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The Gleason grading system remains the most powerful prognostic predictor for patients with prostate cancer since the 1960s. Its application requires highly-trained pathologists, is tedious and yet suffers from limited inter-pathologist reproducibility, especially for the intermediate Gleason score 7. Automated annotation procedures constitute a viable solution to remedy these limitations. In this study, we present a deep learning approach for automated Gleason grading of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining. Our system was trained using detailed Gleason annotations on a discovery cohort of 641 patients and was then evaluated on an independent test cohort of 245 patients annotated by two pathologists. On the test cohort, the inter-annotator agreements between the model and each pathologist, quantified via Cohen’s quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the inter-pathologist agreement (kappa = 0.71). Furthermore, the model’s Gleason score assignments achieved pathology expert-level stratification of patients into prognostically distinct groups, on the basis of disease-specific survival data available for the test cohort. Overall, our study shows promising results regarding the applicability of deep learning-based solutions towards more objective and reproducible prostate cancer grading, especially for cases with heterogeneous Gleason patterns.
Aim: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.
Results: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.
Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.
Highlights
• Stomach content analyses, parasitological and fecal examinations were performed on 73 raccoon dogs from Germany.
• 9 ecto- and 11 endoparasitic species could be identified of which 6 endoparasitic species have a human pathogenic potential.
• Stomach content was composed of one-third vegetable and two-thirds animal components.
• Invasive alien species can have negative impact on native animal species and can act as a carrier of various parasites.
Abstract
Originally from Asia, the raccoon dog Nyctereutes procyonoides is an invasive alien species in Europe, listed since 2019 on the List of invasive alien species of Union concern. The raccoon dog is considered to have negative impact on native biodiversity, as well as a crucial role in hosting and transmitting diverse parasites and pathogens of human and veterinary importance. In the present study, stomach content analyses and parasitological examinations were performed on 73 raccoon dogs from Germany. In addition, fecal samples were analyzed. The results of the study confirm the assumption that the examined raccoon dogs were infested with a various ecto- and endoparasite fauna. A total of 9 ecto- and 11 endoparasites were detected, with 6 of the endoparasites having human pathogenic potential. Trichodectes canis (P = 53.42%), Toxocara canis (P = 50.68%) and Uncinaria stenocephala (P = 68.49%) were the most abundant parasite species. The stomach contents consisted of approximately one-third vegetable and two-thirds animal components, composed of various species of amphibians, fish, insects, mammals and birds. Among them were specially protected or endangered species such as the grass frog Rana temporaria. The study shows that the raccoon dog exerts predation pressure on native species due to its omnivorous diet and, as a carrier of various parasites, poses a potential risk of infection to wild, domestic and farm animals and humans.
Evidence of predation pressure on sensitive species by raccoons based on parasitological studies
(2024)
Highlights
• Parasitological analyses were carried out on 108 free-ranging raccoons in Germany.
• Three endoparasite species were newly discovered, alongside 13 parasites already known.
• A high prevalence of the pathogenic nematode Baylisascaris procyonis was identified.
• Uncovering endoparasites provides insights into predation events from the past.
• Stomach contents show serious negative impact of raccoons on native amphibians.
Abstract
To demonstrate predation and potential impacts of raccoons on various species, a total of 108 raccoons from aquatic-associated nature reserves and natural areas in three federal states of Germany, Hesse (n = 36), Saxony-Anhalt (n = 36) and Brandenburg (n = 36), were investigated from a dietary ecological perspective in the present study. Fecal analyses and stomach content examinations were conducted for this purpose. Additionally, as a supplementary method for analyzing the dietary spectrum of raccoons, the parasite fauna was considered, as metazoan parasites, in particular, can serve as indicators for the species and origin of food organisms. While stomach content analyses allow for a detailed recording of trophic relationships solely at the time of sampling, parasitological examinations enable inferences about more distant interaction processes. With their different developmental stages and heteroxenous life cycles involving specific, sometimes obligate, intermediate hosts, they utilize the food web to reach their definitive host. The results of this study clearly demonstrate that spawning areas of amphibians and reptiles were predominantly utilized as food resources by raccoons in the study areas. Thus, common toad (Bufo bufo), common newt (Lissotriton vulgaris), grass frog (Rana temporaria), and grass snake (Natrix natrix) were identified as food organisms for raccoons. The detection of the parasite species Euryhelmis squamula, Isthmiophora melis, and Physocephalus sexalatus with partially high infestation rates also suggests that both amphibians and reptiles belong to the established dietary components of raccoons from an ecological perspective, as amphibians and reptiles are obligate intermediate hosts in the respective parasitic life cycles of the detected parasites. The study clearly demonstrates that raccoons have a significant impact on occurrence-sensitive animal species in certain areas and, as an invasive species, can exert a negative influence on native species and ecosystems.
Highlights
• 234 raccoons were dissected, 23 parasite species could be detected.
• 14 new parasite species have been identified for raccoons in Europe.
• Compared to literature, a very high prevalence (95%) of B. procyonis was detected.
• The human pathogenic trematode P. muris was detected in raccoons for the first time.
Abstract
The invasive raccoon (Procyon lotor) is an abundant carnivore and considered as an important potential vector of infectious diseases and parasites in Europe. Raccoons show a broad, opportunistic, omnivorous food spectrum. Food supply and habitat quality in urban areas are very attractive for the generalist raccoon. This inevitably leads to increased interaction with humans, domestic animals and livestock, making the raccoon a potentially suitable zoonosis vector. In its autochthonous range, especially in the Eastern and Midwestern United States, the raccoon has been studied very intensively since the beginning of the 20th century. Whereas, basic field biology and parasitology studies in Germany and Europe are lacking and have only been conducted sporadically, regionally and on small sample sizes. In the presented study 234 raccoons from central Germany were comprehensively examined for their metazoan parasite fauna. The present study shows for the first time an extremely diverse parasite fauna in raccoons outside their native range and proves their essential role as intermediate hosts and hosts for ecto- and endoparasites. A total of 23 different parasite species were identified, five of which are human pathogens, 14 of which are new for the parasite fauna of raccoons in Europe. The human pathogenic raccoon roundworm Baylisascaris procyonis is the most common parasite species in this study, with a prevalence of up to 95%. The digenetic trematode Plagiorchis muris, another human pathogenic parasite species, was detected for the first time in raccoons. The ongoing spread of invasive carnivores and the associated spread and transmission of their parasites and other pathogens increases the potential health risk of wild and farmed animals as well as humans. An increase in parasitic diseases in humans (e.g. raccoon roundworm) is to be expected, especially in urban areas, where raccoons are becoming more and more abundant.
The polarization of Λ and Λ¯ hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at √sNN = 200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild pT dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagree with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and pT dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.