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Particulate matter (PM) is the main component of air pollution. Children are vulnerable to PM and acute otitis media (AOM), which is one of the most common diseases in children. However, studies on the relationship between AOM in children and PM are rare and their results are inconsistent. The aim of this study is to investigate the effect of PM on AOM in children on the basis of the Korea National Health Insurance service (NHIS) claims data. NHIS claim data from 2008 to 2015 was used to identify outpatient visits, antibiotic use to treat AOM, and demographic data. This data was combined with the data on PM2.5 (≤ 2.5 μm) and PM10 (≤ 10 μm according to its aerodynamic diameter) level extracted from air pollution data from Korean National Institute of Environmental Research for 16 administrative regions. The children with AOM were divided into three age groups (2.5 of 10 μg/m3, the relative risk of OM increased by 4.5% in children under 2 years of age. The effect of PM2.5 was strongest influence on the day of exposure. The exposure to PM10 was related to the incidence of AOM on the day of exposure and the following seven days in all three age groups. The PM concentrations did not strongly affect either AOM duration or the use of antibiotics to cure AOM. The RR in the each lag day after exposure to PM10 was diverse according to the age groups. Regardless of PM size and children’s age, the PM levels are positively related to the incidence of AOM. Both PM2.5 and PM10 have the most adverse effects on children under 2 years of age and on the day of exposure.

Nonprofit social service agencies in South Korea have dramatically improved their service quality in the last few decades. However, with increasing competition among nonprofit social service agenci...

Ocular axial length (AL) is an important property of eyes used for determining their health prior to surgery. Estimation of AL is also crucial while making artificial lenses to replace impaired natural lenses. However, accurate measurement of AL requires a costly and bulky benchtop optical system. The complex structural features of eyes can be captured by fundus images, which can be easily captured nowadays with portable cameras. Here, we suggest a deep learning method for predicting AL based on fundus images with evidence of decision. This visual interpretation of predictions is achieved by post-processing, separated from the training process, to ensure that the architecture can be freely designed. Through the visualization technique, discriminative regions on input images can be localized to demonstrate specific areas of interest for predictions. In the experiments, we found a significant relationship between the fundus images and AL with achieving a coefficient of determination ( R2 ) of 0.67 and accuracy of 90%, within an error margin of $ \pm 1$ mm. Furthermore, visual evidence proves that the network uses consistent regions for predicting AL. The visual results of this study also point to a link between AL and biological structure of eyes, which paves the way for future research.

Background Lung adenocarcinoma (LUAD) with brain metastasis (BM) occurs frequently and has a poor prognosis. In this study, we aimed to assess the correlation between gene expression signatures and the development of BM after surgical resection of LUAD. Methods We analyzed the immune-related gene expression profiles of 72 LUADs with and without BM after surgery and verified them using NanoString method and immunohistochemistry (IHC). We matched the Tumor, Node, Metastasis (TNM) stage in the groups with and without BM to minimize the effect of TNM stage. Pathway enrichment studies were also performed. Results In the NanoString results, we identified 11 upregulated immune-related gene signature that correlated specifically with BM in the discovery and validation sets [area under the curve (AUC) =0.750 and 0.787, respectively]. The discovery set achieved 94% sensitivity and 62% specificity and the validation set displayed 100% sensitivity and 50% specificity. Eight out of the 11 genes were verified by IHC and had profiles similar to the gene expression profile results (AUC =0.844 for the discovery set and AUC =0.795 for the validation set). Subgroup analysis revealed that 11 immune-related gene signature enabled prediction of BM at all TNM stages. There were no differences in the 11 immune-related gene expression signatures between the primary LUAD samples and the matched brain samples. Pathway enrichment analysis revealed that the cytokine-cytokine receptor interaction pathway was closely correlated with BM. Conclusions The 11 identified immune-related gene expression signatures may be potentially clinically useful predictors for BM and can provide patient-specific treatment options.

BackgroundPenile carcinoma is a rare malignant neoplasm and its molecular pathogenetic mechanism is largely unknown. Telomerase reverse transcriptase (TERT) promoter mutations have been detected in several types of human malignancies, including malignant melanoma, non-melanoma skin cancer, thyroid carcinoma, glioma, and bladder carcinoma. However, TERT-p mutation in penile squamous cell carcinoma (SCC) has not been investigated to date. The aim of this study was to investigate the presence of TERT promoter mutations in penile squamous cell carcinomas and their associations with clinicopathologic features. MethodsSanger sequencing was performed to detect TERT promoter mutations in formalin-fixed paraffin-embedded tissue samples from 37 cases of penile SCC, 16 cases of cutaneous SCC, and 4 cases of non-neoplastic penile/skin tissue. The expression of p16 and Ki67 were investigated by immunohistochemistry. Associations of TERT promoter mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. ResultsRecurrent TERT promoter mutations were identified in 18 of 37 (48.6%) penile SCCs, including all three carcinoma in situ cases. TERT promoter mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT promoter mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, and low Ki67/MIB-1 labelling index. Univariate Cox regression analysis and Kaplan-Meier analysis with the log-rank test indicated that TERT promoter mutation was a favorable factor for disease-free survival. ConclusionsOur study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC, indicating that in case of non-HPV-related penile SCC, TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

Purpose This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.Materials and Methods We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.Results Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).Conclusion Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

With a growing number of nonprofit social service agencies in South Korea, leaders are required to networking among agencies to provide quality services. On the other hand, increasing competitive e...

