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Background: Lung epithelial cells serve as first line of defense against various inhaled pollutant particles. This study focused on assessing the impact of organic extracts of PM2.5 collected in Seoul, South Korea on primary human lung epithelial cells and identifying the relevant components and sources which induced lung epithelial cell injury.Results: We used primary lung epithelial cells isolated directly from healthy donors and evaluated the effects of organic compounds of twelve selected, seasonal PM2.5 on inflammation, cellular aging, and macroautophagy in primary lung epithelial cells. Organic extracts of PM2.5 specifically induced neutrophilic chemokine, interleukin-8, via extracellular signal regulated kinase activation. Moreover, PM2.5 significantly increased the expression of aging markers (p16, p21, and p27) and activated macroautophagy. Average mass concentrations, OC and EC, had no significant correlations with PM2.5 effects. However, regression analysis showed that polycyclic aromatic hydrocarbons and n-alkanes were the most relevant components of PM2.5 correlated with neutrophilic inflammation. Vegetative detritus and residential bituminous coal combustion sources were strongly correlated with neutrophilic inflammation, aging and macroautophagy activation.Conclusions: These data suggest that the chemical composition of PM2.5 is crucially important to determine the adverse health effects of PM2.5. Our study provides encouraging evidence to regulate the harmful components of PM2.5 in Seoul.

Imaging biomarkers support the diagnosis of Alzheimer’s disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P = 0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P = 0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P = 0.094) and MCI (0.85 vs 0.78; P = 0.065).

Objective Dystrophinopathy is an X-linked recessive muscular dystrophy caused by mutations in the DMD gene. Herein we describe the prenatal detection of DMD gene mutations in a patient with no family history, by multiplex ligation-dependent probe amplification (MLPA) after noninvasive prenatal screening (NIPS). Case report A 41-year-old woman underwent NIPS owing to an advanced maternal age. A copy number variation was detected in the maternal X chromosome, and uninformative results were obtained for the fetal sex chromosomes. Following amniocentesis, a duplication was identified in exons 1–29 of the dystrophin gene by MLPA. After interviewing her family members it was confirmed that the patient is a de novo carrier of DMD duplications, and her daughter is a carrier of the same mutation. Conclusion his is the first case report to describe the prenatal diagnosis of duplications in the DMD gene by MLPA following NIPS in a patient with no family history.

Tissue conductivity measurements made with electrical properties tomography (EPT) can be used to define temporal changes in tissue habitats on longitudinal multiparametric MRI. We aimed to demonstrate the added insights for identifying tumor habitats obtained by including EPT with diffusion- and perfusion-weighted MRI, and to evaluate the use of these tumor habitats for determining tumor treatment response in post-treatment glioblastoma. Tumor habitats were developed from EPT, diffusion-weighted, and perfusion-weighted MRI in 60 patients with glioblastoma who underwent concurrent chemoradiotherapy. Voxels from EPT, apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) maps were clustered into habitats, and each habitat was serially examined to assess its temporal change. The usefulness of temporal changes in tumor habitats for diagnosing tumor progression and treatment-related change was investigated using logistic regression. The performance of significant predictors was measured using the area under the curve (AUC) from receiver-operating-characteristics analysis with 1000-fold bootstrapping. Five tumor habitats were identified, and of these, the hypervascular cellular habitat (odds ratio [OR] 5.45; 95% CI, 1.75–31.42; p = .02), hypovascular low conductivity habitat (OR 2.00; 95% CI, 1.45–3.05; p < .001), and hypovascular intermediate habitat (OR 1.57; 95% CI, 1.18–2.30; p = .006) were predictive of tumor progression. Low EPT and low CBV reflected a unique hypovascular low conductivity habitat that showed the highest diagnostic performance (AUC 0.86; 95% CI, 0.76–0.96). The combined habitats showed high performance (AUC 0.90; 95% CI, 0.82–0.98) in the differentiation of tumor progression from treatment-related change. EPT reveals low conductivity habitats that can improve the diagnosis of tumor progression in post-treatment glioblastoma. • Electrical properties tomography (EPT) demonstrated lower conductivity in tumor progression than in treatment-related change. • EPT allowed identification of a unique hypovascular low conductivity habitat when combined with cerebral blood volume mapping. • Tumor habitats with a hypovascular low conductivity habitat, hypervascular cellular habitat, and hypovascular intermediate habitat yielded high diagnostic performance for diagnosing tumor progression.

Background and Purpose: Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. Methods: This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. Results: In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35, P P P P Conclusions: ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study. Registration: URL: https://cris.nih.go.kr/cris/en ; Unique identifier: KCT0004628.

Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, it may prolong the QTc interval. Furthermore, when hydroxychloroquine is administered concomitantly with other drugs, it can exacerbate the risk of QT prolongation. Nevertheless, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and concomitant medications has not yet been identified. To evaluate the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice, we analyzed the electrocardiogram results obtained for 447,632 patients and their relevant electronic health records in a tertiary teaching hospital in Korea from 1996 to 2018. We repeated the case–control analysis for each drug. In each analysis, we performed multiple logistic regression and calculated the odds ratio (OR) for each target drug, hydroxychloroquine, and the interaction terms between those two drugs. The DDIs were observed in 12 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, cyclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, isoniazid, clarithromycin, and furosemide), all with a p value of

BACKGROUND AND PURPOSE: Currently available perfusion parameters are limited in differentiating early tumor progression and pseudoprogression with no insight about vessel size and type. We aimed to investigate differences in vessel size and type between early tumor progression and pseudoprogression in posttreatment glioblastoma and to demonstrate diagnostic performance using vessel architectural imaging. MATERIALS AND METHODS: Fifty-eight patients with enlarging contrast-enhancing masses in posttreatment glioblastomas underwent simultaneous gradient recalled-echo and spin-echo dynamic susceptibility contrast imaging. Relative CBV and vessel architectural imaging parameters, including the relative vessel size index, peak shift between gradient recalled echo and spin-echo bolus signal peaks, and arterial dominance scores using spatial dominance of arterial/venous vessel type, were calculated and compared between the 2 conditions. The area under the curve and cross-validation were performed to compare the diagnostic performance of the relative CBV, vessel architectural imaging parameters, and their combinations. RESULTS: There were 41 patients with early tumor progression and 17 patients with pseudoprogression. Relative to pseudoprogression, early tumor progression showed a lower peak shift (−0.02 versus 0.33, P = .02) and a lower arterial dominance score (1.46 versus 2.11, P = .001), indicating venous dominance. Patients with early tumor progression had higher relative CBV (1.88 versus 1.38, P = .02) and a tendency toward a larger relative vessel size index (99.67 versus 83.17, P = .15) than those with pseudoprogression. Combining arterial dominance scores and relative CBV showed significantly higher diagnostic performance (area under the curve = 0.82; 95% CI, 0.70–0.94; P = .02) than relative CBV alone (area under the curve = 0.64; 95% CI, 0.49–0.79) in distinguishing early tumor progression from pseudoprogression. CONCLUSIONS: Vessel architectural imaging significantly improved the diagnostic performance of relative CBV by demonstrating venous dominance and a tendency toward larger vessel size in early tumor progression.

