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The paper presents Anatomy3DExplorer, a customized ChatGPT designed as a natural language dialogue interface for exploring 3D models of anatomical structures. It illustrates the significant potential of large language models (LLMs) as user-friendly interfaces for database access. Furthermore, it showcases the seamless integration of LLMs and database APIs, within the GPTS framework, offering a promising and straightforward approach., (© 2024. The Author(s).)

Background and Study Aims: The introduction of direct-acting antiviral (DAA) drugs has dramatically improved chronic hepatitis C (CHC) treatment. The pangenotype DAA therapy glecaprevir/pibrentasvir (G/P) was recently recommended for treating CHC in Korea. Unfortunately, given its recent introduction, little real-world data from a Korean population exists. We examined the effectiveness and safety of G/P treatment in Koreans with CHC., Patients and Methods: We analyzed CHC patients at Samsung Changwon Hospital from June 2018 to December 2020. Sustained virologic response at 12 weeks posttreatment (SVR 12) was evaluated after treatment, and the associated factors were analyzed. Furthermore, the degree of liver fibrosis before and after treatment was compared to determine whether liver fibrosis improved., Results: In total, 102 patients were enrolled; 35.3 % had compensated liver cirrhosis (LC), and 11.8 % had received previous treatment. Of the 102 patients, 99 (97.1 %) reached SVR 12. Of the 81 patients who completed 8 weeks of G/P treatment, 80 (98.8 %) reached SVR 12, while 19 of the 21 (90.5 %) patients in the 12- or 16-week group reached SVR 12, with no significant difference between the two groups (P = 0.107). As a secondary endpoint, liver fibrosis before and after treatment was also compared. The Fibrosis-4 index (FIB-4) (3.3 vs 2.8, P = 0.010), aspartate transaminase (AST)-platelet ratio index (APRI) (1.3 vs 1.0, P < 0.001), and liver stiffness measurements (LSM) (9.5 vs 4.6, P < 0.001) were significantly different after G/P treatment., Conclusions: Regardless of genotype, G/P treatment for Koreans with CHC is safe, highly effective, and can improve liver fibrosis., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Acute liver failure (ALF) is a rare disease condition with a dynamic clinical course and catastrophic outcomes. Several etiologies are involved in ALF. Hepatitis A and B infections and indiscriminate use of untested herbs or supplemental agents are the most common causes of ALF in Korea. Noninvasive neurological monitoring tools have been used in patients with ALF in recent times. Ongoing improvements in intensive care, including continuous renal replacement therapy, therapeutic plasma exchange, vasopressor, and extracorporeal membrane oxygenation, have reduced the mortality rate of patients with ALF. However, liver transplantation is still the most effective treatment for patients with intractable ALF. There is a need for further research in the areas of better prognostication and precise selection of patients for emergency transplantation.

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Currently, the only definitive treatment of preeclampsia is delivery of the placenta, which is central to the pathogenesis of the disease. Transcriptional profiling of human placenta from pregnancies complicated by preeclampsia has been extensively performed to identify differentially expressed genes (DEGs). The decisions to investigate DEGs experimentally are biased by many factors, causing many DEGs to remain uninvestigated. A set of DEGs which are associated with a disease experimentally, but which have no known association to the disease in the literature are known as the ignorome. Preeclampsia has an extensive body of scientific literature, a large pool of DEG data, and only one definitive treatment. Tools facilitating knowledge-based analyses, which are capable of combining disparate data from many sources in order to suggest underlying mechanisms of action, may be a valuable resource to support discovery and improve our understanding of this disease. In this work we demonstrate how a biomedical knowledge graph (KG) can be used to identify novel preeclampsia molecular mechanisms. Existing open source biomedical resources and publicly available high-throughput transcriptional profiling data were used to identify and annotate the function of currently uninvestigated preeclampsia-associated DEGs. Experimentally investigated genes associated with preeclampsia were identified from PubMed abstracts using text-mining methodologies. The relative complement of the text-mined- and meta-analysis-derived lists were identified as the uninvestigated preeclampsia-associated DEGs (n=445), i.e., the preeclampsia ignorome. Using the KG to investigate relevant DEGs revealed 53 novel clinically relevant and biologically actionable mechanistic associations.

