Search

Purpose: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection. Procedures: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard. Results: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555–0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571–0.964), respectively. Conclusions: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Applied Ecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Geospatial data have a long history in marketing research that goes back to Huff's seminal gravity model from the 1960s. Their applications in research and practice range from location-based mobile targeting of individual consumers to store competition analysis and city marketing. In the past decades, geospatial data have become more readily available and have grown considerably in both breadth (i.e., countries and regions covered) and depth (i.e., granularity and diversity of information covered). Nonetheless, international marketing research has not yet fully embraced the opportunities that geospatial data bring to the field. To address this shortcoming, this article shows how geospatial data may propel international marketing research in various domains and develops future research questions for the field. In addition, it introduces OpenStreetMap as a rich geospatial data source to the discipline. The authors illustrate the use of geospatial data in general and OpenStreetMap in particular through a concrete application in which they analyze city center composition in nine countries across three continents. In doing so, they reproducibly describe the extraction of geospatial data, constructions of metrics and operationalizations, and visualizations. [ABSTRACT FROM AUTHOR]

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients. Available CT scans and clinical information on mortality, renal outcomes, occurrence of relapses and damage scores were analysed retrospectively from a tertiary rheumatology center in Germany. We included a total of 94 AAV patients (49 with GPA, 41 with MPA). Forty-four patients had lung involvement with available CT scans, 70.5% of which with GPA and 72.7% with renal involvement. Nodule formation and cavities were more frequent among GPA patients, whereas ground-glass opacities (GGO), ILD and pleural effusion were observed predominantly in MPA patients. Over a median follow-up of 37 months, GPA patients had a slightly higher overall mortality, whereas end-stage kidney failure rates were significantly increased in MPA patients. Relapse frequencies were comparable between both entities. The presence of GGO and pleural effusion were associated with higher relapse rates, whereas nodules were negatively correlated with relapses. Notably, RTX-treated patients had less infections as compared to individuals under different therapies. Our data demonstrate the outstanding importance of characteristic CT patterns in AAV diagnosis assessment. Especially certain CT patterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease. [ABSTRACT FROM AUTHOR]

Consumers who are uninterested in or annoyed by a TV ad may avoid the ad, limiting the effectiveness of not only the ad but also the remaining commercial break. Active avoidance of ads by changing the channel—known as "zapping"—is potentially a major concern for both advertisers and broadcasters. In two studies, the authors investigate whether and why ad content drives or mitigates zapping and develop a conceptual framework linking multiple content factors to psychological reactions that then affect zapping. They test the content–zapping relationship by drawing on a data set reflecting the zapping behavior of over 2,500 German television viewers combined with advertising data and content information for 1,315 spots representing 308 brands from 96 categories. The results of the first study show that ad creativity is associated with less zapping, whereas a strong information focus and a prominent or early integration of branding elements are associated with more zapping. The findings also reveal that the effects differ significantly for products with a utilitarian (vs. hedonic) consumption purpose and for search (vs. experience) goods. The results of the second study show that irritation (determined by feeling, e.g., annoyed, offended, or overwhelmed), relative to enjoyment, acts as the central mechanism in explaining why ad content affects zapping. [ABSTRACT FROM AUTHOR]

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Assessing immune responses to cytomegalovirus (CMV) after liver transplant in patients on immunosuppressive therapy remains challenging. In this study, employing ELISPOT assays, 52 liver-transplant recipients were evaluated for antiviral T-cell activity in peripheral blood mononuclear cells (PBMCs), measuring interferon-γ (IFN-γ) secretion upon stimulation with CMV-specific peptides (CMV peptide pool, CMV IE-1, and pp65 antigens). Parameters such as stimulation index, mean spot size, and mean spot count were measured. The study found that heightened immunosuppression, especially with prednisolone in triple therapy, significantly dampened CMV-specific immune responses. This was demonstrated by decreased IFN-γ production by CMV-specific T-cells (CMV peptide pool: p = 0.036; OR = 0.065 [95% CI: 0.005–0.840], pp65 antigen: p = 0.026; OR = 0.048 [95% CI: 0.003–0.699]). Increased immunosuppression correlated with reduced IFN-γ secretion per cell, reflected in smaller mean spot sizes for the CMV peptide pool (p = 0.019). Notably, shorter post-transplant intervals correlated with diminished antiviral T-cell IFN-γ release at two years (CMV peptide pool: p = 0.019; IE antigen: p = 0.010) and five years (CMV peptide pool: p = 0.0001; IE antigen: p = 0.002; pp65 antigen: p = 0.047), as did advancing age (pp65 antigen: p = 0.016, OR = 0.932, 95% CI: 0.881–0.987). Patients with undetectable CMV antigens had a notably higher risk of CMV reactivation within six months from blood collection, closely linked with triple immunosuppression and prednisolone use. These findings highlight the intricate interplay between immunosuppression, immune response dynamics, and CMV reactivation risk, emphasizing the necessity for tailored immunosuppressive strategies to mitigate CMV reactivation in liver-transplant recipients. It can be concluded that, particularly in the early months post-transplantation, the use of prednisolone as a third immunosuppressant should be critically reconsidered. Additionally, the use of prophylactic antiviral therapy effective against CMV in this context holds significant importance. [ABSTRACT FROM AUTHOR]

