AutoXAI4Omics: an automated explainable AI tool for omics and tabular data.

Machine learning (ML) methods offer opportunities for gaining insights into the intricate workings of complex biological systems, and their applications are increasingly prominent in the analysis of omics data to facilitate tasks, such as the identification of novel biomarkers and predictive modeling of phenotypes. For scientists and domain experts, leveraging user-friendly ML pipelines can be incredibly valuable, enabling them to run sophisticated, robust, and interpretable models without requiring in-depth expertise in coding or algorithmic optimization. By streamlining the process of model development and training, researchers can devote their time and energies to the critical tasks of biological interpretation and validation, thereby maximizing the scientific impact of ML-driven insights.

Reprint of: Self-identified prescriber tendencies in sodium-glucose cotransporter-2 inhibitor outpatient prescribing.

Background: Despite expanded indications and demonstrated cardiovascular and renal benefits, prescribing rates of sodium-glucose cotransporter-2 (SGLT-2) inhibitors are low.

Objectives: The study aimed to identify factors impacting prescriber decision-making when prescribing SGLT-2 inhibitors in the outpatient setting and identify differences across specialties in self-identified prescribing patterns.

Methods: An anonymous survey was administered electronically to prescribers in relevant specialties at a large community health system.

Self-identified prescriber tendencies in sodium-glucose cotransporter-2 inhibitor outpatient prescribing.

Background: Despite expanded indications and demonstrated cardiovascular and renal benefits, prescribing rates of sodium-glucose cotransporter-2 (SGLT-2) inhibitors are low.

Objectives: The study aimed to identify factors impacting prescriber decision-making when prescribing SGLT-2 inhibitors in the outpatient setting and identify differences across specialties in self-identified prescribing patterns.

Methods: An anonymous survey was administered electronically to prescribers in relevant specialties at a large community health system.

Coordinated interplay between palmitoylation, phosphorylation and SUMOylation regulates kainate receptor surface expression.

Kainate receptors (KARs) are key regulators of neuronal excitability and synaptic transmission. KAR surface expression is tightly controlled in part by post-translational modifications (PTMs) of the GluK2 subunit. We have shown previously that agonist activation of GluK2-containing KARs leads to phosphorylation of GluK2 at S868, which promotes subsequent SUMOylation at K886 and receptor endocytosis.

SNX27-Retromer directly binds ESCPE-1 to transfer cargo proteins during endosomal recycling.

Coat complexes coordinate cargo recognition through cargo adaptors with biogenesis of transport carriers during integral membrane protein trafficking. Here, we combine biochemical, structural, and cellular analyses to establish the mechanistic basis through which SNX27-Retromer, a major endosomal cargo adaptor, couples to the membrane remodeling endosomal SNX-BAR sorting complex for promoting exit 1 (ESCPE-1). In showing that the SNX27 FERM (4.

Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.

The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting.

Perchloroethylene and Dry Cleaning: It's Time to Move the Industry to Safer Alternatives.

Perchloroethylene (PERC) is the most common solvent used for dry cleaning in the United States. PERC is a reproductive toxicant, neurotoxicant, potential human carcinogen, and a persistent environmental pollutant. The Environmental Protection Agency is evaluating PERC under the Frank R.

Feasibility of virtual reality behavior skills training for preservice clinicians.

Effective training procedures include behavioral skills training (BST), which involves providing written and verbal instructions, modeling of the skill, rehearsal of the skill, and feedback on the performance. This training typically involves in vivo experience in which trainees and students are exposed to risks such as proximity to infectious disease, behavioral issues such as aggression, and errors in teaching performance. Conducting BST in a virtual reality (VR) context involving virtual individuals with problem behavior may be an effective means of mitigating these risks.

Corrigendum: Protein Interactors and Trafficking Pathways That Regulate the Cannabinoid Type 1 Receptor (CB1R).

[This corrects the article DOI: 10.3389/fnmol.2020.

Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting.

Human retromer, a heterotrimer of VPS26 (VPS26A or VPS26B), VPS35 and VPS29, orchestrates the endosomal retrieval of internalised cargo and promotes their cell surface recycling, a prototypical cargo being the glucose transporter GLUT1 (also known as SLC2A1). The role of retromer in the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR, also known as IGF2R) from endosomes back to the -Golgi network remains controversial. Here, by applying knocksideways technology, we develop a method for acute retromer inactivation.

Protein Interactors and Trafficking Pathways That Regulate the Cannabinoid Type 1 Receptor (CB1R).

The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress synaptic transmission and plays a major role in a diverse range of brain functions including, for example, the regulation of mood, energy balance, and learning and memory. The function and dysfunction of the ECS are strongly implicated in multiple psychiatric, neurological, and neurodegenerative diseases. Cannabinoid type 1 receptor (CB1R) is the most abundant G protein-coupled receptor (GPCR) expressed in the brain and, as for any synaptic receptor, CB1R needs to be in the right place at the right time to respond appropriately to changing synaptic circumstances.

Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis.

Biomarkers predicting fingolimod (FTY) treatment response in relapsing-remitting multiple sclerosis (RRMS) are lacking. Here, we performed extensive functional immunophenotyping using multiparametric flow cytometry to examine peripheral immune changes under FTY treatment and explore biomarkers of FTY treatment response. From among 135 RRMS patients who initiated FTY in a 2-year multicentre observational study, 36 were classified as 'Active' or 'Stable' based on clinical and/or radiological activity on-treatment.

Bench-scale column evaluation of factors associated with changes in N-nitrosodimethylamine (NDMA) precursor concentrations during drinking water biofiltration.

Biofiltration has been observed to increase or decrease the concentrations of N-nitrosodimethylamine (NDMA) precursors in the effluents of full-scale drinking water facilities, but these changes have been inconsistent over time. Bench-scale tests comparing biofiltration columns side-by-side exposed to different conditions were employed to characterize factors associated with changes in NDMA precursor concentrations, as measured by application of chloramines under uniform formation conditions (UFC). Side-by-side comparisons of biofiltration media from different facilities fed with water from each of these facilities demonstrated that differences in source water quality were far more important than any original differences in the microbial communities on the biofiltration media for determining whether NDMA precursor concentrations increased, decreased or remained constant across biofilters.

The C-terminal helix 9 motif in rat cannabinoid receptor type 1 regulates axonal trafficking and surface expression.

Cannabinoid type one receptor (CB1R) is only stably surface expressed in axons, where it downregulates neurotransmitter release. How this tightly regulated axonal surface polarity is established and maintained is unclear. To address this question, we used time-resolved imaging to determine the trafficking of CB1R from biosynthesis to mature polarised localisation in cultured rat hippocampal neurons.

ADAR2-mediated Q/R editing of GluK2 regulates kainate receptor upscaling in response to suppression of synaptic activity.

Kainate receptors (KARs) regulate neuronal excitability and network function. Most KARs contain the subunit GluK2 (also known as GRIK2), and the properties of these receptors are determined in part by ADAR2 (also known as ADARB1)-mediated mRNA editing of GluK2, which changes a genomically encoded glutamine residue into an arginine residue (Q/R editing). Suppression of synaptic activity reduces ADAR2-dependent Q/R editing of GluK2 with a consequential increase in GluK2-containing KAR surface expression.

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors.

Kainate receptors (KARs) are glutamate-gated ion channels that play fundamental roles in regulating neuronal excitability and network function in the brain. After being cloned in the 1990s, important progress has been made in understanding the mechanisms controlling the molecular and cellular properties of KARs, and the nature and extent of their regulation of wider neuronal activity. However, there have been significant recent advances towards understanding KAR trafficking through the secretory pathway, their precise synaptic positioning, and their roles in synaptic plasticity and disease.

