Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.

In this study, diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into 3 different study and control groups according to the duration of the OTA administration. Rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks study groups. Three control groups without any treatment were also used in the same periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of 6, 9 and 24 weeks. Plasma values of insulin, glucagon and glucose in study and control groups were determined. Pancreatic lesions were evaluated by histopathological examination; then insulin and glucagon expression in these lesions were determined by immunohistochemical methods. Statistically significant decrease in insulin levels in contrast to increases in glucagon and glucose levels in blood were observed. Slight degeneration in Langerhans islet cells were observed at the histopathological examination in all OTA treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in Langerhans islet and predispose rats to DM.

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain, which has naturally high pathogenic properties for mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity also in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. Besides, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity for mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. Contrarily, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed.

Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on antinociceptive activity and itch-associated scratching behavior (LLS) in mice, and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose, and inhibited IL-31-induced LLS. These results suggested that repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. IL-31 and morphine combination increased analgesic action which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.

The theory that an itch inhibits pain has been refuted; however, previous research did not investigate this theory for interleukin-31 (IL-31)-induced itch. Previously, we have found that morphine-induced antinociception was partially reduced in IL-31 receptor A (IL-31RA)-deficient (IL-31RAKI) mice, indicating that IL-31RA may play an important role in morphine-induced peripheral antinociception. In the present study, we evaluated the effect of IL-31-induced analgesia on a 2,4,6-trinitrochlorobenzene (TNCB)-sensitized mice using a hot-plate test. This test evaluated the antinociceptive activity of morphine, and non-steroidal anti-inflammatory drugs (NSAIDs). Repeated pretreatment with IL-31 showed significant antinociceptive action. Furthermore, its combination with morphine, but not with NSAIDs, increased the analgesic action. In contrast, treatment with TNCB and capsaicin decreased antinociception. Moreover, TNCB increased IL-31RA expression in the dorsal root ganglia at 24 h, whereas capsaicin inhibited it. The comparative action of several analgesics on TNCB or capsaicin was evaluated using a hot-plate test, which revealed that the antinociceptive activity was decreased or disappeared in response to capsaicin-induced pain and in IL-31RAKI mice. These results indicate that the analgesic action of IL-31 involves the peripheral nervous system, which affects sensory nerve. These results provide a basis for developing novel analgesics using this mechanism.

Steels studs are an inevitable part of drywall construction as they are lightweight and offer the required structural stability. However, the studs act as sound bridges between the plasterboards reducing the overall sound insulation of the wall. Overcoming this often calls for wider cavity walls and complex stud decoupling fixtures that increase the installation cost while reducing the floor area. As an alternative approach, this research reveals the potential of perforated studs to improve the acoustic insulation of drywall partitions. The acoustic and structural performance is characterized using a validated finite element model that acted as a prediction tool in reducing the number of physical tests required. The results established that an acoustic numerical model featuring fluid-structure-interaction can predict the weighted sound reduction index of a stud wall assembly at an accuracy of ±1 dB. The model was used to analyze six perforated stud designs and found to outperform the sound insulation of non-perforated drywall partitions by reducing the sound bridging. Overall, the best performing perforated stud design was found to offer improvements in acoustic insulation of up to 4 dB, while being structurally compliant.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

The nitrogen-doped amorphous oxide semiconductor (AOS) thin film transistors (TFTs) with double-stacked channel layers (DSCL) were prepared and characterized. The DSCL structure composed of nitrogen-doped amorphous InGaZnO and InZnO films (a-IGZO:N/a-IZO:N or a-IZO:N/a-IGZO:N) made the corresponding TFT devices exhibit quite large field-effect mobility due to the existence of double conduction channels. Especially, the a-IZO:N/a-IGZO:N TFTs showed even better electrical performance (μ_FE = 15.0 cm²·V^-1·s^-1, SS = 0.5 V/dec, V_TH = 1.5 V, I_ON/I_OFF = 1.1×10⁸) and stability (V_TH shift of 1.5, -0.5, and -2.5 V for positive bias-stress, negative bias-stress and thermal stress tests, respectively) than the a-IGZO:N/a-IZO:N TFTs. Based on the X-ray photoemission spectroscopy measurements and energy band analysis, it was assumed that the optimized interface trap states, the less ambient gas adsorption, and the better suppression of oxygen vacancies in the a-IZO:N/a-IGZO:N hetero-structures might be responsible for the better behaviors of the corresponding TFTs.

Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.

COPD is a "heterogeneous lung condition characterized by chronic respiratory symptoms. It is a leading cause of death and illness and is associated with a substantial economic burden worldwide. Furthermore, it is marked by frequent exacerbations, which significantly contribute to morbidity and mortality, as well as the overall burden. These exacerbations are frequently triggered by bacterial infections.So far, the most commonly implicated Bacteria are Pseudomonas aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.The advent of culture-independent techniques, such as next-generation sequencing techniques (NGS), allows us to characterise the lung microbiome in different disease states.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition with a high mortality rate for which there are no effective therapeutics. The failure of the alveolar-capillary barrier, composed of lung endothelial (EC) and alveolar epithelial (AEC) cells, is a critical factor leading to excessive inflammation and edema characteristics of acute lung injury (ALI). Phosphodiesterases (PDE) are enzymes well-recognized for their roles in regulating endothelial permeability and inflammation. Although PDE inhibitors are used as therapeutics for inflammatory diseases like COPD (chronic obstructive pulmonary disease), their efficacy in treating ARDS has not yet been established. In this study, we investigate the effects of ensifentrine, an FDA-approved novel dual PDE 3/4 inhibitor, on lung endothelial and epithelial dysfunction caused by methicillin-resistant S. aureus (MRSA), a pathogen involved in bacterial ARDS. Human primary lung endothelial cells and alveolar epithelial cell lines (A549 and immortalized AEC) were treated with heat-killed MRSA, and their responses were assessed in the presence or absence of ensifentrine. Ensifentrine given either pre- or post exposure attenuated MRSA-induced increased lung endothelial permeability. VE-cadherin junctions, which serve to stabilize the EC barrier, were disrupted by MRSA; however, ensifentrine effectively prevented this disruption. Pre-treatment with ensifentrine protected against MRSA-induced EC pro-inflammatory signaling by inhibiting the expression of VCAM-1, ICAM-1, and by reducing the IL-6 release. In AEC, MRSA caused upregulation of ICAM-1, activation of NF-kB and production of IL-8, all of which were inhibited by ensifentrine. These results indicate that dual inhibition of phosphodiesterases 3 and 4 by ensifentrine is barrier protective and attenuates MRSA-induced inflammation in both lung endothelial and epithelial cells. The PDE3/4 inhibitor ensifentrine may represent a promising novel strategy for the treatment of ALI.

Background: Cancer stem cells (CSC) are small subpopulation of cancer cells that has the potential to self-renew and has the strong proliferative capacity that sustain tumorigenesis capability. This ability of the CSCs to escape immune responses make the CSCs a primary source of functionally altered, immune-resistant, chemo-resistant aggressive tumor cells. Mentioned characteristic determines the potential advantage of targeting CSCs for the treatment of solid tumor. Method: We downloaded different gene expression datasets of CSCs from the NCBI-GEO database and identified common gens by using suitable Venn tool. Then explored the prognostic significance of the particular genes in particular cancer along with analysis of expression of these genes at protein level in human carcinomas by using different webserver. Finally, using toxicogenomic database we selected several important drugs or chemicals. Result: In this study, we identified common targets between three types of solid tumor and the prognostic significance of the identified genes. The identified drugs capable of targeting the expression or signaling network of designated genes of CSC that may contribute in CSC targeted cancer therapy. Conclusion: We identified several CSC associated genes in human breast, lung and ovarian carcinomas and several drugs that can target the function of these genes. Our study also suggests that there is need for more experimental investigations to find out the actual functional activity and the mechanism of action of the genes of CSC.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Lung cancer is the leading cause of cancer death worldwide therefore studies about the etiological factors and carcinogenesis are important.The aim of the study is to detect the presence and types of Human papilloma virus (HPV) in lung cancer and non-tumoral lung and Epidermal Growth Factor Receptor (EGFR) mutation prevalance in lung cancer with Polymerase Chain Reaction (PCR) method.Fifty patients who were histopathologically diagnosed lung cancer and 7 patients with non-neoplastic lung disease were enrolled in the study. HPV positivity was detected in 75.4% of the patients. The rate of high-risk HPV positivity was 100% in adenocarcinomas, 64.5% in squamous cell carcinomas, and 57% in non-neoplastic lung. HPV 51 was the most frequent type followed by HPV 16 (43.9%). There was no statistically significant relationship between HPV infection and age, gender and smoking history and EGFR mutation. The prevalence of HPV positivity is variable in lung cancer in different studies and this may be due to many factors including HPV detection methods, number of patients, geographic regions. New studies about the role of HPV infection need to be performed in order to obtain information about the use of prophylactic and theurepatic agents in lung cancer.

