Proteolysis-targeting vaccines (PROTAVs) for robust combination immunotherapy of melanoma.

Protein/peptide subunit vaccines are promising to promote the tumor therapeutic efficacy of immune checkpoint blockade (ICB). However, current protein/peptide vaccines elicit limited antitumor T cell responses, leading to suboptimal therapeutic efficacy. Here, we present proteolysis-targeting vaccines (PROTAVs) that facilitate antigen proteolytic processing and cross-presentation to potentiate T cell responses for robust ICB combination immunotherapy of melanoma.

IL-33 Induces Cellular and Exosomal miR-146a Expression as a Feedback Inhibitor of Mast Cell Function.

IL-33 is an inflammatory cytokine that promotes allergic disease by activating group 2 innate lymphoid cells, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. Homeostatic control of IL-33 signaling is poorly understood.

Novel intraocular shielding device for eye plaque brachytherapy using magnetite nanoparticles: A proof-of-concept study using radiochromic film and Monte Carlo simulations.

Purpose: Eye plaque brachytherapy is a mainstay treatment for uveal melanomas despite potential toxicities to normal tissues. This work proposes a nanoparticle ferrofluid as a novel intraocular shielding device. With a modified magnetic plaque, the shielding particles are drawn to the tumor surface, attenuating dose beyond the tumor while maintaining prescription dose to the target.

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells.

There is a clinical need for new treatment options addressing allergic disease. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that have anti-inflammatory properties. We tested the effects of the SSRI fluoxetine on IgE-induced function of mast cells, which are critical effectors of allergic inflammation.

Inhibiting Isoprenylation Suppresses FcεRI-Mediated Mast Cell Function and Allergic Inflammation.

IgE-mediated mast cell activation is a driving force in allergic disease in need of novel interventions. Statins, long used to lower serum cholesterol, have been shown in multiple large-cohort studies to reduce asthma severity. We previously found that statins inhibit IgE-induced mast cell function, but these effects varied widely among mouse strains and human donors, likely due to the upregulation of the statin target, 3-hydroxy-3-methylgutaryl-CoA reductase.

Infectivity of three Mayaro Virus geographic isolates in human cell lines.

Mayaro virus (MAYV) is an emergent arthropod-borne virus that causes an acute febrile illness accompanied by arthralgia, similar to chikungunya virus. Increasing urbanization of MAYV outbreaks in the Americas has led to concerns for geographic expansion and spillover. Given the potential importance of this pathogen, we sought to fill critical gaps in knowledge regarding MAYV infectivity and geographic variation.

Association of Diet Patterns and Post-Operative Tympanostomy Tube Otorrhea: A Pilot Study.

Objective: The objective of this study was to explore diet patterns in children with tympanostomy tube placement (TTP) complicated by postoperative tympanostomy tube otorrhea.

Study Design: Cross-sectional survey and retrospective cohort study.

Methods: Caregivers of children (0-12 years old), at a tertiary-care pediatric hospital who underwent TTP within 6 months to 2 years prior to enrollment were included.

Corrigendum: Phenotypic and genetic parameters of circadian rhythms from core body temperature profiles and their relationships with beef steers' production efficiency profiles during successive winter feeding periods.

[This corrects the article DOI: 10.3389/fgene.2023.

Phenotypic and genetic parameters of circadian rhythms from core body temperature profiles and their relationships with beef steers' production efficiency profiles during successive winter feeding periods.

This 2-year study evaluated differences in circadian parameters obtained from measures of core body temperatures using telemetric reticulo-rumen and rectal devices during two winter feeding regimes in western Canada. The study also estimated phenotypic correlations and genetic parameters associated with circadian parameters and other production traits in each feeding regime. Each year, 80 weaned steer calves (initial age: 209 ± 11 days; BW: 264 ± 20 kg) from the same cohort were tested over two successive regimes, Fall-Winter (FW) and Winter-Spring (WS) at Lanigan, Saskatchewan, Canada.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

Background & Aims: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer.

Methods: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis.

Targeting Mast Cells in Allergic Disease: Current Therapies and Drug Repurposing.

The incidence of allergic disease has grown tremendously in the past three generations. While current treatments are effective for some, there is considerable unmet need. Mast cells are critical effectors of allergic inflammation.

A Multicenter Study of Left Ventricular Assist Device-Related Gastrointestinal Bleeding.

Introduction: Continuous left ventricular assist devices (LVADs) offer hemodynamic support in advanced and decompensated heart failure but are often complicated by gastrointestinal bleeding (GIB) in medically fragile patients.

