Search Results (992)

Enhancer RNAs (eRNAs) are abundant in most human cells and tissues, and quantifying eRNAs has become a robust approach for biomarker discovery. While eRNAs play crucial roles in regulating biological processes and cancer progression, their functions in lung adenocarcinoma (LUAD) remain poorly understood. Here, we developed a LUAD prognostic model based on eRNA expression data from The Cancer Genome Atlas (TCGA). Through rigorous validation, a 7-eRNA signature was identified, which robustly stratified LUAD patients into high-risk and low-risk groups in both training and testing sets. Functional analyses revealed distinct enrichment of pathways related to amino acid biosynthesis, ribosome biogenesis, and proteasome activity in high-risk patients. Somatic mutation profiling highlighted TP53 and TTN as frequently mutated genes, while drug sensitivity prediction identified four potential therapeutic agents (including AZD4547 and Nutlin-3a) for high-risk individuals. Collectively, this study constructed a 7-eRNA prognostic model for LUAD, providing a powerful tool for clinical risk assessment and uncovering eRNA-mediated regulatory mechanisms. Full article

Background: Asthma is the most common chronic disease during childhood. Spirometry is recommended as a reliable lung function test. Several studies have demonstrated the lack of use of spirometry for both diagnostic confirmation and monitoring. Using subjective symptom control tests alone may underestimate the risk for future asthma attacks. Methods/Objectives: We conducted a retrospective, observational study in a single pediatric centre in Romania. The main objectives of the study were to analyse the quality of spirometry in children and to emphasise the importance of performing accurate spirometry for asthma monitoring. The secondary objective was to evaluate if forced expiratory volume in the first second (FEV1) and mid-maximum expiratory flow (MMEF) values are predictive markers for future exacerbations in children with asthma. Results: The study group included 416 patients between 5 and 18 years who performed at least one spirometry. The success rate for spirometry in our study was 66.3%. In a subsequent study group of 88 patients we monitored spirometry initially and after 12 months. We found a statistically significant difference between FEV1 and MMEF in the controlled, partially controlled and uncontrolled groups (p = 0.0102 and p = 0.0001). Our study showed no association between FEV1 and risk for exacerbations (Rs = −0.156, p = 0.146) and an acceptably negative (Rs = −0.30) and statistically significant (p = 0.040) correlation between initial MMEF values and the number of exacerbations. Conclusions: Low initial MMEF values correlate with the number of exacerbations in a 12-month follow-up period. This suggests that evaluating MMEF alongside FEV1 in children with asthma could contribute to better identification of the risk of exacerbation. Full article

Background: Sarcopenia and low muscle mass are prevalent and prognostically relevant in patients with lung cancer, yet their diagnosis remains challenging in routine clinical practice. Opportunistic assessment using computed tomography (CT) has emerged as a valuable tool for body composition evaluation. We aimed to assess the utility of thoracic CT at T12 and T4 levels in identifying sarcopenia and low muscle mass and explore their correlation with morphofunctional tools such as bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and functional performance tests. Methods: In this prospective observational study, 80 patients with lung cancer were evaluated at diagnosis. Body composition was assessed using BIVA-, NU-, and CT-derived parameters at T12 and T4 levels. Functional status was measured using the Timed Up and Go (TUG) and 30-Second Chair Stand Test. Sarcopenia was defined according to EWGSOP2 criteria. Results: Sarcopenia was identified in 20% of patients. CT-derived indices at T12CT demonstrated better diagnostic performance than T4CT. For detecting low muscle mass, the optimal SMI cut-off values were SMI_T12CT < 31.98 cm²/m² and SMI_T4CT < 59.05 cm²/m² in men and SMI_T12CT < 28.23 cm²/m² and SMI_T4CT < 41.69 cm²/m² in women. For sarcopenia diagnosis, the values were SMI_T12CT < 24.78 cm²/m² and SMI_T4CT < 57.23 cm²/m² in men and SMI_T12CT < 21.24 cm²/m² and SMI_T4CT < 49.35 cm²/m² in women. A combined model including SMI_T12CT, RF_CSA, and the 30 s squat test showed high diagnostic accuracy (AUC = 0.826). In multivariable analysis, lower SMA_T12CT was independently associated with risk of sarcopenia (OR = 0.96, 95% CI: 0.92–0.99, p = 0.022), as were older age (OR = 1.23, 95% CI: 1.07–1.47, p = 0.010) and fewer repetitions in the 30 s squat test (OR = 0.78, 95% CI: 0.63–0.91, p = 0.007). Conclusions: CT-derived body composition assessment, particularly at the T12 level, shows good correlation with morphofunctional tools and may offer a reliable and timely alternative for identifying sarcopenia and low muscle mass in patients with lung cancer. Full article