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

Background & aims: Malnutrition in lung transplant (LT) candidates increases postoperative morbidity and mortality. Early diagnosis of malnutrition could attenuate adverse prognostic factors. This study aimed to assess the prevalence of nutritional risk and malnutrition using GLIM criteria in LT candidates and clinically characterize those with malnutrition. Methods: A prospective longitudinal study was conducted from 2000 to 2020 of LT candidates who underwent complete nutritional assessment (nutritional screening, anthropometry, bioelectrical impedance, blood laboratory tests and malnutrition diagnosis using GLIM criteria). Results: Obstructive diseases (45.6%), interstitial diseases (36.6%) and cystic fibrosis/non-cystic fibrosis bronchiectasis (15.4%) were the main conditions assessed for LT. Of the 1060 candidates evaluated, 10.6% were underweight according to BMI, 29% were at risk of malnutrition and 47% were diagnosed with malnutrition using GLIM criteria. Reduced muscle mass was the most frequent GLIM phenotypic criterion. Malnutrition was more prevalent in patients with cystic fibrosis/non-cystic fibrosis bronchiectasis (84.5%), obstructive (45.4%) and interstitial (31.3%) diseases. GLIM criteria detected some degree of malnutrition in all diseases requiring LT and identified patients with higher CRP levels and worse respiratory function, anthropometric measurements and visceral protein and lipid profiles. Conclusions: LT candidates present a high prevalence of malnutrition using the GLIM algorithm. GLIM criteria detected malnutrition in all diseases requiring LT and defined patients with worse clinical-analytical profiles.

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

Rheumatoid arthritis (RA) is an autoimmune disease mainly characterized by joint inflammation. It presents extra-articular manifestations, with the lungs one of the affected areas. Among these, damage to the pulmonary interstitium (Interstitial Lung Disease -ILD) has been linked to proteins involved in the inflammatory process and related to extracellular matrix deposition and lung fibrosis establishment. Peptidyl arginine deiminase enzymes (PAD), which carry out protein citrullination, play a role in this context. A genetic association analysis was conducted on genes encoding two PAD isoforms, PAD2 and PAD4. This analysis also included ancestry informative markers and protein level determination in samples from patients with rheumatoid arthritis, RA-associated ILD, and clinically healthy controls. Significant single nucleotide variations (SNV) and a haplotype were identified as susceptibility factors for ILD-RA development. Elevated levels of PAD4 were found in ILD-RA cases, while PADI2 showed an association with RA susceptibility. This document presents the data obtained from the conducted research, which has been published.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The study investigated 297, 202, and 166 lipids in saliva, plasma, and fecal samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (>2-fold, p<0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes and fecal lipids had weak correlation with those of saliva and plasma. Total triglycerides (TGs) increased (>2–3 folds) in plasma and saliva but decreased in fecal samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC across all sample types. A common ceramide species (d18:1/24:0) decreased in both plasma and saliva but increased in fecal samples. Additionally, phosphatidylinositol 38:4 decreased by approximately 2-fold in plasma and saliva. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. The study identifies 27 salivary, 10 plasma, and 16 fecal lipids as candidate markers for NSCLC by statistical evaluations. Moreover, it highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

Fungi of the genus Aspergillus are widespread in the environment where they produce large quantities of airborne conidia. Inhalation of Aspergillus spp. conidia in immunocompromised individuals can cause a wide spectrum of diseases, ranging from hypersensitivity responses to lethal invasive infections. Upon deposition in the lung epithelial surface, conidia encounter and interact with complex microbial communities that constitute the lung microbiota. The lung microbiota has been suggested to influence the establishment and growth of Aspergillus spp. in the human airways. However, the mechanisms underlying this interaction have not yet been sufficiently investigated. In this study, we aimed to evaluate the presence of commensal bacteria antagonistic to Aspergillus in the lung. To this end, we enriched and isolated bacterial strains able to inhibit the germination of conidia from bronchoalveolar lavage fluid (BALF) samples of lung transplant recipients. We used a novel enrichment method based on a soft agar overlay plate assay in which bacteria are directly in contact with conidia and for which inhibition can be readily observed during enrichment. We isolated a total of five bacterial strains, identified as Pseudomonas aeruginosa, and able to inhibit the germination and growth of Aspergillus fumigatus in a soft agar confrontation assay, as well as in a high-throughput multiplate assay. Moreover, we also showed a strong inhibition of A. fumigatus growth on Calu-3 cell culture monolayers. However, the isolated P. aeruginosa strains were shown to cause significant damage to the cell monolayers. Overall, we validated this novel one-step enrichment approach for the isolation of bacterial strains antagonistic to A. fumigatus from BALF samples. This opens up a new venue for targeted enrichment of antagonistic bacterial strains against specific fungal pathogens.

It is already well known that infants and children infected with COVID-19 develop mild to mod-erate forms of the disease, with fever and oropharyngeal congestion being the most common symptoms. Nevertheless, there are cases in which the patients accuse respiratory symptoms. These cases need lung evaluation, which can be done using lung ultrasound (LUS), because it is a non-irradiating and repeatable imaging technique. 19 children with COVID-19 pneumonia were eval-uated using LUS. The LUS score (LUSS) for each patient varied between 1 to 8 points from a max-imum of 36 points. The arithmetic mean was 4.47 ± 2.36 (S.D), while 95% CI for the Arithmetic mean was 3.33 to 5.61. The lung changes were correlated with their biomarkers, specifically in-flammatory markers. The correlation between LUSS and LDH, D-dimers and IL-6 was a strong positive one with r=0.66 (p=0.01, 95% CI 0.147 to 0.896) between the LUSS and LDH level at symptomatic infants and children (with cough present) and r=0.66 (p=0.01, 95% CI 0.140 to 0.895) between LUSS and D-dimers level at symptomatic infants and children (with cough pre-sent). The results suggest that LUS could be a good imaging technique that can be used both in ini-tial evaluation of children with respiratory diseases, and, also in their follow-up, correlated with symptoms and biomarkers.

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

Studies have shown that STK11 mutation plays a critical role in affecting the lung adenocarcinoma (LUAD) tumor immune environment. By training an Inception-Resnet-v2 deep convolutional neural network model, we were able to classify STK11-mutated and wild type LUAD tumor histopathology images with a promising accuracy (per slide AUROC=0.795). Dimensional reduction of the activation maps before the output layer of the test set images revealed that fewer immune cells were accumulated around cancer cells in STK11-mutation cases. Our study demonstrated that deep convolutional network model can automatically identify STK11 mutations based on histopathology slides and confirmed that the immune cell density was the main feature used by the model to distinguish STK11-mutated cases.

Lung cancer is known as lung carcinoma. It is a disease which is malignant tumor leading to the uncontrolled cell growth in the lung tissue. Lung Cancer disease is one of the most prominent cause of death in all over world. Early detection of this disease can assist medical care unit as well as physicians to provide counter measures to the patients. The objective of this paper is to approach an automated tool that takes influential causes of lung cancer as input and detect patients with higher probabilities of being affected by this disease. A neural network classifier accompanied by cross-validation technique is proposed in this paper as a predictive tool. Later, this proposed method is compared with another baseline classifier Gradient Boosting Classifier in order to justify the prediction performance.

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm², investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).

