Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

Retraction Notice to "New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19" [Multiple Sclerosis and Related Disorders 57 (2022) 103321].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).

Characterization of risk factors for early ambulation in paraplegic dogs with absent pain perception undergoing decompressive surgery for thoracolumbar intervertebral disk extrusions.

Background: Current literature warrants surgical decompression in paraplegic dogs with absent pain perception (APP), but the rate of ambulatory dogs with APP following thoracolumbar (TL) IVDE surgery in a clinical setting remains unknown. Furthermore, the outcome of paraplegic APP French Bulldogs (FBs) is anecdotally considered poor. The aims of this study were threefold within a large population of TL-IVDE paraplegic dogs with APP undergoing decompressive surgery: (1) to characterize early spontaneous pelvic limb movement and ambulation following surgery; (2) to identify risk factors for the recovery of ambulation; and (3) to compare the outcome of FBs and Dachshunds presenting with APP.

Exploring the effects of climate change on child malnutrition: protocol for a scoping review.

Introduction: Rapid climate changes in the early 21st century have triggered a global syndemic intertwining obesity, undernutrition and climate change, profoundly affecting health, especially children. Despite increasing research, a significant gap persists in understanding the mechanisms linking climate change to child malnutrition, particularly in children under 5 years old. This protocol proposes a scoping review to address this gap, with the aim of mapping the available evidence on the relationship between climate change and malnutrition among children under 5 years old.

Tagless LysoIP for immunoaffinity enrichment of native lysosomes from clinical samples.

Lysosomes are implicated in a wide spectrum of human diseases including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models has substantially moved the field forward, but studying lysosomal dysfunction in human patients remains challenging. Here, we report the development of the 'tagless LysoIP' method, designed to enable the rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.