Mental disorder is a serious public health concern that affects the life of millions of people throughout the world. Early diagnosis is essential to ensure timely treatment and to improve the ...well-being of those affected by a mental disorder. In this paper, we present a novel multimodal framework to perform mental disorder recognition from videos. The proposed approach employs a combination of audio, video and textual modalities. Using recurrent neural network architectures, we incorporate the temporal information in the learning process and model the dynamic evolution of the features extracted for each patient. For multimodal fusion, we propose an efficient late fusion strategy based on a simple feed-forward neural network that we call
adaptive nonlinear judge classifier
. We evaluate the proposed framework on two mental disorder datasets. On both, the experimental results demonstrate that the proposed framework outperforms the state-of-the-art approaches. We also study the importance of each modality for mental disorder recognition and infer interesting conclusions about the temporal nature of each modality. Our findings demonstrate that careful consideration of the temporal evolution of each modality is of crucial importance to accurately perform mental disorder recognition.
Neutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial ...pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulate at disease-prone regions of arteries exposed to disturbed flow patterns, and promote vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, we demonstrate that neutrophil microvesicles promote inflammatory gene expression by delivering miR-155, enhancing NF-κB activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-κB at disease-prone sites of disturbed flow in vivo. Enhancement of atherosclerotic plaque formation and increase in macrophage content by neutrophil microvesicles is dependent on miR-155. We conclude that neutrophils contribute to vascular inflammation and atherogenesis through delivery of microvesicles carrying miR-155 to disease-prone regions.
The discovery of microRNAs (miRNAs) 20 years ago has advocated a new era of “small molecular genetics.” About 2000 miRNAs are present that regulate one third of the genome. MiRNA dysregulated ...expression arising as a response to our environment insult or stress or changes may contribute to several diseases, namely non-communicable diseases, including tumor growth. Their presence in body fluids, reflecting level alteration in various cancers, merit circulating miRNAs as the “next-generation biomarkers” for early-stage tumor diagnosis and/or prognosis. Herein, we performed a comprehensive literature search focusing on the origin, biosynthesis, and role of miRNAs and summarized the foremost studies centering on miR value as non-invasive biomarkers in different environment-related non-communicable diseases, including various cancer types. Moreover, during chemotherapy, many miRNAs were linked to multidrug resistance, via modulating numerous, environment triggered or not, biological processes and/or pathways that will be highlighted as well.
Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed ...endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.
The use of technology to optimize the production and management of each individual animal is becoming key to good farming. There is a need for the real-time systematic detection and control of ...disease in animals in order to limit the impact on animal welfare and food supply. Diseases such as footrot and mastitis cause significant pain in sheep, and so early detection is vital to ensuring effective treatment and preventing the spread across the flock. Facial expression scoring to assess pain in humans and non-humans is now well utilized, and the Sheep Pain Facial Expression Scale (SPFES) is a tool that can reliably detect pain in this species. The SPFES currently requires manual scoring, leaving it open to observer bias, and it is also time-consuming. The ability of a computer to automatically detect and direct a producer as to where assessment and treatment are needed would increase the chances of controlling the spread of disease. It would also aid in the prevention of resistance across the individual, farm, and landscape at both national and international levels. In this paper, we present our framework for an integrated novel system based on techniques originally applied for human facial expression recognition that could be implemented at the farm level. To the authors' knowledge, this is the first time that this technology has been applied to sheep to assess pain.
Abstract
Aims
Arterial stiffness is an underlying risk factor and a hallmark of cardiovascular diseases. The endothelial cell (EC) glycocalyx is a glycan rich surface layer that plays a key role in ...protecting against EC dysfunction and vascular disease. However, the mechanisms by which arterial stiffness promotes EC dysfunction and vascular disease are not fully understood, and whether the mechanism involves the protective endothelial glycocalyx is yet to be determined. We hypothesized that endothelial glycocalyx protects the endothelial cells lining the vascular wall from dysfunction and disease in response to arterial stiffness.
