Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.
Antineoplastic Agents ; Classification ; DNA Repair ; Molecular Docking Simulation

Transcriptome analysis has been widely used to make biomarker panels to diagnose cancers. In breast cancer, the age of the patient has been known to be associated with clinical features. As clinical transcriptome data have accumulated significantly, we classified all human genes based on age-specific differential expression between normal and breast cancer cells using public data. We retrieved the values for gene expression levels in breast cancer and matched normal cells from The Cancer Genome Atlas. We divided genes into two classes by paired t test without considering age in the first classification. We carried out a secondary classification of genes for each class into eight groups, based on the patterns of the p-values, which were calculated for each of the three age groups we defined. Through this two-step classification, gene expression was eventually grouped into 16 classes. We showed that this classification method could be applied to establish a more accurate prediction model to diagnose breast cancer by comparing the performance of prediction models with different combinations of genes. We expect that our scheme of classification could be used for other types of cancer data.
Biomarkers ; Breast Neoplasms* ; Breast* ; Classification* ; Gene Expression ; Gene Expression Profiling ; Genome ; Humans ; Methods ; Transcriptome

No abstract available.

Objectives: This study examined the responses to standard stimuli to investigate the mechanisms underlying mismatch negativity (MMN) impairments in schizophrenia. Methods: We obtained MMN data from 68 patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls and analyzed the electrophysiological activity of the responses to two standard stimuli before deviants using time-frequency methods. Results: As a result of RM ANOVA at evoked alpha power, there were differences not only between-subjects (F 1,104=4.35, p<0.05) but also within-subjects (F 1,104=8.62, p<0.01) without groupby-stimulus interaction (F 1,104=1.70, p=0.20). But at single-trial alpha power, there was a difference not between-subjects (F 1,104=3.81, p=0.054), but only within-subjects (F 1,104=10.14, p<0.01) with significant group-by-stimulus interaction (F 1,104=5.71, p<0.05). Moreover, between-group differences were significant in evoked alpha power (t 104=2.02, p<0.05, d=0.41) and single-trial alpha power (t 104=2.49, p<0.01, d=0.50) to standard stimuli presented not at the first instance but second. According to the order that the two standards presented, there were increases of evoked alpha power (t 37=-2.54, p<0.05, d=0.58) and single-trial alpha power (t 37=-3.41, p<0.01, d=0.78) in only the healthy controls. The positive correlations were shown in clinical features between years of education completed and event-related potential amplitude at 100 ms to both standard stimuli (Each Pearson Corr.: r=0.22, p<0.05). Conclusion These outputs suggest that the P1 alpha oscillation to standards is associated with deficits in the inhibitory control of selective attention relative to cognitive dysfunction in schizophrenia.We could also hypothesize that these deficits are involved in computing prediction errors based on the predictive coding perspective. However, further studies on this hypothesis are necessary.

PURPOSE: We attempted to find out the useful urodynamic parameters for diagnosis of bladder outlet obstruction (BOO) in women, prospectively. MATERIALS AND METHODS: 219 patients were available for analysis, of whom 34 were obstructed by clinical definition, 137 with stress urinary incontinence (SUI) and 34 served as a control. To predict obstruction, comparisons were made; receiver operator characteristic (ROC) curve analysis was used to determine the optimum cut-off values for peak flow rate (Qmax), detrusor pressure at maximum flow (PdetQmax) and maximal urethral closing pressure (MUCP). RESULTS: On the basis of ROC curves between control and BOO groups, using single cut-off value at pressure-flow study, sensitivities and specificities of BOO were 97.1% and 77.9% (Qmax<12ml/s), 85.3% and 86.8% (PdetQmax>30cmH2O), 79.4% and 88.2% (MUCP>80cmH2O). By combined cut-off values, sensitivities and specificities of BOO were 85.3% and 92.6% (Qmax<12ml/s and PdetQmax>30cmH2O), and 73.5% and 94.1% (Qmax<12ml/s, PdetQmax>30cmH2O, and MUCP>80cmH2O). CONCLUSIONS: Our results show that BOO might be diagnosed by the criteria of Qmax<12ml/s, PdetQmax>30cmH2O, and MUCP>80cmH2O.
Diagnosis ; Female* ; Humans ; Prospective Studies* ; ROC Curve ; Urinary Bladder Neck Obstruction* ; Urinary Bladder* ; Urinary Incontinence ; Urodynamics

More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.
Computer Simulation ; DNA, Recombinant ; Humans* ; Insulin ; Molecular Dynamics Simulation* ; Proinsulin ; Protein Sorting Signals ; Trypsin