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease with a variety of molecular aberrations and diverse clinical outcomes. BCL2 expression has been implicated for a poor prognosis among patients with DLBCL. However, there is no consensus regarding the interpretation of BCL2 expression in DLBCL. In previous studies, the range of BCL2-positive cases, determined by immunohistochemistry (IHC), was highly variable (24 - 80%) due to subjective and semiquantitative interpretation and the absence of the established cutoff value for BCL2 expression. Consequently, the prognostic impact of BCL2 varies between studies. In addition, only the proportion of BCL2 positive tumor cells are considered in determining the BCL2 positivity. We aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. Methods We retrospectively collected formalin-fixed, paraffin-embedded (FFPE) diagnostic biopsies from 221 patients with de novo DLBCL between January 2007 and December 2012 at our institute. All patients were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line treatment. A separate validation set included 111 patients with de novo DLBCL who received first-line R-CHOP at another tertiary hospital in South Korea. BCL2 expression was analyzed using the tumor-specific Automated Quantitative Analysis (AQUA) scoring system based on multiplex immunofluorescence. The tumor-specific quantified intensity information in pixels was converted to protein expression information on a cell basis using the AQUA scoring system. The AQUA scores for BCL2 was calculated as the signal intensities of BCL2 in the target compartment divided by the pixel area of the target compartment. Cell of origin (COO) was determined according to the Hans classification using IHC. Results Ninety-eight patients (44.3%) were > 60 years old of age, 126 patients (57.0%) were male and 81 patients (36.7%) had an International Prognostic Index of 3-5 in the training set. With a median follow-up duration of 59 months, the 5-year event-free survival (EFS) and overall survival (OS) rate were 62.2% and 69.0%, respectively. The BCL2 AQUA score of 41.47 was determined as the optimal cutoff value in the ROC analysis. A total of 86 patients (38.9%) were classified as high BCL2 AQUA score group according to the determined cutoff value. High BCL2 AQUA score was significantly associated with worse OS and EFS (P = 0.00015; OS, P = 0.00012; EFS) (Figure 1A, B). Multivariate analysis revealed that high BCL2 AQUA score was a significant poor prognostic factor for both OS and EFS independent of the IPI, and COO (P = 0.01; OS, P = 0.015; EFS). The high BCL2 AQUA score group in the validation set was also significantly associated with worse OS and EFS (P = 0.0075; OS, P = 0.0049; EFS) (Figure 1C, D). The poor prognostic impact of BCL2 AQUA score was also in good correlation with both OS and EFS in the entire cohort (P < 0.0001; OS, P < 0.0001; EFS) (Figure 1E, F). The adverse impact of high BCL2 AQUA score was identified within both low (IPI 0-2) and high IPI (IPI 3-5) groups (Figure 2A-D). The high BCL2 AQUA score was also associated with poor prognosis within both GCB (P = 0.0077; OS, P = 0.0055; EFS) and non-GCB type DLBCL (P = 0.059; OS, P = 0.04; EFS), although a marginal statistical significance was observed regarding OS in the non-GCB type (Figure 2E-H). Conclusion Our study demonstrated that BCL2 expression analyzed by AQUA scoring system, incorporating both intensity and proportion, is an independent prognostic factor for patients with DLBCL. Given the growing clinical implications of BCL2 and the therapeutic progress in targeting BCL2 in hematologic malignancies, the concrete definition of BCL2 positivity in DLBCL holds great promise for the study of the pathophysiology of DLBCL and could be used to establish new therapeutic strategies. Disclosures No relevant conflicts of interest to declare.

With recent advancements in communication and smartphone technology, many convenient services, such as SNS, gaming, video streaming, and news, are now available to users. However, this wealth of options is disadvantageous in that it makes smartphone users smombies (i.e., users who focus on their smartphones and ignore their surroundings), which poses a safety hazard. For improving the safety of pedestrian smartphone users, attempts have been made to install traffic lights on sidewalks or warn users of approaching vehicles through mobile apps. However, the effectiveness of these smombie warning systems has not been investigated yet. In this article, we propose Smombie Forecaster, which uses inertial smartphone sensors and the BLE beacon, to detect the three most prevalent smombie settings (walkways, stairs, and crosswalks), provide relevant alerts to users, and log their compliance with these alerts. We conducted a field test with 24 participants under these three settings. The results verified the effectiveness of the proposed system; the smartphone pause time increased by 1.59 times, and the average frequency of steps taken by users decreased from 1.68 Hz to 1.47 Hz. A post-experiment survey, interviews conducted with participants of the experiment, and users' smartphone logs provide important design implications for the proposed smombie alerting system.

Background Nowadays, face masks are a crucial part of our daily life. Previous studies on their impact on the skin usually focused on the adverse effects of face masks. Few studies have assessed their influence on skin characteristics. In a previous study, we identified the short‐term effects of wearing face masks. Herein, we describe the long‐term skin effects of face masks, for a period of 6 months. Materials and methods Healthy volunteers (19 men and women), who wore face masks, participated in the study from June 2020 to December 2020. In all participants, skin characteristics such as trans‐epidermal water loss (TEWL), skin hydration, skin elasticity, skin pore area, skin keratin amount, skin temperature, skin redness, skin temperature, skin redness, and skin color were measured three times. Results TEWL, skin hydration, skin elasticity, skin pore area, skin keratin amount, and skin color changed significantly after 6 months. TEWL, skin hydration, skin pore area, skin keratin amount, and skin color were significantly different between the mask‐wearing and non‐mask‐wearing areas. Conclusion Long‐term daily use of face masks can alter skin characteristics. Special care should be focused on the mask‐wearing regions.