Methods and results
Cells cultured on polyacrylamide (PA) gels of substrate stiffness 10 kPa (mimicking the subendothelial stiffness of aged, unhealthy arteries) showed a significant inhibition of glycocalyx expression compared to cells cultured on softer PA gels (2.5 kPa, mimicking the subendothelial stiffness of young, healthy arteries). Specifically, gene and protein analyses revealed that a glycocalyx core protein Glypican 1 was inhibited in cells cultured on stiff PA gels. These cells had enhanced endothelial cell dysfunction as determined by enhanced cell inflammation (enhanced inflammatory gene expression, monocyte adhesion, and inhibited nitric oxide expression), proliferation, and EndMT. Removal of Glypican 1 using gene-specific silencing with siRNA or gene overexpression using a plasmid revealed that Glypican 1 is required to protect against stiffness-mediated endothelial cell dysfunction. Consistent with this, using a model of age-mediated stiffness, older mice exhibited a reduced expression of Glypican 1 and enhanced endothelial cell dysfunction compared to young mice. Glypican 1 gene deletion in knockout mice (GPC1−/−) exacerbated endothelial dysfunction in young mice, which normally had high endothelial expression, but not in old mice that normally expressed low levels. Endothelial cell dysfunction was exacerbated in young, but not aged, Glypican 1 knockout mice (GPC1−/−).
Conclusion
Arterial stiffness promotes EC dysfunction and vascular disease at least partly through the suppression of the glycocalyx protein Glypican 1. Glypican 1 contributes to the protection against endothelial cell dysfunction and vascular disease in endothelial cells.
Breast cancer (BC) is the leading cause of female cancer-related mortalities. Evidence has illustrated the role of long non-coding RNAs (lncRNA) and microRNAs (miRNA) as promising pool of protein ...non-coding regulators, for tuning the aggressiveness of several malignancies. This research aims to unravel the expression pattern and the emphases of the diagnostic value of the long intergenic ncRNA00511 (LINC00511) and its downstream microRNA (miR-185-3p) and the pathogenic significance of the onco-miR-301a-3p in naïve BC patients. LINC00511 was chosen and validated, and its molecular binding was confirmed using bioinformatics. LINC00511 was measured in 25 controls and 70 patients using qPCR. The association between the investigated ncRNA’s expression and the BC patients’ clinicopathological features was assessed. Receiver operating characteristic (ROC) curve was blotted to weigh out their diagnostic efficacy over the classical tumor markers (TMs). Bioinformatics and Spearman correlation were used to predict the interaction between LINC00511, miR-185-3p, and miR-301a-3p altogether to patients’ features. LINC00511 and miR-301a-3p, in BC patients’ blood, were overexpressed, and their median levels increased significantly, while miR-185-3p was, in contrast, downregulated, being decreased fourfold. LINC00511 was elevated in BC early stages, when compared to late stages (
p
< 0.0003). LINC00511, miR-185-3p, and miR-301a-3p showed AUC superior to classical TMs, allowing us to conclude that the investigated ncRNAs, in BC patients’ liquid biopsy, are novel diagnostic molecular biomarker signatures. Lymph node metastasis (LNM) and advanced tumor grade were directly correlated with LINC00511 significantly. Additionally, both LINC00511 and miR-301a-3p were positively correlated with the aggressiveness of BC, as manifested in patients with larger tumors (>2 cm) at (
p
< 0.001). Therefore, these findings aid our understanding of BC pathogenesis, in the clinical setting, being related in part to the LINC00511/miR axis, which could be a future potential therapeutic target.
Melanin is a ubiquitous natural polyphenolic pigment with versatile applications including physiological functions. This polymeric material is found in a diversity of living organisms from bacteria ...to mammals. The biocompatibility and thermal stability of melanin nanoparticles make them good candidates to work as free radical scavengers and photothermal anticancer substrates. Research studies have identified melanin as an antioxidative therapeutic agent and/or reactive oxygen species (ROS) scavenger that includes neutralization of peroxynitrite. In addition, melanin nanoparticles have emerged as an anticancer photothermal platform that has the capability to kill cancer cells. Recently, melanin nanoparticles have been successfully used as chelating agents to purify water from heavy metals, such as hexavalent chromium. This review article highlights some selected aspects of cutting-edge melanin applications. Herein, we will refer to the recent literature that addresses melanin nanoparticles and its useful physicochemical properties as a hot topic in biomaterial science. It is expected that the techniques of Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and time-resolved Electron Paramagnetic Resonance (EPR) will have a strong impact on the full characterization of melanin nanoparticles and the subsequent exploration of their physiological and chemical mechanisms.
Abstract
This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to ...glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress to nitric oxide production was elucidated in which glypican-1 senses flow and phosphorylates PECAM-1 leading to endothelial nitric oxide synthase phosphorylation and nitric oxide production.