Radiomics-Based Assessment of Primary Sjögren's Syndrome From Salivary Gland Ultrasonography Images

Salivary gland ultrasonography (SGUS) has shown good potential in the diagnosis of primary Sjögren's syndrome (pSS). However, a series of international studies have reported needs for improvements of the existing pSS scoring procedures in terms of inter/intra observer reliability before being established as standardized diagnostic tools. The present study aims to solve this problem by employing radiomics features and artificial intelligence (AI) algorithms to make the pSS scoring more objective and faster compared to human expert scoring. The assessment of AI algorithms was performed on a two-centric cohort, which included 600 SGUS images (150 patients) annotated using the original SGUS scoring system proposed in 1992 for pSS. For each image, we extracted 907 histogram-based and descriptive statistics features from segmented salivary glands. Optimal feature subsets were found using the genetic algorithm based wrapper approach. Among the considered algorithms (seven classifiers and five regressors), the best preforming was the multilayer perceptron (MLP) classifier (κ = 0.7). The MLP over-performed average score achieved by the clinicians (κ = 0.67) by the considerable margin, whereas its reliability was on the level of human intra-observer variability (κ = 0.71). The presented findings indicate that the continuously increasing HarmonicSS cohort will enable further advancements in AI-based pSS scoring methods by SGUS. In turn, this may establish SGUS as an effective noninvasive pSS diagnostic tool, with the final goal to supplement current diagnostic tests

Regulation of TMPRSS6 by BMP6 and iron in human cells and mice.

Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA). Patients with IRIDA have inappropriately elevated levels of the iron regulatory hormone hepcidin, suggesting that TMPRSS6 is involved in negatively regulating hepcidin expression. Hepcidin is positively regulated by iron via the bone morphogenetic protein (BMP)-SMAD signaling pathway. In this study, we investigated whether BMP6 and iron also regulate TMPRSS6 expression. Here we demonstrate that, in vitro, treatment with BMP6 stimulates TMPRSS6 expression at the mRNA and protein levels and leads to an increase in matriptase-2 activity. Moreover, we identify that inhibitor of DNA binding 1 is the key element of the BMP-SMAD pathway to regulate TMPRSS6 expression in response to BMP6 treatment. Finally, we show that, in mice, Tmprss6 mRNA expression is stimulated by chronic iron treatment or BMP6 injection and is blocked by injection of neutralizing antibody against BMP6. Our results indicate that BMP6 and iron not only induce hepcidin expression but also induce TMPRSS6, a negative regulator of hepcidin expression. Modulation of TMPRSS6 expression could serve as a negative feedback inhibitor to avoid excessive hepcidin increases by iron to help maintain tight homeostatic balance of systemic iron levels

Synthesis, structure and solvatochromic properties of some novel 5-arylazo-6-hydroxy-4-phenyl-3-cyano-2-pyridone dyes

Background: A series of some novel arylazo pyridone dyes was synthesized from the corresponding diazonium salt and 6-hydroxy-4-phenyl-3-cyano-2-pyridone using a classical reaction for the synthesis of the azo compounds. Results: The structure of the dyes was confirmed by UV-vis, FT-IR, H-1 NMR and C-13 NMR spectroscopic techniques and elemental analysis. The solvatochromic behavior of the dyes was evaluated with respect to their visible absorption properties in various solvents. Conclusions: The azo-hydrazone tautomeric equilibration was found to depend on the substituents as well as on the solvent. The geometry data of the investigated dyes were obtained using DFT quantum-chemical calculations. The obtained calculational results are in very good agreement with the experimental data

Topological Anisotropy of Stone-Wales Waves in Graphenic Fragments

Stone-Wales operators interchange four adjacent hexagons with two pentagon-heptagon 5|7 pairs that, graphically, may be iteratively propagated in the graphene layer, originating a new interesting structural defect called here Stone-Wales wave. By minimization, the Wiener index topological invariant evidences a marked anisotropy of the Stone-Wales defects that, topologically, are in fact preferably generated and propagated along the diagonal of the graphenic fragments, including carbon nanotubes and graphene nanoribbons. This peculiar edge-effect is shown in this paper having a predominant topological origin, leaving to future experimental investigations the task of verifying the occurrence in nature of wave-like defects similar to the ones proposed here. Graph-theoretical tools used in this paper for the generation and the propagation of the Stone-Wales defects waves are applicable to investigate isomeric modifications of chemical structures with various dimensionality like fullerenes, nanotubes, graphenic layers, schwarzites, zeolites

In Vivo Delivery of Gremlin siRNA Plasmid Reveals Therapeutic Potential against Diabetic Nephropathy by Recovering Bone Morphogenetic Protein-7

