Key frame extraction method for lecture videos based on spatio-temporal subtitles.

Affected by the Corona Virus Disease 2019 (COVID-19), online lecture videos have witnessed an explosive growth. In the face of massive videos, this paper proposes a method for extracting key frames of lecture videos based on spatio-temporal subtitles, which can efficiently and quickly obtain effective information. Firstly, the spatio-temporal slices of subtitle area of the video sequence are extracted and spliced along the time axis to construct the video spatio-temporal subtitle. Then, the video spatio-temporal subtitle is processed in binarization, and the projection method is used to construct the SSPA curve of the video spatio-temporal subtitle. Finally, a selection method for steady-state key frame is designed, that is, the key frame extraction is realized by combining curve edge detection and subtitle existence threshold, which ensures the robustness of the proposed method. The test results of 8 videos show that the average value of the comprehensive index F1-score of the key frame extracted by the algorithm can reach 0.97, the average precision is 0.97, and the average recall rate is 0.98. It can effectively extract the key frames in lecture videos, and compared with other algorithms, the average running time is reduced to 0.072 of the original, which is helpful to extract video information quickly and accurately.

A simple dilution model of the expired jet

Short-range exposure to expired aerosols or droplet nuclei has been considered as the predominant route for SARS-CoV-2. The observed effect of mask wearing, and social distancing suggests the importance of expired jet in the spread of COVID-19. The well-known steady-state dilution model is no longer valid for the interrupted expiratory jet. We reanalysed the existing interrupted jet data and proposed a simple dilution model of expired jet using the two-stage jet model. The interrupted jet consists of two stages, i.e., the jet-like and puff-like stage. Results show dilution factor grows linearly with the distance at the jet-like stage but increases with the cubic of the increasing distance in the puff-like stage. Dilution factor at any distance for the puff-like stage decreases as the activity intensifies, which is still much larger than that estimated via the steady jet model. The findings can be further applied into the short-range airborne exposure assessment. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Measurement of Ventilation Rate and Evaluation of Infection Risk in a Classroom

To quantitatively evaluate the effect of increasing ventilation using the immediately practicable method on infection risk, the ventilation rate in a classroom was measured by the concentration decay method using CO2. The measured value was then substituted into the Wells-Riley model to evaluate aerosol infection risk in steady and non-steady states. In the classroom, the air change rate per hour (ACH) ranged from 3.1 to 10.2, and the local mean age of air tended to be larger near the outlet. It was also shown that opening the windows increased the ventilation rate the most, resulting in a more evenly distributed local mean age of air. We also showed that the aerosol infection risk in the classroom could be significantly reduced by increasing ventilation, suppressing vocalization, and wearing a mask, compared to some outbreaks of COVID-19. © 2022 17th International Conference on Indoor Air Quality and Climate, INDOOR AIR 2022. All rights reserved.

Multiplex measurements of the impacts of ACE2 sequence and cell surface abundance during SARS-like coronavirus entry

