Improved tomato leaf disease classification through adaptive ensemble models with exponential moving average fusion and enhanced weighted gradient optimization.

Tomato is one of the most popular and most important food crops consumed globally. The quality and quantity of yield by tomato plants are affected by the impact made by various kinds of diseases. Therefore, it is essential to identify these diseases early so that it is possible to reduce the occurrences and effect of the diseases on tomato plants to improve the overall crop yield and to support the farmers. In the past, many research works have been carried out by applying the machine learning techniques to segment and classify the tomato leaf images. However, the existing machine learning-based classifiers are not able to detect the new types of diseases more accurately. On the other hand, deep learning-based classifiers with the support of swarm intelligence-based optimization techniques are able to enhance the classification accuracy, leading to the more effective and accurate detection of leaf diseases. This research paper proposes a new method for the accurate classification of tomato leaf diseases by harnessing the power of an ensemble model in a sample dataset of tomato plants, containing images pertaining to nine different types of leaf diseases. This research introduces an ensemble model with an exponential moving average function with temporal constraints and an enhanced weighted gradient optimizer that is integrated into fine-tuned Visual Geometry Group-16 (VGG-16) and Neural Architecture Search Network (NASNet) mobile training methods for providing improved learning and classification accuracy. The dataset used for the research consists of 10,000 tomato leaf images categorized into nine classes for training and validating the model and an additional 1,000 images reserved for testing the model. The results have been analyzed thoroughly and benchmarked with existing performance metrics, thus proving that the proposed approach gives better performance in terms of accuracy, loss, precision, recall, receiver operating characteristic curve, and F1-score with values of 98.7%, 4%, 97.9%, 98.6%, 99.97%, and 98.7%, respectively.

A review of clinical trials registered in India from 2008 to 2022 to describe the first-in-human trials.

Aim: This analysis was conducted to review the number, and describe the characteristics of first-in-human (FIH) Phase 1 clinical trials registered in India from 2008 to 2022. Materials and Methods: The data were extracted from the Clinical Trials Registry - India database for all FIH Phase 1 clinical trials registered between 2008 and 2022. Early-phase trials that were not FIH trials (e.g., pharmacokinetic studies and drug-drug interaction studies) were excluded from the study. Results: A total of 1891 trials were retrieved and 220 were included in the analysis. Most of the investigational products were drugs (55%) followed by vaccines (38.2%). The most common therapeutic class of drugs was cancer chemotherapy (19.8%), followed by antimicrobial chemotherapy and endocrinology (18.2% each). The most common vaccine was the influenza vaccine (21.4%), followed by the measles-mumps-rubella vaccine (15.5%). The pharmaceutical industry was the predominant sponsor for most (91%) of the Phase 1 trials. Of the top five sites where most of the Phase 1 trials were conducted, three were private nonacademic centers (cumulatively 31%) and two were tertiary care medical colleges (cumulatively 9%). Conclusion: Phase 1 clinical trials seem to be conducted in India predominantly with industry sponsorship. There is a need to have an alternate ecosystem to take forward molecules that do not receive adequate attention from the industry and molecules that are of national health priority other than areas such as chemotherapy, antimicrobials, and endocrinology. The Indian Council of Medical Research is setting up Phase 1 clinical trial capacity for molecules that predominantly may arise from nonindustry channels.

Impact of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions in individuals living with epilepsy: a case-control study.

Epilepsy is characterized by repeated seizure activity. Valproate, a commonly used antiepileptic drug, shows large inter-individual variation in plasma valproic levels and causes many adverse drug reactions. Aim: To find the influence of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions and plasma valproic acid levels in people with epilepsy. Methods: We recruited 158 people with epilepsy (79 cases and 79 controls) from an epilepsy clinic. Steady-state plasma valproic acid levels were measured using liquid chromatography-mass spectrometry and genotyping of CYP2C9 variants was carried out with helps of RT-PCR. Results: The presence of a mutant heterozygous genotype showed an odds ratio (OR) of 2.82 (95% CI: 1.10-7.24) and the adjusted OR was 5.39 (95% CI: 1.69-17.16). There was no significant difference in steady-state plasma valproate concentration between genotypes. Conclusion: The presence of a mutant heterozygous CYP2C9 genotype possesses five-times the risk of developing adverse drug reactions to valproate in people with epilepsy.

Efficacy and safety of bempedoic acid lipid-lowering therapy: a systematic review and meta-analysis of randomized controlled trials.

