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Sungyeun Bae,1 Jihoon Kwon,2 Mi-Hye Lee,3 Kyung-Sang Yu,1 SeungHwan Lee1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Department of Statistics, APACE, Seoul, Republic of Korea; 3Yungjin Pharmaceutical Co., Ltd, Seoul, Republic of KoreaCorrespondence: SeungHwan Lee, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-1920, Fax +82-2-742-9252, Email leejh413@snu.ac.krPurpose: Proton pump inhibitors (PPIs) are the first-line therapy for gastroesophageal reflux disorder (GERD). Unlike conventional PPIs, non-enteric coated PPIs with antacid salt enable a faster acid suppression through the rapid absorption of the PPI. YPI-011 is a newly developed fixed-dose combination of a rabeprazole with sodium bicarbonate (NaHCO3). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of YPI-011 to the conventional enteric-coated rabeprazole (Pariet®).Materials and Methods: A randomized, open-label, two-treatment, two-sequence crossover study was conducted with two different doses (10 and 20 mg) and 44 subjects in each group. They randomly received either a test or reference treatment for 7 days in the first period and the other treatment in the second period. Blood samples for the PK analysis were taken after the single- and multiple-dose. Intragastric pH monitoring for the PD analysis was implemented for baseline and after the single- and multiple-dose.Results: Gastric acid suppression evaluated by the percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the multiple-dose was similar between the treatments in both dose groups. The systemic exposure of rabeprazole at steady state after the multiple-dose was also similar between the treatments in both dose groups. The time to reach the maximum rabeprazole concentration was faster in the test treatment. The PK-PD relationship of PPI is well known, and the faster absorption of rabeprazole resulted in a more rapid mode of action in acid suppression.Conclusion: The fixed dose combination of rabeprazole with NaHCO3 showed a faster absorption and consequently, a more rapid gastric acid suppression with a similar systemic exposure of rabeprazole at steady state compared to the conventional enteric-coated rabeprazole.Keywords: comparative pharmacokinetics/pharmacodynamics, intragastric pH monitoring, gastroesophageal reflux disease, immediate release

A new species of the genus Enoploderes Faldermann from South Korea, Enoploderes breviantennatus (이른봄꽃하늘소, i-reun-bom-kkot-ha-neul-so) is described. Full descriptions of both sexes with male genitalia and diagnosable characters comparing to its closest congener, Enoploderes bicolor Ohbayashi, 1941 are provided. Biological notes including photograph of eggs and larvae in nature are also provided.

Lazertinib is a potent, irreversible, brain-penetrant, mutant-selective, and wild type-sparing third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for advanced non-small cell lung cancer (NSCLC). The study aimed to evaluate the effects of food and race on the pharmacokinetics (PK) of lazertinib from a healthy volunteer trial and PK data from NSCLC patients with EGFR mutation.An open-label, single-dose, two-period, single-sequence crossover study was conducted in healthy subjects with two race groups (non-Asian and Asian). Subjects orally received a single dose of lazertinib 240 mg in fasted and fed state (high-fat meal) in each period separated by a 21-day washout. An open-label, multicenter, phase 1/2 study was conducted in Asian and non-Asian patients with NSCLC. Patients were given oral lazertinib 20-320 mg once daily in fasted state continuously in 21-day cycles. PK parameters were evaluated using non-compartmental analysis.A total of 24 healthy subjects (12 non-Asians and 12 Asians) and 52 NSCLC patients (22 non-Asians and 30 Asians) were evaluated. The change in the overall systemic exposure of lazertinib at fed state was less than 15%. Non-Asians showed 58-76% of the systemic exposure than Asians in healthy subjects. In contrast, there were no significant differences in systemic exposure by race both after single and multiple doses among NSCLC patients.Lazertinib can be taken with or without food considering the comparable systemic exposures related to food. Although effect of race was not consistent across studies, there was no evidence for dose adjustment based on race.