SARS-like coronaviruses, including SARS-CoV and SARS-CoV-2, encode spike proteins that bind human ACE2 protein on the cell surface to enter target cells and cause infection. The efficiency of virus entry depends on ACE2 sequence and expression levels in target cells. A small fraction of humans encodes variants of ACE2, thus altering the biochemical properties at the protein interaction interface. All humans possess cells with vastly differing amounts of ACE2 on the cell surface, ranging from cell types with high expression in the gut and lungs to lower expression in the liver and pancreas. Mastering our understanding of spike-ACE2 interaction and infection requires experiments precisely perturbing both variables. Thus, we developed a synthetic cell engineering approach compatible with high throughput assays for pseudo-typed virus infection. Our assay system is capable of assessing both variables individually and in combination. We adapted an engineered HEK293T DNA recombinase landing pad cell line capable of expressing transgenic ACE2 sequences at highly precise levels. Infection with lentiviruses pseudotyped with the spikes of SARS-like coronaviruses revealed that high ACE2 abundance could mask the effects of impaired binding thereby making it challenging to know the role of affinity altering mutations during infection. We limited the ACE2 abundance on the cell surface by expressing transgenic ACE2 behind a suboptimal Kozak sequence, thereby altering its protein translation rate. This allowed us to understand how ACE2 sequence could impact its interaction with coronavirus spike proteins as two human ACE2 variants at the binding interface, K31D and D355N, exhibited reduced infection. Our experiments suggested that we need to better understand how ACE2 expression determines the susceptibility of cells for SARS-like coronavirus binding and infection. We thus created an ACE2 Kozak library consisting of ~4,096 Kozak variants, each conferring a different ACE2 protein translation rate thus resulting in a range of ACE2 steady-state abundances. Combining fluorescence-activated cell sorting and high-throughput DNA sequencing (FACS-seq) revealed the library to span two orders of magnitude of ACE2 abundance. Challenging this library of cells with spike pseudotyped lentiviruses revealed how ACE2 abundance correlated with infection rate. The library-based experiments yielded a dynamic range wider than traditional single sample infection assay, likely more representative of infection dynamics in vivo. Now that we have characterized the impacts of ACE2 abundance on infectivity in engineered cells, our next goal is to expand the comparison to physiologically relevant cells with endogenously expressed proteins. Modulating protein abundance levels will be key to creating maximally informative functional assays for any protein in cell-based assays, and we have laid the groundwork for being able to simultaneously test the impacts of protein abundance and sequence in combination for proteins involved in diverse cellular processes. This research was supported by a National Institute of Health (NIH) grant GM142886 (KAM).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

A PHASE 1B STUDY OF ZOTATIFIN FOR THE TREATMENT OF MILD TO MODERATE COVID (PROpel)

Background: Zotatifin (eFT226) is a potent and selective inhibitor of eukaryotic initiation factor 4A (eIF4A), a host RNA helicase required for SARS-CoV-2 replication. In vitro, zotatifin demonstrates broad spectrum antiviral activity against all human coronaviruses tested. Zotatifin has physicochemical and pharmacokinetic (PK) properties suitable for convenient, single subcutaneous (sc) injection. This study assessed the safety, antiviral activity, and PK of zotatifin in non-hospitalized patients (pts) with mild/moderate COVID. Method(s): PROPEL is a randomized, placebo-controlled, double-blind study in non-hospitalized pts with mild/moderate COVID. At randomization, pts must have had a SARS-CoV-2 positive test within 7 days and at least 1 COVID symptom. Pts were randomized (3:1) to zotatifin or placebo sc in 3 cohorts of 12 pts each. Cohort 1, 2 and 3 received a single dose (SD) of zotatifin of 0.01. 0.02 and 0.035 mg/kg or matching placebo. Safety (adverse event (AE) and laboratory tests), antiviral activity (mid-turbinate nasal swabs and saliva), and plasma PK were collected over 30 days. The primary endpoint was safety;key secondary endpoints included SARS-CoV-2 viral load (VL) and PK. The study was not powered for statistical inferential testing. Result(s): 36 pts were enrolled across all three cohorts and completed a 30-day follow up. Data is currently available for pts in cohorts 1 and 2, 18 and 6 of whom received zotatifin and placebo, respectively. Baseline characteristics were comparable between groups. The most common AE was erythema at injection site in cohort 1 (44%) and cohort 2 (89%), vs. 0% in the zotatifin and pooled placebo groups, respectively. Other AE frequencies were comparable between zotatifin and placebo and no serious AEs were reported. The concentrationtime profile of zotatifin from cohorts 1 and 2 following sc administration was similar to that reported previously following IV administration, demonstrated a terminal elimination half-life (t1/2) of ~ 4 days, high steady-state volume of distribution (Vss) of 31 L/kg, and low plasma clearance (Cl) of 3.9 mL/min/kg. A faster time to viral RNA undetectability was observed with zotatifin vs. placebo (see Fig 1. Not statistically significant). Conclusion(s): Zotatifin was safe, well tolerated and demonstrated a trend in clinical antiviral activity in patients with mild to moderate COVID which supports further clinical development. Zotatifin sc route of administration supports a point of care treatment for COVID.

