Improved liver disease prediction from clinical data through an evaluation of ensemble learning approaches.

PURPOSE: Liver disease causes two million deaths annually, accounting for 4% of all deaths globally. Prediction or early detection of the disease via machine learning algorithms on large clinical data have become promising and potentially powerful, but such methods often have some limitations due to the complexity of the data. In this regard, ensemble learning has shown promising results. There is an urgent need to evaluate different algorithms and then suggest a robust ensemble algorithm in liver disease prediction. METHOD: Three ensemble approaches with nine algorithms are evaluated on a large dataset of liver patients comprising 30,691 samples with 11 features. Various preprocessing procedures are utilized to feed the proposed model with better quality data, in addition to the appropriate tuning of hyperparameters and selection of features. RESULTS: The models' performances with each algorithm are extensively evaluated with several positive and negative performance metrics along with runtime. Gradient boosting is found to have the overall best performance with 98.80% accuracy and 98.50% precision, recall and F1-score for each. CONCLUSIONS: The proposed model with gradient boosting bettered in most metrics compared with several recent similar works, suggesting its efficacy in predicting liver disease. It can be further applied to predict other diseases with the commonality of predicate indicators.

Comparative study of phenotypic-based detection assays for carbapenemases in Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is a serious health concern worldwide, causing high mortality rates and limited medical therapy options. Carbapenem resistance is a significant problem in Acinetobacter baumannii isolates. The synthesis of acquired carbapenemases, such as oxacillinases, IMP, NDM, VIM, and KPC enzymes, causes carbapenem resistance. METHODS: A total of 106 non-repetitive, Acinetobacter baumannii isolates were collected from four major hospitals in Bahrain including 78 carbapenem-resistant Acinetobacter baumannii (CRAB), and 28 carbapenem-susceptible Acinetobacter baumannii (CSAB) isolates. Three phenotypic tests were investigated in this study: including CARBA NP, modified carbapenem inactivation method (mCIM)/EDTA-CIM (eCIM), and modified Hodge test (MHT). RESULTS: CARBA NP was positive in 50 tested CRAB isolates (100%), and the sensitivity was 100%. The MHT was positive in 73/106 isolates (68.8%), while the sensitivity and specificity of the MHT were 77.6% and 100%. Moreover, only 38/106 (35.8%) isolates were positive for mCIM/eCIM. The sensitivity and specificity of mCIM were 40.4% and 100%. CONCLUSION: CARBA NP was ideal for phenotypic detection of carbapenemase production, followed by MHT. The m/eCIM demonstrated a lower detection rate in CRAB. Consequently, combining tests would be more accurate. The mCIM/eCIM can easily distinguish between MBLs and serine-carbapenemases due to the frequent co-production of these enzymes in A. baumannii. In hospital setups where molecular characterization tests are not available, CARBA NP seems to be an alternative test in combination with MHT or mCIM/eCIM.

Probing protein aggregation through spectroscopic insights and multimodal approaches: A comprehensive review for counteracting neurodegenerative disorders.

Aberrant accumulation of protein misfolding can cause aggregation and fibrillation and is one of the primary characteristic features of neurodegenerative diseases. Because they are disordered, misfolded, and aggregated proteins pose a significant setback in drug designing. The structural study of intermediate steps in these kinds of aggregated proteins will allow us to determine the conformational changes as well as the probable pathways encompassing various neurodegenerative disorders. The analysis of protein aggregates involved in neurodegenerative diseases relies on a diverse toolkit of biophysical techniques, encompassing both morphological and non-morphological methods. Additionally, Thioflavin T (ThT) assays and Circular Dichroism (CD) spectroscopy facilitate investigations into aggregation kinetics and secondary structure alterations. The collective application of these biophysical techniques empowers researchers to comprehensively unravel the intricate nature of protein aggregates associated with neurodegeneration. Furthermore, the topics covered in this review have summed up a handful of well-established techniques used for the structural analysis of protein aggregation. This multifaceted approach advances our fundamental understanding of the underlying mechanisms driving neurodegenerative diseases and informs potential therapeutic strategies.

