Targeting the MR1-MAIT cell axis improves vaccine efficacy and affords protection against viral pathogens.

Mucosa-associated invariant T (MAIT) cells are MR1-restricted, innate-like T lymphocytes with tremendous antibacterial and immunomodulatory functions. Additionally, MAIT cells sense and respond to viral infections in an MR1-independent fashion. However, whether they can be directly targeted in immunization strategies against viral pathogens is unclear.

Annexin A5 Inhibits Endothelial Inflammation Induced by Lipopolysaccharide-Activated Platelets and Microvesicles via Phosphatidylserine Binding.

Sepsis is caused by a dysregulated immune response to infection and is a leading cause of mortality globally. To date, no specific therapeutics are available to treat the underlying septic response. We and others have shown that recombinant human annexin A5 (Anx5) treatment inhibits pro-inflammatory cytokine production and improves survival in rodent sepsis models.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.

Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.

A clinician's guide for counseling patients on results of a multigene pharmacogenomic panel.

Purpose: This article explores approaches to pharmacogenomic counseling for patients who have undergone multigene panel testing by describing the collective experience of 5 institutions.

Summary: Multigene panel pharmacogenomic testing has the potential to unlock a myriad of information about a patient's past, present, and future drug response. The multifaceted nature of drug response coupled with the complexity of genetic results necessitates some form of patient education through pharmacogenomic counseling.

Synthesis of major pharmacogenomics pretest counseling themes: a multisite comparison.

The accessibility of pharmacogenomic (PGx) testing has grown substantially over the last decade and with it has arisen a demand for patients to be counseled on the use of these tests. While guidelines exist for the use of PGx results; objective determinants for who should receive PGx testing remain incomplete. PGx clinical services have been created to meet these screening and education needs and significant variability exists between these programs.

North Carolina's multi-institutional pharmacogenomics efforts with the North Carolina Precision Health Collaborative.

The North Carolina Precision Health Collaborative is an interdisciplinary, public-private consortium of precision health experts who strategically align statewide resources and strengths to elevate precision health in the state and beyond. Pharmacogenomics (PGx) is a key area of focus for the North Carolina Precision Health Collaborative. Experts from Atrium Health's Levine Cancer Institute, Duke University/Duke Health System, Mission Health and the University of North Carolina (UNC) at Chapel Hill/UNC Health System have collaborated since 2017 to implement strategic PGx initiatives, including basic sciences research, translational research and clinical implementation of germline testing into practice and policy.

Ultrafiltration and Injection of Islet Regenerative Stimuli Secreted by Pancreatic Mesenchymal Stromal Cells.

The secretome of mesenchymal stromal cells (MSCs) is enriched for biotherapeutic effectors contained within and independent of extracellular vesicles (EVs) that may support tissue regeneration as an injectable agent. We have demonstrated that the intrapancreatic injection of concentrated conditioned media (CM) produced by bone marrow MSC supports islet regeneration and restored glycemic control in hyperglycemic mice, ultimately providing a platform to elucidate components of the MSC secretome. Herein, we extend these findings using human pancreas-derived MSC (Panc-MSC) as "biofactories" to enrich for tissue regenerative stimuli housed within distinct compartments of the secretome.

Development of a Genomic Data Flow Framework: Results of a Survey Administered to NIH-NHGRI IGNITE and eMERGE Consortia Participants.

Precision health's more individualized molecular approach will enrich our understanding of disease etiology and patient outcomes. Universal implementation of precision health will not be feasible, however, until there is much greater automation of processes related to genomic data transmission, transformation, and interpretation. In this paper, we describe a framework for genomic data flow developed by the Clinical Informatics Work Group of the NIH National Human Genome Research Institute (NHGRI) IGNITE Network consortium.

Characterization of a Vimentin /Nestin proteome and tissue regenerative secretome generated by human pancreas-derived mesenchymal stromal cells.

Multipotent/mesenchymal stromal cells (MSCs) exist within a variety of postnatal tissues; however, global proteomic analyses comparing tissue-specific MSC are limited. Using human bone marrow (BM)-derived MSCs as a gold standard, we used label-free mass spectrometry and functional assays to characterize the proteome, secretome, and corresponding function of human pancreas-derived MSCs (Panc-MSCs) with a classical phenotype (CD90+/CD73+/CD105+/CD45-/CD31-). Both MSC subtypes expressed mesenchymal markers vimentin, α-SMA, and STRO-1; however, expression of nestin was increased in Panc-MSCs.

