Methylation of EGFR by Arginine Methyltransferase PRMT1 Enhances EGFR Signaling and Cetuximab resistance

Protein modifications of epidermal growth factor receptor (EGFR) intracellular domain are well known regulators of EGFR functions whereas those of its extracellular domain remain relatively unexplored. Here, we report that methylation at R198 and R200 of EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) upregulates its binding to EGF and subsequent receptor dimerization and signaling activation. Methylation-defective EGFR mutant reduced tumor growth in mouse orthotopic xenograft model. Importantly, increased EGFR methylation sustains its signaling activation and cell proliferation in the presence of therapeutic EGFR monoclonal antibody, cetuximab. EGFR methylation level also correlates with higher recurrence rate after cetuximab treatment and poorer overall survival in colorectal cancer patients. These data suggest that R198/R200 methylation plays important role in regulating EGFR functionality and resistance to cetuximab treatment

Orbital hemangiopericytoma in an Asian population

Background/PurposeHemangiopericytoma is a very rare orbital tumor. The purpose of this study was to report the clinical and histopathological features of six cases of orbital hemangiopericytoma in an Asian population.MethodsClinical and histopathological features were reviewed in six patients who were histopathologically confirmed as having primary orbital hemangiopericytoma in National Taiwan University Hospital between May 2001 and December 2010.ResultsAmong the six cases who were diagnosed as having primary orbital hemangiopericytoma, all lesions were reported as vascular tumors and featured branching “staghorn appearance” vessels. All patients, including one male and five females, presented with progressive proptosis and some associated symptoms such as extraocular motility limitation with diplopia, displacement of the globe, afferent pupillary defect, congested vessels of conjunctiva, or decreased visual acuity. On computed tomography, the orbital tumors tended to manifest as circumscribed masses with homogeneous medium-to-high enhancement with contrast studies. All six patients received surgical treatments, and four of them had additional radiotherapy. Three patients had recurrence after surgeries, and one of them had multiple metastases to lung and liver. All patients were still alive after a follow-up period of 5–10 years.ConclusionOrbital hemangiopericytoma has malignant potential, which may lead to local recurrence and/or metastasis. Histopathological findings alone are insufficient to predict the behavior of this tumor. Therefore, both clinical and histopathological findings are important to evaluate the treatment outcomes. Total excision accompanied with radiotherapy is suggested and long-term follow-up is required

Esophageal Food Impaction: A Homemade Suction Tube Attached to Esophagogastroduodenoscopy for Food Bolus Removal

The most common esophageal foreign body in adults is impacted food bolus. Polypectomy snares, Dormia baskets, retrieval nets, rat-tooth forceps, alligator forceps or polyp graspers are usually used to remove it. Here, we report the case of a 78-year-old woman whose esophagogastroduodenoscopy (EGD) showed a firm goose liver impacted tightly in the lower esophagus; all of the above-mentioned retrieval instruments could not remove it. We used a homemade device by attaching a modified nasogastric tube to an EGD and successfully removed the goose liver by suction under endoscopic visualization. The method is very effective to remove firm and tightly impacted materials in a narrow lumen. When the usual retrieval instruments fail, a homemade suction tube attached to an EGD is an alternative

HIP-KNEE control for gait assistance with Powered Knee Orthosis

A Powered Knee Orthosis (PKO) was developed for the elderly and patients with disordered gait to regain normal walking. In order to enhance the PKO performance and reduce system complexity especially for people with muscle weakness in their knee joints, an algorithm named HIP-KNEE control is proposed. This algorithm is based on the analysis of kinematic gait model, and the desired knee joint angle (KNEE) is estimated from the measurements of hip joint angle (HIP). The relationship between HIP and KNEE is modeled as a polynomial, which can be easily implemented to an embedded controller for real-time control. This control method is suitable to subjects with good function in hip joint, and it can provide help in walking without special training. An Inertia Measurement Units (IMU) is used for obtaining HIP input, and integrated with a footswitch for checking the heel condition; the gait assistance performance can be further improved

Experimental studies on kinematics and kinetics of walking with an assistive knee brace

Assistive knee brace is a species of wearable lower extremity exoskeletons. Such assistive equipment can enhance people's strength and provide desired locomotion to have advantages over wheelchairs, which are commonly used for patients with mobility disorders. However, the integration between the assistive knee brace and the user is challenging as inaccurate alignments may adversely affect the biomechanics of the knee joint. The goal of this study is to evaluate the changes between normal walking and walking with an assistive knee brace in "off" mode. The assistive knee brace was developed by integrating a multifunctional actuator with a custom-made knee-ankle-foot orthosis in order to minimize excessive shifting and to improve alignment to the knee joint. Spatial and temporal gait parameters, joint kinematics and joint kinetics parameters were compared. In general, the observed results showed that most of the gait parameters were not affected when walking with the knee brace. The only significant differences were found in knee flexion and knee rotational motions. These results indicated that walking with the developed knee brace provided minimal hindrance to the user and assured that assistive torque can be applied to the knee joint

VRDMG: Vocal Restoration via Diffusion Posterior Sampling with Multiple Guidance

Restoring degraded music signals is essential to enhance audio quality for downstream music manipulation. Recent diffusion-based music restoration methods have demonstrated impressive performance, and among them, diffusion posterior sampling (DPS) stands out given its intrinsic properties, making it versatile across various restoration tasks. In this paper, we identify that there are potential issues which will degrade current DPS-based methods' performance and introduce the way to mitigate the issues inspired by diverse diffusion guidance techniques including the RePaint (RP) strategy and the Pseudoinverse-Guided Diffusion Models ($\Pi$GDM). We demonstrate our methods for the vocal declipping and bandwidth extension tasks under various levels of distortion and cutoff frequency, respectively. In both tasks, our methods outperform the current DPS-based music restoration benchmarks. We refer to \url{http://carlosholivan.github.io/demos/audio-restoration-2023.html} for examples of the restored audio samples

Gait analysis for designing a new assistive knee brace

Assistive knee brace is a species of wearable lower extremity exoskeletons. In this research, an assistive knee brace was developed by integrating a multifunctional actuator with a custom-made knee-ankle-foot orthosis. In the study, the location of the actuator is moved up to the lateral side of the hip, instead of knee joint. Waist belt and shoulder belt are appended on the knee brace. This paper aimed to improve the design of the assistive knee braces through gait analysis. By walking with the knee braces, the spatial and temporal gait parameters, joint kinematics and joint kinetics parameters were evaluated, and the changes from normal walking were compared as well. The experimental results showed that walking with the developed knee brace provided minimal hindrance to the wearer. © 2011 IEEE