Electric torque wrenches play a crucial role in the assembly of high-strength bolts. This study focuses on three assembly processes for high-strength bolts and introduces a statistical analysis method to assess the quality of the bolt assembly. To enhance the performance, a novel, fully digital, Internet of Things (IoT) electric torque wrench is designed, incorporating a smart meter chip. This wrench achieves integration between the current sensor control method and the torque sensor control method using a simplified hardware circuit, ensuring high precision and stability. Additionally, this study employs the AC voltage self-stabilization method and Savitzky–Golay filtering method to enhance the accuracy and robustness of the wrench. Simulation experiments using Simulink and Matlab validate the effectiveness of these two methods. Furthermore, a cloud platform is utilized to enable rapid IoT access for the wrench, facilitating seamless connectivity and data transmission.

This study investigated novel quantitative traits loci (QTLs) associated with the control of grain shape and size as well as grain weight in rice. We employed a joint strategy multiple GAPIT (Genome Association and Prediction Integrated Tool) models [(Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK)), Fixed and random model Circulating Probability Uniform (FarmCPU), Settlement of MLM Under Progressive Exclusive Relationship (SUPER), and General Linear Model (GLM)]–High Density SNP Chip DNA Markers (60,461) to conduct a Genome-Wide Association Study (GWAS). GWAS was performed using genotype and grain-related phenotypes of 143 recombinant inbred lines (RILs). Data show that parental lines (Ilpum and Tung Tin Wan Hein 1, TTWH1, Oryza sativa L., ssp. japonica and indica, respectively) exhibited divergent phenotypes for all analyzed grain traits), which was reflected in their derived population. GWAS results revealed the association between seven SNP Chip makers and quantitative trait loci (QTLs) for grain length, co-detected by all GAPIT models on (Chr) 1–3, 5, 7, and 11), were qGL1-1BFSG (AX-95918134, Chr1: 3820526 bp) explains 65.2%–72.5% of the phenotypic variance explained (PVE). In addition, qGW1-1BFSG (AX-273945773, Chr1: 5623288 bp) for grain width explains 15.5%–18.9% of PVE. Furthermore, BLINK or FarmCPU identified three QTLs for grain thickness independently, and explain 74.9% (qGT1Blink, AX-279261704, Chr1: 18023142 bp) and 54.9% (qGT2-1Farm, AX-154787777, Chr2: AX-154787777 bp) of the observed PVE. For t length-to-width ratio, the qLWR2BFSG (AX-274833045, Chr2: 10000097 bp) explains nearly 15.2%–32% of PVE for LWR. Likewise, the major QTL for thousand-grain weight (TGW) was detected on Chr6 (qTGW6BFSG, AX-115737727, 28484619 bp) and explains 32.8%–54% of PVE. The qTGW6BFSG QTL coincides with qGW6-1Blink for grain width and explained 32.8%–54% of PVE. Putative Candidate genes pooled from major QTLs for each grain traits have interesting annotated functions that require functional studies to elucidate their function in the control of grain size, shape, or weight in rice. Genome selection analysis proposed makers useful for downstream marker-assisted selection based on genetic merit of RILs.

In Escherichia coli, DNA replication termination is orchestrated by two clusters of Ter sites forming a DNA replication fork trap when bound by Tus proteins. The formation of a ‘locked’ Tus-Ter complex is essential for halting incoming DNA replication forks. However, the absence of replication fork arrest at some Ter sites raised questions about their significance. In this study, we examined the genome-wide distribution of Tus and found that only the six innermost Ter sites (TerA-E and G) were significantly bound by Tus. We also found that a single ectopic insertion of TerB in its non-permissive orientation could not be achieved, advocating against a need for ‘back-up’ Ter sites. Finally, examination of the genomes of a variety of Enterobacterales revealed a new replication fork trap architecture mostly found outside the Enterobacteriaceae family. Taken together, our data enabled the delineation of a narrow ancestral Tus-dependent DNA replication fork trap consisting of only two Ter sites.

Plant life-long organogenesis involves sequential, time and tissue specific expression of developmental genes. This requires activities of Polycomb Group (PcG) and trithorax Group complexes, respectively responsible for repressive Histone 3 trimethylation at lysine 27 (H3K27me3) and activation-related H3K4me3. However, the genome-wide dynamics in histone modifications that occur during developmental processes have remained elusive. Here, we report the distributions of H3K27me3 and H3K4me3 along with transcriptional changes, in a developmental series including Arabidopsis leaf and three stages of flower development. We found that chromatin mark levels are highly dynamic over the time series on nearly half of all Arabidopsis genes. Moreover, during early flower morphogenesis, changes in H3K4me3 prime over changes in H3K27me3 and quantitatively correlate with transcription changes, while H3K27me3 changes occur after prolonged expression changes. Notably, early activation of PcG target genes is dominated by increases in H3K4me3 while H3K27me3 remains present at the locus. Our results reveal H3K4me3 as greater predictor over H3K27me3 for transcription dynamics, unveil unexpected chromatin mechanisms at gene activation and underline the relevance of tissue-specific temporal epigenomics.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

In this paper we investigate analytic automorphisms of complex topological vector spaces and their applications to linear and nonlinear transitive operators. We constructed some examples of polynomial automorphisms which show that a natural analogue of the Jacobian Conjecture for infinite dimensional spaces is not true. Also, we prove that any separable Fréchet space supports a transitive analytic operator which is not a polynomial. We found some connections of analytic automorphisms and algebraic bases of symmetric polynomials and applications to hypercyclisity of composition operators.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

Several biomedical products, like scaffolds, implants, prostheses, and orthoses, require materials having superior physicochemical and biological properties. Polyethylene terephthalate glycol (PETG) is being increasingly used for various biomedical applications. There are a few studies on PETG-based composites, however, natural fibers like silk short fibers reinfored PETG composites have not been attempted. Being a cost-effective widely available material, PETG-Silk combination can be potential biocomposite for several biomedical applications. Here, we report a novel short silk fiber reinforced PETG composite prepared by a wet-mixing route, ensuring homogenous dispersion of the filler. Different ratios (2-10%) of short silk fibers were used to prepare composites with varied compositions. The mechanical, physicochemical, and biological properties of the prepared composites were analyzed. Thermogravimetric analysis showed that such composites are thermally stable up to 390 °C and can be used for thermal extrusion-based manufacturing. The tensile modulus of the samples increased with fiber content; however, the failure strain reduced with fiber content. Furthermore, upon annealing, the tensile modulus increased but, the failure strain of the composites decreased, XRD study revealed that heat treatment has altered the crystalline nature of the composites. Finally, we evaluated the cytocompatibility of the prepared composites to assess their suitability for various biomedical applications.

Federated learning (FL) has emerged as a crucial technology in today’s data-centric technological environment, enabling decentralized machine learning and safeguarding user privacy. This study introduces “Federated Operations (FedOps) Mobile,” a novel FL framework optimized for the dynamic and heterogeneous ecosystem of mobile devices. FedOps Mobile enhances traditional FL approaches for mobile devices by integrating real-time operational control and advanced on-device training capabilities using TensorFlow Lite and CoreML, addressing critical challenges in scalability, efficiency, and system heterogeneity. Our approach utilizes a wide range of devices, facilitated by intelligent client-selection mechanisms. This mechanism evaluates the capabilities and readiness of multiple devices per client to ensure fair and efficient network participation. The framework also utilizes remote device control for seamless task management and sustained engagement, enabling continuous learning without compromising the user experience. We conducted extensive experiments to validate the framework’s performance, focusing on three core aspects: operational efficiency, model personalization, and resource optimization in multi-device environments. The results demonstrate that the proposed method is effective for efficient client selection, energy consumption, and model optimization.

In this paper, a prototype of an automatic lab on PCB for agarose preparation and electrophoresis is developed. The dimensions of the device are 38×34 mm2 and includes a conductivity sensor for detecting the TAE buffer (Tris-Acetate-EDTA buffer), a microheater for mixing, a NTC thermistor for controlling the temperature, a LDR sensor for measuring the transparency of the mixture, and two electrodes for performing the electrophoresis. The agarose preparation functions are governed by a microcontroller. The device requires a PMMA structure to define the wells of the agarose gel, and to release the electrodes from the agarose. The maximum voltage and current that the system requires are 40 V to perform the electrophoresis, and 1 A for activating the microheater. The chosen temperature for mixing is 80ºC, with a mixing time of 10 min. In addition, the curing time is about 30 min. This device is intended to be integrated as a part of a larger lab on PCB system for DNA amplification and detection. However, it can be used to migrate DNA amplified in conventional thermocyclers. Moreover, the device can be modified for preparing larger agarose gels and performing electrophoresis in an automatic manner.