Motivation: Node embedding of biological entity network has been widely investigated for the downstream application scenarios. To embed full semantics of gene and disease, a multi-relational heterogeneous graph is considered in a scenario where uni-relation between gene/disease and other heterogeneous entities are abundant while multi-relation between gene and disease is relatively sparse. After introducing this novel graph format, it is illuminative to design a specific data integration algorithm to fully capture the graph information and bring embeddings with high quality., Results: First, a typical multi-relational triple dataset was introduced, which carried significant association between gene and disease. Second, we curated all human genes and diseases in seven mainstream datasets and constructed a large-scale gene-disease network, which compromising 163,024 nodes and 25,265,607 edges, and relates to 27,165 genes, 2,665 diseases, 15,067 chemicals, 108,023 mutations, 2,363 pathways, and 7.732 phenotypes. Third, we proposed a Joint Decomposition of Heterogeneous Matrix and Tensor (JDHMT) model, which integrated all heterogeneous data resources and obtained embedding for each gene or disease. Forth, a visualized intrinsic evaluation was performed, which investigated the embeddings in terms of interpretable data clustering. Furthermore, an extrinsic evaluation was performed in the form of linking prediction. Both intrinsic and extrinsic evaluation results showed that JDHMT model outperformed other eleven state-of-the-art (SOTA) methods which are under relation-learning, proximity-preserving or message-passing paradigms. Finally, the constructed gene-disease network, embedding results and codes were made available., Data and Codes Availability: The constructed massive gene-disease network is available at: https://hzaubionlp.com/heterogeneous-biological-network/. The codes are available at: https://github.com/bionlp-hzau/JDHMT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bridging heterogeneous mutation data fills in the gap between various data categories and propels discovery of disease-related genes. It is known that genome-wide association study (GWAS) infers significant mutation associations that link genotype and phenotype. However, due to the differences of size and quality between GWAS studies, not all de facto vital variations are able to pass the multiple testing. In the meantime, mutation events widely reported in literature unveil typical functional biological process, including mutation types like gain of function and loss of function. To bring together the heterogeneous mutation data, we propose a 'Gene-Disease Association prediction by Mutation Data Bridging (GDAMDB)' pipeline with a statistic generative model. The model learns the distribution parameters of mutation associations and mutation types and recovers false-negative GWAS mutations that fail to pass significant test but represent supportive evidences of functional biological process in literature. Eventually, we applied GDAMDB in Alzheimer's disease (AD) and predicted 79 AD-associated genes. Besides, 12 of them from the original GWAS, 60 of them are supported to be AD-related by other GWAS or literature report, and rest of them are newly predicted genes. Our model is capable of enhancing the GWAS-based gene association discovery by well combining text mining results. The positive result indicates that bridging the heterogeneous mutation data is contributory for the novel disease-related gene discovery., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background/aims: Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC., Methods: In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications., Results: Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively ( P =1.000). During mean follow-up of 87.6 months (95% confidence interval, 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group ( P =0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEB-TACE vs. 17.2% and 36.3% in RFA group ( P =0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event., Conclusions: Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (Copyright © 2021 by The Korean Liver Cancer Association.)

This study aimed to investigate factors affecting blood glucose control among middle-aged and older diabetic patients taking medications or receiving insulin therapy. In 2015-2017 data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES), 1257 patients with diabetes were divided into a controlled group and an uncontrolled group based on blood glucose levels (cutoff ≥126 mg/dL). After adjusting for confounding factors, the BMI, total cholesterol level, and triglycerides level of the uncontrolled group were significantly higher than the controlled group. The total amount of moderate-intensity activity in controlled patients was significantly higher than that of the controlled group. Total energy, fat, saturated fatty acids, and cholesterol intakes were found to be significantly higher in the uncontrolled than controlled group. Intakes of calcium, phosphorus, potassium, riboflavin, niacin, and vitamin C were significantly lower in the uncontrolled than controlled group. Adequate nutrition intake and physical activity of patients undergoing diabetes therapy are required for effective blood glucose management for both diabetic drug and insulin therapies.

Named entity recognition tools are used to identify mentions of biomedical entities in free text and are essential components of high-quality information retrieval and extraction systems. Without good entity recognition, methods will mislabel searched text and will miss important information or identify spurious text that will frustrate users. Most tools do not capture non-contiguous entities which are separate spans of text that together refer to an entity, e.g., the entity "type 1 diabetes" in the phrase "type 1 and type 2 diabetes." This type is commonly found in biomedical texts, especially in lists, where multiple biomedical entities are named in shortened form to avoid repeating words. Most text annotation systems, that enable users to view and edit entity annotations, do not support non-contiguous entities. Therefore, experts cannot even visualize non-contiguous entities, let alone annotate them to build valuable datasets for machine learning methods. To combat this problem and as part of the BLAH6 hackathon, we extended the TextAE platform to allow visualization and annotation of non-contiguous entities. This enables users to add new subspans to existing entities by selecting additional text. We integrate this new functionality with TextAE's existing editing functionality to allow easy changes to entity annotation and editing of relation annotations involving non-contiguous entities, with importing and exporting to the PubAnnotation format. Finally, we roughly quantify the problem across the entire accessible biomedical literature to highlight that there are a substantial number of non-contiguous entities that appear in lists that would be missed by most text mining systems.

Despite a growing number of natural language processing shared-tasks dedicated to the use of Twitter data, there is currently no ad-hoc annotation tool for the purpose. During the 6th edition of BLAH, after a short review of 19 generic annotation tools, we adapted GATE and TextAE for annotating Twitter timelines. Although none of the tools reviewed allow the annotation of all information inherent of Twitter timelines, a few may be suitable provided the willingness by annotators to compromise on some functionality.

We report on the activities of the 2015 edition of the BioHackathon, an annual event that brings together researchers and developers from around the world to develop tools and technologies that promote the reusability of biological data. We discuss issues surrounding the representation, publication, integration, mining and reuse of biological data and metadata across a wide range of biomedical data types of relevance for the life sciences, including chemistry, genotypes and phenotypes, orthology and phylogeny, proteomics, genomics, glycomics, and metabolomics. We describe our progress to address ongoing challenges to the reusability and reproducibility of research results, and identify outstanding issues that continue to impede the progress of bioinformatics research. We share our perspective on the state of the art, continued challenges, and goals for future research and development for the life sciences Semantic Web., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Vos RA et al.)