HExDB is a database for analyzing exon and splicing pattern information in Homo sapiens. HExDB is useful for specific purposes: 1) to design primers for exon amplification from cDNA and 2) to understand the change of ORFs by alternative splicing. HExDB was constructed by integrating data from AltExtron which is the computationally predicted exon database, Ensemble cDNA annotation, and Affymetrix genome tile published recently. Although it may contain false positive data, HExDB is good starting point due to its sensitivity. At present, there are as many as 2,046,519 exons stored in the HExDB. We found that 16.8% of the exons in the database was constitutive exons and 83.1% were novel gene exons.
Alternative Splicing* ; Animals ; DNA, Complementary ; Ecthyma, Contagious ; Exons* ; Genome ; Humans* ; Open Reading Frames

PURPOSE: To compare the level of accuracy of intraocular pressure (IOP) measurements of a rebound tonometer (RT) Icare(R), and non-contact tonometer (NCT), using Goldmann Applanation tonometer (GAT) as a reference to evaluate the influence of central corneal thickness (CCT) on IOP readings in the Korean population. METHODS: In a prospective study of 273 eyes, IOP was measured with RT, GAT, and NCT and compared to CCT measurements. Patients were assigned to one of 3 groups based on IOP measurements of GAT and 1 of 2 groups based on CCT. The comparison of the IOP values of RT, GAT, and NCT was performed between the IOP and CCT groups, and the differences among tonometers were evaluated. RESULTS: The RT showed statistically significant correlation with the GAT compared to the NCT. The CCT was related to RT measurements. The RT values compared to the GAT was underestimated in thin corneas and overestimated in thick corneas. CONCLUSIONS: There was a significant correlation between the RT and the GAT measurements compared with the NCT. However, RT is influenced by CCT and correlates less with GAT in low IOP ranges, suggesting that corneal thickness should be taken into consideration during such measurements.
Cornea ; Eye ; Humans ; Intraocular Pressure ; Peptides ; Prospective Studies ; Reading

OBJECTIVES: We aimed to develop a common health information exchange (HIE) platform that can provide integrated services for implementing the HIE infrastructure in addition to guidelines for participating in an HIE network in South Korea. METHODS: By exploiting the Health Level 7 (HL7) Clinical Document Architecture (CDA) and Integrating the Healthcare Enterprise (IHE) Cross-enterprise Document Sharing-b (XDS.b) profile, we defined the architectural model, exchanging data items and their standardization, messaging standards, and privacy and security guidelines, for a secure, nationwide, interoperable HIE. We then developed a service-oriented common HIE platform to minimize the effort and difficulty of fulfilling the standard requirements for participating in the HIE network. The common platform supports open application program interfaces (APIs) for implementing a document registry, a document repository, a document consumer, and a master patient index. It could also be used for testing environments for the implementation of standard requirements. RESULTS: As the initial phase of implementing a nationwide HIE network in South Korea, we built a regional network for workers' compensation (WC) hospitals and their collaborating clinics to share referral and care record summaries to ensure the continuity of care for industrially injured workers, using the common HIE platform and verifying the feasibility of our technologies. CONCLUSIONS: We expect to expand the HIE network on a national scale with rapid support for implementing HL7 and IHE standards in South Korea.
Computer Security ; Computer Systems ; Continuity of Patient Care ; Delivery of Health Care ; Electronic Health Records ; Health Level Seven ; Humans ; Information Services* ; Korea ; Privacy ; Referral and Consultation ; Workers' Compensation

Purpose: The purpose of this study was to provide foundational knowledge on nursing tasks performed on patients with COVID-19 in a nationally-designated inpatient treatment unit. Methods: This study employs both quantitative and qualitative approaches. The quantitative method investigated the content and frequency of nursing tasks for 460 patients (age ≥ 18y, 57.4% men) from January 20, 2020, to September 30, 2021, by analyzing hospital information system records. Qualitative data were collected via focus group interviews. The study involved interviews with three focus groups comprising 18 nurses overall to assess their experiences and perspectives on nursing care during the pandemic from February 3, 2022, to February 15, 2022. The data were examined with thematic analysis. Results: Overall, 49 different areas of nursing tasks (n = 130,687) were identified based on the Korean Patient Classification System for nurses during the study period. Among the performed tasks, monitoring of oxygen saturation and measuring of vital signs were considered high-priority. From the focus group interview, three main themes and eleven sub-themes were generated. The three main themes are “Experiencing eventfulness in isolated settings,” “All-around player,” and “Reflections for solutions.” Conclusion During the COVID-19 pandemic, it is imperative to ensure adequate staffing levels, compensation, and educational support for nurses. The study further propose improving guidelines for emerging infectious diseases and patient classification systems to improve the overall quality of patient care.