Increased shunt and dead space in recovered COVID-19 pneumonitis patients

Introduction/Aim: We previously reported impaired pulmonary gas exchange in acute COVID-19 patients resulting from both increased intrapulmonary shunt (SH) and increased alveolar dead space (AD) 1 . The present study quantifies gas exchange in recovered patients. Method(s): Unvaccinated patients diagnosed with acute COVID-19 infection (March-December 2020) were studied 15 to 403 days post first SARS-CoV-2 positive PCR test. Demographic, anthropometric, acute disease severity and comorbidity data were collected. Breathing room air, steady-state exhaled gas concentrations were measured simultaneously with arterial blood gases. Alveolar CO 2 and O 2 (P A CO 2 and P A O 2 ;mid-exhaled volume) determined;AaPO2, aAPCO2, SH% and AD% calculated. 2 Results: We studied 59 patients (33 males, Age: 52[38-61] years, BMI: 28.8[25.3-33.6] kg/m 2 ;median[IQR]). Co-morbibities included asthma (n = 2), cardiovascular disease (n = 3), hypertension (n = 12), and diabetes (n = 9);14 subjects smoked;44 had experienced mild-moderate COVID-19 (NIH category 1-2), 15 severe-critical disease (NIH category 3-5). PaCO 2 was 39.4[35.6-41.1] mmHg, PaO 2 92.1[87.1-98.2] mmHg;P A CO 2 32.8[28.6-35.3] mmHg, P A O 2 112.9[109.4-117.0] mmHg, AaPO 2 18.8[12.6-26.8] mmHg, aAPCO 2 5.9[4.3-8.0] mmHg, SH 4.3 [2.1-5.9]% and AD 16.6 [12.6-24.4]%. 14% of patients had normal SH (<5%) and AD (<10%);1% abnormal SH and normal AD;36% both abnormal SH and AD;49% normal shunt and abnormal AD. Previous severe-critical disease was a strong independent predictor for increased SH (OR 14.8[2.28-96], [95% CI], p < 0.01), increasing age weakly predicted increased AD (OR 1.18[1.01, 1.37], p < 0.04). Time since infection, BMI and comorbidities were not significant predictors (all p > 0.11). Conclusion(s): Prior COVID-19 was associated with increased intrapulmonary shunt and/or increased alveolar dead space in 86% of this cohort up to ~13 months post infection, with those with more severe acute disease, and older patients, at greater risk. Increased intrapulmonary shunt suggests persistent alveolar damage, while increased alveolar dead space may indicate persistent pulmonary vascular occlusion.

Incorporation of awareness programs into a model of the spread of HIV/AIDS among people who inject drugs

Mathematical modeling techniques have been used extensively during the human immunodeficiency virus (HIV) epidemic. Drug injection causes increased HIV spread in most countries globally. The media is crucial in spreading health awareness by changing mixing behavior. The published studies show some of the ways that differential equation models can be employed to explain how media awareness programs influence the spread and containment of disease (Greenhalgh et al. Appl Math Comput. 2015;251:539–563). Here we build a differential equation model which shows how disease awareness programs can alter the HIV prevalence in a group of people who inject drugs (PWIDs). This builds on previous work by Greenhalgh and Hay (1997) and Liang et al. (2016). We have constructed a mathematical model to describe the improved model that reduces the spread of the diseases through the effect of awareness of disease on sharing needles and syringes among the PWID population. The model supposes that PWIDs clean their needles before use rather than after. We carry out a steady state analysis and examine local stability. Our discussion has been focused on two ways of studying the influence of awareness of infection levels in epidemic modeling. The key biological parameter of our model is the basic reproductive number R0$$ {R}_0 $$. R0$$ {R}_0 $$ is a crucial number which determines the behavior of the infection. We find that if R0$$ {R}_0 $$ is less than one then the disease-free steady state is the unique steady state and moreover whatever the initial fraction of infected individuals then the disease will die out as time becomes large. If R0$$ {R}_0 $$ exceeds one there is the disease-free steady state and a unique steady state with disease present. We also showed that the disease-free steady state is locally asymptotically stable if R0$$ {R}_0 $$ is less than one, neutrally stable if R0$$ {R}_0 $$ is equal to one and unstable if R0$$ {R}_0 $$ exceeds one. In the last case, when R0$$ {R}_0 $$ is greater than one the endemic steady state was locally asymptotically stable. Our analytical results are confirmed by using simulation with realistic parameter values. In nontechnical terms, the number R0$$ {R}_0 $$ is a critical value describing how the disease will spread. If R0$$ {R}_0 $$ is less than or equal to one then the disease will always die out but if R0$$ {R}_0 $$ exceeds one and disease is present the disease will sustain itself and moreover the numbers of PWIDs with disease will tend to a unique nonzero value.

Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors

Effective drug delivery to the brain is critical for the treatment of glioblastoma (GBM), an aggressive and invasive primary brain tumor that has a dismal prognosis. Radiation therapy, the mainstay of brain tumor treatment, works by inducing DNA damage. Therefore, inhibiting DNA damage response (DDR) pathways can sensitize tumor cells to radiation and enhance cytotoxicity. AZD1390 is an inhibitor of ataxia-telangiectasia mutated kinase, a critical regulator of DDR. Our in vivo studies in the mouse indicate that delivery of AZD1390 to the central nervous system (CNS) is restricted due to active efflux by P-glycoprotein (P-gp). The free fraction of AZD1390 in brain and spinal cord were found to be low, thereby reducing the partitioning of free drug to these organs. Coadministration of an efflux inhibitor significantly increased CNS exposure of AZD1390. No differences were observed in distribution of AZD1390 within different anatomic regions of CNS, and the functional activity of P-gp and breast cancer resistance protein also remained the same across brain regions. In an intracranial GBM patient-derived xenograft model, AZD1390 accumulation was higher in the tumor core and rim compared with surrounding brain. Despite this heterogenous delivery within tumor-bearing brain, AZD1390 concentrations in normal brain, tumor rim, and tumor core were above in vitro effective radiosensitizing concentrations. These results indicate that despite being a substrate of efflux in the mouse brain, sufficient AZD1390 exposure is anticipated even in regions of normal brain. SIGNIFICANCE STATEMENT Given the invasive nature of glioblastoma (GBM), tumor cells are often protected by an intact blood-brain barrier, requiring the development of brain-penetrant molecules for effective treatment. We show that efflux mediated by P-glycoprotein (P-gp) limits central nervous system (CNS) distribution of AZD1390 and that there are no distributional differences within anatomical regions of CNS. Despite efflux by P-gp, concentrations effective for potent radiosensitization are achieved in GBM tumor-bearing mouse brains, indicating that AZD1390 is an attractive molecule for clinical development of brain tumors.Copyright © 2022 American Society for Pharmacology and Experimental Therapy. All rights reserved.

Modeling of dispersion of aerosolized airborne pathogens exhaled in indoor spaces

Since the beginning of the COVID19 pandemic, there has been a lack of data to quantify the role played by breathing-out of pathogens in the spread of SARS-Cov-2 despite sufficient indication of its culpability. This work aims to establish the role of aerosol dispersion of SARS-Cov-2 virus and similar airborne pathogens on the spread of the disease in enclosed spaces. A steady-state fluid solver is used to simulate the air flow field, which is then used to compute the dispersion of SARS-Cov-2 and spatial probability distribution of infection inside two representative classrooms. In particular, the dependence of the turbulent diffusivity of the passive scalar on the air changes per hour and the number of inlet ducts has been given due consideration. By mimicking the presence of several humans in an enclosed space with a time-periodic inhalation-exhalation cycle, this study firmly establishes breathing as a major contributor in the spread of the pathogen, especially by superspreaders. Second, a spatial gradient of pathogen concentration is established inside the domain, which strongly refutes the well-mixed theory. Furthermore, higher ventilation rates and proximity of the infected person to the inlet and exhaust vents play an important role in determining the spread of the pathogen. In the case of classrooms, a ventilation rate equivalent to 9 air changes or more is recommended. The simulations show that the "one-meter distance rule"between the occupants can significantly reduce the risk of spreading infection by a high-emitter. © 2023 Author(s).

Technology Trends 2023: The Competence Challenge

Competitiveness demands continuous competence growth. At year-end 2022 and within the steady state of post-COVID-19 change, Vector Consulting, with IEEE Software, contacted industry experts about their challenges and resolutions. A lack of competence is the biggest challenge identified in our annual industry survey with IEEE Software. The growing lack of competence is perceived across industries as both the major short-term as well as midterm challenge. Technology companies increasingly suffer from inadequate competencies, both in terms of quantity and quality. In turn, their innovation and competitiveness decrease.

