Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 22 appraisals
Pulmonology
Hypnodensity sleep metrics from fingertip photoplethysmography are better associated with daytime sleepiness and fatigue than traditional metrics from polysomnography
BACKGROUND: Traditional sleep metrics from polysomnography are often limited by the hypnogram, in which each 30-s epoch is classified into one of the five sleep stages. This oversimplifies sleep stage continuity and fragmented sleep, typical in sleep-disordered breathing (SDB). Deep learning offers more dynamic sleep modelling with a higher temporal resolution by providing probabilities for each sleep stage, known as hypnodensities. RESEARCH QUESTION AND METHODS: We investigated whether high-frequency (1/s) hypnodensities captured from nocturnal fingertip photoplethysmography (PPG) recordings better correlate with patient-reported outcomes in SDB than traditional metrics. RESULTS: Among 2,280 patients (65% male, mean age 62 years, mean apnoea-hypopnoea index (AHI) 23.5/h), we found that several PPG-derived hypnodensity metrics correlate with self-reported daytime fatigue and sleepiness. The level of correlation was better or similar compared to traditional hypnogram-based sleep metrics derived from manually scored polysomnography. Specifically, PPG-based hypnodensities for N1 and N3 sleep showed a stronger association (p < 0.005) with fatigue and sleepiness than manually scored N1 and N3 sleep. Multivariable logistic regression (adjusted for age, sex, body mass index, AHI, and total sleep time below 90% blood oxygen saturation) revealed significant associations (p < 0.01) between multiple PPG-based hypnodensity metrics and daytime sleepiness. CONCLUSION: These findings suggest that PPG-based hypnodensities improve the characterisation of sleep quality and better predict patient-reported outcomes in SDB patients. Future uses may include tracking sleep quality with fingertip pulse oximeters outside of sleep centres, potentially over multiple nights due to their simplicity.
14 June 2026
Read appraisal →Journal of ethnopharmacology
Insight of traditional Chinese medicine in treating pulmonary hypertension: Achievements from 2021 to 2025.
ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary hypertension (PH) significantly impairs patients' quality of life and imposes a substantial economic burden. Despite advances in pharmacotherapy, PH remains a life-threatening pulmonary vascular disease. Traditional Chinese Medicine (TCM), with its multi-target and multi-pathway mechanisms, has shown therapeutic potential for PH management. AIMS OF THE REVIEW: This review systematically summarizes TCM formulas, extracts, and active components, along with their pharmacological mechanisms, for the treatment of PH, and highlights the advantages of TCM in managing PH. MATERIALS AND METHODS: A systematic review of the literature on TCM for PH was conducted. The search included scientific publications from January 2021 to August 2025. Relevant articles were identified through comprehensive searches of PubMed, Web of Science, ScienceDirect, and Google Scholar. The search strategy combined keywords including "pulmonary hypertension", "pulmonary arterial hypertension", "Traditional Chinese Medicine", "Chinese herbal medicine", "herb", "formula", "extract", "active component", and "active ingredient". Retrieved publications were screened and analyzed using pre-defined inclusion and exclusion criteria to ensure relevance and methodological quality. RESULTS: This review synthesizes findings on TCM-based theory, experimental models, TCM formulas (both classical and novel), extracts (including ethanol/aqueous extracts, volatile oils, total flavonoids, saponins, and alkaloids), and active components (terpenoids, flavonoids, glycosides, and alkaloids) for the treatment of PH. Predominant models include monocrotaline-induced pulmonary arterial hypertension (PAH) in vivo and hypoxia-induced in vitro models using pulmonary artery smooth muscle cells (PASMCs). Mechanistic studies indicate that TCM target multiple signaling pathways, including NF-κB to alleviate inflammation, PI3K-AKT-mTOR signaling to mitigate oxidative stress, modulation of K+/Ca2+ channels to attenuate pulmonary vascular remodeling, the HIF-2α-Arg-NO signaling pathway to protect endothelial function, inhibition of the TGF-β1/Smad pathway to suppress endothelial-to-mesenchymal transition, and regulation of JAK2-STAT3 and p53-p21 pathways to inhibit abnormal proliferation, migration, apoptosis resistance, and phenotypic transformation. CONCLUSION: TCM, including formulas, extracts, and components exhibit significant therapeutic potential for PH, positioning TCM as a promising complementary strategy for managing this disease.
