Highlights d Proteogenomic characterization reveals the functional impact of genomic alterations d Phosphoproteomics uncovers putative therapeutic targets downstream of KRAS d Multiomics links endothelial cell remodeling and glycolysis to immune exclusion d Proteomics and glycoproteomics reveal candidates for early detection or intervention

Highlights d A systematic inventory of HNSCC-associated proteins, phosphosites, and pathways d Three multi-omic subtypes linked to targeted treatment approaches and immunotherapy d Widespread deletion of immune modulatory genes accounts for loss of immunogenicity d Two modes of EGFR activation inform response to anti-EGFR monoclonal antibodies

Highlights d Unsupervised clustering revealed subtype with EMT and phosphoprotein signatures d Potential therapeutic vulnerabilities included survivin, NSD3, LSD1, and EZH2 d Rb phosphorylation nominated as a biomarker for trials with CDK4/6 inhibitors d Detailed immune landscape analysis highlighted targetable points of immuneregulation

Chemical reaction interface mass spectrometry (CRIMS) was coupled on-line with HPLC using a Vestec particle beam interface. A helium-assisted nebulizer provided added stability with no loss in accuracy or precision as compared to the thermospray nebulizer at flow rates of up to 1.0 mL/min using isocratic conditions. However, mass spectral response was found to be solvent-dependent for both the helium-assisted and thermospray nebulizers. Postcolumn solvent addition of methanol eliminated solvent-dependent decreases in mass spectral response. This allowed gradient HPLC elutions to be performed. Under these conditions, the flow of solvent into the particle beam interface was 2.5 mL/min, so a conventional thermospray nebulizer had to be used instead of the helium-assisted nebulizer. Experiments were conducted with the antianxiety agent buspirone in order to validate the methodology. Metabolites from in vitro incubations of [15N]/[14C]buspirone with rat liver slices were analyzed by gradient LC/CRIMS and by gradient LC/[14C] radioactivity counting. The response from LC/CRIMS analysis for individual metabolites was then compared with that obtained by LC/[14C] radioactivity counting. An excellent correlation was observed between the two methods for metabolites with quite different HPLC characteristics. Thus, gradient LC/CRIMS in combination with stable isotopes provides an alternative to using radioisotopes for carrying out drug metabolism studies.

Patients (n = 81) undergoing total hip replacement (THR) were randomized to receive either standard of care plus fibrin sealant (FS) (10 mL total) or standard of care alone to evaluate the efficacy of FS for reducing blood loss in THR. Considering the 81 intent-to-treat patients, adjusted perioperative blood loss was reduced significantly in the FS group, by 197 mL [95% CI: 45 mL, 319 mL] or 23.5% [95% CI: 5.4%, 38.1%] (p = 0.014). When protocol violators were eliminated, leaving 73 patients, the adjusted FS group perioperative bleeding was reduced by 221 mL [95% CI: 63 mL, 351 mL] or 27.1% [95% CI: 7.6%, 42.5%] (p = 0.0098).