Unusual US Findings of Diffuse Large B-Cell Lymphoma of the Breast: A Case Report.

Lymphoma is an uncommon type of breast malignancy, with low prevalence. The ultrasonographic findings of breast lymphoma have been described as nonspecific. Breast lymphoma most commonly appears as a solitary hypoechoic mass on US, and usually shows hypervascularity on color Doppler US. Herein, we report an unusual case of breast lymphoma that presented as multiple bilateral hyperechoic nodules on US.

Risk factors for hyperglycemia in COVID-19 patients treated with remdesivir.

The primary objective of this study was to investigate the factors contributing to hyperglycemic adverse events (AEs) associated with the administration of remdesivir in hospitalized patients diagnosed with coronavirus disease 2019 (COVID-19). Furthermore, the study aimed to develop a risk score model employing various machine learning approaches. A total of 1262 patients were enrolled in this investigation. The relationship between covariates and hyperglycemic AEs was assessed through logistic regression analysis. Diverse machine learning algorithms were employed for the purpose of forecasting hyperglycemia-related complications. After adjusting for covariates, individuals with a body mass index ≥23 kg/m2 , those using proton pump inhibitors, cholinergic medications, or individuals with cardiovascular diseases exhibited approximately 2.41-, 2.73-, 2.65-, and 1.97-fold higher risks of experiencing hyperglycemic AEs (95% CI 1.271-4.577, 1.223-6.081, 1.168-5.989, and 1.119-3.472, respectively). Multivariate logistic regression, elastic net, and random forest models displayed area under the receiver operating characteristic curve values of 0.65, 0.66, and 0.60, respectively (95% CI 0.572-0.719, 0.640-0.671, and 0.583-0.611, respectively). This study comprehensively explored factors associated with hyperglycemic complications arising from remdesivir administration and, concurrently, leveraged a range of machine learning methodologies to construct a risk scoring model, thereby facilitating the tailoring of individualized remdesivir treatment regimens for patients with COVID-19.

Targeting SARM1 improves autophagic stress-induced axonal neuropathy.

ABBREVIATIONS: AAV: adeno-associated virus; ATF3: activating transcription factor 3; ATG7: autophagy related 7; AVIL: advillin; cADPR: cyclic ADP ribose; CALC: calcitonin/calcitonin-related polypeptide; CMT: Charcot-Marie-Tooth disease; cKO: conditional knockout; DEG: differentially expressed gene; DRG: dorsal root ganglion; FE-SEM: field emission scanning electron microscopy; IF: immunofluorescence; NCV: nerve conduction velocity; PVALB: parvalbumin; RAG: regeneration-associated gene; ROS: reactive oxygen species; SARM1: sterile alpha and HEAT/Armadillo motif containing 1; SYN1: synapsin I.

Machine Learning Approaches for Assessing Risk Factors of Adrenal Insufficiency in Patients Undergoing Immune Checkpoint Inhibitor Therapy.

Adrenal insufficiency is a rare, yet life-threatening immune-related adverse event of immune checkpoint inhibitors (ICIs). This study aimed to establish a risk scoring system for adrenal insufficiency in patients receiving anti-programmed cell death 1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) agents. Moreover, several machine learning methods were utilized to predict such complications. This study included 209 ICI-treated patients from July 2015 to February 2021, excluding those with prior adrenal insufficiency, previous steroid therapy, or incomplete data to ensure data integrity. Patients were continuously followed up at Gyeongsang National University Hospital, with morning blood samples taken for basal cortisol level measurements, facilitating a comprehensive analysis of their adrenal insufficiency risk. Using a chi-squared test and logistic regression model, we derived the odds ratio and adjusted odds ratio (AOR) through univariate and multivariable analyses. This study utilized machine learning algorithms, such as decision trees, random forests, support vector machines (SVM), and logistic regression to predict adrenal insufficiency in patients treated with ICIs. The performance of each algorithm was evaluated using metrics like accuracy, sensitivity, specificity, precision, and the area under the receiver operating characteristic curve (AUROC), ensuring rigorous assessment and reproducibility. A risk scoring system was developed from the multivariable and machine learning analyses. In a multivariable analysis, proton pump inhibitors (PPIs) (AOR 4.5), and α-blockers (AOR 6.0) were significant risk factors for adrenal insufficiency after adjusting for confounders. Among the machine learning models, logistic regression and elastic net showed good predictions, with AUROC values of 0.75 (0.61-0.90) and 0.76 (0.64-0.89), respectively. Based on multivariable and machine learning analyses, females (1 point), age ≥ 65 (1 point), PPIs (1 point), α-blockers (2 points), and antipsychotics (3 points) were integrated into the risk scoring system. From the logistic regression curve, patients with 0, 1, 2, 4, 5, and 6 points showed approximately 1.1%, 2.8%, 7.3%, 17.6%, 36.8%, 61.3%, and 81.2% risk for adrenal insufficiency, respectively. The application of our scoring system could prove beneficial in patient assessment and clinical decision-making while administering PD-1/PD-L1 inhibitors.