Simple Summary It is important to be able to predict brain metastasis in lung adenocarcinoma patients; however, research in this area is still lacking. Much of the previous work on tumor microenvironments in lung adenocarcinoma with brain metastasis concerns the tumor immune microenvironment. The importance of the tumor nonimmune microenvironment (extracellular matrix (ECM), epithelial–mesenchymal transition (EMT) feature, and angiogenesis) has been overlooked with regard to brain metastasis. We evaluated tumor nonimmune-microenvironment-related gene expression signatures that could predict brain metastasis after the surgical resection of lung adenocarcinoma using a machine learning approach. We identified a tumor nonimmune-microenvironment-related 17-gene expression signature, and this signature showed high brain metastasis predictive power in four machine learning classifiers. The immunohistochemical expression of the top three genes of the 17-gene expression signature yielded similar results to NanoString tests. Our tumor nonimmune-microenvironment-related gene expression signatures are important biological markers that can predict brain metastasis and provide patient-specific treatment options. Abstract Using a machine learning approach with a gene expression profile, we discovered a tumor nonimmune-microenvironment-related gene expression signature, including extracellular matrix (ECM) remodeling, epithelial–mesenchymal transition (EMT), and angiogenesis, that could predict brain metastasis (BM) after the surgical resection of 64 lung adenocarcinomas (LUAD). Gene expression profiling identified a tumor nonimmune-microenvironment-related 17-gene expression signature that significantly correlated with BM. Of the 17 genes, 11 were ECM-remodeling-related genes. The 17-gene expression signature showed high BM predictive power in four machine learning classifiers (areas under the receiver operating characteristic curve = 0.845 for naïve Bayes, 0.849 for support vector machine, 0.858 for random forest, and 0.839 for neural network). Subgroup analysis revealed that the BM predictive power of the 17-gene signature was higher in the early-stage LUAD than in the late-stage LUAD. Pathway enrichment analysis showed that the upregulated differentially expressed genes were mainly enriched in the ECM–receptor interaction pathway. The immunohistochemical expression of the top three genes of the 17-gene expression signature yielded similar results to NanoString tests. The tumor nonimmune-microenvironment-related gene expression signatures found in this study are important biological markers that can predict BM and provide patient-specific treatment options.

Generative Adversarial Networks (GANs) have shown satisfactory performance in synthetic image generation by devising complex network structure and adversarial training scheme. Even though GANs are able to synthesize realistic images, there exists a number of generated images with defective visual patterns which are known as artifacts. While most of the recent work tries to fix artifact generations by perturbing latent code, few investigate internal units of a generator to fix them. In this work, we devise a method that automatically identifies the internal units generating various types of artifact images. We further propose the sequential correction algorithm which adjusts the generation flow by modifying the detected artifact units to improve the quality of generation while preserving the original outline. Our method outperforms the baseline method in terms of FID-score and shows satisfactory results with human evaluation.

Optical coherence tomography cannot easily be used for visual identification of the ganglion cell layer (GCL) for diagnosing retinal diseases owing to the extremely low image contrast between adjacent layers. To solve this problem, the authors used a limit-clipping optimisation method along with the image entropy to enhance the image contrast of targeted layers. As a result, the GCL was successfully extracted using an intelligent tracking system without impacting the segmentation of other retinal layers and image morphology. The segmentation results were evaluated through comparisons with manual segmentation results provided by clinical experts. The results of this study should help realise simple and efficient discrimination of important retinal layers for the early diagnosis of glaucoma.

Background Previous studies have demonstrated increased pore size and darkening skin color with total sleep deprivation. There are many studies of skin characteristics with short-term sleep restriction, but there are few studies on skin characteristics when sleep is restricted more than three consecutive days. This study evaluated skin changes with sleep limited to 4 hours per night for six nights. Materials and methods The study included 32 Korean women in their 40s. Skin hydration, desquamation, barrier recovery, texture, gloss, transparency, elasticity, crow's feet, frown lines, and color were measured. Individual sleep time was monitored by smartwatches. Subjects slept 8 hours per night for six nights in week one and 4 hours per night for six nights in week two. Results Skin hydration was significantly reduced after 1 day of sleep deprivation, and it continued to decrease. Skin gloss, desquamation, transparency, elasticity, and wrinkles were significantly aggravated after 1 day of sleep deprivation. Skin texture was significantly aggravated on the fourth day of sleep restriction. Elasticity was most affected by reduced sleep, with a standardized coefficient of -.320, indicating a significant decrease over time as compared to other characteristics. Conclusion Skin hydration was gradually decreased with sleep restriction. Skin texture did not change after only 1 day of sleep restriction. It is a new finding that elasticity decreases more than other skin characteristics with prolonged sleep restriction.

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a rare histiocytic disorder of unknown etiology. Most patients with RDD have spontaneous remission, but in some patients, the disease recurs after complete remission and may not respond to general treatment. Some patients with RDD involving the extranodal system can have serious symptoms such as vital organ dysfunction due to mass effects, neurological symptoms caused by intracranial involvement, and respiratory distress with airway involvement. We report the case of a 7-year-old girl with severe dyspnea due to refractory extranodal RDD that caused progressive upper airway obstruction. She was admitted because of nasal congestion and persistent cervical lymphadenopathy, and diagnosed as having RDD by cervical lymph node incisional biopsy. The initial prednisone treatment did not improve her symptoms. The following contrast-enhanced neck computed tomography revealed a newly developed airway mass protruding in the upper trachea. After 8 weeks of chemotherapy with vinblastine, methotrexate, and prednisone, complete remission was attained. Seven months after chemotherapy cessation, the disease recurred, and chemotherapy with vincristine, cytarabine, and prednisone was resumed. Despite the chemotherapy and emergency radiotherapy, no improvement was observed in the cervical lymph node enlargement and airway obstructive symptom due to the upper tracheal mass. 2-Chlorodeoxyadenosine (cladribine) therapy was initiated, and the patient got complete remission after 6 cycles of the cladribine treatment and maintained no evidence of disease for 2 years. We suggest that cladribine is an effective treatment option for recurrent/refractory RDD.

To determine the relative frequency and change of malignant lymphoma in Korea according to the 4th World Health Organization (WHO) classification and compare with previous reports. Between 2015 and 2016, 7737 new patients with malignant lymphoma were enrolled from 31 institutes, with their clinicopathologic information obtained, and evaluated for the relative frequency of lymphoma subtypes. The relative frequency of non-Hodgkin lymphoma (NHL) was 94.8%, and that of Hodgkin lymphoma (HL) was 5.2%. B cell lymphomas accounted for 83.1% of all NHLs; T/natural killer (NK) cell lymphomas, 16.4%; and immunodeficiency-associated lymphoproliferative disorders, 0.5%. The most common NHL subtypes were diffuse large B cell (41.5%), extranodal marginal zone (MALT, 19.8%), follicular (7.5%), NK/ T cell (4.2%), and peripheral T cell lymphomas, not otherwise specific (PTCL, NOS, 3.4%). Nodular sclerosis was the predominant HL subtype (48.5%), followed by mixed cellularity (28.7%), lymphocyte-rich (6.8%), lymphocyte-depleted (1.5%), lymphocyte-predominant (2.8%), and unclassified HL (11.8%). Compared with a previous report, increased B cell lymphomas (77.6–83.1%) and slightly decreased NK/T cell lymphomas and PTCL were observed. The incidence of follicular lymphoma increased by more than 2.5-fold (2.9–7.5%). Incidence rates of newly diagnosed lymphomas were lower for HL and higher for extranodal NHL, MALT, and nasal type NK/T cell lymphomas in Korea than those in Western countries. A slight increase in the relative frequency of B cell lymphoma and a prominent increase in follicular lymphoma may be attributed to refined diagnostic criteria and Westernized disease patterns.

