Conservation benefits of a large marine protected area network that spans multiple ecosystems.

Marine protected areas (MPAs) are widely implemented tools for long-term ocean conservation and resource management. Assessments of MPA performance have largely focused on specific ecosystems individually and have rarely evaluated performance across multiple ecosystems either in an individual MPA or across an MPA network. We evaluated the conservation performance of 59 MPAs in California's large MPA network, which encompasses 4 primary ecosystems (surf zone, kelp forest, shallow reef, deep reef) and 4 bioregions, and identified MPA attributes that best explain performance.

A tradeoff between safety and freedom: Adults' lived experiences of ARFID.

Background: Avoidant restrictive food intake disorder (ARFID) is characterized as a pattern of restrictive eating leading to significant medical and/or psychosocial impairment (American Psychiatric Association in Diagnostic and statistical manual of mental disorders, American Psychiatric Association, Washington, D.C., 2013).

Serial Trauma Abdominal Ultrasound in Children (STAUNCH): A Pilot Study.

Background: Ultrasound has established utility within pediatric emergency medicine and has an added benefit of avoiding excessive radiation exposure. The serial focused assessment with sonography in trauma (sFAST) examination is a potential alternative to improve pediatric trauma evaluation. We sought to evaluate the accuracy of sFAST in pediatric patients with blunt abdominal trauma.

Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial.

Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan.

Targeting Wnt signaling for improved glioma immunotherapy.

Introduction: Despite aggressive standard-of-care therapy, including surgery, radiation, and chemotherapy, glioblastoma recurrence is almost inevitable and uniformly lethal. Activation of glioma-intrinsic Wnt/β-catenin signaling is associated with a poor prognosis and the proliferation of glioma stem-like cells, leading to malignant transformation and tumor progression. Impressive results in a subset of cancers have been obtained using immunotherapies including anti-CTLA4, anti-PD-1, and anti-PD-L1 or chimeric antigen receptor (CAR) T cell therapies.

A marine protected area network does not confer community structure resilience to a marine heatwave across coastal ecosystems.

Marine protected areas (MPAs) have gained attention as a conservation tool for enhancing ecosystem resilience to climate change. However, empirical evidence explicitly linking MPAs to enhanced ecological resilience is limited and mixed. To better understand whether MPAs can buffer climate impacts, we tested the resistance and recovery of marine communities to the 2014-2016 Northeast Pacific heatwave in the largest scientifically designed MPA network in the world off the coast of California, United States.

Inclusion of 4-1BB Costimulation Enhances Selectivity and Functionality of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells.

Unlabelled: Chimeric antigen receptor (CAR) T cell immunotherapy is emerging as a powerful strategy for cancer therapy; however, an important safety consideration is the potential for off-tumor recognition of normal tissue. This is particularly important as ligand-based CARs are optimized for clinical translation. Our group has developed and clinically translated an IL13(E12Y) ligand-based CAR targeting the cancer antigen IL13Rα2 for treatment of glioblastoma (GBM).

Marine protected areas, marine heatwaves, and the resilience of nearshore fish communities.

Anthropogenic stressors from climate change can affect individual species, community structure, and ecosystem function. Marine heatwaves (MHWs) are intense thermal anomalies where water temperature is significantly elevated for five or more days. Climate projections suggest an increase in the frequency and severity of MHWs in the coming decades.

The Compassion Club: A New Proposal for Transformation of Tobacco Retail.

Introduction: One major assumption in the current tobacco industry is the distribution of tobacco products through a system of commercial for-profit retail. However, other models of distribution that do not rely on this mechanism exist.

Aims And Methods: In this review, we examine the potential of a nonprofit Compassion Club model and discuss how the current existence of independent vape stores might provide the infrastructure to allow the transformation of tobacco distribution.

Barriers and Translational Solutions to Improving Community Living Outcomes among People of Color with Disabilities with Opioid Use Disorder: A Focus Group Perspective.

This investigation examined vocational rehabilitation, substance abuse, and mental health service providers' perceptions about barriers and potentially translational solutions to poor community living outcomes for people of color with disabilities (i.e., African Americans, Latinx, Native Americans and Alaskan Natives, Asian Americans, and Pacific islanders) who have opioid use disorder.

Interfacial electric fields catalyze Ullmann coupling reactions on gold surfaces.

