Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Idiopathic pulmonary fibrosis (IPF) is a difficult to treat condition to treat with a high mortality rate. While preclinical models such as Bleomycin (Bleo)-induced fibrosis recapitulate some aspects of IPF, new models that more closely mimic the disease are warranted. We have developed and characterized a novel model in BALB/c mice using a transient overexpression of IL-6 combined with Bleo. This model’s transcriptomic signature was compared to published human IPF datasets. BALB/c females were treated with AdIL-6 in combination with Bleo (AdIL-6+Bleo) or control comparators, and underwent assessments of histopathology (ECM, α-SMA accumulation), collagen content and lung physiology (Elastance, EST). Flow cytometry was used to characterize T cell and Macrophage subsets, and T cell depletion studies (anti-CD4/CD8) were completed to assess T cells role in fibrosis. Bulk RNA sequencing generated gene signatures were compared to that of other rodent fibrosis models and published human datasets of IPF datasets. The AdIL-6+Bleo treatment resulted in robust fibrosis measures (day21), sustained fibrosis until at least day 50, a unique cytokine profile at day 7, and increased activated CD4+Tcells, CD8+Tcells, and CD16+MHChi/Clec7a/iNOS-/Arg1-/CD206- macrophages. T cell depletion markedly decreased fi-brotic responses and this population of macrophages. The Day 21 AdIL-6+Bleo transcriptome shared more genes with each of two human IPF datasets than Bleo alone in C57Bl/6 mice or other rodent models. We conclude that AdIL-6+Bleo in BALB/c mice offers a superior preclinical model for studying IPF mechanisms and potential therapeutic intervention.

Medication non-adherence remains a substantial obstacle in asthma care, prompting the exploration of novel therapeutic modalities that prioritize rapid symptom relief, anti-inflammatory activity and facilitate patients’ compliance. This task is well served by a new form of therapy - inhaled triple-combination medications ICS/LABA/LAMA (inhaled glucocorticosteroid/long-acting beta2-agonist/long-acting muscarinic antagonist). The integration of three medications within a singular inhalation device culminates in the reduction of the effective dose of the principal therapeutic agent for asthma management, namely, ICS. This consolidation yields a dual benefit of minimizing the likelihood of adverse effects typically linked with ICS while concurrently optimizing bronchodilator efficacy. The accumulated evidence suggests that adding LAMA to a medium- or high-dose ICS/LABA results in a decrease of asthma exacerbations compared to medium- or high-dose ICS/LABA alone, accompanied by sustained enhancements in lung function parameters. We propose in adult patients experiencing suboptimal asthma control despite medium/high-dose ICS/LABA treatment - regardless of adherence to GINA-recommended strategies, such as MART therapy as a first-line approach or alternative second-line strategies - the preferred course for intensifying asthma therapy involves the addition of a LAMA, ideally in the form of SITT.

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

Asthma is a complex syndrome with multiple phenotypes and endotypes, and current diagnostic tools often fail to address this, therefore there is an increasing need for new predicting biomarkers for asthma which can enable personalized treatment strategies. Biomarkers can facilitate earlier diagnosis of asthma, potentially identifying the disease before clinical symptoms appear. This allows for early intervention, which can prevent asthma progression and complications and improve long-term outcomes. Reliable biomarkers can help in monitoring disease activity and treatment efficacy in real-time and can also lead to better disease management, reducing hospitalizations, emergency visits, and overall healthcare costs associated with poorly controlled asthma. Severe asthma patients often do not respond well to standard treatments. New biomarkers can help identify these patients and guide the development of novel therapeutic approaches specifically for severe asthma. In this review we summarize different candidate biomarkers on several levels of investigation: Genetic, subclinical inflammatory, allergen-specific immune response, and trained immunity, which could be promising for the early detection of asthma and better management of exacerbation and severity of symptoms in children.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Extracellular vesicles (EVs) hold enormous potential in the diagnosis and treatment of diseases, benefit from their roles in intercellular signaling, as well as their plentiful presence and stability in body fluids. However, conventional EV isolation methods are labor-intensive, and harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as limited sensitivity and specificity of traditional EV analysis methods hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the separation advantages of microfluidic technology in enhancing EV capture efficiency and precise targeting, while summarizing its analytical role in targeted detection and discussing the significance of EV detection in the tumor microenvironment, providing a direction for achieving automated and high-throughput EV detection in clinical samples.

The current Covid-19 pandemic has hugely disrupted the delivery of routine and established medical care. Patients can develop a wide range of clinical signs and symptoms from a cough and fever to severe respiratory failure. There is an ongoing argument on a concise investigative pathway to ensure the safety of all healthcare workers. The stethoscope can help with any clinical respiratory assessment but the risk of cross infection is high. Computer tomography should not be routinely performed. There is a potential place for lung ultrasound but outcomes are not yet determined.

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

The NCO functional group of 3-isocyanatoproply triethoxysilane (IPTS) and the OH functional group of DOPO-BQ were used to conduct an addition reaction. Following completion of the reaction, triglycidyl isocyanurate (TGIC) was introduced to conduct a ring-opening reaction. Subsequently, a sol-gel method was used to take place a hydrolysis- condensation reaction on TGIC-IPTS-DOPO-BQ to form a hyperbranched nitrogen–phosphorous–silicon (HBNPSi) flame retardant. This flame retardant was incorporated into a polyurethane (PU) matrix to prepare a hybrid material. Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), limiting oxygen index (LOI), UV-VIS spectrophotometry, and Raman analysis were conducted to structure characterization and analyzed transparency, thermal stability, flame retardancy, and residual char to understand the flame retardant mechanism of prepared hybrid materials. After the flame retardant was added, the maximum degradation rate decreased from −36 wt%/min to −17 wt%/min, the integral procedure decomposition temperature (IPDT) increased from 348 ℃ to 488 ℃, and the char yield increased from 0.7 to 8.1 wt%. The aforementioned results verified that thermal stability of PU can be improved after adding HBNPSi. The LOI analysis indicated that the pristine PU was flammable because the LOI of pristine PU was only 19. When the content of added HBNPSi was 40%, the LOI value was 26; thus the PU hybrid became nonflammable.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Background: Features of post-traumatic stress disorder and anxiety may be present in Pulmonary Embolism (PE) patients along with impaired Quality of Life (QoL). We aim to evaluate health related QoL, anxiety and satisfaction with life, during the pandemic, in patients with a PE. Methods: Patients with PE were enrolled during their follow-up. All participants completed the Short Form 36 (SF-36) questionnaire, the State Trait Anxiety Inventory (STAI) X1 and X2 form, and the Satisfaction with Life Scale (SWLS). Results: 92 PE patients were included (mean age±SD=62.50±15.33 years, 56.5% males). Most of the mean values of the SF36 subscales were above the normative value except for “physical role functioning”) (45.92±42.41). “Emotional role functioning” (51.26±43.31) and “general health perceptions” (GH) (54.02±18.79) were slightly above the normative value of 50. Mean STAIX1 levels were 37.05±11.17 and mean STAIX2 levels were 39.80±10.47. Mean SWLS levels were 23.31±6.58. According to multiple linear regression analysis, mental healthscore (MH) and GH were predictive of SWLS(F (10,76) = 10.576, p

