Development of certain aminoquinazoline scaffolds as potential multitarget anticancer agents with apoptotic and anti-proliferative effects: Design, synthesis and biological evaluation.

Newly designed 4 - aminoquinazoline derivatives (5a-f, 6a, b, 7, 8, 9, 10a-c, 11a, b, 12a, b and 13a, b) have been synthesized and evaluated for their potential multitarget anticancer activities, apoptotic and anti-proliferative effects. Thereupon, in vitro cytotoxic activities of all the synthesized compounds were screened against NCI 60 human cancer cell lines (nine subpanels) at NCI, USA. Successfully, 2-morpholino-N-(quinazolin-4-yl) acetohydrazide 5e was granted an NSC code, owing to its significant potency and broad spectrum of activity against various cancer cell lines; leukemia K-562, non-small cell lung cancer NCI-H522 cells, colon cancer SW-620, melanoma LOX IMVI, MALME-3M, renal cancer RXF 393, ACHN and breast cancer MDA-MB231/ATCC (GI% = 99.6, 161, 126.03, 90.22, 174.47, 139.7, 191 and 97, respectively). Compound 5e showed the best inhibitory activity (GI50 = 1.3 µM) against melanoma LOX IMVI, when tested at five doses against NCI 60 cell lines. Furthermore, compound 5e showed comparable EGFR and CDK2 inhibitory activity results (IC50 = 0.093 ± 0.006 µM and 0.143 ± 0.008 µM, respectively) to those of lapatinib and ribociclib (IC50 = 0.03 ± 0.002 µM and 0.067 ± 0.004 µM, respectively). Western blotting analysis of compound 5e against melanoma LOX IMVI marked out significant reduced EGFR and CDK2 protein expression percentages, up to 32.97% and 34.09%, respectively, if compared to lapatinib (31.18%) and ribociclib (29.66%). Moreover, compound 5e caused clear cell cycle arrests at S phase of renal UO-31 cells and at G1 phase of both breast cancer MCF7 and ovarian cancer IGROV1, associated with remarkable increase of DNA content of the controls. In accordance, it demonstrated promising anti- proliferative and apoptotic activities, showing a significant increase in total apoptotic percentages of renal cancer UO-31, breast cancer MCF7 and ovarian IGROV1 cancer cell lines, if compared to the control untreated cells (from 1.79% to 46.72%, 2.19% to 39.02% and 1.66 to 42.51%, respectively). Molecular modelling and dynamic simulation study results supported the main objectives of the present work.

Design, synthesis, biological assessment, and in-Silico studies of 1,2,4-triazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors.

A series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives have been designed and synthesized as combretastatin CA-4 analogs. They were screened for anticancer and tubulin polymerization inhibition activities. The trimethoxyphenyl 1,2,4-triazolo[1,5-a]pyrimidine derivative 4c showed significant antiproliferative activity in which it exhibited IC50 = 0.53 µM against HCT-116 cancer cell line. It was further tested as a tubulin polymerization inhibitor showing an IC50 = 3.84 µM if compared to combretastatin IC50 = 1.10 µM. Further mechanism studies revealed that compound 4c could obviously inhibit the proliferation of HCT-116 cancer cells by inducing apoptosis and arresting the cell cycle at the G2/M phase. Furthermore, docking studies showed that compound 4c illustrated good fitting to the colchicine binding site of tubulin. Thus, it is considered an anticancer lead compound worthy of further development as a tubulin polymerization inhibitor.

