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Simple Summary: Lung nodules detected by computed tomography (CT) often require invasive procedures for definitive diagnosis. With the increasing use of CT, incidental lung nodules have increased significantly. An adjunctive blood-based biomarker test that predicts lung cancer risk could reduce unnecessary interventions and focus diagnostic efforts on high-risk patients. This study introduces a blood-based biomarker test that predicts lung cancer risk in CT-detected nodules with a sensitivity of 78.4% (95% CI: 75.7–81.1) and a specificity of 93.1% (95% CI: 90.0–96.3). Background and Objectives: Lung nodules detected by chest computed tomography (CT) often require invasive biopsies for definitive diagnosis, leading to unnecessary procedures for benign lesions. A blood-based biomarker test that predicts lung cancer risk in CT-detected nodules could help stratify patients and direct invasive diagnostics toward high-risk individuals. Methods: In this multicenter, single-blinded clinical trial, we evaluated a test measuring plasma levels of p53, anti-p53 autoantibodies, CYFRA 21-1, and anti-CYFRA 21-1 autoantibodies in patients with CT-detected lung nodules. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, and subgroup analyses by gender, age, and smoking status were performed. A total of 1132 patients who had CT-detected lung nodules, including 885 lung cancer cases and 247 benign lesions, were enrolled from two academic hospitals in South Korea. Results: The test demonstrated a sensitivity of 78.4% (95% CI: 75.7–81.1) and specificity of 93.1% (95% CI: 90.0–96.3) in predicting lung cancer in CT-detected nodules. The PPV was 97.6%, and the NPV was 54.6%. Performance was consistent across gender (sensitivity 79.3% in men and 76.8% in women) and age groups, with a specificity of 93.4% in men and 92.7% in women. Stage I lung cancer was detected with a sensitivity of 80.6%. Conclusions: The Lung Cancer test based on 9G technology presented here offers a non-invasive method for stratifying lung cancer risk in patients with CT-detected nodules. Its integration into clinical practice could reduce unnecessary interventions and foster earlier detection. [ABSTRACT FROM AUTHOR]

Background: Radial probe endobronchial ultrasound (radial EBUS) is widely used to diagnose pulmonary lesions; however, the diagnostic value of radial EBUS-guided transbronchial biopsy (TBB) varies, and its complications (especially the risk of bleeding) are not properly understood. Objectives: In this study, we evaluated the diagnostic performance and rate of complication of this procedure, and investigated the risk factors associated with the procedure-related bleeding events. Design: A retrospective cohort study. Methods: This was a retrospective study that included consecutive patients who underwent radial EBUS-guided TBB. Radial EBUS was performed under moderate sedation in inpatients or outpatients. The severity of bleeding was graded using the standardized definitions of bleeding. Results: Of 133 patients (median age, 69 years; men 57.1%) included, 41 were outpatients (30.8%). The diagnostic accuracy, sensitivity, and specificity for malignancy were 76.1% (89/117), 71.1% (69/97), and 100% (20/20), respectively. The diagnostic accuracy ranged from 66.9% to 79.0%, depending on the classification of undiagnosed cases as either false negatives or true negatives. Twenty-seven patients (20.3%) developed complications (pneumothorax, 3; pneumonia, 5; complicated pleural effusion, 2; bleeding event grade 2 or higher, 21). Of the 41 outpatients, two developed complications (pneumothorax without intervention, 1; grade 2 bleeding event, 1). Of the 21 patients (15.8%) with procedure-related bleeding events, 18 had grade 2, and three had grade 3 bleeding complications. In multivariate analysis, a large size of ⩾30 mm (adjusted odds ratio (OR), 5.09; p = 0.03) and central lesion (adjusted OR, 3.67; p = 0.03) were significantly associated with the risk of grade 2 or higher bleeding events. Conclusion: Our results suggest that radial EBUS-guided TBB is an accurate and safe method for diagnosing pulmonary lesions. Clinically significant procedure-related bleeding was rare. The central location and larger size (⩾30 mm) of pulmonary lesions were risk factors for grade 2 or higher bleeding events. [ABSTRACT FROM AUTHOR]

