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Simple Summary: The effects of reduced prescription doses on normal tissue toxicity in the treatment of non-Hodgkin lymphomas of the neck/thorax region remain unclear. Acute side effects, which already occur at low organ doses, can only be described to a limited extent by the models given in the literature. Nonetheless, the knowledge about these dose–response relationships is particularly important to predict an acute response in normal tissue adequately. Considering a robust normal tissue toxicity model, dose prescriptions and treatment plans can be optimized to increase the treatment quality and, thus, the outcome for the patient. This biophysical study aimed to determine fitting parameters for the Lyman–Kutcher–Burman (LKB) dose–response model for normal tissue complication probability (NTCP) calculations of acute side effects and to investigate the impact of reduced radiation doses on the probability of their occurrence in supradiaphragmatic non-Hodgkin lymphoma (NHL) irradiation. A cohort of 114 patients with NHL in the cervicothoracic region, treated between 2015 and 2021 at the University Hospitals of Münster, Hamburg, and Essen, with involved site radiation therapy (ISRT), were included. Among them, 68 patients with aggressive NHL (a-NHL) received consolidative radiation therapy with 24–54 Gy following (R-)CHOP chemotherapy. Additionally, 46 patients with indolent NHL (i-NHL) underwent radiotherapy with 22.5–45.0 Gy. Two treatment plans were prospectively created for each patient (a-NHL: 30.0/40.0 Gy; i-NHL: 24.0/30.0 Gy). NTCP were then calculated using the optimized LKB model. The adapted dose–response models properly predicted the patient's probability of developing acute side effects when receiving doses ≤ 50 Gy. In addition, it was shown that reduced radiation doses can influence the NTCP of acute side effects depending on the aggressiveness of NHL significantly. This study provided a foundation to prospectively assess the probability of adverse side effects among today's reduced radiation doses in the treatment of NHL. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant lymphomata originating from the central nervous system are rare entities and usually are characterized by rapid growth, requiring intensified treatment. In contrast, low-grade lymphoma variants may be treated using radiotherapy alone. As the majority of cases arise from the dura, only very few cases of parenchymal low-grade lymphoma have been reported in the literature. We present a retrospective analysis of two patients treated with involved-site radiotherapy at our institution and discuss the available literature. Overall, these patients have a good prognosis and may be treated using primary radiation therapy. Background: Primary lymphoma of the central nervous system (PCNSL) encompasses a variety of lymphoma subtypes, with the majority being diffuse large B-cell lymphomas, which require aggressive systemic treatment. In contrast, low-grade lymphomas are reported infrequently and are mostly limited to dural manifestations. Very rarely, parenchymal low-grade PCNSL is diagnosed, and the cases documented in the literature show a wide variety of treatment approaches. Methods: We screened all cases of PCNSL treated at our department (a tertiary hematooncology and neurooncology center) in the last 15 years and conducted a comprehensive literature research in the PubMed database. Results: Overall, two cases of low-grade primary parenchymal PCNSL treated with irradiation were identified. The dose prescriptions ranged from 30.6 to 36 Gy for the involved site, with sparing of the hippocampal structures. Both patients had an excellent response to the treatment with a mean follow-up of 20 months. No clinical or radiological signs of treatment toxicity were detected. Conclusions: Our analysis corroborates the results from the literature and demonstrates that parenchymal low-grade PCNSL shows a good response to localized radiation treatment, enabling a favorable outcome while avoiding long-term treatment toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy is essential for the management of symptomatic osteolytic lesions in multiple myeloma but usually requires a combination with systemic therapy. This study analyzes the acute toxicities of radiotherapy in this setting and demonstrates the feasibility of modern combined modality treatments without significant increases in hematological and non-hematological side effects. However, high-grade leukocytopenia is more frequent following radiotherapy when systemic therapy is given simultaneously. Treatment of five bones or more was associated with a significant increase in thrombocytopenia and leukocytopenia during radiotherapy. Radiotherapy (RT) is an established treatment modality in the management of patients with multiple myeloma (MM), aiming at analgesia and stabilization of osteolytic lesions. As a multifocal disease, the combined use of RT, systemic chemotherapy, and targeted therapy (ST) is pivotal to achieve better disease control. However, adding RT to ST may lead to increased toxicity. The aim of this study was to evaluate the tolerability of ST given concurrently with RT. Overall, 82 patients treated at our hematological center with a median follow-up of 60 months from initial diagnosis and 46.5 months from the start of RT were evaluated retrospectively. Toxicities were recorded from 30 days before RT up to 90 days after RT. 54 patients (65.9%) developed at least one non-hematological toxicity, with 50 patients (61.0%) showing low-grade (grade I or II) and 14 patients (17.1%) revealing high-grade (grade III and IV) toxicities. Hematological toxicities were documented in 50 patients (61.0%) before RT, 60 patients (73.2%) during RT, and 67 patients (81.7%) following RT. After RT, patients who had received ST during RT showed a significant increase in high-grade hematological toxicities (p = 0.018). In summary, RT can be safely implemented into modern treatment regimens for MM, but stringent monitoring of potential toxicities even after completion of RT has to be ensured. [ABSTRACT FROM AUTHOR]