The purpose of this study was to establish a high-performing radiomics strategy with machine learning from conventional and diffusion MRI to differentiate recurrent glioblastoma (GBM) from radiation necrosis (RN) after concurrent chemoradiotherapy (CCRT) or radiotherapy. Eighty-six patients with GBM were enrolled in the training set after they underwent CCRT or radiotherapy and presented with new or enlarging contrast enhancement within the radiation field on follow-up MRI. A diagnosis was established either pathologically or clinicoradiologically (63 recurrent GBM and 23 RN). Another 41 patients (23 recurrent GBM and 18 RN) from a different institution were enrolled in the test set. Conventional MRI sequences (T2-weighted and postcontrast T1-weighted images) and ADC were analyzed to extract 263 radiomic features. After feature selection, various machine learning models with oversampling methods were trained with combinations of MRI sequences and subsequently validated in the test set. In the independent test set, the model using ADC sequence showed the best diagnostic performance, with an AUC, accuracy, sensitivity, specificity of 0.80, 78%, 66.7%, and 87%, respectively. In conclusion, the radiomics models models using other MRI sequences showed AUCs ranging from 0.65 to 0.66 in the test set. The diffusion radiomics may be helpful in differentiating recurrent GBM from RN..

Purpose This study aimed to examine the inter-method reliability and volumetric differences between NeuroQuant (NQ) and Freesurfer (FS) using T1 volume imaging sequence with different slice thicknesses in patients with mild cognitive impairment (MCI). Materials and methods This retrospective study enrolled 80 patients diagnosed with MCI at our memory clinic. NQ and FS were used for volumetric analysis of three-dimensional T1-weighted images with slice thickness of 1 and 1.2 mm. Inter-method reliability was measured with Pearson correlation coefficient (r), intraclass correlation coefficient (ICC), and effect size (ES). Results Overall, NQ volumes were larger than FS volumes in several locations: whole brain (0.78%), cortical gray matter (5.34%), and white matter (2.68%). Volume measures by NQ and FS showed good-to-excellent ICCs with both 1 and 1.2 mm slice thickness (ICC=0.75-0.97, ES=-1.0-0.73 vs. ICC=0.78-0.96, ES=-0.9-0.77, respectively), except for putamen, pallidum, thalamus, and total intracranial volumes. The ICCs in all locations, except the putamen and cerebellum, were slightly higher with a slice thickness of 1 mm compared to those of 1.2 mm. Conclusion Inter-method reliability between NQ and FS was good-to-excellent in most regions with improvement with a 1-mm slice thickness. This finding indicates that the potential effects of slice thickness should be considered when performing volumetric measurements for cognitive impairment.

In predicting the hepatic elimination of compounds, the extended clearance concept has proven useful. Yet, its experimental proof was scarce partly due to the lack of models with the controlled expression of transporters. Here, the uptake and efflux transporters [NTCP (SLC10A1) and BSEP (ABCB11), respectively] were doubly and transiently expressed in MDCKII cells by electroporation-based transfection (with the BSEP plasmid amount varied and with the NTCP plasmid fixed), achieving the activity levels of NTCP and BSEP comparable to those of sandwich cultured human hepatocytes. The biliary excretion clearance for taurocholate increased proportionally to the BSEP expression level. Under the same conditions, the basal-to-apical transcellular clearance of taurocholate displayed an initial increase, and a subsequent plateau, indicating that the basolateral uptake of taurocholate became rate-limiting. The doubly transfected MDCKII cells were also used to kinetically analyze the inhibitory effects of rifampicin on BSEP and NTCP. The obtained results showed a bell-shaped profile for cell-to-medium concentration ratios over a range of rifampicin concentrations, which were quantitatively captured by kinetic modeling based on the extended clearance concept. The present study highlights the utility of the transient, tunable transporter expression system in delineating the rate-determining process and providing mechanistic insights into intracellular substrate accumulation.

Pemafibrate (PMF) is highly albumin-bound (>99.8%) and a substrate for hepatic uptake transporters (OATP1B) and CYP enzymes. Here, we developed a PBPK model of PMF to capture drug-drug interactions (DDI) incurred by cyclosporine (CsA) and rifampicin (RIF), the two OATP1B inhibitors. Initial PBPK modeling of PMF utilized in vitro hepatic uptake clearance (PSinf) obtained in the absence of albumin, but failed in capturing the blood PMF pharmacokinetic (PK) profiles. Based on the results that in vitro PSinf of unbound PMF was enhanced in the presence of albumin, we applied the albumin-facilitated dissociation model and the resulting PSinf parameters improved the prediction of the blood PMF PK profiles. In refining our PBPK model toward improved prediction of the observed DDI data (PMF co-administered with single dosing of CsA or RIF; PMF following multiple RIF dosing), we adjusted the previously obtained in vivo OATP1B inhibition constants (Ki,OATP1B) of CsA or RIF for pitavastatin by correcting for substrate-dependency. We also incorporated the induction of OATP1B and CYP enzymes after multiple RIF dosing. Sensitivity analysis informed that the higher gastrointestinal absorption rate constant could further improve capturing the observed DDI data, suggesting the possible inhibition of intestinal ABC transporter(s) by CsA or RIF.

OBJECTIVE To compare two clinically available MR volumetry software, NeuroQuant® (NQ) and Inbrain® (IB), and examine the inter-method reliabilities and differences between them. MATERIALS AND METHODS This study included 172 subjects (age range, 55-88 years; mean age, 71.2 years), comprising 45 normal healthy subjects, 85 patients with mild cognitive impairment, and 42 patients with Alzheimer's disease. Magnetic resonance imaging scans were analyzed with IB and NQ. Mean differences were compared with the paired t test. Inter-method reliability was evaluated with Pearson's correlation coefficients and intraclass correlation coefficients (ICCs). Effect sizes were also obtained to document the standardized mean differences. RESULTS The paired t test showed significant volume differences in most regions except for the amygdala between the two methods. Nevertheless, inter-method measurements between IB and NQ showed good to excellent reliability (0.72 < r < 0.96, 0.83 < ICC < 0.98) except for the pallidum, which showed poor reliability (left: r = 0.03, ICC = 0.06; right: r = -0.05, ICC = -0.09). For the measurements of effect size, volume differences were large in most regions (0.05 < r < 6.15). The effect size was the largest in the pallidum and smallest in the cerebellum. CONCLUSION Comparisons between IB and NQ showed significantly different volume measurements with large effect sizes. However, they showed good to excellent inter-method reliability in volumetric measurements for all brain regions, with the exception of the pallidum. Clinicians using these commercial software should take into consideration that different volume measurements could be obtained depending on the software used.

Dramatic cellular reorganization in mitosis critically depends on the timely and temporal phosphorylation of a broad range of proteins, which is mediated by the activation of the mitotic kinases and repression of counteracting phosphatases. The mitosis-to-interphase transition, which is termed mitotic exit, involves the removal of mitotic phosphorylation by protein phosphatases. Although protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) drive this reversal in animal cells, the phosphatase network associated with ordered bulk dephosphorylation in mitotic exit is not fully understood. Here, we describe a new mitotic phosphatase relay in which Wip1/PPM1D phosphatase activity is essential for chromosomal passenger complex (CPC) translocation to the anaphase central spindle after release from the chromosome via PP1-mediated dephosphorylation of histone H3T3. Depletion of endogenous Wip1 and overexpression of the phosphatase-dead mutant disturbed CPC translocation to the central spindle, leading to failure of cytokinesis. While Wip1 was degraded in early mitosis, its levels recovered in anaphase and the protein functioned as a Cdk1-counteracting phosphatase at the anaphase central spindle and midbody. Mechanistically, Wip1 dephosphorylated Thr-59 in inner centromere protein (INCENP), which, subsequently bound to MKLP2 and recruited other components to the central spindle. Furthermore, Wip1 overexpression is associated with the overall survival rate of patients with breast cancer, suggesting that Wip1 not only functions as a weak oncogene in the DNA damage network but also as a tumor suppressor in mitotic exit. Altogether, our findings reveal that sequential dephosphorylation of mitotic phosphatases provides spatiotemporal regulation of mitotic exit to prevent tumor initiation and progression.

