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Concrete undergoes shrinkage regardless of the influence of external forces. The deformation of concrete is crucial for the structural stability of high-rise and large-scale buildings. In this study, the shrinkage and compressive creep of 70-90 MPa high-strength concrete used in high-rise buildings were evaluated based on the curing conditions (sealed/unsealed), and the existing prediction models were examined. It was observed that the curing condition does not significantly affect the mechanical properties of high-strength concrete, but the use of limestone coarse aggregate increases the elastic modulus when compared to granite coarse aggregate. The autogenous shrinkage of high-strength concrete is greater than that of normal-strength concrete owing to self-desiccation, resulting in a large variation from the value predicted by the model. The drying shrinkage was observed to be similar to that predicted by the model. Compressive creep was affected by the curing conditions, compressive strength, loading level, and loading age. The compressive creep of high-strength concrete varied significantly from the prediction results of ACI 209; ACI 209 was modified based on the measured values. The shrinkage and compressive creep characteristics of high-strength concrete must be reflected to predict the deformation of an actual structure exposed to various conditions.

Magnetic resonance imaging (MRI) is increasingly important in the detection and localization of prostate cancer. Regarding suspicious lesions on MRI, a targeted biopsy using MRI fused with ultrasound (US) is widely used. To achieve a successful targeted biopsy, a precise registration between MRI and US is essential. The purpose of our study was to show any decrease in errors using a real-time nonrigid registration technique for prostate biopsy. Nineteen patients with suspected prostate cancer were prospectively enrolled in this study. Registration accuracy was calculated by the measuring distance of corresponding points by rigid and nonrigid registration between MRI and US, and compared for rigid and nonrigid registration methods. Overall cancer detection rates were also evaluated by patient and by core. Prostate volume was measured automatically from MRI and manually from US, and compared to each other. Mean distances between the corresponding points in MRI and US were 5.32 ± 2.61 mm for rigid registration and 2.11 ± 1.37 mm for nonrigid registration ( p < 0.05). Cancer was diagnosed in 11 of 19 patients (57.9%), and in 67 of 266 biopsy cores (25.2%). There was no significant difference in prostate-volume measurement between the automatic and manual methods ( p = 0.89). In conclusion, nonrigid registration reduces targeting errors.

Background: Chordomas, which are rare malignant neoplasms arising from notochordal remnants, often cause gradually progressive clinical symptoms. Intradural cranial chordomas (ICCs) are extremely rare and generally have a favorable prognosis. However, the authors reported the case of a primary ICC originating in the pineal gland presenting with recurrent thalamic hemorrhage and displaying an aggressive postoperative clinical course., Observations: A 41-year-old man arrived at the emergency department with morning headaches and recurrent syncope that had lasted several months. Computed tomography and magnetic resonance imaging (MRI) revealed a pineal gland mass causing obstructive hydrocephalus and a subacute hematoma in the right thalamus. Three weeks after an endoscopic third ventriculostomy was performed, recurrent hemorrhage was observed in the right thalamus. The tumor was promptly removed surgically. The yellowish-white tumor did not exhibit abundant bleeding. No evidence of intratumoral hemorrhage around the hematoma pocket was found. Histopathological examination revealed the characteristics of a chordoma with minimal vascularity. MRI performed 10 weeks postoperatively for worsening headaches revealed abnormal enhancement of multiple cranial nerves, suggesting leptomeningeal seeding (LMS) of the tumor., Lessons: Despite radiotherapy and intrathecal chemotherapy, the patient's neurological status worsened; he died 2 years postoperatively. A pineal ICC may cause recurrent thalamic hemorrhage and potentially fatal LMS, even in the early postoperative period., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2021 The authors.)

Objective: To identify patients who can safely evade the magnetic resonance imaging fusion-targeted biopsy (MRIFTB) for prostate imaging reporting and data system (PI-RADS) 3 lesion., Materials and Methods: Overall, 755 men with PI-RADS 3-5 lesions who underwent MRIFTB were retrospectively analyzed. Univariate and multivariate analyses were performed to determine significant predictors for clinically significant prostate cancer (CSPCa), defined as Gleason grade group ≥ II. Detection rates and negative predictive values of CSPCa were estimated according to various clinical settings., Results: Median age, prostate-specific antigen (PSA), and PSA density of patients were 66.0 years, 7.39 ng/mL, and 0.19 ng/mL, respectively. Overall detection rates of CSPCa according to PI-RADS 3 (n = 347), 4 (n = 260), and 5 (n = 148) lesions were 15.0%, 30.4%, and 80.4%, respectively. The negative predictive value (NPV) of PI-RADS 3 lesion on MRI was 15.0%. On multivariate analysis, age [≥ 65 years, odds ratio (OR) = 0.427], PSA density (≥ 0.20 ng/mL 2 , OR = 0.234), prior negative biopsy history (OR = 2.231), and PI-RADS score (4, OR = 0.427; 5, OR = 0.071) were independent predictors for the absence of CSPCa by MRIFTB. When assessed according to various conditions, NPVs of PI-RADS 3 lesions were relatively high in subgroups with low PSA density (< 0.20 ng/mL 2 ) regardless of age or prior biopsy history (NPV range 91.1-91.9%). Contrarily, NPVs in subgroups with high PSA density were relatively low and varied according to age or prior biopsy history groups (NPV range 50.0-86.8%)., Conclusions: Men with the PI-RADS 3 lesion and low PSA density might safely evade the MRIFTB, regardless of age or prior biopsy history.

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

Subependymoma is a slow-growing, exophytic, intraventricular glial neoplasm that commonly arises in the ventricular system. However, a report found that the frequency of intracerebral subependymoma was 0.4% in 1000 routine autopsies. To the best of our knowledge, only seven cases of intracerebral subependymoma have been reported. We report a rare case of intracerebral subependymoma in a child. An 11-year-old girl with generalized tonic-clonic seizures visited the emergency room and had an intraparenchymal tumor on the left frontal lobe on magnetic resonance imaging (MRI). Craniotomy with gross total removal was performed without any perioperative morbidities. The tumor was finally histopathologically diagnosed as a subependymoma.

Background: Specific correlations between the outcomes of cochlear implantation (CI) and hearing thresholds of the both ears in post-lingual asymmetric hearing loss (AHL) patients were not clear., Aims/objectives: To identify the variables influencing the outcome of CI in post-lingual AHL patients., Method: We included 18 adult subjects who had CI in the worse ear due to post-lingual AHL with average hearing asymmetry of 36 dB. Speech perception scores were evaluated in the sound field with hearing aid on the better ear before CI, and with the cochlear implant in the worse ear at 3, 6, and 12 months after CI switch-on., Results: Average increases in phonetically balanced word score, spondee word score, and everyday sentence score at 12 months from CI switch-on compared with those before CI were 38.9%p, 46.2%p, and 52.4%p, respectively. Multiple linear regression analysis showed that speech perception scores were negatively influenced by age at implantation and hearing threshold difference of both ears (HTD-Both) itself, rather than the worse or better ear hearing thresholds., Conclusions and Significance: Post-lingual AHL subjects with high average hearing asymmetry can benefit from CI in the worse ear, while CI outcomes can be adversely influenced by HTD-Both and age at implantation both in the short- and long-term follow-up.