Immune checkpoint inhibitors (ICIs) improve lung cancer prognosis but are associated with immune-related adverse events, most commonly thyroid dysfunction. While prior studies and guidelines have focused on thyroid dysfunction during ICI therapy, data on hypothyroidism and its monitoring after ICI therapy remain limited. We aimed to investigate hypothyroidism incidence and implementation of thyroid function monitoring after ICI therapy completion in patients with lung cancer. We conducted a retrospective observational study using the DeSC claims database of approximately 12 million individuals in Japan. Patients with lung cancer who received ICI therapy between April 2014 and August 2023 were included; those with a history of thyroid hormone replacement or insufficient follow-up were excluded. Among 6883 eligible patients, 277 (4.0%) developed hypothyroidism requiring hormone replacement post-ICI therapy completion (median onset, 67.0 d). Risk factors included ICI plus bevacizumab therapy and a history of myasthenia gravis, while steroid use for ≥28 d during ICI therapy lowered the risk. Post-ICI therapy completion thyroid monitoring was performed in 73.7% of patients, with test date distribution showing a median of 126.0 d and mode of 21.0 d. Hypothyroidism was frequently found to develop within 2 months post-ICI therapy completion, highlighting the need for continued thyroid monitoring and prospective studies to establish optimal surveillance strategies. Full article

This study aimed to test the reliability of seven functional performance tests in amateur trail runners, including ankle mobility, balance, hopping, and countermovement jump (CMJ) tests. The sample consisted of 35 runners who were evaluated in two sessions separated by 7 to 14 days, which varied due to participants’ scheduling constraints. Relative reliability was assessed using the Intraclass Correlation Coefficient (ICC, which indicates consistency between repeated measures), the Standard Error of Measurement (SEM, which reflects measurement precision), and the Minimal Detectable Change (MDC, which represents the smallest real change beyond measurement error). The results show high reliability in almost all tests. The Lunge Test obtained an ICC of 0.990 and 0.983 for distance, and 0.941 and 0.958 for angular measurements in both legs. The Hop Tests showed moderate reliability with ICC above 0.7 In contrast, the Y Balance Test demonstrated lower reliability, with ICC values ranging from 0.554 to 0.732. The CMJ test showed good reliability, with an ICC ranging from 0.753 to 0.894, an SEM between 5.79% and 11.3%, and an MDC ranging from 15.54% to 31.44%, making it useful for assessing lower limb explosive strength. Both tests presented comparatively higher error values, which should be considered when interpreting individual changes. These findings support the use of these tests as valid and reliable tools for evaluating ankle dorsiflexion, balance, functional symmetry, and lower limb explosive strength in amateur trail runners, prior to training programs or injury prevention strategies, provided that standardized protocols and validated measuring instruments are used. Full article

Background/Objectives: Spheroid cultures in Matrigel are routinely used to study cell behaviour in complex 3D settings, thereby generating preclinical models of disease. Ideally, researchers would like to modulate gene expression ‘in situ’ for testing novel gene therapies while conserving the spheroid architecture. Here, we aim to provide an efficient method to transfect small RNAs (such as microRNAs and small interfering RNAs, i.e., siRNAs) into human induced pluripotent stem cell (iPSC)-derived 3D lung spheroids, specifically alveolar type II epithelial cells (iAT2) and basal cell (iBC) spheroids. Methods: Transfection of iAT2 spheroids within 3D Matrigel ‘in situ’, whole spheroids released from Matrigel or spheroids dissociated to single cells was explored via flow cytometry using a fluorescently labelled siRNA. Validation of the transfection method was performed in iAT2 and iBC spheroids using siRNA and miRNA mimics and measurement of specific target expression post-transfection. Results: Maximal delivery of siRNA was achieved in serum-free conditions in whole spheroids released from the Matrigel, followed by whole spheroids ‘in situ’. ‘In situ’ transfection of SFTPC-siRNA led to a 50% reduction in the SFTPC mRNA levels in iAT2 spheroids. Transfection of miR-29c mimic and miR-21 pre-miR into iAT2 and iBC spheroids, respectively, led to significant miRNA overexpression, together with a significant decrease in protein levels of the miR-29 target FOXO3a. Conclusions: This study demonstrates successful transfection of iPSC-derived lung spheroids without disruption of their 3D structure using a simple and feasible approach. Further development of these methods will facilitate functional studies in iPSC-derived spheroids utilizing small RNAs. Full article

