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Accurate simulation of the loads and motions of floating offshore wind turbines (FOWTs) in operation is key to the commercialisation of this technology. To improve such load predictions, a critical assessment of the capabilities and limitations of simulation methods for FOWTs is mandatory. However, uncertainties arise during the whole validation process of a numerical method. These can drastically impair the quality of the validation. In the case of FOWTs, the interaction between aerodynamic, hydrodynamic and mooring loads on the one hand and platform motions on the other hand causes a high level of uncertainty in the measurement data acquired in model tests. This also applies to comparing a numerical model to the test data, as these interactions make the distinction between cause and effect challenging. To address these challenges, several improvements to the validation process aiming to reduce the uncertainties are proposed and evaluated in this work. The major improvements are the measurement of the rotor thrust force excluding the tower top inertia loads, the wind field quality in the wave tank, a comparison of the rotor aerodynamics in the wind tunnel and wave tank, and the utilisation of hybrid simulations based on the measured platform motions. These steps are applied to wave tank tests of a FOWT utilising a single-point mooring and the subsequent validation of the numerical panel method panMARE. The improvements allowed for a considerable decrease in the random and systematic uncertainty in the model tests and made a valuable contribution to the distinction between cause and effect regarding the deviations between measurements and simulations.

Abstract In esophageal adenocarcinoma, the presence of lymph node metastases predicts patients' survival even after curative resection. Currently, there is no highly accurate marker for detecting the presence of lymph node metastasis. The SEMA3F/NRP2 axis was initially characterized in axon guidance and recent evidence has revealed its significant involvement in lymphangiogenesis, angiogenesis, and carcinogenesis. Hence, the objective of this study was to elucidate the roles of SEMA3F and its receptor NRP2 in esophageal adenocarcinoma. We conducted an immunohistochemical evaluation of SEMA3F and NRP2 protein expression in 776 patients with esophageal adenocarcinoma who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. Total and positive cancer cell counts were digitally analyzed using QuPath and verified by experienced pathologists to ensure accuracy. Positive expression was determined as a cell percentage exceeding the 50th percentile threshold. In our cohort, patients exhibiting SEMA3F positive expression experience significantly lower pT- and pN-stages. In contrast, positive NRP2 expression is associated with the presence of lymph node metastases. Survival analyses showed that the expression status of NRP2 had no impact on patient survival. However, SEMA3F positivity was associated with a favorable patient survival outcome (median OS: 38.9 vs. 26.5 months). Furthermore, SEMA3F could be confirmed as an independent factor for better patient survival in patients with early tumor stage (pT1N0-3: HR = 0.505, p = 0.014, pT1-4N0: HR = 0.664, p = 0.024, pT1N0: HR = 0.483, p = 0.040). In summary, SEMA3F emerges as an independent predictor for a favorable prognosis in patients with early-stage esophageal adenocarcinoma. Additionally, NRP2 expression is linked to a higher risk of lymph node metastases occurrence. We hypothesize that low SEMA3F expression could identify patients with early-stage tumors who might benefit from more aggressive treatment options or intensified follow-up. Furthermore, SEMA3F and its associated pathways should be explored as potential tumor-suppressing agents.