DWP16001 is a novel sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes with selective and sustained sodium-glucose cotransporter 2 inhibition. We aimed to evaluate whether the coadministration of DWP16001 and metformin causes any changes in pharmacokinetics (PK) or pharmacodynamics (PD).A randomized, open-label, single- and multiple-dose, 2-sequence, crossover study was conducted in healthy male subjects. Subjects received the following treatments: a single oral dose of DWP16001 (DWP) 2 mg, metformin immediate release 1000 mg (MET) twice daily for 7 days and a single oral dose of DWP and MET at steady-state for metformin (DWP+MET). Serial blood and interval urine were collected for PK and PD analyses. Safety and tolerability profiles were assessed throughout the study.DWP+MET displayed increased peak concentration and area under the concentration-time curve from time 0 to time of the last quantifiable concentration compared with DWP (per standard bioequivalence boundaries, 0.8-1.25); the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) were 1.22 (1.13-1.31) and 1.09 (1.05-1.14), respectively. DWP+MET and MET showed similar peak concentration and area under the concentration-time curve within a dosing interval at steady state for metformin; the GMRs and 90% CIs were 0.98 (0.90-1.06) and 1.05 (0.98-1.13), respectively. The amount of urinary glucose excretion from time 0 to 144 h was also comparable between DWP+MET and DWP (GMR and 90% CI; 0.99, 0.94-1.05).The results suggest that DWP16001 and metformin could be coadministered without clinically relevant PK and PD interactions.

This study aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of vutiglabridin, a potential anti-obesity treatment under development, for the first time in humans. A randomized, placebo-controlled, single- and multiple-ascending dose study (SAD and MAD, respectively) was performed in healthy Koreans and Whites. Subjects randomly received a single oral dose of 30-720 mg vutiglabridin or placebo at a ratio of 8:2 in the SAD study or 240-480 mg vutiglabridin or placebo once daily for 14 days in the MAD study. Food effect was also evaluated in 240 mg single dose group. Pharmacokinetics were evaluated through plasma concentrations, and pharmacodynamic biomarkers related to obesity or inflammation were analyzed. Safety and tolerability were assessed throughout the study. Single and multiple doses of vutiglabridin were generally well-tolerated. The pharmacokinetic parameters show less than dose-proportionality increase, and plasma concentrations increased more than two-fold after multiple administrations. The mean half-life of Koreans and Whites in the MAD study was 110 and 73 h, respectively. The systemic exposure of vutiglabridin was significantly increased when taken with a high-fat meal, and the systemic exposure was lower in Whites than in Koreans. Vutiglabridin was well-tolerated in healthy Koreans and Whites. The plasma concentration increased less than the dose-proportionality manner. These results justify further investigation of vutiglabridin in patients with obesity.

The genus Tuponia Reuter, 1875 belongs to the subfamily Phylinae and comprises 91 species worldwide. Before this study, only T. koreana Kim & Jung had been recorded from the Korean Peninsula. Two species of Tuponia Reuter, 1910 are recognised from the Korean Peninsula including the first record of T. mongolica Drapolyuk, 1980. T. koreana Kim & Jung, 2021 is proposed as a junior synonym of T. chinensis Zheng & Li, 1992. The species is identified, based on the dorsal habitus and male and female genitalic structures. A brief discussion of the distribution of Korean Tuponia species also is presented.

Objectives: Digital therapeutics (DTx) are software-based therapeutic interventions based on clinical evidence. Randomized clinical trials (RCTs) are often the source of clinical evidence, similar to conventional drugs or medical devices. However, novel approaches such as the use of real-world data or digital biomarkers are also utilized. This article aimed to review how DTx products have been clinically evaluated. Methods: DTx products approved by the US Food and Drug Administration as of 2020 were reviewed and products with sufficient published information were selected. Pivotal clinical trials were analyzed according to the elements of the Consolidated Standards of Reporting Trials (CONSORT) guideline. Case reviews were presented for other clinical evaluation strategies, considering the small number of publications. Results: Most approved DTx products used RCTs for clinical evaluations. Similar to conventional RCTs, parallel-group designs with statistical hypothesis testing were adopted. However, DTx trials were often not blinded due to practical issues and involved various comparator groups. In addition, DTx products could be readily evaluated in home-based settings and delivered through the internet. Other evaluation approaches included retrospective analyses using insurance claims data or usage data, which enabled long-term evaluations of effectiveness. Digital biomarkers obtained from real-time and continuous log data were also used to improve the objectiveness of endpoints. Conclusions: RCTs accounted for the majority of DTx evaluations. The designs of DTx trials were comparable to those of drug or device trials, but blinding and comparator elements were often different. Furthermore, the use of real-world data and digital biomarkers are also being tried.