Background/Objectives: The recent development of four-dimensional X-ray velocimetry (4DXV) technology (three-dimensional space and time) provides a unique opportunity to obtain preclinical quantitative functional lung images. Only single-scan measurements in non-survival studies have been obtained to date; thus, methodologies enabling animal survival for repeated imaging to be accomplished over weeks or months from the same animal would establish new opportunities for the assessment of pathophysiology drivers and treatment response in advanced preclinical drug-screening efforts. Methods: An anesthesia protocol developed for animal recovery to allow for repetitive, longitudinal scanning of individual animals over time. Test–retest imaging scans from the lungs of healthy mice were performed over 8 weeks to assess the repeatability of scanner-derived quantitative imaging metrics and variability. Results: Using a murine model of fibroproliferative lung disease, this longitudinal scanning approach captured heterogeneous progressive changes in pulmonary function, enabling the visualization and quantitative measurement of averaged whole lung metrics and spatial/regional change. Radiation dosimetry studies evaluated the effects of imaging acquisition protocols on X-ray dosage to further adapt protocols for the minimization of radiation exposure during repeat imaging sessions using these newly developed image acquisition protocols. Conclusions: Overall, we have demonstrated that the 4DXV advanced imaging scanner allows for repeat measurements from the same animal over time to enable the high-resolution, noninvasive mapping of quantitative lung airflow dysfunction in mouse models with heterogeneous pulmonary disease. The animal anesthesia and image acquisition protocols described will serve as the foundation on which further applications of the 4DXV technology can be used to study a diverse array of murine pulmonary disease models. Together, 4DXV provides a novel and significant advancement for the longitudinal, noninvasive interrogation of pulmonary disease to assess spatial/regional disease initiation, progression, and response to therapeutic interventions. Full article

Background: Uncontrolled asthma remains a significant clinical challenge, often linked to impaired lung function and increased diaphragmatic workload. Recent studies have shown promising results using a triple inhaled therapy comprising beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G). This study assessed the real-world efficacy of BDP/FF/G on lung function and diaphragmatic workload in patients with uncontrolled asthma. Methods: A prospective observational study enrolled 21 adult patients diagnosed with uncontrolled asthma despite high-dose ICS/LABA therapy. Patients underwent lung function tests and right diaphragmatic ultrasound assessments at baseline and after three months of treatment with BDP/FF/G (172/5/9 mcg, administered as two inhalations every 12 h). Results: After three months, significant improvements were observed in FEV₁ (from 57.75 ± 12.30% to 75.10 ± 18.94%, p < 0.001) and FEF_25–75 (from 47.80 ± 19.23% to 75.10 ± 36.06%, p < 0.001). Additionally, during the same period, we recorded significant reductions in residual volume (from 130.10 ± 28.20% to 92.55 ± 21.18%, p < 0.001) and total airway resistance (R_tot) (from 164.60 ± 83.21% to 140.70 ± 83.25%, p < 0.05). The mean asthma control test (ACT) score increased by 5.6 points (p < 0.001), surpassing the established minimal clinically important difference (MCID) of 3 points and raising the cohort mean above the well-controlled threshold. The right diaphragmatic workload was significantly decreased, as shown by a reduction in thickening fraction (TF) (from 63.86 ± 17.67% to 40.29 ± 16.65%, p < 0.01). Correlation analysis indicated significant associations between diaphragmatic function and some lung function parameters (FEV₁, FEF_25–75, and R_tot). Conclusions: In this real-world pilot, triple BDP/FF/G was linked to improvements in airflow, hyperinflation, symptoms, and a reduction in diaphragmatic thickening fraction, indicating potential physiological benefit. Due to the small sample size, single-centre design, and 3-month follow-up, these results should be viewed as hypothesis-generating and need to be confirmed in larger, controlled, multicentre studies with longer follow-up. Full article

Background/Objectives: Some lung transplant (LungTx) recipients do not achieve the expected lung function within the first year, a condition known as baseline lung allograft dysfunction (BLAD). Our objective was to analyze the risk factors associated with BLAD, focusing on the variables associated with a higher risk of developing a more intense alloimmune response. Methods: We carried out a prospective study including 88 LungTx recipients. BLAD was defined as failure to reach 80% of the predicted value for forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) on two tests conducted at least three weeks apart. Tacrolimus time in therapeutic range (TTR) and mycophenolic acid area under the curve (MPA AUC_0–12h) were measured at the third month. Donor–recipient compatibility was assessed using HLA eplet mismatch analysis, performed via HLA Matchmaker 3.1. Results: BLAD patients showed greater eplet mismatch burden (67, IQR 20 vs. 55, IQR 22, p = 0.018) and had been exposed to a lower TTR (26.6%, IQR 14.0% vs. 39.6%, IQR 24.3%, p = 0.039) and less frequently to an adequate third-month MPA AUC_0–12 > 30 mg × h/L (57.1% vs. 89.2%, p = 0.020). DR/DQ eplet mismatches (β = −0.348, p = 0.002) and third-month MPA AUC_0–12 (β = 0.285, p = 0.009) were independently associated with six-month predicted FEV1%. Conclusions: Among other variables, BLAD and initial lung graft function are associated with greater eplet discordance and lower immunosuppressive drug exposure, suggesting a potential role of underlying alloimmune responses in their pathogenesis. Full article