Background and Purpose: The discovery of new bromo‐ and extra‐terminal inhibitors presents new drugs to treat osteoarthritis (OA). Experimental Approach: The new drug, BBC0403, was identified in the DNA‐encoded library screening system by searching for compounds that target BRD (bromodomain‐containing) proteins. The binding force with BRD proteins was evaluated using time‐resolved fluorescence energy transfer (TR‐FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA. For animal experiments, medial meniscus destabilization was performed to create a 12‐week‐old male C57BL/6 mouse model, and intra‐articular (i.a.) injections were administered. Histological and immunohistochemical analyses were then performed. The underlying mechanism was confirmed by gene set enrichment analysis (GSEA) using RNA‐seq. Key Results: TR‐FRET and binding kinetics assays revealed that BBC0403 exhibited higher binding specificity for BRD2 compared to BRD3 and BRD4. The anti‐OA effects of BBC0403 were tested at concentrations of 5, 10 and 20 μM (no cell toxicity in the range tested). The expression of catabolic factors, prostaglandin E2 (PGE2) production and extracellular matrix (ECM) degradation was reduced. Additionally, the i.a. injection of BBC0403 prevented OA cartilage degradation in mice. Finally, BBC0403 was demonstrated to suppress NF‐κB and MAPK signalling pathways. Conclusion and Implications: This study demonstrated that BBC0403 is a novel BRD2‐specific inhibitor and a potential i.a.‐injectable therapeutic agent to treat OA. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively evaluate whether Lung-RADS classification and volumetric nodule assessment were feasible with ultralow-dose (ULD) chest CT scans with deep learning image reconstruction (DLIR). Methods: The institutional review board approved this prospective study. This study included 40 patients (mean age, 66±12 years; 21 women). Participants sequentially underwent LDCT and ULDCT (CTDIvol, 0.96±0.15 mGy and 0.12±0.01 mGy) scans reconstructed with the adaptive statistical iterative reconstruction-V 50% (ASIR-V50) and DLIR. CT image quality was compared subjectively and objectively. The pulmonary nodules were assessed visually by two readers using the Lung-RADS 1.1 and automatically using a computerized assisted tool. Results: DLIR provided a significantly higher signal-to-noise ratio for LDCT and ULDCT images than ASIR-V50 (all P <.001). In general, DLIR showed superior subjective image quality for ULDCT images (P <.001) and comparable quality for LDCT images compared to ASIR-V50 (P =.01–1). The per-nodule sensitivities of observers for Lung-RADS category 3–4 nodules were 70.6–88.2% and 64.7–82.4% for DLIR-LDCT and DLIR-ULDCT images (P = 1) and categories were mostly concordant within observers. The per-nodule sensitivities of the computer-assisted detection for nodules ≥4 mm were 72.1% and 67.4% on DLIR-LDCT and ULDCT images (P =.50). The 95% limits of agreement for nodule volume differences between DLIR-LDCT and ULDCT images (-85.6 to 78.7 mm3) was similar to the within-scan nodule volume differences between DLIR- and ASIR-V50-LDCT images (-63.9 to 78.5 mm3), with volume differences smaller than 25% in 88.5% and 92.3% of nodules, respectively (P =.65). Conclusion: DLIR enabled comparable Lung-RADS and volumetric nodule assessments on ULDCT images to LDCT images. [ABSTRACT FROM AUTHOR]

Climate change has had a significant impact on apple phenology and fruit quality worldwide. Similarly, a decline in fruit quality has been observed in major apple-producing areas of Korea. It is predicted that the ideal cultivation areas for apples would need to shift toward higher latitudes due to these changes. Hence, the objective of this study was to assess the influence of climate change on apple cultivated in a higher-latitude region. To achieve this goal, we investigated the flowering and harvest times of apples. Additionally, we measured fruit weight, soluble solid content, and titratable acidity over a period of 20 years in a higher-latitude region in Korea. Subsequently, we examined the relationship between temperature, phenology, and fruit quality through the use of linear regression and correlation analysis methods. The 20-year meteorological data revealed a consistent rise in temperatures. Consistent with this trend, we found a significant advancement in budbreak and flowering dates for the two major apple cultivars grown in a higher latitude in Korea. Furthermore, the increase in temperatures has positively influenced fruit quality, indicating that climate change has an impact not only on phenology, but also on the quality of apples in Korea. Considering the projected gradual increase in temperature, our findings strongly support that higher-latitude regions in Korea have the potential to become optimal locations for apple cultivation. [ABSTRACT FROM AUTHOR]