Identification and characterization of recent retrovirus in Rhinolophus ferrumequinum bats.

An investigation into retrovirus was conducted in six species of bats (Myotis aurascens, Myotis petax, Myotis macrodactylus, Miniopterus fuliginosus, Rhinolophus ferrumequinum, and Pipistrellus abramus) inhabiting South Korea. Exogenous retroviruses (XRVs) were detected in the tissue samples of R. ferrumequinum individuals by PCR assay. Proviruses were identified in all tissue samples through viral quantification using a digital PCR assay per organ (lung, intestine, heart, brain, wing, kidney, and liver), with viral loads varying greatly between each organ. In phylogenetic analysis based on the whole genome, the Korean bat retroviruses and the R. ferrumequinum retrovirus (RfRV) strain formed a new clade distinct from the Gammaretrovirus clade. The phylogenetic results determined these viruses to be RfRV-like viruses. In the Simplot comparison, Korean RfRV-like viruses exhibited relatively strong fluctuated patterns in the latter part of the envelope gene area compared to other gene areas. Several point mutations within this region (6,878-7,774 bp) of these viruses were observed compared to the RfRV sequence. One Korean RfRV-like virus (named Y4b strain) was successfully recovered in the Raw 264.7 cell line, and virus particles replicated in the cells were confirmed by transmission electron microscopy. RfRVs (or RfRV-like viruses) have been spreading since their first discovery in 2012, and the Korean RfRV-like viruses were assumed to be XRVs that evolved from RfRV.IMPORTANCER. ferrumequinum retrovirus (RfRV)-like viruses were identified in greater horseshoe bats in South Korea. These RfRV-like viruses were considered exogenous retroviruses (XRVs) that emerged from RfRV. Varying amounts of provirus detected in different organs suggest ongoing viral activity, replication, and de novo integration in certain organs. Additionally, the successful recovery of the virus in the Raw 264.7 cell line provides strong evidence supporting their status as XRVs. These viruses have now been identified in South Korea and, more recently, in Kenya since RfRV was discovered in China in 2012, indicating that RfRVs (or RfRV-like viruses) have spread worldwide.

A Study to Evaluate the Effectiveness and Safety of Prephase Steroid Treatment before Remission Induction Chemotherapy in Patients with Pediatric Acute Lymphoblastic Leukemia Using Common Data Model-Based Real-World Data: A Retrospective Observational Study.

Background: Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥7 days before RIC in 2012-2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed. Results: Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03-0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25-1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses. Conclusion: Prephase steroid treatment for ≥7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.

Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Added to Dual or Triple Treatment in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: We evaluated the effectiveness and safety of sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on treatment in patients with type 2 diabetes mellitus (T2DM) in the real-world setting. METHODS: This single-center retrospective study used the clinical database of Seoul National University Hospital in South Korea. Patients who received metformin monotherapy or combination therapy with ≥ 1 other oral hypoglycemic medication and had a baseline glycosylated hemoglobin (HbA1c) between 7.0% and 10.5% were included. Propensity score matching was applied between patients treated with and without SGLT2 inhibitors (SGLT2i and non-SGLT2i groups, respectively). Changes in HbA1c from baseline to week 26 were compared between the SGLT2i and non-SGLT2i groups, and risk of adverse events (AE) were also assessed. RESULTS: A total of 1106 patients were included. At week 26, HbA1c was significantly more reduced by 0.35 percentage points in the SGLT2i group than in the non-SGLT2i group (95% CI 0.30-0.41, P < 0.001). Likewise, the proportion of patients achieving HbA1c < 7% was also significantly higher (51.9% vs. 37.6%, P < 0.05) in the SGLT2i group than in the non-SGLT2i group. The risk of adverse events in the SGLT2i group was mostly comparable with those in the non-SGLT2i group except for diseases of the liver, pain, hypertensive diseases, and metabolic disorders, which showed significantly higher odds in the SGLT2i group. CONCLUSIONS: SGLT2i add-on treatment is an effective and safe therapeutic option for patients with T2DM in the real-world practice setting.

Automatic Extraction of Comprehensive Drug Safety Information from Adverse Drug Event Narratives in the Korea Adverse Event Reporting System Using Natural Language Processing Techniques.

