GScluster: Network-weighted gene-set clustering analysis

Background: Gene-set analysis (GSA) has been commonly used to identify significantly altered pathways or functions from omics data. However, GSA often yields a long list of gene-sets, necessitating efficient post-processing for improved interpretation. Existing methods cluster the gene-sets based on the extent of their overlap to summarize the GSA results without considering interactions between gene-sets. Results: Here, we presented a novel network-weighted gene-set clustering that incorporates both the gene-set overlap and protein-protein interaction (PPI) networks. Three examples were demonstrated for microarray gene expression, GWAS summary, and RNA-sequencing data to which different GSA methods were applied. These examples as well as a global analysis show that the proposed method increases PPI densities and functional relevance of the resulting clusters. Additionally, distinct properties of gene-set distance measures were compared. The methods are implemented as an R/Shiny package GScluster that provides gene-set clustering and diverse functions for visualization of gene-sets and PPI networks. Conclusions: Network-weighted gene-set clustering provides functionally more relevant gene-set clusters and related network analysis

Efficient pathway enrichment and network analysis of GWAS summary data using GSA-SNP2

Pathway-based analysis in genome-wide association study (GWAS) is being widely used to uncover novel multi-genic functional associations. Many of these pathway-based methods have been used to test the enrichment of the associated genes in the pathways, but exhibited low powers and were highly affected by free parameters. We present the novel method and software GSA-SNP2 for pathway enrichment analysis of GWAS P-value data. GSA-SNP2 provides high power, decent type I error control and fast computation by incorporating the random set model and SNP-count adjusted gene score. In a comparative study using simulated and real GWAS data, GSA-SNP2 exhibited high power and best prioritized gold standard positive pathways compared with six existing enrichment-based methods and two self-contained methods (alternative pathway analysis approach). Based on these results, the difference between pathway analysis approaches was investigated and the effects of the gene correlation structures on the pathway enrichment analysis were also discussed. In addition, GSA-SNP2 is able to visualize protein interaction networks within and across the significant pathways so that the user can prioritize the core subnetworks for further studies. GSA-SNP2 is freely available at https://sourceforge.net/projects/gsasnp2

A New Surgical Approach to Treat the Resistant Hypertension

The sympathetic nervous system was known to play an important role in resistant hypertension. Surgical sympathectomy for renal sympathetic nerve removal were performed since the 1930s. Although effective, it had many serious side effects and complications due to severe invasiveness and non-selective property. Recently, catheter based renal denervation (RDN) system using radiofrequency (RF) ablation was developed to overcome invasiveness of sympathectomy. While RF ablation technology was considered promising, it failed to show effectiveness in a recent sham controlled trial. Therefore, there is a strong need for safe and effective RDN strategies considering the anatomical structure of the renal arteries and sympathetic nerves. In this paper, we propose a novel surgical instrument for laparoscopic RDN and show its feasibility through a 3D realistic model using nephrectomy tissues. Laparoscopic RDN will become a new surgical approach to effectively and safely remove renal sympathetic nerves.2

Highly Sensitive Nondestructive Tunneling Magneto Resistive Imaging: Simulation and Experimental Validation

With the increased use of high-performance thin steels, detecting internal or external micro defects in a manufacturing process has become critical for the steel manufacturing process's cost and quality management. For detecting defects, magnetic-based nondestructive testing (NDT) methods have been researched widely due to their simplicity, ease of use, and contactless nature. However, magnetic-based approaches suffer from low sensitivity, thus limiting their use. Here, we present a highly sensitive tunneling magnetoresistive (TMR) imaging system to detect sub-surface defects in thin steel samples. Artificially created holes in the steel plates were magnetically imaged by measuring magnetic flux leakage (MFL). The experimental results were compared against the simulated results to confirm the visibility of the holes. We also confirmed the successful visualization of the sub-surface defects in the steel plates formed during the real manufacturing processes. Thus, based on these results, we believe the TMR method holds great potential as an NDT technique for steel manufacture management.11Nsciescopu

