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SMARCA4 (BRG1) is a core unit of the SWI/SNF complex, regulating gene transcription through chromatin remodeling. Germline SMARCA4 variants have been reported to be associated with various malignancies. Here, we report the first case of extraskeletal Ewing sarcoma in a young female patient with a germline pathogenic variant of SMARCA4 (c.3546 + 1G>A), diagnosed with next generation sequencing (NGS). This alteration was also identified in her familial lineage, including her sister who was previously diagnosed with small cell carcinoma of the ovary, hypercalcemic type, a malignancy highly associated with SMARCA4 mutations. Despite undergoing radical surgery and receiving systemic treatments including VeIP (vinblastine, ifosfamide, cisplatin), and VDC (vincristine, doxorubicin, cyclophosphamide) regimens, the patient succumbed to death due to disease progression. With the implementation of NGS, we anticipate that more cases with SMARCA4 mutations will be diagnosed in the future. Further research is necessary to unveil therapeutic targets associated for this oncogenic alteration. [ABSTRACT FROM AUTHOR]

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring. [ABSTRACT FROM AUTHOR]

Background The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years. Methods This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable. Results During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity<0.01). Conclusions In patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer. [ABSTRACT FROM AUTHOR]

Purpose: To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection. Methods: Data from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity. Results: The median follow-up was 28.9 months (range, 1.1-62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months' post-PBT (p=0.047) and was maintained until 13 months (p=0.028). Conclusion: Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is a rare condition characterized by abnormal bone mineralization. The manifestations of HPP vary from no symptoms to intrauterine fetal death; short stature is another indication of HPP. A 3 1/2-year-old boy presented with short stature, transient hypercalcemia, and mild gait disturbance without definite bony deformity. Laboratory examination revealed transient hypercalcemia, normal phosphorous and 25-hydroxy vitamin D levels, and mildly low alkaline phosphatase levels. A targeted next-generation sequencing panel associated with inborn errors of metabolism revealed a pathogenic heterozygous mutation in the ALPL gene, c.979T>C (p.Phe327Leu). When a child visits a hospital with short stature, decreased height velocity, and low alkaline phosphatase level, clinicians should consider the possibility of HPP even if definite skeletal dysplasia is not evident. [ABSTRACT FROM AUTHOR]

Metabolomics refers to the technology for the comprehensive analysis of metabolites and low-molecular-weight compounds in a biological system, such as cells or tissues. Metabolites play an important role in biological phenomena through their direct involvement in the regulation of physiological mechanisms, such as maintaining cell homeostasis or signal transmission through protein-protein interactions. The current review aims provide a framework for how the integrated analysis of metabolites, their functional actions and inherent biological information can be used to understand biological phenomena related to the regulation of metabolites and how this information can be applied to safety assessments of crops created using biotechnology. Advancement in technology and analytical instrumentation have led new ways to examine the convergence between biology and chemistry, which has yielded a deeper understanding of complex biological phenomena. Metabolomics can be utilized and applied to safety assessments of biotechnology products through a systematic approach using metabolite-level data processing algorithms, statistical techniques, and database development. The integration of metabolomics data with sequencing data is a key step towards improving additional phenotypical evidence to elucidate the degree of environmental affects for variants found in genome associated with metabolic processes. Moreover, information analysis technology such as big data, machine learning, and IT investment must be introduced to establish a system for data extraction, selection, and metabolomic data analysis for the interpretation of biological implications of biotechnology innovations. This review outlines the integrity of metabolomics assessments in determining the consequences of genetic engineering and biotechnology in plants. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the pathophysiology of recurrent benign paroxysmal positional vertigo (BPPV) in young patients using gene expression profiling combined with bioinformatics analysis. Methods: Total RNA was extracted from the whole blood of four young patients with recurrent BPPV and four controls. The differentially expressed genes (DEGs) between the groups were screened using amicroarray analysis based on the cutoff criteria of |log2 fold change| > 1 and an adjusted p-value of < 0.05. Functional enrichment analysis of DEGs was performed using Gene Ontology analysis, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of the Interacting Genes database. Results: A total of 39 DEGs were detected between the BPPV and control samples, comprising 33 upregulated DEGs and six downregulated DEGs in the BPPV group. Functional enrichment analysis indicated that the upregulated DEGs were significantly enriched in terms related to metabolic processes and the immune system. Two main pathways were extracted from the PPI network: one was associated with oxidative phosphorylation and stress and the other with the adaptive immune system and extracellular matrix degradation. Conclusion: The findings of our bioinformatics analysis indicated that oxidative stress or extracellular matrix degradation due to immune-mediated inflammatory responses may contribute to the development of recurrent BPPV in young patients. [ABSTRACT FROM AUTHOR]