Advanced endoscopy fellowship training in the United States: recent trends in American Society for Gastrointestinal Endoscopy advanced endoscopy fellowship match, trainee experience, and postfellowship employment.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) advanced endoscopy fellowship (AEF) match offers a structured application process for AEF training in the United States. Our aim was to describe recent trends in AEF match, trainee experience, and postfellowship employment. METHODS: ASGE AEF match data from 2012 to 2020 were reviewed. Online surveys were sent to advanced endoscopy trainees in 2019 and 2020 to explore their perceptions about AEF training and postfellowship jobs. RESULTS: Data for 2020 showed 19% of matched applicants were women, 55% foreign medical graduates, and 17.5% U.S. visa holders. The number of AEF match applicants increased by 15.6% (90 in 2012 to 104 in 2020) and number of AEF programs increased by 23.5% (51 in 2012 to 63 in 2020). The average applicant match rate was 57% (range, 52.8%-60.6%) and position match rate 87.9% (range, 79.1%-94.6%). Ninety-one percent of trainees (n = 58) rated the quality of their training as very good/excellent; 75% of trainees participated in >300 ERCPs and 64.1% in >300 EUS cases. Seventy percent of trainees reported that advanced endoscopic procedures comprised ≤50% of their procedure volume in their first job, and 71.9% believed it was not easy to find a job after fellowship; however, 97% believed they would make the same decision to pursue AEF training again. CONCLUSIONS: There has been a steady increase in the number of advanced endoscopy applicants and training positions over recent years. Most graduating fellows reported 50% or less of their upcoming clinical practice would involve advanced endoscopic procedures. Future studies are needed to further clarify employment opportunities and personnel needs for advanced endoscopists.

Design, synthesis and mechanistic study of novel diarylpyrazole derivatives as anti-inflammatory agents with reduced cardiovascular side effects.

Novel diarylpyrazole (5a-d, 6a-e, 12, 13, 14, 15a-c and 11a-g) derivatives were designed, synthesized and evaluated for their dual COX-2/sEH inhibitory activities via recombinant enzyme assays to explore their anti-inflammatory activities and cardiovascular safety profiles. Comprehensively, the structures of the synthesized compounds were established via spectral and elemental analyses, followed by the assessment of both their in vitro COX inhibitory and in vivo anti-inflammatory activities. The most active compounds as COX inhibitors were further evaluated for their in vitro 5-LOX and sEH inhibitory activities, alongside with their in vivo analgesic and ulcerogenic effects. Compounds 6d and 11f showed excellent inhibitory activities against both COX-2 and sEH (COX-2 IC50 = 0.043 and 0.048 µM; sEH IC50 = 83.58 and 83.52 µM, respectively). Moreover, the compounds demonstrated promising results as anti-inflammatory and analgesic agents with considerable ED50 values and gastric safety profiles. Remarkably, the most active COX inhibitors 6d and 11f possessed improved cardiovascular safety profiles, if compared to celecoxib, as shown by the laboratory evaluation of both essential cardiac biochemical parameters (troponin-1, prostacyclin, tumor necrosis factor-α, lactate dehydrogenase, reduced glutathione and creatine kinase-M) and histopathological studies. On the other hand, docking simulations confirmed that the newly synthesized compounds displayed sufficient structural features required for binding to the target COX-2 and sEH enzymes. Also, in silico ADME studies prediction and drug-like properties of the compounds revealed favorable oral bioavailability results. Collectively, the present work could be featured as a promising future approach towards novel selective COX-2 inhibitors with declined cardiovascular risks.

Sheep-Associated Malignant Catarrhal Fever: Role of Latent Virus and Macrophages in Vasculitis.

Malignant catarrhal fever (MCF) is a sporadic, generally fatal disease caused by gammaherpesviruses in susceptible dead-end hosts. A key pathological process is systemic vasculitis in which productively infected cytotoxic T cells play a major role. Nonetheless, the pathogenesis of MCF vasculitis is not yet clear. We hypothesized that it develops due to an interaction between virus-infected cells and immune cells, and we undertook a retrospective in situ study on the rete mirabile arteries of confirmed ovine gammaherpesvirus-2 (OvHV-2)-associated MCF cases in cattle, buffalo, and bison. Our results suggest that the arteritis develops from an adventitial infiltration of inflammatory cells from the vasa vasorum, and recruitment of leukocytes from the arterial lumen that leads to a superimposed infiltration of the intima and media that can result in chronic changes including neointimal proliferation. We found macrophages and T cells to be the dominant infiltrating cells, and both could proliferate locally. Using RNA in situ hybridization and immunohistology, we showed that the process is accompanied by widespread viral infection, not only in infiltrating leukocytes but also in vascular endothelial cells, medial smooth muscle cells, and adventitial fibroblasts. Our results suggest that OvHV-2-infected T cells, monocytes, and locally proliferating macrophages contribute to the vasculitis in MCF. The initial trigger or insult that leads to leukocyte recruitment and activation is not yet known, but there is evidence that latently infected, activated endothelial cells play a role in this. Activated macrophages might then release the necessary pro-inflammatory mediators and, eventually, induce the characteristic vascular changes.