Background Pregnancy concurrent with, shortly before, or after breast cancer poses unique challenges because hormonal changes in pregnancy potentially interact with breast cancer outcomes. Materials and Methods We studied a cohort of 3,687 female patients of reproductive age ( Results Forty-five patients with postpartum breast cancer were significantly more likely to have advanced stage, hormone receptor-negative tumor and to be younger than 35 years at diagnosis than those without postpartum breast cancer. This trend was not observed with 18 patients with breast cancer during pregnancy. The unadjusted 5-year survival rates were 77% versus 96% for patients with postpartum breast cancer versus their counterparts, 89% versus 96% for patients with breast cancer during pregnancy versus their counterparts, and 98% versus 96% for patients with pregnancy after breast cancer versus their counterparts, respectively. In the multivariable analyses, postpartum breast cancer exhibited hazard ratios for death of 1.57 (95% confidence interval [CI], 0.82–2.99), whereas those for breast cancer during pregnancy and pregnancy after breast cancer were 1.09 (95% CI, 0.15–7.91) and 0.86 (95% CI, 0.26–2.83), respectively. Conclusion Postpartum breast cancer, but not breast cancer during pregnancy, was associated with advanced stage, younger age at diagnosis ( Implications for Practice Although pregnancy around the time of diagnosis of breast cancer is expected to become increasingly common with maternal age at first childbirth on the rise, data on the prognostic impact of pregnancy have been inconsistent and rare from Asian populations. In this investigation of a Korean patient cohort with breast cancer, pregnancy-associated breast cancer was associated with advanced stage, younger age at diagnosis (

Objectives Therapies that target programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Hypoxia-related genes are also important regulators of PD-L1, and the role of PD-L1 in NSCLC is still not clear. The objective of this study was to investigate PD-L1 expression and its correlation with hypoxic-inducible factor 1α (HIF1A), vascular endothelial growth factor A (VEGFA), glucose transporter 1 (GLUT1), and carbonic anhydrase 9 (CAIX) expression in NSCLC patients. The association between PD-L1 expression and survival was also determined. Materials and methods PD-L1/protein expression was evaluated in 295 resected NSCLCs and its correlation with HIF1A, VEGFA, GLUT1, CAIX expression and survival was determined based on immunohistochemical and RNA sequencing data obtained from The Cancer Genome Atlas (TCGA) database. Results PD-L1 protein expression was significantly correlated with HIF1A, VEGFA, GLUT1, and CAIX expression only in adenocarcinoma when a 10% or a 50% cut-off was used. PD-L1 mRNA expression was also significantly correlated with HIF1A, VEGFA, GLUT1, and CAIX expression in adenocarcinoma. Univariate analysis revealed that HIF1A expression was associated with poor recurrence-free survival (RFS), and GLUT1 was associated with poor overall survival (OS) and RFS. GLUT1 was an independent prognostic factor for OS in multivariate analysis of immunohistochemical and TCGA data (p = 0.024 and 0.029, respectively). Patients with low expression of both PD-L1 and GLUT1 had longer OS than other patterns in immunohistochemical and TCGA data (p = 0.003 and 0.051, respectively). Conclusions PD-L1 protein and mRNA expression were correlated with HIF1A, VEGFA, GLUT1, and CAIX expression in adenocarcinoma alone. Low expression of GLUT1 and low expression of both PD-L1 and GLUT1 were associated with improved prognosis. Our findings support the rationale for co-targeting hypoxia-related genes and PD-L1 in cancer therapy. Expression of hypoxia-related genes may be helpful in selecting patients appropriate for PD-L1 therapy.

Image area for multiple-color three-dimensional (3-D) off-axis interferometry is extremely restricted because of the Nyquist sampling rate, autocorrelation term, and twin cross-correlation term in the frequency domain for each wavelength. Furthermore, the image area is more restricted in dual-wavelength diffraction phase microscopy, which is an important tool for 3-D biological imaging with subnanometer sensitivity. The reason for this extra restriction is the use of only one pinhole for generating two uniform reference beams, which is not sufficient for imaging large areas. Here, we developed large field-of-view double-pinhole dual-wavelength diffraction phase microscopy as a novel approach to capture maximum possible information using two arbitrary wavelengths in the off-axis arrangement. The rules to optimize the two-dimensional sampling scheme without any crosstalk for two arbitrary wavelengths are theoretically presented. We demonstrate that the loss in the image area of the dual-wavelength holographic system designed with this approach is limited to 0–11% of the maximum possible image area using single-wavelength off-axis interferometry. Total amount of information is more than 170 times that of previously reported dual-wavelength diffraction phase microscopy employing single grating, single pinhole, and no sampling scheme optimization. Feasibility of the technique with sub-nanometer sensitivity is demonstrated by measuring optical thickness of polystyrene microspheres.

Nerve fibers play a critical role in the propagation of electrical impulses in the nervous system, and several studies have demonstrated their electrical and chemical properties. However, because of the lack of practical biophotonics techniques, most of the optical properties of these fibers are unknown. Herein, we propose and demonstrate a novel method of precisely measuring the dispersion of an individual nerve fiber in striatal neurons, using a single-shot label-free triple-wavelength diffraction phase interferometer and employing Cauchy coefficients of the refractive index. Compared with the current techniques of refractive index measurement, the proposed technique employs a common-path arrangement to achieve high temporal stability sensing of dispersion by a monochromatic detector. The dispersion spectra are obtained by reconstructing the triple-color wavefront of the specimen, extracting the thickness from the projected width of the fiber in the image, and then employing a Cauchy relation that is valid for the normal dispersions of transparent materials in the visible range. The feasibility of this technique was confirmed by analyzing the refractive indices of polystyrene microspheres. The technique was then applied to measure refractive index map and dispersion behavior of nerve fibers in medium spiny neurons with high temporal and spatial resolution.