This paper proposes a 6Gb/s receiver for 8K displays and beyond. In the proposed receiver, a novel channel coding with 1.96% overhead is presented to guarantee minimum run-length in the clock embedded interface. It can also reduce bandwidth for effective data transmission compared to 9b/10b coding that requires 11.11% overhead. Furthermore, we present an on-chip eye margin tester that can measure the internal timing margin of receiver with only 1% area overhead. The prototype ICs are implemented using 0.18-µm HVCMOS process and evaluated in an 8K 65-in. panel. [ABSTRACT FROM AUTHOR]

This article is a case report and literature review on familial hypobetalipoproteinemia (FHBL), a genetic disorder characterized by low levels of low-density lipoprotein (LDL) cholesterol or total apolipoprotein B (ApoB). The report presents a case of a Korean boy with a novel mutation in the APOB gene, who had low LDL cholesterol levels and nonalcoholic fatty liver disease (NAFLD). The patient did not exhibit specific symptoms associated with hypocholesterolemia and was managed with vitamin D supplementation, exercise, and a healthy diet. The article emphasizes the importance of monitoring known risk factors for NAFLD progression and considering further genetic testing. [Extracted from the article]

Object: To studymultimodal neuroimaging study including resting state functional MRI (rs-fMRI), anatomical connectivity and brain morphology in patients with bilateral vestibulopathy (BVP) and relationship with clinical correlation. Methods: Thirteen patients with BVP (7 women; mean age ± SD = 63.5 ± 14.7 years, 22-80 years) and eighteen age and gender-matched controls were compared rs-fMRI and anatomical MRI. Also, we analyzed the relationship betweenmultimodal neuroimaging and Dizziness Handicap Inventory score (DHI), Vestibular Disorders Activities of Daily Living Scale (VDRL), Geriatric Depression Scale (GDS) and Hospital Anxiety and Depression Scale (HADS). Results: Compared with controls, BVP patients showed decreased functional connectivity among the key nodes of the salience network, auditory (including vestibular) network, bilateral posterior parahippocampal gyri, bilateral paracingulate gyri, and right frontoparietal network, and the anatomical connectivity in the right cerebellum, corpus callosumtapetum, and left fornix. BVP patients showed decreased gray matter volume in the bilateral parahippocampal gyri, right precentral gyrus, anterior cingulate gyrus, and right middle temporal gyrus and increased gray matter volume in the right superior frontal gyrus compared with controls. Correlation analyses showed rs-fMRI and clinical variables showed no significant result. DHI correlated negatively with anatomical connectivity in the bilateral frontal parahippocampal cingulum, corpus callosum, right inferior fronto-occipital fasciculus, bilateral fornix, and gray matter volumes in the bilateral middle occipital gyri, right superior occipital gyrus, left angular gyrus, and right cuneus in BVP. VADL correlated negatively with Anatomical connectivity in the corpus callosum, bilateral fornix, bilateral cerebellum, bilateral superior and anterior thalamic radiation, right inferior fronto-occipital fasciculus, bilateral fronto-parietal cingulum, right dentatoruburothalamic tract and gray matter volumes in the right angular gyri, bilateral parahippocampal gyri, right middle temporal gyrus, right cuneus, bilateral inferior occipital gyri, left middle occipital gyrus, right superior frontal gyrus, left fusiform gyrus, bilateral caudate, left cerebellar crus, and bilateral calcarine gyri in BVP. Conclusions: This study identified reductions in the volume of the hippocampus and alterations in functional and anatomical connectivity that concurs with previously established characteristics of BVP. The degree of disability can be inferred from the change in the connectivity and volume between vestibular cortical areas and their network. [ABSTRACT FROM AUTHOR]