Methods: We performed a retrospective analysis of 475 consecutive patients who underwent LVAD implantation at the Massachusetts General Hospital and Tufts Medical Center from 2008 to 2019 and identified 128 patients with clinically significant GIB. Clinical characteristics of each bleeding event, including procedures and interventions, were recorded.

Characterization of Humulus lupulus glycosides with porous graphitic carbon and sequential high performance liquid chromatography quadrupole time-of-flight mass spectrometry and high performance liquid chromatography fractionation.

Monoterpenes contribute to the characteristic aroma of several hop varieties and may occur as nonvolatile glycosides. Upon hydrolysis, the volatile terpenes are released from the glycoside precursors. Little is known, however, about the glycoside composition of hops.

High-Dose Celecoxib for Pain After Pediatric Tonsillectomy: A Randomized Controlled Trial.

Objective: Pediatric tonsillectomy causes significant postoperative pain. Newer nonsteroidal anti-inflammatory drugs such as celecoxib control pain without increasing bleeding risk, but in prior studies provided only modest pain reduction at standard doses. We aimed to determine if high-dose celecoxib (double the usual pediatric dose) is effective for pain, without increasing bleeding or other risks.

Stair-step strategy and immunomodulatory feed ingredient supplementation for grazing heat-stressed Bos indicus-influenced beef heifers.

On day 0 of years 1 and 2, 64 Brangus crossbred heifers per year were stratified by initial body weight (BW) and age (mean = 257 ± 20 kg and 271 ± 22 d) and allocated into 16 bahiagrass (Paspalum notatum) pastures (4 heifers per pasture per yr). Treatments were randomly allotted to pastures in a 2 × 2 factorial arrangement of treatments (4 pastures per treatment per yr). Treatments consisted of concentrate dry matter (DM) supplementation at 1.

IL-33 priming amplifies ATP-mediated mast cell cytokine production.

Inflammatory responses are required to block pathogen infection but can also lead to hypersensitivity and chronic inflammation. Barrier tissues actively release IL-33, ATP, and other alarmins during cell stress, helping identify pathogenic stimuli. However, it is unclear how these signals are integrated.

Fluvastatin enhances IL-33-mediated mast cell IL-6 and TNF production.

Statins are HMG-CoA reductase inhibitors prescribed for lowering cholesterol. They can also inhibit inflammatory responses by suppressing isoprenylation of small G proteins. Consistent with this, we previously found that fluvastatin suppresses IgE-mediated mast cell function.

Antibody Responses to SARS-CoV-2 After Infection or Vaccination in Children and Young Adults With Inflammatory Bowel Disease.

Background: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

Methods: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines.

Antibody Responses to SARS-CoV-2 after Infection or Vaccination in Children and Young Adults with Inflammatory Bowel Disease.

Background: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

Methods: e performed a prospective longitudinal cohort study evaluating SARS-CoV-2 Spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines.

Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis.

Background: Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC).

Methods: This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria.

Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo.

Mast cells are found primarily at interfaces with the external environment, where they provide protection from pathogens but also elicit allergic inflammation. Mast cell activation by antigen-induced aggregation of IgE bound to the high affinity receptor, FcεRI, is a critical factor leading to inflammation and bronchoconstriction. We previously found that Stat5 is activated by FcεRI and that Stat5B suppression decreased IgE-induced cytokine production in vitro, but in vivo responses have not been assessed.

Evaluation of Variety, Maturity, and Farm on the Concentrations of Monoterpene Diglycosides and Hop Volatile/Nonvolatile Composition in Five Cultivars.

Pentose-hexose monoterpene alcohol glycosides were isolated and semiquantitatively measured in dried cones using UHPLC-qTOF-MS/MS and HPLC fractionation followed by GC-MS. The samples evaluated included hop cones from five important dual-purpose cultivars (varieties) in the United States, from two locations (farms) per variety and from three distinct harvest time points (maturities) per location, as dictated by dry-matter (% w/w) at the time of harvest. Hop variety accounted for the biggest variation among the concentrations of pentose-hexose monoterpene alcohol glycosides as well as other volatile and nonvolatile chemical factors measured in the samples.

Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes.

Background: The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time.

Results: We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion.

Timing the First Pediatric Tracheostomy Tube Change: A Randomized Controlled Trial.

Objective: The first pediatric tracheostomy tube change often occurs within 7 days after placement; however, the optimal timing is not known. The primary objective was to determine the rate of adverse events of an early tube change. Secondary objectives compared rates of significant peristomal wounds, sedation requirements, and expedited intensive care discharges.

Magnetic resonance angiography (MRA) in preoperative planning for patients with 22q11.2 deletion syndrome undergoing craniofacial and otorhinolaryngologic procedures.

Introduction: Patients with 22q11.2 deletion syndrome (22q11.2DS) have a variety of anatomic anomalies.