Motivation: Most currently available text mining tools share two characteristics that make them less than optimal for use by biomedical researchers: they require extensive specialist skills in natural language processing and they were built on the assumption that they should optimize global performance metrics on representative datasets. This is a problem because most end-users are not natural language processing specialists and because biomedical researchers often care less about global metrics like F-measure or representative datasets than they do about more granular metrics such as precision and recall on their own specialized datasets. Thus, there are fundamental mismatches between the assumptions of much text mining work and the preferences of potential end-users., Results: This article introduces the concept of Agile text mining, and presents the PubAnnotation ecosystem as an example implementation. The system approaches the problems from two perspectives: it allows the reformulation of text mining by biomedical researchers from the task of assembling a complete system to the task of retrieving warehoused annotations, and it makes it possible to do very targeted customization of the pre-existing system to address specific end-user requirements. Two use cases are presented: assisted curation of the GlycoEpitope database, and assessing coverage in the literature of pre-eclampsia-associated genes., Availability and Implementation: The three tools that make up the ecosystem, PubAnnotation, PubDictionaries and TextAE are publicly available as web services, and also as open source projects. The dictionaries and the annotation datasets associated with the use cases are all publicly available through PubDictionaries and PubAnnotation, respectively., (© The Author(s) 2019. Published by Oxford University Press.)

Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A-related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk-prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95% confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c-statistic, 0.56; 95% CI, 0.53-0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76), the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-Stage Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84), and MELD including sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c-statistic, 0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic, 0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD-Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI, 0.61-0.90; P = 0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93; P = 0.41). The model was well-calibrated in both sets. Conclusion: Our disease-specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A., (© 2018 by the American Association for the Study of Liver Diseases.)

In this paper we investigate cross-platform interoperability for natural language processing (NLP) and, in particular, annotation of textual resources, with an eye toward identifying the design elements of annotation models and processes that are particularly problematic for, or amenable to, enabling seamless communication across different platforms. The study is conducted in the context of a specific annotation methodology, namely machine-assisted interactive annotation (also known as human-in-the-loop annotation). This methodology requires the ability to freely combine resources from different document repositories, access a wide array of NLP tools that automatically annotate corpora for various linguistic phenomena, and use a sophisticated annotation editor that enables interactive manual annotation coupled with on-the-fly machine learning. We consider three independently developed platforms, each of which utilizes a different model for representing annotations over text, and each of which performs a different role in the process.

For discovery of new usage of drugs, the function type of their target genes plays an important role, and the hypothesis of "Antagonist-GOF" and "Agonist-LOF" has laid a solid foundation for supporting drug repurposing. In this research, an active gene annotation corpus was used as training data to predict the gain-of-function or loss-of-function or unknown character of each human gene after variation events. Unlike the design of(entity, predicate, entity) triples in a traditional three way tensor, a four way and a five way tensor, GMFD-/GMAFD-tensor, were designed to represent higher order links among or among part of these entities: genes(G), mutations(M), functions(F), diseases( D) and annotation labels(A). A tensor decomposition algorithm, CP decomposition, was applied to the higher order tensor and to unveil the correlation among entities. Meanwhile, a state-of-the-art baseline tensor decomposition algorithm, RESCAL, was carried on the three way tensor as a comparing method. The result showed that CP decomposition on higher order tensor performed better than RESCAL on traditional three way tensor in recovering masked data and making predictions. In addition, The four way tensor was proved to be the best format for our issue. At the end, a case study reproducing two disease-gene-drug links(Myelodysplatic Syndromes-IL2RA-Aldesleukin, Lymphoma- IL2RA-Aldesleukin) presented the feasibility of our prediction model for drug repurposing.

Recently, to speed up the differential-diagnosis process based on symptoms and signs observed from an affected individual in the diagnosis of rare diseases, researchers have developed and implemented phenotype-driven differential-diagnosis systems. The performance of those systems relies on the quantity and quality of underlying databases of disease-phenotype associations (DPAs). Although such databases are often developed by manual curation, they inherently suffer from limited coverage. To address this problem, we propose a text-mining approach to increase the coverage of DPA databases and consequently improve the performance of differential-diagnosis systems. Our analysis showed that a text-mining approach using one million case reports obtained from PubMed could increase the coverage of manually curated DPAs in Orphanet by 125.6%. We also present PubCaseFinder (see Web Resources), a new phenotype-driven differential-diagnosis system in a freely available web application. By utilizing automatically extracted DPAs from case reports in addition to manually curated DPAs, PubCaseFinder improves the performance of automated differential diagnosis. Moreover, PubCaseFinder helps clinicians search for relevant case reports by using phenotype-based comparisons and confirm the results with detailed contextual information., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites., Methods: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS-1)., Results: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS-1. Serum creatinine level was not significantly associated with mortality and development of HRS-1 on multivariate analysis., Conclusion: Serum cystatin C level was an independent predictor of mortality and development of HRS-1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: In the era of semantic web, life science ontologies play an important role in tasks such as annotating biological objects, linking relevant data pieces, and verifying data consistency. Understanding ontology structures and overlapping ontologies is essential for tasks such as ontology reuse and development. We present an exploratory study where we examine structure and look for patterns in BioPortal, a comprehensive publicly available repository of live science ontologies., Methods: We report an analysis of biomedical ontology mapping data over time. We apply graph theory methods such as Modularity Analysis and Betweenness Centrality to analyse data gathered at five different time points. We identify communities, i.e., sets of overlapping ontologies, and define similar and closest communities. We demonstrate evolution of identified communities over time and identify core ontologies of the closest communities. We use BioPortal project and category data to measure community coherence. We also validate identified communities with their mutual mentions in scientific literature., Results: With comparing mapping data gathered at five different time points, we identified similar and closest communities of overlapping ontologies, and demonstrated evolution of communities over time. Results showed that anatomy and health ontologies tend to form more isolated communities compared to other categories. We also showed that communities contain all or the majority of ontologies being used in narrower projects. In addition, we identified major changes in mapping data after migration to BioPortal Version 4., Competing Interests: The authors declare there are no competing interests.

To compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI) with that of computed tomography (CT) during hepatic arteriography and arterial portography (CT HA/AP) for detecting hepatocellular carcinoma (HCC) from small hypervascular nodules.This retrospective study included 38 patients with 131 hypervascular nodules (≤2 cm) who had underwent MRI and CT HA/AP within a 2-week interval. Two observers analyzed MRI while other 2 observers analyzed CT HA/AP. Thereafter, MRI observers reviewed the CT HA/AP and magnetic resonance (MR) images again using both modalities. HCC was diagnosed by pathologic or imaging studies according to American Association for the Study of Liver Diseases (AASLD) criteria. Alternative free-response receiver operating characteristic (ROC) analysis was performed on a lesion-by-lesion basis. Diagnostic accuracy (area under the ROC curve [Az]), sensitivity, specificity, and positive and negative predictive values were calculated.The pooled Az was significantly higher for the combined modalities (0.946) than for MRI alone (0.9, P = 0.004), and for MRI than for CT HA/AP alone (0.827, P = 0.0154). Subgroup analysis for HCC ≤1 cm showed the sensitivity of the combined modalities (79.4%) was significantly higher than for MRI (52.9%) and CT HA/AP alone (50%) (both, P < 0.005). The specificity of the combined modalities was not different from MRI alone (98.8% vs. 97.3%, P = 0.5), but was significantly higher than for CT HA/AP alone (98.8% vs. 92.5%, P = 0.022).Hypervascular HCCs >1 to 2 cm can be diagnosed sufficiently by MRI. The combined modalities increased the diagnostic accuracy of HCCs ≤1 cm, compared with MRI or CT HA/AP alone., Competing Interests: The authors have no conflicts of interest to disclose.

Goals: The purpose of this study was to determine whether total colonic decompression after colonoscopy decreased postcolonoscopy abdominal pain., Background: Abdominal pain that occurs after a colonoscopy may cause significant discomfort in some patients, and residual bowel gas is thought to be a key contributor to this abdominal pain., Study: Asymptomatic 300 patients who underwent colonoscopy under sedation were randomized to either the decompression group or the control group. Initial colonoscopic procedure was performed uniformly in both the groups. After the colonoscopy examination was completed, the colonoscope was reinserted into the cecum, and the intraluminal air was aspirated during withdrawal in the decompression group. Abdominal pain was assessed before discharge and 24 to 48 hours after colonoscopy using a 10-point visual analogue scale (VAS)., Results: The 2 groups were similar with regard to clinical, demographic, and procedural factors. Among 288 patients, the incidence of abdominal pain (VAS≥1) after colonoscopy was 38 (26.6%) of 143 patients in the decompression group and 95 (65.5%) of 145 patients in the control group (VAS 0.68±1.35 vs. 2.14±2.15, P<0.001). There was an 86.1% reduction rate of abdominal pain by colonic decompression, based on multivariate analysis (odds ratio 0.139 [95% confidence interval, 0.077-0.250], P<0.001). Furthermore, independent factors for abdominal pain included female gender and total duration of procedure >800 seconds. There were no reinsertion-related complications in the decompression group., Conclusion: Total colonic decompression after colonoscopy has a beneficial effect and can reduce postcolonoscopy abdominal pain without additional complications.

Aim: To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC)., Methods: A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively., Results: In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P<0.001) and objective tumor response (P=0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P=0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P<0.001). Multivariate analysis identified tumor stage (P<0.001) and tumor type (P=0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P<0.001), surgical treatment (P=0.009), and multi-modal treatment (P=0.002) were identified as independent post-treatment prognostic factors., Conclusion: TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC.

Background/aim: We aimed to clarify the clinical significance of precore (preC)/core promoter (CP) variants of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients., Methods: We assessed serum HBeAg, HBV DNA levels, alanine transferase (ALT) levels, and progression of liver fibrosis in 226 Korean CHB patients, presumed to be infected with genotype C HBV, to analyze HBV variants in the preC region (G1896A) and CP regions (A1762T, G1764A)., Results: CP and preC variants were more frequently found in HBeAg-negative patients than in HBeAg-positive patients (P<0.05). HBeAg-positive patients with CP variants had higher ALT levels and more advanced fibrosis scores (all P<0.01) than those without variants; those with preC variant had lower HBV DNA levels (P=0.009), with no significant difference in ALT levels and fibrosis scores. However, no significant correlation was found between HBV variants and clinicopathologic findings in HBeAg-negative patients. Furthermore, multivariate analysis revealed that (1) progression of liver fibrosis (≥F2) was associated with older age in both HBeAg-positive and HBeAg-negative patients (P<0.05) and with CP variants in the HBeAg-positive group (P=0.007), and (2) HBV DNA levels were positively correlated with ALT levels, irrespective of HBeAg (P<0.05), whereas they were negatively correlated with the presence of preC variant in the HBeAg-positive group (P=0.004)., Conclusions: In HBeAg-positive CHB patients infected with genotype C HBV, preC variant was associated with enhanced host immune response with lower HBV DNA levels, whereas CP variants were associated with severe liver damage and liver fibrosis progression.

