Background: Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE). Methods: Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract.Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings. Results: Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10−6 , showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types. Conclusion Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations. We first performed a literature review of DP guidelines, recommendations, and position papers from major countries, as well as a review of relevant studies validating WSI. Based on that information, we prepared a draft. After several revisions, we released this draft to the public and the members of the Korean Society of Pathologists through our homepage and held an open forum for interested parties. Through that process, this final manuscript has been prepared. This recommendation contains an overview describing the background, objectives, scope of application, and basic terminology; guidelines and considerations for the hardware and software used in DP systems and the validation required for DP implementation; conclusions; and references and appendices, including literature on DP from major countries and WSI validation studies.

BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.
Cefotaxime ; Humans ; Immunization Programs ; Korea ; Levofloxacin ; Multiplex Polymerase Chain Reaction ; Penicillins ; Pneumococcal Vaccines ; Pneumonia ; Serogroup ; Streptococcus pneumoniae ; Streptococcus ; Vaccines

PURPOSE: The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. METHODS: An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. RESULTS: Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. CONCLUSION: Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.
Blotting, Western ; Breast Neoplasms ; Cell Death ; Cell Line ; DNA Nucleotidylexotransferase ; Drosophila ; Fluorescent Antibody Technique ; Glycoproteins ; Humans ; Immunoprecipitation ; In Vitro Techniques ; Interleukin-6 ; Interleukins ; Janus Kinase 2 ; Phosphorylation ; Phosphotransferases ; Polymerase Chain Reaction ; Receptors, Interleukin-6 ; Reverse Transcription ; STAT3 Transcription Factor ; Transducers ; Tyrosine

Steatocystoma multiplex is an uncommon benign skin disease, which typically manifests as numerous intradermal cysts that can be scattered anywhere on the body. Although usually asymptomatic, it can be significantly disfiguring. One type of steatocystoma multiplex is known to be associated with the autosomal dominant inheritance of a mutation in the gene coding for keratin 17 (KRT17). In such cases, it is often concurrent with other developmental abnormalities of the ectoderm-derived tissues, such as the nails, hair, and teeth. To the best of our knowledge, few cases have been reported of steatocystoma multiplex of the oral and maxillofacial region. This report describes a case of steatocystoma multiplex of both sides of the neck and multiple dental anomalies, with a focus on its clinical, radiological, and histopathological characteristics, as well as the possibility that the patient exhibited the familial type of this condition.
Clinical Coding ; Hair ; Humans ; Keratin-17 ; Neck ; Skin Diseases ; Steatocystoma Multiplex ; Tooth ; Wills

PURPOSE: Because primary hyperparathyroidism (PHPT) is difficult to recognize, it has a high likelihood of being underdiagnosed. In this study, we estimated the incidence of PHPT and evaluated PHPT diagnosis in Korea. METHODS: To calculate the prevalence of PHPT, we examined the medical records of patients that were hospitalized for urolithiasis between 2013 and 2016 at a single institute, and then identified those who were diagnosed with PHPT from the same group. A Korea-wide insurance claim database was used to ascertain the number of urolithiasis patients and the number of parathyroidectomies performed in Korea. The incidence of PHPT in the Korean population was estimated using the ratio of patients who presented with urolithiasis as the initial symptom of PHPT. RESULTS: During the 4-year study period, 4 patients from the 925 urolithiasis patients enrolled in this study (0.4%) were diagnosed with PHPT. During this same period, there were 85,267 patients with urolithiasis in Korea, and the estimated number of PHPT patients was 341, which was 0.4% of 85,267. Considering that 12% to 23% of patients with PHPT are initially diagnosed with urolithiasis, the total number of PHPT patients was estimated to range from 1,483 to 2,842. The number of patients who underwent parathyroidectomy due to PHPT was 1,935 during the study period. CONCLUSION: The number of patients we estimated to have PHPT corresponded closely with the number of patients undergoing parathyroidectomy during the study period. Considering the number of nonsymptomatic PHPT patients, PHPT may be properly diagnosed in Korea.
Diagnosis ; Humans ; Hyperparathyroidism, Primary* ; Incidence ; Insurance ; Korea* ; Medical Records* ; Parathyroidectomy ; Prevalence* ; Urolithiasis

In the above article, the financial grant has been erroneously omitted.

