Host-derived Interleukin 1α induces an immunosuppressive tumor microenvironment via regulating monocyte-to-macrophage differentiation.

Tumor-associated macrophages exhibit high heterogeneity and contribute to the establishment of an immunosuppressive tumor microenvironment (TME). Although numerous studies have demonstrated that extracellular factors promote macrophage proliferation and polarization, the regulatory mechanisms governing the differentiation process to generate phenotypically, and functionally diverse macrophage subpopulations remain largely unexplored. In this study, we examined the influence of interleukin 1α (IL-1α) on the development of an immunosuppressive TME using orthotopic transplantation murine models of breast cancer. Deletion of host Il1α led to the rejection of inoculated congenic tumors. Single-cell sequencing analysis revealed that CX3CR1+ macrophage cells were the primary sources of IL-1α in the TME. The absence of IL-1α reprogrammed the monocyte-to-macrophage differentiation process within the TME, characterized by a notable decrease in the subset of CX3CR+ ductal-like macrophages and an increase in iNOS-expressing inflammatory cells. Comparative analysis of gene signatures in both human and mouse macrophage subsets suggested that IL-1α deficiency shifted the macrophage polarization from M2 to M1 phenotypes, leading to enhanced cytotoxic T lymphocyte activity in the TME. Importantly, elevated levels of IL-1α in human cancers were associated with worse prognosis following immunotherapy. These findings underscore the pivotal role of IL-1α in shaping an immune-suppressive TME through the regulation of macrophage differentiation and activity, highlighting IL-1α as a potential target for breast cancer treatment.

Avatar assistant: improving social skills in students with an ASD through a computer-based intervention.

This study assessed the efficacy of FaceSay, a computer-based social skills training program for children with Autism Spectrum Disorders (ASD). This randomized controlled study (N = 49) indicates that providing children with low-functioning autism (LFA) and high functioning autism (HFA) opportunities to practice attending to eye gaze, discriminating facial expressions and recognizing faces and emotions in FaceSay's structured environment with interactive, realistic avatar assistants improved their social skills abilities. The children with LFA demonstrated improvements in two areas of the intervention: emotion recognition and social interactions. The children with HFA demonstrated improvements in all three areas: facial recognition, emotion recognition, and social interactions. These findings, particularly the measured improvements to social interactions in a natural environment, are encouraging.

Clinical case rounds in child and adolescent psychiatry: enuresis and ADHD in older children and an adolescent treated with stimulant medication: a case series.

Uncommonly, older children and adolescents can present with a history of enuresis. Resolution of enuresis followed the diagnosis and treatment of Attention Deficit Hyperactivity Disorder (ADHD) in each child in this case series. Subjects were three children with DSM-IV-TR ADHD, who presented with a history of primary nocturnal enuresis (PNE). Our results reveal that a subgroup of children with ADHD plus enuresis, when treated with stimulant medication, demonstrated resolution of enuresis as well as ADHD. These results suggest clinical implications for providers treating children and adolescents with enuresis and ADHD.