Background: The third edition of the BioNLP Shared Task was held with the grand theme "knowledge base construction (KB)". The Genia Event (GE) task was re-designed and implemented in light of this theme. For its final report, the participating systems were evaluated from a perspective of annotation. To further explore the grand theme, we extended the evaluation from a perspective of KB construction. Also, the Gene Regulation Ontology (GRO) task was newly introduced in the third edition. The final evaluation of the participating systems resulted in relatively low performance. The reason was attributed to the large size and complex semantic representation of the ontology. To investigate potential benefits of resource exchange between the presumably similar tasks, we measured the overlap between the datasets of the two tasks, and tested whether the dataset for one task can be used to enhance performance on the other., Results: We report an extended evaluation on all the participating systems in the GE task, incoporating a KB perspective. For the evaluation, the final submission of each participant was converted to RDF statements, and evaluated using 8 queries that were formulated in SPARQL. The results suggest that the evaluation may be concluded differently between the two different perspectives, annotation vs. KB. We also provide a comparison of the GE and GRO tasks by converting their datasets into each other's format. More than 90% of the GE data could be converted into the GRO task format, while only half of the GRO data could be mapped to the GE task format. The imbalance in conversion indicates that the GRO is a comprehensive extension of the GE task ontology. We further used the converted GRO data as additional training data for the GE task, which helped improve GE task participant system performance. However, the converted GE data did not help GRO task participants, due to overfitting and the ontology gap.

Transcatheter arterial radioembolization (TARE) with Yttrium-90 ((90)Y)-labeled microspheres has an emerging role in treatment of patients with unresectable hepatocellular carcinoma. Although complication of TARE can be minimized by aggressive pre-evaluation angiography and preventive coiling of aberrant vessels, radioembolization-induced gastroduodenal ulcer can be irreversible and can be life-threatening. Treatment of radioembolization-induced gastric ulcer is challenging because there is a few reported cases and no consensus for management. We report a case of severe gastric ulceration with bleeding that eventually required surgery due to aberrant deposition of microspheres after TARE.

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed.

Background/aims: Percutaneous cholecystostomy (PC) is an effective treatment for cholecystitis in high-risk surgical patients. However, there is no definitive agreement on the need for additional cholecystectomy in these patients., Methods: All patients who were admitted to Cheju Halla General Hospital (Jeju, Korea) for acute cholecystitis and who underwent ultrasonography-guided PC between 2007 and 2012 were consecutively enrolled in this study. Among 82 total patients enrolled, 35 underwent laparoscopic cholecystectomy after recovery and 47 received the best supportive care (BSC) without additional surgery., Results: The technical and clinical success rates for PC were 100% and 97.5%, respectively. The overall mean survival was 12.8 months. In the BSC group, mean survival was 5.4 months, and in the cholecystectomy group, mean survival was 22.4 months (p<0.01). However, there was no significant difference between these groups in multivariate analysis (relative risk [RR]=1.92; 95% CI, 0.77-4.77; p=0.16). However, advanced age (RR=1.05; 95% CI, 1.02-1.08; p=0.001) and higher class in the American Society of Anesthesiologists' physical status (RR=3.06; 95% CI, 1.37-6.83, p=0.006) were significantly associated with survival in the multivariate analysis. Among the 47 patients in the BSC group, the cholecystostomy tube was removed in 31 patients per protocol. Recurrent cholecystitis was not observed in either group of patients during the follow-up period., Conclusions: In high-risk surgical patients, PC without additional cholecystectomy might be the best definitive management. Furthermore, the cholecystostomy drainage catheter can be safely removed in certain patients.

Background: Glycoscience is a research field focusing on complex carbohydrates (otherwise known as glycans)a, which can, for example, serve as "switches" that toggle between different functions of a glycoprotein or glycolipid. Due to the advancement of glycomics technologies that are used to characterize glycan structures, many glycomics databases are now publicly available and provide useful information for glycoscience research. However, these databases have almost no link to other life science databases., Results: In order to implement support for the Semantic Web most efficiently for glycomics research, the developers of major glycomics databases agreed on a minimal standard for representing glycan structure and annotation information using RDF (Resource Description Framework). Moreover, all of the participants implemented this standard prototype and generated preliminary RDF versions of their data. To test the utility of the converted data, all of the data sets were uploaded into a Virtuoso triple store, and several SPARQL queries were tested as "proofs-of-concept" to illustrate the utility of the Semantic Web in querying across databases which were originally difficult to implement., Conclusions: We were able to successfully retrieve information by linking UniCarbKB, GlycomeDB and JCGGDB in a single SPARQL query to obtain our target information. We also tested queries linking UniProt with GlycoEpitope as well as lectin data with GlycomeDB through PDB. As a result, we have been able to link proteomics data with glycomics data through the implementation of Semantic Web technologies, allowing for more flexible queries across these domains.

SPARQL queries have become the standard for querying linked open data knowledge bases, but SPARQL query construction can be challenging and time-consuming even for experts. SPARQL query generation from natural language questions is an attractive modality for interfacing with LOD. However, how to evaluate SPARQL query generation from natural language questions is a mostly open research question. This paper presents some issues that arise in SPARQL query generation from natural language, a test suite for evaluating performance with respect to these issues, and a case study in evaluating a system for SPARQL query generation from natural language questions.

