The protection and sustainable use of aquatic resources require a better understanding of fresh water sources, limnic ecosystems, and oceans. The effects of global change, intensive use of natural ...resources and the complex interactions between humans and the environment show different effects at different scales. Current research approaches are not sufficient to appropriately take account of the heterogeneity and dynamics of aquatic ecosystems. A major challenge in applied environmental research is to extend methods for holistic monitoring and long-term observation technologies with enhanced resolution over both space and time. In this study, turbidity and the content of dissolved organic matter (DOM) are key parameters, as they are of importance for assessing the health of aquatic ecosystems and the state of ecosystem services (e.g., the provision of drinking water). Photonics and optical sensors as well as integrated circuits and open-source based components open interesting possibilities to overcome the current lack of adaptive and service-oriented sensor systems. An open source based optical sensor system was developed, which enables a user-specific, modular and adaptive in-situ monitoring of the turbidity and the dissolved organic substance content almost in real time. Quantification is based on attenuation or transmission measurements with two narrowband LEDs and corresponding detectors in the ultraviolet (DOM content) and infrared range (turbidity) of the electromagnetic spectrum. The developed in-situ sensor system shows a very high agreement with the results obtained using a laboratory photometer but with less methodological effort. First tests carried out in the area close to the city of Leipzig (Saxony, Germany) show promising results. The in-situ sensor system is able to acquire the optical attenuation with a sampling rate up to 0.1 Hz. Due to the fact that data is visualized directly with the help of web services, even the quality of data collection can be improved by assisting the selection of sampling points or a direct spatio-temporal data feedback. What this approach illustrates is the fact that open-source technologies and microelectronics can now be used to implement resilient and promising sensor systems that can set new standards in terms of performance and usability within applied environmental research.
Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind ...this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Various surface roughness parameters are utilized to describe the surface in the tooth to ceramics abrasion and to assess the resulting wear. The use of three‐dimensional parameters may offer ...a better estimation for wear and an improved deduced clinical surface treatment. The aim of this study was to determine the influence of various surface roughness parameters of zirconia and lithium disilicate ceramics on the wear of steatite antagonists.
Material and methods
Forty zirconia specimens with a diameter of 7 mm and a thickness of 3 mm and 40 lithium disilicate specimens with the dimensions 10×10×4 mm were each divided into five subgroups. Two subgroups were treated with different clinically established diamond burs; a third subgroup was treated with a silicone polishing set. Two additional subgroups were produced by glazing the surfaces after treatment. Surface roughness parameters were determined by laser scanning microscopy. All specimens underwent 1.2 million loading cycles using steatite antagonists. After regular intervals of cycles, precision impressions were made to assess the wear. The correlation between wear and different roughness parameters was evaluated using the Spearman correlation test.
Results
For the glazed zirconia, unglazed zirconia, and glazed lithium disilicate specimens no significant correlations (p > 0.05) between the investigated roughness parameters and antagonist wear could be found. In the unglazed lithium disilicate groups, significant (p ≤ 0.05) correlations with steatite substance loss could be found for several roughness parameters after 1.2 million cycles.
Conclusions
For lithium disilicate, it seems not sufficient to use only one roughness parameter to indicate the wear behavior of the surface. There was no correlation between wear and the tested roughness parameters of zirconia surfaces.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Up to now, the efficacy of programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade in pancreatic cancer (PC) remains uncertain. Serum levels of soluble PD-1 and PD-L1 ...(sPD-1/sPD-L1) have been reported to be independent prognostic factors in solid tumors susceptible to checkpoint blockade. Provenience, regulation and immunologic function of sPD-1 and sPD-L1 in cancer are poorly understood. To the best of our knowledge, sPD-1 and sPD-L1 have not been measured conjointly in any cancer type yet.
In contrast to other tumor entities, sPD-1/sPD-L1 levels did not indicate an adverse outcome in a cohort of 41 patients with advanced PC. We observed a close positive correlation of sPD-L1 levels with sPD-1 in patients with advanced PC, suggesting a common provenience and regulation of sPD-1 and sPD-L1 in cancer patients. Higher sPD-L1 levels were present in patients with elevated C-reactive protein or strong tumoral T cell infiltration, while no correlation of sPD-L1 levels with tumoral PD-L1 expression was found. Our findings indicate that sPD-1 and sPD-L1 are markers of systemic inflammation in (pancreatic) cancer. In a subset of PC patients, elevation in sPD-L1 levels might be caused by an inflammatory tumor type - independent of tumoral PD-L1 expression.
