Effective cancer immunotherapy depends on the robust activation of tumor-specific antigen-presenting cells (APC). Immune agonists encapsulated within nanoparticles (NP) can be delivered to tumor sites to generate powerful antitumor immune responses with minimal off-target dissemination. Systemic delivery enables widespread access to the microvasculature and draining to the APC-rich perivasculature. We developed an immuno-nanoparticle (immuno-NP) coloaded with cyclic diguanylate monophosphate, an agonist of the stimulator of interferon genes pathway, and monophosphoryl lipid A, and a Toll-like receptor 4 agonist, which synergize to produce high levels of type I IFNb. Using a murine model of metastatic triple-negative breast cancer, systemic delivery of these immuno-NPs resulted in significant therapeutic outcomes due to extensive upregulation of APCs and natural killer cells in the blood and tumor compared with control treatments. These results indicate that NPs can facilitate systemic delivery of multiple immunepotentiating cargoes for effective APC-driven local and systemic antitumor immunity.Significance: Systemic administration of an immunonanoparticle in a murine breast tumor model drives a robust tumor site-specific APC response by delivering two synergistic immune-potentiating molecules, highlighting the potential of nanoparticles for immunotherapy.

Hyperactive and damaging inflammation is a hallmark of severe rather than mild Coronavirus disease 2019 (COVID-19). To uncover key inflammatory differentiators between severe and mild COVID-19, we applied an unbiased single-cell transcriptomic analysis. We integrated two single-cell RNA-seq datasets with COVID-19 patient samples, one that sequenced bronchoalveolar lavage (BAL) cells and one that sequenced peripheral blood mononuclear cells (PBMCs). The combined cell population was then analyzed with a focus on genes associated with disease severity. The immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients in multiple cell types. Within those same cell types, the concurrent detection of other severity-associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. Thus, NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.

Background Continuous positive airway pressure (CPAP) is the gold standard of care in providing non-invasive positive pressure support to neonates in respiratory distress in high-resource settings. While safety has been demonstrated in low-resource settings, there is a lack of knowledge on the barriers and facilitators to proper implementation. Objective To identify and describe the barriers, facilitators, and priorities for future implementation of CPAP for neonates and infants in low-resource settings. Methods A systematic search (database inception to March 6, 2020) was performed on MEDLINE, Embase, Web of Science, CINAHL, Global Health, and the WHO Global Index Medicus using PRISMA-ScR guidelines. Original research articles pertaining to implementation of CPAP devices in low-resource settings, provider or parent perspectives and experiences with CPAP, cost-benefit analyses, and cost-effectiveness studies were included. Inductive content analysis was conducted. Findings 1385 article were screened and 54 studies across 19 countries met inclusion criteria. Six major themes emerged: device attributes, patient experiences, parent experiences, provider experiences, barriers, and facilitators. Nasal trauma was the most commonly reported complication. Barriers included unreliable electricity and lack of bioengineering support. Facilitators included training, mentorship and empowerment of healthcare providers. Device design, supply chain infrastructure, and training models were imperative to the adoption and sustainability of CPAP. Conclusion Sustainable implementation of CPAP in low resource settings requires easy-to-use devices, ready access to consumables, and holistic, user-driven training. Further research is necessary on standardizing metrics, interventions that support optimal provider performance, and conditions needed for successful long-term health system integration.

Hyperactive and damaging inflammation is a hallmark of severe rather than mild COVID-19 syndrome. To uncover key inflammatory differentiators between severe and mild COVID-19 disease, we applied an unbiased single-cell transcriptomic analysis. We integrated a bronchoalveolar lavage (BAL) dataset with a peripheral blood mononuclear cell dataset (PBMC) and analyzed the combined cell population, focusing on genes associated with disease severity. Distinct cell populations were detected in both BAL and PBMC where the immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients. The detection of other severity associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. The lncRNAs NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.