Aim: To evaluate the significance of computed tomography (CT) findings in relation to liver chemistry and the clinical course of acute hepatitis., Methods: Four hundred and twelve patients with acute hepatitis who underwent enhanced CT scanning were enrolled retrospectively. Imaging findings were analyzed for the following variables: gallbladder wall thickness (GWT), arterial heterogeneity, periportal tracking, number and maximum size of lymph nodes, presence of ascites, and size of spleen. The serum levels of alanine aminotransferase, alkaline phosphatase, bilirubin, albumin, and prothrombin time were measured on the day of admission and CT scan, and laboratory data were evaluated every 2-4 d for all subjects during hospitalization., Results: The mean age of patients was 34.4 years, and the most common cause of hepatitis was hepatitis A virus (77.4%). The mean GWT was 5.2 mm. The number of patients who had findings of arterial heterogeneity, periportal tracking, lymph node enlargement > 7 mm, and ascites was 294 (80.1%), 348 (84.7%), 346 (84.5%), and 56 (13.6%), respectively. On multivariate logistic regression, male gender [odds ratio (OR) = 2.569, 95%CI: 1.477-4.469, P = 0.001], toxic hepatitis (OR = 3.531, 95%CI: 1.444-8.635, P = 0.006), level of albumin (OR = 2.154, 95%CI: 1.279-3.629, P = 0.004), and GWT (OR = 1.061, 95%CI: 1.015-1.110, P = 0.009) were independent predictive factors for severe hepatitis. The level of bilirubin (OR = 1.628, 95%CI: 1.331-1.991, P < 0.001) and GWT (OR = 1.172, 95%CI: 1.024-1.342, P = 0.021) were independent factors for prolonged cholestasis in multivariate analysis., Conclusion: In patients with acute hepatitis, GWT on CT scan was an independent predictor of severe hepatitis and prolonged cholestasis.

Background/aims: While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea., Methods: The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated., Results: The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001)., Conclusions: The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.

Aim: To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil (adefovir) in patients with lamivudine-resistant chronic hepatitis B., Methods: We included 154 consecutive patients in two treatment groups: the "add-on" group (n = 79), in which adefovir was added to ongoing lamivudine treatment due to lamivudine resistance, and the "switch/combination" group (n = 75), in which lamivudine was first switched to adefovir and then re-added later as needed. The "switch/combination" group was then divided into two subgroups depending on whether participants followed (group A, n = 30) or violated (group B, n = 45) a proposed treatment strategy that determined whether to add lamivudine based on the serum hepatitis B virus (HBV) DNA levels (< 60 IU/mL or not) after 6 mo of treatment (roadmap concept)., Results: The cumulative probability of virologic response (HBV DNA < 60 IU/mL) was higher in group A than in the "add-on" group and in group B (P < 0.001). In contrast, the cumulative probability of virologic breakthrough was lower in the "add-on" group than in group B (P = 0.002). Furthermore, the risk of virologic breakthrough in the multivariate analysis was significantly lower in the "add-on" group than in group A (hazard ratio = 0.096; 95%CI, 0.015-0.629; P = 0.015)., Conclusion: The selective combination of adefovir with lamivudine based upon early treatment responses increased the odds of virologic breakthrough relative to the use of uniform combination therapy from the beginning of treatment.

Background: Current research has shown that major difficulties in event extraction for the biomedical domain are traceable to coreference. Therefore, coreference resolution is believed to be useful for improving event extraction. To address coreference resolution in molecular biology literature, the Protein Coreference (COREF) task was arranged in the BioNLP Shared Task (BioNLP-ST, hereafter) 2011, as a supporting task. However, the shared task results indicated that transferring coreference resolution methods developed for other domains to the biological domain was not a straight-forward task, due to the domain differences in the coreference phenomena., Results: We analyzed the contribution of domain-specific information, including the information that indicates the protein type, in a rule-based protein coreference resolution system. In particular, the domain-specific information is encoded into semantic classification modules for which the output is used in different components of the coreference resolution. We compared our system with the top four systems in the BioNLP-ST 2011; surprisingly, we found that the minimal configuration had outperformed the best system in the BioNLP-ST 2011. Analysis of the experimental results revealed that semantic classification, using protein information, has contributed to an increase in performance by 2.3% on the test data, and 4.0% on the development data, in F-score., Conclusions: The use of domain-specific information in semantic classification is important for effective coreference resolution. Since it is difficult to transfer domain-specific information across different domains, we need to continue seek for methods to utilize such information in coreference resolution.