SummaryThe aim of the present study was to investigate the effects of porcine follicular fluid (pFF) from large-sized (LFF; >8 mm in diameter) and medium-sized (MFF; 3–6 mm in diameter) follicles on the maturation and developmental competence of porcine oocytes. Cumulus–oocyte complexes (COCs) were collected from follicles 3–6 mm in diameter. The collected COCs were incubated for 22 h with LFF or MFF (in vitromaturation (IVM)-I stage) and were incubated subsequently for 22 h with LFF or MFF (IVM-II stage). Cumulus expansion was confirmed after the IVM-I stage and nuclear maturation was evaluated after the IVM-II stage. Intracellular glutathione (GSH) and reactive oxygen species (ROS) levels were measured and embryonic development was evaluated. Relative cumulus expansion and GSH levels were higher in the LFF group compared with in the MFF group after the IVM-I stage (P <0.05). After the IVM-II stage, the numbers of oocytes in metaphase-II were increased in the LFF group and GSH content was higher in all of the LFF treatment groups compared with in the MFF treatment groups during both IVM stages (P <0.05). ROS levels were reduced by LFF treatment regardless of IVM stage (P <0.05). Blastocyst formation and the total numbers of cells in blastocysts were increased in all LFF treatment groups compared with the control group (P <0.05). These results suggested that pFF from large follicles at the IVM stage could improve nucleic and cytoplasmic maturation status and further embryonic development through reducing ROS levels and enhancing responsiveness to gonadotropins.

We evaluated the diagnostic performance and generalizability of traditional machine learning and deep learning models for distinguishing glioblastoma from single brain metastasis using radiomics. The training and external validation cohorts comprised 166 (109 glioblastomas and 57 metastases) and 82 (50 glioblastomas and 32 metastases) patients, respectively. Two-hundred-and-sixty-five radiomic features were extracted from semiautomatically segmented regions on contrast-enhancing and peritumoral T2 hyperintense masks and used as input data. For each of a deep neural network (DNN) and seven traditional machine learning classifiers combined with one of five feature selection methods, hyperparameters were optimized through tenfold cross-validation in the training cohort. The diagnostic performance of the optimized models and two neuroradiologists was tested in the validation cohort for distinguishing glioblastoma from metastasis. In the external validation, DNN showed the highest diagnostic performance, with an area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.956 (95% confidence interval [CI], 0.918–0.990), 90.6% (95% CI, 80.5–100), 88.0% (95% CI, 79.0–97.0), and 89.0% (95% CI, 82.3–95.8), respectively, compared to the best-performing traditional machine learning model (adaptive boosting combined with tree-based feature selection; AUC, 0.890 (95% CI, 0.823–0.947)) and human readers (AUC, 0.774 [95% CI, 0.685–0.852] and 0.904 [95% CI, 0.852–0.951]). The results demonstrated deep learning using radiomic features can be useful for distinguishing glioblastoma from metastasis with good generalizability.

Background Amide proton transfer (APT) MRI has the potential to demonstrate antitumor effects by reflecting biologically active tumor portion, providing different information from diffusion-weighted imaging (DWI) or dynamic susceptibility contrast (DSC) imaging. Purpose To evaluate whether a change in APT signal intensity after antiangiogenic treatment is predictive of early treatment response in recurrent glioblastoma. Materials and Methods In this retrospective study, APT MRI, DWI, and DSC imaging were performed in patients with recurrent glioblastoma from July 2015 to April 2019, both before treatment and 4-6 weeks after initiation of bevacizumab (follow-up). Progression was based on pathologic confirmation or clinical-radiologic assessment, and progression patterns were defined as local enhancing or diffuse nonenhancing. Changes in mean and histogram parameters (fifth and 95th percentiles) of APT signal intensity, apparent diffusion coefficient, and normalized cerebral blood volume (CBV) between imaging time points were calculated. Predictors of 12-month progression and progression-free survival (PFS) were determined by using logistic regression and Cox proportional hazard modeling and according to progression type. Results A total of 54 patients were included (median age, 56 years [interquartile range, 49-64 years]; 24 men). Mean APT signal intensity change after bevacizumab treatment indicated a low 12-month progression rate (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13, 0.90

Despite being a major breakthrough in multiple myeloma therapy, carfilzomib (CFZ, a second-generation proteasome inhibitor drug) has been largely ineffective against solid cancer, possibly due to its pharmacokinetic drawbacks including metabolic instability. Recently, quinic acid (QA, a low-affinity ligand of selectins upregulated in peritumoral vasculature) was successfully utilized as a surface modifier for nanoparticles containing paclitaxel. Here, we designed QA-conjugated nanoparticles containing CFZ (CFZ@QANP; the surface of poly(lactic-co-glycolic acid) nanoparticles modified by conjugation with a QA derivative). Compared to the clinically used cyclodextrin-based formulation (CFZ-CD), CFZ@QANP enhanced the metabolic stability and in vivo exposure of CFZ in mice. CFZ@QANP, however, showed little improvement in suppressing tumor growth over CFZ-CD against the murine 4T1 orthotopic breast cancer model. CFZ@QANP yielded no enhancement in proteasomal inhibition in excised tumors despite having a higher level of remaining CFZ than CFZ-CD. These results likely arise from delayed, incomplete CFZ release from CFZ@QANP as observed using biorelevant media in vitro. These results suggest that the applicability of QANP may not be predicted by physicochemical parameters commonly used for formulation design. Our current results highlight the importance of considering drug release kinetics in designing effective CFZ formulations for solid cancer therapy.

To establish a diagnostic tree analysis (DTA) model based on ultrasonography (US) findings and clinical characteristics for differential diagnosis of common causes of cervical lymphadenopathy in children. A total of 242 patients (131 boys, 111 girls; mean age, 11.2 ± 0.3 years; range, 1 month–18 years) with pathologically confirmed Kikuchi disease (n = 127), reactive hyperplasia (n = 64), lymphoma (n = 24), or suppurative lymphadenitis (n = 27) who underwent neck US were included. US images were retrospectively reviewed to assess lymph node (LN) characteristics, and clinical information was collected from patient records. DTA models were created using a classification and regression tree algorithm on the basis of US imaging and clinical findings. The patients were randomly divided into training (70%, 170/242) and validation (30%, 72/242) datasets to assess the diagnostic performance of the DTA models. In the DTA model based on all predictors, perinodal fat hyperechogenicity, LN echogenicity, and short diameter of the largest LN were significant predictors for differential diagnosis of cervical lymphadenopathy (overall accuracy, 85.3% and 83.3% in the training and validation datasets). In the model based on categorical parameters alone, perinodal fat hyperechogenicity, LN echogenicity, and loss of fatty hilum were significant predictors (overall accuracy, 84.7% and 86.1% in the training and validation datasets). Perinodal fat hyperechogenicity, heterogeneous echotexture, short diameter of the largest LN, and loss of fatty hilum were significant US findings in the DTA for differential diagnosis of cervical lymphadenopathy in children. • Diagnostic tree analysis model based on ultrasonography and clinical findings would be helpful in differential diagnosis of pediatric cervical lymphadenopathy. • Significant predictors were perinodal fat hyperechogenicity, heterogeneous echotexture, short diameter of the largest LN, and loss of fatty hilum.

