We report comprehensive pathological studies of atheromatous lesions in various inbred mouse strains fed a high-fat, high-cholesterol diet and in two genetically engineered strains that develop spontaneous lesions on a low-fat chow diet. Coronary and aortic lesions were studied with respect to anatomic locations, lesion severity, calcification, and lipofuscin deposition. Surprisingly, the genetic determinants for coronary fatty lesion formation differed in part from those for aortic lesion development. This suggests the existence of genetic factors acting locally as well as systemically in lesion development. We used immunohistochemical analyses to determine the cellular and molecular compositions of the lesions. The aortic lesions contained monocyte/macrophages, lipid, apolipoprotein B, serum amyloid A proteins, and immuno-globulin M and showed expression of vascular cell adhesion molecule-1 and tumor necrosis factor-a, all absent in normal arteries. In certain strains, advanced lesions developed in T he mouse is being increasingly used as a model for the study of atherosclerosis and its risk factors. 1 The model has two unique advantages among mammals. First, the mouse is the most useful mammal for genetic studies. In particular, many inbred strains exhibiting genetic variations relevant to lipoprotein metabolism and atherosclerosis have been identified. 213 Also, a complete linkage map including many highly polymorphic markers has been constructed in the mouse, making genetic analysis feasible for even multigenic traits. 114 Second, techniques for genetic modification in vivo, including construction of transgenic and gene-targeted animals, are much more advanced in the mouse than any other mammal. Such genetic modification has proved particularly useful for analysis of interactions between lipoprotein metabolism and atherosclerosis. 1536 Methods for the quantitative pathological analysis of diet-induced atherosclerosis in the mouse model have been developed. 37 Although these methods have revealed dif-which smooth muscle cells were commonly observed. The lesions in mice targeted for a null mutation in the apolipopro-tein E gene were much larger, more widely dispersed, and more fibrous, cellular, and calcified in nature than the lesions in laboratory inbred strains. When apolipoprotein A-II trans-genic mice were maintained on a low-fat chow diet, the lesions in these mice were relatively small and located in the very proximal regions of the aorta. There were clear differences in the occurrence of arterial wall calcification among genetically distinct inbred mouse strains, indicating for the first time a genetic component in this clinically significant trait. Analysis of a genetic cross indicated a complex pattern of calcification inheritance with incomplete penetrance. (Arterioscler Thromb. 1994;14:1480-1497.) Key Words • apolipoproteins • adhesion molecules • atherosclerosis • calcification • genetics ferences in susceptibility to diet-induced atherosclerosis of the aorta in a variety of inbred strains, there...

In traditional hospital systems, diagnosis and localization of melanoma are the critical challenges for pathological analysis, treatment instructions, and prognosis evaluation particularly in skin diseases. In literature, various studies have been reported to address these issues; however, a prominent smart diagnosis system is needed to be developed for the smart healthcare system. In this study, a deep learning-enabled diagnostic system is proposed and implemented that it has the capacity to automatically detect malignant melanoma in whole slide images (WSIs). In this system, the convolutional neural network (CNN), sophisticated statistical method, and image processing algorithms were integrated and implemented to locate benign and malignant lesions which are extremely useful in the diagnoses process of melanoma disease. To verify the exceptional performance of the proposed scheme, it is implemented in a multicenter database, which has 701 WSIs (641 WSIs from Central South University Xiangya Hospital (CSUXH) and 60 WSIs from the Cancer Genome Atlas (TCGA)). Experimental results have verified that the proposed system has achieved an area under the receiver operating characteristic curve (AUROC) of 0.971. Furthermore, the lesion area on the WSIs is represented by its degree of malignancy. These results show that the proposed system has the capacity to fully automate the diagnosis and localization problem of the melanoma in the smart healthcare systems.

Cutaneous Malignant Melanoma (CMM) incidence has been rising around the world and over the last three decades at rates greater than for any other malignancy. Our objective was to describe geographic trends in incidence and mortality of CMM in Russia between 2001 and 2017 using geo-informatics technique (mapping) and descriptive statistical analysis. Additionally, we aimed to study the associations between ethnicity, geographic latitude/longitude and CMM incidence/mortality rates. We retrospectively analyzed the data from the Moscow Oncology Research Institute, Ministry of Health of Russian Federation for the period of the study. International Classification of Diseases (ICD) C43 code (comprising C43.0-C.43.9) was used to identify cutaneous melanoma cases. Routine methods of descriptive epidemiology were used to study incidence and mortality rates by age groups, years, and jurisdictions (i.e., Federal Districts and Federal Subjects of Russia). In total 141,597 patients were diagnosed with melanoma in Russia over the period 2001-2017, of which 62% were women (p<0.001). The overall age-standardized incidence and mortality rates were 4.27/100,000 and 1.62/ 100,000, respectively. Geographic mapping revealed North-to-South and East-to-West gradients across the country. Intrinsic patient characteristics such as the skin phenotype and the climate zones of the country could be an important risk factors for melanoma development. This study, for the first time, reports the burden and geographic distribution of CMM in Russia and the trends correlate with observations in countries with similar geography.

Conventional monotherapies only benefit a minority of melanoma patients while combined immunotherapy exhibited extremely high rates of treatment-related adverse events. Herein, we created a multifunctional and immunogenic nanoplatform, AuNR@mSiO 2 @DOX-Cu x S-PEG, which integrating photothermal properties of gold nanoparticles, photodynamic properties of CuxS and chemotherapy into a single nanoplatform. Upon near-infrared laser irradiation (NIR), the Cu x S were uncapped and triggered chemotherapy drugs release into tumor environment. The properties and cytotoxicity to melanoma cells were explored in vitro. In addition, the anti-tumor effect and molecular mechanism of inducing tumor-specific immune responses were also explored in vitro and in vivo. The nanoplatform was stabilized, facilely synthesized and exhibited a high drug payload up to 36.37AE2.74%. Compared to control groups, the nanoplatform could forcefully inhibit tumor growth in situ (p<0.001) and lung metastasis with lower time and power intensity. Furthermore, it could promote maturation of dendritic cells and induce the infiltration of both CD8 + and CD4 + T lymphocytes in tumor in vivo. Mechanistically, the nanoplatform not only can eradicate cancer cells by inducing cell apoptosis and/or necrosis directly, but also induce a strong tumor-specific immune response by resulting in calreticulin exposure on the surface of cancer cell (p<0.01) and released highmobility group box 1 (HMGB1) protein (p<0.01). Our study developed a promising NIRtriggered multifunctional and immunogenic nanocomposite, which could induce anti-tumor immunity and would be a potential strategy for melanoma in advanced stage. 828Dermatopathologist-level classification of skin cancer with deep neural networks at multi-magnification Artificial intelligence technologies, as novel diagnostic tools, are now affecting medical

No abstract