Purpose: Recent reports indicate that small for gestational age (SGA) could be a risk factor for delayed thyroid stimulating hormone (dTSH) elevation in preterm infants. The development of dTSH elevation in SGA late-preterm infants with a gestational age of 34–36 weeks has been investigated in only a few studies. Methods: In the present retrospective study, 70 SGA infants and 86 sex- and gestational age-matched controls who presented with normal results on initial thyroid function testing were included. Results: SGA infants had a significantly higher prevalence of dTSH elevation (15.7% vs. 3.5%, P=0.009) compared with appropriate-for-gestational age infants. In SGA infants, the mean age at the time of dTSH was 24 days. Development of dTSH was associated with SGA and medical treatment with dopamine or furosemide. After adjusting for confounding factors, multiple logistic regression analysis showed SGA was a significant risk factor for the development of dTSH elevation (odds ratio, 23.2; 95% confidence interval, 2.27–236.91; P=0.008). Conclusion: SGA infants may be at risk for dTSH and clinicians could consider a second thyroid screening test around the age of 1 month. [ABSTRACT FROM AUTHOR]

Introduction: Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings. Methods: In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional MRI data acquired in n = 2010 healthy participants. After training, maps that represent the probability of a voxel belonging to a particular RSN were generated for each participant, and then used to calculate mean and standard deviation (STD) probability maps, which are made publicly available. Further, we compared our results to previously published resting state and task-based functional mappings. Results: Our results indicate this method can be applied in individual subjects and is highly resistant to both noisy data and fewer RS-fMRI time points than are typically acquired. Further, our results show core regions within each network that exhibit high average probability and low STD. Discussion: The 3DCNN algorithm can generate individual RSN localization maps, which are necessary for clinical applications. The similarity between 3DCNN mapping results and task-based fMRI responses supports the association of specific functional tasks with RSNs. [ABSTRACT FROM AUTHOR]

Purpose: Nutrition support nurse is a member of a nutrition support team and is a health care professional who takes a significant part in all aspects of nutritional care. This study aims to investigate ways to improve the quality of tasks performed by nutrition support nurses through survey questionnaires in Korea. Methods: An online survey was conducted between October 12 and November 31, 2018. The questionnaire consists of 36 items categorized into 5 subscales: nutrition-focused support care, education and counseling, consultation and coordination, research and quality improvement, and leadership. The importance--performance analysis method was used to confirm the relationship between the importance and performance of nutrition support nurses' tasks. Results: A total of 101 nutrition support nurses participated in this survey. The importance (5.56±0.78) and performance (4.50±1.06) of nutrition support nurses' tasks showed a significant difference (t=11.27, P<0.001). Education, counseling/consultation, and participation in developing their processes and guidelines were identified as low-performance activities compared with their importance. Conclusion: To intervene nutrition support effectively, nutrition support nurses should have the qualification or competency through the education program based on their practice. Improved awareness of nutrition support nurses participating in research and quality improvement activity for role development is required. [ABSTRACT FROM AUTHOR]

Background: Interferon (IFN) consensus sequence binding protein (ICSBP) is a transcription factor induced by IFN-γ. We previously reported that ICSBP expression promotes osteosarcoma progression by enhancing transforming growth factor-β signaling. In cancer cells, programmed death-ligand 1 (PD-L1) contributes to immune escape and may also be involved in tumor progression. Because IFN-γ induces the expression of both ICSBP and PD-L1, we explored the association between ICSBP and PD-L1 expression in terms of osteosarcoma progression. Methods: Three osteosarcoma cell lines (Saos2, U2OS, and 143B) were employed. Gene expression was measured by qRT-PCR, and protein levels were assessed by immunoblotting. PD-L1 expression was evaluated in cells overexpressing ICSBP and in ICSBP knockdown cells. The effects of PD-L1 expression on cell growth were examined by MTS assays, Incucyte analysis, soft agar assays, and three-dimensional (3D) culture. Cell cycle and apoptosis were evaluated by FACS analysis of cells stained with propidium iodide (PI) and annexin V/PI, respectively. The antitumor effects of PD-L1 knockdown without or with doxorubicin treatment were evaluated in vivo in nude mice bearing ICSBP-overexpressing 143B cell xenograft. The clinical relevance of PD-L1 and ICSBP expression was evaluated immunohistochemically using a human osteosarcoma microarray and through analysis of publicly available data using Gene Expression Profiling Interactive Analysis2. Results: ICSBP overexpression upregulated PD-L1 expression in all three cell lines, whereas ICSBP knockdown decreased the PD-L1 expression. PD-L1 knockdown attenuated the cell growth and reduced colony-forming capacity in both soft agar assays and 3D culture. PD-L1 knockdown increased apoptosis and induced G2/M arrest, which was associated with decreased expression of survivin, cyclin-dependent kinase 4 (CDK4), cyclin E, and cyclin D1 expression and increased the expression of p27, phosphorylated Cdc2, and phosphorylated Wee1. PD-L1 knockdown decreased the growth of tumor xenografts and increased the doxorubicin sensitivity of ICSBPoverexpressing 143B cells both in vitro and in vivo. PD-L1 was expressed in human osteosarcoma tissues, and its expression was moderately correlated with that of ICSBP in osteosarcoma patients. Conclusion: ICSBP regulates PD-L1 expression in osteosarcoma cells, and PDL1 knockdown combined with doxorubicin treatment could represent a strategy for controlling osteosarcoma expressing ICSBP. [ABSTRACT FROM AUTHOR]