Background and Aim: Although the Psychometric Hepatic Encephalopathy Score (PHES) for the diagnosis of minimal hepatic encephalopathy (MHE) has been validated in several countries, further validation is required for its use in different populations. The aims of this study were thus to standardize the PHES in a healthy Korean population and evaluate the prevalence of MHE among Korean patients with liver cirrhosis., Methods: Two-hundred healthy subjects without evidence of liver disease and 160 patients with liver cirrhosis without overt HE were included. Blood sampling for routine laboratory tests and determination of venous ammonia concentration was performed on the day of PHES neuropsychological testing., Results: The age and education years of the control group were 41 ± 13 years and 13 ± 3 years, respectively; 100 of the subjects (50.0%) were men. The PHES for the control group was -0.31 ± 2.06 and the normal range was thus set at > -5 points. The age and education years of the liver cirrhosis group were 55 ± 8 and 11 ± 4 years, respectively; 102 of those in this group (63.8%) were men. Of the liver cirrhosis patients, 129 (80.6%), 21 (13.1%), and 10 (6.3%) had Child-Pugh grades A, B, and C, respectively. The PHES of the liver cirrhosis group was -2.94 ± 3.39. MHE was diagnosed in 41 patients (25.6%), of which 26 (20.2%), nine (42.9%), and six (60.0%) had Child-Pugh grades A, B, and C, respectively., Conclusions: The PHES was useful for detecting patients with MHE. A significant proportion of Korean patients with liver cirrhosis suffer from MHE., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Aim: We investigated long-term outcomes and prognostic factors in patients with hepatitis B virus (HBV)-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents., Methods: Between January 1999 and February 2009, a total of 240 consecutive patients who had HBV-related cirrhosis without malignancy were treated with lamivudine and second line nucleos(t)ide analogs. The group of historical controls consisted of 481 consecutive patients with HBV-related cirrhosis who were managed without any antiviral treatment prior to 1999., Results: In 78% of the patients who received antiviral treatment, sustained viral suppression (serum HBV DNA < 10(5) copies/mL) was achieved during a mean follow-up period of 46 months. The occurrences of death, hepatic decompensation, and hepatocellular carcinoma (HCC) were less frequent in the treated cohort than in untreated historical controls, with the 5-year cumulative incidences being 19.4% versus 43.9% (log-rank P < 0.001), 15.4% versus 45.4% (P = 0.001), and 13.8% versus 23.4% (P = 0.074), respectively. For patients who received antiviral treatment, suboptimal viral suppression (HBV DNA > 10(5) copies/mL at last follow-up) was an important independent risk factor of death (P < 0.001) and hepatic decompensation (P = 0.019), and was linked to an increased risk of HCC (P = 0.042). Although the Child-Pugh grade remained a useful prognostic factor, no significant differences were found between patients with Child-Pugh grade B and C cirrhosis at the beginning of antiviral treatment (P = 0.656)., Conclusions: Oral antiviral agents have improved the prognosis of patients with HBV-related cirrhosis and affected the prognostic values of factors constituting the Child-Pugh system, necessitating a more efficient prognostic system., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Transcatheter arterial chemoembolization (TACE) has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.

Background: The Genia task, when it was introduced in 2009, was the first community-wide effort to address a fine-grained, structural information extraction from biomedical literature. Arranged for the second time as one of the main tasks of BioNLP Shared Task 2011, it aimed to measure the progress of the community since 2009, and to evaluate generalization of the technology to full text papers. The Protein Coreference task was arranged as one of the supporting tasks, motivated from one of the lessons of the 2009 task that the abundance of coreference structures in natural language text hinders further improvement with the Genia task., Results: The Genia task received final submissions from 15 teams. The results show that the community has made a significant progress, marking 74% of the best F-score in extracting bio-molecular events of simple structure, e.g., gene expressions, and 45% ~ 48% in extracting those of complex structure, e.g., regulations. The Protein Coreference task received 6 final submissions. The results show that the coreference resolution performance in biomedical domain is lagging behind that in newswire domain, cf. 50% vs. 66% in MUC score. Particularly, in terms of protein coreference resolution the best system achieved 34% in F-score., Conclusions: Detailed analysis performed on the results improves our insight into the problem and suggests the directions for further improvements.

Background: Term clustering, by measuring the string similarities between terms, is known within the natural language processing community to be an effective method for improving the quality of texts and dictionaries. However, we have observed that chemical names are difficult to cluster using string similarity measures. In order to clearly demonstrate this difficulty, we compared the string similarities determined using the edit distance, the Monge-Elkan score, SoftTFIDF, and the bigram Dice coefficient for chemical names with those for non-chemical names., Results: Our experimental results revealed the following: (1) The edit distance had the best performance in the matching of full forms, whereas Cohen et al. reported that SoftTFIDF with the Jaro-Winkler distance would yield the best measure for matching pairs of terms for their experiments. (2) For each of the string similarity measures above, the best threshold for term matching differs for chemical names and for non-chemical names; the difference is especially large for the edit distance. (3) Although the matching results obtained for chemical names using the edit distance, Monge-Elkan scores, or the bigram Dice coefficients are better than the result obtained for non-chemical names, the results were contrary when using SoftTFIDF. (4) A suitable weight for chemical names varies substantially from one for non-chemical names. In particular, a weight vector that has been optimized for non-chemical names is not suitable for chemical names. (5) The matching results using the edit distances improve further by dividing a set of full forms into two subsets, according to whether a full form is a chemical name or not. These results show that our hypothesis is acceptable, and that we can significantly improve the performance of abbreviation-full form clustering by computing chemical names and non-chemical names separately., Conclusions: In conclusion, the discriminative application of string similarity methods to chemical and non-chemical names may be a simple yet effective way to improve the performance of term clustering.

Aim: To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients., Methods: We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records., Results: Of the 2242 patients, 165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diagnosis in the positive- and negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P < 0.0001). Furthermore, among 1713 HCC patients with HBV infection, the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%), whereas those out of 1577 patients with negative family history was 197 (12.5%), suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P = 0.0028)., Conclusion: More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.

Background: Bio-molecular event extraction from literature is recognized as an important task of bio text mining and, as such, many relevant systems have been developed and made available during the last decade. While such systems provide useful services individually, there is a need for a meta-service to enable comparison and ensemble of such services, offering optimal solutions for various purposes., Results: We have integrated nine event extraction systems in the U-Compare framework, making them intercompatible and interoperable with other U-Compare components. The U-Compare event meta-service provides various meta-level features for comparison and ensemble of multiple event extraction systems. Experimental results show that the performance improvements achieved by the ensemble are significant., Conclusions: While individual event extraction systems themselves provide useful features for bio text mining, the U-Compare meta-service is expected to improve the accessibility to the individual systems, and to enable meta-level uses over multiple event extraction systems such as comparison and ensemble.