This research paper contributes to the literature of deterrence theory in general, and in particular with respect to white-collar crime, offering valuable inside by using a unique data set of fraud and violation of trust incidents for Paraguay. Descriptive evidence show a clear and continuous misallocation of funds and human capital, and therefore providing less efficient services for the public. Regression analysis suggests that clearance rate exerts a highly significant effect in deterring fraud but results are not clear for violation of trust incidents. Despite the limitations of available data, results confirm deterrence theory in Paraguay. However, to more than two-thirds of victims, not even the attempt was made to seek justice. As a side-result, it seems that a soft on crime strategy, induced from the former German penal code, has led to an increasing share of pre-trial diversion and therefore enhancing white-collar crimes like fraud and violation of trust due to impunity.

Biometric based access control system acts as a weapon against the challenges for reliable authentication mechanism. Although there are many advantages of biometric system, still it is vulnerable to attacks, which decline its security. This leads to propose a new approach to address these open issues and challenges for biometric data security. Smart card have been already used in past with various degree of success to store biometric credentials. Match-on-card biometric framework locks the biometric data inside the microcontroller of the smart card, which leads to minimal risks if card is lost or stolen. It is fast and accurate, balancing security and convenience by never exchanging user data outside the system of smart card and performs fingerprint enrollment as well as matching within a tamperproof environment of smart card.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

The experiments described in this research article were designed to test the effect of rare variants into genomic prediction in dairy cattle. Common polymorphisms are able to explain only a small proportion of the underlying genetic variation of complex phenotypes. Variants representing functional mutations with large effects on complex phenotypes are expected to be rare due to natural (humans) or artificial (livestock) selection pressure. Therefore, it is important to check whether the use of rare variants could increase the accuracy of ranking of animals by providing the tool for more precise differentiation among the bulls with high additive genetic merit. The goal of our study was to verify whether including rare variants in a genomic selection model allows for a more accurate description of the additive genetic background of traits under selection in dairy cattle. We used the linear mixed model for comparison SNP estimates for Holstein-Friesian cattle of the two data sets – a set containing only single nucleotide polymorphisms defined by minor allele frequency ≥ 0.01, which is routinely used in the Polish genomic evaluation system (46,216 SNPs), and a set containing SNPs selected based only on the call rate (54,378 SNPs). Based on the SNP estimates we also calculated DGV and GEBV and compared them between both data sets. In all the analyses we used production, fertility, conformation and udder health traits. We also assessed the time required for the two most computationally demanding components of genomic selection: preparing genotype data, and estimation of SNP effects between those two data sets. The results of our study indicated that the analysis including rare variants resulted in changes in the individual ranking of the top 100 male and female candidates, but had no effect on the outcome of the quality of EBV prediction as expressed by the Interbull validation test.

First-line treatment for advanced large-cell neuroendocrine carcinoma of the lung (LCNEC) has limited efficacy. This study aimed to explore the efficacy and safety of everolimus combined with EP regimen chemotherapy (etoposide + cisplatin, EP) in the first-line treatment for LCNEC. The patients were randomly assigned to the experimental or control group, with 20 patients in each group. The experimental group received the mTOR inhibitor everolimus 5 mg once a day combined with EP ivgtt, d1-3, every 3 weeks for 4–6 cycles. The control group received EP only and the infusion method was the same as that of the experimental group. The safety in the experimental group was controllable and not inferior to that in the control group. Serious adverse effects were observed in approximately 10% of patients. Objective response rate (ORR) for the experimental and control groups were 15% vs. 0 (P=0.231), disease control rate (DCR) was 100% vs. 32% (P

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1>49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p<0.05). In addition, patients diagnosed with adenocarcinoma, PDL1<49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p<0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

The aim of this scoping review was to investigate and synthesize existing evidence on the airway microbiome of preterm infants, to outline the prognostic and therapeutic significance of these microbiomes within the preterm population, and identify gaps in current knowledge, proposing avenues for future research. We performed a scoping review of the literature following the Arskey and O'Malley framework. In accordance with our inclusion criteria and the intended purpose of this scoping review, we identified a total of 21 articles. The investigation of the airway microbiome in preterm infants has revealed new insights into its unique characteristics, highlighting distinct dynamics when compared to term infants. Perinatal factors, such as mode of delivery, chorioamnionitis, the respiratory support, and antibiotic treatment, could impact the composition of the airway microbiome. The 'gut-lung axis’, examining the link between the lung and gut microbiome, as well as modifications in respiratory microbiome across different sites and over time, has also been explored. Furthermore, correlations between the airway microbiome and adverse outcomes, such as bronchopulmonary dysplasia (BPD), have been established. Additional research in neonatal care is essential to understand early colonization of infants’ airways and explore methods for its optimization. The critical opportunity to shape long-term health through microbiome-mediated effects likely lies within the neonatal period.

(1) Background: Bronchial artery embolization has been shown to be effective in the management of neoplastic hemoptysis. However, knowledge of pulmonary artery embolization is lacking. To evaluate safety and efficacy of pulmonary artery embolization in patients presenting with hemoptysis related to lung tumors. (2) Methods: This retrospective study reviewed all consecutive patients with cancer and at least one episode of hemoptysis that required pulmonary artery embolization from December 2008 to December 2020. The endpoints of the study were technical success, clinical success, recurrence of hemoptysis and complications. (3) Results: A total of 92 patients were treated with pulmonary artery embolization (63.1 years ± 9.9; 70 men). Most patients had stage III or IV advanced disease. Pulmonary artery embolization was technically successful in 82 (89%) patients and clinically successful in 77 (84%) patients. Recurrence occurred in 49% of patients. Infectious complications occurred in 15 patients (16%). The 30-days mortality rate was 31%. At 3 years, survival rate was 3.6%. Tumor size, tumor cavitation and necrosis and pulmonary artery pseudo-aneurysm were significantly associated with recurrence and higher mortality. (4) Conclusions: Pulmonary artery embolization is an effective treatment to initially control hemoptysis in patient with lung carcinoma but recurrence rate remains high and overall survival remains poor.

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.

Background： Sepsis-induced acute lung injury (ALI) is characterized by disruption of the epithelial barrier and activation of alveolar macrophages (AMs), which leads to uncontrolled pulmonary inflammation. However, effective treatments for ALI are unavailable. This study aimed to discover potential diagnostic molecular biomarkers based on bioinformatics, which will benefit the diagnosis and treatment of sepsis-induced ALI. Methods: GSE10474 was analyzed for differentially expressed genes (DEGs) in sepsis patients with ALI (sepsis + ALI) compared with sepsis patients without ALI. Functional enrichment analysis and protein-protein interaction (PPI) network were performed. on the DEGs via R package “clusterProfiler”, and visualized via Cytoscape. Prediction analysis of microarrays (PAM) was performed to identify diagnostic biomarkers and the diagnostic ability of diagnostic biomarkers was accessed via receiver operating characteristic (ROC) curves. Moreover, interactions among diagnostic biomarkers were analyzed via GeneMANIA. We also analyzed the function of diagnostic biomarkers and predicted their corresponding drugs via Cytoscape plugin BiNGO and web tool DGIdb. At last, we analyzed the transcriptional regulation of the diagnostic biomarkers via the web tool miRNet. Results: 71 genes were found to be differentially expressed in the sepsis + ALI group, mainly involved in immune-related biological processes and pathways. STRING database indicated 31 DEGs have protein-protein interactions. In addition, the PAM identified 6 diagnostic biomarkers, including HIST1H4H, CDKN1A, HMOX1, NQO2, RHOB, and TREM1, from these 31 DEGs. Conclusion: In conclusion, through bioinformatics analyses, we identified 6 potential diagnostic biomarkers and targets for sepsis-induced ALI.

Primary carcinomas of the lung are vastly represented by the conventional types of adenocarcinomas or squamous cell carcinomas. However, there are other types of non-small cell carcinomas that although uncommon represent a meaningful group that often pose a problem not only in diagnosis but also in classification. Spindle and giant cell carcinomas although uncommon primary lung carcinomas are well known to occur. Important to highlight is that current criteria are rather ambiguous and likely not up to date, which renders the classification of these tumors somewhat more obscure. In addition, with the daily use of immunohistochemical stains, the classification of these tumors may also pose a different problem in the proper allocation of these tumors. Proper classification is highly important in the selection process that takes place using such material for molecular analysis. Current molecular characteristics of these tumors is limited and lacks more in-depth studies and analysis that can provide specific targets for the treatment of patients with these tumors. The current review attempts to highlight the shortcomings in the current classification and definitions of these neoplasms as well as the more current view regarding these tumors when the use of immunohistochemical stains is employed.

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.

Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.