Rationale: It remains unclear whether non-cystic fibrosis bronchiectasis increases the risk of lung cancer, because smoking history was not considered in previous studies. Objectives: To evaluate whether participants with bronchiectasis have a higher risk of incident lung cancer than those without bronchiectasis with information on smoking status. Methods: This was a population-based cohort study of 3,858,422 individuals who participated in the 2009 National Health Screening Program. We evaluated the incidence of lung cancer in participants with bronchiectasis (n = 65,305) and those without bronchiectasis (n = 3,793,117). We followed the cohort up until the date of lung cancer diagnosis, date of death, or December 2018. Cox proportional hazard regression models were used to evaluate the relative risk of lung cancer between participants with bronchiectasis and those without bronchiectasis. Results: The incidence of lung cancer in participants with bronchiectasis was significantly higher than in those without bronchiectasis (2.1 vs. 0.7 per 1,000 person-years; P < 0.001), with an adjusted hazard ratio (aHR) of 1.22 (95% confidence interval [CI], 1.14-1.30) in the model adjusting for potential confounders and accounting for the competing risk of mortality. Regardless of smoking status, the risk of lung cancer was significantly higher in participants with bronchiectasis than in those without bronchiectasis (aHR, 1.28 [95% CI, 1.17-1.41] for never-smokers; aHR, 1.26 [95% CI, 1.10-1.44] for ever-smokers). Although bronchiectasis did not increase the risk of lung cancer among participants with chronic obstructive pulmonary disease (COPD), it significantly increased the risk of lung cancer in participants without COPD (aHR, 1.19 [95% CI, 1.09-1.31]). Conclusions: The presence of bronchiectasis was associated with a higher risk of lung cancer after considering the smoking status. [ABSTRACT FROM AUTHOR]

Background: In critically ill patients, the most common manifestation of brain dysfunction is delirium, which is independently associated with higher morbidity and mortality. While electrolyte imbalance is one of the precipitating factors, the impact of hypomagnesemia on the incidence of delirium remains unknown. Methods: We retrospectively analyzed patients admitted to the medical intensive care unit (ICU) of a tertiary referral center between January and June 2020. Patients with ICU stay ≥48 hours and aged 40-85 years were included. The primary outcome was cumulative incidence of delirium in the ICU. Patients were divided into two groups based on serum magnesium level at ICU admission. Multivariable Cox proportional hazards regression analysis was performed, and covariates were selected using the least absolute shrinkage and selection operator (LASSO) method. Results: A total of 109 patients included 43 (39.4%) women and had a median age of 69.0 years (interquartile range [IQR], 60.0-76.0 years). The median magnesium level was 1.7 mg/dl (IQR, 1.5-1.9 mg/dl), and the cumulative incidence of delirium was 32.1% (35 patients). Hypomagnesemia was independently associated with delirium (adjusted hazard ratio [aHR], 2.12; 95% confidence interval [CI], 1.03-4.38), along with prior use of immunosuppressants (aHR, 3.08; 95% CI, 1.46-6.48) or benzodiazepines (aHR, 4.02; 95% CI, 1.54-10.50), body mass index (aHR, 0.93; 95% CI, 0.84-1.02), and alcohol history (aHR, 1.68; 95% CI, 0.74-3.80). Conclusions: In critically ill adults, hypomagnesemia increases the risk of delirium by more than two-fold compared to patients with normal magnesium level. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the underlying pathogenesis of Meniere's disease (MD) using transcriptome analysis. Methods: Total RNA was extracted from the peripheral blood mononuclear cells of 39 patients with MD and 39 controls. Through microarray analysis for nine patients and controls, the differentially expressed genes (DEGs) of those two groups were screened based on cut-off criteria (|fold changes| > 2.0 and adjusted p-value < 0.05). The functional enrichment analysis of DEGs was performed using Gene Ontology (GO). Results: There were 996 DEGs identified in the MD group: 415 were upregulated and 581 were downregulated. A functional enrichment analysis indicated that the downregulated DEGs were significantly enriched in terms related to immune system processes. Among them, 17 genes were enriched in terms for the major histocompatibility complex (MHC) protein complex, and the relative messenger RNA (mRNA) levels of three markedly downregulated DEGs [fold changes < -5: human leukocyte antigen (HLA)-DMA, HLA-DRB1, and HLA-DPB1] were significantly decreased in another 30 patients with MD compared with normal controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). However, there were no correlations between the expression levels of these three genes and clinical data, such as age, onset age, time course, or hearing threshold. Conclusions: Our transcriptome analysis showed that the downregulated DEGs in MD were mainly associated with the immune system pathways including the MHC protein complex in MD. Remarkably, a breakdown in immunological tolerance mediated by MHC class II may contribute to the MD development, which has implications for targeted treatment. [ABSTRACT FROM AUTHOR]