We aimed to develop and validate a multiparametric MR radiomics model using conventional, diffusion-, and perfusion-weighted MR imaging for better prognostication in patients with newly diagnosed glioblastoma. A total of 216 patients with newly diagnosed glioblastoma were enrolled from two tertiary medical centers and divided into training (n = 158) and external validation sets (n = 58). Radiomic features were extracted from contrast-enhanced T1-weighted imaging, fluid-attenuated inversion recovery, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. After radiomic feature selection using LASSO regression, an individualized radiomic score was calculated. A multiparametric MR prognostic model was built using the radiomic score and clinical predictors. The results showed that the multiparametric MR prognostic model (radiomics score + clinical predictors) exhibited good discrimination (C-index, 0.74) and performed better than a conventional MR radiomics model (C-index, 0.65, P P

Objective: The objective of the study was to investigate whether radiomics features of extrahippocampal regions differ between patients with epilepsy and healthy controls, and whether any differences can identify patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE).Methods: Data from 36 patients with hippocampal sclerosis (HS) and 50 healthy controls were used to construct a radiomics model. A total of 1,618 radiomics features from the affected hippocampal and extrahippocampal regions were compared with features from healthy controls and the unaffected side of patients. Using a stepwise selection method with a univariate t-test and elastic net penalization, significant predictors for identifying TLE were separately selected for the hippocampus (H+) and extrahippocampal region (H–). Each model was independently validated with an internal set of MRI-negative adult TLE patients (n = 22) and pediatric validation cohort with MRI-negative TLE (n = 20) from another tertiary center; diagnostic performance was calculated using area under the curve (AUC) of the receiver-operating-characteristic curve analysis.Results: Forty-eight significant H+ radiomic features and 99 significant H– radiomic features were selected from the affected side of patients and used to create a hippocampus model and an extrahippocampal model, respectively. Texture features were the most frequently selected feature. Training set showed slightly higher accuracy between hippocampal (AUC = 0.99) and extrahippocampal model (AUC = 0.97). In the internal validation and external validation sets, the extrahippocampal model (AUC = 0.80 and 0.92, respectively) showed higher diagnostic performance for identifying the affected side of patients than the hippocampus model (AUC = 0.67 and 0.69).Significance: Radiomics revealed extrahippocampal abnormality in the affected side of patients with TLE and could potentially help to identify MRI-negative TLE.Classification of Evidence: Class IV Criteria for Rating Diagnostic Accuracy Studies.

Background. The risk of hypertension differs according to lifestyle factors and individual constitution types. The aim of this study was to investigate the effect of lifestyle factors on hypertension and to assess whether those effects differ according to the constitution types. Methods. A total of 5,793 men and women were recruited between 2012 and 2014. Odds ratios for hypertension associated with constitution types and lifestyle factors were estimated. Lifestyle factors included smoking status, body mass index, alcohol consumption, physical activity, and sleep quality. Constitution types were estimated based on the Sasang constitutional medicine as the TE type, SE type, and SY type. Results. The risk of hypertension was significantly higher for SY (odds ratio 1.25 (95% confidence interval 1.03 to 1.52) and TE types (1.38 (1.10 to 1.74)) than the SE type even with adjustment of health behaviors. Compared with individuals who had an unhealthy lifestyle, those with healthy lifestyle scores showed significantly lower risk of hypertension in only SY (odds ratio 0.62 (95% confidence interval 0.48 to 0.81)) and TE types (0.69 (0.58 to 0.81)). The difference in risk for hypertension among constitution types was decreased with a healthy lifestyle (1.34 in SY and 2.35 in TE types, as compared with the SE type) versus an unhealthy lifestyle (2.21 in SY and 3.64 in TE types, as compared with the SE type). Conclusion. The risk of hypertension was different by Sasang constitution types. The impact of lifestyle factors differed according to Sasang constitution types, and the difference in risk of hypertension among constitution types was decreased with a healthy lifestyle.

Objectives Transforming growth factor‐beta (TGF‐β) is a multifunctional regulatory factor. Here we measured serum soluble TGF‐β (sTGF‐β) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients. Methods We prospectively enrolled 60 patients treated with FOLFIRINOX as the first‐line palliative chemotherapy. We collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF‐β using an enzyme‐linked immunosorbent assay. Results The patients’ median overall survival (OS) and progression‐free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5‐12.1) and 6.5 (95% CI, 4.9‐8.1) months, respectively. Patients with low sTGF‐β at diagnosis (, Pre‐treatment sTGF‐β levels serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. The dynamics of sTGF‐β during chemotherapy have prognostic value.

Background The effect of temperature and humidity on the incidence of influenza may differ by climate region. In addition, the effect of diurnal temperature range on influenza incidence is unclear, according to previous study findings. Objectives The aim of this study was to analyze the effects of temperature, humidity, and diurnal temperature range on the incidence of influenza in Seoul, Republic of Korea, which is located in a temperate region. Methods We used Korean National Health insurance data to assess the weekly influenza incidence between 2010 and 2016, and used meteorological data from Seoul. To investigate the effect of temperature, relative humidity, and diurnal temperature range levels on influenza incidence, we used a distributed lag non‐linear model. Results The risk of influenza incidence was significantly increased with low daily temperatures of 0‐5°C and low (30%–40%) or high (70%) relative humidity. We found a positive significant association between diurnal temperature range and influenza incidence in this study. Conclusions Influenza incidence increased with low temperature and low/high humidity in a temperate region. Influenza incidence also increased with high diurnal temperature range, after considering temperature and humidity.

To evaluate radiomics studies according to radiomics quality score (RQS) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to provide objective measurement of radiomics research. PubMed and Embase were searched for studies published in high clinical imaging journals until December 2018 using the terms “radiomics” and “radiogenomics.” Studies were scored against the items in the RQS and TRIPOD guidelines. Subgroup analyses were performed for journal type (clinical vs. imaging), intended use (diagnostic vs. prognostic), and imaging modality (CT vs. MRI), and articles were compared using Fisher’s exact test and Mann-Whitney analysis. Seventy-seven articles were included. The mean RQS score was 26.1% of the maximum (9.4 out of 36). The RQS was low in demonstration of clinical utility (19.5%), test-retest analysis (6.5%), prospective study (3.9%), and open science (3.9%). None of the studies conducted a phantom or cost-effectiveness analysis. The adherence rate for TRIPOD was 57.8% (mean) and was particularly low in reporting title (2.6%), stating study objective in abstract and introduction (7.8% and 16.9%), blind assessment of outcome (14.3%), sample size (6.5%), and missing data (11.7%) categories. Studies in clinical journals scored higher and more frequently adopted external validation than imaging journals. The overall scientific quality and reporting of radiomics studies is insufficient. Scientific improvements need to be made to feature reproducibility, analysis of clinical utility, and open science categories. Reporting of study objectives, blind assessment, sample size, and missing data is deemed to be necessary. • The overall scientific quality and reporting of radiomics studies is insufficient. • The RQS was low in demonstration of clinical utility, test-retest analysis, prospective study, and open science. • Room for improvement was shown in TRIPOD in stating study objective in abstract and introduction, blind assessment of outcome, sample size, and missing data categories.