The risk of lung cancer continues to elevate for both smokers and never-smokers. With the increasing morbidities and mortalities related to lung cancer, there is much interest on establishing other confounding factors that lead to lung cancer, other than smoking which is the most common cause. Some of the environmental factors have been identified as potential lung cancer causes. Therefore, the aim of this systematic review is to assess the relationship of environmental factors and lung cancer incidences by investigating various carcinogenic risks exposures that predispose an individual to lung cancer. The objective of this systematic review is thus to assess the evidence of relationship between environmental carcinogens and lung cancer incidence by systematically reviewing relevant studies. A standard criterion for the review methodology was formulated to guide the review process and data extraction. Online databases like PubMed, MEDLINE, Scopus (EMBASE), Google Scholar, Web of Science, and CINAHL were systematically searched for articles published between 2000 and 2021 that explored potential environmental carcinogens that were believed to expose occupational workers and individuals within the environment with lung cancer risks. 25 studies were eligible based on the selection criteria, and were finally included in the systematic review among which four were case-control studies, seven were cohorts, five was prospective, four were previous systematic reviews and four were systematic analysis. Chemical exposures like pesticides were analyzed for their carcinogenesis. Air pollution was also discussed with particulate and coal being the core of evidence of association with lung cancer. Second hand smoke, Asbestos, metal compounds like copper, PVC dust particles and ionizing radiations also provided evidence of environmental carcinogenesis associating to lung cancer cases.

Background: Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ~2.95 X 1010 particles/mL. Lung-derived exosomes were ~146.04 nm in size and ~2.38 X 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.

The quarantine imposed as the response to the COVID 19 pandemic has been related to an increase in cases of thromboembolism in Non-COVID19 patients .We report the case of a patient with pulmonary thromboembolism without usual triggering causes during the quarantine period, related to a previously undiagnosed hypercoagulable condition.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. Idiopathic chronic eosinophilic pneumonia is reported to comprise anywhere from 0-2.5% of cases within the registries of interstitial lung disease. Diagnosis is based on the clinical constellation of symptoms, characteristic radiographic findings and peripheral blood or BAL eosinophilia, in the absence of infection or drug-induced eosinophilia. There is no consensus on the dose and duration of treatment, but most authors recommend initial doses of prednisone at 0.5–1 mg/kg/day with gradual tapering of the dose for total treatment duration of 6–12 months.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as Lung Cancer associated with Cystic Airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs biennial pace of LDCT, choice between opportunistic or population-based recruitment and between uni or multi-center screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention and prospective validation of the biomarkers.

This study presents a transversal investigation, that we performed at Fundeni hospital, into the therapeutic benefits and efficacy of Emicizumab, a non-factor therapy, in the context of hemophilia A. Ten patients diagnosed with hemophilia A were closely monitored, using clinical and laboratory resources, during the course of Emicizumab treatment, with an average of 12.8 months. Among these patients, six exhibited anti-factor VIII inhibitors, changing the medical approach and adding complexity to their clinical profiles. A comprehensive approach was adopted to assess the coagulation status of patients under Emicizumab therapy. The study employed several key coagulation monitoring tools, of which including thrombin generation time (TGT) and thrombelastography (TEG). These methodologies proved highly valuable results in evaluating the patients' coagulation profiles during the treatment regimen. Additionally, traditionally coagulation assays were utilized to gain a comprehensive understanding of the overall coagulation dynamics. Noteworthy, impressive outcomes emerged from the study. During prophylaxis with Emicizumab all patients had experienced a reduced number of bleeding events. Moreover, a subset of these patients underwent major surgical procedures (orthopedic joint replacements) with successful outcomes. These findings underscore the potential of Emicizumab therapy as an effective option for hemophilia A patients, including those that presented a prompt production of anti-factor VIII inhibitors. As for the outcomes, this transversal study sheds some light on the positive impact of Emicizumab therapy in addressing the coagulation challenges posed by hemophilia A. The utilization of global coagulation assays, such as thrombin generation time, thrombelastography and combined with traditional coagulation assays, used as monitoring tools highlights their significance once more in evaluating the therapeutic response. This research contributes by providing physicians with valuable insights to the field, offering a potential avenue for improved patients’ care and treatment strategies that translate in enhanced quality of life for hemophilia A patients undergoing Emicizumab therapy.

Smart, reliable, and connected multi-modal mobility has been a long-standing goal of transit services. This paper focuses on the smart, seamless, and multi-modal mobility service in the context of “Mobility as a Service” (MaaS). Intelligent mobility is the smarter, greener, and more efficient movement of passengers around the world. Increasingly, mobility is approached as a service. This study first conducts an extensive literature review on mobility behavior and demand pattern of MaaS end-users. It then extends the mechanism of supply chain, MaaS, synergy (i.e., vertical cooperation synergy, horizontal competition synergy), and coopetition to develop the multi-tier closed-loop intelligent mobility service supply chain network. This paper explains the intelligent mobility service supply chain network from following perspectives: (i) mobility service taxonomy of MaaS; (ii) aims of intelligent mobility service supply chain network; (iii) urban rail transit (URT)-centered alternatives for integrated multimodal journey planning, i.e. access + URT + egress, and both access and egress can be served by Mobility-On-Demand (MOD) transport; (iv) node member imperatives. From a synthesis of insights from the ‘during’ journey, this study puts forward the synergetic design of intelligent mobility service supply chain network, including: (i) multi-tier closed-loop structure; (ii) key nodes identification for the physical multimodal transport network in the supply chain; (iii) hybrid synergy mechanisms among the partners, i.e., synergy principle, temporal splitting approach for coopetition synergy; (iv) index systems and evaluation methods for synergy measurement. This study also contributes to the integrated multimodal journey planning. In concluding, the paper highlights the important implications of the proposed intelligent mobility service supply chain network for MaaS bundle design and adverse effects reduction, resulting from 1 + 1 > 2 synergy effects.

Polymerase chain reaction (PCR) technique is one of the molecular methods in amplifying DNA for the detection of malaria. However, the limitations of PCR especially when used for routine clinical practice can hamper its sensitivity and specificity. With that, this study focuses on designing a microfluidic device that will mimic the function of a conventional genus-specific PCR based on 18S rRNA gene to detect malaria parasites (Plasmodium falciparum) at low grade parasitemia. The design was drawn and simulated using ANSYS 14.5 Computational Fluid Dynamics (CFD). The simulation shows that adding loops to the design increases its relative deviation but to a minimal extent as compared to having only a straight path design, which indicates that looping is acceptable in designing a microfluidic device to minimize chip length. Also, increasing the cross-sectional area of the fluid path decreases the efficiency of the design, thus, the design with a relatively smaller cross-sectional area is favored. And lastly, among the three materials utilized, the chip made of polypropylene is the most efficient with a relative deviation of 0.94 as compared to polycarbonate and polydimethylsiloxane which have relative deviations of 2.78 and 1.92, respectively.

The market for microfluidic chips is experiencing significant growth; however, their development is hindered by a complex design process and low efficiency. Enhancing microfluidic chips’ design quality and efficiency has emerged as an integral approach to foster their advancement. Currently, the existing structural design schemes lack careful consideration regarding the impact of chip area, microchannel length, and the number of intersections on chip design. This inadequacy leads to redundant chip structures resulting from the separation of layout and wiring design. This study proposes a structural optimization method for microfluidic chips to address these issues utilizing a simulated annealing algorithm. The simulated annealing algorithm generates an initial solution in advance using the fast sequence pair algorithm. Subsequently, an improved simulated annealing algorithm is employed to obtain the optimal solution for the device layout. During the wiring stage, an advanced wiring method is used to designate the high wiring area, thereby increasing the success rate of microfluidic chip wiring. Furthermore, the connection between layout and routing is reinforced through an improved layout adjustment method, which reduces the length of microchannels and the number of intersections. Finally, the effectiveness of the structural optimization approach is validated through six sets of test cases, successfully achieving the objective of enhancing the design quality of microfluidic chips.

As one of the most critical parameters to evaluate the quality and performance of mobile phones, real-time temperature monitoring of the mobile phone integrated chips is vitally important in the electronics industry. Although several different strategies for chip surface temperature measurement have been proposed in recent years, distributed temperature monitoring with the high spatial resolution is still a hot issue to be solved urgently. In this work, a fluorescent film material with photothermal properties containing thermosensitive upconversion nanoparticles (UCNPs) and polydimethylsiloxane (PDMS) is fabricated for chip surface temperature monitor-ing. The presented fluorescent films have thicknesses ranging from 23 to 90 μm and are both flexible and elastic. Using the fluorescence intensity ratio (FIR) technique, the temperature sens-ing properties of these fluorescent films are investigated. The maximum sensitivity of the fluo-rescent film was measured to be 1.43% K-1 at 299 K. By testing the temperature at different posi-tions of the optical film, a distributed temperature monitoring with a high spatial resolution down to 10 μm on the chip surface is successfully achieved. It is worth mentioning that the film maintains stable performance even under pull stretch up to 100%. The correctness of the method is verified by taking infrared images of the chip surface with an infrared camera. These results demonstrate that the as-prepared optical film is a promising anti-deformation material for high spatial resolution temperature monitoring on-chip surfaces.

