit (CPF and GPS data). The post-fit residuals with reference show few tens-of-meters errors for in-track direction for multi-arc batch and sequential-batch orbit estimation results.