Respiratory microbiome and clinical course of carbapenem-resistant Acinetobacter baumannii pneumonia in critically Ill patients.

Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has been a serious problem in the intensive care unit (ICU). However, defined characteristics of respiratory microbiome in CRAB pneumonia are lacking nowadays. This study aimed to analyze respiratory microbiome of CRAB pneumonia compared to non-CRAB pneumonia and reveal the clinical significance of respiratory microbiome data in these patients. Patients diagnosed with severe pneumonia with mechanical ventilation were enrolled in the ICU of a tertiary care hospital. Respiratory specimens were collected on days 1, 4, 7, and 14 in each participant via tracheal aspiration. Clinical data and outcomes of each enrolled patient were collected via electronic medical records. Microbiome analysis was conducted with collected respiratory specimens undergone by next-generation sequencing of microbial 16S ribosomal DNA. Six CRAB pneumonia, 4 non-CRAB pneumonia and 5 healthy controls were enrolled. In CRAB pneumonia, CRAB was detected in 3 patients by sputum culture at day 1, while it was negative at day 1 and detected later in the others by follow-up sputum culture. Beta diversity plot analysis showed differences between each group. Shannon index was decreased markedly at day 4 in CRAB pneumonia compared to the others. Among CRAB pneumonia cases, 3 respiratory specimens were culture-negative, but positive by microbiome analysis. Lower respiratory microbiome in CRAB pneumonia had distinct characteristics and early loss of diversity compared to non-CRAB pneumonia, which might be related to poor clinical course. Moreover, CRAB acquisition and colonization would be predicted by preemptive microbiome analysis, which will contribute to effective infection control in the ICU.

Predicting Asthma Exacerbation Risk in the Adult South Korean Population Using Integrated Health Data and Machine Learning Models.

Asthma is a chronic inflammatory airway disease with significant burden; exacerbations can severely affect quality of life and healthcare costs. Advances in big data analysis and artificial intelligence have made it easier to predict future exacerbations more accurately. This study used an integrated dataset of Korean National Health Insurance, meteorological, air pollution, and viral data from national public databases to develop a model to predict asthma exacerbations on a daily basis in South Korea. We merged these sources and applied random forest, AdaBoost, XGBoost, and LightGBM machine learning models to compare their performances at predicting future exacerbations. Of the models, XGBoost (AUROC of 0.68 and accuracy of 0.96) and LightGBM (AUROC of 0.67 and accuracy of 0.96) were the most promising. Common important variables were the number of visits and exacerbations per year, and medical resource utilization, including the prescription of asthma medications. Comorbid diabetes, hypertension, gastroesophageal reflux, arthritis, metabolic syndrome, osteoporosis, and ischemic heart disease were also associated with elevated exacerbation risk. The models examined in this study highlight the importance of previous exacerbations, use of medical resources, and comorbidities in the prediction of future exacerbations in patients with asthma.

Risk prediction of multiple-station N2 metastasis in patients with upfront surgery for clinical single-station N2 non-small cell lung cancer.

To investigate long-term outcomes and develop a risk model for pathological multi-station N2 (pN2b) in patients who underwent upfront surgery for clinical single-station N2 (cN2a) non-small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p < 0.001), age ≤ 50 years (p < 0.001), preoperatively confirmed N2 metastasis (p < 0.001), and clinical stage IIIB (vs. IIIA) (p = 0.003) were independent risk factors for pN2b metastasis. The risk scoring system based on this model demonstrated good discriminant ability for pN2b disease (area under receiver operating characteristic: 0.779). In cN2a NSCLC patients, those with multiple N2 metastases indicate worse prognosis than those with a single N2 metastasis. Our risk scoring system effectively predicts pN2b in these patients.

Risk Factors for Rapid Cognitive Decline in Amyloid-Negative Individuals Without Cognitive Impairment or With Early-Stage Cognitive Loss in Screening Tests.