To investigate whether clinical condition, imaging session, and locations affect repeatability of amide proton transfer–weighted (APTw) magnetic resonance imaging (MRI) in the brain. 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. 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

Purpose Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and methods We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings. Results In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget.

Radiomics, which involves the use of high-dimensional quantitative imaging features for predictive purposes, is a powerful tool for developing and testing medical hypotheses. Radiologic and statistical challenges in radiomics include those related to the reproducibility of imaging data, control of overfitting due to high dimensionality, and the generalizability of modeling. The aims of this review article are to clarify the distinctions between radiomics features and other omics and imaging data, to describe the challenges and potential strategies in reproducibility and feature selection, and to reveal the epidemiological background of modeling, thereby facilitating and promoting more reproducible and generalizable radiomics research.

The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.

Neuromuscular choristomas are rare tumors with mature skeletal muscle elements admixed with neural elements. Follow-up results are limited, the natural history of neuromuscular choristomas is poorly understood. To date, 14 cases of sciatic nerve neuromuscular choristomas have been reported, but follow-up results were provided only for 10 cases (median duration: 2 years). The natural history of neuromuscular choristomas is therefore poorly understood due to lack of longitudinal data. We describe a case with long-term natural history for 17 years of the disease and provide a literature review of the reported cases. A 6 year old girl, with a 6 year history of left buttock mass with neonatal pathologic diagnosis of neuromusculoar choristoma, presented with intermittent left lower extremity weakness in July 2006. She had a left buttock mass for 6 years, and the neonatal pathologic diagnosis was neuromuscular choristoma. Magnetic resonance imaging (MRI) revealed fusiform enlargement of the left sciatic nerve with mild enhancement similar to that of the muscle. The pathology of a re-biopsy sample was also consistent with neuromuscular. choristoma. In follow up, the mass increased slightly, but MRI findings remained consistent, and her condition remained stable for 11 years after re-biopsy. Aggressive fibrosis known as complication by manipulation of neuromuscular choristoma was also not developed. The patient has been followed up for a total of 17 years and this is the only case of long-term natural history of neuromuscular choristoma.

The present study evaluates the transdifferentiation potential of different region-derived same donor Wharton’s jelly MSCs (WJMSCs) into functional smooth muscle-like cells (SMLCs). All regions showed baseline expression for early smooth muscle cell (SMC) markers (αSMA and SM22-α) whereas mid marker CALPONIN gradually reduced during in vitro culture expansion and late marker myosin heavy chain type-11 (MHY-11) was completely absent. Furthermore, WJMSCs were induced to SMLCs using DMEM containing 10% FBS supplemented with different concentrations/combinations of TGF-β1 and PDGF-BB under normoxia (20% O2) condition. Three treatment groups namely group A: 2.5 ng/ml TGF-β1, group B: 5 ng/ml PDGF-BB and group C: 2.5 ng/ml TGF-β1 + 5 ng/ml PDGF-BB were used for the induction of WJMSCs into SMLCs. Cells were evaluated for SMC-specific marker expression at different time intervals. Finally, selection of the SMC-specific highly potent region along with the most suitable treatment group was done on the basis of highest outcome in terms of SMC-specific marker expression and functional competence of transdifferentiated cells. Among all regions, baby region-derived WJMSCs (B-WJMSCs) exhibited highest SMC marker expression and functional ability. To mimic the in vivo physiological conditions, hypoxic conditions (3% O2) were used to evaluate the effect of low oxygen on the SMLC differentiation potential of selected WJMSCs using previously used same parameters. Annexin-V assay was performed to check the effect of cytokines and different oxygen concentrations, which revealed no significant differences. It was concluded that different induction conditions have different but positive effects on the functional SMLC differentiation ability of WJMSCs.

To test if adding permeability measurement to perfusion obtained from dynamic susceptibility contrast MRI (DSC-MRI) improves diagnostic performance in the differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma. DSC-MRI was acquired in 145 patients with pathologically proven glioblastoma (n = 89) or PCNSL (n = 56). The permeability metrics of contrast agent extraction fraction (Ex), apparent permeability (Ka), and leakage-corrected perfusion of normalized cerebral blood volume (nCBVres) and cerebral blood flow (nCBFres) were derived from a tissue residue function. For comparison purposes, the leakage-corrected normalized CBV (nCBV) and relative permeability constant (K2) were also obtained using the established Weisskoff-Boxerman leakage correction method. The area under the receiver operating characteristics curve (AUC) and cross-validation were used to compare the diagnostic performance of the single DSC-MRI parameters with the performance obtained with the addition of permeability metrics. PCNSL demonstrated significantly higher permeability (Ex, p

The second-in-class proteasome inhibitor (PI) carfilzomib (Kyprolis, Cfz) has contributed to a substantial advancement in multiple myeloma treatment by improving patient survival and quality of life. A considerable portion of patients however display intrinsic resistance to Cfz. Our mechanistic understanding of intrinsic Cfz resistance is limited due to a lack of suitable cell-based models. We report that H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). These results indicate that H727 cells remain dependent on the UPS for cell survival and growth despite harboring intrinsic resistance to Cfz. Alterations in the composition of proteasome catalytic subunits via interferon-γ treatment or siRNA knockdown results in sensitization of H727 cells to Cfz. We postulate that a potential link may exist between the composition of proteasome catalytic subunits and the cellular response to Cfz. Overall, H727 cells may serve as a useful cell-based model for de novo Cfz resistance and our results suggest previously unexplored mechanisms of de novo PI resistance.

Background Prehypertension and hypertension are associated with cardiovascular disease, ischemic heart disease, and stroke morbidity. The purpose of this study is to evaluate the effectiveness and safety of moxibustion in patients with prehypertension or hypertension. Methods Forty-five subjects with prehypertension or stage I hypertension were randomized into three groups: moxibustion treatment group A (2 sessions/week for 4 weeks), moxibustion treatment group B (3 sessions/week for 4 weeks), and control group (nontreated group). The primary outcome measure was the change in blood pressure after 4 weeks of treatment. Safety was assessed at every visit. Results There were no significant differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) among three groups after 4 weeks of treatment (p = 0.4798 and p = 0.3252, respectively). In treatment group B, there was a significant decrease in SBP and DBP from baseline to 4 weeks of treatment (mean difference (MD) −9.55; p = 0.0225, MD −7.55; p = 0.0098, respectively). There were no significant differences among groups in secondary outcome measures after 4 weeks of treatment. Six adverse events (AEs) in the treatment group A and 12 AEs in the treatment group B occurred related to the moxibustion treatment. Conclusion In conclusion, the results of this study show that moxibustion (3 sessions/week for 4 weeks) might lower blood pressure in patients with prehypertension or stage I hypertension and treatment frequency might affect effectiveness of moxibustion in BP regulation. Further randomized controlled trials with a large sample size on prehypertension and hypertension should be conducted. Trial registration This study was registered with the ‘Clinical Research Information Service (CRIS)’, Republic of Korea (KCT0000469), and the protocol for this study was presented orally at the 15th International Council of Medical Acupuncture and Related Techniques (ICMART) in Athens, 25–27 May 2012.