Background Secondary sclerosing cholangitis (SSC) is a rare disease with poor prognosis. Cases of SSC have been reported following coronavirus disease 2019 (COVID-SSC). The aim of this study was to compare COVID-SSC to SSC in critically ill patients (SSC-CIP) and to assess factors influencing transplant-free survival. Methods In this retrospective, multicenter study involving 127 patients with SSC from 9 tertiary care centers in Germany, COVID-SSC was compared to SSC-CIP and logistic regression analyses were performed investigating factors impacting transplant-free survival. Results Twenty-four patients had COVID-SSC, 77 patients SSC-CIP, and 26 patients other forms of SSC. COVID-SSC developed after a median of 91 days following COVID-19 diagnosis. All patients had received extensive intensive care treatment (median days of mechanical ventilation, 48). Patients with COVID-SSC and SSC-CIP were comparable in most of the clinical parameters and transplant-free survival was not different from other forms of SSC (P =.443, log-rank test). In the overall cohort, the use of ursodeoxycholic acid (UDCA) (odds ratio [OR], 0.36 [95% confidence interval {CI},.16–.80], P =.013; log-rank P <.001) and high serum albumin levels (OR, 0.40 [95% CI,.17–.96], P =.040) were independently associated with an increased transplant-free survival, while the presence of liver cirrhosis (OR, 2.52 [95% CI, 1.01–6.25], P =.047) was associated with worse outcome. Multidrug-resistant organism (MDRO) colonization or infection did not impact patients' survival. Conclusions COVID-SSC and CIP-SSC share the same clinical phenotype, course of the disease, and risk factors for its development. UDCA may be a promising therapeutic option in SSC, though future prospective trials are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The benefit of administering an extra dose to the tumor bed (boost) prior or simultaneously to adjuvant breast radiotherapy in terms of local recurrence rate has already been the subject of several studies and, thus, has already found justification in appropriate patient cases. In this study, we compared two boost techniques, an intraoperative radiotherapy (IORT) boost and an intensity-modulated radiotherapy boost (IMRT), analyzing two patient collectives to determine the equivalence of the two techniques or which of the two proves superior. According to our monocenter data on tumor control, survival rates, toxicities, and cosmetic results, no significant differences were revealed between the two boost techniques, and it cannot be generalized that one technique is more advantageous than the other. The aim of this retrospective study is to compare the two boost subgroups, IORT or IMRT, in terms of overall survival (OS), progression-free survival (PFS), cosmesis, and acute and late toxicity. It shall be shown whether and which of the boost techniques offers better results with respect to the facial points, since there are already many studies on applying boost to the tumor bed after/during breast conserving surgery, and there are few which compare the different techniques. For this comparison, two subgroups of 76 patients each (n = 152), treated between 2002 and 2015, were enrolled in the study. In one subgroup, the 9 Gy boost was intraoperatively administered after complete removal of the primary tumor, while the other subgroup received the boost of 8.4 Gy percutaneously and simultaneously integrated into the tumor bed after breast conserving surgery. Both subgroups have subsequently undergone whole breast irradiation (WBI) of 50.4/50 Gy in 1.8–2 Gy per fraction. OS and the incidence of late toxicity did not differ between the two subgroups and no risk factor was found regarding PFS. Acute toxicities initially occurred significantly less (p < 0.001) in the IORT subgroup; however, after WBI took place, this difference vanished. Therefore, boost application by means of IORT or IMRT can be considered equivalent. [ABSTRACT FROM AUTHOR]

