Bayer (Belgium)

46 Background: LDH is a potential prognostic biomarker of outcomes for pts with mCRC. This retrospective, observational cohort study describes RW LDH testing patterns and assesses LDH as a prognostic factor for overall survival (OS) in pts receiving chemotherapy (CT) for mCRC in the USA. Methods: Pts with mCRC, ≥18 years (yrs) of age, who initiated first line (1L) CT (index date) between January 1, 2016, and November 30, 2022, were identified in the nationwide de-identified Flatiron Electronic Health Record-derived database. Practice patterns for LDH testing are described. Pts were categorized into normal vs abnormal LDH baseline (≤3 months prior to/at index date) value based on the lab reference range. Prognostic relationship between normal vs abnormal LDH baseline value and OS was assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Results: Of 15,329 eligible pts, 57% were male, 49% were ≥65 yrs of age and 66% had ECOG performance status 0–1; 59% had stage IV disease at initial diagnosis; 29% had a KRAS mutation (at any time ≤30 days post-index; 35% not tested). Median time from mCRC diagnosis to index was 35 days. Most common 1L regimens were FOLFOX ± bevacizumab (48%), FOLFIRI ± bevacizumab (15%), and capecitabine (13%). Median follow up from index date was 15.6 months (mos); 60% died. LDH testing was performed in 2,547 pts (17%) during baseline and 3,379 pts (22%) post-index. Among those with ≥1 LDH test during each line of therapy (LOT), median number of LDH tests per pt was 4–6 and median time from line initiation to first LDH test was 7–10 days across the first five LOTs (Table). Among LDH tested pts during follow-up (n=3,379), 21% and 40% had abnormal and normal LDH values at baseline, respectively (39% missing). Demographic characteristics of abnormal vs normal LDH pts were similar; abnormal LDH pts were more likely to be ≥65 years (52% vs 49%), African American or Black (12% vs 7%), and reside in the Northeast (30% vs 21%). Median OS (95% CI) in pts with normal vs abnormal baseline LDH was 29.9 (28.3, 31.7) mos vs 16.8 (14.8, 18.2) mos. In multivariate Cox proportional-hazards model, pts with abnormal baseline LDH values had higher risk of death (HR 1.91, p<0.0001) after adjustment for pt demographic and clinical characteristics. Conclusions: In RW clinical practice in the USA, only one-fifth of mCRC pts receiving CT undergo LDH testing even though LDH value has been found to be a prognostic factor of OS. Efforts to increase LDH testing may help guide treatment decisions in this setting. [Table: see text]

PURPOSERogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy.METHODSFORT-1 (ClinicalTrials.gov identifier: NCT03410693) was a phase II/III, randomized, open-label trial. Patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed.RESULTSORRs were 20.7% (rogaratinib, 18/87; 95% CI, 12.7 to 30.7) and 19.3% (chemotherapy, 17/88; 95% CI, 11.7 to 29.1). Median overall survival was 8.3 months (95% CI, 6.5 to not estimable) and 9.8 months (95% CI, 6.8 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P = .67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21; 95% CI, 29.8 to 74.3) for rogaratinib and 26.7% (4/15; 95% CI, 7.8 to 55.1) for chemotherapy.CONCLUSIONTo our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.

Runoff and erosion are the most important transport pathways of water, sediment, and associated pesticides from sloped agricultural fields. This results in the loss of fertile topsoil material, nutrients, irrigation water, and plant protection products (PPP) into adjacent surface water bodies. In the European and US risk assessment for the registration of PPP, runoff and erosion are numerically calculated with the simulation Pesticide Root Zone Model (PRZM) using the US Department of Agriculture (USDA) runoff curve number (CN) concept for the water movement and the MUSS equation to quantify the sediment transfer. This work presents an evaluation of maize field trials conducted in three seasons that considered micro‐dams (i.e., small earthen dams between the rows; also known as “furrow diking,” “furrow damming,” etc.) and/or conservation tillage (via subsoiling) as mitigation measures to investigate the effects on the reduction in runoff and erosion. Measured quantitative reductions and event‐wise calculated CN are presented. Furthermore, the trials were simulated using the PRZM over the complete vegetation period and runoff CN as well as parameter values of the MUSS erosion equation (a relative adaptation of the C‐factor) were inversely estimated. Compared with the control plots (i.e., conventional tillage), micro‐dams or conservation tillage reduced runoff by 24%–71% or 69%–89%, and erosion by 54%–81% or 91%–98%. Based on these data, a robust case can be made to lower CN or parameters in the MUSS equation for surface water exposure scenarios to consider the effects on predicted environmental concentrations (PECs) and estimated environmental concentrations (EECs). Mean resulting CN reductions by micro‐dams or conservation tillage were ascertained to be 6% (±2.5%) or 12% (±3.0%), the C‐factor was reduced by a factor of 0.1 (±0.15) or 0.48 (±0.19). Example calculations show reductions in the ranges of 11%–100% for PECs and 30%–98% for EECs. Integr Environ Assess Manag 2022;18:1348–1363. © 2021 Bayer AG Crop Science. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Scientific conferences are one of the most common venues for researchers and others to present and exchange new findings. In recent years, "unconferences"-i.e., meetings that promote spontaneous discussions rather than predetermined presentations-have emerged as a more collaborative approach. Unconferences differ from conferences in key ways: while conferences have a predefined set of presenters together with an audience, unconferences promote more collaborative and spontaneous interactions across participants A "hackathon" is a special kind of unconference in which people come together to state, discuss, and solve problems by means of collaborative brainstorming, modeling, design, coding, testing, and documenting [2]. Despite the "hack" portion in the term, hackathons welcome not only software developers but anyone involved in creating solutions that can be later consumed or exposed via software. In addition to collaboration, hackathons promote community development around a subject used as the main hackathon topic. Such a topic can correspond to a knowledge domain (e.g., semantics or genomics) or be related to a particular organization (e.g., data and data services offered). There are hackathon-like events that are called by other names, such as "codefests." In this paper, we include such events under the umbrella term "hackathon."

