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An Junho,Nam Yoojin,Cho Hyoun,Chang Jeonga,Kim Duk-Kyung,Lee Kyung Soo 대한의학회 2022 Journal of Korean medical science Vol.37 No.10
In acute pulmonary embolism (PE), circulatory failure and systemic hypotension are important clinically for predicting poor prognosis. While pulmonary artery (PA) clot loads can be an indicator of the severity of current episode of PE or treatment effectiveness, they may not be used directly as an indicator of right ventricular (RV) failure or patient death. In other words, pulmonary vascular resistance or patient prognosis may not be determined only with mechanical obstruction of PAs and their branches by intravascular clot loads on computed tomography pulmonary angiography (CTPA), but determined also with vasoactive amines, reflex PA vasoconstriction, and systemic arterial hypoxemia occurring during acute PE. Large RV diameter with RV/left ventricle (LV) ratio > 1.0 and/or the presence of occlusive clot and pulmonary infarction on initial CTPA, and clinically determined high baseline PA pressure and RV dysfunction are independent predictors of oncoming chronic thromboembolic pulmonary hypertension (CTEPH). In this pictorial review, authors aimed to demonstrate clinical and serial CTPA features in patients with acute massive and submassive PE and to disclose acute CTPA and clinical features that are related to the prediction of oncoming CTEPH.
NoSQL based Web Service System for Sharing of Emotion Information in Cloud Computing
Junho Jung,Jeong Byun,DongKeun Kim3 보안공학연구지원센터 2016 International Journal of Software Engineering and Vol.10 No.3
We present the No-SQL based Web service system for sharing of emotion information regarding the individual emotional states and location information of users using by a MongoDB in cloud computing environments. Pre-processed emotion information represents the individual emotional states categorized as a nine domain based on physiological signals recognition within the database system. However, in order to present individual emotional states regarding to pre-processed user’s emotional states and locations on a Web-based map, the computational overload with large amount of data for a location-query process is to be solved for support sharing Web services. Meanwhile, previous RDBMS-based systems are inadequate due to insufficient scalability and processing time of data processing nodes. Therefore, in this paper, we have designed and implemented an emotion sharing web service by reducing the load on the system using NoSQL database. In addition, it was confirmed that it is possible to effectively utilize resources and visualized by using Google’s FusionTable and it is possible to share on a Web map.
Kim Il Bin,Kim Myeong-Heui,Jung Saehoon,Kim Woo Kyeong,Lee Junehawk,Ju Young Seok,Webster Maree J.,Kim Sanghyeon,Kim Ja Hye,Kim Hyun Jung,Kim Junho,Kim Sangwoo,Lee Jeong Ho 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-
Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p < 0.05). Patients with damaging mutations in the merged gene set had a greater ASD risk than did controls (odds ratio = 3.92, p = 0.025, 95% confidence interval = 1.12–14.79). The findings of this study suggest that brain somatic SNVs and germline SNVs may collectively contribute to ASD-associated pathophysiology.
Preclinical development of a humanized neutralizing antibody targeting HGF
Kim, Hyori,Hong, Sung Hee,Kim, Jung Yong,Kim, In-Chull,Park, Young-Whan,Lee, Song-Jae,Song, Seong-Won,Kim, Jung Ju,Park, Gunwoo,Kim, Tae Min,Kim, Yun-Hee,Park, Jong Bae,Chung, Junho,Kim, In-Hoo Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.3
<P>Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101. To support clinical development, we also evaluated the preclinical pharmacokinetics and toxicokinetics in cynomolgus monkeys, and human and cynomolgus monkey tissue was stained with YYB-101 to test tissue cross-reactivity. We found that YYB-101 inhibited cMET activation <I>in vitro</I> and suppressed tumor growth in the orthotopic mouse model of human glioblastoma. Combination treatment with YYB-101 and temozolomide decreased tumor growth and increased overall survival compared with the effects of either agent alone. Five cancer-related genes (TMEM119, FST, RSPO3, ROS1 and NBL1) were overexpressed in YYB-101-treated mice that showed tumor regrowth. In the tissue cross-reactivity assay, critical cross-reactivity was not observed. The terminal elimination half-life was 21.7 days. Taken together, the <I>in vitro</I> and <I>in vivo</I> data demonstrated the anti-tumor efficacy of YYB-101, which appeared to be mediated by blocking the HGF/cMET interaction. The preclinical pharmacokinetics, toxicokinetics and tissue cross-reactivity data support the clinical development of YYB-101 for advanced cancer.</P>
Lim, Jae Seok,Kim, Woo-il,Kang, Hoon-Chul,Kim, Se Hoon,Park, Ah Hyung,Park, Eun Kyung,Cho, Young-Wook,Kim, Sangwoo,Kim, Ho Min,Kim, Jeong A,Kim, Junho,Rhee, Hwanseok,Kang, Seok-Gu,Kim, Heung Dong,Kim, Nature Publishing Group 2015 Nature medicine Vol. No.