Endothelial dysfunction-induced lipid retention is an early feature of atherosclerotic lesion formation. Apoptosis of vascular smooth muscle cells (VSMCs) is one of the major modulating factors of atherogenesis, which accelerates atherosclerosis progression by causing plaque destabilization and rupture. However, the mechanism underlying VSMC apoptosis mediated by endothelial dysfunction in relation to atherosclerosis remains elusive. In this study, we reveal differential expression of several genes related to lipid retention and apoptosis, in conjunction with atherosclerosis, by utilizing a genetic mouse model of endothelial nitric oxide synthase (eNOS) deficiency manifesting endothelial dysfunction. Moreover, eNOS deficiency led to the enhanced susceptibility against pro-apoptotic insult in VSMCs. In particular, the expression of aggrecan, a major proteoglycan, was elevated in aortic tissue of eNOS deficient mice compared to wild type mice, and administration of aggrecan induced apoptosis in VSMCs. This suggests that eNOS deficiency may elevate aggrecan expression, which promotes apoptosis in VSMC, thereby contributing to atherosclerosis progression. These results may facilitate the development of novel approaches for improving the diagnosis or treatment of atherosclerosis. [BMB Reports 2019; 52(2): 145-150].

Objectives The diagnostic role of an ultrasound (US) and plasma renin activity (PRA) combination is unknown, despite the usefulness of Doppler US as a screening tool for renovascular hypertension (RVHT). The purpose of this study was to evaluate the diagnostic usefulness of US for RVHT in children stratified according to PRA. Methods We identified 336 children who underwent renal Doppler US examinations for hypertension and divided them into a high-renin group (n = 177) and a normal-renin group (n = 159) based on PRA and stratified them by age. The Doppler US findings were retrospectively reviewed, and computed tomographic angiography (CTA) for the same children was used as the reference standard. Results In the high-renin group, 36 patients had positive Doppler US findings that were confirmed by CTA in 32 cases. The sensitivity and specificity values for Doppler US in the high-renin group were 84.2% and 93.6%, respectively. In the normal-renin group, 10 patients had positive Doppler US findings; these positive findings were confirmed by CTA in 9 cases. The sensitivity and specificity values for US in the normal-renin group were 100.0% and 100.0%. There were anatomic variations (n = 3) and segmental artery stenosis (n = 2) among the cases with false-negative US findings, which were confirmed by CTA. Conclusions If patients have high PRA, a Doppler US examination should be performed with caution to avoid false-negative detection. If patients have normal PRA, renal Doppler US might be adequate for diagnosis of RVHT to avoid unnecessary CTA.

The initial steps of steroidogenesis occur in the mitochondria. Dynamic changes in the mitochondria are associated with their fission and fusion. Therefore, understanding the cellular and molecular relationships between steroidogenesis and mitochondrial dynamics is important. The hypothesis of the current study is that mitochondrial fission and fusion are closely associated with steroid hormone synthesis in testicular Leydig cells. Steroid hormone production, induced by dibutyryl cAMP (dbcAMP) in Leydig cells, was accompanied by increased mitochondrial mass. Mitochondrial elongation increased during the dbcAMP-induced steroid production, whereas mitochondrial fragmentation was reduced. Among the mitochondrial-shaping proteins, the level of dynamin-associated protein 1 (Drp1) was altered in response to dbcAMP stimulation. The increase in Drp1 Ser 637 phosphorylation correlated with steroid hormone production in the MA-10 Leydig cells as well as in the primary adult rat Leydig cells. Drp1 was differentially expressed in the Leydig cells during testicular development. Finally, gonadotropin administration altered the status of Drp1 phosphorylation in the Leydig cells of immature rat testes. Overall, mitochondrial dynamics is directly linked to steroidogenesis, and Drp1 plays an important regulatory role during steroidogenesis. This study shows that Drp1 level is regulated by cAMP and that its phosphorylation via protein kinase A (PKA) activation plays a decisive role in mitochondrial shaping by offering an optimal environment for steroid hormone biosynthesis in Leydig cells. Therefore, it is suggested that PKA-mediated Drp1 Ser 637 phosphorylation is indispensable for steroidogenesis in the Leydig cells, and this phosphorylation results in mitochondrial elongation via the relative attenuation of mitochondrial fission during steroidogenesis.

BACKGROUND Accurate preoperative differentiation of primary central nervous system lymphoma (PCNSL) and glioblastoma is clinically crucial because the treatment strategies differ substantially. PURPOSE To evaluate the diagnostic performance of MRI for differentiating PCNSL from glioblastoma. STUDY TYPE Systematic review and meta-analysis. SUBJECTS Ovid-MEDLINE and EMBASE databases were searched to find relevant original articles up to November 25, 2018. The search term combined synonyms for "lymphoma," "glioblastoma," and "MRI." FIELD STRENGTH/SEQUENCE Patients underwent at least one MRI sequence including diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced imaging (DSC), dynamic contrast-enhanced imaging (DCE), arterial spin labeling (ASL), susceptibility-weighted imaging (SWI), intravoxel incoherent motion (IVIM), and magnetic resonance spectroscopy (MRS) using 1.5 or 3 T. ASSESSMENT Quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. STATISTICAL TESTS Hierarchical logistic regression modeling was used to obtain pooled sensitivity and specificity. Meta-regression was performed. RESULTS Twenty-two studies with 1182 patients were included. MRI sequences demonstrated high overall diagnostic performance with pooled sensitivity of 91% (95% confidence interval [CI], 87-93%) and specificity of 89% (95% CI, 85-93%). The area under the hierarchical summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). Studies using DSC or ASL showed high diagnostic performance (sensitivity of 93% [95% CI, 89-97%] and specificity of 91% [95% CI, 86-96%]). Heterogeneity was only detected in specificity (I2 = 66.84%) and magnetic field strength was revealed to be a significant factor affecting study heterogeneity. DATA CONCLUSION MRI showed overall high diagnostic performance for differentiating PCNSL from glioblastoma, with studies using DSC or ASL showing high diagnostic performance. Therefore, MRI sequences including DSC or ASL is a potential diagnostic tool for differentiating PCNSL from glioblastoma. LEVEL OF EVIDENCE 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:560-572.

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.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 P0.01, 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.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%; P0.01).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.

Background Updated response assessment in neuro-oncology (RANO) does not consider peritumoral non-enhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma. Methods This retrospective study enrolled 86 patients with IDH wild-type glioblastoma who underwent consecutive MRI examinations before and after concurrent chemoradiotherapy (CCRT). NEL was classified as edema- or tumor-dominant type on pre-CCRT MRI. CE evolution was categorized into 4 patterns based on post-operative residual CE (measurable vs. non-measurable) and CE volume change (same criteria with RANO) during CCRT. Multivariable logistic regression, including clinical parameters, NEL type, and CE evolution pattern, was used to analyze pseudoprogression rate. TTP and OS according to NEL type and CE evolution pattern was analyzed by the Kaplan–Meier method. Results Pseudoprogression rate was significantly lower (chi-square test, P = .047) and TTP was significantly shorter (hazard ratio [HR] = 2.03, P = .005) for tumor-dominant type than edema-dominant type of NEL. NEL type was the only predictive marker of pseudoprogression on multivariate analysis (odds ratio = 0.26, P = .046). Among CE evolution patterns, TTP and OS was shortest in patients with residual CE compared with those exhibiting new CE (HR = 4.33, P P = .009, respectively). In edema-dominant NEL type, both TTP and OS was stratified by CE evolution pattern (log-rank, P = .001), whereas it was not in tumor-dominant NEL. Conclusions NEL type improves prediction of pseudoprogression and, together with CE evolution pattern, further stratifies TTP and OS in patients with IDH wild-type glioblastoma and may become a helpful biomarker for refining RANO.