12 June 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Muscle sympathetic nerve activity in COPD: a systematic review and meta-analysis
BACKGROUND: Cardiovascular disease is a primary driver of mortality in COPD. Elevated sympathetic nerve activity is a key proposed mechanism, but the magnitude of this autonomic overactivity has not been quantified in a pooled analysis. OBJECTIVE: To determine if adults with COPD exhibit higher resting muscle sympathetic nerve activity (MSNA) than healthy controls, assess associated cardiorespiratory effects, and evaluate the short-term impact of COPD interventions on MSNA. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight databases were searched from inception to 15 May 2025 to inform this systematic review and meta-analysis (PROSPERO CRD420251044931). Eligible studies included adults with spirometry-defined COPD in whom MSNA was measured by microneurography at rest. Primary outcomes were MSNA burst frequency (bursts·min-1) and incidence (bursts per 100 heartbeats). Secondary outcomes included resting heart rate and blood pressure. RESULTS: A total of 11 studies (171 COPD participants, 105 controls) met inclusion criteria. Compared with controls, COPD was associated with markedly higher MSNA, burst frequency (+18.5, 95% CI 9.4-27.7 bursts·min-1) and burst incidence (+21.3, 95% CI 9.2-33.4 bursts per 100 heartbeats). Resting heart rate was also elevated (+10.7, 95% CI 6.1-15.3 beats·min-1), while blood pressure did not differ significantly. Three studies on noninvasive ventilation or inhaled β2-agonists found no significant pooled changes in MSNA. CONCLUSIONS: Resting MSNA is significantly elevated in patients with COPD despite normal blood pressure. This chronic sympathetic excitation likely contributes to COPD-related cardiovascular morbidity and exercise intolerance, highlighting the importance of developing therapies that reduce sympathetic nerve activity.
29 May 2026
Read appraisal →Acta oncologica (Stockholm, Sweden)
Prospective evaluation and clinical outcomes of adaptive radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC)
BACKGROUND AND PURPOSE: Locoregional tumor control is strongly associated with survival for non-small cell lung cancer, emphasizing the importance of precise radiotherapy delivery. This study aims to evaluate a traffic light adaptation protocol regarding target coverage, protocol performance and patient outcomes. MATERIAL AND METHODS: From 2019 to 2022, we prospectively enrolled inoperable non-small cell lung cancer patients. We acquired daily cone-beam computed tomography and traffic light registrations, classifying anatomical changes and need of action. Using repeated computed tomography (rCT) in week 1 and 3 for dosimetric evaluation, we recalculated clinical target volume (CTV) D98% and V95% with and without adaptation, and compared traffic light registrations with the actual dose distribution. Protocol performance was evaluated by the sensitivity and specificity in detecting CTV V95% < 98%. RESULTS: Among 45 patients with complete registrations, baseline shift and tumor shrinkage were most common changes, leading to corrections from bone to tumor match in 37.8% and replanning in 13.3% of patients. Among 38 patients with at least one rCT, 15.8% would have received insufficient CTV coverage without adaptation. Protocol sensitivity, specificity and balanced accuracy were 83.3, 88.6, and 85.7%, respectively. For 38 stage II-III patients, median overall survival was 43.5 months (95% confidence interval [CI]: 32.9-54.1), median time to locoregional failure 27.4 months (95% CI: 0-61.8) and median estimated time to distant failure 30.7 months (CI not estimated due to censoring). INTERPRETATION: The protocol identified relevant changes, improving target coverage without increasing organ at risk doses. With appropriate training, protocol performance was good, and clinical outcomes were consistent with international results.
28 May 2026
Read appraisal →NEJM evidence
Outcomes of Pneumonia in ICUs in Low- and Middle-Income Countries - A Systematic Review
BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of intensive care unit (ICU) admission and death in low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to estimate mortality among patients with CAP admitted to ICUs in LMICs. METHODS: We searched multiple databases using terms related to CAP admitted to the ICU and LMIC. We included both observational studies and clinical trials. The primary outcome was all-cause ICU, 28-day or 30-day mortality. Demographics, comorbidities, clinical characteristics, mechanical ventilation, and length of ICU stay were described. We registered the study in PROSPERO (CRD42022363048). RESULTS: A total of 52 studies from 18 countries met inclusion criteria, encompassing 48,707 patients. Most studies originated in upper-middle-income countries and no studies from low-income countries were identified. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease, and diabetes. Mechanical ventilation was reported in 36 studies, with median use in 59% (interquartile range, 41.4-77.4) of patients. Pooled mortality was 37% (95% confidence interval [CI], 31-42), rising to 61 (44-75) among patients requiring mechanical ventilation. In a meta-regression, age and mechanical ventilation were the strongest moderators of mortality, explaining 55.2% of heterogeneity in short-term mortality. CONCLUSIONS: Mortality among patients with CAP admitted to ICUs in middle-income countries remains high, especially in older and mechanically ventilated patients. The lack of data from low-income countries is notable.