Pharm Aco Kin Etics, Safety, and Tolerability of Upadacitinib in Children with Atopic Dermatitis

BACKGROUND: Upadacitinib is a Janus kinase inhibitor that has been approved for the treatment of adults and adolescents with moderate to severe atopic dermatitis (AD). The objective of this study was to characterize the pharmacokinetics (PK), safety, and tolerability of upadacitinib in children with severe atopic dermatitis. METHOD(S): This is an open-label, multiple-dose study. AD patients (n = 35) were enrolled into four cohorts (Cohort 1, 6 to <12 years, low dose;Cohort 2, 6 to <12 years, high dose;Cohort 3, 2 to <6 years, low dose;Cohort 4, 2 to <6 years, high dose). The low and high doses were selected based on body weight to provide comparable plasma exposure in pediatrics to 15 mg and 30 mg QD doses in adults, respectively. All patients continued on the low dose after the PK assessment on Study Day 7. Safety and exploratory efficacy parameters are assessed in the study. RESULT(S): Geometric mean Cmax and AUC over 0-24 hours at steady state were 33.1 ng/mL and 249 ng.h/mL, respectively, in Cohort 1, 95.5 ng/mL and 523 ng.h/mL, respectively, in Cohort 2, 35.2 ng/mL and 264 ng.h/mL, respectively, in Cohort 3, and 101 ng/mL and 625 ng.h/mL, respectively, in Cohort 4. Upadacitinib was generally safe and well tolerated. The most common AEs were COVID infection, headache, and abdominal discomfort. No new safety risks were identified compared to the known safety profile for upadacitinib. In the 29 subjects with available interim efficacy results at week 12, 34.5% achieved validated Investigator's Global Assessment scale for AD score of 0 or 1 and 69.0% achieved Eczema Area and Severity Index by at least 75% at Week 12 with treatment of upadacitinib. CONCLUSION(S): The findings supported the use of current dosing regimens for further investigation of upadacitinib in upcoming phase 3 clinical trials in pediatric AD patients.

Health risk assessment of volatile organic compounds (VOCs) emitted from landfill working surface via dispersion simulation enhanced by probability analysis

The assessment of the health risks of volatile organic compounds (VOCs) emitted from landfills via dispersion model is crucial but also challenging because of remarkable variations in their emissions and meteorological conditions. This study used a probabilistic approach for the assessment of the health risks of typical VOCs by combining artificial neural network models for emission rates and a numerical dispersion model enhanced by probability analysis. A total of 8753 rounds of simulation were performed with distributions of waste compositions and the valid hourly meteorological conditions for 1 year. The concentration distributions and ranges of the typical health-risky VOCs after dispersion were analyzed with 95% probability. The individual and cumulative non-carcinogenic risks of the typical VOCs were acceptable with all values less than 1 in the whole study domain. For individual carcinogenic risks, only ethylbenzene, benzene, chloroform, and 1, 2-dichloroethane at extreme concentrations showed minor or moderate risks with a probability of 0.1%-1% and an impact distance of 650-3000 m at specific directions. The cumulative carcinogenic risks were also acceptable at 95% probability in the whole study domain, but exceeded 1 x 10-6 or even 1 x 10-4 at some extreme conditions, especially within the landfill area. The vertical patterns of the health risks with height initially increased, and then decreased rapidly, and the peak values were observed around the height of the emission source. The dispersion simulation and health risk assessment of the typical health-risky VOCs enhanced by Monte Carlo can accurately reflect their probabilistic dispersion patterns and health risks to surrounding residents from both spatial and temporal dimensions. With this approach, this study can provide important scientific basis and technical support for the health risk assessment and management of landfills.Copyright © 2022 Elsevier Ltd

Ambient Intelligence Telework System to Enhance Concentration for Each Individual: Easy to Concentrate Based on Neuroticism