Navigating the Maze of Alzheimer's disease by exploring BACE1: Discovery, current scenario, and future prospects.

Alzheimer's disease (AD) is a chronic neurological condition that has become a leading cause of cognitive decline in elder individuals. Hardly any effective medication has been developed to halt the progression of AD due to the disease's complexity. Several theories have been put forward to clarify the mechanisms underlying AD etiology. The identification of amyloid plaques as a hallmark of AD has sparked the development of numerous drugs targeting the players involved in the amyloidogenic pathway, such as the ß-site of amyloid precursor protein cleavage enzyme 1 (BACE1) blockers. Over the last ten years, preclinical and early experimental research has led several pharmaceutical companies to prioritize producing BACE1 inhibitors. Despite all these efforts, earlier discovered inhibitors were discontinued in consideration of another second-generation small molecules and recent BACE1 antagonists failed in the final stages of clinical trials because of the complications associated either with toxicity or effectiveness. In addition to discussing the difficulties associated with development of BACE1 inhibitors, this review aims to provide an overview of BACE1 and offer perspectives on the causes behind the failure of five recent BACE1 inhibitors, that would be beneficial for choosing effective treatment approaches in the future.

The halotolerant exopolysaccharide-producing Rhizobium azibense increases the salt tolerance mechanism in Phaseolus vulgaris (L.) by improving growth, ion homeostasis, and antioxidant defensive enzymes.

Globally, agricultural productivity is facing a serious problem due to soil salinity which often causes osmotic, ionic, and redox imbalances in plants. Applying halotolerant rhizobacterial inoculants having multifarious growth-regulating traits is thought to be an effective and advantageous approach to overcome salinity stress. Here, salt-tolerant (tolerating 300 mM NaCl), exopolysaccharide (EPS) producing Rhizobium azibense SR-26 (accession no. MG063740) was assessed for salt alleviation potential by inoculating Phaseolus vulgaris (L.) plants raised under varying NaCl regimes. The metabolically active cells of strain SR-26 produced a significant amount of phytohormones (indole-3-acetic acid, gibberellic acid, and cytokinin), ACC deaminase, ammonia, and siderophore under salt stress. Increasing NaCl concentration variably affected the EPS produced by SR-26. The P-solubilization activity of the SR-26 strain was positively impacted by NaCl, as demonstrated by OD shift in NaCl-treated/untreated NBRIP medium. The detrimental effect of NaCl on plants was lowered by inoculation of halotolerant strain SR-26. Following soil inoculation, R. azibense significantly (p ≤ 0.05) enhanced seed germination (10%), root (19%) shoot (23%) biomass, leaf area (18%), total chlorophyll (21%), and carotenoid content (32%) of P. vulgaris raised in soil added with 40 mM NaCl concentration. Furthermore, strain SR-26 modulated the relative leaf water content (RLWC), proline, total soluble protein (TSP), and sugar (TSS) of salt-exposed plants. Moreover, R. azibense inoculation lowered the concentrations of oxidative stress biomarkers; MDA (29%), H2O2 content (24%), electrolyte leakage (31%), membrane stability (36%) and Na+ ion uptake (28%) when applied to 40 mM NaCl-treated plants. Further, R. azibense increases the salt tolerance mechanism of P. vulgaris by upregulating the antioxidant defensive responses. Summarily, it is reasonable to propose that EPS-synthesizing halotolerant R. azibense SR-26 should be applied as the most cost-effective option for increasing the yields of legume crops specifically P. vulgaris in salinity-challenged soil systems.

VER-Net: a hybrid transfer learning model for lung cancer detection using CT scan images.

