Publications by authors named "Hyun-Seok Park"

61 Publications

Editor's introduction to the special section on the 7th Biomedical Linked Annotation Hackathon (BLAH7).

Genomics Inform 2021 Sep 30;19(3):e20. Epub 2021 Sep 30.

Center for Convergence Research of Advanced Technologies, Ewha Womans University, Seoul 03760, Korea.

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http://dx.doi.org/10.5808/gi.19.3.e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510870PMC
September 2021

Comparison of transorbital ultrasound measurements to predict intracranial pressure in brain-injured patients requiring external ventricular drainage.

J Neurosurg 2021 Jul 23:1-7. Epub 2021 Jul 23.

3Department of Neurosurgery, Dong-A University College of Medicine, Busan, Korea.

Objective: The optic nerve sheath diameter (ONSD) excluding the dura mater (ONSDE; i.e., the subarachnoid diameter) and the ONSD including the dura mater (ONSDI) have been used differently in studies, but the predictive ability of these two different measurements of the ONSD as measured by invasive intracranial pressure (ICP) monitoring has never been compared. Additionally, studies on the prediction of ICP using central retinal artery (CRA) Doppler ultrasonography are scarce. The authors aimed to determine how the two different ONSD measurements, the ONSD/eyeball transverse diameter (ETD) ratio, and transorbital Doppler ultrasonography parameters are associated with ICP via external ventricular drainage (EVD).

Methods: This prospective observational study included 50 patients with brain injury who underwent EVD between August 2019 and September 2020. The mean of three repeated measurements of the ONSDI and ONSDE was calculated to reduce artifact and off-axis measurements. ETD, an immutable value, was measured from the initial brain CT with a clear outline of the eyeball. Simultaneously, flow velocities in the CRA and posterior ciliary artery (PCA) were compared with the ICP.

Results: The ONSDE, ONSDI, and ONSD/ETD ratio were significantly associated with ICP (p = 0.005, p < 0.001, and p < 0.001, respectively). The ONSD/ETD ratio showed the highest predictive power of increased ICP (area under the curve [AUC] 0.897). The ONSDI was correlated more with the ICP than was the ONSDE (AUC 0.855 vs 0.783). None of the Doppler ultrasonography parameters in the CRA and PCA were associated with ICP.

Conclusions: The ONSD/ETD ratio is a better predictor of increased ICP compared with the ONSDI or ONSDE in brain-injured patients with nonsevere ICP. The ONSDI may be more available for predicting the ICP than the ONSDE.
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http://dx.doi.org/10.3171/2021.1.JNS204218DOI Listing
July 2021

Scaffolding protein Gab2 is involved in postnatal development and lipopolysaccharide-induced activation of microglia in the mouse brain.

Biochem Biophys Res Commun 2021 Aug 17;567:112-117. Epub 2021 Jun 17.

Department of Molecular Neuroscience, Peripheral Neuropathy Research Center (PNRC), College of Medicine, Dong-A University, Busan, Republic of Korea; Department of Neurosurgery, Busan Regional Cardio-Cerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Republic of Korea. Electronic address:

Grb2-associated-binding protein-2 (Gab2) is a member of the Gab/DOS family and functions as an adapter protein downstream of several growth factor signaling pathways. Gab2 is considered an Alzheimer's disease susceptibility gene. However, the role of Gab2 in the brain is still largely unknown. Herein, we report that Gab2 is involved in the postnatal development of microglia in mice. The Gab2 expression in the brain was detected at postnatal day 1 (P1) and increased until P14 but decreased thereafter. The tyrosine phosphorylation of Gab2 (pGab2) was also detected at P1 and increased until P14. Next, we focused on microglial development in Gab2 knockout and heterozygous mice. Although differences were not detected in the cytoplasmic area of Iba1-labeled microglia between Gab2(±) and Gab2(-/-) mice, the analysis of CD68 and cathepsin D (indicators of microglial lysosomal activation) immunolabeling within Iba1+ cells revealed significant underdevelopment of microglial lysosomes in Gab2(-/-) mice at P60. In addition to the developmental abnormality of microglia in Gab2(-/-) mice, lipopolysaccharide-induced lysosomal activation was selectively suppressed in Gab2(-/-) mice compared to that in Gab2(±) mice. Our findings suggest that Gab2 is involved not only in postnatal development but also in lysosomal activation of microglia, therefore Gab2 dysfunction in microglia might potentially contribute to the development of neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.028DOI Listing
August 2021

Impact of Neurointensivist Co-Management in a Semiclosed Neurocritical-Care Unit.

J Clin Neurol 2020 Oct;16(4):681-687

Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea.

Background And Purpose: The importance of the specialized management of neurocritical patients is being increasingly recognized. We evaluated the impact of neurointensivist comanagement on the clinical outcomes (particularly the mortality rate) of neurocritical patients admitted to a semiclosed neurocritical-care unit (NCU).

Methods: We retrospectively included neurocritical patients admitted to the NCU between March 2015 and February 2018. We analyzed the clinical data and compared the outcomes between patients admitted before and after the initiation of neurointensivist co-management in March 2016.

Results: There were 1,785 patients admitted to the NCU during the study period. Patients younger than 18 years (=28) or discharged within 48 hours (=200) were excluded. The 1,557 remaining patients comprised 590 and 967 who were admitted to the NCU before and after the initiation of co-management, respectively. Patients admitted under neurointensivist co-management were older and had higher Acute Physiologic Assessment and Chronic Health Evaluation II scores. The 30-day mortality rate was significantly lower after neurointensivist co-management (=0.042). A multivariate logistic regression analysis demonstrated that neurointensivist co-management significantly reduced mortality rates in the NCU and in the hospital overall [odds ratio=0.590 (=0.002) and 0.585 (=0.001), respectively].