Background: The secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, heralds the onset of the inflammatory cascade and immune effector infiltration in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown. Methods: We recruited 40 participants with asthma who were categorized into four severity groups as per the Global Initiative for Asthma (GINA) classifications (10 in each group of GINA-1/2, -3, -4, and -5). Cells were derived from buccal, nasal and throat brushings, and intracellular alarmin cytokine expression (TSLP, IL-25, and IL-33) was assessed in cytokeratin 8+ (Ck8+) epithelial cells immediately after collection using flow cytometry with fluorescence minus one (FMO) controls. We assessed differences in alarmin cytokine expressions across asthma severity using quantile regression adjusted for age and sex. Results: Of all patients, 24 (60%) were females with a mean (standard deviation [SD]) age of 41 (16) years. TSLP levels in Ck8+ epithelial cells in nasal samples of GINA-5 patients were significantly (p=0.03) higher than other GINA groups after adjusting for age and sex but did not differ between patients with and without nasal comorbidities. However, we did not find any significant changes in TSLP levels in Ck8+ epithelial cells in buccal and throat samples across GINA groups. IL-25 or IL-33 (obtained from nasal, buccal, and throat epithelial cell samples) were not significantly different across GINA groups. Conclusions: Our study demonstrates for the first time that Ck8+ nasal epithelial cells from GINA-5 asthmatics express elevated levels of TSLP.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Based on the major, trace element, and isotope data of the Cenozoic basalts in the study area, it is indicated that the basalts in this region can be classified into three distinct magma systems: alka-li basalts, tholeiite basalts, and Nushan alkali basalts. The geochemical characteristics observed in the studied basalts indicate that the mantle source in this region might have experienced met-asomatic processes prior to partial melting, which could be linked to an ancient subduction pro-cess. Combining the geochemical characteristics in the studied basalts with previous research, we propose that the underlying mantle source in Anhui province may have undergone metaso-matism due to the carbonatitic melts. These melts are believed to have originated from car-bonated eclogite, derived from subducted Pacific slab materials present in the deeper mantle. According to the Sr-Nd isotope data, it is suggested that the mantle source in the Nushan region could be derived from a depleted asthenospheric mantle, while the basaltic composition in the Niugang area may be representative of the mantle's end components associated with the EM-I enriched mantle source present in this study area. Therefore, we propose that the Anhui basalts may have originated from the partial melting of a mantle source representing a mixing of two end-members: DMM (Depleted MORB Mantle) and EM-Ⅰ (Enriched Mantle 1). The Anhui basal-tic magmas may have originated from the partial melting of EM-Ⅰ, potentially influenced by upwelling asthenospheric mantle or asthenospheric diapirism processes. The mantle source in the study area experiences partial melting at 1-5%, 15%, and 1-10%, resulting in the formation of parent magmas for alkali basalt, tholeiitic basalt, and Nushan alkali basalt. Subsequently, the parent magmas experienced fractional crystallization processes, which included minerals like olivine, pyroxene, and plagioclase. This led to the formation of various types of basalt in the study area.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p<0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p<0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p<0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

Background: The aim of this study was to investigate a series of complete blood cell count – based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1,395; IQR: 929–3,334 vs. 945; IQR: 552–1,373, p = 0.025), but only NLR and NMR remained independently related with clinical response in multivariate logistic regression. In univariate analysis white blood cells (OR:1.2202; 95% CI: 1.0339 - 1.4400, p=0.019), neutrophils (OR:1.2916; 95% CI: 1.0692 - 1.5604, p=0.008), NLR (OR:1.3601: 95% CI: 1.0949 - 1.6896, p=0.005) and NMR (OR:1.2159; 95% CI: 1.00396 - 1.4221, p=0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR and MLR were independently associated with survival; NLR at a cut-off value of 4.0 showed the better AUC (0.749) in predicting survival. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions. The presence of ILD poses diagnostic and therapeutic challenges in lung cancer management, including difficulties in interpreting radiological findings, increased susceptibility to treatment-related toxicities, such as acute exacerbation of ILD after surgery and pneumonitis after radiation therapy and immunotherapy. Moreover, due to the lack of large, phase III randomized controlled trials in patients with lung cancer and ILDs, the evidence-based therapeutic options remain limited. The role of antifibrotic treatment in the prevention of lung-cancer-related treatment toxicities remains to be elucidated. Emerging diagnostic modalities and biomarkers, and optimizing personalized treatment strategies are essential to improve outcomes in this patient population.

Objectives: Imaging exams are requested in intensive care units as a diagnostic, evaluation, and clinical monitoring method. While Chest Computed Tomography is the gold standard, Chest X-ray is the exam usually performed in routine care. Lung ultrasound has been gaining ground as it is a reliable exam performed at the bedside without exposure to radiation and at a low cost. This study aimed to evaluate the accuracy of bedside lung ultrasounds performed by pediatric intensivists as a diagnostic method. Methods: A prospective, diagnostic test-type study comparing bedside lung ultrasound performed by a pediatric intensivist with the evaluation of chest X-ray and lung ultrasound performed by a radiologist. Result: 48 patients on mechanical ventilation, aged from 1 month to 14 years, were analyzed, corresponding to 95 chest X-ray exams and 95 lung ultrasound exams. The Kappa agreement coefficients between the pediatric intensivist and the radiologist, both analyzing the lung ultrasound, were: normal report (1.0), atelectasis (1.0), pneumothorax (1.0), consolidation (0.97), pleural effusion (0.95), and pulmonary edema (0.90). Sensitivity, specificity, and accuracy of lung ultrasound were, respectively, normal report (50%; 91.8%; 82.1%), consolidation (88.3%; 57.1%; 76.8%), atelectasis (11.1%; 90.7%; 83.2%), edema (0; 70.2%; 70.5%), pneumothorax (83.3%; 94.4%; 93.7%), and pleural effusion (71.4%; 73%; 72.6%). Conclusion: The pediatric intensivist was skilled in examining and diagnosing lung injuries. Lung ultrasound showed good sensitivity, specificity, and accuracy when the pediatric intensivist performed when diagnosing consolidation, pleural effusion, and pneumothorax. Furthermore, lung ultrasound demonstrated better accuracy in evaluating pulmonary edema when compared with chest X-ray.

This paper proposes a compact planar Wi-Fi antenna with optimized radiation patterns for small uncrewed aerial vehicle (UAV) applications in both urban and open areas. It is suitable for mounting on the outermost side of the non-metallic wing of small UAVs. It has small dimensions of 16.5 mm (L) by 30.3 mm (W) by 1.6 mm (h), and the measured results of its prototype are in agreement with simulated data. Its impedance bandwidths over the two frequency ranges are 2.11 to 2.58 GHz and 5.06 to 7.5 GHz ( ). At 5.8 GHz, it has stronger radiation below the small UAV to reduce interference from rare-use directions. Its maximum radiations, the directions of the maximum radiation in each elevation plane, are below the UAV and between 14° and 29° from the horizontal plane. At 2.4 GHz, it has quasi-omnidirectional radiation to ensure a stable link in all directions, and its maximum radiations are near the horizontal plane. The optimized radiation patterns at 5.8 and 2.4 GHz can provide more antenna gain when the small UAV flies farther in urban and open areas, respectively. In addition, it has good vertically polarized radiation for long-distance applications.