Background: To identify potential prognostic factors among patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6., Methods: From 2003 to 2019, favorable intermediate risk patients who underwent radical prostatectomy were included in this study. All patients were evaluated preoperatively with MRI. Using PI-RADS scores, patients were divided into two groups, and clinic-pathological outcomes were compared. The impact of preoperative factors on significant pathologic Gleason score upgrading (≥ 4 + 3) and biochemical recurrence were assessed via multivariate analysis. Subgroup analysis was performed in patients with PI-RADS ≤ 2., Results: Among the 239 patients, 116 (48.5%) were MRI-negative (PI-RADS ≤ 3) and 123 (51.5%) were MRI-positive (PI-RADS > 3). Six patients in the MRI-negative group (5.2%) were characterized as requiring significant pathologic Gleason score upgrading compared with 34 patients (27.6%) in the MRI-positive group (p < 0.001). PI-RADS score was shown to be a significant predictor of significant pathologic Gleason score upgrading (OR = 6.246, p < 0.001) and biochemical recurrence (HR = 2.595, p = 0.043). 10-years biochemical recurrence-free survival was estimated to be 84.4% and 72.6% in the MRI-negative and MRI-positive groups (p = 0.035). In the 79 patients with PI-RADS ≤ 2, tumor length in biopsy cores was identified as a significant predictor of pathologic Gleason score (OR = 11.336, p = 0.014)., Conclusions: Among the patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6, preoperative MRI was capable of predicting significant pathologic Gleason score upgrading and biochemical recurrence. Especially, the patients with PI-RADS ≤ 2 and low biopsy tumor length could be a potential candidate to active surveillance.

Background: Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists., Methods: Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists' workload, AI-assisted annotation was established in collaboration with university AI teams., Results: A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models., Discussion: Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition., Conclusions: Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.

Background: Outcomes after segmentectomy compare favorably with those after lobectomy in patients with stage I non-small cell lung cancer (NSCLC). Whether long-term outcomes vary by segmentectomy location is unclear. We investigated whether disease-free survival (DFS) and overall survival (OS) differ by segmentectomy location after intentional segmentectomy for clinical T1 N0 M0 NSCLC., Methods: Patients who received intentional segmentectomy for cT1 N0 M0 NSCLC from 2000 to 2018 were reviewed. Patients with prior lung cancer, forced expiratory volume in 1 second of less than 50%, or R1/R2 resection were excluded. Segmentectomy groups were left (L) basilar, L segment 6, L lingula, L trisegment; right (R): basilar (R&#95;Bas), segment 6 (R&#95;S6), and R upper. The 5- and 10-year DFS and OS were estimated using Kaplan-Meier and compared between groups using the log-rank test. Factors associated with DFS and OS were determined using Cox proportional hazards models., Results: In total, 416 patients met the inclusion criteria. Segmentectomy groups differed with regard to surgical approach, mediastinal lymphadenectomy, lymphovascular invasion, tumor histology, margin distance, and adjuvant therapy. Long-term outcomes were worst after R&#95;S6 resection (5-year DFS, 57.6% [95% confidence interval {CI}, 45.7%-72.7%]; OS, 66.3% [95% CI, 54.7%-80.3%]) and best after R&#95;Bas resection (5-year DFS, 77.1% [95% CI, 59.2%-100%]; OS, 79.5% [95% CI, 60.9%-100%]). On multivariable analysis, R&#95;S6 resection was independently associated with DFS vs R&#95;Bas (hazard ratio, 2.89; 95% CI, 1.18-7.08; P = .02) and OS vs R&#95;Bas (hazard ratio, 4.35; 95% CI, 1.61-11.76; P = .004)., Conclusions: Resection of R&#95;S6 is independently associated with worse DFS and OS in patients receiving intentional segmentectomy for cT1 N0 M0 NSCLC and may warrant more extensive resection, complete lymph node dissection, and closer postoperative surveillance., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the diagnostic performance of Vesical Imaging-Reporting and Data System (VIRADS) and to find a quantitative indicator for predicting muscle layer invasion of bladder cancer., Methods: 3-T MRI of 82 patients performed before transurethral resection of bladder tumors or radical cystectomy between July 2018 and June 2019 were retrospectively analyzed. For one index lesion of each patient, two radiologists independently assigned VIRADS score and measured tumor-wall interface (contact length between tumor and bladder wall) on T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. Inter-reader agreement was assessed, and logistic regression analysis was performed to find indicators of muscle layer invasion. Comparison of indicators' diagnostic performance was done with receiver operating characteristic (ROC) curve and generalized linear model analyses. Optimal cutoff point was determined by the Youden index J., Results: Inter-reader agreement was at least substantial for VIRADS categorization (κ 0.77-0.81), and almost perfect for tumor-wall interface (intraclass correlation coefficient 0.88-0.90). Tumor-wall interface (odds ratio [OR] 1.90-2.00) and VIRADS score (OR 8.59-8.89) were independently associated with muscle layer invasion (p ≤ 0.02). For VIRADS, area under the ROC curve (AUROC) was 0.94, and the accuracy was 0.93 at score 3, the optimal threshold for predicting muscle layer invasion. Depending on the MRI sequence, tumor-wall interface showed AUROCs of 0.90-0.92 and accuracy of 0.84-0.90 at suggested thresholds (3 ± 0.3 cm). Tumor-wall interface showed insignificant differences in accuracy compared with VIRADS (p > 0.10), except as measured on diffusion-weighted images (p = 0.01)., Conclusions: VIRADS is a good predictor of muscle layer invasion. As an independent quantitative indicator, tumor-wall interface may complement VIRADS to enhance prediction., Key Points: • Vesical Imaging-Reporting and Data System (VIRADS) is a promising predictor of muscle invasion of bladder cancer with good reproducibility, as suggested by previous studies. • VIRADS score and the tumor-wall interface (curvilinear contact length between the tumor and the bladder wall) are independent predictors of muscle layer invasion. • As an easy-to-use quantitative indicator, tumor-wall interface is expected to be used as an indicator complementary to VIRADS, a qualitative indicator.

Background: There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL)., Objective: To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events., Methods: Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4-12 years, n = 44) and an adult group (age 19-59 years, n = 26)., Results: The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups ( p < 0.001 , both); however, changes in TNSS from baseline did not significantly differ between the two groups ( p = 0.365 ). More patients in adult group were satisfied with SLIT than those in child group ( p = 0.050 ), and changes in RQLQ score from baseline tended to be larger in adult group ( p = 0.089 ). The levels of immunological parameters at baseline were significantly higher in the child group than in the adult group; however, changes in the levels of these parameters were not significantly different., Conclusion: Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.