Identification of miR-143-3p as a diagnostic biomarker in gastric cancer.

BACKGROUND: Gastric cancer (GC) is among the most common types of gastrointestinal cancers and has a high incidence and mortality around the world. To suppress the progression of GC, it is essential to develop diagnostic markers. MicroRNAs regulate GC development, but a clearer insight into their role is needed before they can be applied as a molecular markers and targets. METHODS: In this study, we assessed the diagnostic value of differentially expressed microRNAs as potential diagnostic biomarkers for GC using data for 389 tissue samples from the Cancer Genome Atlas (TCGA) and 21 plasma samples from GC patients. RESULTS: The expression of hsa-miR-143-3p (also known as hsa-miR-143) was significantly downregulated in GC according to the TCGA data and plasma samples. The 228 potential target genes of hsa-miR-143-3p were analyzed using a bioinformatics tool for miRNA target prediction. The target genes correlated with extracellular matrix organization, the cytoplasm, and identical protein binding. Furthermore, the pathway enrichment analysis of target genes showed that they were involved in pathways in cancer, the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, and proteoglycans in cancer. The hub genes in the protein-protein interaction (PPI) network, were matrix metallopeptidase 2 (MMP2), CD44 molecule (CD44), and SMAD family member 3 (SMAD3). CONCLUSIONS: This study suggests that hsa-miR-143-3p may be used as a diagnostic marker for GC, contributing via the pathways involved in the development of GC.

Cancer Incidence in Korean Healthcare Workers in Hospitals.

OBJECTIVES: Healthcare workers in hospitals (HHCWs), a notably increasing workforce, face various occupational hazards. A high incidence of cancer among HHCWs has been observed; however, the cancer incidence status among HHCWs in South Korea is yet to be studied. This study aimed to assess cancer incidence among HHCWs in South Korea. METHODS: We constructed a retrospective cohort of HHCWs using National Health Insurance claims data, including cancer incidence status and vital status, from 2007 to 2015. Those who had worked in hospitals for at least three years were defined as HHCWs. Standardized incidence ratios (SIRs) for all cancer types and standardized mortality ratios were calculated. RESULTS: A total of 107,646 HHCWs were followed up, and the total follow-up duration was 905,503 person-years. Compared to the total workers, female HHCWs showed significantly higher SIR for all cancers (observed cases = 1480; SIR = 1.25; 95% confidence interval [CI] = 1.06-1.47). The incidence of breast cancer among female HHCWs was significantly higher compared to that among total workers (observed cases = 376; SIR = 1.21; 95% CI = 1.09-1.36). CONCLUSIONS: Our findings indicate that female HHCWs have an elevated probability of developing cancer, which suggests that occupational risk factors such as night-shift work, anti-neoplastic medications, stressful jobs, and ionizing radiation should be assessed. Further investigation and occupational environment improvement activities are required.

Association between SYVN1 and SEL1 genetic polymorphisms and remission in rheumatoid arthritis patients treated with TNF-α inhibitors: a machine learning approach.

