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Responses to immunotherapy are uncommon in estrogen receptor (ER)-positive breast cancer and to date, lack predictive markers. This randomized phase II study defines safety and response rate of epigenetic priming in ER-positive breast cancer patients treated with checkpoint inhibitors as primary endpoints. Secondary and exploratory endpoints included PD-L1 modulation and T-cell immune-signatures. 34 patients received vorinostat, tamoxifen and pembrolizumab with no excessive toxicity after progression on a median of five prior metastatic regimens. Objective response was 4% and clinical benefit rate (CR + PR + SD > 6 m) was 19%. T-cell exhaustion (CD8 +  PD-1 + /CTLA-4 + ) and treatment-induced depletion of regulatory T-cells (CD4 + Foxp3 + /CTLA-4 + ) was seen in tumor or blood in 5/5 patients with clinical benefit, but only in one non-responder. Tumor lymphocyte infiltration was 0.17%. Only two non-responders had PD-L1 expression >1%. This data defines a novel immune signature in PD-L1-negative ER-positive breast cancer patients who are more likely to benefit from immune-checkpoint and histone deacetylase inhibition (NCT02395627). ER-positive breast cancer patients do not usually respond to immunotherapy. In this phase II clinical trial, the authors report the safety and efficacy of combining vorinostat and pembrolizumab with tamoxifen in ER-positive breast cancers and provide evidence that T-cell exhaustion may serve as a potential signature for the response of this combination therapy.

Art Museum Practicum, comprises nine graduate students who engage with three texts and several projects to practice practical skills such as SWOT analyses (strengths, weaknesses, opportunities, and threats) and grant-writing exercises as well as addressing the real-word issues of museum work, such as job precarity, pay, and benefits that are incommensurate with experience and education (Gill & Pratt, 2008; Ross, 2022; Wetenhall, 2019; Whitaker, 2021), inconsistencies between stated missions and institutional practices (Ng & Ware 2014), relevance to communities (Gurian, 2021; Simon, 2010), and the legacies of colonialism that permeate museum practices like microscopic filaments (Bennett, 1995; Karp & Levine, 1991; Lonetree, 2009; Sleeper-Smith, 2009). Through these texts, we positioned art museums as open ecosystems that exist within interrelated internal and external environments; troubled existing paradigms of museology through the consideration of \"queer/ing\" ethics, display practices, meaningmaking, and engagement toward a new ontology for museums, and then thought about ways tomorrow's museum workers can \"grow liberation and justice, learn from the world around us how to best collaborate, and how to shape change (brown, 2017, p. 1). [...]zines provide an accessible medium for sharing and decentering knowledge and creativity, while also giving creators a space to reflect on their personal interests, experiences, and opinions. [...]brown (2017) reminds us that growth emerges from consistent, intentional reflection of both ourselves and the systems we participate in-those systems in which we hope to evoke positive change.

We present an analysis of the first 20 second cadence light curves obtained by the TESS space telescope during its extended mission. We find improved precision of 20 second data compared to 2 minute data for bright stars when binned to the same cadence (≈10%–25% better for T ≲ 8 mag, reaching equal precision at T ≈ 13 mag), consistent with pre-flight expectations based on differences in cosmic-ray mitigation algorithms. We present two results enabled by this improvement. First, we use 20 second data to detect oscillations in three solar analogs (γ Pav, ζ Tuc, and π Men) and use asteroseismology to measure their radii, masses, densities, and ages to ≈1%, ≈3%, ≈1%, and ≈20% respectively, including systematic errors. Combining our asteroseismic ages with chromospheric activity measurements, we find evidence that the spread in the activity–age relation is linked to stellar mass and thus the depth of the convection zone. Second, we combine 20 second data and published radial velocities to recharacterize π Men c, which is now the closest transiting exoplanet for which detailed asteroseismology of the host star is possible. We show that π Men c is located at the upper edge of the planet radius valley for its orbital period, confirming that it has likely retained a volatile atmosphere and that the “asteroseismic radius valley” remains devoid of planets. Our analysis favors a low eccentricity for π Men c (<0.1 at 68% confidence), suggesting efficient tidal dissipation (Q/k 2,1 ≲ 2400) if it formed via high-eccentricity migration. Combined, these early results demonstrate the strong potential of TESS 20 second cadence data for stellar astrophysics and exoplanet science.

We present an analysis of the first 20-second cadence light curves obtained by the TESS space telescope during its extended mission. We find a precision improvement of 20-second data compared to 2-minute data for bright stars when binned to the same cadence (~10-25% better for T<~8 mag, reaching equal precision at T~13 mag), consistent with pre-flight expectations based on differences in cosmic ray mitigation algorithms. We present two results enabled by this improvement. First, we use 20-second data to detect oscillations in three solar analogs (gamma Pav, zeta Tuc and pi Men) and use asteroseismology to measure their radii, masses, densities and ages to ~1%, ~3%, ~1% and ~20% respectively, including systematic errors. Combining our asteroseismic ages with chromospheric activity measurements we find evidence that the spread in the activity-age relation is linked to stellar mass and thus convection-zone depth. Second, we combine 20-second data and published radial velocities to re-characterize pi Men c, which is now the closest transiting exoplanet for which detailed asteroseismology of the host star is possible. We show that pi Men c is located at the upper edge of the planet radius valley for its orbital period, confirming that it has likely retained a volatile atmosphere and that the \"asteroseismic radius valley\" remains devoid of planets. Our analysis favors a low eccentricity for pi Men c (<0.1 at 68% confidence), suggesting efficient tidal dissipation (Q/k <~ 2400) if it formed via high-eccentricity migration. Combined, these early results demonstrate the strong potential of TESS 20-second cadence data for stellar astrophysics and exoplanet science.