Background/Aim: Dark tea, made by fermentation of tea leaves using microorganisms, is well known for its antiobesity effect; however, studies to identify this effect have not been sufficiently conducted. Herein, the anti-obesity effects of post-fermented dark tea were studied in high-fat diet mouse. Materials and Methods: Obesity was induced through a highfat diet in C57BL/6 mice, and then dark tea extract powder (DTP) was orally administered daily for 12 weeks to evaluate the body and organ weights. Changes in the biochemical markers of obesity were evaluated to study the mechanism of the anti-obesity effects of DTP. Results: When DTP was administered to obesity mice, the weight and food intake reduced, blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) decreased, whereas highdensity lipoprotein cholesterol (HDL-C) increased. Histopathology showed that steatosis and inflammation scores were reduced within the liver and adipocyte sizes were reduced within epididymal adipocyte. In addition, a significant decrease in blood insulin and hepatic TG and a significant increase in blood adiponectin were also confirmed. The results of western blot and qPCR in week 12, showed a significant decrease in the mRNA and protein levels of C/EBPα, and the mRNA levels of PPARγ in the liver. Conclusion: Dark tea extracts are thought to have an antiobesity effect by reducing the levels of the main transcription factors that promote adipocyte differentiation, such as C/EBPα, and PPARγ. Therefore, diet products using dark tea extracts could be developed. [ABSTRACT FROM AUTHOR]

As a population, middle-aged and older adults are not meeting national guidelines for exercise. The purpose of this study was to describe factors associated with exercise adherence in an 8-month program offered as part of a research study testing the effects of exercise on cognitive performance for persons with a family history of Alzheimer’s disease (AD). After completion of the program, participants provided open-ended responses indicating their reasons for adhering to the exercise program, and they completed the Motives for Physical Activities Measure-Revised. Results indicated that adherence was tied to an interest in contributing to our understanding of AD, the opportunity to join an exercise program, perceived exercise benefits, and social support. In addition, participants reported high levels of extrinsic (fitness-related) and intrinsic (interest/enjoyment) motivation. Other possible motivating factors which emerged from day-to-day observations in the program were identified. Findings suggest directions for exercise professionals with respect to exercise adherence. [ABSTRACT FROM AUTHOR]

Purpose No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults. Materials and Methods We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m² intravenously on day 1, irinotecan, 50 mg/m²/day intravenously on days 1-5, and temozolomide, 100 mg/m²/day orally on days 1-5. Results A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality. Conclusion The VIT regimen was effective and relatively safe in our cohort of sarcoma patients. [ABSTRACT FROM AUTHOR]

Rationale: Although a history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether a history of PTB affects lung cancer development in patients with COPD. Objectives: To investigate whether a history of PTB is associated with an increased risk of lung cancer development in a population with COPD. Methods: This cohort study included a nationwide representative sample of 13,165 Korean men and women with COPD, aged between 50 and 84 years. In addition, to assess whether the relationship between PTB and lung cancer risk differs between participants with and without COPD, a matched cohort without COPD was included. Participants were matched 1:3 for age, sex, smoking history, and PTB status based on the index health screening examination of corresponding participants with COPD. The two cohorts were followed up for 13 years (January 1, 2003, to December 31, 2015). PTB was diagnosed on the basis of the results of chest radiography, and incident lung cancer was identified from hospitalization and outpatient visit claims (International Classification of Diseases, Tenth Revision diagnosis code C33 or C34). Results: During 370,617 person-years (PY) of follow-up (median follow-up, 7.7 yr) in the COPD group, we observed 430 incident cases of lung cancer in participants without a history of PTB (incidence rate, 524 per 100,000 PY) and 148 cases in those with a history of PTB (incidence rate, 931 per 100,000 PY). Compared with participants without a PTB history, the fully adjusted subdistribution hazard ratio (95% confidence interval [CI]) for lung cancer in those with a history of PTB was 1.24 (1.03-1.50). The association of PTB history and lung cancer development was more evident in never-smokers with COPD. In contrast, among participants without COPD, the corresponding hazard ratio (95% CI) was 0.98 (0.78-1.22). There was no interaction among PTB, smoking status, and COPD. Conclusions: A history of PTB was associated with an increased risk of developing lung cancer among patients with COPD in our country with an intermediate tuberculosis burden. Patients with COPD with a history of PTB, particularly never-smokers, might benefit from periodic screening or assessment for lung cancer development. [ABSTRACT FROM AUTHOR]

