Dose-Dependent Production of Anti-PEG IgM after Intramuscular PEGylated-Hydrogenated Soy Phosphatidylcholine Liposomes, but Not Lipid Nanoparticle Formulations of DNA, Correlates with the Plasma Clearance of PEGylated Liposomal Doxorubicin in Rats.

PEGylated lipid nanoparticle-based Covid-19 vaccines, including Pfizer's BNT162b2 and Moderna's mRNA-1273, have been shown to stimulate variable anti-PEG antibody production in humans. Anti-PEG antibodies have the potential to accelerate the plasma clearance of PEGylated therapeutics, such as PEGylated liposomes and proteins, and compromise their therapeutic efficacy. However, it is not yet clear whether antibody titers produced by PEGylated Covid-19 vaccines significantly affect the clearance of PEGylated therapeutics. This study examined how anti-PEG IgM levels affect the pharmacokinetics of PEGylated liposomal doxorubicin (PLD) and compared the immunogenicity of a lipid nanoparticle formulation of linear DNA (DNA-LNP) to standard PEG-HSPC liposomes. DNA-LNP was prepared using the same composition and approach as Pfizer's BNT162b2, except linear double-stranded DNA was used as the genetic material. PEGylated HSPC-based liposomes were formulated using the lipid rehydration and extrusion method. Nanoparticles were dosed IM to rats at 0.005-0.5 mg lipid/kg body weight 1 week before evaluating the plasma pharmacokinetics of clinically relevant doses of PLD (1 mg/kg, IV) or PEGylated interferon α2a (Pegasys, 5 µg/kg, SC). Plasma PEG IgM was compared between pre- and 1-week post-dose blood samples. The results showed that anti-PEG IgM production increased with increasing PEG-HSPC liposome dose and that IgM significantly correlated with the plasma half-life, clearance, volume of distribution, and area under the curve of a subsequent dose of PLD. The plasma exposure of Pegasys was also significantly reduced after initial delivery of 0.005 mg/ml PEG-HSPC liposome. However, a single 0.05 mg/kg IM dose of DNA-LNP did not significantly elevate PEG IgM and did not alter the IV pharmacokinetics of PLD. These data showed that PEGylated Covid-19 vaccines are less immunogenic compared to standard PEGylated HSPC liposomes and that there is an antibody threshold for accelerating the clearance of PEGylated therapeutics.

Studying how administration route and dose regulates antibody generation against LNPs for mRNA delivery with single-particle resolution.

Following the recent approval of both siRNA- and mRNA-based therapeutics, nucleic acid therapies are considered a game changer in medicine. Their envisioned widespread use for many therapeutic applications with an array of cellular target sites means that various administration routes will be employed. Concerns exist regarding adverse reactions against the lipid nanoparticles (LNPs) used for mRNA delivery, as PEG coatings on nanoparticles can induce severe antibody-mediated immune reactions, potentially being boosted by the inherently immunogenic nucleic acid cargo. While exhaustive information is available on how physicochemical features of nanoparticles affects immunogenicity, it remains unexplored how the fundamental choice of administration route regulates anti-particle immunity. Here, we directly compared antibody generation against PEGylated mRNA-carrying LNPs administered by the intravenous, intramuscular, or subcutaneous route, using a novel sophisticated assay capable of measuring antibody binding to authentic LNP surfaces with single-particle resolution. Intramuscular injections in mice were found to generate overall low and dose-independent levels of anti-LNP antibodies, while both intravenous and subcutaneous LNP injections generated substantial and highly dose-dependent levels. These findings demonstrate that before LNP-based mRNA medicines can be safely applied to new therapeutic applications, it will be crucial to carefully consider the choice of administration route.

Receding Horizon Optimization of Ethylene Cracking Operation and Scheduling under Supply Chain Fluctuations