Summary Background Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis. Methods We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul–Seongnam, South Korea). Patients, aged 20–80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460. Findings Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI −4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and −1·1% (−11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient. Interpretation Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis. Funding Ministry of Health and Welfare, South Korea.

Objectives: We investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on tuberculosis (TB) management in the Republic of Korea (ROK).Methods: This retrospective cross-sectional study used nationwide ROK TB notification data (98,346 cases) from 2017 to 2020. The median time from the onset of TB symptoms to treatment initiation and the compliance rates with the required timing for notification and individual case investigations were measured and compared across periods and regions affected by the COVID-19 epidemic.Results: TB diagnosis during the COVID-19 pandemic was delayed. The median time to TB treatment initiation (25 days) in 2020 increased by 3 days compared to that of the previous 3 years (22 days) (p

Recent studies identified germline mutations in HAVCR2 (encoding T-cell immunoglobulin mucin 3) as a genetic factor that predisposes to subcutaneous panniculitis-like T-cell lymphoma (SPTCL). However, the differences between HAVCR2-mutated (HAVCR2MUT) and HAVCR2 wild-type (HAVCR2WT) SPTCLs remain unclear. A nationwide cohort of 53 patients with SPTCL diagnosed at 8 Korean institutions was established. Whole-exome sequencing and RNA-sequencing were performed on 8 patients in the discovery set. In the validation set, targeted gene sequencing or direct sequencing of HAVCR2 was performed. Of 49 patients with available HAVCR2 status, 25 (51.0%) were HAVCR2Y82C. HAVCR2Y82C was associated with younger age (P = .001), development of hemophagocytic lymphohistiocytosis or hemophagocytic lymphohistiocytosis–like systemic illness (P < .001), and short relapse-free survival (RFS) (P = .023). Most mutated genes in SPTCLs were involved in immune responses, epigenetic modifications, and cell signaling. Mutations in UNC13D, PIAS3, and KMT2D were more frequent in HAVCR2WT SPTCLs. At the gene expression level, HAVCR2Y82C SPTCLs were enriched in genes involved in IL6-JAK-STAT3 signaling and in tumor necrosis factor-α signaling via NF-κB. CCR4 was significantly upregulated in HAVCR2WT SPTCLs both at the messenger RNA level and at the protein level. We established a risk stratification system for SPTCL by integrating clinical and histopathological features, including age and HAVCR2 mutation status. This risk stratification system was strongly associated with RFS (P = .031). In conclusion, the HAVCR2Y82C mutation was common in Korean patients with SPTCL and was associated with unique clinicopathological and genetic features. Combining clinicopathological parameters could aid in predicting prognosis for patients with SPTCL.

Background Previous studies have demonstrated the possibility of adverse effects of prolonged wearing of personal protective equipment in healthcare workers. However, there are a few studies about the effects on skin characteristics after wearing a mask for non‐healthcare workers. In this study, we evaluated the dermatologic effects of wearing a mask on the skin over time. Materials and Method Twenty‐one healthy men and women participated in the study. All participants wore masks for 6 hours consecutively. Three measurements were taken (a) before wearing the mask, (b) after wearing the mask for 1 hour, and (c) after wearing the mask for 6 hours. Skin temperature, skin redness, sebum secretion, skin hydration, trans‐epidermal water loss, and skin elasticity were measured. Results The skin temperature, redness, hydration, and sebum secretion were changed significantly after 1 and 6 hours of wearing a mask. Skin temperature, redness, and hydration showed significant differences between the mask‐wearing area and the non–mask‐wearing area. Conclusion Mask‐wearing conditions and time can change several skin characteristics. In particular, it is revealed that the perioral area could be most affected.

Phase unwrapping is one of the major challenges in multiple branches of science that extract three-dimensional information of objects from wrapped signals. In several applications, it is important to extract the unwrapped information with minimal signal resolution degradation. However, most of the denoising techniques for unwrapping are designed to operate on the entire phase map to remove a limited number of phase residues, and therefore they significantly degrade critical information contained in the image. In this paper, we present a novel, smart, and automatic filtering technique for locally minimizing the number of phase residues in noisy wrapped holograms, based on the phasor average filtering (PAF) of patches around each residue point. Both patch sizes and PAF filters are increased in an iterative algorithm to minimize the number of residues and locally restrict the artifacts caused by filtering to the pixels around the residue pixels. Then, the improved wrapped phase can be unwrapped using a simple phase unwrapping technique. The feasibility of our method is confirmed by filtering, unwrapping, and enhancing the quality of a noisy hologram of neurons; the intensity distribution of the spatial frequencies demonstrates a 40-fold improvement, with respect to previous techniques, in preserving the higher frequencies.

Despite the promising preclinical antitumor activity of MET-targeting therapies, most clinical trials have failed. We introduced a new concept of quantitation of stroma-induced hepatocyte growth factor (HGF) to assess the actual MET signalling activity in gastric cancer (GC). We treated serially diluted HGF and conditioned media (CM) from cancer-associated fibroblasts (CAFs) on low MET-expressing cancer cells and investigated the phenotypical and signalling changes. Stromal proportion and MET expression in GC samples were assessed, and gene set enrichment analysis (GSEA) from the public database was performed. The antitumor effect of anti-MET treatment was examined, especially when cancer cells were activated in a ligand-dependent manner. Relatively high doses of HGF or high-concentrated CM fully activated MET signalling cascades and promoted cell proliferation/invasion. High stromal proportion denoted worse patient survival in MET-positive GCs than in MET-negative ones. GSEA showed that the gene sets regarding proliferation, migration, and CAF as well as MET pathway signature were enriched in simultaneously MET- and HGF-positive samples. Sufficient ligand-dependent MET signalling activation increased the sensitivity to crizotinib. We conclude that patients whose tumours have a high stromal proportion and at least low MET expression may benefit more from MET-targeted therapies.

