Short Courses: Flexible Learning Opportunities in Informatics

In today’s fast-paced, data-driven world, researchers need to have a good foundation in informatics to store, organize, process, and analyze growing amounts of data. However, not all degree programs offer such training. Obtaining training in informatics on your own can be a daunting task for both new and established researchers who have little informatics experience. Providing educational opportunities appropriate for various skill levels and that mesh with a full-time schedule can remove barriers and foster a collaborative, informatics-savvy community that is better equipped to push science forward. To enhance informatics education in bioinformatics, VCUs Wright Center for Clinical and Translational Research of- fers a complementary series of seminars and workshops. These short course offerings introduce attendees to bioinformatics concepts and applications, and provide hands-on experience using online Bioinformatics databases. Bioinformatics 101 (B101) is an 8-week long series of 1-hour seminars focused on introducing topics in bioinformatics related to Next Generation Sequencing (NGS). Lectures are application focused and include overviews of NGS technology, practical bioinformatics pipelines, and examples of how the technology can influence downstream bioinformatics analyses. Bioinformatics 102 (B102) is a 5-day, 2 hours per day workshop developed in collaboration with VCU Libraries that provides attendees with hands-on experience accessing and using public data repositories. Sessions include a brief lecture followed by hands-on exercises. A Certificate of Completion is awarded upon meeting certain criteria for either the 101 or 102 courses. Bioinformatics 101 has been offered 3 times with a combined total of 246 registrants, and Bioinformatics 102 has been offered twice with a total of 78 registrants (limited to 30 per session per day). From course surveys, 82% (n=108) and 95% (n=47) of respondents gave B101 and B102 a positive rating, respectively. In addition, 89% of B101 respondents indicated their knowledge was improved, with 100% of B102 respondents indicating the same. A total of 84 and 33 certificates have been awarded for B101 and B102, respectively. The Bioinformatics 101 and 102 courses have become highly anticipated across the university, and have gained the external attention of surrounding businesses and colleges. Registrants have diverse backgrounds including biological, clinical, computational, administrative, librarian, business, and others with a total of 77 departments across VCU and VCU Health represented. Due to this interest, Bioinformatics 101 began offering live online attendance to accommodate those who were unable to travel across campus, or who are attending from outside VCU. This past year, 50% of attendance was online indicating a growing need for flexible education opportunities in informatics. Increasing researcher knowledge of Bioinformatics along with awareness of university resources for informatics support fosters an informatics-savvy research community that is empowered to take advantage of existing and new data sources in the pursuit of new insights and scientific discoveries for the betterment of human health. Future work will include the development of a more comprehensive educational framework by creating new and flexible learning opportunities that will make informatics education easy and convenient for our dedicated researchers

A preliminary longitudinal study of white matter alteration in cocaine use disorder subjects

Background Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. Methods This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. Results The two groups did not show a difference in FA at baseline. The CocUD subjects had significantly greater ΔFA than the controls in the left splenium of the corpus callosum. In CocUD subjects, greater ΔFA in this region was associated with shorter lifetime cocaine use and greater number of positive cocaine urine samples collected during the treatment. Conclusion The finding in the left splenium is consistent with previous animal studies and provide indirect evidence about the effects of chronic cocaine use on white matter alterations. The subject sample size is small, therefore the results should be treated as preliminary

Diffusion tensor imaging of cocaine-treated rodents.

Studies in cocaine-dependent human subjects have shown differences in white matter on diffusion tensor imaging (DTI) compared with non-drug-using controls. It is not known whether the differences in fractional anisotropy (FA) seen on DTI in white matter regions of cocaine-dependent humans result from a pre-existing predilection for drug use or purely from cocaine abuse. To study the effect of cocaine on brain white matter, DTI was performed on 24 rats after continuous infusion of cocaine or saline for 4 weeks, followed by brain histology. Voxel-based morphometry analysis showed an 18% FA decrease in the splenium of the corpus callosum (CC) in cocaine-treated animals relative to saline controls. On histology, significant increase in neurofilament expression (125%) and decrease in myelin basic protein (40%) were observed in the same region in cocaine-treated animals. This study supports the hypothesis that chronic cocaine use alters white matter integrity in human CC. Unlike humans, where the FA in the genu differed between cocaine users and non-users, the splenium was affected in rats. These differences between rodent and human findings could be due to several factors that include differences in the brain structure and function between species and/or the dose, timing, and duration of cocaine administration

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine

Opioid Use Disorder Prediction Using Machine Learning of fMRI Data

According to the Centers for Disease Control and Prevention (CDC) more than 932,000 people in the US have died since 1999 from a drug overdose. Just about 75% of drug overdose deaths in 2020 involved Opioid, which suggests that the US is in an Opioid overdose epidemic. Identifying individuals likely to develop Opioid use disorder (OUD) can help public health in planning effective prevention, intervention, drug overdose and recovery policies. Further, a better understanding of prediction of overdose leading to the neurobiology of OUD may lead to new therapeutics. In recent years, very limited work has been done using statistical analysis of functional magnetic resonance imaging (fMRI) methods to analyze the neurobiology of Opioid addictions in humans. In this work, for the first time in the literature, we propose a machine learning (ML) framework to predict OUD users utilizing clinical fMRI-BOLD (Blood oxygen level dependent) signal from OUD users and healthy controls (HC). We first obtain the features and validate these with those extracted from selected brain subcortical areas identified in our previous statistical analysis of the fMRI-BOLD signal discriminating OUD subjects from that of the HC. The selected features from three representative brain areas such as default mode network (DMN), salience network (SN), and executive control network (ECN) for both OUD participants and HC subjects are then processed for OUD and HC subjects’ prediction. Our leave one out cross validated results with sixty-nine OUD and HC cases show 88.40% prediction accuracies. These results suggest that the proposed techniques may be utilized to gain a greater understanding of the neurobiology of OUD leading to novel therapeutic development

