Investigation of the putative role of antisense transcripts as regulators of sense transcripts by correlation analysis of sense-antisense pairs in colorectal cancers.

Antisense transcription occurs widely more expected than when it was first identified in bacteria in the 1980s. However, the functional relevance of antisense transcripts in transcription remains controversial. Here, we investigated the putative role of antisense transcripts in regulating their corresponding sense transcripts by analyzing changes in correlative relationships between sense-antisense pairs under tumor and normal conditions. A total of 3469 sense-antisense gene pairs (SAGPs) downloaded from BioMart mapped to a list of sense and antisense genes in RNA-seq data derived from 80 paired colorectal cancer (CRC) samples were analyzed. As a result, cancer-related genes were significantly enriched in the significantly correlated SAGPs (SCPs). Differentially expressed genes estimated between normal and tumor conditions were also significantly more enriched in SCPs than in non-SCPs. Interestingly, using differential correlation analysis, we found that tumor samples had a significantly larger density of genes with higher correlation coefficients than normal samples, as verified by various cancer transcriptomes from The Cancer Genome Atlas (TCGA). Moreover, we found that the magnitude of the correlation between SAGPs could distinguish poor prognostic CRCs from good prognostic CRCs, showing that correlation coefficients between the SAGPs of CRCs with a poor prognosis were significantly stronger than CRCs with a good prognosis. Consistent with this finding, the Cox proportion hazards model showed that the survival rates were significantly different between patients with high and low expression of genes in the SCPs. All these results strongly support the idea that antisense transcripts are important regulators of their corresponding sense transcripts.

Gamma-glutamyltransferase and the risk of head and neck cancer mortality.

BACKGROUND: The purpose of this study was to determine the association between baseline serum gamma-glutamyltransferase levels and the mortality risk of head and neck cancers. METHODS: A total of 481 414 Korean participants aged 40-79 years at enrollment were examined. The hazard ratios for head and neck cancer mortality were analyzed using Cox proportional hazards models, which were adjusted for potential confounding factors. RESULTS: In the overall study population, high gamma-glutamyltransferase levels were significantly associated with head and neck cancers mortality in a dose-response linear relation (p < 0.001). After excluding participants (n = 125) who died of head and neck cancers within five years of enrollment, the main results remained similar to those of the analysis of all 313 head and neck cancers deaths in the study population. CONCLUSION: These findings indicate that serum gamma-glutamyltransferase activity is positively associated with an increased mortality risk in head and neck cancers in a dose-dependent manner.

Prevalence and progression of combined pulmonary fibrosis and emphysema in asymptomatic smokers: A case-control study.

OBJECTIVES: We aimed to estimate the prevalence of combined pulmonary fibrosis and emphysema (CPFE) and describe the follow-up CT results of CPFE in asymptomatic smokers. METHODS: This study was retrospective, and approved by an institutional review board. CT images of 2,016 current or previous male smokers who underwent low-dose chest CT at our healthcare centre were reviewed. Quantitative CT analysis was used to assess the extent of emphysema, and two radiologists visually analyzed the extent of fibrosis. Changes in fibrosis (no change, improvement, or progression) were evaluated on follow-up CT imaging (n = 42). Kaplan-Meier survival analysis, multivariate logistic regression and its ROC curve were used for survival and progression analysis. RESULTS: The prevalence of CPFE among asymptomatic male smokers was 3.1 % (63/2,016). The median follow-up period was 50.4 months, and 72.7 % (16/22) of continued smoker had progressing fibrosis on follow-up CT. CPFE progressed more rapidly in continuous smokers than in former smokers (p = 0.002). The 3.5-year follow-up period after initial CPFE diagnosis maximized the sum of sensitivity and specificity of CPFE progression prediction in continuous smokers. CONCLUSIONS: The prevalence of CPFE turned out not to be inconsiderable in asymptomatic male smokers, but serial CT follow-up would be helpful in recognizing disease progression. KEY POINTS: • The prevalence of CPFE in asymptomatic smokers is 3.1 % (63/2,016). • Progression of CPFE is associated with smoking status. • 3.5 years of follow-up period would be needed to identify CPFE progression.

Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules.

BACKGRUOUND: We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules. METHODS: Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group). RESULTS: In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules. CONCLUSION: Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women.