Worldwide, among older adults, infection is the leading mortality cause; chronic nutritional deficits confer significant mortality risk and increase healthcare costs. The association of the Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition with infection-related mortality, especially with renal dysfunction in older patients, remains unevaluated. In older patients hospitalized with infection, stratified by renal function, we investigated the association of malnutrition severity with mortality. This single-center, retrospective cohort study of 1220 participants (age ≥65 years) admitted to Aichi Medical University from 2019 to 2020 used a multivariate Cox proportional hazards model to determine the association of GLIM-defined nutritional status (no, moderate, or severe malnutrition) with all-cause mortality. Compared to no malnutrition, moderate and severe malnutrition conferred significantly higher mortality (adjusted hazard ratio [confidence interval ]: 1.00 [reference], 1.76 [1.28-2.42], and 2.44 [1.78-3.33], respectively), with the highest all-cause mortality in malnutrition with a low estimated glomerular filtration rate (eGFR &lt;30 mL/min/1.73m2; 7.35 [4.57-11.8]) compared to no malnutrition and normal eGFR (≥60 mL/min/1.73m2). GLIM-defined malnutrition confers higher all-cause mortality risk in older adults with infection, especially those with renal dysfunction. This information enables the identification of high-risk older patients with infection and targeted clinical management of those with malnutrition, renal dysfunction, and infection.

Oncological changes in the prostate are a common cause of death among elderly men. Malignant cells are difficult to identify at early stages, which are asymptomatic. The patient often seeks medical assistance when the disease has already progressed, and the treatment is less effective. Early diagnosis of prostate cancer (PC) is thus one of the priority tasks of modern urology and healthcare in general. The aim of this study is the detection of microRNAs (miRNAs), which are known to be associated with PC. The detection of the target miRNAs in human plasma samples has been performed with a nanoribbon biosensor system, which was based on "silicon-on-insulator" structures (SOI-NR biosensor). In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been modified with DNA oligonucleotide probes (oDNA probes), whose nucleotide sequences were complementary to those of the target miRNAs. The high detection sensitivity has been demonstrated with the use of model oDNAs, which are complementary to nanoribbon-immobilized oDNA probes, in buffer solutions. The sensitivity threshold was 1.1 × 10^-17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for PC markers is a step towards personalized medicine.

The one pot hydrogenolysis/hydrogenation reaction of maltose to 2 moles of sorbitol has been carried out over different supported Cu catalysts in water at 180°C and 40 bar of H2. Only the catalysts supported on silicas were found to be effective in this reaction giving up to 86% yield in the desired product while the bare supports and the catalysts supported on alumina or silica alumina gave messy reactions. The peculiar activity of the two Cu/Silica systems tested was ascribed to high metal dispersion and suitable polarity of the catalyst surface. The reduced catalyst, exposing metallic Cu particles on the surface, showed unusual stability in the presence of water as a solvent and could be reused several times without any treatment.

This paper aims to describe the geometrical structure and explicit expressions of family of finitely parametrized probability densities over smooth manifold $M$. The geometry of family of probability densities on $M$ are inherited from probability densities on Euclidean spaces $\left\{U_\alpha \right\}$ via bundle morphisms, induced by an orientation-preserving diffeomorphisms $\rho_\alpha:U_\alpha \rightarrow M$. Current literature inherits densities on $M$ from tangent spaces via Riemannian exponential map $\exp: T_x M \rightarrow M$; densities on $M$ are defined locally on region where the exponential map is a diffeomorphism. We generalize this approach with an arbitrary orientation-preserving bundle morphism; we show that the dualistic geometry of family of densities on $U_\alpha$ can be inherited to family of densities on $M$. Furthermore, we provide explicit expressions for parametrized probability densities on $\rho_\alpha(U_\alpha) \subset M$. Finally, using the component densities on $\rho_\alpha(U_\alpha)$, we construct parametrized mixture densities on totally bounded subsets of $M$. We provide a description of inherited mixture product dualistic geometry of the family of mixture densities.

In this paper, I investigate Hyers-Ulam-Rassias stabilities of the general quintic functional equation and the general sextic functional equation.

The motivation for investigating the issues presented in this article stemmed from a need to understand better the relationship in long-established physics formulas and extract the information they provided using conventional methods. Based on the definition of magnetic flux quantization, which is based on a combination of fundamental physical constants, the Planck constant, and the particle’s elementary charge, this work explores the results that arise when this equation is combined with the equation of the Bohr-level electrostatic force acting on the electron, which leads to a new mathematical relationship between the combined expressions. The new relationship yields novel theoretical findings related to the known universal constants. Following this insight, the formalism developed in this paper indicates that the mass of the electron and other subatomic particles is associated with the magnitude of the square of the magnetic flux quantum, which makes up the particle. This conclusion is not as strange as it may seem, as the square of the magnetic flux quantum appears in the context of magnetic energy in a current loop and, according to Einstein’s special theory of relativity, energy is equivalent to mass. Another aspect described at the end of this paper demonstrates the connection between the square of the magnetic flux quantum through the Bohr radius and the significance of the wave function in the atom. The theoretical results are in full accordance with experimental results published by NIST CODATA 2018 that I’ve used, which validates the existence of the relationship.

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

To identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association, for a personalized application in clinical practice. Methods. 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. Results. Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q, and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p&lt;0.001) with a cut-off ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg scale showed an AUC of 0.883 (p&lt;0.001) with a cut-off &gt;2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p&lt;0.001) with a cut-off &gt;7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p&lt;0.001) with a cut-off ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan's nomogram to calculate the post-test probability of this association. Conclusions. Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients’ characteristics, significantly increases the ability to find out the presence of SSc-ILD.

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

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.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

Lung cancer is a prevalent and aggressive neoplasm worldwide, contributing to significant mortality rates. Dehydroepiandrosterone (DHEA) constitutes the bulk of the steroid hormone in human plasma, has a robust antiproliferative effect, and induces cell death in various tumor cells. However, its role in lung cancer cells remains unexplored. This study aimed to investigate the influence of DHEA on the proliferation, viability, autophagy, and migration of several lung cancer cell lines, including A549, HCC827, and NCI-H2347. Cell proliferation was assessed through crystal violet staining; cell number and viability were evaluated using trypan blue staining; viability was confirmed by MTT reduction, a method that is also an indicator of metabolic activity; migration was assessed via a wound healing assay. Autophagy was evaluated using a specific kit, while cell death was determined by annexin-V-FITC/propidium iodide staining and caspase-3/7 activity assay. The results indicate that DHEA significantly reduced proliferation, cell number, metabolic activity, and migration in all examined lung tumor cells. These effects correlate with an increased autophagy induced by DHEA. No signs of apoptosis or necrosis were observed across the range of DHEA concentrations used. Although these findings are preliminary, they suggest that DHEA could hold promise as an alternative treatment option for various subtypes of lung cancer.

Prostate cancer (PCa) Lung metastases are rarely resected, therefore PCa lung metastases are insufficiently molecularly characterized. We recently identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a potential driver of pulmonary metastatic spread. Here, we show the biological significance of CEACAM6 in PCa cell proliferation, apoptosis and migration. CEACAM6 was silenced by siRNA in PC3 cells. Functional assessment of apoptosis, cell viability, proliferation and migration were performed in siRNA-CEACAM6 PC3 cells. Non-treated and scrambled (scr) RNA PC3 cells were used as control. Following a specific knockdown of CEACAM6 in PC3 cells, the expression of CEACAM6 protein was significantly decreased in comparison to controls. Cell viability and cell counts decreased in CEACAM6 silent PC3 cells. In contrast, caspase-3 activity was highly elevated in siRNA-CEACAM6 PC3. Furthermore, by performing a cell scratch assay, the migration ratio in siRNA-CEACAM6 PC3 cells were significantly diminished compared with the control group after 48 hours of post transfection incubation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumours such as colorectal or gastric cancer. We could show that silencing of CEACAM6 has a significant functional effect on PCa cells. CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation and suppressing apoptosis. CEACAM6 might therefore pose an attractive therapeutic target to prevent metastatic disease.

Background:Malignant pleural effusion (MPE),a frequent complication of advanced malignancies. This pilot study characterized and compared the immune landscapes of breast carcinoma (BC) and lung adenocarcinoma (LADC) primary tumors(PTs) and their corresponding MPEs and tested the incorporation of multiplexed image technology for the study of malignant fluids. Methods: We studied the immune contexture of 6 BC and 5 LADC PT samples and their MPEs using 3 multiplex immunofluorescence panels. We explored associations between sample characteristics and pleural effusion–free survival. Results: Although we found 3 out of 11 PTs PD-L1 positive more than 1% by malignant cells, no MPE samples reached positive expression by malignant cells. In addition, CD3+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs vs. PTs: 45.5% vs. 40.7% and 4.7% vs. 6.6%, respectively). In the BC samples, CD68+ macrophages predominated (median percentages for MPEs vs. PTs:61% vs. 57.1%). Generally, CD3+CD8+FOXP3+ T cells in PTs and the distances from the malignant cells to CD3+CD8+Ki67+ and CD3+PD-1+ T cells were correlated in the first event of MPE after diagnosis. Conclusions: The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but were different for LADC vs. BC.MPE analysis could be used as a substitute for PT analysis, but an expanded study on this topic is essential.

Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscess due to this agent with left heart endocarditis. We describe the case of a 40-year-old man with a brain abscess due to S. intermedius and concomitant lung abscess and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.

In comparison to the general population, lung cancer patients are more likely to suffer from severe Coronavirus disease (COVID-19) and mortality associated with it. Considering this increased risk, and in order to prevent symptoms and severe disease, patients with lung cancer have been prioritized for COVID-19 vaccinations, primary and booster doses. Despite this, the pivotal clinical trials did not include these patients, which leaves open questions regarding vaccine efficacy and humoral immune response. This review outlines the findings of recent investigations into the humoral responses of lung cancer patients to COVID-19 vaccination, particularly the primary doses and first boost.

In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.

Obesity is a significant public health concern with higher morbidity. Obesity patients are at risk of severe COVID-19 infection and obesity is a higher risk factor for intensive Care Unit admission in COVID-19 infection. Obesity status affects lung volumes, cardiac structure and hemodynamics. Obesity is associated with a low inflammation state, endothelial dysfunction, hyperinsulinaemia and metabolic disorders. The authors review cardio-respiratory pathophysiological aspects involved in obesity and propose clinical management in obese patients infected by COVD-19.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Background: Lung cancer is one of the common causes of death worldwide. Although the incidence rate of lung cancer in Western countries is decreasing, it presents a growing trend in developed countries. Since there is no accurate enough information about the epidemiological and Histopathologic features of lung cancer in central Iran, Isfahan, we were motivated to conduct this research. Materials and Methods: This was a descriptive, cross-sectional study carried out in central Iran, Isfahan. All demographic, histopathological and clinical data of the lung cancer patients registered in MACSA, a referral charity-based cancer center in central Iran, was analyzed within 2012-2018 using SPSS v.22 software. Results: Altogether 260 patients with lung cancer were included in this study from 6127 cancer patients registered within 2012-2018 (4.2%). Out of them, 66.2% were men, and 18.8 % of the patients were alive at the time of the study. The mean age of the patients at diagnosis was 61.56 (SD=14.11, range: 9-93). Altogether, 63.1% of patients had metastasis of whom 57.6% were in stage IV at diagnosis. The Frequency of different types of lung cancer was 36.9% adenocarcinomas, 14.2% squamous cell carcinoma, 9.6% bronchogenic carcinoma and 8.1% small cell lung cancer, respectively. Altogether, 128 cases were smokers with an average 35.45 ± 14 pack- years. Only in 36.2% of the patients, the diagnostic and therapeutic biomarkers had been checked, and CK7 was positive in 88.9% of the cases in which the biomarker had been checked. Conclusion: Despite to similar Iranian studies, the most common histopathologic type of lung cancer among the patients was adenocarcinoma that it may be attributed to the lower consumption of smoking in our population and their different genetic context. Molecular biomarkers had been checked in a small portion of the patients. More education of the clinicians along with the development of cancer molecular testing may lead to promote the personalized-based approach.

The metastasis of lung cancer can spread to the lymph nodes around the lungs. Metastasis, rather than the primary cancer, judges patients survival. Wherefore, a more detailed study on transcriptome of metastatic lung adenocarcinoma including primary carcinoma was carried out. LUAD RNA-seq data and the corresponding clinical information were available from The Cancer Genome Atlas (TCGA), which included 522 cases but only 515 cases have transcriptome data. Differential expression analyses between cases and controls, between primary cancer and metastasis subgroup, or between TNM stages, were respectively carried out using edgeR package. Then, the Kruskal-Wallis tests were used to verify the gradient changes of cancer metastasis or staging with the differential expression genes. The survival analyses were calculated using the Kaplan-Meier algorithm and log-rank test. The functional predictions for the differentially expressed genes were porformed with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG). Single gene set enrichment analysis (single GSEA) was run to explore the biological pathways associated with the expressions of RN7SL494P gene based on the Molecular Signatures Database (MSigDB). 406 and 439 differentially expressed genes were identified respectively in lymph node metastasis or TNM stages. 112/296 intersection genes were associated with nodal metastasis and/or staging, among them only 25 genes were associated with the nodal metastasis, 13 genes were associated with the staging with gradient changes. Only one gene (RN7SL494P) was found to be associated with prognosis. But RN7SL494P was not found joining any biological functions or processes or cellular components with GO/KEGG analyses. Finally, single GSEA enrichment and pathway analyses showed that RN7SL494P might be involving in cancer development process and poor outcome in lung adenocarcinoma. These findings highlight the potential applications of RN7SL494P as a promising molecular predictor not only in nodal metastasis but prognosis evalution in lung adenocarcinoma patients.

Recent changes in lung cancer care, including new approvals in first line and the introduction of high throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second and third generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated to the identification of new predictive markers.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

An efficient approach to the previously unknown furo[2',3':2,3]pyrrolo[2,1-a]isoquinoline deriv-atives from readily available 1-R-1-ethynyl-2-vinylisoquinolines is described. The reaction fea-tures a simple procedure, occurs in hexaflouroisopropanol and does not require elevated tem-peratures. It has been found that the addition of glacial acetic acid significantly increases the yields of the target spirolactone products. Using trifluoroethanol instead of hexaflouroisopro-panol results into formation of pyrido[2,1-a]isoquinolines.

Here we report a comparative study of the pyhtochemical profile and a biological activity of the two onion extracts, namely A. cepa L. and A. × cornutum (Clementi ex Visiani 1842). Identification of flavonoids and anthocyanins and their individual quantities were determined by high performance liquid chromatography (HPLC). The potency of both extracts to scavenge free radicals was determined by DPPH (2,2'-diphenyl-1-picrylhydrazyl) radical-scavenging activity and oxygen radical absorbance capacity (ORAC) methods. DNA protective role was further tested by single-cell gel electrophoresis (COMET) assay and by Fenton’s reagent causing double strand brakes on pUC19 plasmid. In the presence of both extracts, a significant decrease in the DNA damage was observed, which indicates a protective role of A. cepa and A. × cornutum on the DNA strand brakes. Additionally, cytotoxicity was tested on glioblastoma and breast cancer cell lines. The results showed that both extracts had antiproliferative effect, but the most prominent decrease in cellular growth was observed with glioblastoma cells

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Diffuse interstitial lung diseases (DILD) are a heterogeneous group of over 200 entities, some with dramatical evolution and poor prognostic. Because of their overlapping clinical, physiopathological and imagistic nature, successful management requires early detection and proper progression evaluation. This paper tests a complex networks (CN) algorithm for imagistic aided diagnosis fitness for the possibility of achieving relevant and novel DILD management data. 65 DILD and 31 normal high resolution computer tomography (HRCT) scans were selected and analyzed with the CN model. The algorithm is showcased in two case reports and then statistical analysis on the entire lot shows that a CN algorithm quantifies progression evaluation with a very fine accuracy, surpassing functional parameters’ variations. The CN algorithm can also be successfully used for early detection, mainly on the ground glass opacity Hounsfield Units band of the scan.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

The Standard Model is not a complete description of reality; it omits the existence of dark matter, dark energy, and an explanation as to why no CP violation has been observed. However, some of these phenomena could be explained through a new force mediated by a new boson. If such a boson were massless it would result in a power law potential and if massive the interaction would be Yukawa-like. A previous experiment employing a micro-mechanical oscillator and a spherical test mass interactions was successful in placing the best limits on a mass-mass Yukawa-like interaction, but the data was never analyzed in the context of a power law. Here that data is analyzed considering a power law for powers n = 1-5 where n is the number of boson exchanges. The results show that the limits obtained through power law analysis of this data are not better than the currently accepted limits. A discussion of an experiment design capable of producing better limits on power law extensions to the Standard Model is presented, and suggests micro mechanical oscillators based experiment remains capable of improving the limits by at least one order of magnitude.

Spiking neural networks (SNNs) promise to perform tasks currently done by classical artificial neural networks (ANNs) faster, in smaller footprints and using less energy. Neuromorphic processors are set out to revolutionize computing at a large scale, but the move to edge-computing applications calls for finely-tuned custom implementations to keep pushing towards more efficient systems. To that end, we have examined the architectural design space for executing spiking neuron models on FPGA platforms, focusing on achieving ultra-low area and power consumption. This work presents an efficient clock-driven spiking neuron architecture used for the implementation of both fully-connected cores and 2D convolutional cores, which rely on deep pipelines for synaptic processing and distributed memory for weight and neuron states. With them, we have developed an accelerator for an SNN version of the LeNet-5 network trained on the MNIST dataset. At around 5.5 slices/neuron and only 348 mW, it is able to use 33% less area and 4 times as less power per neuron as current state-of-the-art implementations while keeping low simulation step times.