Mesenchymal stem-cell (MSC)-based therapies have been recognized as promising strategies for the treatment of various injuries or diseases because of their unique characteristics, such as self-renewal, differentiation potential, and secretion of various bioactive molecules. However, MSC transplantation often results in low efficacy, including a cell viability loss and a low therapeutic activity. Alternatively, MSC spheroids have been studied to improve the viability and therapeutic activity of MSCs. Also, microencapsulation of cells can protect and retain the cells from harsh environments after transplantation. Here, MSC spheroids were formed in hyaluronic acid/alginate (HA@Alg) core-shell microcapsules and employed for neovascularization. A well-defined core-shell structure of HA@Alg microcapsules was produced by optimizing various electrospraying conditions. MSC spheroids could be spontaneously formed in the HA core of the microcapsules after 1 day of incubation. Enhanced secretion of various growth factors was found from MSC spheroids in HA@Alg. In vivo plug assay revealed the significant promotion of angiogenesis by MSC spheroids in HA@Alg compared to that by the controls ( i.e. , MSCs and MSC spheroids), which is likely because of the better retention of MSC spheroid forms in the microcapsules. Thus, the HA@Alg microcapsules embedding MSC spheroids will be greatly beneficial for various stem cell-based therapies.

Since the discovery of ferroelectricity in doped/alloyed HfO 2 and ZrO 2 thin film, many device engineers have been attracted to its sustainable ferroelectricity at the thickness of a few nanometer. While most of the previous studies have mainly focused on the ferroelectric properties of the thermally atomic layer deposited (THALD) Hf 0.5 Zr 0.5 O 2 (HZO), the plasma-enhanced ALD (PEALD) HZO has not received much attention. In this work, a direct comparison between the two types of HZO thin films is carried out, where we found that a tradeoff exists between these two fabrication methods. While the THALD HZO was able to maintain a higher cycling endurance, the PEALD HZO showed more stable characteristics over the cycling with reduced wake-up and fatigue effects, in addition to better tolerance against breakdown under high electric field. Furthermore, the PEALD HZO could be crystallized with post deposition annealing at 350 °C, which is of great interest for the back-end-of-line compatibility with silicon fabrication processes.

Background: Biparametric (bp) magnetic resonance imaging (MRI) could be an alternative MRI for the detection of the clinically significant prostate cancer (csPCa)., Purpose: To compare the accuracies of prostate cancer detection and localization between prebiopsy bpMRI and postbiopsy multiparametric MRI (mpMRI) taken on different days, using radical prostatectomy specimens as the reference standards., Material and Methods: Data of 41 total consecutive patients who underwent the following examinations and procedures between September 2015 and March 2017 were collected: (1) magnetic resonance- and/or ultrasonography-guided biopsy after bpMRI; (2) postbiopsy mpMRI; and (3) radical prostatectomy with csPCa. Two radiologists scored suspected lesions on bpMRI and mpMRI independently using Prostate Imaging Reporting and Data System version 2. The diagnostic accuracy of detecting csPCa and the Dice similarity coefficient were obtained. Apparent diffusion coefficient (ADC) ratios were also obtained for quantitative comparison between bpMRI and mpMRI., Results: Diagnostic accuracies on bpMRI and mpMRI were 0.83 and 0.82 for reader 1; 0.80 and 0.82 for reader 2. There are no significantly different values of diagnostic sensitivities or specificities between the readers or between MRI protocols. Intra-observer Dice similarity coefficient was significantly lower in reader 2, compared to that in reader 1 between the two MRI protocols. The range of mean ADC ratio was 0.281-0.635. There was no statistically significant difference in the ADC ratio between bpMRI and mpMRI., Conclusions: Diagnostic performance of bpMRI without dynamic contrast enhancement MRI is not significantly different from mpMRI with dynamic contrast enhancement MRI in the detection of csPCa., Competing Interests: The authors declare that there is no relevant or material financial interests that relate to the research described in this paper., (© 2020 Asian Pacific Prostate Society, Published by Elsevier Korea LLC.)

Objective: We sometimes encounter unintentional flow of contrast into the facet joints during cervical interlaminar epidural injection, which leads to false-positive epidural injection. The purposes of this study were to evaluate the rate of facet flow of contrast and to investigate various factors associated with injection into the space of Okada during fluoroscopy-guided cervical interlaminar epidural injection., Setting and Subjects: Images from consecutive cases of fluoroscopy-guided cervical interlaminar epidural injection performed at a single institution between July 2015 and July 2018 were obtained and reviewed., Methods: Cases of epidural injection were classified as either facet flow or no facet flow. Multivariate logistic regression was used to identify the predictive factors of unintended injection into the Okada space., Results: A total of 2,006 cases were included. Intra-articular flow was identified in 6.0% of cases (121/2,006). All cases of flow of contrast into the facet joints were recognized, and appropriate epidurograms were obtained during the procedures. The highest rate of unintended facet flow of the contrast (10.1%, 44/436) occurred at C5-6. Cervical interlaminar epidural injection at C5-6 and above (adjusted odds ratio [aOR] = 1.929, P = 0.001) and the paramidline approach for epidural injection (aOR = 2.427, P < 0.001) were associated with injection into the space of Okada., Conclusions: We detected injection into the space of Okada during fluoroscopy-guided cervical interlaminar epidural injection in 6.0% of procedures. Cervical interlaminar epidural injection at C5-6 and above and the paramidline approach for epidural injection were positive predictors of unintentional facet flow of the contrast., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: High-grade glioma (HGG) with primary leptomeningeal seeding (PLS) at initial diagnosis is rare. The purpose of this study was to identify its clinical features and to describe the clinical treatment outcomes., Methods: We retrospectively reviewed the medical records of patients with HGG (World Health Organization grade III or IV) at our institution between 2004 and 2019, and patients with PLS at the initial diagnosis were enrolled in the study. Clinical features, such as the location of leptomeningeal seeding, surgical methods, and degree of resection, were sorted based on electronic medical records also containing performance scale, and hematological and serological evaluations. Radiological findings and immunohistochemical categories were confirmed. Furthermore, we sought to determine whether controlling intracranial pressure (ICP) via early cerebrospinal fluid (CSF) diversion increases overall survival (OS) after the initial diagnosis., Results: Of the 469 patients with HGG in our institution, less than 2% had PLS at the initial diagnosis. Most patients suffered from headache, diplopia, and dizziness. Pathological findings included 7 glioblastomas and 2 anaplastic astrocytomas. Seven of the 9 patients underwent CSF diversion. All patients were administered concurrent chemoradiotherapy (CCRT) with temozolomide, 89% of which started adjuvant temozolomide and 33% of which completed the six cycles of adjuvant temozolomide. The OS of patients with HGG and PLS was 8.7 months (range, 4-37), an extremely poor result compared to that of other studies. Also, the 1-year and 2-year OS rates were 44.4% and 16.7%, respectively., Conclusion: Diagnosis and treatment of HGG with PLS are challenging. Aggressive control of ICP followed by early initiation of standard CCRT seems to be helpful in improving symptoms. However, despite aggressive treatment, the prognosis is poor. A multicenter trial and research may be necessary to create a standardized protocol for this disease., Competing Interests: The authors have no potential conflicts of interest., (Copyright © 2020 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Laser capture microdissection (LCM) coupled with transcriptome profiling is a powerful technique that allows for tissue-specific gene expression analysis in a complex system. One major challenge in using this technique is to obtain RNA without compromising its integrity. Here, we present a protocol optimized for radish root tissue sections using Steedman's wax embedding to obtain high-quality RNA suitable for next-generation sequencing analysis. For complete details on the use and execution of this protocol, please refer to Hoang et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

The prevention and mitigation of spalling in high-strength concrete (HSC) rely on mixing polypropylene (PP) as an additive reinforcement. The dense internal structures of ultra-high-strength concrete (UHSC) result in risks associated with a high thermal stress and high water vapor pressure. Herein, the effects of pore formation and thermal strain on spalling are examined by subjecting fiber-laden UHSC to conditions similar to those under which the ISO-834 standard fire curve was obtained. Evaluation of the initial melting properties of the fibers based on thermogravimetric analysis (TGA) and differential thermal analysis (DTA) demon strated that although nylon fibers exhibit a higher melting point than polypropylene and polyethylene fibers, weight loss occurs below 200 °C. Nylon fibers were effective at reducing spalling in UHSC compared to polypropylene and polyethylene fibers as they rapidly melt, leading to pore formation. We anticipate that these results will serve as references for future studies on the prevention of spalling in fiber-reinforced UHSC.