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetes patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. The work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to a susceptible host surface, evading host defences, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, and development of resistance to the antifungal drug, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p<0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p < 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p<0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

The objective of this study was to investigate the impact of athletes' respiratory muscle strength, as assessed through maximal inspiratory (MIP) and expiratory pressure (MEP), on aerobic endurance, as indicated by maximal oxygen consump-tion (Max VO2) kinetics. Respiratory muscle strength was assessed using a digital spirometer (Pony FX Cosmed, Italy), while maximal oxygen utilization capacity was measured using a breath-by-breath automatic portable gas analysis system (Cosmed K5, Italy). Statistical analysis was conducted utilizing SPSS 22.0. Based on the standardized regression coefficients (β), it was found that MEP (mean ± SD: 130.95 ± 42.82) and inspiratory diaphragmatic circumference values significantly influenced ventilatory equivalent (VE), oxygen consumption (VO2), and carbon dioxide pro-duction (VCO2). Conversely, the remaining predictor variables did not exhibit a sig-nificant effect on VE (mean ± SD: 134.80 ± 36.69), VO2 (mean ± SD: 3877.52 ± 868.47 ml), and VCO2 (mean ± SD: 4301.27 ± 1001.07 ml). In contrast, measurements of chest circumference (mean ± SD: 91.40 ± 10.72 cm), MEP, and diaphragmatic cir-cumference during inspiration (mean ± SD: 95.20 ± 10.21 cm) were found to signifi-cantly impact Max VO2 (mean ± SD: 58.52 ± 10.74 ml/kg/min), while the other pre-dictor variables did not demonstrate a significant effect on Max VO2. Conclusively, the study revealed that measured values of diaphragmatic circumference during inspiration and MEP exerted a notable influence on Max VO2, VE, VO2, and VCO2. Our findings underscore the importance of considering respiratory muscle strength in assessing and enhancing athletes' aerobic performance. These insights contribute to a deeper understanding of the interplay between respiratory function and exercise capacity, offering potential avenues for optimizing training regimens and perfor-mance outcomes in athletic contexts.

Idiopathic pulmonary fibrosis, a chronic and fatal condition with no effective cure, is a challenging disease within the group of interstitial lung diseases. The pathogenic mechanisms of this disease are still not fully understood. In this context, the research on miRNAs, which are small non-coding RNAs that regulate messenger RNAs, is of utmost importance. These miRNAs, released into the circulation outside the cell through exosomes, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. The analysis of miRNAs in the serum/plasma of IPF patients has opened up new possibilities in the search for biomarkers. This review focuses on circulating miRNAs validated by real-time PCR in IPF and the evidence reported about the pulmonary fibrotic process.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p < 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

A primary challenge facing conservationists is reconciling the human needs of forest adjacent communities with the needs of conserving forest biodiversity, especially in tropical regions with growing populations of rural poor. Agroforestry has the potential to simultaneously provide for human needs and enhance forest biodiversity, but the complex interactions and feedbacks between the social and natural dimensions are relatively undescribed and thus systematic implementation is rare. The attributes of trees on farms required for human needs and conservation value may conflict. For example, exotic species in monoculture may provide the most economic value for farmers, while relic or planted indigenous tree mixtures may be more valuable for biological conservation. The objective of this study was to explore whether agroforestry practices in a moist tropical forest ecosystem in Kenya can simultaneously provide timber and fuelwood value to small-holder farmers while extending forest tree biodiversity. We described the agroforestry attributes on farms around a tropical forest, assessed the relationship between number and biomass of timber/fuelwood trees and tree biodiversity, and explored the relationships between forest tree diversity attributes and farm tree diversity attributes on a landscape scale using spatial analysis. We found that the diversity and number of trees on farms in this area are extensive yet variable, but that no significant relationship exists between the number of timber/fuelwood trees and tree diversity. This suggests that the two values of agroforestry may not be in conflict, due mainly to the high diversity of trees used for fuelwood. We also found that trees on farms in the larger landscape add to the conservation value of forest tree biodiversity and could be important components in conservation management. If agroforestry is to play an increasingly active role in conserving biodiversity in human-dominated landscapes, particularly in areas of dense subsistence farmer populations, increase recognition needs to be given to farmer’s perception of the value of trees and their selection of what trees to plant or maintain.

This research develops the Osteoporosis Knowledge, Attitude, and Behaviors Questionnaire (OKABQ) with the intent to evaluate levels of osteoporosis knowledge, attitude and behavior change. The aims of the study were to develop and validate the OKABQ; and to establish a mediation model of the research. A quantitative, descriptive, and instrumental study was conducted in two phases: Phase I—development of the scale through Delphi Method by osteoporosis experts; Phase II—evaluation of the validity and reliability of the scale and construction of a mediation model using SmartPLS. In Phase I, the content validity index (CVI) of the questionnaire was higher than 0.96 and the inter-rater reliability (IRR) kappa was 1.00. In Phase II, exploratory factor analysis showed that two predominating factors of attitude as a mediation were addressed by the 26-item OKABQ. The indirect effect results from the estimated model indicates that attitude mediates the relationship between knowledge and behaviors (β = 0.114, t = 2.627, p < 0.001), which is positive and statistically significant. We concluded that the OKABQ is a valid measure of osteoporosis knowledge, attitude and behaviors for women with osteoporosis. These assessment results could assist healthcare providers in mitigating insufficiency on health education.

Many corporations have now revised their value statements to showcase their commitment to sustainable development and green business due to the pressing issues of climate and environmental damage. Despite the importance of value statements that can direct companies to achieve sustainable goals, what kind of values can be perceived as organizational orientations to sustainability remains unknown. This study explores how the general public views the inclusion of sustainable components in value statements from the listed companies in Hong Kong by using Q-sort methodology (n = 30). Analyzing the final sample of 40 value statements extracted from 27 listed companies, we identified three factors related to sustainability, namely, Empowering business process management, Empowering customer-centric excellence, and Empowering sustainable progress. This study provides an additional component to the traditional triple bottom line by suggesting that internal operation of a company is an emerging idea to understand corporate sustainability.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

The process of preparing anti-glare thin films by spray-coating silica sol-gel to soda-lime glass was exclusively and statistically studied in this paper. The effects of sol-gel deliver pressure, air transport pressure, and spray gun displacement speed on the gloss, haze, arithmetic mean surface roughness, and total transmittance light were analyzed. The experimental results indicate that the factors of sol-gel deliver pressure, air transport pressure, and displacement speed exhibit significant effect on the haze, gloss, and Ra. In contrast, the variation of total transmittance light with these three factors are insignificant. Because the anti-glare property is predominantly determined by low gloss and high haze, therefore, we aim to minimize gloss and maximize haze to achieve high anti-glare. Central composite design and response rurface methodology are employed to analyze the main and interaction effects of the three factors through quadratic polynomial equations, which are confirmed by the analysis of variance and R². The response surface methodology predict the lowest gloss and highest haze are 9.2 GU and 57.0%, corresponding to the sol-gel deliver pressure, air-transport pressure, and displacement speed of 250 kPa, 560 kPa, and 140 mm/s, and 340 kPa, 620 kPa, and 20 mm/s, respectively. Comparing the predicted optimal data with the real experimental results validates the applicability of the mathematical model. This study provides an important basis for the subsequent production of anti-glare glass with different specifications to satisfy the market demand.