Background: Cholangiocarcinomas (CCA) are a group of aggressive malignancies with poor prognosis. The distinct subtypes are related to different etiologies and genetic aberrations that are subject to targeted therapies. Mouse double minute 2 homolog (MDM2) is a potent inhibitor of tumor suppressor p53 and is proven to be altered in certain carcinomas. Novel targeted drugs, such as the MDM2-p53 antagonist Brigimadlin, have shown promising results for therapeutic efficacy in patients with MDM2 amplification and wild-type TP53 . Objectives: This study therefore aimed to characterize CCAs regarding their MDM2 status, compare the concordance between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods, and elucidate the role of MDM2 amplification in prognosis and other clinicopathological characteristics. Design: Retrospective cohort study. Methods: All patients ( n = 52) were diagnosed with CCA and received surgical resection with curative intention at the University Hospital of Cologne. Samples were analyzed retrospectively for MDM2 amplification with FISH and IHC. We correlated results with pre-existing molecular as well as clinical data. Results: We included 52 patients with primary CCA, three of which showed positive MDM2 amplification (5.8%). MDM2 amplification was present only in the intrahepatic CCA type and all patients with positive MDM2 amplification exhibited normal p53 status. Among the large-duct subtypes of intrahepatic CCAs, patients with positive MDM2 amplification demonstrated better survival than patients with negative MDM2 amplification ( p = 0.041). Of the patients with MDM2 amplification, two underwent adjuvant therapy post-surgery (66.7%). There was a strong correlation between MDM2 amplification and positive protein expression in IHC. There were no identifiable molecular co-alterations of MDM2 with FGFR2 or SWI/SNF complex alterations. Conclusion: Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, wherefore targeted therapies have experienced increasing interest. Zolbetuximab is a novel targeted therapy under investigation in patients with PDAC and targets Claudin 18.2 (CLDN18.2), which is a component of tight junctions and is of significance in various solid tumors. As its role in PDAC is not definitively elucidated, this study aims to clarify the significance of CLDN18.2 expression in PDAC in a real-world setting. Methods: All patients (n = 309) were recruited at one of the PANCALYZE study centers and received pancreatic resection with curative intention. Paraffin samples were analyzed using an antibody against CLDN18.2, which is known to be comparable to the antibody used by the SPOTLIGHT and GLOW studies. Results: 94 PDACs are positive for CLDN18.2 (30.4 %). Positive CLDN 18.2 expression was associated with significantly better cancer differentiation (p < 0.001). Patients with positive CLDN18.2 expression showed significantly better overall survival when compared to patients with negative expression (median OS: 30 versus 18 months, p = 0.003). Additionally, in multivariable analyses, CLDN18.2 expression was identified as an independent factor for better survival in patients with PDAC (HR = 0.686, 95 %CI = 0.492–0.956, p = 0.026). Conclusion: Significant improvement in survival could be demonstrated by adding Zolbetuximab to known chemotherapy regimes in patients with gastro-esophageal junction adenocarcinoma with at least 75 % CLDN18.2 positive cancer cells. Our findings demonstrate, that 30.4 % of the included patients with PDAC would potentially be eligible for therapy with Zolbetuximab in a real-world patient cohort. Results of trials targeting Claudin 18.2 are pending in patients with PDAC.

Background and objective: Data regarding open conversion (OC) during minimally invasive surgery (MIS) for renal tumors are reported from big databases, without precise description of the reason and management of OC. The objective of this study was to describe the rate, reasons, and perioperative outcomes of OC in a cohort of patients who underwent MIS for renal tumor initially. The secondary objective was to find the factors associated with OC. Methods: Between 2008 and 2022, of the 8566 patients included in the UroCCR project prospective database (NCT03293563), who underwent laparoscopic or robot-assisted minimally invasive partial (MIPN) or radical (MIRN) nephrectomy, 163 experienced OC. Each center was contacted to enlighten the context of OC: “emergency OC” implied an immediate life-threatening situation not reasonably manageable with MIS, otherwise “elective OC”. To evaluate the predictive factors of OC, a 2:1 paired cohort on the UroCCR database was used. Key findings and limitations: The incidence rate of OC was 1.9% for all cases of MIS, 2.9% for MIRN, and 1.4% for MIPN. OC procedures were mostly elective (82.2%). The main reason for OC was a failure to progress due to anatomical difficulties (42.9%). Five patients (3.1%) died within 90 d after surgery. Increased body mass index (BMI; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01–1.09, p = 0.009) and cT stage (OR: 2.22, 95% CI: 1.24–4.25, p = 0.008) were independent predictive factors of OC. Conclusions and clinical implications: In MIS for renal tumors, OC was a rare event (1.9%), caused by various situations, leading to impaired perioperative outcomes. Emergency OC occurred once every 300 procedures. Increased BMI and cT stage were independent predictive factors of OC. Patient summary: The incidence rate of open conversion (OC) in minimally invasive surgery for renal tumors is low. Only 20% of OC procedures occur in case of emergency, and others are caused by various situations. Increased body mass index and cT stage were independent predictive factors of OC.

