Systemic IFN-I combined with topical TLR7/8 agonists promotes distant tumor suppression by c-Jun-dependent IL-12 expression in dendritic cells.

Dendritic cell (DC) activation by pattern recognition receptors like Toll-like-receptors (TLRs) is crucial for cancer immunotherapies. Here, we demonstrate the effectiveness of the TLR7/8 agonist imiquimod (IMQ) in treating both local tumors and distant metastases. Administered orally, IMQ activates plasmacytoid DCs (pDCs) to produce systemic type I interferons (IFN-I) required for TLR7/8 upregulation in DCs and macrophages, sensitizing them to topical IMQ treatment, which is essential for therapeutic efficacy.

Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression.

Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology.

Estimating the Prevalence of Child Abuse and Neglect Among Adolescents in Primary Care Through Diagnoses Codes and Free-Text EHR Clinical Notes.

Introduction: Adolescents' child abuse and neglect experiences are often under-documented in primary care, leading to missed opportunities for interventions. This study compares the prevalence of child abuse and neglect cases identified by diagnostic codes versus a natural language processing approach of clinical notes.

Method: We retrospectively analyzed data from 8,157 adolescents, using ICD-10 codes and a natural language processing algorithm to identify child abuse and neglect cases and applied topic modeling on clinical notes to extract prevalent topics.

Weak-Field Coherent Control of Ultrafast Molecule Making.

Coherent control of ultrafast molecule making from colliding reactants is crucial for realizing coherent control of binary photoreactions (CCBP). To handle diverse excitation scenarios, feasibility with both weak and strong fields is essential. We experimentally demonstrate here the weak-field feasibility, achieving it even under thermally hot conditions typical of chemical reactions.

"We are protectors, not protestors": global impacts of extractivism on human-nature bonds.

Unlabelled: This article analyzes the global impacts of extractivism on human-nature bonds. To do so, we rely on socio-ecological conflict data from the Global Atlas of Environmental Justice. Over 1800 cases involving resistance to the destruction of nature, cultures, cosmologies, worldviews, ancestral origins, and sacred places are analyzed using log-linear regression compared to 1600 cases that do not report such loss.