This paper sheds light on how crisis management affects post-disaster re-covery. Based on the study of the management of a major environmental disaster, hurricane IRMA, we consider how post-disaster recovery is impacted by crisis management strategies. The perspectives of local stakeholders from the islands of St Martin and St Barthélémy will be shared. We analyze how territories exposed to the same natural phenomena have different outcomes and consider some of the possible reasons. This study reveals underlying risk drivers, to address governance reorganization with a view to better managing socio-economic recovery.

This article presents a wide-band antenna designed for the Cube Satellite (CubeSat). Based on a quadrifilar structure, the antenna provides circular polarization radiation, which is suitable for satellite communication. Moreover, the antenna is designed and fabricated using two 1.6 mm thickness FR4-Epoxy boards that connect together by the metal pins. In order to improve the robustness, a ceramic spacer is placed in the centerboard, and four screws at the corners are added to fix the antenna with the CubeSat structure. These additional parts reduce antenna damage caused by vibrations in the launch vehicle lift-off stage. The proposal has a dimension of 77mm x 77mm x 10mm and covers the LoRa frequency bands of 868 MHz, 915 MHz, and 923 MHz. According to the measurements in an anechoic chamber, antenna gains are obtained with the values of 2.3 dBiC and 1.1 dBiC for the 870 MHz and 920 MHz, respectively. Finally, the antenna is integrated into a 3U CubeSat that was launched by a Soyuz launch vehicle. The terrestrial-to-space communication link was measured, and the antenna performance was confirmed in the real-life scenario.

The purpose of this work is to define optimal growth conditions for batch culture of the cyanobacterium Arthrospira maxima and the microalgae Chlorella vulgaris, Isochrysis galbana and Nannochloropsis gaditana. Thus, we study the effect of three variables on algae growth: i.e., inoculum:culture medium ratio, light:darkness photoperiod and type of culture medium, including both synthetic media and wastewaters. The results showed that the initial inoculum volume did not affect the amount of biomass at the end of the growth (14 days), whereas an excess (18 h) or defect (6 h) in the number of hours of light is determinant for its development. The contribution of nutrients from different culture media modified the growth of the different species. A. maxima was favoured in seawater enriched with Guillard's F/2 as well as C. vulgaris and N. gaditana but in fresh water medium. I. galbana had the greatest growth in the marine environment enriched with Walne’s media. Nitrate was the limiting growth reagent at the end of the exponential phase of growth for C. vulgaris and N. gaditana, while iron was for A. maxima and I. galbana. All species demonstrated their capability to grow in effluents from a wastewater treatment plant and they efficiently consume nitrogen, especially the three microalgae species.

Drug resistance has become an extremely serious problem worldwide. Antibiotic resistance genes (ARGs) entering the environment with wastewaters promote replenishment of the resistome of natural microbioms. Distribution of several clinically significant ARGs in wastewaters of Rostov-on-Don (Southern Russia), lower reaches of the Don River and natural waters of the neighboring region was investigated. Metagenomic DNA samples isolated from 250 ml of wastewaters or natural waters and 200 mg of surface sediments were used for the study. Identification of the ARGs was carried out with end-point detection PCR. Presence of NDM, OXA-48, CTX-M, VanA, VanB, ErmB, and TetM/TetO genes was detected in urban wastewaters. Samples of wastewater treatment plant (WWTP) sewage were enriched with ARGs in contrast to non-treated wastewaters from the sewage collector. NDM, VanA, ErmB, TetM/TetO genes were found only in wastewaters and were absent in samples of natural waters and surface sediments. Only OXA-48, VanB and CTXM genes were found in natural waters and surface sediments. The described ARGs are quite typical for urban and hospital wastewaters. The target ARGs were detected in the samples connected to the anthropogenous sources of pollution such as Rostov municipal WWTP or livestock enterprise effluents.

We report magnetic silver nanoshells (M AgNSs) that have both magnetic and SERS properties for SERS-based detection. The M AgNSs are composed of hundreds of Fe3O4 nanoparticles for rapid accumulation and bumpy silver shell for sensitive SERS detection by near-infrared laser excitation. The intensity of the SERS signal from the M AgNSs was strong enough to provide single particle-level detection. We obtained much stronger SERS signal intensity from the aggregated M AgNSs than from the non-aggregated AgNSs. 4-Fluorothiophenol was detected at concentrations as low as 1 nM, which corresponds to 0.16 ppb. The limit of detection for tetramethylthiuram disulfide was 10 μM, which corresponds to 3 ppm. The M AgNSs can be used to detect trace amounts of organic molecules using a portable Raman system.

Background: Artificial intelligence can help improve the quality of healthcare by analyzing vast amounts of data and providing more effective and personalized treatment plans. Researchers are working on developing AI-powered solutions that can help improve the outcomes of patients. Objective: To explore the potential of AI in improving healthcare outcomes and patient experience. Results: The study suggests that AI can improve healthcare efficiency and patient outcomes but cannot fully replace human healthcare professionals. AI can assist healthcare professionals in their work, leading to better resource utilization and improved patient care. However, there is still a need for human healthcare professionals to oversee AI systems and provide empathy and personalized care to patients. Conclusion: While there is immense potential for AI in healthcare, it is not yet feasible to replace human healthcare workers. Instead, it should be viewed as a tool that can help improve the efficiency and effectiveness of human healthcare.

Time-series analysis is a widely used technique across various fields and industries, as it helps in understanding, predicting, and forecasting the behavior of data points over time. These fields include but are not limited to finance, economics, healthcare, transportation, etc. In the case of this paper, we have focused on finance. Predicting future values of financial time series offers several benefits. Accurate forecasts can help investors make better decisions about their investments. To predict future values, deep learning algorithms are commonly used since it is an effective method with complex data. In this study, we conduct a study that investigates the use of different data pre-processing techniques on deep learning algorithms in predicting the time series values. To conduct this experimental study, we utilize an open source software, which using long short-term memory technique as the representative deep learning technique, published in github software code repository platform. With this study, we investigate the effects of autoencoder and discrete wavelet transform data pre-processing techniques in time-series prediction. We discuss the details of the experimental study and report our results. The results show that time series prediction (using backtesting methodology) without any data pre-processing leads to 12.6% for mean absolute percentage error. The results also show that, time series prediction with the data preprocessing techniques (Wavelet Transform and Stacked Autoencoder) lead to 3.4%

Cigarette smoke (CS) is a major driver of many respiratory diseases including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several bi-ological processes and interfere with several regulatory pathways. The purpose of this study was to assess the effect of active CS on miRNAs expression in AMs obtained from bronchoalveolar lavage (BAL) of ever- or never-smoker subjects and patients with COPD or NSCLC. BAL specimens were collected from 43 sex-matched subjects to determine the expression of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p before and after in vitro CS exposure by RT-PCR. In addition, bioin-formatic analysis of miRNAs target genes linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is noteworthy that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both ever- or never-smokers, 106a-5p in never-smokers and 20a-5p in ever-smokers, shifted towards those found in individuals with COPD, suggesting them like a risk factor in developing this lung condition. Moreover, we identified miRNA targets involved in the immune system or AMs property regulation using in silico analysis. In conclusion, our study iden-tified miRNA signatures in AMs exposed to CS, indicating that CS is an important driver of epige-netic changes that contribute to the onset of various lung diseases.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early-stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early-stage NSCLC. Inclusion criteria prioritized but were not limited to, clinical trials and meta-analyses on surgical approaches to early-stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection have emerged as treatments for early-stage NSCLC. Ground-glass opacities (GGOs) hve shown prognostic significance, especially when analyzing the consolidation-tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusion: The management of early-stage NSCLC requires further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

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.

Purpose: This study analysed the impact of the COVID-19 pandemic on the diagnosis of malignant neoplasia of the bronchus and lung. Cases diagnosed in the Burgos region in the year prior to the official declaration of the pandemic were compared with those in the year after the pandemic. The research sought to identify whether there was a decrease in the number of cases during the pandemic, and whether this may have led to a delay in diagnosis, reflected in more advanced stages of the disease. Mortality and survival time in each of the periods were also analysed.

Background: Interstitial lung disease (ILD) is a frequent complication in systemic sclerosis (SSc). So, an increased awareness of this complication is a real need in the clinical setting, because it may affect the prognosis of patients. In particular, an accurate strategy is desirable in order to detect ILD in its stages. So, we investigate the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to determine its potential in disease progression. Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and respiratory function tests (RFT) were performed. An expert rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. After the baseline assessment, the patients were followed every 3 months for 12 months. Results: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6% respectively. A good inter-observer reliability was observed (k = 0.72). In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitoring the disease progression.