Modularized Electrosurgical System with a Hybrid CPU-FPGA Chip for Real-Time Thermal Lesion Approximation

Electrosurgery that ablates the target tissues such as tumor and nerve cells using radio-frequency (RF) heating has been widely employed in the medical industry. Although the thermal lesion plays a key role in the efficacy and safety for this method, it is still difficult to identify the depth and size of the lesion during the treatment using recent electrosurgical systems. Herein, we propose a novel electrosurgical instrument for real-time approximation of thermal lesions during RF ablation (RFA). Thermal lesions were numerically calculated based on theoretical thermal models using a hybrid central processing unit (CPU)-field-programmable gate array (FPGA) chip. Other functions such as RF control, voltage, and temperature measurements were implemented using RF components in a modular manner. It can solve voltage distribution in 6 ms by repeating the calculation 5000 times and can anticipate the thermal lesion in 15.6 ms within a time step in real-time simulations. As a real-world validation, the feasibility of the system was demonstrated through an animal study using a swine model. The system is modularly designed using off-the-shelf chips and RF components to improve flexibility and scalability. It can be easily compatible with existing RF surgical applications and medical imaging devices and can improve the efficacy of RFA therapy.11Nsciescopu

Circular radio-frequency electrode with MEMS temperature sensors for laparoscopic renal sympathetic denervation

IEEEObjective: Laparoscopic renal denervation (LRDN) ablates sympathetic nerves on the outer wall of a renal artery to treat autonomic nervous system disorders such as hypertension and arrhythmia. Here, we developed a new circular radio frequency (RF) electrode for LRDN using micro-electro-mechanical systems (MEMS) technology. Methods: The electrode consists of a parallel bipolar MEMS electrode, two MEMS thermocouples, and a shape-memory alloy (SMA) substrate. The electrode is automatically wrapped and unwrapped under actuation controlled by the heat generated by RF energy on the electrodetissue interface. The electrode was designed through a computational simulation analysis, and its actuation and temperature-sensing performance were tested in laboratory experiments and a porcine animal study. Results: In an in-vivo study of porcine renal arteries, the electrode could automatically wrap and unwrap around an artery during LRDN. The bipolar MEMS electrode required 13 Vrms for heat generation up to 60 C, while the two MEMS thermocouples reliably measured the temperature without noise signals (a temperature coefficient of 38.3 or 38.5 V/C and an accuracy of 0.44 or 0.49 C). As revealed in a histological analysis using hematoxylin and eosin staining and Massons trichrome staining, the renal artery was intact after LRDN. Conclusion: The circular RF electrode improves the safety of LRDN by reliably measuring the electrode temperature of the electrode during RDN and enhances the effectiveness of LRDN by reducing the complicated manipulations of the surgical instrument. Significance: The developed circular RF electrode will pave the way for LRDN treatment of autonomic nervous system disorders.11Nsciescopu

Development of a nitinol-actuated surgical instrument for laparoscopic renal denervation: feasibility test in a swine survival model

Purpose In this study, we developed a novel nitinol-actuated surgical instrument to conduct laparoscopic renal denervation for the treatment of resistant hypertension. We investigated whether shape and temperature settings of nitinol specimens fit well into the design goals. Furthermore, we conducted a pilot study to validate the mechanical and physiological performance of nerve ablation without damaging the renal artery. Method Tensile tests were performed to observe temperature-dependent thermomechanical properties and the original shape of nitinol specimens was set considering our design goal. We performed strain gage experiments to measure bending strain. We developed surgical instrument and operated laparoscopic renal denervation in a swine model. Subsequent impedance spectroscopy experiments were conducted to measure changes in impedance magnitudes during the operation and histological analyses were performed to visualize thermogenic damage to arteries and nerves. Results Tensile testing showed that the shape memory effect begins above 37 °C. Measured strains on nitinol surfaces were 2.10% ± 0.769%, below the strain limit of 8%. Impedance spectroscopy experiments showed decreases in magnitude in all six trials. After operation of laparoscopic renal denervation following the protocol, renal arteries and nerves were harvested and thermogenic damage was observed in nerves but not arteries. Conclusion We developed a novel nitinol-actuated surgical instrument with which to perform laparoscopic renal denervation. The feasibility of our device was verified using thermomechanical analyses of nitinol, and assessments of mechanical and physiological performance. Our device could be used in other laparoscopic procedures that require large degrees of freedom while restricting to trocar size

