Potent antitumor activity of a designed interleukin-21 mimic.

Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a broad range of affinities while dampening suppressive regulatory T (Treg) cell responses, but current approaches achieve these goals with limited success. Here, we report a IL-21 mimic, 21h10, designed to have augmented stability and high signaling potency in both humans and mice. In multiple animal models and in human melanoma patient derived organotypic tumor spheroids (PDOTS), 21h10 showed robust antitumor activity.

Racial and Educational Isolation are Associated with Worse Outcomes in Congenital Heart Disease.

Background: Sociodemographic factors influence outcomes in children with congenital heart disease (CHD). We predict an association between measures of social isolation and outcomes in infants with complex CHD. These measures, racial (RI) and educational (EI) isolation range from 0 to 1, with 0 being no isolation and 1 being fully isolated within a specific population.

Risk Factors and Outcomes Associated with Gaps in Care in Children with Congenital Heart Disease.

Adults with congenital heart disease (CHD) benefit from cardiology follow-up at recommended intervals of ≤ 2 years. However, benefit for children is less clear given limited studies and unclear current guidelines. We hypothesize there are identifiable risks for gaps in cardiology follow-up in children with CHD and that gaps in follow-up are associated with differences in healthcare utilization.

Metacognitive accuracy predicts self-reported quality of life following traumatic brain injury.

Objective: Metacognition and quality of life (QoL) are both adversely affected by traumatic brain injury (TBI), but the relation between them is not fully understood. As such, the purpose of this study was to determine the degree to which metacognitive accuracy predicts QoL in individuals with TBI.

Methods: Eighteen participants with moderate-to-severe TBI completed a stimulus-response task requiring the discrimination of emotions depicted in pictures of faces and then provided a retrospective confidence judgment after each response.

DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity.

Diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG) signaling by converting DAG to phosphatidic acid, thereby suppressing pathways downstream of T cell receptor signaling. Using a dual DGKα/ζ inhibitor (DGKi), tumor-specific CD8 T cells with different affinities (TRP1 and TRP1), and altered peptide ligands, we demonstrate that inhibition of DGKα/ζ can lower the signaling threshold for T cell priming. TRP1 and TRP1 CD8 T cells produced more effector cytokines in the presence of cognate antigen and DGKi.

Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following infection.

Lyme disease is caused by the bacterial pathogen , which can be readily modeled in laboratory mice. In order to understand the cellular and transcriptional changes that occur during infection, we conducted single-cell RNA sequencing (scRNA-seq) of ankle joints of infected C57BL/6 mice over time. We found that macrophages/monocytes, T cells, synoviocytes and fibroblasts all showed significant differences in gene expression of both inflammatory and non-inflammatory genes that peaked early and returned to baseline before the typical resolution of arthritis.

Blockade of innate inflammatory cytokines TNF, IL-1, or IL-6 overcomes virotherapy-induced cancer equilibrium to promote tumor regression.

Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would antagonize the anti-tumor immune response and lead to tumor outgrowth. We previously demonstrated that continuous treatment with a non-replicating herpes simplex virus 1 expressing interleukin (IL)-12 induces a state of cancer immune equilibrium highly dependent on interferon-γ.

Impact of Prenatal Diagnosis of Critical Congenital Heart Disease on Preoperative and Postoperative Outcomes.

The objective of this study was to assess the relationship of prenatal diagnosis of critical congenital heart disease (CHD) to preoperative and postoperative patient findings. Retrospective analysis of neonates with critical CHD who underwent cardiothoracic surgery at one of four centers in North Carolina between 2008 and 2013. Surgical data collected by sites for submission to the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and the North Carolina CHD Lifespan Database were queried.

IFNγ is a central node of cancer immune equilibrium.

Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune system. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. Using a non-replicating HSV-1 vector expressing interleukin-12 (d106S-IL12), we developed a mouse model of therapy-induced immune equilibrium, a phenomenon previously seen only in humans.

Third-Grade Academic Performance and Episodes of Cardiac Care Among Children with Congenital Heart Defects.

Children with congenital heart defects (CHDs) are at risk for poor academic performance. The degree to which receipt of health care services is associated with adverse academic outcomes is not known. We examined the association between episodes of cardiac care and third-grade performance in children with CHD.