Cambium drives the lateral growth of stems and roots, contributing to diverse plant growth forms. The root crop is one of the outstanding examples of the cambium-driven growth. To understand its molecular basis, we used radish to generate a compendium of root-tissue- and stage-specific transcriptomes from two contrasting inbred lines during root growth. Expression patterns of key cambium regulators and hormone signaling components were validated. Clustering and gene ontology (GO) enrichment analyses of radish datasets followed by a comparative analysis against the newly established Arabidopsis early cambium data revealed evolutionary conserved stress-response transcription factors that may intimately control the cambium. Indeed, an in vivo network consisting of selected stress-response and cambium regulators indicated ERF-1 as a potential key checkpoint of cambial activities, explaining how cambium-driven growth is altered in response to environmental changes. The findings here provide valuable information about dynamic gene expression changes during cambium-driven root growth and have implications with regard to future engineering schemes, leading to better crop yields., Competing Interests: Declaration of Interests The authors have a patent related to this manuscript, which is titled “Method for controlling radial growth of plant root by modulation of environment stress response regulators ERF-1 and STZ.”, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The importance of programmed cell death ligand 1 (PD-L1) expression has emerged in clinical trials of PD-L1 target therapy in renal cell carcinoma (RCC). This study compares PD-L1 assays in RCC., Methods and Results: Two US Food and Drug Administration-approved PD-L1 assays (22C3 and SP142) and one research-use only antibody (E1L3N) were used in a retrospective cohort of 591 patients with RCC. PD-L1 positivity on tumour cells (TCs) and immune cells (ICs) and combined positive score (CPS) were evaluated. With the 22C3, SP142 and E1L3N assays, positive PD-L1 expression on TCs ≥1% was observed in 24 (4.1%), 12 (2.0%) and 16 (2.7%) cases and on ICs ≥1% was observed in 132 (22.3%), 120 (20.3%) and 65 (11.0%) cases, respectively. PD-L1 expression scores among the three assays showed moderate-high positive correlation (ρ = 0.599-0.835, P < 0.001). Assays appeared similar, although staining in ICs was comparatively less frequent with E1L3N. 22C3 showed frequent positivity in TCs. PD-L1 expression on TCs was associated with papillary type 2 RCC (P < 0.001). IC infiltration and PD-L1 expression on ICs were predominantly found in clear cell and papillary type 1 RCC (P < 0.05)., Conclusions: Programmed death 1 (PD-1)/PD-L1 target therapy may be beneficial for patients with papillary type 2 RCC, even if they are categorised as a heterogeneous group. PD-L1 assays should be carefully selected, and accurate histological subtyping of RCC is needed prior to decisions on PD-L1 testing, because of the different PD-L1 expression observed among varying RCC subtypes., (© 2019 John Wiley & Sons Ltd.)

Background: Pleomorphic xanthoastrocytoma (PXA) is a rare type of astrocytoma with a peak incidence from 10 to 19 years of age. PXA is found most commonly in the supratentorium. When it is present in atypical areas such as the infratentorium, it is often overlooked as a potential differential diagnosis., Case Description: This report discusses the case of an 18-year-old woman with a pure PXA in the left cerebellum. The case consists of interesting pathologic and molecular features which do not align with the literature about PXA: a positive finding for BRAF V600E mutation and a negative finding for cluster of differentiation 34 expression. A review of pure PXA cases in the infratentorium has also been completed., Conclusions: To our knowledge, this is the first case of PXA in the infratentorium with BRAF V600E mutation. The case also highlights the clinical relevance of including PXA as a differential diagnosis for lesions of the infratentorium., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Surgery for non-small cell lung cancer has undergone repeated innovations over time. Although medical thoracoscopy has been available for centuries, it was not incorporated into the standard approach until the 1990s, when successful video-assisted thoracoscopic surgery (VATS) techniques were widely reported. Progressive efforts to offer minimally invasive approaches while maintaining oncologic surgical quality led to the development of robotic-assisted thoracic surgery and uniportal VATS, which offer improved pain control, shorter hospital stays, and more patients able to receive adjuvant therapy. Innovations in interventional bronchoscopy, localization methods, and 3D printing have improved the safety, efficacy, and precision of surgery., Competing Interests: Disclosure This work was supported, in part, by the National Institutes of Health/National Cancer Institute (P30 CA008748)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Combined anti-VEGF/anti-programmed death ligand 1 (PD-L1) therapy synergistically improves treatment outcomes in advanced renal cell carcinoma (RCC) compared with anti-PD-L1 or anti-vascular endothelial growth factor (VEGF) monotherapy. Here, we analyzed the expression of VEGF and PD-L1 (SP142) in a retrospective cohort of 513 patients with clear-cell (cc) RCC. PD-L1 expression on tumor cells (TCs) and immune cells (ICs) was evaluated by immunohistochemistry (IHC) with a positive threshold value of ≥1%. Positive staining for PD-L1 on ICs and TCs was found in 115 (22.4%) and 7 (1.4%) cases, respectively. Moderate or strong staining for VEGF on TCs was found in 217 (42.3%) patients. PD-L1 expression on ICs and TCs was positively associated with VEGF expression on TCs. Both VEGF and PD-L1 (IC) positivity (VEGF/PD-L1 [IC]: +/+) was observed in 65 (12.7%) cases. Patients in this subgroup exhibited more aggressive clinicopathologic features, including older age, higher World Health Organization/International Society of Urological Pathology (ISUP) grade, angiolymphatic invasion, tumor necrosis, and sarcomatoid differentiation (P < 0.05). Kaplan-Meier analysis indicated that expression of VEGF and PD-L1 on ICs was positively correlated with tumor recurrence (P < 0.001), whereas expression of PD-L1 on TCs was not (P = 0.554). Tumors with positivity for both antibodies (VEGF/PD-L1 [IC]: +/+) exhibited the worst recurrence-free survival (P < 0.001), and double positivity independently predicted tumor recurrence in ccRCC. The present study provides comprehensive and basic information about VEGF and PD-L1 expression for new combined therapy in primary ccRCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The threat of arsenic contamination to public health, particularly in developing countries, has become a serious problem. Millions of people in their daily lives are still highly dependent on groundwater containing high levels of arsenic, which causes excessive exposure to this toxic element, due to the high cost and lack of water-treatment infrastructures. Therefore, a technique for large-scale treatment of water in rural areas to remove arsenic is needed and should be low-cost, be easily customized, and not rely on electrical power. In this study, in an effort to fulfill those requirements, we introduce a three-dimensional (3D), printed water-filtration system for arsenic removal. Three-dimensional printing can provide a compact, customized filtration system that can fulfill the above-mentioned requirements and that can be made from plastic materials, which are abundant. Armed with the versatility of 3D printing, we were able to design the internal surface areas of filters, after which we modified the surfaces of the 3D, printed filters by using iron (III) oxide as an adsorbent for arsenite. We investigated the effects of the controlled surface area on the flow rate and the deposition of the adsorbent, which are directly related to the adsorption of arsenic. We conducted isotherm studies to quantify the adsorption of arsenic on our 3D, printed filtration system., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion., Materials and Methods: This was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status., Results: The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible., Conclusion: Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