Abstract. This paper proposes a Second Order Terminal Sliding Mode (2TSM) approach to the trajectory tracking of Differential Drive Mobile Robot (DDMR). Within this cascaded control scheme, the 2TSM dynamic controller, at the inner most loop, tracks the robot’s velocity quantities; while a kinematic controller, at the outer most loop, regulates the robot’s positions. In this manner, chattering is greatly attenuated and finite time convergence is guaranteed by the second order TSM manifold which involves higher order derivatives of the state variables, resulting in inherently robust as well as fast and better tracking precision. The simulation results demonstrate the merit of the proposed control methods.

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs 3 days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host’s capacity to deal with infection.

In this study, a composite flame retardant was created by combining fish scale (FS), fishery waste, and ammonium polyphosphate (APP), a commercially available flame retardant. The composite flame retardant was added to epoxy resin (EP) to form an EP/APP/FS composite that prevents burns and is environmentally friendly. The use of FS conforms to the concept of circular economy and lowers costs by reducing the consumption of APP. Thermogravimetric analysis (TGA), integral procedural decomposition temperature (IPDT), pyrolysis kinetics, limiting oxygen index (LOI), the Underwriters Laboratories 94 (UL94) flammability test, scanning election microscopy, Raman spectroscopy, and energy-dispersive X-ray spectroscopy were used to determine the thermal properties, flame retardant properties, flame retardant mechanism, char morphology, and composition of the composites. The TGA results indicated that the addition of 40% flame retardant raised the char residue from 16.45 wt% (pure EP) to 36.07 wt%, IPDT from 685.6 °C (pure EP) to 1143.1°C, LOI from 21% (pure EP) to 30%, and UL94 classification from fail (pure EP) to V-0. These results suggest an increase in char residue, which indicates better protection of the polymer matrix material. The improvements in IPDT, LOI, and UL94 classification, which indicate greater thermal stability, lower flammability (from flammable to fireproof), and higher flammability rating (from fail to V-0), respectively, suggest that the composite material has favorable thermal properties and is less inflammable.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Background: Respiratory syncytial virus[ RSV] is a lethal overwhelming defectiveness that influences people all over the world. The infection gets down in the lower respiratory tract and does not disperse to the remainder of the body. The objective of the study: Bioinformatics was used to create an mRNA vaccine against the Respiratory syncytial virus( RSV). Methodology: Lipid nanoparticle vaccines containing the Respiratory syncytial virus's surface fusion protein's mRNA were created for the current screening experimental investigation. Lipid nanoparticles[ LNP] with a particle size of around 90 nanometres that were created using the hot micro-emulsion process comprise the current vaccine delivery system. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current immunization lacks antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies worsen infection by enhancing viral entrance and replication in the host cells, activating cytokines and the complement cascade through the production of immunological complexes, or both. However, the current LPN-RSV mRNA vaccine of the surface fusion protein resulted in the formation of potent neutralizing antibodies with persistent protection, especially for newborns and elderly individuals who get the ideal dose regimen. Conclusion: The invention of the LNP-mRNA RSV vaccine, which might prevent RSV-caused bronchiolitis and fatal pneumonia, made the current study promising

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

Background: The Advanced Lung Cancer Inflammation Index (ALI) is a novel, comprehensive index that integrates inflammation and nutritional status, incorporating parameters such as albumin, body mass index (BMI), and the neutrophil-to-lymphocyte ratio (NLR). Unlike traditional inflammation biomarkers, this study aims to evaluate the prognosis of IPF patients by considering both inflammation and nutritional status. Method: A total of 102 patients with IPF were included in the study. Clinical data were obtained from the patients' medical records. NLR and ALI score were calculated based on data collected at the initiation of antifibrotic treatment using the following formula: Neut/Lym and albumin × BMI / NLR. Results: IPF subject subgroups in terms of ALI based on gender–age–physiology (GAP) stages (1,2,3), FVC (median split,

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Global public health systems have continuously faced challenges from the advent of novel infectious illnesses, necessitating quick and efficient actions to stop their spread.First discovered in Saudi Arabia in 2012, Middle East respiratory syndrome (MERS) is a viral respiratory disorder caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Since then, the nation has reported most cases and fatalities related to this sickness, with occasional outbreaks happening in other nations and regions. Severe sickness and high mortality are caused by MERS-CoV, especially in older persons and those with underlying chronic conditions. Through intimate contact, the virus can spread from people to dromedary camels and vice versa. It has sparked multiple epidemics both domestically and abroad in the Middle East, raising the possibility of fatalities and widespread transmission, especially in susceptible groups. The Riyadh region was the main target of the most current MERS-CoV outbreak in Saudi Arabia, which began in 2023 and ended on September 1, 2023, with 312 confirmed cases and ninety-seven fatalities. With the use of published studies and their contributions to the field, we hope to present a thorough overview of the MERS-CoV outbreak in Saudi Arabia in this review of the literature, including its epidemiological investigation, public health response, impact, and lessons learned. In addition to highlighting the importance and continued relevance of this problem, our work suggests ways to lower the risk of MERS-CoV transmission and avert further outbreaks.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

Eosinophils are key therapeutic targets in severe asthma as they accumulate in tissues, resulting in local damage through the release of toxic mediators. Benralizumab is a monoclonal antibody with a direct anti-eosinophilic activity that has proved significant clinical efficacy in patients with severe eosinophilic asthma, and its use in real-life went well beyond what we had expected from the pivotal trials, especially in the reduction of asthma exacerbations and oral steroids usage. Benralizumab induces eosinophil apoptosis due to a mechanism of antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells. Within this review, we will discuss benralizumab pharmacological and pharmacokinetic aspects in the treatment of severe asthma, with an emphasis on the novel immunological effects of benralizumab on NK cells. Overall, these findings account for the clinical efficacy and safety profile of benralizuamb, previously described in patients with an eosinophilic phenotype of the disease.

Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity which occur across the tumor microenvironment (TME). The goal of this study is to get insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis Lung Carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains - capillary and extracellular space. Anisotropy in tumor structure causes nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Abstract This study delved into the application of various machine learning (ML) models for the classification of lung cancer levels. Through meticulous monitoring of parameters such as minimum child weight and learning rate, efforts were made to mitigate overfitting while optimizing model performance. The Deep Neural Network (DNN) emerged as a standout performer, showcasing robust performance across training, validation, and testing stages. Ensemble methods like voting and bagging also demonstrated promising results. However, Support Vector Machine (SVM) models with the Sigmoid kernel faced challenges in achieving satisfactory performance. Overall, the investigation sheds light on the efficacy of different ML models in lung cancer level classification and underscores the importance of parameter tuning to address overfitting concerns.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Lung cancer (LC) continues to be an important public health problem being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never smoker early-onset LC patient does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer predisposing genes in non-smokers patients, giving experimental support to a model of a “private genetic epidemiology”. Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib’s model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bio-informatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: i) downregulation in LC tissue (indicating “second hit” in tumor suppressor genes); ii) upregulation in cancer tissue (likely oncogene); iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with functional effect in tumor predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of familial clustering of non-small cell lung cancer. In conclusion, these findings indicate that each patient has his/her own “predisposing signature” to cancer development and suggest the use of personalized therapeutic strategies in lung cancer.

Background: Permanent tracheostomy because of total laryngectomy surgery entails great conse-quences for the patient regarding respiratory physiopathology such as the filtering, humidifying, and heating function of the air by the nose is lost. The use of special stomal filters can determine adequate protection of the trachea-broncho-pulmonary system with a reduction in respiratory pathologies. In fact, in most cases laryngectomee patients are first cigarette smokers who for this reason already have also respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, multiple times, as reported in the literature, the patient tends to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for the laryngectomee patient during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomee patients, subjected to medi-um-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT) which involves a sustained walk lasting six minutes, with evaluation , every 60 seconds, heart rate, oxygen saturation and meters travelled; furthermore, it examines two sub-jective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index.

In the contemporary era, youthful and healthy skin is a pivotal determinant of beauty. Choices pertaining to one's dietary and lifestyle practices wield substantial influence over skin health. Currently, the focal point of attention lies in strategies to delay skin aging and maintain skin quality. Remarkably, the skin, the body's largest organ, serves as the primary defense barrier against external elements. Skin aging encompasses intrinsic and extrinsic categories, both susceptible to genetic, lifestyle, and environmental factors. Given the strides in science and technology, the pursuit of effective and safe interventions for skin aging assumes paramount importance. Thus, this review delves into the intricate relationship between diet, lifestyle, and skin aging, culminating in an exploration of the crucial role played by excess iron in this intricate nexus. Understanding these dynamics holds promise for advancing our knowledge of skincare and the quest for timeless vitality.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a continually advancing respiratory disorder, characterized by enduring airflow limitation along with long-lasting inflammation in the airways. An expanding pool of evidence is emphasizing how mitochondrial dysfunction directly impacts the development and progression of COPD. This comprehensive review delves deeper into the intricate cellular and molecular biology of mitochondria within the framework of COPD, spotlighting significant alterations in structure and function that accompany mitochondrial dysfunction. In this narrative, we delve into the observed changes in mitochondrial shape, behavior, and respiratory chain complex alterations seen in individuals afflicted with COPD. The discussion includes implications on cellular signaling pathways and how this affects the natural process of programmed cellular death (apoptosis) and cellular aging, particularly in reference to COPD. Additionally, we consolidate ongoing therapeutic strategies, honing in on the management of COPD through a focus on mitochondrial dysfunction. Prominent among these strategies is the potential role of antioxidants and mitochondrial biogenesis inducers, which are emerging as promising fields of intervention. Furthermore, we embark on an overview of the possible use of mitochondrial biomarkers as innovative tools in diagnosing COPD, evaluating disease progression, and monitoring the efficacy of COPD treatments. As we unravel the rather complex interplay between mitochondrial biology and COPD, this review highlights the critical importance of formulating treatments that target mitochondrial dysfunction. The ultimate goal of these strategic interventions is to slow down the rate of COPD progression and significantly improve patient outcomes. Lastly, though our understanding of the nexus between COPD and mitochondrial dysfunction has significantly enhanced, ample scope remains for further investigation. Improved insights into the mechanisms of mitochondrial dysfunction, discovered biomarkers, and targeted therapies could encompass a revolutionary step towards comprehensive disease management. The future of COPD treatment seems to lean towards a combination of strategies, prioritizing not only the management of symptoms but also focused on preserving and restoring lung function, improving physical capacity, and enhancing quality of life for COPD patients.

In recent years, the prevalence of tobacco and electronic cigarette (e-cigarette) use among adolescents has raised significant public health concerns worldwide. This study aims to investigate respiratory symptoms among Polish adolescents. We conducted an online survey among Polish school students from all provinces, collecting data over two months in Spring 2021. Students voluntarily complete the anonymous survey, answering questions about respiratory symptoms, smoking habits (both traditional and electronic cigarettes), and demographic information. Analysis focused on four subgroups: non-tobacco users, traditional cigarette smokers, e-cigarette users, and dual users, totaling 10,388 pupils aged 12-18 years, predominantly attending secondary technical and comprehensive schools. A total of 10388 pupils participated in the study, 55.6 % (5778) of whom were girls and 44.4 % (4610) boys. Adolescents, who admitted using both e-cigarettes and traditional cigarettes experienced more frequent episodes of cough during the day (39.70%) and at night (18.40%) compared to their peers in other groups. Chest discomfort, including pain and pressure, was also reported more often by adolescents, who used e-cigarettes and traditional cigarettes concurrently (27.60%) compared to their peers in other groups. Chest pressure was experienced less commonly by non-smoking adolescents (14.40%) than by smokers (18.90%). Higher severity of cough during the day and at night was observed in the group of adolescents using traditional cigarettes and e-cigarettes concurrently compared to the other groups. The adolescents in the dual user group experienced more severe dyspnoea and wheezing compared to the other groups included in the comparison. The results of this study confirm the correlation between the occurrence of respiratory symptoms in adolescents who smoke cigarettes, use e-cigarettes and in dual users. The respiratory symptoms occur most frequently and are the most severe in the group of adolescents who use e-cigarettes and traditional cigarettes

In our previous study, a novel barrier processing on a porous low-dielectric constant (low-k) film was developed: an ultrathin Mn oxide on a nitrogen-stuffed porous carbon-doped organosilica film (p-SiOCH(N)) as a barrier of the Cu film was fabricated. To form a better barrier Mn₂O_3-xN film, an additional annealing at 450°C was implemented. In this study, the electrical characteristics and reliability of this integrated Cu/Mn₂O_3-xN/p-SiOCH(N)/Si structure is investigated. The proposed Cu/Mn₂O_3-xN/p-SiOCH(N)/Si capacitors exhibited poor dielectric breakdown characteristics in the as-fabricted stage, although, less degradation was found after thermal stress. Moreover, its time-dependence-dielectric-breakdown electric-field acceleration factor slightly increased after thermal stress, leading to a larger dielectric lifetime in a low electric-field as compared to other MIS capacitors. Furthermore, its Cu barrier ability under electrical or thermal stress was improved. As a consequent, the proposed Cu/Mn₂O_3-xN/p-SiCOH(N) scheme is a promising integrity for back-end-of-line interconnects.