Effect of Bifidobacterium infantis 35624 (Align) on the Lactulose Breath Test for Small Intestinal Bacterial Overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT. METHODS: Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present. RESULTS: Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an "abnormal" LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal. CONCLUSIONS: This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.

Design, synthesis and analgesic/anti-inflammatory evaluation of novel diarylthiazole and diarylimidazole derivatives towards selective COX-1 inhibitors with better gastric profile.

The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile. Two novel series of 4,5-diarylthiazole and diarylimidazole were designed, synthesized in analogy to selective COX-1 inhibitors (mofezolac and FR122047) which lack gastric damaging effects. The new compounds were evaluated in vitro for their COXs inhibitory activity and in vivo for their anti-inflammatory and analgesic potentials. Four compounds; diphenylthiazole glycine derivatives (15a, 15b) and diphenylimidazolo acetic acid derivatives (19a, 19b), which possess carboxylic acid group exhibited significant activity and selectivity against COX-1 over COX-2. Of these compounds, (4,5-bis(4-methoxyphenyl)thiazol-2-yl)glycine 15b was the most potent compound against COX-1 with an inhibitory half maximal concentration (IC50) of 0.32µM and a selectivity index (COX-2 IC50/COX-1 IC50) of 28.84. Furthermore, an ulcerogenicity study was performed where the tested compounds demonstrated a significant gastric tolerance. Interestingly, the most selective COX-1 inhibitor showed higher analgesic activity in vivo as expected compared to their moderate anti-inflammatory activity. This study underscores the need for further design and development of novel analgesic agents with low tendency to cause gastric damage based on improving their COX-1 affinity and selectivity profile.

Novel diphenylthiazole derivatives with multi-target mechanism: Synthesis, docking study, anticancer and anti-inflammatory activities.

Over the last few decades, a growing body of studies addressed the anticancer activity of NSAIDs, particularly selective COX-2 inhibitors. However, their exact molecular mechanism is still unclear and is not fully investigated. In this regard, a novel series of compounds bearing a COXs privilege scaffold, diphenyl thiazole, was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines. The most active compounds 10b, 14a,b, 16a, 17a,b and 18b were evaluated in vitro for COX-1/COX-2 inhibitory activity. These compounds were suggested to exert their anticancer activity through a multi-target mechanism based on their structural features. Thus, compounds 10b and 17b with the least IC50 values in MTT assay were tested against three known anticancer targets; EGFR, BRAF and tubulin. Compounds 10b and 17b showed remarkable activity against EGFR with IC50 values of 0.4 and 0.2µM, respectively and good activity against BRAF with IC50 values of 1.3 and 1.7µM, respectively. In contrast, they showed weak activity in tubulin polymerization assay. The in vivo anti-inflammatory potential was assessed and interestingly, compound 17b was the most potent compound. Together, this study offers some important insights into the correlation between COXs inhibition and cancer treatment. Additionally, the results demonstrated the promising activity of these compounds with a multi-target mechanism as good candidates for further development into potential anticancer agents.

Frequency of Jackhammer Esophagus as the Extreme Phenotypes of Esophageal Hypercontractility Based on the New Chicago Classification.

