Metabolomics analysis shows great promise in identifying non-invasive biomarkers for interstitial lung diseases (ILDs). However, the relevant data are scattered across numerous disparate publications, hindering their full utilization.

To comprehensively leverage the metabolomic data disseminated throughout the literature, we manually curated and integrated them into the ILDMDB database ( https://ildmdb.shinyapps.io/ILDMDB/ ). This database will be regularly updated and maintained.

We conducted a systematic literature search and extracted key metabolomics data, including changes in metabolites, relevant clinical parameters, and predictive model performance metrics etc. These data were then manually integrated into the ILDMDB database.

The current version of ILDMDB contains 3,969 entries, representing 20 ILD types and over 1,000 metabolites derived from Homo sapiens, animal models, and cell line experiments. Each entry comprises detailed information, including the metabolite name, disease type, and original reference. In addition, we have incorporated model data on metabolites used for ILD diagnosis, disease severity, and prognosis, along with information on metabolites associated with clinical parameters. Users can search for target metabolites freely, view their expression patterns and detailed information, and manage metabolite collections in the database.

ILDMDB serves as an exploratory platform designed to assist researchers in swiftly and conveniently accessing the metabolic landscape of ILDs, thereby advancing research into the diagnosis, prognosis, and treatment of ILDs from a metabolic perspective.

Severe asthma is characterized by persistent airway inflammation and epithelial injury. Pyroptosis, a Caspase-1-dependent inflammatory cell death pathway, has been implicated in airway inflammation. FBXW7, an E3 ubiquitin ligase involved in inflammatory regulation, may play a role in this process; however, its function in severe asthma remains unclear.

Human microarray datasets from the Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes and potential biomarkers using bioinformatics and machine learning approaches. Experimental validation was performed using murine asthma models, including ovalbumin (OVA)-induced and OVA/LPS-induced models. Airway epithelium-specific FBXW7 conditional knockout mice were generated to assess in vivo function. In vitro, murine lung epithelial (MLE12) cells with FBXW7 knockout or overexpression were used to evaluate pyroptosis and inflammatory responses following LPS/ATP stimulation. Cytokine levels, Caspase-1 expression, and signaling pathways were analyzed using ELISA, Western blotting, and immunofluorescence.

FBXW7 expression was significantly decreased in severe asthma compared with mild-to-moderate asthma, while Caspase-1 expression was increased. Machine learning analyses identified FBXW7 and Caspase-1 as potential biomarkers in severe asthma. In murine models, FBXW7 downregulation was more pronounced in severe asthma and was associated with increased inflammatory cell infiltration and cytokine production. FBXW7-deficient mice exhibited significantly elevated bronchoalveolar lavage fluid (BALF) inflammatory cell counts and increased IL-1β secretion compared with wild-type controls. In vitro experiments using MLE12 cell lines with FBXW7 overexpression, knockout, and wild-type backgrounds exhibited significant differences in Caspase-1 expression and altered secretion of inflammatory cytokines IL-18 and IL-1β under LPS/ATP-induced pyroptotic conditions, while pharmacological inhibition of Caspase-1 corrected aberrant cytokine secretion. However, mRNA levels of these cytokines remained stable, indicating that FBXW7 controls IL-18/IL-1β maturation/secretion via Caspase-1. Thus, the association among FBXW7, Caspase-1 and cGAS-STING was tested.

FBXW7 suppresses airway epithelial pyroptosis and inflammation in severe asthma by regulating Caspase-1, potentially via the cGAS-STING pathway. These findings highlight FBXW7 as a potential biomarker for severe asthma.

Diagonal ear lobule fold (DELF)(Frank sign); It is a diagonal fold in the earlobe at an angle of about 45°, running diagonally from the tragus to the edge of the auricle at varying depths. In our study, the relationship between obstructive sleep apnea syndrome (OSAS) and DELF was examined.

A total of 132 patients, including 99 patients with sleep apnea complaints and 33 volunteers without complaints, were included in the study. Ear, nose and throat examination of the participants was performed and their ear lobules were examined. All participants underwent polysomnography. The patients were examined in four groups. Group 1 (AHI < 5)(Normal, n = 33), Group 2 (AHI = 5-15)(Mild, n = 33), Group 3 (AHI = 15-30)(Moderate OSAS, n = 33), Group 4 (AHI > 30)(Severe OSAS, n = 33). Demographic information of all participants was recorded.

There was no significant difference between the ages of the groups (43.48, 44.42, 48.69, 47.27, respectively) (p > 0.05). When evaluated in terms of BMI, group 1 was significantly lower than group 4 (p=0.002). There was no significant difference between the other groups (p > 0.05). There was no significant difference between the groups in terms of chronic diseases (CVO, CAD, HT, DM, COPD) (p > 0.05). DELF presence of groups; group 1: 0.59 ± 0.80, group 2: 0.57 ± 0.78. group 3: 0.80 ± 0.86, group 4: 1.10 ± 0.97. There was a significant increase in group 4 compared to group 1 and group 2 (p=0.004, p=0.006, respectively). There was no significant difference between the other groups (p > 0.05).

The presence of DELF (Frank sign) in patients with severe OSASwas demonstrated for the first time in this study. According to the results we have reached, DELF can be used as a new examination finding in the diagnosis of OSAS. We also think that it can be used as a marker in the clinical course of the disease.

The COVID-19 pandemic affected the epidemiology of respiratory syncytial virus (RSV). We sought to describe tertiary care hospital admissions associated with pediatric RSV in 2022/23 in Canada and to assess pandemic-related changes.

We conducted active surveillance of hospital-admitted infants and children aged 0 to 16 years at 13 Immunization Monitoring Program, Active (IMPACT) centres. We compared RSV-associated hospital admissions in 2022/23 with those in the prepandemic period (2017/18 through 2019/20). We calculated province-specific and age-stratified proportions of all-cause hospital admissions with RSV detection and age-stratified proportions of RSV-associated intensive care unit (ICU) admissions. We performed seasonal autoregressive integrated moving average (SARIMA) time-series analyses.

In 2022/23, 5362 RSV-associated hospital admissions occurred, including 1260 (23.5%) ICU admissions, both more than double the prepandemic yearly averages. Overall, the median age increased from 6 (interquartile range [IQR] 1 to 20) months to 9 (IQR 2 to 27) months (p < 0.001). The proportion of RSV-associated hospital admissions among all-cause admissions increased by 3.5 percentage points (95% confidence interval [CI] 3.3 to 3.7 percentage points), to 6.8% (95% CI 6.6% to 7.0%). Whereas 41.5% of RSV-associated hospital admissions were among infants younger than 6 months, this age group accounted for 62.1% of ICU admissions. Overall, the ICU proportion remained constant; however, the odds of ICU admission among infants younger than 6 months increased (adjusted odds ratio 1.35, 95% CI 1.2 to 1.52) compared with the prepandemic period. National weekly incidence in 2022/23 peaked earlier and higher, and persisted longer than expected by SARIMA.

In 2022/23, the number of RSV-associated hospital admissions and ICU admissions increased dramatically in Canadian pediatric hospitals. The greatest burden remained in infants younger than 6 months. Strategies for RSV immunization for young infants may have a substantial public health impact.

Several SARS-CoV-2 variants have evolved with clinical relevance due to their structural and functional impact on viral proteins and genomic RNA structures. A comprehensive structural and functional characterization of single-nucleotide variations in the 5'-untranslated region (UTR) of SARS-CoV-2 has remained elusive. The co-evolution of 5'-UTR stem-loop 1 (SL1) and non-structural protein (nsp) 1 mutants are of particular importance, as both are key in directing the translation of the viral genome. Here, we investigate the structure and function of the most frequently emerging mutations in SL1 and nsp1. Mutation C21U in the apical loop of SL1 shows changed loop dynamics and reduced escape from repression by nsp1 mutants. Mutation analyses of the pyrimidine loop and the apical helix of SL1 identify preferred sequence motifs for escape from nsp1 repression. Importantly, sequence preferences are governed by the structural features, with suboptimal pyrimidine sequences escaping repression when presented in the SL1 context. Compared to the nsp1 wild type (wt), the currently circulating nsp1 linker variant S135R is much more sensitive toward sequence and structure variations of the apical loop of SL1. Thus, our study provides new insights into the structure-function relationship and co-evolution between viral RNA structures and viral proteins.