Implementing pharmacogenetic testing in rural primary care practices: a pilot feasibility study.

Assess feasibility and perspectives of pharmacogenetic testing/PGx in rural, primary care physician (PCP) practices when PCPs are trained to interpret/apply results and testing costs are covered. Participants included PCPs who agreed to training, surveys and interviews and eligible patients who agreed to surveys and testing. 51 patients from three practices participated.

Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing.

Purpose: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers.

Methods: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption.

Human Multipotent Stromal Cell Secreted Effectors Accelerate Islet Regeneration.

Human multipotent stromal cells (hMSC) can induce islet regeneration after transplantation via the secretion of proteins that establish an islet regenerative niche. However, the identity of hMSC-secreted signals and the mechanisms by which pancreatic islet regeneration is induced remain unknown. Recently, mammalian pancreatic α-cells have been shown to possess considerable plasticity, and differentiate into β-like cells after near complete β-cell loss or overexpression of key transcriptional regulators.

Peptide-modified methacrylated glycol chitosan hydrogels as a cell-viability supporting pro-angiogenic cell delivery platform for human adipose-derived stem/stromal cells.

Cell-based therapies involving the injection of adipose-derived stem/stromal cells (ASCs) within rationally designed biomaterials are a promising approach for stimulating angiogenesis. With this focus, the current work explored the effects of incorporating integrin-binding RGD or IKVAV peptides within in situ-gelling N-methacrylate glycol chitosan (MGC) hydrogels on the response of encapsulated human ASCs. Initial studies focused on hydrogel characterization to validate that the MGC, MGC-RGD, and MGC-IKVAV hydrogels had similar biomechanical properties.

Driver mutations in Janus kinases in a mouse model of B-cell leukemia induced by deletion of PU.1 and Spi-B.

Precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with recurrent mutations that occur in cancer-initiating cells. There is a need to understand how driver mutations influence clonal evolution of leukemia. The E26-transformation-specific (ETS) transcription factors PU.

Implementing a personalized medicine program in a community health system.

The implementation of a de novo personalized medicine program in a rural community health system serving an underserved population is described. Focusing on the safe use of drugs impacted by genetic variations in the non-oncology setting, we first addressed drug-gene pairs designated by the US FDA in black-box warnings (codeine, clopidogrel, abacavir, carbamazepine). The program's first success was a policy change to remove codeine from the pediatric formulary, rather than a testing recommendation.

Inhibition of Retinoic Acid Production Expands a Megakaryocyte-Enriched Subpopulation with Islet Regenerative Function.

Islet regeneration is stimulated after transplantation of human umbilical cord blood (UCB) hematopoietic progenitor cells with high aldehyde dehydrogenase (ALDH)-activity into NOD/SCID mice with streptozotocin (STZ)-induced β cell ablation. ALDH progenitor cells represent a rare subset within UCB that will require expansion without the loss of islet regenerative functions for use in cell therapies. ALDH cells efficiently expand (>70-fold) under serum-free conditions; however, high ALDH-activity is rapidly diminished during culture coinciding with emergence of a committed megakaryocyte phenotype CD41+/CD42+/CD38+.

BMS 493 Modulates Retinoic Acid-Induced Differentiation During Expansion of Human Hematopoietic Progenitor Cells for Islet Regeneration.

Cellular therapies are emerging as a novel treatment strategy for diabetes. Thus, the induction of endogenous islet regeneration in situ represents a feasible goal for diabetes therapy. Umbilical cord blood-derived hematopoietic progenitor cells (HPCs), isolated by high aldehyde dehydrogenase activity (ALDH), have previously been shown to reduce hyperglycemia after intrapancreatic (iPan) transplantation into streptozotocin (STZ)-treated nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice.

Prediction of chemotherapy-induced nausea and vomiting from patient-reported and genetic risk factors.

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is common among cancer patients. Early identification of patients at risk for CINV may help to personalize anti-emetic therapies. To date, few studies have examined the combined contributions of patient-reported and genetic risk factors to CINV.

Inhibition of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid Progenitor Cells with Vascular Regenerative Function.

Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.

Proteomic characterisation reveals active Wnt-signalling by human multipotent stromal cells as a key regulator of beta cell survival and proliferation.

Aims/hypothesis: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration.