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Skin cutaneous melanoma is characterized by significant heterogeneity in its molecular, genomic and immunologic features. Whole transcriptome RNA sequencing data from The Cancer Genome Atlas of skin cutaneous melanoma (n = 328) was utilized. this website CIBERSORT was used to identify immune cell type composition, on which unsupervised hierarchical clustering was performed. Analysis of overall survival was performed using Kaplan-Meier estimates and multivariate Cox regression analyses. Membership in the lymphocytemonocytelow, monocytehigh and M0high cluster was an independently poor prognostic factor for survival (HR 3.03; 95% CI 1.12-8.20; p = 0.029) and correlated with decreased predicted response to immune checkpoint blockade. In conclusion, an M0-macrophage-enriched, lymphocyte-to-monocyte-ratio-low phenotype in the primary melanoma tumor site independently characterizes an aggressive phenotype that may differentially respond to treatment.

Primary gastric melanoma is a rare clinical presentation. The purpose of this review was to compare the 1-year survival in patients who underwent surgery with patients who did not receive treatment.

A systematic search of databases for case reports and case series of primary gastric melanoma was conducted.

The mean survival of patients was 22 months. One-year survival was 56.5% with surgery, rising to 66% with adjuvant therapy. Mean survival of the surgical group was 21.05 months (±20.2) versus 4.5 months (±3.61) in the nonsurgical group.

Primary gastric melanoma has a poor prognosis but early surgical intervention can have a significant impact on patient outcome. We reviewed the biology and clinical diagnosis of gastrointestinal melanoma and the current management options available.

Primary gastric melanoma has a poor prognosis but early surgical intervention can have a significant impact on patient outcome. We reviewed the biology and clinical diagnosis of gastrointestinal melanoma and the current management options available.Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that is endemic in 49 countries of the world and affects or threatens over 890 million people. Strategies to control LF rely heavily on mass administration of anthelmintic drugs including ivermectin (IVM), a macrocyclic lactone drug considered an Essential Medicine by the WHO. However, despite its widespread use the therapeutic mode of action of IVM against filarial nematodes is not clear. We have previously reported that filarial nematodes secrete extracellular vesicles (EVs) and that their cargo has immunomodulatory properties. Here we investigate the effects of IVM and other anti-filarial drugs on parasitic nematode EV secretion, motility, and protein secretion. We show that inhibition of EV secretion was a specific property of IVM, which had consistent and significant inhibitory effects across nematode life stages and species, with the exception of male parasites. IVM inhibited EV secretion, but not parasite motility, at therapeutically relevant concentrations. Protein secretion was inhibited by IVM in the microfilariae stage, but not in any other stage tested. Our data provides evidence that inhibiting the secretion of immunomodulatory EVs by parasitic nematodes could explain, at least in part, IVM mode of action and provides a phenotype for novel drug discovery.The misfolding and fibrillization of the protein, α-synuclein (αsyn), is associated with neurodegenerative disorders referred to as the synucleinopathies. Understanding the mechanisms of αsyn misfolding is an important area of interest given that αsyn misfolding contributes to disease pathogenesis. While many studies report the ability of synthetic lipid membranes to modulate αsyn folding, there is little data pertaining to the mechanism(s) of this interaction. αSyn has previously been shown to associate with small lipid vesicles released by cells called extracellular vesicles (EVs) and it is postulated these interactions may assist in the spreading of pathological forms of this protein. Together, this presents the need for robust characterisation studies on αsyn fibrillization using biologically-derived vesicles. In this study, we comprehensively characterised the ability of lipid-rich small extracellular vesicles (sEVs) to alter the misfolding of αsyn induced using the Protein Misfolding Cyclic Amplificatiolators of αsyn fibrillization, which is mediated by the sEV membrane. In doing so, this work provides strong evidence for a role of sEVs in contributing directly to αsyn misfolding in the synucleinopathy disorders.Tubulinopathies are a heterogeneous group of complex cortical malformations that are associated with mutations in tubulin genes. TUBB3 gene mutation is associated with a broader spectrum of central nervous system malformations and constitutes about 10% of all tubulinopathies. The diagnosis may not be immediately apparent on imaging, though the differential diagnosis may be narrowed based on imaging findings and allow for more directed genetic testing. We report a 22-year-old gravida-1 nulliparous female whose routine second trimester fetal ultrasound revealed ventriculomegaly and possible agenesis of the corpus callosum. Fetal magnetic resonance imaging showed severe lateral and third ventriculomegaly and a dysplastic, z-shaped brainstem without any evidence of ocular abnormalities. Genetic testing revealed a pathogenic mutation in TUBB3.Three-dimensional high-resolution late gadolinium enhancement (3D HR LGE) magnetic resonance imaging (MRI) using compressed sensing can help detect small myocardial infarcts. We discuss the case of an 11-year-old child with an anomalous aortic origin of the left coronary artery. Since he was suspected to have coronary stenosis due to anomalous aortic origin of the left coronary artery, cardiovascular MRI, including conventional two-dimensional (2D) LGE MRI and HR 3D LGE MRI, was conducted. Myocardial scars were not clearly observed via 2D LGE MRI; however, 3D HR MRI revealed subendocardial infarction of the anteroseptal wall, which corresponded to the left coronary artery. By applying the compressed sensing technique, 3D HR LGE, MRI enables a detailed assessment of small myocardial infarcts in a clinically feasible scan time.