This study applies a cluster analysis to identify typical physical activity (PA) and sedentary behaviour (SB) patterns in people with chronic obstructive pulmonary disease (COPD) before starting pulmonary rehabilitation (PR). We implemented an observational design which assessed baseline data on objectively measured PA and SB from the STAR (Stay Active after Rehabilitation) study. 355 persons wore a accelerometer (Actigraph wGT3X) for seven days before the start of their PR. Sociodemographic and disease-related parameters were assessed at the start of PR. We applied cluster analysis and compared groups applying univariate variance analyses. Data was available for 326 persons (31.6% women; age ø = 58 yr.). Cluster analysis revealed four movement clusters with distinct PA and SB patterns: sedentary non-movers (28.5%), sedentary occasional movers (41.7%), sedentary movers (19.6%), and sedentary exercisers (10.1%). The four clusters showed very different levels of moderate PA before rehabilitation (Ø daily minutes: 9; 28; 38; 70). Notably, all four clusters displayed considerably long average sitting time per day (Ø daily minutes: 644; 561; 490; 446). The groups differed significantly in disease-related parameters of GOLD severity, FEV1, CAT, and 6-Min-Walk-Test. In addition to PA promotion, PR programs should consider the reduction of sitting time as a valuable goal.

The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that regulates cellular proliferation, differentiation, apoptosis and tumorigenesis. Although the pro-oncogenic roles of C/EBPβ have been implicated in various human cancers, how it contributes to tumorigenesis or tumor progression has not been determined. Immunohistochemistry with human non-small cell lung cancer (NSCLC) tissues revealed that higher levels of C/EBPβ protein are expressed compared to normal lung tissues. Knockdown of C/EBPβ by siRNA reduced the proliferative capacity of NSCLC cells by delaying G₂/M transition of the cell cycle. In C/EBPβ-knockdown cells, a prolonged increase in phosphorylation of cyclin dependent kinase 1 at tyrosine 15 (Y15-pCDK1) was displayed with increased Wee1 and decreased Cdc25B expression, simultaneously. ChIP analysis showed that C/EBPβ bound to distal promoter regions of WEE1 and repressed WEE1 transcription through the interaction with histone deacetylase 2. Treatment of C/EBPβ-knockdown cells with a Wee1 inhibitor induced a decrease in Y15-pCDK1 and recovered cells from G₂/M arrest. In the xenograft tumors, the depletion of C/EBPβ significantly reduced tumor growth. Taken together, these results indicate that Wee1 is a novel transcription target of C/EBPβ that is required for the G₂/M phase of cell cycle progression, ultimately regulating proliferation of NSCLC cells.

The present work encompasses an application-oriented perspective to the possible employment of gold nanoparticles as nanomedicine in cancer therapeutics. The rationale of the work lies in the growing needs for assessment of advanced alternative treatment of cancer employing functionalized nanoparticles as nanomedicine. Gold nanoparticles fabricated via green chemistry methods by leaves of a time-honored medicinal plant, Piper betle were ascertained for their synthesis and properties under the umbrella of characterization of nanoparticles, through various techniques like UV-vis spectroscopy, FTIR spectroscopy, X-ray diffraction, and scanning electron microscopy. The cytotoxicity assay of well-characterized gold nanoparticles was monitored against lung cancer cell line (A549) by metabolic and imaging assays. MTT assay or the metabolic assay was performed for a range of nanoparticles’ concentrations. The results were promising and proved to be a leading-edge venture, envisaging the possibility of gold nanoparticles for cancer therapeutics.

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50nmol/L) should also ensure any benefits for multiple sclerosis.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Lung and colon cancers are among the leading causes of cancer-related mortality worldwide. Early and accurate detection of these cancers is crucial for effective treatment and improved patient outcomes. False or incorrect detection is more harmful. Accurately detecting cancer in a patient's tissue is crucial to their effective treatment. While analyzing tissue samples is complicated and time-consuming, deep learning techniques have made it possible to complete this process more efficiently and accurately. As a result, researchers can study more patients in a shorter amount of time and at a lower cost. Much research has been conducted to investigate deep learning models that require great computational ability and resources. However, None of these have had a 100% accurate detection rate for these life-threatening malignancies. Misclassified or falsely detecting cancer can have more harmful consequences. This research proposes a new lightweight, parameter-efficient, and mobile-embedded deep learning model based on a 1D convolutional neural network with Squeeze-and-Excitation layers for efficient lung and colon cancer detection. This proposed model diagnoses and classifies lung squamous cell carcinomas and adenocarcinoma of the lung and colon from digital pathology images. Extensive experiment demonstrates that our proposed model achieves 100% accuracy for detecting lung, colon, and lung and colon cancers from the histopathological (LC25000) lung and colon datasets, which is considered the best accuracy for around 0.35 million trainable parameters and around 6.4 million flops. Compared with the existing results, our proposed architecture shows state-of-the-art performance in lung, colon, and lung and colon cancer detection.

In this article, an efficient die bonding technology based on silver sintering due to induction heating is presented. By using this technology, the heat for the sintering reaction is locally limited to the bonding area and the heating of the entire power module is avoided. Furthermore, the sintering reaction is promoted due to current flow between the silver particles and the sintering time is drastically reduced. Next to the experimental trials presented in this paper, FE-simulation methods were applied in order to develop a suitable induction coil geometry for the bonding of a diode to a direct bonded copper (DBC) substrate. Additional heating and sintering tests verified the reliability of the simulation model as well as the technological approach. Diodes were successfully bonded during the experiments and were analyzed by means of scanning electron microscopy (SEM) and function tests in order to qualify the inductive bonding technology. The results presented in this paper demonstrate, that induction heating has high potential for cost effective production in the field of die-attach and can drastically increase the output in power electronics production.

The current emphasis in the advancement of space-based synthetic aperture radar (SAR) is on lightweight payloads under 100kg with resolutions surpassing 1m. This focus is directed towards meeting the launch criteria for multiple satellites on a single rocket and cutting costs. This article discusses the creation and progress of a Ku-band SAR payload for the Taijing-4(03) Satellite, launched on January 23, 2024 accompanied by four other satellites. The SAR payload design was customized to meet the demands of a micro-nano satellite platform, resulting in a lightweight, flat design weighing less than 80kg, seamlessly integrated with the plate-shaped satellite platform. The article also introduces a beam optimization strategy for the phased array SAR antenna, significantly boosting the SAR system’s performance. The SAR payload provides various operating modes like slide-spot, strip, scan 1, scan 2, and others, with a maximum achievable resolution exceeding 1m. Extensive in-orbit testing of the payload produced numerous high-quality SAR images with potential uses in emergency disaster mitigation, safeguarding ecosystems, monitoring forests, managing crops, tracking sea ice, and more.

Photonic circuits find applications in biomedicine, manufacturing, quantum computing and communications. Photonic waveguides are crucial components, typically having cross-sections orders of magnitude inferior compared with other photonic components (e. g. optical fibers, light sources and photodetectors). Several light coupling methods exist, consisting of either on-plane (e. g. adiabatic and end-fire coupling) or off-plane methods (e. g. grating and vertical couplers). The grating coupler is a versatile light transference technique which can be tested at wafer level, not requiring specific fiber terminations or additional optical components, like lenses, polarizers or prisms. This study focuses on fully-etched grating couplers without bottom reflector, made from hydrogenated amorphous silicon (a-Si:H), deposited over a silica substrate. Different coupler designs were tested, of these we highlight two: superimposition of two lithographic masks with different periods and an offset between them to create a random distribution and a technique based on the quadratic refractive index variation along the device’s length. Results were obtained by 2D-FDTD simulation. The designed grating couplers achieve coupling efficiencies for the TE-like mode over -8 dB (mask overlap) and -3 dB (quadratic variation), at a wavelength of 1550 nm. The coupling scheme considers a 220 nm a-Si:H waveguide and an SMF-28 optical fiber.

Electrification of society, increasing renewable energy sources and mobility charging lead to new loading patterns for power transformers. Dynamic load conditions induce enhanced mechanical stress on the transformers’ windings, potentially causing degradation of the solid insulation over time and compromising the transformer's short-circuit withstand capability. Thermal expansion of the windings, caused by losses in the copper conductors, occurring as the transformer is load-ed, increases the stress. Conversely, magnetic losses in the core and tie plate expansion contribute to a reduction in stress. This paper presents the effect of step changes in core losses and copper losses by on-line measurements of the clamping pressure, to better understand the mechanical stresses acting upon the solid insulation cellulose materials.