The lung epithelium regulates gas exchange and is the first line of defense against airborne toxicants and microbial infections. Disruption of the integrity of lung epithelium results in altered permeability and severely impacts normal lung functions. To develop biomarkers of potential harm (BoPH) for assessing adverse health effects of cigarette smoking, we have evaluated lung barrier function. In a single-center, ambulatory, clinical study we measured lung permeability, as the half-life (T1/2) of inhaled 99mTC-DTPA, in 17 subjects consisting of 6 Smokers (SMK), 5 Moist Snuff Consumers (MSC), and 6 Non-Tobacco Consumers (NTC) at three weekly test visits. Smokers, relative to MSC and NTC, exhibited significantly faster clearance of the inhaled probe (shorter T1/2), indicating increased lung permeability. NTC and MSC had comparable clearance times of the inhaled probe (longer T1/2). Least squares regression modeling showed that the variability of the test was minimal and was not significant. Prediction profiling showed that the repeatability of the lung permeability test was robust and was able to differentiate the tobacco product use groups in this study. Thus, altered lung barrier function may serve as a BoPH for assessing the effects of tobacco use.

Definitive surgical resection is the preferred treatment for early-stage non-small-cell lung cancer (NSCLC). Research into genetic alterations, including epidermal growth factor receptor (EGFR) mutation, in early stage NSCLC remains insufficient. Here, we investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutation and recurrence after complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resection at a single regional cancer center were recruited. We compared the clinical and pathological data between the recurrence and non-recurrence groups. Multivariate logistic regression was used to predict the risk factors for recurrence. Among the 659 enrolled cases, the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutation was 43% (194/451). Among them, L858R point mutation and exon 19 deletion was 52.3% and 42%, respectively. ALK rearrangement was found at 5.7% (26/453), and ROS1 fusion was found at 1.6% (7/441). The recurrence rate of the entire population was 19.7%. In multivariate analysis, the presence of EGFR mutation, stage II or III (vs. stage I), and pathologic subtype (presence of solid type) were associated with recurrence. Among the recurred group, 86.5% of the patients with EGFR mutation experienced distant recurrence compared to only 66.7% of wild-type (p = 0.016), with no significant difference in median disease-free survival (p = 0.983). In conclusion, the prevalence of EGFR mutation, ALK rearrangement, and ROS1 fusion was 43.0%, 5.7%, and 1.6%, respectively in patients with early-stage NSCLC who underwent curative resection. Along with stage II/III and solid pathologic subtype, EGFR mutation was an independent risk factor for recurrence. In the recurrence group, the rate of distant metastasis was higher in patients with EGFR mutation than in those with wild-type.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

Indoleamine 2,3-dioxygenase 2 (IDO2) is a paralogue of IDO1, a tryptophan-degrading enzyme producing immunomodulatory molecules. However, the two proteins are unlikely to carry out the same functions. IDO2 shows little or no tryptophan catabolic activity and exerts contrasting immunomodulatory roles in a context-dependent manner, in both cancer and autoimmune diseases. The recently described potential non-enzymatic activity of IDO2 has suggested its possible involvement in alternative pathways resulting in either pro- or anti-inflammatory effects in different models. In a previous study on non-small cell lung cancer (NSCLC) tissues, we found that IDO2 expression, revealed at the plasma membrane level of tumor cells, was significantly associated with poor prognosis. In this study, the A549 human cell line, basally expressing IDO2, was used as an in vitro model of human lung adenocarcinoma to gain more insights on a possible alternative function of IDO2, different from the catalytic one. In these cells, immunocytochemistry and isopycnic sucrose gradient analyses confirmed the IDO2 protein localization in the cell membrane compartment, and immunoprecipitation of tyrosine-phosphorylated proteins revealed that IDO2 can be targeted by kinase activities. The different localization than the cytosolic one and the phosphorylation state are the first indications for the signaling function of IDO2, suggesting that the IDO2 non-enzymatic role in cancer cells is worthy of deeper understanding.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

Lung cancer accounts for the majority of cancer cases. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment, or TMJ, or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body's response to inflammation and infection. Cytokines are important for immunity in lung cancer. It promotes tumor growth (oncogenic cytokines) or inhibits tumor growth (anti-tumor cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system stop the growth or kill cancer cells. Interleukins and interferons are two types of cytokines used to treat cancer. This article begins by addressing the role of the tumor microenvironment (TMJ) and its components in lung cancer. This review also highlights the functions of various cytokines such as IL, TGF and TNF.

Outdoor air pollution is a leading cause of death and premature death globally. Motorcycle-taxi drivers were most at risk associated with occupational exposure to ambient air pollution in urban areas. Therefore, a cross-sectional study was conducted to determine the influencing factors and prediction of lung function impairment in 308 motorcycle-taxi drivers living in Bangkok and adjacent provinces between February and June 2022. The study design included: data collection using questionnaires applied from the Thai version of ATS-DLD-78A: American Thoracic Society Division of Lung Diseases and Department of Disease Control, Ministry of Public Health, Thailand; a collection of respirable dust, and ambient air pollution parameters measured by per-sonal air sampling pump and real-time air quality index (AQI) station, and lung function determined by the spirometer. The results showed that 14 factors were significantly associated with lung function impairment (p<0.05). Apparently, seven influencing factors showing the most association were included: gender, the height of the subjects, history of allergies, exposure to respirable dust, mask types, helmet types, and family history of lung disease. The lung function impairment of motorcycle-taxi drivers was significantly predicted in 28.1% by regression analysis of these seven variables (R2=0.281). Therefore, this is the first report on influencing factors and prediction of lung function impairment among motorcycle-taxi drivers. These findings would be very useful for preventing and controlling measure ambient air pollution, setting policies and strategies to mitigate the risks for motorcycle-taxi drivers and the other ex-posed population.

HMGB1 is a key late inflammatory mediator upregulated during air pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays significant roles in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 level may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense for air pollution-induced oxidative stress lung damage. Here, a standardized bioflavonoid antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis induced by oxidative stress and endotoxemia. Murine hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized in vivo. Effect of the bioflavonoid composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed macrophages in vitro. Hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, western blot analysis for protein and HMGB1 as well as bacterial counts in the lung and airways have been performed. Statistically significant decrease in mortality (50%), reduced proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage, increased bacterial clearance of airways and lungs; reduced airway total protein, and extracellular HMGB1 were observed in vivo. A statistically significant 75.9% reduction in the level of HMGB1 and increased phagocytosis activity were also observed in vitro. The compilation of data in this report strongly suggest that the bioflavonoid composition could be indicated for oxidative stress induced lung damage protection possibly through attenuation of extracellular HMGB1.

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that EPB41L3 increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of the epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549), and the fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5), by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured by RT-PCR, real-time PCR, and western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated mRNA and protein expression of FN1, COL1A1, and VIM. Overall, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest therapeutic potential of EPB41L3 as an anti-fibrotic mediator.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (&gt; 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

Renal Cell Carcinoma (RCC) is generally represented by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT to correctly identify RCC lung metastases using histology as standard of truth. Records of 350 patients affected by RCC and with CT evidence of at least one lung nodule, were retrospectively analyzed. Inclusion criteria were: a) histologically proven RCC; b) [18F]FDG-PET/CT performed prior to lung surgery; c) lung surgery with histological analysis of surgical specimens; d) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven (n=67) patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57/107 of cases, while 50/107 lesions were related to others lung malignancies. Applying a cut-off of SUVmax ≥2, the sensitivity and the specificity of [18F]FDG-PET/CT for detect RCC lung metastases were 33.3% (95% CI: 21.4% - 47.1%) and 26% (95%CI: 14.6% - 40.3%), respectively. The analysis demonstrated sub-optimal diagnostic accuracy of [18F]FDG-PET/CT to discriminate between RCC lung metastases versus other malignancies. However, semiquantitative analysis including also volumetric parameters (MTV and TLG) can support [18F]FDG-PET/CT image interpretation.

The High-Resolution Computed Tomography (HRCT) detection and diagnosis of diffuse lung disease is primarily based on the recognition of a limited number of specific abnormal findings, pattern combinations or their distributions, as well as anamnesis and clinical information. Since texture recognition has a very high accuracy percentage if a complex network approach is used, this paper aims to implement such a technique customized for diffuse interstitial lung diseases (DILD). The proposed procedure translates HRCT lung imaging into complex networks by taking samples containing a secondary lobule, converting them into complex networks and analyzing them in 3 dimensions: emphysema, ground glass opacity and consolidation. This method was evaluated on a 60 patient lot and the results show a clear quantifiable difference between healthy and affected lungs. By deconstructing the image on three pathological axes, the method offers an objective way to quantify DILD details which, so far, have only been analyzed subjectively.