To extract the full revenue potential of their front line, B2B firms use their technical field service force for selling activities. However, as selling is only a complementary activity embedded in technicians' main service tasks, they may struggle to sell effectively. The authors investigate the service situation as a key driver of (i) the technician's decision to engage in selling (selling activity) and (ii) the customer's decision to purchase (selling success). They identify four types of service situations with unique effects on these outcomes. Notably, technicians' selling activity is highest (+ 10% compared to baseline) in service situations that offer a lower (-22%) likelihood of success, whereas activity is lower in the most promising situations. Thus, technicians do not properly exploit sales opportunities. The extent of inefficiencies moreover varies by employee-specific moderators, such that specialized technicians and those with little practical experience have particular difficulty exploiting excellent sales opportunities. [ABSTRACT FROM AUTHOR]

Background and Objectives: Esophageal varices (EV) and variceal hemorrhages are major causes of mortality in liver cirrhosis patients. Detecting EVs early is crucial for effective management. Computed tomography (CT) scans, commonly performed for various liver-related indications, provide an opportunity for non-invasive EV assessment. However, previous CT studies focused on variceal diameter, neglecting the three-dimensional (3D) nature of varices and shunt vessels. This study aims to evaluate the potential of 3D volumetric shunt-vessel measurements from routine CT scans for detecting high-risk esophageal varices in portal hypertension. Methods: 3D volumetric measurements of esophageal varices were conducted using routine CT scans and compared to endoscopic variceal grading. Receiver operating characteristic (ROC) analyses were performed to determine the optimal cutoff value for identifying high-risk varices based on shunt volume. The study included 142 patients who underwent both esophagogastroduodenoscopy (EGD) and contrast-enhanced CT within six months. Results: The study established a cutoff value for identifying high-risk varices. The CT measurements exhibited a significant correlation with endoscopic EV grading (correlation coefficient r = 0.417, p < 0.001). A CT cutoff value of 2060 mm3 for variceal volume showed a sensitivity of 72.1% and a specificity of 65.5% for detecting high-risk varices during endoscopy. Conclusions: This study demonstrates the feasibility of opportunistically measuring variceal volumes from routine CT scans. CT volumetry for assessing EVs may have prognostic value, especially in cirrhosis patients who are not suitable candidates for endoscopy. [ABSTRACT FROM AUTHOR]

Copyright of Journal fuer Verbraucherschutz und Lebensmittelsicherheit is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper presents the development and validation of the Social Acceptance Scale (SAS), an instrument designed to measure social acceptance, particularly in transformative sectors like agricultural livestock farming. Recognizing the need for a nuanced acceptance scale, various facets of acceptance across a three-level continuum were delineated, spanning from opposition to commitment, encompassing eight distinct items. The SAS's creation and validation process included the conceptual and empirical testing of four validity types: content validity, face validity, construct validity, and criterion validity. Content and face validity involved construct definition, item generation, iterative review, and pilot testing to ensure theoretical soundness. Empirical testing encompassed construct validity through statistical validation and assessments of factorial and convergent validity. Furthermore, criterion validity was explored by examining associations with related constructs, enhancing the SAS's external applicability. In conclusion, this paper introduces the SAS as a tool to measure social acceptance within transformative sectors. It underscores the necessity for a comprehensive acceptance scale, offering a detailed account of its development and validation. The discussion section acknowledges limitations and outlines potential directions for future research in this domain. [ABSTRACT FROM AUTHOR]

Copyright of Journal fuer Verbraucherschutz und Lebensmittelsicherheit is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal fuer Verbraucherschutz und Lebensmittelsicherheit is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: IL‐17A and TNF synergistically promote inflammation and tumorigenesis. Their interplay and impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing on mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation. Methods: Flow‐cytometry and immunohistochemistry experiments were employed to identify cellular sources of IL‐17A and TNF. Changes in transcriptomes and secretomes were determined by bulk and single cell RNA sequencing as well as affinity proteomics. Functional consequences were investigated by microscopic analyses and tumor cell adhesion assays. Potential clinical implications were assessed by immunohistochemistry and survival analyses. Results: We identified Th17 cells as the main population of IL‐17A‐ and TNF producers in ascites and detected their accumulation in early omental metastases. Both IL‐17A and its receptor subunit IL‐17RC were associated with short survival of OC patients, pointing to a role in clinical progression. IL‐17A and TNF synergistically induced the reprogramming of mesothelial cells towards a pro‐inflammatory mesenchymal phenotype, concomitantly with a loss of tight junctions and an impairment of mesothelial monolayer integrity, thereby promoting cancer cell adhesion. IL‐17A and TNF synergistically induced the Th17‐promoting cytokines IL‐6 and IL‐1β as well as the Th17‐attracting chemokine CCL20 in mesothelial cells, indicating a reciprocal crosstalk that potentiates the tumor‐promoting role of Th17 cells in OC. Conclusions: Our findings reveal a novel function for Th17 cells in the OC microenvironment, which entails the IL‐17A/TNF‐mediated induction of mesothelial‐mesenchymal transition, disruption of mesothelial layer integrity and consequently promotion of OC cell adhesion. These effects are potentiated by a positive feedback loop between mesothelial and Th17 cells. Together with the observed clinical associations and accumulation of Th17 cells in omental micrometastases, our observations point to a potential role in early metastases formation and thus to new therapeutic options. [ABSTRACT FROM AUTHOR]

