Modeling different infectious phases of hepatitis B with generalized saturated incidence: An analysis and control.

Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are significant because worldwide, approximately 250 million people are infected by chronic hepatitis B. The chronic stage is a long-term, persistent infection that can cause liver damage and increase the risk of liver cancer. In the case of multiple phases of infection, a generalized saturated incidence rate model is more reasonable than a simply saturated incidence because it captures the complex dynamics of the different infection phases. In contrast, a simple saturated incidence rate model assumes a fixed shape for the incidence rate curve, which may not accurately reflect the dynamics of multiple infection phases. Considering HBV and its various phases, we constructed a model to present the dynamics and control strategies using the generalized saturated incidence. First, we proved that the model is well-posed. We then found the reproduction quantity and model equilibria to discuss the time dynamics of the model and investigate the conditions for stabilities. We also examined a control mechanism by introducing various controls to the model with the aim to increase the population of those recovered and minimize the infected people. We performed numerical experiments to check the biological significance and control implementation.

Human and ecological risk assessments of potentially toxic elements in sediments around a pharmaceutical industry.

Potentially toxic elements (PTEs) in sediment can be highly hazardous to the environment and public health. This study aimed to assess the human and ecological risks of PTEs in sediments around a pharmaceutical industry in Ilorin, Nigeria. Physicochemical parameters and the concentrations of lead (Pb), chromium (Cr), cadmium (Cd), cobalt (Co), arsenic (As), and nickel (Ni) were analyzed in sediment samples collected from seven locations in the wet and dry seasons. Standard two-dimensional principal component analysis (PCA) and risk assessments were also conducted. The concentrations of Pb, Co, Ni, Cr, Cd, and As in the sediments ranged from 0.001 to 0.031 mg/kg, 0-0.005 mg/kg, 0.005-0.012 mg/kg, 0.001-0.014 mg/kg, 0.005-0.024 mg/kg, and 0.001-0.012 mg/kg, respectively. The mean concentrations of the total PTEs content were found in decreasing order of concentration: Pb > Cd > Ni > Cr > As > Co. PCA showed that some of the PTEs were highly concentrated in samples obtained at other locations as well as at the discharge point. The Hazard Index was mostly <1 across locations, indicating little to no probable non-cancerous effect. However, the incremental lifetime cancer risk for arsenic and nickel was high and required attention. The ecological risk assessment showed that lead and arsenic were the major PTEs pollutants in all locations. The study identifies PTEs profiles in sediments and emphasises the necessity of continual monitoring and action to stop long-term negative impacts on the local environment and public health.

Enantioselective total synthesis of atisane diterpenoids: (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one.

Enantioselective total synthesis of (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one has been accomplished starting from enantiopure Wieland-Miescher ketone. Key features of the syntheses include a benzannulation step to construct the tricyclic core, an oxidative dearomatization step to generate the diene, and a Diels-Alder reaction with ethylene gas to establish the bicyclo[2.2.2]octane framework. Efficient late-stage functionalisation of the A-ring by aerobic oxidation and Baeyer-Villiger oxidation completed the atisane target molecules.

Advanced stability analysis of a fractional delay differential system with stochastic phenomena using spectral collocation method.

In recent years, there has been a growing interest in incorporating fractional calculus into stochastic delay systems due to its ability to model complex phenomena with uncertainties and memory effects. The fractional stochastic delay differential equations are conventional in modeling such complex dynamical systems around various applied fields. The present study addresses a novel spectral approach to demonstrate the stability behavior and numerical solution of the systems characterized by stochasticity along with fractional derivatives and time delay. By bridging the gap between fractional calculus, stochastic processes, and spectral analysis, this work contributes to the field of fractional dynamics and enriches the toolbox of analytical tools available for investigating the stability of systems with delays and uncertainties. To illustrate the practical implications and validate the theoretical findings of our approach, some numerical simulations are presented.

Detection of Alteration in Carotid Artery Volumetry Using Standard-of-care Computed Tomography Surveillance Scans Following Unilateral Radiation Therapy for Early-stage Tonsillar Squamous Cell Carcinoma Survivors: A Cross-Sectional Internally-Matched Carotid Isodose Analysis.

