NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth.

Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.

On the identity of Opopaea euphorbicola Strand, 1909 and first records of three other non-native goblin spiders from Ascension Island (Araneae: Oonopidae).

N/A.

Impact of California's naloxone co-prescription law on emergency department visits, 30-day mortality, and prescription patterns.

Objective: Opioid overdose is a public health epidemic adversely impacting individuals and communities. To combat this, California passed a law mandating that prescribers offer a naloxone prescription in certain circumstances. Our objective was to evaluate associations with California's naloxone prescription mandate and emergency department (ED) overdose visits/hospitalizations, opioid and naloxone prescribing, and 30-day mortality.

SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.

Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease.

Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.

Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26-27.

RNASEH2B loss and PARP inhibition in advanced prostate cancer.

BACKGROUNDClinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome, and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.

AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease.

Inter- and Intra-Patient Repeatability of Radiomic Features from Multiparametric Whole-Body MRI in Patients with Metastatic Prostate Cancer.

(1) Background: We assessed the test-re-test repeatability of radiomics in metastatic castration-resistant prostate cancer (mCPRC) bone disease on whole-body diffusion-weighted (DWI) and T1-weighted Dixon MRI. (2) Methods: In 10 mCRPC patients, 1.5 T MRI, including DWI and T1-weighted gradient-echo Dixon sequences, was performed twice on the same day.

Computable phenotype for diagnostic error: developing the data schema for application of symptom-disease pair analysis of diagnostic error (SPADE).

Objectives: Diagnostic errors are the leading cause of preventable harm in clinical practice. Implementable tools to quantify and target this problem are needed. To address this gap, we aimed to generalize the Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) framework by developing its computable phenotype and then demonstrated how that schema could be applied in multiple clinical contexts.

An all-inclusive model for predicting invasive bacterial infection in febrile infants age 7-60 days.

Background: Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days.

Methods: Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.

Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BCL-2-associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC.

Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance.

Inflammation is a hallmark of cancer. In patients with cancer, peripheral blood myeloid expansion, indicated by a high neutrophil-to-lymphocyte ratio, associates with shorter survival and treatment resistance across malignancies and therapeutic modalities. Whether myeloid inflammation drives progression of prostate cancer in humans remain unclear.

CA FIRST (California Febrile Infant Risk Stratification Tool) Algorithm Development in a Learning Health System.

Introduction There is considerable variation in the approach to infants presenting to the emergency department (ED) with fever. The authors' primary aim was to develop a robust set of algorithms using community ED data to inform modifications of broader clinical guidance. Methods The authors report the development of California Febrile Infant Risk Stratification Tool (CA FIRST) using key components of the Roseville Protocol (ROS) and American Academy of Pediatrics (AAP) Clinical Practice Guideline (CPG).

Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy.

Unlabelled: The pro-oncogenic activities of estrogen receptor alpha (ERα) drive breast cancer pathogenesis. Endocrine therapies that impair the production of estrogen or the action of the ERα are therefore used to prevent primary disease metastasis. Although recent successes with ERα degraders have been reported, there is still the need to develop further ERα antagonists with additional properties for breast cancer therapy.

The Akt/mTOR and MNK/eIF4E pathways rewire the prostate cancer translatome to secrete HGF, SPP1 and BGN and recruit suppressive myeloid cells.

Cancer is highly infiltrated by myeloid-derived suppressor cells (MDSCs). Currently available immunotherapies do not completely eradicate MDSCs. Through a genome-wide analysis of the translatome of prostate cancers driven by different genetic alterations, we demonstrate that prostate cancer rewires its secretome at the translational level to recruit MDSCs.