Avian influenza (AI) is a highly contagious viral disease that constitutes a significant threat to birds worldwide. Particularly concerning are highly pathogenic AI (HPAI) viruses of the H5 subtype, which have caused extensive losses in both poultry and wild bird flocks. For this reason, the European Union (EU) mandated Member States (MSs) to carry out surveillance for AI in both poultry and wild birds. Passive surveillance, which aims at the virological detection of AI in wild birds found dead or moribund, is part of this surveillance programme. To aid the MSs, a list of wild bird target species for the passive surveillance of H5 HPAI viruses in Europe was first published by the European Food Safety Authority (EFSA) in 2017. This report presents an update of that list. To compile this updated list, both epidemiological and ornithological data were used. Epidemiological data consisted of passive surveillance data submitted by the MSs to EFSA. Ornithological data was derived from literature and expert knowledge. Species were given scores for traits relevant for spreading HPAI among wild birds, such as habitat type and degree of gregariousness. Species were then categorised into ecological groups, based on their relevance for early warning purposes, considering the likelihood of virus transmission to poultry. Within these groups, the ranking of the species was determined by their scores for both HPAI history and ecological traits. The final updated target list comprises 241 bird species, which are all to be considered risk species and can be targeted in passive surveillance programmes. Depending on individual needs and available budget, this report provides suggestions on which ecological groups to focus on and which events to prioritise. This list aims at helping MSs in prioritising passive surveillance sampling efforts, thus increasing insights into the spread of HPAI in wild birds in Europe. [ABSTRACT FROM AUTHOR]

Background: To validate pulmonary computed tomography (CT) perfusion in a porcine model by invasive monitoring of cardiac output (CO) using thermodilution method. Methods: Animals were studied at a single center, using a Swan-Ganz catheter for invasive CO monitoring as a reference. Fifteen pigs were included. Contrast-enhanced CT perfusion of the descending aorta and right and left pulmonary artery was performed. For variation purposes, a balloon catheter was inserted to block the contralateral pulmonary vascular bed; additionally, two increased CO settings were created by intravenous administration of catecholamines. Finally, stepwise capillary occlusion was performed by intrapulmonary arterial injection of 75-μm microspheres in four stages. A semiautomatic selection of AFs and a recirculation-aware tracer-kinetics model to extract the first-pass of AFs, estimating blood flow with the Stewart-Hamilton method, was implemented. Linear mixed models (LMM) were developed to calibrate blood flow calculations accounting with individual- and cohort-level effects. Results: Nine of 15 pigs had complete datasets. Strong correlations were observed between calibrated pulmonary (0.73, 95% confidence interval [CI] 0.6–0.82) and aortic blood flow measurements (0.82, 95% CI, 0.73–0.88) and the reference as well as agreements (± 2.24 L/min and ± 1.86 L/min, respectively) comparable to the state of the art, on a relatively wide range of right ventricle-CO measurements. Conclusions: CT perfusion validly measures CO using LMMs at both individual and cohort levels, as demonstrated by referencing the invasive CO. Relevance statement: Possible clinical applications of CT perfusion for measuring CO could be in acute pulmonary thromboembolism or to assess right ventricular function to show impairment or mismatch to the left ventricle. Key points: • CT perfusion measures flow in vessels. • CT perfusion measures cumulative cardiac output in the aorta and pulmonary vessels. • CT perfusion validly measures CO using LMMs at both individual and cohort levels, as demonstrated by using the invasive CO as a reference standard. [ABSTRACT FROM AUTHOR]

