Early Experience With an Occupational JYNNEOS ( Orthopoxvirus ) Vaccination Program.

Objective: The aim of the study is to identify lessons learned implementing JYNNEOS vaccination for laboratory workers exposed to orthopoxviruses such as mpox.

Methods: Workers at risk of laboratory exposure were offered vaccine in a carefully planned occupational health program. Vaccine was procured from the Centers for Disease Control and Prevention (CDC) Drug Service, which has special requirements.

TAK-676: A Novel Stimulator of Interferon Genes (STING) Agonist Promoting Durable IFN-dependent Antitumor Immunity in Preclinical Studies.

Unlabelled: Oncology therapies targeting the immune system have improved patient outcomes across a wide range of tumor types, but resistance due to an inadequate T-cell response in a suppressive tumor microenvironment (TME) remains a significant problem. New therapies that activate an innate immune response and relieve this suppression may be beneficial to overcome this hurdle. TAK-676 is a synthetic novel stimulator of interferon genes (STING) agonist designed for intravenous administration.

Description of Pharmacogenomic Testing Among Patients Admitted to the Intensive Care Unit After Cardiovascular Surgery.

Background: Pharmacogenomic (PGx) testing has the potential to provide information on specific drug-metabolizing enzymes that may lead to an absence, reduction, or increase in medication effect in patients. There is a paucity of prospective studies examining PGx testing in the intensive care unit (ICU) setting.

Research Aims: To (1) obtain a PGx panel in a sample of cardiovascular (CV) surgical patients with a planned ICU stay and identify phenotypes, and (2) identify PGx variants that may inform treatment regimens and may warrant prescribing adjustments.

Role of tacrolimus in return of hand function after brachial plexus injury in a lung transplantation patient.

We report a patient who has been on tacrolimus for bilateral lung transplantation and presented with a brachial plexus injury (BPI), with unusual improvement of lower trunk innervated hand function. The lower trunk injury with resultant left hand paralysis had developed after his sternotomy 18 months ago. He has been treated with tacrolimus as part of his immunosuppression protocol since the surgery, without severe side effects.

Sample size re-estimation in a superiority clinical trial using a hybrid classical and Bayesian procedure.

When designing studies involving a continuous endpoint, the hypothesized difference in means ( ) and the assumed variability of the endpoint ( ) play an important role in sample size and power calculations. Traditional methods of sample size re-estimation often update one or both of these parameters using statistics observed from an internal pilot study. However, the uncertainty in these estimates is rarely addressed.

Time to achieving therapeutic international normalized ratio increases hospital length of stay after heart valve replacement surgery.

Background: Achieving a therapeutic international normalized ratio (INR) before hospital discharge is an important inpatient goal for patients undergoing mechanical cardiac valve replacement (MCVR). The use of clinical algorithms has reduced the time to achieve therapeutic INR (TTI) with warfarin therapy. Whether TTI prolongs length of stay (LOS) is unknown.

Sample size determination for a binary response in a superiority clinical trial using a hybrid classical and Bayesian procedure.

Background: When designing studies that have a binary outcome as the primary endpoint, the hypothesized proportion of patients in each population experiencing the endpoint of interest (i.e., π ,π ) plays an important role in sample size and power calculations.

Gene signature-based mapping of immunological systems and diseases.

Background: The immune system is multifaceted, structured by diverse components that interconnect using multilayered dynamic cellular processes. Genomic technologies provide a means for investigating, at the molecular level, the adaptations of the immune system in host defense and its dysregulation in pathological conditions. A critical aspect of intersecting and investigating complex datasets is determining how to best integrate genomic data from diverse platforms and heterogeneous sample populations to capture immunological signatures in health and disease.

TLR3 Signaling Promotes the Induction of Unique Human BDCA-3 Dendritic Cell Populations.