BACKGROUND: Lung cancer is the second most common cancer worldwide, with over two million new cases per year. Early identification would allow healthcare practitioners to handle it more effectively. The advancement of computer-aided detection systems significantly impacted clinical analysis and decision-making on human disease. Towards this, machine learning and deep learning techniques are successfully being applied. Due to several advantages, transfer learning has become popular for disease detection based on image data. METHODS: In this work, we build a novel transfer learning model (VER-Net) by stacking three different transfer learning models to detect lung cancer using lung CT scan images. The model is trained to map the CT scan images with four lung cancer classes. Various measures, such as image preprocessing, data augmentation, and hyperparameter tuning, are taken to improve the efficacy of VER-Net. All the models are trained and evaluated using multiclass classifications chest CT images. RESULTS: The experimental results confirm that VER-Net outperformed the other eight transfer learning models compared with. VER-Net scored 91%, 92%, 91%, and 91.3% when tested for accuracy, precision, recall, and F1-score, respectively. Compared to the state-of-the-art, VER-Net has better accuracy. CONCLUSION: VER-Net is not only effectively used for lung cancer detection but may also be useful for other diseases for which CT scan images are available.

Enhancing spinach (Spinacia oleracea L.) resilience in pesticide-contaminated soil: Role of pesticide-tolerant Ciceribacter azotifigens and Serratia marcescens in root architecture, leaf gas exchange attributes and antioxidant response restoration.

This study unveils the detoxification potential of insecticide-tolerant plant beneficial bacteria (PBB), i.e., Ciceribacter azotifigens SF1 and Serratia marcescens SRB1, in spinach treated with fipronil (FIP), profenofos (PF) and chlorantraniliprole (CLP) insecticides. Increasing insecticide doses (25-400 µg kg-1 soil) significantly curtailed germination attributes and growth of spinach cultivated at both bench-scale and in greenhouse experiments. Profenofos at 400 µg kg-1 exhibited maximum inhibitory effects and reduced germination by 55%; root and shoot length by 78% and 81%, respectively; dry matter accumulation in roots and shoots by 79% and 62%, respectively; leaf number by 87% and leaf area by 56%. Insecticide application caused morphological distortion in root tips/surfaces, increased levels of oxidative stress, and cell death in spinach. Application of insecticide-tolerant SF1 and SRB1 strains relieved insecticide pressure resulting in overall improvement in growth and physiology of spinach grown under insecticide stress. Ciceribacter azotifigens improved germination rate (10%); root biomass (53%); shoot biomass (25%); leaf area (10%); Chl-a (45%), Chl-b (36%) and carotenoid (48%) contents of spinach at 25 µg CLP kg-1 soil. PBB inoculation reinvigorated the stressed spinach and modulated the synthesis of phytochemicals, proline, malondialdehyde (MDA), superoxide anions (O2•-), and hydrogen peroxide (H2O2). Scanning electron microscopy (SEM) revealed recovery in root tip morphology and stomatal openings on abaxial leaf surfaces of PBB-inoculated spinach grown with insecticides. Ciceribacter azotifigens inoculation significantly increased intrinsic water use efficiency, transpiration rate, vapor pressure deficit, intracellular CO2 concentration, photosynthetic rate, and stomatal conductance in spinach exposed to 25 µg FIP kg-1. Also, C. azotifigens and S. marcescens modulated the antioxidant defense systems of insecticide-treated spinach. Bacterial strains were strongly colonized to root surfaces of insecticide-stressed spinach seedlings as revealed under SEM. The identification of insecticide-tolerant PBBs such as C. azotifigens and S. marcescens hold the potential for alleviating abiotic stress to spinach, thereby fostering enhanced and safe production within polluted agroecosystems.

Enhancing soil quality and yield through microbial assisted in-situ residue management in rice-rice cropping system in Odisha, Eastern India.