Objectives: To evaluate the clinicopathological differences between Prostate Imaging-Reporting and Data System (PI-RADS) version 2 (v2) category 1 and 2 groups. Materials and Methods . We retrospectively reviewed our two institutional clinical databases: (1) transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy cohort ( n = 706) and (2) radical prostatectomy (RP) cohort ( n = 1403). Subsequently, we performed comparative analyses between PI-RADSv2 category 1 and 2 groups. Clinically significant prostate cancer (csPCa) was defined as the presence of Gleason score (GS) ≥ 3 + 4 in a single biopsy core, and adverse pathology (AP) was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or non-organ-confined disease (pT3/N1). We also performed multivariate logistic regression analyses for AP., Results: In the TRUS/MRI fusion biopsy cohort, no significant differences in detection rates of all cancer (18.2% vs. 29.0%, respectively, P = 0.730) or csPCa (9.1% vs. 9.9%, respectively, P = 0.692) were observed between PI-RADSv2 category 1 and 2 groups. There were no significant differences in pathologic outcomes including Gleason score (≥4 + 3, 21.2% vs. 29.9%, respectively, P = 0.420) or detection rate of AP (27.3% vs. 33.8%, respectively, P = 0.561) between the two groups in the RP cohort either. PI-RADSv2 category 1 or 2 had no significant association with AP, even in univariate analysis ( P = 0.299)., Conclusions: PI-RADSv2 categories 1 and 2 had similar performance to predict clinicopathological outcomes. Consequently, these two categories may be unified into a single category. Negative mpMRI does not guarantee the absence of AP, as with csPCa., Competing Interests: All the authors had no conflicts of interest in this study., (Copyright © 2020 Jung Kwon Kim et al.)

We aimed to evaluate the prognostic value of seminal vesicle invasion (SVI) on preoperative multiparametric MRI (mpMRI) in pathological T3b prostate cancer (PCa). We retrospectively reviewed the clinical data of patients who underwent preoperative mpMRI and subsequent radical prostatectomy (RP). A total of 159 patients with pathologic T3b PCa were stratified into two groups based on mpMRI findings (negative vs. positive SVI). A positive SVI was defined as the presence of mpMRI evidence of SVI. In addition, 290 patients with pathologic T3a were also included in this study for further comparative analysis. Fifty-two patients (32.7%) had a positive SVI on preoperative mpMRI. Biochemical recurrence (BCR) occurred in a total of 45 (28.3%) patients, with 25 (23.4%) cases in the negative SVI group and 20 (38.5%) cases in the positive SVI group. Kaplan-Meier survival analysis of the two groups revealed significantly decreased BCR-free survival in the positive SVI group (median, 21 vs. 9 months, log-rank test, P < 0.001). On multivariate Cox regression analysis, pre-biopsy PSA (P = 0.035) and positive SVI on preoperative mpMRI (P = 0.049) were identified as significant predictors of BCR. Upon further comparative analysis with the pathologic T3a group, we also found significant differences among the groups throughout the Kaplan-Meier curve (P < 0.001). Conclusively, the unpredicted (negative) SVI group had a favorable BCR-free survival compared to the positive SVI group. In addition, significant differences were observed in the prognosis of pathologic T3a and these two groups. This suggests that pathologic T3b can be stratified into two categories.

Accelerated corrosion tests of reinforced concrete (RC) specimens were conducted to estimate the corrosion expansion rate of reinforcing bars. Subsequently, finite element analysis was performed with the estimated expansion rate for RC beams to investigate concrete cracking induced by corrosion. The influence of the different confinement levels on crack behavior was investigated using mainly the amount of transverse reinforcement. An expansion rate of 2 was found to be appropriate when using Lundgren's expansion model. Confinement levels affected the cracking behavior of steel bars. Cracks did not significantly affect structural capacity although they exceeded the allowable crack width. Nevertheless, repair and reinforcement measures are necessary because degrading durability factors such as carbonation or salt diffusion can reach the reinforcing bars through connected cracks.

This study used liquefied red mud (RM) sludge, an aluminum industry by-product, as a construction material. Accordingly, various methods were examined that used the fabricated liquefied red mud (LRM) as an admixture for concrete, and the mechanical properties of concrete were then evaluated according to the cement type and the amount of LRM. The LRM mixing methods (replacement and addition) were compared, and the slump and compressive strengths of concrete were evaluated for each method. To examine the mechanical properties according to the cement type and the amount of LRM, two types of cement (ordinary Portland cement and slag cement (SC)) were used, and 20 and 40 wt% LRM (with respect to the cement weight) were added. The mechanical properties of the stress-strain curve (SSC), compressive strength, peak strain, and elastic modulus were quantified. When the slump and compressive strength of concrete were considered based on the experimental results, the addition LRM mixing method was recommended as the appropriate method for LRM. As the addition of LRM increased, the mechanical properties of concrete degraded. However, when SC was used, the mechanical properties did not significantly change when different amounts of LRM were added (up to 20%). In addition, the SSC of LRM concrete could be approximated based on the use of the relationship of the compressive strength and peak strain according to the cement type and the amount of LRM.

A 23-year-old Korean woman with a residence history in Kenya and Malawi for about 2 years presented with gross hematuria for 1 month. Blood tests were within normal range except eosinophilia. Asymmetrically diffuse wall thickening and calcification were observed at the urinary bladder on CT. Multiple erythematous nodular lesions were observed in the cystoscopy and transurethral resection was done. Numerous eggs of Schistosoma haematobium with granulomatous inflammation were observed in the submucosal layer of the bladder. The patient was diagnosed with schistosomiasis-related cystitis and treated with praziquantel (40 mg/kg/day) twice before and after transurethral resection. This case suggests that S. haematobium infection should be considered as a cause of hematuria in Korea when the patient had a history of traveling endemic areas of schistosomiasis.