This study verified the mediating effects of self-concept clarity and rejection sensitivity in the impact of adolescents' covert narcissism on social anxiety. The subjects of this study were 545 middle and high school students aged 15-19 in South Korea. The study analyzed collected data with the SPSS PROCESS macro (models 4 and 6). The results of this study are as follows: First, it was found that the self-concept clarity of adolescents weakened the effect of covert narcissism on social anxiety, and second, rejection sensitivity strengthened the effect between these two variables. Third, covert narcissism had a positive effect on social anxiety. In addition, the double mediating effect of self-concept clarity and rejection sensitivity were also shown to be significant in the relationship between covert narcissism and social anxiety. Based on the results of this study, we discussed what can be applied in counseling for adolescents with covert narcissistic tendencies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 37-year-old woman with persistent head and neck atopic dermatitis (AD) unresponsive to dupilumab, who showed significant improvement after switching to upadacitinib. It highlights the challenges and potential adverse effects associated with dupilumab, such as conjunctivitis and erythema, and demonstrates upadacitinib's efficacy as an alternative treatment.

Purpose Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non-small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification. Materials and Methods Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients' clinical outcome were retrospectively reviewed. Results A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123). Conclusion Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients. [ABSTRACT FROM AUTHOR]

Physical activity is predictive of better cognitive performance and lower risk of Alzheimer’s disease (AD). The apolipoprotein E gene (APOE) is a susceptibility gene for AD with the e4 allele being associated with a greater risk of AD. Cross-sectional and prospective research shows that physical activity is predictive of better cognitive performance for those at greater genetic risk for AD. However, the moderating role of APOE on the effects of a physical activity intervention on cognitive performance has not been examined. The purpose of this manuscript is to justify the need for such research and to describe the design, methods, and recruitment tactics used in the conductance of a study designed to provide insight as to the extent to which cognitive benefits resulting from an 8-month physical activity program are differentiated by APOE e4 status. The effectiveness of the recruitment strategies and the feasibility of recruiting APOE e4 carriers are discussed. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated. Methods: This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group. Results: Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity. Conclusion: Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods. [ABSTRACT FROM AUTHOR]

Subjective visual vertical (SVV) and subjective visual horizontal (SVH) tests can be used to evaluate the perception of verticality and horizontality, respectively, and can aid the diagnosis of otolith dysfunction in clinical practice. In this study, SVV and SVH screen version tests are implemented using virtual reality (VR) equipment; the proposed test method promotes a more immersive feeling for the subject while using a simple equipment configuration and possessing excellent mobility. To verify the performance of the proposed VR-based SVV and SVH tests, a reliable comparison was made between the traditional screen-based SVV and SVH tests and the proposed method, based on 30 healthy subjects. The average results of our experimental tests on the VR-based binocular SVV and SVH equipment were -0.15° ± 1.74 and 0.60° ± 1.18, respectively. The proposed VR-based method satisfies the normal tolerance for horizontal or vertical lines, i.e., a ±3° error, as defined in previous studies, and it can be used to replace existing test methods. [ABSTRACT FROM AUTHOR]