Conclusions: Despite the higher severity of the condition during neurointensivist co-management, co-management significantly improved clinical outcomes (including the mortality rate) in neurocritical patients.
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http://dx.doi.org/10.3988/jcn.2020.16.4.681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541986PMC
October 2020

Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0.

Genomics Inform 2020 Sep 17;18(3):e33. Epub 2020 Sep 17.

Bioinformatics & Natural Language Processing Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.
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http://dx.doi.org/10.5808/GI.2020.18.3.e33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560450PMC
September 2020

Using the PubAnnotation ecosystem to perform agile text mining on Genomics & Informatics: a tutorial review.

Genomics Inform 2020 Jun 16;18(2):e13. Epub 2020 Jun 16.

Bioinformatics Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

The prototype version of the full-text corpus of Genomics & Informatics has recently been archived in a GitHub repository. The full-text publications of volumes 10 through 17 are also directly downloadable from PubMed Central (PMC) as XML files. During the Biomedical Linked Annotation Hackathon 6 (BLAH6), we experimented with converting, annotating, and updating 301 PMC full-text articles of Genomics & Informatics using PubAnnotation, a system that provides a convenient way to add PMC publications based on PMCID. Thus, this review aims to provide a tutorial overview of practicing the iterative task of named entity recognition with the PubAnnotation/PubDictionaries/TextAE ecosystem. We also describe developing a conversion tool between the Genia tagger output and the JSON format of PubAnnotation during the hackathon.
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http://dx.doi.org/10.5808/GI.2020.18.2.e13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362947PMC
June 2020

Editor's introduction to the special issue of the 6th Biomedical Linked Annotation Hackathon (BLAH6).

Genomics Inform 2020 Jun 24;18(2):e12. Epub 2020 Jun 24.

Center for Convergence Research of Advanced Technologies, Ewha Womans University, Seoul 03760, Korea.

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http://dx.doi.org/10.5808/GI.2020.18.2.e12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362940PMC
June 2020

A new definition for wide-necked cerebral aneurysms.

J Cerebrovasc Endovasc Neurosurg 2019 Dec 31;21(4):193-198. Epub 2019 Dec 31.

Department of Neurosurgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Background: Endovascular management of wide-necked aneurysms often requires assisted-techniques with adjunctive devices. Wide-necked aneurysm can be defined with a dome-to-neck ratio or aspect ratio; however, clinical definitions of wide-necked aneurysms vary. This study aimed to determine the most useful definition of wide-necked aneurysm to predict the need for an adjunctive device.

Methods: Among 552 cases of aneurysms, 343 (62.1%) and 209 (37.9%) cases of unruptured and ruptured aneurysms, respectively, were treated in a single institution. For each aneurysm, the (1) dome-to-neck ratio, (2) aspect ratio, and (3) K-ratio (defined as [dome height+maximum dome width]/[2×maximum neck width]) were measured. We statistically analyzed patient data to determine which of the three ratios was most predictive of the need for adjunctive devices.

Results: Among 552 cases of aneurysms, 277 (50.2%) and 275 (49.8%) cases were treated with and without adjunctive techniques, respectively. The mean dome-to-neck ratio, aspect ratio, and K-ratio were 1.17±0.39, 1.58±0.61, and 1.37±0.47, respectively. The K-ratio was the strongest predictor of the use of adjunctive devices (P<0.001), and 1.3 was the most appropriate K-ratio cut-off value (sensitivity, 72.9%; specificity, 63.6%).

Conclusions: K-ratio was the most useful predictor of the need for adjunctive devices in the treatment of endovascular aneurysms. These results suggest that the K-ratio may be used to define wide-necked aneurysms requiring complicated management via adjunctive devices.
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http://dx.doi.org/10.7461/jcen.2019.21.4.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987033PMC
December 2019

Trends in Genomics & Informatics: a statistical review of publications from 2003 to 2018 focusing on the most-studied genes and document clusters.

Genomics Inform 2019 Sep 27;17(3):e25. Epub 2019 Sep 27.

Bioinformatics Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

Genomics & Informatics (NLM title abbreviation: Genomics Inform) is the official journal of the Korea Genome Organization. Herein, we conduct a statistical analysis of the publications of Genomics & Informatics over the 16 years since its inception, with a particular focus on issues relating to article categories, word clouds, and the most-studied genes, drawing on recent reviews of the use of word frequencies in journal articles. Trends in the studies published in Genomics & Informatics are discussed both individually and collectively.
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http://dx.doi.org/10.5808/GI.2019.17.3.e25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808643PMC
September 2019

Efficacy of Combining Proximal Balloon Guiding Catheter and Distal Access Catheter in Thrombectomy with Stent Retriever for Anterior Circulation Ischemic Stroke.

J Korean Neurosurg Soc 2019 Jul 1;62(4):405-413. Epub 2019 Jul 1.

Busan-Ulsan Regional Cardiocerebrovascular Center, Dong-A University Hospital, Busan, Korea.

Objective: We evaluated efficacy of combining proximal balloon guiding catheter (antegrade flow arrest) and distal access catheter (aspiration at the site of occlusion) in thrombectomy for anterior circulation ischemic stroke.

Methods: We retrospectively analyzed 116 patients who underwent mechanical thrombectomy with stent retriever. The patients were divided by the techniques adopted, the combined technique (proximal balloon guiding catheter and large bore distal access catheter) group (n=57, 49.1%) and the conventional (guiding catheter with stent retriever) technique group (n=59, 50.9%). We evaluated baseline characteristics (epidemiologic data, clinical and imaging characteristics) and procedure details (the number of retrieval attempts, procedure time), as well as angiographic (thrombolysis in cerebral infarction (TICI) score, distal thrombus migration) and clinical outcome (National Institutes of Health Stroke Scale at discharge, modified Rankin Scale [mRS] at 3 months) of them.

