No Arabic abstract
The opioid epidemic in the United States claims over 40,000 lives per year, and it is estimated that well over two million Americans have an opioid use disorder. Over-prescription and misuse of prescription opioids play an important role in the epidemic. Individuals who are prescribed opioids, and who are diagnosed with opioid use disorder, have diverse underlying health states. Policy interventions targeting prescription opioid use, opioid use disorder, and overdose often fail to account for this variation. To identify latent health states, or phenotypes, pertinent to opioid use and opioid use disorders, we use probabilistic topic modeling with medical diagnosis histories from a statewide population of individuals who were prescribed opioids. We demonstrate that our learned phenotypes are predictive of future opioid use-related outcomes. In addition, we show how the learned phenotypes can provide important context for variability in opioid prescriptions. Understanding the heterogeneity in individual health states and in prescription opioid use can help identify policy interventions to address this public health crisis.
Opioid and substance misuse is rampant in the United States today, with the phenomenon known as the opioid crisis. The relationship between substance use and mental health has been extensively studied, with one possible relationship being substance misuse causes poor mental health. However, the lack of evidence on the relationship has resulted in opioids being largely inaccessible through legal means. This study analyzes the substance misuse posts on social media with the opioids being sold through crypto market listings. We use the Drug Abuse Ontology, state-of-the-art deep learning, and BERT-based models to generate sentiment and emotion for the social media posts to understand user perception on social media by investigating questions such as, which synthetic opioids people are optimistic, neutral, or negative about or what kind of drugs induced fear and sorrow or what kind of drugs people love or thankful about or which drug people think negatively about or which opioids cause little to no sentimental reaction. We also perform topic analysis associated with the generated sentiments and emotions to understand which topics correlate with peoples responses to various drugs. Our findings can help shape policy to help isolate opioid use cases where timely intervention may be required to prevent adverse consequences, prevent overdose-related deaths, and worsen the epidemic.
We study the problem of sparse nonlinear model recovery of high dimensional compositional functions. Our study is motivated by emerging opportunities in neuroscience to recover fine-grained models of biological neural circuits using collected measurement data. Guided by available domain knowledge in neuroscience, we explore conditions under which one can recover the underlying biological circuit that generated the training data. Our results suggest insights of both theoretical and practical interests. Most notably, we find that a sign constraint on the weights is a necessary condition for system recovery, which we establish both theoretically with an identifiability guarantee and empirically on simulated biological circuits. We conclude with a case study on retinal ganglion cell circuits using data collected from mouse retina, showcasing the practical potential of this approach.
This report presents the implementation of a protein sequence comparison algorithm specifically designed for speeding up time consuming part on parallel hardware such as SSE instructions, multicore architectures or graphic boards. Three programs have been developed: PLAST-P, TPLAST-N and PLAST-X. They provide equivalent results compared to the NCBI BLAST family programs (BLAST-P, TBLAST-N and BLAST-X) with a speed-up factor ranging from 5 to 10.
Computational chemists typically assay drug candidates by virtually screening compounds against crystal structures of a protein despite the fact that some targets, like the $mu$ Opioid Receptor and other members of the GPCR family, traverse many non-crystallographic states. We discover new conformational states of $mu OR$ with molecular dynamics simulation and then machine learn ligand-structure relationships to predict opioid ligand function. These artificial intelligence models identified a novel $mu$ opioid chemotype.
Many important analgesics relieve pain by binding to the $mu$-Opioid Receptor ($mu$OR), which makes the $mu$OR among the most clinically relevant proteins of the G Protein Coupled Receptor (GPCR) family. Despite previous studies on the activation pathways of the GPCRs, the mechanism of opiate binding and the selectivity of $mu$OR are largely unknown. We performed extensive molecular dynamics (MD) simulation and analysis to find the selective allosteric binding sites of the $mu$OR and the path opiates take to bind to the orthosteric site. In this study, we predicted that the allosteric site is responsible for the attraction and selection of opiates. Using Markov state models and machine learning, we traced the pathway of opiates in binding to the orthosteric site, the main binding pocket. Our results have important implications in designing novel analgesics.