Blood-based biomarkers have been extensively evaluated for their diagnostic potential in Alzheimer's disease. However, their relative prognostic and monitoring capabilities for cognitive decline, amyloid-β (Aβ) accumulation and grey matter loss in cognitively unimpaired elderly require further investigation over extended time periods. This prospective cohort study in cognitively unimpaired elderly [ n = 185, mean age (range) = 69 (53–84) years, 48% female] examined the prognostic and monitoring capabilities of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), Aβ1-42/Aβ1-40 and phosphorylated tau (pTau)181 through their quantification in serum. All participants underwent baseline Aβ-PET, MRI and blood sampling as well as 2-yearly cognitive testing. A subset additionally underwent Aβ-PET (n = 109), MRI (n = 106) and blood sampling (n = 110) during follow-up [median time interval (range) = 6.1 (1.3–11.0) years]. Matching plasma measurements were available for Aβ1-42/Aβ1-40 and pTau181 (both n = 140). Linear mixed-effects models showed that high serum GFAP and NfL predicted future cognitive decline in memory (βGFAP×Time = −0.021, PFDR = 0.007 and βNfL×Time = −0.031, PFDR = 0.002) and language (βGFAP×Time = −0.021, PFDR = 0.002 and βNfL×Time = −0.018, PFDR = 0.03) domains. Low serum Aβ1-42/Aβ1-40 equally but independently predicted memory decline (βAβ1-42/Aβ1-40×Time = −0.024, PFDR = 0.02). Whole-brain voxelwise analyses revealed that low Aβ1-42/Aβ1-40 predicted Aβ accumulation within the precuneus and frontal regions, high GFAP and NfL predicted grey matter loss within hippocampal regions and low Aβ1-42/Aβ1-40 predicted grey matter loss in lateral temporal regions. Serum GFAP, NfL and pTau181 increased over time, while Aβ1-42/Aβ1-40 decreased only in Aβ-PET-negative elderly. NfL increases associated with declining memory (βNfLchange×Time = −0.030 , PFDR = 0.006) and language (βNfLchange×Time = −0.021, PFDR = 0.02) function and serum Aβ1-42/Aβ1-40 decreases associated with declining language function (βAβ1-42/Aβ1-40×Time = −0.020, PFDR = 0.04). GFAP increases associated with Aβ accumulation within the precuneus and NfL increases associated with grey matter loss. Baseline and longitudinal serum pTau181 only associated with Aβ accumulation in restricted occipital regions. In head-to-head comparisons, serum outperformed plasma Aβ1-42/Aβ1-40 (ΔAUC = 0.10, PDeLong, FDR = 0.04), while both plasma and serum pTau181 demonstrated poor performance to detect asymptomatic Aβ-PET positivity (AUC = 0.55 and 0.63, respectively). However, when measured with a more phospho-specific assay, plasma pTau181 detected Aβ-positivity with high performance (AUC = 0.82, PDeLong, FDR < 0.007). In conclusion, serum GFAP, NfL and Aβ1-42/Aβ1-40 are valuable prognostic and/or monitoring tools in asymptomatic stages providing complementary information in a time- and pathology-dependent manner. [ABSTRACT FROM AUTHOR]

Decision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats' choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding. The neural substrates of time perception are still unclear. Here, the authors show that as rats judged tactile stimuli, optogenetic manipulation of somatosensory cortex systematically altered perception of stimulus intensity and of duration, unveiling a multiplexed code. [ABSTRACT FROM AUTHOR]

Simple Summary: Progressive ataxia is an autosomal recessive defect that is lethal due to the irreversible changes it causes to the brain and spinal cord. Only homozygous carriers of the mutated KIF1C allele manifest progressing clinical signs, mostly no earlier than 12–24 months of age. The objectives of this field study were to determine the prevalence of the mutated KIF1C allele, uncover its associations with growth and muscle conformation, and build awareness of this lethal condition among beef cattle breeders in Germany. A total of 1315 samples was sent in for mutation testing. Prevalence of the mutated KIF1C allele was 11.75%, resulting from 293 heterozygous and 8 homozygous mutant animals. Homozygous carriers of the mutated KIF1C allele showed a significant superiority in estimated breeding values for daily weight gain and muscle conformation. In order to reduce the frequency of the mutated KIF1C allele, genetic testing should be introduced for Charolais cattle and should be mandatory for all Charolais breeding bulls. It is important to create awareness of this condition among beef cattle breeders, in addition to the possibilities of preventing the number of affected animals. In addition, genetic testing of eight further beef, dual-purpose, or dairy cattle breeds revealed that two German Angus cattle showed heterozygous mutations for the KIF1C A-allele; therefore, we recommend genetic testing of German Angus to prevent the spread of the KIF1C allele. Bovine progressive ataxia in Charolais cattle was first described in the 1970s; then, cases were reported in Charolais worldwide. A homozygous loss-of-function mutation within the KIF1C gene (c.608G>A) was found to be responsible for this neurodegenerative disease. The aim of this study was to determine whether the mutated KIF1C allele segregates in the German Charolais population and whether the estimated breeding values for growth and muscle conformation are associated with the mutated genotypes. Genetic test results of the KIF1C:c.608G>A variant were available for 1315 Charolais cattle from 35 herds located in Germany. In addition, 324 samples from eight other beef cattle breeds were tested for the mutated KIF1C allele. We were able to demonstrate that the KIF1C mutation is common, with a frequency of 11.75% in the German Charolais population. All but two of the eight (2/8 = 25%) homozygous mutated individuals showed clinical signs consistent with progressive ataxia. The estimated breeding values of muscle conformation in 200- and 365-day-old animals indicated a significant superiority for homozygous mutated animals when compared either with heterozygous or homozygous wild-type genotypes; this was also the case for heterozygous genotypes in comparison with homozygous wild-type genotypes. For the estimated breeding values of daily weight gain in 200- and 365-day-old animals, the significant differences between homozygous mutated and heterozygous or wild-type genotypes were in favour of the homozygous mutant animals. There were no differences in the estimated maternal breeding values among all three KIF1C genotypes. For the first time, two German Angus cattle carrying the KIF1C mutation heterozygous were detected. The breeders' survey highlighted that increased awareness would facilitate increased conviction among breeders of the need for genetic testing in order to eliminate the lethal KIF1C allele. [ABSTRACT FROM AUTHOR]

