Development of AI-based hybrid soft computing models for prediction of critical river water quality indicators.

Prediction of river water quality indicators (RWQIs) using artificial intelligence (AI)-based hybrid soft computing modeling techniques could provide essential predictions required for efficient river health planning and management. The study described the development of a novel AI-based relative weighted ensemble (AIRWE) hybrid model for predicting critical RWQIs, i.e., biochemical oxygen demand (BOD) and total coliform (TC). The study involved comprehensive water quality (WQ) monitoring from 30 locations along the Damodar River to establish the baseline data and delineate the WQ. The representative input features showing a strong association with BOD and TC were identified using Spearman's rank-coupled orthogonal linear transformation (SOT). The relative weighted ensemble (RWE) method was applied to determine the relative weights for base learners in the AIRWE model. The statistical analysis of the developed model revealed that it was most efficient and accurate for predicting BOD (R2, 0.97; RMSE, 0.06; MAE, 0.04) and TC (R2, 0.98; RMSE, 0.06; MAE, 0.05) over the traditional techniques. The tstat (BOD 0.02 and TC 0.47) was lesser than tcrit (1.672), confirming its unbiased predictions. The SOT technique removed the data noise and multicollinearity, whereas RWE curtailed the individual model's limitations and predicted more reliable results. The model resulted 97% accuracy with high precision (96%) in classifying the river water quality for various end uses. The study describes a novel approach for researchers, scientists, and decision-makers for modeling and predicting various environmental attributes.

Acalabrutinib as a novel hope for the treatment of breast and lung cancer: an in-silico proof of concept.

Drug repurposing is proved to be a groundbreaking concept in the field of cancer research, accelerating the pace of de novo drug discovery by investigating the anti-cancer activity of the already approved drugs. On the other hand, it got highly benefitted from the advancement in the in-silico tools and techniques, which are used to build up the initial "proof of concept" based on the drug-target interaction. Acalabrutinib (ACL) is a well-known drug for the treatment of hematological malignancies. But, the therapeutic ability of ACL against solid tumors is still unexplored. Thereby, the activity of ACL on breast cancer and lung cancer was evaluated utilizing different computational methods. A series of proteins such as VEGFR1, ALK, BCL2, CXCR-4, mTOR, AKT, PI3K, HER-2, and Estrogen receptors were selected based on their involvement in the progression of the breast as well as lung cancer. A multi-level computational study starting from protein-ligand docking to molecular dynamic (MD) simulations were performed to detect the binding potential of ACL towards the selected proteins. Results of the study led to the identification of ACL as a ligand that showed a high docking score and binding energy with HER-2, mTOR, and VEGFR-1 successively. Whereas, the MD simulations study has also shown good docked complex stability of ACL with HER2 and VEGFR1. Our findings suggest that interaction with those receptors can lead to preventive action on both breast and lung cancer, thus it can be concluded that ACL could be a potential molecule for the same purpose.Communicated by Ramaswamy H. Sarma.

Green synthesis of novel biochar from Abelmoschus esculentus seeds for direct blue 86 dye removal: Characterization, RSM optimization, isotherms, kinetics, and fixed bed column studies.

The presence of Direct blue 86 dye (DB86) in water can lead to various health hazards to the humans and animals. The study explored efficacy of biochar derived from Abelmoschus Esculentus seeds (AESB) to remove DB86 from an aqueous solution. BET analysis of AESB delineated H4 classification with the predominance of micropores and mesopores spread throughout the surface. FTIR study demonstrated the presence of the alkyl (C-H), Alkene (C]C), Carbonyl (C]O) and O-H bond of the sulphonic group which helped in adsorption of DB86 molecules through various mechanisms i.e., pore filling, π-π interactions, and hydrogen bonding interactions. Response surface methodology (RSM) was used for designing the adsorption experiment and analysing the optimum operating parameters. Batch experiments demonstrated excellent adsorption capacity (277.04 mg/g) of AESB and was efficient in 98.06% removal of DB86 at optimal conditions i.e., dye conc. = 300 mg/L, dose = 2.5 g/L, pH = 2, time of 120 min. Adsorption followed nonlinear Sips model (R2 = 0.999) with an error (X2 = 0.13, RMSE = 0.83, MAPE 0.56 and MSRE = 0.0006). The kinetic analysis revealed intra-particle diffusion being the rate-determining step and followed nonlinear pseudo-first-order kinetics (R2 = 0.997). Thermodynamic study revealed that the adsorption of DB-86 proceeded spontaneously and exhibited endothermic characteristics, with the enthalpy change primarily governed by the physisorption mechanism. Thomas model revealed inverse relation of breakthrough and exhaustion time with flow while it was proportional to bed height. The sorption capacity (N0) (2.2493 mg/l min) and rate constant (Ka) (0.028 L/min. mg) of BDST model can accurately be used for predicting the performance of AESB in full scale column.

Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization.

INTRODUCTION: Preeclampsia (PE) arises due to defective spiral artery remodelling which may be due to deficient migration of trophoblast cells. Migration of human endothelial cells has been shown to be promoted via Hydrogen sulphide(H2S)/Rho GTPase Rac1 axis. This novel role of H2S and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells. METHODS: Placental tissues were obtained post-delivery from consented preeclamptic and normotensive mothers (n = 60). The protein expression levels of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) along with its downstream migratory molecules were compared in both the arms. The pro-migratory role of H2S was investigated in a first trimester placental cell line. RESULTS: H2S promoted the migration of trophoblast cells in a Rho GTPase dependent manner mediated by actin cytoskeleton reorganization. The reduced levels of H2S producing enzymes in the PE placentae along with decreased levels of Rho GTPases (Rac1 and Rho A) corroborate the results of PAG and AOAA treatment in down regulating the Rho GTPases in the in vitro grown placental cultures. Reduction of the migratory potential of trophoblastic cells caused due to hypoxia/reoxygenation was rescued by upregulating the H2S expression with the use of NaHS as a H2S donor. DISCUSSION: Exogenous H2S increases the migratory potential of the placental cells in culture conditions and also post hypoxia/reoxygenation injury. H2S as a gaso-transmitter holds a great potential as a therapeutic agent. Its long-term effects need to be investigated using model systems (rat/mouse) of PE following it up with clinical regulatory trials.

Effect of preoperative ibuprofen on pain after lower third molar removal: A randomized controlled trial.

Aim: The aim of the study is to predict the effect of preemptive analgesics in the third molar surgery and to analyze whether the number and frequency of postoperative analgesics are reduced following the administration of preemptive analgesics. Materials and Methods: The present study was carried out on 50 patients who reported to the Department of Oral and Maxillofacial Surgery for removal of their impacted mandibular third molar. The patients were randomly divided into two groups of 25 patients each - Group A (test group) patients receiving ibuprofen (400 mg) half an hour before the surgery and placebo half an hour after surgery and the Group B (control group) patients receiving placebo half an hour before the surgery and ibuprofen (400 mg) half an hour after surgery. Both groups of patients will be instructed to avoid any drug but those prescribed (ibuprofen 400 mg SOS and rescue medication of tramadol 50 mg SOS) and not to seek any medical help elsewhere for postoperative problems. The pain was recorded using a visual analog scale. Results: Demographic data in the study show females (8%) and male (92%) patients. The average time taken for surgery was more in the control group (58.36 min) as compared to the test group (55.64 min) with no statistically significant difference. Values of pain score, medication score, number of rescue medication, and frequency at different time intervals (at baseline, after 3 h, 6 h, 24 h, and 7 days) are expressed in terms of mean and standard deviation, respectively, and the result shows the statistically significant difference for pain score at baseline and 7th-day time interval only. The distribution of different types of impaction and different types of elevation/odontotomy shows a significant association in test and control groups. Conclusion: Preoperative ibuprofen decreases the frequency and intensity of the pain. We believe that since this preoperative ibuprofen seems to be beneficial without any adverse effects, it may be used routinely in the 3rd molar surgeries and even in routine extraction.

Central myelin-peripheral myelin junction in trigeminal, facial, and vestibulocochlear nerve: A histo-morphometric study.