This report summarises Australia's spontaneous surveillance data for adverse events following immunisation (AEFI) for all vaccines administered in 2023, reported to the Therapeutic Goods Administration (TGA). This report combines coronavirus disease 2019 (COVID-19) and non-COVID-19 AEFI that were previously reported separately in 2022 and 2021. Overall, there were 5,534 AEFI reports for vaccines administered in 2023. This represents an annual AEFI reporting rate of 20.8 per 100,000 population, compared with 79.2 per 100,000 population in 2022. The sharp decrease in the AEFI reporting rate in 2023 was likely driven by a change in COVID-19 vaccination policy. This included limiting COVID-19 vaccine booster dose recommendation to high-risk populations rather than to the wider community, resulting in a steep decline in both the number of administered doses and the number of AEFIs reported. The most commonly reported adverse events were medication errors, injection site reaction, hypersensitivity, pyrexia, and gastrointestinal nonspecific symptoms. The most commonly reported adverse events for new vaccines introduced in 2023 were medication errors and headache for COVID-19 vaccines; hypersensitivity and pyrexia for DTPa-HepB-IPV-Hib vaccine (Vaxelis); and injection site reaction and hypersensitivity for recombinant zoster vaccine (Shingrix). There was reduction in deaths reported following vaccination in 2023 compared to 2022 and 2021. None of the 34 reported deaths in 2023 were determined to be causally related to the vaccine(s) received.

Country-specific estimates of coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) are important for policy making, but analyses of COVID-19 VE in Australia have been limited to date.

We used a modified Cox regression model to estimate, through the linkage of national and state-wide health and administrative datasets, the adjusted relative VE of three vs. two and four vs. three COVID-19 vaccine doses against hospitalisation and death due to COVID-19 among Victorians aged ≥ 50 years after the emergence of the Omicron SARS-CoV-2 variant. Analyses were conducted in two periods: 1 December 2021 to 19 June 2022 (Omicron BA.1/2 period; analyses of three vs. two doses); and 20 June 2022 to 7 November 2022 (Omicron BA.4/5 period; analyses of four vs. three doses).

Approximately 1.8 million people were included in analyses of three vs. two doses and approximately 1.2 million people were included in analyses of four vs. three doses. Adjusted relative VE against death 28 days after boosting with a third dose (compared to two doses) in individuals aged ≥ 65 years in the Omicron BA.1/2-dominant period reached 81.2% (95% confidence interval [95% CI]: 76.9-84.6%). There was also evidence for a relative benefit of a third dose in the Omicron BA.1/2 period against hospitalisation (adjusted relative VE 63.6% [95% CI: 60.1-66.8%] 28 days post-boosting) and for a fourth dose in the Omicron BA.4/5 period against hospitalisation and death in this age group. In contrast, estimates of relative VE in the 50-64 year age group were highly imprecise (for example, 52.4% [95% CI: -16.6-80.6%] against death 28 days after receipt of a third dose in the Omicron BA.1/2-dominant period).

These results confirm the benefits of vaccine boosters in the Omicron era for those aged ≥ 65 years, with the most notable gains evident from a third dose in late 2021 to mid-2022.

Computed tomography pulmonary angiography (CTPA) is the standard imaging modality for diagnosing pulmonary embolism (PE), but diagnostic uncertainty is common due to technical limitations and vague language, leading to inconsistent interpretation and clinician frustration.

This study develops a prompt-free, data-efficient method for assessing diagnostic certainty of PE in CTPA reports using small pretrained language models.

This study examined 173 consecutive CTPA reports from UMass Memorial Health, each annotated by 3 radiologists for PE diagnostic certainty. We developed PECertainty, a lightweight, prompt-free model, and compared it with advanced large language model (LLM)-based methods under limited supervision settings. Baselines included prompt-free methods (support vector machine, random forest, and RoBERTa [Robustly Optimized Bidirectional Encoder Representations From Transformers Pretraining Approach]) and prompt-dependent methods (LLM fine-tuning, in-context learning, and ADAPET [A Densely-Supervised Approach to Pattern Exploiting Training]; UNC Chapel Hill) with open-source Gemma3-4B (Google DeepMind) and Llama3.2-3B (Meta), and the proprietary GPT-3.5 (OpenAI). Sensitivity analyses evaluated performance with 1 to 10 training examples per category for the top performer. Model performance was evaluated against radiologist annotations. External validation on 420 CTPA reports from the Baystate Medical Center, with validation limited to distinguishing certain from uncertain reports. Interpretability of the top-performing models (PECertainty and GPT-3.5) was evaluated using integrated gradients and prompt-based explanations reviewed by radiologists.