Results: The number of retrieval attempts was lower (p=0.002) and the first-pass successful reperfusion rate was higher (56.1% vs. 28.8%; p=0.003) in the combined technique group. And the rate of final result of TICI score 3 was higher (68.4% vs. 28.8%; p<0.01) and distal thrombus migration rate was also lower (15.8% vs. 40.7%; p=0.021) in the combined technique group. Early strong neurologic improvement (improvement of National Institutes of Health Stroke Scale ≥11 or National Institutes of Health Stroke Scale ≤1 at discharge) rate (57.9% vs. 36.2%; p=0.02) and favorable clinical outcome (mRS at 3 months ≤2) rate (59.6% vs. 33.9%; p=0.005) were also better in the combined technique group.

Conclusion: The combined technique needs lesser attempts, decreases distal migration, increases TICI 3 reperfusion and achieves better clinical outcomes.
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http://dx.doi.org/10.3340/jkns.2019.0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616992PMC
July 2019

Safety and Efficacy of Minimally Invasive Stereotactic Aspiration with Multicatheter Insertion Compared with Conventional Craniotomy for Large Spontaneous Intracerebral Hemorrhage (≥50 mL).

World Neurosurg 2019 Aug 9;128:e787-e795. Epub 2019 May 9.

Department of Neurosurgery, Busan Regional Cardio-Cerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Republic of Korea. Electronic address:

Background: Conventional craniotomy (CC) is generally favored for treating large intracerebral hemorrhage (ICH), but the feasibility of minimally invasive stereotactic aspiration for large ICH is controversial. We investigated the efficacy and safety of stereotactic aspiration with multicatheter insertion (SAMCI) for large ICH (≥50 mL).

Methods: In January 2014, we implemented SAMCI for large ICH. The inclusion criteria for SAMCI were as follows: 1) spontaneous supratentorial ICH, 2) ICH volume ≥50 mL, 3) Glasgow Coma Scale score ≥5, and 4) no bilateral fixed dilated pupils. Forty-seven patients who underwent SAMCI from January 2014 to July 2018 composed the SAMCI group, and 34 patients who underwent CC between January 2010 and December 2013 and retrospectively met the inclusion criteria for SAMCI composed the control group (CC group).

Results: The mean preoperative ICH volume in the SAMCI and CC groups was 73.1 ± 22.8 and 72.4 ± 21.5 mL, respectively. There were no significant differences between the groups in baseline characteristics except for ICH location. The deep portion of the ICH was higher in the SAMCI group than in the CC group. Postoperative mortality and rebleeding rates were significantly lower in the SAMCI group than in the CC group (4.3% vs. 26.5% and 0% vs. 14.7%, respectively; P < 0.05). Logistic regression analysis showed that SAMCI contributed to a decrease in the mortality rate (odds ratio, 0.04; P = 0.008).

Conclusions: SAMCI is a feasible therapeutic option for large ICH and has low complication rates.
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http://dx.doi.org/10.1016/j.wneu.2019.04.258DOI Listing
August 2019

Opinion: Strategy of Semi-Automatically Annotating Full Text Corpus of Genomics & Informatics.

Authors:
Hyun-Seok Park

Genomics Inform 2018 Dec 28;16(4):e40. Epub 2018 Dec 28.

Bioinformatics Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

There is a community need for an annotated corpus consisting of the full texts of biomedical journal articles. In response to community needs, a prototype version of full text corpus of Genomics & Informatics, called GNI version 1.0 has been recently published, with 499 annotated full text articles available as a corpus resource. However, GNI needs to be updated, as the texts were shallow-parsed, and annotated with several existing parsers. I list issues associated with upgrading annotations, and give opinion on methodology to develop next version of GNI corpus based on a semi-automatic strategy for more linguistically rich corpus annotation.
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http://dx.doi.org/10.5808/GI.2018.16.4.e40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440653PMC
December 2018

A Short Report on the Markov Property of DNA Sequences on 200-bp Genomic Units of Roadmap Genomics ChromHMM Annotations: A Computational Perspective.

Authors:
Hyun-Seok Park

Genomics Inform 2018 Dec 28;16(4):e27. Epub 2018 Dec 28.

Bioinformatics Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

The non-coding DNA in eukaryotic genomes encodes a language that programs chromatin accessibility, transcription factor binding, and various other activities. The objective of this study was to determine the effect of the primary DNA sequence on the epigenomic landscape across a 200-base pair of genomic units by integrating 127 publicly available ChromHMM BED files from the Roadmap Genomics project. Nucleotide frequency profiles of 127 chromatin annotations stratified by chromatin variability were analyzed and integrative hidden Markov models were built to detect Markov properties of chromatin regions. Our aim was to identify the relationship between DNA sequence units and their chromatin variability based on integrated ChromHMM datasets of different cell and tissue types.
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http://dx.doi.org/10.5808/GI.2018.16.4.e27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440674PMC
December 2018

Revision Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery for Recurrent Acute Ischemic Stroke Due to Delayed Occlusion of the Bypass Graft.

J Cerebrovasc Endovasc Neurosurg 2018 Jun 30;20(2):127-132. Epub 2018 Jun 30.

Department of Neurology, Busan-Ulsan Regional Cardio-cerebrovascular Center, Dong-A University College of Medicine, Busan, Korea.