Objective: Treatment of patients with thymic malignancies metastatic to the pleura or pericardium is challenging, and benefits of aggressive treatment are unclear. We sought to characterize the long-term outcomes in this population., Methods: We retrospectively identified patients who underwent resection for de novo thymic malignancies metastatic to the pleura between May 1997 and December 2017. Patients with pleural recurrence after prior thymectomy were excluded. Patient demographics, perioperative treatments, pathologic findings, and postoperative outcomes were collected. Descriptive statistics and Kaplan-Meier analyses were performed., Results: Seventy-two patients were included (median age, 51 years [range 25-80]; 36/72 women [50%]). Pathologic diagnosis was thymoma in 57 patients (79%) and thymic carcinoma in 15 patients (21%). Most patients (67/72; 93%) received chemotherapy, radiation, or both. Forty-eight patients underwent thymectomy with pleurectomy, 7 patients underwent extrapleural pneumonectomy, 10 patients underwent thymectomy alone, and 7 patients were unresectable. Macroscopic complete resection was achieved in 52 patients (73%). Five-, 10-, and 15-year overall survivals were 73%, 51%, and 18%, respectively, and median overall survival was 11 years (median follow-up, 5.9 years). Forty-six patients (64%) had disease progression (median time to progression, 2.2 years). Repeat episodes of progression and treatment were common (median, 3 episodes/patient). The longest disease-free interval was 12.4 years. Thirteen patients (18%) remain disease-free; 7 patients (10%) were disease-free for more than 5 years. The longest ongoing survival without progression or reintervention is 9.9 years., Conclusions: Prolonged survival and, in some cases, cure can be achieved in patients with thymic malignancies metastatic to the pleura or pericardium. Aggressive multimodality therapy may be appropriate for select patients., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The success rate for the production of animal models of chronic postischemia pain (CPIP) using an O-ring has yet to be improved in the study of complex regional pain syndrome-type I (CRPS-I), and producing a CPIP model is challenging, especially for mice., Objectives: We devised a new CPIP model with a higher success rate that induces ischemia for 3 hours by tying the hind limbs of mice with a rubber band, followed by reperfusion., Study Design: A randomized, controlled animal trial., Methods: Twenty-two male C57BL/6 mice were divided into a sham (n = 6), a ring (n = 8), and a tie group (n = 8). Anesthesia was induced using isoflurane. A precut O-ring was mounted on the upper left ankle in the sham group. A tight-fitting O-ring and a push-pull gauge manometer were mounted at the same location in the ring and tie groups, respectively. Reperfusion was induced 3 hours later. The thickness and circumference of the hind paws were measured before ischemia induction. Measurements were repeated 10 days after reperfusion. Mechanical allodynia was measured with a von Frey filament until 12 weeks after reperfusion., Results: The new tie model required 5 additional days until the onset of allodynia compared with the existing CPIP O-ring model. However, the successful induction rate of CPIP was higher in the tie group than in the ring group, and allodynia was maintained for over 30 days in the tie group. The ring and tie groups exhibited significantly high levels of tumor necrosis factor-alpha than those in the sham group., Limitations: First, we did not evaluate hyperalgesia, cold or heat allodynia. Second, we did not measure blood levels of inflammatory or antiinflammatory cytokines, and research on oxidative stress biomarkers such as isoprostane, 8-hydroxy-2'-deoxyguanosine (a marker of DNA oxidative damage), and malondialdehyde was not performed., Conclusions: The new CPIP tie model has a higher rate of successful induction than existing O-ring models for mice, with longer duration of mechanical allodynia. The model may reduce the number of animals sacrificed in CRPS-I research and could be useful for studying long-term effects of drugs., Key Words: CPIP, mouse, O-ring, rubber band, reperfusion, allodynia, hyperalgesia.

Purpose: To optimize and validate a current (NRG [a newly constituted National Clinical Trials Network group through National Surgical Adjuvant Breast and Bowel Project [NSABP], the Radiation Therapy Oncology Group [RTOG] and the Gynecologic Oncology Group (GOG)]) nomogram for glioblastoma patients as part of continuous validation., Methods: We identified patients newly diagnosed with glioblastoma who were treated with temozolomide-based chemoradiotherapy between 2006 and 2016 at three large-volume hospitals. The extent of resection was determined via postoperative MRI. The discrimination and calibration abilities of the prediction algorithm were assessed; if additional factors were identified as independent prognostic factors, updated models were developed using the data from two hospitals and were externally validated using the third hospital. Models were internally validated using cross-validation and bootstrapping., Results: A total of 837 patients met the eligibility criteria. The median overall survival (OS) was 20.0 (95% CI 18.5-21.5) months. The original nomogram was able to estimate the 6‑, 12-, and 24-month OS probabilities, but it slightly underestimated the OS values. In multivariable Cox regression analysis, MRI-defined total resection had a greater impact on OS than that shown by the original nomogram, and two additional factors-IDH1 mutation and tumor contacting subventricular zone-were newly identified as independent prognostic values. An updated nomogram incorporating these new variables outperformed the original nomogram (C-index at 6, 12, 24, and 36 months: 0.728, 0.688, 0.688, and 0.685, respectively) and was well calibrated. External validation using an independent cohort showed C‑indices of 0.787, 0.751, 0.719, and 0.702 at 6, 12, 24, and 36 months, respectively, and was well calibrated., Conclusion: An updated and validated nomogram incorporating the contemporary parameters can estimate individual survival outcomes in patients with glioblastoma with better accuracy.

Objectives: To validate how established markers of extraprostatic extension (EPE) are applied to anterior prostate cancers (APCs), and to investigate other novel markers if available., Methods: Among 614 histopathologically confirmed APCs from 2011 to 2016, 221 lesions with PiRADS (verion 2) scores ≥ 4 on 3-T multi-parametric MRI were analyzed retrospectively. Two radiologists independently assessed capsular morphology qualitatively with 5-point scale (normal, thinning, bulging, loss, extracapsular disease), and capsule contact length (arc), tumor dimension, and their ratio (arc-dimension ratio) quantitatively. Reproducibility in measurement was assessed with κ and intra-class correlation coefficients (ICCs). Logistic regression analysis was done to find meaningful indicators of EPE. Diagnostic performance of markers was compared to one another with generalized linear model and multi-reader multi-case ROC analysis., Results: Reproducibility was moderate to substantial (κ 0.45-0.73) for qualitative, and moderate to almost perfect (ICC 0.50-0.87) for quantitative features of EPE. Capsular morphology (odds ratio [OR] 1.818), capsule contact length (OR 1.115), tumor dimension (OR 1.035), and arc-dimension ratio (OR 1.846) were independently associated with EPE (p ≤ 0.019). Capsular bulging and capsule contact length of 10 mm as thresholds of EPE demonstrated sensitivity/specificity of 0.58/0.85 and 0.77/0.68, respectively. Capsule contact length yielded greatest AUC (0.784), followed by capsular morphology (0.778), arc-dimension ratio (0.749), and tumor dimension (0.741). Diagnostic performance of capsular morphology, capsule contact length, and arc-dimension ratio was comparable in predicting EPE., Conclusions: Existing markers of EPE applicable regardless of locations of tumors apply similarly to APCs. Arc-dimension ratio may be a novel marker of EPE of APCs., Key Points: • Existing imaging markers of extraprostatic extension (EPE) which have been applied regardless of locations of tumors are reflected similarly to anterior prostate cancers (APCs). • Measuring tumor dimension without capsular assessment may result in insufficient pre-operative prediction of EPE of APCs. • Arc-dimension ratio (capsule contact length divided by tumor dimension) exhibited highest OR and comparable performance to existing features in predicting EPE of APCs.