In recent years, telework has enormously increased because of the COVID-19 pandemic. However, some people believe that teleworkers can concentrate the same as in-person office work, while others do not. Previous studies showed that the work environment necessary for concentration tends to differ depending on the worker's individual attributes. The goal of this study is to propose an Ambient Intelligence (AMI) telework system suited for each individual to enhance concentration. In this paper, we used two videos with different levels of diligence on a task to investigate what kind of environment makes it easier to concentrate, depending on the degree of neuroticism. Concentration was estimated using the auditory steady-state response (ASSR), which is an oscillatory brain signal elicited by repetitive auditory stimulation and used as a hearing test for infants and children. The changes in the power spectral density of the ASSR with concentration were increased by comparing EEG at rest and during concentration. The effect of the two types of videos on concentration was investigated by evaluating the relationship between neuroticism scores and the power spectral density of the ASSR. The results showed that there was a significant difference in concentration influenced by the two types of videos between the high and low neuroticism score groups. In addition, a negative correlation was found between the neuroticism score and the concentration influenced by the two types of videos. We found that people with lower neuroticism tended to easy to concentrate on their work after seeing someone working hard whereas people with higher neuroticism tended to easy to concentrate on their work after seeing someone working lazily. The experimental results suggest the possibility of constructing an AMI system suited to each individual that enhances concentration. © 2023 IEEE.

Simulation of Synchronous and Asynchronous Generators Models for a Virtual Electrical Machines Laboratory

This paper presents the mathematical models for synchronous and asynchronous generators developed in MATLAB App Designer, with the purpose of implementing a virtual laboratory of electrical machines as a teaching tool for engineering students. This tool was needed because of the SARS-CoV-2 virus pandemic, and the parameters of existing machines were used to emulate the results expected in the real laboratory. The dynamic events simulation of both the synchronous machine and the asynchronous machine use models implemented in Simulink to get transient responses and the results of each practice are displayed in graphical interfaces. Finally, the main advantages offered by the software and the benefits given to the user in each module are detailed, focused on supporting learning, and reaching the objectives established in each laboratory practice. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Pharmacokinetics and pharmacodynamics of imatinib in COVID-19 patients

Introduction: In the randomised double-blind placebo-controlled CounterCovid study, imatinib reduced mortality in COVID-19 patients. High levels of alpha-1 acid glycoprotein (AAG) were associated with increased total imatinib concentrations in COVID-19 patients. Aim(s): We aimed to explore possible relationships between pharmacokinetic(PK) profiles of oral imatinib in COVID19 patients and pharmacodynamic (PD) outcomes. We hypothesize that high total imatinib concentrations may be associated with improved clinical outcomes in COVID-19 patients, when adjusted for AAG. Method(s): PK profiles were expressed as trough concentration at steady state(Css). PD responses were the ratio between partial oxygen pressure and fraction of inspired oxygen(P/F), WHO ordinal scale for clinical improvement(WHO-score) and oxygen supplementation liberation(O2lib). Linear regression, linear mixed effects models and time-to-event analysis were performed and adjusted for possible confounders. Result(s): Individual Css could be determined from 168 patients. Css did associate significantly with P/F (beta=-199,42;p-value=0.013) and O2lib (HR 0.75;p-value= 0.021), adjusted for sex, age, neutrophil-lymphocyte ratio, dexamethasone usage, AAG and baseline P/F-and WHO-score. Css did not significantly associate with WHO-score. Concusion: Higher total exposure following oral imatinib in COVID-19 patients did not associate with improved clinical outcomes. Total Css showed an inverse association with PD-outcomes. This association may be biased by disease-course and variability in metabolic rate and protein binding. Therefore, additional PKPD analyses into unbound imatinib and its main metabolite at Css may better explain exposure-response associations.

Stability analysis of a fractional-order SEIR epidemic model with general incidence rate and time delay