Intravenous thrombolysis (IVT) and endovascular treatment (EVT) are currently the main treatments for reperfusion in acute ischemic stroke. Although the EVT recanalization rate has increased, unsuccessful recanalization is still observed in 10-30% cases. Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is considered a rescue therapy in such cases, but in most centers it is not usually performed for acute ischemic stroke. Graft occlusion is rare following STA-MCA bypass, but it might lead to recurrent ischemic stroke. We hereby report on a patient with right MCA infarction and in whom EVT failed due to complete proximal internal carotid artery occlusion. He underwent an emergency STA-MCA bypass, resulting in a full recovery of his motor weakness. However, six months later, the patient experienced recurrent acute ischemic stroke due to bypass graft occlusion. His EVT failed again but revision bypass surgery, using STA remnant branch, was successful with full motor weakness recovery. We recommend a revision bypass surgery as a feasible therapeutic option for recurrent cerebral infarction caused by delayed STA graft occlusion.
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http://dx.doi.org/10.7461/jcen.2018.20.2.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196140PMC
June 2018

GNI Corpus Version 1.0: Annotated Full-Text Corpus of Genomics & Informatics to Support Biomedical Information Extraction.

Genomics Inform 2018 Sep 30;16(3):75-77. Epub 2018 Sep 30.

Bioinformatics Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

Genomics & Informatics (NLM title abbreviation: Genomics Inform) is the official journal of the Korea Genome Organization. Text corpus for this journal annotated with various levels of linguistic information would be a valuable resource as the process of information extraction requires syntactic, semantic, and higher levels of natural language processing. In this study, we publish our new corpus called GNI Corpus version 1.0, extracted and annotated from full texts of Genomics & Informatics, with NLTK (Natural Language ToolKit)-based text mining script. The preliminary version of the corpus could be used as a training and testing set of a system that serves a variety of functions for future biomedical text mining.
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http://dx.doi.org/10.5808/GI.2018.16.3.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187819PMC
September 2018

A Short Report on the Markov Property of DNA Sequences on 200-bp Genomic Units of ENCODE/Broad ChromHMM Annotations: A Computational Perspective.

Authors:
Hyun-Seok Park

Genomics Inform 2018 Sep 30;16(3):65-70. Epub 2018 Sep 30.

Bioinformatics Laboratory, ELTEC College of Engineering, Ewha Womans University, Seoul 03760, Korea.

The non-coding DNA in eukaryotic genomes encodes a language which programs chromatin accessibility, transcription factor binding, and various other activities. The objective of this short report was to determine the impact of primary DNA sequence on the epigenomic landscape across 200-base pair genomic units by integrating nine publicly available ChromHMM Browser Extensible Data files of the Encyclopedia of DNA Elements (ENCODE) project. The nucleotide frequency profiles of nine chromatin annotations with the units of 200 bp were analyzed and integrative Markov chains were built to detect the Markov properties of the DNA sequences in some of the active chromatin states of different ChromHMM regions. Our aim was to identify the possible relationship between DNA sequences and the newly built chromatin states based on the integrated ChromHMM datasets of different cells and tissue types.
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http://dx.doi.org/10.5808/GI.2018.16.3.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187816PMC
September 2018

Safety and Efficacy of Hypothermia (34°C) after Hemicraniectomy for Malignant MCA Infarction.

J Korean Neurosurg Soc 2018 Mar 28;61(2):267-276. Epub 2018 Feb 28.

Department of Neurosurgery, Busan-Ulsan Regional Cardio-Cerebrovascular Center, Medical Science Research Center, Dong-A University College of Medicine, Busan, Korea.

Objective: The beneficial effect of hypothermia after hemicraniectomy in malignant middle cerebral artery (MCA) infarction has been controversial. We aim to investigate the safety and clinical efficacy of hypothermia after hemicraniectomy in malignant MCA infarction.

Methods: From October 2012 to February 2016, 20 patients underwent hypothermia (Blanketrol III, Cincinnati Sub-Zero, Cincinnati, OH, USA) at 34°C after hemicraniectomy in malignant MCA infarction (hypothermia group). The indication of hypothermia included acute cerebral infarction >2/3 of MCA territory and a Glasgow coma scale (GCS) score <11 with a midline shift >10 mm or transtentorial herniation sign (a fixed and dilated pupil). We retrospectively collected 27 patients, as the control group, who had undergone hemicraniectomy alone and simultaneously met the inclusion criteria of hypothermia between January 2010 and September 2012, before hypothermia was implemented as a treatment strategy in Dong-A University Hospital. We compared the mortality rate between the two groups and investigated hypothermia-related complications, such as postoperative bleeding, pneumonia, sepsis and arrhythmia.

Results: The age, preoperative infarct volume, GCS score, National institutes of Health Stroke Scale score, and degree of midline shift were not significantly different between the two groups. Of the 20 patients in the hypothermia group, 11 patients were induced with hypothermia immediately after hemicraniectomy and hypothermia was initiated in 9 patients after the decision of hypothermia during postoperative care. The duration of hypothermia was 4±2 days (range, 1 to 7 days). The side effects of hypothermia included two patients with arrhythmia, one with sepsis, one with pneumonia, and one with hypotension. Three cases of hypothermia were discontinued due to these side effects (one sepsis, one hypotension, and one bradycardia). The mortality rate of the hypothermia group was 15.0% and that of the control group was 40.7% (=0.056). On the basis of the logistic regression analysis, hypothermia was considered to contribute to the decrease in mortality rate (odds ratio, 6.21; 95% confidence interval, 1.04 to 37.05; =0.045).

Conclusion: This study suggests that hypothermia after hemicraniectomy is a viable option when the progression of patients with malignant MCA infarction indicate poor prognosis.
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http://dx.doi.org/10.3340/jkns.2016.1111.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853190PMC
March 2018

Thrombolysis in Large Diffusion-Weighted Imaging Lesions: Lower Chance but Still a Chance.