Diabetic nephropathy is a complex and poorly understood disease process, and our current treatment options are limited. It remains critical, then, to identify novel therapeutic targets. Recently, a developmental protein and one of the bone morphogenetic protein antagonists, Gremlin, has emerged as a novel modulator of diabetic nephropathy. The high expression and strong co-localization with transforming growth factor- β1 in diabetic kidneys suggests a role for Gremlin in the pathogenesis of diabetic nephropathy. We have constructed a gremlin siRNA plasmid and have examined the effect of Gremlin inhibition on the progression of diabetic nephropathy in a mouse model. CD-1 mice underwent uninephrectomy and STZ treatment prior to receiving weekly injections of the plasmid. Inhibition of Gremlin alleviated proteinuria and renal collagen IV accumulation 12 weeks after the STZ injection and inhibited renal cell proliferation and apoptosis. In vitro experiments, using mouse mesangial cells, revealed that the transfect ion of gremlin siRNA plasmid reversed high glucose induced abnormalities, such as increased cell proliferation and apoptosis and increased collagen IV production. The decreased matrix metalloprotease level was partially normalized by transfection with gremlin siRNA plasmid. Additionally, we observed recovery of bone morphogenetic protein-7 signaling activity, evidenced by increases in phosphorylated Smad 5 protein levels. We conclude that inhibition of Gremlin exerts beneficial effects on the diabetic kidney mainly through maintenance of BMP-7 activity and that Gremlin may serve as a novel therapeutic target in the management of diabetic nephropathy

Salivary Gland Ultrasonography in Sjögren’s Syndrome: A European Multicenter Reliability Exercise for the HarmonicSS Project

Objectives: Salivary gland ultrasonography (SGUS) is increasingly applied for the management of primary Sjögren's syndrome (pSS). This study aims to: (i) compare the reliability between two SGUS scores; (ii) test the reliability among sonographers with different levels of experience. Methods: In the reliability exercise, two four-grade semi-quantitative SGUS scoring systems, namely De Vita et al. and OMERACT, were tested. The sonographers involved in work-package 7 of the HarmonicSS project from nine countries in Europe were invited to participate. Different levels of sonographers were identified on the basis of their SGUS experience and of the knowledge of the tested scores. A dedicated atlas was used as support for SGUS scoring. Results: Twenty sonographers participated in the two rounds of the reliability exercise. The intra-rater reliability for both scores was almost perfect, with a Light's kappa of 0.86 for the De Vita et al. score and 0.87 for the OMERACT score. The inter-rater reliability for the De Vita et al. and the OMERACT score was substantial with Light's Kappa of 0.75 and 0.77, respectively. Furthermore, no significant difference was noticed among sonographers with different levels of experience. Conclusion: The two tested SGUS scores are reliable for the evaluation of major salivary glands in pSS, and even less-expert sonographers could be reliable if adequately instructed.publishedVersio

T Lymphocytes Promote the Antiviral and Inflammatory Responses of Airway Epithelial Cells

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV)

The effects of stress on brain and adrenal stem cells

The brain and adrenal are critical control centers that maintain body homeostasis under basal and stress conditions, and orchestrate the body’s response to stress. It is noteworthy that patients with stress-related disorders exhibit increased vulnerability to mental illness, even years after the stress experience, which is able to generate long-term changes in the brain's architecture and function. High levels of glucocorticoids produced by the adrenal cortex of the stressed subject reduce neurogenesis, which contributes to the development of depression. In support of the brain–adrenal connection in stress, many (but not all) depressed patients have alterations in the components of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis, with enlarged adrenal cortex and increased glucocorticoid levels. Other psychiatric disorders, such as post-traumatic stress disorder, bipolar disorder and depression, are also associated with abnormalities in hippocampal volume and hippocampal function. In addition, hippocampal lesions impair the regulation of the LHPA axis in stress response. Our knowledge of the functional connection between stress, brain function and adrenal has been further expanded by two recent, independent papers that elucidate the effects of stress on brain and adrenal stem cells, showing similarities in the way that the progenitor populations of these organs behave under stress, and shedding more light into the potential cellular and molecular mechanisms involved in the adaptation of tissues to stress

A Systematic Review of Three-Dimensional Printing in Liver Disease

The purpose of this review is to analyse current literature related to the clinical applications of 3D printed models in liver disease. A search of the literature was conducted to source studies from databases with the aim of determining the applications and feasibility of 3D printed models in liver disease. 3D printed model accuracy and costs associated with 3D printing, the ability to replicate anatomical structures and delineate important characteristics of hepatic tumours, and the potential for 3D printed liver models to guide surgical planning are analysed. Nineteen studies met the selection criteria for inclusion in the analysis. Seventeen of them were case reports and two were original studies. Quantitative assessment measuring the accuracy of 3D printed liver models was analysed in five studies with mean difference between 3D printed models and original source images ranging from 0.2 to 20%. Fifteen studies provided qualitative assessment with results showing the usefulness of 3D printed models when used as clinical tools in preoperative planning, simulation of surgical or interventional procedures, medical education, and training. The cost and time associated with 3D printed liver model production was reported in 11 studies, with costs ranging from US$13 to US$2000, duration of production up to 100 h. This systematic review shows that 3D printed liver models demonstrate hepatic anatomy and tumours with high accuracy. The models can assist with preoperative planning and may be used in the simulation of surgical procedures for the treatment of malignant hepatic tumours