Rheumatoid arthritis (RA) is a severe chronic inflammatory condition that affects joint synovium. Suppressor/enhancer of lin-12-like (SEL1L)-Synoviolin 1 (SYVN1)-mediated endoplasmic reticulum-associated degradation (ERAD) is highly associated with RA development. Although targeting SEL1L-SYVN1-mediated ERAD can be beneficial, studies that evaluate the association between polymorphisms in their genes and remission from the disease in RA patients taking tumor necrosis factor (TNF)-α inhibitors have yet to be carried out. Hence, the purpose of this study was to investigate the association between SYVN1 and SEL1L polymorphisms and TNF-α inhibitor response using various machine learning models. A total of 12 single-nucleotide polymorphisms (SNPs), including 5 SNPs in SYVN1 and 7 SNPs of SEL1L were investigated. Logistic regression analysis was used to examine the relationship between genetic polymorphisms and response to treatment. Various machine learning methods were employed to evaluate factors associated with remission in patients receiving TNF-α inhibitors. After adjusting for covariates, we found that sulfasalazine and rs2025214 in SEL1L increase the remission rates by approximately 3.3 and 2.8 times, respectively (95% confidence intervals 1.126-9.695 and 1.074-7.358, respectively). Machine learning approaches showed acceptable prediction estimates for remission in RA patients receiving TNF-α inhibitors, with the area under the receiver-operating curve (AUROC) values ranging from 0.60 to 0.65. A polymorphism of the SEL1L gene (rs2025214) and sulfasalazine were found to be associated with treatment response in RA patients receiving TNF-α inhibitors. These preliminary data could be used to tailor treatment for RA patients using TNF-α inhibitors.

Gemcitabine-cisplatin versus MVAC chemotherapy for urothelial carcinoma: a nationwide cohort study.

This study assessed the trends in methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine-cisplatin (GC) regimens in Korean patients with metastatic urothelial carcinoma (UC) and compared the side effects and overall survival (OS) rates of the two regimens using nationwide population-based data. The data of patients diagnosed with UC between 2004 and 2016 were collected using the National Health Insurance Service database. The overall treatment trends were assessed according to the chemotherapy regimens. The MVAC and GC groups were matched by propensity scores. Cox proportional hazard analysis and Kaplan-Meier analysis were performed to assess survival. Of 3108 patients with UC, 2,880 patients were treated with GC and 228 (7.3%) were treated with MVAC. The transfusion rate and volume were similar in both the groups, but the granulocyte colony-stimulating factor (G-CSF) usage rate and number were higher in the MVAC group than in the GC group. Both groups had similar OS. Multivariate analysis revealed that the chemotherapy regimen was not a significant factor for OS. Subgroup analysis revealed that a period of ≥ 3 months from diagnosis to systemic therapy enhanced the prognostic effects of the GC regimen. The GC regimen was widely used as the first-line chemotherapy in more than 90% of our study population with metastatic UC. The MVAC regimen showed similar OS to the GC regimen but needed greater use of G-CSF. The GC regimen could be a suitable treatment option for metastatic UC after ≥ 3 months from diagnosis.

Calumenin, a Ca2+ Binding Protein, Is Required for Dauer Formation in Caenorhabditis elegans.

Caenorhabditis elegans can adapt and survive in dynamically changing environments by the smart and delicate switching of molecular plasticity. C. elegans dauer diapause is a form of phenotypic and developmental plasticity that induces reversible developmental arrest upon environmental cues. An ER (endoplasmic reticulum)-resident Ca2+ binding protein, calumenin has been reported to function in a variety of malignant diseases in vertebrates and in the process of muscle contraction-relaxation. In C. elegans, CALU-1 is known to function in Ca2+-regulated behaviors (pharyngeal pumping and defecation) and cuticle formation. The cuticles of dauer larvae are morphologically distinct from those of larvae that develop in favorable conditions. The structure of the dauer cuticle is thicker and more highly reinforced than that of other larval stages to protect dauer larvae from various environmental insults. Since the calu-1(tm1783) mutant exhibited abnormal cuticle structures such as highly deformed annuli and alae, we investigated whether CALU-1 is involved in dauer formation or not. Ascaroside pheromone (ascr#2) and crude daumone were used under starvation conditions to analyze the rate of dauer formation in the calu-1(tm1783) mutant. Surprisingly, the dauer ratio of the calu-1(tm1783) mutant was extremely low compared to that of the wild type. In fact, the calu-1(tm1783) mutants were mostly unable to enter diapause. We also found that calu-1 is expressed in body-wall muscle and AIA interneurons at the dauer stage. Taken together, our results suggest that CALU-1 is required for normal entry into diapause in C. elegans.

Incidence of Retinal Artery Occlusion and Related Mortality in Korea, 2005 to 2018.