In this paper, we investigate the qualitative behavior of a class of fractional SEIR epidemic models with a more general incidence rate function and time delay to incorporate latent infected individuals. We first prove positivity and boundedness of solutions of the system. The basic reproduction number (Formula presented.) of the model is computed using the method of next generation matrix, and we prove that if (Formula presented.), the healthy equilibrium is locally asymptotically stable, and when (Formula presented.), the system admits a unique endemic equilibrium which is locally asymptotically stable. Moreover, using a suitable Lyapunov function and some results about the theory of stability of differential equations of delayed fractional-order type, we give a complete study of global stability for both healthy and endemic steady states. The model is used to describe the COVID-19 outbreak in Algeria at its beginning in February 2020. A numerical scheme, based on Adams–Bashforth–Moulton method, is used to run the numerical simulations and shows that the number of new infected individuals will peak around late July 2020. Further, numerical simulations show that around 90% of the population in Algeria will be infected. Compared with the WHO data, our results are much more close to real data. Our model with fractional derivative and delay can then better fit the data of Algeria at the beginning of infection and before the lock and isolation measures. The model we propose is a generalization of several SEIR other models with fractional derivative and delay in literature. © 2023 John Wiley & Sons, Ltd.

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.

The Modeling for Anti-Covid-19 Drug Molnupiravir Electrochemical Sensing on C3N4

The cathodic electrochemical determination of molnupiravir on carbon nitride nanoparticles has been investigated for the first time. The electrochemical determination is given in neutral and mildly acidic media, and C3 N4 plays the role of proton and electron transfer mediator. The analysis of the correspondent model confirms that the electrochemical determination of molnupiravir may be efficiently given with the easy interpretation of the analytical signal. As for the oscillatory behavior, its probability is more expressed than in the similar systems. © 2022 by the authors.

Clinical safety and pharmacokinetic evaluation of aqueous extract of Cocculus hirsutus, an anti-viral phytopharmacetical drug as a potential for the treatment of dengue and COVID-19.

Background and aim: Dengue a worldwide concern for public health has no effective vaccine or drug available for its prevention or treatment. There are billions of people who are at risk of contracting the dengue virus (DENV) infections with only anti-mosquito strategies to combat this disease. Based on the reports, particularly in vitro studies and small animal studies showing anti-viral activity of aqueous extract of Cocculus hirsutus (AQCH), studies were conducted on AQCH tablets as a potential for the treatment of dengue and COVID-19 infections. The current study was part of the research on AQCH tablet formulation and was aimed to evaluate safety and pharmacokinetics in healthy human subjects. Materials and methods: Sixty healthy adult human subjects were divided into 5 groups (cohorts: I to V; n = 12 per cohort) and randomized in the ratio of 3:1 to receive active treatment or placebo in a blinded manner. Five doses 100 mg, 200 mg, 400 mg, 600 mg and 800 mg tablets were administered three times daily at an interval of 8 h for days 01-09 under fasting conditions and a single dose in morning on day 10. Safety assessment was based on monitoring the occurrence, pattern, intensity, and severity of adverse events during study period. Blood samples were collected for measurement of the bio-active marker Sinococuline concentrations by a validated LC-MS/MS method followed by pharmacokinetic evaluation. Results and conclusion: The test formulation was well tolerated in all cohorts. Sinococuline peak plasma concentration (Cmax) and total exposure of plasma concentration (AUC) demonstrated linearity up to 600 mg and saturation kinetics at 800 mg dose. There was no difference observed in elimination half-life for all the cohorts, suggesting absence of saturation in rate of elimination. Dose accumulation was observed and steady state was achieved within 3 days. The information on human pharmacokinetics of AQCH tablets would assist in further dose optimization with defined pharmacokinetic-pharmacodynamic relationship.

A Modified SIRV Model for COVID-19

The spread of COVID-19 has caused irreparable and enormous damage to many families around the world, so using mathematical models to further study the changing pattern of the infection's population caused by the spread of the coronavirus can help people to predict the trend of its changes. In this paper, on top of the logistic growth and classical SIR epidemiological models, the author develops a new SIRV model, including the effect of reinfection and breakthrough infection, to illustrate some properties of the spread of COVID-19. This study identified several fundamental properties and basic reproduction numbers of this SIRV COVID-19 model and further searched for the steady-state or equilibrium point of the model using dimensionless methods. This study demonstrated the following: first, the author proved that the solution of the model is positive under non-negative conditions. Second, the author applied the next generation matrix method to determine the basic reproduction number of the COVID-19 virus in the model and found that the calculation of the basic reproduction number in the model is the same as in the classical SIR model. Finally, the author used the dimensionless method to obtain expressions for the equilibrium points of the model in both disease-free and diseased cases. © 2022 SPIE.