Purpose: Radiation induced carotid artery disease (RICAD) is a major cause of morbidity and mortality among survivors of oropharyngeal cancer. This study leveraged standard-of-care CT scans to detect volumetric changes in the carotid arteries of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer, and to determine dose-response relationship between RT and carotid volume changes, which could serve as an early imaging marker of RICAD. Methods and Materials: Disease-free cancer survivors (>3 months since therapy and age >18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Pre- and post-treatment CTs were registered to the planning CT and dose grid. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery subvolumes in 5 Gy increments (i.e. received 50-55 Gy, 55-60 Gy, etc.). The percent-change in sub-volumes across each dose range was statistically examined using the Wilcoxon rank-sum test. Results: Among 46 patients analyzed, 72% received RT alone, 24% induction chemotherapy followed by RT, and 4% concurrent chemoradiation. The median interval from RT completion to the latest, post-RT CT scan was 43 months (IQR 32-57). A decrease in the volume of the irradiated carotid artery was observed in 78% of patients, while there was a statistically significant difference in mean %-change (±SD) between the total irradiated and spared carotid volumes (7.0±9.0 vs. +3.5±7.2, respectively, p<.0001). However, no significant dose-response trend was observed in the carotid artery volume change withing 5 Gy ranges (mean %-changes (±SD) for the 50-55, 55-60, 60-65, and 65-70+ Gy ranges [irradiated minus spared]: -13.1±14.7, -9.8±14.9, -6.9±16.2, -11.7±11.1, respectively). Notably, two patients (4%) had a cerebrovascular accident (CVA), both occurring in patients with a greater decrease in carotid artery volume in the irradiated vs the spared side. Conclusions: Our data show that standard-of-care oncologic surveillance CT scans can effectively detect reductions in carotid volume following RT for oropharyngeal cancer. Changes were equivalent between studied dose ranges, denoting no further dose-response effect beyond 50 Gy. The clinical utility of carotid volume changes for risk stratification and CVA prediction warrants further evaluation.

A Review on Pyrazolines as Colorimetric Fluorescent Chemosensors for Cu2.

The Pyrazoline derivatives display promising potential as sensitive and selective chemosensors for detecting Cu2+ ions. It has undergone screening for its sensing behavior with various metals using absorption, emission spectroscopic techniques. Their unique structure incorporates both donating and accepting sites, characterized by delocalized orbitals. These derivatives exhibit notable chromogenic and fluorogenic capabilities facilitated by intramolecular charge transfer. The sensors based on pyrazoline demonstrate exceptional selectivity, low detection limits, and precise detection of metal ions, particularly Cu2+. This review offers a comprehensive summary of recent discoveries concerning as pyrazoline-based "On-Off" chemosensors. The discussion places emphasis on exploring the design and photophysical properties of these chemosensors, with the primary objective of detecting Cu2+ metal ions. The unique features of pyrazoline derivatives make them promising candidates for practical applications in environmental and biological monitoring, showcasing their potential significance in advancing sensing technologies.

Up-gradation of the dielectric, physical & chemical properties of cottonseed-based, non-edible green nanofluids as sustainable alternatives for high-voltage equipment's insulation fluids.

The use of natural ester oils as electrically insulating fluids has gained significant attention from industries and electrical utilities as they aim to replace traditional mineral oils. However, most natural ester oils are derived from edible products, which has the potential to contribute to the food crisis. Therefore, nonedible green nanofluids made from cottonseed oil (CSO) have been targeted as a keen solution to this issue. However, Al2O3, TiO2, Fe2O3, SiO2, and graphene nanoparticles at (0.025, 0.05, and 0.075 wt/vol%) were used as additives, along with surfactant Olic Ac-id and Ethanol (1:5) due to their promising impact on the dielectric and thermal properties of the nanofluid. The nanofluid synthesis process was practically conducted in HV & Chemical Laboratories using one-step and two-step methods, and their breakdown voltage results and chemical properties (e.g., fire point, flash point, cloud point, pour point, viscosity, acidity, moisture content, resistivity, and dissipation factor) were compared. The physical mechanisms underlying these properties were also analyzed and tested. For the validation of the proposed vegetable oil the results have been compared with traditional mineral oil for high-voltage equipment's. The findings suggest that the proposed nonedible green nanofluids-based cottonseed oil (CSO) has a high potential to be used as electrically insulating fluids, providing a sustainable alternative to conventional mineral oils. Overall, this study provides insights into the use of non-edible green nanofluids as a solution to the potential contribution of natural ester oils to the food crisis. The findings highlight the importance of sustainable solutions in the energy industry and the need for further research in this area.

A rigorous theoretical and numerical analysis of a nonlinear reaction-diffusion epidemic model pertaining dynamics of COVID-19.