Conventional and plasmacytoid dendritic cells (cDCs and pDCs) are the two populations of DCs that can be readily identified in human blood. Conventional DCs have been subdivided into CD1c(+), or blood dendritic cells antigen (BDCA) 1 and CD141(+), or BDCA-3, DCs, each having both unique gene expression profiles and functions. BDCA-3 DCs express high levels of toll-like receptor 3 and upon stimulation with Poly I:C secrete IFN-β, CXCL10, and IL-12p70.

Selection of the effect size for sample size determination for a continuous response in a superiority clinical trial using a hybrid classical and Bayesian procedure.

Background: When designing studies that have a continuous outcome as the primary endpoint, the hypothesized effect size ([Formula: see text]), that is, the hypothesized difference in means ([Formula: see text]) relative to the assumed variability of the endpoint ([Formula: see text]), plays an important role in sample size and power calculations. Point estimates for [Formula: see text] and [Formula: see text] are often calculated using historical data. However, the uncertainty in these estimates is rarely addressed.

Complementarity and redundancy of IL-22-producing innate lymphoid cells.

Intestinal T cells and group 3 innate lymphoid cells (ILC3 cells) control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet-dependent differentiation of NCR(-) ILC3 cells into NCR(+) ILC3 cells.

Selection of the treatment effect for sample size determination in a superiority clinical trial using a hybrid classical and Bayesian procedure.

Specification of the treatment effect that a clinical trial is designed to detect (θA) plays a critical role in sample size and power calculations. However, no formal method exists for using prior information to guide the choice of θA. This paper presents a hybrid classical and Bayesian procedure for choosing an estimate of the treatment effect to be detected in a clinical trial that formally integrates prior information into this aspect of trial design.

Teriflunomide attenuates immunopathological changes in the dark agouti rat model of experimental autoimmune encephalomyelitis.

Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing-remitting multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils.

The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro.

Teriflunomide is an inhibitor of dihydro-orotate dehydrogenase (DHODH), and is hypothesized to ameliorate multiple sclerosis by reducing proliferation of stimulated lymphocytes. We investigated teriflunomide's effects on proliferation, activation, survival, and function of stimulated human peripheral blood mononuclear cell subsets in vitro. Teriflunomide had little/no impact on lymphocyte activation but exerted significant dose-dependent inhibition of T- and B-cell proliferation, which was uridine-reversible (DHODH-dependent).

Robust methods for population stratification in genome wide association studies.

Background: Genome-wide association studies can provide novel insights into diseases of interest, as well as to the responsiveness of an individual to specific treatments. In such studies, it is very important to correct for population stratification, which refers to allele frequency differences between cases and controls due to systematic ancestry differences. Population stratification can cause spurious associations if not adjusted properly.

Evaluating translocation gene fusions by SNP array data.

Somatic cell genetic alterations are a hallmark of tumor development and progression. Although various technologies have been developed and utilized to identify genetic aberrations, identifying genetic translocations at the chromosomal level is still a challenging task. High density SNP microarrays are useful to measure DNA copy number variation (CNV) across the genome.

Naive precursors of human regulatory T cells require FoxP3 for suppression and are susceptible to HIV infection.

CD4+CD25+ human regulatory T cells (Treg cells), which express the transcription factor FoxP3, suppress T cell activation. In this study, we sought to define cellular and molecular mechanisms of human Treg cell differentiation. A subset of human naive CD4+ T cells that are CD25+ express high levels of FoxP3.

Protein kinase C-theta;: signaling from the center of the T-cell synapse.

The hypothesis that protein kinase C (PKC)-theta; plays an important role in T-lymphocyte activation, as indicated by numerous studies in cell lines, was recently confirmed in mice deficient in the expression of this enzyme. In response to TCR stimulation, peripheral T cells lacking PKC-theta; failed to activate NF-kappaB and AP-1, and to express IL-2. This revealed a critical function for this PKC family member in linking membrane-proximal activation cascades to transcriptional responses governing T-cell activation.