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006). UC-CRCs showed a predilection for TP53 alterations, which was the most frequently mutated gene in our cohort (20 of 23, 87%). Interestingly, spatially separated tumor lesions from individual patients tended to harbor distinct TP53 mutations. Similar to CRCs arising in a background of Crohn's colitis, the genetic landscape of UC-CRCs was characterized by TP53 mutations and chromosomal aneuploidies including gains of chromosome arm 5p. Both alterations harbor the potential for early detection in precursor lesions, thus complementing morphologic diagnosis.Proliferative fasciitis (PF) and proliferative myositis (PM) are rare benign soft tissue lesions, usually affecting the extremities of middle-aged or older adults. Presenting as poorly circumscribed masses, they histologically show bland spindle cell proliferation in a myxoid to fibrous background and a hallmark component of large epithelioid "ganglion-like" cells in various numbers, which may lead to their misdiagnosis as sarcoma. PF/PM has been long considered as reactive, akin to nodular fasciitis; however, its pathogenesis has remained unknown. selleck chemicals llc In this study, we analyzed the FOS status in 6 PF/PMs (5 PFs and 1 PM). Five PF/PMs occurred in adults, all showing diffuse strong expression of c-FOS primarily in the epithelioid cells, whereas spindle cell components were largely negative. Using fluorescence in situ hybridization (FISH), all 5 c-FOS-immunopositive tumors showed evidence of FOS gene rearrangement in the epithelioid cells. RNA sequencing in 1 case detected a FOS-VIM fusion transcript, which was subsequently validated by reverse transcriptase-polymerase chain reaction, Sanger sequencing, and VIM FISH. The one pediatric PF case lacked c-FOS expression and FOS rearrangement. c-FOS immunohistochemistry was negative in 45 cases of selected mesenchymal tumor types with epithelioid components that may histologically mimic PF/PM, including pleomorphic sarcoma with epithelioid features and epithelioid sarcoma. Recurrent FOS rearrangement and c-FOS overexpression in PF/PM suggested these lesions to be neoplastic. FOS abnormality was largely restricted to the epithelioid cell population, clarifying the histological composition of at least 2 different cell types. c-FOS immunohistochemistry may serve as a useful adjunct to accurately distinguish PF/PM from mimics.The genetic hallmark of epithelioid hemangioma (EH) is the presence of recurrent gene fusions involving FOS and FOSB transcription factors, which occur in one-third of the cases. Certain clinical, pathologic, and genotypic correlations have been described, with FOS-related fusions being more often detected in skeletal and cellular variants of EH, while FOSB gene rearrangements are more commonly associated with atypical histologic features and penile location. These fusions are infrequently detected in the cutaneous or head and neck EH. Overall, two-thirds of EH lack these canonical fusions and remain difficult to classify, especially when associated with atypical features and/or clinical presentations. Triggered by an index case of an intravascular soft tissue EH with a novel GATA6-FOXO1 gene fusion by targeted RNA sequencing (Archer® FusionPlex® Sarcoma Panel), we have investigated 27 additional EH cases negative for FOS and FOSB gene rearrangements for this novel abnormality to determine its recurrent potential, and its association with clinical and pathologic features. Four additional EH cases were found to display GATA6-FOXO1 fusions (18%). There were three females and two males, with a mean age of 32 years old. Three lesions occurred in the head and neck (dura, nasopharyngeal, and cheek), one in the back and one in the leg. Two of these lesions were cutaneous and one was intravascular in the subcutis of the leg. Microscopically, the tumors showed a variegated morphology, with alternating vasoformative and solid components, extravasated red blood cells and mild to moderate cytologic atypia. None showed brisk mitotic activity or necrosis. Tumors were negative for FOS and FOSB by immunohistochemistry. In conclusion, we report a new GATA6-FOXO1 fusion in a subset of EH, with a predilection for skin, and head and neck location. The relationship of this novel molecular subset with the more common FOS/FOSB fusion-positive EH remains to be determined.Hyperbolic metamaterials were initially proposed in optics to boost radiation efficiencies of quantum emitters. Adopting this concept for antenna design allows approaching long-standing contests in radio physics. For example, broadband impedance matching, accompanied with moderately high antenna gain, is among the existent challenges. Here we propose employing hyperbolic metamaterials for a broadband impedance matching, while a structured layer on top of a metamaterials slab ensures an efficient and directive energy outcoupling to a free space. In particular, a subwavelength loop antenna, placed underneath the matching layer, efficiently excites bulk metamaterial modes, which have well-resolved spatial-temporal separation owing to the hypebolicity of effective permeability tensor. Interplaying chromatic and modal dispersions enable to map different frequencies into non overlapping spatial locations within a compact subwavelength hyperbolic slab. The outcoupling of energy to the free space is obtained by patterning the slab with additional resonant elements, e.g. high index dielectric spheres. As the result, two-order of magnitude improvement in linear gain of the device is predicted. The proposed new architecture can find a use in applications, where multiband or broadband compact devices are required.Multimodal warning displays often pair one signal modality (odor) with a second modality (color) to avoid predation. Experiments with bird predators suggest these signal components interact synergistically, with aversive odors triggering otherwise hidden aversions to particular prey colors. In a recent study, this phenomenon was found in a jumping spider (Habronattus