Economic conditions may significantly affect households' shopping behavior and, by extension, retailers' and manufacturers' firm performance. By explicitly distinguishing between two basic types of economic conditions—micro conditions, in terms of households' personal income, and macro conditions, in terms of the business cycle—this study analyzes how households adjust their grocery shopping behavior. The authors observe more than 5,000 households over eight years and analyze shopping outcomes in terms of what, where, and how much they shop and spend. Results show that micro and macro conditions substantially influence shopping outcomes, but in very different ways. Microeconomic changes lead households to adjust primarily their overall purchase volume—that is, after losing income, households buy fewer products and spend less in total. In contrast, macroeconomic changes cause pronounced structural shifts in households' shopping basket allocation and spending behavior. Specifically, during contractions, households shift purchases toward private labels while also buying and consequently spending more than during expansions. During expansions, however, households increasingly purchase national brands but keep their total spending constant. The authors discuss psychological and sociological mechanisms that can explain the differential effects of micro and macro conditions on shopping behavior and develop important diagnostic and normative implications for retailers and manufacturers. [ABSTRACT FROM AUTHOR]

Digital platforms that aggregate products and services, such as Google Shopping or Amazon, have emerged as powerful intermediaries to brand offerings, challenging traditional product brands that have largely lost direct access to consumers. As a countermeasure, several long-established brands have built their own flagship platforms to resume control and foster consumer loyalty. For example, sports brands such as Nike, Adidas, or Asics launched tracking and training platforms that allow for ongoing versatile interactions among participants beyond product purchase. The authors analyze these emerging platform offerings, whose potential brands struggle to exploit, and provide guidance for brands that aim to platformize their business. This guidance comprises the conceptualization of digital platforms as places of consumer crowdsourcing (i.e., consumers drawing value from platform participants such as the brand, other consumers, or third-party businesses) and crowdsending (i.e., consumers providing value to platform participants) of products, services, and content along with a well-defined framework that brands can apply to assemble different types of flagship platforms. Evaluating the consequences of crowdsourcing and crowdsending for consumer–platform relationships, the authors derive a typology of archetypical relationship states and develop a set of propositions to help offline-born product brands thrive through platformization. [ABSTRACT FROM AUTHOR]

Mutations within the ectodysplasin A (EDA) gene have been associated with congenital hypotrichosis and anodontia (HAD/XHED) in humans, mice, dogs and cattle. We identified a three-generation family of Fleckvieh cattle with male calves exhibiting clinical and histopathological signs consistent with an X-linked recessive HAD (XHED). Whole genome and Sanger sequencing of cDNA showed a perfect association of the missense mutation g.85716041G>A (ss2019497443, rs1114816375) within the EDA gene with all three cases following an X-linked recessive inheritance, but normal EDAR and EDARADD. This mutation causes an exchange of glycine (G) with arginine (R) at amino acid position 227 (p.227G>R) in the second collagen triple helix repeat domain of EDA. The EDA variant was associated with a significant reduction and underdevelopment of hair follicles along with a reduced outgrowth of hairs, a complete loss of seromucous nasolabial and mucous tracheal and bronchial glands and a malformation of and reduction in number of teeth. Thermostability of EDA G227R was reduced, consistent with a relatively mild hair and tooth phenotype. However, incisors and canines were more severely affected in one of the calves, which correlated with the presence of a homozygous missense mutation of RNF111 (g.51306765T>G), a putative candidate gene possibly associated with tooth number in EDA-deficient Fleckvieh calves. [ABSTRACT FROM AUTHOR]

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]