Focal cortical dysplasia type II (FCDII) is a sporadic developmental malformation of the cerebral cortex characterized by dysmorphic neurons, dyslamination and medically refractory epilepsy. It has been hypothesized that FCD is caused by somatic mutations in affected regions. Here, we used deep whole-exome sequencing (read depth, 412–668×) validated by site-specific amplicon sequencing (100–347,499×) in paired brain-blood DNA from four subjects with FCDII and uncovered a de novo brain somatic mutation, mechanistic target of rapamycin (MTOR) c.7280T>C (p.Leu2427Pro) in two subjects. Deep sequencing of the MTOR gene in an additional 73 subjects with FCDII using hybrid capture and PCR amplicon sequencing identified eight different somatic missense mutations found in multiple brain tissue samples of ten subjects. The identified mutations accounted for 15.6% of all subjects with FCDII studied (12 of 77). The identified mutations induced the hyperactivation of mTOR kinase. Focal cortical expression of mutant MTOR by in utero electroporation in mice was sufficient to disrupt neuronal migration and cause spontaneous seizures and cytomegalic neurons. Inhibition of mTOR with rapamycin suppressed cytomegalic neurons and epileptic seizures. This study provides, to our knowledge, the first evidence that brain somatic activating mutations in MTOR cause FCD and identifies mTOR as a treatment target for intractable epilepsy in FCD.
Kim, Junho,Kim, Sanghyeon,Nam, Hojung,Kim, Sangwoo,Lee, Doheon Oxford University Press 2015 Bioinformatics Vol.31 No.19
<P><B>Motivation:</B> Finding somatic mutations from massively parallel sequencing data is becoming a standard process in genome-based biomedical studies. There are a number of robust methods developed for detecting somatic single nucleotide variations However, detection of somatic copy number alteration has been substantially less explored and remains vulnerable to frequently raised sampling issues: low frequency in cell population and absence of the matched control samples.</P><P><B>Results:</B> We developed a novel computational method SoloDel that accurately classifies low-frequent somatic deletions from germline ones with or without matched control samples. We first constructed a probabilistic, somatic mutation progression model that describes the occurrence and propagation of the event in the cellular lineage of the sample. We then built a Gaussian mixture model to represent the mixed population of somatic and germline deletions. Parameters of the mixture model could be estimated using the expectation-maximization algorithm with the observed distribution of read-depth ratios at the points of discordant-read based initial deletion calls. Combined with conventional structural variation caller, SoloDel greatly increased the accuracy in classifying somatic mutations. Even without control, SoloDel maintained a comparable performance in a wide range of mutated subpopulation size (10–70%). SoloDel could also successfully recall experimentally validated somatic deletions from previously reported neuropsychiatric whole-genome sequencing data.</P><P><B>Availability and implementation:</B> Java-based implementation of the method is available at http://sourceforge.net/projects/solodel/</P><P><B>Contact:</B> swkim@yuhs.ac or dhlee@biosoft.kaist.ac.kr</P><P><B>Supplementary information:</B> Supplementary data are available at <I>Bioinformatics</I> online.</P>
Kim, Minjin,Kim, Jihwan,Lee, In-Ho,Han, Woo Hyun,Park, Yun Chang,Kim, Woo Youn,Kim, Bongsoo,Suh, Junho Royal Society of Chemistry 2019 Nanoscale Vol.11 No.12
<P>We report a ternary silver chalcogenide, Ag2Se0.5Te0.5, as a new topological material with improved quantum transport properties. Single-crystalline nanostructures of ternary silver chalcogenides Ag2SexTe1−x are synthesized with a tunable chemical composition <I>via</I> the chemical vapor transport method. Quantum transport studies reveal that Ag2Se0.5Te0.5 nanowires present topological surface states with higher electron mobility and longer mean free path compared to binary Ag-chalcogenides. First-principles calculations also indicate that Ag2Se0.5Te0.5 is a topological insulator, and the observed enhancement in transport properties could imply reduced bulk carrier contribution in the new ternary silver chalcogenide.</P>