BACKGROUND: The study aimed to locate the central myelin and peripheral myelin junction (CNS PNS Junction, CPJ) in trigeminal, facial and vestibulocochlear nerves. METHODS: The cisternal segments of the nerves were cut from the brainstem to the proximal margin of trigeminal ganglia (trigeminal nerve) and internal acoustic meatus (facial and vestibulocochlear nerve) from cadavers. Horizontal sections of H&E stained slides were analysed and histo morphometry was performed. The CPJ was confirmed by immunohistochemistry using monoclonal myelin basic protein antibody. RESULTS: The mean length of the trigeminal, facial and vestibulocochlear nerves were 13.6 ± 3.1 mm, 12.4 ± 1.9 mm and 11.5 ± 2.0 mm respectively; mean length of the centrally myelinated segment at the point of maximum convexity was 4.1 ± 1.5 mm, 3.7 ± 1.6 mm, 3.6 ± 1.4 mm respectively. Six different patterns were observed fortheCPJ.Utilizing the derived values, the CPJwas located at a distance of 18 - 48% and 17 - 61% of the total length of the nerve in all the cases in trigeminal and facial nerve respectively. In vestibulocochlear nerve, it was located at a distance of about 13 - 54% of the total length of the nerve. CONCLUSIONS: The location of the CPJ in the vestibulocochlear nerve was midway between the brainstem and internal acoustic meatus which is a novel observation.For all the nerves, the CPJ was located either at or before the half way along the length of the nerve in huge majority (97%); never crossing the 60% of the nerve length.

Hydrochemical investigation of groundwater in a trans-Himalayan region of Ladakh, India, using geochemical modelling and entropy technique.

Evaluating the hydrogeochemistry and groundwater quality status is vital to understand the sources and extent of groundwater contamination. Chemometric analysis, geochemical modelling and entropy technique were explored to delineate the hydrogeochemistry of groundwater in the trans-Himalayan region. Analysis of hydrochemical facies revealed that 57.14, 39.29, and 3.57% of samples were Ca-Mg-HCO3-, Ca-Mg-Cl- and Mg-HCO3- water types, respectively. Gibbs diagrams illustrate the effects of the dissolution of carbonates and silicates during weathering on groundwater hydrogeochemistry. The PHREEQC modelling depicted that most of the secondary minerals are supersaturated except for halite, sylvite, and magnetite which are undersaturated and in equilibrium with nature. Multivariate statistical techniques, including principal component analysis, were applied for source apportionment indicating that the hydrochemistry of the groundwater was mainly controlled by geogenic sources (rock-water interaction) along with secondary pollution through increased anthropogenic sources. Heavy metal accumulation in groundwater depicted the order of Cd > Cr > Mn > Fe > Cu > Ni > Zn. EWQI analysis revealed that none of the samples fell into excellent and good categories. In total, 92.86% of groundwater samples were in an average category while the rest of the samples (7.14%) were unfit for drinking. This study will provide baseline data and a scientific framework which can be used in source apportionment studies, predictive modelling and efficient management of water resources.

Comparison of Midazolam and Propofol Infusion to Suppress Stress Response in Patients With Severe Traumatic Brain Injury: A Prospective, Randomized Controlled Trial.

Objective: The stress response following traumatic brain injury (TBI) is a preventable cause of secondary brain injury. This can be prevented using sedation in the intensive care unit (ICU). To date, the choice of sedative agent for preventing stress response is not well-studied in literature. Methods: This prospective randomized controlled trial included 60 patients with severe TBI admitted to ICU. The patients were randomized into 2 study groups according to the choice of sedation: propofol (group I) and midazolam infusion (group II). The serum cortisol was measured as the primary outcome at admission to ICU and 48 hours following sedation infusion. The baseline Glasgow coma scale, hemodynamic, optic nerve sheath diameter (ONSD), and computed tomography scan findings were noted at admission. Glasgow outcome scale (GOS) was measured as a neurological outcome at discharge from ICU. Results: There was a statistically significant reduction in serum cortisol level in both the study groups (Δ cortisol, p-value=134.91 (50.5,208.2), 0.00 and 118.8 (42.6,160.4), 0.00, in group I and II, respectively). Serum cortisol levels were comparable among both groups at baseline and 48 hours. Similarly, there was a statistically significant difference in ONSD in both groups, but there was no difference in ONSD value between the groups at 48 hours. The GOS was also similar in both groups at discharge from ICU. Conclusion: The study demonstrated a similar reduction in serum cortisol levels following 48 hours of propofol or midazolam infusion in patients with severe TBI.

Optimisation of process parameters of a thermal digester for the rapid conversion of food waste into value-added soil conditioner.