BACKGROUND: To develop a breast cancer prediction model for Korean women using published polygenic risk scores (PRS) combined with nongenetic risk factors (NGRF). METHODS: Thirteen PRS models generated from single or multiple combinations of the Asian and European PRSs were evaluated among 20,434 Korean women. The AUC and increase in OR per SD were compared for each PRS. The PRSs with the highest predictive power were combined with NGRFs; then, an integrated prediction model was established using the Individualized Coherent Absolute Risk Estimation (iCARE) tool. The absolute breast cancer risk was stratified for 18,142 women with available follow-up data. RESULTS: PRS38_ASN+PRS190_EB, a combination of Asian and European PRSs, had the highest AUC (0.621) among PRSs, with an OR per SD increase of 1.45 (95% confidence interval: 1.31-1.61). Compared with the average risk group (35%-65%), women in the top 5% had a 2.5-fold higher risk of breast cancer. Incorporating NGRFs yielded a modest increase in the AUC of women ages >50 years. For PRS38_ASN+PRS190_EB+NGRF, the average absolute risk was 5.06%. The lifetime absolute risk at age 80 years for women in the top 5% was 9.93%, whereas that of women in the lowest 5% was 2.22%. Women at higher risks were more sensitive to NGRF incorporation. CONCLUSIONS: Combined Asian and European PRSs were predictive of breast cancer in Korean women. Our findings support the use of these models for personalized screening and prevention of breast cancer. IMPACT: Our study provides insights into genetic susceptibility and NGRFs for predicting breast cancer in Korean women.

A genome-wide association study of quantitative computed tomographic emphysema in Korean populations.

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10-8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10-6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10-6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

Risk factors of head and neck cancer mortality compared with those of all-cause and all-cancer mortalities.

This study aimed to clarify the risk factors of head and neck cancer (HNC) mortality, relative to those of all-cause and all-cancer mortalities, using the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data set. Data from 238 HNC deaths, 14,769 all-cancer deaths, and 38,086 all-cause deaths were extracted during a median follow-up period of 9.5 years. Baseline characteristics were assessed via chi-square tests, t tests, and multivariable logistic regression. HNC mortality was found to be positively associated with male sex, past and current smoking habits, moderate-to-heavy alcohol consumption, and being underweight. In addition, serum gamma-glutamyltransferase level was found to be significantly elevated in cases of HNC mortality. In contrast, obesity, a history of diabetes, and fasting blood glucose levels were found to be inversely associated with overall HNC mortality. Among the HNC subtypes, mortality due to laryngeal cancer was most strongly associated with past and heavy cigarette smoking, and mortality due to oro-/hypopharyngeal cancer was most strongly associated with heavy alcohol consumption. The present study demonstrates that this nationwide, population-based NHIS-HEALS data set can provide useful information for health research and policy development.

Epigenome-Wide Association Analysis of Differentially Methylated Signals in Blood Samples of Patients with Non-Small-Cell Lung Cancer.

Lung cancer is a common form of cancer and the leading cause of cancer-related deaths worldwide. Early diagnosis using noninvasive biomarkers may play an important role in increasing the survival rate of patients with lung cancer. Biomarkers of DNA methylation in blood samples may improve the early diagnosis of lung cancer. Here, we used peripheral blood samples obtained from 150 patients diagnosed with non-small-cell lung cancer (NSCLC) and 150 healthy controls. The latter were selected by frequency matching with the 150 patients with NSCLC, based on age, sex, and smoking status. Genome-wide methylation profiles were obtained using a MethylationEPIC BeadChip Kit, which covers the 850k bp cytosine-phosphate-guanine site. This analysis showed two significant differentially methylated changes (cg12169243 [DPH6] and cg25429010 [IMP3]) associated with NSCLC in current smokers, six changes (cg09245319, cg17183999 [USP7], cg06366994 [CPE], cg24992236 [MEG9], cg22144719, and cg22448179 [epidermal growth factor receptor]) associated with epidermal growth factor receptor mutation in patients with adenocarcinoma, and four changes (cg25021476 [RSL24D1], cg04989085 [FAM113B], cg20905681 [CKAP4], and cg26379694) associated with advanced-stage NSCLC compared with stage I NSCLC. The validation of these DNA methylation changes and further research on the related genes may help develop easily accessible biomarkers for the early diagnosis or prognosis of NSCLC.

Inhibitory effects of Angelicae Gigantis Radix on osteoclast formation.

Angelicae Gigantis Radix (AGR) is one of the most widely used herbal medications. AGR is the dried root of Angelica gigas Nakai (Umbelliferae), which is known as Korean angelica. This study investigated the effects of AGR on osteoclast formation using primary bone marrow cells. TNF-alpha treatment increased tartrate-resistant acid phosphatase (Trap) positive cells and Trap activity in bone marrow cells. However, AGR significantly decreased both TNF-alpha-induced Trap positive cells and Trap activity. RT-PCR analyses revealed that AGR decreased mRNA levels of Trap and matrix metalloproteinase-9 in TNF-alpha-treated bone marrow cells. In addition, AGR decreased TNF-alpha-induced activation of NF-kappaB. These results suggest that AGR has an inhibitory effect on the formation of osteoclasts and its effect is partially related to the NF-kappaB pathway.