INTRODUCTION: Concerns have been raised over the quality of drug safety information, particularly data completeness, collected through spontaneous reporting systems (SRS), although regulatory agencies routinely use SRS data to guide their pharmacovigilance programs. We expected that collecting additional drug safety information from adverse event (ADE) narratives and incorporating it into the SRS database would improve data completeness. OBJECTIVE: The aims of this study were to define the extraction of comprehensive drug safety information from ADE narratives reported through the Korea Adverse Event Reporting System (KAERS) as natural language processing (NLP) tasks and to provide baseline models for the defined tasks. METHODS: This study used ADE narratives and structured drug safety information from individual case safety reports (ICSRs) reported through KAERS between 1 January 2015 and 31 December 2019. We developed the annotation guideline for the extraction of comprehensive drug safety information from ADE narratives based on the International Conference on Harmonisation (ICH) E2B(R3) guideline and manually annotated 3723 ADE narratives. Then, we developed a domain-specific Korean Bidirectional Encoder Representations from Transformers (KAERS-BERT) model using 1.2 million ADE narratives in KAERS and provided baseline models for the task we defined. In addition, we performed an ablation experiment to investigate whether named entity recognition (NER) models were improved when a training dataset contained more diverse ADE narratives. RESULTS: We defined 21 types of word entities, six types of entity labels, and 49 types of relations to formulate the extraction of comprehensive drug safety information as NLP tasks. We obtained a total of 86,750 entities, 81,828 entity labels, and 45,107 relations from manually annotated ADE narratives. The KAERS-BERT model achieved F1-scores of 83.81 and 76.62% on the NER and sentence extraction tasks, respectively, while outperforming other baseline models on all the NLP tasks we defined except the sentence extraction task. Finally, utilizing the NER model for extracting drug safety information from ADE narratives resulted in an average increase of 3.24% in data completeness for KAERS structured data fields. CONCLUSIONS: We formulated the extraction of comprehensive drug safety information from ADE narratives as NLP tasks and developed the annotated corpus and strong baseline models for the tasks. The annotated corpus and models for extracting comprehensive drug safety information can improve the data quality of an SRS database.

Drug Attitude and Medication Adherence of Patients with Early Psychosis in South Korea: Mediating Effect of Medication Adherence Self-Efficacy.

Purpose: This study examined the mediating effect of medication adherence self-efficacy (MASE) on the relationship between drug attitude (DA) and medication adherence (MA) in patients with early psychosis. Patients and Methods: A total of 166 patients, aged 20 years or older, and who had received treatment within 5 years of their initial psychotic episode at a University Hospital outpatient center, participated in the study. Data were analyzed using descriptive statistics, t-tests, one-way analysis of variance, Pearson's correlation coefficients, and multiple linear regression. Additionally, a bootstrapping test was conducted to determine the statistical significance of the mediating effect. All study procedures adhered to Strengthening the reporting of observational studies in epidemiology (STROBE) guidelines. Results: This study found a significant correlation between MA and DA (r=0.393, p<0.001), and between MA and MASE (r=0.697, p<0.001). MASE had a partial mediating effect on the association between DA and MA. The model that integrated both DA and MASE accounted for 53.4% of the variation in MA. Bootstrapping analysis indicated that MASE was a significant partial parameter (lower limit confidence interval [CI] 0.114; upper limit CI 0.356). Further, 64.5% of the study participants were either currently enrolled in college or had higher levels of education. Conclusion: These findings could potentially lead to a more personalized approach to medication education and adherence, considering the unique DA and MASE of each patient. By identifying the mediating effect of MASE on the relationship between DA and MA, healthcare providers could tailor interventions to enhance the ability of patients with early psychosis to adhere to prescribed medication regimens.

Targeted Protein Upregulation of STING for Boosting the Efficacy of Immunotherapy.

Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.

Contraceptive Use Among Korean High School Adolescents: A Decision Tree Model.