Full-scale drag penalty predictions of flows over rough walls require surface roughness characterisation from laboratory experiments or numerical simulations. In either approach, it is necessary to determine the so-called equivalent sand-grain roughness height ( k s ). There are several steps involved in determining this aerodynamic roughness lengthscale, but its procedure typically includes a combination of measurement of wall-shear stress ( τ w ) using direct or indirect methods as well as analysis of velocity profiles. Indirect methods usually rely on assumptions made about flow and its scaling including the validity of universal outer-layer similarity. However, the implications of the underlying assumptions involved in full-scale drag prediction are unclear. In this work, we carry out wind tunnel measurements over a realistic rough surface (from a fouled ship-hull) to evaluate the impact of different methods with an emphasis on using the outer-layer similarity hypothesis for full-scale drag predictions. Wall-shear stress is measured using an in-house floating-element drag balance (DB), and velocity profiles are obtained using particle image velocimetry (PIV), allowing the evaluation of k s , and the associated wake parameters through several methods. The aerodynamic roughness parameters hence obtained are used for full-scale drag penalty calculations. It is observed that the predicted drag penalty can vary by over 15 % among the different methods highlighting the care that should be taken when employing such methods. [ABSTRACT FROM AUTHOR]

Seagrasses provide ecosystem services worth USD 2.28 trillion annually. However, their direct threats and our incomplete knowledge hamper our capabilities to protect and manage them. This study aims to evaluate if the NICFI Satellite Data Program basemaps could map Seychelles' extensive seagrass meadows, directly supporting the country's ambitions to protect this ecosystem. The Seychelles archipelago was divided into three geographical regions. Half-yearly basemaps from 2015 to 2020 were combined using an interval mean of the 10th percentile and median before land and deep water masking. Additional features were produced using the Depth Invariant Index, Normalised Differences, and segmentation. With 80% of the reference data, an initial Random Forest followed by a variable importance analysis was performed. Only the top ten contributing features were retained for a second classification, which was validated with the remaining 20%. The best overall accuracies across the three regions ranged between 69.7% and 75.7%. The biggest challenges for the NICFI basemaps are its four-band spectral resolution and uncertainties owing to sampling bias. As part of a nationwide seagrass extent and blue carbon mapping project, the estimates herein will be combined with ancillary satellite data and contribute to a full national estimate in a near-future report. However, the numbers reported showcase the broader potential for using NICFI basemaps for seagrass mapping at scale. [ABSTRACT FROM AUTHOR]

In view of the persisting tension between theoretical predictions and the LHC data for the pp → t t ¯ W ± production process, we present the state-of-the-art full off-shell NLO QCD result for pp → t t ¯ W +j + X. We concentrate on the multi-lepton decay channel at the LHC with s = 13 TeV. In our calculation off-shell top quarks and gauge bosons are described by Breit-Wigner propagators, furthermore, double-, single- as well as non-resonant top-quark contributions along with all interference effects are consistently incorporated at the matrix element level. We present results for both integrated and differential fiducial cross sections for various renormalisation and factorisation scale settings and different PDF sets. With a fairly inclusive choice of cuts and regardless of the scale and PDF choice, non-flat differential K -factors are obtained for many observables that we have examined. Since from an experimental point of view, both processes pp → t t ¯ W ±j + X and pp → t t ¯ W ± + X consist of similar final states we investigate the effect of additional jet activity on the integrated and differential fiducial cross sections. For this purpose, the normalised differential distributions for pp → e+νeμ− ν ¯ μτ+ντ b b ¯ j + X and pp → e+νeμ− ν ¯ μτ+ντ b b ¯ + X are compared. The theoretical results for the latter process are also recalculated. [ABSTRACT FROM AUTHOR]

Many studies have quantified the effects of TV ad spending or gross rating points on brand sales. Yet this effect is likely moderated by the different types of brand-related messages or cues (e.g., logo, brand attributes) embedded in the ads and by the ways (e.g., explicitly or implicitly) these cues are conveyed to TV audiences. The authors thus measure 17 cues often used within ads to build brand awareness (or salience) and brand image and investigate their influence on ad effectiveness. Technically, the study builds a dynamic model to quantify the effects of advertising on sales; builds a robust and interpretable (i.e., nonparametric and sparse) factor model that integrates correlated, left-censored branding cues; and then models the effects of advertising as a function of the factors identified by these cues. An analysis of 177 campaigns aired by 62 brands finds that salience cues (e.g., logo) and benefit and attribute messages moderate ad effectiveness. It also finds that explicit cues are more effective than implicit ones; nonetheless, the primary drivers of ad effectiveness are visual salience cues: the duration and frequency with which the logo and the duration with which the product are displayed. The study can thus suggest ways brand and ad agency managers can improve the effects of creative ad content on sales. [ABSTRACT FROM AUTHOR]