27 May 2026
Read appraisal →Circulation journal : official journal of the Japanese Circulation Society
Regional Disparities in Access to Specialized Facilities and Prescription Preference for Initial Pulmonary Arterial Hypertension Treatment - A Nationwide Study Using the National Database of Health Insurance Claims
BACKGROUND: Improved prognosis of pulmonary arterial hypertension (PAH) has been reported from specialized facilities, though nationwide patient access to both specialized centers and initial treatment regimen in Japan remains unclear. METHODS AND RESULTS: The study group comprised patients with PAH defined as having disease-specific ICD-10 code, administration of medications and diagnostic testing between 2012 and 2023 in the National Database of Health Insurance Claims. Among 13,228 patients across the country, 30.7% accessed Japan Pulmonary Hypertension Registry facilities and 23.7% were initiated with disease-specific combination therapy, though numbers varied across regions. CONCLUSIONS: Regional disparities in access to disease-specific specialized treatment for PAH need to be addressed.
25 May 2026
Read appraisal →Scientific reports
A randomized controlled trial of adjunctive speleotherapy in asthma, COPD and long COVID
Speleotherapy (underground climate therapy) is a non-pharmacological intervention for chronic respiratory diseases. This randomized controlled trial investigated whether a 3-week speleotherapy course (6 sessions, 2 h/week) improves respiratory outcomes in patients on standard background therapy with asthma, COPD, or Long COVID, and whether it affects blood CO2 levels. The control group did not receive speleotherapy but continued their standard therapy. A total of 208 patients (asthma: n = 107; COPD: n = 59; Long COVID: n = 42) were enrolled across nine centers in Germany, Austria, and Italy. Assessments were conducted pre-intervention (T1), post-intervention (T2), and at 3-month follow-up (T3). Outcome measures included airway inflammation (FeNO), pulmonary function parameters (FVC% predicted values, FEV₁% predicted values, FEV₁/FVC, PEF% predicted values), and respiratory muscle strength (MIP and MEP in absolute values). In addition the following validated questionnaires were administered: Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Nijmegen Questionnaire (NQ), and Fatigue Assessment Scale (FAS), along with the Long COVID questionnaire from the Median Clinic Group. CO2 levels were assessed via capillary blood (SpCO2) and end-tidal CO2 (PetCO2). Between-group comparisons used the Mann-Whitney U test; within-group changes were assessed with the Wilcoxon signed-rank test (Bonferroni-Holm corrected). In patients with asthma, the predefined primary endpoint (FeNO) showed no significant improvement. In contrast, patient-reported outcomes improved significantly, with clinically relevant gains in asthma control (ACT: p < 0.001) and asthma-related quality of life (total AQLQ: p = 0.005). Lung function parameters showed statistically significant but modest improvements at T2 (FVC: p = 0.011; PEF: p = 0.010; FEV₁ in participants < 70 years: p = 0.035). In patients with COPD, symptom burden improved according to CAT scores (p = 0.036), while no improvements in lung function were observed. Patients with Long COVID reported significant improvements in dysfunctional breathing (NQ: T2: p = 0.014), dyspnea (T2: p = 0.026; T3: p = 0.001), and "problems with stair climbing/muscle exertion" (T2: p = 0.042), as well as improvements in anxiety and sleep-related symptoms (T2: p = 0.021). No improvements in lung function were observed in this group. In the total cohort, the intervention group showed statistically significant improvements compared to controls in respiratory muscle strength (MIP: p = 0.002; MEP: p = 0.018) and dysfunctional breathing (NQ scores at T2: p = 0.007; T3: p = 0.017). In CO₂-rich speleotherapy centers, both SpCO₂ (p = 0.026) and PetCO₂ (p < 0.001) increased at T2. While speleotherapy did not improve FeNO, it was associated with clinically relevant improvements in patient-reported outcomes across disease groups. Changes in lung function and respiratory muscle strength were statistically significant but modest and should be interpreted with caution. Overall, speleotherapy may have direct effects on the airways and breathing regulation, with more consistent evidence for improvements in breathing patterns than for direct effects on the airways.Trial registration: DRKS00033365 (retrospectively registered).
24 May 2026
Read appraisal →ACS sensors
Moisture-Gated Bio-Semiconductor Electronic Tattoos for Continuous and Imperceptible On-Skin Respiratory Monitoring
Continuous respiratory monitoring remains one of the most critical yet unmet needs in personal and clinical healthcare. To overcome the limitations of cumbersome systems and motion-prone wearables, we present a moisture-gated bio-semiconductor-based electronic tattoo (BSET) that enables imperceptible, skin-conformable, and wireless respiratory monitoring by leveraging the hydration-sensitive ionic-electronic conductivity of melanin and the skin-compatibility of silk. Fabricated from a silk fibroin-melanin nanofiber bio-composite, the BSET is ultrathin at 18 μm and highly breathable, achieving a water vapor transmission rate exceeding 3000 g·m-2·d-1. By detecting exhaled moisture directly on the philtrum, the sensor exhibits a rapid response time of 1 s and a recovery time between 2 and 10 s. A direct-spun nanofiber-based wiring strategy ensures robust integration, accommodating a 10 mm displacement under 10.4 MPa of stress without failure. Driven by a compact 3 g circuit with 20 mW of power consumption, the system supports continuous wireless data transmission for over 7.3 h. During vigorous exercise and sleep, the BSET reliably monitored respiratory dynamics, identifying 10-20 s apnea events and enabling multiparameter analysis of breathing frequency and exhalation intensity. This lightweight system establishes a scalable and clinically relevant solution for continuous respiratory surveillance.