The spatial movement of the human population from one region to another and the existence of super-spreaders are the main factors that enhanced the disease incidence. Super-spreaders refer to the individuals having transmitting ability to multiple pathogens. In this article, an epidemic model with spatial and temporal effects is formulated to analyze the impact of some preventing measures of COVID-19. The model is developed using six nonlinear partial differential equations. The infectious individuals are sub-divided into symptomatic, asymptomatic and super-spreader classes. In this study, we focused on the rigorous qualitative analysis of the reaction-diffusion model. The fundamental mathematical properties of the proposed COVID-19 epidemic model such as boundedness, positivity, and invariant region of the problem solution are derived, which ensure the validity of the proposed model. The model equilibria and its stability analysis for both local and global cases have been presented. The normalized sensitivity analysis of the model is carried out in order to observe the crucial factors in the transmission of infection. Furthermore, an efficient numerical scheme is applied to solve the proposed model and detailed simulation are performed. Based on the graphical observation, diffusion in the context of confined public gatherings is observed to significantly inhibit the spread of infection when compared to the absence of diffusion. This is especially important in scenarios where super-spreaders may play a major role in transmission. The impact of some non-pharmaceutical interventions are illustrated graphically with and without diffusion. We believe that the present investigation will be beneficial in understanding the complex dynamics and control of COVID-19 under various non-pharmaceutical interventions.

The epidemiological and clinicopathological features of breast cancer in Riyadh, Saudi Arabia.

OBJECTIVES: To investigate the epidemiological and clinicopathological features of breast cancer (BC) in Saudi Arabia to improve decisions regarding resource allocation, disease control, and management. METHODS: We retrieved the records of all patients who presented with histologically proven BC at King Fahad Medical City between 2019 and 2020. The data were analyzed quantitatively, and the results were expressed as percentages and frequencies. RESULTS: This study comprised 419 patients. The mean age was 50.13 (± 10.96) years. The majority of the patients were obese (56.6%), and approximately a quarter had a history of oral contraceptive pill use, breast biopsy, or an affected family member. Most cases were from the central region (80.1%), followed by the southern provinces (12.7%). Breast lumps were the most common complaint (89%), whereas hypertension and diabetes mellitus were the most common comorbidities. Invasive ductal carcinoma was the most common pathologic type (89.7%). Most patients presented with TNM stages II and III (55.2%), and 27.7% had metastasis. The main therapeutic modalities included radical mastectomy (63.8%), neoadjuvant chemotherapy (60.4%), and adjuvant radiotherapy (82.9%). CONCLUSION: In Saudi Arabia, a trend of BC incidence migration towards older patients may be ensuing. However, prediction of an advanced and aggressive presentation requires the enhancement of screening programs and standardized protocols for disease management.

Numerical simulation of a fractional stochastic delay differential equations using spectral scheme: a comprehensive stability analysis.

The fractional stochastic delay differential equation (FSDDE) is a powerful mathematical tool for modeling complex systems that exhibit both fractional order dynamics and stochasticity with time delays. The purpose of this study is to explore the stability analysis of a system of FSDDEs. Our study emphasizes the interaction between fractional calculus, stochasticity, and time delays in understanding the stability of such systems. Analyzing the moments of the system's solutions, we investigate stochasticity's influence on FSDDS. The article provides practical insight into solving FSDDS efficiently using various numerical techniques. Additionally, this research focuses both on asymptotic as well as Lyapunov stability of FSDDS. The local stability conditions are clearly presented and also the effects of a fractional orders with delay on the stability properties are examine. Through a comprehensive test of a stability criteria, practical examples and numerical simulations we demonstrate the complexity and challenges concern with the analyzing FSDDEs.

Frequency regulation of interconnected hybrid power system with Assimilation of electrical vehicles.

Recent widespread connections of renewable energy resource (RESs) in place of fossil fuel supplies and the adoption of electrical vehicles in place of gasoline-powered vehicles have given birth to a number of new concerns. The control architecture of linked power networks now faces an increasingly pressing challenge: tie-line power fluctuations and reducing frequency deviations. Because of their nature and dependence on external circumstances, RESs are analogous to continually fluctuating power generators. Using a fractional order-based frequency regulator, this work presents a new method for improving the frequency regulation in a two-area interconnected power system. In order to deal with the frequency regulation difficulties of the hybrid system integrated with RES, the suggested controller utilizes the modified form of fractional order proportional integral derivative (FOPID) controller known as FOI-PDN controller. The new proposed controllers are designed using the white shark optimizer (WSO), a current powerful bioinspired meta heuristic algorithm which has been motivated by the learning abilities of white sharks when actively hunting in the environment. The suggested FOI-PDN controller's performance was compared to that of various control methodologies such as FOPID, and PID. Furthermore, the WSO findings are compared to those of other techniques such as the salp swarm algorithm, sine cosine algorithm and fitness dependent optimizer. The recommended controller and design approach have been tested and validated at different loading conditions and different circumstances, as well as their robustness against system parameter suspicions. The simulation outcomes demonstrate that the WSO-based tuned FOI-PDN controller successfully reduces peak overshoot by 73.33%, 91.03%, and 77.21% for region-2, region-1, and link power variation respectively, and delivers minimum undershoot of 89.12%, 83.11%, and 78.10% for both regions and tie-line. The obtained findings demonstrate the new proposed controller's stable function and frequency controlling performance with optimal controller parameters and without the requirement for a sophisticated design process.

