Plasma Exosome Analysis for Protein Mutation Identification Using a Combination of Raman Spectroscopy and Deep Learning.

Protein mutation detection using liquid biopsy can be simply performed periodically, making it easy to detect the occurrence of newly emerging mutations rapidly. However, it has low diagnostic accuracy since there are more normal proteins than mutated proteins in body fluids. To increase the diagnostic accuracy, we analyzed plasma exosomes using nanoplasmonic spectra and deep learning. Exosomes, a promising biomarker, are abundant in plasma and stably carry intact proteins originating from mother cells. However, the mutated exosomal proteins cannot be detected sensitively because of the subtle changes in their structure. Therefore, we obtained Raman spectra that provide molecular information about structural changes in mutated proteins. To extract the unique features of the protein from complex Raman spectra, we developed a deep-learning classification algorithm with two deep-learning models. Consequently, controls with wild-type proteins and patients with mutated proteins were classified with high accuracy. As a proof of concept, we discriminated the lung cancer patients with mutations in the epidermal growth factor receptor (EGFR), L858R, E19del, L858R + T790M, and E19del + T790M, from controls with an accuracy of 0.93. Moreover, the protein mutation status of the patients with primary (E19del, L858R) and secondary (+T790M) mutations was clearly monitored. Overall, our technique is expected to be applied as a novel method for companion diagnostic and treatment monitoring.

Dynamic metallization of spherical DNA via conformational transition into gold nanostructures with controlled sizes and shapes.

Despite the reversible condensation properties of DNA, DNA metallization during controlled conformational transitions has been rarely investigated. We perform dynamic metallization of spherically condensed DNA nanoparticles (DNA NPs) via a globule-to-coil transition. A positively charged new Au3+ reagent is prepared via ligand-exchange of conventional complex Au3+ ions, which was used to synthesize spherically condensed DNA NPs simply based on the fundamental electrostatic and coordinative interactions between DNA and Au3+ions. Interestingly, the size of the Au3+-condensed DNA NPs (Au3+-DNA NPs) and the type of reducing agents lead to the formation of different Au nanostructures with unprecedented morphologies (cracked NPs, bowl-shaped NPs, and small NPs), owing to the controlled conformational changes in the Au3+-DNA NPs during metallization. The condensed DNA NPs play significant roles for Au nanostructures as (1) the dynamic template for the synthesis, (2) the reservoir and supply of Au3+ for the growth, and (3) the surface stabilizer. The synthesized Au nanostructures are remarkably stable against high ionic strength and exhibit catalytic activities and excellent SERS properties. This is the first study on the morphological control and concomitant dynamic metallization of spherically condensed DNA, proposing new synthetic routes for bioinorganic nanomaterials.

Aqueous synthesis of highly monodisperse sub-100 nm AgCl nanospheres/cubes and their plasmonic nanomesh replicas as visible-light photocatalysts and single SERS probes.

Despite the distinctive electrochemical and photocatalytic properties of nanostructured silver chloride (AgCl), the shape- and size-dependence of their properties have not been thoroughly investigated to date. The most substantial reason responsible for this incomplete study and the subsequent limited applications is the failure in controlling the structure of AgCl nanomaterials, mainly owing to the challenging synthetic conditions including organic phase and high reaction temperature. In this work, we reported a rapid one-pot room-temperature aqueous synthesis of highly monodisperse sub-100 nm AgCl nanomaterials with various shapes and sizes by controlling the precursor (Ag+ and AuCl4 -) ratios. The remaining unreacted metal precursors (Ag+ and AuCl4 -) used to produce AgClNC were subsequently reduced by ascorbic acid on the surface of the synthesized AgCl nanomaterials to form Ag/Au bimetallic nanomesh structures (AgClNC#AuAgCMs and SMs). After the removal of the AgCl nanotemplates, only nanomesh structures (AuAgCMs and SMs) were obtained. Importantly, we successfully decreased the size of the AgCl nanomaterials which were replicated into bimetallic spherical and cubic nanomesh structures that were small enough (∼100 nm) to show intense surface-plasmon-absorption bands. Based on these unique chemical and physical properties, we could take advantage of the plasmonic photocatalysis properties of the complex comprising semiconducting AgCl/metallic nanomesh replica for the complete removal of the environmentally harmful Cr6+ in the presence of sacrificial agents such as formic acid. Finally, the novel bimetallic nanomesh structures proved themselves to exhibit intense surface-enhanced Raman scattering properties in a single-particle enhancing the electromagnetic field.

Pipeline Embolization Device for Large/Giant or Fusiform Aneurysms: An Initial Multi-Center Experience in Korea.