The maintenance of traditional agricultural practices in protected small islands is closely linked to the preservation of the land, the protection of natural resources, and the conservation of local traditions. For this purpose, the Tuscan Archipelago National Park promoted the census of ancient horticultural varieties preserved by some farmers on the island of Elba. The survey revealed a deep-rooted historical, cultural, social, and economic link between this germplasm and the island’s territory. A scientific characterization of the landrace under ethnobotanical, morphological, and genetic aspects was carried out. Among these local varieties, two landraces of the Brassica species and three landraces of the Phaseolus species were identified and analyzed in this study. To ascertain their distinguishability and uniqueness, similar varieties were also identified based on morpho-physiological characteristics or territorial proximity and compared with the Elban landraces. Morpho-phenological data were collected, and molecular analyses were carried out using Simple Sequence Repeats (SSR) markers. Ten different SSR loci were considered for the Phaseolus species and nine for the Brassica species. The Tuscan Archipelago landraces showed a high level of internal variability but were clearly distinct from each other and from the analyzed varieties, as shown by AMOVA (Analysis of Molecular Variance). Their distinctness was further highlighted by the UPGMA dendrogram obtained from the genetic distance matrix. The same results were confirmed by Principal Coordinate Analysis (PCoA). This study confirms the peculiarity of the Elban landraces, their biodiversity is a heritage to be safeguarded, which can also be used in future breeding programs. These ancient Elban landraces were allocated to local farmers (most were young farmers) to protect them from extinction and to promote more resilient varieties cultivation compared to commercial hybrids widely spread in the area. Local farmhouses also play a strategic role in safeguarding the germplasm and dissemination of sustainable agricultural practices. There is high demand for ancient Elban landraces, this has led to the development of a new local economy balanced between agricultural tradition and innovation.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing some antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrating remarkable efficacy against planktonic cells and biofilms of MRSA, outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, was showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wound in mice. Together the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Consumers are attracted by the increasing number of available SVOD platforms, but subscribing to all of them would be too expensive. To reduce costs, consumers could combine the use of proprietary subscriptions, non-proprietary subscriptions, and illegal streaming sites. In turn, platforms could enforce access control, a decision that could produce the desired reduction in non-proprietary subscriptions but also an undesired reduction in proprietary subscriptions. The effects of this decision and the determinants of SVOD content demand remain largely unexplored. We propose a baseline model where the SVOD content demand is driven by variety seeking, household financial situation, ethical evaluation, and social norms, as well as a change model where the subscription variation is driven by users’ trait reactance and perceived fairness of the decision. We conducted a survey on the current ways of SVOD content consumption and the responses to a hypothetical access control enforcement, with four randomized versions of the authentication mode. Results confirmed many of the proposed determinants and showed a noteworthy reduction in proprietary subscriptions due to the control enforcement but no effect due to the authentication modes. All these findings may help improve future models on SVOD content consumption and better address the difficult challenge of converting unauthorized users into authorized ones.

This study aimed to identify and categorize the influencing factors on the purchase of dairy products among customers of dairy companies in Mashhad city. This study is a mixed research (qualitative and quantitative), conducted with the aim of identifying and categorizing the influencing factors on consumers’ purchase. Therefore, the theoretical foundations were examined in the initial step, after which the customers and their needs and demands were addressed in terms of the company and its products. In the qualitative part, interviews were conducted in the focus group (23 people in 5 groups) to identify and extract these factors using the theme analysis technique. The reliability of the interviews was confirmed by retesting and the reliability between two encoders. Sixty themes (factors) that affected the purchase of dairy products were collected. In quantitative part, 517 questionnaires were collected from 13 regions of Mashhad city to perform statistic tests. A questionnaire was designed using the extracted themes in the previous (qualitative) stage to assess customers’ feedback. The validity of the questionnaire was confirmed by content and structure validity (exploratory and confirmatory factor analysis), and its reliability was checked by Cronbach’s alpha. Fourteen components were obtained by exploratory and confirmatory factor analyses, after which the variables were labeled as intrinsic, psychological, and personality factors, the identity of the company, production power of the company, competitive power of the company, competitive prices, social awareness, and store capabilities. The construct validity was confirmed using confirmatory factors.

Surface-enhanced Raman spectroscopy (SERS) can boost the pristine Raman signal by ~ 108 times that could be exploited for producing innovative sensing devices with advanced properties. However, the inherent complexity of SERS systems restricts their further applications in rapid detection, especially in situ detection in narrow aera. Here, we construct an efficient and flexible SERS-based LOP sensor by integrating Ag/Au nanocap arrays obtained by Ag/Au coating polystyrene nanospheres on the optical fiber face. We obtain rich “hotspots” at the nanogaps between neighboring nanocaps and further achieve the excellent SERS performance with the assistance of laser induced thermophoresis on the metal film that can achieve high efficiency aggregation of detected molecules. We achieve a high Raman enhancement with a low detection limitation of 10-7 mol/L for the most efficient samples based on the above sensor. This sensor also exhibits good repeatability and stability under multiple detections, revealing the potential application in situ detection based on the reflexivity of optical fiber.

Meals on Wheels (MoWs) provide access to daily meals and social contact to adults with care and support needs.MoWs could be essential for the increasing rates of an ageing population and adults living with complex needs in England, yet many do not know that the service exists. This study aimed to explore the perceptions of MoWs service users, and people who refer them to MoWs (‘referrers’), with accessing and setting up the service in England, and what information would be valued when considering accessing MoWs services.Semi-structured interviews were conducted in May-July 2022 with seven service users and 21 referrers, recruited from four MoWs providers across England. Data were analysed using thematic analysis. Participants indicated various pathways into the service, but referrers (family members) were more likely to be the ones enquiring about, and setting up, MoWs for service users. Once an enquiry about MoWs had been made, the service was perceived as straightforward to set up.However, existing preconceptions and stereotypes about the service (e.g. bringing to mind ‘school meals’, aimed solely at older adults) were perceived to act as barriers to accessing MoWs.Information that participants deemed important to have available when deciding on whether to access MoWs related to the meals (e.g. nutritional value, variety, need for any preparation, catering for individual needs), the specific services provided (e.g. wellbeing checks, daily social contact), the reliability and flexibility of delivery, and the cost of services. These findings could inform MoWs providers’ public awareness strategies about MoWs, in order to facilitate referrals to the service for adults with care and support needs.

Precision agriculture and open-source data repositories provide a plethora of field-specific ecological data about agroecosystems, but few mechanisms have been developed to turn that information into management recommendations for crop production. The On-Farm Precision Experiments (OFPE) framework is an agroecological model-based methodology to improve crop manager’s abilities to make field-scale agronomic input decisions. This work evaluates the use of field-specific experiments that employ open-source data and the data emanating from precision agriculture technologies to gain local knowledge of the spatial and temporal variability in agroeconomic performance at the sub-field scale. Quantification of the temporal variability in crop response to inputs (e.g., crop seeding rates, crop rotations, fertilizers, other soil amendments, pesticides, etc.) allows for estimation of the probability that a future management scenario will outcompete another, in terms of crop yield, crop quality, farmer net return, or environmental quality. The challenge is to integrate OFPE into applied management with minimal disruption of stakeholder practices while drawing on historic knowledge about the field and economic constraints. OFPE is the basis of a decision support system that includes a six-step cyclical process that harnesses precision agriculture technology to apply experiments and gather field-specific data, incorporates modern data management and analytical approaches, and generates management recommendations as probabilities of outcomes. The OFPE framework allows field managers to assess the tradeoffs in agronomic input management between the maximization of crop production, quality and profits from production while considering environmental effects.

Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof of concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures as an in vitro model of autologous chondrocyte implantation (ACI), an established cellular therapy for osteoarthritis. Microvalve-based bioprinting uses microvalves to deposit cells suspended in a liquid in a consistent and repeatable manner. In this case MSCs and chondrocytes have been sequentially deposited into an insert based transwell system in order to create a laminar co-culture, with variations in the ratios of the cell types used to investigate the potential for MSCs to stimulate improved repair. Histological and indirect immunofluorescence staining revealed the formation of dense tissue structures within the chondrocyte and MSC-chondrocyte cell co-cultures, alongside the establishment of a proliferative region at the base of the tissue. No stimulatory or inhibitory effect in terms of ECM production was observed through the introduction of MSCs, although the potential for an immunomodulatory benefit remains. This proof-of-concept study therefore provides a novel method to enable the scalable production of therapeutically relevant micro-tissue models that can be used for in vitro research to optimise ACI procedures.