J Stroke Cerebrovasc Dis 2018 Jun 3;27(6):1511-1516. Epub 2018 Feb 3.

Cerebrovascular center, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea. Electronic address:

Background: We sought to investigate whether early thrombolytic treatment can result in favorable functional outcome even in patients with large diffusion-weighted imaging (DWI) lesions.

Materials And Methods: We analyzed 566 patients who received intravenous alteplase within 4.5 hours from onset, initially underwent DWI and magnetic resonance angiography, and had acute infarction confined to anterior circulation. DWI lesion volumes were measured semiautomatically. The association between DWI lesion volume and 3-month outcome in patients who achieved early recanalization was assessed. The DWI lesion volume cutoff, which predicts unfavorable outcome despite recanalization, was determined. In patients with large DWI lesions, the distributions of modified Rankin Scale (mRS) score were compared according to the recanalization status.

Results: Four hundred thirty-six patients achieved early recanalization. Among these patients, 283 (65%) patients had a favorable functional outcome (mRS score 0-2). DWI lesion volume (odds ratio [OR], 1.38 per 10 mL; 95% confidence interval [CI], 1.22-1.56) was an independent variable associated with poor outcome, along with hypertension (OR, 1.87; 95% CI, 1.12-3.10), National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.13; 95% CI, 1.08-1.19), and onset-to-needle time (OR, 1.08 per 10 minutes; 95% CI, 1.03-1.13). The DWI lesion of 60 mL or higher highly predicted an unfavorable outcome with a positive predictive value of 95.3%. In patients with a DWI lesion of 60 mL or higher, recanalization had no benefit for an mRS score of 0-2 but was significantly associated with an mRS score of 0-3 (OR, 4.64; 95% CI, 1.08-19.97).

Conclusions: Despite early recanalization, the probability of favorable outcome is low in patients with a DWI lesion of 60 mL or higher. Nevertheless, the benefit of recanalization still persists in large DWI lesions.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.12.037DOI Listing
June 2018

Factors associated with early dramatic recovery following successful recanalization of occluded artery by endovascular treatment in anterior circulation stroke.

J Clin Neurosci 2017 Dec 3;46:171-175. Epub 2017 Oct 3.

Busan-Ulsan Regional Cardiocerebrovascular Center, Dong-A University Hospital, Busan, Republic of Korea; Department of Neurology, College of Medicine, Dong-A University, Busan, Republic of Korea.

Endovascular treatment (EVT) significantly increases the recanalization rate and improves functional outcomes in acute ischemic stroke. However, despite successful recanalization by EVT, some stroke patients demonstrate no early dramatic recovery (EDR). We assessed factors associated with EDR following recanalization by EVT. We included subjects with anterior circulation stroke treated with EVT who met the following criteria: Thrombolysis in Cerebral Ischemia scores (TICI) 2b-3 after EVT, lesion volume <70mL as seen on the pre-treatment diffusion-weighted imaging (DWI) scan and a baseline NIHSS score ≥6. EDR was defined as a ≥8-point reduction in the NIHSS score, or NIHSS score of 0 or 1 measured 24h following treatment. Multivariate regression analyses were performed to identify the predictors associated with EDR. Of the 102 patients (mean age, 64.3years; median National Institutes of Health Stroke Scale score, 14), EDR was achieved in 39 patients (38.2%). The median DWI lesion volume was 12mL (interquartile range, 5-25mL). Median onset-to-recanalization time in these patients was 320min (interquartile range, 270-415min). Logistic regression analysis identified a higher initial NIHSS score (OR 1.17, 95% CI 1.03-1.33, P=0.016) and shorter time from onset to recanalization (OR 0.99, 95% CI 0.986-0.997, P=0.003), to be independently associated with EDR. In the setting of pretreatment DWI lesion volume <70mL, a higher initial NIHSS score and faster time from onset to recanalization may be important predictors of EDR following successful EVT.
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http://dx.doi.org/10.1016/j.jocn.2017.09.015DOI Listing
December 2017

Patient Selection and Clinical Efficacy of Urgent Superficial Temporal Artery-Middle Cerebral Artery Bypass in Acute Ischemic Stroke Using Advanced Magnetic Resonance Imaging Techniques.

Oper Neurosurg (Hagerstown) 2017 10;13(5):552-559

Department of Neurosurgery, Busan-Ulsan Regional Cardiocerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Republic of Korea.

Background: Selected patients with acute ischemic stroke might benefit from superficial temporal artery-middle cerebral artery (STA-MCA) bypass, but the indications for urgent STA-MCA bypass are unknown.

Objective: To report our experiences of urgent STA-MCA bypass in patients requiring urgent reperfusion who were ineligible for other reperfusion therapies, using advanced magnetic resonance imaging (MRI) techniques.

Methods: The inclusion criteria for urgent STA-MCA bypass were as follows: acute infarct volume <70 mL with a ratio of perfusion/diffusion lesion volume ≥1.2, and a regional cerebral blood volume ratio >0.85. From January 2013 to October 2015, 21 urgent STA-MCA bypass surgeries were performed. The control group included 19 patients who did not undergo bypass surgery mainly due to refusal of surgery or the decision of the neurologist. Clinical and radiological data were compared between the surgery and control group.

Results: The median age of the control group (70 years, interquartile range [IQR] 58-76) was higher than that of the surgery group (62 years, IQR 49-66), but the median preoperative diffusion and perfusion lesion volumes of the surgery group (13.8 mL, IQR 7.5-26.0 and 120.9 mL, IQR 84.9-176.0, respectively) were higher than those of the control group (5.6 mL, IQR 2.1-9.1 and 69.7 mL, IQR 23.9-125.3, respectively). Sixteen (76.2%) patients in the surgery group and 2 (10.5%) patients in the control group had favorable outcomes ( P < .001). Logistic regression analysis identified bypass surgery as the strongest predictive factor.

