Eurofins (Netherlands)

Wing tilt and associated defects at the coalescence boundary in GaN were completely eliminated in a maskless homoepitaxial overgrowth process, whereas SiO2-masked homoepitaxial overgrowth showed the same effects as samples grown on sapphire or SiC. X-ray diffraction and transmission electron microscopy were used to investigate the structures and defect behavior in the epitaxial layers. Crystallographic tilt and the generation of new dislocations with a-type Burgers vectors were observed in the SiO2-masked sample, consistent with the wing tilt phenomenon, while high crystal quality and dislocation-free layers were grown in the maskless process. This shows that the mask is the primary cause for tilt and dislocations during overgrowth, while lattice and thermal mismatch have a contributing but smaller role. The wing tilt phenomenon is completely eliminated via a homoepitaxial, mask-free scheme.

Wee1-like protein kinase (Wee1) is a serine/threonine kinase essential for cell cycle regulation and the DNA damage response (DDR), acting as a tumor suppressor in normal cells. Its overexpression in cancers such as melanoma, hepatocellular carcinoma, and glioblastoma underscores its potential as a therapeutic target. Wee1 inhibition has emerged as a strategy to sensitize tumor cells to genotoxic therapies, though no inhibitors have yet received broad clinical approval. In the first round of screening, we employed ESSENCE-Dock virtual screening to identify potential Wee1 inhibitors from the Eurofins-Villapharma library. Of the 12 compounds experimentally validated, six exhibited IC50 values below 100 µM, with compound 1 demonstrating promising activity (IC50 = 240 nM). Based on this initial hit, we synthesized and tested additional compounds, culminating in compound 20, which showed an almost order of magnitude improvement in potency (IC50 = 33 nM). Structure–activity relationship (SAR) analysis highlighted key activity determinants, including the effects of methyl substitution on the phenylpiperazine and double-chlorine halogenation on the terminal phenyl group. Compound 20 compared favorably to known Wee1 inhibitors such as MK-1775, while maintaining a distinct chemical scaffold. To further validate these findings, molecular dynamics simulations were employed to elucidate the binding interactions and conformational dynamics of the high-affinity compounds. These simulations revealed stabilizing interactions that aligned with the observed SAR trends, solidifying compound 20 as a strong lead for further development. In addition, in vitro ADME profiling demonstrated favorable physicochemical properties and drug-likeness, including high solubility and metabolic stability, supporting its potential as a drug candidate. Kinome-wide profiling at 10 µM revealed modest selectivity, highlighting a key consideration for future optimization.

Understanding the effects of artificial structures in marine landscapes is required for ecosystem-based management. Global demand for oil and gas and accelerated commitments to renewable energy development has led to the proliferation of marine artificial structures. Investigating the cumulative effects of these structures on marine ecosystems requires data on the benthic community over large geographical and long-time scales. It is imperative to share the data collected by many stakeholders in an integrated information system to benefit science, industry and policy. BISAR is the first data product containing harmonised and quality-checked international data on benthos from artificial structures in the North Sea. BISAR was compiled from environmental impact assessment studies and scientific projects (3864 samples, 890 taxa). Data derive from 34 artificial structures and surrounding soft sediments (years: 2003 to 2019). Structures include offshore wind turbines, oil and gas platforms and a research platform. Data from a geogenic reef, allow comparison of natural and artificial reef communities. We aim to host future BISAR data dynamically in the CRITTERBASE web portal.

A complementary description of Neoseiulus longilaterus (Athias-Henriot) is presented based on adult female specimens collected in Iran, marking the first record of this species in the country. Specimens of this species were collected in galls of an unidentified eriophyid mite on desert thorn leaves (Lycium shawii Roem. & Schult., Solanaceae). While Chant & McMurtry (2003) categorized this species within the cucumeris species group of Neoseiulus Hughes, its morphological characteristics align more closely with some species from the paspalivorus group. Therefore, we provisionally classify N. longilaterus within the paspalivorus group. In addition, an updated and revised key for identifying the known species in the latter group is also provided. We also consider N. engaddensis syn. nov. as a junior synonym of N. longilaterus.

En esta nota se informa sobre la presencia del pez Salaria fluviatilis Asso, 1801 en la cuenca del río Segura, una especie catalogada como extinta en esta región y cuyos últimos registros datan de hace más de medio siglo. La especie se redescubrió durante los muestreos del año 2021, cuando se capturó un único individuo en el río Mundo. Un año después, la especie mostró una notable explosión poblacional y expansión geográfica, alcanzando densidades considerables en otras localidades del río Mundo, así como en el propio eje del río Segura y sus afluentes Benízar y Argos.

Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

Introduction/BackgroundRecent guidelines propose a binary grading for endometrial cancer (EC) in low- or high grade, in which all endometrioid EC (EEC) grade 1 and 2 are considered low-grade and treated accordingly. However, pre- and postoperative agreement was the lowest in grade 2 with clinically relevant upgrading in 14% in a previously published study. This presents a potential risk of undertreatment within this group. A dual immunohistochemical staining approach with progesteron receptor (PR) and p53 has been demonstrated to be helpful in improving pre- and postoperative concordance in grade 2 EECs. The aim of this study was to evaluate the impact of preoperative PR and p53 expression on prognosis in grade 2 EEC.MethodologyThree European EC study cohorts were merged. Preoperative non-EECs and grade 2 EECs without preoperative p53 or PR status were excluded from analysis. A total of 1150 patients were included, incorporating 400 patients with grade 2 EECs. Kaplan Meier and Cox-regression analyses were performed.ResultsPatients with preoperative grade 2 EEC and p53 wild-type plus PR positive expression showed a similar survival to patients with grade 1 EEC, while survival of patients with aberrant p53 and/or negative PR expression was more comparable to grade 3 EECs (Figure 1). The combination of these markers was an independent prognostic factor in multivariate regression analyses.ConclusionThe prognostic impact of preoperative p53 and PR expression in patients with grade 2 EEC supports a modified binary grading system, in which grade 2 EECs should be preoperatively classified as low- or high-grade depending on p53 and PR expression.DisclosuresNo disclosures. 823 Figure 1

Introduction/BackgroundThe European guideline for endometrial cancer (EC) advises lymph node staging for patients with high-intermediate-risk/high-risk disease. The ENDORISK-model can estimate risk of lymph node metastases (LNM) more accurately by combining preoperative biomarkers. Despite the development of several EC risk models, limited literature is available on clinical implementation. With this qualitative study we aim to study healthcare providers’ (HCP) perspectives on the use of such a risk model and on barriers and facilitators for implementation into clinical practice.MethodologyWe performed a focus group study amongst HCP within the EC care process in three oncological care regions in the Netherlands and a sample from several other hospitals within the Netherlands, on general use of ENDORISK-model in daily practice and barriers and facilitators for implementation using a semi-structured interview guide based on the Grol and Wensing model (2004).ResultsFocus groups (n=8) were organized with gynaecologists, pathologists radiation oncologists and a nurse specialist. Participants agreed that a risk model predicting LNM could support counseling of patients and shared decision making for optimal treatment, both surgical and adjuvant. A risk cut-off of 10% was suggested above which lymph node staging should be performed. Barriers for implementation were: 1. difficulty in explaining the model and risk estimation to patients, 2. difference in preoperative tests preferred by general versus university hospitals and 3. use in perspective of the sentinel node procedure. Facilitators for implementation were 1. a guideline for the model, with a clear risk cut-off, and for counseling patients, 2. ease of use and reach, and 3. implementation within an oncological network at once.ConclusionBased on the perspectives of HCP, the ENDORISK-model provides additional value to current care for counseling of patients. Implementation could be facilitated if the ENDORISK-model is easy to understand and use, and supported by guidelines to use the model to counsel patients.DisclosuresNone.

Agricultural soils are usually deficient in phosphorus (P), causing yield reduction. To boost crop production and P availability in acid soil, rock phosphate (RP) can be used with single super phosphate (SSP), which can also supply available P for the long-term during a crop cycle. The study was conducted to show the effect of SSP and rock RP on the P release and fixation pattern and its uptake by paddy variety CAU-R1 in acid soil. The experimental design was randomized block design having six treatments, where P supplied through i) only SSP, ii) only RP, iii) 3/4th SSP + 1/4th RP, iv) half SSP + half RP, v)1/4th SSP + 3/4th RP and vi) control. The addition of P in general increased all inorganic P forms with time over untreated control. There was an increase in saloid-P, Aluminum-P, Iron-P, Calcium-P, and available P concentration reaching maximum on 50th day with gradual decline till harvest. Phosphorus application significantly increased P uptake, dry matter yield, tiller number, and plant height of paddy during the entire growth period. Comparatively higher P uptake and grain yield were observed in soil applied with SSP and RP at 1:1, as SSP predominantly supplied P at the earlier growth stage and RP released P slowly. Therefore, the combined use of SSP and RP at 1:1 can provide a constant pool of available P and improve agronomic efficiencies under acid soil.