Clinical MetaData ontology: a simple classification scheme for data elements of clinical data based on semantics

Background The increasing use of common data elements (CDEs) in numerous research projects and clinical applications has made it imperative to create an effective classification scheme for the efficient management of these data elements. We applied high-level integrative modeling of entire clinical documents from real-world practice to create the Clinical MetaData Ontology (CMDO) for the appropriate classification and integration of CDEs that are in practical use in current clinical documents. Methods CMDO was developed using the General Formal Ontology method with a manual iterative process comprising five steps: (1) defining the scope of CMDO by conceptualizing its first-level terms based on an analysis of clinical-practice procedures, (2) identifying CMDO concepts for representing clinical data of general CDEs by examining how and what clinical data are generated with flows of clinical care practices, (3) assigning hierarchical relationships for CMDO concepts, (4) developing CMDO properties (e.g., synonyms, preferred terms, and definitions) for each CMDO concept, and (5) evaluating the utility of CMDO. Results We created CMDO comprising 189 concepts under the 4 first-level classes of Description, Event, Finding, and Procedure. CMDO has 256 definitions that cover the 189 CMDO concepts, with 459 synonyms for 139 (74.0%) of the concepts. All of the CDEs extracted from 6 HL7 templates, 25 clinical documents of 5 teaching hospitals, and 1 personal health record specification were successfully annotated by 41 (21.9%), 89 (47.6%), and 13 (7.0%) of the CMDO concepts, respectively. We created a CMDO Browser to facilitate navigation of the CMDO concept hierarchy and a CMDO-enabled CDE Browser for displaying the relationships between CMDO concepts and the CDEs extracted from the clinical documents that are used in current practice. Conclusions CMDO is an ontology and classification scheme for CDEs used in clinical documents. Given the increasing use of CDEs in many studies and real-world clinical documentation, CMDO will be a useful tool for integrating numerous CDEs from different research projects and clinical documents. The CMDO Browser and CMDO-enabled CDE Browser make it easy to search, share, and reuse CDEs, and also effectively integrate and manage CDEs from different studies and clinical documents.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number:HI18C2386). KHIDI had no participation in the study design or data collection and analysis process. KHIDI did not participate in the writing of the manuscript

Assessment of Change in Palatal Sensation in Obstructive Sleep Apnea Patients by Using Two-Point Palatal Discrimination

Objectives. Patients with obstructive sleep apnea syndrome (OSAS) have impaired responses to inspiratory resistive loading during sleep. This may be due, in part, to a change in the upper airway sensation. Therefore, we hypothesized that patients with OSAS have diminished upper airway sensation due to snoring. Methods. A total of 53 participants were selected based on clinical evaluation and polysomnography. Two-point discrimination was measured with modified calipers in the tongue and soft palate. Results. A total of 10 participants were included in the control group, 12 participants in the simple snoring group, and 27 participants in the OSAS group. There were 12 patients in the impaired sensation group of the OSAS group. On comparing polysomnography, patients with impairment of their palatal sensory input in two-point discrimination (TPD) had a more protracted duration of the longest snoring episode than those with simple snoring and normal sensation. Patients with decreased sensory input in TPD had longer average duration of snoring episodes and relative snoring time than those with simple snoring and normal sensory input in cold uvular TPD. Comparison of the cold uvular TPD for normal sensation and impaired sensation in patients with OSAS after treatment showed a different trend. Conclusion. Impaired sensation of the soft palate was correlated with the longest snoring episode duration, average snoring episode duration, and relative snoring time. It is helpful in detecting the early stage of neural degradation in OSAS patients by assessing snoring components of polysomnography and TPD in the soft palate

Scutellaria baicalensis

Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of Scutellaria baicalensis and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of S. baicalensis. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of S. baicalensis compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of S. baicalensis. L6 cells treated with flavonoids and extracts of S. baicalensis increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the S. baicalensis extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function

Clinically Conserved Genomic Subtypes of Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions

A Case of Hypothyroidism and Type 2 Diabetes Associated with Type V Hyperlipoproteinemia and Eruptive Xanthomas

Primary hypothyroidism and type 2 diabetes are both typically associated with the increased level of triglycerides. To date, there have been only a few case reports of type 2 diabetes patients with both type V hyperlipoproteinemia and eruptive xanthomas, but there have been no reports of hypothyroidism patients associated with eruptive xanthomas. We report here on a case of a 48-yr old female patient who was diagnosed with type 2 diabetes and primary hypothyroidism associated with both type V hyperlipoproteinemia and eruptive xanthomas. We found rouleaux formation of RBCs in peripheral blood smear, elevated TSH, and low free T4 level, and dyslipidemia (total cholesterol 18.1 mM/L, triglyceride 61.64 mM/L, HDL 3.0 mM/L, and LDL 2.54 mM/L). She has taken fenofibrate, levothyroxine, and oral hypoglycemic agent for 4 months. After treatment, both TSH level and lipid concentration returned to normal range, and her yellowish skin nodules have also disappeared