There has been a large amount of research applying deep learning to the medical field. However, obtaining sufficient training data is challenging in the medical domain because annotation requires specialized knowledge and significant effort. This is especially true for segmentation tasks, where preparing fully annotated data for every pixel within an image is difficult. To address this, we propose methods to extract useful features for segmentation using two types of U-net-based networks and partially supervised learning with incomplete annotated data. This research specifically focuses on the segmentation of diffuse lung disease opacities in chest CT images. In our dataset, each image is partially annotated with a single type of lung opacity. To tackle this, we designed two distinct U-net architectures: a multi-head U-net, which utilizes a shared encoder and separated decoders for each opacity type, and a multi-channel U-net, which shares the encoder and decoder layers for more efficient feature learning. Furthermore, we integrated partially supervised learning with these networks. This involves employing distinct loss functions to both bring annotated regions (ground truth) and segmented regions (predictions) closer, and to push them apart, thereby suppressing erroneous predictions. In our experiments, we trained the models on partially annotated data and subsequently tested them on fully annotated data to compare the segmentation performance of each method. The results show that the multi-channel model applying partially supervised learning achieved the best performance while also reducing the number of weight parameters. Full article

Objective: To synthesize the available evidence on field tests used to assess functional capacity in children with CLDs other than asthma, such as cystic fibrosis (CF), and non-CF bronchiectasis (NCFB). Still, the application and reliability of the field tests in non-asthmatic pediatric CLDs populations is scarce. Methods: Three databases (PubMed, Medline via EBSCOhost, and Web of Science) were searched from inception to 20 May 2025. Two researchers independently screened the retrieved articles and rated the methodological quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Information was extracted about study design, field test used, outcomes measured, and methodological quality. Results: Out of 784 records, 8 studies met the inclusion criteria. Most studies focused on CF. Five different field tests were identified: six-minute walk test (6MWT), modified shuttle walk test (mSWT), one-minute sit-to-stand test (1mSTS), three-minute step test (3mST), and TGlittre-P test. The 6MWT (n = 3) and mSWT (n = 2) were the most frequently used and demonstrated good reliability and clinical applicability. Reported outcomes included distance walked, total steps, task’ repetitions, and cardiopulmonary parameters, such as heart rate and perceived exertion of dyspnea/leg fatigue. Conclusions: Field exercise tests appear to be feasible in children with CLDs other than asthma, with most data available in CF. They can be used to monitor functional capacity over time, to assess the effectiveness of rehabilitation programs, and to complement symptom assessment with tools such as the Borg scale. Evidence in NCFB and PCD is still limited, and additional pediatric studies are needed. Full article

Background: HER1 and HER2 are critical receptors involved in tumorigenesis and the development of targeted therapies for various carcinomas. However, most antibodies and drugs currently in development do not recognize murine orthologs, which restricts their evaluation in immunocompetent models. Methods: We generated nine tumor models through the lentiviral transduction of murine prostate (RM1), lung (3LL-D122), and breast (4T1) carcinoma cell lines, subsequently validating them in immunocompetent BALB/c and C57BL/6 hosts. Receptor expression and functionality were characterized using flow cytometry, immunoblotting, proliferation assays, and therapeutic sensitivity testing. Results: Transduced cells exhibited stable membrane expression of HER1/HER2 and ligand-induced phosphorylation, confirming receptor functionality. In all three tumor models generated, the expression of HER1 and/or HER2 significantly enhanced cell proliferation compared to parental lines. Furthermore, treatment with specific monoclonal antibodies and the tyrosine kinase inhibitor markedly reduced the viability of cells expressing HER1 and/or HER2, without affecting negative controls. Conclusions: These models provide a robust and reproducible platform for the preclinical evaluation of HER1/HER2-targeted therapies in immunocompetent hosts. Although the current model relies on subcutaneous implantation and does not fully replicate the native tumor microenvironment, it represents a crucial first step toward the development of orthotopic and immunologically relevant models for translational cancer research. Full article