23 May 2026
Read appraisal →Journal of the American Heart Association
Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial
BACKGROUND: COVID-19 and other respiratory viral infections can cause cardiovascular complications. SARS-CoV-2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID-19 and enrolled in the ACTIV-4a (Accelerating COVID-19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy. METHODS: We quantified SARS-CoV-2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine-Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death. RESULTS: In 93 patients, SARS-CoV-2 RNA and N-antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90-day death (hazard ratio [HR], 1.31 [95% CI, 1.17-1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24-1.47]). Viral RNA more effectively predicted survivorship than N-antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%-32.3%; P=0.048) after adjustment for age and sex of the relationship between viral RNA and the 90-day mortality rate. CONCLUSIONS: Elevated plasma SARS-CoV-2 RNA levels are associated with death in ACTIV-4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung-blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04505774.
20 May 2026
Read appraisal →Journal of vascular and interventional radiology : JVIR
A Deep Learning Model for Artery of Adamkiewicz Detection in Bronchial Artery Embolization: A Multicenter Retrospective Study
PURPOSE: To evaluate the effectiveness of a deep learning model for recognizing the artery of Adamkiewicz and anterior spinal artery (ASA) to prevent spinal artery non-target embolization during bronchial artery embolization (BAE). MATERIALS AND METHODS: This multicenter, retrospective study included 2036 patients from January 2019 to December 2023 with hemoptysis who underwent de novo BAE. A deep learning-based framework was proposed for spinal artery identification, comprising region of interest (ROI) perception and target spinal artery identification. The ROI perception extracted vessel-related regions to improve the conspicuity of the spinal artery. The target spinal artery identification utilized a progressive refinement learning network, localizing the artery from the global view, and progressively refined the identification results through cross-scale information interaction. RESULTS: Seventy-eight patients (3.8%) had an identifiable artery of Adamkiewicz and ASA on right intercostal-bronchial artery angiography. The sensitivity of the proposed method was 92.1% and the specificity was 84.6%, with no statistically significant difference from a fellow radiologist interpretation. CONCLUSIONS: The deep learning system for spinal artery detection during BAE exhibited high sensitivity and performance, comparable to radiology fellows.
4 May 2026
Read appraisal →Journal of proteome research
Stability-Based Machine Learning Identifies a Minimal Two-Protein Serum Signature for Early Silicosis
BACKGROUND: The early diagnosis of silicosis, an irreversible fibrotic lung disease, is challenged by the low sensitivity of current radiological methods in early-stage disease and their susceptibility to interobserver variability. Consequently, a pressing need exists for noninvasive, objective biomarkers to facilitate timely detection and intervention. METHODS: We employed a multistage study design comprising a discovery cohort (57 Stage I silicosis patients, 57 matched controls) and an independent, unmatched validation cohort (40 patients, 40 controls). Serum protein profiles were generated using Olink targeted proteomics. We utilized a rigorous, stability-based machine learning framework, which integrated Lasso, Random Forest, and SVM-RFE algorithms over 100 iterations, to perform feature selection and identify a robust biomarker signature from the discovery cohort. Based on the selected features, a logistic regression model was subsequently constructed, and its performance was evaluated using both internal and external validation. RESULTS: Our discovery strategy identified a two-protein signature comprising IL8 and CCL3. This signature demonstrated excellent diagnostic performance in the discovery cohort, achieving a cross-validation AUC of 0.986 (95% CI: 0.975-1.000). Importantly, the model's robustness was confirmed in the heterogeneous validation cohort, where it achieved an outstanding AUC of 0.973 (95% CI: 0.936-1.000), with 95.0% specificity and 77.5% sensitivity. Bioinformatic analysis revealed that decreased serum levels of IL8 and CCL3 were associated with silicosis, providing novel diagnostic biomarkers and highlighting a complex, paradoxical shift in circulating chemokines during early-stage disease.
4 May 2026
Read appraisal →Journal of occupational and environmental medicine
Combining MEA-Net and LAP-Net for Pneumoconiosis Staging Framework
OBJECTIVE: Pneumoconiosis is a common and highly hazardous occupational disease. The staging of pneumoconiosis is mainly carried out by experienced doctors on the basis of the shadows and textures on lung x-ray films. Despite well-defined criteria, the process remains influenced by individual clinical judgment. METHODS: To improve the subjective process of pneumoconiosis diagnosis, this study proposes a new deep learning framework for pneumoconiosis staging framework using MEA-Net and LAP-Net. RESULTS: The experimental results show that the accuracy, precision, recall, specificity, F1-score, and area under the curve in the four-stage classification reached 95.24%, 95.15%, 95.15%, 90.58%, 94.85%, and 98.87%, respectively. CONCLUSION: The proposed method can help doctors to identify the different stages of pneumoconiosis more accurately in the diagnosis of the disease.