Copyright of Die Gastroenterologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Multispectral sensors are important instruments for Earth observation. In remote sensing applications, the near-infrared (NIR) band, together with the visible spectrum (RGB), provide abundant information about ground objects. However, the NIR band is typically not available on low-cost camera systems, which presents challenges for the vegetation extraction. To this end, this paper presents a conditional generative adversarial network (cGAN) method to simulate the NIR band from RGB bands of Sentinel-2 multispectral data. We adapt a robust loss function and a structural similarity index loss (SSIM) in addition to the GAN loss to improve the model performance. With 45,529 multi-seasonal test images across the globe, the simulated NIR band had a mean absolute error of 0.02378 and an SSIM of 89.98%. A rule-based landcover classification using the simulated normalized difference vegetation index (NDVI) achieved a Jaccard score of 89.50%. The evaluation metrics demonstrated the versatility of the learning-based paradigm in remote sensing applications. Our simulation approach is flexible and can be easily adapted to other spectral bands. [ABSTRACT FROM AUTHOR]

Microenvironmental bystander cells are essential for the progression of chronic lymphocytic leukemia (CLL). We have discovered previously that LYN kinase promotes the formation of a microenvironmental niche for CLL. Here we provide mechanistic evidence that LYN regulates the polarization of stromal fibroblasts to support leukemic progression. LYN is overexpressed in fibroblasts of lymph nodes of CLL patients. LYN-deficient stromal cells reduce CLL growth in vivo. LYN-deficient fibroblasts show markedly reduced leukemia feeding capacity in vitro. Multi-omics profiling reveals that LYN regulates the polarization of fibroblasts towards an inflammatory cancer-associated phenotype through modulation of cytokine secretion and extracellular matrix composition. Mechanistically, LYN deletion reduces inflammatory signaling including reduction of c-JUN expression, which in turn augments the expression of Thrombospondin-1, which binds to CD47 thereby impairing CLL viability. Together, our findings suggest that LYN is essential for rewiring fibroblasts towards a leukemia-supportive phenotype.The survival of chronic lymphocytic leukemia cells strongly depends on the presence of a supportive microenvironment. Here, the authors show that LYN kinase is essential for the reprogramming of stromal cells towards a leukemia-supportive phenotype that facilitates disease progression. [ABSTRACT FROM AUTHOR]

Change detection in urban areas can be helpful for urban resource management and smart city planning. The effects of human activities on the environment and ground have gained momentum over the past decades, causing remote sensing data sources analysis (such as satellite images) to become an option for swift change detection in the environment and urban areas. We proposed a semi-transfer learning method of EfficientNetV2 T-Unet (EffV2 T-Unet) that combines the effectiveness of composite scaled EfficientNetV2 T as the first path or encoder for feature extraction and convolutional layers of Unet as the second path or decoder for reconstructing the binary change map. In the encoder path, we use EfficientNetV2 T, which was trained by the ImageNet dataset. In this research, we employ two datasets to evaluate the performance of our proposed method for binary change detection. The first dataset is Sentinel-2 satellite images which were captured in 2017 and 2021 in urban areas of northern Iran. The second one is the Onera Satellite Change Detection dataset (OSCD). The performance of the proposed method is compared with YoloX-Unet families, ResNest-Unet families, and other well-known methods. The results demonstrated our proposed method's effectiveness compared to other methods. The final change map reached an overall accuracy of 97.66%. [ABSTRACT FROM AUTHOR]

Removing occluding objects such as vehicles from drivable areas allows precise extraction of road boundaries and related semantic objects such as lane-markings, which is crucial for several applications such as generating high-definition maps for autonomous driving. Conventionally, multiple images of the same area taken at different times or from various perspectives are used to remove occlusions and to reconstruct the occluded areas. Nevertheless, these approaches require large amounts of data, which are not always available. Furthermore, they do not work for static occlusions caused by, among others, parked vehicles. In this paper, we address occlusion removal based on single aerial images using generative adversarial networks (GANs), which are able to deal with the mentioned challenges. To this end, we adapt several state-of-the-art GAN-based image inpainting algorithms to reconstruct the missing information. Results indicate that the StructureFlow algorithm outperforms the competitors and the restorations obtained are robust, with high visual fidelity in real-world applications. Furthermore, due to the lack of annotated aerial vehicle removal datasets, we generate a new dataset for training and validating the algorithms, the Aerial Vehicle Occlusion Removal (AVOR) dataset. To the best of our knowledge, our work is the first to address vehicle removal using deep learning algorithms to enhance maps. [ABSTRACT FROM AUTHOR]

