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Background and objective: In patients with oligorecurrent prostate cancer (PCa), prostate-specific membrane antigen–targeted radioguided surgery (PSMA-RGS) prolongs treatment-free survival. Data on patient-reported outcome measures (PROMs) are lacking. Methods: A retrospective assessment of validated PROMs (12-item Short Form Health Survey [SF-12], 26-item Expanded Prostate Index Composite, and Decision Regret Scale [DRS]) was performed before and after PSMA-RGS for oligorecurrent PCa. Mixed models were used. Key findings and limitations: A total of 373 patients were analyzed at a median (interquartile range [IQR]) age of 66 (61, 70) yr and prostate-specific antigen of 0.8 (0.4, 1.5) ng/ml. Six months after PSMA-RGS, the median (IQR) scores for the PROMs were as follows: SF-12 physical 54 (49, 56), SF-12 mental 53 (43, 56), urinary incontinence 86 (52, 100), urinary irritation 94 (88, 100), sexual 27 (9, 57), hormonal 90 (79, 100), and bowel 96 (83, 100). Only the sexual score decreased in a significant fashion from baseline over time (median [IQR], 17 [8,38]) after 3 yr vs 37 [13, 63] at baseline, p = 0.01). The decision regret remained low (median [IQR] DRS at 1 yr: 5 [0, 20]). More than 90% of the patients reported that PSMA-RGS was the correct decision after 1 yr. Conclusions and clinical Implications: We recorded no significant decrease in quality of life or any functional status domain, except sexual. While decision regret was low, sexual functioning might deteriorate further. Patient summary: No significant deterioration in health-related quality of life was reported after removing early prostate cancer metastases. Very few patients expressed remorse about their decision for salvage surgery.

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.

The slowing and reduction of auditory responses in the brain are recognized side effects of increased pure tone thresholds, impaired speech recognition, and aging. However, it remains controversial whether central slowing is primarily linked to brain processes as atrophy, or is also associated with the slowing of temporal neural processing from the periphery. Here we analyzed electroencephalogram (EEG) responses that most likely reflect medial geniculate body (MGB) responses to passive listening of phonemes in 80 subjects ranging in age from 18 to 76 years, in whom the peripheral auditory responses had been analyzed in detail (Schirmer et al., 2024). We observed that passive listening to vowels and phonemes, specifically designed to rely on either temporal fine structure (TFS) for frequencies below the phase locking limit (

Applications of the two-source energy balance (TSEB) scheme require either in-situ meteorological data to characterize the upper boundary conditions or the implementation of complex multi-scale approaches (ALEXI/DisALEXI). Over remote areas, detailed meteorological forcing (i.e., air temperature and wind speed) are often missing, limiting the quality of the simulated fluxes. To compute surface energy fluxes, the use of wet and dry boundary conditions, commonly referred to as hot and cold pixels, is a widely adopted strategy in thermal-based, single-source surface energy balance models for defining the relationship between satellite land-surface temperature (LST) and the surface-atmosphere temperature gradient. This contextual scaling approach reduces model sensitivity to biases in LST retrievals, but it has been previously tested within the TSEB modelling framework only in limited capacity. An automatic procedure for retrieving the two boundary temperatures is here proposed, removing the need for external meteorological data and leading to temperature values that are unbiased compared to ideal estimations (from in-situ observations) and characterized by deviations on the order of 1.5 and 4.5 °C for cold and hot conditions, respectively. Despite the lower accuracy in the hot pixel temperature, this does not seem to significantly affect the overall capability of the model to reproduce observed fluxes, with errors in instantaneous sensible and latent heat fluxes in the order of 60 W m−2 (slightly above 1 mm d−1 on daily evapotranspiration) over a set of 16 sites in the US and Italy, characterized by typical Mediterranean crops. The proposed TSEB implementation is fully remote sensing based, meaning satellite-consistent retrievals of air temperature and wind speed are obtained directly from information available within the satellite scene itself. This approach represents a suitable alternative to accurately model evapotranspiration and other surface energy fluxes in the absence of reliable meteorological data.

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.

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.

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.

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.

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.

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.

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.