trimaculatus), with the defensive odor from a coreid bug (Acanthocephala femorata) triggering an aversion to red. Here, we explore how generalizable this phenomenon is by giving H. trimaculatus the choice between red or black prey in the presence or absence of defensive odors secreted from (1) eastern leaf-footed bugs (Leptoglossus phyllopus, Hemiptera), (2) grass stinkbugs (Mormidea pama, Hemiptera), (3) Asian ladybird beetles (Harmonia axyridis, Coleoptera), and (4) eastern lubber grasshoppers (Romalea microptera, Orthoptera). As expected, in the presence of the hemipteran odors, spiders were less likely to attack red prey (compared to no odor). Unexpectedly, the beetle and grasshopper odors did not bias spiders away from red. Our results with the hemipteran odors were unique to red; follow-up experiments indicated that these odors did not affect biases for/against green prey. We discuss our findings in the context of generalized predator foraging behavior and the functions of multimodal warning displays.Gas-hydrate occurrences along the Chilean margin have been widely documented, but the processes associated with fluid escapes caused by the dissociation of gas hydrates are still unknown. We report a seabed morphology growth related to fluid migration offshore Lebu associated with mud cones by analysing oxygen and deuterium stable water isotopes in pore water, bathymetric, biological and sedimentological data. A relief was observed at - 127 m water depth with five peaks. Enrichment values of δ18O (0.0-1.8‰) and δD (0.0-5.6‰) evidenced past hydrate melting. The orientation of the relief could be associated with faults and fractures, which constitute pathways for fluid migration. The benthic foraminifera observed can be associated with cold seep areas. We model that the mud cones correspond to mud growing processes related to past gas-hydrate dissociation. The integration of (i) the seismic data analysis performed in the surrounding area, (ii) the orientation of our studied relief, (iii) the infaunal foraminifera observed, (iv) the grain size and (v) the total organic matter and isotope values revealed that this area was formerly characterised by the presence of gas hydrates. Hence, this part of the Chilean margin represents a suitable area for investigating fluid-migration processes.Globally aquaculture contributes 8% of animal protein intake to the human diet, and per capita consumption is increasing faster than meat and dairy consumption. Reports have documented antimicrobial use in the rapidly expanding aquaculture industry, which may contribute to the rise of antimicrobial resistance, carrying potential consequences for animal-, human-, and ecosystem-health. However, quantitative antimicrobial use across a highly diversified aquaculture industry is not well characterized. Here, we estimate global trends in antimicrobial use in aquaculture in 2017 and 2030 to help target future surveillance efforts and antimicrobial stewardship policies. We estimate antimicrobial use intensity (mg kg-1) for six species groups though a systematic review of point prevalence surveys, which identified 146 species-specific antimicrobial use rates. We project antimicrobial use in each country by combining mean antimicrobial use coefficients per species group with OECD/FAO Agricultural Outlook and FAO FishStllance capacities to monitor global trends in antimicrobial use. Current evidence, while subject to considerable uncertainties, suggests that for some species groups antimicrobial use intensity surpasses consumption levels in terrestrial animals and humans. Acknowledging the fast-growing nature of aquaculture as an important source of animal nutrition globally, our findings highlight the urgent need for enhanced antimicrobial stewardship in a high-growth industry with broad links to water and ecosystem health.The cognate interaction of ROBO1/4 with its ligand SLIT2 is known to be involved in lung cancer progression. However, the precise role of genetic variants, disrupting the molecular interactions is less understood. All cancer-associated missense variants of ROBO1/4 and SLIT2 from COSMIC were screened for their pathogenicity. Homology modelling was done in Modeller 9.17, followed by molecular simulation in GROMACS. Rigid docking was performed for the cognate partners in PatchDock with refinement in HADDOCK server. Post-docking alterations in conformational, stoichiometric, as well as structural parameters, were assessed. The disruptive variants were ranked using a weighted scoring scheme. In silico prioritisation of 825 variants revealed 379 to be potentially pathogenic out of which, about 12% of the variants, i.e. ROBO1 (14), ROBO4 (8), and SLIT2 (23) altered the cognate docking. Six variants of ROBO1 and 5 variants of ROBO4 were identified as "high disruptors" of interactions with SLIT2 wild type. Likewise, 17 and 13 variants of SLIT2 were found to be "high disruptors" of its interaction with ROBO1 and ROBO4, respectively. Our study is the first report on the impact of cancer-associated missense variants on ROBO1/4 and SLIT2 interactions that might be the drivers of lung cancer progression.Systemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death. While targeted therapies are emerging, biomarkers for sub-stratifying patients based on individual profiles are lacking. Herein, we investigated how levels of serum metabolites correlated with different stages of SSc and SSc-ILD. Serum samples of patients with SSc without ILD, stable and progressive SSc-ILD as well as of healthy controls (HC) were analysed using liquid targeted tandem mass spectrometry. The best discriminating profile consisted of 4 amino acids (AA) and 3 purine metabolites. L-tyrosine, L-tryptophan, and 1-methyl-adenosine distinguished HC from SSc patients. L-leucine, L-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. In SSc-ILD, both, L-leucine and xanthosine negatively correlated with changes in FVC% predicted. Additionally, xanthosine was negatively correlated with changes in DLco% predicted and positively with the prognostic GAP index.