Visually stratified CT honeycombing as a survival predictor in combined pulmonary fibrosis and emphysema.

OBJECTIVE: To determine whether visually stratified CT findings and pulmonary function variables are helpful in predicting mortality in patients with combined pulmonary fibrosis and emphysema (CPFE). METHODS: We retrospectively identified 113 patients with CPFE who underwent high-resolution CT between January 2004 and December 2009. The extent of emphysema and fibrosis on CT was visually assessed using a 6- or 5-point scale, respectively. Univariate and multivariate Cox proportional regression analyses were performed to determine the prognostic value of visually stratified CT findings and pulmonary function variables in patients with CPFE. Differences in 5-year survival rates in patients with CPFE according to the extent of honeycombing were calculated using Kaplan-Meier analysis. RESULTS: An increase in the extent of visually stratified honeycombing on CT [hazard ratio (HR), 1.95; p = 0.018; 95% confidence interval (CI), 1.12-3.39] and reduced diffusing capacity of lung for carbon monoxide (DLCO) (HR, 0.97; p = 0.017; 95% CI, 0.94-0.99) were independently associated with increased mortality. In patients with CPFE, the 5-year survival rate was 78.5% for <5% honeycombing, 55.7% for 5-25% honeycombing, 32% for 26-50% honeycombing and 33.3% for >50% honeycombing on CT. CONCLUSION: The >50% honeycombing on CT and reduced DLCO are important prognostic factors in CPFE. ADVANCES IN KNOWLEDGE: Visual estimation of honeycombing extent on CT can help in the prediction of prognosis in CPFE.

Metal selenides as a new class of electrocatalysts for quantum dot-sensitized solar cells: a tale of Cu(1.8)Se and PbSe.

The development of a Pt-free, highly active electrocatalyst for a counter electrode (CE) is vital to the construction of highly efficient quantum dot-sensitized solar cells (QDSSCs). As an alternative to Pt, the use of various metal sulfides, such as Cu2S, CoS, and PbS, has been successfully demonstrated; however, the studies on the utilization of non-sulfide materials have been scarcely reported. In this regard, we examined eight different types of binary metal selenides as new candidate materials, and found that the electrocatalytic activity of Cu1.8Se and PbSe toward polysulfide reduction was superior to that of Pt. In depth investigation into these two materials further revealed that, while the electrocatalytic activity of both metal selenides surpasses that of Pt, the long-term utilization of the PbSe CE is hindered by the formation of PbO on the surface of PbSe, which is attributed to the instability of PbSe under air. Unlike PbSe, Cu1.8Se was found to be chemically stable with a polysulfide electrolyte and was even better than Cu2S, a commonly used CE material for QDSSCs. Using the Cu1.8Se CE, we obtained a power conversion efficiency of 5.0% for CdS/CdSe-sensitized solar cells, which was an efficiency almost twice that obtained from Pt CE. This work provides a new application for metal selenides, which have been traditionally utilized as sensitizers for QDSSCs.

[A case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis caused by chronic hepatitis C].

Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.

Highly electrocatalytic Cu2ZnSn(S1-xSex)4 counter electrodes for quantum-dot-sensitized solar cells.

Traditional Pt counter electrode in quantum-dot-sensitized solar cells suffers from a low electrocatalytic activity and instability due to irreversible surface adsorption of sulfur species incurred while regenerating polysulfide (S(n)(2-)/S(2-)) electrolytes. To overcome such constraints, chemically synthesized Cu(2)ZnSn(S(1-x)Se(x))(4) nanocrystals were evaluated as an alternative to Pt. The resulting chalcogenides exhibited remarkable electrocatalytic activities for reduction of polysulfide (S(n)(2-)) to sulfide (S(2-)), which were dictated by the ratios of S/Se. In this study, a quantum dot sensitized solar cell constructed with Cu(2)ZnSn(S(0.5)Se(0.5))(4) as a counter electrode showed the highest energy conversion efficiency of 3.01%, which was even higher than that using Pt (1.24%). The compositional variations in between Cu(2)ZnSnS(4) (x = 0) and Cu(2)ZnSnSe(4) (x = 1) revealed that the solar cell performances were closely related to a difference in electrocatalytic activities for polysulfide reduction governed by the S/Se ratios.

Idiopathic retroperitoneal fibrosis associated with Hashimoto's thyroiditis in a patient with a single functioning kidney.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibroinflammatory tissue around the abdominal aorta and ureteral entrapment in most cases. Idiopathic RPF is frequently reported in association with autoimmune diseases; however, there have been few reports of idiopathic RPF associated with Hashimoto's thyroiditis. Here, we report a case of idiopathic RPF with Hashimoto's thyroiditis in a patient with a single functioning kidney, which was successfully treated by corticosteroid therapy and transient intraureteral stent insertion with a double-J catheter.