BACKGROUND To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. METHODS The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. RESULTS The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naive patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naive patients with one early postoperative seizure (

Introduction:endometrial cancer is the most common type of cancer in the female genital tract. Most patients are diagnosed during postmenopausal periods. This study aimed to investigate the demographic characteristics as well as cutoff value of endometrial thickness and ultrasound characteristics of endometrial cancer in postmenopausal patients. Methods:we retrospectively analyzed 244 postmenopausal women who underwent endometrial sampling from February 2016 to December 2019. Information of patients was obtained through medical records. The patients were divided into two groups according to histopathological results. Group A included patients with endometrial cancer and group B included patients with non-malignant lesions. Data were summarized based on demographic and ultrasound characteristics. Results:hypertension and history of endometrial hyperplasia were associated with the incidence of endometrial cancer in this study. Endometrial cancer was diagnosed in all ranges when the endometrial thickness was ≥5 mm. Endometrial fluid collection, with increased endometrial thickness, was a risk factor associated with endometrial cancer. Conclusion:regardless of symptoms and risk factors, endometrial histological confirmation in postmenopausal women should be conducted immediately if endometrial abnormalities such as an endometrial thickness ≥5 mm or endometrial fluid collection are detected by transvaginal ultrasound.

Background In high fidelity simulation used in an educational context, measuring the psychological safety levels of students enables the understanding and analysis of the relation between the characteristics of simulation design and the factors that create a psychologically safe environment. Objective To develop a new measurement of psychological safety in simulation-based learning settings using high fidelity manikins and to validate its reliability and validity. Methods This is a methodological study to develop a scale of Psychological Safety in High Fidelity Simulation. A convenience sample of 242 participants recruited from four universities in Korea was analyzed. The content validity of the scale and feasibility test were conducted to assess the scale's relevance, and comprehensiveness. An exploratory factor analysis with the principal component method and a varimax rotation, a concurrent validity analysis, and known group comparisons were conducted. Reliability was evaluated through the scale's internal consistency. Results Four factors were extracted, and 14 items were retained for these four factors, accounting for 72% of the total variance: (1) “Dealing with uncertainty (four items),” (2) “being exposed (four items),” (3) “being unsupported (three items),” and (4) “interpersonal risk (three items).” The Psychological Safety in High Fidelity Simulation scale score exhibited a statistically significant positive correlation with the Academic Safety Assessment tool and the Educational Satisfaction Scale in Simulation scores (p 〈001). Cronbach's α was .91 and ranged from .75 to .88 for the sub-factors. Conclusion The Psychological Safety in High Fidelity Simulation scale is a reliable and valid tool for assessing the psychological safety of nursing students during high fidelity simulation. The scale reflects the nature of psychological safety based on the elements of simulation education and measures the degree to which specific guidance is useful for nursing educators fostering psychological safety in students.

Background. Machine learning may be a useful tool for predicting metabolic syndrome (MetS), and previous studies also suggest that the risk of MetS differs according to Sasang constitution type. The present study investigated the development of MetS prediction models utilizing machine learning methods and whether the incorporation of Sasang constitution type could improve the performance of those prediction models. Methods. Participants visiting a medical center for a health check-up were recruited in 2005 and 2006. Six kinds of machine learning were utilized (K-nearest neighbor, naive Bayes, random forest, decision tree, multilayer perceptron, and support vector machine), as was conventional logistic regression. Machine learning-derived MetS prediction models with and without the incorporation of Sasang constitution type were compared to investigate whether the former would predict MetS with higher sensitivity. Age, sex, education level, marital status, body mass index, stress, physical activity, alcohol consumption, and smoking were included as potentially predictive factors. Results. A total of 750/2,871 participants had MetS. Among the six types of machine learning methods investigated, multiplayer perceptron and support vector machine exhibited the same performance as the conventional regression method, based on the areas under the receiver operating characteristic curves. The naive-Bayes method exhibited the highest sensitivity (0.49), which was higher than that of the conventional regression method (0.39). The incorporation of Sasang constitution type improved the sensitivity of all of the machine learning methods investigated except for the K-nearest neighbor method. Conclusion. Machine learning-derived models may be useful for MetS prediction, and the incorporation of Sasang constitution type may increase the sensitivity of such models.

Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.

Current image processing methods for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) do not capture complex dynamic information of time-signal intensity curves. We investigated whether an autoencoder-based pattern analysis of DSC MRI captured representative temporal features that improves tissue characterization and tumor diagnosis in a multicenter setting. The autoencoder was applied to the time-signal intensity curves to obtain representative temporal patterns, which were subsequently learned by a convolutional neural network. This network was trained with 216 preoperative DSC MRI acquisitions and validated using external data (n = 43) collected with different DSC acquisition protocols. The autoencoder applied to time-signal intensity curves and clustering obtained nine representative clusters of temporal patterns, which accurately identified tumor and non-tumoral tissues. The dominant clusters of temporal patterns distinguished primary central nervous system lymphoma (PCNSL) from glioblastoma (AUC 0.89) and metastasis from glioblastoma (AUC 0.95). The autoencoder captured DSC time-signal intensity patterns that improved identification of tumoral tissues and differentiation of tumor type and was generalizable across centers.

Background Achieving high-spatial-resolution pituitary MRI is challenging because of the trade-off between image noise and spatial resolution. Deep learning-based MRI reconstruction enables image denoising with sharp edges and reduced artifacts, which improves the image quality of thin-slice MRI. Purpose To assess the diagnostic performance of 1-mm slice thickness MRI with deep learning-based reconstruction (DLR) (hereafter, 1-mm MRI+DLR) compared with 3-mm slice thickness MRI (hereafter, 3-mm MRI) for identifying residual tumor and cavernous sinus invasion in the evaluation of postoperative pituitary adenoma. Materials and Methods This single-institution retrospective study included 65 patients (mean age ± standard deviation, 54 years ± 10; 26 women) who underwent a combined imaging protocol including 3-mm MRI and 1-mm MRI+DLR for postoperative evaluation of pituitary adenoma between August and October 2019. Reference standards for correct diagnosis were established by using all available imaging resources, clinical histories, laboratory findings, surgical records, and pathology reports. The diagnostic performances of 3-mm MRI, 1-mm slice thickness MRI without DLR (hereafter, 1-mm MRI), and 1-mm MRI+DLR for identifying residual tumor and cavernous sinus invasion were evaluated by two readers and compared between the protocols. Results The performance of 1-mm MRI+DLR in the identification of residual tumor was comparable to that of 3-mm MRI (area under the receiver operating characteristic curve [AUC], 0.89-0.92 vs 0.85-0.89, respectively; P ≥ .09). In the identification of cavernous sinus invasion, the diagnostic performance of 1-mm MRI+DLR was higher than that of 3-mm MRI (AUC, 0.95-0.98 vs 0.83-0.87, respectively; P ≤ .02). Conventional 1-mm MRI (AUC, 0.82-0.83) showed comparable diagnostic performance to 3-mm MRI (AUC, 0.83-0.87) (P ≥ .38). With 1-mm MRI+DLR, residual tumor was diagnosed in 20 patients and cavernous sinus invasion was diagnosed in 14 patients, in whom these diagnoses were not made with 3-mm MRI. Conclusion In the postoperative evaluation of pituitary adenoma, 1-mm slice thickness MRI with deep learning-based reconstruction showed higher diagnostic performance than 3-mm slice thickness MRI in the identification of cavernous sinus invasion and comparable diagnostic performance to 3-mm slice thickness MRI in the identification of residual tumor. © RSNA, 2020 Online supplemental material is available for this article.

