Background: Renal function declines with age as the kidneys become more vulnerable to inflammation and cellular senescence. This study examined gene expression changes linked to renal aging and assessed whether short-term calorie restriction (CR), a known anti-aging intervention, could reverse these alterations. Methods: Using RNA-seq data, we applied bioinformatics, systems biology, and molecular biology approaches to identify differentially expressed genes during aging and under CR. Gene Ontology and pathway analyses revealed that both aging and CR altered the expression of key senescence-associated secretory phenotype (SASP) genes, including cytokines and chemokines (Il1b, Ccl3, Ccl5, Il19, and Il24) and growth factors (Timp1 and Mmp12). Results: Renal aging is also associated with an increased expression of cell cycle arrest markers (p15INK4B (Cdkn2b), p16INK4A (Cdkn2a), and p21 (Cdkn1a)), which are suppressed by CR, suggesting a link to cellular senescence. Quantitative analysis of renal tissue samples confirmed the age-associated upregulation of these genes at the transcriptional level, and CR effectively attenuated these changes. Among these genes, we focused on the members of the interleukin 20 (IL-20) family, particularly Il19 and Il24. Furthermore, experimental induction of cellular senescence using H2O2 resulted in elevated Il19 and Il24 expression alongside other senescence markers. These findings suggest that aging and short-term CR regulate the IL-20 family expression, potentially influencing cellular senescence. Conclusion Our study suggests that Il19 and Il24 are associated with age-related renal decline and may represent hypothesis-generating candidates, highlighting potential molecular targets for future mechanistic and therapeutic investigations.

Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

Objectives: . Obstructive sleep apnea (OSA) is associated with chronic intermittent hypoxia and systemic inflammation, both of which contribute to vascular and metabolic complications. Monocytes, as key immune cells of innate immunity, have been implicated in this inflammatory state. However, the effect of OSA treatment on monocyte function and inflammatory phenotype remains poorly understood. Methods: . In this prospective cohort study, OSA patients were evaluated before and after 3 months of continuous positive airway pressure (CPAP) therapy. Circulating monocytes were isolated, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) was assessed at baseline and post-treatment, both at rest and after lipopolysaccharide (LPS) stimulation. Monocyte polarization (M1/M2-like marker expression) was measured by flow cytometry. Clinical severity parameters, including the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), were correlated with immune changes. Results: . Following CPAP treatment, LPS-induced inflammatory cytokine secretion and LPS responsiveness, defined as the increase in cytokine levels upon stimulation, both declined after CPAP in proportion to baseline ODI, but not AHI. Apart from TNF-α, baseline IL-1β and IL-6 levels were below the quantifiable range of the assay, which precluded reliable comparison after treatment. This effect may be explained by a parallel post-treatment shift in monocyte phenotype toward an anti-inflammatory M2-like (CD163+CD206+) profile, as demonstrated by our flow cytometry data, which was also significantly associated with baseline ODI. Conclusion . CPAP alleviates systemic inflammation in OSA by reducing hypoxic burden and reprogramming monocytes toward an anti-inflammatory phenotype. The magnitude of immune modulation was more closely linked to ODI than AHI, suggesting that oxygen desaturation burden serves as a meaningful adjunct to AHI in assessing monocyte-driven immune dysregulation in OSA.

Background/Aims: The absence of standardized clinical minimum inhibitory concentration (MIC) breakpoints for Helicobacter pylori infection has resulted in inconsistent resistance definitions, even within the same research group in Korea. Therefore, establishing epidemiological cutoff values (ECOFFs) is essential for standardization. Methods: The MIC distributions for antibiotics commonly used against H. pylori infection in South Korea were analyzed from 2015 to 2023. A total of 5,925 primary H. pylori isolates were collected from five data sources, and MIC values were determined using the serial 2-fold agar dilution method. The ECOFFinder program was used to establish ECOFFs for six antibiotics. Results: The tentative ECOFFs for amoxicillin and clarithromycin were 0.125 μg/mL. The ECOFFs for levofloxacin, metronidazole, and tetracycline were 0.5, 8.0, and 0.25 μg/mL, respec-tively. The ECOFF for rifabutin could not be determined due to insufficient data. On the basis of these ECOFFs, the resistance rate was 17.9% for amoxicillin, 31.9% for clarithromycin, 40.9% for levofloxacin, 24.7% for metronidazole, and 11.5% for tetracycline. Conclusions This comprehensive analysis defined regional antibiotic resistance patterns and established Korea-specific ECOFFs, providing a foundation for determining clinical breakpoints and optimizing H. pylori eradication strategies.

Background and Objectives: Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort. Methods: The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs). Results: Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective. Conclusions Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.

In forensic science, age estimation is essential for identifying both living and deceased individuals. Teeth and jawbones serve as reliable indicators due to their gradual age-related changes and resistance to environmental factors. Among the various methods, attrition and pulp cavity size are commonly used to estimate adult age. This study aimed to enhance the accuracy of age estimation in Korean adults by combining measurements of tooth attrition and pulp cavity size obtained from panoramic radiographs of mandibular first molars. We evaluated 118 patients (62 male, 56 female) who visited Pusan National University Dental Hospital between 2010 and 2024. Radiographs and clinical photographs were analyzed for grade C teeth with exposed dentin using Takei’s method, and the pulp chamber height ratio (PCHR) and width ratio (PCWR) were measured using Jeon’s method. Intraobserver reliability was high (intraclass correlation coefficient>0.6), with no significant sex-based differences in PCHR and PCWR. Both ratios negatively correlated with age, with PCWR showing a stronger correlation, particularly in females (r=–0.606). This study derived an improved age estimation formula with R² values ranging from 0.540 to 0.546 when both PCHR and PCWR were combined. Despite the limitations of this study, such as its small sample size and reliance on panoramic radiographs, the findings suggest that combining tooth wear and pulp cavity size offers a more robust tool for age estimation in clinical and forensic settings.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.