BACKGROUND: Jackhammer Esophagus is defined as intact esophageal peristaltic contractions with extremely elevated amplitudes. We conducted a retrospective study to identify the frequency of esophageal hypercontractility and the clinical characteristics of Jackhammer Esophagus. METHODS: Charts for the patients referred for manometric study at a tertiary-care motility center were reviewed. Data were collected utilizing the new Chicago classification criteria for Jackhammer Esophagus. Concomitant clinical variables were also explored. RESULTS: Eight patients were identified with Jackhammer Esophagus from a total of 205 (127 female/77 male) patients referred for high-resolution esophageal manometry. Jackhammer patients had an average distal contractile integral (DCI) of 9061 mmHg/ sec/ cm and median maximal DCI of 16,433 mmHg/ sec/ cm. The greatest DCI from 15 swallows was 28,875 mmHg/ sec/ cm. Hypercontractility was associated with multipeaked contractions in every Jackhammer patient. The mean lower esophageal sphincter (LES) pressure was 41 mm Hg with 4 patients having a hypertensive pressure of >40 mm Hg. Three of the 8 (37.5%) Jackhammer group had incomplete LES relaxation by integrated relaxation pressure criteria (>15 mm Hg residual pressure). Dysphagia (8/8) was the dominant indication for the manometric study, whereas the clinical background setting was gastroesophageal reflux disease (4/8) and hiatal hernia (1/8). Treatments included smooth muscle relaxation, antireflux regimens, and pneumatic dilation of the LES. CONCLUSIONS: Jackhammer Esophagus, an extreme manometric phenotype, was identified in 4.0% of patients referred to a University Motility Center. The patients with these esophageal hypercontractility states present mainly with dysphagia. A subgroup of Jackhammer did have accompanying incomplete LES relaxation and responded to targeted therapy with pneumatic dilatation.

Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort.

BACKGROUND: There is increased awareness about risks and benefits of using domperidone to treat gastroparesis. AIM: To describe the outcome of treating patients with refractory gastroparesis symptoms with domperidone. METHODS: Domperidone 10 mg QID or TID was prescribed to patients with refractory gastroparesis symptoms; follow-up obtained at 2-3 months assessing symptoms and side effects. Patients filled out Patient Assessment of Upper GI Symptoms prior to treatment and at follow-up along with Clinical Patient Grading Assessment Scale (CPGAS, +7 = completely better; 0 = no change). RESULTS: Of 125 patients initially prescribed domperidone, 7 did not take this medication and 3 were lost to follow-up. Of the 115 known patients treated with domperidone, 88 had idiopathic, 16 diabetic, and 9 postsurgical gastroparesis. Side effects were reported by 44 patients (most common-headache, tachycardia/palpitations, diarrhea); 14 patients stopped treatment. Hundred and one patients were seen at follow-up taking domperidone (2.4 ± 2.7 months, average dose 36 ± 13 mg/day). CPGAS averaged 2.7 ± 2.7 (p < 0.01) with 69 patients reporting symptom improvement and 45 patients at least moderately improved with CPGAS ≥ 4. Improvements were seen in most symptoms, especially postprandial fullness, nausea, vomiting, and stomach fullness. CONCLUSIONS: In this large single-center study of patients treated with domperidone, side effects necessitating discontinuing treatment occurred in 12 %. The majority of patients remaining on treatment experienced an improvement in symptoms of gastroparesis, particularly postprandial fullness, nausea, vomiting, and stomach fullness. Thus, domperidone treatment is beneficial for many patients with symptoms of gastroparesis. This study provides needed benefit and risk information concerning treating patients with domperidone. FDA IND Number: 71,089.

Molecular identification of Anaplasma platys in cattle by nested PCR.

Background and Objectives: Anaplasmosis is a zoonotic disease caused by Gram-negative bacterium from Anaplasmataceae family. Anaplasma causes high economic losses worldwide. 16S rRNA analysis was used to diagnose Anaplasma platys in Cattle. Phylogenetic tree and estimation of evolutionary divergence between A. platys isolates were performed. Materials and Methods: A total of 60 blood samples were collected from a cattle farm in AL-Diwaniyah province. 16S rRNA gene was identified using nested PCR. Overall, 40% of cattle that were chosen to collect the blood were identified to be infected with A. platys. Results: The results have shown presence of targeting partial region of 16S rRNA gene in 24 samples out of 60. Sequencing results of 10 samples have revealed that the phylogenetic tree was divided in to two separate clades. Five isolates of A. platys-Iraq (accession no. OP646782, OP646783, OP646784, OP646790, and OP646791) were located in one clade with the A. platys-China (accession no. MN193068.1). While, five isolates (accession no. OP646785, OP646786, OP646787, OP646788, OP646789) were in different clade with two isolates of A. platys-Africa and A. platys-Zambia in distinct branches, close to the Rickettsiales. Conclusion: The phylogenetic study of A. platys sequences indicated that the isolates were collected from a cattle farm in Al-Dewaniyah were similar and close related to A. platys-China, A. platys-Zambia and A. platys-Africa). This study suggests that cattle can be considered a reservoir of A. platys.

