Transcriptional mediators of treatment resistance in lethal prostate cancer.

Metastatic castration-resistant prostate cancer is typically lethal, exhibiting intrinsic or acquired resistance to second-generation androgen-targeting therapies and minimal response to immune checkpoint inhibitors1. Cellular programs driving resistance in both cancer and immune cells remain poorly understood. We present single-cell transcriptomes from 14 patients with advanced prostate cancer, spanning all common metastatic sites. Irrespective of treatment exposure, adenocarcinoma cells pervasively coexpressed multiple androgen receptor isoforms, including truncated isoforms hypothesized to mediate resistance to androgen-targeting therapies2,3. Resistance to enzalutamide was associated with cancer cell-intrinsic epithelial-mesenchymal transition and transforming growth factor-ß signaling. Small cell carcinoma cells exhibited divergent expression programs driven by transcriptional regulators promoting lineage plasticity and HOXB5, HOXB6 and NR1D2 (refs. 4-6). Additionally, a subset of patients had high expression of dysfunction markers on cytotoxic CD8+ T cells undergoing clonal expansion following enzalutamide treatment. Collectively, the transcriptional characterization of cancer and immune cells from human metastatic castration-resistant prostate cancer provides a basis for the development of therapeutic approaches complementing androgen signaling inhibition.

Observation of Genuine One-Way Einstein-Podolsky-Rosen Steering.

Within the hierarchy of inseparable quantum correlations, Einstein-Podolsky-Rosen steering is distinguished from both entanglement and Bell nonlocality by its asymmetry-there exist conditions where the steering phenomenon changes from being observable to not observable, simply by exchanging the role of the two measuring parties. While this one-way steering feature has been previously demonstrated for the restricted class of Gaussian measurements, for the general case of positive-operator-valued measures even its theoretical existence has only recently been settled. Here, we prove, and then experimentally observe, the one-way steerability of an experimentally practical class of entangled states in this general setting. As well as its foundational significance, the demonstration of fundamentally asymmetric nonlocality also has practical implications for the distribution of the trust in quantum communication networks.

Timing of specimen collection for blood cultures from febrile patients with bacteremia.

Bloodstream infections are an important cause of morbidity and mortality. Physician orders for blood cultures often specify that blood specimens be collected at or around the time of a temperature elevation, presumably as a means of enhancing the likelihood of detecting significant bacteremia. In a multicenter study, which utilized retrospective patient chart reviews as a means of collecting data, we evaluated the timing of blood culture collection in relation to temperature elevations in 1,436 patients with bacteremia and fungemia. The likelihood of documenting bloodstream infections was not significantly enhanced by collecting blood specimens for culture at the time that patients experienced temperature spikes. A subset analysis based on patient age, gender, white blood cell count and specific cause of bacteremia generally also failed to reveal any associations.