4 May 2026
Read appraisal →Current allergy and asthma reports
Interception of Regulatory RNAs on TGF-β Signaling in the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Systematic Review
PURPOSE OF REVIEW: Idiopathic Pulmonary Fibrosis is a type of interstitial lung disease characterized by lung scarring due to excessive extracellular matrix (ECM) deposition. The transforming growth factor-beta (TGF-β) signaling pathway is the master regulator of fibrosis, driving myofibroblast activation and differentiation, epithelial-mesenchymal transition (EMT), and inhibition of ECM degradation. While individual classes of non-coding RNAs (ncRNAs) have been studied in IPF, a comprehensive understanding of how microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (LncRNAs) collectively regulate canonical TGF-β signaling remains lacking. Addressing this gap, this systematic review was conducted which presents current evidence on the integrated roles of ncRNAs in modulating TGF-β signaling in IPF pathogenesis. RECENT FINDINGS: A comprehensive search of PubMed and Web of Science databases (2015-2025), identified 45 eligible studies. miRNAs (19 antifibrotic, 11 profibrotic) directly targeted the core components of the TGF-β signaling pathway, whereas circRNAs (5 antifibrotic, 5 profibrotic) and LncRNAs (6 profibrotic) acted as competing endogenous RNAs and sponged their target miRNAs. Notably, all identified LncRNAs were profibrotic, amplifying the fibrotic signaling pathway. We found that ncRNAs critically fine-tune TGF-β signaling at multiple regulatory nodes, including ligand activation, receptor expression, Smad protein phosphorylation, nuclear translocation, and inhibitory feedback mechanism. The ncRNA-mediated regulatory mechanisms provide valuable insight into IPF pathogenesis and may help identify potential biomarkers and therapeutic targets. Future efforts should prioritize validating in vitro and animal model data in human samples, integrating regulatory network analysis, in vivo functional validation of RNA-based therapeutics, and exploring therapeutic delivery systems to develop an effective ncRNA-based antifibrotic therapy.
3 May 2026
Read appraisal →ACS sensors
Wearable Multimodal Detection System for Real-Time In Situ Analysis of Exhaled Breath Condensate
Exhaled breath condensate (EBC) analysis, a promising noninvasive respiratory monitoring method, has emerged as a pivotal technique for assessing the health status of patients with respiratory disorders and is widely used in clinical research and daily health management. However, conventional analytical methods face challenges in real-time in situ detection of physicochemical indicators and active EBC collection in a power-free way. Herein, a wearable multimodal detection system (WMDS) with efficient collection and real-time analysis of EBC is developed. Specifically, the WMDS consists of a bio-inspired collector, an electrochemical sensor (EBC analysis), a respiratory sensor (humidity and respiratory rate), a temperature sensor, and a flexible printed circuit board. The miniature-sized collector with a cactus spine-like structure can actively harvest 4.1 μL of EBC within 1 min without power consumption. Leveraging self-developed sensors and wireless data transmission circuitry, the WMDS enables real-time in situ monitoring of multimodal EBC analytes (hydrogen peroxide, nitrite, urea) and respiratory parameters (temperature, humidity, and rate). Remarkably, the WMDS exhibits dual-range detection capability covering both physiological and pathological conditions: the low-concentration range of 0-500 μmol/L is applicable for routine health monitoring and early disease screening, with detection limits (LODs) of 0.209, 0.155, and 0.573 μmol/L and sensitivities of 2.7 × 10-2, 3.4 × 10-2, and 9.0 × 10-3 μA/(μmol/L) for EBC analytes; the high-concentration range exceeding 500 μmol/L is designed for severe pathological condition detection, where LODs and sensitivities are 302.2, 278.7, 325.2 μmol/L and 1.9 × 10-2, 1.3 × 10-2, 3.9 × 10-3nA/(μmol/L) respectively. As a proof-of-concept, the WMDS is applied to on-body respiratory monitoring, validating its potential application in real-time in situ health monitoring.