The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and ensuing computational problems. In Korea, the amount of genomic data has been increasing rapidly in the recent years. Leveraging these big data requires researchers to use large-scale computational resources and analysis pipelines. A promising solution for addressing this computational challenge is cloud computing, where CPUs, memory, storage, and programs are accessible in the form of virtual machines. Here, we present a cloud computing-based system, Bio-Express, that provides user-friendly, cost-effective analysis of massive genomic datasets. Bio-Express is loaded with predefined multi-omics data analysis pipelines, which are divided into genome, transcriptome, epigenome, and metagenome pipelines. Users can employ predefined pipelines or create a new pipeline for analyzing their own omics data. We also developed several web-based services for facilitating downstream analysis of genome data. Bio-Express web service is freely available at https://www.bioexpress.re.kr/.

Minimally invasive intraoperative imaging plays a crucial role in delicate microsurgeries for precise operation monitoring in which fiber optic imaging can be considered as an endoscopy and surgical proximity guidance tool due to its compactness. This paper presents a near-infrared time-domain reflectometric common-path optical coherence tomography imaging technique using a bare-fiber probe mounted directly on a scanning galvanometer. The common-path setup allows the use of a freely adjustable optical path length and a disposable fiber probe, as well as eliminating the need for an additional dedicated reference optical path. Experimental results demonstrate clear discrimination between the brain tumor tissue and the normal tissue for mouse brains with the images acquired in real-time over a wide area. The proposed method enables real-time and in situ visualization of tumor resection for intraoperative imaging, and this study demonstrates the feasibility of its application to microsurgical interventions.

OBJECTIVE Age-related changes in lip morphological and physiological characteristics are key indices for estimating age based on facial features, as reported in many studies. Yet, a majority of studies have focused on Caucasian individuals, with few studies characterizing these changes in Asian female populations. Therefore, the aim of this study was to investigate lip morphological and physiological characteristics in a cohort of Korean women. METHODS A total of 114 volunteers participated in the study. Linear distances (length of philtrum, length of lip, width of lip, and lengths of lower and upper oral commissures), angle of the upper lip, 3D lip heights, and wrinkles were calculated and averaged for each age-group. We also measured lip color, hydration, trans-epidermal water loss (TEWL), and blood flow. Statistical analyses were performed using SPSS version 20.0 (significance level P

Testing process in industrial profiling depends on the characterization of three-dimensional (3-D) objects with high sensitivity in spatial and temporal domains. Ordinary 3-D measurement instruments scan the image area in the temporal domain; therefore, these techniques experience low temporal stability especially for industrial and biomedical sensing. We propose a novel scan-free extended image instrument for sensing the area of 3-D microscopic objects using an interferometric technique with fixed optical parameters, such as resolution, and without mechanical movement. The technique could accelerate the control process in industrial fault detection and images of biological samples could be obtained in a shorter time. First, a stable system for doubling the image area is introduced. Second, the principles underlying the two-dimensional sampling scheme are introduced to record the maximum image area using a dual multiplexing technique at subsampling frequency. Moreover, a standard factor is presented as a figure of merit to determine the exact image area enhancement. Finally, the feasibility of this technique was demonstrated by sensing reflective and transparent objects with image area of up to 4.3-times that of a single-hologram recording using the square scheme. Furthermore, scan-free monitoring of the photolithography process was demonstrated in real-time. The standard deviation of thickness is 0.48 nm, which demonstrates the subnanometer temporal sensitivity of this technique.

Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate.The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes.The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS.The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.

The predictive significance of osteolysis-related proteins was evaluated in bortezomib-treated multiple myeloma. The clinicopathological characteristics were collected retrospectively. Immunohistochemistry was performed for analyzing receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), macrophage inflammatory protein 1 alpha (MIP1α), and dickkopf-1 (DKK1) expression. Among clinicopatholgical characteristics, osteolytic lesion was associated with higher response to bortezomib treatment (79% vs. 46%). High DKK1 expression was significantly correlated with osteolytic lesion (

Synchronous scanning of multiple objects is essential to health monitoring of cells with high reliability. In general, monitoring multiple objects with fixed optical resolution in a total area larger than the sensor size of the camera requires asynchronous scanning; therefore, the recorded images of different scanned areas are asynchronous. We have developed a novel single-shot triple field of view (FOV) interferometric technique that rectifies this asynchronous problem and the effect of high-frequency noise due to the motorized scanning components utilized to extend imaging area. The proposed technique is a novel setup, calibration, and correction algorithm that facilitates a wider 3-D imaging area and higher mechanical stability with fixed imaging parameters. In addition, objects are exposed to a low-power light source and images can be formed with lower intensity light, which is important for sensitive objects in practical applications. The technique separates the light exiting a microscope using four mirrors, which results in all beams having the same intensity and the recorded image possessing a higher fringe contrast than with techniques that use beam splitters. Furthermore, the arrangement it adopts, in which a pinhole is employed to produce a clear reference beam, makes it appropriate for complex industrial fabrication monitoring. A sub-Nyquist sampling scheme is also employed to facilitate recording of the maximum possible FOV for single-shot three holograms recording, and the phase retrieval process is modified to refocus the beam on different image planes. The feasibility of the proposed technique for monitoring multiple biological cells with different morphologies is demonstrated by using it to image human embryonic kidney 293 cells.