Dose rate versus gantry speed performance evaluation for slow gantry speeds using DICOM RT plans.

Purpose: Varian provides a DICOM RT Plan file that users can deliver to the electronic portal imaging device (EPID) panel to confirm the linear accelerator delivers consistent dose output across several regions of interest for varying dose rates and gantry speeds (DRGS). This work investigates if (a) the vendor-provided DRGS DICOM RT Plan is valid within the gantry speed range of stereotactic body radiation therapy (SBRT) treatments, and (b) if output constancy is maintained at those gantry speeds on a TrueBeam.

Methods: Python code was written to iterate through all control points in the DICOM RT Plan files for 21 SBRT patients and the MU per degree values were calculated for each control point.

Implementation and Evaluation of a TG-275 Key Recommendation: An Additional Early Physics Check.

Purpose: We report our experience of performing an extra, earlier physics plan check as recommended by the American Association of Physicists in Medicine Task Group 100 and Task Group 275 reports. We assessed utilization and timing of the extra check as well as the time required in a medium-sized clinic.

Methods And Materials: We retrospectively extracted and analyzed timestamp data from the record and verify system for the quality checklist (QCL) items related to treatment planning and physics "prechecks" for 3487 patients treated at our institution from February 2017 to February 2021.

The Role of Neuroinflammation in Neuropsychiatric Disorders Following Traumatic Brain Injury: A Systematic Review.

Background: Neuropsychiatric symptoms are common following traumatic brain injury (TBI), but their etiological onset remains unclear. Mental health research implicates neuroinflammation in the development of psychiatric disorders. The presence of neuroinflammatory responses after TBI thus prompts an investigation of their involvement in the emergence of neuropsychiatric disorders postinjury.

Using Biomarkers to Predict Memantine Effects in Alzheimer's Disease: A Proposal and Proof-Of-Concept Demonstration.

Memantine's benefits in Alzheimer's disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual's clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid).

Simultaneous Characterization of Implant Wear and Tribocorrosion Debris within Its Corresponding Tissue Response Using Infrared Chemical Imaging.

Biotribology is one of the key branches in the field of artificial joint development. Wear and corrosion are among fundamental processes which cause material loss in a joint biotribological system; the characteristics of wear and corrosion debris are central to determining the bioreactivity. Much effort has been made elucidating the debris-induced tissue responses.

Evaluating emissions reductions from zero waste strategies under dynamic conditions: A case study from Boston.

In 2018 and 2019 the City of Boston (Massachusetts, USA) conducted zero waste and carbon neutral planning efforts. Here we present the results of an accompanying analysis of the impacts of zero waste strategies on greenhouse gases (GHG) emissions associated with waste treatment. Emissions analysis in the waste sector is complicated by the contribution of significant indirect impacts that can exhibit temporal and spatial heterogeneity.

Checkpoint blockade toxicities: Insights into autoimmunity and treatment.

Checkpoint blockade has transformed not only the way cancers are treated, but also highlighted the importance of mounting a proper immune response against tumors. Despite advances in the field of immunotherapy, many patients develop a range of inflammatory toxicities that limit the efficacy of these therapies. These toxicities range from barrier site injury, such as colitis, to endocrine organ dysfunction, such as diabetes.

Increasing the value and efficiency of herbicide resistance surveys.

The scale of herbicide resistance within a cropping region can be estimated and monitored using surveys of weed populations. The current approach to herbicide resistance surveys is time-consuming, logistically challenging and costly. Here we review past and current approaches used in herbicide resistance surveys with the aims of (i) defining effective survey methodologies, (ii) highlighting opportunities for improving efficiencies through the use of new technologies and (iii) identifying the value of repeated region-wide herbicide resistance surveys.

Infrared spectral microscopy as a tool to monitor lung fibrosis development in a model system.

Tissue fibrosis is a progressive and destructive disease process that can occur in many different organs including the liver, kidney, skin, and lungs. Fibrosis is typically initiated by inflammation as a result of chronic insults such as infection, chemicals and autoimmune diseases. Current approaches to examine organ fibrosis are limited to radiological and histological analyses.