Simple Summary: Reciprocal interactions between tumor and host cells in the tumor microenvironment critically influence the clinical outcome in ovarian carcinoma patients. Therefore, the identification of factors triggering central communication pathways controlling tumor growth and metastasis is highly relevant. This study was conducted to uncover the contribution of lipid mediators to this signaling network by different cell types in the tumor microenvironment and subsequent functional evaluation of clinically relevant candidates. We found that prostacyclin is mainly secreted by cancer-associated fibroblast and selectively acts on prostacyclin receptor-expressing macrophages to induce pro-tumorigenic and immunosuppressive features. Our findings improve the understanding of the tumor-promoting role of prostacyclin in ovarian carcinoma and identify prostacyclin synthesis in cancer-associated fibroblast as a potential target for improved treatment approaches. Metastasis of high-grade ovarian carcinoma (HGSC) is orchestrated by soluble mediators of the tumor microenvironment. Here, we have used transcriptomic profiling to identify lipid-mediated signaling pathways encompassing 41 ligand-synthesizing enzymes and 23 cognate receptors in tumor, immune and stroma cells from HGSC metastases and ascites. Due to its strong association with a poor clinical outcome, prostacyclin (PGI2) synthase (PTGIS) is of particular interest in this signaling network. PTGIS is highly expressed by cancer-associated fibroblasts (CAF), concomitant with elevated PGI2 synthesis, whereas tumor-associated macrophages (TAM) exhibit the highest expression of its surface receptor (PTGIR). PTGIR activation by PGI2 agonists triggered cAMP accumulation and induced a mixed-polarization macrophage phenotype with altered inflammatory gene expression, including CXCL10 and IL12A repression, as well as reduced phagocytic capability. Co-culture experiments provided further evidence for the interaction of CAF with macrophages via PGI2, as the effect of PGI2 agonists on phagocytosis was mitigated by cyclooxygenase inhibitors. Furthermore, conditioned medium from PGI2-agonist-treated TAM promoted tumor adhesion to mesothelial cells and migration in a PTGIR-dependent manner, and PTGIR activation induced the expression of metastasis-associated and pro-angiogenic genes. Taken together, our study identifies a PGI2/PTGIR-driven crosstalk between CAF, TAM and tumor cells, promoting immune suppression and a pro-metastatic environment. [ABSTRACT FROM AUTHOR]

Purpose: This article reports on the long‐term impact of radiotherapy adapted to stage, histology, and previous resection in a large cohort of patients with intestinal lymphoma (iL) treated with definitive or adjuvant curative‐intent radiation therapy (RT) ± chemotherapy (CHOP, MCP, or COP). Patients and Methods: In two consecutive prospective study designs, 134 patients with indolent (stage IE–IIE) or aggressive (stage IE–IVE) iL were referred to 61 radiotherapeutic institutions between 1992 and 2003. Patients with indolent iL received extended field (EF) 30 Gy (+10 Gy boost in definitive treatment); patients with aggressive iL received involved field (IF) (EF) 40 Gy by means of stage‐, histology‐, and operation‐adapted radiation fields. Results: The patients had median age 58 years and were predominantly male (2:1). Histology showed aggressive prevalence (1.6:1), stage IE–to–stage IIE ratio of iL 1.04:1, and localized stages–to–advanced stages ratio of aggressive lymphoma 23:1. Median follow‐up was in total 11.7 years: 10.0 years in the first study, GIT (GastroIntestinal‐Tract) 1992, and 11.8 years in the second study, GIT 1996. Lymphoma involvement was predominantly a single intestinal lesion (82.1%). Decrease of radiation field size from EF to IF in stage I aggressive iL from GIT 1992 to GIT 1996 resulted in a nonsignificant partial reduction of chronic toxicity while maintaining comparable survival rates (5‐year overall survival 87.9 vs. 86.7%, 10‐year overall survival 77.4 vs. 71.5%) with nonsignificant difference in event‐free survival (5‐year event‐free survival 82.6 vs. 86.7%, 10‐year event‐free survival 69.7 vs. 71.5%) and lymphoma‐specific survival (5‐year lymphoma‐specific survival 90.1 vs. 91.9%, 10‐year lymphoma‐specific survival 87.6% vs. 91.9%). Comparative dose calculation of two still available indolent duodenal lymphoma computed tomography scans revealed lower radiation exposure to normal tissues from applying current standard involved site RT (ISRT) 30 Gy in both cases. Conclusion: RT adapted to stage, histology, and resection in multimodal treatment of iL, despite partially decreasing field size (EF to IF), achieves excellent local tumor control and survival rates. The use of modern RT technique and target volume with ISRT offers the option of further reduction of normal tissue complication probability. Implications for Practice: Although patients with intestinal lymphoma (iL) are heterogeneous according to histology and subtype, they benefit from radiotherapy. Prospective study data from 134 patients with indolent iL (stage IE–IIE) or aggressive iL (stage IE–IVE) show 100% tumor control after definitive or adjuvant curative‐intent radiation therapy ± chemotherapy. Radiation treatment was applied between 1992 and 2003. Median follow‐up in total was 11.7 years. No radiotherapy‐associated death occurred. Relapse developed in 15.7% of the entire cohort; distant failure was more frequent than local (4:1). Normal tissue complication probability can be further improved using modern involved site radiation therapy techniques. This article reports the details of radiation therapy in the therapeutic multimodality approach for treatment of patients with intestinal lymphoma. [ABSTRACT FROM AUTHOR]