PURPOSE: Although rapid cognitive decline (RCD) is an important unfavorable prognostic factor, not much is known about it, especially in amyloid-negative individuals. The purpose of this study was to investigate risk factors for RCD in amyloid-negative individuals. PATIENTS AND METHODS: We retrospectively enrolled 741 individuals who were either cognitively unimpaired or had early-stage cognitive ability loss and who underwent 18F-florbetaben (FBB) (n = 402) or 18F-flutemetamol (FMM) (n = 339) PET/CT. Based on visual and semiquantitative (SUV ratio [SUVR]-based) analysis, the following amyloid-negative groups were established: visual-negative FBB (n = 232), visual-negative FMM (n = 161), SUVR-negative FBB (n = 104), and SUVR-negative FMM (n = 101). Univariable and multivariable logistic regression analyses were performed for RCD using 5 SUVRs, 5 cortical thicknesses, and 5 neuropsychological domains and clinico-demographic factors. RESULTS: In the amyloid-negative groups, a decline in language function was commonly identified as a significant risk factor for RCD (P = 0.0044 in the visual-negative FBB group, P = 0.0487 in the visual-negative FMM group, P = 0.0031 in the SUVR-negative FBB group, and P = 0.0030 in the SUVR-negative FMM group). In addition, declines in frontal/executive function, frontal SUVR, and parietal SUVR; a longer duration of education; and mild cognitive decline in the amyloid-negative groups were also significant risk factors for RCD. CONCLUSIONS: Even in amyloid-negative individuals without cognitive impairment or with early-stage cognitive ability loss, those with decreased language and frontal/executive functions on neuropsychological testing are at risk of progression to RCD.

Single point insulin sensitivity estimator index for identifying metabolic syndrome in US adults: NHANES 2017-march 2020.

PURPOSE: Single Point Insulin Sensitivity Estimator (SPISE) index was recently introduced as a reliable indirect indicator of insulin resistance, applicable to large population-based research. Here, we aimed to 1) examine racial/ethnic differences in SPISE index among US adults, 2) compare predictive power of SPISE index for metabolic syndrome (MetSyn) by race/ethnicity, and 3) evaluate its predictive power for MetSyn against other well-known IR indices including Triglyceride/HDL-C, Triglyceride-glucose index, homeostatic model assessment for insulin resistance, and inverse fasting insulin. METHODS: A total of 2168 adults (814 white, 690 black, and 664 Hispanic) from NHANES 2017-March 2020 Pre-Pandemic Data was analyzed in this study. MetSyn was defined by the AHA/NHLBI criteria. SPISE index and insulin resistance indices were calculated by using physical and cardiometabolic parameters. RESULTS: SPISE index was lowest in Hispanic, followed by black and white, with no difference between white vs. black. The area under the curve of receiver operating characteristics of SPISE index for predicting MetSyn was highest in white (88 %), followed by Hispanic (86 %) and black (82 %) (P < 0.05 vs. black), with optimal cutoffs of 5.03, 4.84, and 4.89, respectively. In the total cohort, the predictive power of the SPISE index for MetSyn was 85 %, higher than the other insulin resistance indices (all P < 0.05). CONCLUSIONS: SPISE index outperforms various insulin resistance indices for predicting MetSyn in US adults, signifying its potential in large-scale observational studies. Race/ethnicity should be stratified when using the SPISE index as its predictive power and cutoffs for predicting MetSyn vary by race/ethnicity.

A Mathematical Model-Derived Disposition Index Without Insulin Validated in Youth with Obesity.

AIMS: The gold standard clamp measurements for insulin sensitivity (cSI), ß-cell function (cBCF) and disposition index (cDI = cSI*cBCF), are not practical in large-scale studies. We sought to: 1) validate a mathematical model-derived DI from oral glucose tolerance tests (OGTT) with insulin (mDI) and without (mDI-woI) against cDI and oral disposition index (oDI) evaluate the ability of the novel indices to detect prediabetes and type 2 diabetes. METHODS: We carried out a secondary analysis of previously reported cross-sectional observational studies. The Insulin Sensitivity and Secretion mathematical model for glucose-insulin dynamics was applied to five-point and three-point OGTTs synchronized with hyperinsulinemic-euglycemic and hyperglycemic clamps from 130 youth with obesity (68 NGT, 33 IGT, 29 T2D). RESULTS: Model-derived DI correlated well with clamp DI (R = 0.76 (logged)). Between NGT and IGT, mDI and mDI-woI decreased more than oDI and cDI, (60 and 59% vs 29 and 27%), and by receiver operating characteristic (ROC) analysis were superior at detecting IGT than oDI and cDI (AUC 0.88, 0.87 vs 0.68, 0.65), as was mean glucose (AUC 0.87). CONCLUSIONS: mDI-woI is better than oDI or the labor-intensive cDI for detecting dysglycemia in obese youth. Bypassing insulin measurements with mDI-woI from the OGTT provides a cost-effective approach for large-scale epidemiological studies of dysglycemia in youth.