Aiding the well celebrated Kuk's randomized response technique through auxiliary and prior information.

Asking direct questions in face to face surveys about sensitive traits is an intricate issue. One of the solutions to this issue is the randomized response technique (RRT). Being the most widely used indirect questioning technique to obtain truthful data on sensitive traits in survey sampling RRT has been applied in a variety of fields including behavioral science, socio-economic, psychological, epidemiology, biomedical, criminology, data masking, public health engineering, conservation studies, ecological studies and many others. This paper aims at exploring the methods to subsidize the randomized response technique through additional information relevant to the parameter of interest. Specifically, we plan to contribute by proposing more efficient hybrid estimators compared to existing estimator based on (Kuk, 1990) [31] family of randomized response models. The proposed estimators are based on the methodology of incorporating the pertinent information, available on the basis of either historical records or expert opinion. Specifically, in case of availability of auxiliary information, the regression-cum-ratio estimator is found to be the best to further enhance the estimation through (Kuk, 1990) [31] model while the (Thompson, 1968) [49] shrinkage estimation is observed to be yielding more precise and accurate estimator of sensitive proportion. The findings in this study signify the importance of the proposed methodology. Additionally, to support the mathematical findings, a detailed numerical investigation to evaluate the comparative performances is also conducted. Based on performance analysis, overwhelming evidences are witnessed in the favor of proposed strategies.

In Silico Insights into the Arsenic Binding Mechanism Deploying Application of Computational Biology-Based Toolsets.

An assortment of environmental matrices includes arsenic (As) in its different oxidation states, which is often linked to concerns that pose a threat to public health worldwide. The current difficulty lies in addressing toxicological concerns and achieving sustained detoxification of As. Multiple conventional degradation methods are accessible; however, they are indeed labor-intensive, expensive, and reliant on prolonged laboratory evaluations. Molecular interaction and atomic level degradation mechanisms for enzyme-As exploration are, however, underexplored in those approaches. A feasible approach in this case for tackling this accompanying concern of As might be to cope with undertaking multivalent computational methodologies and tools. This work aimed to provide molecular-level insight into the enzyme-aided As degradation mechanism. AutoDock Vina, CABS-flex 2.0, and Desmond high-performance molecular dynamics simulation (MDS) were utilized in the current investigation to simulate multivalent molecular processes on two protein sets: arsenate reductase (ArsC) and laccase (LAC) corresponding arsenate (ART) and arsenite (AST), which served as model ligands to comprehend binding, conformational, and energy attributes. The structural configurations of both proteins exhibited variability in flexibility and structure framework within the range of 3.5-4.5 Å. The LAC-ART complex exhibited the lowest calculated binding affinity, measuring -5.82 ± 0.01 kcal/mol. Meanwhile, active site residues ILE-200 and HIS-206 were demonstrated to engage in H-bonding with the ART ligand. In contrast to ArsC, the ligand binding affinity of this bound complex was considerably greater. Additional validation of docked complexes was carried out by deploying Desmond MDS of 100 ns to capture protein and ligand conformation behavior. The system achieved stability during the 100 ns simulation run, as confirmed by the average P-L RMSD, which was ∼1 Å. As a preliminary test of the enzyme's ability to catalyze As species, corresponding computational insights might be advantageous for bridging gaps and regulatory consideration.

Fabrication of an affordable and sensitive corticosteroid-binding globulin immunosensor based on electrodeposited gold nanoparticles modified glassy carbon electrode.