Russian shelf is one of the most important areas for hydrocarbon forecast and mineral resources development. The main features of the geological structure of the shelves of the Far Eastern seas are discussed in the paper. The most promising basins on the Okhotsk shelf are located around Sakhalin island where the majority of the hydrocarbon fields have been discovered. The Bering and the Japan shelf has not been sufficiently studied by now but nevertheless has high oil and gas potential.The main focus is made on the geological and geophysical data, licensing, lithological and stratigraphic structure, seismic interpretation, oil and gas fields distribution. The structuraltectonic zoning of the entire Far Eastern region has been done in order to identify zones of deep troughs with thick sedimentary cover to predict the sources of hydrocarbon generation.

Unconventional oil and gas resource development and exploration is the one of the most prospective concept in petroleum geology. High carbon Khadum facies are investigated as unconventional resources in the Precaucas basin and contain gas, gas condensate and oil accumulations. Oligocene and Lower Miocene structure, prospectivity and fields distribution are the one of the most relevant subjects nowadays.This study is focused on the main stages Late Eocene and Early Oligocene deposits formation and the paleogeography of the Khadum formation in the Precaucas oil and gas basin. The new prospective zones are developed in Khadum formation based on the complex analysis of seismic, paleogeography and lithofacies analysis.

AIM: In this study, we use Artificial Intelligence (AI), including Machine (ML) and Deep Learning (DL), to predict the long-term survival of resectable esophageal cancer (EC) patients in a high-volume surgical center. Our objective is to evaluate the predictive efficacy of AI methods for survival prognosis across different time points of oncological treatment. This involves comparing models trained with clinical data, integrating either Tumor, Node, Metastasis (TNM) classification or tumor biomarker analysis, for long-term survival predictions. METHODS: In this retrospective study, 1002 patients diagnosed with EC between 1996 and 2021 were analyzed. The original dataset comprised 55 pre- and postoperative patient characteristics and 55 immunohistochemically evaluated biomarkers following surgical intervention. To predict the five-year survival status, four AI methods (Random Forest RF, XG Boost XG, Artificial Neural Network ANN, TabNet TN) and Logistic Regression (LR) were employed. The models were trained using three predefined subsets of the training dataset as follows: (I) the baseline dataset (BL) consisting of pre-, intra-, and postoperative data, including the TNM but excluding tumor biomarkers, (II) clinical data accessible at the time of the initial diagnostic workup (primary staging dataset, PS), and (III) the PS dataset including tumor biomarkers from tissue microarrays (PS + biomarkers), excluding TNM status. We used permutation feature importance for feature selection to identify only important variables for AI-driven reduced datasets and subsequent model retraining. RESULTS: Model training on the BL dataset demonstrated similar predictive performances for all models (Accuracy, ACC: 0.73/0.74/0.76/0.75/0.73; AUC: 0.78/0.82/0.83/0.80/0.79 RF/XG/ANN/TN/LR, respectively). The predictive performance and generalizability declined when the models were trained with the PS dataset. Surprisingly, the inclusion of biomarkers in the PS dataset for model training led to improved predictions (PS dataset vs. PS dataset + biomarkers; ACC: 0.70 vs. 0.77/0.73 vs. 0.79/0.71 vs. 0.75/0.69 vs. 0.72/0.63 vs. 0.66; AUC: 0.77 vs. 0.83/0.80 vs. 0.85/0.76 vs. 0.86/0.70 vs. 0.76/0.70 vs. 0.69 RF/XG/ANN/TN/LR, respectively). The AI models outperformed LR when trained with the PS datasets. The important features shared after AI-driven feature selection in all models trained with the BL dataset included histopathological lymph node status (pN), histopathological tumor size (pT), clinical tumor size (cT), age at the time of surgery, and postoperative tracheostomy. Following training with the PS dataset with biomarkers, the important predictive features included patient age at the time of surgery, TP-53 gene mutation, Mesothelin expression, thymidine phosphorylase (TYMP) expression, NANOG homebox protein expression, and indoleamine 2,3-dioxygenase (IDO) expressed on tumor-infiltrating lymphocytes, as well as tumor-infiltrating Mast- and Natural killer cells. CONCLUSION: Different AI methods similarly predict the long-term survival status of patients with EC and outperform LR, the state-of-the-art classification model. Survival status can be predicted with similar predictive performance with patient data at an early stage of treatment when utilizing additional biomarker analysis. This suggests that individual survival predictions can be made early in cancer treatment by utilizing biomarkers, reducing the necessity for the pathological TNM status post-surgery. This study identifies important features for survival predictions that vary depending on the timing of oncological treatment.