Clinical Features and Visual Outcome of Infectious Keratitis Associated with Orthokeratology Lens in Korean Pediatric Patients.

Purpose: To investigate the clinical features and visual outcome of infectious keratitis associated with Orthokeratology (Ortho-K) lens in Korean pediatric patients. Methods: We retrospectively reviewed medical records of patients diagnosed with Ortho-K lens-associated infectious keratitis from June 2005 to April 2020 at a tertiary referral hospital. Patients' demographics, clinical features, microbiological evaluation, and treatment methods were assessed and factors related to final visual outcomes were analyzed. Results: The study included 26 eyes of 26 patients (19 female, 7 male; mean age: 11.9 years), with an average Ortho-K lens wear duration of 33.7 ± 21.2 months. The highest number of cases occurred in summer (42.3%, 11/26). Central or paracentral corneal lesions were observed in 96.2% (25/26) of cases, with a mean corneal epithelial defect size of 5.13 mm². Pseudomonas aeruginosa was the most commonly isolated organism (n = 5), followed by Serratia marcescens (n = 4). All patients responded to medical treatment without needing surgical intervention. 72% of cases achieved favorable visual outcomes (Snellen BCVA > 6/12), while 8% experienced severe visual impairment (Snellen BCVA ≤ 6/60) due to residual central corneal opacities. Multivariable analysis showed that non-summer seasons, duration from symptom onset to presentation, and corneal epithelial defect size were significantly associated with final logMAR BCVA (p = 0.043, p = 0.040, and p = 0.002, respectively). Failed autorefraction at presentation due to an Ortho-K-related infectious keratitis lesion was a significant predictor of poor final visual outcome (Snellen BCVA ≤ 6/12) (OR = 38.995, p = 0.030). Conclusions: Ortho-K lens-related infectious keratitis can lead to permanent corneal opacities and potentially devastating visual outcomes in children. Delayed time to presentation, large corneal lesions, failure of autorefraction, and non-summer seasons were associated with poorer outcomes. Proper education and early detection would be key to safe use of orthokeratology lenses in pediatric patients.

Realization of Extremely High-Gain and Low-Power in nMOS Inverter Based on Monolayer WS2 Transistor Operating in Subthreshold Regime.

In this work, we report an n-type metal-oxide-semiconductor (nMOS) inverter using chemical vapor deposition (CVD)-grown monolayer WS2 field-effect transistors (FETs). Our large-area CVD-grown monolayer WS2 FETs exhibit outstanding electrical properties including a high on/off ratio, small subthreshold swing, and excellent drain-induced barrier lowering. These are achieved by n-type doping using AlOx/Al2O3 and a double-gate structure employing high-k dielectric HfO2. Due to the superior subthreshold characteristics, monolayer WS2 FETs show high transconductance and high output resistance in the subthreshold regime, resulting in significantly higher intrinsic gain compared to conventional Si MOSFETs. Therefore, we successfully realize subthreshold operating monolayer WS2 nMOS inverters with extremely high gains of 564 and 2056 at supply voltage (VDD) of 1 and 2 V, respectively, and low power consumption of ∼2.3 pW·µm-1 at VDD = 1 V. In addition, the monolayer WS2 nMOS inverter is further expanded to the demonstration of logic circuits such as AND, OR, NAND, NOR logic gates, and SRAM. These findings suggest the potential of monolayer WS2 for high-gain and low-power logic circuits and validate the practical application in large areas.

Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage NSCLC.

OBJECTIVES: The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected NSCLC. METHOD: We analyzed presurgical plasma samples from 895 patients with EGFR and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histologic diagnosis, histologic subtypes, and clinical-to-pathologic TNM upstaging. RESULTS: Presurgical ctDNA detection was observed in 55 of 414 patients (13%) with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (2-year recurrence-free survival 69% versus 91%; log-rank p < 0.001), approaching that of clinical stage II LUAD. Presurgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict presurgical ctDNA detection. Moreover, presurgical ctDNA detection was predictive of the postsurgical discovery of International Association for the Study of Lung Cancer grade 3 tumors (p < 0.001) and pathologic TNM upstaging (p < 0.001). Notably, presurgical ctDNA detection strongly correlated with higher programmed death-ligand 1 expression in tumors (positive rates 28% versus 55%, p < 0.001), identifying a subgroup likely to benefit from anti-programmed death-ligand 1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need for tumor tissue profiling. Furthermore, it is clinically useful in identifying patients at high risk who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

Multimodal Imaging Approach for Tumor Treatment Response Evaluation in the Era of Immunotherapy.