With the growing adoption of CLO 3D in the fashion industry and educational settings, the need for accurate material representation and fit simulation in virtual environments is increasing. This study aimed to evaluate whether CLO 3D, without the aid of physical samples, can reliably simulate clothing pressure for compression wear made from different materials. Unlike previous CLO 3D studies that focused on design or pattern accuracy, this study critically examined material-specific simulation limitations and proposed technical enhancements. Two types of leggings with varying spandex content were tested across five yoga poses using the CLO 3D software(version 2024.2.214). The results showed that CLO 3D did not detect differences in clothing pressure caused by variations in spandex content. Furthermore, the pressure values remained constant across different poses for both fabrics, failing to reflect realistic mechanical differences. The highest total clothing pressure was recorded in the Lunge pose (277.02 kPa), and the lowest in the Plow pose (241.37 kPa). These findings suggest that the current simulation engine lacks sensitivity to fabric-specific mechanical properties and movement-based variation. To address these limitations, this study proposes five optimization functions for CLO 3D, including material property input, technical textile databases, environmental condition settings, AI-based comfort prediction, and data management tools. These proposals are expected to strengthen the scientific validity, functional realism, and user-centered applicability of CLO 3D in designing sportswear, medical compression garments, and customized apparel. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is the most common form of pulmonary fibrosis (PF) and serves as a key reference for disease severity. Progressive pulmonary fibrosis (PPF), a distinct yet heterogeneous entity arising from various interstitial lung diseases (ILDs), shares similar pathogenetic mechanisms and clinical courses driven by self-perpetuating fibrosis. Antifibrotic therapy, notably nintedanib, can slow disease progression. However, real-world data on antifibrotic therapy’s impact on survival, especially in PPF, are limited. This study aims to compare IPF and PPF regarding phenotype, radiological patterns, comorbidities, prognostic factors, and response to nintedanib, focusing on identifying the patient subsets most likely to benefit. Outcomes assessed include safety, survival, and disease progression over one year, considering various prognostic factors. Methods: This retrospective observational study evaluated patients with fibrosing ILD, affected by either IPF or PPF, and treated with nintedanib. Data collected encompassed clinical, radiological, functional, and treatment-related information. Assessments included chest CT, pulmonary function tests, comorbidities, and survival analysis, utilizing standardized methods and statistical tools to interpret outcomes and tolerability. Results: The study population was composed of 97 patients: 64 were diagnosed with IPF and 33 with PPF. The analysis showed that in PPF patients, ongoing antifibrotic treatment resulted in higher survival (71.1 months vs. 27.4 months, p < 0.001), while no statistically significant differences were found in the IPF group (67.4 months vs. 52.5 months, p = 0.216). Nintedanib was generally well tolerated. Gastrointestinal side effects, predominantly diarrhea, were reported in 61% of patients with IPF and 50% of those with PPF. Dose reduction occurred in 43.75% of IPF patients and 36% of PPF patients, while treatment discontinuation was required in 21.87% of IPF and 21% of PPF patients. Conclusions: This study highlights that in PPF patients, antifibrotic therapy with nintedanib can improve survival. This statement underlines that the primary outcome of antifibrotic treatment should focus on improving patients’ survival. Full article

Objective: We aimed to assess the expression and localization of renin-angiotensin system (RAS) receptors in lung tissue and the plasma concentration of related peptides in IPF patients. Materials and Methods: This case–control study involved 19 patients from southern Brazil undergoing lung resection or transplantation. Plasma levels of Angiotensin I, II, A, 1-7, Alamandine were measured via liquid chromatography–tandem mass spectrometry. Lung tissue expression and localization of angiotensin type 1 (AT1), Mas, and Mas-related G-protein-coupled receptor D (MrgD) receptors were evaluated using Western blot and immunohistochemistry. Clinical data and the 6-min walk test were analyzed to correlate receptor expression with lung function and oxygen dependence. Results: IPF patients showed reduced forced vital capacity (FVC) at 49 ± 13% and forced expiratory volume (FEV1) at 51 ± 14%, with a 60% increase in oxygen dependence. Plasma peptide concentrations were similar between the groups, except for Angiotensin I, which was significantly higher in the control group. In IPF lungs, AT1 and Mas receptors were expressed 2.31 and 2.13 times more, respectively, while MrgD expression was lower. Mas receptors were mostly found in bronchiole areas, whereas MrgD was predominant in the lung parenchyma. Conclusions: This study indicates that the RAS operates independently within tissue, in addition to its systemic functions, highlighting distinct differences between tissue and plasma RAS activities. The distinct roles of MrgD and Mas receptors in lung structure and function could be pivotal for new therapies, potentially leading to more effective IPF treatments. Full article