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Functional & Integrative Genomics Jun 2024Lung adenocarcinoma (LUAD) has a malignant characteristic that is highly aggressive and prone to metastasis. There is still a lack of suitable biomarkers to facilitate...
Lung adenocarcinoma (LUAD) has a malignant characteristic that is highly aggressive and prone to metastasis. There is still a lack of suitable biomarkers to facilitate the refinement of precision-based therapeutic regimens. We used a combination of 10 known clustering algorithms and the omics data from 4 dimensions to identify high-resolution molecular subtypes of LUAD. Subsequently, consensus machine learning-related prognostic signature (CMRS) was developed based on subtypes related genes and an integrated program framework containing 10 machine learning algorithms. The efficiency of CMRS was analyzed from the perspectives of tumor microenvironment, genomic landscape, immunotherapy, drug sensitivity, and single-cell analysis. In terms of results, through multi-omics clustering, we identified 2 comprehensive omics subtypes (CSs) in which CS1 patients had worse survival outcomes, higher aggressiveness, mRNAsi and mutation frequency. Subsequently, we developed CMRS based on 13 key genes up-regulated in CS1. The prognostic predictive efficiency of CMRS was superior to most established LUAD prognostic signatures. CMRS demonstrated a strong correlation with tumor microenvironmental feature variants and genomic instability generation. Regarding clinical performance, patients in the high CMRS group were more likely to benefit from immunotherapy, whereas low CMRS were more likely to benefit from chemotherapy and targeted drug therapy. In addition, we evaluated that drugs such as neratinib, oligomycin A, and others may be candidates for patients in the high CMRS group. Single-cell analysis revealed that CMRS-related genes were mainly expressed in epithelial cells. The novel molecular subtypes identified in this study based on multi-omics data could provide new insights into the stratified treatment of LUAD, while the development of CMRS could serve as a candidate indicator of the degree of benefit of precision therapy and immunotherapy for LUAD.
Topics: Humans; Adenocarcinoma of Lung; Immunotherapy; Machine Learning; Lung Neoplasms; Prognosis; Tumor Microenvironment; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Genomics; Multiomics
PubMed: 38935217
DOI: 10.1007/s10142-024-01388-x -
International Archives of Allergy and... Jun 2024Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects...
INTRODUCTION
Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey.
METHODS
The files of 295 patients who had received SCIT were evaluated retrospectively.
RESULTS
SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively).
CONCLUSION
Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.
PubMed: 38934162
DOI: 10.1159/000539027 -
Physical Chemistry Chemical Physics :... Jun 2024CO is a major component of the icy mantles surrounding dust grains in planet and star formation regions. Understanding its photodesorption is crucial for explaining gas...
CO is a major component of the icy mantles surrounding dust grains in planet and star formation regions. Understanding its photodesorption is crucial for explaining gas phase abundances in the coldest environments of the interstellar medium irradiated by vacuum-UV (VUV) photons. Photodesorption yields determined experimentally from CO samples grown at low temperatures ( = 15 K) have been found to be very sensitive to experimental methods and conditions. Several mechanisms have been suggested for explaining the desorption of CO, O and CO from CO ices. In the present study, the cross-sections characterizing the dynamics of photodesorption as a function of photon fluence (determined from released molecules in the gas phase) and of ice composition modification (determined in the solid phase) are compared for the first time for different photon flux conditions (from 7.3 × 10 photon per s cm to 2.2× 10 photon per s cm) using monochromatic synchrotron radiation in the VUV range (on the DESIRS beamline at SOLEIL). This approach reveals that CO and O desorptions are decorrelated from that of CO. CO and O photodesorption yields depend on photon flux conditions and can be linked to surface chemistry. In contrast, the photodesorption yield of CO is independent of the photon flux conditions and can be linked to bulk ice chemical modification, consistently with indirect desorption induced by an electronic transition (DIET) process.
PubMed: 38934118
DOI: 10.1039/d4cp01177e -
Heliyon Jun 2024This study aimed to optimise metal extraction from secondary hazardous sources, such as basic oxygen steelmaking dust (BOS-D). Initially, three batch systems approaches,...
This study aimed to optimise metal extraction from secondary hazardous sources, such as basic oxygen steelmaking dust (BOS-D). Initially, three batch systems approaches, including bioleaching using , chemical leaching using choline chloride-ethylene glycol (ChCl-EG) and a combined approach were compared. Then, scaling up was evaluated through a semi-continuous bioleaching column system with varied leachate recirculation over 21 days, focusing on Y, Ce, Nd, Li, Co, Cu, Zn, Mn, and Al. Bioleaching outperformed the control experiments within 3 days in the batch, demonstrating the key role of . Chemical leaching conducted with a solid concentration of 12.5 % (w/v) successfully dissolved over 50 % of all metals within 2 h. For rare earth elements (REE), both bioleaching and hybrid leaching outperformed chemical leaching. However, considering factors such as process duration, overall efficiency, and ease of extraction, chemical leaching was the most effective method. Leachate recirculation reached a plateau after 11 days, resulting in extraction efficiency of 39 % when semi-continuous column set-up was used. Interestingly, variations in recirculation rates did not influence the extraction efficiency. Overall, this study emphasizes the considerable potential of bioleaching for metal recovery, but also highlights the need for further studies for enhancing permeability for percolation methods and optimisation, particularly in parameters such as aeration rate, when transitioning to larger scale systems.
PubMed: 38933961
DOI: 10.1016/j.heliyon.2024.e32437 -
Advanced Science (Weinheim,... Jun 2024The sand-dust weather and sand-dust storms have become a serious environmental disaster worldwide. It is an important challenge to develop technologies for desert sand...