Herein, we fabricated an ultrasensitive electrochemical immunosensor for the quantitative detection of corticosteroid-binding globulin (CBG). CBG is a protein that regulates glucocorticoid levels and is an important biomarker for inflammation. A decrease in CBG levels is a key biomarker for inflammatory diseases, such as septic shock. To enhance the electrochemical performance and provide a large surface area for anti-CBG immobilization, we functionalized the glassy carbon electrode surface with AuNPs. Electrochemical characterization methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to examine the construction of the fabricated immunosensor. The electrochemical signal demonstrated a remarkable sensitivity to the CBG antigen, with a detection range from 0.01 to 100 µg/mL and a limit of detection of 0.012 µg/mL, making it suitable for both clinical and research applications. This label-free immunosensor offers significant advantages, including high sensitivity, low detection limits and excellent selectivity, making it a promising tool for detecting CBG in complex biological samples. Its potential applications include early disease diagnosis, treatment monitoring and studying CBG-related physiological processes.

Synthesis of Fluorescent Pyrazoline Sensors as Versatile Tool for Zinc ion Detection: A Mini-Review.

Zinc ions are one of the 2nd most abundant mineral after iron and it is important for immune system, enzymatic catalysis, DNA synthesis, and maintaining structural integrity in humans. But, monitoring the Zn levels in human body poses more challenges. This review paper investigates (paper from 2010 to 2023) the synthesis of pyrazoline derivatives by different methods, including conventional methods and green chemistry protocol. These Pyrazoline derivatives highlighted for their potential application as chemo-sensor for Zn2+ ions recognition. Pyrazoline compounds exhibit excellent sensitivity & selectivity and emitting blue-light with high quantum yields and electroluminescence, along with a superior limit of detection. These derivatives are stable bioactive molecule, with well-known diverse biological activities. This review not only gives valuable insights into the essential role of Zinc in human physiology but also provides a practical method for accurate Zinc detection in various samples. Which holds the potential for advancements in health diagnostics and environmental monitoring. Because of their significant biological application and selectivity as sensors, researchers have much more attention to prepare green environmentally-friendly pyrazoline derivatives.

Synthesis, Physicochemical and Third Order Nonlinear Optical Properties of Bis-Chalcone (BBDP) as Donor-pi Acceptor Chromophore in Organize Medium.

Bis-Chalcone (BBDP) has been prepared by condensation of N, N-dimethyl benzaldehyde and 1,1'-([1,1'-biphenyl]-4,4'-diyl) di (ethan-1-one), and structure of BBDP was characterized by Mass Spectra, 13C-NMR, 1H-NMR, and IR. Physicochemical properties including Dipole-moments, Stoke-Shifts, Oscillator-strength, dielectric constant and quantum-yields of fluorescence of BBDP were investigated by the emission and absorbances in different solvents. Compound (BBDP) displayed bathochromic shift upon increasing the solvent polarity (from n-Hexane to DMSO). Furthermore, we have exploited third-order nonlinear optical characteristics of the bisChalone were invigilated by the Z-scan techniques in Chloroform. The measurements were taken with a continuous-wave (CW) diode laser having a wavelength of 520 nm in CHCl3 solvent. The third-order nonlinear optical properties, such as the nonlinear refractive index (NLRI) n2, nonlinear absorption coefficient (NLAC) ß, and nonlinear susceptibility χ(3), were measured at various solution concentrations and laser powers. The obtained values of n2, ß, and χ(3) were estimated to be high, of the order of 10-7(cm2/W), 10-3 (cm/W), and 10-6 (esu), respectively. As a result, bis-chalcone (BBDP) is considered as a promising candidate for applications in nonlinear optical (NLO) devices and optical limiting (OL).

Lithiated porous silicon nanowires stimulate periodontal regeneration.

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/ß-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/ß-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.

Trends in Monkeypox transmission: Investigation into 30 most affected countries.

This research is based on the analysis of Monkeypox transmission, from may 7, 2022 to October 11, 2022, in 30 most affected countries around the globe. The most affected countries are selected through the cut point of at least 100 reported confirmed cases of infected persons over the aforementioned time span. We novely argue the exhibition of distributional similarities between the viral flow and well known power law in context of this neglected zoonotic disease. Moreover, model-based evidence suggesting the capability of pathogen to spread far and wide around its nucleus, are collected and presented. It is estimated that 70 % of the reported confirmed cases belonged to 20 % of the top most affected countries. Also, 70 % of the reported transmission was inflicted in 34 % of the days of reporting at least one case, on average.

Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

New paracetamol hybrids as anticancer and COX-2 inhibitors: Synthesis, biological evaluation and docking studies.

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC50 ) values ranging from 1.51 to 6.31 µM and anti-COX-2 activity with IC50 = 0.29 µM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy.