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).

Quantitative Electroencephalography Alpha:Delta Ratio and Suppression Ratio Monitoring During Infant Aortic Arch Reconstruction.

Background: During infant aortic arch reconstruction, traditional electroencephalography (EEG) provides only qualitative data limiting neuromonitoring efficacy. Interhemispheric differences in the alpha:delta ratio (ADR) and suppression ratio (SR) measured using quantitative EEG generate numerical trends that may suggest cerebral ischemia. We hypothesized that the ADR and SR during cardiopulmonary bypass (CPB) would correlate with hemodynamics, and that ADR and SR interhemispheric differences would precede neurological injury from infants requiring aortic arch reconstruction.

TRIO RVEMVS: A Bayesian framework for rare variant association analysis with expectation-maximization variable selection using family trio data.

It is commonly reported that rare variants may be more functionally related to complex diseases than common variants. However, individual rare variant association tests remain challenging due to low minor allele frequency in the available samples. This paper proposes an expectation maximization variable selection (EMVS) method to simultaneously detect common and rare variants at the individual variant level using family trio data.

Search for Soft Unclustered Energy Patterns in Proton-Proton Collisions at 13 TeV.

The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.