Structure-activity relationship studies of allosteric inhibitors of EYA2 tyrosine phosphatase.

Human eyes absent (EYA) proteins possess Tyr phosphatase activity, which is critical for numerous cancer and metastasis promoting activities, making it an attractive target for cancer therapy. In this work, we demonstrate that the inhibitor-bound form of EYA2 does not favour binding to Mg , which is indispensable for the Tyr phosphatase activity. We further describe characterization and optimization of this class of allosteric inhibitors.

The Usefulness of FEF in Predicting Airway Hyperresponsiveness to Mannitol.

Background And Objective: Despite the usefulness of airway hyperresponsiveness (AHR) testing in diagnosing and monitoring asthma, it is challenging to perform in a real-world setting. Forced expiratory flow between 25% and 75% of vital capacity (FEF), a pulmonary measurement that can be obtained easily during routine spirometry, represents the status of medium-sized and small airways. However, the performance of FEF in predicting AHR has not been well elucidated.

Short-Acting Beta2-Agonist Use in Asthma in Korea: A 10-Year Population-Based Study.

Short-acting β-agonist (SABA) use is known to be lower in Korean patients with asthma than in those from other countries, while the rate of asthma exacerbations in Korea is higher than in other countries. Thus, an epidemiologic study on SABA use and the relationship between SABA overuse and treatment outcomes in asthma is needed in Korea. We performed a cross-sectional study using the National Health Insurance Service-National Sample Cohort 2002-2012 database.

Functional metagenomic analysis of quorum sensing signaling in a nitrifying community.

Quorum sensing (QS) can function to shape the microbial community interactions, composition, and function. In wastewater treatment systems, acylated homoserine lactone (AHL)-based QS has been correlated with the conversion of floccular biomass into microbial granules, as well as EPS production and the nitrogen removal process. However, the role of QS in such complex communities is still not fully understood, including the QS-proficient taxa and the functional QS genes involved.

Neonatal presentations to the paediatric emergency department in Singapore.

Introduction: This study aimed to characterise neonatal paediatric emergency department (PED) visits, analyse the main paediatric illnesses and establish associations of these demographics with the readmission rates and severity of their presentation.

Methods: A retrospective analysis of neonates (aged <28 days) presenting to the PEDs of our hospital over seven months was performed. Associations between the clinical and demographic data of admissions to the PED and inpatient admissions were analysed.

SALM4 negatively regulates NMDA receptor function and fear memory consolidation.

Many synaptic adhesion molecules positively regulate synapse development and function, but relatively little is known about negative regulation. SALM4/Lrfn3 (synaptic adhesion-like molecule 4/leucine rich repeat and fibronectin type III domain containing 3) inhibits synapse development by suppressing other SALM family proteins, but whether SALM4 also inhibits synaptic function and specific behaviors remains unclear. Here we show that SALM4-knockout (Lrfn3) male mice display enhanced contextual fear memory consolidation (7-day post-training) but not acquisition or 1-day retention, and exhibit normal cued fear, spatial, and object-recognition memory.

Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses.

Incident Type 2 Diabetes Risk of Selective Estrogen Receptor Modulators in Female Patients with Breast Cancer.

Accumulating evidence indicates a link between diabetes and cancer. Selective estrogen receptor modulators (SERMs) may increase diabetes risk via antiestrogen effects. This study investigated incident diabetes risk of SERM treatment and its effects on metastatic cancer and death prevention in breast cancer survivors.

Optimizing hepatitis B virus screening in the United States using a simple demographics-based model.

Background And Aims: Chronic hepatitis B (CHB) affects >290 million persons globally, and only 10% have been diagnosed, presenting a severe gap that must be addressed. We developed logistic regression (LR) and machine learning (ML; random forest) models to accurately identify patients with HBV, using only easily obtained demographic data from a population-based data set.

Approach And Results: We identified participants with data on HBsAg, birth year, sex, race/ethnicity, and birthplace from 10 cycles of the National Health and Nutrition Examination Survey (1999-2018) and divided them into two cohorts: training (cycles 2, 3, 5, 6, 8, and 10; n = 39,119) and validation (cycles 1, 4, 7, and 9; n = 21,569).

Additive Effect of Obesity and Dyslipidemia on Wheezing in Korean Adults: A Nationwide Representative Survey Study.

Besides obesity, there are limited studies regarding the relationship between the individual components of metabolic syndrome and wheezing. It is largely unknown whether the co-existence of other metabolic syndrome components has additive effects on wheezing in the adult population. The association between the individual components of metabolic syndrome and current wheezing was evaluated in adults using data from the Korea National Health and Nutrition Examination Survey from 2008 to 2012.