Conclusion: STA-MCA bypass can be used as a therapeutic tool for acute ischemic stroke. Advanced MRI techniques are helpful for selecting patients and for decision making.
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http://dx.doi.org/10.1093/ons/opx041DOI Listing
October 2017

The Incidence and Characteristics of Patients with Small Ruptured Aneurysms (<5 mm) in Subarachnoid Hemorrhage.

J Korean Neurosurg Soc 2017 Jul 31;60(4):424-432. Epub 2017 Jul 31.

Department of Neurosurgery, Busan-Ulsan Regional Cardio-Cerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Korea.

Objective: Small unruptured aneurysms (<5 mm) are known for their very low risk of rupture, and are recommended to be treated conservatively. However, we encounter many patients with small ruptured aneurysms in the clinical practice. We aimed to investigate the incidence and characteristics of patients with small ruptured aneurysms.

Methods: We reviewed all patients admitted to our hospital with subarachnoid hemorrhage from January 2005 to December 2015. The patients were divided into two groups: those with aneurysms <5 mm (group S) and those with aneurysms ≥5 mm (group L). The patient's age and sex, size and location of aneurysms, and risk factors such as hypertension, diabetes, alcohol use, and smoking were compared between the two groups.

Results: Eight-hundred eleven patients were diagnosed with ruptured aneurysms, and 337 (41.6%) were included in group S. The mean size of all aneurysms was 6.10±2.99 mm (range, 0.7-37.7); aneurysms with a diameter of 4-5 mm accounted for the largest subgroup of all aneurysms. Female sex was significantly associated with the incidence of small ruptured aneurysms (odds ratio [OR] 1.50, 95% confidence intervals [CI] 1.02-2.19, =0.037). Despite female predominance in the incidence of small ruptured aneurysms, the proportion of small ruptured aneurysms in young (<50 years) men was high. In men, there were no significant differences regarding the location of the aneurysms between group S and group L (=0.267), with the most frequent location being the anterior communicating artery (ACoA) in both group S (50.9%) and group L (51.4%). However, in women, there were significant differences regarding the location of the aneurysms between group S and group L (=0.023), with the most frequent locations being the ACoA (33.0%) in group S, and the posterior communicating artery (30.6%) in group L. In women, two locations were significantly associated with small (<5 mm) ruptured aneurysms: the ACoA (OR 2.14, 95% CI 1.01-4.54, =0.047) and anterior cerebral artery (OR 3.54, 95% CI 1.19-10.54, =0.023). Multiplicity and smoking were significantly associated with large (≥5 mm) ruptured aneurysms in women. The use of alcohol was related to small ruptured aneurysms in men over 50 years of age (OR 2.23, 95% CI 1.03-4.84, =0.042).

Conclusion: In this study, small (<5 mm) ruptured aneurysms exhibited different incidences by age, sex, location, and risk factors such as multiplicity, smoking, and alcohol use.
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http://dx.doi.org/10.3340/jkns.2016.0910.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544372PMC
July 2017

Emergent Double-barrel Bypass Shortly after Intravenous Administration of Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke.

J Cerebrovasc Endovasc Neurosurg 2016 Sep 30;18(3):258-263. Epub 2016 Sep 30.

Department of Neurosurgery, Busan-Ulsan Regional Cardio-Cerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Korea.

Although intravenous recombinant tissue plasminogen activator (IV rt-PA) is effective in many cases of acute ischemic stroke, the neurologic symptoms can worsen after IV rt-PA because of sustained vessel occlusion. For such cases, several reperfusion modalities are available, including intra-arterial thrombolysis (IAT), carotid endarterectomy, and superficial temporal artery-middle cerebral artery (STA-MCA) bypass. Invasive procedures, such as major surgery, should be generally avoided within 24 hours after the administration of IV rt-PA. A 66-year-old man with no previous medical history developed left hemiparesis. A computed tomography scan revealed no acute lesion and he received IV rt-PA within 1.5 hours after symptom onset. Emergent magnetic resonance imaging showed significant diffusion-perfusion mismatch. He received IAT 2 hours after IV rt-PA administration, but IAT failed because of total occlusion of the cervical internal carotid artery. We initially planned to perform STA-MCA bypass the next morning because he had received IV rt-PA, but, 8 hours after IV rt-PA administration, his hemiparesis worsened from motor grade 3/4 to motor grade 1/2. Because of the large perfusion defect in both MCA divisions, double-barrel STA-MCA bypass was performed 10 hours after IV rt-PA administration. His symptoms rapidly improved after surgery and his modified Rankin Scale score 3 months later was grade 0. We suggest that emergent double-barrel bypass can be a viable option in patients who have perfusion defects of both MCA divisions in acute ischemic stroke after IV rt-PA administration.
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http://dx.doi.org/10.7461/jcen.2016.18.3.258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104852PMC
September 2016

Estimation of Prognostic Marker Genes by Public Microarray Data in Patients with Ovarian Serous Cystadenocarcinoma.

Yonsei Med J 2016 Jul;57(4):872-8

Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.

Purpose: Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long-term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years.

Materials And Methods: Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool.

Results: We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI.

Conclusion: The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI.
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http://dx.doi.org/10.3349/ymj.2016.57.4.872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951462PMC
July 2016

Impact of Prehospital Intervention on Delay Time to Thrombolytic Therapy in a Stroke Center with a Systemized Stroke Code Program.

J Stroke Cerebrovasc Dis 2016 Jul 7;25(7):1665-1670. Epub 2016 Apr 7.

