A Python-based educational software tool for visualizing bioinformatics alignment algorithms

Bioinformatics education can be defined as the teaching and learning of how to use software tools, along with mathematical and statistical analysis, to solve biological problems. Although many resources are available, most students still struggle to understand even the simplest sequence alignment algorithms. Applying visualizations to these topics benefits both lecturers and students. Unfortunately, educational software for visualizing step-bystep processes in the user experience of sequence alignment algorithms is rare. In this article, an educational visualization tool for biological sequence alignment is presented, and the source code is released in order to encourage the collaborative power of open-source software, with the expectation of further contributions from the community in the future. Two different modules are integrated to enable a student to investigate the characteristics of alignment algorithms.

TcellInflamedDetector: an R package to distinguish T cell inflamed tumor types from non–T cell inflamed tumor types

A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non–T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non–T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non–T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.

Estimation of the journal distance of Genomics & Informatics from other bioinformatics-driven journals, 2003-2018

This study explored the trends of Genomics & Informatics during the period of 2003-2018 in comparison with 11 other scholarly journals: BMC Bioinformatics, Algorithms for Molecular Biology: AMB, BMC Systems Biology, Journal of Computational Biology, Briefings in Bioinformatics, BMC Genomics, Nucleic Acids Research, American Journal of Human Genetics, Oncogenesis, Disease Markers, and Microarrays. In total, 22,423 research articles were reviewed. Content analysis was the main method employed in the current research. The results were interpreted using descriptive analysis, a clustering analysis, word embedding, and deep learning techniques. Trends are discussed for the 12 journals, both individually and collectively. This is an extension of our previous study (PMCID: PMC6808643).

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

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.

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

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.

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

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.

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

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.

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

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 (n=28) or discharged within 48 hours (n=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 (p=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 (p=0.002) and 0.585 (p=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.

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

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.

A new definition for wide-necked cerebral aneurysms

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.

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

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.

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

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.

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

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% (p=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; p=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.

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

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.

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

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.

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

There is a communal need for an annotated corpus consisting of the full texts of biomedical journal articles. In response to community needs, a prototype version of the full-text corpus of Genomics & Informatics, called GNI version 1.0, has recently been 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 an opinion on the methodology for developing the next version of the GNI corpus, based on a semi-automatic strategy for more linguistically rich corpus annotation.

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

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 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% (p=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; p=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.

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

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.

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

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, p=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 (p=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 (p=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, p=0.047) and anterior cerebral artery (OR 3.54, 95% CI 1.19–10.54, p=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, p=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.

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

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.