Background: The inflation-deflation (ID) method has long been the standard for intraoperative margin assessment in segmentectomy. However, with advancements in vision technology, the use of near-infrared mapping with indocyanine green (ICG) has become increasingly common. This study was conducted to compare the perioperative outcomes and resection margins achieved using these methods. Methods: This retrospective study included patients who underwent direct segmentectomy for clinical stage I lung cancer between January 2018 and September 2022. We compared perioperative factors, including bronchial and parenchymal resection margins, according to the margin assessment method and the type of segmentectomy performed.Since the ICG approach was adopted in April 2021, we also examined a recent subgroup of patients treated from then onward. Results: A total of 319 segmentectomies were performed. ID and ICG were utilized for 261 (81.8%) and 58 (18.2%) patients, respectively. Following April 2021, 61 patients (51.3%) were treated with ID, while 58 (48.7%) received ICG. We observed no significant difference in resection margins between ID and ICG for bronchial (2.7 cm vs. 2.3 cm, p=0.07) or parenchymal (2.5 cm vs. 2.3 cm, p=0.46) margins. Additionally, the length of hospitalization and the complication rate were comparable between groups. Analysis of the recent subgroup confirmed these findings, showing no significant differences in resection margins (bronchial: 2.6 cm vs. 2.3 cm, p=0.25; parenchymal: 2.4 cm vs. 2.3 cm, p=0.75), length of hospitalization, or complication rate. Conclusion The perioperative outcomes and resection margins achieved using ID and ICG were comparable, suggesting that both methods can safely guide segmentectomy procedures.

Background: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. Methods: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP). Results: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. Conclusion Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Many studies about Electrical muscle stimulation (EMS) have been performed to determine the effectiveness of EMS. However, most studies enrolled only elderly patients.Moreover, only a few studies have verified the effect of a whole body (WB)-EMS suit on young healthy women. Thus, the main purpose of this study was to verify the physiological effects of exercise training with a WB-EMS suit in young women. During the study periods, 24 young women were randomly assigned into two groups: 1) the WB-EMS training group, and 2) the control. All participants in the two groups performed the same low-intensity resistance exercise three times a week for 6 weeks at a training center. Group 1 used an electric current for WB-EMS suit which was switched on during the exercise period. Outcome measures were body composition, body circumference of hips and abdomen, isokinetic muscle function of knees, balance functions, Magnetic resonance imaging (MRI)s, cardiopulmonary functions, and lipid profiles. All outcomes were measured before and after the exercise protocol over 6 weeks. A total of 23 young women (group 1, n=11; group 2, n=12) completed a 6-week exercise regimen. After exercise, we compared the differences before and after the exercise program in each group. There were significant differences (p≤0.05) in body circumference, cardiopulmonary function in group 1 and 2. In particular, group 1 that activated WB-EMS showed significant differences in the isokinetic muscle function on knee flexors and balance functions. The results of this study show that exercise with a WB-EMS suit can be considered as an effective exercise addition for young women.

Incidental thyroid nodules are commonly detected on ultrasonography (US). This has contributed to the rapidly rising incidence of low-risk papillary thyroid carcinoma over the last 20 years. The appropriate diagnosis and management of these patients is based on the risk factors related to the patients as well as the thyroid nodules. The Korean Society of Thyroid Radiology (KSThR) published consensus recommendations for US-based management of thyroid nodules in 2011 and revised them in 2016. These guidelines have been used as the standard guidelines in Korea. However, recent advances in the diagnosis and management of thyroid nodules have necessitated the revision of the original recommendations. The task force of the KSThR has revised the Korean Thyroid Imaging Reporting and Data System and recommendations for US lexicon, biopsy criteria, US criteria of extrathyroidal extension, optimal thyroid computed tomography protocol, and US follow-up of thyroid nodules before and after biopsy. The biopsy criteria were revised to reduce unnecessary biopsies for benign nodules while maintaining an appropriate sensitivity for the detection of malignant tumors in small (1–2 cm) thyroid nodules. The goal of these recommendations is to provide the optimal scientific evidence and expert opinion consensus regarding US-based diagnosis and management of thyroid nodules.

Purpose: The discriminatory performance of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was investigated by correlating their values with chronological age (CA), bone age (BA), and pubertal status (PS) for diagnosis of isolated growth hormone deficiency (IGHD). Methods: We evaluated IGF-1 and IGFBP-3 levels in 310 short-stature subjects subdivided into 2 groups: IGHD (n=31) and non-IGHD (n=279). IGF-1 and IGFBP-3 were assayed using immune-radiometric assay and transformed into standard deviation score (SDS) according to CA, BA, and PS. Results: The highest sensitivity was found in IGF-1-SDS for CA and IGFBP-3-SDS for CA (22.6% and 30.0%, respectively). The highest specificity was found in IGF-1-SDS for PS and IGFBP-3-SDS for PS (98.2% and 94.4%, respectively). Groups with the highest positive predictive values were IGF-1-SDS for BA and IGFBP-3-SDS for BA (10.9% and 5.1%, respectively). Highest negative predictive values were seen in IGF-1-SDS for CA and IGFBP-3-SDS for CA (98.4% and 98.4%, respectively). Conclusion IGF-1-SDS for CA, instead of IGF-1-SDS for BA or PS, could be used as a standard variable for IGHD screening. The sufficiently high specificity of IGF-1-SDS for PS suggests that this value is a useful tool for identification of IGHD.