AIM: This systematic review and meta-analysis was conducted to synthesize the efficacy and safety of bempedoic acid in patients requiring lipid-lowering therapy. METHODS: PubMed, Embase, and Scopus databases were searched for randomized controlled trials from inception till June 2023. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes were all-cause mortality, serum lipid profile, and adverse events between bempedoic acid and comparators. ROB2 was used for risk of bias assessment. We pooled mean differences or relative risks (RR) along with 95% confidence intervals (random-effects model). RESULTS: Five-hundred and thirty-one studies were screened and 17 (n = 21,131) were included for review. There was a significant reduction in the risk of MACE [RR, 0.88 (95% CI: 0.77 to 0.99), p = 0.03)] and all-cause mortality [RR, 0.90 (95% CI: 0.82 to 0.98), p = 0.02] following bempedoic acid treatment. Treatment with bempedoic acid led to a significant reduction in the mean serum total cholesterol [- 34.41 mg/dl (95% CI: - 42.43 to - 26.39), p < 0.001], low-density lipoprotein cholesterol (LDL-C) [- 33.91 mg/dl (95% CI: - 39.66 to - 28.17), p < 0.001], as well as high-density lipoprotein cholesterol (HDL-C) [- 2.40 mg/dl (95% CI: - 3.09 to - 1.71), p < 0.001] levels. However, there was a significant increase in the risk of hyperuricemia [RR, 2.05 (95% CI: 1.81 to 2.33), p < 0.001] following bempedoic acid treatment. The number needed to harm was large for all safety outcomes. The GRADE of evidence was moderate for all outcomes. CONCLUSION: Bempedoic acid reduces the risk of MACE and all-cause mortality, lowers serum total cholesterol and LDL-C levels, and has a favorable safety profile. Trial registration ClinicalTrial.gov Identifier: CRD42023412837.

Genetic polymorphisms of microsomal epoxide hydrolase and UDP-glucuronosyltransferase (UGT) and its effects on plasma carbamazepine levels and metabolic ratio in persons with epilepsy of South India: A cross-sectional genetic association study.

OBJECTIVES: Carbamazepine (CBZ), an anti-seizure drug, is widely prescribed for the management of focal seizures. At a given therapeutic dose, CBZ exhibits marked interindividual variation in the plasma CBZ levels. The aim wasto study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on plasma carbamazepine (CBZ) levels in persons with epilepsy (PWE) from South India. METHODS: 115 PWE belong to South India origin who are on carbamazepine monotherapy were recruited. Genotyping of the two variants weredone using RT-PCR method. PWE who had seizure freedom for one year and their last dose which was not changed for one year duration were included and their plasma levels of CBZ and its active metabolite CBZ 10,11 epoxide were analysed by reverse phase HPLC. RESULTS: In EPHX1 c. 337 (T>C) polymorphism, the PWE carrying CC had lower plasma CBZ levels when compared to CT genotype (2.45 µg/ml vs 3.15 µg/ml. In UGT2B7*2, PWE carrying homozygous mutant TT had higher levels when compared with CT (3.09 µg/ml vs 2.74 µg/ml) genotype but found no statistical significance. Mutant genotype of EPHX1 (CC) had higher metabolic ratio compared to TT genotype (1.33 vs 1.17) but not found to be statistically significant. Mutant genotype of UGT2B7*2 (TT) was found to be having lower metabolic ratio when compared with CC genotype (1.18 vs 1.35; p value =0.08). CONCLUSION: PWE carrying EPHX1 c.337 T>C (rs1051740) and UGT2B7*2 (rs7439366) genetic polymorphisms did not affect the plasma CBZ levels and metabolic ratio of PWE of South Indian origin. However, this finding should be confirmed in a larger sample size which may help in optimization and personalized CBZ therapy in South Indians.

Influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study.

OBJECTIVES: Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having a role in the requirement of CBZ maintenance dose. The aim was to study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy. METHODS: Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10% EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of EPHX1 c.337 T>C and UGT2B7*2, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between the genotypes and CBZ maintenance dose requirement for dominant and recessive models of EPHX1 c.337 T>C and UGT2B7*2. A value of p<0.05 was considered to be statistically significant. RESULTS: For UGT2B7*2 (rs 7439366), CT required a higher dose (CT 626 mg/day and TT 523 mg/day) but not found to be significant (p-value 0.167). PWE carrying CT genotype of EPHX1 c.337 T>C had 62 mg higher dose when compared to homozygous mutant CC (590 mg/day for CT and 528 mg/day for CC) but p-value was not found to be significant (p-value 0.835). CONCLUSIONS: The results of our study done in 115 PWE showed there was a lack of association between SNPs of EPHX1 c.337 T>C, UGT2B7*2 and CBZ maintenance dose requirement in Southern part of India and this finding has to be confirmed in a larger sample size.