Ecofriendly LC-MS/MS and TLC-densitometric methods for simultaneous quantitative assay and monitoring of BEGEV regimen, in vivo pharmacokinetic study application.

To date no analytical method has been developed for the determination of the BEGEV regimen and no study has investigated the kinetic interaction between the drugs, to give us priorities for further clinical study, so two rapid, accurate, sensitive and ecofriendly chromatographic methods were developed for the simultaneous determination of bendamustine (BEN), gemcitabine (GEM) and vinorelbine (VIB) using sildenafil (SIL) as an internal standard (IS) for the purpose of an in vivo pharmacokinetics study in rats. Firstly, the LC-MS/MS method was performed using a mixture of methanol and a 0.1% aqueous solution of formic acid as the mobile phase on a ZORBAX Eclipse Plus C18 (4.6 mm × 150 mm, 5 µm) column as the stationary phase. BEN, GEM and VIB were ionized by positive ions and detected in the multi-reaction monitoring (MRM) mode using precursor → products of m/z 358.20 → 228.25 for BEN, m/z 264.05 → 112.15 for GEM, m/z 779.55 → 122.20 for VIB and m/z 475.00 → 58.35 for SIL. Secondly, TLC-densitometry was applied on TLC silica gel plates using methanol : ethyl acetate (8 : 2, v/v) as the developing system when the separated peaks were scanned at 280 nm. FDA guidelines were followed for validation of the proposed methods, which presented acceptable ranges; then they were applied for an in vivo study in rats with a quantitative determination of each drug after single or combined administration for an investigation of any suspected drug-drug interaction, and all pharmacokinetic parameters were calculated for therapeutic drug monitoring of those drugs. Green analytical chemistry principles were considered during all the procedural steps to ensure the greenness and the safety of the methods, which were evaluated using four assessment tools, eco-scale assessment, the national environmental method index (NEMI), the green analytical procedure index (GAPI) and the analytical greenness metric approach (AGREE), and the results were satisfactory.

Pyrrolizine/indolizine-bearing (un)substituted isoindole moiety: design, synthesis, antiproliferative and MDR reversal activities, and in silico studies.

Two new series of pyrrolizine/indolizine derivative-bearing (un)substituted isoindole moiety were designed and synthesized. The anticancer potential of the new compounds was evaluated against hepatocellular carcinoma (HepG-2), colorectal carcinoma, colon cancer (HCT-116), and breast cancer (MCF-7) cell lines. Compounds 6d and 6o were the most potent derivatives with IC50 values ranging from 6.02 to 13.87 µM against HePG-2, HCT-116, and MCF-7 cell lines. Moreover, methyl analog of the fluoro-substituted indolizine derivative 6m revealed significant antiproliferative activity against HePG-2, HCT-116, and MCF-7 cancer cell lines with IC50 values of 11.97, 28.37, and 19.87 µM, respectively. The most active anticancer analogs, 6d, 6m, and 6o, were inspected for their putative mechanism of action by estimating their epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK 2) inhibitory activities. Thus, compound 6o displayed the most inhibitory activity against EGFR and CDK 2 with IC50 values of 62 and 118 nM, respectively. Additionally, the quantitative real-time PCR analysis for the P-glycoprotein effect of compounds 6d, 6m, and 6o was performed, in which compound 6o illustrated significant down-regulation of P-gp against the HepG-2 cell line by 0.2732 fold. Mechanistic studies for the most active compounds involving the reversal doxorubicin (DOX) effect of compounds 6d, 6m, and 6o were performed, which illustrated cytotoxic activity with IC50 22.27, 3.88, and 8.79 µM, respectively. Moreover, the apoptotic activity of the most active derivative 6o on HCT-116 cancer cells showed accumulation in the G1 and S phases of the cell cycle.