The global supply chain is experiencing ongoing turmoil after COVID-19, which inevitably affects the supply and demand of the chemical industry. Ethylene plants are regarded as one of the most profitable chemical industry chains, and thus, there is a need to track fluctuations in the supply chain and responsively adjust their operations and scheduling decisions to achieve optimal economic benefits. However, previous studies about ethylene cracking optimization are mostly limited to fixed supply chain parameters and cannot meet the need for real-time updates according to supply chain fluctuations. To address this problem, we propose an ethylene cracking optimization framework which combines parameter prediction and receding horizon optimization (predictive RHO) for real-time optimal operation and scheduling under supply chain fluctuations. This optimization framework uses historical supply chain data (supply quantities, feedstock prices, and product prices) to predict future parameters and uses the predicted parameters to optimize the operation and scheduling of ethylene cracking furnace systems in a receding horizon way. Two industrial case studies were used to validate the efficacy of the proposed optimization framework. In case 1, the predictive-RHO framework achieved comparable economic profits of 147,370 and 146,483 $/day without violating daily inventory constraints (vs 151,204 $/day from the original model violating inventory constraints) and a faster calculation speed of 40 s (vs 32 min) under two fluctuating feed supply modes. In case 2, predictive RHO improves economic profits by 1.8% through integrating operations with scheduling and 1.1% by tracking the feed and product price fluctuations. These two cases show the strong capability of predictive RHO in tracking supply chain fluctuations and improving the inventory management level as well as the economic profits of ethylene cracking plants. © 2023 American Chemical Society.

Copper Sulfate-Induced Diphenylamine for Rapid Colorimetric Point-of-Care Detection of Contagious Pathogens Combined with Loop-Mediated Isothermal Amplification

Here, we developed a copper sulfate (CuSO4)-initiated diphenylamine (DPA)-based colorimetric strategy coupled with loop-mediated isothermal amplification (LAMP) for rapid detection of two critical contagious pathogens, SARS-CoV-2 and Enterococcus faecium. To detect the DNA, acid hydrolysis of LAMP amplicons was executed, enabling the development of a blue color. In the LAMP amplicons, the bond between the purines and deoxyribose is extremely labile. It can be broken using 70% sulfuric acid followed by phosphate group elimination, which generates a highly active keto aldehyde group. CuSO4 plays an imperative role inducing DPA to rapidly react with the keto aldehyde group, producing an intense blue color within 5 min. Moreover, low quantities such as 103 copies μL-1 of SARS-CoV-2 RNA and 102 CFU mL-1 of E. faecium were successfully detected, revealing the advantages of the introduced method. To confirm practical applicability, multiplex detection of pathogens was performed using a foldable microdevice comprising reaction and detection zones. Various reactions such as DNA extraction, LAMP, and acid hydrolysis occurred in the reaction zone. Then, colorimetric reagents (DPA, CuSO4, and ethylene glycol) contained in the detection zone were mixed with the keto aldehyde group by simply folding the microdevice, which was heated at 65 °C for 5 min for colorimetric detection. An intense blue color was developed where the target DNA was present. These results indicate that the method proposed in this study is highly suitable for point-of-care applications, especially in resource-limited settings for the rapid detection of harmful pathogens. © 2023 American Chemical Society.

On entropy measures of polycyclic hydroxychloroquine used for novel coronavirus (COVID-19) treatment

The molecular structure of hydroxychloroquine (HCQ) used in the treatment of malaria is recently suggested for emergency used in COVID-19. The chemical compound of HCQ is produced by chemical alteration of ethylene oxide from human products, such as waxy maize starch. The molecular graph is a graph comprising of atoms called vertices and the chemical bond between molecules is called edges. A topological index is a numerical representation of a chemical structure which correlates certain physico-chemical characteristics of underlying chemical compounds besides its numerical representation. To distinguish the creation of entropy-based measures from the structure of chemical graphs, several graph properties have been utilized. For computing the structural information of chemical graphs, the graph entropies have become the information-theoretic quantities. The graph entropy measure has attracted the research community due to its potential application in discrete mathematics, biology, and chemistry. In this paper, our contribution is to explore graph entropies for molecular structure of HCQ based on novel information function, which is the number of different degree vertices along with the number of edges between various degree vertices. More precisely, we have explored the degree-based topological characteristics of hydroxyethyl starch conjugated with hydroxychloroquine (HCQ-HEC). Also, we computed entropies of this structure by making a relation of degree-based topological indices with the help of information function. Moreover, we presented the numerical and graphical comparison of the computed results.

Block catiomers with flanking hydrolyzable tyrosinate groups enhance in vivo mRNA delivery via π-π stacking-assisted micellar assembly.

Messenger RNA (mRNA) therapeutics have recently demonstrated high clinical potential with the accelerated approval of SARS-CoV-2 vaccines. To fulfill the promise of unprecedented mRNA-based treatments, the development of safe and efficient carriers is still necessary to achieve effective delivery of mRNA. Herein, we prepared mRNA-loaded nanocarriers for enhanced in vivo delivery using biocompatible block copolymers having functional amino acid moieties for tunable interaction with mRNA. The block copolymers were based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) modified with glycine (Gly), leucine (Leu) or tyrosine (Tyr) via ester bonds to generate block catiomers. Moreover, the amino acids can be gradually detached from the block copolymers after ester bond hydrolyzation, avoiding cytotoxic effects. When mixed with mRNA, the block catiomers formed narrowly distributed polymeric micelles with high stability and enhanced delivery efficiency. Particularly, the micelles based on tyrosine-modified PEG-PG (PEG-PGTyr), which formed a polyion complex (PIC) and π-π stacking with mRNA, displayed excellent stability against polyanions and promoted mRNA integrity in serum. PEG-PGTyr-based micelles also increased the cellular uptake and the endosomal escape, promoting high protein expression both in vitro and in vivo. Furthermore, the PEG-PGTyr-based micelles significantly extended the half-life of the loaded mRNA after intravenous injection. Our results highlight the potential of PEG-PGTyr-based micelles as safe and effective carriers for mRNA, expediting the rational design of polymeric materials for enhanced mRNA delivery.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine.

Despite the success of mRNA-based vaccines against infectious diseases (including COVID-19), safety concerns have been raised relating to the lipid nanoparticles (LNPs) used to deliver the mRNA cargo. Antibodies against the polyethylene glycol (PEG) coating on these non-viral vectors are present in the general population and can in some instances induce allergic reactions. Furthermore, treatment with PEGylated therapeutics may increase the plasma concentration of such anti-PEG antibodies. The widespread use of PEGylated nanoparticles for mRNA vaccines concerns researchers and clinicians about a potential rise in future cases of allergic reactions against mRNA vaccines and cross-reactions with other PEGylated therapeutics. To determine if vaccination with Comirnaty increased the plasma concentration of antibodies against LNPs, we investigated the blood plasma concentration of anti-LNP antibodies in healthy individuals before and after vaccination with the mRNA-based COVID-19 vaccine Comirnaty (BNT162b2). Blood samples were acquired from 21 healthy adults before vaccination, 3-4 weeks after the first vaccination dose but before the second dose, and 2-6 months after the second (booster) dose. The blood plasma concentration of antibodies recognizing the LNPs was analyzed using a microscopy-based assay capable of measuring antibody-binding to individual authentic LNPs. No significant increase in anti-LNP antibodies was observed after two doses of Comirnaty. The LNPs used for intramuscular delivery of mRNA in the vaccine against COVID-19, Comirnaty, do, therefore, not seem to induce the generation of anti-vector antibodies.

Molecularly imprinted polymer-based nanodiagnostics for clinically pertinent bacteria and virus detection for future pandemics

There seems to be a growing curiosity for utilizing MIPs to recognize molecules that can be applied in numerous fields, such as biomimetic antibodies, detection of viruses and bacteria, the broad range of sensing devices, etc., owing to its scalability and economic viability. MIPs have higher thermal and chemical stability, delivering a promising potential for recognizing bacteria and viruses. The bacteria and virus imprinted polymer exhibit elongated product life-time, reproducible fabrication, robustness, reusability, sensitivity, and high target selectivity. Moreover, the MIPs could give consistent screening along with negligible false positive/negative outcomes, which is vital for the control and prevention of viral and bacterial infections. In the viral and bacterial imprinting process, critical aspects, such as compositional complexity, fragility, solubility, and target size, should be systematically evaluated and analytically considered. Although, the application of MIPs has a number of drawbacks and challenges that require solving to develop sensing platforms with high specificity and sensitivity for clinical application. In the present review, current progress and advancement regarding the reasoning and applications of MIPs as recognition molecules in various biosensors for detecting bacteria and viruses and its existing noteworthy challenges along with future perspectives are also reflected.

Copper Sulfate-Induced Diphenylamine for Rapid Colorimetric Point-of-Care Detection of Contagious Pathogens Combined with Loop-Mediated Isothermal Amplification