Crop residue management has become more challenging with intensive agricultural operations. Zero tillage and crop residue returns, along with the enhancement of in-situ residue decomposition through microbial intervention, are essential measures for preserving and enhancing soil quality. To address this problem in view of stubble burning, field experiments were conducted in rice-rice (variety Swarna) cropping systems under lowland conditions, wherein the following different residue management practices were adopted viz., conventional cultivation (CC), residue incorporation (RI @ 6 t paddy straw ha-1), residue retention (RR @6 t paddy straw ha-1), and zero tillage (ZT). In this experiment, two microbial products i.e. solid microbial consortium (SMC) at 2.0 kg ha-1) and capsule (10 numbers ha-1), were evaluated in both Rabi (dry) and Kharif (wet) seasons under different residue management practices. The results on soil microbial properties showed that application of either SMC or capsule based formulation could significantly improve the soil organic carbon (SOC) content in ZT (9.51 g/kg), followed by RI (9.36 g/kg), and RR (9.34 g/kg) as compared to CC (7.61 g/kg). There were significant differences in the soil functional properties (AcP, AkP, FDA, and DHA) with microbial interventions across all residue management practices. SOC was significantly positive correlated with cellulase (R2 = 0.64, p < 0.001), ß-glucosidase (R2 = 0.61, p < 0.001), and laccase (R2 = 0.66, p < 0.001) activity; however, the regression coefficients varied significantly with microbial intervention. Moreover, the availability of N, P, and K in soil was significantly (p < 0.05) improved under microbial treatments with either RR or RI practices. Among the different methods of residues management practices, RI with microbial intervention registered a consistent yield improvement (8.4-17.8%) compared to conventional practices with microbial intervention. The present findings prove that the application of decomposing microbial consortia for in-situ rice residue management under field conditions significantly enhances soil quality and crop yield compared to conventional practices.

Recent Advances in Graphene-Enabled Materials for Photovoltaic Applications: A Comprehensive Review.

Graphene's two-dimensional structural arrangement has sparked a revolutionary transformation in the domain of conductive transparent devices, presenting a unique opportunity in the renewable energy sector. This comprehensive Review critically evaluates the most recent advances in graphene production and its employment in solar cells, focusing on dye-sensitized, organic, and perovskite devices for bulk heterojunction (BHJ) designs. This comprehensive investigation discovered the following captivating results: graphene integration resulted in a notable 20.3% improvement in energy conversion rates in graphene-perovskite photovoltaic cells. In comparison, BHJ cells saw a laudable 10% boost. Notably, graphene's 2D internal architecture emerges as a protector for photovoltaic devices, guaranteeing long-term stability against various environmental challenges. It acts as a transportation facilitator and charge extractor to the electrodes in photovoltaic cells. Additionally, this Review investigates current research highlighting the role of graphene derivatives and their products in solar PV systems, illuminating the way forward. The study elaborates on the complexities, challenges, and promising prospects underlying the use of graphene, revealing its reflective implications for the future of solar photovoltaic applications.

Understanding the Modulation of α-Synuclein Fibrillation by N-Acetyl Aspartate: A Brain Metabolite.

α-Synuclein (α-Syn) fibrillation is a prominent contributor to neuronal deterioration and plays a significant role in the advancement of Parkinson's Disease (PD). Considering this, the exploration of novel compounds that can inhibit or modulate the aggregation of α-Syn is a topic of significant research. This study, for the first time, elucidated the effect of N-acetyl aspartate (NAA), a brain osmolyte, on α-Syn aggregation using spectroscopic and microscopic approaches. Thioflavin T (ThT) assay revealed that a lower concentration of NAA inhibits α-Syn aggregation, whereas higher concentrations of NAA accelerate the aggregation. Further, this paradoxical effect of NAA was complemented by ANS, RLS, and the turbidity assay. The secondary structure transition was more pronounced at higher concentrations of NAA by circular dichroism, corroborating the fluorescence spectroscopic observations. Confocal microscopy also confirmed the paradoxical effect of NAA on α-Syn aggregation. Interaction studies including fluorescence quenching and molecular docking were employed to determine the binding affinity and critical residues involved in the α-Syn-NAA interaction. The explanation for this paradoxical nature of NAA could be a solvophobic effect. The results offer a profound understanding of the modulatory mechanism of α-Syn aggregation by NAA, thereby suggesting the potential role of NAA at lower concentrations in therapeutics against α-Syn aggregation-related disorders.

Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.

Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.

