Systems-level liquid biopsy in advanced prostate cancer.

Treatment for castration-resistant prostate cancer (CRPC) primarily involves suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling or lineage plasticity that drives emergence of AR-independent phenotypes.

Closure of Earth's Global Seasonal Cycle of Energy Storage.

The global seasonal cycle of energy in Earth's climate system is quantified using observations and reanalyses. After removing long-term trends, net energy entering and exiting the climate system at the top of the atmosphere (TOA) should agree with the sum of energy entering and exiting the ocean, atmosphere, land, and ice over the course of an average year. Achieving such a balanced budget with observations has been challenging.

Observational Assessment of Changes in Earth's Energy Imbalance Since 2000.

Satellite observations from the Clouds and the Earth's Radiant Energy System show that Earth's energy imbalance has doubled from 0.5 ± 0.2 Wm during the first 10 years of this century to 1.

North Atlantic Heat Transport Convergence Derived from a Regional Energy Budget Using Different Ocean Heat Content Estimates.

This study uses an oceanic energy budget to estimate the ocean heat transport convergence in the North Atlantic during 2005-2018. The horizontal convergence of the ocean heat transport is estimated using ocean heat content tendency primarily derived from satellite altimetry combined with space gravimetry. The net surface energy fluxes are inferred from mass-corrected divergence of atmospheric energy transport and tendency of the ECMWF ERA5 reanalysis combined with top-of-the-atmosphere radiative fluxes from the clouds and the Earth's radiant energy system project.

AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients.

Circulating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone.

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.

Longitudinal Impact of a Novel Condolence Expression Curriculum.

Pediatric residents lack training in expressing condolences to bereaved families after a child's death. We previously developed a novel curriculum that improved residents' comfort with expressing condolences, and now we report assessment of the longitudinal impact of this curriculum on residents' practices of condolence expression. We applied Kern's 6-step approach to develop, implement, and evaluate a condolence expression curriculum.

Role of PPARγ in dyslipidemia and altered pulmonary functioning in mice following ozone exposure.

Exposure to ozone causes decrements in pulmonary function, a response associated with alterations in lung lipids. Pulmonary lipid homeostasis is dependent on the activity of peroxisome proliferator activated receptor gamma (PPARγ), a nuclear receptor that regulates lipid uptake and catabolism by alveolar macrophages (AMs). Herein, we assessed the role of PPARγ in ozone-induced dyslipidemia and aberrant lung function in mice.

Radiofrequency ablation prior to total knee arthroplasty does not improve post-surgical pain or recovery: a double-blinded, multi-center, randomized clinical trial.

Background: Radiofrequency ablation (RFA) targeting the genicular nerves is an effective treatment for knee pain due to osteoarthritis. The aim of this study was to determine the effects of two RFA interventions delivered preoperatively on early postoperative pain management and subjective outcomes after total knee arthroplasty (TKA).

Methods: One hundred forty-three participants were enrolled in this double blinded, sham-controlled prospective randomized trial.

Endangered Nectar-Feeding Bat Detected by Environmental DNA on Flowers.

(the Mexican long-nosed bat) is an endangered nectar-feeding bat species that follows "nectar corridors" as it migrates from Mexico to the southwestern United States. Locating these nectar corridors is key to their conservation and may be possible using environmental DNA (eDNA) from these bats. Hence, we developed and tested DNA metabarcoding and qPCR eDNA assays to determine whether could be detected by sampling the agave flowers on which it feeds.

Cooled radiofrequency ablation of genicular nerves provides 24-Month durability in the management of osteoarthritic knee pain: Outcomes from a prospective, multicenter, randomized trial.

Objective: To assess long-term outcomes of cooled radiofrequency ablation (CRFA) of genicular nerves for chronic knee pain due to osteoarthritis (OA).

Methods: A prospective, observational extension of a randomized, controlled trial was conducted on adults randomized to CRFA. Subjects were part of a 12-month clinical trial comparing CRFA of genicular nerves to a single hyaluronic injection for treatment of chronic OA knee pain, who then agreed to visits at 18- and 24-months post CRFA and had not undergone another knee procedure since.

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial.

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.

CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study.

Background: Standard chemotherapy remains inadequate in metastatic pancreatic adenocarcinoma. Combining an agonistic CD40 monoclonal antibody with chemotherapy induces T-cell-dependent tumour regression in mice and improves survival. In this study, we aimed to evaluate the safety of combining APX005M (sotigalimab) with gemcitabine plus nab-paclitaxel, with and without nivolumab, in patients with pancreatic adenocarcinoma to establish the recommended phase 2 dose.

Cooled Radiofrequency Ablation Compared with a Single Injection of Hyaluronic Acid for Chronic Knee Pain: A Multicenter, Randomized Clinical Trial Demonstrating Greater Efficacy and Equivalent Safety for Cooled Radiofrequency Ablation.

Background: Knee osteoarthritis is a painful and sometimes debilitating disease that often affects patients for years. Current treatments include short-lasting and often repetitive nonsurgical options, followed by surgical intervention for appropriate candidates. Cooled radiofrequency ablation (CRFA) is a minimally invasive procedure for the treatment of pain related to knee osteoarthritis.

Cooled radiofrequency ablation provides extended clinical utility in the management of knee osteoarthritis: 12-month results from a prospective, multi-center, randomized, cross-over trial comparing cooled radiofrequency ablation to a single hyaluronic acid injection.

Background: Safe and effective non-surgical treatments are an important part of the knee osteoarthritis (OA) treatment algorithm. Cooled radiofrequency ablation (CRFA) and hyaluronic acid (HA) injections are two commonly used modalities to manage symptoms associated with knee OA.

Methods: A prospective 1:1 randomized study was conducted in 177 patients comparing CRFA to HA injection with follow-ups at 1, 3, 6 and 12 months.

The Italian Network for Tumor Bio-Immunotherapy (NIBIT) Foundation: ongoing and prospective activities in immuno-oncology.

The ongoing revolution in cancer immunotherapy stems from the knowledge that distinct immune-checkpoints regulate the physiological crosstalk between and among immune cells by delivering inhibitory or activating signals. These notions, and the availability of mAb directed to diverse immune-checkpoint molecules, have led to a significant clinical improvement in cancer treatment. In this scenario, further achievements are undoubtedly to be expected from the contribution of novel, proof-of-principle clinical trials designed to explore the therapeutic efficacy of new immunotherapy-based combinations and treatment sequences.

Caregiver knowledge and preferences for gross motor function information in cerebral palsy.

Aim: To determine caregiver knowledge and preferences for gross motor information and examine differences across Gross Motor Function Classification System (GMFCS) levels.

Method: A questionnaire was developed. Respondents reported GMFCS knowledge, preference for knowledge, and experience with GMFCS and motor curve information.

Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.

Tailored Educational Approaches for Consumer Health: A Model to Address Health Promotion in an Era of Personalized Medicine.

Purpose: To develop a model, based on market segmentation, to improve the quality and efficiency of health promotion materials and programs.

Design: Market segmentation to create segments (groups) based on a cross-sectional questionnaire measuring individual characteristics and preferences for health information. Educational and delivery recommendations developed for each group.

A geo-view into historical patterns of smoke-free policy coverage in the USA.

Introduction: Ample evidence shows that implementation of smoke-free policies can significantly reduce tobacco use. The indoor smoke-free policy coverage in the U.S.