Machine learning analysis of the orbitofrontal cortex transcriptome of human opioid users identifies Shisa7 as a translational target relevant for heroin-seeking leveraging a male rat model.

Background: Identifying neurobiological targets predictive of the molecular neuropathophysiological signature of human opioid use disorder (OUD) could expedite new treatments. OUD is characterized by dysregulated cognition and goal-directed behavior mediated by the orbitofrontal cortex (OFC), and next-generation sequencing could provide insights regarding novel targets.

Methods: Here, we used machine learning to evaluate human post-mortem OFC RNA-sequencing datasets from heroin-users and controls to identify transcripts predictive of heroin use.

Dextromethorphan inhibits collagen and collagen-like cargo secretion to ameliorate lung fibrosis.

Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis.

Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1.

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues.

The impact of patient-facility language discordance on potentially inappropriate prescribing of antipsychotics in long-term care home in Ontario, Canada: a retrospective population health cohort study.

Background: Appropriate use of medication is a key indicator of the quality of care provided in long-term care (LTC). The objective of this study was to determine whether resident-facility language concordance/discordance is associated with the odds of potentially inappropriate prescribing of antipsychotics (PIP-AP) in LTC.

Methods: We conducted a population-based, retrospective cohort study of LTC residents in Ontario, Canada from 2010 to 2019.