Trichoderma Inoculation Alleviates Cd and Pb-Induced Toxicity and Improves Growth and Physiology of Vigna radiata (L.).

Heavy metals (HMs) pose a serious threat to agricultural productivity. Therefore, there is a need to find sustainable approaches to combat HM stressors in agriculture. In this study, we isolated Trichoderma sp. TF-13 from metal-polluted rhizospheric soil, which has the ability to resist 1600 and 1200 µg mL-1 cadmium (Cd) and lead (Pb), respectively. Owing to its remarkable metal tolerance, this fungal strain was applied for bioremediation of HMs in Vigna radiata (L.). Strain TF-13 produced siderophore, salicylic acid (SA; 43.4 µg mL-1) and 2,3-DHBA (21.0 µg mL-1), indole-3-acetic acid, ammonia, and ACC deaminase under HM stressed conditions. Increasing concentrations of tested HM ions caused severe reduction in overall growth of plants; however, Trichoderma sp. TF-13 inoculation significantly (p ≤ 0.05) increased the growth and physiological traits of HM-treated V. radiata. Interestingly, Trichoderma sp. TF-13 improved germination rate (10%), root length (26%), root biomass (32%), and vigor index (12%) of V. radiata grown under 25 µg Cd kg-1 soil. Additionally, Trichoderma inoculation showed a significant (p ≤ 0.05) increase in total chlorophyll, chl a, chl b, carotenoid content, root nitrogen (N), and root phosphorus (P) of 100 µg Cd kg-1 soil-treated plants over uninoculated treatment. Furthermore, enzymatic and nonenzymatic antioxidant activities of Trichoderma inoculated in metal-treated plants were improved. For instance, strain TF-13 increased proline (37%), lipid peroxidation (56%), catalase (35%), peroxidase (42%), superoxide dismutase (27%), and glutathione reductase (39%) activities in 100 µg Pb kg-1 soil-treated plants. The uptake of Pb and Cd in root/shoot tissues was decreased by 34/39 and 47/38% in fungal-inoculated and 25 µg kg-1 soil-treated plants. Thus, this study demonstrates that stabilizing metal mobility in the rhizosphere through Trichoderma inoculation significantly reduced the detrimental effects of Cd and Pb toxicity in V. radiata and also enhanced development under HM stress conditions.

Bacoside-A repressed the differentiation and lipid accumulation of 3T3-L1 preadipocytes by modulating the expression of adipogenic genes.

Obesity is one of the more complicated diseases, it can induce numerous life-threatening diseases mainly diabetes mellitus, cardiovascular disease, hypertension, and certain cancers. In this study, we assessed the efficacy of bacoside-A (a dammarane-type triterpenoid saponin derived from the plant Bacopa monniera Linn.) on the adipogenesis of 3T3-L1 preadipocytes. Results of this study illustrated that bacoside-A decreased the differentiation of 3T3-L1 cell, as evidenced by diminution of lipid droplets, which contains triglycerides and other lipids. During the differentiation process, transcription factors, which are mainly participating in adipogenesis such us CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPß, peroxisome proliferator-activated receptor-γ (PPARγ), and sterol regulatory element-binding protein-1c (SREBP-1c), expressions were significantly suppressed by bacoside-A. In addition, bacoside-A showed a potent reduction in genes precise to adipocytes such as lipoprotein lipase (LPL), fatty acid synthase (FAS), adipocyte fatty acid-binding protein (FABP4), and leptin expressions. Further, bacoside-A stimulated the phosphorylation of acetyl CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK). These results demonstrated that bacoside-A has anti-adipogenic effects by regulating the transcription factors involved in adipocyte differentiation. Therefore, bacoside-A might be considered as a potent therapeutic agent for alleviating obesity and hyperlipidemia.

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men.

Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.

Attenuation of quorum sensing regulated virulence functions and biofilm of pathogenic bacteria by medicinal plant Artemisia annua and its phytoconstituent 1, 8-cineole.