Here, we developed a copper sulfate (CuSO4)-initiated diphenylamine (DPA)-based colorimetric strategy coupled with loop-mediated isothermal amplification (LAMP) for rapid detection of two critical contagious pathogens, SARS-CoV-2 and Enterococcus faecium. To detect the DNA, acid hydrolysis of LAMP amplicons was executed, enabling the development of a blue color. In the LAMP amplicons, the bond between the purines and deoxyribose is extremely labile. It can be broken using 70% sulfuric acid followed by phosphate group elimination, which generates a highly active keto aldehyde group. CuSO4 plays an imperative role inducing DPA to rapidly react with the keto aldehyde group, producing an intense blue color within 5 min. Moreover, low quantities such as 103 copies μL-1 of SARS-CoV-2 RNA and 102 CFU mL-1 of E. faecium were successfully detected, revealing the advantages of the introduced method. To confirm practical applicability, multiplex detection of pathogens was performed using a foldable microdevice comprising reaction and detection zones. Various reactions such as DNA extraction, LAMP, and acid hydrolysis occurred in the reaction zone. Then, colorimetric reagents (DPA, CuSO4, and ethylene glycol) contained in the detection zone were mixed with the keto aldehyde group by simply folding the microdevice, which was heated at 65 °C for 5 min for colorimetric detection. An intense blue color was developed where the target DNA was present. These results indicate that the method proposed in this study is highly suitable for point-of-care applications, especially in resource-limited settings for the rapid detection of harmful pathogens. © 2023 American Chemical Society

Antiseptic drugs and disinfectants with experience of the second year of COVID-19 pandemic-related side effects

This review covers publications during the period January 2021 to December 2021 on adverse reactions to antiseptic drugs and disinfectants. Specific agents discussed are alcohols (ethanol, isopropanol), aldehydes (formaldehyde), ethylene oxide, guanidines (chlorhexidine, polyhexamethylene guanidine, and polyhexamethylene biguanidine), benzalkonium compounds, triclosan, povidone-iodine, and sodium hypochlorite. No new data were identified for glutaraldehyde, cetrimide, tosylchloramide, triclocarban, and phenolic compounds. The use of antiseptic drugs and disinfectants has increased considerably since 2020 in various medical and occupational settings, in commerce and gastronomy, as well as in the home, due to their antiviral properties against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the still ongoing Coronavirus Disease 2019 (COVID-19) pandemic. Irritant effects on the respiratory system, the skin and eyes were the most common adverse reaction, while the widespread and occasionally excessive use led to increased reports of poisonings as well as of oral misuse of disinfectants, sometimes associated with serious outcomes such as death from methanol intoxication. Eye exposures in children caused by inadvertent exposures due to unsupervised dispensers in public spaces were pointed out as being specifically problematic. Side effects in the eye may also occur in the general population by improper and unprotected use of UV lamps. The need to improve the safe use of disinfectant devices was pointed out in general.

Teicoplanin and vancomycin derivatives with perfluorilated alkyl groups are active against influenza and coronavirus

Background: As we have seen in the last six months, emerging and re-emerging viruses could be the biggest threat for the human population nowadays in our modern, accelerated and globalized world. Both of influenza and coronaviruses have the potential to cause serious pandemics worldwide. Unfortunately, there are no effective enough medications against most of these viruses. Aims: As some glycopeptide antibiotics and their derivatives proved to be effective against several viruses1, therefore we planned to synthesize some new derivatives equipped with highly fluorinated lipophilic groups. Methods: Perfluorobutyl and perfluorooctyl groups were conjugated to the N-terminus of teicoplanin pseudoaglycone and vancomycin aglycone derivatives through ethylene glycol and tetraethylene glycol linkers by means of photoinitiated addition and azide-alkyne click reaction. The effect of the derivatives were evaluated against several viruses including influenza and human coronavirus. Results: Vancomycin aglycone derivatives were inactive against all of the studied influenza strains, while 3 out of the 4 perfluorobutyl and perfluorooctyl derivatives of teicoplanin pseudoaglycone displayed very good activity against influenza H1N1, H3N2 and B strains. Two of the derivatives were active against human coronavirus as well. Conclusion: We hope that these results can open a new way in finding more effective antivirals based on glycopeptide antibiotics.

Influence of Biofillers on the Properties of Regrind Crystalline Poly(ethylene terephthalate) (CPET).

As the demand for plastics only increases, new methods are required to economically and sustainably increase plastic usage without landfill and environmental accumulation. In addition, the use of biofillers is encouraged as a way to reduce the cost of the final resin by incorporating agricultural and industrial waste by-products, such as rice hulls and coffee chaff to further reduce waste being sent to landfills. Crystalline poly(ethylene terephthalate) (CPET) is a resin commonly used for microwave and ovenable food packaging containers that have not been fully explored for recycling. In this article, we investigate how the incorporation of biofillers at 5% wt. and 10% wt. impacts critical polymer properties. The thermal and mechanical properties were not significantly altered with the presence of rice hulls or coffee chaff in the polymer matrix at 5% wt. loading, but some reduction in melt temperature, thermal stability, and maximum stress and strain was more noticed at 10% wt. The complex viscosity was also reduced with the introduction of biofillers. The levels of heavy metals of concern, such as Cd, Cr, and Pb, were below the regulatory limits applicable in the United States and Europe. Additional studies are suggested to improve the performance of CPET/biofiller blends by pre-treating the biofiller and using compatibilizers.

Biopolymeric sustainable materials and their emerging applications

Advancements in polymer science and engineering have helped the scientific community to shift its attention towards the use of environmentally benign materials for reducing the environmental impact of conventional synthetic plastics. Biopolymers are environmentally benign, chemically versatile, sustainable, biocompatible, biodegradable, inherently functional, and ecofriendly materials that exhibit tremendous potential for a wide range of applications including food, electronics, agriculture, textile, biomedical, and cosmetics. This review also inspires the researchers toward more consumption of biopolymer-based composite materials as an alternative to synthetic composite materials. Herein, an overview of the latest knowledge of different natural- and synthetic-based biodegradable polymers and their fiber-reinforced composites is presented. The review discusses different degradation mechanisms of biopolymer-based composites as well as their sustainability aspects. This review also elucidates current challenges, future opportunities, and emerging applications of biopolymeric sustainable composites in numerous engineering fields. Finally, this review proposes biopolymeric sustainable materials as a propitious solution to the contemporary environmental crisis. © 2022 Elsevier Ltd.

Structural analysis and simulation of solid microneedle array for vaccine delivery applications.

This paper promotes a basic, quick, stature adaptable, and direct approach to selecting exceptionally suitable materials in polyethylene glycol diacrylate (PEGDA) and silicon for microneedle fabrication. Researchers and scientists are facing challenges in readily selecting biocompatible materials for microneedle fabrication. Solid porous silicon and PEGDA microneedles are particularly biocompatible and desirable for vaccine delivery by the transdermal vaccine delivery method if microneedle arrays are fabricated successfully using lithography techniques as they belong to enhanced patient concurrence and well-being. Moreover, silicon and PEGDA microneedles are the ultimate for conveying coronavirus vaccines. In this work, we applied the ANSYS workbench tool to investigate the properties of triangular pyramidal-shaped solid silicon and PEGDA microneedle array to perform structural analysis on microneedle for estimating the capability of an array of needles to enter and convey vaccines along with the skin. These outcomes demonstrated that microneedles of porous silicon are better than polymers such as PEGDA as far as mechanical strength and capacity to convey drugs. Buckling was anticipated as the fundamental method to estimate the failure of microneedles and finally, by analysis, it was clear that buckling does not impact the potential of the silicon microneedle needle array. Silicon and PEGDA microneedles are penetrated against human skin surfaces in explicit dynamics by utilizing the ANSYS tool to select the best material. Along these lines, the current strategy can work with silicon and PEGDA microneedles for useful applications. The von Mises stresses generated by applying loads on silicon and PEGDA arrays were greater than the skin resistance of 3.18 MPa and suitable for skin insertion. Silicon microneedles are sustained due to buckling but PEGDA needles fail if the loading is more than 0.1 N. Vaccination can be provided to humans if needle arrays are fabricated based on this approach and design analysis and considering parameters.

Effect of Wearing Surgical Face Masks on Gas Detection from Respiration Using Photoacoustic Spectroscopy.

Wearing surgical face masks is among the measures taken to mitigate coronavirus disease (COVID-19) transmission and deaths. Lately, concern was expressed about the possibility that gases from respiration could build up in the mask over time, causing medical issues related to the respiratory system. In this research study, the carbon dioxide concentration and ethylene in the breathing zone were measured before and immediately after wearing surgical face masks using the photoacoustic spectroscopy method. From the determinations of this study, the C2H4 was established to be increased by 1.5% after one hour of wearing the surgical face mask, while CO2 was established to be at a higher concentration of 1.2% after one hour of wearing the surgical face mask, when the values were correlated with the baseline (control).

Microbial Consortia and Mixed Plastic Waste: Pangenomic Analysis Reveals Potential for Degradation of Multiple Plastic Types via Previously Identified PET Degrading Bacteria.