The project 'Application of remote sensing for the early detection of drought stress at vulnerable forest sites (ForDroughtDet)' is funded by the German Federal Agency of Agriculture and Food and aims to detect drought stress in an early phase using remote sensing techniques. In this project, three test sites in the south and middle part of Germany are selected. Three levels of observation and analyses are performed. In the first level, close-range stereo images and spectral information are captured with a research crane in Kranzberg forest. In the second level, three study sites are imaged twice in three years by airborne hyperspectral and stereo cameras. In the third level, the drought stress detection approach will be transferred to regional scale by satellite image. In this paper, we will briefly report our results from the first and second levels. In the first level, 3D models of the forest canopies are generated with the MC-CNN based dense matching approaches, with which the 3D shapes of the stressed and healthy trees are analysed. In addition, for the spectral analyses, different chlorophyll-sensitive indices are calculated and compared for the stressed and healthy trees. In order to further analyse the tree drought stress in the second level, a novel individual tree crown (ITC) segmentation approach is proposed and tested on the airborne stereo dataset. [ABSTRACT FROM AUTHOR]

All six sturgeon species naturally occurring in the Danube River from the Black Sea (BS) to the upstream reaches in Germany today are under severe pressure and classified as either vulnerable, critically endangered or already extinct in the Danube River Basin (DRB). This sharp decline of populations is the result of two major drivers: habitat alteration and unsustainable harvest. The Danube River Basin can be divided in three functionally separated sections by its hydromorphology and character: The Lower Danube (LD) and BS, now also separated ecologically from the Middle Danube (MD) by two hydropower stations at the Iron Gate gorge, 800 km from the sea, currently restricting the remaining anadromous sturgeon species (A. gueldenstaedtii, A. stellatus, Huso huso) to the LD and BS also restraining migrations of potamodromous species. The Upper Danube (UD) is nowadays disconnected from the approx. 850 km long MD by Gabčikovo Dam. The UD itself, as well as many tributaries along the Danube, are fragmented by numerous barriers, leaving no more than a total of 300 km free flowing river out of 700 km. Overharvest led to disappearance of most sturgeon species in the UD already in the Middle Ages, with populations in the MD following in the subsequent centuries. Today the potamodromous sterlet (A. ruthenus) still exists in small decreasing populations in the UD and MD basins, where its occurrence is supported by stocking. Most probably the potamodromous ship sturgeon (A. nudiventris) is extirpated in the whole basin. The Danube basin comprises 19 countries, being the most international river basin in the world, rendering coordinated conservation efforts a challenge. Strategic guidelines for the conservation of the Danube sturgeons are available in form of several action plans, but implementation remains insufficient as of yet. This paper attempts an analysis of the potential for sturgeon restoration in the UD and MD basin and highlights the need for concerted approaches when it comes to ex situ actions and reintroductions. [ABSTRACT FROM AUTHOR]

The vast number of channel types and broad range of possible channel configurations makes identifying a product's most efficient route to end-users challenging for today's managers. This study analyzes drivers of a firm's distribution intensity and their respective effects on performance. The simultaneous analysis of the two dimensions of distribution intensity (i.e., the variety of channels and the degree of channel usage) reveals the two decisions to be positively interrelated, reflecting a firm's intention to achieve market coverage. Moreover, firms align their distribution intensity to their individual context (their business strategy and environmental conditions), leading to efficient intensity levels. Inefficient intensity levels get penalized by market mechanisms. The results reveal that more is not necessarily better: a more offensive-minded intensity of distribution particularly creates a positive performance effect when complex products are being offered and even more so when the customer base contains a large share of demanding key accounts. [ABSTRACT FROM AUTHOR]