Expanding the Reach of Effective PTSD Treatment Into Primary Care: Prolonged Exposure for Primary Care.

Posttraumatic stress disorder (PTSD) is a costly mental health issue in the United States and throughout the world. Effective treatments are available; however, most people with PTSD never access these treatments. Prolonged exposure (PE) therapy has emerged as an effective, first-line treatment for PTSD and is provided in specialty mental health in eight to 15 sessions, each lasting 90 minutes.

Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity.

Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity.

Dimethyl fumarate-induced lymphopenia in MS due to differential T-cell subset apoptosis.

Objective: To examine the mechanism underlying the preferential CD8 vs CD4 T-cell lymphopenia induced by dimethyl fumarate (DMF) treatment of MS.

Methods: Total lymphocyte counts and comprehensive T-cell subset analyses were performed in high-quality samples obtained from patients with MS prior to and serially following DMF treatment initiation. Random coefficient mixed-effects analysis was used to model the trajectory of T-cell subset losses in vivo.

SENP3-mediated deSUMOylation of Drp1 facilitates interaction with Mff to promote cell death.

The GTPase dynamin-related protein 1 (Drp1) is essential for physiological and pathophysiological mitochondrial fission. DeSUMOylation of Drp1 by the enzyme SENP3 promotes cell death during reperfusion after ischaemia by enhancing Drp1 partitioning to the mitochondrial outer membrane (MOM), which causes cytochrome c release and apoptosis. However, how deSUMOylation recruits Drp1 to the MOM is unknown.

Mortality outcomes after busulfan-containing conditioning treatment and haemopoietic cell transplantation in patients with Gilbert's syndrome: a retrospective cohort study.

Background: Gilbert's syndrome is a common inherited disorder of bilirubin metabolism, characterised by mild, unconjugated hyperbilirubinaemia. However, the effect of Gilbert's syndrome on the disposition of some drugs can lead to unexpected toxicity. We tested the hypothesis that patients undergoing myeloablative conditioning and haemopoietic cell transplantation would have different mortality outcomes depending on whether or not they had laboratory evidence of Gilbert's syndrome.

SUMOylation of Syntaxin1A regulates presynaptic endocytosis.

Neurotransmitter release from the presynaptic terminal is under very precise spatial and temporal control. Following neurotransmitter release, synaptic vesicles are recycled by endocytosis and refilled with neurotransmitter. During the exocytosis event leading to release, SNARE proteins provide most of the mechanical force for membrane fusion.

Fibrosing cholestatic hepatitis C after hematopoietic cell transplantation: report of 3 fatal cases.

Development of liver disease after hematopoietic cell transplantation is common and the causes diverse. Infection by hepatitis C virus (HCV) can be seen in patients who are chronically infected before transplant or from passage of virus from an infected donor; the normal 10-year course of hepatitis C after transplant is one of waxing and waning of serum aminotransferase enzymes, with little morbidity. In the series of 3 patients reported here, the course of hepatitis C was rapidly fatal, with the onset of jaundice at day 60 to 80 after transplant and liver histology typical of fibrosing cholestatic hepatitis (marked bile ductular proliferation, ballooned hepatocytes, and associated collagenous fibrosis centered around ductules).

A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation.

Background: Macrophage activation plays a crucial role in regulating adipose tissue inflammation and is a major contributor to the pathogenesis of obesity-associated cardiovascular diseases. On various types of stimuli, macrophages respond with either classic (M1) or alternative (M2) activation. M1- and M2-mediated signaling pathways and corresponding cytokine production profiles are not completely understood.

A review and expert opinion of the use of certolizumab for Crohn's disease.

Introduction: Crohn's disease (CD) is a chronic, idiopathic, inflammatory bowel disease with no known cure. In those patients with moderate to severe disease, the result is often a clinically debilitating condition. In the last decade, one of the most significant developments in therapy has been a class of biological agents that neutralize TNFa.