The present study compared the contralateral suppression and the amplitude of distortion product otoacoutsic emissions (DPOAEs) between smokers and non-smokers to determine the influence of smoking. Thirty smokers and thirty non-smokers within the age range of 18-40 years with a normal hearing sensitivity were considered for the study. For both the groups, DPOAEs were measured and the efferent auditory system functioning was measured by presenting the white noise of 50 dB HL to the contralateral side, while recording the DPOAEs. There was no significant effect of age on the amplitude of DPOAEs in both the groups. However, there were significant differences in the amplitude of DPOAEs between smokers and non-smokers. The amount of suppression and DPOAE amplitude were reduced in smokers when compared to non-smokers. The study found no significant correlation between the amount of smoking and amount of suppression between smokers and non-smokers. However, there were significant correlations between the amount of smoking and DPOAE at low and mid frequencies between smokers and non-smokers. Therefore, the present study highlights the increased damage to the efferent auditory system risk and the smoking ill-effects on the efferent auditory system.

The purpose of this paper is to build a new bridge between category theory and a generalized probability theory known as noncommutative probability or quantum probability, which was originated as a mathematical framework for quantum theory, in terms of states as linear functional defined on category algebras. We clarify that category algebras can be considered as generalized matrix algebras and that the notions of state on category as linear functional defined on category algebra turns out to be a conceptual generalization of probability measures on sets as discrete categories. Moreover, by establishing a generalization of famous GNS (Gelfand-Naimark-Segal) construction, we obtain a representation of category algebras of †-categories on certain generalized Hilbert spaces which we call semi-Hilbert modules over rigs.

This research analyzed the impact of quality of service as perceived by Hapkido students on their exercise continuation and recommendation intentions. It also identified the measures to reduce the rate of student dropout, strengthen competitiveness, and create more efficient marketing strategies for consumer patterns that are rapidly diversifying Hapkido. A questionnaire survey method was conducted with 300 middle and high school students aged 14–19 years having Hapkido training of three months to two years in Incheon and Bucheon during March–April 2019. Frequency, factor, reliability, correlation, and standard multiple regression analyses were conducted on the surveyed data. The conclusions are as follows. First, considering the impact of service quality on exercise continuation intention, service quality positively affects reliability, personification, and perceptual openness; in terms of possibility, it positively affects typicality, personification, and perceptual openness; and in terms of reinforcement, it positively affects reliability and perceptual openness. Second, examining the impact of service quality on recommendation intention positively affects reliability, personification, and perceptual openness. Third, exercise continuation intention positively affects recommendation intention.

We study strong optical coupling of metal nanoparticle arrays with dielectric substrates. Based on the Fermi Golden Rule, the particle-substrate coupling is derived in terms of the photon absorption probability assuming a local dipole field. An increase in photocurrent gain is achieved through the optical coupling. In addition, we describe light-induced, mesoscopic electron dynamics via the nonlocal hydrodynamic theory of charges. At small nanoparticle size (<20nm), the impact of this type of spatial dispersion becomes sizable. Both absorption and scattering cross section of the nanoparticle are significantly increased through the contribution of additional nonlocal modes. We observe a splitting of local optical modes spanning several tenths of nanometers. This is a signature of semi-classical, strong optical coupling via the dynamic Stark effect, known as Autler-Townes splitting. The photocurrent generated in this description is increased by up to 2%, which agrees better with recent experiments than compared to identical classical setups with up to 6%. Both, the expressions derived for the particle-substrate coupling and the additional hydrodynamic equation for electrons are integrated into COMSOL for our simulations.

This paper reports 2 × 4 hybrid Mach-zehnder interferometer (MZI) - multi-mode interferometers (MMI) based compact thermo-optical switch consisting of slab waveguides on silicon-on-insulator, SOI, platform. The device consists of two identical MMIs, each of 6 μm wide and 140 μm long connected with two phase shifters MMIs each with 2 μm wide and 8 μm long and linear tappers each 4 μm long, connected at both ends of the MMIs to minimize the power coupling loss. The loss for linear taper is found to be below 0.02dB. The footprint of the whole device is six 6 μm × 324 μm. This structure is based on unique multimode region shape, which leads optical switch to have less coupling loss and reduced cross-talk. The average thermo-optical switching power consumption is 1.4 mW, the excess losses are 0.8 dB, and the imbalances are 0.1 dB. Aluminum is used as a heating pad, and a trench is created around this pad to prevent from spreading of heat and reduce power loss almost by a factor of 2 to the adjacent phase shifter. Our new heating method has advantages of compact size and ease of fabrication with the current CMOS technology.

Besides the Lagrangian and the Eulerian descriptions, the motion of a body can also be expressed relative to the present configuration of the body, known as the relative motion description. It is interesting to consider such a relative motion description in general to formulate the basic system of field equations for solid bodies. In doing so, when the time increment from the present state is small enough, the nonlinear constitutive equations can be linearized relative to the present state so that the resulting system becomes linear. This will be done for thermoelastic materials with a brief comment on the exploitation of entropy principle in general. Relative Lagrangian formulation is based on the well-known ``small-on-large'' idea, and can be implemented for solving problems with large deformation in successive incremental manner. Some applications of such a formulation in numerical simulations are briefly reviewed.

The existence of semantic inaccuracy §2 articles by A. Einstein “On the electrodynamics of moving bodies”, illustrating the principle of the relativity of simultaneity. In a sentence “The observers co-moving with the moving rod would thus find that the two clocks do not run synchronously while the observers in the system at rest would declare them synchronous”, the preposition “not” must be moved and placed before the word “synchronous”, at the end of the sentence. The criterion for synchronism of the clocks on the rod is the time it takes for the beam to travel from clock A to clock B and back, and for observers on the rod it will be the same both when the rod is at rest and when the rod is moving. Otherwise, observers on the rod would have had at their disposal an experiment that would allow them to determine whether the rod is moving or at rest, which contradicts the first postulate of the Special Theory of Relativity. The inaccuracy is found unchanged in modern editions in English and Russian, and can become a source of difficulties when teaching the basics of the Special Theory of Relativity based on primary sources, as well as make it difficult to understand the author’s logic when studying independently. Nobel laureate R. Feynman, having expanded and modified A. Einstein's thought experiment, eliminated the inaccuracy described in the article.

The aim of this work is to broaden the theory of computation by making use of fuzzy sets and multisets, which are generalization of ordinary sets. We study fuzzy multiset finite automata (FMFA), which are characterized by the incorporation of vagueness when it comes to the choice of the next state and multiple occurrences of the same input symbol. The resulting automaton is a genaralization of both classical automata and fuzzy automata. We discuss the algebraic characteristics of FMFA sub-automata—separatedness, strongly connectedness, cyclic, directable, and triangular FMFA in terms of equivalence classes induced by an equivalence relation defined on state set of FMFA. Intrestingly, for a given FMFA, a new FMFA can be constructed that is a homomorphic image of the original FMFA. We define different posets structures that can be associated with a given FMFA and show that some of them are upper semilattices and discuss the inter-relationship of a given poset, a finite upper semilattice (FUSL), a FMFA and a posets/FUSL associated with a given FMFA. Finally, we introduce the concept of decomposition of a FMFA in two different ways and characterize the strongly connected, triangular and directable FMFA.

Background The aims of this study were to assess the peri-operative morbidity, mortality and long-term survival of octogenarians undergoing ATAAD repair, and to compare open and closed distal anastomosis techniques. Methods This was a single-centre retrospective study (2007-2021). Open versus closed distal anastomosis were compared. Uni and multi-variable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Kaplan-Meier and Cox proportional hazards methods were used to compare long-term survival. Results Fifty octogenarians patients were included (median age - 82 years, closed distal – 22, open distal - 28). Median CPB time was 187 minutes (open distal vs closed distal group; 219 minutes vs 115.5 minutes, p30 days or return to theatre; HR; 4.1, p=0.02) predicted adverse survival. Open distal anastomosis did no impact survival. Conclusions – ATAAD repair in selected octogenarians has favourable short and long-term survival. There is no significant difference between open versus closed distal anastomosis strategies.