A novel thermal digester for converting food waste (FW) into nutrient-rich soil conditioner was designed and explored. The process variables, that is, temperature, the volume of the digestion chamber and the rotational speed of the digester were optimised using response surface methodology (RSM). The study revealed that the digester temperature of 150°C and rotational speed of 40 RPM required minimum time (180 minutes) for attaining the equilibrium moisture with a minimum energy consumption of 0.218 kWh kg-1. The process resulted in 80 ± 2.5% reduction in total volume of the FW. Detailed characterisation revealed that the end product was comparable to the organic fertiliser as per the Fertiliser Association of India norms. The digestion helps in breakdown of cellulose content of FW into hemicellulose which supports formation of primary and secondary walls, seed storage carbohydrates, and facilitates plant growth. 1H-Nuclear magnetic resonance (1H-NMR) spectra of the end product revealed mineralisation of organics during digestion. Decrease in ultraviolet (UV) absorbance value at 280 nm also revealed the humification of the end product. X-ray diffraction (XRD) analysis disclosed extremely low crystallinity and non-recalcitrant nature of the end product. A low humification index value (HI-3.43), high fertilising index (FI-4.8), and clean index (CI-5.0) revealed that the end product could safely be utilised as an organic fertiliser. The cost-benefit analysis revealed that thermal digestion technique is profitable and economically viable with benefit-cost ratio (BCR) of 1.35. The study offers a unique approach for the rapid and hassle-free production of value-added soil conditioner from FW.

Investigation of molecular interaction and conformational stability of disease concomitant to HLA-DRß3.

Human leucocyte antigen DRß3 is associated with specific autoimmune thyroid disease and plays a vital role in the progression of Grave's disease. The available crystallographic structure of the HLA DRA, DRß3*0101, was selected and used to generate mutation at position 57 from valine amino acid to Aspartic acid (D), Glutamic acid (E), Alanine (A), and Serine (S) amino acids by computational modeling approach. Mutant models were minimized, and stable conformation was chosen based on the lowest root mean square deviation value. Molecular docking assessed the best binding affinity of ligands C1, C2, C3, and C4 with wild-type and mutant HLA-DRß3 models. Molecular dynamics simulation studies were executed to evaluate the stability of selected hits with wild-type and mutant dock complexes. The C3 has shown good binding affinity with wild-type and selected mutants; V57A, V57E, and V57D. Structural and molecular dynamics insights reveal the differences between wild-type and mutant-type HLA-DRß3, which could help design novel antagonist molecules against autoimmune thyroid disorder.Communicated by Ramaswamy H. Sarma.

Perspective on Cav-1 for its Potential as Newer Therapeutics for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting around 10 million people worldwide. Dopamine agonists that mimic the action of natural dopamine in the brain are the prominent drugs used in the management of PD symptoms. However, the therapy is limited to symptomatic relief with serious side effects. Phytocompounds have become the preferable targets of research in the quest for new pharmaceutical compounds. In addition, current research is directed towards determining a newer specific target for the better treatment and management of PD. Cav-1, a membrane protein present on the caveolae of the plasma membrane, acts as a transporter for lipid molecules in the cells. Cav-1 has been implicated in the pathogenesis of neurodegenerative diseases, like Alzheimer's disease (AD), PD, etc. In this review, we have extensively discussed the role of Cav-1 protein in the pathogenesis of PD. In addition, molecular docking of some selective phytochemical compounds against Cav-1 protein (Q03135) was performed to understand their role. The best phytochemical compounds were screened based on their molecular interaction and binding affinity with the Cav-1 protein model.

Application of Monte Carlo simulation for carcinogenic and non-carcinogenic risks assessment through multi-exposure pathways of heavy metals of river water and sediment, India.

Heavy metal contamination has severe detrimental impacts on the entire river ecosystem's quality and causes potential risks to human health. An integrated approach comprising deterministic and probabilistic (Monte Carlo simulation) models with sensitivity analysis was adopted to determine heavy metals' chronic daily intake (CDI) and their associated health risks from the riverine ecosystem. Both carcinogenic and non-carcinogenic risks of water and sediment were estimated through multi-exposure pathways. The analytical results indicated that the concentration patterns of heavy metals in sediment (Fe > Mn > Sr > Zn > Cr > Cu > Cd) were slightly different and higher than in water (Fe > Zn > Cr > Sr > Mn > Cu > Cd). The potential carcinogenic risks of Cr and Cd in sediment (5.06E-02, 5.98E-04) were significantly (p < 0.05) higher than in water (9.08E-04, 8.97E-05). Moreover, 95th percentile values of total cancer risk (TCR) for sediment (1.80E-02, 3.37E-02) were about 22 and 143 times higher than those of water (8.10E-04, 2.36E-04) for adults and children, respectively. The analysis of non-carcinogenic risk revealed a significantly higher overall hazard index (OHI) for both sediment (adults: 1.26E+02, children: 1.11E+03) and water (adults: 3.26E+00, children: 9.85E+00) than the USEPA guidelines (OHI ≤ 1). The sensitivity analysis identified that the concentration of heavy metals was the most influencing input factor in health risk assessment. Based on the reasonable maximum exposure estimate (RME), the study will be advantageous for researchers, scientists, policymakers, and regulatory authorities to predict and manage human health risks.

