Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Pectic oligosaccharide structure-function relationships: prebiotics, inhibitors of Escherichia coli O157:H7 adhesion and reduction of Shiga toxin cytotoxicity in HT29 cells

Shiga toxin (Stx)-producing, food-contaminating Escherichia coli (STEC) is a major health concern. Plant-derived pectin and pectic-oligosaccharides (POS) have been considered as prebiotics and for the protection of humans from Stx. Of five structurally different citrus pectic samples, POS1, POS2 and modified citrus pectin 1 (MCP1) were bifidogenic with similar fermentabilities in human faecal cultures and arabinose-rich POS2 had the greatest prebiotic potential. Pectic oligosaccharides also enhanced lactobacilli growth during mixed batch faecal fermentation. We demonstrated that all pectic substrates were anti-adhesive for E. coli O157:H7 binding to human HT29 cells. Lower molecular weight and deesterification enhanced the anti-adhesive activity. We showed that all pectic samples reduced Stx2 cytotoxicity in HT29 cells, as measured by the reduction of human rRNA depurination detected by our novel TaqMan-based RT-qPCR assay, with POS1 performing the best. POS1 competes with Stx2 binding to the Gb3 receptor based on ELISA results, underlining the POS anti-STEC properties

Games in Tholkappiyam and Aganaanooru

Tamil culture places a high value on grammar and literature. A sport thought of as a hobby  that  focuses on the civilization and culture of every people. From the sangam era to the present, the contribution of games has dominted grammar and literature. The greatest treasure that can never be destroyed is the world of games. Humans benefit greatly from sport in terms of agility and fun. The best medicine for the human body and for life is sports. Additionally, it is clamied to rejuvenate peoples life. They provide the body with the necessary energy, health, and sense of community. The game improves navigation and speaking skills for both kids and adults. As a result, every ones capacity for rational, in-depth thought improves.The lyrics allusions to the games played in Tholkappiaym and Aganaanooru are dispersed through Sout and arranged harmoniously. Tamil community values sport as a significant aspect

Parkinson disease prediction using improved crayfish optimization based hybrid deep learning

Background Predicting the course of Parkinson's disease is essential for prompt diagnosis and treatment, which may enhance patient outcomes. Objective This study presents a novel method for Parkinson's disease prediction using freely accessible resources. The suggested approach starts with band-pass filter data preprocessing and uses Empirical Mode Decomposition (EMD) for feature extraction. Then, for classification, these features are supplied into an Attention-based Efficient Bidirectional Network (ImCfO_Attn_EffBNet) based on Improved Crayfish Optimization. EfficientNet-B7, BiLSTM, and Attention modules are integrated by ImCfO_Attn_EffBNet to effectively gather temporal and geographic data. Methods Additionally, we use the Improved Crayfish Optimization (ImCfO) algorithm to maximize convergence rates, optimize the loss function, and find the global best solutions. Results ImCfO enhances performance by adding a self-adaptation criterion to the traditional crayfish algorithm. The classifier's configurable parameters are adjusted using the ImCfO resultant solution, which raises the prediction accuracy overall. Conclusion Based on a number of assessments, the ImCfO_Attn_EffBNet analyzed the performance and found that the results were as follows: accuracy (95.068%), recall (92.948%), specificity (92.89%), F-Score (92.89%), precision (92.89%), and FPR (2.1%), in that order

IMPROVED EVOLUTIONARY SUPPORT VECTOR MACHINE CLASSIFIER FOR CORONARY ARTERY HEART DISEASE PREDICTION AMONG DIABETIC PATIENTS

Soft computing paves way many applications including medical informatics. Decision support system has gained a major attention that will aid medical practitioners to diagnose diseases. Diabetes mellitus is hereditary disease that might result in major heart disease. This research work aims to propose a soft computing mechanism named Improved Evolutionary Support Vector Machine classifier for CAHD risk prediction among diabetes patients. The attribute selection mechanism is attempted to build with the classifier in order to reduce the misclassification error rate of the conventional support vector machine classifier. Radial basis kernel function is employed in IESVM. IESVM classifier is evaluated through the performance metrics namely sensitivity, specificity, prediction accuracy and Matthews correlation coefficient (MCC) and also compared with existing work and our earlier proposed works