Epstein-Barr virus (EBV) is a significant contributor to the development of classical Hodgkin's lymphoma (cHL). Recent studies have documented associations between angiogenesis and EBV-associated malignancies. No study has yet examined the associations among, and prognostic implications of, EBV infection, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD) in cHL patients. Diagnostic tissues from 135 cHL patients treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) were retrospectively evaluated by in situ hybridization of EBV-encoded small RNA (EBER) and immunohistochemical staining for VEGF and CD31 (a measure of MVD). EBER and VEGF expression were positively correlated (P = 0.038). The mean MVD value of EBER-positive tumors was significantly higher than that of EBER-negative tumors (P = 0.034). The mean MVD of tumors positive for both EBER and VEGF was significantly higher than that of tumors negative for both markers (P = 0.008). EBER-positive patients had a lower 5-year overall survival (OS) rate than EBER-negative patients (P = 0.046). A high MVD was also associated with a poorer OS (P = 0.01); multivariate analysis showed that this was a significant and independent prognostic factor (P = 0.026). We found positive correlations between EBER and VEGF levels, and the MVD, indicating that EBV plays an important role in tumor angiogenesis. Targeting of both angiogenesis and EBV may be important when treating cHL patients who are EBER-positive and/or have a high MVD.

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

Background/Purpose: The skin protects against external factors and this skin function can be affected by environmental conditions, including low temperature, low humidity, and high altitude. Therefore, it is important to study the relationship between the environment and the skin. The purpose of this study is to determine how the skin barrier functions change at low temperatures. Methods: This study was performed at a Korean ski resort on January 2015 and evaluated 10 subjects skin condition during skiing. Skin properties were examined at 2 sites (cheeks and dorsal hands) and four time points (indoor; baseline, outdoor; after first skiing and after second skiing, indoor; after taking a shower). Results: The skin hydration on the cheek decreased after the second skiing session and the erythema decreased only after the first skiing while this value on dorsal hand was not changed by skiing. The brightness and yellowness of cheek skin increased and redness decreased therefore, skin color became pale during skiing. The extensibility of cheeks and dorsal hands decreased after skiing. We found positive correlation between skin temperature and redness (r2 = 0.707, p < 0.000). Also the skin properties changed according to ambient temperature. The cheek skin temperature, erythema, redness and extensibility increased when people moved from outdoor to indoor while skin brightness and yellowness decreased. The skin hydration on both cheeks and dorsal hands and the skin properties except skin temperature of dorsal hands didn’t change significantly. Conclusions: Low temperatures can affect human skin color so that the skin color becomes pale because capillary blood vessels shrink when skin is exposed to cold environment. The cheek skin tends to change easily than dorsal hand during ambient temperature change.

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×109/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.

Although virtual reality (VR) programs to provide firefighting training continue to be developed and adopted, our investigation with 15 firefighters indicates that a current VR training system tends to convey behavioral tips and does not sufficiently reflect actual firefighters’ needs and realities in the field. It often provides somewhat simplified fire simulations and actually lowers the effectiveness of the training. In this paper, we employ Human-Computer Interaction (HCI) methods to examine and identify core elements in firefighting scenarios and develop a VR system that incorporates such elements. We evaluate our system with respect to presence and three design components of the VR simulation (i.e., reality, meaning, play) through a user study with 22 participants. Our study results demonstrate greater user experience and perception toward the four elements in firefighting training with our VR system compared to the existing one. We discuss design implications (e.g., move control, degree of freedom, sight hindrance by smoke, unexpected events) of our study that are expected to help implement and provide an effective VR training system for firefighters.

Segmenting the retinal layers in optical coherence tomography (OCT) images helps to quantify the layer information in early diagnosis of retinal diseases, which are the main cause of permanent blindness. Thus, the segmentation process plays a critical role in preventing vision impairment. However, because there is a lack of practical automated techniques, expert ophthalmologists still have to manually segment the retinal layers. In this paper, we propose an automated segmentation method for OCT images based on a feature-learning regression network without human bias. The proposed deep neural network regression takes the intensity, gradient, and adaptive normalized intensity score (ANIS) of an image segment as features for learning, and then predicts the corresponding retinal boundary pixel. Reformulating the segmentation as a regression problem obviates the need for a huge dataset and reduces the complexity significantly, as shown in the analysis of computational complexity given here. In addition, assisted by ANIS, the method operates robustly on OCT images containing intensity variances, low-contrast regions, speckle noise, and blood vessels, yet remains accurate and time-efficient. In the evaluation of the method conducted using 114 images, the processing time was approximately 10.596 s per image for identifying eight boundaries, and the training phase for each boundary line took only 30 s. Further, the Dice similarity coefficient used for assessing accuracy gave a computed value of approximately 0.966. The absolute pixel distance of manual and automatic segmentation using the proposed scheme was 0.612, which is less than a one-pixel difference, on average.

In the analysis of sequential data, the detection of abrupt changes is important in predicting future changes. In this paper, we propose statistical hypothesis tests for detecting covariance structure changes in locally smooth time series modeled by Gaussian Processes (GPs). We provide theoretically justified thresholds for the tests, and use them to improve Bayesian Online Change Point Detection (BOCPD) by confirming statistically significant changes and non-changes. Our Confirmatory BOCPD (CBOCPD) algorithm finds multiple structural breaks in GPs even when hyperparameters are not tuned precisely. We also provide conditions under which CBOCPD provides the lower prediction error compared to BOCPD. Experimental results on synthetic and real-world datasets show that our new tests correctly detect changes in the covariance structure in GPs. The proposed algorithm also outperforms existing methods for the prediction of nonstationarity in terms of both regression error and log likelihood., Comment: IJCAI 2019 Comments: 12 pages, LaTeX; Revised conditions of Theorems in section 4, results unchanged

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disease manifesting with a persistent high-spiking fever, a typical rash, and lymphadenopathy. Endogenous factors related to interleukin-1, such as S100A8/A9 and several chemokines including CXCL10, CXCR3, and CXCL13, potentially play roles in its pathogenesis. We describe the histopathological features and chemokine expression pattern in lymph nodes (LNs) of patients with AOSD. Formalin-fixed, paraffin-embedded excisional LN tissues from 48 patients with AOSD were histologically reviewed. CXCL10, CXCR3, CXCL13, and S100A8/A9 expression was evaluated immunohistochemically. The pathology of LN was characterized by paracortical hyperplasia with proliferation of histiocyte, immunoblast, CD8-positive lymphoid cell and blood vessel. Most cases required differential diagnosis from dermatopathic lymphadenitis (n = 16, 33.3%), T cell lymphoma (n = 11, 22.9%), and histiocytic necrotizing lymphadenitis (HNL) (n = 9, 18.8%). The expression levels of CXCL10 and CXCR3 were higher in patients with AOSD than in those with T cell lymphoma, HNL, tuberculous lymphadenitis, and reactive hyperplasia. It is important to recognize the aforementioned histopathologic findings of nodal involvement of AOSD because improper diagnosis and treatment can be avoided. Immunohistochemical staining for chemokines, CXCL10 and CXCR3, may aid in differentiating AOSD from other mimickers.