We aimed to develop multiparametric physiologic MRI-based spatial habitats and to evaluate whether temporal changes in these habitats help to distinguish tumor progression from treatment-related change in post-treatment glioblastoma. This retrospective, single-institution study included patients with glioblastoma treated by concurrent chemoradiotherapy who had newly developed or enlarging, measurable contrast-enhancing mass. Contrast-enhancing mass was divided into three spatial habitats by K-means clustering of voxel-wise ADC and CBV values. Temporal changes of these habitats between two consecutive examinations prior to the diagnosis of tumor progression or treatment-related change were assessed. Predictors were selected using logistic regression and the performance was measured with an area under the receiver operating characteristics curve (AUC). Spatiotemporal habitats were further analyzed for correlation with the site of tumor progression. There were 75 patients (mean, 58 years; range, 26−81 years; 43 men) with 48 cases of tumor progression and 39 cases of treatment-related change including 12 patient overlaps at different time points. Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. Increase in the hypervascular cellular (OR 4.55, p = .002) and hypovascular cellular habitat (OR 1.22, p < .001) was predictive of tumor progression. Combination of spatiotemporal habitats yielded a high diagnostic performance with an AUC of 0.89 (95% CI, 0.87–0.92). An increase in hypovascular cellular habitat predicted the site of tumor progression in 84% [21/25] of cases with tumor progression. Temporal changes in spatial habitats derived from multiparametric physiologic MRI provided diagnostic value in distinguishing tumor progression from treatment-related change and predicted site of tumor progression in post-treatment glioblastoma. • In post-treatment glioblastoma, three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified, and an increase in the hypervascular cellular (OR 4.55, p = .002) and hypovascular cellular habitat (OR 1.22, p < .001) was predictive of tumor progression. • Combination of spatiotemporal habitats yielded a high diagnostic performance with an AUC of 0.89 (95% CI, 0.87–0.92). • An increase in hypovascular cellular habitat predicted the site of tumor progression in 84% (21/25) of cases with tumor progression.

To investigate the impact of acceleration factors on reproducibility of radiomic features in sensitivity encoding (SENSE) and compressed SENSE (CS), compare between SENSE and CS, and identify reproducible radiomic features.Three-dimensional turbo spin echo T1-weighted imaging was performed in 14 healthy volunteers (mean age, 57 years; range, 33-67 years; 7 men) under SENSE and CS with accelerator factors of 5.5, 6.8, and 9.7. Eight anatomical locations (brain parenchyma, salivary glands, masseter muscle, tongue, pharyngeal mucosal space, eyeballs) were evaluated. Reproducibility of radiomic features was evaluated by calculating concordance correlation coefficient (CCC) in reference to the original image (SENSE with acceleration factor of 3.5). Reproducibility of radiomic features among acceleration factors and between SENSE and CS was compared.Proportion of radiomic features with CCC0.85 in reference to the original image was lower with higher acceleration factors in both SENSE and CS across all anatomical locations (p.001). Proportion of radiomic features with CCC0.85 in reference to the original image was higher in SENSE compared with CS (SENSE, 6.7-7.3% vs CS, 4.4-5.0%; p.001). Run percentage of gray-level run-length matrix (GLRLM) with wavelet D showed CCC0.85 in reference to the original image in both SENSE and CS at acceleration factor of 9.7 in the highest number of anatomical locations.Higher acceleration factors resulted in lower reproducibility of radiomic features in both SENSE and CS, and SENSE showed higher reproducibility of radiomic features than CS in reference to the original image. Run percentage of GLRLM with wavelet D was identified as the most reproducible feature.• Reproducibility of radiomic features in reference to the original image was lower with higher acceleration factors in both sensitivity encoding (SENSE) and compressed SENSE (CS) across all anatomical locations (p.001). • SENSE showed higher proportions of radiomic features with CCC0.85 in reference to the original image (SENSE, 6.7-7.3% vs CS, 4.4-5.0%; p.001) compared with CS. • Run percentage of gray-level run-length matrix (GLRLM) with wavelet D showed CCC0.85 in reference to the original image in both SENSE and CS with the highest acceleration factor.

Background and purpose We aimed to determine the intermethod reproducibility between the commercial software Inbrain (MIDAS IT) and the established research-purpose method FreeSurfer, as well as the effect of MRI resolution and the pathological condition of subjects on their intermethod reproducibility. Methods This study included 45 healthy volunteers and 85 patients with mild cognitive impairment (MCI). In 43 of the 85 patients with MCI, three-dimensional, T1-weighted MRI data were obtained at an in-plane resolution of 1.2 mm. The data of the remaining 42 patients with MCI and the healthy volunteers were obtained at an in-plane resolution of 1.0 mm. The within-subject coefficient of variation (CoV), intraclass correlation coefficient (ICC), and effect size were calculated, and means were compared using paired t-tests. The parameters obtained at 1.0-mm and 1.2-mm resolutions in patients with MCI were compared to evaluate the effect of the in-plane resolution on the intermethod reproducibility. The parameters obtained at a 1.0-mm in-plane resolution in patients with MCI and healthy volunteers were used to analyze the effect of subject condition on intermethod reproducibility. Results Overall the two methods showed excellent reproducibility across all regions of the brain (CoV=0.5-3.9, ICC=0.93 to >0.99). In the subgroup of healthy volunteers, the intermethod reliability was only good in some regions (frontal, temporal, cingulate, and insular). The intermethod reproducibility was better in the 1.0-mm group than the 1.2-mm group in all regions other than the nucleus accumbens. Conclusions Inbrain and FreeSurfer showed good-to-excellent intermethod reproducibility for volumetric measurements. Nevertheless, some noticeable differences were found based on subject condition, image resolution, and brain region.

Objective The purposes of this study were to analyze the radiation doses for pediatric abdominopelvic and chest CT examinations from university hospitals in Korea and to establish the local diagnostic reference levels (DRLs) based on the body weight and size. Materials and Methods At seven university hospitals in Korea, 2494 CT examinations of patients aged 15 years or younger (1625 abdominopelvic and 869 chest CT examinations) between January and December 2017 were analyzed in this study. CT scans were transferred to commercial automated dose management software for the analysis after being de-identified. DRLs were calculated after grouping the patients according to the body weight and effective diameter. DRLs were set at the 75th percentile of the distribution of each institution's typical values. Results For body weights of 5, 15, 30, 50, and 80 kg, DRLs (volume CT dose index [CTDIvol]) were 1.4, 2.2, 2.7, 4.0, and 4.7 mGy, respectively, for abdominopelvic CT and 1.2, 1.5, 2.3, 3.7, and 5.8 mGy, respectively, for chest CT. For effective diameters of < 13 cm, 14–16 cm, 17–20 cm, 21–24 cm, and > 24 cm, DRLs (size-specific dose estimates [SSDE]) were 4.1, 5.0, 5.7, 7.1, and 7.2 mGy, respectively, for abdominopelvic CT and 2.8, 4.6, 4.3, 5.3, and 7.5 mGy, respectively, for chest CT. SSDE was greater than CTDIvol in all age groups. Overall, the local DRL was lower than DRLs in previously conducted dose surveys and other countries. Conclusion Our study set local DRLs in pediatric abdominopelvic and chest CT examinations for the body weight and size. Further research involving more facilities and CT examinations is required to develop national DRLs and update the current DRLs.