BACKGROUND: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized. METHODS: The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured. RESULTS: Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric. CONCLUSIONS: Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.
Adenosine Triphosphate ; Animals ; Asian Continental Ancestry Group ; Blotting, Western ; Carcinogenesis ; Colitis ; Colon ; Curcuma ; Curcumin ; Cyclin D1 ; Cyclooxygenase 2 ; Dextran Sulfate ; Dextrans ; DNA ; Drinking Water ; Herbal Medicine ; Humans ; Inflammatory Bowel Diseases ; Mice ; Nitric Oxide Synthase Type II ; Phosphorylation ; Phosphotransferases ; Plants ; Scutellaria baicalensis

OBJECTIVE: To assess the efficacy and safety of thyroid radiofrequency (RF) ablation for benign thyroid nodules by trained radiologists according to a unified protocol in a multi-center study. MATERIALS AND METHODS: From 2010 to 2011, 345 nodules from 345 patients (M:F = 43:302; mean age ± SD = 46.0 ± 12.7 years, range = 15–79) who met eligibility criteria were enrolled from five institutions. At pre-ablation, the mean volume was 14.2 ± 13.2 mL (1.1–80.8 mL). For 12 months or longer after treatment, 276 lesions, consisting of 248 solid and 28 predominantly cystic nodules, were followed. All operators performed RF ablation with a cool-tip RF system and two standard techniques (a transisthmic approach and the moving-shot technique). Volume reduction at 12 months after RF ablation (the primary outcome), therapeutic success, improvement of symptoms as well as of cosmetic problems, and complications were evaluated. Multiple linear regression analysis was applied to identify factors that were independently predictive of volume reduction. RESULTS: The mean volume reduction at 12 months was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n = 198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed significant improvements (p < 0.001). The rate of major complications was 1.0% (3/276). Solidity and applied energy were independent factors that predicted volume reduction. CONCLUSION: Radiofrequency ablation performed by trained radiologists from multiple institutions using a unified protocol and similar devices was effective and safe for treating benign thyroid nodules.
Catheter Ablation ; Follow-Up Studies ; Humans ; Linear Models ; Prospective Studies ; Thyroid Gland ; Thyroid Nodule ; Ultrasonography

PURPOSE: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenance of the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellular matrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airway obstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) induces MMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). MATERIALS AND METHODS: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins were detected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance (TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while the levels of tight junction proteins and phosphorylation were determined using Western blotting. RESULTS: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interfering RNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfection with ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. An extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. CONCLUSION: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulated and influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeutic strategies for airway diseases.
Airway Obstruction ; Asthma ; Blattellidae* ; Blotting, Western ; Cockroaches ; Collagenases ; DNA ; Electric Impedance ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells* ; Epithelium ; Extracellular Matrix ; Fluorescent Antibody Technique ; Humans* ; Matrix Metalloproteinase 1* ; Matrix Metalloproteinases ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; RNA, Small Interfering ; Tight Junction Proteins ; Tight Junctions* ; Transcription Factors ; Transfection

Non-muscle invasive bladder cancer (NMIBC) patients frequently fail to respond to treatment and experience disease progression because of their clinical and biological diversity. In this study, we identify a prognostic molecular signature for predicting the heterogeneity of NMIBC by using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profiles of 404 patients with bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. Of the 14 molecules with significant copy number alterations that were previously reported, 13 were significantly correlated with copy number and expression changes. Prognostic gene sets based on the 13 genes were developed, and their prognostic values were verified in three independent patient cohorts (n=501). Among them, a signature of CCNE1 and its coexpressed genes was significantly associated with disease progression and validated in the independent cohorts. The CCNE1 signature was an independent risk factor based on the result of a multivariate analysis (hazard ratio=6.849, 95% confidence interval=1.613–29.092, P=0.009). Finally, gene network and upstream regulator analyses revealed that NMIBC progression is potentially mediated by CCND1-CCNE1-SP1 pathways. The prognostic molecular signature defined by copy number and expression changes of CCNE1 suggests a novel diagnostic tool for predicting the likelihood of NMIBC progression.
Biodiversity ; Cohort Studies ; Computational Biology* ; Disease Progression ; Gene Expression ; Gene Regulatory Networks ; Genome ; Humans ; Multivariate Analysis ; Population Characteristics ; Risk Factors ; Transcriptome ; Urinary Bladder Neoplasms* ; Urinary Bladder*