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Parikh, R.

Publications and source records attributed to Parikh, R..

4 recordsLinked to original sources

Large-scale neuron cell classification of single-channel and multi-channel extracellular recordings in the anterior lateral motor cortex

Identification of neuron cell type helps us connect neural circuitry and behavior; greater specificity in cell type and subtype classification provides a clearer picture of specific relationships between the brain and behavior. With the advent of high-density probes, large-scale neuron classification is needed, as typical extracellular recordings are identity-blind to the neurons they record. Current methods for identification of neurons include optogenetic tagging and intracellular recordings, but are limited in that they are expensive, time-consuming, and have a limited scope. Therefore, a more automated, real-time method is needed for large-scale neuron identification. Data from two recordings was incorporated into this research; the single-channel recording included data from three neuron types in the motor cortex: FS, IT, and PT neurons. The multi-channel recording contained data from two neuron subtypes also in the motor cortex: PT_L and PT_U neurons. This allowed for an examination of both general neuron classification and more specific subtype classification, which was done via artificial neural networks (ANNs) and machine learning (ML) algorithms. For the single-channel neuron classification, the ANNs achieved 91% accuracy, while the ML algorithms achieved 98% accuracy, using the raw electrical waveform. The multi-channel classification, which was significantly more difficult due to the similarity between the neuron types, yielded an ineffective ANN, reaching 68% accuracy, while the ML algorithms reached 81% using 8 calculated features from the waveform. Thus, to distinguish between different neuron cell types and subtypes in the motor cortex, both ANNs and specific ML algorithms can facilitate rapid and accurate near real-time large-scale classification.

neuroscience

Developing a unique medical-grade honey which maximizes glucose oxidase activity

In the fight against cancer and infection, honey is a compelling solution by virtue of its unique chemical composition; however, current medical-grade honeys are expensive and limited in their scope. In this study, a novel medical-grade honey was developed by maximizing the activity of glucose oxidase (GOX), an enzyme in honey that synthesizes hydrogen peroxide; maximization was done by neutralizing the effects of catalase and methylglyoxal (MGO), compounds in honey that interfere with H2O2 accumulation. Expressed GOX activity was quantified via H2O2 accumulation in honey after catalase, MGO, or both were inhibited. Results indicate the honeys tested have significant quantities of H2O2 inhibitors, greatly affecting expressed GOX activity; neutralization resulted in at least a 100% increase in H2O2 accumulation in all honeys. Blueberry honey with catalase inhibition by EGCG saw a 938% increase in H2O2 accumulation, reaching nearly three times the H2O2 accumulation in current medical grade honey for a tenth of the cost. This research presents a novel and readily reproducible method for maximizing H2O2 accumulation in any honey through neutralization of GOX inhibitors. GOX activity enhancement, combined with honeys diverse antioxidants, enables the emergence of global low-cost medical-grade honeys with immense potential to revolutionize cancer and infection treatment.\n\nThis paper is based on work presented at the Regional Science and Engineering Fair on March 15, 2018 at Riverside High School (Loudoun County, Virginia), the Virginia State Science and Engineering Fair on April 14, 2018 at the Virginia Tech Carilion School of Medicine (Roanoke, Virginia).\n\nAuthor SummaryWith cancer and post-operative infections on the rise, a natural, low-cost alternative treatment is necessary. Honey is an ideal candidate due to its diverse antioxidants and glucose oxidase, an enzyme that produces hydrogen peroxide. The purpose of this research was to maximize glucose oxidase activity by neutralizing compounds that interfere with H2O2 accumulation. This research yielded medical-grade honeys that are economical and more effective than current ones, presenting a novel method that is reproducible on a large scale, scalable to different needs, and applicable to any honey to create low-cost medical-grade honeys that can revolutionize cancer and infection treatment globally.

biochemistry

A machine learning approach to predicting short-term mortality risk in patients starting chemotherapy

BackgroundCancer patients who die soon after starting chemotherapy incur costs of treatment without benefits. Accurately predicting mortality risk from chemotherapy is important, but few patient data-driven tools exist. We sought to create and validate a machine learning model predicting mortality for patients starting new chemotherapy.\n\nMethodsWe obtained electronic health records for patients treated at a large cancer center (26,946 patients; 51,774 new regimens) over 2004-14, linked to Social Security data for date of death. The model was derived using 2004-11 data, and performance measured on non-overlapping 2012-14 data.\n\nFindings30-day mortality from chemotherapy start was 2.1%. Common cancers included breast (21.1%), colorectal (19.3%), and lung (18.0%). Model predictions were accurate for all patients (AUC 0.94). Predictions for patients starting palliative chemotherapy (46.6% of regimens), for whom prognosis is particularly important, remained highly accurate (AUC 0.92). To illustrate model discrimination, we ranked patients initiating palliative chemotherapy by model-predicted mortality risk, and calculated observed mortality by risk decile. 30-day mortality in the highest-risk decile was 22.6%; in the lowest-risk decile, no patients died. Predictions remained accurate across all primary cancers, stages, and chemotherapies--even for clinical trial regimens that first appeared in years after the model was trained (AUC 0.94). The model also performed well for prediction of 180-day mortality (AUC 0.87; mortality 74.8% in the highest risk decile vs. 0.2% in the lowest). Predictions were more accurate than data from randomized trials of individual chemotherapies, or SEER estimates.\n\nInterpretationA machine learning algorithm accurately predicted short-term mortality in patients starting chemotherapy using EHR data. Further research is necessary to determine generalizability and the feasibility of applying this algorithm in clinical settings.

bioinformatics

mRNA detection in budding yeast with single fluorophores

Quantitative measurement of mRNA levels in single cells is necessary to understand phenotypic variability within an otherwise isogenic population of cells. Single-molecule mRNA Fluorescence In Situ Hybridization (FISH) has been established as the standard method for this purpose, but current protocols require a long region of mRNA to be targeted by multiple DNA probes. Here, we introduce a new single-probe FISH protocol termed sFISH for budding yeast, Saccharomyces cerevisiae using a single DNA probe labeled with a single fluorophore. In sFISH, we markedly improved probe specificity and signal-to-background ratio by using methanol fixation and inclined laser illumination. We show that sFISH reports mRNA changes that correspond to protein levels and gene copy number. Using this new FISH protocol, we can detect more than 50% of the total target mRNA. We also demonstrate the versatility of sFISH using FRET detection and mRNA isoform profiling as examples. Our FISH protocol with single-fluorophore sensitivity significantly reduces cost and time compared to the conventional FISH protocols and opens up new opportunities to investigate small changes in RNA at the single cell level.

genetics