Increasingly many patients are being relisted for repeat kidney transplantation due to longer survival times after transplantation. This study compared the outcomes of second living donor kidney transplantations (LDKTs) with those of first LDKTs.Data were collected retrospectively for 1,429 LDKTs performed from 1995 to 2020 at Samsung Medical Center. The demographics of recipients and donors, immunologic factors, and outcomes of second LDKTs were compared to those of first LDKTs.Among 1,429 cases of LDKT, 1,355 were first LDKT cases and 74 were second LDKT cases. Basic demographic data were comparable for the two groups of patients. The 5- and 10-year graft survival rates were 94% and 84% for first LDKTs and 96% and 86% for second LDKTs, respectively, with neither difference statistically significant (P=0.399). The 5- and 10-year patient survival rates were 98% and 94% for the first and 96% and 93% for the second LDKTs, respectively; neither difference was statistically significant (P=0.766). Multivariate analysis confirmed that a history of previous transplantation was not a statistically significant risk factor for graft loss (hazard ratio [HR], 0.83; P=0.677) or patient death (HR, 1.68; P=0.396).These results indicate that repeat kidney transplantation from living donors is a reasonable choice for patients who have experienced graft loss.

Because a transmitter-side controller of an inductive power transfer (IPT) system cannot directly measure its load conditions, i.e. receiver-side output voltages and currents, wireless communications are commonly used in many IPT systems. However, the wireless communication can cause a devastating failure of the IPT system because of its tens of milliseconds delays and frequent data losses. The mismatch between the transmitted and the received power can destroy the receiver-side power converters. In this study, receiver-side load voltage and current observers for a seriesseries tuned IPT system are proposed using well-known disturbance observer theories. A load current observer that has a 10kHz estimation bandwidth and a load voltage observer that has a 200Hz bandwidth are proposed. Estimated load voltage and current have much faster dynamics than the wireless feedback signals without data loss. Therefore, the proposed observers can bring significant advances in reliability and performance of the IPT system. Design guidelines for the observers that have low steady state errors and fast dynamics are suggested. Theoretical performances of the proposed observers are evaluated by simulations and experiments. Estimated current followed its actual value in 0.1ms and the estimated voltage followed its measured value in 4ms as expected from the simulations.

The plant but genus Orthotylus Fieber, 1858 in Korea is reviewed. One species, O. riparius Kulik is newly recorded from the Korean peninsula. Diagnostic characters of each species are discussed, with the images of adult specimen and genitalic structures. Additionally, a key to the Korean Orthotylus species is presented. Chinese record of O. riparius is excluded based on critical literature reviews. Observed variant of O. riparius Kulik and O. salicis Jakovlev are discussed.

The sparse precision matrix plays an essential role in the Gaussian graphical model since a zero off-diagonal element indicates conditional independence of the corresponding two variables given others. In the Gaussian graphical model, many methods have been proposed, and their theoretical properties are given as well. Among these, the sparse precision matrix estimation via scaled lasso (SPMESL) has an attractive feature in which the penalty level is automatically set to achieve the optimal convergence rate under the sparsity and invertibility conditions. Conversely, other methods need to be used in searching for the optimal tuning parameter. Despite such an advantage, the SPMESL has not been widely used due to its expensive computational cost. In this paper, we develop a GPU-parallel coordinate descent (CD) algorithm for the SPMESL and numerically show that the proposed algorithm is much faster than the least angle regression (LARS) tailored to the SPMESL. Several comprehensive numerical studies are conducted to investigate the scalability of the proposed algorithm and the estimation performance of the SPMESL. The results show that the SPMESL has the lowest false discovery rate for all cases and the best performance in the case where the level of the sparsity of the columns is high., Comment: To appear in Computational Statistics

The influence of complexation between porcine gastric mucin (PGM) and lysozyme (LYZ) solutions (pH⁓7.0) on their lubricating properties was studied at a hydrophobic self-mated polydimethylsiloxane (PDMS) tribopair. To this end, LYZ solutions with varying heating time, namely 1

PURPOSE This study aimed to identify the underlying dimensions of brand (professional sport team) authenticity and to develop a valid, reliable scale to measure these dimensions.METHODS A pool of 67 potential items was drawn through a literature review, content analysis, qualitative research (n=43), and an expert evaluation. The identified items were subjected to exploratory factor analysis (n=248) and confirmatory factor analysis (n=285). In addition, multiple regressions were conducted to examine the criterion validity of the scale.RESULTS The results showed that the brand authenticity scale for professional sport teams consists of 42 items representing 8 dimensions: continuity, originality, quality commitment, heritage, symbolism, credibility, stakeholder-related integrity, and consumer-related integrity. The study has proven evidences of internal consistency and convergent, discriminant, and criterion validity of the scale.CONCLUSIONS The findings suggest that the scale developed in this study offers a vital foundation to understand the structure of brand authenticity in the context of sport fans and its impact on sport consumer behavior.