Although the rate of sexual intercourse among adolescents has increased in Asian countries, including Korea, many sexually active adolescents still do not use contraception. The aim of this study was to identify the risk factors for contraceptive nonuse among adolescents using decision tree analysis of the 2018 Korea Youth Risk Behavior Survey data from 2,460 high school students who had an experience of sexual intercourse. The findings indicated that the highest risk group who did not use contraception during sexual intercourse did not receive sexual health education in school and was involved in habitual or purposeful drug use. The experience of ever receiving treatment due to violence and the experience of sexual intercourse after drinking were also identified as risk factors for contraceptive nonuse. To encourage contraceptive use, development of standard sexual health education, counseling, and educational intervention intended to prevent risky behaviors is needed.

Effect of a Wireless Vital Sign Monitoring System on the Rapid Response System in the General Ward.

While wireless vital sign monitoring is expected to reduce the vital sign measurement time (thus reducing the nursing workload), its impact on the rapid response system is unclear. This study compared the time from vital sign measurement to recording and rapid response system activation between wireless and conventional vital sign monitoring in the general ward, to investigate the impact of wireless vital sign monitoring system on the rapid response system. The study divided 249 patients (age > 18 years; female: 47, male: 202) admitted to the general ward into non-wireless (n = 101) and wireless (n = 148) groups. Intervals from vital sign measurement to recording and from vital sign measurement to rapid response system activation were recorded. Effects of wireless system implementation for vital sign measurement on the nursing workload were surveyed in 30 nurses. The interval from vital sign measurement to recording was significantly shorter in the wireless group than in the non-wireless group (4.3 ± 2.9 vs. 44.7 ± 14.4 min, P < 0.001). The interval from vital sign measurement to rapid response system activation was also significantly lesser in the wireless group than in the non-wireless group (27.5 ± 12.9 vs. 41.8 ± 19.6 min, P = 0.029). The nursing workload related to vital sign measurement significantly decreased from 3 ± 0.87 to 2.4 ± 9.7 (P = 0.021) with wireless system implementation. Wireless vital sign monitoring significantly reduced the time to rapid response system activation by shortening the time required to measure the vital signs. It also significantly reduced the nursing workload.

Design and Synthesis of Conformationally Diverse Pyrimidine-Embedded Medium/Macro- and Bridged Cycles via Skeletal Transformation.

The rigidity and flexibility of small molecules are complementary in 3-dimensional ligand-protein interaction. Therefore, the chemical library with conformational diversity would be a valuable resource for investigating the influence of skeletal flexibility on the biological system. In this regard, we designed and synthesized ten conformationally diverse pyrimidine-embedded medium/macro- and bridged cyclic scaffolds covering 7- to 14-member rings via an efficient skeletal transformation strategy. Their high conformational and shape diversity was confirmed by chemoinformatic analysis.

An annotated corpus from biomedical articles to construct a drug-food interaction database.

MOTIVATION: While drug-food interaction (DFI) may undermine the efficacy and safety of drugs, DFI detection has been difficult because a well-organized database for DFI did not exist. To construct a DFI database and build a natural language processing system extracting DFI from biomedical articles, we formulated the DFI extraction tasks and manually annotated texts that could have contained DFI information. In this article, we introduced a new annotated corpus for extracting DFI, the DFI corpus. RESULTS: The DFI corpus contains 2270 abstracts of biomedical articles accessible through PubMed and 2498 sentences that contain DFI and/or drug-drug information (DDI), a substantial amount of information about drug/food entities, evidence-levels of abstracts and relations between named entities. BERT models pre-trained on the biomedical domain achieved a F1 score 55.0% in extracting DFI key-sentences. To the best of our knowledge, the DFI corpus is the largest public corpus for drug-food interaction. AVAILABILITY AND IMPLEMENTATION: Our corpus is available at https://github.com/ccadd-snu/corpus-for-DFI-extraction.

A structural equation modeling of reproductive health promoting behaviors among female adolescents in the Philippines.