The electric fields created at solid-liquid interfaces are important in heterogeneous catalysis. Here we describe the Ullmann coupling of aryl iodides on rough gold surfaces, which we monitor using the scanning tunneling microscope-based break junction (STM-BJ) and using mass spectrometry and fluorescence spectroscopy. We find that this Ullmann coupling reaction occurs only on rough gold surfaces in polar solvents, the latter of which implicates interfacial electric fields.

Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy.

IL13Rα2 is an attractive target due to its overexpression in a variety of cancers and rare expression in healthy tissue, motivating expansion of interleukin 13 (IL13)-based chimeric antigen receptor (CAR) T cell therapy from glioblastoma into systemic malignancies. IL13Rα1, the other binding partner of IL13, is ubiquitously expressed in healthy tissue, raising concerns about the therapeutic window of systemic administration. IL13 mutants with diminished binding affinity to IL13Rα1 were previously generated by structure-guided protein engineering.

Highly conducting single-molecule topological insulators based on mono- and di-radical cations.

Single-molecule topological insulators are promising candidates as conducting wires over nanometre length scales. A key advantage is their ability to exhibit quasi-metallic transport, in contrast to conjugated molecular wires which typically exhibit a low conductance that decays as the wire length increases. Here, we study a family of oligophenylene-bridged bis(triarylamines) with tunable and stable mono- or di-radicaloid character.

Antibody-based redirection of universal Fabrack-CAR T cells selectively kill antigen bearing tumor cells.

Background: Chimeric antigen receptor (CAR) T cells engineered to recognize and target tumor associated antigens have made a profound impact on the quality of life for many patients with cancer. However, tumor heterogeneity and intratumoral immune suppression reduce the efficacy of this approach, allowing for tumor cells devoid of the target antigen to seed disease recurrence. Here, we address the complexity of tumor heterogeneity by developing a universal CAR.

Spatial organization of heterogeneous immunotherapy target antigen expression in high-grade glioma.

High-grade (WHO grades III-IV) glioma remains one of the most lethal human cancers. Adoptive transfer of tumor-targeting chimeric antigen receptor (CAR)-redirected T cells for high-grade glioma has revealed promising indications of anti-tumor activity, but objective clinical responses remain elusive for most patients. A significant challenge to effective immunotherapy is the highly heterogeneous structure of these tumors, including large variations in the magnitudes and distributions of target antigen expression, observed both within individual tumors and between patients.

3D-organoid culture supports differentiation of human CAR iPSCs into highly functional CAR T cells.

Unlimited generation of chimeric antigen receptor (CAR) T cells from human-induced pluripotent stem cells (iPSCs) is an attractive approach for "off-the-shelf" CAR T cell immunotherapy. Approaches to efficiently differentiate iPSCs into canonical αβ T cell lineages, while maintaining CAR expression and functionality, however, have been challenging. We report that iPSCs reprogramed from CD62L naive and memory T cells followed by CD19-CAR engineering and 3D-organoid system differentiation confers products with conventional CD8αβ-positive CAR T cell characteristics.

Off-the-shelf, steroid-resistant, IL13Rα2-specific CAR T cells for treatment of glioblastoma.

Background: Wide-spread application of chimeric antigen receptor (CAR) T cell therapy for cancer is limited by the current use of autologous CAR T cells necessitating the manufacture of individualized therapeutic products for each patient. To address this challenge, we have generated an off-the-shelf, allogeneic CAR T cell product for the treatment of glioblastoma (GBM), and present here the feasibility, safety, and therapeutic potential of this approach.

Methods: We generated for clinical use a healthy-donor derived IL13Rα2-targeted CAR+ (IL13-zetakine+) cytolytic T-lymphocyte (CTL) product genetically engineered using zinc finger nucleases (ZFNs) to permanently disrupt the glucocorticoid receptor (GR) (GRm13Z40-2) and endow resistance to glucocorticoid treatment.

Emerging Conceptual Frameworks for Co-Serving Veterans of Color Across the State-Federal Vocational Rehabilitation Program: SVRAs, AIVRPs, and VA-VR&E.

Existing models of interagency collaborations serving the United States (U.S.) Armed Forces veterans of color, i.

Community Living Outcome Factors for People of Color with Disabilities and Concomitant Opioid Use Disorder: A Scoping Review.

This scoping review mapped the pertinent extant published and grey literature and policy to assess factors that promote positive community living outcomes among people of color with disabilities and concomitant opioid use disorder (OUD) in the United States (U.S.).