In our previous study, we demonstrated that the microalgae Phaeodactylum tricornutum can bioaccumulate bisphenol A analogues. Since this microalgae species is part of the diet of marine filter-feeding organisms, such as bivalves, in this study we tested the hypothesis that a diet based on contaminated microalgae can exert negative effects on the clam Ruditapes philippinarum. Microalgae were exposed for 7 days to 300 ng/L of bisphenol AF, bisphenol F, and bisphenol S, alone or as a mixture, to allow bioaccumulation. Microalgae were then supplied as food to bivalves. After 7 and 14 days of diet, the effects of contaminated microalgae were evaluated on a battery of biomarkers measured in haemolymph/haemocyte, gills and digestive gland of clams. In addition, bioaccumulation of the three bisphenols was investigated in clams by UHPLC-HRMS. Results obtained demonstrated that total haemocyte count, and haemocyte proliferation were affected in clams fed with contaminated microalgae. The activity of some immune-related enzymes was also influenced. Significant alterations in antioxidant enzyme activities and oxidative damage to proteins and lipids were recorded in both gills and digestive gland from clams fed with contaminated microalgae. Alterations in epigenetic-involved enzyme activity were also found. No bioaccumulation of BPA analogues was detected in clam soft tissues. Overall, this study demonstrated that a diet of BPA analogues-contaminated microalgae can induce significant alterations of some important biological responses of R. philippinarum. To our knowledge this is the first study demonstrating the effects of ingestion of BPA analogues-contaminated microalgae in the clam R. philippinarum, suggesting a potential ecotoxicological risk for the marine food chain, at least at the first levels.

A Europe-wide outbreak of invasive pediatric Group a streptococcal infections (iGAS) began in fall 2022. Here we report the evolution of GAS hospitalizations in children and adolescents during the second outbreak year in 2023-2024 at a tertiary center in Switzerland. Using prospective monitoring of all in-patient GAS cases below 16 years of age including those with iGAS, we compared case frequencies and clinical characteristics in three time periods (2013-2020; 2022-2023; 2023-2024). Annual GAS hospitalizations increased from a median of 25 case (range 11-28) in 2013-2020 to 89 and 63 cases, respectively, in 2022-2023 and 2023-2024. iGAS cases evolved similarly (2013-2020, 4 cases (3-8); 2022-2023, 32 cases; 2023-2024, 21 cases). The decline in cases from 2022-2023 to 2023-2024 included all types of GAS organ involvement except suppurative infections in the head area, which remained largely unchanged (48 vs. 45 cases). Pleural empyema declined from 13 to 7 cases, possibly explained by a poor overlap of the GAS and influenza curves, respectively, in 2023-2024 compared to 2022-2023. These data document the prolongation of the GAS outbreak into its second winter season in 2023-2024, however with a decline of iGAS, pleural empyema, skin and soft tissue infection and infections of bone, joint and muscle.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p&lt;0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p&lt;0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p&lt;0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p&lt;0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol &lt;40 mg/dL in men or &lt;50 mg/dL in women (OR = 1.70); (p&lt;0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

Eutrophication, a global concern, impacts water quality, ecosystems, and human health. It’s crucial to monitor algal blooms in freshwater reservoirs, as they indicate the trophic condition of a waterbody through Chlorophyll-a (Chla) concentration. Traditional monitoring methods, however, are expen-sive and time-consuming. Addressing this hindrance, we developed models using remotely sensed data from the Sentinel-2 satellite for large-scale coverage, including its bands and spectral indexes, to estimate the Chla concentration on 149 freshwater reservoirs in Ceará, Brazil. Several machine learning models were trained and tested, including k-nearest neighbours, random forests, extreme gradient boosting, the least absolute shrinkage, group method of data handling (GMDH), and sup-port vector machine models. A stepwise approach determined the best subset of input parameters. Using a 70/30 split for the training and testing datasets, the best-performing model was the GMDH, achieving an R2 of 0.91, MAPE of 102.34%, and RMSE of 20.38 g/L, which are values consistent with the ones found in the literature. Nevertheless, the predicted Chla concentration values were most sensitive to the red, green, and near infra-red bands.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO-incompatible. The immuno-hematologic investigationsmay evaluate donor/recipient ABO mismatch and anti-A/B isohemoagglutinins (IHAs) titration in pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can appear post-HSCT. Some preventive treatmentstake into consideration the manipulation of the product and decision-making algorithms based on the titration of IHAs in the recipient with clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Currently, the best approach in the managementof ABO-incompatibletransplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHAs titration are not standardized. The transfusion strategy must consider both the blood group systems of the recipient and the donor until the RBC engraftment and the confirmed ABO conversion (forward and reverse typing) on two consecutive and independent samples. Therefore, ABO incompatibility in the HSCT is an important immuno-hematologic challenge and request all necessary preventive measures including the appropriate selection of ABO blood components for transfusion.

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

Cardiovascular diseases (CVD) are chronic diseases associated with a high risk of mortality and morbidity. Early detection of CVD is crucial to initiating timely interventions, such as appro- priate counseling and medication, which can effectively manage the condition and improve patient outcomes. Preventive measures should be implemented at the general public level, promoting a healthy lifestyle, and at the individual level, that is, in people with moderate to high risk of CVD or patients already diagnosed with CVD by addressing an unhealthy lifestyle. Personalized early diagnostic systems based on artificial intelligence (AI), ontologies, and other medical information processing systems may prove to be a great preventive measure. In this paper, we focus on the use of ontology-inspired database models in the diagnosis of cardiovascular disease, as well as their potential for use in web application development.

An undescribed diterpene, stellerterpenoid A (1) and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV and HR-ESI-MS). The absolute configuration of 1-3 were elucidated based on ECD calculation. Among of them, stellerterpenoid A was a rare 13, 14 - seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity to suppress NO production in LPS - simulated macrophages with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed inhibitory influenza virus and tumor activity.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

Background: It is known that Preeclampsia affects the lactogenesis. However, data on effects of this pathology on the human milk neurobiomarkers composition are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobi-omarker known to play an important role in the development and protection of the central nerv-ous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an ELISA test. To investigate the effect of Preeclampsia on the Activin A concentration in the 3 lactation phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between Preeclamptic and Normotensive women. The only significant effect is related to the lactation phase: it is significant the difference between colostrum and mature milk (p<0.01). In conclusion these results allow us to affirm that breast milk beneficial properties are maintained even if preeclampsia occurs.

Arthrospira platensis is a class of microalgae with high economic value. Its high adaptability, high photosynthetic efficiency, and fast growth rate make it one of the few microalgae that can be cultivated on a large scale. Therefore, using the selenium enrichment property of Arthrospira platensis to cultivate selenium-enriched Arthrospira platensis will not only enhance the physiological efficacy of Arthrospira platensis but also increase its economic value significantly. In this study, we investigated the effects of sodium selenite on the growth and photosynthetic performance of Arthrospira platensis selenium by setting different amounts and methods of sodium selenite addition, and we explored the optimal culture conditions. The results showed that the experimental group treated with sodium selenite at 120 mg/L had the fastest growth, and the contents of soluble protein, phycocyanin, and Chlorophyll a increased by approximately 67.9%, 1.44 times, and 38.8%, respectively, compared to the control group. Superoxide dismutase (SOD) and catalase (CAT) activity increased by 1.88-fold and 65%, respectively, and malondialdehyde (MDA) levels were reduced by 62% compared to the control group. The results of the OJIP assay showed that the J and I points were significantly higher at the batch addition and treatment concentration of 120 mg/L, with the rate of QA being reduced and the proportion of the slowly reduced PQ pool being increased. The values of the maximum light energy conversion efficiency (Fv/Fm) per unit of reaction center were higher in both sodium selenite treatment groups than in the control group, indicating that the light energy conversion efficiency of Arthrospira was promoted under all concentration treatment conditions. The batch addition of sodium selenite at concentrations less than 120 mg/L resulted in significantly higher ABS/RC values than the control, and they were far superior to the one-time addition method. The reason for this may have been that the batch addition of sodium selenite at low concentrations increased the light absorption capacity of the unit reaction center of the Arthrospira PSII, resulting in a rise in captured light energy, a rise in the energy captured by the reaction center for electron transfer (ETo/RC), a decrease in the energy dissipated in the absorption of light energy by the reaction center (DIo/RC), and an increase in the photosynthetic performance index (PI abs).