Among prompt-dependent methods, GPT-3.5 fine-tuning (F1-score 0.86; 95% CI 0.71-1.0) and in-context learning (F1-score 0.87; 95% CI 0.71-1.0) performed best, and the performance of in-context learning consistently outperformed 0-shot learning for Gemma3-4B (F1-score 0.63, 95% CI 0.56-0.79 vs F1-score 0.45; 95% CI 0.29-0.56) and Llama3.2-3B (F1-score 0.54; 95% CI 0.41-0.71 vs F1-score 0.43, 95% CI 0.28-0.62). PECertainty demonstrated numerically better or equivalent performance compared with both the top-performing prompt-dependent methods and all prompt-free baselines. Compared with fine-tuned ClinicalBERT (Bidirectional Encoder Representations From Transformers Pretrained on Clinical Text), PECertainty achieved statistically significant improvements across all metrics (paired bootstrap significance test, P<.05). RoBERTa (Robustly Optimized Bidirectional Encoder Representations From Transformers Pretraining Approach) fine-tuning lagged (F1-score 0.52; 95% CI 0.35-0.71), and simple models such as support vector machine underperformed. In few-shot settings (10 examples/category), PECertainty (F1-score 0.80; 95% CI 0.59-0.94) outperformed both GPT-3.5 fine-tuning (F1-score 0.74; 95% CI 0.58-0.88) and in-context learning (F1-score 0.65; 95% CI 0.47-0.83). External validation on the Baystate dataset showed good generalization for distinguishing certain from uncertain cases (F1-score 0.77; 95% CI 0.70-0.83). Despite its strong performance, PECertainty was rated as less interpretable than fine-tuned GPT-3.5 by radiologists (t test, P<.05).

PECertainty enables accurate and data-efficient assessment of diagnostic certainty from free-text CTPA reports in low-resource settings. As an open-source, lightweight alternative to proprietary LLMs, it may support more precise communication between radiologists and referring physicians, with interpretability identified as a key direction for improvement.

To investigate the role of the gut-lung axis in respiratory infection under hypobaric hypoxia and the therapeutic potential of fecal microbiota transplantation (FMT).

Rats were exposed to hypobaric hypoxia (simulated 5000 m) for 14 days. Gut microbiota and serum short-chain fatty acids (SCFAs) were analyzed via 16S rRNA sequencing and GC-MS. Rats were then infected with Streptococcus pneumoniae and treated with FMT. Lung inflammation, NLRP3 inflammasome activity, cytokines, bacterial load, and secretory IgA (sIgA) were assessed.

Hypobaric hypoxia triggered gut dysbiosis, marked by reduced abundance of Firmicutes D and Lactobacillus, elevated Bacteroidota, and decreased SCFA levels..FMT restored microbiota composition, increased acetic and butyric acid levels, and attenuated lung inflammation. FMT also enhanced NLRP3 inflammasome activation (NLRP3, ASC, Caspase-1), elevated IL-1β, IL-6, and TNF-α in BALF, reduced bacterial colonies, and increased airway sIgA in infected rats.

FMT alleviates hypobaric hypoxia-aggravated respiratory infection by restoring gut microbiota, modulating SCFAs, and enhancing NLRP3-mediated mucosal immunity, highlighting the gut-lung axis as a therapeutic target.

Sepsis-associated acute lung injury (SALI) is characterized by endothelial barrier dysfunction and capillary leakage. Ulinastatin (UTI), a serine protease inhibitor with recognized clinical benefits in sepsis, has been reported to protect endothelial function, but the underlying mechanisms remain incompletely defined. This study investigated the protective effects of UTI against SALI and its specific mechanism of action. We found that UTI attenuated lung injury and endothelial dysfunction in both cecal ligation and puncture (CLP)-induced septic rats and LPS-stimulated human umbilical vein endothelial cells (HUVECs). UTI treatment reduced the expression of angiopoietin-2 (Ang-2), a key mediator of vascular destabilization, and exerted similar protective effects on endothelial function as dexamethasone (DEX). Mechanistically, UTI was demonstrated to have a stable interaction and favorable binding affinity to PI3K by docking and activating the PI3K/Akt signaling pathway. This led to phosphorylation and subsequent nuclear export of the transcription factor FoxO1, thereby suppressing FoxO1-dependent Ang-2 transcription. The protective effects of UTI on capillary leakage and junctional protein integrity were abolished by the PI3K inhibitor wortmannin. In conclusion, our findings demonstrate that UTI alleviates SALI by disrupting an Ang-2-mediated vicious cycle via the PI3K/Akt/FoxO1 pathway, revealing a novel mechanistic insight into its therapeutic action against sepsis-induced vascular leakage.