Head and neck squamous cell carcinoma (HNSCC) patients have a poor prognosis, with invasion and metastasis as major causes of mortality. The phosphatidylinositol 3-kinase (PI3K) pathway regulates a wide range of cellular processes crucial for tumorigenesis, and PIK3CA amplification and mutation are among the most common genetic alterations in human HNSCC. Compared with the well-documented roles of the PI3K pathway in cell growth and survival, the roles of the PI3K pathway in tumor invasion and metastasis have not been well delineated. We generated a PIK3CA genetically engineered mouse model (PIK3CA-GEMM) in which wild-type PIK3CA is overexpressed in head and neck epithelium. Although PIK3CA overexpression alone was not sufficient to initiate HNSCC formation, it significantly increased tumor susceptibility in an oral carcinogenesis mouse model. PIK3CA overexpression in mouse oral epithelium increased tumor invasiveness and metastasis by increasing epithelial-mesenchymal transition and by enriching a cancer stem cell phenotype in tumor epithelial cells. In addition to these epithelial alterations, we also observed marked inflammation in tumor stroma. AKT is a central signaling mediator of the PI3K pathway. However, molecular analysis suggested that progression of PIK3CA-driven HNSCC is facilitated by 3-phosphoinositide-dependent protein kinase (PDK1) and enhanced transforming growth factor β (TGFβ) signaling rather than by AKT. Examination of human HNSCC clinical samples revealed that both PIK3CA and PDK1 protein levels correlated with tumor progression, highlighting the significance of this pathway. In summary, our results offer significant insight into how PIK3CA overexpression drives HNSCC invasion and metastasis, providing a rationale for targeting PI3K/PDK1 and TGFβ signaling in advanced HNSCC patients with PIK3CA amplification.

We report a new determination of q, the jet transport coefficient of the quark-gluon plasma. We use the JETSCAPE framework, which incorporates a novel multistage theoretical approach to in-medium jet evolution and Bayesian inference for parameter extraction. The calculations, based on the Matter and Lbt jet quenching models, are compared to experimental measurements of inclusive hadron suppression in Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC) and Pb+Pb collisions at the CERN Large Hadron Collider (LHC). The correlation of experimental systematic uncertainties is accounted for in the parameter extraction. The functional dependence of q on jet energy or virtuality and medium temperature is based on a perturbative picture of in-medium scattering, with components reflecting the different regimes of applicability of Matter and Lbt. In the multistage approach, the switch between Matter and Lbt is governed by a virtuality scale Q0. Comparison of the posterior model predictions to the RHIC and LHC hadron suppression data shows reasonable agreement, with moderate tension in limited regions of phase space. The distribution of q/T3 extracted from the posterior distributions exhibits weak dependence on jet momentum and medium temperature T, with 90% credible region (CR) depending on the specific choice of model configuration. The choice of Matter+Lbt, with switching at virtuality Q0, has 90% CR of 240 GeV/c. The value of Q0, determined here for the first time, is in the range 2.0-2.7 GeV.

We study the properties of the strongly coupled quark-gluon plasma with a multistage model of heavy-ion collisions that combines the TRENTo initial condition ansatz, free-streaming, viscous relativistic hydrodynamics, and a relativistic hadronic transport. A model-to-data comparison with Bayesian inference is performed, revisiting assumptions made in previous studies. The role of parameter priors is studied in light of their importance for the interpretation of results. We emphasize the use of closure tests to perform extensive validation of the analysis workflow before comparison with observations. Our study combines measurements from the Large Hadron Collider (LHC) and the Relativistic Heavy Ion Collider (RHIC), achieving a good simultaneous description of a wide range of hadronic observables from both colliders. The selected experimental data provide reasonable constraints on the shear and the bulk viscosities of the quark-gluon plasma at T≈ 150-250 MeV, but their constraining power degrades at higher temperatures, T 250 MeV. Furthermore, these viscosity constraints are found to depend significantly on how viscous corrections are handled in the transition from hydrodynamics to the hadronic transport. Several other model parameters, including the free-streaming time, show similar model sensitivity, while the initial condition parameters associated with the TRENTo ansatz are quite robust against variations of the particlization prescription. We also report on the sensitivity of individual observables to the various model parameters. Finally, Bayesian model selection is used to quantitatively compare the agreement with measurements for different sets of model assumptions, including different particlization models and different choices for which parameters are allowed to vary between RHIC and LHC energies.

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350  MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

The JETSCAPE framework is a modular and versatile Monte Carlo software package for the simulation of high energy nuclear collisions. In this work we present a new tune of JETSCAPE, called PP19, and validate it by comparison to jet-based measurements in p+p collisions, including inclusive single jet cross sections, jet shape observables, fragmentation functions, charged hadron cross sections, and dijet mass cross sections. These observables in p+p collisions provide the baseline for their counterparts in nuclear collisions. Quantifying the level of agreement of JETSCAPE results with p+p data is thus necessary for meaningful applications of JETSCAPE to A+A collisions. The calculations use the JETSCAPE PP19 tune, defined in this paper, based on version 1.0 of the JETSCAPE framework. For the observables discussed in this work calculations using JETSCAPE PP19 agree with data over a wide range of collision energies at a level comparable to standard Monte Carlo codes. These results demonstrate the physics capabilities of the JETSCAPE framework and provide benchmarks for JETSCAPE users.

We study parton energy-momentum exchange with the quark gluon plasma (QGP) within a multistage approach composed of in-medium Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution at high virtuality, and (linearized) Boltzmann transport formalism at lower virtuality. This multistage simulation is then calibrated in comparison with high-pT charged hadrons, D mesons, and the inclusive jet nuclear modification factors, using Bayesian model-to-data comparison, to extract the virtuality-dependent transverse momentum broadening transport coefficient q. To facilitate this undertaking, we develop a quantitative metric for validating the Bayesian workflow, which is used to analyze the sensitivity of various model parameters to individual observables. The usefulness of this new metric in improving Bayesian model emulation is shown to be highly beneficial for future such analyses.

Hot QCD physics studies the nuclear strong force under extreme temperature and densities. Experimentally these conditions are achieved via high-energy collisions of heavy ions at the Relativistic Heavy Ion Collider (RHIC) and the Large Hadron Collider (LHC). In the past decade, a unique and substantial suite of data was collected at RHIC and the LHC, probing hydrodynamics at the nucleon scale, the temperature dependence of the transport properties of quark-gluon plasma, the phase diagram of nuclear matter, the interaction of quarks and gluons at different scales and much more. This document, as part of the 2023 nuclear science long range planning process, was written to review the progress in hot QCD since the 2015 Long Range Plan for Nuclear Science, as well as highlight the realization of previous recommendations, and present opportunities for the next decade, building on the accomplishments and investments made in theoretical developments and the construction of new detectors. Furthermore, this document provides additional context to support the recommendations voted on at the Joint Hot and Cold QCD Town Hall Meeting, which are reported in a separate document.