ABSTRACT: Immunotherapy is likely the most remarkable advancement in lung cancer treatment during the past decade. Although immunotherapy provides substantial benefits, their therapeutic responses differ from those of conventional chemotherapy and targeted therapy, and some patients present unique immunotherapy response patterns that cannot be judged under the current measurement standards. Therefore, the response monitoring of immunotherapy can be challenging, such as the differentiation between real response and pseudo-response. This review outlines the various tumor response patterns to immunotherapy and discusses methods for quantifying computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) in the field of lung cancer. Emerging technologies in magnetic resonance imaging (MRI) and non-FDG PET tracers are also explored. With immunotherapy responses, the role for imaging is essential in both anatomical radiological responses (CT/MRI) and molecular changes (PET imaging). Multiple aspects must be considered when assessing treatment responses using CT and PET. Finally, we introduce multimodal approaches that integrate imaging and nonimaging data, and we discuss future directions for the assessment and prediction of lung cancer responses to immunotherapy.

18F-Fluorodeoxyglucose Positron Emission Tomography-Based Risk Score Model for Prediction of Five-Year Survival Outcome after Curative Resection of Non-Small-Cell Lung Cancer.

The aim of our retrospective study is to develop and assess an imaging-based model utilizing 18F-FDG PET parameters for predicting the five-year survival in non-small-cell lung cancer (NSCLC) patients after curative surgery. A total of 361 NSCLC patients who underwent curative surgery were assigned to the training set (n = 253) and the test set (n = 108). The LASSO regression model was used to construct a PET-based risk score for predicting five-year survival. A hybrid model that combined the PET-based risk score and clinical variables was developed using multivariate logistic regression analysis. The predictive performance was determined by the area under the curve (AUC). The individual features with the best predictive performances were co-occurrence_contrast (AUC = 0.675) and SUL peak (AUC = 0.671). The PET-based risk score was identified as an independent predictor after adjusting for clinical variables (OR 5.231, 95% CI 1.987-6.932; p = 0.009). The hybrid model, which integrated clinical variables, significantly outperformed the PET-based risk score alone in predictive accuracy (AUC = 0.771 vs. 0.696, p = 0.022), a finding that was consistent in the test set. The PET-based risk score, especially when integrated with clinical variables, demonstrates good predictive ability for five-year survival in NSCLC patients following curative surgery.

Luminescent Cs8PbBr64+ Quantum Dots Centered on the Octahedral PbBr64- Cluster within Zeolite LTA: Exploring the Edge of Three-Dimensional Crystal Structure and Its Stability.

The perovskite quantum dots (QDs) of CsPbX3 (X = Cl, Br, I) exhibit exceptional photoluminescent properties, but their sensitivity to moisture and heat poses a challenge. This study presents a solvent-free synthesis approach for incorporating CsPbBr3 perovskite QDs into zeolite A. The introduction of [Cs8PbBr6]4+ perovskite QDs into the zeolite framework resulted in a highly stable configuration, maintaining its initial luminescence properties even after being underwater or exposed to heat. The structure is determined by 3-dimensional single-crystal crystallography. Each octahedral PbBr64- ion is surrounded by Cs+ ions and [Cs8PbBr6]4+ perovskite QDs being formed at the 32% of the center of a large cavity. Further, [Na12CsBr8]5+ QDs are formed at the very center of another 46% large cavities by combining Cs+, Na+, and Br- ions. The peak in the emission spectrum of Pb,Br,Cs,Na-A is similar to those of the CsPbBr3 nanocrystal, Cs4PbBr6 0-dimensional perovskite QDs, and Pb,Br,H,Cs,Na-FAU(X and Y). This work demonstrates that Pb,Br,Cs,Na-A can be produced using a simplified solvent-free synthesis procedure, which exhibits excellent stability against moisture and heat. Moreover, through a straightforward process, various quantum dots (QDs) can be incorporated into zeolite cavities to develop materials with variety photoluminescent properties.

