Respiratory Diseases Diagnosis Using Audio Analysis and Artificial Intelligence: A Systematic Review.

Respiratory diseases represent a significant global burden, necessitating efficient diagnostic methods for timely intervention. Digital biomarkers based on audio, acoustics, and sound from the upper and lower respiratory system, as well as the voice, have emerged as valuable indicators of respiratory functionality. Recent advancements in machine learning (ML) algorithms offer promising avenues for the identification and diagnosis of respiratory diseases through the analysis and processing of such audio-based biomarkers. An ever-increasing number of studies employ ML techniques to extract meaningful information from audio biomarkers. Beyond disease identification, these studies explore diverse aspects such as the recognition of cough sounds amidst environmental noise, the analysis of respiratory sounds to detect respiratory symptoms like wheezes and crackles, as well as the analysis of the voice/speech for the evaluation of human voice abnormalities. To provide a more in-depth analysis, this review examines 75 relevant audio analysis studies across three distinct areas of concern based on respiratory diseases' symptoms: (a) cough detection, (b) lower respiratory symptoms identification, and (c) diagnostics from the voice and speech. Furthermore, publicly available datasets commonly utilized in this domain are presented. It is observed that research trends are influenced by the pandemic, with a surge in studies on COVID-19 diagnosis, mobile data acquisition, and remote diagnosis systems.

Antibacterial Activity of Copper Nanoparticles against Xanthomonas campestris pv. vesicatoria in Tomato Plants.

Copper-based bactericides have appeared as a new tool in crop protection and offer an effective solution to combat bacterial resistance. In this work, two copper nanoparticle products that were previously synthesized and evaluated against major bacterial and fungal pathogens were tested on their ability to control the bacterial spot disease of tomato. Growth of Xanthomonas campestris pv. vesicatoria, the causal agent of the disease, was significantly suppressed by both nanoparticles, which had superior function compared to conventional commercial formulations of copper. X-ray fluorescence spectrometry measurements in tomato leaves revealed that bioavailability of copper is superior in the case of nanoparticles compared to conventional formulations and is dependent on synthesis rather than size. This is the first report correlating bioavailability of copper to nanoparticle efficacy.

Synthesis and Characterization of Novel Copper Nanoparticles for the Control of Leaf Spot and Anthracnose Diseases of Olive.

Olive crop is frequently treated with copper fungicides to combat foliar and fruit diseases such as olive leaf spot caused by Fusicladium oleagineum and anthracnose caused by Colletotrichum spp. The replacement of copper-based products with more eco-friendly alternatives is a priority. Metal nanoparticles synthesized in several ways have recently revolutionized crop protection with applications against important crop pathogens. In this study, we present the development of four copper-based nanoparticles (CuNP Type 1 to 4) synthesized with a wet chemistry approach. The CuNPs were characterized using Transmission Electron Microscopy, Dynamic Light Scattering, Laser Doppler Electrophoresis, and Attenuated Total Reflection measurements. In addition, the activity of the four CuNP types was tested in vitro and in planta against F. oleagineum and Colletotrichum spp. In vitro sensitivity measurements showed that for both pathogens, mycelial growth was the most susceptible developmental stage to the tested compounds. Against both pathogens, CuNP Type 1 and Type 2 were found to be more active in reducing mycelial growth compared to the reference commercial compounds of copper oxide and copper hydroxide. In planta experiments showed that CuNP Type 3 and CuNP Type 4 exhibited a strong protectant activity against both F. oleagineum and Colletotrichum acutatum with control efficacy values significantly higher than those achieved by the applications of either reference product.

Plant-Derived Extracellular Vesicles as Therapeutic Nanocarriers.

Mammalian exosomes have emerged as a promising class of functional materials, inspiring novel applications as therapeutic vehicles and nutraceutical compounds. Despite this, their immunogenicity has been an issue of controversy within the scientific community. Although, exosome-like vesicles, innately formed in plants and inherent to eukaryotic cell-derived vesicles, could soothe most of the concerns, they are notably underutilized as therapeutic modalities. This review highlights all efforts published so far, on the use of plant-derived extracellular vesicles (EVs) as therapeutic delivery systems. A summary of the physicochemical characteristics of plant-derived EVs is provided along with their main biological composition and in vitro/in vivo evidence of their therapeutic efficacy provided where available. Despite only a hand full of clinical trials being underway, concerning these vesicles, they arguably possess significant potential as nanodelivery systems of natural origin.

Antibacterial Effect of Colloidal Suspensions Varying in Silver Nanoparticles and Ions Concentrations.