Changes in Sensitization Rate to Weed Allergens in Children with Increased Weeds Pollen Counts in Seoul Metropolitan Area

The prevalence of allergic diseases in children has increased for several decades. We evaluated the correlation between pollen count of weeds and their sensitization rate in Seoul, 1997-2009. Airborne particles carrying allergens were collected daily from 3 stations around Seoul. Skin prick tests to pollen were performed on children with allergic diseases. Ragweed pollen gradually increased between 1999 and 2005, decreased after 2005 and plateaued until 2009 (peak counts, 67 in 2003, 145 in 2005 and 83 grains/m3/day in 2007). Japanese hop pollen increased between 2002 and 2009 (peak counts, 212 in 2006 and 492 grains/m3/day in 2009). Sensitization rates to weed pollen, especially ragweed and Japanese hop in children with allergic diseases, increased annually (ragweed, 2.2% in 2000 and 2.8% in 2002; Japanese hop, 1.4% in 2000 and 1.9% in 2002). The age for sensitization to pollen gradually became younger since 2000 (4 to 6 yr of age, 3.5% in 1997 and 6.2% in 2009; 7 to 9 yr of age, 4.2% in 1997 and 6.4% in 2009). In conclusion, sensitization rates for weed pollens increase in Korean children given increasing pollen counts of ragweed and Japanese hop

The Revised Edition of Korean Calendar for Allergenic Pollens

The old calendar of pollens did not reflect current pollen distribution and concentrations that can be influenced by changes of weather and environment of each region in South Korea. A new pollen calendar of allergenic pollens was made based on the data on pollen concentrations obtained in eight regions nationwide between 1997 and 2009. The distribution of pollen was assessed every day at 8 areas (Seoul, Guri, Busan, Daegu, Jeonju, Kwangju, Kangneung, and Jeju) for 12 years between July 1, 1997 and June 30, 2009. Pollens were collected by using Burkard 7-day sampler (Burkard Manufacturing Co Ltd, UK). Pollens which were stained with Calberla's fuchsin staining solution were identified and counted. Pine became the highest pollen in May, and the pollen concentrations of oak and birch also became high. Ragweed appeared in the middle of August and showed the highest pollen concentration in the middles of September. Japanese hop showed a high concentration between the middle of August and the end of September, and mugwort appeared in the middles of August and its concentration increased up until early September. In Kangneung, birch appeared earlier, pine showed a higher pollen concentration than in the other areas. In Daegu, Oriental thuja and alder produced a large concentration of pollens. Pine produced a large concentration of pollens between the middle of April and the end of May. Weeds showed higher concentrations in September and mugwort appeared earlier than ragweed. In Busan the time of flowering is relatively early, and alder and Oriental thuja appeared earliest among all areas. In Kwangju, Oriental thuja and hazelnut appeared in early February. Japanese cedar showed the highest pollen concentration in March in Jeju. In conclusion, update information on pollen calendar in South Korea should be provided for allergic patients through the website to manage and prevent the pollinosis

Genome-wide analysis of DNA methylation patterns in horse

Background: DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. Results: We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density. Conclusions: We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.open1

Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

Background Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone

Voltage Balance Switching Scheme for Series-Connected SiC MOSFET LLC Resonant Converter

To achieve high efficiency and power density, silicon carbide (SiC)-based Inductor-Inductor-Capacitor (LLC) resonant converters are applied to the DC/DC converter stage of a solid-state transformer (SST). However, because the input voltage of an SST is higher than the rated voltage of a commercial SiC device, it is essential to connect SiC devices in series. This structure is advantageous in terms of voltage rating, but a parasitic capacitance tolerance between series-connected SiC devices causes voltage imbalance. Such imbalance greatly reduces system stability as it causes overvoltage breakdown of SiC device. Therefore, this paper proposes a switching scheme to solve the voltage imbalance between SiC metal-oxide-semiconductor field-effect transistors (MOSFETs). The proposed scheme sequentially turns off series-connected SiC MOSFETs to compensate for the turn-off delays caused by parasitic capacitor tolerances. In addition, dead-time selection methods to achieve voltage balance and zero voltage switching simultaneously are provided in detail. To verify the effectiveness of the proposed scheme, experiments were conducted on a 2 kW series-connected SiC MOSFET LLC resonant converter prototype