A 77-year-old female with a history of osteoarthritis visited our clinic complaining of lower back pain, paresthesia in both legs, and voiding difficulty. Her pain and temperature sensations were diminished below the L1 dermatome, and proprioception was decreased in both feet. The findings of a routine laboratory workup, echocardiogram, and cerebrospinal fluid studies were normal. Spine magnetic resonance imaging revealed high T2-weighted signal intensities and diffusion restriction in the posterior conus medullaris. The patient was diagnosed and treated for posterior spinal artery infarction.
Aged ; Arteries ; Cerebrospinal Fluid ; Conus Snail ; Diffusion ; Female ; Foot ; Humans ; Infarction ; Leg ; Low Back Pain ; Magnetic Resonance Imaging ; Osteoarthritis ; Paresthesia ; Proprioception ; Sensation ; Spinal Cord Compression ; Spinal Cord Ischemia ; Spinal Cord Vascular Diseases ; Spinal Cord ; Spine

PURPOSE: Recently, transoral endoscopic thyroidectomy (TOET) is receiving attention because it is regarded as a true minimally invasive surgery in that it does not leave scars on any part of the body and the area of flap dissection is similar to that of open surgery. In this study, we present the surgical procedures and initial outcomes of TOET in the treatment of papillary thyroid microcarcinoma (PTMC) patients. METHODS: The medical records of patients who underwent TOET for PTMC between July 2016 and February 2017 were retrospectively reviewed. Indication of TOET was PTMC without capsular invasion or lymph node metastasis on preoperative imaging studies. RESULTS: Ten female patients were enrolled. Seven patients underwent thyroid lobectomy and three patients underwent isthmusectomy. The mean age and tumor size was 43.3 ± 11.5 years and 0.6 ± 0.2 cm, respectively. Operation time for lobectomy and isthmusectomy was 121.1 ± 30.7 (range, 65–148) and 90.0 ± 9.2 minutes (range, 82–100 minutes), respectively. The mean number of retrieved lymph nodes was 2.7 ± 1.7. Two patients had transient vocal cord palsy, which recovered in three months. There was no case with subcutaneous emphysema, surgical site infection, postoperative bleeding, or mental nerve injury. CONCLUSION: TOET was feasible and could be performed safely for PTMC. TOET might become a new treatment option for the patients who do not want to leave visible scars on the body.
Cicatrix ; Female ; Hemorrhage ; Humans ; Lymph Nodes ; Medical Records ; Minimally Invasive Surgical Procedures ; Natural Orifice Endoscopic Surgery ; Neoplasm Metastasis ; Retrospective Studies ; Subcutaneous Emphysema ; Surgical Wound Infection ; Thyroid Gland* ; Thyroidectomy* ; Vocal Cord Paralysis

The diagnosis of hepatocellular carcinoma (HCC) is based on imaging studies particularly in high-risk patients without histologic confirmation. This study evaluated the prevalence and characteristics of false-positively diagnosed HCC in a liver resection cohort for HCC. A retrospective review was performed of 837 liver resection cases for clinically diagnosed HCC between 2005 and 2010 at our institute. High-risk patients with tumors > 1 cm with one or two image findings consistent with HCC and tumors < 1 cm with two or more image findings consistent with HCC with persistently increased serum alpha-fetoprotein (AFP) levels above the normal range with underlying inhibited hepatitis activity underwent liver resection. The false-positive rate was 2.2% (n = 18). Of the 18 patients, 7 patients (0.8%) were diagnosed with benign conditions (one each of hemangioma, inflammation, cortical adenoma, dysplastic nodule, angiomyolipoma, bile duct adenoma, and non-neoplastic liver parenchyme) and 11 patients (1.3%) were diagnosed with malignancies (cholangiocarcinoma [n = 6], hepatoblastoma [n = 2], and one each of lymphoepithelioma-like carcinoma, ovarian cystadenocarcinoma, and nasopharynx carcinoma metastasis). The clinical characteristics of pathologically diagnosed HCC patients were similar (P > 0.05) compared to non-HCC patients except for higher rate of history of alcoholism (P < 0.05) observed in non-HCC patients. Four of 18 non-HCC patients (22.2%) showed diagnostic discordance on the dynamic imaging study. Despite the recent progression in diagnostic imaging techniques, 2.2% of cases were false-positively diagnosed as HCC in a liver resection patient cohort; and the final diagnosis was benign disease in 0.8% of liver resection patients clinically diagnosed with HCC.
Adenoma ; Adenoma, Bile Duct ; Alcoholism ; alpha-Fetoproteins ; Angiomyolipoma ; Carcinoma, Hepatocellular* ; Cohort Studies ; Cystadenocarcinoma ; Diagnosis* ; Diagnostic Imaging ; Hemangioma ; Hepatitis ; Hepatoblastoma ; Humans ; Inflammation ; Liver* ; Nasopharynx ; Prevalence ; Reference Values ; Retrospective Studies