Animal model evaluation of a novel renal denervation system for future laparoscopic treatment of resistant hypertension

Purpose: Although percutaneous catheter-based ablation of renal sympathetic nerve fibers has been used in the treatment of patients with resistant hypertension, a recent phase III study did not confirm its efficacy. In this study, we developed a novel laparoscopic renal denervation system and evaluated its safety and initial feasibility using an animal model. Materials and Methods: A novel surgical instrument that uses a smart algorithm with temperature-monitoring feedback was developed. We used 4 male pigs (6 weeks old, weighing approximately 45 kg each) to evaluate the safety and efficacy of the laparoscopic renal denervation system. We performed immunohistochemical staining analysis after renal denervation using various tip temperatures and over various durations through an open approach. Results: When the temperature of the outer wall of the renal artery was maintained at 90 degrees C for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson's trichrome staining. When the temperature ranged from 70 degrees C to 90 degrees C and the duration ranged from 90 to 420 seconds, partial or complete denervation without significant vessel injury was confirmed with anti- growth-associated protein 43 and anti-S100 staining. Conclusions: This animal study confirmed the safety and feasibility of the novel laparoscopic renal denervation system. A safe and effective protocol was developed with ablation at a constant tissue temperature of 70 degrees C to 90 degrees C within 180 seconds. However, further developments are necessary before its clinical use.1

Developing a Computational Model of Renal Nerves and Surgical System for Laparoscopic Renal Denervation

The sympathetic nervous system was known to play an important role in resistant hypertension. Surgical sympathectomy for renal sympathetic nerve removal were performed since the 1930s. Although effective, it had many serious side effects and complications due to non-selective property. Recently, catheter based RDN system using radiofrequency (RF) ablation was developed and considered promising, however, it failed in sham controlled trial. Therefore, there are needs for safe and effective RDN strategies considering the anatomical structure of the renal arteries and sympathetic nerves. In this paper, we propose a novel surgical instruments for laparoscopic renal denervation (RDN) to treat of resistant hypertension through a 3D realistic model using nephrectomy tissues. Laparoscopic RDN is a new surgical approach to remove renal sympathetic nerves.1

Thermal Ablation and High-Resolution Imaging Using a Back-to-Back (BTB) Dual-Mode Ultrasonic Transducer: In Vivo Results

We present a back-to-back (BTB) structured, dual-mode ultrasonic device that incorporates a single-element 5.3 MHz transducer for high-intensity focused ultrasound (HIFU) treatment and a single-element 20.0 MHz transducer for high-resolution ultrasound imaging. Ultrasound image-guided surgical systems have been developed for lesion monitoring to ensure that ultrasonic treatment is correctly administered at the right locations. In this study, we developed a dual-element transducer composed of two elements that share the same housing but work independently with a BTB structure, enabling a mode change between therapy and imaging via 180-degree mechanical rotation. The optic fibers were embedded in the HIFU focal region of ex vivo chicken breasts and the temperature change was measured. Images were obtained in vivo mice before and after treatment and compared to identify the treated region. We successfully acquired B-mode and C-scan images that display the hyperechoic region indicating coagulation necrosis in the HIFU-treated volume up to a depth of 10 mm. The compact BTB dual-mode ultrasonic transducer may be used for subcutaneous thermal ablation and monitoring, minimally invasive surgery, and other clinical applications, all with ultrasound only.11Nsciescopu