AIMS: Integrated reproductive health promoting behaviors, including safe sexual intercourse, preventing sexually transmitted diseases, sexual responsibility, and genital health management, are essential for adolescents in developing countries. The Philippines is currently facing several reproductive health threats. The aim of this study was to identify factors affecting reproductive health promoting behaviors based on a theoretical model using structural equation modeling. METHODS: In this cross-sectional study and a structural equation modeling, a total of 227 female adolescents in the Philippines participated in a self-reported questionnaire survey. RESULTS: The results indicated that reproductive health knowledge (ß = .14, p = .033), attitudes regarding reproductive health behaviors (ß = .31, p = .027), and reproductive health self-efficacy (ß = .31, p = .002) influenced participants' reproductive health promoting behaviors. Social norms (ß = .31, p = .021) influenced reproductive health self-efficacy and indirectly influenced reproductive health promoting behaviors. Attitude toward gender roles (ß = .20, p = .020) was associated with reproductive health knowledge. CONCLUSIONS: This study confirmed the direct effect of reproductive health knowledge, attitudes regarding reproductive behaviors, and reproductive health self-efficacy, as well as the indirect effect of social norms, on reproductive health promoting behaviors using structural equation modeling.

Deep Learning-Based Stroke Disease Prediction System Using Real-Time Bio Signals.

The emergence of an aging society is inevitable due to the continued increases in life expectancy and decreases in birth rate. These social changes require new smart healthcare services for use in daily life, and COVID-19 has also led to a contactless trend necessitating more non-face-to-face health services. Due to the improvements that have been achieved in healthcare technologies, an increasing number of studies have attempted to predict and analyze certain diseases in advance. Research on stroke diseases is actively underway, particularly with the aging population. Stroke, which is fatal to the elderly, is a disease that requires continuous medical observation and monitoring, as its recurrence rate and mortality rate are very high. Most studies examining stroke disease to date have used MRI or CT images for simple classification. This clinical approach (imaging) is expensive and time-consuming while requiring bulky equipment. Recently, there has been increasing interest in using non-invasive measurable EEGs to compensate for these shortcomings. However, the prediction algorithms and processing procedures are both time-consuming because the raw data needs to be separated before the specific attributes can be obtained. Therefore, in this paper, we propose a new methodology that allows for the immediate application of deep learning models on raw EEG data without using the frequency properties of EEG. This proposed deep learning-based stroke disease prediction model was developed and trained with data collected from real-time EEG sensors. We implemented and compared different deep-learning models (LSTM, Bidirectional LSTM, CNN-LSTM, and CNN-Bidirectional LSTM) that are specialized in time series data classification and prediction. The experimental results confirmed that the raw EEG data, when wielded by the CNN-bidirectional LSTM model, can predict stroke with 94.0% accuracy with low FPR (6.0%) and FNR (5.7%), thus showing high confidence in our system. These experimental results demonstrate the feasibility of non-invasive methods that can easily measure brain waves alone to predict and monitor stroke diseases in real time during daily life. These findings are expected to lead to significant improvements for early stroke detection with reduced cost and discomfort compared to other measuring techniques.

School Health Needs Assessment in Chanchamayo, Peru: A Health Promoting School Project.

Background: School-based health promotion can be particularly valuable in developing countries. However, there is a lack of information about the health needs of Peruvian school students. The purpose of this study was to conduct a health needs assessment to develop strategies for a school health promotion program in a jungle and indigent region in Chanchamayo, Peru. Methods: This study was conducted using a mixed method approach that included a literature review, national and local statistics, stakeholder interviews, and a survey. Participants of the survey were 210 teachers, 2,504 elementary school students, and 2,834 secondary school students from six 'schools in two planned project implementation regions. A self-administered questionnaire for students was developed based on WHO's Global School-based Student Health Survey. Collected data were analyzed using descriptive statistics, chi-square tests, and t-tests for the survey data and content analysis for the interviews. Results: Weak school health systems were identified, including school health policies, curriculum, trained health care personnel, and health-related facilities and equipment. Common health problems of students were anemia, nutritional deficiency, infectious diseases, tuberculosis, drug abuse, poor hygiene, and sex-related problems. High absence rates from school due to family problems and high dropout rates due to pregnancy were also critical issues. Teachers identified personal hygiene, nutrition, reproductive health, and sex education as high priorities for school health education, while students identified prevention of infectious diseases, nutrition education, psychological health, and healthy lifestyles as priorities. Identified strategies included: establishment of school health policies, curriculum-based interventions, increasing community participation and raising school health awareness, capacity building for health care promotors, training of trainers, and partnership between schools and communities. Conclusions: Findings from this study will help guide the development and implementation of a school-based health promotion program in Chanchamayo. Multicomponent school-based interventions that consider feasibility and sustainability will be developed and evaluated based on WHO's Health Promoting School concepts.