There is growing concern about the rising levels of dissolved organic matter (DOM) in surface waters across the Northern hemisphere. However, only limited research has been conducted to unveil its ...precise origin. Compositional changes along terrestrial-aquatic pathways can help determine the terrestrial sources of DOM in streams. Stream water, soil water and soil horizons were sampled at four sites representing typical settings within a forested catchment in the Ore Mountains (Erzgebirge, Germany) from winter 2020 to spring 2022. The samples were analyzed using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The resulting data were successfully subjected to semi-automatic processing of the molecular composition of DOM, reaching a percentage of identified peaks up to 98 %. Principal component analysis (PCA) and cluster analyses were carried out to identify distinct differences between DOM from the potential sources and in the streams. According to the PCA, organic soil horizons, soil water, and stream water samples could be clearly distinguished. Cluster analysis revealed that soil water DOM at all depths of Peats and deeper horizons of the Peaty Gleysols contributed the most to DOM in the stream section dominated by organic soils. In areas dominated by mineral soils, stream DOM resembled the DOM from the deeper mineral horizons of Cambisols and Podzols. Overall, our results suggested that most of the DOM exported from the catchment was derived from deeper mineral soil horizons, with little contribution of DOM derived from organic soils. Therefore, DOM fingerprint analysis of in-situ soil water proved to be a promising approach for tracing back the main sources of stream water DOM.
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•Chemical signature was used to identify sources of DOM in stream water.•Solid organic matter samples were of limited use for source identification.•Peats contributed hardly to downstream DOM.•Peaty Gleysol signals still detectable downstream the source location.•Mineral soil horizons exerted the strongest overall control on stream DOM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of the tumor suppressor mothers against decapentaplegic homolog 4 (SMAD4) has not yet been defined in patients (pts) with advanced pancreatic cancer (aPC). This translational research study ...was designed to evaluate the impact of tumoral SMAD4 loss on clinicopathological parameters and outcome in PC patients receiving palliative chemotherapy. Using immunohistochemistry, we examined SMAD4 expression in tumor tissue of 143 aPC pts treated within completed prospective clinical and biomarker trials. In uni- and multivariate analyses, SMAD4 expression status was correlated to clinicopathological patient characteristics and outcome. At chemotherapy initiation, 128 pts had metastatic PC; most pts (
= 99) received a gemcitabine-based regimen. SMAD4 loss was detected in 92 pts (64%); patient characteristics such as gender, age, tumor grading, disease stage or number of metastatic sites had no significant impact on tumoral SMAD4 status. In univariate analyses, SMAD4 loss had no impact on overall survival (hazard ratio (HR) 1.008,
= 0.656); however, we observed a prolonged progression-free survival (HR 1.565,
= 0.038) in pts with tumoral SMAD4 loss. This finding was confirmed in multivariate analyses (HR 1.790,
= 0.040), but only for gemcitabine-treated pts. In contrast to previous studies in resectable PC, loss of SMAD4 expression was not associated with a negative outcome in patients with advanced PC receiving systemic chemotherapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The 2015 European Guidelines on Pulmonary Hypertension did not only cover pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung ...disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase‑5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians sometimes feel inclined to treat other forms of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Paediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were created, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The 2018 updated recommendations of this working group are summarized in the present paper.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Neoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the ...optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.
Data on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.
Patients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).
Representing one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary ...cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes.
Methods
Overall survival (OS) analysis of patients undergoing curative resection of ampullary cancer.
Results
Elevated preoperative CEA (
P
= 0.013) and CA 19-9 levels (
P
= 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk IT
CEA
−
subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%;
P
= 0.047) and lymph node involvement (pN+, 30 vs. 65%;
P
= 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8;
P
< 0.001). By multivariate survival analysis, the patient age, the PT subtype, and an elevated pre-resection serum CEA value were identified as independent prognostic variables.
Conclusions
In AC, the histomorphologic subclassification is highly relevant regarding the prognostic value of preoperative serum CEA and CA 19-9. IT-patients with normal preoperative CEA represent a favorable subgroup with excellent long-term survival.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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