Simple Summary: Mantle cell lymphoma (MCL) is a very rare subtype of non-Hodgkin's lymphoma, predominantly affecting men, where most patients at initial presentation show an advanced spread of the disease with poor prognosis. We analyzed the long-term outcome of 22 patients treated with total body irradiation (TBI)-based conditioning prior to stem cell transplantation (SCT) at the University Hospital of Muenster, Germany. The present results of multimodal treatment support the published reports that TBI-based high-dose therapy followed by SCT is highly effective in this unfavorable disease. Both recently approved agents and traditional SCT open up possibilities of a personalized treatment approach for MCL with the aim of a cure. Introduction: In patients with mantle cell lymphoma (MCL), long-term remissions can be achieved by stem cell transplantation (SCT). Different conditioning treatment protocols exist with or without total body irradiation (TBI). There are few data published on the role of TBI before autologous stem cell transplantation (autoSCT) or allogenic stem cell transplantation (alloSCT). We report on the long-term survival data of patients treated by TBI prior to autologous or allogenic SCT at our center. Patients: In a retrospective analysis, the data of patients treated at the University Hospital of Muenster from May 2004 to February 2015 were collected and evaluated. For the analysis, all data of patients who were histopathologically diagnosed with MCL and underwent TBI prior to stem cell transplantation (SCT) were evaluated. Results: A total of 22 patients (19 men and 3 women) were treated with a TBI-based conditioning prior to SCT. The median age at initial diagnosis was 57.5 years (38–65 years). Seventeen patients had Ann Arbor stage IV, two patients had Ann Arbor stage III, and three patients Ann Arbor stage II disease. AutoSCT was performed in 19 patients and alloSCT was performed in 3 patients. In 18 patients, autoSCT was applied as part of first-line therapy, and in one patient after relapse. Two patients received alloSCT after relapse of MCL, and one patient received alloSCT during first-line therapy after an inadequate treatment response. TBI was performed in 12 patients with 10 Gy and in 6 patients with 12 Gy, these patients subsequently received autoSCT. In the group of four patients who received TBI with four Gy, four patients subsequently received alloSCT and one patient received autoSCT. Median overall survival after autoSCT and previous TBI was 11.4 years (142 months). In total, 11 out of 19 patients treated with autoSCT lived longer than 6.8 years (82–202 months). After alloSCT and previous TBI, the median overall survival was 3.25 years (14–59 months). Conclusions: A large proportion of patients with advanced MCL survived remarkably longer than 11.4 years after high-dose chemotherapy, TBI, and SCT. The present results of multimodal treatment support the published reports that TBI-based high-dose therapy followed by autoSCT is highly effective in this prognostically unfavorable disease situation. [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]

Marketing managers and creatives alike believe that authenticity is an essential element for effective advertising. However, no common understanding of authenticity in advertising exists, and empirical knowledge about its impact on consumer behavior is limited. In this study, the authors use a comprehensive literature review and qualitative studies to identify four dimensions of authenticity in an advertising context. By examining 323 television ads across 67 brands and four years, they investigate these dimensions' effects on the sales performance of advertised products. Because the impact of authenticity may depend on brand or product characteristics, the authors also analyze how these effects vary with brand size or across hedonic and utilitarian products. The results suggest that authenticity influences consumer behavior in a more nuanced manner than previously recognized. For instance, whereas an ad congruent with the brand's essence has a positive effect on sales in most cases, an overly honest advertising message can actually hurt performance; the latter is true especially for hedonic products, for which consumers rely more on subjective information when making purchase decisions. [ABSTRACT FROM AUTHOR]

Background: Basal cell adhesion molecule (BCAM) is a laminin α5 (LAMA5) binding membrane‐bound protein with a putative role in cancer. Besides full‐length BCAM1, an isoform lacking most of the cytoplasmic domain (BCAM2), and a soluble form (sBCAM) of unknown function are known. In ovarian carcinoma (OC), all BCAM forms are abundant and associated with poor survival, yet BCAM's contribution to peritoneal metastatic spread remains enigmatic. Methods: Biochemical, omics‐based and real‐time cell assays were employed to identify the source of sBCAM and metastasis‐related functions of different BCAM forms. OC cells, explanted omentum and a mouse model of peritoneal colonisation were used in loss‐ and gain‐of‐function experiments. Results: We identified ADAM10 as a major BCAM sheddase produced by OC cells and identified proteolytic cleavage sites proximal to the transmembrane domain. Recombinant soluble BCAM inhibited single‐cell adhesion and migration identically to membrane‐bound isoforms, confirming its biological activity in OC. Intriguingly, this seemingly anti‐tumorigenic potential of BCAM contrasts with a novel pro‐metastatic function discovered in the present study. Thus, all queried BCAM forms decreased the compactness of tumour cell spheroids by inhibiting LAMA5 – integrin β1 interactions, promoted spheroid dispersion in a three‐dimensional collagen matrix, induced clearance of mesothelial cells at spheroid attachment sites in vitro and enhanced invasion of spheroids into omental tissue both ex vivo and in vivo. Conclusions: Membrane‐bound BCAM as well as sBCAM shed by ADAM10 act as decoys rather than signalling receptors to modulate metastasis‐related functions. While BCAM appears to have tumour‐suppressive effects on single cells, it promotes the dispersion of OC cell spheroids by regulating LAMA5‐integrin‐β1‐dependent compaction and thereby facilitating invasion of metastatic target sites. As peritoneal dissemination is majorly mediated by spheroids, these findings offer an explanation for the association of BCAM with a poor clinical outcome of OC, suggesting novel therapeutic options. [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]