The sand-dust weather and sand-dust storms have become a serious environmental disaster worldwide. It is an important challenge to develop technologies for desert sand solidification in order to prevent and control sand-dust weather. The biomineralization technology for solidifying desert sands has been a novel method for reinforced soils in recent years. The biomineralization solidification sand field tests are completed at the Wuma Highway solidification section in the Tengger Desert. The superiority of the biomineralization for solidifying sands is verified by measuring the water storage capacity of different reinforcement zones including bare sand zone, plant zone, biomineralization solidifying sand zone, and biomineralization combined plant solidifying sand zone. Simultaneously, the molecular dynamics calculation analysis is used to verify the role of biomineralization solidifying sands in preventing sand-dust storms. All results demonstrate that the biomineralization solidification sand method is effective for controlling and preventing sandstorm disasters.
PubMed: 38932474
DOI: 10.1002/advs.202403961 -
Vaccines Jun 2024Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens...
Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs' pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine.
PubMed: 38932349
DOI: 10.3390/vaccines12060620 -
Microorganisms Jun 2024The anti-fungal properties of the probiotic bacterium have been studied extensively in agriculture and ecology, but their applications in the built environment remain...
The anti-fungal properties of the probiotic bacterium have been studied extensively in agriculture and ecology, but their applications in the built environment remain to be determined. Our work aims to utilize this biological component to introduce new diverse anti-mold properties into paint. "Mold" refers to the ubiquitous fungal species that generate visible multicellular filaments commonly found in household dust. The development of mold leads to severe health problems for occupants, including allergic response, hypersensitivity pneumonitis, and asthma, which have significant economic and clinical outcomes. We here demonstrate the robust effect of a commercial paint enhanced with Bacillus subtilis cells against the common mold agent, , and identify three biosynthetic clusters essential for this effect. Our results lay the foundation for bio-convergence and synthetic biology approaches to introduce renewable and environmentally friendly bio-anti-fungal agents into the built environment.
PubMed: 38930607
DOI: 10.3390/microorganisms12061226 -
Microorganisms Jun 2024Microbial contamination poses a threat to both the preservation of library and archival collections and the health of staff and users. This study investigated the...
Microbial contamination poses a threat to both the preservation of library and archival collections and the health of staff and users. This study investigated the microbial communities and potential health risks associated with the UNESCO-classified Norwegian Sea Trade Archive (NST Archive) collection exhibiting visible microbial colonization and staff health concerns. Dust samples from book surfaces and the storage environment were analysed using culturing methods, qPCR, Next Generation Sequencing, and mycotoxin, cytotoxicity, and azole resistance assays. sp., sp., and sp. were the most common fungi identified, with some potentially toxic species like sp., sp., and section Fungal resistance to azoles was not detected. Only one mycotoxin, sterigmatocystin, was found in a heavily contaminated book. Dust extracts from books exhibited moderate to high cytotoxicity on human lung cells, suggesting a potential respiratory risk. The collection had higher contamination levels compared to the storage environment, likely due to improved storage conditions. Even though overall low contamination levels were obtained, these might be underestimated due to the presence of salt (from cod preservation) that could have interfered with the analyses. This study underlines the importance of monitoring microbial communities and implementing proper storage measures to safeguard cultural heritage and staff well-being.
PubMed: 38930597
DOI: 10.3390/microorganisms12061215 -
Materials (Basel, Switzerland) Jun 2024This paper describes a study of the chloride content in the concrete lagging of prestressed concrete elements of the roof structure of an aluminium foundry building....
This paper describes a study of the chloride content in the concrete lagging of prestressed concrete elements of the roof structure of an aluminium foundry building. Sources of chloride pollution in industrial facilities are discussed. Methods for collecting dust deposited on the structure and sampling concrete for chloride concentration testing are presented in detail. The test methods used and the apparatus used to assess the chloride content at the thickness of concrete reinforcement lagging are presented. Investigations of the chloride content in the concrete of the reinforcement cover showed a very high concentration of chloride in the near-surface layer, depending on the location of the element in relation to the source of chloride emission into the environment. In contrast, the concrete of the deeper layers of the lagging contained very small amounts of Cl chlorides. The results of the chloride content of the lagging concrete were plotted against the distance from the surface of the specimen and approximated by the function (,) based on Fick's second law and its solution. A satisfactory fit of the course of this function to the experimental results was obtained. Based on the obtained (,) function, the durability of the main structural components of an aluminium foundry industrial hall operating in a chloride environment was estimated.
PubMed: 38930354
DOI: 10.3390/ma17122985 -
Children (Basel, Switzerland) Jun 2024Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually...
Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually (SLIT). The aim of the current study was to evaluate and compare the efficacy of SCIT and SLIT for the treatment of allergic asthma in children. Our study included 69 children with allergic asthma who underwent immunotherapy for house dust mites or pollen for at least 3 consecutive years. After 3 years of SCIT and SLIT, the median number of asthma exacerbations in the last three months decreased from 2 to 0 ( < 0.01) and from 1 to 0 ( < 0.01), respectively. When comparing the efficacy of SCIT and SLIT, our study revealed a significantly better efficacy of SCIT only in terms of increasing lung function. The median increase in forced expiratory volume in one second (FEV1) after 3 years was 8% with SCIT and -1% with SLIT ( < 0.01). Daily controller therapy could be withdrawn or reduced in 9 out of 16 (56.3%) children who received it before SCIT ( < 0.01) and in 19 of 29 (65.6%) children who received it before SLIT ( < 0.01), but the difference in efficacy was not significant ( = 0.88). Both SCIT and SLIT are effective treatments for allergic asthma in children.
PubMed: 38929271
DOI: 10.3390/children11060692