26 Apr 2026
Read appraisal →PloS one
Biomarkers of mitochondrial dynamics in idiopathic pulmonary fibrosis: Identification and validation through transcriptomic and single-cell analyses
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has increasingly been associated with dysregulated mitochondrial quality control and dynamics. However, the molecular mechanisms underlying these alterations remain incompletely understood. This study aimed to systematically identify and validate candidate biomarkers related to mitochondrial dynamics in IPF and to characterize their cell-type specificity and putative regulatory relationships. METHODS: We integrated bulk transcriptomic datasets from the Gene Expression Omnibus (GEO), single-cell RNA sequencing (scRNA-seq) data, and literature-derived mitochondrial dynamics gene sets. Candidate genes were identified through differential expression analysis and consensus clustering, followed by functional enrichment and protein-protein interaction (PPI) network analyses. A total of 101 machine-learning model combinations-including random forest, LASSO, and support vector machine-were constructed to select optimal feature genes. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and further evaluated with artificial neural network (ANN) modeling. Additional analyses included chromosomal localization, immune infiltration profiling, multilayer regulatory network construction (transcription factors, lncRNAs, circRNAs), molecular docking prediction, and single-cell expression and pseudotime trajectory analysis. Key biomarkers were further evaluated by RT-qPCR in an independent clinical cohort. RESULTS: Integrated multi-omics and machine-learning analyses identified CD247, IL7R, and RETN as candidate biomarkers related to mitochondrial dynamics-associated pathways in IPF. Across independent transcriptomic datasets, RETN was upregulated, whereas CD247 and IL7R were downregulated, and each showed diagnostic value (single-gene AUC > 0.7). The ANN model based on these genes achieved encouraging discriminative performance (training AUC = 0.91; validation AUC = 0.82), and expression differences were confirmed by RT-qPCR in a modest independent cohort. Enrichment analyses indicated convergence on spliceosome-related pathways, and regulatory-network analysis highlighted interactions involving transcription factors and non-coding RNAs, including circRNA CDR1as. Molecular docking suggested putative interactions with selected compounds. Single-cell analyses suggested that dysregulation was most evident in monocyte-associated compartments in one publicly available scRNA-seq dataset, and pseudotime analysis indicated dynamic expression patterns, with early transient increases in CD247 and IL7R and progressive elevation of RETN. CONCLUSION: Through multi-omics integration and machine-learning approaches, we identified and preliminarily validated CD247, IL7R, and RETN as candidate biomarkers related to mitochondrial dynamics-associated pathways in IPF. These findings provide transcriptomic and cell-type-specific evidence suggesting potential immune-mitochondrial associations in IPF and may inform future biomarker validation and mechanistic hypothesis generation.
26 Apr 2026
Read appraisal →Sleep
Augmenting management of obstructive sleep apnea with consumer wearable devices to increase use of positive airway pressure therapy: a pilot randomized trial
STUDY OBJECTIVES: This pilot randomized trial measured the effects of a consumer-grade wearable-augmented program, which provides nightly pulse oximetry data to patients in a weekly report, on positive airway pressure (PAP) use in adults with obstructive sleep apnea (OSA) recruited from an outpatient sleep center. METHODS: This single-blind, parallel, two-group waitlist-controlled, single-site randomized trial recruited individuals with OSA with insufficient PAP use from a Department of Veterans Affairs medical center and randomized them to immediate participation in the consumer wearable-augmented self-monitoring program versus waitlist. The primary outcome was the change in modem-measured PAP use (mean hours or minutes per night over a 7-day period) from baseline (T1) to T3 assessment, which was 35 days following randomization (7 days post-intervention for the immediate group and prior to intervention for the waitlist group). RESULTS: We randomized 50 participants (mean age 47.9 years [SD 11.4]; 88% male). The change in PAP use was +1.33 hours (+79.8 minutes) for the immediate group and -0.17 hours (-10.2 minutes) for the waitlist control group, with a between-group difference of 1.50 hours (90 minutes) (p = .0097). The change in the number of days PAP was used for 4 hours or more over a 7-day period was +1.32 days for the immediate and 0.12 days for the waitlist control group, with a between-group difference of 1.20 (p = .0401). CONCLUSIONS: This pilot trial demonstrated that the consumer-grade wearable-augmented program is a promising intervention for increasing PAP use. A future full-scale trial that follows participants for a longer period is needed. Statement of Significance This pilot trial tested a novel use of the pulse oximetry feature available on some consumer-grade wearable devices to increase use of positive airway pressure (PAP) devices among adults with obstructive sleep apnea (OSA) and insufficient PAP use. The widespread and growing use of consumer-grade wearable devices offers an opportunity to leverage the features on these devices to tackle a common, problematic issue among individuals with OSA-insufficient use of PAP therapy. The randomized controlled design provides support for future research involving these devices.