In Korean women, a westernized lifestyle is associated with an increased risk of breast cancer. Fertility preservation has become an increasingly important issue for women with breast cancer, in accordance with substantial improvements in survival rate after cancer treatment. The methods of controlled ovarian hyperstimulation (COH) for fertility preservation in breast cancer patients have been modified to include aromatase inhibitors to reduce the potential harm associated with increased estradiol levels. Random-start COH and dual ovarian stimulation are feasible options to reduce the total duration of fertility preservation treatment and to efficiently collect oocytes or embryos. Using a gonadotropin-releasing hormone agonist as a trigger may improve cycle outcomes in breast cancer patients undergoing COH for fertility preservation. In young breast cancer patients with BRCA mutations, especially BRCA1 mutations, the possibility of diminished ovarian reserve may be considered, although further studies are necessary. Herein, we review the current literature on the practical issues surrounding COH for fertility preservation in women with breast cancer. [ABSTRACT FROM AUTHOR]

Purpose Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. Materials and Methods In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. Results Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031). Conclusion Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: The world is currently facing the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The total number of cases of coronavirus disease 2019 (COVID-19) is rising daily and no vaccine has yet been approved. While the pathophysiology behind the virus is still being studied, many possible several risk factors using small sample sizes have been found. Material and methods: We conducted a pooled analysis using several databases such as Medline, Scopus, Wangfang, Web of Science, Research Square, medrxiv, and Google Scholar to identify studies reporting severe and non-severe groups of COVID-19 patients. The odds ratios as well as the 95% confidence intervals for hypertension, diabetes, and cerebrovascular disease leading to severe COVID-19 were calculated using R-software. Results: Fifty-three articles were used for our analysis and they involved 30,935 confirmed cases of COVID-19 from several countries across the world. The odds ratio for severe COVID-19 in hypertensive patients, diabetics, and patients with a history of cerebrovascular disease was 2.58 (95% confidence interval (CI): 2.16-3.08, from 53 studies), 2.17 (95% CI: 1.72-2.74, from 44 studies), and 2.63 (95% CI: 1.80-3.85, from 25 studies), respectively. Conclusions: Our analysis confirms that patients with hypertension, diabetes, or cerebrovascular disease are at a higher risk of a severe outcome of COVID-19. It is thus vital for physicians to identify the main risk factors for a severe outcome of this disease. [ABSTRACT FROM AUTHOR]

It has been more than a year since the new virus called severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. The disease it causes was named Coronavirus disease 2019 (COVID-19), and on 11 March 2020 it was declared a pandemic. As the virus continues to spread, the number of patients worldwide has already crossed the 100 million mark with more than 2 million deaths. We sought to provide an update on the progress made in identifying the virus, its pathophysiology, risk factors such as hypertension, diabetes, and smoking, as well as various methods of treatment. Our review also provided an overview of the different vaccines. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is not differentiated clinically from other respiratory infections, and intensive care units (ICUs) are vulnerable to in-hospital transmission due to interventions inducing respiratory aerosols. This study evaluated the effectiveness of universal SARS-CoV-2 screening in ICUs in terms of screened-out cases and reduction in anxiety of healthcare personnel (HCP). Materials and Methods: This prospective single-armed observational study was conducted in 2 ICUs of a single hospital. The number of patients diagnosed with SARS-CoV-2 infection by the screening program and healthcare workers in ICUs that visited the SARS-CoV-2 screening clinic or infection clinic were investigated. Results: During the 7-week study period, no positive screening case was reported among a total of 142 patients. Among 86 HCP in the ICUs, only 2 HCP sought medical consultation for SARS-CoV-2 infection during the initial 2 weeks. Conclusion: A universal screening program for SARS-CoV-2 infection in ICUs with the coordination of other countermeasures in the hospital was reasonably effective in preventing in-hospital transmission in a pandemic situation and making clinical practices and HCP stable. [ABSTRACT FROM AUTHOR]

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status. [ABSTRACT FROM AUTHOR]

Purpose: In 2018, the Act on Decisions on Life-Sustaining Treatment for Patients in Hospice and Palliative Care or at the End of Life was implemented and the scope of official recognition for terminally ill patients was expanded. The purpose of this study was to investigate the decisions made by patients with end-stage liver disease about their life-sustaining treatment in a clinical setting. Methods: The subjects of this study were patients with endstage liver disease hospitalized at a tertiary hospital in Seoul, Korea who wrote physician orders for life-sustaining treatment (POLST). Data collection was done using patients' electronic medical records, and a retrospective analysis of POLST was conducted. Results: Among 101 patients, 18.8% were female and 81.2% were male, and their mean age was 61.8 (±10.61) years. Sixty-three patients (62.4%) wrote their POLST by themselves. Three patients withdrew the POLST, of whom two did so for liver transplantation, and one did so for chemotherapy. Conclusion: This study shows that sufficient consideration of liver transplantation is needed for end-stage liver disease patients before making decisions on life-sustaining treatment. The self-determination of patients must be respected and effective guidelines are urgently needed. [ABSTRACT FROM AUTHOR]