Identification of a putative transcription factor in Candida albicans that can complement the mating defect of Saccharomyces cerevisiae ste12 mutants

We have isolated an acid proteinase-related gene, ACPR, from Candida albicans using a partial clone (Ganesan, K., Banerjee, A., and Datta, A. (1991) Infect. Immun. 59, 2972-2977) as a probe. Sequencing of the full-length gene revealed an open reading frame that can encode a protein of 699 amino acids. The deduced NH2-terminal amino acid sequence did not correspond with that determined from the purified secretory acid proteinase; however, the encoded protein is antigenically related to secretory acid proteinase and has a putative active site for acid proteinase. Interestingly, the amino acid sequence of the NH2-terminal 215 residues of Acprp is highly similar to the DNA binding domain of Ste12p of Saccharomyces cerevisiae. Gel retardation experiments showed that this region of Acprp, like Ste12p, could bind to S. cerevisiae pheromone response elements, suggesting that Acprp has a function similar to Ste12p. Chimeric constructs composed of S. cerevisiae STE12 and C. albicans ACPR genes complemented the mating defect of S. cerevisiae a or alpha ste12 mutants. Our results suggest the presence of a signal transduction system in C. albicans similar to that of S. cerevisiae mating pathway

STABILITY INDICATING RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF METFORMIN AND GLIPIZIDE

A novel, precise and accurate stability indicating RP-HPLC method was developed and validated for the simultaneous estimation of Metformin and Glipizide in combined pharmaceutical dosage form. Chromatographic separation was achieved on Microsorb-MV C18 column (250 × 4.6 mm, 5 μm) with UV detection at 257 nm. The mobile phase consists of acetate buffer (pH 4.0) and acetonitrile in the ratio of 60:40 v/v and at a flow rate of 1.0 mL/min. The method was linear over the concentration range of 60-140 μg/mL for Metformin and 10-50 μg/mL for Glipizide. The retention times for Metformin and Glipizide were found to be 2.434 min and 5.710 min respectively. The mean percentage recoveries of Metformin and Glipizide were found to be 100.42% and 100.39% respectively. The method was validated and was successfully employed for the routine quantitative analysis of pharmaceutical formulations containing Metformin and Glipizide in combined pharmaceutical formulation

Effectiveness of therapeutic play on the level of anxiety among hospitalized children between 3-6 years

Today’s children are tomorrow’s citizen, so the health of the children is very important in determining the prosperity of a country. Indian journal of pediatrics (2005) indicated that 20% of children have some form of psychological problem and that of 70% of these are helped through the use of psychological based therapies such as play and creative arts. According to Jean Piaget, knowledge arises neither from objects nor the child, but from interactions between the child and those objects. Therapeutic play is one type of play therapy. Constructive play helps to relieve anxiety of the child. Play is essential for a child to be healthy as well as to grow healthy. A study was conducted to assess the effectiveness of therapeutic play on the level of anxiety among hospitalized children between 3- 6 years in Stanley Hospital,Chennai. The objective of the study was to determine the effectiveness of therapeutic play on the level of anxiety among hospitalized children between 3-6 years. The study was conducted by adopting a one group pre test post test research design. The sample size was sixty children between 3-6 years who fulfilled the inclusive criteria and they were selected by convenient sampling technique. During pre test the required data were collected by using the observation checklist. Therapeutic play was given to the child for 2 hours on each day for 3 days. After the intervention completes post test was conducted by using the same observation checklist. The analysis revealed that there was marked decrease in the mean value from 43.93 in the pre test level to 31.86 in the post test level of anxiety. The standard deviation is increased from 7.57 in pre test to 17.71 in post test. The‘t’ value at 18.47 is highly significant at p<0.001 level. So there was significant decrease in the post test level of anxiety among hospitalized children between 3-6 yrs. Therefore therapeutic play can be used as a safe and effective tool, which helps in reducing anxiety