17 Apr 2026
Read appraisal →BMJ open respiratory research
Occupational exposure to toxic particles and risk of pulmonary sarcoidosis: a systematic review and meta-analysis
INTRODUCTION: The onset of sarcoidosis is likely the result of a complex genetic-environment-immunological interaction. This systematic review and meta-analysis aimed to identify occupational toxic particles associated with an increased risk of developing pulmonary sarcoidosis. METHODS: Publications in English, published from January 2000 to January 2025, were searched in PubMed, Scopus and JSTOR. The risk of bias was assessed for all included studies. Sensitivity analyses stratified by study quality were conducted to evaluate the robustness of the findings and potential bias. To assess publication bias, a funnel plot was used when more than six studies were included in the analysis. RESULTS: Five categories of toxic particles were identified to be associated with increased risk of the onset of sarcoidosis: chemicals, inorganic dusts, metals, mixed dusts and fumes and organic dusts. The quantitative analysis includes data from 13 studies. The results suggested that occupational silica, pesticides, mould/mildew and World Trade Center ((WTC) dust exposures were associated with increased odds of pulmonary sarcoidosis. Sensitivity analysis confirmed the robustness of the association for WTC dust and mould, whereas the risk associated with silica appeared attenuated in high-quality studies. However, gold exposure was identified as a protective factor. CONCLUSION: Pulmonary sarcoidosis is associated with occupational silica, pesticides, WTC dust and mould. Future research should prioritise gene-environment interactions and granuloma mineralogy to refine preventive strategies and disease management.
12 Apr 2026
Read appraisal →BMJ open respiratory research
Parasternal electromyography in participants with mild or moderate chronic obstructive pulmonary disease in primary care: cohort study to assess technical and clinical application
BACKGROUND: Neural respiratory drive (NRD) measurement, reflecting the balance between respiratory muscle load and capacity, is quantified using surface parasternal electromyography (EMGpara). EMGpara tracks recovery from severe exacerbations of chronic obstructive pulmonary disease (COPD). Among stable COPD participants, we hypothesised the existence of a relationship between NRD, breathlessness and airway obstruction. STUDY AIMS: (1) assessing the feasibility of measuring EMGpara in COPD participants with forced expiratory volume in 1 s (FEV1) ≥50% predicted in primary care; (2) investigating relationships between NRD measures, self-reported breathlessness, airflow obstruction severity and health-related quality of life (HRQoL). METHODS: Participants with stable mild/moderate COPD, using inhaled corticosteroid (ICS) therapy, were recruited from 20 general practices. Participants were randomly allocated to continue using ICS (maintenance group) or to withdraw ICS (withdrawal group) over 6 weeks. EMGpara, spirometry, self-reported breathlessness (modified Borg dyspnoea scale), COPD Assessment Test and Chronic Respiratory Disease Questionnaire Self-Administered Standardised were measured at baseline, 3- and 6-month follow-up. Bland-Altman plots examined agreement between serial measurements. RESULTS: Forty COPD participants were recruited: age 70±9.2 years; body mass index 26±5.3 kg/m2; FEV1 1.74±0.54 L; and FEV1% pred 69.6±14.0%. High-quality EMGpara data were obtained from 35 participants at baseline and 31 participants on three occasions. High intra-rater and inter-rater agreement for EMGpara (intraclass correlation coefficient >0.9) and moderate correlation between EMGpara and FEV1% predicted (r=-0.42; p=0.01) were recorded. No correlation was observed between resting EMGpara and breathlessness or HRQoL measures across the three time points. CONCLUSIONS: EMGpara measurement is feasible in primary care. In this group of COPD patients, lung function was stable across the three time points and EMGpara was associated with the degree of airflow obstruction. In the resting stable state in mild/moderate disease, there was no association between EMGpara and participant-reported outcomes. Further work should investigate the utility of EMGpara in mild/moderate COPD participants during acute exacerbation and recovery.
12 Apr 2026
Read appraisal →The European respiratory journal
A European multicentre, randomised controlled trial of pirfenidone in bronchiolitis obliterans syndrome after bilateral lung transplantation
BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a major obstacle to improving outcomes after lung transplantation. Bronchiolitis obliterans syndrome (BOS), characterised by progressive decline in forced expiratory volume in 1 s (FEV1) due to fibrotic scarring of the small airways, accounts for most CLAD cases. Pirfenidone, an antifibrotic agent used for idiopathic pulmonary fibrosis, was assessed for treating progressive BOS. METHODS: An investigator-initiated, international, multicentre, randomised, double-blind, placebo-controlled phase II trial was conducted in nine European lung transplant centres. Adults with bilateral lung transplants and progressive BOS were randomised (1:1) to receive pirfenidone 2403 mg·day-1 or placebo with standard care for 26 weeks. The primary end-point was change in FEV1 from baseline to week 26, with imputation for missing values. FINDINGS: From 1 May 2015 to 1 December 2019, 477 patients were screened, and 90 were randomised to pirfenidone (n=48) or placebo (n=42). Both groups showed continued decline in FEV1 from baseline to week 26, with no significant difference in intention to treat (ITT), ITT with imputation, or per-protocol analyses. Secondary end-points (graft loss, death, re-transplantation) were similar between groups. Treatment-related serious adverse events were distributed equally. INTERPRETATION: Pirfenidone did not show superiority over placebo and standard care in this exploratory trial. It cannot be recommended for treating BOS. Further research is needed to explore other treatments for CLAD to improve long-term outcomes after lung transplantation.