Establishing a nurse-managed health center for the urban poor in Dhaka, Bangladesh.

OBJECTIVES: Despite the rise in community health problems in populations living in urban slums, activities of community health nurses are limited in Bangladesh. This study aimed to describe how a nurse-managed health center (NMHC) was developed in Dhaka, Bangladesh. DESIGN: An exploratory-descriptive research design was used. SAMPLE AND MEASUREMENTS: The commitment phase was conducted to establish partnerships in the community. Involvement of community leaders and members and partnerships with various organizations were established successfully in the commitment phase. The assessment phase was completed by implementing personal interviews, community site visits, and household surveys of 172 households in the community. Action plans were developed and strategies were followed to change the community during the planning phase. RESULTS: Household survey results showed that community people suffered from non-communicable diseases, risk behaviors, and inadequate housing conditions. The high-priority community needs included nutrition and chronic management services, behavior change programs, and a clean environment. Action plans for health programs based on community needs and strategies such as securing manpower and equipment were developed. CONCLUSIONS: The systematic process of creating a NMHC, and the necessity of the community health nurse's role in responding to health needs of the urban poor in Dhaka, Bangladesh was confirmed.

A divergent synthetic pathway for pyrimidine-embedded medium-sized azacycles through an N-quaternizing strategy.

Medium-sized heterocycles have recently received significant attention because of their potential roles as modulators of protein-protein interactions, but their molecular diversity and synthetic availability are still inadequate to meet the demand. To address these issues, we developed a new divergent synthetic pathway for skeletally distinct pyrimidine-containing medium-sized azacycles. We introduced N-quaternized pyrimidine-containing polyheterocycles as novel key intermediates for diversity-generating reactions via selective bond cleavages or migrations and prepared 14 discrete core skeletons in an efficient manner. The skeletal diversity of the resulting molecular frameworks was confirmed by chemoinformatic analysis.

A Brief Overview of Two Major Strategies in Diversity-Oriented Synthesis: Build/Couple/Pair and Ring-Distortion.

In the interdisciplinary research field of chemical biology and drug discovery, diversity-oriented synthesis (DOS) has become indispensable in the construction of novel small-molecule libraries rich in skeletal and stereochemical diversity. DOS aims to populate the unexplored chemical space with new potential bioactive molecules via forward synthetic analysis. Since the introduction of this concept by Schreiber, DOS has evolved along with many significant breakthroughs. It is therefore important to understand the key DOS strategies to build molecular diversity with maximized biological relevancy. Due to the length limitations of this mini review, we briefly discuss the recent DOS plans using build/couple/pair (B/C/P) and ring-distortion strategies for the synthesis of major biologically relevant target molecules like natural products and their related compounds, macrocycles, and privileged structures.

A Review of Trend of Nursing Theories related Caregivers in Korea.

BACKGROUND: The prevalence of chronic diseases has been rapidly increased due to population aging. As the duration of care needs increase, the caregivers' socioeconomic burdens have also increased. OBJECTIVE: This review examines the attributes of caregiving experience and quality of life of caregivers in Korea with a focus on the application of nursing theory. METHOD: We reviewed studies on caregivers' caring for adult patients published till 2016 in 4 bio-medical research portal websites or data bases. A total of 1,939 studies were identified through the keyword search. One hundred forty five studies were selected by a process; of which, 17 studies were theory-applied. Selected studies were analyzed in accordance with the structured analysis format. RESULTS: Quantitative studies accounted for 76.6%, while 22.1% were qualitative studies and 1.3% were triangulation studies. Caregiver-related studies increased after 2000. Most frequently, the caregivers were spouses (28.4%), and most frequently, care was provided to a recipient affected by stroke (22.5%). The 17 theory-based studies described 20 theories (70% psychology theories, 30% nursing theories). The most frequent nursing theory was the theory of stress, appraisal and coping. CONCLUSION: This study sought to better understand caregiving through the analysis of Korean studies on the caregiving experience and caregivers' QOL and this finding helped presenting empirical data for nursing by identifying the nursing theories applied to the caregiving experience and caregivers' QOL. The results suggest that the need for further expansion of nursing theories and their greater utilization in the studies of caregiving.