Stereo satellites provide height information of the earth's surface with increasing accuracy. High temporal resolution and wide regional coverage are the great advantages of satellites compared with aerial surveys. There is currently little experience of how accurate forest attributes can be modelled using high-resolution stereo satellite data, especially for highly structured forests in Central Europe. Thus, the potential of Cartosat-1 and WorldView-2 was assessed for timber volume estimation in a complex forest in Germany. Digital surface models were generated using Semi-Global Matching. Canopy height models (CHMs) were computed by subtracting a Light detection and ranging (LiDAR) terrain model. The CHMs were co-registered with field plots of a forest inventory. Explanatory variables were derived from the CHMs for timber volume estimation using regressions. Accuracies were evaluated at plot and stand levels. Results were compared with estimations based on a LiDAR-CHM. At plot level the following root mean squared errors (RMSEs) for timber volume estimation were obtained: 50.26 per cent for Cartosat-1, 44.40 per cent for WorldView-2 and 38.02 per cent for LiDAR. The RMSEs were smaller than the standard deviation of the observed timber volume. The RMSEs at a stand level yielded 21.49 per cent for Cartosat-1, 19.59 per cent for WorldView-2 and 17.14 per cent for LiDAR. The study demonstrates the potential of satellite stereo images for regionalization of sample plot inventories. [ABSTRACT FROM AUTHOR]

Background Human beta-defensins ( hBDs) and the C- C chemokine ligand 20 ( CCL20) produced by gingival epithelial cells ( GECs) and fibroblasts ( HGFs) are antimicrobial peptides ( AMPs) that play an important role in innate immunity. The aim of this study was to determine the differential immune response of GECs and HGFs to the oral commensal Streptococcus gordonii ( SG) and the pathogen Porphyromonas gingivalis ( PG). Material and Methods In addition to the analysis of gingival biopsies, primary GECs and HGFs were exposed to SG and/or PG, and expression of various AMPs and pro-inflammatory mediators was studied by real-time PCR and ELISA. Results Gene expression of AMPs was detected in gingival connective tissue. Both SG and PG induced the mRNA-expression of hBD-2 and hBD-3 in GECs as well as HGFs after 24 h ( p < 0.05). In HGFs, the commensal bacterium SG stimulated the mRNAs of hBD-3 and CCL20 after 24 h ( p < 0.05), while not in GECs. In GECs, the inductive effect of PG on the mRNA-expression of hBD-2 was amplified when cells were first exposed to commensal SG (for 1 h) prior to stimulation with PG ( SG- PG; p < 0.05). Conclusion Our data indicate that cell-bacteria interactions and/or bacteria-bacteria cross-talk may have an impact on AMP-regulation in gingiva. [ABSTRACT FROM AUTHOR]

Abstract: During the HRS (High Resolution Stereo) Scientific Assessment Program the French space agency CNES delivered data sets from the HRS camera system with high precision ancillary data. Two test data sets from this program were evaluated: one is located in Germany, the other in Spain. The first goal was to derive orthoimages and digital surface models (DSM) from the along track stereo data by applying the rigorous model with direct georeferencing and without ground control points (GCPs). For the derivation of DSM, the stereo processing software, developed at DLR for the MOMS-2P three line stereo camera was used. As a first step, the interior and exterior orientation of the camera, delivered as ancillary data from positioning and attitude systems were extracted. A dense image matching, using nearly all pixels as kernel centers provided the parallaxes. The quality of the stereo tie points was controlled by forward and backward matching of the two stereo partners using the local least squares matching method. Forward intersection lead to points in object space which are subsequently interpolated to a DSM in a regular grid. DEM filtering methods were also applied and evaluations carried out differentiating between accuracies in forest and other areas. Additionally, orthoimages were generated from the images of the two stereo looking directions. The orthoimage and DSM accuracy was determined by using GCPs and available reference DEMs of superior accuracy (DEM derived from laser data and/or classical airborne photogrammetry). As expected the results obtained without using GCPs showed a bias in the order of 5–20 m to the reference data for all three coordinates. By image matching it could be shown that the two independently derived orthoimages exhibit a very constant shift behavior. In a second step few GCPs (3–4) were used to calculate boresight alignment angles, introduced into the direct georeferencing process of each image independently. This method improved the absolute accuracy of the resulting orthoimages and DSM significantly. [Copyright &y& Elsevier]