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[This corrects the article DOI: 10.3389/fmed.2026.1804455.].

Chronic Obstructive Pulmonary Disease (COPD) requires accurate severity staging for treatment planning and prognosis. Machine learning models for COPD severity prediction typically treat Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages as nominal categories, ignoring their natural ordering. We developed an ordinal neural network framework that explicitly models the ordered structure of GOLD stages (1–4) while learning from heterogeneous clinical datasets with differing feature sets. The model employs shared encoders for common clinical variables and private encoders for dataset-specific features, with value-mask encoding for missing data. Training used two publicly available COPD datasets ( N  = 224 source, N  = 101 target) with stratified validation splits. The full shared-private ordinal model achieved 76.9% accuracy, mean absolute error 0.234 stages, and quadratic weighted kappa 0.894 on the validation set ( N  = 20). Ablation studies showed both encoder types are essential (removing either reduced accuracy to <30% with complete loss of ordinal agreement). Baseline comparisons demonstrated improvements over standard multiclass classification (37.3% accuracy, QWK 0.093) and logistic regression (57.8% accuracy, QWK 0.766). Over 95% of misclassifications occurred within ±1 GOLD stage. This work demonstrates that explicit ordinal modeling combined with heterogeneous data integration can achieve strong predictive performance for COPD severity staging, though validation on larger external cohorts is needed.

Chronic obstructive pulmonary disease (COPD) exacerbations require accurate severity assessment for optimal management. This study investigated serum cystatin C as a potential biomarker for evaluating acute exacerbations of COPD (AECOPD) severity and its correlation with established clinical assessment tools. A cross-sectional study enrolled 389 consecutive AECOPD patients hospitalized from June 2021 to December 2023. Patient demographics, laboratory parameters, arterial blood gases, CAT scores, mMRC grading, and GOLD staging were collected. Statistical analyses included Spearman correlation, ANOVA, multiple regression, ROC curve analysis, and restricted cubic spline modeling. Patients averaged 68.71 ± 0.8 years with 71.7% male pre-dominance. Cystatin C levels progressively increased across CAT score severity groups: mild (< 10 points) 1.080 ± 0.32 mg/L, moderate (10-20) 1.380 ± 0.41 mg/L, severe (21-30) 1.720 ± 0.52 mg/L, and very severe (>30) 2.150 ± 0.68 mg/L ( = 78.42, < 0.001). Strong positive correlations existed between cystatin C and CAT scores ( = 0.687), mMRC grading ( = 0.612), and GOLD staging ( = 0.534, all < 0.001). Multiple regression confirmed cystatin C as an independent CAT score predictor (β = 5.89, 95%CI: 4.72-7.06, < 0.001). For severe AECOPD prediction (CAT ≥ 21), cystatin C demonstrated good diagnostic performance with AUC 0.847 (95%CI: 0.807-0.887), optimal cutoff 1.52 mg/L, sensitivity 81.5%, and specificity 78.2%. Restricted cubic spline analysis revealed a significant non-linear dose-response relationship ( = 0.023). Serum cystatin C strongly correlates with AECOPD severity across multiple assessment scales and demonstrates good diagnostic accuracy, supporting its potential as a reliable biomarker for clinical severity evaluation in COPD exacerbations.

Background: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects “at risk” of developing the disease. Methods: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20–44 years) were analysed. Results: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II–III. Moderate to heavy smoking (⩾15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p<0.001), with no difference between stage 0 and COPD. Conclusions: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.

COPD presents with an array of extra-pulmonary symptoms of which skeletal muscle dysfunction, particularly of the quadriceps, is well recognized. This contributes to impaired quality of life and increased health care utilization. Work on the quadriceps originated from the observation that a good proportion of COPD patients stop exercise due to the feeling of leg fatigue rather than breathlessness. This study was carried out with the aim of finding the prevalence of quadriceps weakness in a population set and correlate it with severity of COPD. This cross-sectional study was conducted in 75 subjects suffering from COPD aged 45 years or above. COPD severity in the subjects was graded based on the GOLD staging system. A digital hand held dynamometer (HHD) was used to measure quadriceps muscle strength. Descriptive statistics were done, and Pearson's Correlation Coefficient and ANOVA analysis was used for expressing the results. Ninety two percent of subjects were suffering from quadriceps muscle weakness. Quadriceps weakness was present in significantly high proportions even in those suffering from mild disease and belonging to a younger age group. The mean quadriceps muscle force value decreased with disease severity and this relation was found to be significant (P<0.01). Majority of the COPD patients were found to be suffering from quadriceps weakness, which was also present in significant proportions in subjects belonging to younger age groups and suffering from mild disease. These findings indicate that onset of muscle weakness in COPD may precede the onset of symptoms. These findings suggest need for early remedial measure to prevent occurrence of associated systemic diseases.

There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD. It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors. We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013. Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline. Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies. We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria. The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies). The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%). The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for \"real-life patients.\" The tiotropium RCTs tended to include patients with more severe disease than the observational studies.

4 Years of looking at the \"Fletcher diagram\" 7 have anchored the impression of rapid decline so firmly in our minds that we may tend to forget that, through impaired growth of lung function in childhood and early adolescence, any superimposed airflow obstruction at a later age could very well start the patient off in COPD stage II. 8 For this and other reasons, more work on the concept of staging of COPD is clearly needed.

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

This study aims to evaluate the feasibility of a label-free nanobiosensor based on blood plasma surface-enhanced Raman spectroscopy (SERS) method for exploring variability of different tumor (T) stages in nasopharyngeal cancer (NPC). Au nanoparticles as the SERS-active nanostructures were directly mixed with human blood plasma to enhance the Raman scattering signals. High quality SERS spectra can be acquired from blood plasma samples belong to 60 healthy volunteers, 25 NPC patients with T1 stage and 75 NPC patients with T2–T4 stage. A diagnostic accuracy of 83.5% and 93.3%, respectively, can be achieved for classification between early T (T1) stage cancer and normal; and advanced T (T2–T4) stage cancer and normal blood groups. This exploratory study demonstrates that the nanobiosensor based on SERS technique in conjunction with PCA-LDA has great potential as a clinical complement for different T stages detection in nasopharyngeal cancer.

Tumor stages detection and histologic grades classification are essential for the diagnosis and prognosis of oral squamous cell carcinoma (OSCC). In this research, we apply surface-enhanced Raman spectroscopy (SERS) of blood serum to detect the tumor stages and histologic classification of OSCC. According to TNM classification and World Health Organization histologic grading system, the blood serum samples were collected from a total of 135 OSCC patients in the different tumor stages and histologic grades. Then the SERS spectra of serum samples from OSCC patients were diagnosed and classified into different groups using principal component analysis (PCA) and linear discriminant analysis (LDA) based on the tumor sizes, lymph node metastasis and histologic grades. The SERS spectra of blood serum samples have shown the distinct changes and differences compared with each other, which were assigned to the biomolecule alterations (nucleic acids, proteins, lipids, and so on) in blood serums. And all accuracies of detection and classification reached above 85%. This study demonstrated that the SERS based on blood serum test had an enormous potential to carry out the preoperative assessment and prediction of the OSCC patients in different tumor stages and histologic classification.