Zolmitriptan and human aggression: interaction with alcohol

Abstract Rationale The serotonin 1 B/D (5-HT1 B/D ) receptor has shown potential as a target for decreasing aggression. The 5-HT1 B/D agonist zolmitriptan's ability to reduce aggressive behavior in humans and its interaction with the well-known aggression-enhancing drug alcohol were examined. Objectives Our objective was to investigate zolmitriptan's potential to modify human aggression in a laboratory paradigm across a range of alcohol doses. Alcohol has been consistently associated with aggression and violence, thus we hoped to expand current understanding of alcohol's role in aggressive behavior via manipulation of the serotonin (5-HT) system. Methods Eleven social drinkers, seven male, were recruited to participate in a research study lasting 3-4 weeks. Aggression was measured using the point-subtraction aggression paradigm (PSAP), a laboratory model widely used in human aggression studies. Subjects were administered 5-mg zolmitriptan and placebo capsules along with alcohol doses of 0.0, 0.4 and 0.8 g/kg in a within-subject, counterbalanced dosing design. Data were analyzed as the ratio of aggressive/monetary-earning responses, to account for possible changes in overall motor function due to alcohol. Results There was a significant alcohol by zolmitriptan interaction on the aggressive/monetary response ratio. Specifically, compared to placebo, zolmitriptan decreased the aggressive/monetary ratio at the 0.4-and 0.8-g/kg alcohol doses. Conclusions A 5-mg dose of zolmitriptan effectively reduced alcohol-related aggression in an acute dosing protocol, demonstrating an interaction of 5-HT and alcohol in human aggressive behavior

Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study

Background: Human cocaine abuse is associated with alterations in white matter integrity revealed upon brain imaging, an observation that is recapitulated in an animal model of continuous cocaine exposure. The mechanism through which cocaine may affect white matter is unknown and the present study tested the hypothesis that cocaine self-administration results in changes in DNA methylation that could result in altered expression of several myelin genes that could contribute to the effects of cocaine on white matter integrity. Methods: In the present study, we examined the impact of forced abstinence from cocaine self-administration on chromatin associated changes in white matter. To this end, rats were trained to self-administer cocaine (0.75 mg/kg/0.1 mL infusion) for 14 days followed by forced abstinence for 1 day (n = 6) or 30 days (n = 6) before sacrifice. Drug-free, sham surgery controls (n = 7) were paired with the experimental groups. Global DNA methylation and DNA methylation at specific CpG sites in the promoter regions ofmyelin basic protein (Mbp), proteolipid protein-1 (Plp1), and SRY-related HMG-box-10 (Sox10) genes were analyzed in DNA extracted from corpus callosum. Results: Significant differences in the overall methylation patterns of the Sox10 promoter region were observed in the corpus callosum of rats at 30 days of forced abstinence from cocaine self-administration relative to sham controls; the −189, −142, −93, and −62 CpG sites were significantly hypomethylated point-wise at this time point. After correction for multiple comparisons, no differences in global methylation or the methylation patterns of Mbp or Plp1 were found. Conclusion: Forced abstinence from cocaine self-administration was associated with differences in DNA methylation at specific CpG sites in the promoter region of the Sox10 gene in corpus callosum. These changes may be related to reductions in normal age related changes in DNA methylation and could be a factor in white matter alterations seen after withdrawal from repeated cocaine self-administration. Further research is warranted examining the effects of cocaine on DNA methylation in white matter

Increased Orbitofrontal Brain Activation after Administration of a Selective Adenosine A2A Antagonist in Cocaine Dependent Subjects

Background: Positron Emission Tomography imaging studies provide evidence of reduced dopamine function in cocaine dependent subjects in the striatum, which is correlated with prefrontal cortical glucose metabolism, particularly in the orbitofrontal cortex. However, whether enhancement of dopamine in the striatum in cocaine dependent subjects would be associated with changes in prefrontal cortical brain activation is unknown. One novel class of medications that enhance dopamine function via heteromer formation with dopamine receptors in the striatum is the selective adenosine A2A receptor antagonists. This study sought to determine the effects administration of the selective adenosine A2A receptor antagonist SYN115 on brain function in cocaine dependent subjects. Methodology/Principle Findings: Twelve cocaine dependent subjects underwent two fMRI scans (one after a dose of placebo and one after a dose of 100 mg of SYN115) while performing a working memory task with three levels of difficulty (3, 5, and 7 digits). fMRI results showed that for 7-digit working memory activation there was significantly greater activation from SYN115 compared to placebo in portions of left (L) lateral orbitofrontal cortex, L insula, and L superior and middle temporal pole. Conclusion/Significance: These findings are consistent with enhanced dopamine function in the striatum in cocaine dependent subjects via blockade of adenosine A2A receptors producing increased brain activation in the orbitofrontal cortex and other cortical regions. This suggests that at least some of the changes in brain activation in prefrontal cortical regions in cocaine dependent subjects may be related to altered striatal dopamine function, and that enhancement of dopamine function via adenosine A2A receptor blockade could be explored further for amelioration of neurobehavioral deficits associated with chronic cocaine use

Untapped Potential of Clinical Text for Opioid Surveillance

Accurate surveillance is needed to combat the growing opioid epidemic. To investigate the potential volume of missed opioid overdoses, we compare overdose encounters identified by ICD-10-CM codes and an NLP pipeline from two different medical systems. Our results show that the NLP pipeline identified a larger percentage of OOD encounters than ICD-10-CM codes. Thus, incorporating sophisticated NLP techniques into current diagnostic methods has the potential to improve surveillance on the incidence of opioid overdoses