Determination of Gemcitabine and Sorafenib in Spiked Human Plasma Using Multivariate Model Update Chemometric Methods.

BACKGROUND: Gemcitabine (GEM), a pyrimidine nucleoside, has been used as a first-line treatment in non-small-cell lung cancer (NSCLC). Sorafenib (SOR), a nonselective multi-kinase inhibitor, is used as a chemotherapeutic agent in different types of cancers including NSCLC in preclinical studies. Co-administration of GEM and SOR was found to be effective and well-tolerated in the treatment of NSCLC. OBJECTIVE: The aim of the present work is to determine the studied drugs in spiked human plasma simultaneously through resolving the overlapping spectra and removing the interference of the plasma matrix. METHOD: Two updated chemometric models were developed using UV absorbance of the drugs, which named principal component regression (PCR) and partial least-squares (PLS) for determination of GEM and SOR in the ranges of 5-25 and 2-22 µg/mL, respectively. RESULTS: Validation of the two updated models has been achieved in accordance with US Food and Drug Administration (FDA) guidelines, and the results were satisfactory. The two methods had the advantages of high predictive ability of the studied drugs with high precision and accuracy. Moreover, there was no significant difference obtained when statistical comparison was done between the developed and reported methods, showing good validity of the suggested methods. CONCLUSIONS: The two updated models have the advantages of being rapid, accurate, sensitive, and cost-effective for the determination of GEM and SOR in quality control laboratories without any need for initial separation procedures. HIGHLIGHTS: Two updated chemometric methods, PCR and PLS, were developed for the estimation of GEM and SOR in spiked human plasma using their UV absorbance data.

Determination of Bendamustine, Gemcitabine and Vinorelbine (BEGEV) regimen in spiked human plasma using multivariate model update chemometric methods.

Combination of bendamustine (BEN), gemcitabine (GEM), and vinorelbine (VIB), (BEGEV) regimen, has been proved to be a tolerable, safe and effective regimen in relapsed/refractory classical hodgkin lymphoma (R/R cHL). Two chemometric models named principal component regression (PCR) and partial least squares (PLS) were established for determination and quantification of BEN, GEM and VIB simultaneously in the ranges of 5-25 µg/mL for each of BEN and VIB, while in the range of 10 -30 µg/mL for GEM in pure and spiked plasma using their UV absorbance. The updated methods have been proven their ability to predict the concentrations of the studied drugs and validated according to FDA guidelines showing good results. There was no significant difference between the developed methods and the reported LC-MS/MS method upon statistical comparison was applied. Furthermore, the updated chemometric methods have advantages of being sensitive, accurate and cost effective for estimation of BEN, GEM and VIB and monitoring their concentration.

Corrigendum to "A comprehensive review on modelling the adsorption process for heavy metal removal from waste water using artificial neural network technique" [Heliyon 9(4) (April 2023) e15455].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15455.].

A comprehensive review on modelling the adsorption process for heavy metal removal from waste water using artificial neural network technique.

Water is the most necessary and significant element for all life on earth. Unfortunately, the quality of the water resources is constantly declining as a result of population development, industry, and civilization progress. Due to their extreme toxicity, heavy metals removal from water has drawn researchers' attention. A lot of scientific applications use artificial neural networks (ANNs) because of their excellent ability to map nonlinear relationships. ANNs shown excellent modelling capabilities for the water treatment remediation. The adsorption process uses a variety of variables, making the interaction between them nonlinear. Selecting the best technique can produce excellent results; the adsorption approach for removing heavy metals is highly effective. Different studies show that the ANNs modelling approach can accurately forecast the adsorbed heavy metals and other contaminants in order to remove them.