The emergence of multidrug resistance (MDR) in bacterial pathogens is a serious public health concern. A significant therapeutic target for MDR infections is the quorum sensing-regulated bacterial pathogenicity. Determining the anti-quorum sensing abilities of certain medicinal plants against bacterial pathogens as well as the in-silico interactions of particular bioactive phytocompounds with QS and biofilm-associated proteins were the objectives of the present study. In this study, 6 medicinal plants were selected based on their ethnopharmacological usage, screened for Anti-QS activity and Artemisia annua leaf extract (AALE) demonstrated pigment inhibitory activity against Chromobacterium violaceum CV12472. Further, the methanol active fraction significantly inhibited the virulence factors (pyocyanin, pyoverdine, rhamnolipid and swarming motility) of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 at respective sub-MICs. The inhibition of biofilm was determined using a microtiter plate test and scanning electron microscopy. Biofilm formation was impaired by 70%, 72% and 74% in P. aeruginosa, C. violaceum and S. marcescens, respectively at 0.5xMIC of the extract. The phytochemical content of the extract was studied using GC-MS and 1, 8-cineole was identified as major bioactive compound. Furthermore, 1, 8-cineole was docked with quorum sensing (QS) proteins (LasI, LasR, CviR, and rhlR) and biofilm proteins (PilY1 and PilT). In silico docking and dynamics simulations studies suggested interactions with QS-receptors CviR', LasI, LasR, and biofilm proteins PilY1, PilT for anti-QS activity. Further, 1, 8-cineole demonstrated 66% and 51% reduction in violacein production and biofilm formation, respectively to validate the findings of computational analysis. Findings of the present investigation suggests that 1, 8-cineole plays a crucial role in the QS and biofilm inhibitory activity demonstrated by Artemisia annua extract. RESEARCH HIGHLIGHTS: Artemisia annua leaf extract (AALE) methanol fraction demonstrated broad-spectrum QS and biofilm inhibition Scanning electron microscopy (SEM) confirmed biofilm inhibition Molecular docking and simulation studies suggested positive interactions of 1,8-cineol with QS-receptors and biofilm proteins.

Characterization of physiochemical parameters & their effect on microbial content of smokeless tobacco products marketed in north India.

BACKGROUND OBJECTIVES: Smokeless tobacco (SLT) product consumption has profound public health implications for its users. The p H and moisture of SLTs determine the bioavailability of nicotine, the microbial structure dynamics and the amount of microbial conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines. This study aimed to characterize and compare the p H, moisture and alkaloid content of various SLT products. METHODS: Thirty-seven SLT samples including khaini , snus, moist snuff, gul , pan masala , zarda , Mainpuri kapoori and qiwam were collected from the retail market around the National Capital Region in north India and their p H, moisture, nicotine and alkaloid content were measured. The p H and total nicotine were used to calculate the amount of free nicotine, the readily absorbed form, for each product by applying the Henderson-Hasselbalch equation. RESULTS: The investigation showed that the SLTs varied drastically in their p H (5.36 to 10.27), moisture content (4.7 to 51.7%) and alkaloid content (0.82 to 35.87 mg/g). The p H and free nicotine levels of a product were found to be positively correlated, and the highest free nicotine content was reported in snus samples. Further, the moisture content was seen to impact the bacterial and fungal diversity in these samples. INTERPRETATION CONCLUSIONS: Studies to detect the presence of pathogenic microbiological genera as well as potentially toxic constituents are warranted. The use of SLTs as an alternative to cigarette smoking should be discouraged, and cessation programmes must call attention to their detrimental effects and emphasize on benefits of quitting SLT consumption.

Chronic kidney disease prediction using boosting techniques based on clinical parameters.

Chronic kidney disease (CKD) has become a major global health crisis, causing millions of yearly deaths. Predicting the possibility of a person being affected by the disease will allow timely diagnosis and precautionary measures leading to preventive strategies for health. Machine learning techniques have been popularly applied in various disease diagnoses and predictions. Ensemble learning approaches have become useful for predicting many complex diseases. In this paper, we utilise the boosting method, one of the popular ensemble learnings, to achieve a higher prediction accuracy for CKD. Five boosting algorithms are employed: XGBoost, CatBoost, LightGBM, AdaBoost, and gradient boosting. We experimented with the CKD data set from the UCI machine learning repository. Various preprocessing steps are employed to achieve better prediction performance, along with suitable hyperparameter tuning and feature selection. We assessed the degree of importance of each feature in the dataset leading to CKD. The performance of each model was evaluated with accuracy, precision, recall, F1-score, Area under the curve-receiving operator characteristic (AUC-ROC), and runtime. AdaBoost was found to have the overall best performance among the five algorithms, scoring the highest in almost all the performance measures. It attained 100% and 98.47% accuracy for training and testing sets. This model also exhibited better precision, recall, and AUC-ROC curve performance.

Antibiofilm and anti-quorum sensing activity of Psidium guajava L. leaf extract: In vitro and in silico approach.

The quorum sensing mechanism relies on the detection and response to chemical signals, termed autoinducers, which regulate the synthesis of virulence factors including toxins, enzymes, and biofilms. Emerging therapeutic strategies for infection control encompass approaches that attenuate quorum-sensing systems. In this study, we evaluated the antibacterial, anti-quorum sensing, and anti-biofilm activities of Psidium guajava L. methanolic leaf extracts (PGME). Minimum Inhibitory Concentrations (MICs) of PGME were determined as 500 µg/ml for C. violaceum and 1000 µg/ml for P. aeruginosa PAO1. Significantly, even at sub-MIC concentrations, PGME exhibited noteworthy anti-quorum sensing properties, as evidenced by concentration-dependent inhibition of pigment production in C. violaceum 12742. Furthermore, PGME effectively suppressed quorum-sensing controlled virulence factors in P. aeruginosa PAO1, including biofilm formation, pyoverdin, pyocyanin, and rhamnolipid production, with concentration-dependent inhibitory effects. Phytochemical analysis utilizing GC-MS revealed the presence of compounds such as alpha-copaene, caryophyllene, and nerolidol. In-silico docking studies indicated a plausible mechanism for the observed anti-quorum sensing activity, involving favorable binding and interactions with QS-receptors, including RhlR, CviR', LasI, and LasR proteins. These interactions were found to potentially disrupt QS pathways through suppression of AHL production and receptor protein blockade. Collectively, our findings propose PGME as a promising candidate for the treatment of bacterial infections. Its attributes that mitigate biofilm development and impede quorum-sensing mechanisms highlight its potential therapeutic value.

Molecular Screening of Carbapenem-Resistant K. pneumoniae (CRKP) Clinical Isolates for Concomitant Occurrence of Beta-Lactam Genes (CTX-M, TEM, and SHV) in the Kingdom of Bahrain.

The emergence of extended-spectrum ß-lactamase-producing Klebsiella pneumoniae, including CRKP infections, has resulted in significant morbidity and mortality worldwide. We aimed to explore the presence of bla genes (CTX-M, TEM, and SHV) in CRKP isolates. A total of 24 CRKP isolates were randomly selected from the Salmaniya Medical Complex Microbiology Laboratory. These isolates, which were positive for carbapenemases, were further explored for CTX-M, TEM, and SHV genes using PCR. All the CTX-M PCR amplicons were sent for sequencing. To determine genetic relatedness, molecular typing by ERIC-PCR was performed. The bla gene testing demonstrated that a significant proportion of these isolates harbored SHV, CTX-M, and TEM genes (100%, 91.6%, and 45.8%), respectively. Bioinformatic analyses confirmed CTX-M-15 in these isolates. ERIC-PCR analysis showed three clusters demonstrating genetic relatedness. The study findings reveal the concomitant carriage of the SHV and CTX-M-15 and a comparatively lower carriage of TEM genes in CRKP isolates. Our findings highlight the significance of routinely reporting the presence of antibiotic resistance genes along with regular antibiotic sensitivity reports, as this will aid clinicians in prescribing appropriate antibiotics.