Substantial gaps in evaluation and treatment of patients with hepatitis B in the US.

Background & Aims: The occurrence of HBV-associated liver complications is reduced by antiviral therapy. However, prior studies using local institutional cohorts have suggested that evaluation and treatment are suboptimal. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort.

Systematic review with meta-analysis: prevalence of hepatic steatosis, fibrosis and associated factors in chronic hepatitis B.

Background: As the prevalence of hepatitis steatosis (HS) increases, the prevalence of HS among those with chronic hepatitis B (CHB) may also be increasing but data on the effect of HS on CHB disease progression are lacking.

Aims: To determine the prevalence of HS in CHB and associated factors, prevalence of fibrosis and its association with HS.

Methods: Two researchers independently searched the literature and extracted data.

A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice.

Stem cell factor (SCF) and its receptor, cKIT, are novel regulators of pathological neovascularization in the eye, which suggests that inhibition of SCF/cKIT signaling may be a novel pharmacological strategy for treating neovascular age-related macular degeneration (AMD). This study evaluated the therapeutic potential of a newly developed fully human monoclonal antibody targeting cKIT, NN2101, in a murine model of neovascular AMD. In hypoxic human endothelial cells, NN2101 substantially inhibited the SCF-induced increase in angiogenesis and activation of the cKIT signaling pathway.

A Cervical Smear Scare due to Monsel's Solution: A Case Report.

Monsel's solution has been in use since the end of the 19th century for its valuable property of creating hemostasis in minor disruptions of the epithelium. Its styptic effect was first described by Leon Monsel, a pharmacist in the French army, in a letter dated on October 13, 1852. Containing ferric subsulphate, it is used as a topical hemostatic agent in minor procedures such as biopsies in gynecology, proctology, dermatology, otorhinolaryngology and odontology.

Acute generalized exanthematous pustulosis: Epidemiology, clinical course, and treatment outcomes of patients treated in an Asian academic medical center.

Background: Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse drug reaction. Although acutely patients have significant morbidity and occasional systemic involvement, the clinical course is generally self-limited. To date, there has been no consensus on treatment.

Comparative analysis of Achilles tendon healing outcomes after open tenotomy versus percutaneous tenotomy: An experimental study in rats.

There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required.

Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis.

Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients.

The Association between Serum Vitamin D Concentration and Colon Polyp: A Cross-Sectional Study Using Health Care Screening Database in a Tertiary Hospital in Korea.

Background: As indoor activity increases with modern lifestyles changes, reduced exposure to sunlight may lead to reduced vitamin D synthesis. Previous studies demonstrated that increased vitamin D level is associated with decreased risk of colon cancer; therefore, this study attempted to determine the association between vitamin D and colon polyps, which may be precancerous lesions, in participants who underwent colonoscopy exams.

Methods: A total of 31,004 participants who underwent routine health checkups, including vitamin D level and colonoscopy, at Samsung Medical Center in South Korea from 2010 to 2018 were included in the study.

Gastrointestinal bleeding is associated with higher in-hospital mortality, longer length of stay and higher cost in patients with in-hospital cardiac arrest.

Background: In-hospital cardiac arrest (IHCA) carries a high mortality and significant morbidity in survivors. Gastrointestinal bleeding (GIB) can complicate cardiac arrests. We aim to study the association between GIB and the in-hospital outcomes of patients with IHCA.

Individual 5-Year Lung Cancer Risk Prediction Model in Korea Using a Nationwide Representative Database.

Early detection of lung cancer by screening has contributed to reduce lung cancer mortality. Identifying high risk subjects for lung cancer is necessary to maximize the benefits and minimize the harms followed by lung cancer screening. In the present study, individual lung cancer risk in Korea was presented using a risk prediction model.

Headless Henipaviral Receptor Binding Glycoproteins Reveal Fusion Modulation by the Head/Stalk Interface and Post-receptor Binding Contributions of the Head Domain.

Cedar virus (CedV) is a nonpathogenic member of the (HNV) genus of emerging viruses, which includes the deadly Nipah (NiV) and Hendra (HeV) viruses. CedV forms syncytia, a hallmark of henipaviral and paramyxoviral infections and pathogenicity. However, the intrinsic fusogenic capacity of CedV relative to NiV or HeV remains unquantified.

Impact of 6-Month Exposure to Aerosols From Potential Modified Risk Tobacco Products Relative to Cigarette Smoke on the Rodent Gastrointestinal Tract.

Cigarette smoking causes adverse health effects that might occur shortly after smoking initiation and lead to the development of inflammation and cardiorespiratory disease. Emerging studies have demonstrated the role of the intestinal microbiome in disease pathogenesis. The intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome changes in smokers.