Robust information on consumptive water use (evapotranspiration, ET) derived from remote sensing can significantly benefit water decision-making in agriculture, informing irrigation schedules and water management plans over extended regions. To be of optimal utility for operational usage, these remote sensing ET data should be generated at the sub-field spatial resolution and daily-to-weekly timesteps commensurate with the scales of water management activities. However, current methods for field-scale ET retrieval based on thermal infrared (TIR) imaging, a valuable diagnostic of canopy stress and surface moisture status, are limited by the temporal revisit of available medium-resolution (100 m or finer) thermal satellite sensors. This study investigates the efficacy of a data fusion method for combining information from multiple medium-resolution sensors toward generating high spatiotemporal resolution ET products for water management. TIR data from Landsat and ECOSTRESS (both at ~ 100-m native resolution), and VIIRS (375-m native) are sharpened to a common 30-m grid using surface reflectance data from the Harmonized Landsat-Sentinel dataset. Periodic 30-m ET retrievals from these combined thermal data sources are fused with daily retrievals from unsharpened VIIRS to generate daily, 30-m ET image timeseries. The accuracy of this mapping method is tested over several irrigated cropping systems in the Central Valley of California in comparison with flux tower observations, including measurements over irrigated vineyards collected in the GRAPEX campaign. Results demonstrate the operational value added by the augmented TIR sensor suite compared to Landsat alone, in terms of capturing daily ET variability and reduced latency for real-time applications. The method also provides means for incorporating new sources of imaging from future planned thermal missions, further improving our ability to map rapid changes in crop water use at field scales.

Abstract With the beginning of the Early Bronze Age in Central Europe ~ 2200 BC, a regional and supra-regional hierarchical social organization emerged with few individuals in positions of power (chiefs), set apart by rich graves with extensive burial constructions. However, the social organization and stratification within the majority of people, who represent the non-elite, remain unclear. Here, we present genome-wide data of 46 individuals from the Early Bronze Age burial ground of Leubingen in today’s Germany, integrating archaeological, genetic and strontium isotope data to gain new insights into Early Bronze Age societies. We were able to reconstruct five pedigrees which constitute the members of close biological kinship groups (parents and their offspring), and also identify individuals who are not related to individuals buried at the site. Based on combined lines of evidence, we observe that the kinship structure of the burial community was predominantly patrilineal/virilocal involving female exogamy. Further, we detect a difference in the amount of grave goods among the individuals buried at Leubingen based on genetic sex, age at death and locality but see no difference in the types of grave goods.

Objective: To examine the perioperative impact of factor V Leiden mutation on thromboembolic events' risk in radical prostatectomy (RP) patients. With an incidence of about 5%, factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia. The increased risk of thromboembolic events is three- to seven-fold in heterozygous and to 80-fold in homozygous patients. Methods: Within our prospectively collected database, we analysed 33 006 prostate cancer patients treated with RP between December 2001 and December 2020. Of those, patients with factor V Leiden mutation were identified. All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation. Thromboembolic complications (deep vein thrombosis and pulmonary embolism) were assessed during hospital stay, as well as according to patient reported outcomes within the first 3 months after RP. Results: Overall, 85 (0.3%) patients with known factor V Leiden mutation were identified. Median age was 65 (interquartile range: 61–68) years. There was at least one thrombosis in 53 (62.4%) patients and 31 (36.5%) patients had at least one embolic event in their medical history before RP. Within all 85 patients with factor V Leiden mutation, we experienced no thromboembolic complications within the first 3 months after surgery. Conclusion: In our cohort of patients with factor V Leiden mutation, no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept. This may reassure patients with this hereditary condition who are counselled for RP.