Introduction Despite the significant disease burden of bronchiectasis in Korea, no large-scale, representative prospective cohort studies have been conducted to evaluate the clinical characteristics of Korean patients with bronchiectasis, indicating an urgent need for cohort studies on bronchiectasis. Methods and analysis The Korean Multicenter Bronchiectasis Audit and Research Collaboration (KMBARC) is a prospective, non-interventional observational cohort study on bronchiectasis in Korea. The inclusion criteria of this registry are as follows: (1) adult patients (aged 18 years) with or without respiratory symptoms (cough, chronic sputum and/or recurrent respiratory infection) and chest computed tomography revealing bronchiectasis affecting one or more lobes and (2) stable status at the time of registration: patients with bronchiectasis who were admitted for a respiratory aetiology can be enrolled at least 4 weeks after hospital discharge. The exclusion criteria are as follows: (1) bronchiectasis due to cystic fibrosis; (2) traction bronchiectasis associated with interstitial lung disease; (3) patients actively being treated for pneumonia, pulmonary tuberculosis or non-tuberculous mycobacterial infection; (4) patients who are unable or unwilling to provide informed consent; and (5) pregnant patients. Although the KMBARC questionnaires for baseline and annual follow-up data are similar to the European Multicentre Bronchiectasis Audit and Research Collaboration questionnaires, KMBARC has distinctive features such as use of Bronchiectasis Health Questionnaires, measurement with fatigue and depression scales, blood tests, use of consensus definition of exacerbations and information on emergency room or hospitalisation. We aim to recruit at least 1200 patients over the study period from more than 26 hospitals in South Korea. Patients will undergo a detailed baseline and yearly assessment for up to 5 years. The study objectives of the KMBARC registry are as follows: (1) uncovering the natural course of bronchiectasis; (2) aiding in establishing evidence-based bronchiectasis guidelines in Korea; and (3) encouraging and facilitating studies on bronchiectasis in Korea. Ethics and dissemination This study received necessary approval from the Institutional Review Boards of all participating institutions. The Asan Medical Center Institutional Review Board gave overall approval for the study. Results will be disseminated via peer-reviewed publications and conference presentations. Trial registration number KCT0003088. [ABSTRACT FROM AUTHOR]

The purpose of these practice guidelines is to offer and share strategies for preventing extravasation and measures for handling drugs known to cause tissue necrosis, which may occur even with the most skilled experts at intravenous (IV) injection. Herein, general knowledge about extravasation is first described, including its definition, incidence, risk factors, diagnosis, differential diagnosis, and extravasation injuries. Management of extravasation includes nursing intervention and thermal application. At the first sign of extravasation, nursing intervention with following steps is recommended: stop administration of IV fluids immediately, disconnect the IV tube from the cannula, aspirate any remaining drug from the cannula, administer drug-specific antidote, and notify the physician. Local thermal treatments are used to decrease the site reaction and absorption of the infiltrate. Local cooling (ice packs) aids in vasoconstriction, theoretically limiting the drug dispersion. Although clear benefit has not been demonstrated with thermal applications, it remains a standard supportive care. The recommended application schedule for both warm and cold applications is 15 to 20 minutes, every 4 hours, for 24 to 48 hours. For prevention of extravasation, health professionals should be familiar with the extravasation management standard guidelines. They should regularly check the extravasation kit, assess patients' sensory changes, tingling or burning, and always pay attention to patients' words. The medical team's continuous education on extravasation is essential. With the practical use of these guidelines, it is expected to reduce the occurrence rate of extravasation and contribute to patient care improvement. [ABSTRACT FROM AUTHOR]

A three-dimensional simulator was used to analyze the field-emission mechanism of a carbon nanotube (CNT) emitter layer as a surface electron emitter in a triode structure for field-emission display. An electrostatic image potential was added to the Fowler-Nordheim equation to improve the accuracy of the calculation, and then several important parameters affecting the field-emission characteristics were studied. We calculated the field enhancement factor (β) and emission factor (κ) of the CNT emitter layer using the experimentally obtained current-voltage (I-V) values and the extended Fowler-Nordheim equation by the least-squares-fitting method. By simulating 211 structures, we confirmed the existence of a shielding effect between the emitters and a penetration phenomenon of the anode voltage. [ABSTRACT FROM AUTHOR]