Cigarette smoking and air pollution (particulate matter) are recognized as two major etiological factors for lung cancer. Of all the risk factors, cigarette smoking is significantly associated with lung carcinogenesis. The main mechanism lies in the metabolically activated carcinogens (majorly polycyclic aromatic hydrocarbons and nitrosamines), which could covalently bind with DNA molecules and lead to irreversible mutations in pivotal cancer genes, such as TP53 and KRAS. Another major etiological factor for lung cancer is air pollution, which is with complex compositions and ubiquitous in daily life, especially in developing countries as China and India. The latest literatures on lung cancer epidemiology and etiology have been briefly summarized and reviewed in this work.

Metamorphosis is a critical process for most anurans to transition from water to land. The appearance of air-breathing lungs occurs during the change in oxygen medium from water to air. Revealing the structural construction and molecular switches of lung organogenesis is essential to understand the realization of air-breathing function. In this study, histology and transcriptomics were combinedly conducted to explore these issues in Microhyla fissipes lungs during metamorphosis. During the pro-metamorphic phase, histological structure improving of the alveolar wall was accompanied by robust substrate metabolism and protein turnover. The lungs, at the metamorphic climax phase, are characterized by an increased number of cilia in the alveolar epithelial cells and collagenous fibers in the connective tissues, corresponding to the transcriptional upregulation of cilia and extracellular matrix-related genes. The post-metamorphic lungs strengthen the contracting function, as suggested by the thickened muscle layer and the upregulated expression of genes involved in muscle contraction. The blood–gas barrier is fully developed in adult lungs whose transcriptional features are tissue growth and differentiation regulation and immunity. Importantly, significant transcriptional switches of pulmonary surfactant protein and hemoglobin facilitate air-breathing. Our results illuminated four key steps of lung development for amphibians to transition from water to land.

Despite the many advantages of lung ultrasound (LUS) in the diagnosis and management of patients with dyspnea, adoption among hospitalists has been slow. We performed semi-structured interviews of hospitalists from 4 diverse health systems in the US to understand determinants of adoption within a range of clinical settings. We used the Diffusion of Innovation Theory to guide a framework analysis of the data. Of 27 hospitalists invited, we performed in-terviews of 22 from 4 hospitals of diverse types. Median years post-residency of interviewees was 10.5 [IQR:5-15]. Four main themes emerged: 1) There are important clinical advantages to LUS despite operator dependence, 2) LUS enhances patient and clinician experience, 3) Investment of clinician time to learn and perform LUS is a barrier to adoption but yields improved efficiency for the health system and 4) Mandated training and use may be necessary to achieve broad adoption as monetary incentives are less effective. Despite perceived benefits of LUS for patients, clinicians and health systems, an important barrier to broad LUS adoption is the experience of time scarcity by hospitalists. Future implementation strategies should focus on changes to the clinical environment that address clinician barriers to learning and adoption of new skills.

Background; Programmed death-1 (PD-1) and PD-1 ligand 1 (PD-L1) are target molecules for immunotherapy in non-small cell lung cancer. PD-L1 is expressed not only in cancer cells, but also on macrophages, and has been suggested to contribute to macrophage-mediated immune suppression. Methods; Clinical significance of PD-L1 expression on macrophages in human lung adenocarcinoma was examined. The mechanisms of PD-L1 overexpression on macrophages were investigated by means of cell culture studies. Results; High PD-L1 expression on macrophages was correlated with the presence of EGFR mutation, a lower cancer grade, and a shorter cancer-specific overall survival. In an in vitro study using lung cancer cell lines and human monocyte-derived macrophages, the conditioned medium from cancer cells was found to up-regulate PD-L1 expression on macrophages via STAT3 activation, and a cytokine array revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was a candidate factor that induced PD-L1 expression. Culture studies using recombinant GM-CSF, neutralizing antibody, and inhibitors indicated that PD-L1 overexpression was induced via STAT3 activation by GM-CSF derived from cancer cells. Conclusions; PD-L1 overexpression on macrophages via the GM-CSF/STAT3 pathway was suggested to promote cancer progression in lung adenocarcinoma. Cancer cell-derived GM-CSF might be a promising target for anti-cancer therapy.

Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..

There are numerous challenges involved in the diagnosis and treatment of lung cancer. Globally, majority of people suffers from cancerous disease involving throat cancer, lung cancer, stomach cancer, cancerous brain tumor. Among these the most common ones is the lung cancer or lung carcinoma. The leading cause of the lung cancer is the smoking. Around 80% to 90% of deaths are caused due to Non-small cell lung cancer (NSCLC). The inadequate diagnostic techniques and low chances for the survival of lung cancer patients results from the lack of an early prognosis and incompetency in traditional therapies. However, such challenges involved in the prognosis and treatment of lung cancer are on decline with the progression in magnetic nanoparticle (MNP) technology. Many break-through discoveries and inventions have been made in the field of cancer therapy by using magnetic nanoparticles. The implication of nanotechnology has led to the recent advancement in nanomedicine field. This has encouraged the improvement in different therapeutic and diagnosis strategies employing nanotechnology. The generation of immense technological benefits for nanoparticles systems has been accredited to its remarkable nanoscale physico-chemical properties. This in turns provides the early detection of lung cancer and active drugs delivery for an improved theranostics strategy. The present review provides a general idea of the current progression in the therapeutic and prognosis purpose of magnetic nanoparticles. Further, we disclose the development in the lung cancer theranostics by functionalization of magnetic nanoparticles. The established importance of magnetic nanoparticles in the theranostics centers for lung cancer has been revealed in this paper. The challenges existing in the theranostics of lung cancer are addressed through the functioning of magnetic nanoparticles in the process.

The recent COVID-19 outbreak in China led to a worldwide pandemic associated with a severe acute respiratory illness. A higher incidence of COVID-19 infection was demonstrated in cancer patients, including patients with lung cancer. This study was conducted to get insights into the reasons for this enhanced frequency of COVID-19 infection. Methods: Using different bioinformatic tools, the expression and methylation pattern of ACE2 and TMPRSS2 gene were analyzed in healthy and malignant tissues with a focus on lung adenocarcinoma (LUAD) and correlated to clinical parameters and smoking history. Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression in digestive, urinary and reproductive organs, while their expression was significantly lower in 36 cancer tissues. In LUAD, ACE2, but not TMPRSS2 was overexpressed, which inversely correlated to the promoter methylation. An age-dependent upregulation of ACE2 expression was found in LUAD compared to normal lung tissues. In a healthy lung, TMPRSS2 expression was dependent on sex and smoking history and downregulated in LUAD of smokers. Cancer progression was associated with decreased TMPRSS2, but unaltered ACE2 expression, while ACE2 expression in lung metastases of different cancers was higher than in metastasis of other sites. TMPRSS2, but not ACE2 expression, was associated with LUAD patients’ survival. Conclusions: Comprehensive molecular analyses revealed a heterogeneous, distinct expression and methylation profile of ACE2 and TMPRSS2 in healthy lung vs LUAD tissues across sex, age and smoking history, which is associated with clinical parameters and might have implications for COVID-19 disease.

Background: Lung CT provides an effective modality to evaluate patients with suspected COVID-19. However, overlapping imaging findings with cardiogenic pulmonary oedema have been reported. Reports comparing lung CT features of these diseases have not been elaborated. Thus, we aimed to investigate these gaps in the knowledge regarding low-dose lung CT features of patients with COVID-19 pneumonia with those with acute heart failure (HF). Methods: This retrospective analysis enrolled hospitalized patients with COVID-19 (n=10) and acute heart failure (n=9) that exclusively underwent low-dose lung CT scans within 24-hours of admission. Clinical and lung CT characteristics were collected and analysed. Results: Ground-glass-opacities (GGO) appearance has been recorded in all subjects in HF and COVID-19 group. There was no significant statistical difference between the two groups for rounded morphology, consolidation, crazy paving pattern, lesion distribution, parenchymal band (P> 0.05). However, diffuse lesions were more frequent in HF cases (55.6% vs. 0%) than in COVID-19 pneumonia, which had predominantly multifocal pattern. Notably, CT images in HF patients were more likely to have signs of interstitial tissue thickening such as the interlobular septums, fissures and peribronchovascular interstitium (55.6% vs 0%, 88.9% vs 20% and 44.4% vs 0%,respectively), as well as cardiomegaly (77.8% vs 0%), increased artery to bronchus ratio (55.6% vs 0%), and pleural effusions (77.8% vs 0%). Conclusions: Major overlaps of lung CT imaging features existed between COVID-19 pneumonia and acute HF cases. However, signs of fluid redistribution are clues that favour HF over COVID-19 pneumonia.