Methods sections are often missing essential details. Methodological shortcut citations, in which authors cite previous papers instead of describing the method in detail, may contribute to this problem. This meta-research study used 3 approaches to examine shortcut citation use in neuroscience, biology, and psychiatry. First, we assessed current practices in more than 750 papers. More than 90% of papers used shortcut citations. Other common reasons for using citations in the methods included giving credit or specifying what was used (who or what citation) and providing context or a justification (why citation). Next, we reviewed 15 papers to determine what can happen when readers follow shortcut citations to find methodological details. While shortcut citations can be used effectively, they can also deprive readers of essential methodological details. Problems encountered included difficulty identifying or accessing the cited materials, missing or insufficient descriptions of the cited method, and shortcut citation chains. Third, we examined journal policies. Fewer than one quarter of journals had policies describing how authors should report previously described methods. We propose that methodological shortcut citations should meet 3 criteria; cited resources should provide (1) a detailed description of (2) the method used by the citing authors', and (3) be open access. Resources that do not meet these criteria should be cited to give credit, but not as shortcut citations. We outline actions that authors and journals can take to use shortcut citations responsibly, while fostering a culture of open and reproducible methods reporting.

Abstract Esophageal adenocarcinoma exhibits one of the highest mortality rates among all cancer entities. Multimodal therapy strategies have improved patients’ survival significantly. However, patients in early stages are currently limited to receiving only local therapies, even though some patients within this group showcase short survival periods. Until now, there has been no widely established clinically used biomarker to detect these high-risk patients. Telomerase reverse transcriptase (TERT), a gene encoding a crucial subunit of the telomerase enzyme, plays a significant role in establishing cancer cell immortality and is under suspicion for its potential contribution to tumor progression. Therefore, we aimed to evaluate the clinical relevance of the TERT amplification status. We included 643 patients with esophageal adenocarcinoma, who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. The TERT amplification status was characterized using fluorescence in situ hybridization. Clinicopathological values and patients’ overall survival were compared between patients with and without TERT amplification. Further sub-cohort analyses were conducted for patients with pT1N0-3 tumor stage. Eighty-One patients (12.6%) exhibited TERT amplification. Patients with amplified TERT showed significantly worse overall survival (median OS: 22.6 vs. 36.8 months, p = 0.009). Interestingly, TERT amplification could be characterized as an independent risk factor for worse overall survival in multivariate analysis in patients with pT1N0-3 tumor stage (HR = 2.440, 95% CI 1.095–5.440, p = 0.029). In this study, we describe the TERT amplification status as an independent risk factor for worse survival in patients diagnosed with esophageal adenocarcinoma at pT1N0-3 tumor stage, encompassing cases involving tumor infiltration of the lamina propria, muscularis mucosae, and/or submucosa. Based on our findings, we put forth the proposition that evaluating the TERT amplification status may serve as a valuable tool in identifying a specific subgroup of patients, namely those with TERT amplification and pT1N0-3 tumor-stage esophageal adenocarcinoma. The patients of this subgroup could potentially benefit from enhanced follow-up protocols, more aggressive treatment approaches, or possible targeted TERT inhibition therapies, all aimed at improving their overall clinical outcomes.

Abstract Background In 2010, a political and social crisis pushed thousands of Venezuelans out of their country; today, seven million Venezuelans live abroad. In addition, during the COVID-19 pandemic, border closure increased and affected specific vulnerable migration flows, such as Venezuelans trying to migrate to Chile through the Northern borders. In this context, there is little evidence of migrants’ health status and needs, their access to health services, and other basic needs (e.g., housing) from a human rights perspective. Therefore, we qualitatively explored the effects of border closure due to the COVID-19 pandemic on Venezuelan migrants’ health and human rights, focusing on access to healthcare in the Northern Chilean border that adjoins Peru and Bolivia. Methods Following a case-study qualitative design, we conducted an ethnography that included participatory observation of relevant sites (e.g., hospitals, main squares, migrant shelters) in Antofagasta, Iquique, and Arica and 30 in-depth interviews with actors in the health sector (n = 7), experts from the non-governmental sector (n = 16), and governmental actors (n = 7) in three large cities close to the Northern border. Results We found four main dimensions: (i) border and migration processes, (ii) specific groups and intersectionality, (iii) barriers to healthcare services, and (iv) regional and local responses to the crisis during the COVID-19 pandemic. Programs characterized by the presence of healthcare providers in the field were essential to attend to migrants’ health needs at borders. Conclusions Coordination between actors is crucial to implement regional protocols that respond to current migration phenomena and migrants’ health needs. Health policies using a human rights approach are urgently required to respond to migrants’ healthcare needs at borders in South America.