Busan-Ulsan Regional Cardiocerebrovascular Center, Dong-A University Hospital, Busan, Republic of Korea; Department of Neurology, College of Medicine, Dong-A University, Busan, Republic of Korea.

Background: The use of emergency medical services (EMS) and notification to hospitals by paramedics for patients with suspected stroke are crucial determinants in reducing delay time to acute stroke treatment. The aim of this study is to investigate whether EMS use and prehospital notification (PN) can shorten the time to thrombolytic therapy in a stroke center with a systemized stroke code program.

Methods: Beginning in January 2012, stroke experts in our stroke center received direct calls via mobile phone from paramedics prenotifying the transport of patients with suspected stroke. We compared baseline characteristics and prehospital/in-hospital delay time in stroke patients treated with intravenous recombinant tissue plasminogen activator for 44 months with and without EMS use and/or PN.

Results: Intravenous thrombolytic therapy was performed on 274 patients. Of those patients, 215 (78.5%) were transported to the hospital via EMS and 59 (21.5%) were admitted via private modes of transportation. The patients who used EMS had shorter median onset-to-arrival times (62 minutes versus 116 minutes, P < .001). There was no difference in in-hospital delay time between the 2 groups. In 28 cases (13%) of EMS transport, EMS personnel called the clinical staff to notify the incoming patient. Prenotification by EMS was associated with shorter median door-to-imaging time (9 minutes versus 12 minutes, P = .045) and door-to-needle time (20 minutes versus 29 minutes, P = .011).

Conclusions: We found that EMS use reduces prehospital delay time. However, EMS use without prenotification does not shorten in-hospital processing time in a stroke center with a systemized stroke code program.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.02.011DOI Listing
July 2016

Building the Frequency Profile of the Core Promoter Element Patterns in the Three ChromHMM Promoter States at 200bp Intervals: A Statistical Perspective.

Genomics Inform 2015 Dec 31;13(4):152-5. Epub 2015 Dec 31.

Bioinformatics Laboratory, School of Engineering, Ewha Womans University, Seoul 03760, Korea.

Recently, the Encyclopedia of DNA Elements (ENCODE) Analysis Working Group converted data from ChIP-seq analyses from the Broad Histone track into 15 corresponding chromatic maps that label sequences with different kinds of histone modifications in promoter regions. Here, we publish a frequency profile of the three ChromHMM promoter states, at 200-bp intervals, with particular reference to the existence of sequence patterns of promoter elements, GC-richness, and transcription starting sites. Through detailed and diligent analysis of promoter regions, researchers will be able to uncover new and significant information about transcription initiation and gene function.
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http://dx.doi.org/10.5808/GI.2015.13.4.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742326PMC
December 2015

High residual platelet reactivity (HRPR) for adenosine diphosphate (ADP) stimuli is a determinant factor for long-term outcomes in acute ischemic stroke with anti-platelet agents: The meaning of HRPR after ADP might be more prominent in large atherosclerotic infarction than other subtypes of AIS.

J Thromb Thrombolysis 2016 Jul;42(1):107-17

Department of Visual optics, KyungWoon University, Gumi, Republic of Korea.

High residual platelet activation (HRPA) after ADP stimuli has associated with recurrent vascular events in acute atherothrombosis with the use of antiplatelet agents (APAs). However, there has been little evidence supporting this association in acute ischemic stroke (AIS). In this study, we evaluated the influences of HRPR after ADP stimuli on the 1-year incidence of recurrent cardiovascular events and mortality in AIS with APAs. We conducted an observational, referral center cohort study on 968 AIS patients with APAs from January 2010 to December 2013 who were evaluated using optical platelet aggregometry (OPA). All patients received the dual APA combination of aspirin and clopidogrel or aspirin alone. We evaluated their platelet function 5 days after hospital admission using OPA. HRPR after ADP stimuli was defined as platelet aggregation of 70 % or greater according to OPA after 10 µM ADP stimuli. The primary endpoint was a composite of all causes of death, myocardial infarction, and stroke at the 1-year follow-up. The secondary endpoints were each component of the primary endpoint. The event rate of primary endpoint was 11.3 % (109/968). Its rate was significantly higher in the patients with HRPR (16.7 %) than in those without (9.7 %). HPRP was independently associated with the primary endpoint (OR = 1.97, CI 1.22-3.18, p < 0.01). According to the AIS subtype, the presence of HRPR was independently significant for the occurrence of the primary endpoint in the large artery atherosclerosis (LAA) subtype only (OR = 2.26, CI 1.15-4.45, p = 0.02). In this study, the presence of HRPR after ADP stimuli is associated with a poor long-term outcome after acute ischemic stroke. In particular, the influence of this factor might be more prominent in LAA compared with other types of AIS.
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http://dx.doi.org/10.1007/s11239-015-1304-5DOI Listing
July 2016

Preliminary testing for the Markov property of the fifteen chromatin states of the Broad Histone Track.

Biomed Mater Eng 2015 ;26 Suppl 1:S1917-27

Bioinformatics Laboratory, Ewha Womans University, Seoul, Korea.

Epigenetic computational analyses based on Markov chains can integrate dependencies between regions in the genome that are directly adjacent. In this paper, the BED files of fifteen chromatin states of the Broad Histone Track of the ENCODE project are parsed, and comparative nucleotide frequencies of regional chromatin blocks are thoroughly analyzed to detect the Markov property in them. We perform various tests to examine the Markov property embedded in a frequency domain by checking for the presence of the Markov property in the various chromatin states. We apply these tests to each region of the fifteen chromatin states. The results of our simulation indicate that some of the chromatin states possess a stronger Markov property than others. We discuss the significance of our findings in statistical models of nucleotide sequences that are necessary for the computational analysis of functional units in noncoding DNA.
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http://dx.doi.org/10.3233/BME-151494DOI Listing
July 2016

Comparative Analysis of Endovascular Stroke Therapy Using Urokinase, Penumbra System and Retrievable (Solitare) Stent.