A lot of effort has been dedicated recently to provide a better insight into the mechanism of the antibacterial activity of silver nanoparticles (AgNPs) colloidal suspensions and their released silver ionic counterparts. However, there is no consistency regarding whether the antibacterial effect displayed at cellular level originates from the AgNPs or their ionic constitutes. To address this issue, three colloidal suspensions exhibiting different ratios of AgNPs/silver ions were synthesized by a wet chemistry method in conjunction with tangential flow filtration, and were characterized and evaluated for their antimicrobial properties against two gram-negative, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), and two gram-positive, Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), bacterial strains. The produced samples contained 25% AgNPs and 75% Ag ions (AgNP_25), 50% AgNPs and 50% Ag ions (AgNP_50), and 100% AgNPs (AgNP_100). The sample AgNP_100 demonstrated the lowest minimum inhibitory concentration values ranging from 4.6 to 15.6 ppm for all four bacterial strains, while all three samples indicated minimum bactericidal concentration (MBC) values ranging from 16.6 ppm to 62.5 ppm against all strains. An increase in silver ions content results in higher bactericidal activity. All three samples were found to lead to a significant morphological damage by disruption of the bacterial cell membranes as analyzed by means of scanning electron microscopy (SEM). The growth kinetics demonstrated that all three samples were able to reduce the bacterial population at a concentration of 3.1 ppm. SEM and growth kinetic data underline that S. epidermidis is the most sensitive among all strains against the investigated samples. Our results showed that all three AgNPs colloidal suspensions exhibited strong antibacterial properties and, thus, they can be applied in medical devices and antimicrobial control systems.

Bactericides Based on Copper Nanoparticles Restrain Growth of Important Plant Pathogens.

Copper nanoparticles (CuNPs) can offer an alternative to conventional copper bactericides and possibly slow down the development of bacterial resistance. This will consequently lower the accumulation rate of copper to soil and water and lower the environmental and health burden imposed by copper application. Physical and chemical methods have been reported to synthesize CuNPs but their use as bactericides in plants has been understudied. In this study, two different CuNPs products have been developed, CuNP1 and CuNP2 in two respective concentrations (1500 ppm or 300 ppm). Both products were characterized using Dynamic Light Scattering, Transmission Electron Microscopy, Attenuated Total Reflection measurements, X-ray Photoelectron Spectroscopy, X-ray Diffraction and Scattering, and Laser Doppler Electrophoresis. They were evaluated for their antibacterial efficacy in vitro against the gram-negative species Agrobacterium tumefaciens, Dickeya dadantii, Erwinia amylovora, Pectobacterium carotovorum, Pseudomonas corrugata, Pseudomonas savastanoi pv. savastanoi, and Xanthomonas campestris pv. campestris. Evaluation was based on comparisons with two commercial bactericides: Kocide (copper hydroxide) and Nordox (copper oxide). CuNP1 inhibited the growth of five species, restrained the growth of P. corrugata, and had no effect in X. c. pv campestris. MICs were significantly lower than those of the commercial formulations. CuNP2 inhibited the growth of E. amylovora and restrained growth of P. s. pv. savastanoi. Again, its overall activity was higher compared to commercial formulations. An extensive in vitro evaluation of CuNPs that show higher potential compared to their conventional counterpart is reported for the first time and suggests that synthesis of stable CuNPs can lead to the development of low-cost sustainable commercial products.

Recent developments in nanocarrier-aided mucosal vaccination.

To date, most of the licensed vaccines for mucosal delivery are based on live-attenuated viruses which carry the risk of regaining their pathogenicity. Therefore, the development of efficient nonviral vectors allowing the induction of potent humoral and cell-mediated immunity is regarded as an imperative scientific challenge as well as a commercial breakthrough for the pharma industries. For a successful translation to the clinic, such nanocarriers should protect the antigens from mucosal enzymes, facilitate antigen uptake by microfold cells and allow the copresentation of robust, safe for human use, mucosal adjuvants to antigen-presenting cells. Finally, the developed formulations should exhibit accuracy regarding the administered dose, a major drawback of mucosal vaccines in comparison with parenteral ones.

Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics.