Three-dimensional (3D) cell printing is a versatile technique enabling the creation of 3D constructs containing hydrogel and cells in the desired shape or pattern. Bioinks exhibiting appropriate mechanical properties and biological activities to support cell growth and/or differentiation toward a specific lineage play critical roles in 3D cell printing and tissue engineering applications. Herein, we explored alginate/graphene oxide (GO) composites as bioinks for their potential to improve printability, structural stability, and osteogenic activities for osteogenic tissue engineering applications. The addition of GO (0.05-1.0 mg mL -1 ) to 3% alginate significantly enhanced the printing performances of the alginate bioink. In addition, mesenchymal stem cells (MSCs) printed with alginate/GO showed good proliferation and higher survival in an oxidative stress environment. The 3D scaffolds printed with MSCs and alginate/GO demonstrated significantly enhanced osteogenic differentiation compared with those printed with MSCs and alginate. Overall, a bioink of 3% alginate and 0.5 mg mL -1 GO showed the most balanced characteristics in terms of printability, structural stability, and osteogenic induction of the printed MSCs. Alginate/GO composite bioinks will be useful for bioprinting research for various tissue engineering applications.

Background and Objectives: We review the intraoperative findings and postoperative outcomes of ossiculoplasty in subjects with second pharyngeal arch (SPA)-derived ossicular anomalies. We summarize potential intraoperative complications and recommend precautions that may reduce the risk of fracture., Materials and Methods: Twenty-four patients with SPA-derived ossicular anomalies were included, and pre- and postoperative audiometric results were compared., Results: The mean air conduction threshold (56.0 ± 12.4 dB HL) was significantly improved 1 month (27.6 ± 10.1 dB HL) and 6 months (23.8 ± 13.2 dB HL) after surgery ( p < 0.001). The preoperative air-bone gap (ABG) (40.4 ± 7.4 dB HL) was significantly decreased at 1 month (15.1 ± 5.9 dB HL) and 6 months (11.3 ± 8.9 dB HL) postoperation. ABG closure was successful (<20 dB HL) in 21 (87.5%) patients 6 months after surgery. Intraoperative footplate fractures occurred in 3 of 24 patients. The fractures were managed successfully, and the ABG closure was successful in all cases., Conclusions: The stapes footplate is likely to be relatively thin in subjects with SPA-derived ossicular anomalies because the footplate is partially or totally derived from the SPA. Thus, a fragile footplate should be expected, and care is needed when handling the footplate. However, when complications are overcome, the audiological outcomes are excellent in most cases.

Mesenchymal stem cell (MSC) transplantation is promising for repairing heart tissues post myocardial infarction (MI). In particular, paracrine effects of the transplanted MSCs have been highlighted to play major roles in heart regeneration by secreting multiple growth factors and immune-modulatory cytokines. Nevertheless, its therapeutic efficacy still remains low, which is strongly associated with low viability and activity of the transplanted stem cells, because the transplanted MSCs are exposed to high shear stress during injection and harsh environments (e.g., high oxidative stress and host immune reactions) post injection. In this study, we aimed to develop novel injectable MSC-delivery microgel systems possessing high anti-oxidant activities. Specifically, we encapsulated MSCs in graphene oxide (GO)/alginate composite microgels by electrospraying. To further enhance the anti-oxidizing activities of the gels, we developed reduced MSC-embedded GO/alginate microgels (i.e., r(GO/alginate)), which have the potential to protect MSCs from the abovementioned harsh environments within MI tissues. Our in vitro studies demonstrated that the MSCs encapsulated in the r(GO/alginate) microgels showed increased viability under oxidative stress conditions with H 2 O 2 . Furthermore, cardiomyocytes (CMs), co-cultured with the encapsulated MSCs in transwells with H 2 O 2 treatment, showed higher cell viability and cardiac maturation compared to monolayer cultured CMs, likely due to ROS scavenging by the gels and positive paracrine signals from the encapsulated MSCs. In vivo experiments with acute MI models demonstrated improved therapeutic efficacy of MSC delivery in r(GO/alginate) microgels, exhibiting significant decreases in the infarction area and the improvement of cardiac function. We believe that our novel MSC encapsulation system with GO, alginate, and mild reduction, which exhibits high cell protection capacity (e.g., anti-oxidant activity), will serve as an effective platform for the delivery of stem cells and other therapeutic cell types to treat various injuries and diseases, including MI., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We aimed to evaluate the effect of 5 alpha-reductase inhibitor (5-ARI) treatment on prostate cancer (PCa) and clinically significant PCa (csPCa) detection in patients undergoing transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy in the current era of multi-parametric MRI (mpMRI). We retrospectively reviewed our TRUS/MRI fusion biopsy database (n = 706). Eighty (11.3%) patients who had used 5-ARI for more than one year at the time of biopsy were stratified as 5-ARI group. Subsequently, we performed comparative analyses of 5-ARI and non-5-ARI groups. csPCa was defined by a Gleason score ≥3 + 4 in a single biopsy core. Chi-squared test was used to evaluate the performance of mpMRI in predicting PCa/csPCa between the two groups. Multivariate logistic regression analyses were performed to evaluate the significant variables associated with PCa detection. There were no significant differences in PCa/csPCa detection rates between 5-ARI and non-5-ARI groups (all, P > 0.05). In multivariate logistic regression analyses for the evaluation of variables associated with csPCa detection, age (odds ratio [OR], 1.062; 95% confidence interval [CI], 1.035-1.090; P < 0.001), pre-biopsy PSA (OR, 1.062; 95% CI, 1.034-1.090; P < 0.001), prostate volume on TRUS (OR, 0.956; 95% CI, 0.943-0.970, P < 0.001), and PI-RADsV2 category (OR, 5.528; 95% CI, 3.017-10.131; P < 0.001) were found to be significant predictors. However, 5-ARI had no significant association with PCa detection (P = 0.384). Conclusively, 5-ARI therapy did not adversely affect PCa/csPCa detection after TRUS/MRI fusion biopsy, which suggests that exposure to 5-ARI may not impair the performance of mpMRI.

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated Listeria monocytogenes engineered to express mesothelin, a tumor-associated antigen highly expressed in MPM. CRS-207 induces antitumor immune responses and increases susceptibility of neoplastic cells to immune-mediated killing., Patients and Methods: Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and pulmonary function were enrolled in this multicenter, open-label phase Ib study. They received two priming infusions of 1 × 10 9 CFU CRS-207, followed by pemetrexed/cisplatin chemotherapy, and CRS-207 booster infusions. Primary objectives were safety and induction of immune response. Secondary/exploratory objectives included tumor response, progression-free survival (PFS), overall survival (OS), immune subset analysis, and gene-expression profiling of tumor., Results: Of 35 evaluable patients, 89% (31/35) had disease control with one complete response (3%), 19 partial responses (54%), and 10 stable disease (29%). The estimated median duration of response was 5.0 months (95% CI, 3.9-11.5). The median PFS and OS were 7.5 (95% CI, 7.0-9.9) and 14.7 (95% CI, 11.2-21.9) months, respectively. Tumor size reduction was observed post-CRS-207 infusion prior to chemotherapy in 11 of 35 (31%) patients. No unexpected treatment-related serious adverse events or deaths were observed. IHC analysis of pre- and post-CRS-207 treatment tumor biopsies revealed possible reinvigoration and proliferation of T cells, increased infiltration of dendritic and natural killer cells, increased CD8:T reg ratio, and a shift from immunosuppressive M2-like to proinflammatory M1-like macrophages following CRS-207 administration., Conclusions: Combination of CRS-207 and chemotherapy induced significant changes in the local tumor microenvironment and objective tumor responses in a majority of treated patients., (©2019 American Association for Cancer Research.)