Objective: Lipiodol transcatheter arterial chemoembolization (TACE) is widely used to treat hepatocellular carcinoma (HCC). Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. The purpose of this study was to compare the efficacy and safety of intra-arterial injection of DEB loaded with doxorubicin versus conventional, Lipiodol-based TACE regimens in Asian patients with HCC., Methods: The study was designed as a case-control, single-institution clinical trial. Twenty patients with HCC who received DEB loaded with 50 mg doxorubicin ('cases') were matched with 20 patients who had undergone conventional TACE ('controls'). The primary efficacy endpoint was tumor response at 1 month according to modified Response Evaluation Criteria in Solid Tumors. The primary safety endpoint was liver toxicity., Results: The rate of objective response by modified Response Evaluation Criteria in Solid Tumors was 85% (17 of 20 patients) in the DEB arm versus 30% (six of 20 patients) in the conventional TACE arm (P=0.001). Subgroup analyses conducted in patients with large (>5 cm) or multinodular tumor confirmed significantly higher objective response rates in patients receiving DEB as compared with those treated with conventional TACE (P=0.003 and P=0.005, respectively). At the dose of 50 mg doxorubicin, there was no statistically significant difference in liver toxicity between DEB and conventional TACE (P>0.05)., Conclusion: In Asian patients with HCC, transcatheter treatment with DEB loaded with doxorubicin offers a distinct advantage in objective tumor response rate as compared with conventional, Lipiodol-based TACE regimens.

Background/aims: Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer., Methods: A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used., Results: Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88)., Conclusions: LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.

Unlabelled: Often, the most informative genes have to be selected from different gene sets and several computer gene ranking algorithms have been developed to cope with the problem. To help researchers decide which algorithm to use, we developed the analysis of gene ranking algorithms (AGRA) system that offers a novel technique for comparing ranked lists of genes. The most important feature of AGRA is that no previous knowledge of gene ranking algorithms is needed for their comparison. Using the text mining system finding-associated concepts with text analysis. AGRA defines what we call biomedical concept space (BCS) for each gene list and offers a comparison of the gene lists in six different BCS categories. The uploaded gene lists can be compared using two different methods. In the first method, the overlap between each pair of two gene lists of BCSs is calculated. The second method offers a text field where a specific biomedical concept can be entered. AGRA searches for this concept in each gene lists' BCS, highlights the rank of the concept and offers a visual representation of concepts ranked above and below it., Availability and Implementation: Available at http://agra.fzv.uni-mb.si/, implemented in Java and running on the Glassfish server., Contact: simon.kocbek@uni-mb.si.

Background/aims: Pegylated interferon plus ribavirin combination therapy has been the standard of therapy for patients with chronic hepatitis C. Although previous studies have reported long term durability after the sustained virologic response (SVR) with standard therapy for chronic hepatitis C, it is still unclear in Korea. The aim of this study was to evaluate the relapse rate and related factors after SVR to pegylated interferon therapy in Korean patients with chronic hepatitis C., Methods: A total of 119 chronic hepatitis C patients were treated with pegylated interferon plus ribavirin, and 73 patients achieved SVR (61.3%). Among 73 patients who achieved SVR, 68 patients (genotype 1, n=40; genotype non-1, n=28) were evaluated for virological response after SVR., Results: SVR rate in genotype 1 and genotype non-1 were 52.5%, and 65.1%, respectively. Relapse after SVR occurred in 5 patients (7.4%) with genotype 1, and the median time to relapse from SVR was 10 months. Univariate analysis revealed that the dose reduction of pegylated interferon (p=0.005) and cirrhosis (p=0.03) were significantly associated with relapse., Conclusions: These results suggested that the relapse could occur even after SVR achievement in Korean patients with chronic hepatitis C, and the dose reduction of pegylated interferon during treatment or having cirrhosis may increased the risk for relapse.

Background: There are no convincing data supporting the routine use of pre-emptive therapy against HBV reactivation in various loco-regional therapies for hepatocellular carcinoma (HCC). This study investigated the incidence, severity and risk factors of HBV reactivation during loco-regional therapies., Methods: A total of 205 prospectively enrolled patients were classified in order of increasing intensity of loco-regional therapies: local ablation therapy (LAT; 43 patients), transarterial chemotherapy using adriamycin (TAC-ADR; 93 patients) or combined epirubicin-cisplatin (TAC-EC; 26 patients), and combined chemo-radiotherapy (TAC-EC+RT; 43 patients)., Results: During the follow-up, 62 (30.2%) patients developed HBV reactivation. Multivariate analysis identified HBV DNA levels >10⁴ copies/ml (P=0.041) and treatment option (P=0.001) to be independent predictors of HBV reactivation. There was a significant trend for increasing risk of reactivation with increasing intensity of therapy, with hazard ratios of 1.0 for LAT, 2.45 for TAC-ADR, 4.19 for TAC-EC and 10.17 for TAC-EC+RT. The severity of reactivated disease was also increased with increasing treatment intensity (P-value for trend <0.05). Only one of the patients with low-level viraemia receiving LAT alone developed reactivation, whereas a substantial number of patients with high-level viraemia eventually developed reactivation., Conclusions: High-level viraemia and high-level treatment intensity are the major risk factors for HBV reactivation during loco-regional therapy. Trends are evident for the increased risk and severity of reactivation with the aggressiveness of treatment. Pre-emptive antiviral therapy should be recommended for all patients with high-level viraemia irrespective of treatment option, or those undergoing any intensive therapy.

Background/aims: Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC., Methods: The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m(2) on days 1~3) and cisplatin (60 mg/m(2) on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks., Results: Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group., Conclusions: High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.