Objective.Release of neutrophil extracellular traps (NET) has been described as an effector mechanism of polymorphonuclear neutrophils in several inflammatory diseases. Thus, this study was performed to evaluate the role of NET in the pathogenesis of adult-onset Still disease (AOSD).Methods.We determined the serum levels of NET molecules and investigated their associations with clinical disease activities in patients with AOSD. Further, we analyzed the differences in the NETosis response in AOSD patients compared to healthy controls (HC). To explore the in vivo involvement of NET in AOSD, we performed immunohistochemical analysis of skin and lymph node (LN) biopsies for proteins related to NET in patients with active AOSD.Results.Serum levels of cell-free DNA, myeloperoxidase (MPO)-DNA complex, and α-defensin were significantly increased in patients with AOSD compared to HC. Serum levels of the NET molecules, cell-free DNA, MPO-DNA, and α-defensin were correlated with several disease activity markers for AOSD. In followup of patients with AOSD after treatment with corticosteroid, the levels of cell-free DNA and α-defensin decreased significantly. On immunohistochemistry, neutrophil elastase–positive and MPO-positive inflammatory cells were detected in skin and LN of patients with AOSD, and were expressed in fiber form in the lesions. The serum from patients with active AOSD induced NETosis in neutrophils from HC. NET molecules induced interleukin 1β production in monocytes, representing a novel mechanism in the pathogenesis of AOSD.Conclusion.The findings presented here suggest that NET may contribute to the inflammatory response and pathogenesis in AOSD.

Aberrant expression of CD5 has been reported in 5–10% of diffuse large B-cell lymphomas (DLBCLs). CD5+ DLBCL had been recognized as an aggressive immunophenotypic subgroup of DLBCL in the 2008 WHO classification of haematolymphoid neoplasm; however, it was eliminated from the list of subgroups of DLBCLs in the revised 2016 classification. Nevertheless, there is much controversy regarding the clinical significance of CD5 expression, and many researchers still assert that this subgroup exhibits an extremely unfavorable prognosis with frequent treatment failure. We retrospectively investigated 405 DLBCLs recruited from three university hospitals in Korea from 1997 to 2013. The clinical profile, immunophenotype, and chromosomal structural alterations of the BCL2 and MYC genes were compared according to CD5 expression. A total of 29 cases of de novo CD5+ DLBCL were identified out of 405 in our series (7.4%). Clinicopathologic correlation was performed in all 29 CD5+ DLBCLs and 166 CD5- DLBCLs which were eligible for full clinical review and further pathologic examination. Compared with CD5- counterparts, CD5+ DLBCLs showed female preponderance, frequent bone marrow involvement, higher lactate dehydrogenase level, advanced Ann Arbor stages and poorer prognosis (all p

In September 2011, the Korean Society of Hematology Lymphoma Working Party held a nationwide conference to establish a consensus for assessing bone marrow (BM) involvement in patients with lymphoma. At this conference, many clinicians, hematopathologists, and diagnostic hematologists discussed various topics for a uniform consensus in the evaluation process to determine whether the BM is involved. Now that the discussion has matured sufficiently to be published, we herein describe the consensus reached and limitations in current methods for assessing BM involvement in patients with lymphoma.

Natural killer (NK) cell-associated lymphoproliferative disorder includes NK/T cell lymphoma, nasal type and aggressive NK cell leukemia which exhibit poor outcomes. However, benign NK cell proliferative lesion has been recognized in the gastrointestinal tract under the name of NK-cell enteropathy or lymphomatoid gastropathy. We report a case of a similar CD56-positive NK-cell proliferative disorder involving the gallbladder and gastrointestinal tract in a 33-year-old woman who presented with chronic cholecystitis and underwent cholecystectomy. The gallbladder showed a few scattered polyps which were infiltrated by medium-sized atypical lymphoid cells with eosinophilic cytoplasmic granules. On immunohistochemistry, the lymphoid cells were positive for CD2, CD56, T-cell-restricted intracellular antigen-1, and granzyme B, but negative for CD3, CD4, CD5, CD8, CD20, CD30, CD34, CD68 and myeloperoxidase. In situ hybridization for Epstein–Barr virus-encoded RNA was negative and T-cell receptor gene rearrangement was polyclonal. The patient is under close observation for 36months without any evidence of lymphoma.

The commonly employed calibration methods for laboratory-made spectrometers have several disadvantages, including poor calibration when the number of characteristic spectral peaks is low. Therefore, we present a wavelength calibration method using relative k -space distribution with low coherence interferometer. The proposed method utilizes an interferogram with a perfect sinusoidal pattern in k -space for calibration. Zero-crossing detection extracts the k -space distribution of a spectrometer from the interferogram in the wavelength domain, and a calibration lamp provides information about absolute wavenumbers. To assign wavenumbers, wavelength-to- k -space conversion is required for the characteristic spectrum of the calibration lamp with the extracted k -space distribution. Then, the wavelength calibration is completed by inverse conversion of the k -space into wavelength domain. The calibration performance of the proposed method was demonstrated with two experimental conditions of four and eight characteristic spectral peaks. The proposed method elicited reliable calibration results in both cases, whereas the conventional method of third-order polynomial curve fitting failed to determine wavelengths in the case of four characteristic peaks. Moreover, for optical coherence tomography imaging, the proposed method could improve axial resolution due to higher suppression of sidelobes in point spread function than the conventional method. We believe that our findings can improve not only wavelength calibration accuracy but also resolution for optical coherence tomography.