J Korean Neurosurg Soc 2015 May 31;57(5):342-9. Epub 2015 May 31.

Department of Diagnostic Radiology, Busan-Ulsan Regional Cardiocerebrovascular Center, Medical Science Research Center, College of Medicine, Dong-A University, Busan, Korea.

Background: Higher reperfusion rates have been established with endovascular treatment for acute ischemic stroke patients. There are limited data on the comparative performance of mechanical thrombectomy devices. This study aimed to analyse the efficacy and safety of the stent retriever device (Solitaire stent) by comparing procedure time, angiographic outcome, complication rate and long term clinical outcome with previous chemical thrombolysis and mechanical thrombectomy using penumbra system.

Methods: A retrospective single-center analysis was undertaken of all consecutive patients who underwent chemical thrombolysis and mechanical thrombectomy using Penumbra or Solitaire stent retriever from March 2009 to March 2014. Baseline characteristics, rate of successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b-3), symptomatic intracerebral hemorrhage, procedure time, mortality and independent functional outcomes (mRS ≤2) at 3 month were compared across the three method.

Results: Our cohort included 164 patients, mechanical thrombectomy using stent retriever device had a significant impact on recanalization rate and functional independence at 3 months. In unadjusted analysis mechanical thrombectomy using Solitaire stent retriever showed higher recanalization rate than Penumbra system and chemical thrombolysis (75% vs. 64.2% vs. 49.4%, p=0.03) and higher rate of functional independence at 3 month (53.1% vs. 37.7% vs. 35.4%, p=0.213). In view of the interrelationships between all predictors of variables associated with a good clinical outcome, when the chemical thrombolysis was used as a reference, in multiple logistic regression analysis, the use of Solitaire stent retriever showed higher odds of independent functional outcome [odds ratio (OR) 2.62, 95% confidence interval (CI) 0.96-7.17; p=0.061] in comparison with penumbra system (OR 1.57, 95% CI 0.63-3.90; p=0.331).

Conclusion: Our initial data suggest that mechanical thrombectomy using stent retriever is superior to the mechanical thrombectomy using penumbra system and conventional chemical thrombolysis in achieving higher rates of reperfusion and better outcomes. Randomized clinical trials are needed to establish the actual benefit to specific patient populations.
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http://dx.doi.org/10.3340/jkns.2015.57.5.342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479715PMC
May 2015

A review of three different studies on hidden markov models for epigenetic problems: a computational perspective.

Genomics Inform 2014 Dec 31;12(4):145-50. Epub 2014 Dec 31.

Ewha Information and Telecommunication Institute, Ewha Womans University, Seoul 120-750, Korea. ; Bioinformatics Laboratory, School of Engineering, Ewha Womans University, Seoul 120-750, Korea. ; Center for Convergence Research of Advanced Technologies, Ewha Womans University, Seoul 120-750, Korea.

Recent technical advances, such as chromatin immunoprecipitation combined with DNA microarrays (ChIp-chip) and chromatin immunoprecipitation-sequencing (ChIP-seq), have generated large quantities of high-throughput data. Considering that epigenomic datasets are arranged over chromosomes, their analysis must account for spatial or temporal characteristics. In that sense, simple clustering or classification methodologies are inadequate for the analysis of multi-track ChIP-chip or ChIP-seq data. Approaches that are based on hidden Markov models (HMMs) can integrate dependencies between directly adjacent measurements in the genome. Here, we review three HMM-based studies that have contributed to epigenetic research, from a computational perspective. We also give a brief tutorial on HMM modelling-targeted at bioinformaticians who are new to the field.
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http://dx.doi.org/10.5808/GI.2014.12.4.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330247PMC
December 2014

Relative CBV ratio on perfusion-weighted MRI indicates the probability of early recanalization after IV t-PA administration for acute ischemic stroke.

J Neurointerv Surg 2016 Mar 12;8(3):235-9. Epub 2015 Jan 12.

Busan-Ulsan Regional Cardio-Cerebral Vascular Center, Dong-A University Hospital, Busan, Korea.

Background: We hypothesized that the relative cerebral blood volume (rCBV) ratio on perfusion-weighted imaging (PWI) using MRI might serve as a predictor of early recanalization (ER) after intravenous tissue plasminogen activator (IV t-PA) administration for acute ischemic stroke.

Methods: Patients with acute middle cerebral artery (MCA) ischemic stroke (IS) were enrolled in the study. They were evaluated by MRI, including PWI and diffusion-weighted imaging, before administration of IV t-PA and underwent digital subtraction angiography (DSA) of the brain within 2 h after t-PA administration. We compared the rCBV ratio on PWI between patients with and without ER on DSA and investigated the proportion of patients with an excellent outcome at 90 days after t-PA administration (modified Rankin Scale score 0-1) among those with and without ER.

Results: 85 patients with acute MCA IS were included; 16 patients (18.8%) experienced ER on DSA after IV t-PA administration. Patients with ER more frequently had an excellent outcome at 90 days than those without ER. The rCBV ratio on PWI was higher in the ER group (1.01±0.21, p<0.01) than in the non-ER group (0.82±0.18). After adjusting for the presence of atrial fibrillation and the serum glucose level, the rCBV ratio on PWI (OR 1.07; 95% CI 1.02 to 1.12; p<0.01) was a significant independent indicator of ER.

Conclusions: The results of this study suggest that the rCBV ratio on PWI might serve as a useful indicator of ER after IV t-PA administration.
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http://dx.doi.org/10.1136/neurintsurg-2014-011501DOI Listing
March 2016
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