REC-NN: A reconstruction error compensation neural network for Magnetic Resonance Electrical Property Tomography (MREPT).

Electrical properties (EPs) are expected as biomarkers for early cancer detection. Magnetic resonance electrical properties tomography (MREPT) is a technique to non-invasively estimate the EPs of tissues from MRI measurements. While noise sensitivity and artifact problems of MREPT are being solved progressively through recent efforts, the loss of tissue contrast emerges as an obstacle to the clinical applications of MREPT. To solve the problem, we propose a reconstruction error compensation neural network scheme (REC-NN) for a typical analytic MREPT method, Stab-EPT. Two NN structures: one with only ResNet blocks, and the other hybridizing ResNet blocks with an encoder-decoder structure. Results of experiments with digital brain phantoms show that, compared with Stab-EPT, and conventional NN based reconstruction, REC-NN improves both reconstruction accuracy and tissue contrast. It is found that, the encoder-decoder structure could improve the compensation accuracy of EPs in homogeneous region but showed worse reconstruction than only ResNet structure for tumorous tissues unseen in the training samples. Future research is required to address overcompensation problems, optimization of NN structure and application to clinical data.

Effect of changes in Skin Thickness on pain-relief Transcutaneous Electrical Nerve Stimulation (TENS).

Transcutaneous Electrical Nerve Stimulation (TENS) suppresses chronic pain by stimulating deep nerves near the fascia from electrodes on the skin's surface. TENS has different effects on patients of different ages due to the variation of the thickness of skin layers when one becomes older.In this paper, we aim to optimize the stimulation effectiveness of TENS for patients of different ages through investigation of TENS stimulations of three different skin types categorized by age, Young, Old, and Older. In this investigation, the skin layer (stratum corneum, epidermis layer, dermis layer) in each model was created, and the thickness was varied. The effect of sin wave stimulation at 1 Hz, 100 Hz, and 10 kHz on the nerve stimulation effect near the fascia was examined.It is found that besides the well-known effect of stratum corneum, the thickness of the dermis layer significantly affects the stimulating effect. In addition, by using a lumped circuit model, it is showed that the change in the current path causes a mitigation in the stimulation effect in the dermis layer.

Optimization of biguanide derivatives as selective antitumor agents blocking adaptive stress responses in the tumor microenvironment.

Adaptive cellular responses resulting from multiple microenvironmental stresses, such as hypoxia and nutrient deprivation, are potential novel drug targets for cancer treatment. Accordingly, we focused on developing anticancer agents targeting the tumor microenvironment (TME). In this study, to search for selective antitumor agents blocking adaptive responses in the TME, thirteen new compounds, designed and synthesized on the basis of the arylmethylbiguanide scaffold of phenformin, were used in structure activity relationship studies of inhibition of hypoxia inducible factor (HIF)-1 and unfolded protein response (UPR) activation and of selective cytotoxicity under glucose-deprived stress conditions, using HT29 cells. We conducted luciferase reporter assays using stable cell lines expressing either an HIF-1-responsive reporter gene or a glucose-regulated protein 78 promoter-reporter gene, which were induced by hypoxia and glucose deprivation stress, respectively, to screen for TME-targeting antitumor drugs. The guanidine analog (compound 2), obtained by bioisosteric replacement of the biguanide group, had activities comparable with those of phenformin (compound 1). Introduction of various substituents on the phenyl ring significantly affected the activities. In particular, the o-methylphenyl analog compound 7 and the o-chlorophenyl analog compound 12 showed considerably more potent inhibitory effects on HIF-1 and UPR activation than did phenformin, and excellent selective cytotoxicity under glucose deprivation. These compounds, therefore, represent an improvement over phenformin. They also suppressed HIF-1- and UPR-related protein expression and secretion of vascular endothelial growth factor-A. Moreover, these compounds exhibited significant antiangiogenic effects in the chick chorioallantoic membrane assay. Our structural development studies of biguanide derivatives provided promising candidates for a novel anticancer agent targeting the TME for selective cancer therapy, to be subjected to further in vivo study.