This study used the sol–gel method to synthesize a non-halogenated hyperbranched flame retardant containing nitrogen, phosphorus and silicon, HBNPSi, which was then added to a polyurethane (PU) matrix to form an organic–inorganic hybrid material. Using 29Si nuclear magnetic resonance, energy-dispersive X-ray spectroscopy of P- and Si-mapping, scanning electron microscopy, and X-ray photoelectron spectroscopy, this study determined the organic and inorganic dispersity, morphology, and flame retardance mechanism of the hybrid material. The condensation density of the hybrid material PU/HBNPSi was found to be 74.4%. High condensation density indicates a dense network structure of the material. The P- and Si-mapping showed that adding inorganic additives in quantities of either 20% or 40% results in homogeneous dispersion of the inorganic fillers in the polymer matrix without agglomeration, indicating that the organic and inorganic phases had excellent compatibility. In the burning test, adding HBNPSi to PU resulted in the material passing the UL-94 standard at the V2 level, unlike the pristine PU, which did not meet the standard. The results demonstrated that after non-halogenated flame retardant was added to PU, the material’s flammability and dripping were lower, thereby proving that flame retardants containing elements such as nitrogen, phosphorus, and silicon exert an excellent flame retardant synergistic effect.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Vascular endothelial growth factor (VEGF) is a important biomarker with significant clinical importance. It plays a key role in angiogenesis, would healing, tumor growth, lung development, and in retinal diseases. Hence, detecting and quantifying VEGF is crucial in clinical diagnosis and prognosis of various diseases. In this work, a simple but highly cost-effective platform is developed for VEGF protein detection by using commercially available interdigitated sensors that are modified through surface chemistry tagged with DNA aptamer grafting. The dielectric characteristics between the fingers of sensor is modulated by the negatively charged aptamer-VEGF capture and the impedance is estimated using impedance analyzer. Impedance spectra tests was compared between pristine unmodified, functionalized monolayer surfaces and aptamer-grafted surfaces in order to evaluate the efficacy of VEGF detection. In our results, the sensitivity experiments as conducted had shown the ability of the interdigitated sensor to detect VEGF at a low concentration of 5 pM. The specificity of the functionalized sensor in detecting VEGF is further studied by comparing the impedance to platelet-derived growth factor (PDGF), and the results confirm the specificity of the sensor. Finally, an alternative illustration of impedance spectra is also proposed to improve the data visualization, and such presentation may be potential for intelligent VEGF detection.

The application of artificial intelligence to point-of-care testing (POCT) disease detection has become a hot research field, in which breath detection which detects the patient's exhaled VOCs combined with sensor arrays of Convolutional Neural Network (CNN) algorithms as a new lung cancer detection is attracting more researchers' attention. However, due to low accuracy, high complexity computation and large number of parameters make the CNN algorithms difficult transplant to the embedded system of POCT devices. A lightweight neural network (LTNet) in this work is proposed to deal with this problem, and meanwhile, achieve high-precision classification of acetone and ethanol gases, which are respiratory markers for lung cancer patients. Compared to currently popular lightweight CNN models such as EfficientNet, LTNet has fewer parameters (32K) and its training weight size is only 0.155 MB. LTNet achieved an overall classification accuracy of 99.06% and 99.14% in the own mixed gas dataset and the University of California (UCI) dataset, which are both higher than that of the five existing models’, and it also offers the shortest training (844.38s and 584.67s) and inference time (23s and 14s) in the same validation set. Compared to the existing CNN models, LTNet is more suitable for resource-limited POCT devices.

A case-crossover study examined how PM_2.5 from Asian Dust Storms (ADS) affects the number of emergency room (ER) admissions for cardiovascular diseases (CVDs) and respiratory diseases (RDs). Our data indicated that PM_2.5 concentration from ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR) increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per increase 10 µg/m³ in PM_2.5 levels, for CVDs and RDs, respectively. A 10 µg/m³ increase in PM_2.5 from ADSs was significantly associated with increase in ER visits for CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for females (an increase of 3.09 in OR). In contrast, PM_2.5 levels had a significant impact on RD ER visits among those under 65 years of age (OR=1.77). The risk of ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the day after (lag 0 and lag 1); the corresponding risk increase for RDs only increased on the fifth day after the ADS (lag 5). In Taiwan’s late winter and spring, the severity of ER visits for CVDs and RDs increases. Environmental protection agencies should employ an early warning system for ADS to reduce high-risk groups’ exposure to PM_2.5.

Lung cancer remains a pervasive global health challenge, necessitating precise and efficient classification methods to inform optimal treatment strategies. In this study, we investigate the potential of machine learning algorithms in developing a computer-aided diagnostic tool for early and accurate lung cancer classification, leveraging essential protein biomarkers as predictive features. Our investigation reveals the superiority of Deep Neural Networks (DNNs) in lung cancer classification, achieving an impressive accuracy of 96.91%. This highlights the transformative potential of DNNs in facilitating real-world clinical applications, offering clinicians a powerful tool for accurate diagnosis and prognosis. Additionally, we analyze the performance of Ensemble Methods, including Voting (91.75%) and Bagging (93.81%), as viable alternatives to DNNs. These ensemble techniques demonstrate robust performance, further underlining their utility in lung cancer classification tasks. Furthermore, our study underscores the critical role of hyperparameter tuning, particularly in adjusting parameters such as min child weights and learning rates, in mitigating overfitting and enhancing the generalizability of diverse machine learning models. For instance, Support Vector Machines (SVM) exhibit varying accuracies ranging from 74.23% to 95.88% across different hyperparameter configurations, emphasizing the importance of hyperparameter optimization in maximizing model performance. In summary, our comprehensive comparative analysis sheds light on the efficacy of different machine learning approaches in lung cancer classification. By leveraging advanced algorithms and optimizing model parameters, researchers and clinicians can harness the power of machine learning to advance early detection and personalized treatment strategies for lung cancer patients.

Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEPNETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, role of EGFR in carcinogenesis, presence of transcription factors, and immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may im-prove our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.

Lung cancer, including both non-small cell lung cancer and small cell lung cancer, remains the leading cause of cancer-related mortality worldwide representing 18% of the total cancer deaths in 2020. Many patients are identified already at an advanced stage with metastatic disease and have a worsening prognosis. Recent advances in the genetic understanding of lung cancer have opened new avenues for personalized treatments and targeted therapies. This review examines the latest discoveries in the genetics of lung cancer, discusses key biomarkers, and analyzes current clinical therapies based on this genetic information. It will conclude with a discussion of future prospects and potential research directions.

Patients who survived critical COVID-19 frequently reported post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during ICU stay. The association between ICU predictors and psychosomatic, respiratory and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

Breast cancer (BC) is a prevalent malignancy with various subtypes, each presenting unique diagnostic and therapeutic challenges. Triple-negative breast cancer (TNBC), which comprises 12-17% of breast cancers, is particularly aggressive due to its lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. This case report details the management of a 64-year-old woman with TNBC. Initially presenting with a left breast nodule, she underwent a biopsy that confirmed triple-negative infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and a newly detected right breast lesion led to a bilateral mastectomy. Post-surgery imaging revealed multiple hypodense nodules and a spiculated pulmonary nodule, prompting further investigation. An endoscopic lung biopsy identified a primary pulmonary carcinoma with histological features similar to the breast cancer, indicating the lung as the primary source. This case underscores the complexity of TNBC, the importance of comprehensive diagnostic evaluations, and the need for considering extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated evaluations in atypical BC presentations.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Respiratory Syncytial Virus is a common respiratory pathogen known for causing respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and the elderly. This virus is responsible for one-third of pneumonia deaths in the pediatric population, but there are currently only a few effective vaccines and pharmacological treatments. The frac-talkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and a diversity of immune cells. Recent research has highlighted the role of CX3CR1 in the host immune response to RSV infection, and its potential role in the development of an efficient vaccine and novel treatments.