The oral administration of protein therapeutics is hindered by the multitude of barriers confronted by these molecules along the gastrointestinal tract (i.e., acidic environment, proteolytic degradation, mucosal barrier, etc.). Their unique properties (e.g., high molecular weight, hydrophilicity, charge, etc.) and labile structure are mainly responsible for their instability in the harsh conditions along the gastrointestinal tract (GIT) and dictate the employment of alternative routes for their administration (e.g., parenteral). The association of proteins with colloidal carriers represents an interesting approach to overcome the aforementioned issues. However, certain requirements, such as stability in the GIT, stimuli-responsiveness, protection of the encapsulated biomolecule from enzymatic degradation and permeability of the mucosa, have to be met in order to efficiently deliver the sensitive payload to the intended site of action, thus resulting in enhanced bioavailability. The formation of colloidal polyelectrolyte complexes (PECs) seems to be a promising strategy towards this direction, and the present review aims to provide an insight into PECs (e.g., preparation methods, characteristics) along with their advantages and drawbacks as drug delivery vehicles for the oral administration of protein-based therapeutics.

Lipid-based nanocarriers for the oral administration of biopharmaceutics.

Biopharmaceutics have been recognized as the drugs of choice for the treatment of several diseases, mainly due to their high selectivity and potent action. Nonetheless, their oral administration is a rather challenging problem, since their bioavailability is significantly hindered by various physiological barriers along the GI tract, including their acid-induced hydrolysis in the stomach, their enzymatic degradation throughout the GI tract and their poor mucosa permeability. Lipid-based nanocarriers represent a viable means for enhancing the oral bioavailability of biomolecules while diminishing toxicity-related issues. The present review describes the main physiological barriers limiting the oral bioavailability of macromolecules and highlights recent advances in the field of lipid-based carriers as well as the respective lipid intestinal absorption mechanisms.

Effective incorporation of insulin in mucus permeating self-nanoemulsifying drug delivery systems.

The development of a novel, mucus permeating SNEDDS formulation for oral insulin delivery containing a hydrophobic ion pair of insulin/dimyristoyl phosphatidylglycerol (INS/DMPG) is presented. Three oil/surfactant/cosurfactant combinations and 27 weight ratios of oil, surfactant and cosurfactant for each combination were evaluated with the aid of ternary phase diagrams, for the incorporation of the protein/phospholipid complex. The developed formulation was characterized by an average droplet diameter of 30-45 nm. Depending on the initial protein concentration, the loading of insulin in SNEDDS varied between 0.27 and 1.13 wt%. The therapeutic protein was found to be efficiently protected from enzymatic degradation by intestinal enzymes (i.e., trypsin, α-chymotrypsin). The SNEDDS formulation exhibited increased mucus permeability and did not appear to be affected by ionic strength. The incorporation of INS/DMPG in SNEDDS prevented an initial burst release of insulin. INS/DMPG loaded SNEDDS were found to be non-cytotoxic up to a concentration of 2mg/ml. According to the reported results, the incorporation of the hydrophobic ion pair of INS/DMPG in SNEDDS could be regarded as a promising strategy for the oral delivery of insulin.

On the synthesis of mucus permeating nanocarriers.

The synthesis of nanocarriers with "slippery" surface (i.e., poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) and polyelectrolyte complexes (PECs) of polyacrylic acid (PAA) with poly-L-lysine (PLL) and/or polyarginine (PArg)) and of nanocarriers (i.e., PLGA NPs, PLGA-PEG NPs, liposomes) containing a mucolytic agent (i.e., 4-mercaptobenzoic acid (4MBA)) is presented. Depending on the molecular weight (MW) of PEG (i.e., 2, 5 kDa), PLGA-PEG NPs with a "brush" or "dense brush" PEG configuration were prepared. The PLGA-PEG NPs exhibited increased mucus permeability in comparison with non-pegylated PLGA NPs when tested in fresh porcine intestinal mucus. The NPs that were prepared using PEG with a MW equal to 5 kDa and had a "dense brush" PEG configuration, were found to exhibit the highest mucus permeability. The average size and the surface charge of PECs could be effectively tuned by varying the PAA/polycation charge ratio, thus resulting in the synthesis of neutral as well as positively and negatively charged PECs. The PECs with negative surface charges were found to exhibit the highest mucus permeability followed by the neutral and finally the positively charged PECs. Depending on the initial concentration of the mucolytic agent, 4MBA loadings up to 13.65, 13.1 and 18.43 wt% were achieved for PLGA NPs, PLGA-PEG NPs and liposomes, respectively. PLGA and PLGA-PEG NPs were characterized by a rapid release of the mucolytic agent (i.e., >80 wt% of 4MBA was released in 20 min) whereas, its encapsulation in liposomes allowed a more controlled release (i.e., up to 30 wt% of 4MBA was released in 45 min). 4MBA loaded liposomes were found to exhibit increased mucus permeability depending on the composition of the phospholipid bilayer.