Importance: It remains unclear whether comorbidities in patients with retinal artery occlusion (RAO), a rare retinal vascular disorder, differ by subtype and whether mortality is higher. Objective: To examine the nationwide incidence of clinically diagnosed, nonarteritic RAO, causes of death, and mortality rate in patients with RAO compared with that in the general population in Korea. Design, Setting, and Participants: This retrospective, population-based cohort study examined National Health Insurance Service claims data from 2002 to 2018. The population of South Korea was 49 705 663, according to the 2015 census. Data were analyzed from February 9, 2021, to July 30, 2022. Main Outcomes and Measures: The nationwide incidence of any RAO, including central RAO (CRAO; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code, H34.1) and noncentral RAO (other RAO; ICD-10 code, H34.2) was estimated using National Health Insurance Service claims data from 2002 to 2018, with 2002 to 2004 as the washout period. Furthermore, the causes of death were evaluated and the standardized mortality ratio was estimated. The primary outcomes were the incidence of RAO per 100 000 person-years and the standardized mortality ratio (SMR). Results: A total of 51 326 patients with RAO were identified (28 857 [56.2%] men; mean [SD] age at index date: 63.6 [14.1] years). The nationwide incidence of any RAO was 7.38 (95% CI, 7.32-7.44) per 100 000 person-years. The incidence rate of noncentral RAO was 5.12 (95% CI, 5.07-5.18), more than twice that of CRAO (2.25 [95% CI, 2.22-2.29]). Mortality was higher in patients with any RAO than in the general population (SMR, 7.33 [95% CI, 7.15-7.50]). The SMR for CRAO (9.95 [95% CI, 9.61-10.29]) and for noncentral RAO (5.97 [95% CI, 5.78-6.16]) showed a tendency toward a gradual decrease with increasing age. The top 3 causes of death in patients with RAO were diseases of the circulatory system (28.8%), neoplasms (25.1%), and diseases of the respiratory system (10.2%). Conclusions and Relevance: This cohort study found that the incidence rate of noncentral RAO was higher than that of CRAO, whereas SMR was higher for CRAO than noncentral RAO. Patients with RAO show higher mortality than the general population, with circulatory system disease as the leading cause of death. These findings suggest that it is necessary to investigate the risk of cardiovascular or cerebrovascular disease in patients newly diagnosed with RAO.

Temperature instability of a mutation at a multidomain junction in Na,K-ATPase isoform ATP1A3 (p.Arg756His) produces a fever-induced neurological syndrome.

ATP1A3 encodes the α3 isoform of Na,K-ATPase. In the brain, it is expressed only in neurons. Human ATP1A3 mutations produce a wide spectrum of phenotypes, but particular syndromes are associated with unique substitutions. For arginine 756, at the junction of membrane and cytoplasmic domains, mutations produce encephalopathy during febrile infections. Here we tested the pathogenicity of p.Arg756His (R756H) in isogenic mammalian cells. R756H protein had sufficient transport activity to support cells when endogenous ATP1A1 was inhibited. It had half the turnover rate of wildtype, reduced affinity for Na+, and increased affinity for K+. There was modest endoplasmic reticulum retention during biosynthesis at 37 °C but little benefit from the folding drug phenylbutyrate (4-PBA), suggesting a tolerated level of misfolding. When cells were incubated at just 39 °C, however, α3 protein level dropped without loss of ß subunit, paralleled by an increase of endogenous α1. Elevated temperature resulted in internalization of α3 from the surface along with some ß subunit, accompanied by cytoplasmic redistribution of a marker of lysosomes and endosomes, lysosomal-associated membrane protein 1. After return to 37 °C, α3 protein levels recovered with cycloheximide-sensitive new protein synthesis. Heating in vitro showed activity loss at a rate 20- to 30-fold faster than wildtype, indicating a temperature-dependent destabilization of protein structure. Arg756 appears to confer thermal resistance as an anchor, forming hydrogen bonds among four linearly distant parts of the Na,K-ATPase structure. Taken together, our observations are consistent with fever-induced symptoms in patients.

Protective Effects of Fermented Houttuynia cordata Against UVA and H2O2-Induced Oxidative Stress in Human Skin Keratinocytes.