The Pocadius-complex (Nitidulidae: Nitidulinae) from Korea is reviewed. A total of nine species are recognized, including four new records in Korea: Atarphia cincta Jelinek, Jia & Hajek, 2012, Atarphia fasciculata Reitter, 1884, Pocadites corpulentus Reitter, 1884, and Pocadites rufobasalis Reitter, 1884. Descriptions, photographs of external morphology, biological information, and a key to all Korean species are provided.

Nocturnal acid breakthrough has been considered an unmet need of proton-pump inhibitors. Tegoprazan, a novel potassium-competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night-time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid-suppressive effects.A randomized, open-label, 3-period, 6-sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing.Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night-time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night-time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes.Tegoprazan produced more rapid, potent and well sustained night-time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.

Blockchain is a novel data architecture characterized by a chronological sequence of blocks in a decentralized manner. We aimed to evaluate the real-world feasibility of a blockchain-based dynamic consent platform (METORY) in a decentralized and multicenter trial. The study consisted of three visits (i.e., screening and 2 follow-up visits) with a 2-week interval. Each subject was required to report the self-measured body temperatures and take a virtual investigational drug by entering the unique drug code on the application. To simulate real-world study settings, two major (i.e., changes in the schedule of body temperature measurement) and three minor protocol amendments (i.e., nonsignificant changes without any changes in the procedures) were set. Overall study completion rates, proportion of consent, and response time to each protocol amendment and adherence were evaluated. A total of 60 subjects (30 in each center) were enrolled in two study centers. All subjects completed the study, and the overall proportion of consent to each protocol amendment was 95.7 ± 13.7% (mean ± SD), with a median response time of 0.2 h. Overall, subjects took 90.8% ± 19.2% of the total drug, whereas compliance with the schedule was 69.1% ± 27.0%. Subjects reported 96.7% ± 4.2% of the total body temperature measurements whereas the adherence to the schedule was 59.0% ± 25.0%, which remarkably decreased after major protocol amendments. In conclusion, we evaluated a blockchain-based dynamic consent platform in real clinical trial settings. The results suggested that major changes should be avoided unless subjects' proper understanding is warranted.

The lace bug genus Alloiothucha Drake, 1927 (Hemiptera: Heteroptera: Tingidae) is recorded from Laos for the first time with the redescription of Alloiothucha artocarpi (Horváth, 1926), which has been originally described from Indonesia (Java Island) in Latin. This species was collected on jackfruit, Artocarpus heterophyllus Lam. (Moraceae) in Laos, and may represent a pest of potential future concern. An identification key to all described species of Alloiothucha and arguments for a junior synonymy of Cetiothucha is presented: Alloiothucha Drake, 1927 = Cetiothucha Drake & Ruhoff, 1965, syn. nov. Two new combinations are proposed: Alloiothucha constanti (Guilbert, Pham & Soulier-Perkins, 2018), comb. nov. and Alloiothucha physalia (Drake & Ruhoff, 1965), comb. nov. from Cetiothucha.

Mealybugs (Hemiptera: Pseudococcidae, Rhizoecidae and Xenococcidae) are important organisms for understanding processes of evolution, especially microbial symbiotic systems and interactions with host plants. Molecular phylogenetic trees were reconstructed for 128 species of mealybug using DNA fragments of eight loci, namely a mitochondrial (COI), nuclear ribosomal RNA (18S and 28S D2 and D10) and nuclear protein-encoding genes (EF-1α 5′ and 3′, Dynamin and wingless). In addition, data on the types of obligate endosymbionts were used to test the monophyly of major groups resulting from this molecular phylogeny. Based on the data from DNA sequences, morphology and obligate endosymbionts, we present a phylogeny supporting the families Rhizoecidae and Xenococcidae separate from Pseudococcidae, and the separation of Rastrococcus Ferris from Phenacoccinae and Pseudococcinae. Consequently, Rastrococcus is excluded from Phenacoccinae and elevated to subfamily Rastrococcinae subfam. nov. We also found support for Putoidae as a family distinct from the true mealybugs. Phenacoccus rubicola Kwon, Danzig & Park is transferred to Coccura Šulc.

Hypertension and hyperlipidemia are often comorbid, requiring combination therapies of antihypertensive drugs and antihyperlipidemia drugs. Taking 1 fixed-dose combination (FDC) may increase patient compliance rather than taking each of the drugs separately. This study aimed to evaluate the pharmacokinetic bioequivalence between an FDC of pitavastatin/valsartan 4/160 mg and the corresponding individual components. Considering that valsartan is a highly variable drug for maximum plasma concentration (C

ALD/MLD hybrid 2D tincone films were investigated structurally post-annealing. GIWAXS showed that individual benzene ring bonds were combined with the SnO layer in a repeated arrangement of the tincone monomer.