The global utilization of single-use, non-biodegradable plastics, such as bottles made of polyethylene terephthalate (PET), has contributed to catastrophic levels of plastic pollution. Fortunately, microbial communities are adapting to assimilate plastic waste. Previously, our work showed a full consortium of five bacteria capable of synergistically degrading PET. Using omics approaches, we identified the key genes implicated in PET degradation within the consortium's pangenome and transcriptome. This analysis led to the discovery of a novel PETase, EstB, which has been observed to hydrolyze the oligomer BHET and the polymer PET. Besides the genes implicated in PET degradation, many other biodegradation genes were discovered. Over 200 plastic and plasticizer degradation-related genes were discovered through the Plastic Microbial Biodegradation Database (PMBD). Diverse carbon source utilization was observed by a microbial community-based assay, which, paired with an abundant number of plastic- and plasticizer-degrading enzymes, indicates a promising possibility for mixed plastic degradation. Using RNAseq differential analysis, several genes were predicted to be involved in PET degradation, including aldehyde dehydrogenases and several classes of hydrolases. Active transcription of PET monomer metabolism was also observed, including the generation of polyhydroxyalkanoate (PHA)/polyhydroxybutyrate (PHB) biopolymers. These results present an exciting opportunity for the bio-recycling of mixed plastic waste with upcycling potential.

Deep Learning Enabling Analysis of Exhaled Breath Using Fourier Transform Spectroscopy in the Mid-Infrared

Exhaled breath analysis is a promising noninvasive method for rapid diagnosis of diseases by detecting different types of volatile organic compounds (VOCs) that are used as biomarkers for early detection of various diseases such as lung cancer, diabetes, anemias, etc... and more recently COVID-19. Infrared spectroscopy seems to be a promising method for VOCs detection due to its ease of use, selectivity, and existence of compact low-cost devices. In this work, the use of Fourier transforms infrared (FTIR) spectrometer to analyze breath samples contained in a gas cell is investigated using deep learning and taking into account the practical performance limits of the spectrometer. Synthetic spectra are generated using infrared gas spectra databases to emulate real spectra resulted from a breath sample and train the neural network model (NNM). The dataset is generated in the spectral range of 2000 cm-1 to 6500 cm-1 and assuming a light-gas interaction length of 5 meters. The FTIR device performance is assumed with a signal-to-noise ratio (SNR) of 20,000:1 and a spectral resolution of 40 cm-1. The proposed NNM contains a locally connected and 4 fully connected layers. The concentrations of 9 biomarker gases in the exhaled breath are predicted with r2 score higher than 0.93, including carbon dioxide, water vapor, acetone, ethene, ammonia, methane, carbonyl sulfide, carbon monoxide and acetaldehyde demonstrating the possibility of detection. © 2021 IEEE.

Clinical Relevance of Pre-Existing and Treatment-Induced Anti-Poly(Ethylene Glycol) Antibodies.

Abstract: Poly(ethylene glycol) (PEG) is a nontoxic, hydrophilic polymer that is often covalently attached to proteins, drugs, tissues, or materials; a procedure commonly referred to as PEGylation. PEGylation improves solubility, circulation time, and reduces immunogenicity of therapeutic molecules. Currently, there are 21 PEGylated drugs approved by the Food and Drug Administration (FDA), and more in the developmental stage. In addition to the polymer's applications in the clinic, PEG is widely used as a solvent and emulsifying agent in the formulation of cosmetics, cleaning, and personal care products. Due to the ubiquitous presence of the polymer in everyday products, patients can develop antibodies against PEG (αPEG Abs) that can be problematic when a PEGylated drug is administered. These αPEG Abs can provoke hypersensitivity reactions, accelerated drug clearance, and decreased therapeutic efficacy. Herein, we review how the prevalence of PEG in everyday products has induced αPEG Abs within the general public as well as the effect of these Abs on the performance of PEGylated therapeutics. We will focus on clinical manifestations following the administration of PEGylated drugs. Lay Summary: Poly(ethylene glycol) (PEG) is a polymer found in products including cosmetics, personal care products, cleaning agents, medicine, and food. Due to the prevalence of PEG, people can develop antibodies (αPEG Abs) against the polymer, which recognize PEG as foreign. Of note, PEG is frequently incorporated into drug formulations to improve therapeutic efficacy. Complications can arise when a patient receiving a PEGylated drug has previously developed αPEG Abs from interactions with PEG in everyday products. The presence of high concentrations of αPEG Abs in blood can result in decreased treatment efficacy and allergic reactions to a wide range of therapeutics.