Development of fuzzy leachate pollution index for treatability-based classification of solid waste landfills.

The fuzzy leachate pollution index (FLPI) was established to classify the landfill sites on the basis of their leachate pollution potential by considering the limitations of traditional methods. The FLPI was developed adopting 9 critical input parameters, i.e., TDS, pH, Cl, Cu, Pb, Cr, Zn, BOD, and COD, from 22 major landfill sites across India. Using these critical parameters, 3 groups, i.e., inorganic leachate strength (INLS), organic leachate strength (ORLS), and heavy metal leachate strength (HMLS), were generated to estimate the FLPI. The regression analysis, ANOVA, and sensitivity analysis were also performed to determine the significance and uncertainty of the index. The results showed that among all MFs, the triangular with overlapping open ends (TOO) MF was best fitted (R = 0.90) for FLPI estimation. Accordingly, 41% of the landfill sites showed less treatment while the others (59%) required moderate degree of treatment. The regression (R2 = 0.92) and ANOVA (F value = 15.003, p = 0.000031) analyses described that the developed tool was significant (p < 0.05). The sensitivity analysis showed that Zn (R = 0.99) was the most influencing factor followed by BOD > COD > pH > Cr > Cu > Cl > Pb > TDS. The study provides an important tool that can also be used by researchers and scientists for investigating and evaluating various environmental problems.

Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy.

Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

Investigating the dynamics of ammonia volatilisation and the role of additives in thermal digestion of food waste.

Averting nutrient volatilisation in thermal treatment of organic waste is a challenging task. The dynamics of ammonia volatilisation and the role of additives in preventing the losses of nutrients in thermal digestion of food waste (FW) were explored. The experimental trials were performed in a convective dehydrator at different combinations of temperatures and airflow velocities. The study dictated that ammonia volatilisation rate increased with increase in temperature and airflow velocity. The losses reached to its peak during the initial drying period and then gradually declined in the falling rate period. An artificial intelligence-based random forest model was explored to precisely predict the ammonia losses during the drying process. The SEM-EDX images confirmed enhanced N (2.25%) in the alum treated end product compared to blank (N - 1.8%) and thus reveals alum induced mineralization of nutrients. Higher intensities of the N containing compounds peaks observed in FTIR spectra also supported the mineralization of nitrogen. XRD analysis indicated formation of stable ammonium compounds in the sample digested with alum. Cost benefit analysis of the alum aided digestion revealed that it enhances the nutrient retention and overall cost of N in the end product by ₹626/tonne. The study revealed high potential of alum in reducing the ammonia volatilisation and enhancing the agronomical value of nutrients in the thermal digestion process.

Performance study of fly-ash-derived coagulant in removing natural organic matter from drinking water: synthesis, characterization, and modelling.

This study is an attempt to develop a liquid coagulant using fly ash (FAC) for removing natural organic matter (NOM) from drinking water systems. Acid-alkali leaching and polymerization technique was used for developing FAC. Characterization of FAC was performed using Fourier-transform infrared spectroscopy (FESEM), field emission scanning electron microscopy (FTIR), and X-ray diffraction (XRD) to assess the surface morphology and functional groups present. FE SEM analysis revealed uneven, coarse, and irregular structure with numerous pores, an indicative of their high adsorption capacity. XRD study revealed that Al, Fe, and Si are the major constituent group of FAC. FAC demonstrated excellent potential in removing THMs precursors: dissolved organic carbon (84.46%), UV254 (90.57%), and turbidity (96.85%) from the drinking water systems. Charge neutralization followed by adsorption is the main mechanism behind NOM removal. Moreover, FAC also showed good capability in minimizing the reactivity of NOM (ASI-72.86%) towards THM formation. FAC proved to be a good alternative for conventional coagulant used in drinking water treatment and can be effectively used for reducing NOM content of raw water which leads to the formation of THMs on chlorination.