Investigation of symmetric dimethylarginine as a serologic marker for kidney function in striped skunks (Mephitis mephitis).

IMPORTANCE: Kidney disease is prevalent among veterinary species, including zoo animals; however, investigations into this condition in striped skunks (Mephitis mephitis) are scarce. Diagnostic tools for kidney diseases in this species also remain limited. OBJECTIVE: This study aimed to assess the utility of symmetric dimethylarginine as a biomarker for kidney disease in captive striped skunks in Korea. METHODS: This retrospective study analysed 11 striped skunks housed at the Everland Zoo between 2017 and 2021. Blood samples were collected during health checks. Kidney function was assessed through blood analysis and diagnostic ultrasound, with necropsies conducted on deceased animals. Symmetric dimethylarginine levels were measured in 27 plasma samples collected from 11 skunks. RESULTS: Over the study period, seven skunks were diagnosed with kidney disease. Analysis of 27 blood samples revealed a concurrent increase in SDMA levels with concentrations of blood urea nitrogen and blood creatinine. In 3 of the 7 skunks with kidney disease, symmetric dimethylarginine exceeded 14 µg/dL prior to the elevation of blood urea nitrogen and blood creatinine above the upper reference limit. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first study investigating symmetric dimethylarginine in captive striped skunks in Korea. Our findings suggest that symmetric dimethylarginine may serve as an early and consistent biomarker for renal dysfunction in striped skunks. Further studies with larger clinical sample size from striped skunks are needed to validate the clinical utility of blood symmetric dimethylarginine concentration.

Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition.

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.

Prognostic Significance of 18F-FDG PET/CT Radiomics in Patients With Resectable Pancreatic Ductal Adenocarcinoma Undergoing Curative Surgery.

PURPOSE: This study aimed to investigate the prognostic significance of PET/CT radiomics to predict overall survival (OS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: We enrolled 627 patients with resectable PDAC who underwent preoperative 18F-FDG PET/CT and subsequent curative surgery. Radiomics analysis of the PET/CT images for the primary tumor was performed using the Chang-Gung Image Texture Analysis toolbox. Radiomics features were subjected to least absolute shrinkage and selection operator (LASSO) regression to select the most valuable imaging features of OS. The prognostic significance was evaluated by Cox proportional hazards regression analysis. Conventional PET parameters and LASSO score were assessed as predictive factors for OS by time-dependent receiver operating characteristic curve analysis. RESULTS: During a mean follow-up of 28.8 months, 378 patients (60.3%) died. In the multivariable Cox regression analysis, tumor differentiation, resection margin status, tumor stage, and LASSO score were independent prognostic factors for OS (HR, 1.753, 1.669, 2.655, and 2.946; all P < 0.001, respectively). The time-dependent receiver operating characteristic curve analysis showed that the LASSO score had better predictive performance for OS than conventional PET parameters. CONCLUSION: The LASSO score using the 18F-FDG PET/CT radiomics of the primary tumor was the independent prognostic factor for predicting OS in patients with resectable PDAC and may be helpful in determining therapeutic and follow-up plans for these patients.

Safety, tolerability, and immunogenicity of an adult pneumococcal conjugate vaccine, V116 (STRIDE-3): a randomised, double-blind, active comparator controlled, international phase 3 trial.

BACKGROUND: The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. METHODS: This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50-64, 65-74, 75-84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18-49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 - PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18-49 years to 50-64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). FINDINGS: Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1-30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18-49 years were non-inferior compared with V116 participants aged 50-64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. INTERPRETATION: V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. FUNDING: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Clinical significance of chronic bronchitis in different racial groups.

BACKGROUNDS: Limited data are available on racial differences in the clinical features of chronic bronchitis (CB) patients with chronic obstructive pulmonary disease (COPD). In this study, we aimed to compare clinical features among CB patients of different races. We also analyzed the clinical significance of CB, defined classically and based on the COPD Assessment Test (CAT), to validate the CAT-based definition. METHODS: We analyzed patient data extracted from the Korean COPD Subgroup Study (KOCOSS) cohort (2012-2021) and US Genetic Epidemiology of COPD (COPDGene) study (2008-2011). We compared clinical characteristics among CB and non-CB patients of three different races using two CB definitions. RESULTS: In this study, 3,462 patients were non-Hispanic white (NHW), 1,018 were African American (AA), and 1,793 were Asian. The proportions of NHW, AA, and Asian patients with CB according to the classic definition were 27.4%, 20.9%, and 10.7%, compared with 25.2%, 30.9%, and 23.0% according to the CAT-based definition, respectively. The risk of CB prevalence was highest in NHW and lowest in Asian COPD patients. Among all races, CB patients were more likely to be current smokers, have worse respiratory symptoms and poorer health-related quality of life (HrQoL), and to have decreased lung function and exercise capacity. Most of these characteristics showed similar associations with the outcomes between the two definitions of CB. A binominal regression model revealed that CB patients of all races had an increased risk of future exacerbations according to both CB definitions, except for Asian patients with classically defined CB. CONCLUSIONS: The presence of CB was associated with worse respiratory symptoms, HrQoL, exercise capacity and lung function, and more exacerbations, regardless of race or CB definition. The CAT-based definition may be more useful for assessing the risk of future exacerbations in Asian COPD patients.

Comparison of HIV characteristics across 3 datasets: the Korea HIV/AIDS Cohort Study Prospective, Retrospective, and National Reporting System.

Objectives: The Korea HIV/AIDS Cohort Study has been conducted prospectively for 18 years. However, it faces limitations in representing the entire population of patients with HIV in Korea. To address these limitations and validate the study design, we analyzed characteristics across several HIV datasets. Methods: We compared epidemiological and clinical characteristics from 3 datasets: the Korea HIV/AIDS Cohort Study (dataset 1, n=1,562), retrospective cohort data (dataset 2, n=2,665), and the national HIV reporting system of the Korea Disease Control and Prevention Agency (KDCA) (dataset 3, n=17,403). Results: The demographic characteristics of age, sex, and age at HIV diagnosis did not differ significantly across datasets. However, dataset 3 contained a higher percentage of patients diagnosed after 2008 (69.5%) than the other datasets. Regarding transmission routes, same-sex contact accounted for a greater proportion of dataset 1 (59.8%) compared to datasets 2 (20.9%) and 3 (32.6%). The percentage of patients with CD4 T-cell counts below 200/mm3 at HIV diagnosis was higher in datasets 1 (39.4%) and 2 (33.3%) compared to dataset 3 (16.3%). Initial HIV viral load measurements were not obtained for dataset 3. Conclusion: The Korea HIV/AIDS Cohort Study demonstrated representativeness regarding the demographic characteristics of Korean patients. Of the sources, dataset 1 contained the most data on transmission routes. While the KDCA data encompassed all HIV patients, it lacked detailed clinical information. To improve the representativeness of the Korea HIV/AIDS Cohort Study, we propose expanding and revising the cohort design and enrolling more patients who have been recently diagnosed.

Spirometric Transition of at Risk Individuals and Risks for Progression to Chronic Obstructive Pulmonary Disease in General Population.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a dynamic disease with a high socioeconomic burden. Using data collected prospectively from the general population, we examined factors related to the transition of at-risk individuals to COPD. METHODS: We used the Korean Genome Epidemiology Study (KoGES) database, defining pre-COPD based on respiratory symptoms and radiological abnormalities suggestive of COPD; the preserved ratio impaired spirometry (PRISm) was defined as a forced expiratory volume in 1s (FEV1)/forced vital capacity ratio≥70% and FEV1<80%, as predicted by spirometry. We determined group differences in the rate of lung function decline, risk of future airflow obstruction (AFO). RESULTS: The study included 4762 individuals, and longitudinal analysis revealed distinct trends in pulmonary function indicators. Compared to the normal group, the pre-COPD group showed a more rapid decline in lung function, while the PRISm group showed a slower decline. In the pre-COPD and PRISm groups, 4.4% and 3.5%, and 13.6% and 10.8%, respectively, of patients had progressed to COPD at the first and second visits. Pre-COPD and PRISm contributed to an earlier time to first AFO, but consideration of comorbid cardiovascular disease weakened this relationship in the PRISm group. Multivariate logistic regression showed that pre-COPD and PRISm are significant risk factors for future development of COPD (OR 1.80, p<0.001; OR 4.26, p<0.001, respectively). CONCLUSION: Pre-COPD and PRISm patients showed different trends in lung function changes over time and both were significant risk factors for future development of COPD.