Background: The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas., Methods: A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis., Results: According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDHmut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDHmut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDHmut, 11 diffuse astrocytoma, IDHwt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDHmut, eight anaplastic astrocytoma, IDHwt, NOS; and 35 glioblastoma, IDHwt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDHmut and 1p/19q co-deleted and diffuse astrocytoma IDHmut showed significantly higher survival than those with diffuse astrocytoma IDHwt, NOS (p<.01)., Conclusions: Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.

In this study, a new method is developed to control the Cl-to-I ratio in MAPbI 3- x Cl x perovskite solar cells (PSCs) more easily and precisely using single-source vapor deposition of MAPbCl 3 thin films and a subsequent anion exchange by repeated spin-coatings of methylammonium iodide (MAI) solution. This method can overcome the problems of previous vapor-deposition techniques for PSCs such as the occurrence of morphological defects in the films and difficulty in controlling the stoichiometry of the elements. The repetitive MAI treatments gradually fill the interstitial voids in the perovskite film and increase the average grain size up to 1.2 μm, which improves the charge-transfer property of the cells. The atomic Cl content, i.e., the x value, of the MAPbI 3- x Cl x film can also be simply controlled by changing the number of MAI treatments. The energy levels and resistive elements of the cells are strongly dependent on the x value of the MAPbI 3- x Cl x film. A maximum power conversion efficiency of 19.1% is achieved at x = 0.005.

Programmed death ligand 1 (PD-L1) expression provides significant value to predict prognosis and response following immunotherapy in several types of cancers. However, its clinicopathological and prognostic significance in melanoma remains unclear. PD-L1 and the number of tumor infiltrating lymphocytes (TILs) were investigated in 63 Korean patients with melanoma based on the melanoma scoring system. We also compared the results using the PD-L1 antibodies-22C3 and E1L3N clones. In addition, BRAF gene mutation was detected using anti-BRAF antibody and real-time polymerase chain reaction. Overall, 29 (46.0%), 16 (25.4%), and 18 (28.6%) patients exhibited the acral lentiginous type, nodular type, and other histological subtypes of melanoma, respectively. PD-L1 expression was detected in 37 (58.7%) cases and was closely associated with a CD8+TIL high phenotype ( P < 0.001). Combined survival analysis depending on PD-L1 and CD8+TILs status showed that the PD-L1-/CD8+TIL high group demonstrated the best survival outcome, whereas patients with PD-L1+/CD8+ TIL low showed the worst prognosis ( P = 0.039). However, PD-L1+/CD8+ TIL low was not an independent prognostic factor. The 22C3 and E1L3N clones showed a high concordance rate (kappa value, 0.799). BRAF mutation status was not correlated with PD-L1 expression. We suggest that evaluation of the combined status of PD-L1 and TIL might be useful to predict the survival of patients with melanoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Purpose: To evaluate the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) classification, a clinical scoring system, for predicting disease control status in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate prognostic factors., Materials and Methods: In total, 134 CRSwNP patients who underwent functional endoscopic sinus surgery after maximal medical treatment were enrolled. These patients were categorized into four groups according to JESREC classification: 1) non-eosinophilic CRSwNP (non-ECRSwNP), 2) mild eosinophilic CRSwNP (ECRSwNP), 3) moderate ECRSwNP, and 4) severe ECRSwNP. Disease control status among the patients was evaluated at 1 year after surgery, and the patients were divided into two groups (disease-controlled and disease-uncontrolled groups) for the investigation of prognostic factors., Results: There was no significant difference in disease control status between non-ECRSwNP and ECRSwNP groups ( p =0.970). Age, Lund-Mackay CT scores, global osteitis scores, tissue neutrophil count, and tissue eosinophil count were associated with disease control status. In subgroup analysis of the non-ECRSwNP group, only high tissue neutrophil count was related with disease control status, whereas for the ECRSwNP group, young age, high Lund-Mackay CT scores, high global osteitis scores, and high tissue and blood eosinophil counts were associated with disease control status., Conclusion: No difference in disease control status was identified between non-ECRSwNP and ECRSwNP cases. Tissue neutrophilia, however, appeared to be associated with disease control status in non-ECRSwNP cases, whereas tissue and blood eosinophilia was associated with ECRSwNP cases., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Structure from small motion has become an important topic in 3D computer vision as a method for estimating depth, since capturing the input is so user-friendly. However, major limitations exist with respect to the form of depth uncertainty, due to the narrow baseline and the rolling shutter effect. In this paper, we present a dense 3D reconstruction method from small motion clips using commercial hand-held cameras, which typically cause the undesired rolling shutter artifact. To address these problems, we introduce a novel small motion bundle adjustment that effectively compensates for the rolling shutter effect. Moreover, we propose a pipeline for a fine-scale dense 3D reconstruction that models the rolling shutter effect by utilizing both sparse 3D points and the camera trajectory from narrow-baseline images. In this reconstruction, the sparse 3D points are propagated to obtain an initial depth hypothesis using a geometry guidance term. Then, the depth information on each pixel is obtained by sweeping the plane around each depth search space near the hypothesis. The proposed framework shows accurate dense reconstruction results suitable for various sought-after applications. Both qualitative and quantitative evaluations show that our method consistently generates better depth maps compared to state-of-the-art methods.

Purpose: To determine the efficacy of a biodegradable collagen matrix implant (Ologen, Aeon Astron Europe BV, Leiden, the Netherlands) in reducing adhesions in a rabbit model of restrictive strabismus., Methods: A prospective, masked-observer, controlled experimental study was performed. Sixty superior rectus muscles of 30 rabbits were resected and Marlex mesh was fixed beneath the resected muscle using nonabsorbable suture. Forty eyes underwent one of two different procedures; the resected muscle was wrapped with preserved human amniotic membrane (AM group) or Ologen (Ologen group). Randomly selected 20 eyes served as controls. Eyes were enucleated at 4 weeks after surgery to measure the severity of adhesion using a push pull gauge. Histopathological examination was performed., Results: At postoperative week four, the average tensile strength of the myoscleral adhesion was significantly lower in the Ologen group (151.8 ± 42.7 gram force) compared to controls (347.9 ± 68.6 gram force) and AM group (193.0 ± 44.3 gram force) (p < 0.001 and p = 0.045, respectively). Ologen group showed significantly lower degree of acute inflammation, chronic inflammation and rectus muscle fibrosis compared with controls (all p < 0.01). The degree of chronic inflammation was significantly lower in the Ologen group compared with AM group (p = 0.012)., Conclusion: Compared to amniotic membrane, Ologen is more effective in reducing mesh-related extraocular muscle adhesions in a rabbit model of restrictive strabismus., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)