OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

Traditionally, diagnostic pathology uses histology representing structural alterations in a disease’s cells and tissues. In many cases, however, it is supplemented by other morphology-based methods such as immunohistochemistry and fluorescent in situ hybridization. Single-cell RNA sequencing (scRNA-seq) is one of the strategies that may help tackle the heterogeneous cells in a disease, but it does not usually provide histologic information. Spatial sequencing is designed to assign cell types, subtypes, or states according to the mRNA expression on a histological section by RNA sequencing. It can provide mRNA expressions not only of diseased cells, such as cancer cells but also of stromal cells, such as immune cells, fibroblasts, and vascular cells. In this review, we studied current methods of spatial transcriptome sequencing based on their technical backgrounds, tissue preparation, and analytic procedures. With the pathology examples, useful recommendations for pathologists who are just getting started to use spatial sequencing analysis in research are provided here. In addition, leveraging spatial sequencing by integration with scRNA-seq is reviewed. With the advantages of simultaneous histologic and single-cell information, spatial sequencing may give a molecular basis for pathological diagnosis, improve our understanding of diseases, and have potential clinical applications in prognostics and diagnostic pathology.

Purpose: The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients. Materials and Methods: Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients. Results: Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC. Conclusion Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

BACKGROUND: Several factors had been suggested to contribute to the development of hypertension in chronic glomerulonephritis (GN). This study was conducted to find the association of baseline blood pressure (BP) with pathophysiologic findings and later renal progression in chronic GN. METHODS: Clinico-pathological findings including serum creatinine (Cr), proteinuria, pathological findings, and urinary Na excretion were analyzed in a total of 233 patients with IgA nephropathy from The Kyung-Hee Cohort of GN. Glomerular surface area (GSA) was measured by imaging analysis and urine angiotensinogen (AGT) concentrations by human ELISA kits. RESULTS: Systolic BP was ≥130mmHg in 124 patients (53%). Systolic BP was negatively correlated with follow-up eGFR (r=−0.32, p<0.0001) and positively serum uric acid concentrations, while it had no significant relationships with initial serum Cr and eGFR. As compared with patients with systolic BP<130 mmHg, those with ≥130 mmHg were older and showed higher serum Cr, proteinuria, 24 hr urinary Na excretion, mean GSA, and T-I fibrosis, lower follow-up eGFR, and steeper decline in slope of eGFR. The results in patients with normal serum Cr concentrations were comparable to those in whole group. Systolic BP was positively correlated with age, baseline and follow-up proteinuria, serum uric acid concentrations and IgM deposit and negatively with follow-up eGFR. In subgroup analysis, systolic BP was also positively correlated with mean GSA and urinary AGT concentrations. CONCLUSION This study showed that baseline systolic BP is related to urinary Na excretion, glomerulomegaly, T-I fibrosis and later renal progression in patients with IgA nephropathy.

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (−)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (−) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (−) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (−) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (−) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (−) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (−)) SCCs. Our data indicate that HPV (+) and HPV (−) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (−) vulvar SCCs and may aid in the development of clinical treatment strategies.

Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy. In this study, we performed whole-exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7 frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS, the same variant initially identified in the tumor tissue was also detected with low variant allele frequency. This mutation was subsequently validated by digital polymerase chain reaction in liquid biopsy. Our result confirm that driver alterations identified in the tumor tissue were detected in liquid biopsy by targeted NGS as well, and suggest that a higher depth of sequencing coverage is needed for detection of genomic alterations in a liquid biopsy.
Biopsy ; Breast Neoplasms* ; Breast* ; DNA* ; Frameshift Mutation ; Gene Frequency ; Plasma* ; Polymerase Chain Reaction ; Population Characteristics

A 24-year-old male visited our hospital because of pain in both flanks. His biochemistry profile showed an elevated serum creatinine level and low serum uric acid level. History taking revealed that he had undertaken exercise prior to the acute kidney injury (AKI) event, and he stated that family members had a history of urolithiasis. His renal profile improved after hydration and supportive care during hospitalization. Although the patient was subsequently admitted again due to AKI, his status recovered with similar treatment. Since the diagnosis of the patient was familial renal hypouricemia with exercise-induced AKI, we performed genotyping of SLC22A12, which encodes human urate transporter 1. The diagnosis was confirmed by the detection of a homozygous mutation of W258X. We herein, report a case of familial renal hypouricemia confirmed by genotyping of SLC22A12, and review the relevant literature.
Acute Kidney Injury ; Biochemistry ; Creatinine ; Diagnosis ; Hospitalization ; Humans ; Male ; Uric Acid ; Urolithiasis ; Young Adult

BACKGROUND: In many countries, nephrologists follow clinical practice guidelines for mineral bone disorders to control secondary hyperparathyroidism (SHPT) associated with abnormal serum calcium (Ca) and phosphorus (P) levels in patients undergoing maintenance hemodialysis (MHD). The Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines have long been used in Korea, and this study was undertaken to investigate the current status of serum Ca and P control in MHD patients. METHODS: Data were collected from a total of 1,018 patients undergoing MHD without intercurrent illness, in 17 hemodialysis centers throughout the country. Serum levels of Ca, P, and intact parathyroid hormone (iPTH) were measured over 1 year, and the average values were retrospectively analyzed. RESULTS: Serum levels of Ca, P, and the CaxP product were 9.1+/-0.7mg/dL, 5.3+/-1.4mg/dL, and 48.0+/-13.6mg2/dL2, respectively. However, the percentages of patients with Ca, P, and Ca x P product levels within the KDOQI guideline ranges were 58.7%, 51.0%, and 70.7%, respectively. Of the 1,018 patients, 270 (26.5%) had iPTH >300pg/mL (uncontrolled SHPT), whereas 435 patients (42.7%) showed iPTH <150pg/mL. Patients with uncontrolled SHPT had significantly higher values of serum Ca, P, and CaxP product than those with iPTH < or =300pg/mL. CONCLUSION: Despite the current clinical practice guidelines, SHPT seems to be inadequately controlled in many MHD patients. Uncontrolled SHPT was associated with higher levels of serum Ca, P, and Ca x P product, suggestive of the importance of SHPT management.
Calcium* ; Humans ; Hyperparathyroidism, Secondary ; Kidney Diseases ; Korea ; Parathyroid Hormone ; Phosphorus* ; Renal Dialysis* ; Retrospective Studies

No abstract available.
Prostate ; Prostatic Neoplasms

No abstract available.
Frameshift Mutation ; Microsatellite Instability ; Microsatellite Repeats