The development of high-throughput genotyping has made genome-wide association (GWAS) and genomic selection (GS) applications possible for both model and non-model species. The exploitation of genome-assisted approaches could greatly benefit breeding efforts in American cranberry (Vaccinium macrocarpon) and other minor crops. Using biparental populations with different degrees of relatedness, we evaluated multiple GS methods for total yield (TY) and mean fruit weight (MFW). Specifically, we compared predictive ability (PA) differences between univariate and multivariate genomic best linear unbiased predictors (GBLUP and MGBLUP, respectively). We found that MGBLUP provided higher predictive ability (PA) than GBLUP, in scenarios with medium genetic correlation (8–17% increase with corg~0.6) and high genetic correlations (25–156% with corg~0.9), but found no increase when genetic correlation was low. In addition, we found that only a few hundred single nucleotide polymorphism (SNP) markers are needed to reach a plateau in PA for both traits in the biparental populations studied (in full linkage disequilibrium). We observed that higher resemblance among individuals in the training (TP) and validation (VP) populations provided greater PA. Although multivariate GS methods are available, genetic correlations and other factors need to be carefully considered when applying these methods for genetic improvement.

In the last decade, the view of circadian oscillators has expanded from transcriptional feedback to incorporate post-transcriptional, post-translational, metabolic processes and ionic signalling. In plants and animals, there are circadian oscillations in the concentration of cytosolic-free Ca2+ ([Ca2+]cyt), though their purpose has not been fully characterised. We investigated whether circadian oscillations of [Ca2+]cyt regulate the circadian oscillator of Arabidopsis thaliana. We report that in Arabidopsis, [Ca2+]cyt circadian oscillations can regulate circadian clock function through the Ca2+-dependent action of CALMODULIN-LIKE24 (CML24). Genetic analyses demonstrate a linkage between CML24 and the circadian oscillator, through pathways involving the circadian oscillator gene TIMING OF CAB2 EXPRESSION1 (TOC1).

BackgroundGrowth is an important parameter to consider when studying the impact of treatments or mutations on plant physiology. Leaf area and growth rates can be estimated efficiently from images of plants, but the experiment setup, image analysis, and statistical evaluation can be laborious, often requiring substantial manual effort and programming skills.ResultsHere we present rosettR, a non-destructive and high-throughput phenotyping protocol for the measurement of total rosette area of seedlings grown in plates in sterile conditions. We demonstrate that our protocol can be used to accurately detect growth differences among different genotypes and in response to light regimes and osmotic stress. rosettR is implemented as a package for the statistical computing software R and provides easy to use functions to design an experiment, analyze the images, and generate reports on quality control as well as a final comparison across genotypes and applied treatments. Experiment procedures are included as part of the package documentation.ConclusionsUsing rosettR it is straight-forward to perform accurate, reproducible measurements of rosette area and relative growth rate with high-throughput using inexpensive equipment. Suitable applications include screening mutant populations for growth phenotypes visible at early growth stages and profiling different genotypes in a wide variety of treatments.

Appropriate canopy management, including planting density and pruning, and application of fertilizer may increase flowering success and seed and oil yields of Jatropha curcas L. Two field experiments were performed from 2009 to 2011 in Balaka, Malawi, to assess the effect of planting density and pruning regime and single fertilizer application (N, P, and K) on male and female flower number and seed and oil yields of J. curcas. Planting density influenced flower sex ratio and female flower number. Branch pruning treatments did not influence the flower sex ratio but reduced seed and final oil yield by 55 % in the following year. It is claimed that J. curcas can be grown on soils with low nutrient content, but this study revealed that yield was low for non-fertilized trees. We observed higher seed and oil yields at higher N application rates (up to 203 ± 42 % seed and 204 ± 45 % oil yield increase) compared with the non-fertilized control. The study suggests thatcurrently used heavy pruning practice is not recommended for J. curcas cultivation, although it needs further longer term investigation. Applying nitrogen fertilizer is effective in increasing yield.