Bovine respiratory disease (BRD) is a major health problem within the global cattle industry. This disease has a complex aetiology, with viruses playing an integral role. In this study, metagenomics was used to sequence viral nucleic acids in the nasal swabs of BRD affected cattle. Viruses detected included those well known for their association with BRD in Australia (bovine viral diarrhea virus 1), as well as viruses known to be present but not fully characterised (bovine coronavirus) and viruses that have not been reported in BRD affect cattle in Australia (bovine rhinitis, bovine influenza D, and bovine nidovirus). Nasal swabs from a case control study were subsequently tested for 10 viruses and the presence of at least one virus was found to be significantly associated with BRD. Some of the more recently detected viruses had inconsistent association with BRD. Full genome sequences for bovine coronavirus, a virus increasingly associated with BRD, and bovine nidovirus were complete. Both viruses belong to the Coronaviridae family, which are frequently associated with disease in mammals. This study has provided greater insights into the viral pathogens associated with BRD and highlighted the need for further studies to elucidate more precisely the roles viruses play in BRD.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.

This purpose of the study presented in this article is to comparing different service quality measurements between Kano and TRIZ that plays the critical roles in the catering industrial. Data collected from a DINESERV questionnaire comprises service-quality standards to increase customer satisfaction of mobile dining car. Finally, the TRIZ is standardized measure designed to improve the idealization of strategy for selecting the most appropriate service quality model. In addition, the preferences of more than one decision maker are internally aggregated into the TOPSIS procedure. All these things provide several important theoretical and practical implications for developing a successful mobile catering app.

Several Lung diseases can result in lung damage structural changes, with lung transplantation as a only therapeutic option when the disease reaches an advanced progression, unfortunately, the success of lung transplantation is limited. In this context, lung bioengineering is considered a potential therapeutic alternative and the current approach is based on the use of the natural extracellular matrix (ECM) of the decellularized lung. The use of undifferentiated cells to seed an ECM can be a more practical strategy for lung bioengineering but the sterilization of the organ for this recellularization process is still a challenge. In this sense, Low-Level Laser Therapy (LLLT) can emerge as a potential treatment alternative. Therefore, the objective of this study was to verify if LLLT, can optimize lung recelularization with mesenchymal stem cells by cytokine modulation. For this, we decellularized lungs from C57BL/6 mice perfusing SDS 1% via pulmonary artery, sterilized with LLL (660nm, 100mW, 30s). Whole lung scaffolds were recellularized: (1) Recellularized Lung (2) Recellularized Lung + LLLT. Mesenchymal stem cells derived from human tooth pulp (DPSc) were seeded into lungs and incubated for 24 hours at 37ºC, 5% CO₂, in a bioreactor-like conditions, maintaining CPAP at 20cmH2O, 90% O2, and LLL at wavelength of 808nm, 100mW, 30s. Culture medium were analyzed at 24 hours. H&amp;E, immunostaining, SEM and ELISA assay were performed. We produced viable biological scaffolds absent of DNA content, preserving glycosaminoglycans and collagen I, III and IV, fibronectin, laminin and elastin and lung structure (SEM). The levels of IL-6 and IL-8 were stable during the 24 hours of culture. IFN-γ levels showed significant difference in the DPSc and DPSc+LLLT group in the 24-hour evaluation. The levels of IL-10 decreased after LLLT. These findings highlight LLLT's role in cytokine regulation and contamination prevention during lung recellularization with mesenchymal stem cells. Overall, these results demonstrated that LLLT's modulated cytokine levels and could prevent contamination during the lung recellularization process with mesenchymal stem cells, offering promise for enhanced therapeutic strategies in lung bioengineering.

Despite the development of targeted therapeutics, immunotherapy, and strategies for early detection, lung cancer carries a high mortality. Further, significant racial disparities in outcomes exist for which the molecular drivers have yet to be fully elucidated. The growing field of Epitranscriptomics has introduced a new layer of complexity to the molecular pathogenesis of cancer. RNA modifications can occur in coding and non-coding RNAs, such as miRNAs, possibly altering their gene regulatory function. The potential role for such modifications as clinically informative biomarkers remains largely unknown. Here, we concurrently profiled canonical miRNAs, shifted isomiRs (templated and non-templated), miRNAs with single-point modification events (RNA and DNA) in White American (W) and Black or African American (B/AA) lung adenocarcinoma (LUAD) patients. We found that while most deregulated miRNA isoforms were similar in W and B/AA LUAD tissues compared to normal adjacent tissues, there was a subgroup of isoforms with deregulation according to race. We specifically investigated an edited miRNA, miR-151a-3p with an A-to-I editing event at position 3, to determine how its altered expression may be associated with activation of divergent biological pathways between W and B/AA LUAD patients. Finally, we identified distinct race-specific miRNA isoforms that correlated with prognosis for both Ws and B/AAs. Our results suggest that concurrently profiling canonical and non-canonical miRNAs may have potential as a strategy for identifying additional distinct biological pathways and biomarkers in lung cancer.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.

The study aimed to estimate the prevalence of respiratory symptoms and to assess respiratory health risks associated with Particulate Matter (PM) exposure among the residents of Windhoek, Namibia. Objectives: To measure particulate pollution concentration in Windhoek through monitoring of particulate matter concentration and to identify any associations between particulate pollution, individual location and respiratory health among the Windhoek resident’s. Methods: an adapted standardized self-administered questionnaire was used to collect respiratory health related data as well as previous exposure, while PM monitoring was done using ASTM D1739 reference method. Results: A high prevalence was observed for cough (43%), breathlessness (25%), and Asthma (11.2%). PM was found to be a significant risk factor for episode of cough and phlegm, while high PM exposure category had increased odds ratio for episode of phlegm and cough (OR: 2.5, 95% CI: 0.8-8.0). No association was observed between location and respiratory health outcomes. Conclusion: The study found high levels of PM concentration across all Windhoek suburbs which were above the German, American and EPA. Enactment of legislation relating to the control and monitoring of PM related emissions at point of generation is required at country and city level.

Purpose Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20-50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods Patients (N=36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results Median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and 9 (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and 15(42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax, and 9 (25%) to the abdomen or pelvis. Total dose ranged from 18 to 42.5 Gy in 6-17 fractions/ 2.67-5 Gy per fraction. Median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86), and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. Two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort, and 100, 87 (95%CI: 56.4-96.5%) and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI:59.9-90.5%), and 100, 66.1 (95% CI: 36.4-84.4%) and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusion HFRT in HM provides excellent local control without any increase in toxicity.