Background: Identity diffusion plays a central role in the onset of borderline personality and disorders. The Dialectical Behavioral Therapy for Adolescents (DBT-A) is a treatment program for adolescents with emotional instability and dysregulation. The interest of this study is to examine the influence of a standardized and certified DBT-A therapy program on identity development of adolescents with emotion dysregulation in an inpatient setting. Methods: 138 adolescents aged 13 to 18 years with symptoms of emotional instability were assessed before and after a curricular 12-weeks in-patient DBT-A program with standardized instruments for the assessment of identity (AIDA), emotion regulation (FEEL-KJ, SEE) and general psychopathology (SCL-90-R, DIKJ). Results: The results indicate a significant change in identity development, emotion regulation and general symptoms of psychopathology after treatment with DBT-A. A connection between identity scales and psychopathological symptoms of adolescents with diagnosed borderline disorders and impaired emotion regulation could be established. Conclusion: In this large sample of adolescents, DBT-A significantly improved identity and reduced identity diffusion. As identiy disturbance is a core symptom of borderline personality disorder, our results may become clinically relevant for the prevention of personality disorders in emotionally unstable adolescents

The Lluta River is the northernmost coastal wetland in Chile, representing a unique ecosystem and an important source of water in the extremely arid Atacama Desert. During peak season, the wetland is home to more than 150 species of wild birds and is the first stopover point for many migratory species that arrive in the country along the Pacific migratory route, representing a priority site for avian influenza virus (AIV) surveillance in Chile. The aim of this study was to determine the prevalence of influenza A virus (IAV) in the Lluta River wetland, to identify subtype diversity and to evaluate ecological and environmental factors that drive the prevalence at the study site. The wetland was studied and sampled from September 2015 to October 2020. In each visit, fresh fecal environmental samples (n = 178) of wild birds were collected for IAV detection by real-time RT-PCR. Furthermore, a count of wild birds present at the site was performed and environmental variables, such as temperature, rainfall, vegetation coverage (Normalized Difference Vegetation Index - NDVI) and water body size were determined. A generalized linear mixed model (GLMM) was built to assess the association between AIV prevalence and explanatory variables. Influenza positive samples were sequenced, and the host species was determined by barcoding. Of the 4,349 samples screened during the study period, overall prevalence in the wetland was 2.07% (95% CI: 1.68 to 2.55) and monthly prevalence of AIV ranged widely from 0% to 8.6%. A great diversity of hemagglutinin (HA) and neuraminidase (NA) subtypes were identified, and 10 viruses were isolated and sequenced, including low pathogenic H5, H7 and H9 strains. In addition, several reservoir species were recognized (both migratory and resident birds), including the newly identified host Chilean flamingo (Phoenicopterus chilensis). Regarding environmental variables, prevalence of AIV was positively associated with NDVI (OR=3.65, p<0.05) and with the abundance of migratory birds (OR=3.57, p<0.05). These results emphasize the importance of the Lluta wetland as a gateway to Chile for viruses that come from the Northern Hemisphere and contribute to the understanding of AIV ecological drivers.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

Terminalia arjuna possesses significant cardio protective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna. Spectroscopic characterization identified one of them as a new flavonoid “Terminalone A (1)” and two known flavonoids i.e. 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (2) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (3). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH was used as a scavenger) potential for all the three compounds 1-3 where the compound 1 showed strong antibacterial and antioxidant activity.

Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species which includes B. burgdorferi, B. afzelii, and B. garinii. The majority of patients with early LD can be cured by standard treatment, yet some still suffer from post-treatment Lyme disease syndrome (PTLDS). The presence of Borrelia persisters has been proposed as a contributing factor, which cannnot be completely killed by the currently used antibiotics for Lyme disease. Finding new pharmaceuticals targeting Borrelia persisters is crucial in developing more effective treatment. Here, we first confirmed the existence of persisters in cultures of B. garinii and B. afzelii and then conducted high-throughput screening of a custom drug library against persister-rich stationary-phase cultures of B. garinii and B. afzelii. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs, and topical antibiotics along with some other natural compounds were identified to have strong potential in killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA’s target is the cell membrane where HA-triggered reactive oxygen species (ROS) generation took place in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against Gram-positive and Gram-negative bacteria. Identification of the above-mentioned drug candidates may help to develop more effective therapies for LD.

Matrix metalloproteinases are involved in extracellular matrix remodeling through the degradation of extracellular matrix components and are involved in the inflammatory response by regulating the activities of TNF-alpha and IL-1beta, which are pro-inflammatory cytokines, in addition to extracellular matrix components. Since the regulation of inflammatory response and changes in the extracellular matrix by MMPs are related to the development of various diseases including lung and cardiovascular diseases, many studies have been conducted on the role of MMPs in pathogenesis. In addition, various studies have demonstrated that MMPs are involved in the pathogenesis of infectious diseases by regulating the expression and activity of MMPs by infection with pathogens. In this review, we discuss the role of MMPs in infectious diseases and the role of MMPs in inflammatory responses and present their potential as therapeutic targets in infectious diseases.

Fungal spores are universal atmospheric components associated to allergic reactions. Alternaria (Ascomycota) is considered the most allergenic spore taxa. Alt a 1 is the major allergen of Alternaria and is present also in other Pleosporales. In this study, standard Hirst-based sampling and analyzing methods for measuring spore daily concentrations of Alternaria, Curvularia, Drechslera-Helminthosporium, Epicoccum, Leptosphaeria, Pithomyces, Pleospora and Stemphyllium (all included in the taxon Pleosporales) have been used besides two high-volume samplers, Burkard Cyclone (2017) and MCV CAV-A/mb (2019-2020), and ELISA Kits for measuring the allergen. The detection and quantification of Alt a 1 was only possible in the samples from the MCV sampler. Although Alt a 1 was better correlated with Alternaria spores than with Pleosporales spores, the three of them showed high correlations. It is shown, for the first time, a high and significant correlation of Alt a 1 with temperature, a negative one with relative humidity and no correlation with precipitation. The aerobiological monitoring of these three elements ensures the best information for understanding the affectation to allergy sufferers but, if not possible, as a minimum public health service aiming at the detection, treatment and prevention of allergy, the study of the airborne Alternaria spores should be ensured.

Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

Benzo[a]pyrene (B[a]P), is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant and neurotoxicant that contribute to the development of cancer. Microtubules are polymers of tubulin that form part of the cytoskeleton and target for anticancer drugs. Furthermore, NPY significantly increased the percentage of cells in S and G2/M phases. However, little is known about the specific role of NPY in proliferation and the underlying protective mechanism remains unclear. Hence, the aim of this work was to investigate the effect of B[a]P on SH-SY5Y neuroblastoma cells and to explore the potential mechanism for alteration of tubulin-microtubule equilibrium causing mitotic arrest and NPY expression. The present findings showed B[a]P treatment significantly increase number of SH-SY5Y cells in S and G2/M phase as compared to G1 phase and provokes cell cycle arrest that correlated with significant decrease in G0/G1 cells. Immunofluorescence study showed significantly distorted tubulin arrangement from metaphasic plate in formation of bipolar mitotic spindle apparatus. Further, higher doses of B[a]P treatment lead to chromosomal abnormalities accompanied by DNA damage due ROS causing oxidative stress showing significant decrease in tubulin protein around spindle. The results of present study demonstrated that NPY exerts a proliferative and protective effect on B[a]P-induced oxidative stress in a dose-dependent manner in vitro and importantly, these effects may be mediated via mitotic arrest and involved in spindle arrangement during cell division. Our findings addresses a novel pathological outcomes of B[a]P-induced NPY expression by oxidative stress through spindle abnormalities leading to microtubule disruption.

In this study, we evaluated the effects of Cyclosporine A (CsA) on Lipopolysaccharide (LPS)-induced cytokine production in the genital tract of female rabbits. Twelve sexually mature and healthy female rabbits were randomly divided into four groups (n = 3 each). The rabbits in the LPS group were given an intrauterine infusion of Escherichia coli LPS (4 mg/kg body weight (BW)). Rabbits in the CsA group were given CsA (20 mg/kg BW). Rabbits in the LPS + CsA group were given LPS (4 mg/kg BW) and CsA (20 mg/kg BW). The control group received only LPS and CsA carrier. The gene expression and protein levels of pro- and anti-inflammatory cytokines were observed using qRT-PCR and immuno-histochemical (IHC) assay, respectively. Our study showed that IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-4, IL-10, IL-13, and TGF-β were expressed in female genital organs. The LPS challenge increased the mRNA expression of IL-6 and TNF-α in the uterine body and IL-1β in the uterotubal junction compared to the control group. CsA increased the basal mRNA expression of anti-inflammatory cytokines (i.e., IL-4 in the uterine body, uterotubal junction, and oviductal ampulla; IL-10 in the cervix, oviductal isthmus, and ampulla; and TGF-β in the uterotubal junction and oviductal ampulla) and pro-inflammatory cytokines (i.e., IL-6 and IL-8 in the cervix; IL-1β in the oviductal isthmus; TNF-α in the oviductal ampulla; and IFN-γ in the uterine body compared to the control group). In addition, CsA inhibited the mRNA expression of pro-inflammatory cytokines, such as IL-6 in the uterine body, uterotubal junction, and oviductal isthmus; TNF-α in the uterine body; and IFN-γ in the uterotubal junction and oviductal isthmus induced by the LPS challenge. The IHC assay showed the LPS-induced increase in protein production of IL-6 in the uterine body and oviductal isthmus. CsA increased the protein production of IL-10 in the cervix, uterine body, oviductal ampulla, and isthmus. Moreover, CsA decreased the protein production of IL-6 in the uterine body and oviductal isthmus induced by LPS.

Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates, however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age. The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the 1^st trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order and age at SDQ completed. The median concentrations of BPA, MnBP, MiBP, MEHP and MECPP were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. BPA level was associated with increased hyperactivity/inattention risk among girls (OR=1.66, 95% CI: 0.95-2.90) and∑DBP_m (MnBP + MiBP) level was associated with decreased total difficulties risk overall and among girls (OR=0.48, 95% CI: 0.20-1.13, OR=0.24, 95% CI: 0.06-1.03, respectively) without significance. MECPP level was associated with increase conduct problems risk (OR=2.78, 95% CI: 1.36-5.68). Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age, however, suggested possible association between MECPP levels and increased risk of conduct problems.

Due to the fact that abrasive media can deform flexibly in abrasive flow machining (AFM) making this method easily to polish the complex holes and the curved surface of the hard machining shapes. Although abrasive media dominate the polishing behavior in AFM process, the mechanism of the abrasive media are not easy to understand because of the high viscous gels, therefore, many finishing works need lots of time to design AFM process. Power laws of the abrasive gels is studied here to evaluate the non-Newtonian flow of abrasive gels in complex holes polishing firstly, at the mean time different abrasive gels are utilized to finish the complex holes to follow the results by non-Newtonian flow calculation. Moreover, traditional AFM has difficulty to achieve a uniform roughness of radial distribution in the complex holes polishing because of the non-uniform abrasive forces. So a helical passageway is proposed to create a multiple motion of abrasive medium and to obtain the even surface of the complex holes in AFM process.

The alkylation of 1,1,2-trimethyl-1H-benzo[e]indole with 2-chloroacetamide, followed by work-up of the reaction mixture with a base and the subsequent treatment of a crude product with acetic acid gives 10a,11,11-trimethyl-10a,11-dihydro-8H-benzo[e]imidazo[1,2-a]indol-9(10H)-one. The structure assignments were based on data from ¹H, ¹³C and ¹⁵N NMR spectroscopy. The optical properties of the obtained compound were studied by UV-vis and fluorescence spectroscopy.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

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

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

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

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

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

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

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs &gt; 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Extracorporeal membrane oxygenation (ECMO) can be a life-saving intervention in cases of potentially reversible refractory respiratory failure. One such indication can be bleomycin-induced lung injury. However, in some cases, the injury can be so severe that it becomes irreversible and creates complex medical decisions regarding life support and the continuation of care when no additional therapeutic options are feasible, particularly in cases of patients who were young and fully functional prior to an acute illness. In cases of full pulmonary replacement with mechanical support and the degree of functionality that can be attained utilizing modalities such as ECMO can obscure the true severity of illness and make end-of-life decisions significantly harder for families and caregivers.

Nanosized drug delivery systems (DDS) have been studied as a novel strategy against cancer due to their potential to simultaneously decrease drug inactivation and systemic toxicity and increase passive and/or active drug accumulation within the tumor(s). Triterpenes are plant-derived compounds with interesting therapeutic properties. Betulinic acid (BeA) is a pentacyclic triterpene which has great cytotoxic activity against different cancer types. Herein, we developed a nanosized protein-based DDS of bovine serum albumin (BSA) as the drug carrier combining two compounds: doxorubicin (Dox) and the triterpene BeA using an oil-water-like micro-emulsion method. Spectrophotometric assays were performed to determine protein and drug concentrations in the DDS. The biophysical properties of these DDS were characterized using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy confirming nanoparticle (NP) formation and drug loading into the protein structure, respectively. The encapsulation efficiency was 77% for Dox and 18% for BeA. More than 50% of both drugs were released within 24 h, at pH 6.8, while less drug was released at pH 7.4 in this time period. Co-incubation viability assays of Dox and BeA alone for 24 h demonstrated synergistic cytotoxic activity in the low μM range against the non-small cell lung carcinoma (NSCLC) A549 cells. Viability assays of the BSA(Dox+BeA) DDS demonstrated a higher synergistic cytotoxic activity than the two drugs with no carrier. Moreover, confocal microscopy analysis confirmed cellular internalization of the DDS and nucleus accumulation of the Dox. We determined the mechanism of action of the BSA(Dox+BeA) DDS, confirming S-phase cell cycle arrest, DNA damage, caspase cascade activation, and downregulation of the epidermal growth factor receptor (EGFR) expression. This DDS has the potential to synergistically maximize the therapeutic effect of Dox and diminish chemoresistance induced by EGFR expression using a natural triterpene against NSCLC.

Background: Limited research has been done to measure ambulatory respiratory behavior, in particular those associated with tobacco use, in the natural environment due to a lack of monitoring techniques. Respiratory topography parameters provide useful information for modelling particle deposition in the lung and assessing exposure risk and health effects associated with tobacco use. Commercially available Wearable Respiratory Monitors (WRM), such as the Hexoskin Smart Garment, have embedded sensors which measure chest motion and may be adapted for measuring ambulatory lung volume. Methods: Self-reported ‘everyday’ and ‘some days’ Hookah and Cigarette smokers were recruited for a 3-day natural environment observation study. Participants wore the Hexoskin shirt while using their preferred tobacco product. The shirt was calibrated on them prior to, during, and after the observation period. A novel method for calculating the calibration parameters is presented. Results: N=5 Hookah and N=3 Cigarette participants were enrolled. Calibration parameters were obtained and applied to the observed chest motion waveform from each participant to obtain their lung volume waveform. Respiratory topography parameters were derived from the lung volume waveform. Conclusion: The feasibility of using the Hexoskin for measuring ambulatory respiratory topography parameters in the natural environment is demonstrated..

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Background. This study aims to estimate the rate of death by cancer, according to Radio Base Stations (RBS) radiofrequency exposure, especially for the types of breast, cervix, lung and esophagus cancer. Methods. We collected information about the number of deaths by cancer, gender, age group, Gross Domestic Product per capita, death year and the amount of exposure over the lifetime. We investigated all cancer types and some specific types (breast, cervix, lung and esophagus cancers). Results. In capitals where RBS radiofrequency exposure was higher than 2,000/antennas-year, the average mortality rate was 112/100,000 for all cancers. The adjusted analysis showed that the higher the exposure to RBS radiofrequency, the higher cancer mortality. The highest adjusted risk was observed for cervix cancer (Rate Ratio = 2.18). The spatial analysis showed that the highest RBS radiofrequency exposure was observed in a city in southern Brazil, which also showed the highest mortality rate for all types of cancer and specifically for lung and breast cancer. Conclusion. The balance of our results indicates that the exposure to radiofrequency electromagnetic fields from RBS increases the rate of death by all types of cancer.

Objective: Application of ERA methods to investigate the atmospheric pollution and built environment factors influencing lung cancer incidence rate in Chinese women. Methods: Lung cancer incidence rate among Chinese women at 339 cancer registries were obtained from the China Cancer Registry Annual Report 2017, air quality and built environment data were obtained from the Greenpeace and China Construction Yearbook. After multiple covariates variables were eliminated, an exploratory regression analysis was performed using the world standardized population incidence rate as the dependent variable. Air quality and built environment factors as the independent variable. Results: Shandong Peninsula, Hebei and Liaoning are high incidence rate areas of female lung cancer in China, with significant regional aggregation. In addition to air quality factors such as industrial smoke emission data, the association between built environmental factors such as urbanization rate, development LUI, population density and greening coverage of built-up areas and female lung cancer incidence rate is statistically significant. Conclusion: In addition to air quality factors, urban spatial factors can also significantly affect respiratory health. The LUI is positively while urbanization rates and population density are negatively correlated with the incidence rate of lung cancer. The role of green space for respiratory health has not been proven. In addition, there is little relationship between income and health, and similar findings are found for indicators such as the public transportation and roads network.