4 Apr 2026
Read appraisal →Int J Surg
Multi-omics dissection of high TWAS-active endothelial pathogenesis in pulmonary arterial hypertension: bridging single-cell heterogeneity, machine learning-driven biomarkers, and developmental reprogramming
BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a leading cause of cardiovascular-related mortality worldwide. The emergence of single-cell RNA sequencing (scRNA-seq) has enhanced the ability to dissect cellular heterogeneity in PAH at a granular level. Transcriptome-wide association studies (TWAS) leverage expression quantitative trait loci (eQTL) and genome-wide association study (GWAS) data to identify novel susceptibility genes whose genetically predicted expression correlates with disease risk. However, no study has systematically integrated TWAS with scRNA-seq to unravel the pathogenesis of PAH at single-cell resolution. METHODS: Using TWAS analysis, we identified a set of candidate genes genetically associated with PAH. We then evaluated the differential activity of these genes across PAH cell types at single-cell resolution using AUCell, Ucell, ssGSEA (Single Sample Gene Set Enrichment Analysis), and AddModuleScore algorithms. A subset of endothelial cells exhibiting elevated TWAS activity was identified via quartile-based stratification and designated as the high TWAS activity state (HTS) group. Multi-dimensional analyses, including observed-to-expected ratio (RO/E), CellChat, CytoTRACE (CytoTRACE is based on the robust observation that transcriptional diversity decreases during cell differentiation), and scMetabolism, were employed to characterize the functional and communicative properties of HTS cells. Machine learning algorithms were integrated to identify signature genes of the HTS subpopulation, and a benchmarked random forest model was trained to predict HTS status. We performed immunohistochemistry and quantitative reverse transcription- polymerase chain reaction (qRT-PCR) validation of the signature genes (KLF2, RASIP1 and DEPP1) in PAH and control lung tissues to support their expression patterns. RESULTS: We demonstrated that HTS endothelial cells are strongly associated with PAH pathogenesis, exhibiting significant tissue tropism, enhanced roles in intercellular communication, and a progenitor-like function in endothelial differentiation. Machine learning-based feature selection revealed three robust signature genes: KLF2, RASIP1, and DEPP1. These genes demonstrated exceptional predictive power for identifying HTS cells, suggesting their potential as drivers of endothelial dysfunction in PAH. The random forest model, benchmarked against multiple algorithms, achieved high accuracy in predicting PAH progression using these genes. Immunohistochemical analysis of pulmonary artery and qRT-PCR result of lung tissues addressed the elevated expression of KLF2, RASIP1 and DEPP1 in arterial wall post-PAH. CONCLUSION: This study elucidates endothelial cell heterogeneity in PAH and establishes the central role of HTS cells in disease progression, cellular crosstalk, and developmental reprogramming. Our findings bridge the gap between GWAS and scRNA-seq methodologies and provide a transformative framework for understanding PAH mechanisms.
1 Feb 2026
Read appraisal →Cell
Generation of antigen-specific paired-chain antibodies using large language models.
The traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize existing antibodies and generate antibody sequences in a target-agnostic manner. In this work, we present MAGE (monoclonal antibody generator), a sequence-based protein language model (PLM) fine-tuned for the task of generating paired human variable heavy- and light-chain antibody sequences against targets of interest. We show that MAGE can generate novel and diverse antibody sequences with experimentally validated binding specificity against SARS-CoV-2, an emerging avian influenza H5N1, and respiratory syncytial virus A (RSV-A). MAGE represents a first-in-class model capable of designing human antibodies against multiple targets with no starting template.
1 Dec 2025
Read appraisal →Science
Deep generative models design mRNA sequences with enhanced translational capacity and stability
Despite the success of messenger RNA (mRNA) COVID-19 vaccines, extending this modality to more diseases necessitates substantial enhancements. We present GEMORNA, a generative RNA model that uses transformer architectures tailored for mRNA coding sequences (CDSs) and untranslated regions (UTRs) to design mRNAs with enhanced expression and stability. GEMORNA-designed full-length mRNAs exhibited up to a 41-fold increase in firefly luciferase expression compared with an optimized benchmark in vitro. GEMORNA-generated therapeutic mRNAs achieved up to a 15-fold enhancement in human erythropoietin (EPO) expression and substantially elicited antibody titers of COVID vaccine in mice. Additionally, GEMORNA's versatility extends to circular RNA, substantially enhancing circular EPO expression and boosting antitumor cytotoxicity in chimeric antigen receptor T cells. These advancements highlight the vast potential of deep generative artificial intelligence for mRNA therapeutics.
1 Nov 2025
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