Trailing Blackberry Genotypes Differ in Yield and Postharvest Fruit Quality during Establishment in an Organic Production System

Four blackberry (Rubus L. subgenus Rubus Watson) cultivars (‘Obsidian’, ‘Black Diamond’, ‘Metolius’, ‘Onyx’) and two advanced selections (ORUS 1939-4 and ORUS 2635-1) were evaluated during the establishment years of an organic production system for fresh market. The planting was established in Spring 2010 using approved practices for organic production and was certified organic in 2012, the first fruiting year. Plants were irrigated using a dripline under a woven polyethylene groundcover (weed mat) installed for weed management. Liquid fertilizers injected through the drip system were used at rates of 56 kg·ha⁻¹ total nitrogen (N) in 2011–12 and 90 kg·ha⁻¹ total N in 2013. Genotypes differed in the level of nutrients measured in primocane leaves. Tissue phosphorus (P), potassium (K), sulfur (S), iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) concentrations were within the recommended standards, but tissue calcium (Ca), magnesium (Mg), and boron (B) were deficient in some or all genotypes. Although two cultivars and both advanced selections responded well in terms of plant growth and yield to the organic production system used, yields in ‘Onyx’ and ‘Metolius’ were considered low for commercial production. In contrast, the higher yielding ‘Obsidian’ and ORUS-2635-1 appeared to be the best suited for organic fresh market production as a result of larger fruit size, greater fruit firmness, higher sugar-to-acid ratios, lower postharvest percentmoisture loss in ORUS-2635-1, and the longest number of marketable storage days at 5°C in ‘Obsidian’.This is the publisher’s final pdf. The published article is copyrighted by the American Society for Horticultural Science and can be found at: http://hortsci.ashspublications.org/.Keywords: Firmness, Brix, Shelf life, Rubus, Titratable acidity, Percent soluble solids, Storage, p

Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study.

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.We thank the patients and families who participated in this study, caregivers, the study investigators, and their staff, and the JPCE (NCT02779751) clinical trial team. Pembrolizumab was provided by Merck & Co., Inc., Kenilworth, NJ, USA. We thank Anne Chain from the Department of Quantitative Pharmacology & PharmacometricsImmune/Oncology, Merck & Co., Inc., Kenilworth, NJ, USA for her contributions to this work, which included pembrolizumab PK and ADA analysis. This work and medical writing support was funded by Eli Lilly and Company.S

A review of satellite-based global agricultural monitoring systems available for Africa

Abstract The increasing frequency and severity of extreme climatic events and their impacts are being realized in many regions of the world, particularly in smallholder crop and livestock production systems in Sub-Saharan Africa (SSA). These events underscore the need for timely early warning. Satellite Earth Observation (EO) availability, rapid developments in methodology to archive and process them through cloud services and advanced computational capabilities, continue to generate new opportunities for providing accurate, reliable, and timely information for decision-makers across multiple cropping systems and for resource-constrained institutions. Today, systems and tools that leverage these developments to provide open access actionable early warning information exist. Some have already been employed by early adopters and are currently operational in selecting national monitoring programs in Angola, Kenya, Rwanda, Tanzania, and Uganda. Despite these capabilities, many governments in SSA still rely on traditional crop monitoring systems, which mainly rely on sparse and long latency in situ reports with little to no integration of EO-derived crop conditions and yield models. This study reviews open-access operational agricultural monitoring systems available for Africa. These systems provide the best-available open-access EO data that countries can readily take advantage of, adapt, adopt, and leverage to augment national systems and make significant leaps (timeliness, spatial coverage and accuracy) of their monitoring programs. Data accessible (vegetation indices, crop masks) in these systems are described showing typical outputs. Examples are provided including crop conditions maps, and damage assessments and how these have integrated into reporting and decision-making. The discussion compares and contrasts the types of data, assessments and products can expect from using these systems. This paper is intended for individuals and organizations seeking to access and use EO to assess crop conditions who might not have the technical skill or computing facilities to process raw data into informational products

Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

Abstract Background Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1–4 CKD. Methods Patients with stages 1–4 CKD (18–74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. Results Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52–5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. Conclusion Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 )https://deepblue.lib.umich.edu/bitstream/2027.42/148285/1/12967_2019_Article_1808.pd

Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer.

Endocrine therapies for prostate cancer inhibit the androgen receptor (AR) transcription factor. In most cases, AR activity resumes during therapy and drives progression to castration-resistant prostate cancer (CRPC). However, therapy can also promote lineage plasticity and select for AR-independent phenotypes that are uniformly lethal. Here, we demonstrate the stem cell transcription factor Krüppel-like factor 5 (KLF5) is low or absent in prostate cancers prior to endocrine therapy, but induced in a subset of CRPC, including CRPC displaying lineage plasticity. KLF5 and AR physically interact on chromatin and drive opposing transcriptional programs, with KLF5 promoting cellular migration, anchorage-independent growth, and basal epithelial cell phenotypes. We identify ERBB2 as a point of transcriptional convergence displaying activation by KLF5 and repression by AR. ERBB2 inhibitors preferentially block KLF5-driven oncogenic phenotypes. These findings implicate KLF5 as an oncogene that can be upregulated in CRPC to oppose AR activities and promote lineage plasticity

Predicting September Arctic Sea Ice: A Multi-Model Seasonal Skill Comparison

Abstract This study quantifies the state-of-the-art in the rapidly growing field of seasonal Arctic sea ice prediction. A novel multi-model dataset of retrospective seasonal predictions of September Arctic sea ice is created and analyzed, consisting of community contributions from 17 statistical models and 17 dynamical models. Prediction skill is compared over the period 2001–2020 for predictions of Pan-Arctic sea ice extent (SIE), regional SIE, and local sea ice concentration (SIC) initialized on June 1, July 1, August 1, and September 1. This diverse set of statistical and dynamical models can individually predict linearly detrended Pan-Arctic SIE anomalies with skill, and a multi-model median prediction has correlation coefficients of 0.79, 0.86, 0.92, and 0.99 at these respective initialization times. Regional SIE predictions have similar skill to Pan-Arctic predictions in the Alaskan and Siberian regions, whereas regional skill is lower in the Canadian, Atlantic, and Central Arctic sectors. The skill of dynamical and statistical models is generally comparable for Pan-Arctic SIE, whereas dynamical models outperform their statistical counterparts for regional and local predictions. The prediction systems are found to provide the most value added relative to basic reference forecasts in the extreme SIE years of 1996, 2007, and 2012. SIE prediction errors do not show clear trends over time, suggesting that there has been minimal change in inherent sea ice predictability over the satellite era. Overall, this study demonstrates that there are bright prospects for skillful operational predictions of September sea ice at least three months in advance.</jats:p

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair.

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required for homologous recombination. Collectively, these findings reveal that CRY1 is hormone-induced in tumors, is further stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation. These studies identify the circadian factor CRY1 as pro-tumorigenic and nominate CRY1 as a new therapeutic target