The PRO-RCC study:a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for ‘Trial within Cohorts’ study designs

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs).METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician.TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620).DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.</p

Prognostic Significance of Promoter Hypermethylation and Diminished Gene Expression of SYNPO2 in Melanoma.

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Excavations at Tell Fadous-Kfarabida:Preliminary report on the 2106 season of excavations

This report presents the main results of the final season of excavations in 2016at Tell Fadous-Kfarabida, located on the north Lebanese coast 2 km south of Batroun.Excavations focused on four areas. In Area II we worked only in Squares 310/295and parts of 305/295, where the excavations in 2015 did not reach a satisfactory end. We continued to excavate in and under the northern rooms of Building 4 (Phase III, Early Bronze Age III) and reached the earlier Phases II (Early Bronze Age II) and Phase I (Chalcolithic) in very limited areas. In Areas III and IV, we continued the work begun in 2014 and 2015. Area III is located on the southern slope of the tell. In 2016, work mainly focused on exposing domesticarchitecture from Phase III (Early Bronze Age III). Area IV is situated at the eastern edge of the site, where we continued the investigation of the Early Bronze Age fortification system with a monumental gate (Phase III, Early Bronze Age III). Area V, situated in the northcentral part of the tell, was newly opened in 2016. Here remains of substantial buildings, attributable to Phase III (Early Bronze Age III) were uncovered. In addition to the general overviews of the main features exposed in the different areas during the 2016 season, this report contains specialist reports on ceramic material and small finds from various phases as well as progress reports of ongoing archaeozoological and isotopic investigations

Storylines of weather-induced crop failure events under climate change

Unfavourable weather is a common cause for crop failures all over the world. Whilst extreme weather conditions may cause extreme impacts, crop failure commonly is induced by the occurrence of multiple and combined anomalous meteorological drivers. For these cases, the explanation of conditions leading to crop failure is complex, as the links connecting weather and crop yield can be multiple and non-linear. Furthermore, climate change is likely to perturb the meteorological conditions, possibly altering the occurrences of crop failures or leading to unprecedented drivers of extreme impacts. The goal of this study is to identify important meteorological drivers that cause crop failures and to explore changes in crop failures due to global warming. For that, we focus on a historical failure event, the extreme low soybean production during the 2012 season in the midwestern US. We first train a random forest model to identify the most relevant meteorological drivers of historical crop failures and to predict crop failure probabilities. Second, we explore the influence of global warming on crop failures and on the structure of compound drivers. We use large ensembles from the EC-Earth global climate model, corresponding to present-day, pre-industrial +2 and 3° C warming, respectively, to isolate the global warming component. Finally, we explore the meteorological conditions inductive for the 2012 crop failure and construct analogues of these failure conditions in future climate settings. We find that crop failures in the midwestern US are linked to low precipitation levels, and high temperature and diurnal temperature range (DTR) levels during July and August. Results suggest soybean failures are likely to increase with climate change. With more frequent warm years due to global warming, the joint hot-dry conditions leading to crop failures become mostly dependent on precipitation levels, reducing the importance of the relative compound contribution. While event analogues of the 2012 season are rare and not expected to increase, impact analogues show a significant increase in occurrence frequency under global warming, but for different combinations of the meteorological drivers than experienced in 2012. This has implications for assessment of the drivers of extreme impact events

Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of primary cutaneous melanoma is associated with increased thickness and disease progression

Loss of E-cadherin expression in melanoma correlates with increased tumor thickness and reduced disease-free survival. The molecular mechanisms underpinning its differential expression in melanoma tissue remain elusive. Micro-RNAs (miRNAs) have been implicated in tumor progression and regulation of E-cadherin expression. Here, we demonstrate a significant correlation between tumor thickness and loss of expression of miR-200a, miR-200c, and miR-203 in a series of 2.frozen primary melanomas, where it was confirmed in two subsequent validation series (series 1: six nevi, 15 primary melanomas, and 16 metastases; series 2:11 matched pairs of primary melanomas andmetastases). Decreased levels of miR-200a, miR-200c, and miR-203 correlated with increasing thickness in the combined validation series (P=0.024, 0.033, and 0.031, respectively). In addition, progressive loss of miR-200. expression with disease progression was observed in series 1 (P<0.001) and in series 2 (P=0.029). MiR-200 in situ hybridization and E-cadherin immunohistochemistry demonstrated reduced expression of both at the deep invasive margin of the tumor. Furthermore, a functional validation study using an anti-miR200 strategy demonstrated that loss of miR-200 expression in melanoma cell lines reduced E-cadherin expression. Collectively, our data point towards an important role for miR-200 and miR203 expression in regulating E-cadherin during melanoma progression. © Springer-Verlag 2012.SCOPUS: ar.jinfo:eu-repo/semantics/publishe