The biological activities of Houttuynia cordata (H. cordata) fermented with Aureobasidium pullulans (A. pullulans) was investigated for human skin keratinocyte-induced chemical and photo oxidations. In this research, H2O2/UVA-induced HaCaT cell lines were treated with H. cordata water/ethanol extracts (HCW/HCE) and fermented with A. pullulans water/ethanol extracts (HCFW/HCFE). A. pullulans fermented with H. cordata (HCFW) increased in 5.4-folds of total polyphenol (HCFW 46.89 mg GAE/extract g), and 2.3-folds in flavonoids (HCFW 53.80 mg GAE/extract g) compared with water extracts of H. cordata (HCW). Further, no significant cytotoxicity for HaCaT cells showed by all the extracts of H. cordata fermented with A. pullulans. HCFW extracts have significantly lowered inflammation factors such as COX-2 and Hsp70 proteins in oxidative stressed HaCaT cells induced by H2O2 and UVA treatments. All H. cordata extracts significantly downregulated gene expression involved in oxidative stress and inflammation factors, including IL-1ß, IL-6, COX-2, TNF-α, NF-κB, and MMP-1 in the H2O2/UVA-treated HaCaT cells. However, keratin-1 gene expression in the UVA-treated HaCaT cells was increased in twofolds by HCFW extracts. Further, A. pullulans fermented H. cordata extracts (HCFW/HCFE) reduced the genes involved in oxidative stresses more effectively than those of H. cordata extract only. Overall, the polyphenol-rich extracts of H. cordata fermented with A. pullulans showed synergistic protective effects for human epidermal keratinocytes to prevent photoaging and intrinsic aging by anti-oxidation and anti-inflammatory functions.

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03).

PURPOSE: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient's body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. RESULTS: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2-positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). CONCLUSION: This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Predictors for short-term and long-term automatic PAP compliance.

STUDY OBJECTIVES: Positive airway pressure (PAP) is considered a standard treatment for obstructive sleep apnea (OSA), but there are compliance issues. As compliance to PAP tends to decrease with time, it is necessary to consider reasons affecting compliance at each period. Therefore, this study aimed to define factors affecting short-term and long-term compliance to PAP therapy. METHODS: One hundred eighty-seven patients with OSA who started PAP treatment between July 2018 to March 2020 were included. Acceptance and compliance rates were monitored. Demographics, polysomnography (PSG) profiles, cephalometric data, and physical examination results were analyzed to identify factors predictive of PAP compliance at short-term (3 months) and long-term (12 months) periods. RESULTS: The acceptance rate of PAP was 92.5%. Compliance at 3 months and 12 months was 79.1% and 51.3%, respectively. Higher apnea-hypopnea index (odds ratio [OR] 1.018, P = .049) and older age (OR 1.032, P = .039) were predictive factors of good automatic PAP (APAP) compliance at 3 months. However, long-term compliance was affected by the percentage of duration with O2 desaturation of < 90% (CT90; OR 1.032, P = .011) and baseline self-reported symptom scores such as nasal obstruction (OR 0.819, P = .038) and awakening (OR 0.796, P = .045). CONCLUSIONS: In PAP use, indicators of OSA severity such as apnea-hypopnea index affect short-term compliance. On the other hand, the mandibular plane to hyoid distance and self-reported symptoms such as nasal obstruction and awakening can affect long-term compliance. CITATION: Park SI, Kim BK, Lee KE, Hong SD, Jung YG, Kim HY. Predictors for short-term and long-term automatic PAP compliance. J Clin Sleep Med. 2023;19(1):17-26.

Analysis of HR-HPV Infection Concordance Rates in Cervical and Urine Specimens; Proposal of Additional Cervical Screening Process for Women Who Refuse Invasive Cervical Sampling.

This study aimed to provide basic data for the clinical application of urine samples to prevent cervical cancer due to persistent HR-HPV infection in women who refuse invasive cervical sampling. Pairs of cervical swabs and urine samples were collected from 210 asymptomatic women who visited the obstetrics and gynecology department from August to December 2020, and a total of 420 samples were collected. Using the PANA RealTyper™ HPV Screening Kit as a real-time PCR method, paired cervical swabs and random urine samples were tested. A total of 19 samples (9.1%) were both HPV positive and 177 (84.3%) were both negative. The concordance between the two types of samples was 93.3%, with κ = 0.69 (moderate, 95% CI 0.54-0.84). The HPV infection rate by age was highest in both cervical swabs and urine samples in women in their 30s, followed by those in their 20s. Thus, the HPV infection rate was high in young women under 40 at 69.2% in cervical swabs and 61.8% in urine samples. Urine samples are considered a valuable screening test for women who refuse invasive Pap tests to prevent cervical cancer caused by persistent HPV infection.

Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: A nationwide cohort study.

PURPOSE: This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. MATERIALS AND METHODS: We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. RESULTS: Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49-1.40, p = 0.477). CONCLUSION: The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.

Respiratory Tract Cancer Incidences across Industry Groups: A Nationwide Cohort Study with More Than 70 Million Person-Years of Follow-Up.

The number of cases and incidence rates of laryngeal and lung cancers have been increasing globally. Therefore, identifying the occupational causes of such cancers is an important concern for policymakers to prevent cancers and deaths. We used national health insurance service claims data in Korea. We included 10,786,000 workers aged between 25 and 64 years. In total, 74,366,928 total person-years of follow-up were included in this study with a mean follow-up of 6.89 years for each person. The standardized incidence ratio (SIR) and 95% confidence intervals (CIs) referenced with the total workers were estimated. For laryngeal cancer, increased SIRs were observed in the land transportation industry among male workers (SIR [95% CI]: 1.65 [1.02-2.53]). For lung cancer, elevated SIRs were observed in the industries including animal production (1.72 [1.03-2.68]), fishing (1.70 [1.05-2.60]), mining (1.69 [1.22-2.27]), travel (1.41 [1.00-1.93]), and transportation (1.22 [1.15-1.30]) among male workers. For female works, healthcare (2.08 [1.04-3.72]) and wholesale (1.88 [1.18-2.85]) industries were associated with a high risk of lung cancer. As an increased risk of respiratory tract cancers has been identified in employees associated with certain industries, appropriate policy intervention is needed to prevent occupational cancers.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

Risk and Status of Gastrointestinal Cancer According to the International Standard Industrial Classification in Korean Workers.

To compare the risk of developing gastrointestinal (GI) cancer according to industrial groups, we performed a retrospective cohort study using the database of the Korea National Health Insurance Service (NHIS). We calculated the age-standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) for the types of GI cancers according to the Korean Standard Industrial Classification (KSIC) compared with the whole employee population. The highest SIR for all GI cancer was found in the "Mining and quarrying" section (SIR, 1.30; 95% CI, 1.14-1.47), followed by the "Transportation and storage" section (SIR, 1.27; 95% CI, 1.24-1.30). Miners and quarriers had the highest risk of developing gastric cancer (SIR, 1.29; 95% CI, 1.06-1.55) and cancer of the liver and intrahepatic bile ducts (SIR, 1.48; 95% CI, 1.17-1.86). Transportation workers had the highest SIR of cancer of the lip, oral cavity, and pharynx (SIR, 1.27; 95% CI, 1.13-1.43) and cancers of the rectum, anus, and anal canal (SIR, 1.27; 95% CI, 1.19-1.35). There were distinct GI cancers with an elevated risk in each industry group. Our findings imply that distinct cancer prevention programs should be developed for each industrial sector.

Discovering Breast Cancer Biomarkers Candidates through mRNA Expression Analysis Based on The Cancer Genome Atlas Database.

Background: Research on the discovery of tumor biomarkers based on big data analysis is actively being conducted. This study aimed to secure foundational data for identifying new biomarkers of breast cancer via breast cancer datasets in The Cancer Genome Atlas (TCGA). Methods: The mRNA profiles of 526 breast cancer and 60 adjacent non-cancerous breast tissues collected from TCGA datasets were analyzed via MultiExperiment Viewer and GraphPad Prism. Diagnostic performance was analyzed by identifying the pathological grades of the selected differentially expressed (DE) mRNAs and the expression patterns of molecular subtypes. Results: Via DE mRNA profile analysis, we selected 14 mRNAs with downregulated expression (HADH, CPN2, ADAM33, TDRD10, SNF1LK2, HBA2, KCNIP2, EPB42, PYGM, CEP68, ING3, EMCN, SYF2, and DTWD1) and six mRNAs with upregulated expression (ZNF8, TOMM40, EVPL, EPN3, AP1M2, and SPINT2) in breast cancer tissues compared to that in non-cancerous tissues (p < 0.001). Conclusions: In total, 20 DE mRNAs had an area under cover of 0.9 or higher, demonstrating excellent diagnostic performance in breast cancer. Therefore, the results of this study will provide foundational data for planning preliminary studies to identify new tumor biomarkers.