Abstract: Lung cancer, characterized by its heterogeneity, presents a significant challenge in ther-apeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumour’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article ex-plores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. The review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small cell lung cancer and small cell lung cancer, underlining the need for subtype-specific treatments. Key signalling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. The article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. The review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

Driven by the importance of early detection for improving patient outcomes, this study investigates the effectiveness of various machine learning algorithms in predicting lung cancer based on clinical data. Lung cancer remains a significant global health concern, and this research seeks to contribute to advancements in early diagnosis through the application of machine learning techniques. The dataset consists of 385 training and 97 test samples, with a k-fold cross-validation approach (k=5) utilized to mitigate overfitting. Additionally, the ADASYN oversampling technique is employed to address class imbalance. Our analysis includes traditional algorithms such as Logistic Regression and Decision Trees, as well as ensemble methods like XGBoost, LGBM, and AdaBoost. Furthermore, we explore the effectiveness of deep learning models, particularly Deep Neural Networks (DNN). Results demonstrate promising accuracy rates across all models, with some outperforming others in terms of precision, recall, and F1-score. Our findings reveal that LGBM achieves the highest accuracy among all models, with an accuracy rate of 96.91%. It also exhibits superior performance in terms of precision, recall, and F1-score, particularly in classifying both positive and negative instances of lung cancer.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (&gt;200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p&lt;.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

The artificial intelligence (AI) is a machine or computing platform that is capable of making intelligent decision similarly to the human mind. The AI could improve diagnosis, treatment prognosis, and clinical workflow, particularly in the field of radiology. Concerning acute respiratory distress syndrome (ARDS) is a rather heterogeneous syndrome characterized by an inflammatory lung edema leading to an increased lung weight, decreased lung aeration with the presence of alveolar collapse and interstitial opacities mainly in the dependent area. Thus, lung imaging is an essential tool to assess not only the morphology but also the mechanical characteristics of ARDS patients. Chest computed tomography (CT) and ultrasound have a higher sensitivity and specificity than conventional chest radiography. This narrative review summarizes the state of art of AI in the field of lung imaging, focusing on CT and ultrasound technique in ARDS patients. A total number of 18 articles were retrieved. The application of AI in lung imaging was mainly devoted to assess the prediction of ARDS, the quantification of alveolar recruitment, the possible alternative diagnosis and the outcome. Although the presence of a physician is still essential to ensure a high quality of examinations the AI could assist the clinical team to provide the best possible care.

Diseases of the lung account for more than 5 million deaths worldwide and are a burden to healthcare. Improving clinical outcomes including mortality and quality of life involves a holistic understanding the etiopathogenesis, which can be provided by multi-omics integration of lung data. An enhanced understanding of large comprehensive datasets provides opportunities to mine those datasets for features that contribute to prevention and amelioration of disease. In this review, we evaluate lung disease models including animal models, organoids and single cell lines as mechanisms to study multiomics in lung health and disease. We provide examples of lung diseases where multi-omics investigations have provided a deeper insight into pathogenesis that has resulted in improved preventive and therapeutic interventions.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Heat dissipation from Li-ion batteries is a potential safety issue for large-scale energy storage applications. Maintaining low and uniform temperature distribution, and low energy consumption of the battery storage is very important. We studied the fluid dynamics and heat transfer phenomena of a single cell, 16-cell modules, battery packs, and cabinet through computer simulations and experimental measurements. The results show that the temperature distribution of single cell is relatively uniform when the cell is facing the air flow. In a module, very high air flow rate and large gap between the cells can reduce the cell temperature. A pack with a good thermally conductive case is very important to ensure good heat dissipation of the battery module. Due to limited space in the cabinet, additional air inlets and outlets can be opened outside of the cabinet to slightly lower the pack temperature. Installing fins outside the cabinet can also slightly reduce the temperature inside the cabinet. Liquid cooling medium, such as water, is much better than the air-cooling medium.

During the COVID-19 pandemic, the circulation of non–SARS-CoV-2 respiratory viruses changed throughout the world. This study aimed to analyze the effect of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus (RV), and parainfluenza (PIV)-3 single infection, dual co-infection, and viral load on cytokine and chemokine expression in 300 Mexican patients with ARIs negative for SARS-CoV-2. Molecular detection and viral load were performed by RT-qPCR. Cytokine and chemokine expression was determined in samples positive for single RSV, MPV, RV, or PIV-3 infection, and in the most frequent dual co-infections, by a cytokine panel using a magnetic-bead-based multiplex immunoassay. Of the patients positive for viral infection, 91.7% had a single infection and 8.3% had dual co-infections. In this study, RSV was the respiratory virus with the highest prevalence, and the most common dual co-infection was RV+RSV. On the other hand, RV infections had the highest viral loads compared to the other viruses detected. FGF basic, MIP-1α IL-8, IP-10, MCP-1, IFN-γ, and RANTES showed differential expression between single infections and dual co-infections compared to healthy patients. We report, for the first time, the circulation of non-SARS-CoV-2 viruses in the south of Mexico and the cytokine and chemokine profiles associated with these viruses.

A machine learning method for classifying Lung UltraSound is here proposed to pro- vide a point of care tool for supporting a safe, fast and accurate diagnosis, that can also be useful during a pandemic like as SARS-CoV-2. Given the advantages (e.g. safety, rapidity, portability, cost-effectiveness) provided by the ultrasound technology over other methods (e.g. X-ray, computer tomography, magnetic resonance imaging), our method was validated on the largest LUS public dataset. Focusing on both accuracy and efficiency, our solution is based on an efficient adaptive ensembling of two EfficientNet-b0 models reaching 100% of accuracy, which, to our knowledge, outperforms the previous state-of-the-art. The complexity of this solution keeps the number of parameters in the same order as an EfficientNet-b0 by adopting specific design choices that are adaptive ensembling with a combination layer, ensembling performed on the deep features, minimal ensemble only two weak models. Moreover, a visual analysis of the saliency maps on sample images of all the classes of the dataset reveals where the focus is on an inaccurate weak model versus an accurate model.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two medical conditions, and the effect modification by sex and neuropsychiatric comorbidities in a nationwide population. To compare the risk of precocious puberty between ASD and non-ASD cases, we conducted Cox regression analysis, using ASD as exposure and time-to-precocious puberty as outcome. We adjusted for sex, attention-deficit/hyperactivity disorder (ADHD), tics disorder, obsessive–compulsive disorder (OCD), anxiety disorder, intellectual disability, and epilepsy. We performed a moderation analysis to examine the potential moderating effects by sex or comorbidities. Patients with ASD were prone to have precocious puberty, with an adjusted hazard ratio (aHR) of 1.80 (95% CI: 1.61-2.01). For the effect modification, sex, specifically females, moderated the association between ASD and precocious puberty, with relative excess risk due to interaction (RERI) 7.35 (95% CI 4.90-9.80). No significant effect modification was found for any of the comorbidities within the scope of additive effect modification. We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders. Girls with ASD are at particularly higher risk to develop precocious puberty.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p