PURPOSE: The purpose of this study was to assess the safety and early outcomes of the Pipeline device for large/giant or fusiform aneurysms. MATERIALS AND METHODS: The Pipeline was implanted in a total of 45 patients (mean age, 58 years; M:F=10:35) with 47 large/giant or fusiform aneurysms. We retrospectively evaluated the characteristics of the treated aneurysms, the periprocedural events, morbidity and mortality, and the early outcomes after Pipeline implantation. RESULTS: The aneurysms were located in the internal carotid artery (ICA) cavernous segment (n=25), ICA intradural segment (n=11), vertebrobasilar trunk (n=8), and middle cerebral artery (n=3). Procedure-related events occurred in 18 cases, consisting of incomplete expansion (n=8), shortening-migration (n=5), transient occlusion of a jailed branch (n=3), and in-stent thrombosis (n=2). Treatment-related morbidity occurred in two patients, but without mortality. Both patients had modified Rankin scale (mRS) scores of 2, but had an improved mRS score of 0 at 1-month follow-up. Of the 19 patients presenting with mass effect, 16 improved but three showed no changes in their presenting symptoms. All patients had excellent outcomes (mRS, 0 or 1) during the follow-up period (median, 6 months; range, 2-30 months). Vascular imaging follow-up (n=31, 65.9%; median, 3 months, range, 1-25 months) showed complete or near occlusion of the aneurysm in 24 patients (77.4%) and decreased sac size in seven patients (22.6%). CONCLUSION: In this initial multicenter study in Korea, the Pipeline seemed to be safe and effective for large/giant or fusiform aneurysms. However, a learning period may be required to alleviate device-related events.

Effect of vagus nerve stimulation in post-traumatic epilepsy and failed epilepsy surgery : preliminary report.

OBJECTIVE: Vagus nerve stimulation (VNS) has been used in epilepsy patients refractory to standard medical treatments and unsuitable candidates for resective or disconnective surgery. In this study, we investigated the efficacy of VNS to patients who had refractory result to epilepsy surgery and patients with post-traumatic epilepsy. METHODS: We analyzed the effect of VNS in 11 patients who had undergone previous epilepsy surgery and patients with intractable post-traumatic epilepsy associated with brain injury. All patients underwent VNS implantation between October 2005 and December 2006. RESULTS: We evaluated seizure frequency before and after implantation of VNS and maximum follow up period was 24 months. In the first 6 months, 11 patients showed an average of 74.3% seizure reduction. After 12 months, 10 patients showed 85.2% seizure reduction. Eighteen months after implantation, 9 patients showed 92.4% seizure reduction and 7 patients showed 97.2% seizure reduction after 24 months. Six patients were seizure-free at this time. CONCLUSION: We conclude that the VNS is a helpful treatment modality in patients with surgically refractory epilepsy and in patients with post-traumatic epilepsy due to severe brain injury.

Combined surgical approach with intraoperative endovascular embolization for inaccessible dural arteriovenous fistulas.

BACKGROUND: We describe an alternative treatment modality for inaccessible intracranial DAVFs caused by local thrombosis or tortuous feeder vessels. Special consideration is given to the efficacy of intraoperative endovascular embolization and to the use of various operative routes depending on the location of the lesions. METHODS: Between August 1999 and January 2006, 7 of 65 patients were diagnosed with DAVFs with the limitation of endovascular access. Thus, we adopted a combined surgical approach with intraoperative endovascular embolization. We reviewed and analyzed the patients' medical records and their outcomes. RESULTS: Depending on tumor location, a surgical approach combined with simultaneous intraoperative endovascular embolization was successfully performed via the SOV, the TS-SS junction, and the SSS. No complication related to the treatment was reported, and, subsequently, all the patients recovered completely. CONCLUSION: A combined surgical approach with simultaneous intraoperative embolization is an effective and safe treatment for DAVFs that are of limited angiographic access.

Gamma knife radiosurgery for epilepsy related to dysembryoplastic neuroepithelial tumor.

Dysembryoplastic neuroepithelial tumor (DNT) is a well-known epileptogenic lesion with favorable seizure outcome after surgical resection. However, sometimes surgery may be difficult technically, and epilepsy may continue throughout the patient's lifetime despite surgical intervention. We report a case of intractable epilepsy related to DNT that was treated with gamma knife radiosurgery (GKRS). The frequency of seizure was reduced remarkably after GKRS, and finally a seizure-free state was accomplished in two years. Neuropsychological tests also showed improvement. It is suggested that GKRS may be an effective and less invasive alternative treatment for the patients in whom surgical treatment is difficult.